meta_pmid
int64 | meta_language
string | meta_mesh_ids
list | meta_mesh_terms
list | meta_pubdate_year
string | meta_pubdate_month
string | text
string |
|---|---|---|---|---|---|---|
9,633,794
|
eng
|
[
"D000804",
"Q000037",
"Q000494",
"D000818",
"D000959",
"Q000494",
"D001127",
"Q000037",
"Q000494",
"D066298",
"D008297",
"D011725",
"Q000494",
"D051381",
"D017208",
"D012079",
"Q000187",
"D013152",
"Q000187",
"D013237"
] |
[
"Angiotensin II",
"Animals",
"Antihypertensive Agents",
"Arginine Vasopressin",
"In Vitro Techniques",
"Male",
"Pyridines",
"Rats",
"Rats, Wistar",
"Renal Circulation",
"Splanchnic Circulation",
"Stereoisomerism"
] |
1998
|
May
|
Inhibition by (-)-cicletanine of the vascular reactivity to angiotensin II and vasopressin in isolated rat vessels.
In pithed rats, the levorotatory (-)-enantiomer of cicletanine reduces the pressor responses to angiotensin II (AII) and also, to a lesser extent, those to arginine-vasopressin (AVP). Here we have attempted to characterize further these inhibitory effects by studies of isolated perfused rat kidney and mesenteric vascular beds. In the isolated rat kidney, (-)-cicletanine behaves as a noncompetitive antagonist of AII- and AVP-receptor stimulation, with Ki values of 9.6 and 208 micromol/L respectively. In the isolated mesenteric vascular bed, (-)-cicletanine antagonized both AII dependent contractions with an inhibitory concentration (IC50) of 54.0 +/- 20.5 micromol/L (n = 6), and AVP dependent contractions with an IC50 of 31.6 +/- 5.0 micromol/L (n = 8). In conclusion, (-)-cicletanine antagonizes AII more effectively in rat kidney than in mesenteric vascular beds. Moreover, in rat kidney vascular beds (-)-cicletanine is more potent in blocking the pressor responses to AII than in blocking those to AVP. A selective blockade of AII induced contractions in kidney vascular beds can be one factor explaining both the greater antagonistic potency of (-)-cicletanine against AII compared with AVP in pithed rats, and the renal protective properties of cicletanine in both hypertensive and aged rats.
|
9,633,795
|
eng
|
[
"D000818",
"D000838",
"Q000494",
"D002712",
"Q000494",
"D006224",
"Q000235",
"D006020",
"Q000494",
"D006973",
"Q000201",
"Q000235",
"D007668",
"Q000187",
"Q000201",
"D015260",
"Q000378",
"D009994",
"D011480",
"Q000494",
"D015244",
"Q000494"
] |
[
"Animals",
"Anions",
"Chlorides",
"Cricetinae",
"Glycopeptides",
"Hypertension",
"Kidney",
"Neprilysin",
"Osmolar Concentration",
"Protease Inhibitors",
"Thiorphan"
] |
1998
|
May
|
Increased tissue neutral endopeptidase 24.11 activity in spontaneously hypertensive hamsters.
The purpose of this study was to determine whether tissue neutral endopeptidase (NEP) 24.11 activity, a membrane-bound metalloenzyme widely distributed in the peripheral circulation that cleaves and inactivates vasodilator peptides, is increased in spontaneously hypertensive hamsters relative to genetically/age-matched normotensive hamsters. Mean arterial pressure and heart rate were 163 +/- 11 mm Hg and 312 +/- 7 beats/min in spontaneously hypertensive hamsters and 99 +/- 3 mm Hg and 302 +/- 10 beats/min in normotensive hamsters, respectively (mean +/- SEM). NEP 24.11 activity is significantly increased in the kidney, cheek pouch, and spinotrapezius muscle, and significantly decreased in the heart and aorta of spontaneously hypertensive hamsters relative to controls (P < .05). Lung and brain NEP 24.11 activity is similar in both groups. Renal NEP 24.11 activity increases and to a similar extent in spontaneously hypertensive and normotensive hamsters as chloride anion concentration in the assay buffer is increased. Substituting citrate for chloride anion significantly attenuates renal NEP 24.11 activity. Taken together, these data indicate that NEP 24.11 activity in spontaneously hypertensive hamsters is increased in two organs that contribute appreciably to peripheral vascular resistance, skeletal muscle, and kidney. We suggest that the spontaneously hypertensive hamster is a suitable model to study the role of skeletal muscle and renal NEP 24.11 in regulating vasomotor tone in essential hypertension.
|
9,633,796
|
eng
|
[
"D000172",
"Q000188",
"Q000503",
"Q000601",
"D000328",
"D001794",
"Q000187",
"D002940",
"Q000502",
"D005260",
"D006339",
"Q000187",
"D006728",
"Q000627",
"D019382",
"Q000097",
"D006801",
"D008297",
"D008875",
"D015282",
"Q000627",
"D010902",
"Q000601",
"D016896"
] |
[
"Acromegaly",
"Adult",
"Blood Pressure",
"Circadian Rhythm",
"Female",
"Heart Rate",
"Hormones",
"Human Growth Hormone",
"Humans",
"Male",
"Middle Aged",
"Octreotide",
"Pituitary Gland",
"Treatment Outcome"
] |
1998
|
May
|
Effect of octreotide on 24-h blood pressure profile in acromegaly.
The aim of the study was to investigate the effect of octreotide, a somatostatin analog drug potentially able to inhibit growth hormone (GH), on the circadian blood pressure profile in a group of patients with acromegaly. Ten patients with GH-secreting pituitary adenoma were studied before and 6 months after treatment with subcutaneous octreotide 0.2 to 0.6 mg/day. Twenty-four hour blood pressure and heart rate were measured every 15 min at daytime (07:00 to 22:59) and every 30 min at nighttime (23:00 to 06:59) using a TM-2420 recorder. No correlation was found between GH levels and 24-h blood pressure in baseline conditions. Untreated patients had a significant nocturnal decrease of both systolic and diastolic blood pressure (P < .01), and all showed a circadian systolic or diastolic blood pressure rhythm. During octreotide treatment, 24 h as well as nighttime systolic and diastolic blood pressures significantly increased (P < .05), whereas daytime systolic and diastolic blood pressures did not change. Treated patients did not have a nocturnal decline in both systolic and diastolic blood pressures (P = NS), and eight lost their systolic or diastolic blood pressure rhythm. In conclusion, blood pressure circadian rhythm seems to be maintained in acromegaly. Octreotide treatment is associated with an increase of 24-h and nighttime blood pressure, and with loss of circadian blood pressure rhythm. Splanchnic vasoconstriction by this drug, shifting blood to peripheral vessels, may explain this phenomenon.
|
9,633,797
|
eng
|
[
"D000959",
"Q000627",
"D004562",
"D006339",
"Q000187",
"D006801",
"D006973",
"Q000188",
"Q000503",
"D008297",
"D013997"
] |
[
"Antihypertensive Agents",
"Electrocardiography",
"Heart Rate",
"Humans",
"Hypertension",
"Male",
"Time Factors"
] |
1998
|
May
|
Comparison of effects of antihypertensive drugs on heart rate: changes from baseline by baseline group and over time. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.
Baseline heart rate is becoming recognized as a predictor of cardiovascular risk. Various antihypertensive drugs have differing effects on heart rate. A randomized controlled clinical trial of 1292 ambulatory men with stage 1 or 2 hypertension was conducted in 15 Veterans Affairs medical centers. Patients were treated with hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or placebo for up to 2 years. Heart rates were measured at baseline, the end of titration, 1 year, and 2 years. Data were also stratified by baseline heart rate. A subset of patients had heart rate also determined by electrocardiogram. All drugs except prazosin reduced heart rate from baseline; additional small decreases were obtained over time with hydrochlorothiazide and placebo. The decrease initially achieved with clonidine was attenuated over time. The overall reduction in heart rate was greatest for atenolol (-12.2 beats/min) and least for prazosin (+3.8 beats/min). Only atenolol effected a further reduction of heart rate for patients whose baseline rate was < or =65 beats/min. All drugs reduced heart rate when the baseline was > or =85 beats/min. Data derived by electrocardiogram yielded similar results. The drugs used in this study differ in their ability to reduce heart rate, sustain that reduction over time, and to change heart rate in groups with high or low rates at baseline. The importance of these comparative changes as independent cardiac risk factor variables remains to be determined.
|
9,633,798
|
eng
|
[
"D000328",
"D000368",
"D001794",
"Q000502",
"D001795",
"Q000379",
"D018660",
"D005260",
"D006801",
"D006973",
"Q000503",
"D008297",
"D008875",
"D009819",
"D011446",
"D012621"
] |
[
"Adult",
"Aged",
"Blood Pressure",
"Blood Pressure Determination",
"Blood Pressure Monitoring, Ambulatory",
"Female",
"Humans",
"Hypertension",
"Male",
"Middle Aged",
"Office Visits",
"Prospective Studies",
"Seasons"
] |
1998
|
May
|
No relevant seasonal influences on office and ambulatory blood pressure: data from a study in borderline hypertensive primary care patients.
Our objective was to study seasonal influences on office and ambulatory blood pressure. We therefore designed a prospective 7-month study of 47 borderline hypertensive patients in a primary care setting. We used no interventions. Our main outcome measures were the differences between summer and winter office and ambulatory blood pressures and 95% confidence intervals. Results showed that winter minus summer differences ranged from 0 to 3 mm Hg. Only one significant difference was found: ambulatory systolic daytime pressure was significantly higher (3 mm Hg) in winter than in summer. Our results do not confirm the data of earlier studies in hypertensives. In view of the small and clinically irrelevant winter-summer differences, it seems unnecessary to modify antihypertensive treatment of borderline hypertensives according to the season.
|
9,633,799
|
eng
|
[
"D000328",
"D001794",
"Q000502",
"D018660",
"D002909",
"Q000502",
"D002940",
"Q000502",
"D003971",
"D005260",
"D006801",
"D007297",
"D008297",
"D010045",
"D013599"
] |
[
"Adult",
"Blood Pressure",
"Blood Pressure Monitoring, Ambulatory",
"Chronobiology Phenomena",
"Circadian Rhythm",
"Diastole",
"Female",
"Humans",
"Inpatients",
"Male",
"Outpatients",
"Systole"
] |
1998
|
May
|
How reliable is nighttime blood pressure dipping?
This report examines the reliability of nighttime blood pressure dipping. Twenty-one individuals were studied twice with ambulatory blood pressure monitoring. On one occasion they were studied as outpatients, and on the other as inpatients on a clinical research ward. Blood pressure monitoring revealed the expected dip in blood pressure at nighttime. However, there was little test-retest reliability across the two settings. The test-retest correlations for the dip in blood pressure across the two settings were nonsignificant for systolic, diastolic, and mean arterial blood pressure. Caution is advised before diagnosing dipping or nondipping on the basis of one 24-h ambulatory blood pressure recording.
|
9,633,800
|
eng
|
[
"D000328",
"D003142",
"D003376",
"D004501",
"Q000379",
"D005260",
"D006801",
"D006973",
"Q000503",
"Q000628",
"D008297",
"D010353",
"D013337"
] |
[
"Adult",
"Communication",
"Counseling",
"Education, Medical",
"Female",
"Humans",
"Hypertension",
"Male",
"Patient Education as Topic",
"Students, Medical"
] |
1998
|
May
|
Training students in education of the hypertensive patient: enhanced performance after a simulated patient instructor (SPI)-based exercise.
The process whereby a physician explains to the ill patient what has gone wrong and what can be done about it can be taught and evaluated by simulated patients (SPIs). This study was designed to determine whether a training experience in educating a diabetic SPI improves subsequent performance with a hypertensive SPI. Competence in educating a hypertensive SPI by students who had no prior training experience (n = 26) was compared to that of an experimental group (n = 20) that had a prior training session. Performance was assessed with a counseling skills scale and a case-specific content checklist (1 = poor to 5 = excellent). Students in the experimental group performed better than controls in both counseling skills (4.46 v 3.86, P < .01) and completeness of coverage of content (3.28 v 2.65, P < .01). Students in both groups focused more on clinical features and treatment than on laboratory testing and follow-up. The ability to counsel "patients" with hypertension can be enhanced by a prior learning experience with a diabetic SPI. Clinical application of knowledge about hypertension can be assessed by SPIs.
|
9,633,801
|
eng
|
[
"D000319",
"Q000627",
"D000959",
"Q000627",
"D001794",
"Q000187",
"D002227",
"Q000627",
"D002302",
"Q000187",
"D000077261",
"D004305",
"D005260",
"D006339",
"Q000187",
"D006439",
"Q000187",
"D006801",
"D006973",
"Q000188",
"Q000503",
"D008297",
"D008790",
"Q000627",
"D008875",
"D011412",
"Q000627",
"D016037",
"D014655",
"Q000187"
] |
[
"Adrenergic beta-Antagonists",
"Antihypertensive Agents",
"Blood Pressure",
"Carbazoles",
"Cardiac Output",
"Carvedilol",
"Dose-Response Relationship, Drug",
"Female",
"Heart Rate",
"Hemodynamics",
"Humans",
"Hypertension",
"Male",
"Metoprolol",
"Middle Aged",
"Propanolamines",
"Single-Blind Method",
"Vascular Resistance"
] |
1998
|
May
|
Hemodynamic differences between metoprolol and carvedilol in hypertensive patients.
Resting hemodynamics were measured before, at 2 and 24 h after the first dose, and after 4 weeks of monotherapy with either metoprolol or carvedilol in a randomized single-blind study. We analyzed results from 24 hypertensive patients (30-68 years of age) with adequate blood-pressure lowering on monotherapy. Acutely, both drugs lowered systolic blood pressure and heart rate. Whereas metoprolol reduced cardiac output and increased both systemic and femoral artery resistance, carvedilol did not alter cardiac output but led to reductions in the systemic and regional resistances. After 4 weeks of therapy, cardiac output remained reduced and vascular resistances increased in the metoprolol group, whereas in carvedilol patients cardiac output continued to be unchanged and the trend for vascular resistances to be decreased persisted. Acutely and chronically the differences in the hemodynamic effects of the two medications were statistically significant. The study results indicate that carvedilol's vasodilatory action is not subject to tolerance development. Chronic afterload reduction associated with the decrease in systemic vascular resistance may lead to additional savings in myocardial oxygen consumption, a beneficial feature particularly in those patients with concomitant ischemic heart disease. It may also have a favorable influence on concentric cardiac hypertrophy and changes in the walls of arteriolar resistance vessels.
|
9,633,802
|
eng
|
[
"D000959",
"Q000191",
"D002561",
"Q000517",
"D003363",
"D016527",
"D006801",
"D006973",
"Q000188",
"D009203",
"Q000517",
"D012680"
] |
[
"Antihypertensive Agents",
"Cerebrovascular Disorders",
"Cost Control",
"Drug Costs",
"Humans",
"Hypertension",
"Myocardial Infarction",
"Sensitivity and Specificity"
] |
1998
|
May
|
Cost-minimization and the number needed to treat in uncomplicated hypertension.
The goal of this study was to compare the direct costs associated with the prescription of thiazide diuretics, beta-receptor blockers (beta-blockers), angiotensin converting enzyme inhibitors (ACEI), a-receptor blockers (alpha-blockers), and calcium channel blockers (CCB) for the prevention of stroke, myocardial infarction (MI) and premature death in uncomplicated hypertension. We performed a cost-minimization analysis based on numbers-needed-to-treat (NNT) derived from the metaanalysis of 15 major clinical trials of hypertension treatment, and the average wholesale prices of both the most commonly prescribed and the least expensive drugs in each class. The inclusion criteria for clinical trials were that they be randomized, controlled trials of drug therapy of uncomplicated mild-to-moderate hypertension with stroke, MI, or death as endpoints. The wholesale drug costs and the total direct outpatient treatment costs to prevent a stroke, MI or death among middle-aged and elderly hypertensives were our outcome measures. The estimated wholesale drug acquisition cost to prevent one major event (MI or stroke or death) ranged from $4730 to $346,236 among middle-aged patients, and from $1595 to $116,754 in the elderly; generic diuretic or beta-blocker therapy was more economical than treatment with an ACEI, alpha-blocker, or CCB. The associated 5-year NNT was 86 for middle-aged patients and 29 for elderly patients. Diuretic therapy remained more cost-effective even under the unlikely assumption that the newer drugs were 50% more effective than diuretics at preventing these major events. The costs associated with potassium supplementation did not eliminate the advantage of diuretics. Treatment costs to prevent major hypertensive complications are much lower with diuretics and beta-blockers than with ACEI, CCB, or alpha-blockers, especially in middle-aged patients.
|
9,633,803
|
eng
|
[
"D000818",
"D002478",
"D002490",
"Q000293",
"Q000502",
"D018920",
"D017077",
"D007249",
"D008262",
"D008264",
"Q000502",
"D008297",
"D017628",
"Q000502",
"D009416",
"Q000502",
"D009569",
"Q000378",
"D009900",
"Q000502",
"D020221",
"D009924",
"D009928",
"D059348",
"D010525",
"Q000502",
"D010587",
"D051381",
"D017208",
"D012584",
"Q000293",
"Q000502",
"D016212",
"Q000502"
] |
[
"Animals",
"Cells, Cultured",
"Central Nervous System",
"Coculture Techniques",
"Culture Media, Conditioned",
"Inflammation",
"Macrophage Activation",
"Macrophages",
"Male",
"Microglia",
"Nerve Regeneration",
"Nitric Oxide",
"Optic Nerve",
"Optic Nerve Injuries",
"Organ Culture Techniques",
"Organ Specificity",
"Peripheral Nerve Injuries",
"Peripheral Nerves",
"Phagocytosis",
"Rats",
"Rats, Wistar",
"Sciatic Nerve",
"Transforming Growth Factor beta"
] |
1998
|
Jul
|
Differential effects of central and peripheral nerves on macrophages and microglia.
The poor ability of injured central nervous system (CNS) axons to regenerate has been correlated, at least partially, with a limited and suppressed postinjury inflammatory response. A key cell type in the inflammatory process is the macrophage, which can respond in various ways, depending on the conditions of stimulation. The aim of this study is to compare the activities of macrophages or microglia when encountering CNS and peripheral nervous systems (PNS), on the assumption that nerve-related differences in the inflammatory response may have implications for tissue repair and thus for nerve regeneration. Phagocytic activity of macrophages or of isolated brain-derived microglia was enhanced upon their exposure to sciatic (PNS) nerve segments, but inhibited by exposure to optic (CNS) nerve segments. Similarly, nitric oxide production by macrophages or microglia was induced by sciatic nerve segments but not by optic nerve segments. The previously demonstrated presence of a resident inhibitory activity in CNS nerve, could account, at least in part, for the inhibited phagocytic activity of blood-borne macrophages in CNS nerve as well as of microglia resident in the brain. It seems that the CNS microglia are reversibly immunosuppressed by the CNS environment, at least with respect to the activities examined here. It also appears from this study that the weak induction of early healing-related activities of macrophages/microglia in the environment of CNS might explain the subsequent failure of this environment to acquire growth-supportive properties in temporal and spatial synchrony with the needs of regrowing axons.
|
9,633,804
|
eng
|
[
"D000818",
"D000911",
"Q000276",
"D001253",
"Q000166",
"Q000378",
"D015415",
"D001921",
"Q000166",
"Q000196",
"Q000254",
"D016203",
"Q000378",
"D019070",
"D016764",
"D002531",
"Q000166",
"Q000196",
"Q000254",
"D004797",
"D008938",
"D019579",
"Q000166",
"Q000196",
"Q000254",
"D009419",
"Q000032",
"Q000378",
"D009457",
"Q000737",
"Q000145",
"Q000166",
"D010446",
"Q000276",
"D010750",
"Q000032",
"Q000378",
"D010766",
"D011499",
"D051381",
"D014746",
"Q000032",
"Q000276",
"Q000378"
] |
[
"Animals",
"Antibodies, Monoclonal",
"Astrocytes",
"Biomarkers",
"Brain",
"CDC2 Protein Kinase",
"Cell Lineage",
"Cell Polarity",
"Cerebellum",
"Enzyme-Linked Immunosorbent Assay",
"Mitosis",
"Neocortex",
"Nerve Tissue Proteins",
"Neuroglia",
"Peptide Fragments",
"Phosphoproteins",
"Phosphorylation",
"Protein Processing, Post-Translational",
"Rats",
"Vimentin"
] |
1998
|
Jul
|
Visualization of mitotic radial glial lineage cells in the developing rat brain by Cdc2 kinase-phosphorylated vimentin.
Although accumulating data reveal patterns of proliferation, migration, and differentiation of neuronal lineage cells in the developing brain, gliogenesis in the brain has not been well elucidated. In the rat brain, vimentin is selectively expressed in radial glia and in their progeny, not in oligodendrocytes or neurons from embryonic day 15 (E15) until postnatal day 15 (P15). Here we examined mitotic radial glial lineage cells in the rat brain E17-P7, using the monoclonal antibody 4A4, which recognizes vimentin phosphorylated by a mitosis-specific kinase, cdc2 kinase. In the neocortex, mainly radial glia in the ventricular zone, but not their progeny, underwent cell division. In contrast, not only radial glia but also various types of radial glial progeny including Bergmann glia continued to proliferate in the cerebellum. Radial glia in the neocortex divided horizontally, obliquely, and vertically against the ventricular surface. The percentage of the vertical division increased with progress in the stage of development, concurrently with the decrease of the population of horizontal divisions. Thus, the monoclonal antibody 4A4 provides an useful tool to label mitotic glia in the developing brain and revealed different patterns of gliogenesis in the neocortex and cerebellum. A possibility is discussed that the dynamics of mitotic orientation observed here may be related to the change of the pattern of gliogenesis during development.
|
9,633,805
|
eng
|
[
"D000818",
"D001253",
"Q000737",
"Q000145",
"Q000378",
"D017403",
"D017136",
"D008856",
"D009206",
"Q000737",
"D062559",
"D009419",
"Q000032",
"Q000187",
"Q000235",
"D009928",
"D016133",
"D012333",
"Q000032",
"Q000096",
"D051381",
"D017207",
"D012964",
"Q000378",
"D015222",
"Q000032",
"D013116",
"Q000166",
"D013779",
"Q000494"
] |
[
"Animals",
"Astrocytes",
"In Situ Hybridization",
"Ion Transport",
"Microscopy, Fluorescence",
"Myocardium",
"NAV1.8 Voltage-Gated Sodium Channel",
"Nerve Tissue Proteins",
"Organ Specificity",
"Polymerase Chain Reaction",
"RNA, Messenger",
"Rats",
"Rats, Sprague-Dawley",
"Sodium",
"Sodium Channels",
"Spinal Cord",
"Tetrodotoxin"
] |
1998
|
Jul
|
Glial cells have heart: rH1 Na+ channel mRNA and protein in spinal cord astrocytes.
Astrocytes in vitro express several distinct voltage-sensitive sodium currents, including tetrodotoxin (TTX)-resistant in non-stellate astrocytes and TTX-sensitive currents in stellate astrocytes. However, the molecular identity of the underlying channels, and the mechanisms that regulate their expression, have yet to be identified. Since spinal cord astrocytes in vitro express sodium currents that are nearly ten-fold greater that those of astrocytes derived from other regions, we used reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization, and immunocytochemistry to search for a sodium channel mRNA and protein corresponding to a TTX-resistant channel in these cells. RT-PCR did not detect transcripts for SNS, which is known to encode a TTX-resistant current in dorsal root ganglion neurons. However, RT-PCR demonstrated the presence of rH1 mRNA in cultured spinal cord astrocytes derived from postnatal day 0 (P0) Sprague Dawley rats at 7 days in vitro and in also intact spinal cords of P0 and P7 rats. Hybridization signal for rH1 mRNA was detected by in situ hybridization cytochemistry in most non-stellate and, at varying levels, in stellate astrocytes in these cultures. Immunocytochemical studies, utilizing a polyclonal antibody (R-12) generated against a conserved polypeptide sequence of sodium channels, demonstrated sodium channel immunoreactivity in non-stellate and stellate astrocytes in these cultures. Spinal cord cultures reacted with a rH1-specific polyclonal antibody also showed rH1 immunostaining in non-stellate and stellate astrocytes, although the intensity of the rH1 immunoreactivity in both astrocyte morphologies was attenuated compared to that observed with the R-12 generic sodium channel antibody. The presence of rH1 mRNA and protein in non-stellate astrocytes in vitro provides a possible correlate for the TTX-resistant current that has been recorded in these cells. Since TTX-resistant current is not present in stellate astrocytes, the presence of rH1 mRNA and protein in these cells suggests, in addition, that post-translational mechanisms participate in the control of sodium channel expression in these cells.
|
9,633,807
|
eng
|
[
"D000818",
"D001253",
"Q000378",
"Q000473",
"D015415",
"D001933",
"Q000378",
"Q000473",
"D002455",
"D051152",
"D003167",
"D003169",
"Q000378",
"D003165",
"Q000096",
"Q000235",
"D005260",
"D005786",
"D005904",
"Q000096",
"Q000235",
"D006023",
"Q000096",
"Q000235",
"D007074",
"Q000378",
"D017403",
"D017628",
"Q000502",
"D018832",
"D009419",
"Q000235",
"Q000378",
"D009457",
"Q000378",
"Q000473",
"D009836",
"Q000378",
"Q000473",
"D016376",
"Q000032",
"D009928",
"D010587",
"D012333",
"Q000032",
"D051381",
"D017207",
"D019051",
"D012584",
"Q000293",
"Q000473",
"D013126",
"Q000293",
"Q000473",
"D014855"
] |
[
"Animals",
"Astrocytes",
"Biomarkers",
"Brain Stem",
"Cell Division",
"Clusterin",
"Complement Activation",
"Complement Inactivator Proteins",
"Complement System Proteins",
"Female",
"Gene Expression Regulation",
"Glial Fibrillary Acidic Protein",
"Glycoproteins",
"Immunoglobulin G",
"In Situ Hybridization",
"Microglia",
"Molecular Chaperones",
"Nerve Tissue Proteins",
"Neuroglia",
"Oligodendroglia",
"Oligonucleotides, Antisense",
"Organ Specificity",
"Phagocytosis",
"RNA, Messenger",
"Rats",
"Rats, Sprague-Dawley",
"Rhizotomy",
"Sciatic Nerve",
"Spinal Nerve Roots",
"Wallerian Degeneration"
] |
1998
|
Jul
|
Glial cell responses, complement, and clusterin in the central nervous system following dorsal root transection.
We have examined the glial cell response, the possible expression of compounds associated with the complement cascade, including the putative complement inhibitor clusterin, and their cellular association during Wallerian degeneration in the central nervous system. Examination of the proliferation pattern revealed an overall greater mitotic activity after rhizotomy, an exclusive involvement of microglia in this proliferation after peripheral nerve injury, but, in addition, a small fraction of proliferating astrocytes after rhizotomy. Immunostaining with the phagocytic cell marker ED1 gradually became very prominent after rhizotomy, possibly reflecting a response to the extensive nerve fiber disintegration. Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG) deposition or complement expression in the spinal cord dorsal horn, dorsal funiculus, or gracile nucleus. This is in marked contrast to the situation after peripheral nerve injury, which appears to activate the entire complement cascade in the vicinity of the central sensory processes. Clusterin, a multifunctional protein with complement inhibitory effects, was markedly upregulated in the dorsal funiculus in astrocytes. In addition, there was an intense induction of clusterin expression in the degenerating white matter in oligodendrocytes, possibly reflecting a degeneration process in these cells. The findings suggest that 1) complement expression by microglial cells is intimately associated with IgG deposition; 2) axotomized neuronal perikarya, but not degenerating central fibers, undergo changes which induce such deposition; and 3) clusterin is not related to complement expression following neuronal injury but participates in regulating the state of oligodendrocytes during Wallerian degeneration.
|
9,633,806
|
eng
|
[
"D000293",
"D000818",
"D002118",
"Q000494",
"D004790",
"D005136",
"Q000037",
"Q000235",
"Q000378",
"D005786",
"D006168",
"D006801",
"D017136",
"D008274",
"Q000494",
"D008297",
"D009955",
"Q000378",
"D018408",
"D011188",
"Q000378",
"D026902",
"D015221",
"Q000235",
"Q000378",
"D024661",
"D011817",
"D012160",
"Q000166",
"Q000378",
"D013095",
"Q000096",
"Q000494",
"Q000502",
"D013096",
"Q000096",
"Q000494",
"Q000502",
"D013552"
] |
[
"Adolescent",
"Animals",
"Calcium",
"Enzyme Induction",
"Eye Proteins",
"Gene Expression Regulation",
"Guinea Pigs",
"Humans",
"Ion Transport",
"Magnesium",
"Male",
"Ornithine Decarboxylase",
"Patch-Clamp Techniques",
"Potassium",
"Potassium Channel Blockers",
"Potassium Channels",
"Potassium Channels, Inwardly Rectifying",
"Rabbits",
"Retina",
"Spermidine",
"Spermine",
"Swine"
] |
1998
|
Jul
|
Spermine/spermidine is expressed by retinal glial (Müller) cells and controls distinct K+ channels of their membrane.
There is recent evidence that polyamines such as spermine (spm) and spermidine (spd) may act as endogenous modulators of the activity of inwardly rectifying K+ channels. This type of K+ channels is abundantly expressed by retinal glial (Müller) cells where they are involved in important glial cell functions such as the clearance of excess extracellular K+ ions. This prompted us to study the following questions, i) do mammalian Müller cells contain endogenous spm/spd?; ii) do Müller cells possess the enzymes (e.g., ornithine decarboxylase, ODC) necessary to produce spm/spd?; and iii) does application of exogenous spm/spd exert specific effects onto inwardly rectifying K+ channels of Müller cells? Immunocytochemical studies were performed on histological sections of guinea-pig, rabbit, porcine, and human retinae, and on enzymatically dissociated Müller cells. Whole-cell and patch-clamp recordings were performed on enzymatically dissociated porcine and guinea-pig Müller cells. All above-mentioned questions could be answered with "yes." Specifically, the majority of Müller cells were labeled with antibodies directed to spm/spd, both within retinal sections and enzymatically isolated from retinal tissue. Müller cells in normal retinae express low levels of ODC but increase this expression markedly in cases of retinal pathology such as experimental epiretinal melanoma. Externally applied polyamines (1 mM) reduce (predominantly inward) whole-cell K+ currents, with the efficacies being spm > spd > put. If applied at the inside of membrane patches, spm (1 mM) blocks completely the outward currents through inwardly rectifying K+ channels but fails to affect the activity of large conductance, Ca2+-activated K+ channels. It is concluded that Müller cells contain endogenous channel-active polyamines, the synthesis of which may be up-regulated in pathological situations, and which may be involved in the control of both glial function and cell proliferation.
|
9,633,809
|
eng
|
[
"D000367",
"D000690",
"Q000235",
"Q000473",
"D000818",
"D001253",
"Q000502",
"D015415",
"D018450",
"D005904",
"Q000032",
"D000949",
"Q000032",
"D006801",
"D051379",
"D008822",
"D017628",
"Q000502",
"D009046",
"Q000473",
"D009569",
"Q000378",
"D018384",
"D017382",
"Q000378",
"D011993",
"Q000096",
"D013116",
"Q000473",
"D013482",
"Q000096",
"Q000235",
"D000072105",
"D013997"
] |
[
"Age Factors",
"Amyotrophic Lateral Sclerosis",
"Animals",
"Astrocytes",
"Biomarkers",
"Disease Progression",
"Glial Fibrillary Acidic Protein",
"Histocompatibility Antigens Class II",
"Humans",
"Mice",
"Mice, Transgenic",
"Microglia",
"Motor Neurons",
"Nitric Oxide",
"Oxidative Stress",
"Reactive Oxygen Species",
"Recombinant Fusion Proteins",
"Spinal Cord",
"Superoxide Dismutase",
"Superoxide Dismutase-1",
"Time Factors"
] |
1998
|
Jul
|
Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS.
Transgenic mice that highly over-express a mutated human CuZn superoxide dismutase (SOD1) gene [gly93-->ala; TgN(SOD1-G93A)G1H line] found in some patients with familial ALS (FALS) have been shown to develop motor neuron disease that is characterized by motor neuron loss in the lumbar and cervical spinal regions and a progressive loss of motor activity. The mutant Cu,Zn SOD exhibits essentially normal SOD activity but also generates toxic oxygen radicals as a result of an enhancement of a normally minor peroxidase reaction. Consequently, lipid and protein oxidative damage to the spinal motor neurons occurs and is associated with disease onset and progression. In the present study, we investigated the time course of microglial (major histocompatibility-II antigen immunoreactivity) and astrocytic (glial fibrillary acidic protein immunoreactivity) activation in relation to the course of motor neuron disease in the TgN(SOD1-G93A)G1H FALS mice. Four ages were investigated: 30 days (pre-motor neuron pathology and clinical disease); 60 days (after initiation of pathology, but pre-disease); 100 days (approximately 50% loss of motor neurons and function); and 120 days (near complete hindlimb paralysis). Compared to non-transgenic littermates, the TgN(SOD1-G93A)G1H mice showed significantly increased numbers of activated astrocytes (P < 0.01) at 100 days of age in both the cervical and lumbar spinal cord regions. However, at 120 days of age, the activation lost statistical significance. In contrast, microglial activation was significantly increased several-fold at both 100 and 120 days. We hypothesize that astrocytic activation may exert a trophic influence on the motor neurons that is insufficiently maintained late in the course of the disease. On the other hand, the sustained, intense microglial activation may conceivably contribute to the oxidative stress and damage involved in the disease process. If true, then agents which inhibit microglia may help to limit disease progression.
|
9,633,808
|
eng
|
[
"D000818",
"D001253",
"Q000378",
"Q000473",
"D020934",
"D005260",
"D005911",
"Q000378",
"Q000473",
"D007124",
"D017403",
"D009409",
"D009416",
"D009419",
"Q000096",
"Q000235",
"D009900",
"Q000378",
"Q000473",
"Q000502",
"D020221",
"D009928",
"D012333",
"Q000096",
"Q000235",
"D051381",
"D017207",
"D020794",
"Q000096",
"Q000235",
"D020801",
"D017475",
"Q000096",
"Q000235",
"D012583",
"Q000378",
"D012584",
"Q000293",
"Q000378",
"Q000473",
"Q000502",
"D014855"
] |
[
"Animals",
"Astrocytes",
"Ciliary Neurotrophic Factor",
"Female",
"Gliosis",
"Immunoenzyme Techniques",
"In Situ Hybridization",
"Nerve Crush",
"Nerve Regeneration",
"Nerve Tissue Proteins",
"Optic Nerve",
"Optic Nerve Injuries",
"Organ Specificity",
"RNA, Messenger",
"Rats",
"Rats, Sprague-Dawley",
"Receptor Protein-Tyrosine Kinases",
"Receptor, Ciliary Neurotrophic Factor",
"Receptors, Nerve Growth Factor",
"Schwann Cells",
"Sciatic Nerve",
"Wallerian Degeneration"
] |
1998
|
Jul
|
Lesion-induced changes in the expression of ciliary neurotrophic factor and its receptor in rat optic nerve.
There is evidence that ciliary neurotrophic factor (CNTF) is involved in reactive changes following lesions of the nervous system. To investigate, whether differences in the regulation of CNTF and CNTF receptor alpha (CNTFRalpha) contribute to the differences in PNS and CNS responses to injury, we have studied their expression on the mRNA and protein level in the rat optic nerve following a crush lesion to compare them with the situation in peripheral nerve. Seven days after the lesion, CNTF mRNA and protein levels were markedly decreased at the lesion site, concommitant with the disappearance of GFAP- and CNTF-immunopositive astrocytes. CNTF levels in proximal and distal parts were less affected. This was in contrast to the situation in the PNS, where CNTF was downregulated at and distal to the lesion site. Different from other CNS regions, optic nerve astrocytes expressed CNTFRalpha mRNA under normal conditions. Following lesion, CNTFRalpha was reduced substantially only in distal and proximal parts of the optic nerve but continued to be expressed at high levels at the lesion site, suggesting that GFAP-negative, CNTF-responsive cells are present there. Our results suggest that differences in lesion-induced changes in the optic and sciatic nerve reflect differences in the response to injury of astrocytes and Schwann cells. In the light of the known actions of CNTF in inducing astrogliosis, the expression pattern observed in the optic nerve indicates that CNTF and CNTFRalpha are involved in glial scar formation in the lesion area.
|
9,633,810
|
eng
|
[
"D020410",
"D000818",
"D000954",
"D001369",
"Q000502",
"D002448",
"D019062",
"Q000494",
"D015816",
"Q000096",
"Q000235",
"D002478",
"D018920",
"D029941",
"D005786",
"D006054",
"D017403",
"D016253",
"D009409",
"D009416",
"D009419",
"Q000096",
"Q000235",
"D009836",
"Q000378",
"Q000473",
"D015345",
"D016376",
"D009900",
"Q000502",
"D012333",
"Q000096",
"D051381",
"D012165",
"Q000473",
"Q000502",
"D013045"
] |
[
"Activated-Leukocyte Cell Adhesion Molecule",
"Animals",
"Antigens, Surface",
"Axons",
"Cell Adhesion",
"Cell Adhesion Molecules, Neuron-Glia",
"Cell Adhesion Molecules, Neuronal",
"Cells, Cultured",
"Coculture Techniques",
"Fish Proteins",
"Gene Expression Regulation",
"Goldfish",
"In Situ Hybridization",
"Microscopy, Immunoelectron",
"Nerve Crush",
"Nerve Regeneration",
"Nerve Tissue Proteins",
"Oligodendroglia",
"Oligonucleotide Probes",
"Oligonucleotides, Antisense",
"Optic Nerve",
"RNA, Messenger",
"Rats",
"Retinal Ganglion Cells",
"Species Specificity"
] |
1998
|
Jul
|
E587 antigen is upregulated by goldfish oligodendrocytes after optic nerve lesion and supports retinal axon regeneration.
The properties of glial cells in lesioned nerves contribute quite substantially to success or failure of axon regeneration in the CNS. Goldfish retinal axons regenerate after optic nerve lesion (ONS) and express the L1-like cell adhesion protein E587 antigen on their surfaces. Goldfish oligodendrocytes in vitro also produce E587 antigen and promote growth of both fish and rat retinal axons. To determine whether glial cells in vivo synthesize E587 antigen, in situ hybridizations with E587 antisense cRNA probes and light- and electron microscopic E587 immunostainings were carried out. After lesion, the goldfish optic nerve/tract contained glial cells expressing E587 mRNA, which were few in number at 6 days after ONS, increased over the following week and declined in number thereafter. Also, E587-immunopositive elongated cells with ultrastructural characteristics of oligodendrocytes were found. Thus, glial cells synthesize E587 antigen in spatiotemporal correlation with retinal axon regeneration. To determine the functional contribution of E587 antigen, axon-oligodendrocyte interactions were monitored in co-culture assays in the presence of Fab fragments of a polyclonal E587 antiserum. E587 Fabs in axon-glia co-cultures prevented the normal tight adhesion of goldfish retinal growth cones to oligodendrocytes and blocked the preferential growth of fish and rat retinal axons on the oligodendrocyte surfaces. The ability of glia in the goldfish visual pathway to upregulate the expression of E587 antigen and the growth supportive effect of oligodendrocyte-associated E587 antigen in vitro suggests that this L1-like adhesion protein promotes retinal axon regeneration in the goldfish CNS.
|
9,633,811
|
eng
|
[
"D000105",
"Q000378",
"D000818",
"D001224",
"Q000378",
"D001253",
"Q000166",
"Q000378",
"D002247",
"D002478",
"D002525",
"Q000166",
"Q000378",
"D002540",
"Q000166",
"Q000378",
"D002952",
"D004734",
"D005947",
"Q000494",
"D006019",
"Q000187",
"D007461",
"Q000494",
"D019807",
"D019344",
"Q000378",
"D009682",
"D051379",
"D009474",
"Q000378",
"D011773",
"Q000378"
] |
[
"Acetyl Coenzyme A",
"Animals",
"Aspartic Acid",
"Astrocytes",
"Carbon Isotopes",
"Cells, Cultured",
"Cerebellar Cortex",
"Cerebral Cortex",
"Citric Acid Cycle",
"Energy Metabolism",
"Glucose",
"Glycolysis",
"Iodoacetates",
"Iodoacetic Acid",
"Lactic Acid",
"Magnetic Resonance Spectroscopy",
"Mice",
"Neurons",
"Pyruvates"
] |
1998
|
Jul
|
[U-13C] aspartate metabolism in cultured cortical astrocytes and cerebellar granule neurons studied by NMR spectroscopy.
The metabolism of [U-13C]aspartate was studied in cultured cortical astrocytes and cerebellar granule neurons in the presence of glucose and during inhibition of glycolysis. Redissolved, lyophilized cell extracts and incubation media were analyzed by 13C nuclear magnetic resonance spectroscopy for the determination of metabolites labeled from aspartate. Uniformly labeled lactate was prominent in control media of astrocytes and cerebellar granule neurons. In both cell types, aspartate entered the tricarboxylic acid (TCA) cycle, as shown by labeling patterns in glutamate and, in astrocytes, in glutamine. From the complex labeling patterns in aspartate in astrocytic perchloric acid extracts it was clear that acetylcoenzyme A (acetyl-CoA) derived from aspartate via oxaloacetate and pyruvate could enter the TCA cycle. Such "recycling," however, could not be detected in cerebellar granule neurons. Inhibition of glycolysis reduced aspartate uptake and metabolism in both cell types. Most notably, lactate derived from aspartate showed a large reduction, and in astrocytes, incorporation of labeled acetyl-CoA into the TCA cycle was significantly reduced. Thus, astrocytes and cerebellar granule neurons differ in their handling of aspartate. Furthermore, inhibition of glycolysis clearly affected aspartate metabolism by such cells.
|
9,633,812
|
eng
|
[
"D000818",
"D002818",
"D005786",
"D007124",
"D017403",
"D004676",
"Q000096",
"Q000235",
"D009419",
"Q000096",
"Q000235",
"D009836",
"Q000378",
"Q000473",
"D012333",
"Q000096",
"Q000235",
"D051381",
"D011917",
"D013119",
"Q000378",
"Q000473",
"D013997"
] |
[
"Animals",
"Cordotomy",
"Gene Expression Regulation",
"Immunoenzyme Techniques",
"In Situ Hybridization",
"Myelin Basic Protein",
"Nerve Tissue Proteins",
"Oligodendroglia",
"RNA, Messenger",
"Rats",
"Rats, Inbred Lew",
"Spinal Cord Injuries",
"Time Factors"
] |
1998
|
Jul
|
Oligodendroglial reaction following spinal cord injury in rat: transient upregulation of MBP mRNA.
The reaction of oligodendrocytes in response to traumatic injury of the CNS are poorly understood. In the present report we studied changes in the expression of a major constituent of CNS myelin, myelin basic protein (MBP), by immunohistochemistry and in situ hybridization from 6 h up to 2 weeks following partial transection of the spinal cord in adult rats. MBP immunohistochemistry showed degeneration of myelin at the lesion center and signs of myelin breakdown in necrotic foci in the dorsal and ventral funiculi proximal and distal to the lesion. In situ hybridization revealed that mRNA for MBP was downregulated at the local lesion site within the first day following injury, probably reflecting oligodendrocytes to undergo cell death. From 2 days on, however, MBP mRNA was conspicuously upregulated at the border of the lesion area. This "reactive" response of surviving oligodendrocytes, as indicated by increased levels of MBP mRNA, peaked around 8 days. At this time, oligodendrocytes displaying strong MBP in situ signal formed stripe-like structures which were oriented radially toward the lesion center and arranged in parallel to neurofilament-positive axons. At around 2 weeks post-injury, MBP mRNA at the border of the lesion area was again downregulated to levels comparable to uninjured controls. These results show that traumatic injury of the spinal cord induces a "reactive" response of surviving oligodendrocytes adjacent to lesion sites. This response might represent an important component of local repair mechanisms.
|
9,633,814
|
eng
|
[
"D019943",
"D016158",
"D019337",
"Q000235",
"Q000473",
"D006801",
"D009154",
"D016159",
"Q000235"
] |
[
"Amino Acid Substitution",
"Genes, p53",
"Hematologic Neoplasms",
"Humans",
"Mutation",
"Tumor Suppressor Protein p53"
] |
Pooled analysis of p53 mutations in hematological malignancies.
A computerized database is described that contains information about 507 mutations in the p53 gene of hematologic tumors and corresponding cell lines. Analysis of these mutations indicated the following findings: First, mutational spectrum analysis in these tumors was found to be similar to the pattern found for other solid tumors. However, when the patterns of base substitutions were examined separately according to the types of hematologic malignancies, followed by subgroup analysis, notable differences (in some cases of statistical significance) emerged. Second, mutational pattern analysis indicates that about 48% of base substitutions in hematologic tumors are suspected to be associated with carcinogen exposure. Third, deletions and insertions are localized mainly to exons 5-8 and repeated DNA sequences. However, the unusual profile of variations in frequency within each type of tumor suggests that, in addition to endogenous damage to template DNA, there is the factor of exposure to environmental physical and chemical carcinogens/mutagens. Fourth, p53 protein alterations analysis indicate that most of the changes in the amino acids are "semiconservative," presumably in order to avoid disrupting the structure of the p53 monomer. Consistent with this notion, structural mutations are more conservative than the binding mutations. Finally, molecular mechanisms that lead to p53 mutations, etiological factors that play a role in their formation, and the pathophysiological significance of consequent p53 protein alterations are discussed.
|
||
9,633,815
|
eng
|
[
"D000592",
"Q000097",
"Q000453",
"Q000235",
"D001483",
"D004247",
"D005060",
"Q000453",
"D018740",
"D006579",
"D006720",
"D006801",
"D006867",
"Q000235",
"D019083",
"Q000453",
"D009154",
"D018807",
"D014443",
"Q000097"
] |
[
"Amino Acid Metabolism, Inborn Errors",
"Base Sequence",
"DNA",
"Europe",
"Genetic Heterogeneity",
"Heterozygote",
"Homozygote",
"Humans",
"Hydrolases",
"Mediterranean Region",
"Mutation",
"Polymorphism, Single-Stranded Conformational",
"Tyrosine"
] |
Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries.
Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a deficient activity of the enzyme fumarylacetoacetase (FAH). To investigate the molecular heterogeneity of tyrosinemia, the geographic distribution and the genotype-phenotype relationship, we have analyzed the FAH genotype of 25 HT1 patients. Mutation screening was performed by PCR amplification of exons 1-14 of the FAH gene, followed by SSCP analysis and direct sequencing of the amplified exons. Fourteen different mutations were found, of which seven were novel, viz. three missense mutations (G158D, P261L, F405H), a deletion of three nucleotides causing a deletion of serine (DEL366S) and three splice site mutations: IVS2+1(g-t), IVS6-1(g-c), IVS8-1(g-c). The splice site mutations IVS6-1(g-t) and IVS12+5(g-a) were frequently found in countries around the Mediterranean and northwestern Europe, respectively. No clear correlation between the genotype and the three major HT1 subtypes could be established.
|
||
9,633,816
|
eng
|
[
"D000328",
"D001483",
"D017931",
"D005260",
"D006012",
"Q000175",
"Q000235",
"D006801",
"D008297",
"D009154",
"D010375",
"D006005",
"Q000235",
"D016133"
] |
[
"Adult",
"Base Sequence",
"DNA Primers",
"Female",
"Glycogen Storage Disease Type V",
"Humans",
"Male",
"Mutation",
"Pedigree",
"Phosphorylases",
"Polymerase Chain Reaction"
] |
Molecular diagnosis of McArdle disease: revised genomic structure of the myophosphorylase gene and identification of a novel mutation.
McArdle disease is a rare autosomal recessive disorder of the muscle glycogen metabolism caused by mutations in the muscle glycogen phosphorylase gene. Until now, a total number of 11 different mutations in the coding region or splice sites of the myophosphorylase gene have been identified. In contrast to a wealth of data on the RNA and protein level, little information is available on the genomic sequence of the corresponding gene. To facilitate molecular diagnosis of McArdle disease, we reinvestigated the genomic structure of the myophosphorylase gene and sequenced about 9.8 kilobases (kb) on the genomic level. By choosing 14 intronic primer pairs, we were able to amplify the complete human coding sequence as well as the adjacent splice sites of the 20 exons. Direct sequencing of the amplification products of a consanguineous Turkish family with typical McArdle disease revealed a novel single base pair deletion in exon 18, which predicts a frameshift and a premature termination of the protein. In summary, we established a system for molecular diagnosis of McArdle disease based on a revised genomic structure of the myophosphorylase gene and demonstrated its feasibility by identification of a novel mutation.
|
||
9,633,817
|
eng
|
[
"D002031",
"D002895",
"D017362",
"D005260",
"D017353",
"D005838",
"D006801",
"D008297",
"D009134",
"Q000235",
"D009419",
"Q000235",
"D051616",
"D010375",
"D010641",
"D016601",
"D055532"
] |
[
"Bulgaria",
"Chromosomes, Human, Pair 5",
"Cyclic AMP Response Element-Binding Protein",
"Female",
"Gene Deletion",
"Genotype",
"Humans",
"Male",
"Muscular Atrophy, Spinal",
"Nerve Tissue Proteins",
"Neuronal Apoptosis-Inhibitory Protein",
"Pedigree",
"Phenotype",
"RNA-Binding Proteins",
"SMN Complex Proteins"
] |
Deletion analysis of Bulgarian SMA families.
All three types of autosomal recessive spinal muscular atrophy map to chromosome region 5q13. Recent reports suggest that they are associated with deletions of two adjacent genes: SMN and NAIP. Here we report the first deletion analysis of Bulgarian SMA families. Homozygous deletion of exons 7 and 8 of the SMN gene were found in 85% of our patients, but the NAIP gene (exons 5 and 6) was deleted in only 26% of patients. To our knowledge, these frequencies are some of the lowest reported so far. The NAIP gene was deleted predominantly in severely affected patients (type I), while in the group with milder types SMA only deletions of the SMN gene were detected. Our phenotype-genotype correlation study confirmed that larger deletions are associated with more severe clinical course. The Bulgarian data support the thesis that the telomeric SMN gene could play a major role in determining SMA, while the NAIP or the centromeric SMN copy have a modifying effect on the phenotype.
|
||
9,633,818
|
eng
|
[
"D001483",
"D002412",
"D017931",
"D005260",
"D006801",
"D008297",
"D009154",
"D010195",
"Q000235",
"D010375",
"D016133",
"D014362",
"Q000235"
] |
[
"Base Sequence",
"Cations",
"DNA Primers",
"Female",
"Humans",
"Male",
"Mutation",
"Pancreatitis",
"Pedigree",
"Polymerase Chain Reaction",
"Trypsinogen"
] |
Mutations of the cationic trypsinogen in hereditary pancreatitis.
Hereditary pancreatitis (OMIM 167800) is thought to be associated with a mutation of the exon 3 of cationic trypsinogen (Nature Genet (1996): 14:141-145). This paper reports sequence data of two independent families suffering from this disease. PCR amplificates from leukocyte or buccal swab DNA showed no mutation of exon 3 of cationic trypsinogen. Instead, in exon 2, an A-to-T tranversion was found that led to the substitution of Asn by Ile in the sixth amino acid of the active trypsin. In exons 4 and 5, silent mutations were found. In the other expressed trypsinogens, several homozygous alterations not associated to hereditary pancreatitis were identified. As a model of pathogenesis, we hypothesize that mutation of trypsinogen in exon 2 could lead to premature cleavage of the activation peptide of trypsinogen or to altered intracellular transport.
|
||
9,633,819
|
eng
|
[
"D019943",
"D000818",
"D001483",
"D002478",
"D015217",
"Q000235",
"D017931",
"D005260",
"D005838",
"D006579",
"D006639",
"Q000235",
"D006801",
"D007313",
"D008049",
"Q000235",
"D008247",
"Q000201",
"D008297",
"D009154",
"D010641",
"D011392",
"Q000235",
"D012326"
] |
[
"Amino Acid Substitution",
"Animals",
"Base Sequence",
"Cells, Cultured",
"Cholesterol Ester Storage Disease",
"DNA Primers",
"Female",
"Genotype",
"Heterozygote",
"Histidine",
"Humans",
"Insecta",
"Lipase",
"Lysosomes",
"Male",
"Mutation",
"Phenotype",
"Proline",
"RNA Splicing"
] |
Different missense mutations in histidine-108 of lysosomal acid lipase cause cholesteryl ester storage disease in unrelated compound heterozygous and hemizygous individuals.
Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity of lysosomal acid lipase (LAL), that leads to the tissue accumulation of cholesteryl esters in endosomes and lysosomes. WD is caused by genetic defects of LAL that leave no residual enzymatic activity, while in CESD patients a residual LAL activity can be identified. We have analyzed the LAL cDNA in three CESD patients from two nonrelated families and identified the mutations responsible for the disease. The associated genetic defects characterized revealed compound heterozygosity for a splice defect leading to skipping of exon 8, due to a G-->A transition at position -1 of the exon 8 splice donor site, and a point mutation leading to a Hisl08Pro change (CAT-->CCT) in two patients (siblings) with mild CESD phenotype. A further CESD patient was hemizygous for a His108-->Arg missense mutation (CAT-->CGT) in combination with a partial deletion of the LAL gene and was affected more severely. Expression of the LAL enzymes with the His108-->Pro and His108-->Arg mutation in insect cells revealed residual enzymatic activities of 4.6% versus 2.7%, respectively, compared with controls. Therefore, His108 seems to play a crucial role in folding or catalytic activity of the lysosomal acid lipase. This is the first description of two different, naturally occurring mutations involving the same amino acid residue in the lysosomal acid lipase in unrelated CESD patients. Moreover, our results demonstrate that the variable manifestation of CESD can be explained by mutation-dependent, variable inactivation of the LAL enzyme.
|
||
9,633,820
|
eng
|
[
"D000293",
"D000328",
"D017668",
"D000368",
"D000369",
"D001483",
"D017931",
"D004272",
"Q000235",
"D003638",
"Q000235",
"D003924",
"Q000235",
"D005260",
"D006801",
"D008297",
"D008875",
"D009154",
"D010375",
"D015203"
] |
[
"Adolescent",
"Adult",
"Age of Onset",
"Aged",
"Aged, 80 and over",
"Base Sequence",
"DNA Primers",
"DNA, Mitochondrial",
"Deafness",
"Diabetes Mellitus, Type 2",
"Female",
"Humans",
"Male",
"Middle Aged",
"Mutation",
"Pedigree",
"Reproducibility of Results"
] |
Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age at onset of diabetes and deafness.
The mitochondrial mutation A3243G has been shown to be associated with a syndrome of diabetes mellitus and sensorineural hearing loss. Using a solid-phase-based sequencing method we have investigated the relation between the proportion of mutant mitochondrial genomes and the time of disease onset among members of three families where the mutation segregates. A striking association was observed between the level of heteroplasmy and time of onset of disease, particularly hearing loss. Accordingly, this syndrome shares features of diseases caused by dynamic mutations in that variable transmission of the level of heteroplasmy between generations influences disease severity.
|
||
9,633,821
|
eng
|
[
"D002607",
"Q000150",
"Q000235",
"D002869",
"D002886",
"D017630",
"Q000235",
"D005260",
"D005387",
"D006801",
"D008297",
"D009154",
"D018993",
"Q000235",
"D009185",
"Q000235",
"D009422",
"Q000150",
"Q000235",
"D010375",
"D000097002"
] |
[
"Charcot-Marie-Tooth Disease",
"Chromosome Aberrations",
"Chromosomes, Human, Pair 17",
"Connexins",
"Female",
"Finland",
"Humans",
"Male",
"Mutation",
"Myelin P0 Protein",
"Myelin Proteins",
"Nervous System Diseases",
"Pedigree",
"Gap Junction beta-1 Protein"
] |
Spectrum of mutations in Finnish patients with Charcot-Marie-Tooth disease and related neuropathies.
Our patient material included families and sporadic patients of Finnish origin with the diagnosis of Charcot-Marie-Tooth (CMT) disease types 1 and 2, Dejerine-Sottas syndrome (DSS), and hereditary neuropathy with liability to pressure palsies (HNPP). We screened for mutations in the peripheral myelin protein genes connexin 32 (Cx32), myelin protein zero (P0) and peripheral myelin protein 22 (PMP22) by direct sequencing. All patients chosen for mutation screening were negative for the 1.5 Mb duplication/deletion at 17p11.2-p12. Eleven Cx32 mutations were found in 12 families, six with a CMT2 diagnosis, three with a CMT1 diagnosis and three with unclassified CMT. The total number of patients in these 12 CMTX families was 61, giving a minimum prevalence of 1.2/100,000 for CMTX in Finland. Four of the mutations, Pro58Arg, Pro172Leu, Asn175Asp and Leu204Phe, have not been previously reported. One male patient with an early onset CMT had a double Cx32 mutation, Arg22Gln and Val63Ile. The double de novo mutation was found to be of maternal grandpaternal origin. In the P0 gene a Ser78Leu mutation was found in one family with severe CMT1 and a de novo Tyr82Cys mutation was found in one DSS patient. Both mutations have been previously reported in other CMT1 families. A novel PMP22 mutation, deletion of Phe84, was found in one sporadic DSS patient. Our mutation screening results show the necessity of molecular diagnosis, in addition to clinical and electrophysiological evaluation, for proper subtyping of the disease and for accurate genetic counseling.
|
||
9,633,822
|
eng
|
[
"D000818",
"D002455",
"Q000187",
"D016373",
"D004789",
"D016220",
"Q000096",
"Q000502",
"D016222",
"Q000096",
"Q000494",
"Q000502",
"D007527",
"Q000378",
"D007700",
"D008297",
"D011471",
"Q000473",
"Q000503",
"D011493",
"Q000378",
"D051571",
"D051745",
"D051744",
"D051381",
"D011994",
"Q000096",
"D015398",
"Q000187",
"Q000502",
"D013755",
"Q000494",
"D014158",
"D014162",
"D014407",
"D018631",
"Q000378"
] |
[
"Animals",
"Cell Division",
"DNA, Antisense",
"Enzyme Activation",
"Fibroblast Growth Factor 1",
"Fibroblast Growth Factor 2",
"Isoenzymes",
"Kinetics",
"Male",
"Prostatic Neoplasms",
"Protein Kinase C",
"Protein Kinase C-alpha",
"Protein Kinase C-delta",
"Protein Kinase C-epsilon",
"Rats",
"Recombinant Proteins",
"Signal Transduction",
"Tetradecanoylphorbol Acetate",
"Transcription, Genetic",
"Transfection",
"Tumor Cells, Cultured",
"ras Proteins"
] |
Fibroblast growth factor-2 and TPA enhance prostate-cancer-cell proliferation and activate members of the Ras and PKC signal transduction pathways.
Rat prostate-cancer-cell stable-transfectants expressing either antisense-fibroblast growth factor (FGF-1) or antisense-FGF-2 transcripts that respectively have either undetectable FGF-1 or profoundly diminished FGF-2 protein content, were used for analyses of FGF-2 and/or 12-O-tetradecanoylphorbol 12-acetate (TPA) modulation of cell proliferation. Antisense-FGF-2 transfectant doubling-time was 2.6-fold greater than that of vector-control transfectants. FGF-2 and TPA respectively caused 2.5- and 3.0-fold reductions in antisense-FGF-2 transfectant doubling-time. Culture of antisense-FGF-2 transfectants in medium containing both FGF-2 and TPA further reduced their doubling time; however, this effect was not statistically different from that achieved by TPA treatment alone. Antisense-FGF-1 transfectant doubling-time was 2.2-fold greater than that of vector-control transfectants and was reduced 2.0- or 2.3-fold, respectively, when these cells were cultured in medium containing FGF-2 or TPA. In contrast to the results for antisense-FGF-2 transfectants, culture of antisense-FGF-1 transfectants in medium containing both FGF-2 and TPA caused a 2.6-fold reduction in transfectant doubling-time that was significantly greater than that caused by independent treatment with either FGF-2 or TPA. FGF-2 promoted rapid activation of rat prostate-cancer-cell PKCalpha and PKCepsilon, as assessed by isozyme translocation from the soluble to particulate cell fraction, and only moderately altered PKCdelta distribution. By contrast, TPA promoted rapid activation of all three PKC isozymes. Both the TPA- and FGF-2-mediated PKC activation were prolonged and possibly involved cyclic redistribution of isozymes between soluble and particulate cell fractions. FGF-2 also caused rapid phosphorylation of prostate-cancer-cell Shc, the adapter protein that mediates FGF-receptor-modulated ras signaling. The results of these studies indicate that FGF-2 and TPA independently and conjointly modulate rat prostate-cancer-cell antisense-transfectant doubling time and suggest that effector modulation of rat prostate-cancer-cell proliferation is achieved by processes involving PKC and/or ras mediated signaling.
|
||
9,633,823
|
eng
|
[
"D000818",
"D002110",
"Q000494",
"D002118",
"Q000378",
"Q000494",
"D002460",
"D002999",
"D004229",
"Q000494",
"D010450",
"Q000378",
"D007700",
"D007976",
"Q000187",
"D009119",
"D018482",
"Q000502",
"D011480",
"Q000494",
"D051381",
"D012519",
"Q000187",
"Q000378",
"D015398"
] |
[
"Animals",
"Caffeine",
"Calcium",
"Cell Line",
"Clone Cells",
"Dithiothreitol",
"Endopeptidases",
"Kinetics",
"Leupeptins",
"Muscle Contraction",
"Muscle, Skeletal",
"Protease Inhibitors",
"Rats",
"Sarcoplasmic Reticulum",
"Signal Transduction"
] |
Calcium mediated proteolysis enhances calcium release in skinned L6 myotubes.
The mechanism for calcium (Ca2+) release in heart and skeletal muscle during excitation-contraction coupling is currently unknown. A widely held hypothesis is that a small amount of Ca2+ enters the cell and elicits a larger intracellular release of Ca2+ from the sarcoplasmic reticulum (SR), termed "Ca2+-induced Ca2+-release" (CICR). In addition to its role in excitation-contraction coupling, Ca2+ is also known to activate the cysteine protease calpain, which has been recently found to specifically cleave the ryanodine receptor in vitro. The authors investigated the question of whether Ca2+ sensitive protease activation could account for an apparent CICR. The authors first reproduced the phenomenon of CICR using detergent treated L6 myotubes ("skinned cells"). Leupeptin, a cysteine protease inhibitor, reduced the initial velocity and extent of Ca2+ release from the SR; a similar result was obtained when skinned cells were treated with iodoacetate, a sulfhydryl alkylating agent. Dithiothreitol enhanced both the rate and extent of Ca2+ release. Caffeine-induced Ca2+-release was unaffected by the thiol protease inhibitors or activators. This suggests that a cysteine protease may be responsible, in part, for CICR in vitro. The authors also found that vesicles exposed to Ca2+ to induce CICR were unable to fully reaccumulate Ca2+ a second time. Yet, when caffeine released comparable amounts of Ca2+, the initial Ca2+ level was fully restored. Similarly, leupeptin protected the vesicles from the reaccumulation deficit induced by Ca2+. The authors' findings suggest that proteolysis activated by a Ca2+-sensitive protease may account for the direct in vitro demonstration of CICR; such an effect may more likely reflect a role in apoptosis than excitation-contraction coupling.
|
||
9,633,824
|
eng
|
[
"D000818",
"D017209",
"Q000502",
"D002455",
"Q000187",
"D002460",
"D002470",
"Q000187",
"D006412",
"D055504",
"D007334",
"Q000494",
"D007377",
"Q000494",
"D047908",
"D051379",
"D016297",
"D010750",
"Q000172",
"Q000502",
"D017354",
"D020794",
"Q000378",
"D017526",
"Q000096",
"Q000502",
"D011972",
"Q000502",
"D011994",
"Q000096",
"D015398",
"D014162"
] |
[
"Animals",
"Apoptosis",
"Cell Division",
"Cell Line",
"Cell Survival",
"Hematopoietic Stem Cells",
"Insulin Receptor Substrate Proteins",
"Insulin-Like Growth Factor I",
"Interleukin-3",
"Intracellular Signaling Peptides and Proteins",
"Mice",
"Mutagenesis, Site-Directed",
"Phosphoproteins",
"Point Mutation",
"Receptor Protein-Tyrosine Kinases",
"Receptor, IGF Type 1",
"Receptor, Insulin",
"Recombinant Proteins",
"Signal Transduction",
"Transfection"
] |
IGF-I receptor protection from apoptosis in cells lacking the IRS proteins.
The type I insulin-like growth factor receptor (IGF-IR) plays a crucial role in cell growth, transformation and protection from apoptosis. Although the mitogenic function of the IGF-IR may require the activation of insulin receptor substrate-1 (IRS-1) or IRS-2, an overexpressed IGF-IR is able to protect 32D cells, which lack IRS-1 and IRS-2, from apoptosis caused by Interleukin-3 (IL-3) withdrawal. Here, using mutational analysis, the authors identify domains of the IGF-IR necessary to protect from apoptosis without downstream signaling from IRS-1 and IRS-2. A receptor mutant of the tyrosine kinase (TK) domain only partially inhibited antiapoptotic signaling, whereas a mutant displaying constitutive autophosphorylation of the receptor did not show enhanced survival activity. Surprisingly, survival signaling was dependent upon tyrosine 950, the binding site for IRS-1, IRS-2, and Shc proteins. Yet, overexpressed Shc and/or IRS-1 could not replace the IGF-IR survival signal, suggesting the existence of other critical substrates. Finally, the C-terminus may encode a proapoptotic signal, as receptors truncated at C-terminal residues 1229 or 1245 were found to inhibit apoptosis better than the wild type (WT) IGF-IR.
|
||
9,633,825
|
eng
|
[
"D000595",
"D000818",
"D001483",
"D002460",
"D017124",
"D017931",
"D005347",
"D006801",
"D008168",
"D008322",
"D008969",
"D016133",
"Q000379",
"D017027",
"Q000096",
"Q000737",
"Q000235",
"D012333",
"Q000096",
"D016415",
"D017386",
"D012689",
"D015398",
"Q000502",
"D009626",
"D014158"
] |
[
"Amino Acid Sequence",
"Animals",
"Base Sequence",
"Cell Line",
"Conserved Sequence",
"DNA Primers",
"Fibroblasts",
"Humans",
"Lung",
"Mammals",
"Molecular Sequence Data",
"Polymerase Chain Reaction",
"Protein Tyrosine Phosphatases",
"RNA, Messenger",
"Sequence Alignment",
"Sequence Homology, Amino Acid",
"Sequence Homology, Nucleic Acid",
"Signal Transduction",
"Terminology as Topic",
"Transcription, Genetic"
] |
Multiple phosphotyrosine phosphatase mRNAs are expressed in the human lung fibroblast cell line WI-38.
Protein tyrosine phosphatases are important components of signal transduction pathways. The authors have used reverse transcription/polymerase chain reactions to accomplish a comprehensive examination of the RNA expression for 58 distinct mammalian protein tyrosine and dual specificity phosphatase (PTPase) and PTPase-like genes in the normal human diploid fibroblast cell line WI-38. Thirty-seven of these PTPase genes express easily measurable RNA, and four simultaneously express the RNA for two or more isoforms. Messages for an additional eight PTPase genes are detectable at low levels. Only 14 known PTPase genes do not express measurable RNA under our conditions. For purposes of comparison, the authors also assessed the PTPases expressed in the WI-38 cell line using highly degenerate primers to conserved motifs found in the classical tyrosine-specific PTPases. Only eight of the 22 classic tyrosine-specific PTPases detected using the specific primers were detected using these degenerate primers. Our panel of specific PTPase primers should be very useful for semiquantitatively assessing the repertoire of PTPases expressed by cells.
|
||
9,633,826
|
eng
|
[
"D000818",
"D001665",
"D003001",
"D005786",
"D006801",
"D007700",
"D008024",
"D016297",
"D014176",
"D011487",
"D011817",
"D018160",
"Q000737",
"Q000378",
"D011965",
"Q000737",
"Q000378",
"D011980",
"Q000737",
"Q000378",
"D018168",
"Q000096",
"Q000737",
"Q000378",
"D011994",
"Q000096",
"Q000737",
"Q000378",
"D012156",
"Q000378",
"D000072482",
"D047488",
"D017384",
"D015398",
"D014157",
"Q000737",
"Q000378",
"D014158",
"D014357",
"Q000378"
] |
[
"Animals",
"Binding Sites",
"Cloning, Molecular",
"Gene Expression Regulation",
"Humans",
"Kinetics",
"Ligands",
"Mutagenesis, Site-Directed",
"Protein Biosynthesis",
"Protein Conformation",
"Rabbits",
"Receptors, Cytoplasmic and Nuclear",
"Receptors, Glucocorticoid",
"Receptors, Progesterone",
"Receptors, Retinoic Acid",
"Recombinant Proteins",
"Reticulocytes",
"Retinoic Acid Receptor alpha",
"Retinoid X Receptors",
"Sequence Deletion",
"Signal Transduction",
"Transcription Factors",
"Transcription, Genetic",
"Trypsin"
] |
Limited proteolysis for assaying ligand binding affinities of nuclear receptors.
The binding of natural or synthetic ligands to nuclear receptors is the triggering event leading to gene transcription activation or repression. Ligand binding to the ligand binding domain of these receptors induces conformational changes that are evidenced by an increased resistance of this domain to proteases. In vitro labeled receptors were incubated with various synthetic or natural agonists or antagonists and submitted to trypsin digestion. Proteolysis products were separated by SDS-PAGE and quantified. The amount of trypsin-resistant fragments was proportional to receptor occupancy by the ligand, and allowed the determination of dissociation constants (kDa). Using the wild-type or mutated human retinoic acid receptor alpha as a model, kDa values determined by classical competition binding assays using tritiated ligands are in agreement with those measured by the proteolytic assay. This method was successfully extended to human retinoic X receptor alpha, glucocorticoid receptor, and progesterone receptor, thus providing a basis for a new, faster assay to determine simultaneously the affinity and conformation of receptors when bound to a given ligand.
|
||
9,633,827
|
eng
|
[
"D000236",
"Q000473",
"Q000503",
"D002118",
"Q000378",
"D002478",
"D019332",
"Q000378",
"Q000494",
"D019334",
"Q000378",
"Q000494",
"D004847",
"Q000187",
"Q000473",
"Q000502",
"D005347",
"Q000187",
"Q000473",
"Q000502",
"D006801",
"D006961",
"Q000473",
"Q000503",
"Q000601",
"D006965",
"D018761",
"Q000473",
"Q000503",
"D010280",
"Q000473",
"Q000503",
"D010281",
"Q000378",
"D010282",
"Q000473",
"Q000503",
"Q000601",
"D015398",
"Q000187",
"Q000502",
"D014407"
] |
[
"Adenoma",
"Calcium",
"Cells, Cultured",
"Endothelin-1",
"Endothelin-3",
"Epithelial Cells",
"Fibroblasts",
"Humans",
"Hyperparathyroidism",
"Hyperplasia",
"Multiple Endocrine Neoplasia Type 1",
"Parathyroid Glands",
"Parathyroid Hormone",
"Parathyroid Neoplasms",
"Signal Transduction",
"Tumor Cells, Cultured"
] |
Endothelin-induced calcium signaling and secretion in chief cells and fibroblasts from pathological human parathyroid glands.
Endothelins (ETs) are 21 amino acid peptides with vasoactive and mitogenic properties. The three isopeptides (ET-1, -2, and -3) and their receptors (E1A and ETB subtypes) display expression in numerous tissues and possibly mediate autocrine/paracrine actions. The present investigation shows that ET-1 triggers biphasic increases of the concentration of cytoplasmic Ca2+ ([Ca2+]i) in pathological human parathyroid cells. Both the peak and sustained [Ca2+]i increase, as well as the proportion of responding cells, are dose-dependent in the 10(-10)-10(-7) mol/L range of ET-1. In absence of external Ca2+, the ET-1-induced [Ca2+]i peak is attenuated. ET-3 has no effect on [Ca2+]i indicating functional dominance of the ETA receptor subtype. ET-1 (10 nmol/L) lowers parathyroid hormone secretion in 0.5 mmol/L but not in higher external Ca2+ concentrations, and parathyroid cell ET release is inhibited by increases of external Ca2+. Fibroblasts overgrowing the parathyroid chief cells during monolayer culture respond to ET-1 with biphasic [Ca2+]i increases or repetitive [Ca2+]i spikes, but show no response to elevation of external Ca2+. These findings imply that ET secretion and ET receptor expression may constitute an autocrine/paracrine mechanism in the regulation of human PTH secretion.
|
||
9,633,828
|
eng
|
[
"D017871",
"Q000378",
"D006528",
"D015500",
"Q000096",
"D004789",
"D005786",
"Q000187",
"D016762",
"Q000187",
"D016758",
"Q000187",
"D006801",
"D008113",
"D008748",
"Q000494",
"D019950",
"D048052",
"D020928",
"D011401",
"D016760",
"Q000096",
"D016755",
"Q000096",
"D011993",
"Q000096",
"D015398",
"Q000187",
"Q000502",
"D013755",
"Q000494",
"D014162",
"D014407"
] |
[
"Calcium-Calmodulin-Dependent Protein Kinases",
"Carcinoma, Hepatocellular",
"Chloramphenicol O-Acetyltransferase",
"Enzyme Activation",
"Gene Expression Regulation",
"Genes, fos",
"Genes, jun",
"Humans",
"Liver Neoplasms",
"Methylcholanthrene",
"Mitogen-Activated Protein Kinase 1",
"Mitogen-Activated Protein Kinase 3",
"Mitogen-Activated Protein Kinases",
"Promoter Regions, Genetic",
"Proto-Oncogene Proteins c-fos",
"Proto-Oncogene Proteins c-jun",
"Recombinant Fusion Proteins",
"Signal Transduction",
"Tetradecanoylphorbol Acetate",
"Transfection",
"Tumor Cells, Cultured"
] |
Signaling pathways in the induction of c-fos and c-jun proto-oncogenes by 3-methylcholanthrene.
3-methylcholanthrene (MC), a potent promutagen and procarcinogen, is also an inducer of mammalian CYPIAI (cytochrome P1-450) gene. The CYPIAI enzyme is responsible for the detoxification of MC and its oxidation into reactive epoxide intermediates. Through its epoxide metabolites, MC functions also as an inducer of drug-metabolizing enzyme glutathione S-transferase (GST) gene expression. Induction of murine GST Ya gene by MC and a variety of other chemical agents is mediated by a regulatory element composed of two adjacent AP-1-like sites, and activated by the Fos/Jun heterodimeric complex (AP-1). In cultured cells, MC causes the induction of AP-1 activity, which is the result of an increased expression of c-Fos and c-Jun proteins. The mechanisms involved in MC activation of c-fos and c-jun gene expression were examined in the present study. Evidence is presented that stimulation of c-fos transcription by MC involves a signal transduction pathway, which includes activation of the small G protein Ras, Raf-1 kinase, and the mitogen-activated protein (MAP) kinases, ERK1 and ERK2. Furthermore, we find that phorbol 12-myristate 13-acetate, which uses both protein kinase C and protein-tyrosine kinase activities to induce c-fos promoter, may share a common pathway with MC downstream of Ras. The signal transduction pathway induced by MC to stimulate c-jun promoter involves Ras activation and the JNK group of MAP-kinases.
|
||
9,633,829
|
eng
|
[
"D000375",
"Q000502",
"D000818",
"D000831",
"D003600",
"Q000378",
"D004958",
"Q000378",
"Q000494",
"D005260",
"D011863",
"D011869",
"D051381",
"D017208",
"D011960",
"Q000378",
"D014316",
"D014621",
"Q000166",
"Q000187",
"Q000502"
] |
[
"Aging",
"Animals",
"Animals, Newborn",
"Cytosol",
"Estradiol",
"Female",
"Radioimmunoassay",
"Radioligand Assay",
"Rats",
"Rats, Wistar",
"Receptors, Estrogen",
"Tritium",
"Vagina"
] |
Responsiveness of vaginal cells to estradiol during postnatal development of rat.
Ontogeny of responsiveness to hormones is mainly regulated by the presence of receptors; their type, number, and location in the hormone target cells. Some of these parameters have been used to study the responsiveness of rat vagina to estradiol. The estrogen binding sites (EBS) in the cytosol of rat vagina are present immediately at birth, however the animal becomes responsive to the hormone only after 25 +/- 5 d of age. The authors demonstrate how the serum and tissue levels of estradiol affect the EBS in this tissue during the postnatal development of the rat. The various responses observed after a single i.p. injection of estradiol in the immature rats are explained based on the status of the binding sites for estrogen in this tissue.
|
||
9,633,830
|
eng
|
[
"D000818",
"D000906",
"D000911",
"D000918",
"D001667",
"D002462",
"Q000502",
"D006063",
"Q000378",
"D003338",
"Q000502",
"D005260",
"D006801",
"D007986",
"Q000378",
"D046911",
"D051379",
"D011817",
"D011974",
"Q000276",
"Q000502",
"D012756"
] |
[
"Animals",
"Antibodies",
"Antibodies, Monoclonal",
"Antibody Specificity",
"Binding, Competitive",
"Cell Membrane",
"Chorionic Gonadotropin",
"Corpus Luteum",
"Female",
"Humans",
"Luteinizing Hormone",
"Macromolecular Substances",
"Mice",
"Rabbits",
"Receptors, LH",
"Sheep"
] |
Demonstration of complimentarity between monoclonal antibodies (MAbs) to human chorionic gonadotropin (hCG) and polyclonal antibodies to luteinizing hormone/hCG receptor (LH-R) and their use in better understanding hormone-receptor interaction.
We have earlier reported that polyclonal antisera raised in rabbits to a luteinizing hormone/chorionic gonadotropin receptor (LH-R) purified from sheep luteal tissue has antibodies exhibiting hormone agonistic and antagonistic activities. Western blot analysis showed this antibody (LHR-anti IgG) to be highly specific to sheep luteal LH receptor (LH-R) (Jeyakumar and Moudgal, 1991). Using this, along with a battery of mouse monoclonal antibodies (MAbs) to hCG, an attempt has been made to better understand the interaction of LH/hCG with its receptor. Of the eight hCG MAbs screened, three (B14/B7, B52/18 and A7/G4) were specific to the beta-subunit; while a second set of three (G10/F7, H9/E9 and B52/21) were specific to the alpha-subunit. Two additional MAbs (B52/28 and F9/G8) did not recognize individual subunits, but bound like the rest intact hCG. Both 125I hCG and 125I anti LHR-IgG bound specifically to ovine luteal membrane LH-R. Assuming that a certain degree of similarity should exist between hCG and LHR-anti IgG, different hCG MAbs were tested for their ability to block the binding of either 125I hCG or 125I LHR-anti IgG to sheep luteal LH-R. It appears that hCG and LH-R share a minimum of four sites that are complementary to each other and these are recognized by the hCG MAbs B14/B7, G10/F7, A7/G4, and H9/E9. Whereas two of the MAbs B14/B7 and G10/F7 blocked the binding of both 125I labeled hCG and LHR-anti IgG to the receptor, MAbs A7/G4 and H9/E9 only inhibited the binding of 125I LHR-anti IgG to the LH-R. Although individually B14/B7 and G10/F7 blocked the binding of 125I LHR-anti IgG to LH-R to a maximum extent of 43%, together they inhibited binding by as much as 80%. The ability of B14/B7 to inhibit binding of 125I LHR-anti IgG to the receptor was also significantly increased by the addition of A7/G4. Finally, by demonstrating direct binding of the immobilized hCG MAbs B14/B7, G10/F7, A7/G4, and H9/E9 to LHR-anti IgG, we have been able to establish that the receptor binding sites of hCG and LHR-anti IgG are complementary and that a set of four sites are recognizable by the hCG MAbs. From the degree of interaction, it appears that two sites recognized by MAbs B14/B7 and G10/F7 (representing a site each in the beta- and alpha-subunit of hCG) have a prominent role in the interaction of hCG with its receptor. Thus, this study has provided us with an opportunity to investigate the interaction of LH/hCG with its receptor by an indirect approach of monitoring the binding of their respective antibodies with each other.
|
||
9,633,831
|
eng
|
[
"D000293",
"D000328",
"D003866",
"Q000150",
"D006801",
"D007360",
"D009518",
"D011379",
"D011569",
"D012189",
"D018570",
"D012559",
"Q000150",
"Q000175",
"D014888"
] |
[
"Adolescent",
"Adult",
"Depressive Disorder",
"Humans",
"Intelligence",
"New York",
"Prognosis",
"Psychiatric Status Rating Scales",
"Retrospective Studies",
"Risk Assessment",
"Schizophrenia",
"Wechsler Scales"
] |
1998
|
May
|
The New York High-Risk Project: social and general intelligence in children at risk for schizophrenia.
Social deficits, as well as low performance on intelligence tests, are known early symptoms of schizophrenia. We studied whether impairment of social intelligence can be detected before the outbreak of the disorder. In the New York High-Risk Project, children at risk for schizophrenia (HRSz) or affective disorder (HRAff) and a normal control group (NC) were studied over the past 26 years. The children are now in mid-adulthood, with known psychiatric outcomes. Developmental and clinical data from childhood can now be related to adulthood diagnoses. We compared mean WISC (or WISC-R) and WAIS (or WAIS-R) scores from childhood and adolescence, and change of IQ, between the risk groups, as well as between the adulthood outcomes. We were specifically interested in the development of social intelligence (the Picture Arrangement and Comprehension subtests). We used logistic regression analyses to generate a model predicting adulthood schizophrenia. IQ at age 9,7 was lower in children with HRSz than with HRAff. Adulthood schizophrenia, compared with major depressive disorder and no psychiatric diagnosis could not be related conclusively to low IQ. This may be a result of the study design, since children with IQ below 70 or behavioral problems were not eligible as study subjects. There was no evidence of lower scores or more decline in social intelligence related to age or group membership (risk or outcome). Subtest-Scatter, a nondirectional measure of the differences between all subtests and Vocabulary, reflecting a lesser difference between crystallized and fluid intelligence, was identified as a significant predictor of adulthood schizophrenia, in the whole group as well as in the HRSz group alone.
|
9,633,832
|
eng
|
[
"D000328",
"D002452",
"D002540",
"Q000000981",
"Q000378",
"D005260",
"D007839",
"D006801",
"D008297",
"D011744",
"Q000493",
"D011985",
"Q000378",
"D012559",
"Q000000981",
"Q000378",
"D014055"
] |
[
"Adult",
"Cell Count",
"Cerebral Cortex",
"Female",
"Functional Laterality",
"Humans",
"Male",
"Pyrimidinones",
"Receptors, Serotonin",
"Schizophrenia",
"Tomography, Emission-Computed"
] |
1998
|
May
|
No serotonin 5-HT2A receptor density abnormality in the cortex of schizophrenic patients studied with PET.
To investigate putative abnormalities of cortical 5-HT2A receptor density in schizophrenia, we used positron emission tomography and [18F]setoperone, a high-affinity 5-HT2A receptor radioligand, in 14 neuroleptic-free or -naive schizophrenic patients and in 15 normal controls. No significant difference between the groups was observed in the whole or regional cortical binding potential of [18F]setoperone, indicating an absence of major 5-HT2A receptor cortical density abnormalities in schizophrenics.
|
9,633,833
|
eng
|
[
"D000208",
"D000328",
"D014150",
"Q000009",
"D001549",
"D001921",
"Q000000981",
"Q000378",
"D018492",
"D006220",
"Q000009",
"D006801",
"D008875",
"D011596",
"Q000139",
"Q000175",
"D011759",
"D011930",
"D011954",
"Q000187",
"D018967",
"Q000009",
"D012559",
"Q000150",
"Q000188",
"D015899"
] |
[
"Acute Disease",
"Adult",
"Antipsychotic Agents",
"Benzamides",
"Brain",
"Dopamine Antagonists",
"Haloperidol",
"Humans",
"Middle Aged",
"Psychomotor Disorders",
"Pyrrolidines",
"Reaction Time",
"Receptors, Dopamine",
"Risperidone",
"Schizophrenia",
"Tomography, Emission-Computed, Single-Photon"
] |
1998
|
May
|
Psychomotor slowing, negative symptoms and dopamine receptor availability--an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients.
Anhedonia and psychomotor slowing in schizophrenia have been attributed to a dysfunction of dopaminergic neurotransmission. To differentiate between disease and drug-induced negative symptoms, we examined eight drug-free and eight neuroleptic-treated schizophrenic patients. Positive and negative symptoms and extrapyramidal side effects were assessed using standardized rating scales (PSAS, AMDP, SANS). 'Reaction time' and 'motor speed' were measured using a computer-aided system and striatal dopamine D2/D3 receptor availability was assessed using [I-123]IBZM SPECT. Psychomotor reaction time, parkinsonism, affective flattening and avolition were increased in treated patients relative to the untreated cohort and were negatively correlated with dopamine D2/D3 receptor availability. Significant positive correlations were found between parkinsonism and affective flattening and between psychomotor slowing and avolition. Positive symptoms were not significantly associated with striatal IBZM binding. These findings support the hypothesis that neuroleptic-induced dopamine D2/D3 blockade in the striatum can mimic certain negative symptoms, such as affective flattening and avolition, and indicates that psychomotor testing may be helpful in differentiating between disease and drug-induced negative symptoms.
|
9,633,834
|
eng
|
[
"D000700",
"Q000494",
"D000818",
"D003514",
"Q000494",
"D004298",
"Q000378",
"D004357",
"D008297",
"D016202",
"Q000378",
"Q000494",
"D009478",
"Q000494",
"D010423",
"Q000494",
"D017397",
"Q000187",
"D011759",
"Q000494",
"D051381",
"D017207",
"D011954",
"Q000187"
] |
[
"Analgesics",
"Animals",
"Cyclohexylamines",
"Dopamine",
"Drug Synergism",
"Male",
"N-Methylaspartate",
"Neuropeptide Y",
"Pentazocine",
"Prefrontal Cortex",
"Pyrrolidines",
"Rats",
"Rats, Sprague-Dawley",
"Receptors, Dopamine"
] |
1998
|
May
|
Neuropeptide Y-mediated enhancement of NMDA-stimulated [3H]dopamine release from rat prefrontal cortex is reversed by sigma1 receptor antagonists.
Sigma (sigma) receptors are located in limbic areas, including the prefrontal cortex, where decreased dopamine levels have been linked to negative symptoms. Although the endogenous ligands for sigma receptors are unknown, neuropeptide Y (NPY) has been named as the potential endogenous agonist at these receptors. NPY enhanced NMDA-stimulated [3H]dopamine release in rat prefrontal cortex. This was in contrast to the inhibition produced by the sigma agonists (+)pentazocine and BD737. However, four sigma antagonists, including one which is sigma1 selective, that reverse (+)pentazocine- or BD737-mediated inhibition all reversed the NPY-mediated enhancement. In addition, PYX-1, a Y receptor antagonist, reversed both the (+)pentazocine- and BD737-mediated inhibition and the NPY-mediated enhancement of release. Peptide YY (PYY), [Leu31,Pro34]NPY and NPY(13-36) did not mimic the effect of NPY. Our findings are consistent with NPY acting as an endogenous ligand for a subtype of sigma receptor with characteristics different from Y1, Y2 and Y3 receptors but sensitive to PYX-1. These findings suggest a role for NPY, via sigma receptors, as a modulator of dopamine levels in the prefrontal cortex.
|
9,633,835
|
eng
|
[
"D000255",
"Q000378",
"D000328",
"D005260",
"D005625",
"Q000378",
"D006801",
"D008279",
"D008297",
"D008875",
"D009483",
"D010725",
"Q000378",
"D010759",
"D012559",
"Q000175"
] |
[
"Adenosine Triphosphate",
"Adult",
"Female",
"Frontal Lobe",
"Humans",
"Magnetic Resonance Imaging",
"Male",
"Middle Aged",
"Neuropsychological Tests",
"Phosphocreatine",
"Phosphorus Isotopes",
"Schizophrenia"
] |
1998
|
May
|
High-energy phosphates in the frontal lobe correlate with Wisconsin Card Sort Test performance in controls, not in schizophrenics: a 31phosphorus magnetic resonance spectroscopic and neuropsychological investigation.
In recent years, a number of 31phosphorus magnetic resonance spectroscopy (P-MRS) studies on the frontal lobe of schizophrenics have been performed, reporting alterations of phospholipids and high-energy phosphates. Deicken et al. (1994b) recently found positive correlations between left frontal phosphomonoester% (PME%) levels and the performance of a specific frontal lobe task, the Wisconsin Card Sorting Test (WCST), in schizophrenics. In the present paper, the correlations between phospholipids and high-energy phosphates in the frontal lobe of 26 schizophrenics and 23 controls measured with a volume-selective P-MRS method were investigated. Overall, we could not find any correlations between WCST results and phospholipid levels, but in controls phosphocreatine% (PCr%) and PCr/adenenosine triphosphate (ATP) ratios were negatively correlated with test performance. Since PCr behaves as a buffer of ATP, in the sense that when ATP is consumed by neuronal activity PCr is catalysed rapidly to ATP, increased PCr% values and, moreover, increased PCr/ATP ratios point to a decreased ATP consumption. Thus, the correlations found between PCr% and PCr/ATP and test performance in controls point to an association between reduced performance in a specific frontal lobe task and decreased energy demanding processes at rest. This association was not found in schizophrenics, possibly due to the influence of neuroleptic medication or the disease process per se.
|
9,633,836
|
eng
|
[
"D000328",
"D000368",
"D015496",
"Q000276",
"D018414",
"Q000276",
"D005260",
"D005434",
"Q000379",
"D006801",
"D007136",
"Q000097",
"D017493",
"Q000097",
"Q000276",
"D008297",
"D008875",
"D012559",
"Q000097",
"Q000276"
] |
[
"Adult",
"Aged",
"CD4-Positive T-Lymphocytes",
"CD8-Positive T-Lymphocytes",
"Female",
"Flow Cytometry",
"Humans",
"Immunoglobulins",
"Leukocyte Common Antigens",
"Male",
"Middle Aged",
"Schizophrenia"
] |
1998
|
May
|
Increased levels of CD8+ and CD4+ 45RA+ lymphocytes in schizophrenic patients.
Peripheral blood (PB) lymphocyte subpopulations, IgG, IgM, IgA and IgE serum immunoglobulins and C3 and C4 complement fractions were evaluated in 29 schizophrenic patients, 31 of their relatives and 20 healthy subjects. The patients fulfilled DSM-III criteria for schizophrenia, and were unmedicated for 3 months prior to the PB sample collection. When compared to healthy controls and their own relatives, the schizophrenic patients showed a lower level of CD4+ cells, while the CD4+ 45RA+ (naive) subset was significantly higher. Conversely, the number of CD4+ 45RA- (memory) lymphocytes was significantly lower in schizophrenic patients in comparison to their relatives and controls, while the CD8+ supressor/cytotoxic T-cell percentage was significantly higher. No significant differences were observed for the IgG, IgM, IgA, IgE and C3 and C4 complement fraction levels among the three groups. The present data confirm the presence of immunological abnormalities in schizophrenic patients and suggest a possible role of environmental factors in the triggering of an autoimmune pathogenic mechanism.
|
9,633,837
|
eng
|
[
"D006801",
"D012559",
"Q000175",
"D012565"
] |
[
"Humans",
"Schizophrenia",
"Schizophrenic Psychology"
] |
1998
|
May
|
The structure of schizophrenic symptoms: a meta-analytic confirmatory factor analysis.
To quantitatively review all presently available evidence about the interrelations between positive and negative schizophrenic symptoms, we created an aggregate matrix of the intercorrelations among schizophrenic symptoms by combining data from 28 independent samples using meta-analytic procedures (net bivariate dfs ranging from 683 to 1657). Using confirmatory factor analyses, we then statistically compared four theoretically derived models of the structure of schizophrenic symptoms. Although a three-factor model (Liddle, 1987) best fit the data, results suggest that either more factors or different symptoms are required to account well for the latent structure underlying schizophrenic symptomatology. The nature of such augmented approaches, the opportunities and constraints inherent to multifactorial models, and the limitations of current instruments are discussed.
|
9,633,839
|
eng
|
[
"D005260",
"D006801",
"D015994",
"D010051",
"Q000453",
"Q000235",
"D012307",
"D014481",
"Q000453"
] |
[
"Female",
"Humans",
"Incidence",
"Ovarian Neoplasms",
"Risk Factors",
"United States"
] |
1998
|
Jun
|
Epidemiology and risk assessment for ovarian cancer.
The incidence of ovarian cancer varies internationally with higher rates among women of North America and northern Europe. In the United States, there has been relatively little change in the incidence of ovarian cancer in recent decades. The incidence rate of ovarian cancer is highest among white and Hawaiian women, intermediate among African-American, Hispanic and Asian-American women, and lowest among Native American women. The most intensively studied risk factors have been family history, pregnancy history, and oral contraceptive use. Multiparity, lactation, oral contraceptive use, and tubal ligation/hysterectomy all decrease a woman's risk of ovarian cancer. One exposure that has been consistently associated with increased ovarian cancer risk is cosmetic talc applied to the perineum.
|
9,633,840
|
eng
|
[
"D019313",
"Q000235",
"D024682",
"D002869",
"Q000235",
"D003123",
"Q000235",
"D005260",
"D011905",
"D005820",
"D006801",
"D009363",
"Q000235",
"D015513",
"Q000235",
"D010051",
"Q000235",
"Q000401",
"Q000473",
"Q000517",
"D010375",
"D017346",
"Q000235",
"D011518",
"D051057",
"D014157",
"Q000235"
] |
[
"BRCA1 Protein",
"BRCA2 Protein",
"Chromosome Aberrations",
"Colorectal Neoplasms, Hereditary Nonpolyposis",
"Female",
"Genes, ras",
"Genetic Testing",
"Humans",
"Neoplasm Proteins",
"Oncogene Proteins",
"Ovarian Neoplasms",
"Pedigree",
"Protein Serine-Threonine Kinases",
"Proto-Oncogene Proteins",
"Proto-Oncogene Proteins c-akt",
"Transcription Factors"
] |
1998
|
Jun
|
Genetics and ovarian carcinoma.
Ovarian cancer is a disease that will affect approximately 1% of American women during their lifetime, and contributes to more than 14,000 deaths annually. If not detected early, this disease has a 5-year survival rate of less than 20%. Ovarian cancer develops predominantly from the malignant transformation of a single cell type, the surface epithelium. Although the biological mechanisms of transformation remain unclear, it is probably a multistep process requiring an accumulation of genetic lesions in a number of different gene classes. Several proto-oncogenes, such as AKT2 and Ki-RAS, are activated during ovarian cancer development, with putative oncogene-containing chromosomal regions showing imbalances and DNA amplifications. A number of chromosomal regions are also lost in ovarian tumors, indicating that the inactivation of tumor suppressor genes, such as TP53, may also contribute to cancer development. An important recent advancement in the field of ovarian cancer research is the identification of the breast/ovarian cancer susceptibility genes, BRCA1 and BRCA2. Mutations in these two tumor suppressor genes are responsible for the majority of heritable forms of epithelial ovarian cancers. A second class of genes involved in DNA mismatch repair (MMR) are responsible for most cases of hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC or Lynch II cancer syndrome patients are also at an increased risk for developing ovarian cancer. Individuals in cancer-prone kindreds are currently being screened for germline mutations in BRCA1, BRCA2, and several MMR genes (eg, MSH2, MLH1), and mutant allele carriers counseled for cancer risks. Issues related to counseling and management of women at high risk for developing ovarian cancer are discussed. Although BRCA1, BRCA2, and a number of MMR genes have been identified, many more genes involved in gynecologic malignancies remain to be discovered and the clinical significance of the cancer genes already known is still in its infancy.
|
9,633,841
|
eng
|
[
"D002471",
"D004273",
"Q000187",
"D019008",
"D004847",
"D004848",
"D005260",
"D015972",
"D016147",
"D006801",
"D009154",
"D009375",
"Q000188",
"Q000209",
"Q000235",
"Q000473",
"D009857",
"D010051",
"Q000188",
"Q000209",
"Q000235",
"Q000473",
"D010053",
"Q000166",
"Q000502"
] |
[
"Cell Transformation, Neoplastic",
"DNA, Neoplasm",
"Drug Resistance, Neoplasm",
"Epithelial Cells",
"Epithelium",
"Female",
"Gene Expression Regulation, Neoplastic",
"Genes, Tumor Suppressor",
"Humans",
"Mutation",
"Neoplasms, Glandular and Epithelial",
"Oncogenes",
"Ovarian Neoplasms",
"Ovary"
] |
1998
|
Jun
|
The biology of ovarian cancer.
The biology of ovarian cancer broadly defined covers essentially all aspects of the disease from how it arises to how it responds to chemotherapy, often becomes refractory to treatment, and ultimately kills the patient. In this article, we take the liberty of discussing many of these issues to some degree in context of the "natural/clinical" history/biology of the disease. We focus on concepts of how the disease develops, efforts to identify histologic changes that may precede the development of overt ovarian cancer, efforts to define how the growth and function of the normal ovarian surface epithelium are regulated to gain insights into how aberrant function of these pathways may contribute to the initiation of the disease, molecular biological studies on clinical ovarian cancer specimens, efforts to experimentally induce the malignant transformation of ovarian surface epithelial cells, and efforts to understand why ovarian cancer is often initially responsive to chemotherapy but ultimately becomes refractory.
|
9,633,842
|
eng
|
[
"D019008",
"D005260",
"D016147",
"D006801",
"D015999",
"D009367",
"D009375",
"Q000145",
"Q000235",
"Q000401",
"Q000473",
"D010051",
"Q000235",
"Q000401",
"Q000473",
"Q000628",
"D011379"
] |
[
"Drug Resistance, Neoplasm",
"Female",
"Genes, Tumor Suppressor",
"Humans",
"Multivariate Analysis",
"Neoplasm Staging",
"Neoplasms, Glandular and Epithelial",
"Ovarian Neoplasms",
"Prognosis"
] |
1998
|
Jun
|
Prognostic factors in ovarian cancer.
There is obvious merit in being able to accurately predict outcome and tailor treatment according to individual risk and potential for benefit. Epithelial ovarian cancers are characterized by a broad spectrum of biological behavior ranging from tumors that have an excellent prognosis and high likelihood of cure to those that progress rapidly and have a very poor prognosis. This wide clinical spectrum is partly reflected by a number of clinicopathological prognostic variables which include International Federation of Gynecology and Obstetrics stage, histologic subtype and grade, volume of residual tumor remaining after surgical resection, performance status, and age. There has been increasing interest by many groups to incorporate the independent prognostic variables into multivariate models that could better predict outcome. This approach does appear to allow the identification of different prognostic subsets and requires confirmation in prospective studies. There has been, and there continues to be a lot of effort in identifying new prognostic factors that have a biologic rationale and these will be discussed. Most of these new prognostic factors have not been subjected to rigorous testing and this will be clearly necessary before they find clinical application. This is an area that is rapidly evolving with the increased understanding of the molecular basis for ovarian carcinogenesis and progression coupled with technological advances such as DNA arrays and automated polymerase chain reaction. We are at the threshold of developing a new and more objective as well as rational approach to predict prognosis and response to therapy.
|
9,633,843
|
eng
|
[
"D000465",
"D014408",
"D018394",
"D003365",
"D005260",
"D006801",
"D008403",
"Q000191",
"Q000592",
"D010051",
"Q000175",
"Q000000981",
"Q000517",
"D014463"
] |
[
"Algorithms",
"Biomarkers, Tumor",
"CA-125 Antigen",
"Costs and Cost Analysis",
"Female",
"Humans",
"Mass Screening",
"Ovarian Neoplasms",
"Ultrasonography"
] |
1998
|
Jun
|
Ovarian cancer screening.
Despite advances in molecular biology, surgical oncology, and chemotherapy, the prognosis for ovarian cancer remains poor. The excellent survival rates for stage I disease provide the rationale for efforts to screen for early-stage ovarian cancer. However, there are doubts about the feasibility of screening related to the natural history of the disease, the performance of the available tests, and health economic considerations. The investigators use the World Health Organization criteria for a screening program as a framework for discussing current issues in ovarian cancer screening. These include screening modalities and strategies, high- and low-risk populations, and the acceptability, psychological impact, and cost of screening. As a result of developments during the last decade, there are now real prospects for practical and effective ovarian cancer screening programs. Research to date has made important progress, but information about the impact of screening on mortality from ovarian cancer is still awaited. Three large randomized controlled trials of ovarian cancer screening are currently recruiting volunteers and will yield important results in the next few years.
|
9,633,844
|
eng
|
[
"D002986",
"D005260",
"D005298",
"D006801",
"D010535",
"D007813",
"D009367",
"D010051",
"Q000473",
"Q000601"
] |
[
"Clinical Trials as Topic",
"Female",
"Fertility",
"Humans",
"Laparoscopy",
"Laparotomy",
"Neoplasm Staging",
"Ovarian Neoplasms"
] |
1998
|
Jun
|
The role of surgery in the management of ovarian cancer: primary and interval cytoreductive surgery.
Ovarian cancer remains the number one cause of mortality in gynecologic malignancies and the fifth most common cause of death among all malignancies in women. Unfortunately, recent data confirm that only approximately 90% of "apparent" early ovarian cancer are inadequately staged, and only approximately 80% of patients with advanced-stage disease are adequately staged. Interval debulking surgery, a newer treatment modality, appears to have a promising role for patients who cannot be adequately debulked at their initial surgery. Second-look laparotomy continues to be the most accurate way to document responses to chemotherapy in protocol settings, but additional clinical trials with newer second-line chemotherapy will be necessary before definitive statements can be made with regard to survival advantages in patients who undergo second-look laparotomy.
|
9,633,845
|
eng
|
[
"D000971",
"Q000627",
"D002986",
"D003131",
"D005260",
"D006801",
"D008207",
"D009367",
"D010051",
"Q000473",
"Q000601",
"Q000628"
] |
[
"Antineoplastic Combined Chemotherapy Protocols",
"Clinical Trials as Topic",
"Combined Modality Therapy",
"Female",
"Humans",
"Lymphatic Metastasis",
"Neoplasm Staging",
"Ovarian Neoplasms"
] |
1998
|
Jun
|
Management of early ovarian cancer.
About one third of the women diagnosed with ovarian cancer present with localized disease. Accurate surgical staging is required to properly evaluate these patients, define appropriate treatment, and establish prognosis. A series of recent studies have clarified which patients can be managed with comprehensive surgical staging and disease removal alone, and which may benefit from adjuvant therapy. A series of national and international prospective randomized trials are evaluating a variety of adjuvant treatments that may enhance long-term survival in those patients with early ovarian cancer who do require additional therapy.
|
9,633,846
|
eng
|
[
"D000971",
"Q000627",
"D016190",
"Q000008",
"D002945",
"Q000008",
"D002986",
"D005260",
"D006801",
"D010051",
"Q000188",
"D017239",
"Q000008"
] |
[
"Antineoplastic Combined Chemotherapy Protocols",
"Carboplatin",
"Cisplatin",
"Clinical Trials as Topic",
"Female",
"Humans",
"Ovarian Neoplasms",
"Paclitaxel"
] |
1998
|
Jun
|
Chemotherapy of advanced ovarian cancer.
Combination chemotherapy with paclitaxel plus a platinum compound (carboplatin or cisplatin) is the current regimen of choice for the treatment of advanced epithelial ovarian cancer. The two most widely used combinations are paclitaxel (135 mg/m2, 24-hour infusion) plus cisplatin (75 mg/m2) or paclitaxel (175 mg/m2, 3-hour infusion) plus carboplating dosed to an area under curve of 7.5. Randomized trials are in progress comparing these two regimens. Numerous other clinical issues remain regarding how to maximize the effectiveness of this therapy, including dose and schedule, duration of treatment, route of administration, and incorporation of other agents with novel mechanisms of cytotoxicity. New agents currently undergoing evolution as part of novel induction regimens have been shown to have significant activity in recurrent ovarian cancer and include topotecan, gemcitabine, oral etoposide, and encapsulated doxorubicin.
|
9,633,847
|
eng
|
[
"D000971",
"Q000008",
"Q000627",
"D003115",
"Q000627",
"D004334",
"D005260",
"D018380",
"D006801",
"D010051",
"Q000188"
] |
[
"Antineoplastic Combined Chemotherapy Protocols",
"Colony-Stimulating Factors",
"Drug Administration Schedule",
"Female",
"Hematopoietic Stem Cell Transplantation",
"Humans",
"Ovarian Neoplasms"
] |
1998
|
Jun
|
Multiple cycles of high-dose chemotherapy for ovarian cancer.
Recent advances in hematopoietic support have extended the application of high-dose chemotherapy in the treatment of malignancy. The use of colony-stimulating factors and peripheral blood progenitor cells significantly have decreased the morbidity and mortality of such treatment compared with traditional autologous bone marrow transplantation. These innovations facilitate the use of multiple cycles of high-dose chemotherapy as consolidation after achieving best response to conventional chemotherapy or as initial treatment. Developing data suggest that this approach in both of these settings merit further evaluation for the treatment of epithelial ovarian carcinoma.
|
9,633,848
|
eng
|
[
"D000971",
"Q000008",
"Q000627",
"D002945",
"Q000008",
"D002986",
"D005260",
"D006801",
"D007274",
"D010051",
"Q000188",
"D017239",
"Q000008",
"D016879"
] |
[
"Antineoplastic Combined Chemotherapy Protocols",
"Cisplatin",
"Clinical Trials as Topic",
"Female",
"Humans",
"Injections, Intraperitoneal",
"Ovarian Neoplasms",
"Paclitaxel",
"Salvage Therapy"
] |
1998
|
Jun
|
Intraperitoneal therapy of ovarian cancer.
During the past decade, intraperitoneal chemotherapy has evolved from a theoretical concept into a rational therapeutic strategy for a select group of individuals with ovarian cancer. Patients who may potentially benefit from this approach include those with small volume intraperitoneal disease at the initiation of initial chemotherapy and individuals with microscopic and very small volume macroscopic cancer after the completion of front-line systemic treatment. Further exploration to define an ultimate role for regional antineoplastic drug delivery in the management of ovarian cancer is warranted.
|
9,633,850
|
eng
|
[
"D003131",
"D015914",
"D005260",
"D006801",
"D009367",
"D018297",
"Q000401",
"Q000473",
"Q000628",
"D010051",
"Q000401",
"Q000473",
"Q000628",
"D011379"
] |
[
"Combined Modality Therapy",
"Estrogen Replacement Therapy",
"Female",
"Humans",
"Neoplasm Staging",
"Neoplasms, Cystic, Mucinous, and Serous",
"Ovarian Neoplasms",
"Prognosis"
] |
1998
|
Jun
|
Management of borderline tumors of the ovary: state of the art.
Evidence published during several decades has shown that there is a group of epithelial ovarian tumors having histological and biological features between those of clearly benign and frankly malignant tumors. In 1963, FIGO accepted an intermediate group of ovarian carcinomas of low malignant potential. In 1973, WHO adopted the term borderline malignancies to describe these tumors. Borderline tumors represent approximately 10% to 15% of all epithelial ovarian malignancies. There are considerable discrepancies in the reported incidence of ovarian tumors of borderline malignancies. Some centers do not recognize tumors of this type and include them among invasive cancers. The prognosis for patients with borderline tumors is generally considered to be excellent. Although the standard treatment for older patients is abdominal hysterectomy and bilateral salpingo-oophorectomy, many young patients who have not completed childbearing can be safely treated with unilateral salpingo-oophorectomy coupled with comprehensive surgical staging, thereby preserving fertility potential. Even ovarian cystectomy has been reported, but the recurrence rate in the ovary approximates 15%. Many experts strongly believe that surgery is the only effective treatment for borderline tumors. Others routinely use postoperative chemotherapy for at least some subsets of patients with peritoneal implants. Currently, insufficient information is available to make a definitive statement regarding the efficacy of postoperative therapy. Nevertheless, clinicians are faced with the difficult task of making treatment recommendations to anxious patients. In the past, extensive application of automated methods for analytical cytology has resulted in large quantities of data on ploidy abnormalities in different types of human cancers. The main purpose has been to obtain additional parameters for the characterization of various types of malignancy to give more precise information on their biological behavior. Data from the Norwegian Radium Hospital showed that the majority of borderline tumors have DNA diploid tumors and good prognosis, DNA aneuploidy indicates high risk. Several other investigators have shown the same results on DNA ploidy as a predictor of recurrence and survival, but a few others have shown conflicting results. Early studies suggest that p53 mutation does not appear to play a role in the pathogenesis of these tumors. Studies on other molecular markers have not yet uncovered a reliable predictor of biologic behavior. However, it is hoped that future studies of genetics and molecular biology of these tumors will lead to useful laboratory tests.
|
9,633,851
|
eng
|
[
"D000911",
"Q000627",
"D019496",
"D002986",
"D066246",
"D005260",
"D006801",
"D018796",
"Q000627",
"D007155",
"Q000627",
"D007167",
"D000922",
"Q000627",
"D016173",
"D009361",
"D009389",
"D010051",
"Q000276",
"Q000628",
"D018719",
"D018121"
] |
[
"Antibodies, Monoclonal",
"Cancer Vaccines",
"Clinical Trials as Topic",
"ErbB Receptors",
"Female",
"Humans",
"Immunoconjugates",
"Immunologic Factors",
"Immunotherapy",
"Immunotoxins",
"Macrophage Colony-Stimulating Factor",
"Neoplasm Invasiveness",
"Neovascularization, Pathologic",
"Ovarian Neoplasms",
"Receptor, ErbB-2",
"Receptors, Cytokine"
] |
1998
|
Jun
|
Biological therapy of ovarian cancer: current directions.
Despite recent advances in the chemotherapy of ovarian cancer, the development of alternative therapies that retain activity against drug-resistant tumors remains a high priority. Our knowledge regarding growth factors, cytokines, and the immune response continues to expand, and molecular biology has provided an increased diversity of reagents for clinical evaluation. This review focuses on regulatory targets in ovarian cancer, including Her2/neu (c-erbB2) and other growth factor receptors; interferons, interleukins, and other immunoregulatory cytokines; cellular adhesion molecules; antigen-specific T lymphocytes and adoptive immunotherapy; choice of monoclonal antibody reagents and advances in antibody engineering, including recombinant single-chain binding sites, chimeric proteins, radioconjugates, cytotoxic drug conjugates, immunotoxins, and bispecific antibodies. Although specific roles for biologic therapy in the management of ovarian cancer have yet to be defined, current priorities for clinical research are reviewed.
|
9,633,852
|
eng
|
[
"D018432",
"Q000235",
"D019008",
"Q000235",
"D005260",
"D015972",
"Q000187",
"D018014",
"D015316",
"Q000379",
"Q000639",
"D006801",
"D007155",
"Q000627",
"D007167",
"D016296",
"D010051",
"Q000235",
"Q000628",
"D011355"
] |
[
"Drug Resistance, Multiple",
"Drug Resistance, Neoplasm",
"Female",
"Gene Expression Regulation, Neoplastic",
"Gene Transfer Techniques",
"Genetic Therapy",
"Humans",
"Immunologic Factors",
"Immunotherapy",
"Mutagenesis",
"Ovarian Neoplasms",
"Prodrugs"
] |
1998
|
Jun
|
Gene therapy for ovarian carcinoma.
Originally conceived and applied for the treatment of inherited monogenetic defects such as adenosine deaminase deficiency and cystic fibrosis, gene therapy was later applied to the treatment of cancer. Such a genetic strategy seemed rational given the recognition that cancer typically develops in a multistep process involving alterations of a number of different genes as demonstrated in familial polyposis and colorectal cancer through the work of Vogelstein et al. Because of the numerous alterations that may result in the eventual development of cancer, there is no obvious single choice for a therapeutic gene. Although one may view this as an obstacle, it also allows for a variety of possible therapeutic interventions. This review focuses on the known genetic defects that occur in ovarian cancer, the gene therapy strategies suggested by such defects, and the approaches under current development for the treatment of this disease. As such, this work also describes some of the approved human gene therapy protocols. Finally, an overview of the problems and directions for future growth and research is presented.
|
9,633,853
|
eng
|
[
"D000971",
"Q000627",
"D003131",
"D004407",
"Q000175",
"Q000628",
"D005260",
"D018237",
"Q000175",
"Q000473",
"Q000628",
"D006801",
"D007813",
"D009367",
"D010051",
"Q000175",
"Q000473",
"Q000628",
"D011379"
] |
[
"Antineoplastic Combined Chemotherapy Protocols",
"Combined Modality Therapy",
"Dysgerminoma",
"Female",
"Germinoma",
"Humans",
"Laparotomy",
"Neoplasm Staging",
"Ovarian Neoplasms",
"Prognosis"
] |
1998
|
Jun
|
Ovarian germ cell tumors: an update.
Ovarian germ cell tumors, while very rare, are important beyond their incidence because they occur in young people and they are highly responsive to appropriate treatment. Since 1991, when this topic was last discussed in Seminars in Oncology, there have been a few important publications specifically devoted to ovarian germ cell tumors. In addition, a number of important studies have added to the knowledge base of chemotherapy in testis cancer. This article reviews and updates progress made in this field.
|
9,633,864
|
eng
|
[
"D003363",
"Q000706",
"Q000639",
"D004651",
"Q000706",
"Q000639",
"D005544",
"D019981",
"Q000706",
"Q000639",
"D006291",
"Q000639",
"D006280",
"Q000706",
"D016304",
"Q000706",
"D006779",
"Q000706",
"D006801",
"D014481"
] |
[
"Cost Control",
"Employment",
"Forecasting",
"Health Care Sector",
"Health Policy",
"Health Workforce",
"Hospitals, Private",
"Hospitals, Public",
"Humans",
"United States"
] |
Health cost containment: what it will mean for workers and local economies.
After decades of rapid growth, the rate of increase in health services spending appears to be moderating. Although a slowdown in health expenditure growth would release resources for other uses in the economy, concerns have been raised about the effects of a spending slowdown on health workers and regional economies. Based on projections carried out by the Bureau of Labor Statistics during the health reform debate and on state health sector employment data, the author concludes that health workers may experience costly dislocation as health spending growth slows, and some regions may be more affected than others. However, the appropriate response is a general economic policy supporting economic growth and full employment policy with regard to health expenditure growth cannot be held hostage to concerns about employment effects.
|
||
9,633,866
|
eng
|
[
"D000293",
"D000328",
"D017677",
"D000368",
"D000369",
"D002423",
"D002648",
"D002675",
"D005260",
"D006801",
"D007223",
"D008297",
"D008875",
"D009026",
"Q000639",
"D011041",
"Q000145",
"Q000209",
"Q000401",
"D017678",
"D014481",
"Q000453"
] |
[
"Adolescent",
"Adult",
"Age Distribution",
"Aged",
"Aged, 80 and over",
"Cause of Death",
"Child",
"Child, Preschool",
"Female",
"Humans",
"Infant",
"Male",
"Middle Aged",
"Mortality",
"Poisoning",
"Sex Distribution",
"United States"
] |
Poisoning mortality, 1985-1995.
Poisoning was reported as the underlying cause of death for 18,549 people in the United States in 1995 and was ranked as the third leading cause of injury mortality, following deaths from motor vehicle traffic injuries and firearm injuries. Poisoning was the leading cause of injury death for people ages 35 to 44 years. Poisoning death rates were higher in 1995 than in any previous year since at least 1979. From 1990 to 1995, the age-adjusted rate of death from poisoning increased 25%; all of the increase was associated with drugs. About three-fourths of poisoning deaths (77%) in 1995 were caused by drugs. The age-adjusted rate of drug-related poisoning deaths for males (7.2 per 100,000) in 1995 was more than twice that for females (3.0 per 100,000). From 1985 to 1995, poisoning death rates for males ages 35-54 years nearly doubled to 20.4 per 100,000, and the drug-related poisoning death rate for males ages 35-54 years nearly tripled, reaching 16.1 per 100,000. From 1990 to 1995, death rates associated with opiates and cocaine more than doubled among males ages 35-54 years. The numbers of opiate and cocaine poisoning deaths for 1995 more than doubled when all multiple cause of death codes were examined instead of only the underlying cause of death codes.
|
||
9,633,871
|
eng
|
[
"D000818",
"D004199",
"D016527",
"D017721",
"D006801",
"D015994",
"D008404",
"Q000453",
"D010607",
"Q000191",
"Q000706",
"D011818",
"Q000191",
"Q000453",
"Q000517",
"Q000635",
"Q000662",
"D011819",
"Q000191",
"Q000276",
"D011821"
] |
[
"Animals",
"Disease Vectors",
"Drug Costs",
"Hospital Costs",
"Humans",
"Incidence",
"Massachusetts",
"Pharmacy Service, Hospital",
"Rabies",
"Rabies Vaccines",
"Raccoons"
] |
The cost of rabies postexposure prophylaxis: one state's experience.
This study was undertaken to evaluate trends in the use of rabies postexposure prophylaxis (PEP) before, during, and following an epidemic of raccoon rabies in Massachusetts. The authors reviewed initiation of PEP as reported to the Massachusetts Department of Public Health (MDPH) from August 1994 to December 1995 and surveyed hospital pharmacies to determine the number of vials of Human Rabies Immune Globulin (HRIG) dispensed from 1991 through 1995 and charges to patients per vial. PEP use increased dramatically, from 1.7 per 100,000 population in 1991 (pre-epidemic) to 45 per 100,000 in 1995 (after the first stages of the epidemic). The median costs per patient for biologics was $1646 (range: $632-$3435). Including physician and emergency room charges, per-patient median costs were $2376 (range: $1038-$4447). Total health care charges for PEP in Massachusetts in 1995 were estimated at $2.4 million to $6.4 million. Given the rapid increase in use of PEP, further studies should be undertaken to determine the appropriateness of use, and other alternatives, such as oral wildlife vaccines, should be considered.
|
||
9,633,873
|
eng
|
[
"D000328",
"D000818",
"D000829",
"D000835",
"D001733",
"Q000453",
"D002415",
"D002648",
"D004285",
"D006801",
"D011818",
"Q000453",
"Q000517",
"Q000635",
"Q000662",
"D011819",
"Q000276",
"D012189",
"D014611",
"Q000706",
"Q000662",
"D014768",
"Q000453"
] |
[
"Adult",
"Animals",
"Animals, Domestic",
"Animals, Wild",
"Bites and Stings",
"Cats",
"Child",
"Dogs",
"Humans",
"Rabies",
"Rabies Vaccines",
"Retrospective Studies",
"Vaccination",
"Virginia"
] |
Potential rabies exposures in a Virginia county.
Although records of animal bites and scratches are kept at most local health departments, little is known about the epidemiology and characteristics of these potential rabies exposures on a local level. Bite and scratch records for a four-and-a-half-year period from Montgomery County, Virginia, were examined in order to identify preventable trends. The author retrospectively reviewed animal bite and scratch records from the Montgomery County Health Department dating from January 1992 through July 1996. Cat bites or scratches involved stray or feral animals more than eight times as often as dog bites or scratches. Cats were involved in the majority of incidents in which rabies postexposure prophylaxis (PEP) was recommended. Overall, PEP was recommended following 5.9% of reported incidents. The records also indicated that 65% of owned cats were unvaccinated at the time of the incident, while only 28% of owned dogs were unvaccinated. Children under the age of 18 were significantly more likely to be involved in a potential exposure than adults. Potential exposures should be analyzed periodically by local health departments. Suggestions for minimizing the number of potential rabies exposures in Montgomery County based on the results of the study reported here include: reducing the stray and feral cat population, targeting educational programs to children, and encouraging owners to vaccinate their pets.
|
||
9,633,879
|
eng
|
[
"D000293",
"D000328",
"D002908",
"D000077543",
"D005293",
"Q000097",
"D006526",
"Q000097",
"Q000473",
"D006801",
"D007502",
"Q000627",
"D008103",
"Q000097",
"D008134",
"D011728",
"Q000627",
"D017086",
"Q000188",
"Q000473"
] |
[
"Adolescent",
"Adult",
"Chronic Disease",
"Deferiprone",
"Ferritins",
"Hepatitis C",
"Humans",
"Iron Chelating Agents",
"Liver Cirrhosis",
"Long-Term Care",
"Pyridones",
"beta-Thalassemia"
] |
1998
|
Jun
|
Liver iron and fibrosis during long-term treatment with deferiprone in Swiss thalassaemic patients.
Serum ferritin levels, hepatic histology and iron concentration were studied in a 'veteran' group of seven Swiss beta-thalassaemic patients after 93-99 months of treatment with the oral iron chelator deferiprone (L1), and another four patients who had received 54-82 months of L1 therapy. Despite continuous compliance, unexplained resurgence of serum ferritin levels occurred in 4/7 patients of the 'veteran' group after 4-5 years on L1. In three of these a concomitant increase of liver iron was also observed. Hepatic histology revealed significantly higher degrees of fibrosis in 6/11 hepatitis C (HC)-positive patients (fibrosis scores 1-5, mean 3.0) than in the HC-negative group (fibrosis score 0-2, mean 0.8). Two HC-negative patients had no detectable fibrosis after 98 and 93 months on deferiprone. Therefore the hepatic pathology in these patients cannot definitely be attributed as a side-effect of deferiprone. Chronic active hepatitis C and the accumulation of iron are the major causative factors to be considered.
|
9,633,878
|
eng
|
[
"D000740",
"Q000097",
"D001457",
"Q000378",
"D016022",
"D002648",
"D002675",
"D004612",
"Q000097",
"D004913",
"Q000378",
"D006801",
"D016778",
"Q000097",
"D010219",
"D018512",
"Q000378",
"D011446",
"D017085",
"Q000097"
] |
[
"Anemia",
"Anion Exchange Protein 1, Erythrocyte",
"Case-Control Studies",
"Child",
"Child, Preschool",
"Elliptocytosis, Hereditary",
"Erythrocytes, Abnormal",
"Humans",
"Malaria, Falciparum",
"Papua New Guinea",
"Parasitemia",
"Prospective Studies",
"alpha-Thalassemia"
] |
1998
|
Jun
|
Red cell morphology and malaria anaemia in children with Southeast-Asian ovalocytosis band 3 in Papua New Guinea.
Southeast-Asian ovalocytosis (SAO) was diagnosed in children from Madang, Papua New Guinea, by detection of the SAO band 3 gene variant using the polymerase chain reaction. SAO band 3 was present in 16/241 (6.6%) children living in the community and 32/389 (8.2%) children with acute Plasmodium falciparum malaria (P=0.42). SAO band 3 was detected in 8.2% (23/281) of alpha+-thalassaemia homozygotes, 9.4% (20/214) of heterozygotes and 2.4% (2/85) of children with a normal alpha-globin genotype (P=0.12). The most consistent feature of SAO band 3 on microscopy of thin blood films was red cells with two or more linear or irregularly-shaped pale regions. In children living in the community, these were present in 15 with SAO band 3 (sensitivity 93.8%) and only two normals (specificity 99.1%). The presence of > or = 20% ovalocytosis was a poorer indicator of SAO band 3 (sensitivity 68.8% and specificity 100%). Haematological data were similar in SAO band 3 and normal children. However, in children with acute malaria, haemoglobin levels and red cell counts were significantly lower in SAO band 3 than normal children. The degree of ovalocytosis was lower in children with SAO band 3 during acute malaria, suggesting that a selective loss of ovalocytes may contribute to malaria anaemia in Southeast-Asian ovalocytosis.
|
9,633,872
|
eng
|
[
"D000293",
"D000328",
"D017677",
"D000368",
"D000818",
"D001733",
"Q000453",
"Q000209",
"Q000517",
"D002415",
"D016009",
"D002648",
"D002675",
"D004285",
"D005260",
"D006801",
"D015994",
"D007223",
"D007231",
"D008297",
"D008875",
"D011897",
"D017678",
"D013781",
"Q000453",
"D014505",
"Q000706"
] |
[
"Adolescent",
"Adult",
"Age Distribution",
"Aged",
"Animals",
"Bites and Stings",
"Cats",
"Chi-Square Distribution",
"Child",
"Child, Preschool",
"Dogs",
"Female",
"Humans",
"Incidence",
"Infant",
"Infant, Newborn",
"Male",
"Middle Aged",
"Random Allocation",
"Sex Distribution",
"Texas",
"Urban Population"
] |
Dog and cat bites: epidemiologic analyses suggest different prevention strategies.
To examine the characteristics of reported dog and cat bite incidents in El Paso, Texas, and their implications for local bite prevention programs. The authors reviewed a random sample of reported dog bites and all reported cat bites in El Paso, Texas, in 1995 using existing animal control surveillance data. The majority of cat bites (89.4%) were provoked, with females (57.5%) and adults (68.3%) more likely to be victims than males or children. In contrast, just under half of dog bites (44.6%) were provoked, with males (65.6%) and children (63%) more likely to be victims than females or adults. Dogs that had not been vaccinated for rabies were involved in 65% of dog bites and cats that had not been vaccinated for rabies were involved in 92% of cat bites. Effective bite prevention programs should address the finding that both restrained and unrestrained dogs may bite even when unprovoked and that unrestrained cats usually bite when provoked.
|
||
9,633,874
|
eng
|
[
"D000328",
"D001741",
"Q000706",
"D002423",
"D000013",
"Q000208",
"Q000401",
"D005260",
"D006801",
"D007226",
"Q000639",
"D007231",
"D009035",
"Q000706",
"D015996",
"D014481",
"Q000453",
"D044465",
"Q000706"
] |
[
"Adult",
"Black or African American",
"Cause of Death",
"Congenital Abnormalities",
"Female",
"Humans",
"Infant Mortality",
"Infant, Newborn",
"Mothers",
"Survival Rate",
"United States",
"White People"
] |
The effect of using "race of child" instead of "race of mother" on the black-white gap in infant mortality due to birth defects.
For at least 20 years, birth defects have been the leading cause of infant mortality in the United States. Some studies have reported higher rates for black infants than white infants of mortality due to birth defects, while other studies have reported no black-white differences. The authors analyzed the effect on these rates of a change in the way the National Center for Health Statistics (NCHS) tabulates "race" for newborns. The authors calculated infant mortality rates due to birth defects for 1980-1993 using two standard methods of assigning newborns to "racial" categories: a "race of child" algorithm and the "race of mother" approach currently used by NCHS. From 1980 through 1993, birth defect-specific infant mortality rates (BD-IMRs) were significantly higher for black infants than white infants 12 of the 14 years by "race of mother" and only 5 of 14 years by "race of child." Calculation of BD-IMRs by "race of mother" reduced the rate for white infants and increased the rate for black infants in each of the 14 years. The choice of method for assigning newborns to "racial" categories had a progressively greater effect over time on the black-white gap in BD-IMRs. Calculations of trends in "race"-specific BD-IMRs by may vary substantially by whether "race of mother" or "race of child" is used. Identifying the method of tabulation is imperative for appropriate comparisons and interpretations.
|
||
9,633,868
|
eng
|
[
"D000328",
"D000368",
"D001428",
"Q000009",
"Q000191",
"D006801",
"D007252",
"Q000009",
"Q000191",
"D007603",
"D016365",
"Q000191",
"D008875",
"D013296",
"Q000276",
"D014481",
"D014483",
"D014611",
"Q000009",
"Q000191",
"Q000331"
] |
[
"Adult",
"Aged",
"Bacterial Vaccines",
"Humans",
"Influenza Vaccines",
"Jurisprudence",
"Liability, Legal",
"Middle Aged",
"Streptococcus pneumoniae",
"United States",
"United States Dept. of Health and Human Services",
"Vaccination"
] |
Should the vaccine injury compensation program be expanded to cover adults?
In 1996, the National Vaccine Advisory Committee (NVAC) asked for a review of the pros and cons of including adult influenza and pneumococcal vaccines in the Vaccine Injury Compensation Program (VICP). The authors, as staff to the subcommittees charged with undertaking this assessment, looked at the following questions: (a) Would inclusion in VICP of these two vaccines, used primarily for adults, increase adult vaccination levels? (b) Is this Federal involvement warranted based on the liability burden for these vaccines? (c) Does the risk of adverse events following vaccinations warrant inclusion of these vaccines? (d) Is there a consensus among stakeholders favoring their inclusion? To address these questions, the authors reviewed information on adult vaccines, including data on l lawsuits filed and reports of injuries, and sought input from interested groups. They found no evidence that the use of influenza and pneumococcal vaccines would increase if they were included in VICP. They found a low liability burden for these vaccines, that serious adverse events were rare, and that no consensus existed among stakeholders. After considering the staff report, NVAC chose, in 1996, not to advise the Department of Health and Human Services to include adult vaccines in VICP.
|
||
9,633,881
|
eng
|
[
"D000293",
"D000328",
"D000368",
"D001854",
"Q000502",
"D004797",
"D005260",
"D006801",
"D008297",
"D008533",
"Q000502",
"D008875",
"D009190",
"Q000097",
"D010976",
"D013921",
"Q000097",
"D013926",
"Q000097"
] |
[
"Adolescent",
"Adult",
"Aged",
"Bone Marrow Cells",
"Enzyme-Linked Immunosorbent Assay",
"Female",
"Humans",
"Male",
"Megakaryocytes",
"Middle Aged",
"Myelodysplastic Syndromes",
"Platelet Count",
"Thrombocytopenia",
"Thrombopoietin"
] |
1998
|
Jun
|
Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes.
To evaluate the diagnostic value of thrombopoietin (TPO, c-mpl ligand) measurements, and clarify the regulatory mechanisms of TPO in normal and in thrombocytopenic conditions, the plasma TPO concentration was determined in normal individuals (n = 20), umbilical cord blood (n = 40), chronic idiopathic thrombocytopenic purpura (ITP; n = 16), in severe aplastic anaemia (SAA; n = 3), chemotherapy-induced bone marrow hypoplasia (n = 10), myelodysplastic syndrome (MDS; n = 11), and sequentially during peripheral blood progenitor cell transplantation (n = 7). A commercially available ELISA and EDTA-plasma samples were used for the analysis. The plasma TPO concentration in the normals and umbilical cord blood were 52 +/- 12 pg/ml and 66 +/- 12 pg/ml, respectively. The corresponding values in patients with SAA and chemotherapy-induced bone marrow hypoplasia were 1514 +/- 336 pg/ml and 1950 +/- 1684 pg/ml, respectively, and the TPO concentration, measured sequentially after myeloablative chemotherapy and peripheral blood progenitor cell transplantation, was inversely related to the platelet count. In contrast, the plasma TPO recorded in patients with ITP (64 +/- 20 pg/ml) and MDS (68 +/- 23 pg/ml) were only slightly higher than normal levels. In conclusion, TPO levels were significantly elevated in patients in which bone marrow megakaryocytes and platelets in circulation were markedly reduced, whereas TPO levels were normal in ITP patients, and only slightly increased in the MDS patients. These latter patients displayed a preserved number of megakaryocytes in bone marrow biopsies. Our data support the suggestion that megakaryocyte mass affects the plasma TPO concentration. In thrombocytopenic patients a substantially increased plasma TPO implies deficient megakaryocyte numbers. However, TPO measurements do not distinguish between ITP and thrombocytopenia due to dysmegakaryopoiesis, as seen in MDS patients.
|
9,633,875
|
eng
|
[
"D000293",
"D000328",
"D016009",
"D002648",
"D002675",
"D004423",
"D005194",
"Q000706",
"D006801",
"D007223",
"D007231",
"D007259",
"D008875",
"D010372",
"Q000706",
"D011897",
"D011795",
"D013821",
"Q000706",
"D014432",
"D014481"
] |
[
"Adolescent",
"Adult",
"Chi-Square Distribution",
"Child",
"Child, Preschool",
"Ear",
"Family Practice",
"Humans",
"Infant",
"Infant, Newborn",
"Infrared Rays",
"Middle Aged",
"Pediatrics",
"Random Allocation",
"Surveys and Questionnaires",
"Thermometers",
"Tympanic Membrane",
"United States"
] |
The use of infrared ear thermometers in pediatric and family practice offices.
To describe the use of infrared (IR) ear thermometers in pediatric and family practice offices. The authors mailed a questionnaire to 350 randomly selected members of the American Academy of Pediatrics and to 355 randomly selected members of the American Academy of Family Physicians. Of respondents in clinical practice, 78% had used IR ear thermometers at least once in the past; 65% of pediatricians and 64% of family practice physicians were current users. Seventeen percent of pediatric offices and 18% of family practice offices that had used IR ear thermometers had discontinued use, most citing inaccuracy or lack of staff trust in the device. Pediatric offices were less likely than family practice offices to use the device in well neonates and sick neonates and more likely to use it in sick children. Advantages cited included rapid readings, ease of use, and accuracy. Seventy-five percent of current users reported at least one problem, including low readings and lack of staff trust. IR ear thermometers are widely used in pediatric and family practice offices. Some offices limit use of these devices to older children and adults, and most of the offices surveyed report using other devices as a check on the accuracy of IR thermometers. Statements by professional organizations that provide user guidelines and establish appropriate age cut-offs would be helpful.
|
||
9,633,880
|
eng
|
[
"D000328",
"D004920",
"Q000502",
"D005319",
"Q000378",
"D006411",
"Q000502",
"D006801",
"D006918",
"Q000627",
"D008297",
"D017086",
"Q000097",
"Q000188"
] |
[
"Adult",
"Erythropoiesis",
"Fetal Hemoglobin",
"Hematopoiesis, Extramedullary",
"Humans",
"Hydroxyurea",
"Male",
"beta-Thalassemia"
] |
1998
|
Jun
|
Regression of extramedullary haemopoiesis and augmentation of fetal haemoglobin concentration during hydroxyurea therapy in beta thalassaemia.
Hydroxyurea increases fetal haemoglobin in many patients with sickle cell anaemia, but its effectiveness in thalassaemia appears to be less consistent. We describe the response to hydroxyurea in an adult male with homozygous beta thalassaemia, symptomatic paraspinal extramedullary haemopoiesis, bone pain, and progressive tissue iron loading. Prior to therapy with hydroxyurea the circulating haemoglobin (Hb) concentration was 7.0 g/dl and absolute fetal haemoglobin concentration was 5.0 g/dl. Administration of sodium phenylbutyrate had induced no increase in either parameter. Subsequent therapy with hydroxyurea was associated with increases in total haemoglobin to 9.0 g/dl, and in fetal haemoglobin to 7.6 g/dl. Ineffective erythropoiesis was reduced and extramedullary haemopoiesis regressed during therapy.
|
9,633,882
|
eng
|
[
"D036541",
"D051997",
"D015703",
"D018952",
"Q000502",
"D000943",
"Q000502",
"D002455",
"D002478",
"D005312",
"Q000166",
"D006412",
"Q000166",
"D006801",
"D019891",
"Q000502",
"D008533",
"Q000166",
"D008562",
"D009244",
"Q000502",
"D010641",
"D011003",
"D013926",
"Q000502"
] |
[
"ADP-ribosyl Cyclase",
"ADP-ribosyl Cyclase 1",
"Antigens, CD",
"Antigens, CD34",
"Antigens, Differentiation",
"Cell Division",
"Cells, Cultured",
"Fetal Blood",
"Hematopoietic Stem Cells",
"Humans",
"Leukopoiesis",
"Megakaryocytes",
"Membrane Glycoproteins",
"NAD+ Nucleosidase",
"Phenotype",
"Ploidies",
"Thrombopoietin"
] |
1998
|
Jun
|
Effects of thrombopoietin on the proliferation and differentiation of primitive and mature haemopoietic progenitor cells in cord blood.
Thrombopoietin (TPO) is considered to be the primary growth factor for regulating megakaryopoiesis and thrombopoiesis. In this study we investigated the in vitro effect of TPO on relatively immature and mature CD34+ progenitor cells in cord blood. Cells were cultured in both liquid and semi-solid cultures containing 50 ng/ml TPO. The CD34+/CD45RA- and CD34+/CD38- subfractions in cord blood were both enriched for megakaryocyte progenitors as determined in a semisolid CFU-meg assay. Progenitor cells derived from the CD34+/CD45RA- and CD34+/CD38- subfractions showed high proliferative capacity in liquid cultures. We observed a mean 19-fold expansion of the total CD34+ cell fraction, whereas in the CD34+/CD45RA- and CD34+/CD38- subfractions the mean expansion was 23- and 50-fold respectively. The expansion of the immature progenitor cell subfractions resulted in a highly purified megakaryocyte suspension containing > 80% megakaryocytes after 14 d in culture. However, these expanded megakaryocytes remained in a diploid (2N) and tetraploid (4N) state. Maturation could not be further induced by low concentration of TPO (0.1 ng/ml). The majority of the cells were 2N (80%) and 4N (15%) and only 5% of the cells had a ploidy of more than 4N. These results indicate that megakaryocyte progenitor cells in cord blood residing in the immature stem cell fraction exhibit a high proliferative capacity when cultured in the presence of TPO as the single growth factor, without maturation to hyperploid megakaryocytes.
|
9,633,883
|
eng
|
[
"D000262",
"Q000378",
"D000911",
"Q000502",
"D002448",
"D015672",
"Q000276",
"D006410",
"Q000276",
"D006412",
"Q000276",
"D006801",
"D018960",
"Q000276",
"D011505",
"Q000378",
"D017154",
"Q000276"
] |
[
"Adenylyl Cyclases",
"Antibodies, Monoclonal",
"Cell Adhesion",
"Erythroid Precursor Cells",
"Hematopoiesis",
"Hematopoietic Stem Cells",
"Humans",
"Hyaluronan Receptors",
"Protein-Tyrosine Kinases",
"Stromal Cells"
] |
1998
|
Jun
|
Evidence for differences in the mechanisms by which antibodies against CD44 promote adhesion of erythroid and granulopoietic progenitors to marrow stromal cells.
Adhesive interactions between haemopoietic progenitor cells and stromal elements involve a number of different molecules, some of which may be progenitor- lineage- and stage-specific. CD44 is one such molecule, although little is known about the mechanism(s) by which it is involved. In this study, several anti-CD44 monoclonal antibodies (mAb) increased the adherence of clonogenic cells, without affecting the total number of types of progenitors recoverable from the adhesion cultures. All of these mAb recognized epitopes on the globular head of CD44. In contrast, two mAb that recognized other regions of CD44 reduced progenitor adhesion to stroma. The mechanism by which one of the anti-CD44 mAb (L178) enhanced progenitor adhesion did not involve CD44-crosslinking, and was independent of VLA-4-, VLA-5- or LFA-1-mediated interactions, Ca or Mg cations, or accessory cells. In addition, CD44 expression on both progenitors and stromal cells contributed to L178-enhanced progenitor adhesion. Baseline adherence of erythroid progenitors to stroma required tyrosine kinase activity, whereas that of granulopoietic progenitors did not. However, the increase in adhesion did require tyrosine kinase activation. Additional experiments suggested that enhanced adhesion of CFU-GM to stroma may also be adenylate cyclase-dependent. Taken together, the present studies indicate both similarities and differences in the mechanisms of CD44-mediated adhesion of erythroid and granulopoietic progenitors to stromal cells.
|
9,633,884
|
eng
|
[
"D015153",
"D002450",
"D002460",
"D006412",
"Q000201",
"D006801",
"D016898",
"Q000494",
"D011505",
"Q000378",
"D015398"
] |
[
"Blotting, Western",
"Cell Communication",
"Cell Line",
"Hematopoietic Stem Cells",
"Humans",
"Interferon-alpha",
"Protein-Tyrosine Kinases",
"Signal Transduction"
] |
1998
|
Jun
|
Interferon alpha activates the tyrosine kinase Lyn in haemopoietic cells.
We investigated whether the src-family tyrosine kinase Lyn is involved in the generation of interferon alpha (IFN alpha) signals in haemopoietic cells. In vitro kinase assays using IFN alpha-sensitive cells of B-cell origin demonstrated the presence of IFN alpha-dependent kinase activity in anti-Lyn immunoprecipitates. Further studies demonstrated that Lyn associates via its src homology 2 (SH2) domain with the Janus family tyrosine kinase Tyk-2. This interaction was IFN alpha-dependent and involved direct binding of the SH2 domain of Lyn to the IFN alpha-activated form of Tyk-2. Thus, during binding of IFN alpha to its receptor in malignant haemopoietic cells, Lyn is engaged in an IFN alpha-signalling pathway, probably downstream of Tyk-2.
|
9,633,885
|
eng
|
[
"D000328",
"D000368",
"D000369",
"D000553",
"Q000379",
"D000925",
"Q000008",
"D001281",
"Q000188",
"D004305",
"D004334",
"D006801",
"D019934",
"D008875",
"D011446",
"D012189",
"D014859",
"Q000008"
] |
[
"Adult",
"Aged",
"Aged, 80 and over",
"Ambulatory Care",
"Anticoagulants",
"Atrial Fibrillation",
"Dose-Response Relationship, Drug",
"Drug Administration Schedule",
"Humans",
"International Normalized Ratio",
"Middle Aged",
"Prospective Studies",
"Retrospective Studies",
"Warfarin"
] |
1998
|
Jun
|
A warfarin induction regimen for out-patient anticoagulation in patients with atrial fibrillation.
Currently available protocols for induction of warfarin anticoagulation employ initial doses of 10 mg and are best suited to in-patient use. However, with the increasing number of elderly patients with atrial fibrillation requiring anticoagulation, there is a need for a less intense regimen which could be used for out-patients. We have established such a regimen and report on its prospective evaluation in 3 7 patients referred for out-patient initiation of warfarin, and a non-randomized comparison with 37 in-patients, with similar diagnoses, commenced on a traditional warfarin protocol. After exclusion of five patients on amiodarone, all of whom experienced supratherapeutic International Normalized Ratio (INR) results, the new out-patient regimen, employing an initial 5 mg dose, resulted in a lower maximum INR during the first 21 d therapy (median 2.9 v 4.0; P = 0.0001) and fewer INRs >4.5 (2/36 v 9/33) compared to the traditional 10 mg regimen. Time to reach stable anticoagulation was similar with each regimen; however, the 5 mg regimen gave a more accurate prediction of maintenance dose (correlation coefficient for predicted versus actual maintenance dose, r = 0.985). In comparison to a traditional 10 mg protocol, the proposed 5 mg warfarin induction regimen proved both safer and more reliable for initiation of prophylactic anticoagulation in patients with atrial fibrillation.
|
9,633,876
|
eng
|
[
"D017677",
"D000368",
"D000369",
"D003625",
"D003643",
"D003644",
"D003704",
"Q000453",
"D005260",
"D006801",
"D008297",
"D016017",
"D015995",
"D017678",
"D011795",
"D014481",
"Q000453"
] |
[
"Age Distribution",
"Aged",
"Aged, 80 and over",
"Data Collection",
"Death",
"Death Certificates",
"Dementia",
"Female",
"Humans",
"Male",
"Odds Ratio",
"Prevalence",
"Sex Distribution",
"Surveys and Questionnaires",
"United States"
] |
Prevalence and correlates of dementia: survey of the last days of life.
To estimate the prevalence and correlates of dementia at death and to assess the usefulness of death certificate data in the reporting of dementia. The authors analyzed next-of-kin interviews for 599 male and 628 female decedents using data from the National Institute on Aging's Survey of the Last Days of Life. Death certificate data in this population show the prevalence of dementia to be less than 1%, consistent with previous reports based on death certificates but a substantial underestimate compared to the 11.9% reported in a national survey. Using a dementia index based on the informant's report of whether the decedent had been diagnosed with a dementing illness and the extent of her or his cognitive and functional limitations, this study found a prevalence of dementia of 8.5%. A high score on the dementia index was significantly associated with older age, Parkinson's disease, and incontinence. Lower relative odds for dementia at death were found for people with either a lifetime history or a death certificate report of cancer. Similarly, people with a lifetime history of coronary heart disease were found to have lower relative odds for dementia at death. These results suggest that informant interviews may be a useful source of data to examine factors associated with dementia and to estimate the prevalence of dementia in the last year of life.
|
||
9,633,886
|
eng
|
[
"D000925",
"Q000378",
"D007611",
"Q000378",
"D002315",
"D004797",
"D006487",
"Q000502",
"D006490",
"Q000378",
"D006493",
"Q000378",
"D006801",
"D066298",
"D007958",
"D008955",
"D010976",
"D013921",
"Q000378",
"D014914"
] |
[
"Anticoagulants",
"Aprotinin",
"Cardiopulmonary Bypass",
"Enzyme-Linked Immunosorbent Assay",
"Hemostasis",
"Hemostatics",
"Heparin",
"Humans",
"In Vitro Techniques",
"Leukocyte Count",
"Models, Cardiovascular",
"Platelet Count",
"Thrombocytopenia",
"Whole Blood Coagulation Time"
] |
1998
|
Jun
|
Aprotinin complements heparin bonding in an in vitro model of cardiopulmonary bypass.
The relative contribution of full-dose aprotinin, used with heparin-bonded surfaces, to contact activation during cardiopulmonary bypass was examined. In vitro Carmeda-bonded cardiopulmonary bypass circuits were perfused with whole blood anticoagulated with heparin (3.3 U/ml). Aprotinin (300 kIU/ml) was added to the circuits of one set of experiments. Samples were taken prior to perfusion and at 30, 60, 120 and 360 min. The activated coagulation time was extended in the aprotinin experiments, significantly at 30 min (P=0.003) and 120 min (P=0.001). Thrombin-antithrombin complexes and prothrombin fragment F1+2 were both higher in the non-aprotinin experiments at 120 min (P=0.02 each) and 360 min (P=0.005 and 0.001, respectively). Plasma leucocyte elastase was raised in the non-aprotinin experiments in comparison to the aprotinin experiments at each timepoint (30 min, P=0.04; 60 min, P=0.006; 120 min, P=0.001; 360 min, P=0.0001), as was interleukin-8 at 120 min (P=0.05) and 360 min (P=0.0001). No differences were found for the platelet activation marker P-selectin. Platelet and white blood cell counts fell significantly in the non-aprotinin experiments compared with the aprotinin experiments at 360 min (P=0.05 and 0.03, respectively). It would appear that the use of aprotinin has additional haemostatic beneficial effects to those found with heparin-bonded circuits in terms of effects on contact activation and inflammation.
|
9,633,887
|
eng
|
[
"D001780",
"Q000592",
"D002138",
"D003374",
"Q000097",
"D006801",
"D011517",
"D012016",
"D012680",
"D013925",
"Q000032"
] |
[
"Blood Coagulation Tests",
"Calibration",
"Coumarins",
"Humans",
"Prothrombin Time",
"Reference Values",
"Sensitivity and Specificity",
"Thromboplastin"
] |
1998
|
Jun
|
A comparison of artificially-depleted, lyophilized coumarin and fresh coumarin plasmas in thromboplastin calibration. European Concerted Action on Anticoagulation.
Artificially-depleted lyophilized plasmas and lyophilized coumarin plasmas were prepared and compared with fresh coumarin plasmas to assess their comparative reliability in local thromboplastin calibration using the manual prothrombin time (PT) technique. Their certified PT values were inserted in turn on the vertical axis in place of the PT obtained with fresh coumarin plasmas. PT results were obtained at eight ECAA national laboratories ('test centres') and inserted on the horizontal axis. The resulting thromboplastin calibration slopes were compared with conventional fresh coumarin plasma calibration slopes at the same 'test centres'. When 60 artificially-depleted plasmas were substituted for 60 fresh plasmas, the mean calibration slopes with the human plain International Reference Preparation (IRP) were 4.2% higher. For comparison with 20 lyophilized coumarins, three sets of 20 artificially-depleted plasmas were selected in sequential order from the 60. The lyophilized coumarin plasmas gave a mean deviation of 9.6% from the fresh plasma calibration slopes compared with values of 2.0%, 6.1% and 11.7% for the three sets of 20 depleted plasmas. Although both types of lyophilized plasma calibration slopes give measurable differences from conventional fresh plasmas, these may be regarded as acceptable in clinical terms.
|
9,633,888
|
eng
|
[
"D000328",
"D000906",
"Q000032",
"D017153",
"Q000032",
"D000918",
"D000998",
"Q000276",
"Q000627",
"D004797",
"D005260",
"D006023",
"Q000276",
"D019698",
"Q000188",
"Q000276",
"D006801",
"D007074",
"Q000032",
"D007075",
"Q000032",
"D016898",
"Q000276",
"Q000627",
"D008297",
"D008875",
"D011446",
"D011516",
"Q000276",
"D053482"
] |
[
"Adult",
"Antibodies",
"Antibodies, Anticardiolipin",
"Antibody Specificity",
"Antiviral Agents",
"Enzyme-Linked Immunosorbent Assay",
"Female",
"Glycoproteins",
"Hepatitis C, Chronic",
"Humans",
"Immunoglobulin G",
"Immunoglobulin M",
"Interferon-alpha",
"Male",
"Middle Aged",
"Prospective Studies",
"Prothrombin",
"beta 2-Glycoprotein I"
] |
1998
|
Jun
|
Prevalence and significance of anticardiolipin, anti-beta2 glycoprotein I and anti-prothrombin antibodies in chronic hepatitis C.
Antiphospholipid antibodies have been demonstrated in chronic hepatitis C, but their clinical and pathogenetic significance remains elusive. We prospectively studied 115 patients (85 men, mean age 36.9 years) with chronic hepatitis C without cirrhosis and treated by alpha-interferon (alpha-IFN). Antiphospholipid determinations comprised anticardiolipin (ACA), anti-beta2-glycoprotein I and anti-prothrombin antibodies of the IgG and IgM classes. At entry, 24 patients (21%) were found to possess low to moderate ACA levels (18 IgG, two IgM and four both isotypes) compared with only 4/115 age- and sex-matched control subjects (3.5% P=0.001). ACA positivity rate increased to 31% (P=0.01) after a 6-month course of alpha-IFN treatment. In contrast, the prevalence of anti-beta2-glycoprotein I and anti-prothrombin antibodies was not significantly different from controls at either time point. The presence of ACA correlated with that of antinuclear antibodies (P=0.0002), but was not associated with parameters such as histological activity, viral burden and response to alpha-IFN, nor with a history of thrombosis or pregnancy loss. However, a non-significant trend of higher incidence of mild thrombocytopenia among ACA-positive patients was observed. We conclude that low-titre ACA positivity is a common finding in patients with chronic hepatitis C, especially following alpha-IFN treatment, but does not select a category with different clinical features. These data are in keeping with the absence of associated anti-beta2GPI and anti-prothrombin antibodies, and do not support a role for HCV infection in the pathogenesis of the antiphospholipid syndrome.
|
9,633,889
|
eng
|
[
"D017088",
"Q000139",
"D018791",
"D002177",
"Q000139",
"D006678",
"Q000302",
"D015658",
"Q000150",
"Q000188",
"D006467",
"Q000150",
"Q000821",
"D006474",
"Q000209",
"D006801",
"D011446",
"D011480",
"Q000009",
"Q000627",
"D012367",
"Q000032",
"D016896",
"D014397",
"Q000139",
"D019562"
] |
[
"AIDS-Related Opportunistic Infections",
"CD4 Lymphocyte Count",
"Candidiasis",
"HIV",
"HIV Infections",
"Hemophilia A",
"Hemorrhagic Disorders",
"Humans",
"Prospective Studies",
"Protease Inhibitors",
"RNA, Viral",
"Treatment Outcome",
"Tuberculosis, Pulmonary",
"Viral Load"
] |
1998
|
Jun
|
Successful use of protease inhibitors in HIV-infected haemophilia patients.
The haemophilias are a group of inherited haemostatic disorders that require regular clotting factor replacement therapy in the severe and moderately severe subgroups. Prior to the introduction of adequate viral inactivation methods in 1985, haemophilia patients were at exceptionally high risk of contracting blood-borne viruses from factor concentrates as each batch was derived from the plasma of thousands of donors. As a result, approximately 60% of these patients were infected with HIV between 1979 and 1985, and HIV infection now contributes significantly to the morbidity and mortality seen in this group. Protease inhibitors (PIs) have been shown to significantly log reduce viral loads and increase CD4 cell counts in HIV-infected individuals. Recently, there has been concern about their use in HIV-infected haemophilia patients following increased bleeding episodes in some patients during PI therapy. We prospectively studied the effect of PI therapy in 20 HIV-infected haemophilia patients at our centre over a 6-month period. The mean increase in CD4 cell count was 70 x 10(6)/l and the mean log decrease in viral load was 1.59 over the study period. Gastrointestinal side-effects (nausea and vomiting in five, diarrhoea in two) were the most frequent and resulted in discontinuation of the medication in two patients. Factor concentrate usage for the group on and off study was similar. One severe FVIII patient reported a single episode of an unusual bleed which responded promptly to FVIII concentrate infusion. The significant clinical and laboratory benefits in terms of HIV disease and the paucity of added bleeding complications suggest that PI therapy should not be withheld from HIV-infected haemophilics. Further prospective studies evaluating the efficacy and possible haemostatic complications related to these promising inhibitors of the HIV protease are needed.
|
9,633,890
|
eng
|
[
"D000293",
"D000328",
"D000368",
"D000369",
"D005165",
"Q000235",
"D005260",
"D005787",
"D006579",
"D006720",
"D006801",
"D008297",
"D008875",
"D009154",
"D011110",
"D012307",
"D013923",
"Q000235",
"D014409",
"Q000235"
] |
[
"Adolescent",
"Adult",
"Aged",
"Aged, 80 and over",
"Factor V",
"Female",
"Gene Frequency",
"Heterozygote",
"Homozygote",
"Humans",
"Male",
"Middle Aged",
"Mutation",
"Polymorphism, Genetic",
"Risk Factors",
"Thromboembolism",
"Tumor Necrosis Factor-alpha"
] |
1998
|
Jun
|
A common polymorphism in the tumour necrosis factor-alpha gene associated with high TNF levels is not a risk factor for venous thromboembolism.
The odds ratio of homozygosity or heterozygosity for the TNF2 polymorphism in 575 patients with venous thromboembolism compared to controls was found to be 1.0 (95% CI 0.4-2.1) and 1.1 (95% CI 0.8-1.4) respectively. Comparing subgroups of patients and controls with the factor V Leiden mutation the odds ratio for the TNF2 polymorphism was 0.7 (95% CI 0.2-2.2). Despite evidence of a link between high tumour necrosis factor (TNF) levels and hypercoagulability, our results do not indicate a link between the genetic regulation of TNF production and venous thromboembolic disease.
|
9,633,891
|
eng
|
[
"D000328",
"D000925",
"Q000008",
"D002405",
"Q000009",
"D002408",
"Q000009",
"D019337",
"Q000188",
"D006801",
"D012189",
"D013350",
"D013927",
"Q000517",
"D013997",
"D014859",
"Q000008"
] |
[
"Adult",
"Anticoagulants",
"Catheterization, Central Venous",
"Catheters, Indwelling",
"Hematologic Neoplasms",
"Humans",
"Retrospective Studies",
"Subclavian Vein",
"Thrombosis",
"Time Factors",
"Warfarin"
] |
1998
|
Jun
|
Prevention of central venous catheter associated thrombosis using minidose warfarin in patients with haematological malignancies.
Thrombosis is a well-recognized complication following insertion of central venous catheters and is associated with significant morbidity. In an attempt to reduce line-associated thrombosis, 108 consecutive patients with haematological malignancies were commenced on prophylactic 'minidose' warfarin, 1 mg/d, at the time of line insertion. This group of patients were compared with a historic group of 115 consecutive patients who had not received warfarin. Clinically-suspected venous thrombosis was confirmed by Doppler ultrasound or venography. Patients taking prophylactic warfarin had their prothrombin time measured three times per week with the aim of maintaining an INR <1.6. Five (5%) of the 108 patients who received minidose warfarin developed a thrombosis, at a median of 72 d (range 5-166) from the time of catheter insertion. In the 115 patients who were not anticoagulated 15 (13%) developed a catheter-associated thrombosis at a median of 16 d (range 1-35). There was a significant reduction in line-associated thrombosis in patients receiving warfarin (P=0.03). These data suggest that minidose warfarin reduces the incidence of central venous catheter related thrombosis in patients with haematological malignancies.
|
9,633,892
|
eng
|
[
"D000328",
"D000368",
"D002897",
"Q000235",
"D018450",
"D006801",
"D017404",
"Q000379",
"D016393",
"Q000235",
"D016403",
"Q000235",
"D008875",
"D014314"
] |
[
"Adult",
"Aged",
"Chromosomes, Human, Pair 7",
"Disease Progression",
"Humans",
"In Situ Hybridization, Fluorescence",
"Lymphoma, B-Cell",
"Lymphoma, Large B-Cell, Diffuse",
"Middle Aged",
"Trisomy"
] |
1998
|
Jun
|
Gain of chromosome 7 marks the progression from indolent to aggressive follicle centre lymphoma and is a common finding in patients with diffuse large B-cell lymphoma: a study by FISH.
Gain of chromosome 7 represents one of the most frequent cytogenetic findings in B-cell lymphomas with a follicular growth pattern. We used fluorescence in situ hybridization (FISH) and a probe specifying chromosome 7 on lymph node imprints and/or bone marrow (BM) and peripheral blood (PB) smears from six consecutive patients with follicle centre lymphomas (FCLs) grade I or II (low-grade lymphomas), four patients with FCLs grade III and 11 patients with diffuse large B-cell lymphomas (DLBCLs) (high-grade lymphomas). We found gains of chromosome 7 in 14/18 successfully analysed cases (i.e. 2/6 FCLs grade I-II, 3/3 FLCs grade III and in 9/9 DLBCLs) using lymph node imprints. Moreover, the FISH technique demonstrated gains of chromosome 7 in 1/4 BM and 0/4 PB samples from FCLs grade I-II, in 2/4 BM and 2/4 PB specimens from FCLs grade III and in 4/9 BM and 2/9 PB samples from the DLBCLs. In contrast, morphologically recognizable lymphoma cells were seen in only 1/4 BM and 0/4 PB samples from the FCLs grade III and in 1/11 BM and 1/11 PB samples from the DLBCLs. We conclude that: (i) gain of chromosome 7 marks the progression from indolent to aggressive FCL and would appear to be a common finding in patients with FCLs grade III and in DLBCLs, (ii) clonal lymphoid cells occur frequently in BM and PB in high-grade lymphomas, making traditional staging by cytomorphology uncertain, and (iii) using gains of chromosome 7 as a marker of lymphoma cells, FISH is a useful method to detect minimal residual disease in FCLs grade III and DLBCLs.
|
9,633,893
|
eng
|
[
"D004279",
"Q000302",
"D016679",
"D006566",
"Q000150",
"D016199",
"Q000235",
"Q000302",
"D006689",
"Q000821",
"D006801",
"D007150",
"D017403",
"Q000379",
"D016133",
"Q000379",
"D019562"
] |
[
"DNA, Viral",
"Genome, Viral",
"Herpesviridae Infections",
"Herpesvirus 7, Human",
"Hodgkin Disease",
"Humans",
"Immunohistochemistry",
"In Situ Hybridization",
"Polymerase Chain Reaction",
"Viral Load"
] |
1998
|
Jun
|
Human herpesvirus type 7 in Hodgkin's disease.
Several lines of evidence have pointed to the involvement of a viral agent in the pathogenesis of Hodgkin's disease (HD). Therefore we investigated the presence of human herpesvirus type 7 (HHV-7) in 53 cases of HD by polymerase chain reaction (PCR), DNA in situ hybridization (ISH) and immunohistochemistry. HHV-7 DNA was frequently detected (68% of the cases) in HD biopsies by PCR independently of the histological type, whereas only 32% (P<0.05) of positive cases were found in 19 reactive lymph nodes. However, by applying the quantitative PCR technique, the majority of the samples showed a low level of viral load. Moreover, ISH for HHV-7 DNA was positive in a low number of small T lymphocytes and consistently negative in Hodgkin and Reed-Sternberg (HRS) cells, which appeared negative for HHV-7 also at immunohistochemistry. These results indicate that the high frequency of HHV-7 infection in HD: (i) is probably non-productive, (ii) mainly involves small lymphocytes belonging to the T-lineage, and (iii) is probably due to the recruitment of non-malignant reactive cells in HD tissue.
|
9,633,894
|
eng
|
[
"D001483",
"D015139",
"D017637",
"D004279",
"Q000235",
"D015368",
"D006801",
"D015459",
"Q000235",
"Q000821",
"D008297",
"D008875",
"D008969",
"D016133",
"Q000379",
"D013601",
"Q000821",
"D016662",
"Q000235",
"D014779",
"Q000235"
] |
[
"Base Sequence",
"Blotting, Southern",
"Clonal Deletion",
"DNA, Viral",
"Human T-lymphotropic virus 1",
"Humans",
"Leukemia-Lymphoma, Adult T-Cell",
"Male",
"Middle Aged",
"Molecular Sequence Data",
"Polymerase Chain Reaction",
"T-Lymphocytes",
"Virus Integration",
"Virus Replication"
] |
1998
|
Jun
|
Oligoclonal proliferation of human T-cell leukaemia virus type 1 bearing T cells in adult T-cell leukaemia/lymphoma without deletion of the 3' provirus integration sites.
We report a new case of an asymptomatic carrier with a deletion of a 3' HTLV-1 integration site. We further investigated whether these 3' deletions of flanking sequences may explain the oligoclonal pattern of HTLV-1 replication, evidenced by inverse PCR (IPCR) analysis of tumourous samples from patients with adult T-cell leukaemia (ATLL). 48 HTLV-1 3' integration sites, derived from tumourous DNA of five ATLL patients were sequenced. One dominant flanking sequence was obtained in the four samples harbouring a unique band after Southern-blotting. In one sample, which harboured two signals after Southern-blotting, IPCR amplification of diluted tumourous DNA revealed that these two sequences corresponded to one clone harbouring two integrated proviruses rather than to two distinct cellular clones, a result consistent with superinfection of the tumourous sample. In addition to integration sites corresponding to malignant clones, two to six oligoclonal forms were sequenced in four samples. No flanking sequence homology was found between clones derived from each patient, indicating that integration sites deletion in the vicinity of the provirus is a rare event in ATLL. The oligoclonal pattern of HTLV-1 replication in ATLL may result from clonal expansion of non-malignant HTLV-1-bearing clones within the sample and partly from HTLV-1 superinfection of monoclonal tumour cells.
|
9,633,895
|
eng
|
[
"D000328",
"D000368",
"D015703",
"Q000032",
"D015153",
"D003587",
"Q000302",
"D003586",
"Q000150",
"D004279",
"Q000032",
"D005260",
"D015333",
"D016679",
"D015490",
"Q000150",
"D015491",
"Q000150",
"D006566",
"Q000150",
"D004854",
"Q000302",
"D015368",
"Q000302",
"D015367",
"Q000302",
"D006801",
"D007165",
"Q000009",
"D016030",
"Q000009",
"D007945",
"Q000821",
"D008297",
"D009894",
"Q000150",
"D011948",
"Q000032"
] |
[
"Adult",
"Aged",
"Antigens, CD",
"Blotting, Western",
"Cytomegalovirus",
"Cytomegalovirus Infections",
"DNA, Viral",
"Female",
"Gene Rearrangement, beta-Chain T-Cell Antigen Receptor",
"Genome, Viral",
"HTLV-I Infections",
"HTLV-II Infections",
"Herpesviridae Infections",
"Herpesvirus 4, Human",
"Human T-lymphotropic virus 1",
"Human T-lymphotropic virus 2",
"Humans",
"Immunosuppression Therapy",
"Kidney Transplantation",
"Leukemia, Lymphoid",
"Male",
"Opportunistic Infections",
"Receptors, Antigen, T-Cell"
] |
1998
|
Jun
|
Large granular lymphocyte leukaemia occurring after renal transplantation.
Post-transplantation lymphoproliferative disorders (PTLD) are a clinicopathologically heterogeneous group of lymphoid proliferations. The majority are of B-cell origin and associated with Epstein-Barr virus (EBV) infection. In contrast, the development of T-cell PTLD is much less common and EBV does not appear to be involved in pathogenesis. In this report we describe three patients who developed large granular lymphocyte (LGL) leukaemia after renal transplantation. These patients had clonal expansion of CD3+, CD8+, CD57+, CD56- LGL. We were unable to detect CMV antigen or find evidence for EBV or human T-cell leukaemia/lymphoma virus genome in the LGL from these patients. These data show that LGL leukaemia should be included as one of the types of T-cell proliferations which can occur post transplant.
|
9,633,896
|
eng
|
[
"D000328",
"D000903",
"Q000627",
"D000964",
"Q000627",
"D002880",
"Q000235",
"D003561",
"Q000627",
"D003630",
"Q000627",
"D005260",
"D006801",
"D007947",
"Q000188",
"Q000235",
"D015470",
"Q000188",
"Q000235",
"D007958",
"D008297",
"D008875",
"D010976",
"D016896",
"D014314"
] |
[
"Adult",
"Antibiotics, Antineoplastic",
"Antimetabolites, Antineoplastic",
"Chromosomes, Human, Pair 11",
"Cytarabine",
"Daunorubicin",
"Female",
"Humans",
"Leukemia, Megakaryoblastic, Acute",
"Leukemia, Myeloid, Acute",
"Leukocyte Count",
"Male",
"Middle Aged",
"Platelet Count",
"Treatment Outcome",
"Trisomy"
] |
1998
|
Jun
|
Clinical characteristics of patients with de novo acute myeloid leukaemia and isolated trisomy 11: a Cancer and Leukemia Group B study.
Isolated trisomy 11 is the third most common sole trisomy in de novo acute myeloid leukaemia (AML). However, only 49 cases have been published, and for only a fraction of these cases has full description of clinical and haematological features been provided. As a result, little is known about the clinical characteristics of de novo AML patients with solitary trisomy 11. We have identified 13 patients (0.9%) with isolated trisomy 11 among a total of 1496 consecutive adult patients successfully karyotyped as part of a prospective Cancer and Leukemia Group B (CALGB) cytogenetic study (CALGB 8461). Nine patients (69%) were over the age of 60 (range 29-73 years). Eight patients (62%) were diagnosed with AML of FAB M2 subtype, three patients (23%) had FAB M1 AML and one patient each had AML of FAB M0 and M7, respectively. Seven patients (54%) had high, >100 x 10(9)/l, platelet counts (median 102 x 10(9)/l; range 17-207 x 10(9)/l). All patients received CALGB induction therapy with standard doses of cytarabine and daunorubicin. Six patients (46%) achieved a complete remission (CR). The median CR duration was 17.5 months (range 8.7-49.8). Only one patient, who underwent bone marrow transplantation in first CR, continues in initial CR. The median survival was 14.3 months (range 0.5-50.7); only one patient survives. We conclude that de novo AML with isolated trisomy 11 is predominantly associated with older age, M2 and M1 FAB subtypes, high platelet count and few long-term disease-free survivals, although it is currently unknown whether isolated trisomy 11 constitutes an independent prognostic factor.
|
9,633,897
|
eng
|
[
"D000208",
"D015153",
"D017871",
"Q000378",
"D004273",
"Q000378",
"D004268",
"Q000378",
"D004789",
"D006801",
"D007951",
"Q000201",
"D008894",
"D019950",
"D010766",
"D011485",
"D050796",
"D050799",
"D015534",
"Q000378",
"D014407",
"D025521",
"D014443",
"Q000378"
] |
[
"Acute Disease",
"Blotting, Western",
"Calcium-Calmodulin-Dependent Protein Kinases",
"DNA, Neoplasm",
"DNA-Binding Proteins",
"Enzyme Activation",
"Humans",
"Leukemia, Myeloid",
"Milk Proteins",
"Mitogen-Activated Protein Kinase 1",
"Phosphorylation",
"Protein Binding",
"STAT3 Transcription Factor",
"STAT5 Transcription Factor",
"Trans-Activators",
"Tumor Cells, Cultured",
"Tumor Suppressor Proteins",
"Tyrosine"
] |
1998
|
Jun
|
Differential constitutive activation between STAT-related proteins and MAP kinase in primary acute myelogenous leukaemia.
Many cytokines and growth factors stimulate multiple signal transduction pathways essential for proliferation in human acute leukaemia cells, including a mitogen-activated protein (MAP) kinase pathway and a Janus kinase (JAK)-STAT (signal transducers and activators of transcription) pathway. We have previously shown constitutive activation of MAP kinase in approximately 50% of acute myelogenous leukaemia (AML) samples. Recently, STAT proteins have been reported to be constitutively activated in 10-20% of AML cases. STAT3 and STAT5 are the main STAT proteins activated in haemopoietic progenitors in response to cytokines such as IL-3, GM-CSF, erythropoietin and thrombopoietin. Although the possibility of STAT1 protein as a substrate for MAP kinase at a serine residue has been suggested, the cross-talk between STATs and MAP kinase pathways in vivo, especially in leukaemia cells, remains unknown. We examined the phosphorylation of STAT 3 and STAT 5 at the tyrosine residues in AML samples in which MAP kinase activity had already been found. 40/50 primary AML cases (80%) exhibited constitutive tyrosine phosphorylation of STAT5. Electrophoretic mobility shift assay showed DNA binding activity of STAT5 correlated with tyrosine phosphorylation of STAT5. Similarly, with respect to STAT3, 17/23 cases examined (74%) showed constitutive tyrosine phosphorylation of STAT3. In addition, we examined the tyrosyl-phosphorylation of STAT5 isoforms, STAT5A and STAT5B, in 20 AML cases, and found selective STAT5B phosphorylation in the absence of STAT5A phosphorylation in three cases. Furthermore, in certain AML cases, constitutive activation of MAP kinase and STAT proteins occurred independently. No significant correlation of MAP kinase activation was observed with either tyrosine phosphorylation of STAT3/STAT5 or positive DNA binding of STAT proteins. These results suggest that constitutive activation of STAT proteins occurs commonly and that the causes of constitutive activation of these two major cascades are heterogeneous in AML.
|
9,633,898
|
eng
|
[
"D000208",
"D000818",
"D017209",
"Q000187",
"D002087",
"Q000494",
"Q000633",
"D020148",
"D002455",
"Q000187",
"D004247",
"Q000032",
"D053938",
"D005260",
"D000091344",
"D018922",
"D006801",
"D007951",
"Q000378",
"Q000473",
"D008297",
"D051379",
"D009005",
"Q000494",
"D013936",
"Q000378",
"D014407"
] |
[
"Acute Disease",
"Animals",
"Apoptosis",
"Butyrates",
"Butyric Acid",
"Cell Division",
"DNA",
"DNA Fragmentation",
"Female",
"Filaggrin Proteins",
"HL-60 Cells",
"Humans",
"Leukemia, Myeloid",
"Male",
"Mice",
"Monosaccharides",
"Thymidine",
"Tumor Cells, Cultured"
] |
1998
|
Jun
|
Butyrate-stable monosaccharide derivatives induce maturation and apoptosis in human acute myeloid leukaemia cells.
The rapid degradation and subsequent lack of efficacy of n-butyric acid in vivo has been improved by the synthesis of monosaccharide stable pro-drugs of butyric acid. We studied the effects of D1 (O-n-butanoyl-2,3-O-isopropylidene-alpha-D-mannofuranoside), G1 (1-O-n-butanoyl-D,L-xylitol), and F1 (1-O-n-butanoyl 2,3-O-isopropylidene-D,L-xylitol) on the maturation and proliferation of AML cell lines HL 60 and FLG 29.1 and of purified blast cells from 10 cases of de novo acute myeloid leukaemia (AML). AML cell maturation was measured by surface antigen expression, morphology and cytochemistry. Toxicology in mice was also evaluated (DL50 1000 mg/kg). In HL 60 cells G1 and D1 increased the expression of CD15 and CD11a (presenting 62% of promyelo-metamyelocytes), and in 7/10 cases of primary AMLs that of CD11a, CD11b, CD15, and myeloperoxidase. D1, G1 and F1 induced a dose-dependent inhibition of tritiated thymidine uptake. Apoptosis (evaluated by flow cytometry and agarose gel electrophoresis) was induced in AML blasts by D1 and F1 (79% and 94% respectively for HL 60 cells) and, with less effect, by G1 (27%). The persistence of maturative and apoptotic activity in these new pro-drugs of butyric acid, hydrolysed only inside the tumour cell, suggests a possible use in differentiation therapy of myelodysplastic syndromes and AMLs.
|
9,633,899
|
eng
|
[
"D000903",
"Q000627",
"D000906",
"Q000378",
"D017209",
"Q000187",
"D004317",
"Q000627",
"D004357",
"D053222",
"D005434",
"D006801",
"D007074",
"Q000378",
"D007075",
"Q000378",
"D007938",
"Q000188",
"Q000378",
"Q000473",
"D015459",
"Q000188",
"Q000378",
"D008562",
"Q000378",
"D014407",
"D019014",
"Q000378"
] |
[
"Antibiotics, Antineoplastic",
"Antibodies",
"Apoptosis",
"Doxorubicin",
"Drug Synergism",
"Fas Ligand Protein",
"Flow Cytometry",
"Humans",
"Immunoglobulin G",
"Immunoglobulin M",
"Leukemia",
"Leukemia-Lymphoma, Adult T-Cell",
"Membrane Glycoproteins",
"Tumor Cells, Cultured",
"fas Receptor"
] |
1998
|
Jun
|
Chemotherapeutic drug-induced apoptosis in human leukaemic cells is independent of the Fas (APO-1/CD95) receptor/ligand system.
The potential role of the Fas (CD95/APO-1) receptor/ligand system in chemotherapeutic drug-induced apoptosis was examined in a number of human leukaemic cell lines. Flow cytometric profiles of doxorubicin-treated HL-60, K562, U937 and Jurkat cells failed to show any significant increase in Fas or Fas ligand expression over 24 h, despite the induction of significant levels of apoptosis in these cells. Although preincubation of human leukaemic cells with a neutralizing anti-Fas IgG antibody blocked anti-Fas IgM-induced apoptosis, this strategy failed to inhibit chemotherapeutic drug-induced apoptosis. To determine whether recruitment of the Fas/Fas ligand complex during drug-induced apoptosis was a cell-specific event we utilized the CEM cell line. Doxorubicin treatment of CEM cells over 24 h failed to show any up-regulation in Fas or Fas ligand protein levels as detected by flow cytometry. Furthermore, neutralizing anti-Fas IgG Ab failed to inhibit chemotherapeutic drug-induced apoptosis in CEM cells. The present studies do, however, demonstrate a role for anti-Fas IgM Ab in producing a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs. Low-dose anti-Fas IgM treatment in combination with doxorubicin, methotrexate, camptothecin and etoposide produced an augmented cytoxicity in CEM cells. Taken together these observations demonstrate that although recruitment of the Fas/APO-1/CD95 receptor/ligand system is not a necessary requirement for chemotherapeutic drug-induced apoptosis, combination of anti-Fas IgM and drug treatment produces a synergistic cytotoxic effect which may prove useful in the treatment of human leukaemias.
|
9,633,901
|
eng
|
[
"D000970",
"Q000627",
"D005260",
"D016044",
"D006801",
"D017404",
"Q000379",
"D016898",
"Q000627",
"D007399",
"D015464",
"Q000473",
"Q000628",
"D015465",
"Q000473",
"Q000628",
"D015466",
"Q000473",
"Q000628",
"D008297",
"D008875",
"D018365",
"D016133",
"Q000379",
"D011446",
"D012333",
"Q000032",
"D012680"
] |
[
"Antineoplastic Agents",
"Female",
"Fusion Proteins, bcr-abl",
"Humans",
"In Situ Hybridization, Fluorescence",
"Interferon-alpha",
"Interphase",
"Leukemia, Myelogenous, Chronic, BCR-ABL Positive",
"Leukemia, Myeloid, Accelerated Phase",
"Leukemia, Myeloid, Chronic-Phase",
"Male",
"Middle Aged",
"Neoplasm, Residual",
"Polymerase Chain Reaction",
"Prospective Studies",
"RNA, Messenger",
"Sensitivity and Specificity"
] |
1998
|
Jun
|
Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in patients with chronic myeloid leukaemia during interferon-alpha therapy.
There is a need for fast and sensitive methods to evaluate the response of patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha) therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome-positive metaphases. We have used interphase FISH (fluorescence in situ hybridization) and competitive RT-PCR (reverse transcriptase-polymerase chain reaction) techniques for detection of BCR-ABL-positive cells to measure suppression of leukaemic clone in a series of 51 follow-up samples from 24 CML patients undergoing IFN-alpha treatment. Interphase FISH analysis of the malignant clone in bone marrow using BCR and ABL probes was found to be highly correlated to conventional G-banding metaphase examination (r = 0.98). RT-PCR quantification of BCR-ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph-positive metaphases (r = 0.93). In addition, the degree of cytogenetic response did not influence the equivalence between karyotype analysis and molecular methods. We concluded that interphase FISH and competitive RT-PCR provide reliable information on residual tumour burden and response to IFN-alpha in CML patients. These molecular methods may significantly improve the efficiency of residual disease monitoring during IFN-alpha therapy of CML.
|
9,633,900
|
eng
|
[
"D000903",
"Q000627",
"D000951",
"D000972",
"Q000627",
"D015139",
"D002470",
"D003520",
"Q000031",
"Q000627",
"D004250",
"Q000235",
"Q000378",
"D004268",
"D003630",
"Q000627",
"D004305",
"D019008",
"Q000235",
"D005047",
"Q000627",
"D015870",
"D006801",
"D007527",
"Q000235",
"Q000378",
"D007951",
"Q000188",
"Q000201",
"D016372",
"Q000378",
"D012333",
"Q000378",
"D014407"
] |
[
"Antibiotics, Antineoplastic",
"Antigens, Neoplasm",
"Antineoplastic Agents, Phytogenic",
"Blotting, Southern",
"Cell Survival",
"Cyclophosphamide",
"DNA Topoisomerases, Type II",
"DNA-Binding Proteins",
"Daunorubicin",
"Dose-Response Relationship, Drug",
"Drug Resistance, Neoplasm",
"Etoposide",
"Gene Expression",
"Humans",
"Isoenzymes",
"Leukemia, Myeloid",
"RNA, Antisense",
"RNA, Messenger",
"Tumor Cells, Cultured"
] |
1998
|
Jun
|
Evidence for a critical role of DNA topoisomerase IIalpha in drug sensitivity revealed by inducible antisense RNA in a human leukaemia cell line.
To examine the role of human DNA topoisomerase IIalpha (topo IIalpha) in drug resistance, we selectively inhibited topo IIalpha gene expression in U937 human monocytic leukaemia cells stably transfected with a plasmid that allowed for Zn-mediated conditional expression of a human alpha-topo IIalpha antisense sequence. Expression of topo IIalpha mRNA was reduced to <30%, whereas no significant alteration of topo IIbeta mRNA expression was observed. Under these conditions, drug sensitivity to the topo-II-directed agents, etoposide and daunorubicin, was reduced to approximately 50%, whereas sensitivity to 4-hydroperoxy-cyclophosphamide (4-HC) was not altered. This suggests that a reduced amount of topo IIalpha mRNA may be sufficient for the resistance to topo II inhibitors in leukaemia cells.
|
9,633,902
|
eng
|
[
"D000368",
"D015139",
"D019941",
"Q000378",
"D018450",
"D005260",
"D015870",
"D006801",
"D008297",
"D008745",
"D008875",
"D009101",
"Q000378",
"D016133",
"Q000379",
"D014407"
] |
[
"Aged",
"Blotting, Southern",
"Cyclin-Dependent Kinase Inhibitor p16",
"Disease Progression",
"Female",
"Gene Expression",
"Humans",
"Male",
"Methylation",
"Middle Aged",
"Multiple Myeloma",
"Polymerase Chain Reaction",
"Tumor Cells, Cultured"
] |
1998
|
Jun
|
Methylation of the p16INK4A gene in multiple myeloma.
The p16INK4A (p16) binds to both cyclin D-CDK4 and cyclin D-CDK6 and inhibits the progression of the cell cycle from G1 to S phase. Loss of expression of this protein can occur by several mechanisms including structural alterations. Recent studies have suggested that the loss of expression of p16 can occur by hypermethylation of the gene. The methylation status of the p16 gene in multiple myeloma was examined in three myeloma cell lines (U266, RPMI8226 and IM9) and 16 primary myeloma samples using methylation-specific polymerase chain reaction (MSP). The U266 and RPMI8226 cell lines contained a completely methylated p16 gene and the IM9 line had a partially methylated p16 gene. Identical results were obtained by another polymerase chain reaction (PCR)-based methylation assay system as well as Southern blotting after using a methylation-sensitive restriction enzyme. The U266 cell line expressed no p16, and the IM9 had weak expression as determined by reverse transcript (RT-)PCR. The U266 cells began to express, and IM9 increased the accumulation of, the p16 RNA after treatment with the demethylating agent 5'-aza-2-deoxycytidine (10(-6)-10(-5) M). This suggested that the levels of methylation of the p16 gene detected by the MSP technique correlated with the regulation of transcription of this gene. Examination of the primary myeloma samples showed that eight of 16 (50%) contained a methylated p16 gene. We have previously found that alterations of the p16 gene, such as deletions and point mutations, are rare in primary multiple myeloma; none of the 16 samples included in this study had p16 gene alterations. Our results suggest that methylation of the p16 gene may contribute to the development and/or progression of multiple myeloma.
|
9,633,904
|
eng
|
[
"D000208",
"D000328",
"D018952",
"Q000378",
"D016026",
"Q000379",
"D005260",
"D006410",
"Q000502",
"D006412",
"Q000473",
"D006801",
"D017404",
"D007951",
"Q000097",
"Q000628",
"D008297",
"D008875",
"D014182",
"D014407"
] |
[
"Acute Disease",
"Adult",
"Antigens, CD34",
"Bone Marrow Transplantation",
"Female",
"Hematopoiesis",
"Hematopoietic Stem Cells",
"Humans",
"In Situ Hybridization, Fluorescence",
"Leukemia, Myeloid",
"Male",
"Middle Aged",
"Transplantation, Autologous",
"Tumor Cells, Cultured"
] |
1998
|
Jun
|
Haemopoietic defect and decreased expansion potential of bone marrow autografts from patients with acute myeloid leukaemia in first remission.
Autologous bone marrow (BM) transplantation for acute myeloid leukaemia (AML) in complete remission (CR) is frequently followed by a slow haemopoietic recovery. We assessed the haemopoietic capacity of purified BM stem cell (CD34+ DR-) and progenitor cell (CD34+ DR+) populations from patients with AML in CR, and compared these data with those of normal BM. The feasibility of ex vivo expansion in stroma-conditioned medium supplemented with cytokines was also investigated. The number of CFU-GM produced by initial patient CD34+ DR- cells was decreased compared to normal, whereas these values were similar to normal for CD34+ DR+ cells. BFU-E, HPP-CFC and LTC-IC were reduced for both patient CD34+ DR- and CD34+ DR+ subpopulations. In contrast to normal, the patient CD34+ DR- fraction was not enriched in LTC-IC. CFU-GM expansion from patient CD34+ DR- cells was poor and decreased after 14 d of culture. No HPP-CFC expansion could be observed for patient cells. LTC-IC were below the level of detection after 14-21 d of expansion culture of CD34+ DR- patient cells, whereas they were variably maintained or expanded for normal cells. After expansion culture, cytogenetic and/or FISH analyses did not reveal the anomalies present at diagnosis, regardless of the cell subpopulation analysed. In conclusion, BM cells of patients with AML in CR show a profound defect at the level of a stem cell enriched population. No meaningful ex vivo expansion could be obtained in culture conditions allowing for a significant expansion from a normal stem cell population.
|
9,633,903
|
eng
|
[
"D016026",
"Q000379",
"D005434",
"Q000379",
"D006086",
"Q000276",
"D006087",
"Q000276",
"D006801",
"D007108",
"D007118",
"Q000379",
"D015464",
"Q000276",
"Q000628",
"D008212",
"Q000379",
"D006377",
"Q000276",
"D014184"
] |
[
"Bone Marrow Transplantation",
"Flow Cytometry",
"Graft vs Host Disease",
"Graft vs Host Reaction",
"Humans",
"Immune Tolerance",
"Immunoassay",
"Leukemia, Myelogenous, Chronic, BCR-ABL Positive",
"Lymphocyte Depletion",
"T-Lymphocytes, Helper-Inducer",
"Transplantation, Homologous"
] |
1998
|
Jun
|
Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions.
Accumulating evidence indicates that alloreactive donor T cells confer both graft-versus-host (GVH) and graft-versus-leukaemia (GVL) reactivity following allogeneic bone marrow transplantation. We have developed a method to deplete alloreactive donor T cells with an immunotoxin targeting the alpha chain of the IL-2 receptor. In patients with chronic myeloid leukaemia and their HLA-identical sibling donors, we measured donor helper T-lymphocyte precursor frequencies (HTLPf) against recipient peripheral blood mononuclear cells (PBMNC; donor versus host), recipient leukaemia cells (donor versus leukaemia) and third-party PBMNC, before and after the depletion. In seven pairs there was a 4.3-fold reduction of donor-versus-host HTLPf (P=0.017), without a significant change in the donor frequencies against third party (P=0.96). In eight further donor-recipient pairs, immunotoxin-depleted donor versus patient PBMNC HTLPf 4.5-fold (mean 1/155,000 before and 1/839,000 after depletion, P=0.007). There was a smaller non-significant 1.8-fold reduction in donor-versus-leukaemia HTLPf from 1/192,000 to 1/334,000 (P=0.19). These results suggest that selective T-cell depletion can significantly deplete donor anti-host reactivity while conserving anti-leukaemia reactivity in HLA-matched donor-recipient pairs.
|
9,633,905
|
eng
|
[
"D000328",
"D000368",
"D018952",
"Q000378",
"D000970",
"Q000627",
"D004306",
"D005260",
"D000069585",
"D016179",
"Q000008",
"D019650",
"Q000379",
"D006412",
"Q000378",
"D006801",
"D008297",
"D008875",
"D009101",
"Q000378",
"Q000628",
"D011994"
] |
[
"Adult",
"Aged",
"Antigens, CD34",
"Antineoplastic Agents",
"Dose-Response Relationship, Immunologic",
"Female",
"Filgrastim",
"Granulocyte Colony-Stimulating Factor",
"Hematopoietic Stem Cell Mobilization",
"Hematopoietic Stem Cells",
"Humans",
"Male",
"Middle Aged",
"Multiple Myeloma",
"Recombinant Proteins"
] |
1998
|
Jun
|
The dose of granulocyte colony-stimulating factor administered following cytotoxic chemotherapy is not related to the rebound level of circulating CD34+ haemopoietic progenitor cells during marrow recovery.
We report on the RmetHuG-CSF (filgrastim)-related mobilization efficiency in 120 patients with multiple myeloma who received cytotoxic chemotherapy. Three schedules of G-CSF administration starting 24h after the end of chemotherapy were used: (1) a standard dose of 300 microg/d until the completion of PBSC collection; (2) dose escalation from 300 to 600-1200 microg/d during marrow recovery; (3) 600 or 1200 microg/d starting 24 h after cytotoxic chemotherapy. As a result, the individual dose per kg bodyweight varied between 2.83 and 23.08 microg. No relationship was found between the dose of G-CSF administered and the peak level of circulating CD34+ cells or the CD34+ cell counts recorded over the entire collection period.
|
9,633,906
|
eng
|
[
"D004252",
"Q000379",
"D005091",
"D005260",
"D016368",
"D005820",
"Q000379",
"D006801",
"D008297",
"D009154",
"D010375",
"D017354",
"D016133",
"Q000379",
"D018807",
"D011296",
"Q000379",
"D018123",
"Q000235",
"D016511",
"Q000235"
] |
[
"DNA Mutational Analysis",
"Exons",
"Female",
"Frameshift Mutation",
"Genetic Testing",
"Humans",
"Male",
"Mutation",
"Pedigree",
"Point Mutation",
"Polymerase Chain Reaction",
"Polymorphism, Single-Stranded Conformational",
"Prenatal Diagnosis",
"Receptors, Interleukin",
"Severe Combined Immunodeficiency"
] |
1998
|
Jun
|
Mutation analysis by a non-radioactive single-strand conformation polymorphism assay in nine families with X-linked severe combined immunodeficiency (SCIDX1).
X-linked severe combined immunodeficiency (SCIDX1) is an inherited disease characterized by profound abnormalities of cell-mediated and humoral immunity. Patients with SCIDX1 have defects in the common cytokine receptor gamma chain gene (IL2RG) that encodes a shared, essential component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9 and IL-15. We have characterized nine SCIDX1 families by using a DNA-based, non-radioactive screening method and DNA sequencing. Nine different mutations were found, scattered from exon 1 to exon 5 of the IL2RG gene. Two of these mutations have been previously identified in other unrelated patients; the other seven are novel mutations that differ from all of the 95 already reported in the IL2RG mutation data base. In addition to describing novel mutations in the IL2RG gene, this study shows that the knowledge of the genetic defect and the use of an efficient, non-radioactive, and rapid screening approach have important implications for prenatal and postnatal diagnosis, carrier female identification, and possibly prenatal therapy.
|
9,633,913
|
eng
|
[
"D000818",
"D017209",
"Q000502",
"D001710",
"D004247",
"Q000032",
"D053938",
"D003856",
"D004587",
"D004730",
"Q000473",
"Q000648",
"D007962",
"Q000473",
"Q000648",
"D008297",
"D008854",
"D018485",
"Q000473",
"Q000648",
"D009203",
"Q000473",
"Q000503",
"D011817",
"D012685",
"D013194",
"D014945",
"Q000502"
] |
[
"Animals",
"Apoptosis",
"Biotin",
"DNA",
"DNA Fragmentation",
"Deoxyuracil Nucleotides",
"Electrophoresis, Agar Gel",
"Endothelium, Vascular",
"Leukocytes",
"Male",
"Microscopy, Electron",
"Muscle Fibers, Skeletal",
"Myocardial Infarction",
"Rabbits",
"Sepharose",
"Staining and Labeling",
"Wound Healing"
] |
1998
|
Jun
|
Role of apoptosis in the disappearance of infiltrated and proliferated interstitial cells after myocardial infarction.
Myocardial infarction (MI) progresses from the acute death of myocytes and the infiltration of inflammatory cells into granulation, followed by scars. During the healing process, the myocardial interstitial cell population in the infarcted tissues increases markedly and then decreases. We postulated that apoptosis is responsible for this process. Twenty-four male Japanese white rabbits underwent a 30-minute occlusion of the left coronary artery followed by reperfusion for 2 days, 2 weeks, or 4 weeks (n=8 each). The histological features consisted of dead cardiomyocytes and marked leukocyte infiltration at 2 days after MI and granulation consisting of numerous alpha-smooth muscle actin-positive myofibroblasts, macrophage antigen-positive macrophages, and neovascularization at 2 weeks. At 4 weeks, the cellularity decreased markedly, and scars were evident. Interstitial cells with positive nick end labeling were significantly more frequent at the light microscopic level in the 2-day MI samples (5.3+/-3.6% in the center and 6.9+/-3.3% in the periphery of the infarct region) than in the 2-week (2.5+/-1.0%) and 4-week (0.5+/-0.5%) samples. DNA electrophoresis showed a clear ladder in tissues from the ischemic areas at 2 days after MI but not at 2 and 4 weeks after MI. Ultrastructurally, typical apoptotic figures, including apoptotic bodies and condensed nuclei without ruptured plasma membranes, were detected in leukocytes from all hearts with 2-day MI and in myofibroblasts, endothelial cells, and macrophages from all hearts with 2-week MI. In the electron microscopic in situ nick end labeling, immunogold particles intensely labeled the condensed chromatin of the typical apoptotic nuclei. These particles were also accumulated on nuclei of the interstitial cells showing homogeneous density but not definite condensation as typical apoptotic nuclei, suggesting an early stage of apoptosis. Thus, apoptosis plays an important role in the disappearance of both the infiltrated leukocytes and the proliferated interstitial cells after MI. This finding may have therapeutic implications for postinfarct ventricular remodeling through apoptosis handling during the healing stage of MI.
|
9,633,914
|
eng
|
[
"D000584",
"Q000031",
"Q000494",
"D000818",
"D000831",
"D000889",
"Q000494",
"D000900",
"Q000494",
"D017209",
"Q000187",
"Q000502",
"D002118",
"Q000378",
"D002478",
"D004305",
"D004734",
"Q000187",
"Q000502",
"D004791",
"Q000494",
"D006863",
"D018942",
"D018485",
"Q000187",
"Q000201",
"D009206",
"Q000201",
"D006180",
"Q000037",
"Q000378",
"D051381",
"D017207",
"D019831",
"Q000378",
"D017923",
"Q000037",
"Q000378",
"D014617",
"Q000201"
] |
[
"Amiloride",
"Animals",
"Animals, Newborn",
"Anti-Arrhythmia Agents",
"Anti-Bacterial Agents",
"Apoptosis",
"Calcium",
"Cells, Cultured",
"Dose-Response Relationship, Drug",
"Energy Metabolism",
"Enzyme Inhibitors",
"Hydrogen-Ion Concentration",
"Macrolides",
"Muscle Fibers, Skeletal",
"Myocardium",
"Proton-Translocating ATPases",
"Rats",
"Rats, Sprague-Dawley",
"Sodium-Calcium Exchanger",
"Sodium-Hydrogen Exchangers",
"Vacuoles"
] |
1998
|
Jun
|
Effect of vacuolar proton ATPase on pHi, Ca2+, and apoptosis in neonatal cardiomyocytes during metabolic inhibition/recovery.
Recently, we found that vacuolar proton ATPase (VPATPase) operates in cardiomyocytes as a complementary proton-extruding mechanism. Its activity was increased by preconditioning with resultant attenuation of intracellular acidification during ischemia. In this study, we examined whether VPATPase-mediated proton efflux during metabolic inhibition/recovery may spare Na+ overload via Na+-H+ exchange, attenuate Na+-Ca2+ exchange, and decrease apoptosis. Neonatal rat cardiomyocytes were subjected to 2- to 3-hour metabolic inhibition with cyanide and 2-deoxyglucose and 24-hour recovery. The effect of VPATPase inhibition by 50 nmol/L bafilomycin A1 on apoptosis, pHi, and [Ca2+]i was studied by flow cytometry with propidium iodide, seminaphthorhodafluor (SNARF)-1-AM, and indo-1-AM staining, respectively. VPATPase inhibition increased the amount of apoptosis measured after 24 hours of recovery and abrogated the protective effect of inhibition of Na+-H+ exchange by (5-N-ethyl-N-isopropyl)amiloride (EIPA). Dual blockade of VPATPase and Na+-H+ exchange was additive in effect with EIPA on pHi during metabolic inhibition/recovery and recovery from the acid challenge with sodium propionate. VPATPase blockade increased the rate of accumulation of intracellular Ca2+ at the beginning of metabolic inhibition and abrogated the delaying effect of EIPA on intracellular Ca2+ accumulation. These results indicate that VPATPase plays an important accessory role in cardiomyocyte protection by reducing acidosis and Na+-H+ exchange-induced Ca2+ overload.
|
9,633,915
|
eng
|
[
"D000804",
"Q000494",
"D000818",
"D006332",
"Q000378",
"Q000473",
"D048429",
"Q000187",
"D002478",
"D008297",
"D018613",
"D018485",
"Q000737",
"Q000166",
"Q000187",
"D009203",
"Q000188",
"Q000378",
"Q000473",
"D009206",
"Q000737",
"Q000166",
"D051381",
"D017207",
"D011945",
"Q000032",
"Q000378",
"D015854",
"Q000187",
"Q000502",
"D014662",
"Q000494",
"D016277",
"D016278"
] |
[
"Angiotensin II",
"Animals",
"Cardiomegaly",
"Cell Size",
"Cells, Cultured",
"Male",
"Microscopy, Confocal",
"Muscle Fibers, Skeletal",
"Myocardial Infarction",
"Myocardium",
"Rats",
"Rats, Sprague-Dawley",
"Receptors, Angiotensin",
"Up-Regulation",
"Vasoconstrictor Agents",
"Ventricular Function, Left",
"Ventricular Function, Right"
] |
1998
|
Jun
|
Angiotensin II stimulation in vitro induces hypertrophy of normal and postinfarcted ventricular myocytes.
To determine whether angiotensin II (Ang II) stimulation of adult ventricular myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume and protein content per cell were examined by confocal microscopy. Moreover, the possibility was considered that the upregulation of Ang II receptors on myocytes after infarction may potentiate and/or accelerate Ang II-mediated myocyte growth. Left ventricular myocytes isolated from control and failing hearts 3 days after infarction were cultured for 3 and 7 days in the presence of Ang II. Normal myocytes did not show an increase in volume and protein content at 3 days, but a 16% and 20% increase in these respective parameters was found at 7 days. Cell growth was faster and greater in myocytes from postinfarcted hearts. In these cells, myocyte volume increased 23% and protein content increased 28% at 3 days after Ang II administration. The higher hypertrophic reaction of myocytes from infarcted hearts occurred in spite of a 19% larger volume at isolation. In both groups of myocytes, the AT1 receptor blocker losartan completely inhibited the consequences of Ang II. Conversely, the AT2 receptor antagonist PD123319 had no effect on Ang II-induced hypertrophy. In conclusion, Ang II promotes myocyte growth through the activation of AT1 receptors, which modulate the time and magnitude of this cellular response.
|
9,633,917
|
eng
|
[
"D019307",
"Q000494",
"D000367",
"D000818",
"D016375",
"Q000494",
"D002458",
"D002478",
"D004791",
"Q000494",
"D005260",
"D005786",
"Q000187",
"D019833",
"Q000494",
"D006133",
"Q000494",
"D036341",
"D007527",
"Q000235",
"Q000378",
"D018485",
"Q000166",
"Q000187",
"Q000201",
"D009206",
"Q000166",
"Q000201",
"D018995",
"Q000378",
"D011247",
"D011493",
"Q000235",
"Q000378",
"D051571",
"D051745",
"D051744",
"D011505",
"Q000037",
"D012333",
"Q000378",
"D051381",
"D017207",
"D011994",
"Q000494",
"D015398",
"Q000187",
"D019311",
"Q000494"
] |
[
"1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine",
"Age Factors",
"Animals",
"Antisense Elements (Genetics)",
"Cell Fractionation",
"Cells, Cultured",
"Enzyme Inhibitors",
"Female",
"Gene Expression Regulation",
"Genistein",
"Growth Substances",
"Intercellular Signaling Peptides and Proteins",
"Isoenzymes",
"Muscle Fibers, Skeletal",
"Myocardium",
"Myosin Heavy Chains",
"Pregnancy",
"Protein Kinase C",
"Protein Kinase C-alpha",
"Protein Kinase C-delta",
"Protein Kinase C-epsilon",
"Protein-Tyrosine Kinases",
"RNA, Messenger",
"Rats",
"Rats, Sprague-Dawley",
"Recombinant Proteins",
"Signal Transduction",
"Staurosporine"
] |
1998
|
Jun
|
Increased protein kinase C activity in myotrophin-induced myocyte growth.
Myotrophin, a novel protein that has been shown to stimulate myocyte growth, has been isolated, purified, and sequenced from the hearts of spontaneously hypertensive rats and dilated cardiomyopathic human tissue. Recently, the cDNA clones encoding myotrophin have been isolated and expressed in Escherichia coli, and the recombinant myotrophin was found to be as biologically and immunologically active as natural myotrophin. The mechanism by which myotrophin stimulates protein synthesis and initiates myocardial hypertrophy is not known. To evaluate the involvement of protein kinase C (PKC) in myotrophin-induced hypertrophy, PKC activity and its distribution in the subcellular fraction were determined in cultured neonatal and adult myocytes. PKC activity was determined by measuring the incorporation of 32P into histone type III-S and PKCepsilon substrate peptide (epsilon(pep)) from [gamma-32P]ATP in neonatal myocytes. Myotrophin significantly stimulated PKC activity in neonatal myocytes and was associated with a significant increase in protein synthesis. The effect of myotrophin on the stimulation of PKC activity and [3H]leucine incorporation was abolished by pretreatment with either staurosporine or H-7, two selective, pharmacological PKC inhibitors. Pretreatment of myocytes with staurosporine also reduced the myotrophin-induced mRNA levels of c-fos and beta-myosin heavy chain. To evaluate the subcellular events whose occurrence was due to myotrophin and translocation of PKC, we studied the effect of genistein, a tyrosine kinase inhibitor, on myotrophin-induced neonatal myocyte growth. Genistein attenuated the [3H]leucine incorporation induced by myotrophin. To define the specificity of the PKC isoform(s) involved in myotrophin-stimulated myocyte growth, both neonatal and adult myocytes were treated with myotrophin, and Western blot analyses were performed by using the antibodies of different PKC isoforms. Results showed that both PKCalpha and PKCepsilon isoforms participated in the myotrophin-induced neonatal myocyte growth, whereas only the PKCepsilon isoform was involved in myotrophin-induced adult myocyte hypertrophy. PKCdelta and PKCzeta do not seem to participate in either neonatal or adult myocyte growth induced by myotrophin. Treatment with antisense oligonucleotides specific for PKCalpha and PKCepsilon isoforms further supported this result. PKCalpha is the major PKC isoform in neonatal myocytes and needs Ca2+ and phospholipids for its activation, and PKCepsilon (the Ca2+-independent PKC isoform) is present in both neonatal and adult myocytes; the 15-mer antisense oligodeoxynucleotides of each were used for this study. Treatment of neonatal myocytes with the PKCalpha and PKCepsilon antisense oligodeoxynucleotides for 5 days significantly reduced Ca2+-dependent and Ca2+-independent PKC activity, respectively, as well as the [3H]leucine incorporation induced by myotrophin. Furthermore, myotrophin-induced PKC activity was primarily located in the particulate fraction and did not result in a concomitant decrease in the cytosolic fraction. Myotrophin does not change PKC isoform expression (both Ca2+ dependent and independent PKC isoforms used in this study) in rat neonatal cardiac fibroblasts. Our data suggest that myotrophin exerts its action on protein synthesis, possibly through a tyrosine kinase-coupled pathway and translocation of PKC from the cytosol to the cell membrane.
|
9,633,916
|
eng
|
[
"D000256",
"D000316",
"Q000494",
"D000818",
"D000831",
"D009320",
"Q000032",
"D006332",
"Q000473",
"Q000503",
"D005109",
"Q000737",
"Q000378",
"D015967",
"Q000502",
"D006352",
"Q000737",
"Q000473",
"D019012",
"Q000737",
"Q000235",
"Q000378",
"D007536",
"D009206",
"Q000737",
"Q000473",
"D010656",
"Q000494",
"D011401",
"Q000187",
"Q000502",
"D051381",
"D017207",
"D015398",
"Q000502",
"D014162"
] |
[
"Adenoviridae",
"Adrenergic alpha-Agonists",
"Animals",
"Animals, Newborn",
"Atrial Natriuretic Factor",
"Cardiomegaly",
"Extracellular Matrix",
"Gene Expression Regulation, Viral",
"Heart Ventricles",
"Integrin beta1",
"Isomerism",
"Myocardium",
"Phenylephrine",
"Promoter Regions, Genetic",
"Rats",
"Rats, Sprague-Dawley",
"Signal Transduction",
"Transfection"
] |
1998
|
Jun
|
Beta1 integrins participate in the hypertrophic response of rat ventricular myocytes.
Multiple signaling pathways have been implicated in the hypertrophic response of ventricular myocytes, yet the importance of cell-matrix interactions has not been extensively examined. Integrins are cell-surface molecules that link the extracellular matrix to the cellular cytoskeleton. They can function as cell signaling molecules and transducers of mechanical information in noncardiac cells. Given these properties and their abundance in cardiac cells, we evaluated the hypothesis that beta1 integrin function is involved in the alpha1-adrenergic mediated hypertrophic response of neonatal rat ventricular myocytes. The hypertrophic response of this model required interaction with extracellular matrix proteins. Specificity of these results was confirmed by demonstrating that ventricular myocytes plated onto an anti-beta1 integrin antibody supported the hypertrophic gene response. Adenovirus-mediated overexpression of beta1 integrin augmented the myocyte hypertrophic response when assessed by protein synthesis and atrial natriuretic factor production, a marker gene of hypertrophic induction. DNA synthesis was not altered by integrin overexpression. Transfection of cultured cardiac myocytes with either the ubiquitously expressed beta1A integrin or the cardiac/skeletal muscle-specific beta1 isoform (beta1D) activated reporter expression from both the atrial natriuretic factor and myosin light chain-2 ventricular promoters, genetic markers of ventricular cell hypertrophy. Finally, suppression of integrin signaling by overexpression of free beta1 integrin cytoplasmic domains inhibited the adrenergically mediated atrial natriuretic factor response. These findings show that integrin ligation and signaling are involved in the cardiac hypertrophic response pathway.
|