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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 343 records · Page 19Linked to original sources

Nutrition and somatomedin: nutritionally regulated release of somatomedins and somatomedin inhibitors from perfused livers in rats.

Circulating somatomedin activity reflects the presence of both somatomedins and somatomedin inhibitors, factors which antagonize the growth-promoting actions of somatomedins. Although both are regulated by nutrition, somatomedin inhibitors respond more rapidly than somatomedins to refeeding in fasted animals. To explore the role of the liver in such responses, release of somatomedin activity and somatomedin inhibitor activity was assessed during perfusion of livers from normal, fasted, and fasted-refed rats. Size-exclusion high-performance liquid chromatography (HPLC) revealed that liver perfusates contain both somatomedin and somatomedin inhibitor activity of apparent molecular weight (mol wt) comparable to that found in the circulation (approximately 7,000 and approximately 30,000, respectively), as well as activity of apparently higher wt. In subsequent studies, responses to nutrition were evaluated as fluctuations in bioactivity only of mol wt comparable to that found in the circulation. Release of both somatomedin and somatomedin inhibitor activity was progressive over at least two hours of recirculating perfusion. Perfusates of livers from normal fed rats had somatomedin activity (stimulation of cartilage SO4 uptake) 94 +/- 19% above buffer (P less than .01), which fell to undetectable levels after three days of fasting. With refeeding, perfusate somatomedin activity rose within three hours to approximately 25% of levels in fed rats, but did not become significant until after 12 hours (29 +/- 7%, P less than .02). Perfusates of livers of fed rats also contained somatomedin inhibitor activity (42 +/- 10% inhibition of cartilage stimulation by normal serum), which rose after three days of fasting to 114 +/- 22% (P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Glucocorticoid effects on IGF-1/somatomedin-C and somatomedin inhibitor in streptozotocin-diabetic rats.

Diabetes is associated with a fall in serum levels of insulin-like growth factor-1/somatomedin-C (IGF-1/Sm-C) and a rise in somatomedin inhibitor, a factor which antagonizes somatomedin action. We attempted to determine if the presence of glucocorticoids was required for diabetes-related alterations in these circulating growth factors. Diabetes was induced with streptozotocin in intact or adrenalectomized rats. Adrenalectomized-nondiabetic and adrenalectomized-diabetic rats were given either no glucocorticoids or daily hydrocortisone acetate at 0.5 or 50 mg/kg body weight, and killed 48 hours after streptozotocin treatment. After serum fractionation via size exclusion high performance liquid chromatography (HPLC), IGF-1/Sm-C was determined by radioimmunoassay, and somatomedin inhibitor by bioassay according to the ability of serum fractions to blunt cartilage stimulation by normal serum. Intact-diabetic rats had 22% weight loss, glucose 427 mg/dL, and beta-hydroxybutyrate 7.2 mmol/L (all P less than .001 v control). Serum IGF-1/Sm-C levels in intact-diabetic rats were decreased 71%, while somatomedin inhibitor rose to 470% of the control values (both P less than .004). Adrenalectomized-diabetic rats displayed comparable hyperglycemia (greater than 400 mg/dL) and decline in IGF-1/SmC, with or without glucocorticoid replacement. However, adrenalectomized-diabetic rats had greatly reduced weight loss (10%), beta-hydroxybutyrate (1.5 mmol/L), and somatomedin inhibitor (59% of control), all P less than .01 v intact-diabetic. Hydrocortisone 0.5 mg/kg in these animals increased weight loss but had no significant effect on beta-hydroxybutyrate or somatomedin inhibitor levels.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

Human placental microvilli as a source of antigen for the preparation of a polyclonal antibody directed against the LDL receptor.

Polyclonal antibodies were prepared by immunization of rabbits with partially purified LDL receptor obtained from human placental microvilli. The antiserum reacted with membranes from human placental microvilli and human fibroblasts, as assessed by immunobinding studies. It also reacted with purified LDL receptors of both origins. The antiserum markedly inhibited 125I-labeled LDL binding to cultured human fibroblasts.

Antibody Formation↗

Photosensitization of Wi26-VA4 transformed human fibroblasts by low density lipoprotein loaded with the anticancer porphyrin mixture photofrin II: evidence for endoplasmic reticulum alteration.

Wi26 VA4 cells (SV40-transformed human lung fibroblasts) were incubated with low density lipoprotein (LDL) loaded with the anticancer porphyrin mixture photofrin II (P2). After labelling with 51Cr sodium chromate, cells were exposed to near UV light. After light exposure, kinetics of 51Cr release by cells were studied as a probe of cell damage. The activity of acyl-coenzyme A:cholesterol-O-acyltransferase, a key enzyme of cholesterol metabolism localized in endoplasmic reticulum (ER), was decreased as a function of the irradiation time in cells pre-incubated with P2-LDL. This result suggests that ER alteration occurred during cell photosensitization by P2-LDL.

Cell Line↗

Studies on the molecular-genetic basis of replicative senescence in Werner syndrome and normal fibroblasts.

Based on evidence that human diploid fibroblasts (HDF) from the Werner syndrome (WS) of premature aging might overexpress an inhibitor of DNA synthesis (IDS), we prepared a eukaryotic cDNA expression library from WS mRNA and tested it for IDS activity in a transient assay. Two of six WS cDNA pools tested gave IDS activity, then on plus/minus screening revealed several differentially expressed cDNA clones. By slot blot and Northern analysis, one cDNA clone was found to be overexpressed in WS and normal senescent HDF, but not in quiescent normal HDF, indicating that it is senescence-specific. Further studies are needed to clarify: a) whether this cDNA truly acts as an IDS; b) if so, whether it acts alone or in concert with other cDNAs; and c) whether it is involved in the degenerative and malignant sequelae of WS and normal aging.

Aging↗

Predictors of total mortality and sudden death in mild to moderate heart failure. Captopril-Digoxin Study Group.

The relation between baseline clinical variables and subsequent mortality was examined in 295 patients with mild to moderate heart failure who participated in a multicenter trial comparing the effect on treadmill exercise tolerance of captopril, digoxin and placebo given in addition to a diuretic drug. At baseline study, all patients had a left ventricular ejection fraction less than or equal to 40%; 81% were in New York Heart Association functional class II. The etiology of heart failure was ischemic in 62% and nonischemic in 38%. During an average follow-up period of 16 months, 47 patients (16%) died and 24 deaths were classified as sudden. By univariate analysis, left ventricular ejection fraction, ventricular premature beat frequency, couplet frequency, ventricular tachycardia frequency, functional class, treadmill exercise time and nonischemic heart disease were statistically associated with mortality. With multiple logistic regression analysis, left ventricular ejection fraction was identified as the variable most closely associated with total mortality (p = 0.006). Twenty-seven percent of patients with an ejection fraction less than or equal to 20% died compared with 7% with an ejection fraction greater than or equal to 30%. Ventricular tachycardia frequency on Holter monitoring was independently associated with both total mortality (p = 0.008) and sudden death (p = 0.003). Patients with a ventricular tachycardia frequency of greater than 0.088 events/h had a mortality rate of 34% compared with 12% in those without ventricular tachycardia. In the multivariate model, functional class (p = 0.02) and etiology of nonischemic heart disease (p = 0.04) remained as independent predictors of mortality, whereas treadmill exercise duration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗

Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure.

The effects of intravenous captopril and intravenous digoxin given separately and in combination on rest and exercise hemodynamics were studied in 16 patients with severe heart failure and sinus rhythm. When given separately, both captopril and digoxin decreased the pulmonary capillary wedge pressure by, respectively, 24% (p = 0.003) and 34% (p = 0.004) and systemic vascular resistance by 23% (p = 0.09) and 20% (p = 0.03). Only digoxin increased cardiac index by 23% (p = 0.03) and stroke work index by 52% (p = 0.01). During maximal exercise, captopril alone decreased systemic vascular resistance by 28% (p = 0.0002) and increased cardiac index by 33% (p = 0.02). Digoxin alone decreased pulmonary capillary wedge pressure by 11% (p = 0.04) and increased stroke work index by 44% (p = 0.01). The combination of captopril and digoxin resulted in a decrease in pulmonary capillary wedge pressure and systemic vascular resistance and an increase in cardiac index and stroke work index both at rest and during exercise that was greater than values observed with either drug given alone. Cardiac index response to the combination of captopril and digoxin correlated with baseline serum aldosterone concentration (r = 0.81, p less than 0.001) and plasma renin activity (r = 0.74, p less than 0.0002). A significant decrease in norepinephrine concentration was noted after digoxin was administered alone or added to captopril. These findings demonstrate that in patients with severe heart failure, the acute administration of captopril and digoxin has an independent salutary hemodynamic effect. The combination of these agents, however, has an adjunctive effect on cardiac function at rest and during exercise.

Adult↗

The effect of sequential sampling on crevicular fluid volume and enzyme activity.

Gingival crevicular fluid (GCF) volume and constituents in static samples were compared to volume and constituents in subsequent GCF samples collected during a 60-min interval. Using deep intracrevicular placement of precut filter paper strips, GCF was collected from interproximal and facial sites from patients with gingivitis (N = 14; 28 interproximal sites, 28 facial sites) and chronic adult periodontitis (N = 11; 26 interproximal sites, 18 facial sites). The strips were inserted for 30 s at 0, 4, 8, 30 and 60 min. The amount of fluid on each strip was determined and microspectrophotometric techniques were used to assess cytoplasmic and lysosomal enzyme activity. Within each group of sites, mean GCF volume showed minimal fluctuation with repeated sampling. In contrast, the static GCF sample contained the greatest amount of total enzyme activity, and differences were detected between groups. The interproximal sites and the gingivitis-facial sites displayed a similar pattern of change in total enzyme activity during the test period. The highest total enzyme activity was observed in the first sample and decreased at 4 and 8 minutes. At 30 and 60 min, the amount of enzyme either remained at the level detected at 8 min, or displayed a mild tendency to recover towards baseline. A different pattern of total enzyme activity was observed for the periodontitis-facial sites, where a significant decrease was first observed at 30 min. Enzyme concentration was higher in the facial sites than the interproximal sites, and enzyme concentration was generally highest in the static samples. The concentration data, however, is difficult to interpret since a number of sites demonstrated a converted GCF volume of 0 microliter. Our data suggests that total enzyme activity and enzyme concentration are generally greater in the static GCF samples compared to subsequent samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The normalcy of self-proclaimed "normal volunteers".

Volunteers who claimed they were "healthy and normal" and did not reveal any physical or mental abnormality or medication use during brief structured interviews underwent detailed structured interviews with the Schedule for Affective Disorders and Schizophrenia. Diagnoses were based on the Research Diagnostic Criteria (RDC), and family history was determined with the Family History RDC. Of the 121 volunteers, 16.5% met criteria for diagnoses of current mental disorders. Of the 104 without current DSM-III axis I diagnoses, 35.6% had past histories and 39.4% had family histories of mental illness. These results emphasize the need for thorough assessment of "normal volunteers."

Adolescent↗

Nutritional and hormonal regulation of articular collagen production in diabetic animals.

Although changes in collagen production probably play a major role in the connective tissue defects of diabetes, we do not know to what extent these changes are attributable to hormonal/metabolic versus nutritional alterations. To study collagen production as influenced separately by nutrition versus hormonal/metabolic factors, rats were given 50 mg/kg i.v. streptozocin (STZ) (mild weight-gaining diabetes) or 100 mg/kg STZ (severe weight-losing diabetes) and compared with nondiabetic food-restricted rats to match weight changes in diabetic animals. Articular cartilage was incubated with [3H]proline, and uptake of [3H]proline into both collagen and noncollagen proteins was determined with purified bacterial collagenase. Collagen decreased to 49% in mildly diabetic rats and 16% in severely diabetic rats, compared with control rats fed ad libitum and decreased to 85 and 73%, respectively, in food-restricted rats (both P less than .01 vs. diabetes). Diabetes induced a greater defect in collagen production than food restriction and a greater decrease in collagen than noncollagen protein production within each group, suggesting a specific effect on collagen. With comparable levels of metabolic severity (glucose, beta-hydroxybutyrate), diabetic animals that lost weight produced significantly less collagen than animals that gained weight, suggesting separate mechanisms. Quantitation of the impact of undernutrition on collagen production in diabetes demonstrated that approximately 31 to 32% of the defect was due to undernutrition, leaving approximately 68-69% of the defect due to the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Urban-rural and educational differentials in marital status in China.

Since 1950, laws aimed at delaying marriage have been 1 of the major means of slowing population growth in China, where marriage is nearly universal. Age at marriage has risen in recent decades, but not to the same extent in all localities. This article uses cross-tabulated data from China's 1982 census to assess the effects of urban-rural residence and educational level on the ages at which men and women have been marrying. The data also reveal the effects of residence and education on widowhood, divorce, and current marital status. As expected, exposure to development, indicated by urban residence and higher education, is associated with later marriage, but it also increases the likelihood of ever marrying, especially for men. Women's tendency to seek social mobility by marrying men from economically more developed areas results in bachelorhood for a substantial percentage of rural men, especially those who are illiterate.

Asia↗

Review of beta blocker myocardial infarction trials.

This is a brief review of the current state of knowledge of beta adrenergic-blocking agents in the treatment of acute myocardial infarction. Their effects when administered in the acute phase of infarction, and in special subgroups of patients who have sustained an acute infarction, are discussed. Particular emphasis is directed to their effect on arrhythmias and in patients with left ventricular dysfunction. In addition, data are presented which suggest the advantage of permanent therapy of beta blockers in patients who have sustained a myocardial infarction and in whom the drug is tolerated.

Adrenergic beta-Antagonists↗

Biologic theories of aging.

Many theories have been proposed to explain aging. Currently, the most important theories include genetic control, deterioration of the immune system, somatic mutation, accumulated damage by free radicals, cross-linkage of macromolecules, and metabolic causes. While no single theory accounts for all of the observations about aging, recent research suggests that the primary process is under genetic control, with contributions from environmental factors.

Aging↗