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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 595 records · Page 33Linked to original sources
PubMed1978

Cultured human fibroblasts: distribution of cell generations and a critical limit.

In circular outgrowths of human skin fibroblasts we found that mitotic cells at the circumference had consumed more of their replicative lifespan than cells located more centrally. The lifespan remaining in cells at a given radial position could be predicted by determining their generation level based on the rate at which the outgrowth expanded and the cell doubling time. The data also show that outgrowths contain a heterogeneous mixture of cells described by a linear distribution of generations which can account for the variable replicative capacity observed in clones and the exponential increase in the fraction of nondividing cells with serial passage. These results support the concept that a critical limit of cell divisions determines the replicative lifespan.

Cell Division↗
PubMed1978

Conservation of genes coding for proteins synthesized in human mitochondria.

Proteins synthesized in mitochondria of 27 different human cell lines, identified by labeling with [35S]methionine in the presence of cycloheximide, have been enumerated and their electrophoretic mobilities determined by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis and fluorography. Twelve bands were observed in all cell lines. In 24 cell lines, the electrophoretic mobilities of the proteins were the same regardless of race, sex, tissue of origin, cell type, viral transformation, or premature biological aging syndromes. The patterns obtained for the remaining cell lines, HeLa, KB, and Hep-2 were identical. These cell lines showed one protein component that was absent in the 24 others, and lacked a component present in these cell lines. Since it has been previously asserted that KB and Hep-2 are HeLa cells, the data indicate that one basic pattern exists in human cells with a variant of unknown origin occurring in HeLa cells.

Cell Line↗
PubMed1978

The effect of magnesium on the response of smooth muscle to 5-hydroxytryptamine.

1 The responses to 5-hydroxytryptamine (5-HT) of rabbit isolated mesenteric artery and vein and longitudinal smooth muscle of guinea-pig ileum were examined in Krebs solution containing 0, 1.2 or 2.4 mM Mg2+. 2 When the concentration of Mg2+ was raised the spontaneous contractile activity of rabbit mesenteric vein was depressed. The responses to 5-HT in rabbit mesenteric artery and vein and guinea-pig ileum were greater in the absence of Mg2+. The initial fast component of 5-HT-induced contractions in rabbit mesenteric vein was reduced more consistently than the subsequent slow component by increasing the Mg2+ concentration. 3 Exposure of mesenteric vein to Ca-free solution containing ethyleneglycoltetra-acetic acid (EGTA) promptly abolished 5-HT contraction in normal-Mg but not in low-Mg Krebs solution. 4 In mesenteric veins, no difference was observed in either the 'lanthanum-resistant' uptake of 45Ca or total tissue Ca, measured by atomic absorption spectrophotometry, after 60 min exposure to either low-Mg or normal-Mg Krebs solution. On the other hand, after 5 min exposure, the 'lanthanum-resistant' uptake of 45Ca was greater in the absence of Mg2+ than in the presence of higher Mg2+ concentrations. 5 It is suggested that Mg2+ depressed the 5-HT response at least partly by reducing the availability of Ca2+ from a rapidly equilibrating intracellular pool.

Animals↗
PubMed1978

Phenylalanyl synthetase function in cultured fibroblasts from subjects with progeria.

Since progeria cells contain a diversity of altered proteins, some aspects of phenylalanyl synthetase function were examined in semipurified extracts of cultured skin fibroblasts using mixed rabbit tRNA as acceptor. No significant differences were found in the Km and Vmax for phenylalanine or ATP in progeria cells compared with controls. Initial velocities of both progeria and control synthetases were lower at late passage owing to either reduced enzyme content or reduced catalytic efficiency. Reverse phase 5 chromatography of tRNAs acylated by progeria and control synthetases gave a single peak of labeled phenylalanine tRNA in all cases with no secondary peaks evident. Total activity of phenylalanyl synthetase in progeria cells was similar to that of control cells at early passage while late-passage control cells had lower specific activities of these synthetases per unit protein.

Adenosine Triphosphate↗
PubMed1978

Interspecific variations in proteins synthesized by mammalian mitochondria.

The products of mitochondrial protein synthesis in established cell lines of various mammalian species were labelled with [35S]methionine and their number and apparent molecular weights determined by sodium dodecyl sulfate polyacrylamide slab gel electrophoresis and fluorography. Proteins synthesized by isolated rat liver mitochondria were labelled with [3H]valine and similarly characterized. Each species had a distinctive pattern of from 10 to 13 mitochondrially synthesized proteins with apparent molecular weights between 10,000 and 50,000. No differences were detected in the number or electrophoretic mobility of the mitochondrially synthesized proteins of SV-40-transformed and nontransformed WI-38 cells.

Animals↗
PubMed1978

Echocardiographic diagnosis of left ventricular hypertrophy.

Echocardiograms were obtained on 27 adults with electrocardiographic criteria of left ventricular hypertrophy (LVH) to determine how echocardiograms might best identify LVH. Both the left ventricular (LV) posterior wall thickness and interventricular septal thickness were found by echocardiography to be increased (greater than or equal to 12 mm) in only 13 of 27 patients (48%) with LVH. The LV was dilated (greater than or equal to 58 mm) in the absence of posterior wall thickening in 9 of 27 patients (33%). The LV mass, estimated from standardly measured dimensions, was increased (greater than 200 g) in 21 of 27 patients (78%) and when measurements were made by the Penn method, mas was increased in all patients. These observations indicate that the echocardiographic estimation of LV mass is a more sensitive indicator of LVH than LV posterior wall and septal thickness. Since LVH is defined as an increased mass of LV muscle, these observations are consistent with this fundamental definition of left ventricular hypertrophy.

Adult↗
PubMed1978

Partial purification, characterization, and assay of a slightly acidic insulin-like peptide (ILAs) from human plasma.

An insulin radioreceptor assay (RRA) using human placental microsomal membranes was used to measure insulin-like activity (ILA) extracted from human plasma concentrates (Cohn fraction IV-4) by acid ethanol. The soluble activity (ILAs), chromatographed on Sephadex G-75 in 1 M acetic acid, migrated as a small molecule (fractional elution volume, 0.56) ahead of insulin (fractional elution volume, 0.70), whereas at neutral pH, ILAs migrated as a large molecular weight species. The ILAs peak from acid gel filtration on Sephadex was further purified by chromatography on carboxymethyl cellulose (CMC). The ILAs peak from both Sephadex and CMC diluted parallel to the porcine insulin standard in the insulin RRA and was totally unreactive in an insulin RIA. The CMC-purified material was iodinated and purified by binding to and elution from human placental membranes. The binding of [125I]ILAs to human placental membranes was inhibited only minimally by insulin and proinsulin and not at all by epidermal growth factor, nerve growth factor, glucagon, or lactogenic hormones, including human growth hormone. Multiplication-stimulating activity (MSA) inhibited in a manner parallel to ILAs. A Scatchard plot of the binding data was nonlinear. Sephadex ILAs was subjected to isoelectric focusing. The fractions assayed in both insulin and ILAs RRAs yielded comparable results. Peaks of ILA were observed at pHs 5.3, 6.6, and 8.4. When CMC-ILA was subjected to isoelectric focusing in polyacrylamide, a single peak of activity migrating between pH 6.2-6.8 was seen. [125I]ILAs focused at exactly the same pH. Electrophoresis of CMC-ILAs in acid-urea revealed a sharp peak of activity migrating with one of the five protein bands seen after staining. Again, [125I]ILAs comigrated with unlabeled ILAs. The molecular weight of ILAs, as determined on a calibrated Sephadex G-150 column at neutral pH, was 9,000-10,000 daltons. CMC-ILAs stimulated [14C]glucose incorporation into triglycerides of rat adipose tissue and augmented [3H]thymidine incorporation into human fibroblasts, chicken embryo fibroblasts, and BALB 3T3 cells as well as [35S]sulfate incorporation into macromolecules of rabbit chondrocyte culture medium. In summary, ILAs isolated on the basis of a RRA for insulin is a slightly acidic peptide with some of the biological activities expected of a somatomedin.

Adipose Tissue↗
PubMed1978

Correlation of exercise 201thallium myocardial scan with coronary arteriograms and the maximal exercise test.

Myocardial scans obtained by injecting radioactive 201thallium during exercise were correlated with electrocardiograms obtained at rest and during exercise, with coronary arteriographic abnormalities, and with left ventriculograms in 55 patients suspected of having coronary arterial disease. Thirty-nine patients had significant coronary arterial disease, 34 of whom had abnormal myocardial scans after exercise and 21 of whom had abnormal ECGs during exercise. The myocardial scan after exercise was most frequently abnormal in the presence of significant abnormalities in the Q wave or localized left ventricular asynergy and when ST-segment depression persisted for longer than ten minutes after exercise. All patients with single-vessel disease had abnormal myocardial scans after exercise, whereas five of 29 patients with two or more abnormal vessels had normal scans. Patients with coronary arterial disease were more likely to have a normal myocardial scan after exercise when the resting ECG and left ventriculogram were normal and when exercise-induced ST-segment depression persisted for less than ten minutes. The combination of the myocardial scan after exercise and the ECG during maximal exercise had a sensitivity of 98 percent. The myocardial scan after exercise alone had a specificity of 100 percent. These observations indicate that the myocardial scan obtained by injecting 201thallium during exercise is an important diagnostic adjunct in the identification of patients with coronary arterial disease.

Adult↗
PubMed1978

Heat-labile enzymes in circulating erythrocytes of a progeria family.

Cultured skin fibroblasts from subjects with progeria contain an increased fraction of heat-labile enzymes and other altered proteins. To determine whether freshly obtained cells are similarly affected, erythrocytes from a progeric female and her clinically normal parents were analyzed for heat-lability of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Hemolysates of the child's whole erythrocyte populations and young erythrocytes isolated by equilibrium density centrifugation contained significantly higher heat-labile fractions of both enzymes compared to control hemolysates. Values in both parents were intermediate to those of their daughter and controls, consistent with autosomal recessive inheritance in this family. The primary source of these multiple protein defects is unknown but may reside in a mutant gene producing abnormal protein turnover or defective DNA repair. An increased fraction of thermolabile enzymes in circulating erythrocytes should be useful in identifying persons at risk for progeria and other disorders of premature aging.

Adult↗
PubMed1977

Comparative studies on human skin fibroblasts: life span and lipid metabolism in medium containing fetal bovine or human serum.

Three strains of human skin fibroblasts were cultivated in nutrient medium supplemented either with human serum or fetal bovine serum, and growth and lipid synthesis were compared. Rates of cellular growth were similar in both kinds of medium, but the replicative life spans of all three strains were curtailed significantly in human-serum medium. Incorporation of label into the major classes of neutral lipids from [14C]acetate and 3H2O was increased also in human-serum medium. Since human serum contained higher concentrations of cholesterol known to reduce endogenous cholesterol synthesis, these results were unexpected. Nonlipid factors in human serum may account for the shortened cellular life spans and increased lipogenesis and perhaps for the potential to develop atherosclerosis.

Adult↗
PubMed1977

Biochemical and immunological evidence for the presence of an apolipoprotein B-like component in the serum low-density lipoproteins of several animal species.

The major component of the protein moiety of human LDL, i.e. apolipoprotein B, has been compared biochemically and immunologically with its counterpart in the LDL of several groups of animals (mammals, birds, snakes and fish). A marked resemblance was found in the amino acid composition of the apo-B fractions from all the phylogenetic groups, although immunological cross-reactivity with human apolipoprotein B occurred only in the case of non-human primate (Old World monkey), non-primate mammalian (pig and guinea pig) and bird (chicken) apo-B components (63%, 24% and about 8% respectively). The cross-reactivity of each animal apo-B component with its human counterpart was 7-14% lower than that observed between the parent LDL's. The resemblance in amino acid composition between the various apo-B preparations suggests that certain structural characteristics are required in this protein in order for it to bind and stabilise the lipid complement of serum LDL.

Amino Acids↗
PubMed1977

Hormone receptors: VI. On the nature of the binding of glucagon and insulin to human circulating mononuclear leukocytes.

Several characteristics of the binding of insulin and glucagon to human circulating mononuclear leukocytes have been studied. Functional analysis (latex bead ingestion) revealed that cell mixtures, as prepared according to Boyum and used generally in studies of insulin resistance in humans, consist of 20-29% phagocytic monocytes, with the remainder being lymphocytes. Partial separation of monocytes from lymphocytes on columns of Sephadex G-10, followed by correlation of insulin binding with cell type, confirms that the monocyte is the binding species. Insulin influenced neither glucose uptake nor the further conversion of glucose to lipids and CO2 by the leukocytes. The transport of alpha-aminoisobutyrate, a nonmetabolizable amino acid, into these cells was also unaffected by insulin. Monocyte/lymphocyte mixtures specifically bound glucagon and prostaglandin E1. At physiological concentrations of these hormones, steady states were reached in 15 min and 45 min, respectively. In contrast to the 8-10-fold increases in cellular cyclic AMP produced by prostaglandins, the effect of glucagon was very small but apparently real. Under appropriate preincubation conditions, sodium azide and iodoacetamide inhibited phagocytosis and insulin binding in parallel. The binding of glucagon was unaffected by these agents. Although both antimycin A and actinomycin D inhibited phagocytosis of the monocytes, only the former inhibited insulin binding; there was only a slight effect on glucagon binding. We would conclude that the binding of insulin to human circulating monocytes, although reflective of insulin resistance in diabetes mellitus and obesity, may not be to traditional receptors. In contrast, the binding of glucagon to lymphocyte/monocyte mixtures may be to function-linked receptors.

Blood Glucose↗