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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 613 records · Page 34Linked to original sources

Hypothermic lung preservation functions, six or more years later.

The functions of each lung were measured 41 and 79 months following hypothermic twenty-four four lung preservation and autotransplantation in six and four dogs respectively. Functional results were compared with long-term autotransplanted canine lungs. Compliance, total lung capacity, functional reserve capacity and ventilation of preserved lungs were similar to autotransplanted lungs, and only slightly decreased as compared with normal animals. There was no statistically significant difference between the pulmonary diffusion capacity and oxygen uptake of the preserved and autotransplanted lungs group and autotransplants alone. However, in both groups, diffusion capacity and oxygen uptake were decreased as compared with intact animals. Pulmonary hypertension was found on occlusion of the contralateral lung's artery: it was due to increased pulmonary vascular resistance. No gross narrowing of the pulmonary artery or venous anastomosis was found that could explain the increased resistance. Diffuse emphysema of various degrees was observed in all animals. This study seems to indicate that hypothermic preservation of the lung does not affect significantly the long-term functional ability of the organ, and probably will have practical value in future clinical lung transplantation.

Animals↗

Attempted suicide among the aged.

Although the rate for suicide in old age is high, the rate for attempted (unsuccessful) suicide is low. Among the elderly, suicide-attempt groups have more physical disorders, more psychoses, and more psychopathologic findings, and are under-represented demographically. Fifty percent of the elderly suicide attempters have organic brain syndrome (OBS), compared to only 5-10 percent of the "normal" population over age 60. Among what might be expected to be a high-risk suicide population, OBS apparently interferes with the success of suicide attempts by impairing coordination, planning, determination, and awareness of reality.

Aged↗

Normal insulin binding to cultured fibroblasts from patients with lipoatrophic diabetes.

Confluent fibroblasts were assayed for insulin binding to determine whether there was an inherent abnormality in receptor function to explain the insulin resistance of lipoatrophic diabetes (LD). Cells from three patients and four controls were compared for confluent density, receptor saturation, specific and non-specific binding and the concentration of unlabelled hormone producing 50% competition for binding with labelled ligand. Cells from patients with LD did not differ significantly in any of these characteristics from the controls. These findings indicate that there is not a basic defect in insulin receptors of LD patients. A secondary disruption of binding, e.g. by a circulating factor, remains possible.

Adolescent↗

Insulin binding to cultured human fibroblasts increases with normal and precocious aging.

Specific and nonspecific [125I]insulin binding and concentration of unlabeled hormone producing 50 percent competition with 1.0 nanomolar [125I]insulin for specific binding sites correlated positively with age of fibroblast donors. Cells from four children with precocious aging--three with progeria and one with Rothmund syndrome-resembled those from the chronologically old.

Adolescent↗

Determination of cyanocobalamin by thermal decomposition of the cyano group using an ion-selective electrode.

A method for the simultaneous determination of cyanocobalamin, cobinamide (Factor B), and hydroxocobalamin in the solid state is described. The method is based on heating at 120 degrees for cobinamide and at 140-145 degrees for cyanocobalamin (15-20 min). The cyano content in the sample is distilled as hydrocyanic acid, trapped in 0.1 M potassium nitrate at pH 12-13, and determined by means of the cyanide ion-selective electrode. The error of this method, statistically established, does not exceed +/-3%.

Electrodes↗

Comparative immunochemical studies of the serum low-density lipoprotein in several animal species.

The antigenic reactivities of the serum LDLs of several groups of animals (mammals, birds, snakes, and fish) have been compared by qualitative and quantitative immunological techniques. The cross-reactivities of the various LDLs were evaluated qualitatively by gel diffusion techniques and quantitatively by the precipitation and inhibition of precipitation tests. The degrees of cross-reaction between human and animal LDLs ranged from 80-88% in the Old World monkeys to 36-58% in the pig, 26-37% in the guinea pig, 1-10% in the chicken, and about 1% in the snakes and fish. These antigenic relationships are consistent with the taxonomic classification of these species, but are relatively closer than those observed for other serum proteins (e.g., albumin, transferrin, and hemoglobin). These results indicate a relatively high conservation of LDL structure through evolution, and are consistent with a common function for this lipoprotein in the transport and metabolism of cholesterol in the higher animals.

Animals↗

Toxicity testing in vitro. I. The effects of delta 9-tetrahydrocannabinol and aflatoxin B1 on the growth of cultured human fibroblasts.

The acute toxicity of delta 9-tetrahydrocannabinol (delta 9-THC) and aflatoxin B1 to two strains of cultured human fibroblasts has been studied. delta 9-THC had no effect on cell plating efficiency or on the growth of mass cultures at doses of 1 mug/ml (3.18 muM) or less; at 10 mug/ml plating efficiency was reduced by approximately half and at 20 mug/ml colony formation was zero. Aflatoxin B1 reduced plating efficiency at dose levels of 0.1 mug/ml (0.32 muM) and above; in mass clultures it retarded growth at 1 mug/ml and produced complete inhibition at 5 mug/ml. The potential usefulness of cultured human fibroblasts in toxicity testing is discussed and the importance of using normal diploid cells rather than aneuploid permanent lines is emphasized. The limitations of cell cultures in assessing toxicity, and possible solutions to these are considered.

Adult↗

Toxicity testing in vitro. II. Use of a microsome - cultured human fibroblast system to study the cytotoxicity of cyclophosphamide.

The toxicity of cyclophosphamide (CP), has been studied using a human fibroblast cell culture system. A method is described in which CP is incubated with liver microsomes and appropriate co-factors before addition to the cells. This permits activation of the CP to its cytotoxic metabolite but avoids the necessity of adding microsomes directly to the cell culture. It was demonstrated that under these conditions CP was irreversibly toxic to the cells within hours at dose levels larger than or equal to 0.3 mg/ml. In the absence of microsomal activation it was toxic at similar dose levels but the toxic effects required several days to develop.

Adult↗

Fibrin clot retraction by human skin fibroblasts: effects of ADP and thrombin.

Thrombin stimulated human skin fibroblasts to retract fibrin clots. When Bothrops marajoensis thrombinlike enzyme was substituted for thrombin, no retraction occurred. Fibroblasts were found to contain 12 nmole of ATP and 3.6 nmole of ADP/mg of protein, a value closely resembling that of nonmetabolic adenine nucleotides in platelets. Thrombin caused neither release of adenine nucleotides from the suspension of fibroblasts harvested enzymatically nor did addition of ADP stimulate fibroblasts to retract fibrin clots.

Adenosine Diphosphate↗

Impulse control.

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Adult↗

Protein kinase stimulation of a reconstituted cholesterol side chain cleavage enzyme system in the bovine corpus luteum.

A solubilized preparation of cytochrome P-450, obtained by treatment of mitochondria from bovine corpora lutea with phospholipase A, contained all of the necessary components for the cholesterol side chain cleavage activity. The solubilized cytochrome -450 preparation could be isolated essentially free of endogenous cholesterol side chain cleavage activity by various fractionation techniques. A cholesterol side chain cleavage enzyme system was reconstituted using the isolated cytochrome P-450 preparation and purified adrenodoxin and adrenodoxin reductase (components of the enzyme system purified from the adrenal cortex). Protein kinase was partially purified from the cytosol fraction of bovine corpora lutea. It was purified 43-fold and the activity was highly dependent on cyclic adenosine 3:5-monophosphate (cyclic AMP). When ATP and this partially purified cyclic AMP-dependent protein kinase were added to the reconstituted cholesterol side chain cleavage enzyme assay in which cytochrome P-450 was limiting, a stimulation (20 to 74%) of the conversion of cholesterol into pregnenolone was observed. This stimulation was statistically significant with p value less than 0.001. The stimulatory effect of the protein kinase appeared to be dependent on ATP and was not mimicked by bovine serum albumin, indicating that the effect was specific for protein kinase. Protein kinase caused a phosphorylation of the cytochrome P-450 preparation when large amounts of this preparation were used in the assay. It is concluded from these results that the direct activation of the cytochrome P-450 component of the cholesterol side chain cleavage by protein kinase may be one of the ways by which cyclic AMP mediates the effect of luteinizine.

Adenosine Triphosphate↗

Heat-labile enzymes in skin fibroblasts from subjects with progeria.

To characterize further the genetic basis of progeria, thermolability studies were performed on three genetically distinct enzymes in crude extracts of cultured skin fibroblasts derived from two subjects with that syndrome. At early passage the progeric fibroblasts, as compared to controls, contained a significantly higher percentage of heat-labile glucose-6-phosphate dehydrogenase (12.83 plus or minus 1.72 vs 1.11 plus or minus 0.44 [mean plus or minus S.E.M.], p smaller than 0.001), 6-phosphogluconate dehydrogenase (9.71 plus or minus 0.68 vs. 0.67 plus or minus 0.22, p smaller than 0.001), and hypoxanthine-guanine phosphoribosyltransferase (31.41 plus or minus 1.89 vs 7.67 plus or minus 1.71, p smaller than 0.001), and the differences were maintained throughout the in vitro life-span. These data, in conjunction with previous reports of defective HL-A antigens, indicate a widespread defect in genetic expression. The most likely cause appears to be an aberration in protein synthesis or degradation, or both, although multiple somatic mutations cannot be ruled out. Increased thermolability of enzymes in cultured cells may provide a screening test for persons predisposed to progeria and other disorders of premature aging.

Adult↗