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Biomedical subjects

A Chait

Publications and source records attributed to A Chait.

At least 145 records · Page 8Linked to original sources
PubMed1982

Defective thyroid hormone action in fibroblasts cultured from subjects with the syndrome of resistance to thyroid hormones.

Two preadolescent girls and their mother with the syndrome of central and peripheral resistance to thyroid hormones are reported. The sisters had goiters, high radioiodine uptakes, high plasma levels of thyroid hormones, normal TSH levels, and brisk increases in TSH after TRH administration, but had no clinical evidence of thyrotoxicosis. The mother, who had undergone partial thyroidectomy and radioiodine therapy, presented with mild hypothyroid symptoms, normal thyroid hormone levels, and a high TSH level. On T4 treatment, her TSH fell toward normal, and thyroid levels became elevated without thyrotoxic symptoms. Special studies were performed with cultured skin fibroblasts. T3 stimulated low density lipoprotein receptor activity in cells from normal subjects, but failed to do so in fibroblasts form the three patients, indicating that their fibroblasts had a defective response to T3. However, after incubation of fibroblasts with labeled T3, no abnormalities in the binding capacity or affinity of nuclei were observed. These findings suggest that in this family, the thyroid hormone resistance demonstrable in vivo and in vitro results from a cellular defect at a site other than at the nuclear binding site.

Adult↗
PubMed1982

Catabolism of very-low-density lipoproteins in subjects with broad beta disease: comparison with endogenous hypertriglyceridemia.

The catabolic rates of VLDL apo-B from subjects with broad beta disease (type III hyperlipoproteinemia) and from subjects with endogenous hypertriglyceridemia (type IV hyperlipoproteinemia) were compared in recipients with these disorders. In subjects with broad beta disease, disappearance of autologous VLDL apo-B was slower than that of isologous VLDL apo-B from subjects with a type IV lipoprotein pattern (FCR 0.049 +/- 0.03 hr-1 for autologous vs. 0.068 +/- 0.035 for isologous, n = 6, p less than 0.05). However, the FCRs of autologous and isologous VLDL apo-B in subjects with type IV hyperlipoproteinemia were the same (0.110 +/- 0.051 hr-1 for autologous vs. 0.110 +/- 0.063 for isologous, n = 4, p = NS). In vitro studies suggested that 125I-VLDL from subjects with endogenous hypertriglyceridemia retained most of the smaller peptides (87.5% +/- 1.8 apo E and 75.7% +/- 1.6 apo C) when incubated with plasma from subjects with broad beta disease. By contrast, 125I-labeled IDLs from subjects with broad beta disease exchanged these lipoproteins rapidly (retaining only 7.9% +/- 0.03 apo-E and 8.2% +/- 0.3 apo-C) when incubated with plasma from subjects with endogenous hypertriglyceridemia. Similarly, beta-VLDL isolated from a subject with broad beta disease by preparative electrophoresis, when incubated with plasma from a subject with endogenous hypertriglyceridemia, exchanged its apo-E with the normal VLDL (56% being recovered in VLDL of alpha2 mobility). Normal VLDL, however, retained most (93.3%) of its VLDL apo-E radioactivity when incubated with plasma from a subject with broad beta disease. These observations suggest that the abnormal composition of autologous VLDL may in part be responsible for its delayed clearance in subjects with broad beta disease.

Adult↗
PubMed1981

The effect of hydrocortisone on cholesterol metabolism of cultured human skin fibroblasts.

Hydrocortisone in physiologic concentrations resulted in a reduction in sterol synthesis by cultured normal human skin fibroblasts. These changes were observed when [14C]acetate, [14C]octanoic acid and 3H2O were used as precursors. However, the incorporation of [3H]mevalonic acid lactone into digitonin-precipitable sterols was not affected by hydrocortisone, suggesting that hydrocortisone inhibits sterol synthesis at a site prior to the formation of mevalonic acid. In contrast, the activity of hydroxymethylglutaryl-CoA reductase was stimulated several-fold by the hormone. Thus, the inhibitory effect of hydrocortisone on the cholesterol synthetic pathway may be on hydroxymethylglutaryl-CoA synthase.

Acetates↗
PubMed1981

Uptake of chylomicron remnants by the native LDL receptor in human monocyte-derived macrophages.

Human chylomicron remnants were taken up by cultured human monocyte-derived macrophages. Competition studies using 125I-labeled and unlabeled lipoproteins demonstrated that the remnant particles were not taken up by the modified LDL (acetyl LDL) receptor in these cells, which also contain a receptor for native LDL. The data thus suggest that the apolipoprotein E- and B-containing remnant particles are mainly taken up through an extra-hepatic E and B receptor (the classical LDL receptor pathway) in macrophages as is the case in cultured human skin fibroblasts.

Biological Transport↗
PubMed1981

Lysosomal enzyme activities and low density lipoprotein receptors in circulating mononuclear cells. Effect of insulin therapy in diabetic patients.

Methods for the measurement of the lysosomal enzymes acid cholesterol-ester hydrolase and N-acetyl-beta-glucosaminidase were adapted for use with freshly isolated circulating mononuclear cells. Activities of both these enzymes increased (to 259 and 147% of control values respectively) after 7 days of insulin therapy in diabetic subjects. Low density lipoprotein degradation by freshly isolated mononuclear cells increased simultaneously by 67% (p less than 0.05). The findings in this pilot study suggest [1] that circulating mononuclear cells can be used to evaluate the effect of metabolic changes in vivo on lysosomal enzymes and low density lipoprotein metabolism, and [2] that insulin can stimulate cellular lysosomal enzyme activity.

Acetylglucosaminidase↗
PubMed1981

Acceleration of low-density lipoprotein catabolism in man by total parenteral nutrition.

Since insulin enhances the catabolism of low-density lipoprotein (LDL) by cultured human cells, a potential role of insulin in the regulation of plasma LDL levels in man is suggested. To evaluate the possible effect of insulin on LDL catabolism in vivo, the disappearance rates of injected 125I-labeled autologous LDL were determined before and after endogenous hyperinsulinemia was evoked by total parenteral nutrition. Multicompartmental analysis of plasma decay curves showed a 26% increase in the fractional catabolic rate of LDL after total parenteral nutrition was started. An associated reduction of plasma cholesterol levels resulted from changes in both LDl and high-density lipoprotein. These results suggest that the reduction of LDL levels during total parenteral nutrition is at least partly accounted for by enhanced LDL catabolism. It is postulated that the enhanced LDL catabolism may result from the hyperinsulinemia that accompanies total parenteral nutrition, via insulin stimulation of receptor-mediated LDL catabolism.

Cholesterol↗
PubMed1980

Postprandial adipose tissue lipoprotein lipase activity in primary hypertriglyceridemia.

The fasting activity of adipose tissue lipoprotein lipase has been previously reported to be either normal or reduced in subjects with a primary form of hypertriglyceridemia. The postprandial activity of adipose tissue lipoprotein lipase has not been previously reported in these subjects. In subjects with primary hypertriglyceridemia the fasting lipoprotein lipase activity eluted from pieces of adipose tissue by heparin and the enzyme activity present in extracts of acetone--ether tissue powders were similar to the level of enzyme activity found in normal subjects. There also was no difference in the postprandial adipose tissue heparin-elutable lipoprotein lipase activity between these two groups when measured after high carbohydrate feeding. When the subjects with primary hypertriglyceridemia were further subdivided by genetic diagnosis, there was no difference in the level of adipose tissue lipoprotein lipase of subjects with familial hypertriglyceridemia, familial combined hyperlipidemia, or in those in whom no specific genetic diagnosis could be made. The change in lipoprotein lipase activity after feeding was inversely related to the fasting enzyme level in both the normal subjects (r = -0.58, p less than 0.05, n = 12) and the hypertriglyceridemic subjects (r = -0.92, p less than 0.01, n = 11). In the normal subjects, the plasma triglyceride response to feeding correlated inversely with the postprandial change in lipoprotein lipase activity (r = -0.76, p less than 0.02, n = 12). Adipose tissue lipoprotein lipase activity in patients with primary lipoprotein lipase deficiency was markedly reduced in the fasting state and remained essentially zero after feeding. This suggests that a functional role exists for the enzyme activity as measured.

Adipose Tissue↗
PubMed1980

Platelet-derived growth factor stimulates activity of low density lipoprotein receptors.

Partially purified platelet-derived growth factor stimulates low density lipoprotein binding and degradation in cultured aortic smooth muscle cells of monkeys by increasing the number of available low density lipoprotein receptors. When platelet-derived growth factor was added to quiescent cells, low density lipoprotein binding increased within 4-8 hr. Stimulation of low density lipoprotein receptor activity preceded stimulation of DNA synthesis by platelet-derived growth factor by 8-12 hr. Enhancement of endogenous cholesterol synthesis by platelet-derived growth factor preceded stimulation of low density lipoprotein receptor activity. These findings suggest that the platelet-derived growth factor can increase both the exogenous and endogenous supplies of cholesterol to the cell for its use during cell proliferation.

Animals↗
PubMed1979

Reduction of plasma triglyceride concentration by acute stress in man.

Three different forms of stress all resulted in acute reduction of plasma triglyceride concentrations. Pyrogen reactions in two hypertriglyceridemic men resulted in the lowering of very-low-density lipoprotein (VLDL) triglyceride levels by 93% and 73% due to decreased secretion of this lipoprotein into plasma. More modest reductions in plasma triglycerides were observed after 2-deoxyglucose-induced intracellular glucopenia and insulin-induced hypoglycemia. With hypoglycemia, the lowering of plasma triglyceride concentration correlated significantly with the stimulation of urinary epinephrine output (r = 0.86) but with neither the urinary norepinephrine response nor with the increase in plasma immunoreactive glucagon levels. To further test whether these changes in plasma triglyceride levels were mediated via the sympathetic nervous system, hypoglycemia was evoked by insulin in subjects with traumatic spinal cord transactions. Two such subjects, who demonstrated sympathetic stimulation in response to hypoglycemia, had evidence of reduced VLDL secretion into plasma, while in two who had no evidence of an adrenergic response. VLDL secretion was not inhibited. Thus, acute lowering of plasma triglyceride concentrations by certain forms of stress appears to be mediated via the sympathetic nervous system.

Acute Disease↗
PubMed1979

Effect of dietary fructose on triglyceride transport and glucoregulatory hormones in hypertriglyceridemic men.

Effects of dietary fructose on triglyceride metabolism and on basal levels and meal responses of glucose, insulin, and glucagon were studied in six hypertriglyceridemic men, two of whom were also diabetic. Constant composition, weight-maintaining formula diets were used with substitution of fructose for 20% of the carbohydrate calories in both fat-containing (45% carbohydrate) and fat-free (85% carbohydrate) periods; each of the four dietary periods was at least 2 weeks long in every subject. No effect of fructose on fasting levels of triglycerides could be seen in any of the diets. No alterations of triglyceride transport occurred with fructose substitution in the fat-containing diets, but significant reductions of triglyceride transport rates were seen with fructose substitution in the 85% carbohydrate diets using both the heparin infusion lipolytic rate method and the 3H-glycerol methods of assessment of tryglyceride turnover (- 16 and - 21%, respectively). Dietary fructose induced no significant changes in either basal levels or responses during a "formula tolerance test" of glucose, insulin, or glucagon. Thus, dietary fructose given for several weeks does not appear to cause further elevations of plasma triglyceride levels in hypertriglyceridemic men.

Adult↗
PubMed1979

Effect of donor age on the binding and degradation of low density lipoproteins by cultured human arterial smooth muscle cells.

The ability of human arterial smooth muscle cells growing in tissue culture to bind, incorporate and degrade low density lipoproteins (LDL) was studied as a function of cell donor age from 5 to 71 years. LDL binding to cell surface receptors did not change with donor age. However, LDL degradation was significantly decreased in cells from older donors. These results may be relevant to the enhanced accumulation of cellular cholesterol and LDL observed in the aging human artery. Thus, impaired LDL degradation by arterial smooth muscle cells may be one of several factors involved in the accelerated development of atherosclerosis with aging.

Adolescent↗
PubMed1979

Lipodystrophy with hyperlipidaemia: the role of insulin in very low density lipoprotein over-synthesis.

A patient with partial lipodystrophy is described in whom hypertriglyceridaemia was accompanied by marked hyperinsulinaemia. The hyperlipidaemia was due to increased plasma levels of very low density lipoprotein (VLDL). Kinetic studies, performed after injection of autologous radioiodinated VLDL, indicated that the raised VLDL levels were associated with over-production of this lipoprotein. Administration of diazoxide led to a substantial fall in serum insulin levels, accompanied by reduction in VLDL production and in serum triglyceride concentration. The possible role of insulin in inducing hyperlipidaemia by causing over-production of VLDL is discussed.

Adult↗
PubMed1979

Low-density lipoprotein receptor activity in cultured human skin fibroblasts. Mechanism of insulin-induced stimulation.

Low-density lipoproteins (LDL) receptor activity, as reflected by LDL degradation, was stimulated by the addition of insulin to cultures of human skin fibroblasts. These changes occurred independently of the glucose concentration of the incubation medium and occurred whether or not LDL receptor activity was suppressed. A comparison of the saturation kinetics of LDL receptor activity in the presence and absence of insulin indicated that insulin produced a 35% increase in Vmax with no difference in "apparent Km". These results suggest that insulin enhances LDL receptor activity by increasing the number of LDL receptors rather than by influencing binding affinity. In confirmation, LDL degradation by receptor negative cells was not enhanced by insulin. Sterol synthesis from [14C]acetate was also stimulated by insulin, but egress of cholesterol and cellular cholesterol content were unaffected by the hormone. The effect of insulin on LDL receptors was not dependent on its known ability to enhance cellular DNA synthesis and proliferation, because insulin stimulated LDL receptor activity in cells kept quiescent by maintenance in plasma-derived serum that was devoid of platelet derived growth factor. Nevertheless, the effect of insulin in enhancing LDL receptor number, coupled with stimulation of endogenous cholesterol synthesis, provides a mechanism whereby the cell could theoretically increase its supply of cholesterol during times of additional need.

Animals↗
PubMed1979

Regulatory role of triiodothyronine in the degradation of low density lipoprotein by cultured human skin fibroblasts.

Degradation of [125I]-labeled low density lipoprotein (LDL) by cultured normal human skin fibroblasts was enhanced by exposure to concentrations of L-triiodothyronine (T3) spanning the physiological range. Analysis of LDL concentration curves suggests that T3 may increase LDL receptor number rather than alter the affinity of LDL for its receptor. No effect of T3 on LDL degradation was observed in receptor negative cells. Thus thyroid hormone appears to regulate receptor-mediated LDL degradation by increasing the binding of the lipoprotein to its cell-surface receptor.

Cells, Cultured↗