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Biomedical subjects

J D Bagdade

Publications and source records attributed to J D Bagdade.

At least 73 records · Page 4Linked to original sources
PubMed1980

Low density lipoprotein-activated lysolecithin acylation by human plasma lecithin-cholesterol acyltransferase. Identity of lysolecithin acyltransferase and lecithin-cholesterol acyltransferase.

There is in normal plasma an enzyme activity which converts labeled lysolecithin to lecithin by an energy-independent low density lipoprotein-activated pathway. Studies were undertaken to compare the identity of this enzyme with lecithin-cholesterol acyltransferase. During purification of the enzyme by ultracentrifugation and by chromatography on high density lipoprotein affinity column, DEAE-Sepharose column, and hydroxylapatite column, both the lysolecithin acyltransferase activity and the lecithin-cholesterol acyl transferase activity were found in the same fractions and were enriched to the same extent at each step. The final purified preparation which had 16,000- to 24,000-fold higher specific activities than starting plasma gave a single protein band on polyacrylamide gel electrophoresis and this single band contained both the activities. Also, the effects of pH, heat, and chemical inhibitors on the enzyme activities were similar. Plasma from patients with familial lecithin-cholesterol acyltransferase deficiency also lacked lysolecithin acyltransferase activity. These results indicate that a single enzyme carries out both lecithin-cholesterol acyltransferase and lysolecithin acyltransferase activities. The purified enzyme required apolipoprotein A-I for lecithin-cholesterol acyltransferase activity, but required low density lipoprotein for lysolecithin acyltransferase activity.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1980

Impaired granulocyte adherence in mildly diabetic patients: effects of tolazamide treatment.

Granulocyte adherence in 10 of 15 untreated asymptomatic hyperglycemic diabetic outpatients (mean fasting glucose +/- SEM, 289 +/- 16 mg/100 ml) was 62 +/- 7% of control values. After treatment (2--4 wk) with tolazamide (500 mg daily), adherence to the nylon fiber columns employed in this study returned to control levels in the seven patients whose fasting glucose levels fell, (mean, 192 +/- 16 mg/100 ml) and deteriorated in the three in whom fasting hyperglycemia worsened. Results of this study indicate that, even in some mildly diabetic patients, a reduction in granulocyte adherence similar to that found in insulin-dependent diabetics may impair the inflammatory response.

Cell Adhesion↗
PubMed1980

Oral contraceptive steroids and atherosclerosis: lipogenesis in human arterial smooth muscle cells and dermal fibroblasts in presence of lipoprotein-deficient serum from oral contraceptive users.

The incorporation of [14C]-acetate into lipids by cultured human arterial smooth muscle cells and dermal fibroblasts was studied in the presence of lipoprotein-deficient serum from oral contraceptive users (OC) and control women. Exposure to OC serum: 1) significantly increased the synthesis of cholesterol above controls in both fibroblasts (+25-56%) and smooth muscle cells (+28-42%) without a significant change in the synthesis of lecithin; and 2) resulted in increased cholesterol/lecithin ratios in newly synthesized lipids which were higher than controls in both fibroblasts (+50%) and smooth muscle cells (+30%). In vitro addition of the steroid ingredients of the "pill" to the growth medium containing control serum did not result in a stimulation of lipogenesis by the cells. [3H] - mevalonate incorporation into cholesterol was no different with OC and control serum, indicating that the stimulation noted in cholesterol synthesis by OC serum was due to an increased HMG-CoA reductase activity. These findings suggest that increased sterol synthesis in arterial smooth muscle cells of oral contraceptive users may be one pathogenetic factor which adversely influences their risk of atherosclerosis.

Adult↗
PubMed1979

Association of lysolecithin acyltransferase with the high density lipoproteins and its activation by the low density lipoproteins in normal human plasma.

The lysolecithin acyltransferase of human plasma is shown to be associated with the high-density lipoprotein fraction. Although the low density lipoproteins do not have intrinsic enzyme activity, their presence activated the enzyme 3--7-fold. This activation is not affected by heat-treatment of the low density lipoproteins, but is abolished by the addition of heparin.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1979

Polyamines: an unrecognised cardiovascular risk factor in chronic dialysis?

The significance of raised polyamine (P.A.) levels in chronic-dialysis patients is unknown. Since these biologically active substances have hormone-like properties and promote cell-growth in plant and animal tissues, it is possible that they stimulate proliferation of arterial smooth-muscle cells (S.M.C.)--a central process in atherogenesis--and thereby contribute to the rapidly accelerated cardiovascular disease observed during dialysis. Such a role for P.A. is supported by tissue-culture studies, which show not only that P.A.-rich serum from dialysis patients stimulates S.M.C. growth, but also that this mitogenic effect is lost when P.A. are selectively removed from uraemic serum and restored by their addition. Although these observations provide new insights into possible mechanisms of atherogenesis, they are not surprising in view of the many known biological actions of P.A.

Arteries↗
PubMed1979

Chronic renal failure and atherogenesis--Serum factors stimulate the proliferation of human arterial smooth muscle cells.

To assess the role of serum factors in the genesis of accelerated vascular disease in chronic renal failure, human arterial smooth muscle cells (SMC) and dermal fibroblasts were grown in culture and the effects of serum from chronic dialysis patients on cell proliferation was studied. Exposure to serum from these renal failure patients was associated with significantly greater growth of both SMC and fibroblasts than that observed with control serum. A portion of this mitogenic effect appears to be related to the presence of a factor(s) which is heat stable, dialysable, and is contained in the lipoprotein deficient fraction of plasma of density greater than 1.25 g/dl. These findings suggest that circulating substances which stimulate the proliferation of SMC may contribute to accelerated cardiovascular disease in patients undergoing chronic dialysis treatment.

Arteries↗
PubMed1979

Disorders of glucose metabolism in uremia.

Chronic renal failure results in a variety of metabolic derangements that perturb glucose homeostasis. These may in part result from the fact that the kidney plays a prominent role in the metabolism of insulin as well as a number of other low-molecular-weight peptide hormones that affect carbohydrate metabolism. Specific abnormalities in glucose utilization that appear to be related to alterations in membrane receptors, resulting in increased glucagon sensitivity and decreased insulin action, are a newly recognized factor in intolerance to oral glucose. Glucose production and utilization are both abnormally increased in patients with chronic uremia, and these disturbances are only partially corrected by hemodialysis treatment. The mechanism(s) contributing to these changes is unclear, but seems to involve a combination of humoral and cellular factors. These include some degree of insulin resistance, probably inadequately modulated proteolytic responses to glucagon and parathyroid hormone, and a basic defect in energy production that alters intracellular concentrations of high-energy phosphate-containing nucleotides. It is unclear whether these changes in carbohydrate tolerance pose an increased risk for the premature development of cardiovascular disease in patients with renal failure, as they appear to do in the nonuremic population. The occasional patient with renal failure may develop clinical hypoglycemia when glucose utilization continues in a setting in which the hepatic capacity to produce glucose is reduced, probably as a consequence of altered substrate delivery and/or inhibition of one or more key gluconeogenic enzymes.

Blood Glucose↗
PubMed1979

Effects of clofibrate on plasma lipids and high-density lipoprotein levels in renal allograft recipients.

Thirteen successfully transplanted renal patients with normal and elevated plasma lipids were treated as out-patients for two-month intervals with placebo and clofibrate (2 g/day) and whole plasma and lipoprotein triglyceride and cholesterol concentrations were measured. With clofibrate treatment, plasma triglyceride (194 +/- 11 to 157 +/- 10 mg/100 ml; P less than .01) and cholesterol (242 +/- 8 to 212 +/- 8 mg/100 ml; P less than .002) concentrations both decreased significantly despite the continued administration of stable immunosuppressive doses of prednisolone. While the absolute changes in cholesterol in the low and high-density lipoprotein classes varied considerably following clofibrate administration, the ratio of cholesterol in the low and high-density lipoproteins fell from 3.8 to 3.3. This theoretically beneficial anti-atherogenic effect was significant (P less than .01) in male allograft recipients only. These findings indicate that clofibrate treatment favorably influences the cardiovascular risk posed by both qualitative and quantitative disturbances in lipoprotein transport following successful renal allografting.

Cholesterol↗
PubMed1978

Impaired granulocyte adherence. A reversible defect in host defense in patients with poorly controlled diabetes.

When the ability of granulocytes from 10 poorly controlled diabetic patients with fasting hyperglycemia and no evidence of ketoacidosis (mean fasting glucose 293 +/- 20 mg. per 100 ml.; mean +/- S.E.M.) to adhere to a nylon fiber column was assessed, the number of adherent granulocytes from whole blood was only 53 +/- 6 per cent of the values observed in controls. After antidiabetic treatment for one to two weeks and lowering of fasting glucose levels (mean 198 +/- 29 mg. per 100 ml.), adherence improved significantly (p less than 0.01) in the diabetics; however, their values were still subnormal (diabetic 74 per cent +/- 8 of control; p less than 0.02). Adherence values before and after treatment correlated with the fasting glucose level (r = 0.88, p less than 0.001). These findings suggest that, in addition to previously reported abnormalities in migration and the ingestion and killing of bacteria, granulocyte adherence may also be impaired in poorly controlled diabetic patients. This functional abnormality correlates directly with the fasting glucose and is reversed by insulin treatment. A defect of this type may compromise the normal inflammatory response in some diabetics and impair their capacity to resist infection.

Blood Glucose↗
PubMed1978

Hyperlipidemia in renal failure: studies of plasma lipoproteins, hepatic triglyceride production, and tissue lipoprotein lipase in a chronically uremic rat moedl.

To determine whether hypertriglyceridemia in chronic renal failure resulted from altered production and/or removal, Sprague-Dawley rats in which chronic uremia had been induced by five-sixths nephrectomy were studied. In this model, basal plasma TG levels were higher than in controls (uremic 141 +/- 52 mg/100 ml; control 83 +/- 25; mean +/- SD; p less than 0.001) at 1 month after nephrectomy and remained significantly elevated throughout the 10-week duration of study. In the uremic animals hepatic TGSR's (Triton) were not increased (uremic 0.56 +/- 0.11 mg/min; control 0.63 +/- 0.13) and AcCoAc, the rate-limiting enzyme in hepatic lipogenesis, was significantly reduced (control 24.5 +/- 3.8 nM/min/mg protein; uremic 18.2 +/- 1.1; p less than 0.005). The TG removal system--heparin-elutable LPL activities--was similar in control and uremic animals in heart, diaphragm, and adipose tissue. However, serum from both acute and chronically uremic rats lowered adipose LPL activity (P less than 0.01). These observations suggest that in uremia (1) TG production is not increased and (2) the clearance of TG-rich lipoprotein from the circulation is reduced because of a functional impairment in LPL.

Acetyl-CoA Carboxylase↗
PubMed1977

Plasma high-density lipoprotein concentrations in chronic-hemodialysis and renal-transplant patients.

Since epidemiologic studies show that the risk of clinically evident atherosclerosis correlates negatively with concentrations of high-density lipoprotein, we sought to determine whether patients on chronic hemodialysis or recipients of renal transplants had alterations in this lipoprotein similar to those described in other disorders associated with accelerated forms of atherosclerosis. High-density-lipoprotein cholesterol concentrations in both groups of renal patients were significantly lower than control values (P less than 0.01), and their ratios of low-density-lipoprotein to high-density-lipoprotein cholesterol were significantly higher (P less than 0.01) than those observed in both randomly selected controls and in controls matched for plasma lipid levels (control, 2.4 +/- 1.2, dialysis, 3.7 +/- 2.1, and transplant, 5.4 +/- 2.3 mg per 100 ml [mean +/- S.D.]) if, as experimental evidence suggests, high-density lipoprotein retards the development of atherosclerosis, and low-density lipoprotein has opposite effects, the higher ratio of low-density-lipoprotein to high-density-lipoprotein cholesterol found in chronic-dialysis and renal-transplant patients may be related to their premature morbidity and mortality from cardiovascular causes.

Cholesterol↗
PubMed1977

Evidence for an accelerated adaptation to starvation in chronic uremia.

During a 72-hr period of starvation plasma levels of glucose and immunoreactive insulin fell to a greater extent, and alanine, free fatty acid, and glycerol concentrations were higher in fasted chronically uremic rats than in nonuremic controls. These changes, in conjunction with a significant increase in the uremic group's activity of phosphoenolypyruvate-carboxykinase, the rate-limiting enzyme in hepatic gluconeogenesis, after only 12 hr of fasting suggest that alterations in glucose metabolism in uremia may contribute to an exaggeration and acceleration of the metabolic consequences of starvation.

Adaptation, Physiological↗
PubMed1976

Glucocorticoids and triglyceride transport: effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat.

In order to elucidate the mechanism(s) of hyperlipidemia following glucocorticoid administration, dexamethasone (0.125 mg/Kg) was administered daily intramuscularly for 2 wk to male Sprague-Dawley rats and the effects on plasma triglyceride (TG) and cholesterol (Chol), lipoprotein neutral lipids, hepatic triglyceride secretion rates (TGSR; Triton), and epididymal fat lipoprotein lipase (LPL) were determined. Special measures were taken to maintain positive caloric balance and keep the weights of control and dexamethasone-treated animals comparable. Significant increases (p less than 0.001) in TG and very-low density lipoprotein (VLDL) triglyceride associated with no change in Chol and actual reduction in both triglyceride and cholesterol in low density lipoprotein (ldl) were observed in the steroid-treated animals. Dexamethasone treatment was associated with increased basal insulin and glucose levels, an insignificant increment in TGSR, and a highly significant reduction (p less than 0.001) in LPL. These findings suggest that glucocorticoid treatment increases splanchnic triglyceride production rates, but the resulting hypertriglyceridemia is primarily a consequence of impaired VLDL removal due to low adipose tissue LPL activity.

Animals↗