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Biomedical subjects

H Ginsberg

Publications and source records attributed to H Ginsberg.

At least 37 records · Page 2Linked to original sources
PubMed1984

Diet and the decrease of coronary heart disease.

Total plasma cholesterol is a powerful predictor of death related to coronary heart disease (CHD). Strong evidence indicates that reducing the plasma cholesterol level results in in a decrease in the expected incidence of CHD. The decline in the death rate from CHD in the U.S. population over the past 2 decades has occurred simultaneously with a reduction in the consumption of cholesterol and saturated fat and a dramatic increase in the use of unsaturated vegetable oils. Over the same period, the mean cholesterol level has decreased at least 5%. This finding explains up to one-third of the decline in CHD mortality observed since 1968.

Adult↗
PubMed1984

Very low-density lipoprotein metabolism in an unusual case of lipoatrophic diabetes.

Complete acquired lipoatrophic diabetes (LD) is characterized by nonketotic insulin-resistant diabetes, elevated very low-density lipoprotein (VLDL) triglyceride (TG) levels, and absent subcutaneous fat. We studied a young child in whom LD atypically developed after the onset of type 1 diabetes mellitus. On uncontrolled home diet the patient had triglyceride levels over 1,000 mg/dL on multiple occasions. In order to demonstrate the effects of caloric and dietary-fat restriction on VLDL metabolism, 3H-glycerol and autologous 125I-VLDL were used to quantitate the turnover of VLDL-TG and VLDL-apolipoprotein B (apo B) during two periods of caloric restriction. Consumption of a 900-kcal 40-g fat diet resulted in a plasma triglyceride level of 1383 mg/dL (ten-fold elevation). This hypertriglyceridemia was associated with markedly increased production rates of both VLDL-TG (73.7 mg/kg/h) and VLDL-apo B (126.9 mg/kg/d). Consumption of a 900-kcal 25-g fat diet resulted in a plasma TG level of 663 mg/dL. This reduction in plasma TG was associated with a 40% decrease in VLDL-TG production rate (PR) (45.1 mg/kg/h). There was no change in the production rate (PR) of VLDL-apo B. The hypertriglyceridemia in this patient was due to marked over production of VLDL. Furthermore, the studies demonstrate: (1) the independent benefits of caloric and dietary-fat restriction in the treatment of LD, and (2) that fat restriction lowered plasma triglyceride by its effect on the VLDL-TG production rate.

Apolipoproteins↗
PubMed1984

The effect of chronic hypocholesterolemia in myeloproliferative disease on the distribution of plasma and erythrocyte tocopherol.

The presence of hypocholesterolemia and increased erythrocyte lipid peroxidation susceptibility in myeloproliferative disorders raised the possibility of coexistent tocopherol deficiency. Plasma and red blood cell (RBC) alpha-tocopherol, beta- + gamma-tocopherol, and free cholesterol were determined simultaneously by high performance liquid chromatography in 22 patients and 26 controls. Plasma alpha-tocopherol was correlated most highly with plasma free cholesterol and secondarily with RBC alpha-tocopherol in both groups. Plasma-free cholesterol and alpha-tocopherol were significantly reduced in myeloproliferative disease, although the ratio between the two remained normal. Erythrocyte tocopherol and free cholesterol concentrations were normal in myeloproliferative disease. High relative retention of tocopherol by erythrocytes was most pronounced in patients with the lowest plasma alpha-tocopherol and free cholesterol levels. The normal RBC tocopherol levels in these patients with chronic hypocholesterolemia indicate that the observed increase in RBC peroxidation susceptibility is not explainable by a deficiency of RBC vitamin E.

Cholesterol↗
PubMed1984

Reduced plasma concentrations of total, low density lipoprotein and high density lipoprotein cholesterol in patients with Gaucher type I disease.

Plasma lipid and serum apoprotein concentrations were determined in twenty-nine individuals with Gaucher type I disease. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were all significantly reduced in the patients with Gaucher disease compared to a group of matched control subjects. Total, LDL and HDL cholesterol were lower in males than in females with Gaucher disease. These sex differences appeared to be inversely correlated with the severity of disease manifestations which were greater in the males. Serum levels of apoprotein-B and apoprotein-AI, the major structural apoproteins of LDL and HDL, respectively, were decreased in the subjects with Gaucher disease. Thus, the reductions in LDL and HDL cholesterol were associated with reduced numbers of lipoprotein particles in plasma. In contrast, apoprotein-E, a protein which is secreted by several tissues, including activated macrophages and which may mediate hepatic catabolism of lipoproteins, was elevated in the patients. Since macrophages may also catabolize lipoproteins, Gaucher disease may serve as a model for the effect of activated macrophages upon human lipoprotein metabolism.

Adolescent↗
PubMed1984

Evidence that the penton base of adenovirus is involved in potentiation of toxicity of Pseudomonas exotoxin conjugated to epidermal growth factor.

When KB cells are incubated for 1 h with human adenovirus type 2 or type 5 (1 microgram/ml) and a conjugate of epidermal growth factor and Pseudomonas exotoxin (EGF-PE), protein synthesis is inhibited by 80 to 90%. Under these conditions, neither adenovirus nor EGF-PE alone has any effect on host protein synthesis. Thus, adenovirus enhances the toxicity of EGF-PE. A number of antibodies to intact virus and capsid components were tested for their ability to block the enhancing activity and virus uptake. At appropriate dilutions, antibodies prepared against intact virus and penton base blocked the enhancing activity without affecting virus uptake. Antibodies against hexon and fiber blocked virus uptake and enhancing activity in parallel. These studies suggest that the penton base is important in lysis of the vesicles which contain adenovirus and EGF-PE, and this base allows virus and toxin to enter the cytoplasm.

Adenoviruses, Human↗
PubMed1984

Increased erythrocyte susceptibility to lipid peroxidation in myeloproliferative disorders.

The recognition of abnormal lipoprotein metabolism that produces chronic hypocholesterolemia in myeloproliferative disorders and the known influence of altered plasma lipid levels on erythrocyte membranes prompted a study of erythrocyte susceptibility to lipid peroxidation in myeloproliferative disease. Malonyldialdehyde generation during an oxidant challenge of erythrocyte suspensions of standardized hemoglobin concentration with H2O2 was significantly greater in 32 patients with myeloproliferative disease than in 47 hematologically normal subjects. The myeloproliferative disease group had significantly lower plasma total, HDL-, and LDL-cholesterol, erythrocyte indices, and erythrocyte deformability, and higher reticulocyte counts and serum lactic dehydrogenase. In the myeloproliferative disease group, mean corpuscular hemoglobin concentration, reticulocyte count, and erythrocyte count were significant variables in accounting for the observed variation in peroxidation susceptibility. Erythrocytes of patients with myeloproliferative disease had elevated concentrations of reduced glutathione, normal glutathione stability, and normal alpha-tocopherol content. These studies demonstrate increased susceptibility to oxidative damage in myeloproliferative disease despite normal or increased concentrations of the major antioxidant compounds of the erythrocyte. The presence of reticulocytosis, elevated serum lactic dehydrogenase, and decreased erythrocyte deformability suggests that lipid peroxidation susceptibility is associated with in vivo hemolysis and may contribute to the anemia that complicates myeloproliferative disease.

Cholesterol↗
PubMed1983

Hypocholesterolemia as a manifestation of disease activity in chronic myelocytic leukemia.

A patient with chronic myelocytic leukemia and hypocholesterolemia displayed marked fluctuations in plasma cholesterol in response to several therapeutic maneuvers. During chemotherapy there was a reciprocal relation between low density lipoprotein (LDL) cholesterol levels and the degree of leukocytosis and splenomegaly. LDL cholesterol increased after splenectomy, but continued to cycle inversely with the leukocyte count. Receptor-mediated degradation of 125I-labeled LDL (125I-LDL) by mononuclear cells in vitro also showed cyclical changes which were unrelated to the number of immature myeloid cells in the population or the level of plasma cholesterol. 125I-LDL degradation rate was normal or slightly increased during relapse and after remission was achieved, but was greatly increased when tested during periods of remission induction. This patient illustrates that significant changes in plasma total and LDL cholesterol occur in chronic myelocytic leukemia in association with alterations in proliferative state. Tumor load, the presence of an enlarged spleen, and changes in lipid metabolism of circulating cells all appear to contribute to the reduction in LDL cholesterol levels.

Adult↗
PubMed1982

Very low density lipoprotein metabolism in non-ketotic diabetes mellitus: effect of dietary restriction.

We have measured the turnover of very low density lipoprotein (VLDL) triglyceride as well as plasma glucose, insulin and non-esterified fatty acid levels in nine mildly obese non-ketotic, insulinopenic diabetic subjects before and during an energy restricted diet. During the baseline period, subjects were hypertriglyceridaemic, hyperglycaemic and insulinopenic. During dietary restriction (mean weight loss: 2.3 +/- 0.4 kg) plasma triglyceride fell from 8.4 +/- 3.0 to 3.4 +/- 0.89 mmol/l (mean +/- SEM: p less than 0.05), and plasma glucose fell from 13.9 +/- 1.7 to 9.8 +/- 1.4 mmol/l (p less than 0.01). Neither fasting plasma insulin nor the insulin response to an oral glucose load changed. Plasma non-esterified fatty acid concentrations remained constant as well. During the baseline period, the transport rate of VLDL-triglyceride in the diabetic subjects was more than twice that in an age-weighted matched control group (27.4 +/- 2.9 versus 12.1 +/- 0.8 mg/kg ideal body weight per h). The fractional catabolic rates were similar in the two groups (0.20 +/- 0.05 versus 0.21 +/- 0.02/h). During energy restriction of the diabetic subjects, the VLDL-triglyceride transport rate fell to 17.4 +/- 2.9 mg/kg ideal body weight per h (p less than 0.05 versus baseline) while the fractional catabolic rate remained constant at 0.21 +/- 0.06/h (NS versus baseline). These data indicate that the major abnormality in triglyceride metabolism in these non-ketotic, insulinopenic diabetic patients was over-production of VLDL-triglyceride.

Aged↗
PubMed1982

Metabolism of cholesterol and plasma triglycerides in nonketotic diabetes mellitus.

The metabolism of cholesterol and plasma triglycerides (TG) was studied in 14 diabetic men: these patients did not have marked obesity nor did they develop ketoacidosis without insulin. Before insulin therapy, measurements were made of (1) plasma lipoproteins, (2) postheparin lipolytic enzymes, (3) turnover to TG in very-low-density lipoproteins (VLDL) and chylomicrons, (4) cholesterol balance, and (5) biliary lipids. After baseline measurements, the patients were treated with enough long-acting insulin to maintain their fasting plasma glucose in the range of 100--125 mg/dl. When plasma glucose and lipid levels reached a new steady state, all of the above measurements were repeated. Before insulin, most patients had fasting hypertriglyceridemia. This was due mainly to overproduction of VLDL-TG. Insulin therapy lowered both synthesis and concentrations of VLDL-TG to near normal. Also, patients with normotriglyceridemia, both before and during insulin therapy, had essentially normal clearance of chylomicrons. Those with high fasting TG had delayed clearance of chylomicrons, but clearance returned to normal in most with insulin therapy. Postheparin lipolytic enzymes were not decreased. Before insulin, synthesis rates of cholesterol and bile acids usually were greater than normal, and bile commonly was supersaturated with cholesterol. During insulin therapy, synthesis of both cholesterol and bile acids remained elevated, possibly because of imperfect control of hyperglycemia. Furthermore, saturation of bile with cholesterol was accentuated by insulin therapy.

Aged↗
PubMed1982

Increased low-density-lipoprotein catabolism in myeloproliferative disorders.

Hypocholesterolemia reported in patients with myeloproliferative disorders prompted our investigation of lipoprotein metabolism in these patients. The production and fractional catabolic rates of very-low-density lipoprotein (VLDL) apoprotein-B were measured using 131I-VLDL; those of VLDL triglyceride, using 3H-glycerol; and those of low-density lipoprotein (LDL) apoprotein-B, using 125I-LDL. Plasma total and LDL cholesterol levels (mean +/- SD) were significantly reduced in seven patients with myeloproliferative diseases, compared to five normal subjects (93.1 +/- 20.3 mg/dL versus 166.8 +/- 24.6 mg/dL and 50.3 +/- 14.8 mg/dL versus 107 +/- 20.8 mg/dL, respectively). The production rates of VLDL apoprotein-B and VLDL triglyceride were normal in the patients. The fractional catabolic rate of LDL apoprotein-B was increased in the patients with myeloproliferative diseases (0.89 +/- 0.32/d versus 0.52 +/- 0.10/d; p less than 0.05); this increased rate was associated with reduced plasma LDL apoprotein-B levels (41.7 +/- 7.1 mg/dL versus 57.0 +/- 11.3 mg/dL; p less than 0.05) despite normal or elevated LDL apoprotein-B production (16.7 +/- 5.3 mg/kg body weight . d versus 12.9 +/- 1.2 mg/kg body weight . d). The site (or sites) of increased LDL catabolism in these hypocholesterolemic patients with myeloproliferative disorders is under investigation.

Adult↗
PubMed1981

Characterization of hypocholesterolemia in myeloproliferative disease. Relation to disease manifestations and activity.

Characterization of the hypocholesterolemia observed in polycythemia vera and agnogenic myeloid metaplasia revealed significant reductions in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol in an age- and sex-matched comparison with the Framingham population. Men with myeloproliferative disease also had significantly lower total and LDL cholesterol levels than did those with relative or secondary polycythemia. LDL and HDL cholesterol were significantly correlated, suggesting a generalized disturbance of cholesterol metabolism, unexplained by nutritional status. Evaluation of the relationship among hematic cell proliferation, degree of myeloid metaplasia and hypocholesterolemia by multiple regression analysis revealed that spleen size was the variable of most significance in explaining the variation in plasma total, LDL and HDL cholesterol levels. Uncontrolled disease activity was accompanied by a decline in LDL cholesterol levels. Splenectomy or control of proliferation with chemotherapy or splenic irradiation reversed this abnormality. Levels of plasma total and lipoprotein cholesterol provide information that may be of value in diagnosis and assessment of myeloproliferative disease activity.

Aged↗
PubMed1981

Metabolism of plasma triglycerides in hypothyroidism and hyperthyroidism in man.

Studies on plasma triglycerides (TG) were performed in 10 nonobese and 16 obese patients with hypothyroidism and in 13 with hyperthyroidism. Nonobese, hypothyroid patients generally had normal levels of TG, but obese patients often had hypertriglyceridemia. In most hypothyroid patients 1-thyroxine treatment lowered plasma TG, and most hyperthyroid patients had low TG. One mechanism whereby thyroid hormones might decrease plasma TG could be to increase lipoprotein lipase (LPL). However, post-heparin LPL was not increased after therapy, nor was it increased in hyperthyroid patients. In contrast, hypothyroid patients had abnormally low levels of post-heparin hepatic triglyceride lipase. In hypothyroid patients without hypertriglyceridemia, clearance of chylomicrons was normal. A few obese, hypothyroid patients with fasting hypertriglyceridemia had low clearance of chylomicrons, which may have been due in part to competition for removal of excess endogenous TG. Thus, no evidence was obtained for a significant abnormality in chylomicron metabolism in hypothyroidism. Nonobese, hypothyroid patients had normal synthesis and clearance of very low density lipoprotein (VLDL)-TG. In contrast, VLDL-TG synthesis was increased in 8 obese, hypothyroid patients, and fractional clearance rates were relatively low compared to obese, euthyroid subjects. In striking contrast, hyperthyroid patients had remarkable facility in clearing VLDL-TG. Thus, TG metabolism is not grossly deranged in hypothyroidism, but thyroid hormones apparently can promote catabolism of VLDL.

Adult↗
PubMed1980

Order of polyadenylic acid addition and splicing events in early adenovirus mRNA formation.

A study of the processing of mRNA from two early adenovirus type 2 transcription units (regions 2 and 4 of adenovirus type 2 genome; [J. Flint, Cell 10:153--166, 1977]) revealed that polyadenylic acid [poly(A)] was added in most if not all cases to an unspliced nuclear RNA molecule whose coordinates extended from the apparent initiation site for RNA synthesis to the single poly(A) site in each transcription unit. An intermediate RNA molecule in the processing of the mRNA for the 72,000-M, single-stranded DNA binding protein showed that the first of the two intervening sequences, the one closest to the 5' end of the molecule, was removed first at least in the majority of the processed molecules. Finally, in cells labeled for 10 min and then treated with actinomycin D to stop further RNA synthesis, the majority, if not all, of the poly(A)-terminated nuclear RNA specific for region 2 was successfully processed and transported to the cytoplasm.

Adenoviruses, Human↗
PubMed1980

Dissociation of apoprotein B and triglyceride production in very-low-density lipoproteins.

As a first step toward understanding the regulation of apoprotein B (apoB) secretion in man, we have simultaneously studied the production of very-low-density lipoprotein (VLDL) apoB and VLDL triglycerides (TG) in six subjects with plasma TG levels of 153-344 mg/dl, during consumption of control and high-carbohydrate diets. 125I-labeled VLDL and [3H]glycerol were injected intravenously, and blood samples obtained over a 48-h period were used to isolated VLDL 125I-labeled apoB and VLDL 3H-labeled TG. The complex radioactivity curves obtained were analyzed by a multicompartmental model of VLDL metabolism. In accord with previous data, plasma VLDL TG levels were increased in five of six subjects (mean increase of 76% for the group), and in four of the six subjects the VLDL apoB concentrations were increased significantly during the high-carbohydrate period. The estimated rate of secretion of VLDL TG was higher in all six subjects, from 9.4 to 23.5 mg/kg-1 X h-1 on the control diet to 14.0-65.5 mg X kg-1 X h-1 on the carbohydrate diet (P < 0.001). In contrast, there was no increase in the rate of secretion of VLDL apoB in any of the subjects compared to their control period with values ranging from 0.60 to 1.59 mg X kg-1 X h-1 during the control period to 0.63-1.47 mg X kg-1 X h-1 after carbohydrate induction. These results indicate that physiological perturbations of VLDL TG production need not be accompanied by an alteration in VLDL apoB production.

Adult↗
PubMed1976

Induction of hypertriglyceridemia by a low-fat diet.

We have studied the effects of moderate dietary fat restriction on plasma triglyceride, cholesterol, glucose, and insulin response in 27 subjects. Compared with a control diet (45% fat, 40% carbohydrate [CHO], 15% protein) the low fat (higher CHO) diet (30% fat, 55% CHO, 15% protein) produced a 41% increase in fasting triglyceride level (155 +/- 17 to 219 +/- 23 mg%) with no change in fasting plasma cholesterol level. Furthermore, this increase in triglyceride levels; induced by the higher CHO content of the low fat diet, was seen in 26 out of 27 subjects. Postprandial triglyceride, glucose, and insulin levels were also higher on the low fat (higher CHO) diet. Since hypertriglyceridemia is a significant risk factor for the development of coronary heart disease, and since our data indicate that the moderate increase in dietary CHO associated with a low fat diet will elevate plasma triglyceride levels, we believe that more caution is necessary before recommending the wide-spread use of low fat diets for heart disease prevention.

Adult↗