PubMed Health⌕ Search

Biomedical subjects

D Gavish

Publications and source records attributed to D Gavish.

At least 37 records · Page 2Linked to original sources
PubMed1989

Heritable allele-specific differences in amounts of apoB and low-density lipoproteins in plasma.

Low-density lipoprotein (LDL) concentrations correlate with risk of coronary heart disease, and genetic variation affecting LDL levels influences atherosclerosis susceptibility. The principal LDL protein is apolipoprotein B (apoB); apoB is not exchangeable between lipoprotein particles and there is only one apoB per LDL particle. Plasma LDL therefore consists of two populations, one containing apoB derived from the maternal and one from the paternal apoB alleles. Products of the apob gene with high or low affinity for the MB-19 monoclonal antibody can be distinguished, and this antibody was used to identify heterozygotes with allele-specific differences in the amount of apoB in their plasma. A family study confirmed that the unequal expression phenotype was inherited in an autosomal dominant manner and was linked to the apob gene locus. Significant apoB genetic variation affecting plasma LDL levels may be more common than previously appreciated.

Adult↗
PubMed1989

HMG CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels.

Lp(a) is a plasma lipoprotein particle consisting of a plasminogenlike protein [apo(a)] disulfide bonded to the apo B moiety of low-density lipoprotein (LDL). Increased plasma levels of Lp(a), either independently or interactively with LDL levels, have been shown to be a risk factor for atherosclerosis. Recently, a new class of lipid-lowering drugs, HMG CoA reductase inhibitors, have been introduced. These drugs act by decreasing liver cholesterol synthesis resulting in up-regulation of LDL receptors, increased clearance of LDL from plasma, and diminution of plasma LDL levels. In this study, we examined the effect of HMG CoA reductase inhibitors on Lp(a) levels in three groups of subjects, five volunteers and two groups of five and 14 patients. In all 24 subjects, mean decreases were observed in total cholesterol (43 +/- 5%), total triglyceride (35 +/- 8%), very low-density lipoprotein (45 +/- 9%), and LDL cholesterol (43 +/- 5%). The mean change in high-density lipoprotein cholesterol was an increase of 7 +/- 8%. Despite the very significant decrease in LDL cholesterol levels (p less than 0.001), Lp(a) levels increased by 33 +/- 12% (p less than 0.005). This was not associated with a measurable change in the chemical composition or size of the Lp(a) particle. This emphatically suggests that Lp(a) particles, despite consisting principally of LDL, are cleared from plasma differently than LDL. The surprising finding of an increase in Lp(a) levels suggests this class of drugs may have a direct effect on Lp(a) synthesis or clearance independent of its effect on LDL receptors.

Adult↗
PubMed1989

Plasma Ip(a) concentration is inversely correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene.

Plasma Lp(a) levels correlate with atherosclerosis susceptibility. This lipoprotein consists of an LDL-like particle attached to a large glycoprotein called apo(a). Apo(a) is a complex glycoprotein containing multiple Kringle domains, found to be highly homologous to plasminogen Kringle IV, and a single Kringle domain homologous to plasminogen Kringle V. Lp(a) levels appear to be inversely correlated with apo(a) size in a given individual. In this study, we have used probes specific to the Kringles IV and V domains of apo(a) cDNA in quantitative Southern blotting analysis. By this method, we have determined the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene of 53 unrelated individuals with different plasma concentrations of Lp(a). This ratio was found to be inversely correlated with log Lp(a) levels (r = -0.90, P less than 0.0001) and directly correlated with apo(a) apparent molecular weight (Mr) (r = 0.79, P less than 0.0001). In summary, by showing that Lp(a) concentrations and apo(a) apparent size are highly correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene, we provide a DNA marker for this atherosclerosis risk factor as well as an important insight into the genetic mechanism regulating Lp(a) levels.

Apolipoproteins A↗
PubMed1988

Interactions between human and carp (Cyprimus carpio) low density lipoproteins (LDL) and LDL receptors.

1. We have compared the concentration and chemical composition of carp and human plasma lipoproteins and studied their interaction with human fibroblast LDL receptors. 2. The main lipoproteins in carp are of high density (HDL) in contrast to low density lipoproteins (LDL) in human. 3. Carp lipoproteins are devoid of apolipoprotein (apo) E, a major ligand for interaction with LDL receptors in mammals. 4. Carp very low density lipoproteins (VLDL) and LDL but not HDL nor apoA-I cross react with human LDL in their interaction with LDL receptors on human cultured fibroblasts. 5. Carp liver membranes possess high affinity receptors that are saturable and have calcium dependent ligand specificity (apoB and apoE) similar to human LDL receptor. Carp VLDL and LDL but not HDL nor its major apolipoprotein complexed to L-alpha-phosphatidylcholine dimyristoyl (apoA-I-DMPC) competed with the specific binding of human LDL to this receptor.

Adult↗
PubMed1987

Diurnal variations of plasma lipids, tissue and plasma lipoprotein lipase, and VLDL secretion rates in the rat. A model for studies of VLDL metabolism.

Circadian rhythms of plasma lipids and lipoproteins, lipoprotein lipase activities and VLDL secretion rates were studied in fed and food-deprived (12 h) male rats after a light/dark synchronization of 14 days. In ad libitum fed rats, a circadian rhythm of plasma triacylglycerol, blood glucose and liver glycogen was clearly identified. A rhythm was also identified for plasma cholesterol, but not phospholipids. The peak of plasma triacylglycerol occurred 2 h after the beginning of the light period (7.00 a.m.), and the nadir, 2 h after the beginning of the dark period (7.00 p.m.). The differences of plasma triacylglycerol at these two circadian stages were even more pronounced in food-deprived rats and were confined to the very-low-density lipoprotein (VLDL) fraction. Plasma post-heparin and heart and muscle lipoprotein lipase activities were 50-100% higher at 7.00 p.m., the time when plasma triacylglycerol were lowest, as compared to 7.00 a.m. Plasma post-heparin hepatic lipase and adipose tissue lipoprotein lipase activities, in contrast, did not change. VLDL secretion rates were somewhat higher at 7.00 a.m. compared to 7.00 p.m., but this difference was not significant. It is concluded that physiological variation of heart and muscle lipoprotein lipase together with small differences of VLDL secretion rates are responsible for normal range oscillations of plasma VLDL triacylglycerol levels.

Animals↗
PubMed1987

Bulimia. An underlying behavioral disorder in hyperlipidemic pancreatitis: a prospective multidisciplinary approach.

Between 1978 and 1985, we conducted a prospective study of 21 patients who survived several attacks of pancreatitis and were diagnosed as having primary hyperlipidemia. None of the patients suffered from chronic alcoholism, primary diabetes, or cholelithiasis or was receiving prolonged steroid therapy. Lowering of plasma lipid values toward normal was achieved in all patients following a program of combined dietary and drug (bezafibrate) therapy. Five patients had recurrent episodes of pancreatitis during the treatment program. These patients were diagnosed subsequently as suffering from bulimia and were all given cognitive behavioral therapy. One patient died following an attack of pancreatitis. An underlying eating disorder should be suspected in patients who relapse after treatment for pancreatitis and hyperlipidemia. Multidisciplinary treatment should be used in these patients to improve therapeutic efficacy and uncover behavioral patterns that have a direct impact on their life expectancy.

Adult↗
PubMed1987

Infection with Streptococcus milleri.

Streptococcus milleri is unique among the viridans streptococci because it produces abscesses. Five serious S. milleri infections were seen in our hospital in 1 year. The English literature dealing with S. milleri was reviewed. An infection caused by S. milleri is often associated with a gastro-intestinal source. Thus, the speciation of viridans streptococci from pus or blood cultures is clinically relevant. The identification of S. milleri from blood cultures suggests the possibility of serious purulent infection, the source of which may lie in the gastro-intestinal tract. The resultant clinical approach to S. milleri infection is discussed.

Abscess↗
PubMed1987

Hypolipidemic therapy modulates expression of apolipoprotein B epitopes on low density lipoproteins. Studies in mild to moderate hypertriglyceridemic patients.

Low density lipoproteins (LDL) of untreated moderate to severe hypertriglyceridemic patients (HTG-LDL) are smaller in size and are relatively enriched in triglycerides and proteins compared with normal LDL (N-LDL). HTG-LDL also manifest defective binding to the LDL receptors of normal cultured human fibroblasts. These structural and functional defects are reversible by effective hypolipidemic therapy. The aims of the present study were to confirm the reversibility of the structural and functional defects in mild to moderate hypertriglyceridemic patients and also to test the hypothesis that therapy improved the binding of HTG-LDL to cells by modulating epitopes of apolipoprotein B (apoB-100) on the surfaces of LDL particles. Fasting plasma samples were obtained from five mild to moderate hypertriglyceridemic patients before and 3 weeks after bezafibrate therapy when mean triglyceride levels were 436 and 157 mg/dl (P less than 0.01), respectively. LDL particles were isolated by zonal ultracentrifugation, characterized chemically, and assayed for cell association and proteolytic degradation in-up regulated normal human skin fibroblasts. LDL immunoreactivity was tested in solid phase competitive binding radioimmunoassays (RIA) using three monoclonal antiLDL antibodies (Mab). Mab 464B1B3 and Mab 465B6C3 react against epitopes in the COOH-terminal (T2/K4) fragment of apoB-100. Mab D7.1 reacts with an epitope in the midportion (T3/K3) fragment. Mab 464B1B3 inhibits the binding of LDL to the LDL receptor. Hypolipidemic treatment altered the composition of LDL. Mean LDL triglycerides fell from 9.4 to 5.8% of LDL mass (P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1987

In vivo conversion of human HDL3 to HDL2 and apoE-rich HDL1 in the rat: effects of lipid transfer protein.

In this study we determined in vivo conversions of human 3H-labeled cholesteryl ester-labeled HDL3 [( 3H]CE-HDL3) in male rats and the effects of partially purified lipid transfer protein on the conversion processes. Zonal centrifugation techniques were used to prepare the [3H]CE-HDL3 and to follow the conversion processes. One hour after the injection, a complete conversion of HDL3 to the HDL2-density species was found. With time, [3H]CE separated with apoE-rich HDL1 and, by 18 hr, 35.9% of plasma radioactivity was associated with the apoE-rich HDL1 lipoprotein fraction. In vitro incubation of [3H]CE-HDL3 in rat plasma reproduced in part the HDL3----HDL2 conversion, but no movement of radioactivity to HDL1 was observed. Injection of the rats with partially purified lipid transfer proteins induced [3H]CE exchange between lipoproteins. The conversion of HDL3 to HDL2, however, was minimally affected. Formation of [3H]CE-HDL1, in contrast, was reduced to about one-half of that found in control animals. It is concluded that in vivo conditions are necessary for conversions of HDL3 (and HDL2) to HDL1, and that lipid transfer reactions delay this process.

Animals↗
PubMed1986

Quinidine-induced hepatitis. A common and reversible hypersensitivity reaction.

In a retrospective survey of drug-induced hepatitis during a ten-year period, we found that quinidine sulfate was the most common offending agent. We analyzed the clinical and laboratory data of the 33 cases of quinidine-induced hepatitis and noted the following: (1) It is an easily recognized drug reaction, because, in most patients, fever preceded liver damage. (2) The clinical picture usually includes fever and sometimes is accompanied by gastrointestinal symptoms, rash, and thrombocytopenia, which resolved after discontinuation of drug therapy, but reappeared promptly after a rechallenge. (These features suggest a hypersensitivity mechanism.) (3) The histologic findings of the liver biopsy specimens consisted of portal and parenchymal, acute and chronic hepatitis, combined with granulomas. (4) In a long-term follow-up study of 15 patients, no liver function abnormalities were found. We thus conclude that quinidine-induced hepatitis, when recognized early, is a reversible drug reaction.

Adult↗
PubMed1986

Change in very low-, low-, and high-density lipoproteins during lipid lowering (bezafibrate) therapy: studies in type IIA and type IIb hyperlipoproteinaemia.

The effects of lipid lowering therapy (bezafibrate) on plasma lipoproteins was investigated in twelve patients with familial hypercholesterolaemia (type IIA) and eight with familial combined hyperlipidaemia (type IIB). Bezafibrate caused a decrease of plasma cholesterol, plasma triglycerides, plasma apolipoprotein B, VLDL cholesterol and LDL cholesterol and an increase of HDL cholesterol. Post-heparin plasma lipoprotein and hepatic lipase activities increased in both groups (significant only in type IIB). Lipoprotein composition showed the following changes: Increased protein and phospholipids and decreased triglycerides and cholesteryl esters in VLDL. Decreased protein and triglycerides and increased free and esterified cholesterol in LDL. Decreased triglycerides and increased phospholipids in HDL. Cholesteryl ester to protein ratios decreased in VLDL and increased in LDL. The hydrated density of LDL (both groups) and of HDL3 (type IIB) decreased following bezafibrate therapy. These changes were in general similar to those observed in hypertriglyceridaemic patients and could be ascribed, at least in part, to the increase of plasma lipase activities and the decrease of lipid transfer reactions. Comparing the present data with that previously reported, it was found that bezafibrate caused decreased LDL cholesterol in types IIA and IIB but increased levels in type IV. This change was correlated with the initial plasma triglycerides (r = 0.74, P less than 0.0001) and initial plasma LDL cholesterol (r = 0.66, P less than 0.001). It is concluded that varied response of LDL to therapy reflects a complex interaction of metabolic events, including changing rates of VLDL conversion to LDL, lipoprotein compositional changes and effects of therapy on LDL degradation rates.

Adult↗
PubMed1986

Methemoglobinemia, muscle damage and renal failure complicating phenazopyridine overdose.

A 19-year-old woman with no history of renal or hematologic dysfunction developed methemoglobinemia, muscle damage, rhabdomyolysis and severe acute renal failure after an overdose of phenazopyridine hydrochloride (pyridium). The methemoglobinemia reversed after 24 h, but the patient remained oliguric, with myalgia and increased muscle enzymes. The patient received supportive treatment and recovered completely after 3 weeks. Since phenazopyridine is a commonly used drug, the physician should be alert to these possible severe complications.

Acute Kidney Injury↗
PubMed1985

Guillain-Barré syndrome: a possible extraintestinal manifestation of ulcerative colitis.

In two elderly patients with ulcerative colitis, acute Guillain-Barré syndrome developed while the inflammatory bowel disease was in remission. The patients were treated with corticosteroids and recovered. Since both disorders are relatively uncommon, we suggest that the Guillain-Barré syndrome may have been causally related to the preexisting chronic inflammatory bowel disease. Guillain-Barré syndrome may be regarded as a possible extraintestinal complication of chronic ulcerative colitis.

Adrenal Cortex Hormones↗
PubMed1985

Early and late onset ulcerative colitis: distinct clinical features.

A review of 93 patients with ulcerative colitis revealed that in 47 (50.5%) symptoms first appeared between 21 and 30 years of age--"early-onset"--and in 26 (27.9%) at the age of 51 years or above--"late-onset." Proctocolitis was more common in late-onset patients (p = 0.077) and in males of both age groups (p = 0.002). Extensive colitis was significantly more common in females (p = 0.002). Patients with late-onset proctocolitis had more bowel movements/day and liver involvement than patients with early-onset disease. The first episode of proctocolitis was more protracted and the ensuing remission of shorter duration in late-onset patients. Most patients with early-onset disease improved on steroid enemas, whereas most patients with late-onset disease required systemic corticosteroid therapy (p = 0.0028). Female patients with early-onset proctocolitis tended to be more severely afflicted than males, with an increased incidence of weight loss, leukocytosis, increased erythrocyte sedimentation rate (ESR), and need for systemic corticosteroid therapy. We conclude that late-onset ulcerative colitis is distinct from early-onset disease in its relative refractoriness to therapy and its predilection for distal colonic involvement.

Adult↗
PubMed1985

Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts. Normalization with bezafibrate therapy.

The metabolism of hypertriglyceridemic low density lipoprotein (HTG-LDL) was investigated in upregulated cultured human skin fibroblasts. Low density lipoprotein (LDL) was isolated by zonal centrifugation from the plasma of seven HTG subjects, before and 2 wk after the initiation of bezafibrate (BZ) therapy. HTG-LDL is a cholesterol-poor, triglyceride-rich lipoprotein of smaller diameter than BZ-LDL or normal LDL (N-LDL). Binding, cell association, and proteolytic degradation of HTG-LDL were compared with that of BZ-LDL and N-LDL and were found to be significantly lower by a paired t test analysis (P less than 0.001). After 6 h preincubation with unlabeled HTG-LDL, the incorporation of [14C]acetate to sterols was significantly higher than with BZ-LDL or N-LDL (577 +/- 43.7; 330 +/- 41.5; 262 +/- 47, mean +/- SE, picomoles sterols per milligram cell protein per 2 h, respectively; P less than 0.001 by paired t test). To determine the effectiveness of HTG-LDL and BZ-LDL on the down-regulation of LDL receptor activity, up-regulated cells were incubated for 48 h with HTG-LDL and BZ-LDL. LDL receptor activity was significantly higher after preincubation with HTG-LDL compared with BZ-LDL, and the rates of sterol synthesis were similarly increased. These results demonstrate that HTG-LDL does not down-regulate the LDL receptor activity as efficiently as BZ-LDL and that its cholesterol content is not enough to adequately suppress cellular sterol synthesis. Significant correlation between LDL composition and cholesterol synthesis by cultured cells was found with all LDL preparations over a wide range of cholesteryl ester to protein ratio (0.8-2.2). This correlation indicates that the compositional and structural abnormalities of HTG-LDL, and especially the low cholesterol content of the lipoprotein, alter LDL metabolism and cellular cholesterol formation.

Bezafibrate↗