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Biomedical subjects

T Chajek-Shaul

Publications and source records attributed to T Chajek-Shaul.

At least 55 records · Page 3Linked to original sources
PubMed1989

Mechanism of the hypertriglyceridemia induced by tumor necrosis factor administration to rats.

4 h after intravenous injection of recombinant HuTNF-alpha to fed rats, an increase in heart, diaphragm, and plasma lipoprotein lipase activity was observed. At the same time, a 40-60% decrease in enzymic activity in epididymal fat pad and kidney and 40% decrease in hepatic lipase activity in liver had occurred. Similar results were obtained 20 h after injection of recombinant HuTNF-alpha into fasted rats. Pretreatment with Indomethacin did not affect the changes in tissue lipoprotein lipase activity observed following recombinant HuTNF-alpha administration. Serum triacylglycerol concentration increased by 2- and 6-fold; 4 and 20 h after recombinant HuTNF-alpha administration. Disappearance of 14C-labeled triacylglycerol from the circulation after injection of small chylomicrons, biosynthetically labeled in their triacylglycerol and cholesterol moieties, was lower in TNF-treated than in control rats. However, the clearance rate of triacylglycerol was the same or even higher in recombinant HuTNF-alpha treated rats (assuming that 14C-labeled chylomicron triacylglycerol represents the serum triacylglycerol pool). The livers of recombinant HuTNF-alpha-treated rats and controls contained similar amounts of 14C-labeled lipids, but less [3H]cholesterol, suggesting that in recombinant HuTNF-alpha-treated rats, the liver took up chylomicron remnant particles enriched with triacylglycerol. Separation of the d less than 1.04 g/ml fraction of serum obtained from control and recombinant HuTNF-alpha treated rats by zonal ultracentrifugation revealed that in recombinant HuTNF-alpha-treated rats the lipoprotein particles were less lipolyzed than in controls. The secretion rate of [3H]triacylglycerol into the serum was determined 90 min after injection of [3H]palmitate albumin complex and Triton WR 1339. In recombinant HuTNF-alpha-treated rats, the secretion of [3H]triacylglycerol into plasma was 48% higher than in controls. It is suggested that the increase in lipoprotein lipase activity of heart and diaphragm resulted from an indirect effect of TNF. It is concluded that the increase in serum triacylglycerol in the recombinant HuTNF-alpha-treated rats is due mainly to an increased secretion of triacylglycerol by the liver. Impaired lipolysis, probably due to a fall in hepatic lipase could also contribute to the rise in plasma triacylglycerol.

Animals↗
PubMed1989

Pulmonary manifestations in Behçet's syndrome.

Among 72 patients with Behçet's syndrome, seven had pulmonary vascular involvement. Additional data from 42 cases in the literature are discussed. Recurrent episodes of dyspnea, cough, chest pain, and hemoptysis were the primary clinical signs, mainly in young men, appearing 3.6 years after the first manifestation of Behçet's syndrome. Fever, elevated ESR, and anemia were common, and chest x-ray films showed pulmonary infiltrates, pleural effusions, and prominent pulmonary arteries. Ventilation-perfusion scans showed perfusion defects even when chest x-ray films were normal. Pulmonary artery aneurysms were seen in 7/13 in whom angiography was done. Of 42 patients, 16 died, 15 from fatal pulmonary hemorrhage, 80 percent within two years from the development of pulmonary disease. Histopathologic study results showed vasculitis of pulmonary vessels of various sizes, leading to thrombosis, destruction of the elastic laminae, aneurysms, and arteriobronchial fistula. In addition, pulmonary emboli and the aphthous lesion of the tracheobronchial tree may aid the clinical picture. Anticoagulant therapy may be hazardous in patients with aneurysmal dilatation of the pulmonary vascular tree, and the beneficial effect of corticosteroid therapy is discussed. Pulmonary vasculitis in Behçet's syndrome is a unique clinical and pathologic picture, differing from other vasculitides affecting the lung, presents a major threat to the patient's life.

Adult↗
PubMed1988

Fate of lipoprotein lipase taken up by the rat liver. Evidence for a conformational change with loss of catalytic activity.

When isolated rat livers were perfused with medium containing lipoprotein lipase, 40-60% was taken up during a single passage. This value was similar for lipoprotein lipase derived from culture medium of rat preadipocytes, and for lipoprotein lipase purified from bovine milk. It was also, similar, irrespective of the lipoprotein lipase concentration, at least up to 1 microgram/ml. Immediately following its uptake by the liver, a large fraction of the lipoprotein lipase could be released by heparin, but the magnitude of this fraction decreased with time. The enzyme lost its catalytic activity rather rapidly, but its degradation to acid-soluble products, or to larger fragments, was much slower. On heparin-agarose chromatography, the enzyme taken up by the liver eluted at a lower salt concentration than the original lipoprotein lipase preparation. This change in affinity for heparin suggests that the originally dimeric lipoprotein lipase had dissociated into monomers, in analogy to the findings in model experiments. It is suggested that the initial uptake of lipoprotein lipase occurs by binding to a polyanion at the liver cell surface. This is followed by endocytosis and dissociation of the enzyme from its heparan sulfate-like binding site. Acidification of the endosome may cause a conformational change in the lipase molecule with dissociation to inactive monomers, preceding ultimate proteolytic degradation.

Animals↗
PubMed1988

Modulation of lipoprotein lipase activity in mouse peritoneal macrophages by recombinant human tumor necrosis factor.

Thioglycollate-elicited mouse peritoneal macrophages spontaneously secrete lipoprotein lipase during culture. Exposure of the cultures to 50 ng/ml of recombinant human tumor necrosis factor (rTNF) for 48 h resulted in a 69% reduction in lipoprotein lipase activity in the culture medium with a concomitant decrease in cellular enzyme activity. The decrease in enzyme activity was not the result of rTNF-dependent reduction in the total protein synthesis, since the presence of rTNF did not affect [3H]leucine incorporation into cellular proteins. The effect of rTNF on lipoprotein lipase was reversible; upon TNF withdrawal, enzyme activity returned to basal levels after 60 h. The reduction of lipoprotein lipase in rTNF-treated cultures could be completely prevented by preincubation with a specific antiserum against recombinant human TNF. The late onset of decrease of lipoprotein lipase (LPL) activity suggests that rTNF might induce a mediator, which in turn suppresses LPL production. While rTNF was very effective in reducing lipoprotein lipase activity in mouse peritoneal macrophages, it did not affect lipoprotein lipase activity when added to the murine J774 cell line and to CT2 macrophage-like cells, a variant of the J774 cell line.

Animals↗
PubMed1988

Tunicamycin-treated rat heart cell cultures synthesize an inactive nonreleasable lipoprotein lipase.

Cells isolated from newborn rat hearts were cultured in the presence of 100 mM Hepes (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid). Lipoprotein lipase activity was present in an intracellular and heparin-releasable pool and was also secreted into the culture medium. Treatment of the cultures with 5 micrograms/ml tunicamycin caused almost complete loss of lipoprotein lipase activity in all three compartments. In control cultures, immunoblotting of lipoprotein lipase derived from all three pools revealed a single band of lipoprotein lipase with an apparent Mr of 56,000. In the tunicamycin-treated cultures, the enzyme appeared only intracellularly and had an apparent Mr of 49,000. No immunoreactive enzyme was found in the medium. Thus, glycosylation of lipoprotein lipase in heart cell cultures is mandatory for enzyme activity and translocation from an intracellular to the heparin-releasable pool and for secretion into the medium.

Animals↗
PubMed1988

Lipoprotein lipase in heart cell cultures is suppressed by bacterial lipopolysaccharide: an effect mediated by production of tumor necrosis factor.

Exposure of rat heart cell cultures, consisting mainly of nonbeating mesenchymal cells, to 50 ng/ml of bacterial lipopolysaccharide (LPS) for 24 h resulted in a more than 80% reduction in lipoprotein lipase activity. The loss of enzymic activity was accompanied by a concomitant reduction in enzyme protein, as shown by immunoblotting. Addition of LPS to the culture medium resulted also in the production of tumor necrosis factor (TNF), and the fall in lipoprotein lipase in LPS-treated cultures could be prevented by an antibody to TNF. Addition of recombinant human TNF to the heart cell cultures also depressed lipoprotein lipase activity. LPS treatment of preadipocytes in culture resulted in a fall in lipoprotein lipase activity and TNF production. Since TNF is known as a macrophage product, the cultures were tested for phagocytic capacity, and only 0.2-1.3% of the cells were shown to engulf Staphylococcus albus. Immunofluorescent staining with monoclonal antibodies OX-1, which identify leukocyte common antigen, was negative, and only 0.1 +/- 0.07% of the cells were positive after staining with OX-42 antibody to iC3b receptor. Both antibodies stained more than 98% of rat peritoneal macrophages used as controls. Since LPS treatment of macrophages at numbers comparable to or exceeding the number of phagocytic cells present in the heart cell cultures did not induce measurable amounts of TNF, it is suggested that in the heart cell cultures, TNF may be produced by cells other than macrophages.

Animals↗
PubMed1988

Regulation of lipoprotein lipase activity in the sand rat: effect of nutritional state and cAMP modulation.

The sand rat (Psammomys obesus) is a desert rodent in which obesity and diabetes mellitus appeared only subsequent to feeding laboratory animal chow. To study the role of lipoprotein lipase in the development and maintenance of obesity in the sand rat, enzyme activity in various organs and in plasma of sand rats or albino rats was determined following a 20-hour fast, or 16 hours after injection of cholera toxin. Despite comparable change in body weight, an altered pattern of enzyme distribution and regulation was observed in the sand rat. Neither fasting nor cholera toxin had an effect on heart and daiphragm muscle lipoprotein lipase activity of the sand rat, but caused a 1.5- to 2-fold increase in the treated albino rats. By using an isolated perfused heart system, we were able to measure enzyme activity present in the heparin-releasable fraction that represents the functional pool of the enzyme. In both species, the heparin-releasable fraction of the heart increased twofold following fasting, though initial values were lower in sand rat. In both species, fasting and cholera toxin administration resulted in an increase in plasma and liver lipoprotein lipase activity. Adipose tissue lipoprotein lipase activity of sand rat, unlike the albino rats, was similar in the various fat regions and was not lowered by food deprivation or cholera toxin administration. After both treatments, sand rat plasma insulin levels exceeded fivefold those of albino rats. Adipose tissue lipoprotein lipase activity of fed and fasted normal and diabetic sand rats correlated negatively with plasma insulin and glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1988

Metabolic fate of rat heart endothelial lipoprotein lipase.

When isolated rat hearts were perfused with medium containing 125I-labeled bovine lipoprotein lipase (LPL), they bound both lipase activity and radioactivity. More than 80% of the bound lipase could be rapidly released by heparin. Low concentrations of bovine LPL displaced 50-60% of the endogeneous, endothelial-bound LPL. Higher concentrations caused additional binding. Both binding and exchange were rapid processes. The hearts continuously released endogenous LPL into the medium. An antiserum that inhibited bovine but not rat LPL was used to differentiate endogeneous and exogeneous LPL activity. When the pool of endothelial LPL was labeled with bovine 125I-labeled LPL and then chased with unlabeled bovine LPL, approximately 50% of the labeled lipase was rapidly displaced. During chase perfusion with medium only, catalytically active bovine LPL appeared in the perfusate. The rate of release was similar to that observed for endogeneous LPL activity and amounted to 10-13% of the heparin-releasable fraction in the first 5 min of perfusion. There was little or no degradation of bovine 125I-labeled LPL to fragments or acid-soluble products. These results indicate that endothelial LPL is accessible for exchange with exogeneous LPL and that detachment rather than degradation may be the pathway for catabolism of endothelial LPL.

Animals↗
PubMed1988

Amiodarone pulmonary toxicity presenting as a solitary lung mass.

Following treatment with amiodarone, a patient developed weight loss, fatigue and severe myopathy, without respiratory symptoms. A solitary lung infiltrate, impaired thyroid and liver function tests, and leukocytosis were evident. Biopsies from the lung lesion, liver, and bone marrow revealed foam cells. All these signs and symptoms subsided following cessation of amiodarone therapy. It is demonstrated that amiodarone may induce a localized lung lesion rather than diffuse pulmonary disease.

Aged↗
PubMed1987

Enhanced release and synthesis of lipoprotein lipase in rat heart cell cultures exposed to high concentrations of Hepes.

While attempting to optimize conditions for synthesis of lipoprotein lipase by cultured heart cells, we encountered an unexpected rise in enzyme activity when media were supplemented inadvertently with 100 mM Hepes buffer (4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid). This finding was further investigated and optimal results were obtained at pH 7.0-7.2. The increase in lipoprotein lipase activity was time dependent; after 3-6 h there was a rise in medium activity but cellular activity increased only after 24 h. The increased enzyme activity was defined as lipoprotein lipase by inhibition with antiserum to rat adipose tissue lipoprotein lipase. A 72-h exposure to Hepes resulted in a 30% increase in the incorporation of [35S]methionine into cellular proteins and a 2-fold increase into heparin-releasable proteins. Using heparin Sepharose chromatography and stepwise elution, a lipoprotein lipase enriched fraction was recovered with 2 M NaCl. The amount of [35S]methionine and [3H]galactose incorporated into protein of this fraction derived from Hepes-treated cells was 2-6-fold that of controls. A 4-fold increase in cellular lipoprotein lipase mass in Hepes-treated cells was shown by immunoblotting. Results obtained with Hepes-conditioned medium suggest the presence of cell-derived compounds that enhance release and subsequent synthesis of lipoprotein lipase. The effect of Hepes-conditioned medium on lipoprotein lipase resembled to some extent that of the addition of heparin. Therefore, it appears that when Hepes is first added to the culture medium, it might promote a release of heparan sulfate or related compounds, possibly by virtue of its negatively charged sulfonic acid residue. The accumulated heparan sulfate could then promote a sustained release of lipoprotein lipase into the culture medium which in turn leads to increased enzyme synthesis.

Animals↗
PubMed1987

HLA-B51 may serve as an immunogenetic marker for a subgroup of patients with Behçet's syndrome.

Epidemiologic data, family history, clinical data, HLA typing, neutrophilic chemotaxis, and immunofluorescence of clinically normal non-sun-exposed skin were studied in 46 Israeli non-Ashkenazi Jewish and Arab patients with Behçet's syndrome. HLA-B51 was present in 71 percent of the patient group as compared with 13 percent of the control group (relative risk = 17.1). In four of 30 families in the B51-positive group, there was a close relative of the proband with Behçet's syndrome who was carrying the HLA-B51 antigen. Neutrophilic chemotaxis in this group was enhanced in 80 percent of the patients, and in most patients no deposition of immunoglobulin in the dermo-epidermal junction was observed, whereas C3 was present in papillary vessels. In the B51-negative group, the family history was negative for Behçet's syndrome, neutrophilic chemotaxis was enhanced in only two of eight patients, and in four of six patients, IgM deposition was detected in the dermo-epidermal junction. It is concluded that in Israeli non-Ashkenazi Jews and Arabs, there is a significant association between HLA-B51 and the risk of developing Behçet's syndrome. The B51-positive patient group has a family history of the disease, enhanced neutrophilic chemotaxis, and a lack of immunoglobulin deposition in the dermo-epidermal junction.

Behcet Syndrome↗
PubMed1986

Beta-adrenergic stimulation enhances translocation, processing and synthesis of lipoprotein lipase in rat heart cells.

Cells isolated from newborn rat hearts were cultured for 10-14 days, and lipoprotein lipase activity was present in an intracellular and heparin-releasable pool. Treatment of the cultures with 10(-7) M isoproterenol for 3 min resulted in a 3-fold increase in heparin-releasable lipoprotein lipase and a concomitant decrease in residual cellular enzyme activity. Similar results were obtained by treatment with dibutyryl cAMP. Treatment with isoproterenol or dibutyryl cAMP for 2 h affected glycosylation of immunoadsorbable lipoprotein lipase, so that the ratio of [3H]galactose to [14C]mannose in the heparin-releasable enzyme increased from 3.8 (control) to 13.0 (isoproterenol-treated). The change in the ratio of the sugars in the cellular fraction of the enzyme was from 3.1 to 9.9. 2 h treatment with isoproterenol did not enhance new enzyme synthesis, as determined by incorporation of [3H]leucine into immunoadsorbable lipoprotein lipase. 24 h after addition of either isoproterenol or dibutyryl cAMP to the culture medium, stimulation of enzyme synthesis was demonstrated. The present results permit three effects of isoproterenol on lipoprotein lipase to be distinguished: stimulation of translocation from a cellular to heparin-releasable pool; enhanced processing of mannose residues and terminal glycosylation; stimulation of synthesis of enzyme protein.

Animals↗
PubMed1986

Characterization of the lipoprotein lipase in the functional pool of rat heart by immunoblotting.

Rat hearts were perfused with heparin for 2 min at 4 degrees C. The lipoprotein lipase activity in the perfusate was inhibited by antiserum to rat adipose tissue lipoprotein lipase. By immunoblotting, the lipoprotein lipase derived from the functional pool of the heart was found to be a protein with an apparent Mr of 69 000. After incubation of the perfusate at 37 degrees C for 24 h an immunologically reactive protein with an apparent Mr of 28 000 was found. This protein is not a physiological derivative of the enzyme but a degradation product.

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↗
PubMed1985

Endogenous plasma lipoprotein lipase activity in fed and fasting rats may reflect the functional pool of endothelial lipoprotein lipase.

In this study, a correlation was sought between the circulating lipoprotein lipase activity and nutritional state in the rat. In fed rats, the plasma lipoprotein lipase activity was between 30 and 120 munits/ml, whereas after an overnight fast in restraining cages, the lipoprotein lipase plasma levels were between 280 and 500 munits/ml. The plasma lipoprotein lipase activity was inhibited by a specific high titre goat antiserum to rat lipoprotein lipase. No effect of fasting was seen on the plasma hepatic triacylglycerol lipase. 6 h after fasting, adipose tissue lipoprotein lipase decreased maximally, but plasma lipoprotein lipase was not changed and rose only after 16 h. Thus, it seems that most of the lipoprotein lipase activity in the fasting plasma was related to the 3-fold rise in lipoprotein lipase activity in the heart, which may represent total muscle lipoprotein lipase. The increase in heart lipoprotein lipase was due in part to an increase in the t1/2 of the enzyme from 1.2 to 2.9 h. To determine whether the high plasma levels in the fasting rats might result from impaired clearance of the enzyme by the liver, functional hepatectomy was carried out. 15 min after hepatectomy, plasma lipoprotein lipase rose up to 20-fold in fed and about 6-fold in fasting rats. Lipoprotein lipase activity extracted by the liver was calculated to be 30-60 munits/ml in the fed and 171-247 munits/ml plasma per min in fasting rats. An increase in lipoprotein lipase activity in extrahepatic tissues (heart, lung, kidney, diaphragm and adrenal) occurred 30 min after hepatectomy in fed rats. The increase in heart lipoprotein lipase was due to an increase in heparin-releasable fraction. Since no impairment of hepatic clearance of circulating plasma lipoprotein lipase was found, the high fasting plasma lipoprotein lipase activity may be related to an increase in enzyme synthesis, decreased enzyme turnover and an expansion of the functional pool in tissues such as the heart and probably muscle. The present findings indicate that measurement of endogenous plasma lipoprotein lipase can provide information with respect to the size of the functional pool under normal and pathological conditions.

Animals↗
PubMed1985

Importance of the different steps of glycosylation for the activity and secretion of lipoprotein lipase in rat preadipocytes studied with monensin and tunicamycin.

Lipoprotein lipase synthesized by cultured rat preadipocytes is present in three compartments: an intracellular, a surface-related 3-min heparin-releasable, and that secreted into the culture medium. 30 min after addition of 6 microM monensin, the lipoprotein lipase activity in the heparin-releasable compartment starts to decrease; by 4 h of monensin treatment the lipoprotein lipase activity in the heparin-releasable pool and in the culture medium is about 10% of that found in control dishes. The intracellular activity, which had been identified as lipoprotein lipase by an antiserum to lipoprotein lipase, increases slowly and doubles by 24 h. However, since the cellular compartment accounts for 10-25% of total activity, this increase does not account for the missing enzyme activity. To determine whether this enzyme molecule is synthesized but is not active, incorporation of labeled leucine, mannose and galactose into immunoadsorbable lipoprotein lipase was studied in control, monensin- or tunicamycin-treated cells. Addition of tunicamycin (5 micrograms/ml) for 24 h caused a 30-50% reduction in immunoadsorbable lipoprotein lipase, but the enzyme activity was reduced by 90%. On the other hand, 4 h monensin treatment reduced both incorporation of [3H]leucine into immunoadsorbable lipoprotein lipase and heparin-releasable and medium lipoprotein lipase activity by 57 to 77%. The immunoadsorbable lipoprotein lipase in the intracellular compartment has a [14C]mannose to [3H]galactose ratio of 0.15 and this ratio increased 6-fold in monensin-treated cells. The intracellular lipoprotein lipase in monensin-treated cells had the same affinity for both the native and synthetic substrate as the lipoprotein lipase in control cells, yet its spontaneous secretion into the culture medium and its release by 3 min heparin treatment was markedly decreased. The present results indicate that: the presence of asparagine-linked oligosaccharide (formation of which is inhibited by tunicamycin) is mandatory for the expression of lipoprotein lipase activity; lipoprotein lipase is active also in a high mannose form; and terminal glycosylation and oligosaccharide processing, which is inhibited by monensin, may be important for the appearance of heparin-releasable lipoprotein lipase and secretion of lipoprotein lipase into the medium.

Adipose Tissue↗