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Biomedical subjects

J Rosenbaum

Publications and source records attributed to J Rosenbaum.

At least 91 records · Page 5Linked to original sources
PubMed1988

Toxicity of phorbol myristate acetate-stimulated polymorphonuclear neutrophils against rat hepatocytes. Demonstration and mechanism.

Human polymorphonuclear neutrophils (PMN), when exposed to soluble or particulate stimuli, can destroy various types of cells. The purpose of the present work was to investigate the toxicity of phorbol myristate acetate (PMA)-stimulated PMN against hepatocytes. Neutrophils were incubated in basal conditions or after stimulation by 100 ng/ml PMA in the presence of rat hepatocytes isolated by collagenase digestion. Cytotoxicity was quantified by the percentage of alanine aminotransferase (ALAT) activity released by hepatocytes in the culture medium. Whereas unstimulated PMN had only minor effects, PMA-stimulated PMN induced, after a 16-hour incubation, a 29.5% ALAT activity release at a PMN/hepatocyte ratio of 20/1. At the same ratio, stimulated PMN induced a 1.5% and a 16.6% ALAT activity release at 1 and 4 hours, respectively. At 1 hour, electron microscopy showed intimate contacts between PMN and hepatocytes; hepatocytes appeared morphologically normal. Hepatocytic lesions were moderate at 4 hours and marked at 16 hours. Neutrophil-induced hepatocyte toxicity could not be explained by the production of reactive oxygen intermediates since: (a) hepatocyte toxicity was not prevented by either superoxide dismutase or by catalase; (b) PMN obtained from a subject with chronic granulomatous disease were as toxic as PMN obtained from a normal subject. By contrast, a proteinase-mediated mechanism could be implicated since: (a) the supernatant of stimulated PMN induced a 45.9% ALAT activity release, after 16 hours of incubation; (b) three neutral proteinase inhibitors (i.e., alpha 1-proteinase inhibitor, phenylmethylsulfonylfluoride, soybean trypsin inhibitor) as well as fetal calf serum decreased this toxic effect by 82, 86, 81 and 70%, respectively. These inhibitors had no or minor protective effect on the toxicity of stimulated PMN coincubated with hepatocytes. This could be explained by the existence of intimate contacts between PMN and hepatocytes impeding the action of antiproteinases. Our results suggest that PMA-stimulated PMN can damage hepatocytes through the release of proteinases and that the existence of close contacts between PMN and hepatocytes might play a major role in this toxic effect.

Animals↗
PubMed1988

Measurement and characterisation of circulating anti-endothelial cell IgG in connective tissue diseases.

We have detected circulating IgG antibodies that bind with high affinity to human umbilical vein endothelial cells in 74% of patients with systemic lupus erythematosus (SLE), 30% of those with scleroderma and 28% of those with rheumatoid arthritis. IgG binding was F(ab) mediated, and did not involve immune complexes. Anti-endothelial IgG were apparently unrelated to other circulating autoantibodies, including anti-cardiolipin or antiDNA IgG. Bound IgG from SLE or scleroderma patients was displaced by IgG from certain unrelated patients whereas others were ineffective. Anti-endothelial cell IgG from all sera tested were adsorbed by human dermal fibroblasts; erythrocytes and leucocytes each adsorbed a fraction of the activity. Purified IgG did not induce complement-mediated cytotoxicity. We conclude that a discrete group of IgG antibodies is common in connective tissue disease patients, reacts predominantly with endothelial cells and dermal fibroblasts, and may be important in the pathogenesis of vascular damage.

Arthritis, Rheumatoid↗
PubMed1987

Pharmacokinetics of erythromycin in patients with severe cirrhosis. Respective influence of decreased serum binding and impaired liver metabolic capacity.

Pharmacokinetic parameters were studied after i.v. infusion of erythromycin (500 mg) in five patients with alcoholic cirrhosis and six normal subjects. Serum AAG levels were 4.7 +/- 2.4 mumol l-1 in cirrhotics and 10.3 +/- 2.1 +/- mumol l-1 in normals. The unbound fraction (fu) of erythromycin was significantly higher in cirrhotic patients (58.3 +/- 17.7%) than in normal subjects (30.5 +/- 2.8%, P less than 0.01), and a negative correlation was found between fu values and serum AAG (r = -0.867, P less than 0.01). Due to increase in fu, volume of distribution (Vss) was significantly augmented in cirrhotics (85.5 +/- 23.8 l vs 57.6 +/- 14.8 l, P less than 0.05). Serum clearance of unbound erythromycin (CLu) was significantly reduced in cirrhotic patients (42.2 +/- 10.1 l h-1 vs 113.2 +/- 44.2 l h-1 in normal subjects, P less than 0.01). This led to marked elevation of serum concentrations of unbound drug and was entirely explained by the decrease of non renal (i.e. hepatic intrinsic) clearance (31.6 +/- 7.5 l h-1 in cirrhotics, 98.6 +/- 41.5 l h-1 in normals, P less than 0.02); renal clearance remained unchanged. It is concluded that in cirrhotic patients, low serum AAG levels and reduced liver metabolic capacity may lead to marked changes in pharmacokinetics of erythromycin, and that similar results might be expected for drugs which exhibit the same serum binding and pharmacokinetic behaviour as erythromycin.

Adult↗
PubMed1986

Modulation of endothelial cells growth induced by heparin.

We have previously shown that heparin was bound and internalized by cultured human endothelial cells. In this study, we have investigated the effect of heparin on endothelial cells growth. We found that heparin inhibited 3H-thymidine uptake as well as actual cell growth in a dose-dependent manner in the presence of low concentrations of human serum. Inhibition was maximal at 1% serum concentration and was abolished at 10%. Chasing experiments supported the role of membrane-bound heparin in this inhibition. Low molecular weight heparin fractions, or pentosan polysulfate, were equally effective in inhibiting 3H-thymidine uptake. On the other hand, the simultaneous addition of heparin and ECGS was synergic in stimulating 3H-thymidine uptake. These results suggest a modulatory role of heparin in endothelial cells growth.

Cell Division↗
PubMed1986

Dothiepin hydrochloride: treatment efficacy and safety.

Dothiepin, a thio analogue of amitriptyline, has been used extensively in Europe during the past 15 years. It is a safe and effective agent for the treatment of major depressive disorder. Although the onset of action is comparable to that of other tricyclic antidepressants, dothiepin may cause fewer intolerable side effects and have less cardiotoxicity than these other compounds. In addition, dothiepin reduces the anxiety associated with some major depressive episodes. These features suggest that dothiepin may be particularly helpful for treating anxious depressed patients and patients who have underlying cardiac disease or who are elderly.

Adult↗
PubMed1984

Aortic endothelial cells in culture secrete glycoproteins reacting with blood platelets.

The culture medium of bovine aortic endothelial cells contains proteins which inhibit the aggregation of platelets induced by aortic microfibrils but not by type III collagen. From this medium, fibronectin, thrombospondin and a glycoprotein with MW of 128 Kd (GP 128), similar to a glycoprotein described in a microfibrillar extract from bovine aorta were separated by affinity and ion exchange chromatography. GP 128 was further purified by molecular sieve chromatography on SW 3000 column. GP 128 inhibited the aggregation of platelets by microfibrils. This suggests a role of GP 128 in the platelet/subendothelium interaction.

Amino Acids↗
PubMed1984

[Hepatic fibrosis and portal hypertension in chronic vitamin A poisoning].

The authors report the case of a 36-year-old man who was hospitalized for portal hypertension. The patient had been receiving 200 millions units of vitamin A for ten years duration as treatment of psoriasis. There were no extrahepatic signs of hypervitaminosis A and the serum concentration of vitamin A was low. Microscopic examination of a liver specimen showed: a) spontaneous fluorescence due to vitamin A accumulation in sinusoidal cells; b) portal, periportal and perisinusoidal fibrosis; c) hyperplasia and hypertrophy of Ito cells. Hepatic vitamin A concentration was markedly increased. Hemodynamic study showed increased wedged hepatic venous pressure. Low serum concentration of retinol binding protein, which could be due to severe denutrition, explained the low serum vitamin A. This case report emphasizes that severe hepatic injury due to chronic hypervitaminosis A may be observed in the absence of extrahepatic signs of vitamin A intoxication and increase in serum vitamin A concentration. In such cases, histologic examination of a liver specimen and determination of hepatic vitamin A concentration are the only means of diagnosis.

Adult↗
PubMed1980

Hepatotoxicity associated with use of D-penicillamine in rheumatoid arthritis.

Two patients with rheumatoid arthritis developed evidence of hepatotoxicity while receiving D-penicillamine. Both recovered after withdrawal of the drug. These cases and a review of the literature suggested that hepatotoxicity, though rare, should be added to the list of adverse reactions to D-penicillamine.

Adult↗