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Biomedical subjects

I Kedar

Publications and source records attributed to I Kedar.

At least 37 records · Page 2Linked to original sources
PubMed1990

Phase I and immunomodulatory study of a muramyl peptide, muramyl tripeptide phosphatidylethanolamine.

Muramyl tripeptide phosphatidylethanolamine (MTP-PE; CGP 19835A from Ciba Geigy) is a synthetic muramyl tripeptide structurally related to bacterial cell wall constituents. MTP-PE activates monocytes in vitro to a tumoricidal state and has in vivo antitumor effects in animal models. We studied the toxicity and immunomodulatory effects of once weekly i.v. administration of liposomal-encapsulated MTP-PE for 8 weeks in 27 patients with advanced malignancies. Doses ranged from 0.1 to 2.7 mg/m2. No major tumor responses were seen; 11 patients had stable disease after 8 weeks of therapy and 3 continued on maintenance therapy because of minor tumor regressions and/or clinical improvement. MTP-PE at these doses was well tolerated. Shaking chills and fevers were the most common toxicities and occurred at all dose levels. There was no treatment-induced loss of performance status. Immunomodulatory studies revealed evidence of a biological effect on monocytes. C-reactive protein levels rose in the majority of patients with end-of-treatment values 2 to 10 times higher than baseline. Serum neopterin levels were consistently increased 24 h after MTP-PE administration and significant decreases in expression of two different types of Fc receptors on peripheral blood monocytes were noted 6 h after treatment. Although no major tumor responses were seen in this group of patients with advanced malignancies, MTP-PE was well tolerated and exerted biological effects on monocytes. Serum neopterin levels may be a useful marker for the biological effects of MTP-PE.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

A noninvasive screening of systemic reactive (secondary) AA amyloidosis, based on reduced amyloid degrading activity of amyloidotic serum.

Standardization of the measurement of amyloid degrading activity (ADA) by diffusion of serum in amyloid-impregnated agar plates may either indicate or exclude with reasonable certainty the presence of systemic AA amyloidosis. In certain cases, it may obviate the need for a diagnostic biopsy. The sera of 38 patients with systemic amyloidosis were tested and compared with sera of 38 controls matched for age, serum creatinine and albumin blood levels, and with sera of 48 additional controls with the same basic diseases as the amyloidotic patients but without amyloidosis. The difference between ADA of amyloidotic and control patients was significant, with no overlap in the range of activity between the two groups. A positive correlation was found between ADA and serum albumin concentration in the nonamyloidotic matched controls but not in patients with amyloidosis. Our data do not support the view that the decline in ADA of sera of amyloidotic patients is due to hypoalbuminemia.

Adipose Tissue↗
PubMed1987

Functional diversity of Ia epitopes on macrophages.

A panel of monoclonal antibodies directed against various epitopes of mouse Iak was used to block functions mediated by Iak on CBA/J macrophages in two different assay systems. The first system was the recently described proliferation inhibition of an H-2k T cell clone (8.1.11.2) by a combination of CBA/J (nonactivated) macrophages and anti-Iak (Kedar, I. et al. J. Immunol. 1986. 136: 3166). The second system was the well known macrophage cytotoxicity induced by interferon against various transformed cells. We found that anti-Iak antibodies directed against serological specificity number 2 (on the alpha chain of IA) blocked the proliferative stimulus of the macrophage Iak for the 8.1.11.2 T cell clone. Both an IgG and an IgM antibody with this specificity were effective, whereas seven other anti-Iak (including several for other specificities on the alpha chain of IA) were not. Conversely, two different monoclonal anti-Iak antibodies directed against serological specificity number 17 (on the beta chain of IA) inhibited the cytolytic activity of the activated macrophages for the 8.1.11.2 T cell clone as well as the P815 (H-2d) mastocytoma as target, whereas four other antibodies were ineffective in this regard. In addition to providing evidence that Ia may participate in the cytolytic activity of activated macrophages, these studies demonstrate that different epitopes of Iak on macrophages are differentially involved in different biological functions.

Animals↗
PubMed1986

Growth regulation of transformed T cells by nonactivated macrophages: the role of Ia expression.

We studied the influence of unactivated mouse peritoneal macrophages on the proliferative capacity of a spontaneously transformed MRL-lpr/lpr T cell clone. Macrophages, 25%, induced a reduction in proliferative rate from 20% to 95% measured by [3H]thymidine incorporation and microscopic cytometry. MHC-compatible (H-2k) macrophages caused growth inhibition reciprocal to the amount of Ia expression on the macrophage. Thus, with increasing preculture of the macrophages there was both decreasing Ia and increasing suppression. H-2-incompatible macrophages had maximal inhibitory capacity without preincubation. Macrophages derived from the peritoneum of MRL-lpr/lpr mice were less suppressive than macrophages from other H-2k mice. In contrast to the case of activated macrophages in other studies, in the present system there was no killing of T cells, only reduction in proliferation. The inhibitory effect of the macrophages correlated with the spontaneous formation of rosettes between the macrophages and the T cell clone. The number of rosettes forming a single layer of T cells around the macrophages, but not the number of rosettes with multiple layers of cells, was reciprocally related to the amount of Ia expression. The results suggest that macrophages bear a surface structure that influences and modulates the growth of T cells.

Animals↗
PubMed1985

Treatment of diabetic perforating ulcers (mal perforant) with local dimethylsulfoxide.

Perforating foot ulcers constitute a major problem in diabetics with peripheral neuropathy for which no specific therapy is available. Twenty patients with chronic, resistant mal perforant were treated by local application of dimethylsulfoxide (DMSO) solution. Complete healing of the ulcers was achieved in 14 patients following 4-15 weeks of daily treatment. Partial resolution was observed in another four patients, and in the remaining two there was no effect. A control group, equal in number, was treated conventionally. Complete healing of the ulcers took place in only two patients. The therapeutic effect of DMSO most probably results from an increase in tissue oxygen saturation via a combined mechanism of local vasodilatation, decreased thrombocyte aggregation, and increased oxygen diffusion. Local DMSO is effective, simple, devoid of systemic side effects, and inexpensive. It should be employed for diabetic foot ulcers prior to the consideration of surgical measures.

Aged↗
PubMed1985

Ascorbic acid-induced regression of amyloidosis in experimental animals.

Ascorbic acid was found to accelerate amyloid degradation in an experimental animal model. Based on experiments in vitro which demonstrated the ability of ascorbic acid to restore the amyloid-degrading activity of amyloidotic human serum, the effect of orally administered ascorbic acid was tested in casein-induced murine amyloidosis. Histopathological examination of splenic tissue of mice killed at different times after the termination of the amyloidogenic stimulus showed a markedly decreased amyloid deposition in ascorbic acid-treated animals as compared to the controls. The effect of ascorbic acid was to a certain degree dose-dependent. Colchicine blocked amyloid synthesis when administered during amyloid induction. In animals which were given the drug during the post-induction period it had no effect. The amyloid-degrading activity of mouse serum was reduced in amyloidotic mice. Administration of ascorbic acid partially restored the amyloid-degrading activity of these animals.

Amyloidosis↗
PubMed1983

The protective effect of dimethyl sulfoxide in experimental ischemia of the intestine.

Experiments with two models of intestinal ischemia were performed in order to examine the protective effect of dimethyl sulfoxide (DMSO). Segmental ischemia of the small intestine for 150 minutes caused necrosis of the affected bowel in 90% of the animals. Intravenous administration of DMSO or impregnation of the peritoneum with this substance prevented the development of gangrene in 28 of 29 rats. 30 or 60 minutes of complete ischemia of the small intestine, produced by clamping of the superior mesenteric artery, resulted in partial or complete necrosis of bowel segments with a high incidence of perforation and peritonitis and a high mortality rate within the first 24 hours. Intravenous DMSO, given upon declamping of the artery, effectively protected the bowel from the ischemic damage. There were no deaths among DMSO-treated animals and at 24 h there was no evidence of ischemic damage to the intestine. Though the exact mechanism of action of DMSO is unknown, the results of these and other experiments may warrant clinical trials especially in cases of mesenteric thrombosis.

Animals↗
PubMed1983

Dimethyl sulfoxide in acute ischemia of the kidney.

Renal ischemia was produced in rats by clamping of the renal artery for 1 h. Upon termination of the ischemic period a 20% solution of DMSO (5 g kg-1 b.w.) was given intravenously to 33 rats. Eighteen control animals received normal saline. All DMSO-treated animals survived while all control animals died within the subsequent seven days. At 24 h following the experiment, the mean blood urea of the control rats was 254 mg/100 ml and the mean plasma creatinine 7.2 mg/100 ml. By contrast, the DMSO-treated rats had a mean blood urea of 69 mg/100 ml and plasma creatinine of 1.6 mg/100 ml. In 17 animals the kidney was perfused with DMSO prior to the closure of the renal artery. All these rats survived the procedure and showed near normal kidney function at 24 h. The renal artery was clamped for 60 min in ten dogs. Five dogs received DMSO (3 g kg-1 b.w.) and the other five received an equivalent dose of normal saline. Three weeks later a contralateral nephrectomy was performed. Renal function was normal in the DMSO-treated dogs. One control dog died of uremia, in the remaining four a transient renal failure was observed. These experiments in two different animals highlight the protective effect of DMSO on the ischemic kidney when the drug is administered after the ischemic period.

Acute Kidney Injury↗
PubMed1982

Prolonged dimethylsulphoxide treatment in 13 patients with systemic amyloidosis.

Continuous oral dimethylsulphoxide (DMSO) treatment (7-15 g/day) was given to 3 patients with amyloidosis of familial Mediterranean fever (FMF), 3 patients with idiopathic amyloidosis, and 7 patients with secondary amyloidosis. The nephrotic syndrome and various degrees of renal insufficiency were the major clinical manifestation in all case. Renal function was used as the main parameter for evaluation of therapy. DMSO treatment for 7-16 months produced no effect in the FMF patients and in the patient with idiopathic amyloidosis; they all ran the predictable clinical course of their disease and either died of cardiac failure or have been maintained on chronic haemodialysis. In the 7 patients with secondary amyloidosis an unequivocal improvement of renal function was observed following 3-6 months of DMSO treatment. It was shown by a 30-100% rise of creatinine clearance and a decline in proteinuria. This new equilibrium has been maintained as long as DMSO was administered. No serious side effects of DMSO wee encountered. Mild nausea and an unpleasant breath odour were the patients' main concern. We conclude that a therapeutic trial with oral DMSO is warranted in all patients with secondary amyloidosis. This treatment is unpleasant but bears no exceptional risks. It may significantly prolong life, though its effect on amyloid deposits themselves is doubtful.

Adult↗
PubMed1982

Degradation of amyloid by a serum component and inhibition of degradation.

ADA of human serum was demonstrated and investigated with an agar gel diffusion technique using amyloid-impregnated agar plates. Sera of 20 healthy adults, 40 patients with AA-amyloidosis, and 86 nonamyloidotic patients were tested. The presence of an ADF, showing enzymatic properties and strongly bound to albumin, was demonstrated in normals and amyloidotic and nonamyloidotic patients. ADA in the serum of amyloidotic and cirrhotic patients was markedly decreased due to the presence of an inhibitor of ADF. ADA of amyloidotic sera was restored to normal by EDTA, citric acid, and ascorbic acid. The ADA of 16 FMF patients and four of 34 patients with rheumatoid arthritis without amyloidosis was intermediate between normal and amyloidotic values, indicating the presence of lADF at low concentrations in these patients. These findings suggest that amyloid is a normal protein metabolite, possibly with a high metabolic turnover. Accumulation of amyloid may be caused by decrease of the ADA of the serum by its inhibitor, rather than by accelerated production.

Adult↗
PubMed1981

Alleviation of experimental ischemic acute renal failure by dimethyl sulfoxide.

Acute, ischemic renal failure was induced in rats by clamping of the renal vessels for 1 h. Following the termination of the ischemic period 5 g/kg of dimethyl sulfoxide (DMSO) were administered intravenously as a 20% solution in saline. Control animals received normal saline. There were not deaths among the DMSO-treated animals. Urine flow began within 15 min of DMSO infusion. 24 h after the experiment the mean blood urea was 73 +/- (SEM) 14 mg/100 ml (n = 29). All the control rats died during the week following the experiment. The mean blood urea at 24 h was 276 +/- 18 mg/100 ml (n = 20). In 10 additional animals perfusion of the kidney with DMSO prior to the closure of renal vessels protected the organ from ischemic damage. These experiments have a bearing on the therapeutic approach to ischemic renal failure in man, and on preservation methods of donor kidneys for transplantation.

Acute Kidney Injury↗
PubMed1980

The role of polymorphonuclear leucocytes and T lymphocytes in experimental murine amyloidosis.

Washed cells, from ascitic fluid, which contained predominantly polymorphonuclear leucocytes from casein treated donor mice, induced accelerated amyloid formation in untreated syngeneic recipient animals. A similar transfer model, with lymph node cell suspension, was ineffective. Amyloidogenesis was completely blocked by colchicine treatment of the donors while treatment of the recipients had no effect. A casein induced amyloidogenic stimulus was transferred from nude C3H mice to their normal littermates. When the order was reversed, no amyloidosis occurred in the nude recipients. These experiments indicate the possible involvement of two cells in the biphasic process of casein induced murine amyloid formation: the polymorphonuclear leucocyte in the first phase and the T lymphocyte in the second.

Amyloidosis↗
PubMed1979

Regression of amyloidosis secondary to granulomatous ileitis following surgical resection and colchicine administration.

A patient with nephrotic syndrome was found to have amyloidosis secondary to an otherwise asymptomatic Crohn's disease. Resection of a major portion of the affected bowel and long-term colchicine therapy were followed by a complete clinical remission of the nephrotic syndrome, most probably due to a significant resolution of amyloidosis. The combination of resection of affected bowel segments, together with long-term colchicine therapy may offer a better prognosis than either method alone.

Adult↗
PubMed1977

Treatment of experimental murine amyloidosis with dimethyl sulfoxide.

Dimethyl sulfoxide was administered intravenously for 60 days to twenty mice with casein-induced amyloidosis. Partial or total disappearance of amyloid deposits occurred in all treated animals. The urine of these animals contained a substance from which amyloid fibrils could be synthesized. A control group of mice with casein-induced amyloidosis given saline injections showed massive amyloid deposition in the liver and in the spleen at the end of the experiment. Neither the urine of these mice nor the urine of normal control mice treated with dimethyl sulfoxide contained substances from which amyloid fibrils could be synthesized. It is our assumption that dimethyl sulfoxide treatment of mice with amyloidosis resulted in a break up of amyloid fibres into small subunits which were excreted in the urine.

Amyloid↗
PubMed1977

Prolonged colchicine treatment in four patients with amyloidosis.

The natural clinical course of four patients with systemic amyloidosis was favourably altered by continuous colchicine therapy. One patient had primary amyloidosis, and the other three suffered from amyloidosis of familial Mediterranean fever. All had a nephrotic syndrome, and one showed features of intestinal malabsorption. The institution of colchicine therapy was followed by a gradual remission of the nephrotic syndrome, a rise of serum albumin to normal values, a slight improvement of renal function, and regression of the intestinal malabsorption. This pattern has remained steady during an observation period of 30 months.

Adolescent↗
PubMed1976

In vitro synthesis of "amyloid"fibrils from insulin, calcitonin and parathormone.

Insulin, calcitonin and parathyroid hormone subjected to one of two procedures-acidification and heating or incubation with mouse kidney lysosomal extracts-assumed a nonbranching fibrillar structure, 7 to 10 nm in diameter. The preparations showed green birefringence after Congo red staining. The in vitro synthesis from different hormonal polypeptides of fibrils, fulfilling the criteria for the identification of amyloid, indicates that these criteria are related to conformational rather than to compositional properties, and suggests that these hormones may provide the subunit of the amyloid formed in the corresponding endocrine organs.

Amyloid↗