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Biomedical subjects

H Joshua

Publications and source records attributed to H Joshua.

At least 55 records · Page 3Linked to original sources
PubMed1981

Familial systemic lupus erythematosus and C4 deficiency.

A heterozygous state for C4 deficiency was found in 14 members of a family with familial SLE. The HLA analysis in this family permitted us to re-establish the linkage assumed to exist between the gene (or genes) controlling the synthesis of the fourth component of the complement and the major histocompatibility complex. In addition, it was found that the complement deficiency is not necessarily associated with any serological or clinical abnormality. The heterozygous state for C4 deficiency can be added to the various serological abnormalities described in asymptomatic members of families with familial SLE. It is as yet unknown whether this deficiency may predispose to the subsequent development of SLE.

Adolescent↗
PubMed1981

Dihydromevinolin, a potent hypocholesterolemic metabolite produced by Aspergillus terreus.

A new, potent hypocholesterolemic agent is produced by cultures of Aspergillus terreus. The isolation of the compound and its characterization as 4a,5-dihydromevinolin containing a trans-fused octahydro-naphthalene system are described. Comparative data for dihydromevinolin and mevinolin in three biological assays are given: in vitro inhibition of HMG-CoA reductase, inhibition of sterol synthesis in cell cultures, and inhibition of cholesterol synthesis in vivo in rats.

Animals↗
PubMed1980

A new class of angiotensin-converting enzyme inhibitors.

Much current attention focuses on the renin-angiotensin system in relation to mechanisms controlling blood pressure and renal function. Recent demonstrations (ref. 1, ref. 2 and refs therein) that angiotensin-converting enzyme inhibitors show promising clinical antihypertensive properties have been of particular interest. We now report on the design of a novel series of substituted N-carboxymethyl-dipeptides which are active in inhibiting angiotensin-converting enzyme at nanomolar levels. We suggest that these compounds are transition-state inhibitors and that extensions of this design to other metalloendopeptidases merit further study.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1980

Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.

Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolini and its open acid form, mevinolinic acid, were determined by a combination of physical techniques. Mevinolin was shown to be 1,2,6,7,8,8a-hexahydro-beta, delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutoxy)-1-naphthalene-hepatanoic acid delta-lactone. Mevinolin in the hydroxy-acid form, mevinolinic acid, is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]; its Ki of 0.6 nM can be compared to 1.4 nM for the hydroxy acid form of the previously described related inhibitor, ML-236B (compactin, 6-demethylmevinolin). In the rat, orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay (50% inhibitory dose = 46 microgram/kg). Furthermore, it was shown that mevinolin was an orally active cholesterol-lowering agent in the dog. Treatment of dogs for 3 weeks with mevinolin at 8 mg/kg per day resulted in a 29.3 +/- 2.5% lowering of plasma cholesterol.

Animals↗
PubMed1980

Identification of T & B lymphocytes on skin sections from patients with lymphoproliferative disorders of the skin.

The T & B lymphocytes in frozen sections of skin obtained from patients with various lympho-infiltrating disorders of the skin were identified using an immunofluorescent technique. Anti T-lymphocytes serum was used as a T marker and anti Ig GMA serum and HL-B alloantigens as B markers. The method confirmed to be efficient in preliminary experiments. Specimens were obtained from patients with lymphocytic infiltration of the skin (LIS), lymphadenosis benigna cutis (LBC), lymphoma cutis (LC) and mycosis fungoides (MF). In LIS and LBC the dominant cell was found to be the T lymphocyte, suggesting that a local immune reaction of the cell mediated type may play a role in their etiology.

B-Lymphocytes↗
PubMed1980

Autoimmune antibodies after splenectomy.

Sera of 41 splenectomized subjects were tested for presence of autoantibodies by the indirect immunofluorescent method. 11 of them (26%) revealed the presence of one or more types of autoantibodies. Antiheart antibodies were the most common type (9 subjects). The incidence of antibodies was higher in the subjects splenectomized for trauma than in those who underwent elective splenectomy (39 and 25%, respectively). There was no significant difference between the subjects with positive and negative results with respect to mean age at examination, but the positive results tend to occur more frequently in those who underwent splenectomy at younger age. None of the subjects with any type of antibodies suffered from autoimmune disease. Although it is still impossible to evaluate the clinical importance of these findings, they suggest that splenectomy may disturb the regulatory processes in the immune system. We postulate that this is due to the reduction of the number of suppressor T cells for which the spleen is a major pool.

Adolescent↗
PubMed1980

HLA antigens in ulcerative colitis and Crohn's disease in Israel.

The frequency of HLA antigens was studied in 60 Israeli Jewish patients with ulcerative colitis (UC) and in 18 with Crohn's disease (CD), and it was compared to that in healthy, ethnically-matched controls. From this study it would appear that HLA-BW 35 is highly associated with UC in Israeli Jewish patients and that HLA-AW 24 is present at a high frequency in the "early onset" group and also in the group with "severe" disease, which was composed mainly of female patients. In the CD group, the frequency of the HLA antigens did not differ significantly from that in the control group.

Adult↗
PubMed1979

Inhibition of ADP-induced platelet aggregation by dipyrone in patients with acute myocardial infarction.

ADP induced platelet aggregation was investigated in 48 patients within three days of the first signs of acute myocardial (AMI). Thirty six of them received 1 gram of dipyrone. Twelve patients who did not receive dipyrone served as controls. Platelet aggregation was found severely inhibited in 11 patients who had received dipyrone up to 12 hours before investigation and moderately inhibited among 25 patients who were given the drug 12-24 hours prior to the investigation. All the patients with AMI who did not receive dipyrone, exhibited a state of hyperaggregability evidenced by the presence of a second phase of aggregation even with 0.5 microM ADP. The inhibitory activity of dipyrone on the second phase of platelet aggregation resembles that of other non steroidal anti-inflammatory drugs.

Acute Disease↗
PubMed1979

The influence of homologous plasma and fetal calf serum on human lymphocytic cortisol metabolism.

The influence of a) tissue culture medium (RPMI), b) homologous plasma (HP), and c) fetal calf serum (FCS) on lymphocytic cortisol metabolism was compared to that of phosphate buffered saline alone. RPMI was found to enhance the conversion rate 1.71 times, whereas HP and FCS enhanced it about 3.2 times. Raising the temperature of the HP and FCS to 100 degrees C before incubation reduced the enhancing effect to the level of that obtained with RPMI.

Blood↗
PubMed1979

Further studies on cell-mediated immunity to myelin basic protein in schizophrenic patients.

Cell-mediated immunity (CMI) toward myelin human basic protein (HBP) was studied in 19 chronic drug-free schizophrenic patients and in 30 patients with primary affective disorders receiving psychoactive drugs, 74% of the schizophrenics showed an inhibition of macrophage migration, whereas only one patient from the affective group showed such a response. These results indicate that drugs are not responsible for the appearance of CMI to HBP in schizophrenics. One out of 9 ECT-treated patients developed a CMI to HBP.

Adult↗
PubMed1979

Metabolism of cortisol by human thrombocytes.

A study was made in order to see whether human thrombocytes are capable to metabolize cortisol. Known concentrations of thrombocytes were incubated with 1.23H-cortisol and the products isolated and identified by t.l.c., paper chromatography, and derivations. Two metabolites were found to be produced by thrombocytes: 20beta-hydroxycortisol and tetrahydrocortisol. The enzymatic nature of the reactions was proved by (1) heat treatment (2) finding out NADPH to be a specific cofactor and (3) the dependence of the activity on the number of thrombocytes in suspensions.

Blood Platelets↗
PubMed1979

Lupus nephritis. Electron-dense and immunofluorescent deposits and their correlation with proteinuria and renal function.

Thirteen patients who had systemic lupus erythematosus were studied for the purpose of correlating the findings of light and electron microscopy and immunofluorescent studies with renal function and the presence of proteinuria. Subendothelial deposits of electron-dense material were found in all biopsy specimens, whereas mesangial and subepithelial deposits were not always present. IgG and beta 1c were constant findings in the glomerular membrane. The seven patients who were found to have extensive subendothelial deposits had moderate to massive proteinuria, and four of these patients had decreases in renal function. Most of the patients who had smaller subendothelial deposits had slight or insignificant proteinuria. Massive subendothelial deposits were mainly found in specimens showing histologic evidence of active lesions. Correlation was also found between proteinuria and the overall amount of deposits and their distribution. The prognosis was dependent on the severity of subendothelial deposits, the overall amount of deposits, and the morphologic form of lupus nephropathy.

Adolescent↗
PubMed1979

HLA antigens in genetic neutropenia of Yemenite Jews.

The HLA antigenic system was studied in Yemenite Jews with genetic neutropenia. No deviation in antigen frequency was observed when compared with matched controls from the same ethnic group. HLA antigen frequency and common haplotypes of the Yemenite Jews were found entirely different from those of the African blacks, known to have the same anomaly.

Adult↗
PubMed1979

Avermectins, new family of potent anthelmintic agents: isolation and chromatographic properties.

The avermectins, a family of new anthelmintic agents, were isolated from the mycelia of Streptomyces avermitilis. Four closely related major components and four homologous minor components were separated from the complex. Solvent extraction, solvent partition, and adsorption methods were used to isolate and purify the complex; novel partition chromatography systems using Sephadex LH-20 were used to separate the components. A reverse-phase high-pressure liquid chromatography assay for the quantitative determination of all components was used extensively to monitor the purification methods.

Anthelmintics↗