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H Joshua

Publications and source records attributed to H Joshua.

At least 19 recordsLinked to original sources
PubMed1995

Studies on conformational consequences of i to i + 3 side-chain cyclization in model cyclic tetrapeptides.

In an effort to explore the effect of ring size on the biologically active conformation of cyclic analogs of the mating pheromone alpha-factor (WHWLQLKPGQPMY) from Saccharomyces cerevisiae, eight cyclic tetrapeptides corresponding to the KPGQ portion of alpha-factor were synthesized. These N-alpha-acetyl/carboxyl amide terminal cyclic tetrapeptides were prepared on a 4-methylbenzhydrylamine resin using orthogonal Boc, Fmoc, OFm and OtBut protecting groups and HOBt-DIPC accelerated active esters or urethane-protected N-carboxyanhydrides. On-resin cyclization of the side-chain amino and carboxyl groups of the first and fourth residues, respectively, was performed with the BOP reagent to generate lactams containing 14-18 atoms. HF cleavage resulted in two products, the desired cyclic tetrapeptide and a major side product. All peptides were purified to near homogeneity (> 99%) by using reversed-phase HPLC and were characterized by FBMS and 1H NMR. Certain constrained cyclic tetrapeptides appear to be a mixture of isomers at room temperature as evidenced by HPLC and NMR. The major side product has been identified as a cyclo dimer, obtained as a consequence of interchain cyclization on the resin. CD analysis in several solvents gives evidence that some of the cyclic tetrapeptides exist in beta-turn conformations.

Amino Acid Sequence↗
PubMed1992

Pneumocandins from Zalerion arboricola. I. Discovery and isolation.

HPLC bioautography of the directed biosynthesis of Zalerion arboricola led to the discovery of pneumocandin B0 (L-688,786), a new antifungal and anti-Pneumocystis carinii lipopeptide. Isolation techniques were developed to separate this component from pneumocandin A0 (L-671,329) in fermentations of a mutant of Zalerion arboricola. A number of related compounds were also isolated, which differ from pneumocandins A0 and B0 in the hydroxylation patterns on the ornithine, homotyrosine, and proline.

Anti-Bacterial Agents↗
PubMed1991

Hemophagocytosis by small cell lung carcinoma.

A 60-year-old woman with disseminated small cell carcinoma of the lung and hemophagocytosis by the metastatic cells in the bone marrow is presented. It is the first clinicopathologic report on phagocytosis of erythrocytes by lung tumor cells in concordance with a recently described evidence of a macrophage origin of small cell carcinoma of the lung.

Bone Marrow↗
PubMed1991

L-669,262, a potent HMG-CoA reductase inhibitor.

The microbial transformation of simvastatin (MK-733) by Nocardia autotrophica subspecies amethystina yielded iso-simvastatin-6-one as a minor component. This transformation product is a dienone and is one of the more potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase found to date.

Animals↗
PubMed1990

Macrophage migration inhibition factor (MIF) in drug eruption.

A controlled study was conducted to evaluate the macrophage migration inhibition factor test as a diagnostic aid in 50 patients with drug eruption. Two groups of patients served as controls: group A, 110 patients being treated with drugs without known cutaneous adverse reactions, and group B, 15 patients suffering from dermatologic disorders unrelated to drugs being taken. Positive macrophage migration inhibition factor responses were found toward a variety of drugs in 35 (70%) of the patients with drug eruptions, with no relation to the type of eruption or the duration of drug intake. The percentage of positive macrophage migration inhibition factor responses toward drugs in the patients with drug eruptions was higher than that in the two control groups (4.5% and 6.7%, respectively). The percentage of positive macrophage migration inhibition factor responses recorded for clinically "suspected" drugs was significantly higher than that recorded for the "nonsuspected" drugs.

Cell Migration Inhibition↗
PubMed1990

A method for the determination of circulating aggregated platelets and its application to patients in the course of unstable angina.

A method for the quantitative and qualitative determination of the number of aggregated platelets is described. One milliliter of venous blood was separated equally into two solutions. One solution composed of EDTA (ethylenediaminetetraacetic acid) and formaldehyde (solution F) contained reversibly and irreversibly aggregated platelets, and the second solution, composed of EDTA alone (solution E), contained irreversibly aggregated platelets. By microscopic readings, the percentage of platelets forming aggregates was determined. Reversibly aggregated platelets were estimated by subtracting the percentage of aggregated platelets in solution E from that in solution F. The average amount of platelets per aggregate was calculated by dividing the number of aggregated platelets in solution F by the number of aggregates per 1000 platelets counted. The reference ranges (means +/- SDs) established in 100 healthy persons were 5.8% +/- 2.4% (1% to 9%) for solution F, 3.9% +/- 1.8% (0% to 7%) for solution E, and 2.2 +/- 0.18 (2.0 to 2.5) for the average number of platelets per aggregate. Twenty hospitalized patients without heart disease had values similar to those of 100 normal subjects. In 50 patients with acute myocardial infarction, the percentage of aggregated platelets in solution F was 23.8% +/- 10.3%; in solution E, 4.0% +/- 3.0%; and the average number of platelets per aggregate, 2.9 +/- 0.7. The mean variance for five daily consecutive measurements was 0.52% for solution F, 0.63% for solution E, and 0.002 for the average number of platelets per aggregate. An even lesser mean variance was observed when the interobserver-vs-intraobserver and the intersmear-vs-intrasmear variations were tested. In patients with acute myocardial infarction, the interobserver-vs-intraobserver variance was 5.6% for solution F, 2.2% for solution E, and 0.005 for the average number of platelets per aggregate. The parameters studied were unaffected by different blood drawings, assay tubes, or venous stasis. In 80 patients with unstable angina, the studied parameters as well as the percentage of "big" platelets were measured on hospital days 1, 2, and 5. In 25 patients in whom acute myocardial infarction developed during hospitalization, the percentage of aggregated platelets was 28.1% +/- 8.3%. Most of them (71%) were reversibly aggregated and did not change during hospitalization. The average number of platelets per aggregate was 3.9 +/- 1.6, and the percentage of big platelets was 12.5% +/- 7.2%, both values not undergoing subsequent changes. In patients in whom acute myocardial infarction did not develop, the percentage of aggregated platelets decreased to 14.2% +/- 6.1% on day 5. Most aggregated platelets (58.8% to 90%) were irreversibly aggregated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Identification and isolation of medicarpin and a substituted benzofuran as potent leukotriene inhibitors in an anti-inflammatory Chinese herb.

In a search for new inhibitors of leukotriene formation, a methylene chloride extract of the plant Dalbergia odorifera (Jiangxiang) was found to be a potent inhibitor of LTC4 formation in AB-CXBG Mct-1 mastocytoma cells. Following LH-20 and reverse phase HPLC chromatography, two compounds were isolated that had potent LTC4 inhibitory activity: medicarpin and 6-hydroxy-2-(2-hydroxy-4-methoxyphenyl) benzofuran (IV) with IC50s of 0.5 and 0.05 microM respectively. IV was shown to be a specific inhibitor of 5-lipoxygenase with an IC50 against the soluble rat enzyme of 0.08 microM, whereas it was inactive against cyclooxygenase. In neutrophils IV inhibited LTB4 production at comparable concentrations but had no effect on neutrophil degranulation or adhesion.

Animals↗
PubMed1987

Circulating aggregated platelets in coronary artery disease.

Circulating aggregated platelets were assessed in 30 patients with stable angina, 22 with unstable angina and 50 with acute myocardial infarction (AMI). Fifty healthy volunteers and 20 noncardiac patients served as controls. One milliliter of venous blood was separated into 2 solutions: 1 composed of ethylenediamine tetraacetic acid (EDTA) and formalin containing reversible and aggregates and 1 composed of EDTA alone containing irreversible aggregates only. By direct microscopic readings the percentage of platelets forming aggregates/1,000 counted platelets was determined in the 2 solutions. The number of reversibly aggregated platelets was estimated by subtracting the percentage of aggregated platelets in the second solution from that in the first solution. In patients with stable angina the percentage of aggregated platelets was higher than in control subjects (15 +/- 4% vs 7 +/- 2%, p less than 0.001). Most aggregated platelets (72% and 76%, respectively) were irreversibly aggregated. In the unstable angina group the percentage of aggregated platelets was similar to that of the AMI group (24 +/- 13% and 24 +/- 10%) and significantly higher than in the stable angina group. Only 11% and 17% of aggregated platelets in patients with stable angina and AMI were irreversibly aggregated and 89% and 83% of them were reversibly aggregated. Participation of platelets in the pathogenesis of unstable angina and AMI may be related to the early reversible phase of platelet activation.

Angina Pectoris↗
PubMed1987

The appearance of macrophage migration-inhibition factor in drug reactions.

Drug-induced adverse reactions were suspected in 2030 patients with known exposure to 243 different drugs. A modified direct macrophage migration-inhibition factor (MIF) test for the different drugs was carried out on blood samples from these patients. There was a positive MIF response toward one or more of the suspected drugs in 53.4% of the patients as compared to 4.9% of the control group; 155 of the 243 drugs elicited a positive MIF response. The percentage of positive responses for each particular drug was not related to the number of patients tested, reflecting the variability in specific immunogenicity of the different drugs. The high percentage of positive MIF reactions in relation to the clinical diagnosis suggests that this test can be a useful aid in the detection of the offending drug in cases of suspected drug-induced reactions.

Animals↗
PubMed1987

Plasma viscosity and haematocrit in the course of acute myocardial infarction.

Plasma viscosity and haematocrit were determined in 44 patients with acute myocardial infarction on the 1st, 2nd, 3rd and 10th day of hospitalization. The highest haematocrit value for the entire group was found on the 1st day of acute myocardial infarction--43.3 SD +/- 4.6% declining progressively to 38.8 SD +/- 3.5% on the 10th day (P less than 0.001). Plasma viscosity for the entire group was normal on the first day of acute myocardial infarction (1.44 SD +/- 0.10 cp) and started to increase on the second day (1.51 SD +/- 0.16 cp, P less than 0.001). A relationship was found between reinfarction or death (17 patients) occurring during hospitalization and changes in haematocrit and plasma viscosity. In this group plasma viscosity rose to 1.63 SD +/- 0.19 cp on the second day of acute myocardial infarction (P less than 0.001 vs plasma viscosity value on the first day). This elevation persisted on the third day. Haematocrit values in this group were 47.9 SD +/- 3.6% on the first day of acute myocardial infarction declining progressively and significantly afterwards. In the remaining patients both plasma viscosity and haematocrit were normal and did not change. No correlation of plasma viscosity and haematocrit were found when tested for other clinical complications, sex, age, maximal creatine phosphokinase values and coronary risk factors. We suggest that variations in haematocrit and plasma viscosity during acute myocardial infarction exist in a group of patients in whom reinfarction or death occurs. The changes in haematocrit and plasma viscosity precede the complications by 4-8 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Difficidin and oxydifficidin: novel broad spectrum antibacterial antibiotics produced by Bacillus subtilis. II. Isolation and physico-chemical characterization.

The isolation of difficidin (1) and oxydifficidin (2) from fermentation broth of Bacillus subtilis ATCC 39320 and the physico-chemical characterization of these labile antibiotics are described. The structures of the compounds represent a new class of antibiotics, characterized as highly unsaturated 22-membered macrolide phosphates. Difficidin and oxydifficidin undergo reversible thermal isomerization to 3 and 4 respectively. Biological evaluation of the isomers is presented.

Alkaline Phosphatase↗
PubMed1986

The detection of a common idiotype of anti-DNA antibodies in the sera of patients with monoclonal gammopathies.

The sera of 265 patients with monoclonal gammopathies were examined for the presence of a dominant idiotype of the anti-DNA antibody [16/6 idiotype (Id)] and for anti-DNA activity. An enzyme-linked immunosorbent assay (ELISA) with a rabbit anti-16/6 antibody revealed 23 (8.7%) sera that contained increased concentrations of the idiotype. Seven of the patients had benign monoclonal gammopathy, three multiple myeloma, three Waldenström macroglobulinemia, five essential mixed cryoglobulinemia, and five monoclonal cryoglobulinemia. In 5 of the 23 sera, antinuclear activity was also noted. In 11 of the 16/6 Id-positive sera the anti-nucleic acid antibody reactions were found to be polyspecific, reacting with polydeoxythymidilic acid and polyinosinic acid, in addition to single-stranded DNA and double-stranded DNA. Similar results were achieved with the purified serum monoclonal components. The specificity of the idiotype analysis was demonstrated with an unrelated dominant idiotype of anti-HBsAg antibody. In none of the patients, except one (with essential mixed cryoglobulinemia), was lupus symptomatology noted.

Antibodies, Anti-Idiotypic↗
PubMed1986

Circulating platelet aggregate size in ischemic heart disease.

Platelet aggregate size was measured in 178 patients with ischemic heart disease, among whom 56 had stable angina, 42 suffered from unstable angina, and 80 had had uncomplicated acute myocardial infarction. A group of 50 healthy volunteers and 20 hospitalized noncardiac patients served as controls. Venous blood (0.5 cc) was introduced into a solution containing 11.7 mM EDTA and 1.0 g formaldehyde. Platelet aggregate size was determined by microscopic reading as the number of platelets forming aggregates (per 1000 counted platelets) divided by the number of aggregates. Mean aggregate size was found not significantly different in both control groups, as well as in patients with stable angina and acute myocardial infarction (2.21 +/- 0.36 platelets, 2.20 +/- 0.58 platelets, 2.28 +/- 0.19 platelets, 2.76 +/- 1.07 platelets, respectively, p = NS). The highest value was found in the unstable angina group: 4.00 +/- 1.40 platelets (p less than 0.001 vs other studied groups). Platelet aggregate size was found not to be related to sex, age, medication, or coronary risk factors. Unstable angina may thus be a unique entity in ischemic heart disease concerning its platelet behavior, demonstrated in this study by the increased size of peripheral platelet aggregates, which may have pathogenetic, diagnostic, and eventual therapeutic implications.

Adult↗
PubMed1986

Cellular immunity in patients with acquired immunodeficiency syndrome (AIDS) in Israel: effects of THF, a thymic hormone in vitro.

Markers and functions of T cell subsets were studied in 3 Israeli males suffering from AIDS, two of whom were homosexuals and one heterosexual developing AIDS after a coronary bypass operation followed by multiple blood transfusions. Two healthy homosexual partners of one of the AIDS patients were also studied. Sera from these individuals were also tested for suppressive activity on control normal donor lymphocytes. Monitoring of T-cell subsets during a period of 3-12 months demonstrated a reversed T helper: T suppressor ratio in the 3 AIDS patients and in one of the healthy homosexuals. Addition of AIDS sera to normal T helper cells abolished the helper activity whereas its addition to normal isolated T suppressor cells enhanced the suppressor activity. Incubation of the patients lymphocytes with THF, a calf thymus hormone, restored the impaired helper cell activity. A suppressor factor unrelated to acid labile interferon was demonstrated in the sera of the AIDS patients but was not found in the sera of the healthy homosexuals. THF neutralized the suppressor effect of this serum factor when tested on normal lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Human monoclonal anti-DNA antibodies react as lymphocytotoxic antibodies.

Two out of 25 monoclonal anti-DNA autoantibodies that were produced by human-human hybridoma were found to have lymphocytotoxic activity. The antibodies reacted with normal B and T lymphocytes at cold (4 degrees C) as well as at warm (37 degrees C) temperatures. The lymphocytotoxic activity of the monoclonal anti-DNA antibodies could be inhibited by prior incubation of the antibodies with either polynucleotides, e.g. poly(I), poly(dT) or anti-idiotypic antibodies, that had been raised against a dominant anti-DNA antibody. The cross-reactivity between nuclear material and lymphocyte membrane raises the question whether these apparently diverse materials have a shared epitope. The cross-reactivity between anti-DNA antibodies and lymphocyte membrane may account in part for the lymphopenia observed in systemic lupus erythematosus patients.

Antibodies, Monoclonal↗