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Biomedical subjects

W Howard

Publications and source records attributed to W Howard.

15 recordsLinked to original sources

Evaluation of the rat bone marrow and peripheral blood micronucleus test using monocrotaline.

The present study was performed as part of the 9th collaborative trial of the CSGMT (Collaborative Study Group for the Micronucleus Test) to evaluate the performance of the rat micronucleus test in detection of clastogenic agents. Temporary fluorescent staining using acridine orange (AO) was compared with permanent staining using a modified Feulgen technique for bone marrow and Giemsa for blood. The Feulgen and AO methods were both found to be suitable for demonstrating micronucleus induction in rat bone marrow following oral administration of monocrotaline and cyclophosphamide. Induction of micronuclei was also shown using rat blood. The simple AO supravital method described produced uniformly stained preparations which were extremely easy to assess and interpret. The AO method was preferred to Giemsa for analysis of blood, but it was essential to analyse samples within 4 days of collection to avoid excessive deterioration of cells. Because of the relatively low number of micronucleated cells found in rat blood, it is suggested that examination of a larger number of cells may be necessary to achieve a similar sensitivity to the bone marrow assay for routine screening.

Acridine Orange

Effect of trivalent and pentavalent arsenic in causing chromosome alterations in cultured Chinese hamster ovary (CHO) cells.

Sodium salts of trivalent and pentavalent arsenic were tested for their effect in inducing chromosome aberrations and sister-chromatid exchange (SCE) in cultured Chinese hamster ovary (CHO) cells. It was discovered that arsenite (As 3) produced excessive endoreduplication of the chromosomes at higher levels. No endoreduplication was observed with arsenate (As 5) treatment. These agents also elevated the frequencies of SCE, but less so compared to aberrations. The results obtained indicate that arsenic may be carcinogenic in animal system.

Animals

Induction of chromosome changes by metal compounds in cultured CHO cells.

The effect of 4 metal salts on the induction of chromosome aberrations and sister chromatid exchange (SCE) in cultured Chinese hamster ovary (CHO) cells was investigated. It was observed that CdCl2, NiCl2, CrO3 and HgCl2 were effective in causing various types of chromosome aberrations. The percentages of abnormalities increased with increasing doses of the metals used. These metal compounds also raised the SCE rates compared to 5-bromo-2'-deoxyuridine controls. The importance of rapid screening of potentially hazardous metals is described.

Animals

Lovastatin inhibits gallstone formation in the cholesterol-fed prairie dog.

The efficacy of lovastatin, an inhibitor of hepatic cholesterol synthesis in the prevention of cholesterol gallstone formation, was evaluated in the prairie dog model. Two groups of animals were maintained on either nonlithogenic or 1.2% cholesterol-enriched chow for 21 days. Seven of the animals in each group received lovastatin, and the remaining six received only distilled water. All of the cholesterol-fed/water-treated animals had crystals and 83% had gallstones, but none of the cholesterol-fed/lovastatin-treated animals had gallstones and only three had microscopic crystals. These data indicate that lovastatin inhibits cholesterol gallstone formation in a diet-induced model of gallstone disease.

Animals

Serum beta 2-microglobulin decreases in patients with AIDS or ARC treated with azidothymidine.

Abnormally elevated serum beta 2-microglobulin has been associated with progression of human immunodeficiency virus (HIV) disease and could reflect in vivo HIV activity. We prospectively studied the effect of azidothymidine therapy on serum beta 2-microglobulin concentration in 41 patients with AIDS or AIDS-related complex. Median beta 2-microglobulin concentration decreased from 4.02 mg/L before therapy to 3.73 mg/L at week 24 of therapy (P = .016). Individual changes in beta 2-microglobulin during azidothymidine therapy correlated with changes in serum HIV p24 antigen (Spearman, r = .42, P = .007). Also, in a randomized placebo-controlled study, median beta 2-microglobulin concentration decreased after 16 w of therapy in 5 azidothymidine-treated patients compared with levels in 7 placebo-treated controls (P = .05). Serum beta 2-microglobulin appears to be a sensitive marker for in vivo antiretroviral drug activity and may be a better marker than serum p24 antigen for early intervention trials involving antiretroviral agents.

AIDS-Related Complex

Quasielastic light scattering studies of tubulin aggregation.

A quasielastic light scattering study of purified tubulin has resulted in a monomer diffusion coefficient of 6.0 X 10(-7) cm2/s. In an attempt to characterize the small tubulin oligomers which are predicted to form as intermediates in the self-assembly into double rings, magnesium ions (10 mM) were incorporated into the PG (10 mM NaPi, 0.1 mM GTP, pH 7.0) buffer. With magnesium-containing buffers, a second slow diffusing species was identified with D = 0.56 X 10(-7) cm2/s. This corresponds to the tubulin double rings. A study of the small oligomers was precluded by the presence in all preparations of traces of aggregates resulting from the slow aging process of the protein (V. Prakash and S. N. Timasheff (1982) J. Mol. Biol. 160, 499-515). While colchicine was shown to inhibit this aging process, the presence of these irreversible aggregates, even to the extent of 1% by mass, precludes equilibrium studies of the self-association of tubulin into small oligomers.

Animals

In vitro inhibitory and bactericidal activity of cefpiramide and seven antipseudomonal agents against Pseudomonas aeruginosa.

Cefpiramide was tested against 493 clinical isolates of Pseudomonas aeruginosa and the results of minimal inhibitory concentration, minimal bactericidal concentration, bactericidal rate, and time-kill synergy studies were compared with those obtained with seven other antipseudomonal agents. The minimal inhibitory concentrations of cefpiramide for P. aeruginosa were comparable to all of the agents tested. Minimal bactericidal concentration results were generally within one twofold dilution of the minimal inhibitory concentration values for all agents tested. Bactericidal rate studies showed that at concentrations of four times the minimal inhibitory concentration, all of the agents produced rapid killing. Results of time-kill synergy studies showed a marked synergistic interaction between cefpiramide and each of three aminoglycosides, gentamicin, tobramycin, and amikacin. These results suggest that cefpiramide may be useful in the therapy of infections due to P. aeruginosa.

Amikacin

Perturbations of granulocyte counts induced by procedural, chemical and physiological events occurring during filtration leukapheresis in rats.

During filtration leukapheresis a factor(s) is produced, released or extracted into rat blood which causes a transient granulocytosis in pheresed animals and in recipients of homologous plasma from these animals. To identify which factors contribute to this granulocytosis, the procedural steps involved in filtration leukapheresis as well as a number of chemical agents which are potentially extracted from of produced by the procedure, were tested for their ability to stimulate granulocytosis. Procedural steps tested included the depth of anesthesia, effect of the anticoagulant and possible interactions of blood cells with the plastic tubing in the system (sham-pheresis). Chemical agents tested included common mediators of inflammation and proteinases released by polymorphonuclear leukocytes (PMNs), extracts of nylon fibers and Tygon tubing, nylon monomers and solvents used in the manufacture of nylon, oxidized and decomplemented plasma and lysates of PMNs or microorganisms. Our findings demonstrate that several of these agents contribute to the granulocytosis seen during filtration leukapheresis of rats.

Anesthetics

Sulconazole nitrate 1.0 percent cream: a comparison with miconazole in the treatment of tinea pedis and tinea cruris/corporis.

Sulconazole nitrate 1.0 percent cream was compared to miconazole nitrate 2.0 percent cream in a double-blind, parallel study involving ninety-six patients with cutaneous dermatophytosis. Both agents were highly effective, with no statistically significant differences in the parameters studied. Among tinea pedis patients, all of seven treated with sulconazole and six of nine treated with miconazole were mycologically cured (negative culture and potassium hydroxide test) at the end of four weeks of twice a day treatment, and there were no relapses by week 9. Among tinea cruris/corporis patients, the rates of mycological cure after three weeks of twice a day treatment with sulconazole or miconazole were, respectively, twenty-nine of thirty-two (91 percent) and 100 percent of thirty one (accompanied in all cases by complete or significant clearing of signs and symptoms); the respective relapse rates were four of twenty-five (16 percent) and eight of twenty-three (35 percent). Miconazole resulted in two cases of severe irritant dermatitis requiring discontinuation of treatment, whereas sulconazole produced no severe irritant reactions.

Adolescent