Search PubMed⌕ Search

Biomedical subjects

L Levy

Publications and source records attributed to L Levy.

At least 217 records · Page 12Linked to original sources

The disposition of dapsone and monoacetyldapsone in the dog (38516).

Four female dogs receiving 1.0 mg dapsone (DDS)/kg iv exhibited logarithmic decline of plasma levels of DDS with a mean half-time of disappearance (T-1/2 of 11.7 hr. No evidence of acetylation of DDS to monoacetyl DDS (MADDS) was found. An equimolar dose of MADDS was deacetylated slowly to DDS by the same dogs. The mean T 1/2 of MADDS was 6.5 hr, significantly less than that of DDS. In 2-hr plasma samples after these doses of drugs, protein-binding of DDS and MADDS averaged 71 and 84%, respectively. Tests of protein-binding of the two drugs in vitro confirmed the observations in vivo.

Acetylation↗

Disposition of dapsone and monoacetyldapsone in rats.

Female Buffalo and Lewis rats receiving 1.0 mg DDS/kg ip exhibited higher plasma levels of DDS and its monoacetylated metabolite, MADDS, than did male rats of each strain receiving the same dose. The fraction of the total measured drug in plasma as MADDS at 8 hr in female rats of both strains ranged from 43 to 62% compared with a range of 28-31% in male rats. Plasma half times of disappearance (T1/2) of DDS ranged from 5.0 to 6.8 hr and were not different among sexes and strains. Deacetylation of MADDS to DDS occurred when equimolar doses of MADDS were administered. An approach to a steady state of acetylation-deacetylation was indicated by comparing the percentage MADDS of the total drug in plasma in the respective sexes and strains receiving both drugs. T1/2 values of MADDS were significantly lower than values for DDS in Lewis rats. They were not different in Buffalo rats. Protein binding studies in plasma from rats receiving 5.0 mg DDS or 5.8 mg MADDS/kg showed 67-72% binding of DDS and 91% binding of MADDS. These in vivo observations were confirmed by in vitro binding studies. Comparison of these results with those of earlier studies in mice and man indicates that the rat is a better model of man than is the mouse for studies on the disposition of DDS.

Animals↗

Acral keratoderma.

Three siblings displayed an unusual form of keratoderma characterized by diffuse and striate hyperkeratosis of the palms and soles, hyperkeratotic plaques over the dorsum of the hands and toes, and linear hyperkeratotic lesions over the Achilles tendon area, ankles, elbows, and knees. The predominant location of these lesions led to the term acral keratoderma for this disorder. Histologically, besides thickening of all epidermal layers with that of the stratum corneum being most notable, various dyskeratotic changes were evident in the epidermis. Pedigree analysis of the family suggested an autosomal recessive inheritance pattern. There were similarities and differences between the type of keratoderma displayed by these three patients and that of patients described previously with the disorder known as keratoma hereditarium mutilans.

Adolescent↗

Persistence of DNA in the circulation of immunized rabbits.

The clearance of deoxyribonucleic acid (DNA) from the circulation was studied in non-immunized New Zealand rabbits and in rabbits immunized with heat-denatured, single-strand DNA (ss-DNA). Animals were injected intravenously with 1-3 mug/kg of 125-I-calf thymus ss-DNA. Initial clearance rates were -0.154 +/- 0.005 per cent (dose/ml/min) in non-immunized rabbits as compared to rates of -0.064 to -0.123 per cent (dose/ml/min) in rabbits immunized with ss-DNA. In immunized rabbits, clearance rates were inversely correlated with relative amounts of antibody, and increased amounts of circulating radiolabel were precipitable with 50 per cent saturated ammonium sulfate, suggesting binding to rabbit immunoglobulin. Thus, the presence of antibody to ss-DNA may delay the usually rapid clearance of ss-DNA from the blood. This observation is similar to that made for a variety of small molecular weight materials, such as insulin, digoxin, and morphine, and is in contrast to that for multivalent protein antigens, such as serum albumin and thyroglobulin. Persistence of DNA in the circulation may be important in the pathogenesis of DNA-anti-DNA-induced immune complex disease.

Animals↗

Resistance to Mycobacterium leprae in Mice Infected with Toxoplasma gondii and Besnoitia jellisoni.

Mice chronically infected with the intracellular protozoan Toxoplasma gondii or Besnoitia jellisoni were resistant to footpad challenge with Mycobacterium leprae. Resistance was manifested by lower numbers of recoverable M. leprae in the footpads of protozoal-infected mice and was enhanced in Toxoplasma-infected mice by a booster injection of Toxoplasma antigen in the infected footpad. The results suggest a major role for the activated macrophage in the control of M. leprae infection.

Journal Article↗

Immune response to Mycobacterium leprae: plaque-forming cells in mice.

Intravenous immunization with a cell extract of Mycobacterium leprae produced a primary immune response of considerable magnitude, followed by an equally large response after secondary stimulation, as measured by assay of plaque-forming cells (PFC). Infection with M. leprae or immunization with cell extract by the footpad route produced a lower level of response than that seen in the intravenous group. Identical patterns of response, although not of the same magnitude, were observed after both primary and secondary challenges in the two footpad groups, one infected with viable M. leprae and the other immunized with M. leprae cell extract. The secondary response after a booster dose to all these groups appeared to be an enhanced immunoglobulin M response. Control studies confirmed that the immune response was a direct result of the host-parasite interaction and that the PFC observed resulted from stimulation of antibody-forming cells by antigens of M. leprae. The similarity in time of appearance of peak PFC levels in the two footpad groups may be attributed to the live challenge passing through a latent phase. Alternatively, the challenge is known to contain a large proportion on nonviable cells, and it may also contain soluble M. leprae antigens. Studies of the cross-reactivity of the antigens have extended previous observations on antigens shared between M. leprae and other mycobacterial species. Use of the two antigen-containing fractions of the M. leprae cell extract has suggested that one of the fractions contains some shared antigens, whereas the other has an antigen specific to M. leprae.

Animals↗

Leukocyte antimicrobial function in patients with leprosy.

Patients with lepromatous leprosy are unresponsive to lepromin skin-test material and possess defective lymphocyte function in vitro, including impaired mitogenesis in response to antigens of Mycobacterium leprae. It has been claimed that their macrophages cannot digest M. leprae in vitro; such a defect could explain both lepromin nonreactivity and impaired lymphocyte function on the basis of failure of the afferent limb of the immune response (i.e., defective macrophage "processing" of M. leprae). The present studies indicate that macrophages from patients with lepromatous and tuberculoid leprosy and from normal donors do not differ in their ability to digest heat-killed M. leprae in vitro, or in their ability to sustain the viability of M. leprae in tissue culture; that monocytes, macrophages, and polymorphonuclear leukocytes of leprosy patients and controls possess equivalent microbicidal activity against Listeria monocytogenes, Escherichia coli, Proteus vulgaris, Staphylococcus aureus, and Candida albicans; and that polymorphonuclear leukocytes from patients with lepromatous leprosy iodinate ingested bacteria normally. Whether the basic immune defect leading to the development of lepromatous leprosy resides in the lymphocyte or in the macrophage remains to be determined. However, the present study shows that phagocytic cells from patients with either principal form of leprosy function normally in a variety of sophisticated tests of antimicrobial function.

Candida albicans↗