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Biomedical subjects

J Convit

Publications and source records attributed to J Convit.

At least 73 records · Page 4Linked to original sources

In situ detection of amastigotes in American cutaneous leishmaniasis, using monoclonal antibodies.

Using an immunoperoxidase technique we have applied monoclonal antibodies against American Leishmania for the detection of amastigotes in biopsies from cutaneous leishmaniasis patients. The immunocytochemical procedure was notably superior to conventional histological staining in terms of the visualization and definition of the amastigotes. This technique could eventually prove to be of value in epidemiological studies, and possibly have prognostic importance, by allowing the in situ characterization of the species of infecting organism.

Antibodies, Monoclonal↗

Density of epidermal Langerhans cells in psoriasis patients treated with an aromatic retinoid (RO 10-9359). An immunoperoxidase study using anti-T6 and anti-Ia monoclonal antibodies.

Immunocytochemical techniques using antibodies to the specific T6 and Ia (Major Histocompatibility Complex, class II, human HLA-Dr) antigens were used to determine the densities of epidermal Langerhans cells (LC) in psoriasis patients treated with the aromatic retinoid RO 10-9359. Fourteen patients were treated with the aromatic retinoid and were skin biopsied before, during and after therapy. Two psoriasis patients receiving PUVA (systemic 8-methoxypsoralen + UVA irradiation) were included in the study. The results showed an increase in LC numbers during aromatic retinoid administration, which coincided with an improvement in the clinical severity of the lesions. At the end of retinoid administration the LC numbers were similar to those found in the initial psoriatic plaques. The density of Ia+ LC, in comparison with T6+ LC in the epidermis of psoriatic plaques were significantly different. Dendritic and non-dendritic Ia+ cells were also observed in the dermis of the plaques. Unlike aromatic retinoid treated patients, PUVA treated patients showed a decrease of both T6+ and Ia+ epidermal LC by the middle of therapy, a total absence of immunoreaction by the end of therapy, and a return to normal skin values a few weeks after treatment. This immunocytochemical study helps in distinguishing between dendritic and other possible Ia-expressing cells from the infiltrate that may penetrate the epithelium. These results do not conclusively demonstrate the role of LC in the pathogenesis of psoriasis. Other factors, such as the interrelationship with other immune response cell types and alterations in the lymphokine cascade may be important.

Adult↗

HLA-linked control of predisposition to lepromatous leprosy.

In a study of the relation between HLA and lepromatous leprosy, HLA haplotype segregation was analyzed in 28 families with multiple cases of different types of leprosy. The inheritance of HLA-DR2, HLA-DR3, and HLA-MT1, which had previously been shown to be associated with susceptibility to leprosy or with a leprosy type, was analyzed separately. Segregation occurred in a significantly nonrandom fashion in both polar tuberculoid leprosy and lepromatous leprosy. This finding indicated HLA-encoded control of a predisposition to both of these forms of the disease. In both cases the segregation observed among healthy siblings was random. Thus, susceptibility to leprosy per se is probably not controlled by HLA-linked genes. HLA-DR3 was inherited preferentially by children with polar tuberculoid leprosy rather than lepromatous disease (P = .02), and HLA-MT1 was inherited preferentially by children with lepromatous leprosy (P = .04). The results confirmed the association of these genetic markers with leprosy type.

Female↗

In situ characterization of the cellular immune response in American cutaneous leishmaniasis.

American cutaneous leishmaniasis is a spectrum of granulomatous disease caused by related species of an intracellular parasite. The host response in localized cutaneous leishmaniasis (LCL) is effective in that few organisms can be found in tissue lesions. In contrast, diffuse cutaneous leishmaniasis (DCL) patients mount a poor response with numerous parasites present in multiple skin lesions. Immunopathological correlates were sought in LCL and DCL with immunoperoxidase techniques using monoclonal antibodies directed against T lymphocyte subpopulations and interleukin-2 in tissue lesions. Both LCL and DCL granulomas showed a mixture of T lymphocyte subpopulations with the ratio of helper:suppressor phenotypes less than one. This ratio and localization of cells is more similar to the ineffective lepromatous leprosy granuloma than the effective tuberculoid leprosy granuloma. In contrast, interleukin-2 was identified in equivalent numbers of cells in LCL and tuberculoid leprosy, an order of magnitude greater than DCL and lepromatous leprosy lesions. Cells expressing Tac, the receptor for interleukin-2, were present in approximately equal numbers in all disorders. The immunological effectiveness of granulomas appear to related less to the numbers and location of T cell phenotypes than to the functional aspects of these cells, particularly the ability to generate lymphokines.

Granuloma↗

Association of HLA specificity LB-E12 (MB1, DC1, MT1) with lepromatous leprosy in a Venezuelan population.

To investigate whether an association could be found between HLA and lepromatous leprosy a population study was performed in Tachira, Venezuela. This was done in the same endemic area in which recently both non-random parental HLA-haplotype and preferential segregation of the HLA specificity LB-E12 (MB1, DC1, MT1) was demonstrated in lepromatous leprosy patients from multicase families. In this study 32 lepromatous patients and 32 healthy controls were typed for HLA-A, -B, -C, -DR and the specificities MB and MT. The frequency of LB-E12 (MB1, DC1, MT1) showed a significant increase in lepromatous leprosy patients (p = 0.04). This is the first report concerning HLA and leprosy which confirms in the same endemic area an association observed in families on the population level.

HLA Antigens↗

Leishmania species: comparative ultrastructure of experimental nodules and diffuse human cutaneous lesions in American leishmaniases.

Experimental nodules of American leishmaniases were obtained by inoculating 0.1-1 x 10(5) amastigotes into the dorsum of the hindpaws of golden hamsters and of C57Bl/6J mice. The amastigotes were obtained by biopsy of lesions in six human cases of cutaneous leishmaniases and were serially maintained in golden hamsters and in a fetal calf serum-containing medium. Human nodules were obtained by biopsy from several patients with diffuse cutaneous leishmaniases, always prior to treatment. Within the same host species, no ultrastructural differences were seen in the tissue response to isolates of Leishmania mexicana, L. brasiliensis, or L. garnhami, nor were there differences between the host species in response to a particular isolate of the genus Leishmania. The typical inflammatory response was a macrophage granuloma with abundant polymorphonuclear neutrophils, some eosinophils, and plasma cells. Simple human cutaneous leishmanial lesions, as well as experimental nodules in regression, show many fibroblasts, much collagen fiber, but very few parasites. In typical lesions, parasites occurred within macrophage phagolysosomes, within distended lacunar cells, and in the intercellular spaces. Leishmaniae strongly adhered to parasitophorous vacuoles by a site of their plasma membrane directly opposite the flagellum, and the host cell cytoplasm close to the adherence site became highly vacuolated. In most cases the intra- and extracellular parasites show normal morphology, which suggest the inability of phagocytic cells to attack them.

Adolescent↗

IgE in leprosy; effect of a Mycobacterium leprae-BCG vaccine.

Since some previous studies have reported elevated total serum IgE levels in leprosy, that may be associated with the existence of a state of generalized T cell anergy, we undertook a carefully controlled study of this immunoglobulin in such patients before and after treatment with a Mycobacterium leprae-BCG vaccine. We found, firstly, that lepromatous leprosy patients suffering active disease had only a moderate elevation of IgE levels that was not statistically significant when compared to appropriate controls. In addition, multiple injections of the vaccine did not cause alterations in the concentration of this immunoglobulin. We were, therefore, unable to confirm the possible existence of a generalized immunodeficiency in lepromatous leprosy that could cause hyper-production of IgE.

BCG Vaccine↗

Delayed-type hypersensitivity and immunoglobulin E in American cutaneous leishmaniasis.

Delayed-type hypersensitivity (DTH) and both total and specific immunoglobulin E (IgE) antibody levels were studied during an outbreak of American cutaneous leishmaniasis. Direct correlations were detected between DTH reactivity and either age or the period of evolution of the infection, and a clear association with sex (strongest response in females) was observed. Extremely high, age-dependent, total serum IgE levels were measured in the study group, probably due to concurrent intestinal helminthiasis. A low proportion of the group also had detectable levels of specific anti-Leishmania IgE antibody. Total and specific IgE levels were also sex dependent (lowest in females), and an inverse correlation was found between these levels and DTH responsiveness, possibly reflecting the intervention of regulatory influences of T-lymphocyte activity.

Adolescent↗

Cutaneous leishmaniasis in mice: resistance to glucan immunotherapy, either alone or combined with chemotherapy.

Leishmania braziliensis, L. mexicana, and L. garnhami were studied for their ability to produce American cutaneous leishmaniasis, using C57BL/6 female mice as the animal model. No significant difference in the clinical course of mouse foot pad infection was found between the three American Leishmania species studied. In general, the incubation period varied from 2-4 weeks. Mice developed only local swelling and sometimes ulceration at the sites of inoculation. After 4 weeks of progress lesions began to decrease without obvious impact on the general health of the mice. When glucan immunotherapy (120 - 240 mg/kg body weight) was initiated previous to, or simultaneously with, infection the development of foot pad lesions was not significantly inhibited, this despite clear evidence of generalized stimulation of the reticuloendothelial system. On the other hand, pentavalent antimony at high doses (1,000 - 1,500 mg/kg) induced only a significant lengthening of the latent period. However, different combinations of glucan and pentavalent antimony (various doses of each drug, timing of administration, or changes in the sequence of use of both drugs) did not significantly alter the clinical course of American Leishmania infection as compared with pentavalent antimony alone. Thus, not only were glucan or glucantime alone unable to cure the infection (as evidenced by some animals which showed rapidly growing lesions some time after the end of treatment), but no potentiation was observed.

Animals↗

Immunotherapy with a mixture of Mycobacterium leprae and BCG in different forms of leprosy and in Mitsuda-negative contacts.

A total of 529 weak or non-reactors to M. leprae, including Mitsuda-negative contacts and patients with leprosy, were vaccinated once or repeatedly, as necessary, with a mixture of 6 x 10(8) purified, heat-killed M. leprae and 0.01 mg to 0.2 mg of viable BCG. Clinical, histopathological and immunological criteria were used to evaluate the response of these individuals. Clinical changes, including sharper definition of borders and progressive flattening and regression of lesions, were observed in 57% of the active LL cases and 76% of the active BL cases. Histopathological study revealed infiltration of the lesions by mononuclear cells, appearance of epithelioid differentiation, and fragmentation of the microorganisms. Delayed-type skin tests with soluble antigen from purified M. leprae became positive in significant numbers of each group studied. These results demonstrate the efficacy of combined immunotherapy in low-resistance forms of leprosy and potential utility in the immunoprophylaxis of the disease.

BCG Vaccine↗

Serological and immunohistological studies on lepromatous leprosy.

Sera of patients with lepromatous leprosy were studied for the presence of a variety of antibodies and immune complexes (IC). The frequencies of heterophile, Hanganutziu-Deicher and Forssman antibodies were 61 and 43%, respectively, which were significantly higher than those in other diseases. The frequency of antibodies to cardiolipin was 89% and the frequency of rheumatoid factor was 34%. Circulating IC were demonstrated in 54% of the patients' sera by Raji-cell test and in 43% by anti-antibody inhibition test. Analyses of immunoglobulin classes of IC revealed that IgG was predominant in IC of patients with lepra reaction (LR) and IgM in patients without LR. Immune deposits were found in and between cells of dermis in skin biopsy specimens of patients with LR.

Animals↗