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Biomedical subjects

I Nath

Publications and source records attributed to I Nath.

At least 55 records · Page 3Linked to original sources
PubMed1986

Influence of delayed immune reactions on human epidermal keratinocytes.

The epidermal changes that occur in human cutaneous immune responses have been investigated in the tuberculin reaction and in the lesions of tuberculoid and lepromatous leprosy and cutaneous leishmaniasis. In each situation, there was a dermal accumulation of monocytes and T cells, and the epidermis exhibited thickening. In the tuberculin response, the thickness of the epidermis sometimes doubled in 48-72 hr, and this was attributed to increases in both size and number of keratinocytes. In addition, the phenotype of the keratinocytes changed from Ia- to Ia+. Similar changes in keratinocyte Ia-antigen expression occurred in the epidermis overlying untreated tuberculoid leprosy and cutaneous leishmaniasis lesions, but not in lepromatous leprosy. We suggest that one or more epidermal growth factors may be generated in the course of a delayed immune reaction in the dermis.

Antigens, Bacterial↗
PubMed1985

Characteristics of histamine receptors present on suppressor T cells in "healthy individuals".

Twelve to 30% histamine receptor bearing cells were detectable in the peripheral blood mononuclear cells of healthy tuberculin sensitive individuals. The number of binding sites per cell ranged from 2.1 X 10(4) to 5.08 X 10(4) (mean 2.5 X 10(4)) with an affinity ranging from 2.5 X 10(-6) M to 10.9 X 10(-6) M (mean 3.6 X 10(-6) M). The histamine receptors on these cells were found to be of H2 type as indicated by the abrogation of binding of 3H-histamine by cimetidine. It was further confirmed that histamine receptor bearing cells in the peripheral blood belonged to a T cell subset which formed rosettes with AET treated sheep erythrocytes and had receptors for Fc portion of IgG and phenotype markers of T3 and T8. Deletion of such cells by means of affinity chromatography on histamine bound Sepharose columns, led to enhanced antigen induced lymphoproliferation indicating the suppressor nature of these T cells.

Adult↗
PubMed1985

Regulation of histamine receptor concentration on human PBMC by homologous hormone.

Human peripheral blood mononuclear cells (PBMC) preincubated with 10(-3)M histamine at 37 degrees C, washed and incubated with 3H-histamine showed a reduction in the binding of the labelled hormone as compared to cells which had not been pretreated with histamine. Using competitive binding assays it was further shown that the number of specific binding sites for histamine was reduced by 46-62%. However, the affinity of receptors as indicated by Kd values remained unaltered. It would thus appear that elevated levels of histamine lead to down-regulation of histamine receptors on human PBMC with a quantitative reduction in the number of binding sites without an alteration in their affinity characteristics. In view of the fact that histamine receptors have been shown to be present on suppressor lymphocytes, the down-regulation of these receptor sites may have relevance in physiological and disease states where perturbations in the levels of histamine are observed.

Adult↗
PubMed1985

Natural emergence of antigen-reactive T cells in lepromatous leprosy patients during erythema nodosum leprosum.

Fifteen lepromatous leprosy (LL) patients undergoing erythema nodosum leprosum (ENL) reactions were compared with 13 stable, uncomplicated, anergic individuals of the same leprosy background. ENL patients showed significant antigen-induced leukocyte migration inhibition (migration index = 0.058 +/- 0.01), paralleling the values obtained with a responder tuberculoid leprosy population (migration index = 0.04 +/- 0.004). Both phytohemagglutinin-induced general T-cell proliferation and, more significantly, antigen-induced lymphoproliferation were enhanced during the acute phase of the reaction. Suppressor cell activity, monitored by a costimulant assay, showed enhanced antigen-stimulated suppression of mitogen responses. Interestingly, the improvement in in vitro T-cell responses was not reflected in dermal reactivity, since 48-h delayed-type hypersensitivity responses after intradermal injection of soluble Mycobacterium leprae antigens continued to be poor. After subsidence of reactional lesions, leukocyte migration inhibition, lymphoproliferation, and suppressor cell activity were reduced to the unresponsive state seen in stable LL patients. Significantly, perturbations of T-cell reactivity are detectable in ENL reactions, indicating the natural but transient emergence of antigen-induced T cells in LL.

Antigens, Bacterial↗
PubMed1985

Comparison of radiometric macrophage assay and the mouse foot pad infection for the evaluation of Mycobacterium leprae sensitivity/resistance to dapsone.

Studies were undertaken in three independent centers to compare the newer, in vitro radiometric macrophage (M phi) assay with the conventional mouse foot pad infection for the diagnosis of dapsone resistance. Results obtained on 12 bacilliferous patients showed good concordance in both assays. One strain diagnosed as sensitive in the M phi assay was found to be resistant in the mouse foot pad. Three Mycobacterium leprae strains considered to be partially resistant in the mouse infection behaved as resistant strains in the M phi cultures. Attention is drawn to a rapid in vitro method for the identification of drug-resistant bacilli in leprosy patients.

Adolescent↗
PubMed1984

Inhibition of interleukin-2 production by adherent cell factors from lepromatous leprosy patients.

Twenty-four hour supernatants (MoF) were obtained from monocyte rich 2 h adherent cells of 19 leprosy patients and four healthy contacts. MoF from borderline and lepromatous patients produced 52-61% inhibition of human interleukin-2 (IL-2) production by a PHA conditioned T cell line (Jurkat). Non-adherent cell supernatants and MoF from tuberculoid and healthy individuals had little effect on IL-2 production. The suppression effected by MoF was in the first 12 h of initiation of PHA stimulated Jurkat cell cultures. Suppressive MoF did not interfere with (1) IL-2 release, (2) IL-2 utilization by Con A-induced T cell blasts or (3) constitutive proliferation of Jurkat cells. Such MoF were released spontaneously from adherent cells of bacilliferous leprosy patients but required in vitro antigen triggering in long term treated lepromatous patients. It is possible that the unresponsiveness associated with lepromatous leprosy is related to the inhibition of IL-2 production by suppressive factors, thereby, preventing the further expansion of antigen reactive T cells.

Cell Adhesion↗
PubMed1984

Evidence for the presence of M. leprae reactive T lymphocytes in patients with lepromatous leprosy.

Evidence for the presence of Mycobacterium leprae reactive T cells in many lepromatous leprosy (LL) patients was obtained using in vitro antigen-induced lymphoproliferative responses. (1) Co-cultures of T enriched cells from LL patients when combined with 2 h adherent cells (AC) from HLA-D compatible tuberculoid leprosy individuals showed significant levels of 3H-thymidine incorporation in the presence of soluble and integral M. leprae antigens. (2) More interestingly, autologous T cell + AC co-cultures also showed significant improvement in antigen-induced lymphoproliferation in nine of 16 lepromatous patients. Insignificant improvement was observed in similar co-cultures of tuberculoid leprosy patients. (3) Addition of exogenous, purified human interleukin-2 (IL-2) to antigen stimulated PBMC from some lepromatous patients showed the best improvement in terms of overall 3H-thymidine incorporation, indicating that lepromatous patients possess T cells which can differentiate to an IL-2 responsive state. Significantly, the level of proliferation varied within the group. A proportion of clinically similar lepromatous patients failed to show improvement by any of the above methods.

Antigens, Bacterial↗
PubMed1984

Differences in predominant T cell phenotypes and distribution pattern in reactional lesions of tuberculoid and lepromatous leprosy.

The nature and histological pattern of the cutaneous infiltrates of 17 leprosy patients in reversal reactions (Type I) and erythema nodosum leprosum (Type II, ENL) were compared with tissues from 18 non-reactional borderline leprosy (BT, BL) and lepromatous leprosy (LL) patients using monoclonal antibodies and immunofluorescence. Reactional BT lesions showed a mild increase in OKT11+ pan T cells as compared to non-reactional tissues and a significant influx of OKT8+ (suppressor/cytotoxic) cells which were peripherally localized in the lymphocyte mantle surrounding the epithelioid cells. The Leu 3a+ (helper/inducer) cells were scattered amongst the lymphocytes and macrophages. The mean ratio (+/- s.d.) of Leu 3a+/OKT8+ cells was 1.88 +/- 0.64 in Type I BT reactions as compared to 2.95 +/- 0.95 in BT lesions. In contrast, lesions of BL reversal reactions and ENL showed a more marked increase in pan T cells with a preponderance of the helper/inducer subset, Leu 3a+/OKT8+ ratio being 2.26 +/- 0.61 and 0.93 +/- 0.57 in BL reactional and non-reactional lesions, respectively. Interestingly, this increase in the numbers of the T cells reached levels observed in BT lesions. The distribution pattern of OKT8+ cells was similar to Leu 3a+, both being diffusely scattered amongst the bacilli laden macrophages. Ia like antigens were present in all granulomas and were abundant on lymphocytes and macrophages and less conspicuous on epithelioid cells. T6+ Langerhans cells were uniformly increased in all reactional lesions. It would appear that the changes observed in both Type I and Type II reactions are similar in the lepromatous group of patients. They differ significantly from the BT reversal reaction in terms of the dominant T cell subset and the microanatomical distribution of the OKT8+ cells in the lesions.

Antibodies, Monoclonal↗
PubMed1983

Radiometric macrophage culture assay for rapid evaluation of antileprosy activity of rifampin.

The antileprosy effect of rifampin was evaluated by a newly developed rapid in vitro assay wherein 31 human-derived strains and 1 armadillo-derived strain of Mycobacterium leprae were maintained for 2 and 3 weeks, respectively, in murine and human macrophages in the presence of [3H]thymidine. Of these strains, 27 showed significant incorporation of the radiolabel in cultures of live bacilli as compared with control cultures of heat-killed bacilli of the same strain. Consistent and significant inhibition of [3H]thymidine uptake was observed in M. leprae resident cultures with 3 to 200 ng of rifampin per ml as compared with similar cultures without the drug. In general, an increase in percent inhibition was seen from 3 to 20 ng/ml, with marginal increases at 40, 50, and 100 ng/ml. M. leprae strains appear to be remarkably susceptible to this drug in the in vitro assay.

Animals↗
PubMed1983

Monocyte-derived soluble suppressor factor(s) in patients with lepromatous leprosy.

Peripheral blood monocytes from polar lepromatous leprosy (LL) patients were unable to support Mycobacterium leprae-induced in vitro lymphoproliferation of HLA-D-matched T cells from tuberculoid leprosy subjects, whereas those from responder individuals were able to do so. Monocyte-rich adherent cells from untreated LL patients released de novo soluble factors which inhibited antigen-induced lymphoproliferation to a greater extent and mitogenic responses to a lesser extent. Suppressive activity varied in different LL patients. However, the degree of suppression was similar in soluble factors obtained de novo and after treatment of adherent cells with heat-killed and freshly extracted, cryopreserved M. leprae. Treated patients showed less inhibition with de novo released soluble factors (27 +/- 7.7%) as compared to parallel soluble factors obtained after antigen treatment (44 +/- 4.8%) or with de novo soluble factors from untreated LL patients (62 +/- 14.2%). Similar supernatants from tuberculoid individuals showed no or insignificant effects on antigen-induced lymphoproliferation. The suppressive activity of LL soluble factors was produced for up to 72 h, was heat stable at 56 degrees C for 30 min, was indomethacin resistant, and resided in the greater than 25,000 molecular weight fraction.

Blood Proteins↗
PubMed1983

Rapid, radiolabeled-microculture method that uses macrophages for in vitro evaluation of Mycobacterium leprae viability and drug susceptibility.

This paper describes a microculture rapid assay using radiolabeling and mouse macrophages to determine the viability and the drug susceptibility or resistance of Mycobacterium leprae. Comparison of M. leprae resident macrophage cultures maintained in 96-well flat-bottomed plates showed results for viability and susceptibility or resistance to dapsone that were similar to results for concurrent cultures in Leighton tubes with greater numbers of bacilli and macrophages.

Adult↗
PubMed1983

T cell subsets in leprosy lesions: in situ characterization using monoclonal antibodies.

Cryostat sections of dermal lesions from 30 untreated leprosy patients were studied by indirect immunofluorescence using monoclonal antibodies defining T cell subsets and Ia like antigens. Most lymphocytes in leprosy lesions were positive for OKT3 and Ia like antigens indicating thereby the presence of activated T cells. Maximal numbers of these cells were seen in localized paucibacillary tuberculoid leprosy lesions in close association with epithelioid cells. A decline in their numbers was observed over the leprosy spectrum with a marked reduction in disseminated, multi-bacillary, lepromatous leprosy where only scattered OKT3+ cells were visualized. OKT4 and OKT8 positive cells defining T cell subsets, were frequently found within the OKT3+ lymphocytes throughout the leprosy spectrum. The ratio of OKT4+/OKT8+ cells ranged from 1.2 to 5.0 in tuberculoid and from 0.2 to 1.0 in lepromatous lesions. Macrophages in the granulomas stained intensely with anti-Ia antisera. Ia like antigens were expressed to the same degree on macrophages with or without intracellular acid fast bacilli.

Antibodies, Monoclonal↗