Biomedical subjects

K Saha

Publications and source records attributed to K Saha.

At least 73 records · Page 4Linked to original sources

PubMed1993

Immunohistopathological spectrum in cutaneous tuberculosis.

Granulomas of lupus vulgaris were characterized by a raised CD4+/CD8+ ratio, while in scrofuloderma this was significantly decreased. Tuberculosis verrucosa cutis showed intermediate changes. These immunological variations suggest that cutaneous tuberculosis forms a spectrum with strong cell-mediated immunity seen in lupus vulgaris, and weaker cell-mediated responses in scrofuloderma; tuberculosis verrucosa cutis is intermediate between the two.

Antigens, CD↗

PubMed1993

Tumor necrosis factor: status in reactions in leprosy before and after treatment.

BACKGROUND: Tumor necrosis factor-alpha (TNF) is an important mediator of immunologic responses to chronic infections. METHOD: Sera from 25 patients with acute reactions (6 with type 1 upgrading, 8 with type 1 downgrading, and 11 with type 2 reaction) were assayed for TNF before treatment and after clinical remission of the acute episode. The results were compared with serum TNF levels in healthy controls and fresh pauci- and multibacillary leprosy patients. RESULTS: TNF levels in acute reactions were higher than in the control groups (significant only in upgrading reaction). In type 1 reaction, serum TNF concentrations fell to approximately the levels of the control patients following treatment and clinical remission. In type 2 reaction, however, levels of TNF were seen to rise further (became statistically significant) as a result of therapy induced clinical remission. CONCLUSIONS: The rise in TNF-alpha level in reactions in leprosy is significant and indicates its active role in immunopathogenesis. The corresponding decline in TNF-alpha levels seen following regression of type 1 (lepra) reactions was not observed in the case of type 2 (ENL) reaction. This probably reflects the enhancement of cellular immunity in such cases and/or an attempt by the immunologic process to overcome specific inhibitors.

Administration, Oral↗

PubMed1993

Correlation of specific virus-astrocyte interactions and cytopathic effects induced by ts1, a neurovirulent mutant of Moloney murine leukemia virus.

ts1 is a highly neuropathogenic and lymphocytopathic mutant of Moloney murine leukemia virus TB (MoMuLV-TB). We previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-->Ile, in precursor envelope protein gPr80env. This Val-25-->Ile substitution apparently renders gPr80env inefficient for transport from the endoplasmic reticulum to the Golgi apparatus. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to the accumulation of gPr80env in the endoplasmic reticulum. Since endothelial and glial cells are targets of ts1 infection in the central nervous system, we established primary endothelial and astrocyte cultures to investigate the mechanism of cell killing caused by ts1. A continuous cell line, TB, was used as a control. Our results showed that both ts1 and MoMuLV-TB replicated and induced a cytopathic effect in astrocyte cultures, albeit to different degrees; ts1 appeared to be more lethal than MoMuLV-TB. On the other hand, ts1 and MoMuLV-TB infections of endothelial or TB cells were not cytopathic. The cytopathic effect in infected astrocytes correlated with the inefficiency of gPr80env transport and the intracellular accumulation of gPr80env as well as aberrant virus particles.

Animals↗

PubMed1993

Chest malignancies & serum immunoglobulin E.

Serum IgE levels were measured by the radioimmunoassay technique in the sera of 53 patients with neoplastic chest diseases. Forty seven patients had malignant chest tumours and another 6 had benign tumours or mediastinal cysts. They included 33 smokers and 20 non-smokers. For comparison, 30 normal non-smoking controls matched for age and sex were included. The serum IgE levels in patients with chest malignancies showed an increase as compared to controls. The IgE levels increased significantly in adenocarcinoma (P < 0.01) and squamous cell carcinoma (P < 0.001), while they were not raised in poorly differentiated carcinoma. There was no significant difference between the serum IgE levels of 32 smokers and 15 non-smokers with malignant chest tumours.

Adolescent↗

PubMed1993

Clinical spectrum of pulmonary hydatidosis and raised serum IgE levels in the Indian southern peninsula.

Fifteen patients with surgically proven hydatid disease of the lung aged between 4 and 51 years were studied. The disease spectrum varied from single to multiple cysts of different sizes, with associated pyogenic chest infections or parasitic infestations of the gut. The serum IgE level varied widely in these cases and very high levels were found in 60% of the patients. This high IgE response was related to the vitality of the cysts, associated bacterial infection of the chest, infection with helminths and smoking habit.

Adolescent↗

PubMed1993

Serum immunoglobulin E response in sputum positive patients with pulmonary tuberculosis.

A marked elevation of serum IgE level (6939 +/- 5651 IU/ml) was observed in 20 untreated and drug sensitive patients with sputum AFB positive pulmonary tuberculosis. Of them 18 were freshly diagnosed and were totally untreated. Their mean serum IgE level was 6715 +/- 5545 IU/ml. The remaining two patients presented with a relapse of the disease but were sensitive to all anti-tuberculosis drugs. Their serum IgE levels before retreatment were 2828 and 15079 IU/ml respectively. In the 13 chronic drug resistant patients who never had sputum conversion, the serum IgE level (1116 +/- 1897 IU/ml) was significantly lower (P < 0.01). It is suggested that the high serum IgE response in freshly diagnosed untreated and drug sensitive patients with illness of short duration may be related to strong early tuberculin hypersensitivity reaction and protective immunity, whereas low serum IgE response in chronic drug resistant cases with high bacterial load for prolonged duration may be related to the generation of suppressor CD8 lymphocytes eventually leading to suppression of B cells committed to the synthesis of protective serum IgE.

Adolescent↗

PubMed1992

A simple method of concentrating monoclonal antibodies from culture supernatant by ultrafiltration.

How to obtain concentrated monoclonal antibodies from culture supernatant is of great importance to many scientists today. In this report, a simple, single-step technique is described to concentrate monoclonal antibodies directly from hybridoma-culture supernatant. The contaminants can be removed from the supernatant by using an ultrafiltration unit which allows macromolecules of less than 100,000 MW to pass through leaving behind monoclonal antibodies which is purified and concentrated more than 25-fold.

Antibodies, Monoclonal↗

PubMed1992

Protective role of cytotoxic lymphocytes against murine leukemia virus-induced neurologic disease and immunodeficiency is enhanced by the presence of helper T cells.

We examined the role of T cells and their separated subsets in providing immunity against ts1 (a mutant of the Moloney murine leukemia virus) induced paralysis and immunodeficiency. Adoptive transfer of syngeneic total T cells from immunized mice protected newborn mice, at least partially, from ts1-induced disease syndrome. In infected mice who received total immune T cells, virus replication was reduced and the mice survived longer. When only separated immune CD8+ T cells were transferred to infected mice, similar protection, albeit to a lesser extent, was observed. Transfer of separated immune CD4+ T cells alone gave no protection. However, when recombined CD4+ and CD8+ cells were transferred together, an immune response similar to that when total T cells were transferred was observed. Cytotoxic assays from ts1-immunized mice revealed the presence of virus-specific CD8+ cytotoxic T lymphocytes that could lyse virus-expressing cells at a high effector/target ratio. We conclude that CD8+ T cells alone can provide immunity against ts1-induced paralysis and immunodeficiency and that the simultaneous presence of CD4+ T cells can also significantly enhance the immune response.

Animals↗

PubMed1992

Reconstruction of anti-leprosy drug depleted complement haemolytic activity by addition of zymosan-treated sera (a source of C142) and CratEDTA (a source of C3-C9).

This paper describes the mechanism of in vitro interaction of human serum complement system with anti-leprosy drugs (dapsone and clofazimine) and anti-lepra reaction drugs such as chloroquine. These drugs could inhibit the complement-mediated lysis of erythrocytes both via direct and alternative pathways, but only at hypertherapeutic doses. Attempts were made to restore the drug depleted complement-mediated lysis of erythrocytes by adding zymosan-treated guinea-pig sera (a source of C142) and also by adding Crat-EDTA sera (a source of C3-C9). Destroyed complement-mediated haemolytic activity by dapsone could be restored by early complement (C142) components, while complement-mediated haemolytic activity blocked by clofazimine could be regenerated by adding both late (C3-C9) and early (C142) complement component. However, chloroquine-mediated inhibition of the complement-mediated haemolysis activity could not be appreciably restored by adding both early and late complement reagents.

Animals↗

PubMed1992

Anti-leprosy drugs inhibit the complement-mediated solubilization of pre-formed immune complexes in vitro.

Incubation of pre-formed immune complexes (IC) (125I-HSA--anti-HSA) with normal human serum resulted in solubilization of IC. When various anti-leprosy drugs were added to human sera, solubilization of IC was fairly explicit with clofazimine, whereas this effect was marginal with dapsone. Rifampicin hardly displayed this effect. Aspirin, chloroquine, and prednisolone, the drugs used in addition to multi-drug therapy to control reactions in leprosy, were in a position to inhibit the solubilization of 125I HSA--anti-HSA by normal serum only at a very high dose. From the current data of the inhibition of solubilization of pre-formed IC along with our earlier observations on the modulation of complement-mediated haemolysis by these drugs, it may be possible to postulate that clofazimine as well as chloroquine affect early complement components. This may in turn be responsible for preventing the deposition of C3 complement onto IC.

Antigen-Antibody Complex↗

PubMed1992

In vivo effects of anti-leprosy drugs on the rat peritoneal macrophages and lymphocyte subpopulations.

The present study describes the in vivo effects of anti-leprosy drugs on rat peritoneal macrophages and T-cell homeostasis. It was observed that BCG-elicited rat peritoneal macrophages produced more H2O2 and expressed more Ia antigen on their cell surfaces compared with resident peritoneal macrophages. Furthermore, elicited macrophages isolated from rats administered multidrug therapy (MDT), consisting of dapsone, clofazimine and rifampicin in high dose (10 x MDT) released more O2-. On the contrary, there was a significant decrease in the Ia antigen expression on these macrophages. Anti-leprosy drug treatment in high dose (10 x MDT) decreased the total number of blood T-helper (W3/25+) cells and increased the total number of blood T-suppressor (OX-8+) cells which resulted in a significant decrease in a W3/25: OX-8 ratio. Electron microscopy of elicited macrophages isolated from 10 x MDT treated rats showed development of many filipodia compared with control macrophages. These data show that 10 x MDT treatment in rats for 1 month alters the homeostasis of blood T-cell subpopulations which perhaps decreases the Ia expression on macrophages. However, the increase in O2- production and the appearance of filipodia on the macrophages is due to a direct effect of drugs on the macrophages. MDT treatment for 1 month in a therapeutic dose has no effect on the above-mentioned parameters.

Animals↗

PubMed1992

Retrovirus-induced immunodeficiency in mice exacerbates gastrointestinal candidiasis.

Dysfunction of neutrophils in patients infected with human immunodeficiency virus is at least partly responsible for secondary microbial diseases in these individuals, including invasive gastrointestinal (GI) candidiasis. Immunoregulatory disturbances associated with the development of AIDS in human immunodeficiency virus-infected patients exacerbates Candida albicans infection of the upper GI tract and frequently leads to oropharyngeal and esophageal candidiasis. In this article, we present the first report of a murine model of invasive GI candidiasis associated with an AIDS-related murine immunodeficiency syndrome that results from infection of C57BL/6 mice with a previously described retrovirus complex (LP-BM5). Mice of the inbred strain were infected with C. albicans by oral-intragastric inoculation as infants and with the retrovirus by the intraperitoneal route 30 days later. Control mice of the same strain were infected with C. albicans as above and subsequently infected with the avirulent, ecotropic helper virus (MBI-5). Animals were killed 90 days after retroviral challenge. Total and differential blood cell counts, CD4+ T-cell counts in the spleen, and the histopathology of the gastric mucosa of experimental and control animals were determined. The virulent LP-BM5-infected animals developed murine AIDS and showed eruptive and suppurative lesions, with associated C. albicans mainly in regions of the cardial-atrium fold of the stomach. Well-defined abscesses with entrapped C. albicans hyphae were observed in the region of the cardial-atrium fold of control mice. A significant increase in the number of C. albicans CFU in homogenized and plated segments of the GI tract was recognized in mice with murine AIDS versus the control animals. The murine model of GI candidiasis reported here permits examination of the nature of C. albicans interaction with the gastric mucosa both in the immunocompetent host under conditions in which the yeast exists predominantly as a commensal organism and in the immunosuppressed host during progressive stages of AIDS induced by a retroviral infection.

Animals↗

PubMed1992

ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, can infect both CD4+ and CD8+ T cells but requires CD4+ T cells in order to cause paralysis and immunodeficiency.

When neonatal FVB/N mice were inoculated with ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, they developed a progressive bilateral hindlimb paralysis and immunodeficiency leading to death 4 to 6 weeks after inoculation. T lymphocytes have been shown to be primarily responsible for this ts1-induced syndrome. Here we compare the role played by each subset of T lymphocytes, i.e., CD4+ and CD8+ T cells, in disease development. Mice were depleted of a specific subset for the first 10 days of their lives by using either anti-CD4 or anti-CD8 monoclonal antibodies in vivo. Disease development in these mice was then monitored. Depletion of CD4+ T cells significantly attenuated the ts1-induced syndrome: virus replication was decreased, disease latency was extended, and death was prevented in 60% of the mice. Similar treatment with anti-CD8 antibody had almost no effect on disease progression. However, when depletion was begun 2 weeks after neonatal ts1 inoculation, CD4+ T cell depletion did not affect disease development. ts1 infected CD4+ and CD8+ T lymphocytes equally well in vivo, as shown by flow cytometric analysis, but virus replication was restricted primarily to the CD4+ subset of T cells, as found by in vitro assay. Hence, CD4+ T lymphocytes play an important role in the development of ts1-induced paralysis and immunodeficiency. The mechanism of this CD4+ T-cell-mediated disease production by ts1 is not clear; however, increased replication of ts1 in the CD4+ T cells, especially in the early stages of the disease, seems to play a crucial role.

Animals↗

PubMed1992

Colonic immunity in patients and amoebic liver abscess.

Secretory immunoglobulin A (S-IgA), coproantibody titre (antiamoebic) and IgA, IgG, IgM immunocytes in rectal mucosa were studied in 13 patients with amoebic liver abscess (ALA) prior to and 4-6 weeks after completion of antiamoebic therapy. Ten asymptomatic Entamoeba histolytica cyst passers and 17 healthy age and sex matched volunteers served as controls. Fecal S-IgA levels and counts of IgA bearing immunocytes in mucosa were significantly higher in patients with ALA and cyst passers as compared to healthy controls and showed a significant fall after treatment. Fecal antiamoebic antibodies were high in cyst passers and in cases of ALA after treatment. Raised levels of S-IgA and IgA class immunocyte counts probably indicate a local mucosal immune response directed at containing the infection.

Antibodies, Protozoan↗

PubMed1992

Delayed clearance of circulating immune complexes in mice following administration of antileprosy drugs.

In this report we describe an animal experiment which showed delayed clearance of preformed 125I-HSA-anti-HSA immune complexes (with five times excess HSA) from the circulation of mice treated with antileprosy drugs (dapsone, clofazimine, and rifampin--multidrug therapy for 7 days) in comparison with normal (untreated) mice. The results also showed delayed retention of the preformed immune complexes in the spleen and kidneys of the antileprosy-drug-treated animals. The exact mechanism of the delayed handling of preformed immune complexes in mice fed antileprosy drugs could not be ascertained. However, in light of the anticomplementary effects of clofazimine and dapsone, as reported earlier, and in light of the large accumulation of clofazimine and rifampin in macrophages, it has been postulated that in the drug-fed animals either the immune complexes could not be phagocytosed by macrophages, through the avenue of their C3b receptors, or the immune complexes could not be downgraded easily within the macrophages overloaded with clofazimine and rifampin. These results might have clinical significance and might throw some light on the prolonged persistence of circulating immune complexes in the vascular bed of lepromatous patients even after clinical remission of erythema nodosum leprosum.

Animals↗

PubMed1992

Nutritional status of children of urban leprosy patients staying at preventoria based on biochemical parameters.

Measurements of nutritionally relevant biochemical and endocrine variables were made on 60 apparently healthy children (group A) whose parents suffered from leprosy and who had been separated at the age of 4 years and brought up in preventoria. Most of the measurements were also made on a comparison group of healthy children from the same poor socio-economic class (group B). In both groups the serum concentrations of cholesterol and triglycerides were well below those found in Western populations. Almost all the children in both groups were anaemic, but serum iron and ferritin levels were satisfactory. Folate and vitamin B12 levels were measured in group A only and were low in a significant proportion. Deficiency of these water-soluble vitamins may be a cause of the anaemia. Low albumin levels were found in 40% of group A children, compared with 2% in group B. The concentrations of calcium and magnesium were lower and that of phosphate higher in group A than in B. In both groups one-third of the children had low levels of serum zinc. Fifteen per cent of group A children had biochemical evidence of vitamin A deficiency, but none were deficient in vitamin E. Levels of total T3 and total T4 were below the lower limit of normal in a substantial proportion of children in both groups. Concentrations of parathyroid hormone were increased in parallel with the low values for serum calcium. Radiological studies of ossification centres in 57 group A children showed delayed maturation in 11 cases. The relevance of these findings to previous studies of the children of lepers in India is discussed.

Adolescent↗

PubMed1992

Murine leukemia virus induced central nervous system diseases.

The ts1 mutant of Moloney murine leukemia virus TB (MoMuLV-TB) causes a degenerative neurologic and immunologic disease in mice characterized by development of spongiform encephalomyelopathy that results in hind-limb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. T cells, particularly CD4+ helper T cells, play a key role in the pathogenesis of the disease induced by ts1. Therefore, ts1 is unique among the described murine retroviruses in its ability to afflict both the central nervous system (CNS) and the T-cell compartment of the immune system in the same host. This particular ability to cause degenerative diseases involving both the CNS and immune system is shared by the lentiviruses responsible for development of the acquired immunodeficiency syndromes of humans and macaques. Our goal has been to elucidate the specific cellular and molecular mechanisms that underlie this neuro- and immunopathogenicity of ts1. We have previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-Ile, in the precursor envelope protein gPr80env. Further, at the restrictive temperature, the Val-25-Ile substitution did not prevent oligomerization of the gPr80env proteins; however, the structure of the oligomer was incompetent for transport from the ER to the Golgi. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to accumulation of the gPr80env oligomers in the ER. Since glial cells are targets of ts1 infection in vivo, primary astrocytic cultures were established and the cytopathic effect of ts1 and MoMuLV-TB on these cells assessed. Both viruses replicate well in astrocytes and their replication is cytopathic, albeit to different degrees. The ts1 mutant appears to produce greater cell killing than the wild-type virus. Furthermore, it was found that the rate of processing of gPr80env of ts1 in astrocytes is slower than that of MoMuLV-TB. Therefore, the inefficient transport and processing of gPr80env of ts1 appears to correlate with its cytopathic effect in these cells. Electron microscopic studies of the ts1-infected astrocytes revealed large numbers of aberrant particles in the ER. The in vitro cytopathic effect of ts1 on astrocytes may reflect what happens in vivo. An indirect mechanism of neuronal-cell killing by ts1 is proposed.

Animals↗

PubMed1991

Alteration from T- to B-cell tropism reduces thymic atrophy and cytocidal effects in thymocytes but not neurovirulence induced by ts1, a mutant of Moloney murine leukemia virus TB.

The ts1 mutant of Moloney murine leukemia virus TB causes degenerative neurologic and immunologic disease in mice, characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. To investigate the pathogenesis of the thymic atrophy caused by ts1, we constructed a chimeric virus, ts1-Cas(NS), in which a major portion of the U3 region of the long terminal repeat of ts1, a T-lymphotropic and neurovirulent murine leukemia virus, was replaced by the corresponding U3 region of Cas-Br-E, a B-lymphotropic and neurovirulent murine leukemia virus. In FVB/N mice, ts1-Cas(NS) induced paralytic and wasting disease with incidence, severity, and latency similar to that induced by ts1, but it failed to cause thymic atrophy as severe as that observed in ts1-infected mice. Furthermore, thymocytes cultured from ts1-Cas(NS)-infected mice died at a much slower rate than those of ts1-infected mice. The U3 substitution in ts1-Cas(NS) specifically diminished the ability of the virus to replicate in the thymus, whereas viral replication in the spinal cord was not significantly affected; thus, neurovirulence was not changed. The correlation of reduced thymic atrophy with decreased thymic viral titers and the decreased ability of ts1-Cas(NS) to cause thymocyte death in mice suggest strongly that the marked thymic atrophy in ts1-infected mice is not an indirect effect occurring secondary to neurodegenerative and wasting disease but is a direct cytopathic effect of high-level viral replication in the thymus.

Animals↗