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Biomedical subjects

K Saha

Publications and source records attributed to K Saha.

At least 37 records · Page 2Linked to original sources
PubMed2000

Efficacy of single-dose ROM therapy plus low-dose convit vaccine as an adjuvant for treatment of paucibacillary leprosy patients with a single skin lesion.

The recent World Health Organization multicentric field study on the treatment of paucibacillary (PB) leprosy patients with single skin lesion (SSL) and a single dose of rifampin-ofloxacin-minocycline (ROM) brought new hope to those who are engaged in the eradication of leprosy from India. Being encouraged by the WHO report, we undertook the present hospital-based study and found that PB leprosy patients with SSL were morphologically and histopathologically heterogeneous. The histological spectrum of SSL ranged from indeterminate through tuberculoid (TT) to borderline tuberculoid (BT) leprosy, and most patients had active BT leprosy. Ninety new, untreated PB leprosy patients with SSL were included in the present study for comparative assessment of the efficacies of ROM and ROM plus Convit vaccine therapies. Children, pregnant women, lactating mothers and patients with any thickening of nerves were excluded. All patients were bacteriologically negative (skin-smear test) but lepromin reactive. The patients were divided into two groups after proper matching for morphological and histological status of SSL: a) The test group included 60 patients and the control group included 30 patients. The test group was given a single dose of ROM initially and two injections of low-dose Convit vaccine, one initially and the other at the end of 3 months. b) The control group was given only a single dose of ROM initially. Both groups were followed clinically every 2 weeks for 6 months and retested for histological, bacteriological and lepromin status at the end of 6 months. Thereafter, they were followed clinically every month for another 6 months. In the test group, the SSL resolved in 33.3%, regressed in 48.3%, and remained active in 18.3% of the patients, while the granuloma disappeared in 70% of the cases. Only one patient developed neuritis, and in another patient the disease relapsed on the eighth month. On the other hand, the SSL in the control patients resolved, regressed and remained active in 13.3%, 63.3% and 23.3% of the cases, respectively, while the granuloma disappeared in 53.3% of the cases. In the seven patients who remained active, the disease course was progressive, and two of them developed neuritis. The clinical outcome of the patients treated with ROM plus low-dose Convit vaccine was statistically superior to those treated with single-dose ROM therapy alone.

Adjuvants, Immunologic↗
PubMed1999

Resistance against syncytium-inducing human immunodeficiency virus type 1 (HIV-1) in selected CD4(+) T cells from an HIV-1-infected nonprogressor: evidence of a novel pathway of resistance mediated by a soluble factor(s) that acts after virus entry.

A panel of CD4(+) T-cell clones were generated from peripheral blood lymphocytes from a patient with a nonprogressing infection of human immunodeficiency virus type 1 (HIV-1) by using herpesvirus saimiri as described recently. By and large, all of the clones expressed an activated T-cell phenotype (Th class 1) and grew without any further stimulation in interleukin-2-containing medium. None of these clones produced HIV-1, and all clones were negative for HIV-1 DNA. When these clones were infected with primary and laboratory (IIIB) strains of HIV-1 with syncytium-inducing (SI) phenotypes, dramatic variation of virus production was observed. While two clones were highly susceptible, other clones were relatively or completely resistant to infection with SI viruses. The HIV-resistant clones expressed CXCR4 coreceptors and were able to fuse efficiently with SI virus env-expressing cells, indicating that no block to virus entry was present in the resistant clones. Additionally, HIV-1 DNA was detectable after infection of the resistant clones, further suggesting that HIV resistance occurred in these clones after virus entry and probably after integration. We further demonstrate that the resistant clones secrete a factor(s) that can inhibit SI virus production from other infected cells and from a chronically infected producer cell line. Finally, we show that the resistant clones do not express an increased amount of ligands (stromal-derived factor SDF-1) of CXCR4 or other known HIV-inhibitory cytokines. Until now, the ligands of HIV coreceptors were the only natural substances that had been shown to play antiviral roles of any real significance in vivo. Our data from this study show that differential expression of another anti-HIV factor(s) by selected CD4(+) T cells may be responsible for the protection of these cells against SI viruses. Our results also suggest a novel mechanism of inhibition of SI viruses that acts at a stage after virus entry.

CD4-Positive T-Lymphocytes↗
PubMed1998

Constitutive activation of TCR signaling molecules in IL-2-independent Herpesvirus saimiri-transformed T cells.

Both human T cell leukemia virus type I and simian Herpesvirus saimiri (HVS) transform human T cells in vitro. Although IL-2-independent growth in human T cell leukemia virus type I-transformed T cells is associated with constitutive phosphorylation of JAK/STAT kinases, we now demonstrate that different mechanisms may be responsible for the ability of HVS-transformed T cells to proliferate in the absence of exogenous cytokines. The IL-2 independence of an HVS-transformed cell line correlated with constitutive activation of protein tyrosine kinases known to be induced following TCR engagement. Thus, in these cells we observed increased phosphotransferase activity of Lck as well as constitutive tyrosine phosphorylation of the TCR-associated ZAP-70 kinase and expression of the related Syk protein tyrosine kinase. While Syk is generally not expressed in activated T cells, its introduction has been shown to enhance TCR responsiveness. These results suggest that distinct signal transduction cascades can participate in the transition of T cells to IL-2 independence.

Cell Division↗
PubMed1998

Screening of anti-diarrhoeal profile of some plant extracts of a specific region of West Bengal, India.

Ethanol extract of four different plants of the Khatra region of the Bankura district of West Bengal, India were evaluated for anti-diarrhoeal activity against different experimental models of diarrhoea in rats. The extracts of Ficus bengalensis Linn. (hanging roots), Eugenia jambolana Lam. (bark), Ficus racemosa Linn. (bark) and Leucas lavandulaefolia Rees (aerial parts) showed significant inhibitory activity against castor oil induced diarrhoea and PGE2 induced enteropooling in rats. These extracts also showed a significant reduction in gastrointestinal motility in charcoal meal tests in rats. The results obtained establish the efficacy of all these plant materials as anti-diarrhoeal agents.

Animals↗
PubMed1998

Endogenous production of beta-chemokines by CD4+, but not CD8+, T-cell clones correlates with the clinical state of human immunodeficiency virus type 1 (HIV-1)-infected individuals and may be responsible for blocking infection with non-syncytium-inducing HIV-1 in vitro.

Recent studies have demonstrated that the beta-chemokines RANTES, MIP-1alpha, and MIP-1beta suppress human immunodeficiency virus type 1 (HIV-1) replication in vitro and may play an important role in protecting exposed but uninfected individuals from HIV-1 infection. However, levels of beta-chemokines in AIDS patients are comparable to and can exceed levels in nonprogressing individuals, indicating that global beta-chemokine production may have little effect on HIV-1 disease progression. We sought to clarify the role of beta-chemokines in nonprogressors and AIDS patients by examination of beta-chemokine production and HIV-1 infection in patient T-lymphocyte clones established by herpesvirus saimiri immortalization. Both CD4+ and CD8+ clones were established, and they resembled primary T cells in their phenotypes and expression of activated T-cell markers. CD4+ T-cell clones from all patients had normal levels of mRNA-encoding CCR5, a coreceptor for non-syncytium-inducing (NSI) HIV-1. CD4+ clones from nonprogressors and CD8+ clones from AIDS patients secreted high levels of RANTES, MIP1alpha, and MIP-1beta. In contrast, CD4+ clones from AIDS patients produced no RANTES and little or no MIP-1alpha or MIP-1beta. The infection of CD4+ clones with the NSI HIV-1 strain ADA revealed an inverse correlation to beta-chemokine production; clones from nonprogressors were poorly susceptible to ADA replication, but clones from AIDS patients were highly infectable. The resistance to ADA infection in CD4+ clones from nonprogressors could be partially reversed by treatment with anti-beta-chemokine antibodies. These results indicate that CD4+ cells can be protected against NSI-HIV-1 infection in culture through endogenously produced factors, including beta-chemokines, and that beta-chemokine production by CD4+, but not CD8+, T cells may constitute one mechanism of disease-free survival for HIV-1-infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Coronary artery bypass grafting without cardiopulmonary bypass.

Coronary artery bypass surgery on a beating heart is now an accepted modality to treat selected patients of ischaemic heart disease. From June '92 through Sep '97, 162 patients underwent this procedure. There was no mortality and none of the patients had any respiratory or neurological morbidity, though 24% of the patients form a high risk group for conventional coronary bypass surgery. It is definitely cost effective in comparison to any other modalities for treatment of ischaemic heart disease. We conclude that continous use of this technique is justified and all cardiac surgeons should have exposure to this procedure.

Adult↗
PubMed1998

Why relapse occurs in PB leprosy patients after adequate MDT despite they are Mitsuda reactive: lessons form Convit's experiment on bacteria-clearing capacity of lepromin-induced granuloma.

It is amazing how after years of scientific research and therapeutic progress many simple and basic questions about protective immunity against Mycobacterium leprae remain unanswered. Although the World Health Organization (WHO) has recommended short-term multidrug therapy (WHO/MDT) for the treatment of paucibacillary (PB) leprosy patients, from time to time several workers from different parts of the globe have reported inadequate clinical responses in a few tuberculoid and indeterminate leprosy patients following adequate WHO/MDT despite the fact that they are Mitsuda responsive. A few borderline tuberculoid patients harbor acid-fast bacilli (AFB) in their nerves for many years even though they become clinically inactive following MDT, a fact which has been ignored by many leprosy field workers. Keeping these patients in mind, we have attempted to investigate the cause of the persistence of AFB in PB cases and have looked into the question of why Mitsuda positivity in tuberculoid and indeterminate leprosy patients, as well as in healthy contacts, is not invariably a guarantee for protectivity against the leprosy bacilli. We have: a) analyzed the histological features of lepromin-induced granulomas, b) studied the bacteria-clearing capacity of the macrophages within such granulomas, and c) studied the in vitro leukocyte migration inhibition factor released by the blood leukocytes of these subjects when M. leprae sonicates have been used as an elicitor. The results of these three tests in the three groups of subjects have been compared and led us to conclude that the bacteria-clearing capacity of the macrophages within lepromin-induced granuloma (positive CCB test) may be taken as an indicator of the capability of elimination of leprosy bacilli and protective immunity against the disease. This important macrophage function is not invariably present in all tuberculoid and indeterminate leprosy patients or in all contacts even though they are Mitsuda responsive and are able to show a positive leukocyte migration inhibition (LMI) test. It is likely but not certain that this deficit of the macrophage is genetically predetermined and persists after completion of short-term WHO/MDT. Thus, after discontinuation of treatment slow-growing, persisting M. leprae multiply within macrophages leading to relapse.

Adolescent↗
PubMed1997

Improvement of Herpesvirus saimiri T cell immortalization procedure to generate multiple CD4+ T-cell clones from peripheral blood lymphocytes of AIDS patients.

Herpesvirus saimiri (HVS) can infect and immortalize human T lymphocytes of both CD4- and CD8-positive phenotypes. We have previously shown that infection of peripheral blood lymphocytes (PBL) from AIDS patients with HVS predominantly yielded immortalized CD8-positive T cell clones. Here we show that CD4-positive T cells from AIDS patients can be efficiently immortalized by HVS if patient PBL are enriched for CD4-positive T cell subpopulation prior to HVS infection. Such cells can be cloned and maintained in culture for prolonged times, and they exhibit activated T cell phenotype of Th1 class and are susceptible to HIV-1 infection. Several immortalized T cell clones obtained from one out of three AIDS patients tested here were HIV-1 positive and produced infectious virus. This approach permits efficient generation of multiple CD4-positive T cell clones from AIDS patients for functional and virological studies.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Human immunodeficiency virus type 1 (HIV-1) infection of herpesvirus saimiri-immortalized human CD4-positive T lymphoblastoid cells: evidence of enhanced HIV-1 replication and cytopathic effects caused by endogenous interferon-gamma.

Herpesvirus saimiri (HVS) is a nonhuman primate gamma herpesvirus which can immortalize human T lymphocytes similar to Epstein-Barr virus immortalization of B cells. The HVS-immortalized T cell lines can be cloned and they remain functional, including susceptibility of CD4 expressing T cells to infection with human immunodeficiency virus type 1 (HIV-1). In this report, we have used five such HVS-transformed CD4-positive T cell clones to reevaluate the role of endogenous interferon gamma (IFN gamma) in HIV-1 replication in T cells. All five clones had similar phenotypes; and four clones constitutively produced IFN gamma and one clone did not. All five clones could be efficiently infected with HIV-1. HIV-1 infection of the IFN gamma-positive cells also upregulated IFN gamma mRNA production and IFN gamma secretion but not production of IL-2 or IL-4. In contrast, infection of IFN gamma-negative cells did not induce IFN gamma, IL-2, or IL-4. Exposure to anti-IFN gamma antibodies after HIV-1 infection significantly reduced virus production and inhibited virus-induced death of IFN gamma-positive cells but had no effect on IFN gamma-negative cells. We conclude that in CD4-positive T lymphocytes immortalized by HVS endogenous IFN gamma does not inhibit HIV-1 but enhances HIV-1 replication and cytolysis. The potential augmenting effects of IFN gamma on HIV-1 replication in CD4-positive T cells recommend caution in a therapeutic use of this cytokine in AIDS.

CD4-Positive T-Lymphocytes↗
PubMed1997

Studies on in vivo antitussive activity of Leucas lavandulaefolia using a cough model induced by sulfur dioxide gas in mice.

The methanol extract of Leucas lavandulaefolia was investigated for its effects on a cough model induced by sulfur dioxide gas in mice. It exhibited significant antitussive activity when compared with control in a dose-dependent manner. The antitussive activity of the extract was comparable to that of codeine phosphate (10 mg/kg), a prototype antitussive agent. The Leucas lavandulaefolia extract at 100, 200, and 400 mg/kg. p.o. showed inhibition of cough by 35.0, 51.9, and 56.5% within 1 h of performing the experiment.

Animals↗
PubMed1997

Effect of Nelumbo nucifera rhizome extract on blood sugar level in rats.

Oral administration of the ethanolic extract of rhizomes of Nelumbo nucifera markedly reduced the blood sugar level of normal, glucose-fed hyperglycemic and streptozotocin-induced diabetic rats, when compared with control animals. The extract improved glucose tolerance and potentiated the action of exogenously injected insulin in normal rats. When compared with tolbutamide, the extract exhibited activity of 73 and 67% of that of tolbutamide in normal and diabetic rats, respectively.

Animals↗
PubMed1997

Studies on antitussive activity of Drymaria cordata Willd. (Caryophyllaceae).

The methanol extract of Drymaria cordata Willd. was investigated for its effect on a cough model induced by sulfur dioxide gas in mice. It exhibited significant antitussive activity when compared with the control in a dose-dependent manner. The antitussive activity of the extract was comparable to that of codeine phosphate, a prototype antitussive agent. The D. cordata extract (100, 200, 400 mg/kg) showed 11.6%, 31.6% and 51.5% inhibition of cough with respect to the control group.

Animals↗
PubMed1997

Wound healing activity of Leucas lavandulaefolia Rees.

Leucas lavandulaefolia Rees (Labiatae), commonly known as Halkusha, is a well-known plant in Indian traditional medicine. On the basis of its traditional use and literature references, this plant was selected for evaluation of its wound healing potential. A methanol extract of L. lavandulaefolia was examined for its wound healing activity both in the form of an ointment as well as an injection in two types of wound model in rats: (i) the excision wound model and (ii) the incision wound model. Both the injection and the ointment of the methanol extract of the plant material produced a significant response in both of the wound types tested. The results were also comparable to those of a standard drug, nitrofurazone, in terms of wound contracting ability, wound closure time, tensile strength and regeneration of tissues at the wound site.

Animals↗
PubMed1997

Studies on the anti-inflammatory activity of rhizomes of Nelumbo nucifera.

The anti-inflammatory activity of the methanol extract of Nelumbo nucifera rhizome as well as of betulinic acid, a steroidal triterpenoid isolated from it, were evaluated on carrageenin and serotonin induced rat paw edema. Methanol extract at doses of 200 and 400 mg/kg and betulinic acid at doses of 50 mg/kg and 100 mg/kg p.o., showed significant anti-inflammatory activity in both the models of inflammation in rats. The effects produced were comparable to that of phenylbutazone and dexamethasone, two prototype anti-inflammatory drugs.

Animals↗
PubMed1997

Immunotherapy of lepromin-negative borderline leprosy patients with low-dose Convit vaccine as an adjunct to multidrug therapy; a six-year follow-up study in Calcutta.

The present report, which describes management of lepromin-negative borderline leprosy patients with low-dose Convit vaccine, is an extension of our earlier study on the treatment of lepromatous leprosy patients with low-dose Convit vaccine as an adjunct to multidrug therapy (MDT). The test Group I, consisting of 50 lepromin-negative, borderline leprosy patients, were given low-dose Convit vaccine plus MDT. The control group II consisted of 25 lepromin-negative, borderline leprosy patients given BCG vaccination plus MDT and 25 lepromin-negative, borderline leprosy patients given killed Mycobacterium leprae (human) vaccine plus MDT. The control group III consisted of 50 lepromin-positive, borderline leprosy patients not given any immunostimulation but given only MDT. Depending upon the lepromin unresponsiveness, the patients were given one to four inoculations of the various antileprosy vaccines and were followed up every 3 months for 2 years for clinical, bacteriological and immunological outcome. All patients belonging to the test and control groups showed clinical cure and bacteriological negativity within 2 years. However, immunologic potentiation, assessed by lepromin testing and the leukocyte migration inhibition test (LMIT), was better in the test patients receiving low-dose Convit vaccine plus MDT than in the control patients receiving BCG vaccine plus MDT or killed M. leprae vaccine plus MDT or MDT alone. But the capacity of clearance bacteria (CCB) test from the lepromin granuloma showed poor bacterial clearance in the test patients. However, there was no relapse during 6 years of follow up. Two mid-borderline (BB) patients had severe reversal reactions with lagophthalmos and wrist drop during immunotherapy despite being given low-dose Convit vaccine.

Adult↗
PubMed1996

Herpesvirus saimiri-transformed human CD4+ T cells can provide polyclonal B cell help via the CD40 ligand as well as the TNF-alpha pathway and through release of lymphokines.

We have developed human CD4+ T cell lines from the PBL of normal donors by infection with Herpesvirus saimiri (HVS), to evaluate functional properties of these immortalized lymphocytes. In this report, we characterize two such CD4+ T cell lines, CHCD4 and MHCD4, which were derived from two different donors. These cells grew independent of exogenous IL-2 stimulation for over 1 yr, and expressed surface markers (CD25+, CD69+, HLA-DR+, and B7+) associated with an activated T cell phenotype. Both lines constitutively produced and released IFN-gamma, but no IL-2 or IL-4. However, the surface expression of the two cell lines differed in that CHCD4 constitutively expressed CD40 ligand (CD40L) and membrane TNF-alpha, but MHCD4 did not. Also, CHCD4, but not MHCD4, potently induced polyclonal B cell activation and differentiation in the absence of PWM, in an MHC-unrestricted fashion. The B cell help afforded by CHCD4 included contact-dependent and soluble components. Contact-dependent help was strongly inhibited by mAb against CD40L (5C8) and to a lesser extent, by anti-TNF-alpha Ab. The CD40L-dependent helper function of CHCD4 contrasts with the recent description of other HVS-transformed CD4+ T cells that provide B cell help primarily via the membrane TNF-alpha and TNF-alphaR pathways. Furthermore, CHCD4 cells also secreted soluble factors that could mediate CD40-linked B cell differentiation into Ab-producing cells. Interestingly, this factor is not likely to be IL-2, IL-4, IL-6, IL-10, IL-15, TNF-alpha, or IFN-gamma as Abs against these cytokines were not able to inhibit the contact-independent B cell help by CHCD4. These results indicate that HVS-immortalization of CD4+ lymphocytes may produce T cell clones with a spectrum of important contact-dependent, as well as contact-independent, B cell helper function capacities.

B-Lymphocytes↗