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Biomedical subjects

K Saha

Publications and source records attributed to K Saha.

At least 55 records · Page 3Linked to original sources
PubMed1996

Long-term cultivation and productive infection of primary thymocyte cultures by a thymocytopathic murine retrovirus.

ts1, a mutant of MoMuLV, selectively kills T cells and neurons in the infected host resulting in neuroimmunodegeneration. In the infected thymus there is an early increase in mitosis of thymocytes followed by rapid death, suggesting that thymocyte death may be induced by viral mitogenic activation. Studies on thymocytes obtained from ts1-infected mice indicated that the ts1-induced depletion of thymocytes is mediated through activation-induced death by apoptosis. To further investigate the interaction between ts1 and thymocytes, we have established long-term primary murine thymocyte cultures by placing the thymocytes together with thymic remnants in culture medium containing IL-2 and IL-7. These thymocytes retained their immature phenotype and we susceptible to infection by ts1 and its parental wild-type MoMuLV. ts1-infected thymocytes proliferated initially at accelerated rate but subsequently produced more infectious virus and died much faster than control or MoMuLV-infected thymocytes. These in vitro studies to some extent reflect our in vivo studies reported previously.

Animals↗
PubMed1996

Studies on psychopharmacological effects of Nelumbo nucifera Gaertn. rhizome extract.

Methanolic extract of rhizomes of Nelumbo nucifera (NNRE) was investigated for different psychopharmacological actions in rats and mice. The extract was found to cause reduction in spontaneous activity, decrease in exploratory behavioural pattern by the head dip and Y-maze test, reduction in muscle relaxant activity by rotarod, 30 degrees inclined screen and traction test and potentiated the pentobarbitone induced sleeping time in mice significantly.

Animals↗
PubMed1996

Immunotherapy of far-advanced lepromatous leprosy patients with low-dose convit vaccine along with multidrug therapy (Calcutta trial).

This report describes a promising mode of treatment of lepromin-unresponsive, far-advanced, lepromatous (LL) leprosy patients with antileprosy vaccines as an adjunct to multidrug therapy (MDT). The Trial Groups included 50 highly bacilliferous, lepromin-negative, untreated LL patients. They were given MDT for 2 years. Of them, 30 patients were administered a mixed antileprosy vaccine containing killed Mycobacterium leprae of human origin plus M. bovis BCG. The remaining 20 patients were given M. bovis BCG. Depending on the severity of lepromin unresponsiveness, they were given one to six inoculations at 3-month intervals. Another 20 similar LL patients were taken in the Control Group. They were given only MDT for 2 years. From the start of the study, all patients belonging to the Trial and Control Groups were followed every 3 months for clinical, bacteriological and immunological outcomes. Within 2 years all 50 patients of the Trial Groups and 19 of the 20 patients of the Control Group became clinically inactive and bacteriologically negative. However, the clinical cure and the falls of the bacterial and morphological indexes were much faster in those patients receiving the mixed vaccine therapy than in those patients who were given BCG plus MDT or only MDT. The immunological improvements in the patients of the Trial and Control Groups were assessed by: a) lepromin testing at the beginning of the study and at 3-month intervals and also by b) the in vitro leukocyte migration inhibition (LMI) test at both the beginning and end of the study. As the patients were given more and more vaccinations, the incidence of lepromin conversion increased, more so in the patients receiving the mixed vaccine. Thus, 63%, 15% and 5% of the patients became lepromin positive in those patients receiving the mixed vaccine, BCG, and MDT only, respectively. Lamentably, the vaccine-induced lepromin positivity was temporary and faded away within several months. At the beginning of the study, the LMI test against specific M. leprae antigen was negative in all patients of both the Trial and Control Groups. After the end of the chemo-immunotherapy schedule, the LMI test became positive in 50% and 20% of LL patients receiving the mixed vaccine and BCG, respectively. None of the Control Group could show LMI positivity after completion of the MDT schedule. These results show that treatment of LL patients with the mixed vaccine and MDT could quickly reverse the clinical course of the disease, remove immunologic anergy in some patients, and induce a rapid decrease in the bacterial load in them.

Adult↗
PubMed1996

Antipyretic activity of Nelumbo nucifera rhizome extract.

Antipyretic activity of methanolic extract of rhizome of N. nucifera was studied on normal body temperature and yeast induced pyrexia in rats. Yeast suspension (10 ml/kg, s.c.) increased rectal temperature after 19 hr of administration. The extract, in doses of 200, 300 or 400 mg/kg (po) produced significant dose dependent lowering of normal body temperature and yeast provoked elevation of body temperature in rats. The effect produced was comparable with the standard antipyretic drug, paracetamol (150 mg/kg, i.p.).

Analgesics, Non-Narcotic↗
PubMed1995

Dysregulation of homeostasis of blood T-lymphocyte subpopulations persists in chronic multibacillary pulmonary tuberculosis patients refractory to treatment.

DESIGN: The dysregulation of homeostasis of blood-T lymphocyte subpopulations was studied in 21 cases of chronic, multibacillary pulmonary tuberculosis refractory to treatment. The clinico-bacteriological and immunological parameters studied in these cases (Gr A) were compared with those of a group of 10 newly-diagnosed drug sensitive cases of pulmonary tuberculosis (Gr B) at the beginning of the study and after 3 months of chemotherapy for tuberculosis. The chronic cases were treated with drugs selected from a reserve line. 10 normal healthy individuals were included in this study as a control group. RESULTS: At the beginning of the study the mean CD4/CD8 lymphocyte ratios in the refractory cases (0.69) and the newly diagnosed cases (0.81) were significantly lower than those of the normal control subjects (1.84). After 3 months of chemotherapy all but 3 of the newly-diagnosed cases showed clinical improvement, and all became sputum-negative. Their CD4/CD8 ratio recorded a rise to near normal (1.54). On the contrary, following 3 months of reserve-line regimen, only 7 of the 21 group A cases showed sputum conversion. In all of the refractory cases, irrespective of sputum conversion, the CD4/CD8 ratio remained low (1.05). CONCLUSION: This probably indicates that due to a long-standing bacillary load in drug resistant pulmonary tuberculosis patients the dysregulation of homeostasis of blood-T lymphocytes becomes persistent. This in turn delays their clinical and immunological recovery, even when therapy is adequate.

Adolescent↗
PubMed1995

Univentricular repair. Early and midterm results.

A total of 202 patients (62 with tricuspid atresia and 140 without tricuspid atresia) underwent univentricular repair at our unit from January 1990 to September 1994. Of these patients, 182 had nonfenestrated and 20 had fenestrated interatrial baffles. Early mortality was 15.9% (29/182) in the group with nonfenestrated baffles and 5% (1/20) in the group with fenestrated baffles. The follow-up period ranged from 2 to 58 months. Seven late deaths occurred, and five patients were lost to follow-up. Of 160 patients who have been evaluated in the outpatient department in the past 3 months, 142 (88.75%) required no cardiac medicines and were in functional class I. Risk factors analyzed for early mortality and significant effusion were age, preoperative diagnosis, type of Fontan modification, cardiopulmonary bypass time, aortic crossclamp time, pulmonary artery size, associated pulmonary arterioplasty, takedown of systemic-pulmonary artery shunt, and pulmonary artery debanding, along with the Fontan operation. Bypass time exceeding 120 minutes was associated with a higher early mortality (12/47 vs 18/155; p = 0.0187). Bypass time exceeding 120 minutes (p = 0.0456) and aortic crossclamp time exceeding 60 minutes (p = 0.0278) were associated with significant postoperative effusion. Other factors were not associated with any significantly increased risk for early mortality or postoperative effusions. Fenestration of the interatrial baffle appeared to decrease early mortality, although the numbers are too small to be statistically significant. The prevalence of effusions did not differ significantly between the group with fenestrated baffles and the group without fenestrated baffles.

Cardiopulmonary Bypass↗
PubMed1995

Biometals in skin and sera of leprosy patients and their correlation to trace element contents of M. leprae and histological types of the disease; a comparative study with cutaneous tuberculosis.

The present study has provided information on the biometal contents of killed and dried Mycobacterium leprae as well as dermal granulomas induced by the invading mycobacteria in various histological types of leprosy patients. For comparison, the biometal contents of the contralateral leprosy-unaffected skin of the same patients also were measured. The study also reports changes of serum levels of the biometals in these patients which were compared with those in healthy control subjects and patients with skin tuberculosis. These data show that M. leprae is rich in zinc. During the course of the evolution of the disease there is gross alteration of the dynamics of the inflammatory cell population that infiltrates into leprosy granulomas, resulting in the alterations of trace element contents of the disease-affected skin lesions. Interestingly, the changes of the biometal contents in the granulomas of the patients with skin tuberculosis are similar to those in leprosy patients. It is postulated that the significant decrease of the contents of copper, zinc, iron, calcium and magnesium in the disease-affected skin in comparison to that of the contralateral healthy skin is a local effect, perhaps due to erosion or influx of biometal-deficient inflammatory cells into the affected skin with eventual loss of connective tissue of skin and mobilization of tissue-bound microelements into the vascular compartment. On the contrary, the changes in biometal levels in the sera of leprosy patients appear to be a general effect perhaps due to the release of interleukin-1, a product of inflammatory cells, causing hypercupremic, hypozincemic and hypoferremic responses in the hosts. Moreover, growth and multiplication of M. leprae, especially in polar lepromatous leprosy patients with a high bacillary load, demand essential biometals which may be mobilized into the bacterial bodies from the hosts. This perhaps results in the change in the homeostasis of the essential biometals in the hosts.

Adult↗
PubMed1995

Raised serum IgE levels in chronic inflammatory lung diseases.

OBJECTIVE: To study the serum IgE response in nonallergic subjects with chronic inflammatory lung diseases. SETTING: Christian Medical College Hospital, Vellore. SUBJECTS: Twenty six patients with bronchiectasis, five with pulmonary mycosis referred from all over India and 30 healthy subjects. MAIN OUTCOME MEASURES: Serum IgE value (determined by radioimmuno assay) above the upper limit of normal control range (136 to 948 iu/ml) was considered as raised level. RESULTS: Of the 26 patients with bronchiectasis 13 had pyogenic infections, six had pulmonary tuberculosis; in six patients sputum culture was sterile while another patient had herpes zoster. Five cases of mycosis included one each of actinomycosis, aspergillosis, blastomycosis, cryptococcosis and nocardiasis. The serum IgE levels were raised in 20 (65%) of the 31 patients. CONCLUSION: Associated bacterial, fungal and parasitic infections were probably responsible for inducing an hyper-IgE response in these non-allergic subjects.

Adult↗
PubMed1995

Orthotopic pulmonary valve replacement with a homograft.

Eight pulmonary valve replacements (PVR) have been performed from January 1992 to October 1994. Three patients (mean age 7.7 years, range two to 16 years) had absent pulmonary valve with tetralogy of Fallot and underwent primary PVR at the time of surgical correction. Five other patients, who had correction of tetralogy of Fallot (four cases) and of double outlet right ventricle with ventricular septal defect and pulmonary stenosis (one case), were reoperated for pulmonary regurgitation with progressive right ventricular dysfunction. Mean age at the time of reoperation was 18 years (range seven to 34 years). There was no early death. Early postoperative recovery was satisfactory in all of them. The follow up ranges from six to 35 months (mean 19 months). Seven patients were in functional class I and one in functional class II when they were last evaluated in the out-patient department and five of them were off diuretics and vasodilator. In the presence of right ventricular dysfunction pulmonary regurgitation is poorly tolerated. A competent and non-obstructive pulmonary valve is often life saving in these critically ill patients.

Adolescent↗
PubMed1994

Mother-to-baby transfer of humoral immunity against retrovirus-induced neurologic disorders and immunodeficiency.

Neonatal FVB/N mice inoculated with ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, developed fatal immunodeficiencies and neurologic disorders. In this study, we tested the role of transfer of maternal humoral immunity in preventing ts1-induced disease syndrome in the neonatal mice. We compared the levels of protection provided through maternal antibodies both pre- and postnatally by separating infected neonatal mice into four different groups. The first group was born of and nursed by nonimmune mothers, the second was born of immune mothers but nursed by nonimmune mothers, the third was born of nonimmune mothers but nursed by immune mothers, and the fourth was born of and nursed by immune mothers. Our major findings are: (1) adult mice generate a strong antiviral antibody response; (2) maternal antibody is protective for the newborns and primarily transferred by breast milk; (3) virus titers were cleared in the periphery and the CNS of neonates nursing on immune mothers; and (4) the majority of antiviral antibody generated was specific for the gp70. These results indicate that humoral immunity can be passed efficiently from mother to baby through breast milk and can provide strong protection against neurotropic retrovirus.

Animals↗
PubMed1994

A simple method for obtaining highly viable virus from culture supernatant.

Traditionally density-gradient methods are used to purify viruses. However, these procedures are not only time consuming and cumbersome, recovery of viable viruses are often quite low. In this report, a single-step concentration technique was used to concentrate a mutant of Moloney murine leukemia virus (ts1) virus from culture supernatants by ultrafiltration. A special ultrafiltration unit with a 100,000 mol wt cut-off was able to concentrate viruses about 30-fold without losing any infectivity. In comparison, traditional sucrose density gradient purified viruses lost a significant portion of their infectivity. This technique could be used for concentrating other viruses for many useful purposes where more viable viruses are needed, e.g., study of virus-cell binding.

Cell Line↗
PubMed1994

Murine retrovirus-induced depletion of T cells is mediated through activation-induced death by apoptosis.

ts1, a mutant of Moloney murine leukemia virus, causes neurologic disorders and acute immunodeficiency associated with the destruction of thymocytes and helper T cells. In this study, we examined whether apoptosis was involved in ts1-induced killings of T cells. Neonatal mice were inoculated with ts1, and 20 to 23 days postinoculation, when cytopathic effects on T cells normally appear, thymocytes and splenic lymphocytes were isolated and examined. Our results showed that several features of apoptosis were present in ts1-infected thymocytes and splenic lymphocytes. Apoptotic fragmented DNA, condensation of the chromatin, and enhanced cell death after stimulation with mitogens which was preventable with protein synthesis inhibitors, all of which are common features of apoptotic cell death, were observed in ts1-infected cells. Several other viruses, including human immunodeficiency virus, have been shown to cause apoptotic death of T cells. Here we show for the first time that a murine retrovirus which also induces immunodeficiency can cause apoptotic T-cell death. Future studies with this murine retrovirus may provide important results to help us better understand the mechanisms of retrovirus-induced apoptosis of T cells.

Animals↗
PubMed1994

An eight-year field trial on antileprosy vaccines among high-risk household contacts in the Calcutta metropolis.

One-hundred-seventy-nine lepromin-negative household contacts were vaccinated with heat-killed Mycobacterium leprae, BCG, or a combination of the two. Vaccination induced lepromin positivity in 131 of these contacts. Over an 8-year follow-up period, 12 lepromin-positive contacts developed leprosy, all tuberculoid; while 2 lepromin-negative vaccinated contacts developed leprosy, both lepromatous. Overall, 7.8% of the vaccinated contacts developed the disease. Seven-hundred-fourteen household contacts were not vaccinated, and served as controls. Among the 504 who were lepromin positive, leprosy developed in 35, all tuberculoid, over the 8-year follow up. Among the 210 lepromin-negative unvaccinated contacts, 61 developed leprosy: tuberculoid in 29, borderline in 4, lepromatous in 8, and indeterminate in 20. Overall, 13.5% of the 714 unvaccinated contacts and 29.0% of the 210 unvaccinated, lepromin-negative contacts developed leprosy. Vaccination could not induce lepromin positivity in all contacts. The three vaccines were equally effective in inducing lepromin positivity. Vaccination reduced the overall incidence of leprosy from 13.5% to 7.8% among household contacts but did not reduce the incidence of lepromatous leprosy (1.2% of all the vaccinated and 1.1% of all the unvaccinated contacts).

BCG Vaccine↗
PubMed1994

Modulation of Fc and C3b receptor activity of mouse peritoneal macrophages elicited by preformed immune complexes.

A study was undertaken to reveal the role of Fc and C3b receptor of mouse peritoneal macrophages (MPM) in the uptake of radiolabelled immune complexes. Large latticed preformed complexes consisting of human serum albumin (HSA)-anti HSA at equivalence (IC-Eq) and with antibody excess (IC-Ab) were observed to be avidly taken up by resident macrophages unlike small size complexes with antigen excess (IC-Ag). Macrophages elicited by thioglycollate (Tg) showed higher IC-binding capacity while IC-elicited MPM showed reduction in the same when compared to the resident cells. However, complement coated complexes were significantly taken up by these IC-elicited macrophages. Uptake studies were further extended to determine the expression of Fc and C3b receptor activity in MPM when elicited with preformed IC. Tg-elicited MPM were observed to bind greater number of IgG-coated erythrocytes (E-IgG) than resident MPM whereas IC-elicited MPM bound E-IgG poorly. When Fc receptors were blocked by in vitro IC treatment, poor binding of complement coated E-IgG [E(IgG)C] was recorded in resident MPM. The present complement medicated rosetting data tends to show enhanced expression of C3b receptors on IC-elicited macrophages.

Animals↗
PubMed1993

Rudimentary thymus of SCID mouse plays an important role in the development of retrovirus-induced neurologic disorders.

The role of the thymus in neurologic disorders induced by the murine retrovirus, ts1, a neuropathogenic and lymphocytopathic mutant of the Moloney murine leukemia virus-TB, was examined using severe combined immune deficiency (SCID) mice. Athymic nude mice are resistant to ts1-induced neurologic disease. All SCID mice inoculated neonatally with ts1 developed neurologic disorders similar to those of inoculated BALB/c mice, albeit after a longer latency period. In some experiments, instead of inoculating ts1 directly, purified thymocytes, CD4+, or CD8+ T cells from ts1-infected BALB/c mice were transferred to neonatal H-2 compatible SCID mice. We found that SCID mice that received infected thymocytes developed the disease faster than those that received infected CD4+ T cells. SCID mice that received infected CD8+ T cells did not develop any disease. Thus, the (rudimentary) thymus of SCID mouse plays a key role in ts1-induced neurologic disease. In addition, flow cytometric analysis of the reconstituted SCID mice showed that CD8+ T cells migrate and preferentially colonize the thymus while CD4+ T cells were found in the spleen and to a lesser extent in the thymus. However, the significance of this organ specific movements of transferred cells in relation to the virus infection remains unclear. In view of the involvement of the thymus and the CD4+ T cells in human immunodeficiency virus infection, which also infects the central nervous system (CNS) in most cases, our findings in this murine model may help us better understand how the thymus may contribute to the damage of the CNS in retrovirus infections.

Animals↗
PubMed1993

Antibody dependent haemolysin, complement and opsonin in sera of a major carp, Cirrhina mrigala and catfish, Clarias batrachus and Heteropneustes fossilis.

The present communication is a continuation of our earlier study on the natural serum haemagglutinin/lectins of Cirrhina mrigala, Clarias batrachus and Heteropneustes fossilis. Sera of Cirrhina mrigala, belonging to the major carp family, could not only agglutinate heterologous rabbit erythrocytes, but also lyse them spontaneously. This lysis of rabbit RBC by Cirrhina mrigala sera was calcium ion dependent and heat sensitive, indicating thereby that the haemolysis was mediated by the fish serum complement system via the classical pathway. Quantification of CH50 and APCH50 levels in the sera of Clarias batrachus and Heteropneustes fossilis as well as in the sera of amphibia, aves and mammals showed that lower vertebrates predominantly possessed an alternative pathway of the complement system, while on the other hand, in the higher vertebrates the major pathway of complement activation was classical. Furthermore sera of Clarias batrachus and Heteropneustes fossilis had opsonins, which could stimulate heterologous rat peritoneal macrophages to engulf Staphylococcus aureus with the production of superoxide anion. From this study we concluded that fishes have been armed with various powerful natural humoral defense systems for their protection against environmental pathogens.

Animals↗