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Gajendra Singh

Publications and source records attributed to Gajendra Singh.

6 recordsLinked to original sources

Paraneoplastic neurodegeneration in a murine host following progressive growth of a spontaneous T-Cell lymphoma: role of proinflammatory internal responses.

OBJECTIVE(S): In the present study, the mechanism of paraneoplastic neurodegeneration associated with progressive in vivo growth of a T-cell lymphoma of spontaneous origin has been investigated. METHODS: Histologically, the brain was investigated by hematoxylin-eosin staining of brain sections. Western blotting was performed to detect the expression of cytokines and other proteins. Macrophage-derived interleukin-1 (IL-1) and tumor necrosis factor (TNF) was estimated by immunoassays. Induction of apoptosis in brain and tumor cells was determined by percent specific DNA fragmentation. RESULTS: Tumor growth was associated with the development of multiple lesions in various regions of the brain along with alterations in the structure and alignment of Purkinje cells, and an increase in the water content in the brain. Brain extract and serum of tumor-bearing mice showed higher levels of proinflammatory cytokines. Induction of apoptosis is suggested to be the cause underlying the loss of cellularity of tumor-bearing hosts in the brain owing to an augmentation in the induction of the caspase-dependent pathway of programmed cell death. Further, the study presents investigations to show the role of nitric oxide and proinflammatory cytokines IL-1, TNF, interferon-gamma and alkaline phosphatase in the manifestation of paraneoplastic neurodegeneration. CONCLUSIONS: Growth of a T-cell lymphoma is associated with the manifestation of neurodegeneration caused by soluble proinflammatory factors of tumor and/or host origin.

Alkaline Phosphatase↗

Phenotypic and genotypic detection of ESBL mediated cephalosporin resistance in Klebsiella pneumoniae: emergence of high resistance against cefepime, the fourth generation cephalosporin.

OBJECTIVES: Cephalosporins belonging to second and third generation are commonly used in India for the treatment of Klebsiella pneumoniae. Report on resistance among K. pneumoniae strains to second and third generation cephalosporins are on rise in this country, which has been attributed to emergence of strains expressing extended-spectrum beta-lactamases (ESBLs). The aim of this study was to evaluate the in vitro susceptibility of K. pneumoniae to broad-spectrum cephalosporins particularly to cefepime, a recently introduced fourth generation cephalosporin in relation to ESBL production. METHODS: This study has been carried out in two phases among K. pneumoniae strains isolated between October 2001 and September 2002 (phase I, before marketing of cefepime in India) and between August 2003 and July 2004 (phase II, after marketing of cefepime in India). Minimum Inhibitory Concentration (MIC) was determined by a commercial strip containing gradient of antimicrobials (Strip E-test). Detection for ESBL production was carried out by DDST, E-test ESBL and PCR. RESULTS: Antimicrobial resistance profile of K. pneumoniae strains to five cephalosporins as analyzed by WHONET 5 identified 15 different resistance profiles among the 108 phase I isolates, ranging from resistance to none (19.44%) to all the five cephalosporin (8.33%) and eight different resistance profiles among the 99 phase II isolates, ranging from resistance to none (9.1%) to all the five cephalosporins (36.4%). Among the 108 phase I isolates a total of 71 (65.72%) and out of 99 phase II isolates, a total of 87 (88.0%) could be identified as ESBL producers. Among the isolates, regardless of the phase of the isolation, those characterized by production of ESBL showed overall higher frequency of resistance to cephalosporins (range 19.7-85.9% and 51.7-100% in phase I and phase II, respectively) compared to those for ESBL non-producers (range 0-13.5% and 0-25% in phase I and phase II, respectively). Ten randomly selected isolates from the most common resistance phenotypes probably belonged to a single strain as evident by MIC patterns, genotypic characterization and resistance profile to non-cephalosporin group of antimicrobials thereby pointing out the possibility of an outbreak. CONCLUSIONS: PCR may be regarded as a reliable method for detection of ESBL since in addition to the strains that could be identified as ESBL producers by DDST and E-test ESBL; PCR could demonstrate ESBL production among additional 32 strains (15 in phase I and 17 in phase II). Continued uses of cephalosporin group appear to be a potential risk factor for emergence of ESBL producing K. pneumoniae strains. In addition, as noted in the present study, the rise of resistance to cefepime that has been introduced recently in this country for therapeutic use could be of concern.

Anti-Bacterial Agents↗

Role of host's antitumor immunity in exercise-dependent regression of murine T-cell lymphoma.

We have reported that the ascitic growth of a transplantable T cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), is associated with a concomitant immunosuppression. We have also reported that progressive in vivo growth of DL resulted in an inhibition of macrophage functions. In present investigation we report that physical exercise by DL-bearing mice, on a treadmill on a daily basis for various time durations for 10 days, increased the life span along with an inhibition of tumor growth. A significant decrease in the volume of ascitic fluid and number of cells in the tumor was obtained in mice, which underwent exercise. DL cells obtained from exercised groups showed a decreased proliferation in vitro. An augmentation in the percent of cells showing apoptotic morphology and percent specific DNA fragmentation was observed, suggesting that physical exercise increased the incidence of apoptosis in tumor cells. Moreover, macrophages obtained from tumor-bearing mice, which underwent exercise training, showed an augmented tumoricidal activity and production of tumoricidal molecules like interleukin-1 (IL-1), tumor necrosis factor (TNF) and nitric oxide (NO). On the basis of this study it is suggested that the regression of tumor growth consequent to physical exercise training of tumor bearing host, may be due to an exercise-dependent augmentation of macrophage tumoricidal functions.

Animals↗

Restoration of thymic homeostasis in a tumor-bearing host by in vivo administration of medicinal herb Tinospora cordifolia.

In vivo administration of alcoholic extract of medicinal plant Tinospora cordifolia (TC) to mice bearing a spontaneous T cell lymphoma designated as Dalton's lymphoma prevented tumor growth-dependent regression of thymus. TC was found to augment proliferation of thymocytes with a concomitant decrease in thymocyte apoptosis. It also resulted in a decrease in the number of Hassal's corpuscles. Restoration of thymus homeostasis was caused by TC-dependent augmentation in production of thymocyte growth promoting cytokines Interleukin-2 and Interferon-gamma from thymocytes. TC was found to downregulate thymocyte apoptosis by modulation of Caspase pathway. TC administration retarded tumor growth and prolonged survival of tumor-bearing mice. The possible mechanisms are discussed.

Animals↗