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Articles by V Kumar
Total Records ( 4 ) for V Kumar
  R Behera , V Kumar , K Lohite , S Karnik and G. C. Kundu
 

Deregulation of signal transducer and activator of transcription (STAT)-3 signaling plays crucial role in oncogenesis of various cancers. However, the molecular mechanism by which osteopontin (OPN), a chemokine-like extracellular matrix-associated protein, regulates STAT3 activation that leads to tumor progression and inhibits apoptosis in breast cancer cells is not well understood. In this study, we for the first time report that OPN upregulates vβ3 integrin-mediated Janus kinase 2 (JAK2) phosphorylation and STAT3 activation in breast cancer (MDA-MB-468 and MCF-7) cells. Pretreatment of cells with JAK2 inhibitor (AG 490) suppresses OPN-induced STAT3 phosphorylation, its nuclear localization and DNA binding indicating that JAK2 is involved in this process. Transfection of cells with wild-type (wt) STAT3 enhanced whereas mutant STAT3 (STAT3 Y705F) suppressed OPN-induced breast tumor cell migration. Treatment of cells with OPN followed by staurosporine (STS) showed that OPN protects the cells from STS-induced apoptosis. Moreover, transfection of cells with wt STAT3 upregulates whereas STAT3 Y705F downregulates Bcl2 and cyclin D1 expressions in response to OPN. Interestingly, STAT3-overexpressing cells when injected to non-obese diabetic/severe combined immunodeficiency mice followed by OPN treatment, the mice developed enhanced tumor growth as compared with STAT3 Y705F-injected mice or mice injected with OPN alone. The levels of Bcl2 and cyclin D1 in wt STAT3 tumors were significantly higher than controls. Clinical specimen analysis revealed that increased OPN and pSTAT3 expressions correlate with enhanced breast tumor progression. Thus, targeting OPN and its regulated STAT3 signaling could be a potent therapeutic approach and understanding these mechanisms may form the basis of new therapeutic regimen for the management of breast cancer.

  A. K Salahudeen , V Kumar , N Madan , L Xiao , A Lahoti , J Samuels , J Nates and K. Price
 

Background and objectives: Oliguric, hypotensive patients who require large amounts of fluids may benefit from sustained low-efficiency dialysis performed continuously (C-SLED). C-SLED through higher clearance may improve survival, or through greater nutritional loss may worsen survival. No studies have assessed survival on C-SLED. The objective was to examine patient outcomes and survival predictors on C-SLED.

Design, setting, participants, & measurements: The data of 199 consecutive cancer patients treated with C-SLED were analyzed. The median duration of C-SLED was 50 h. With 48 h of C-SLED, the blood urea nitrogen (BUN) and serum creatinine levels had decreased by 80% and 73%, respectively. The mean arterial pressure (MAP) was maintained despite higher ultrafiltration and reduced vasopressor use. The 30-d mortality rate was 65%. Despite excellent dialysis, the sequential organ failure assessment (SOFA) score remained predictive of mortality. In the univariate model, higher SOFA scores and lower values for MAP, blood pH, and serum albumin and creatinine levels were associated with higher mortality. Administration of total parenteral nutrition (TPN) was, however, associated with lower mortality.

Results: In the multivariate model, the higher SOFA score and lower blood pH, MAP and C-SLED duration were associated with higher mortality. In a subset analysis of 129 patients who received C-SLED for at least 48 h, those with higher BUN levels, which were associated with higher TPN infusion, had a lower mortality risk.

Conclusion: This first detailed report on C-SLED indicates that C-SLED can be effective and suggests a link between nutrition and survival.

  V Kumar , P Atherton , K Smith and M. J. Rennie
 

Skeletal muscle demonstrates extraordinary mutability in its responses to exercise of different modes, intensity, and duration, which must involve alterations of muscle protein turnover, both acutely and chronically. Here, we bring together information on the alterations in the rates of synthesis and degradation of human muscle protein by different types of exercise and the influences of nutrition, age, and sexual dimorphism. Where possible, we summarize the likely changes in activity of signaling proteins associated with control of protein turnover. Exercise of both the resistance and nonresistance types appears to depress muscle protein synthesis (MPS), whereas muscle protein breakdown (MPB) probably remains unchanged during exercise. However, both MPS and MPB are elevated after exercise in the fasted state, when net muscle protein balance remains negative. Positive net balance is achieved only when amino acid availability is increased, thereby raising MPS markedly. However, postexercise-increased amino acid availability is less important for inhibiting MPB than insulin, the secretion of which is stimulated most by glucose availability, without itself stimulating MPS. Exercise training appears to increase basal muscle protein turnover, with differential responses of the myofibrillar and mitochondrial protein fractions to acute exercise in the trained state. Aging reduces the responses of myofibrillar protein and anabolic signaling to resistance exercise. There appear to be few, if any, differences in the response of young women and young men to acute exercise, although there are indications that, in older women, the responses may be blunted more than in older men.

  S. P Thotan , V Kumar , A Gupta , A Mallya and S. Rao
 

Subcutaneous phycomycosis is a rare fungal infection of the deeper layers of skin. We describe a representative case. A 10-year-old boy presented with a large swelling on the back of 3 months duration. Biopsy of the lesion confirmed the diagnosis of subcutaneous phycomycosis. There was complete resolution of the lesion after treatment with oral potassium iodide for 3 months.

 
 
 
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