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Somajiguda, India

Mukherjee R.M.,Asian Health Care Foundation | Bansode B.,Asian Health Care Foundation | Gangwal P.,Asian Health Care Foundation | Jakkampudi A.,Asian Health Care Foundation | And 4 more authors.
Journal of Clinical and Experimental Hepatology | Year: 2012

Background: The interferon regulatory factors (IRFs) are a family of transcription factors known to be involved in the modulation of cellular responses to interferons (IFNs) and viral infection. While IRF-1 acts as a positive regulator, IRF-2 is known to repress IFN-mediated gene expression. The increase in the IRF-1/IRF-2 ratio is considered as an important event in the transcriptional activation of IFN-α gene toward development of the cellular antiviral response. Objective: This study was performed to assess the expression of IRF mRNAs along with the expression level of IFN-α, its receptor (IFNAR-1), and the signal transduction factor (STAT-1) in treatment naive hepatitis C virus (HCV)-infected subjects. Materials: Thirty-five chronically infected (CHC) patients and 39 voluntary blood donors as controls were included in the study. Quantification of HCV-RNA (ribonucleic acid) and genotyping were done by real-time polymerase chain reaction (PCR) and hybridization assays, respectively, using patient's serum/plasma. In both controls and patients, the serum level of IFN-α and IFN-α was measured by flow cytometry. Target gene expressions were studied by retro-transcription of respective mRNAs extracted from peripheral blood mononuclear cells (PBMCs) followed by PCR amplification and densitometry. Minus-strand HCV-RNA as a marker of viral replication in PBMCs was detected by an inhouse PCR assay. Results: Both IRF-1 and IRF-2 genes were significantly enhanced in CHC than in control subjects (P < 0.001). A significant positive correlation (r2 = 0.386, P <0.01) was obtained between higher IRF-2 gene expression and increasing level of HCV-RNA. Chronically infected subjects (13%) harboring replicating HCV in PBMCs showed no significant differences in gene expressions than the subjects without HCV in PBMCs. Conclusion: Our findings indicate that HCV modulates host immunity by inducing IRF-2 gene to counteract IRF-1-mediated IFN-α gene expression. Since the IRF-2 gene is known to encode oncogenic protein, the role of IRF-2 in CHC patients developing hepatocellular carcinoma warrants further studies. © 2012 INASL. Source


Mitnala S.,Asian Health Care Foundation | Pondugala P.K.,Asian Health Care Foundation | Guduru V.R.,Asian Institute of Gastroenterology | Rabella P.,Asian Institute of Gastroenterology | And 5 more authors.
Pancreas | Year: 2010

Objectives: The present study was conducted to monitor the expression of pancreas and duodenal homeobox gene (PDX-1) for assessing β-cell function in islets from patients with chronic pancreatitis (CP). Methods: Islets isolated from the pancreata of 40 surgical patients categorized as control group, patients with mild CP, and patients with advanced CP were assessed for their yield, size, and glucose-stimulated insulin secretion. Expressions of genes coding for PDX-1, insulin, and glucagon were simultaneously monitored by reverse transcription polymerase chain reaction and confirmed by immunohistochemistry. Results: In comparison with the control group (2673 ± 592 islet equivalents [IEq]/g), islet yield did not differ much in the patients with mild CP (2344 ± 738 IEq/g) but was significantly reduced (P < 0.0001) in the patients with advanced CP (731 ± 167 IEq/g). Although the marginal decrease in islet size observed in the patients with mild CP was not significantly different from that observed in the control group, there was a 58% decrease observed in the patients with advanced CP that was also accompanied by a significant reduction in β-cell mass (P < 0.05). The expression of insulin and PDX-1 genes, but not of glucagon, was significantly reduced in the patients with advanced CP as confirmed by immunohistochemistry. Islets obtained from the patients with advanced CP retained 53% glucose-stimulated insulin secretion function in comparison with those of the control group. Conclusion: The results indicate that β-cell dysfunction during progression of CP correlates with the decrease in PDX-1 gene expression. Copyright © 2010 by Lippincott Williams & Wilkins. Source


Mukherjee R.M.,Asian Health Care Foundation | Shravanti G.V.,Asian Institute of Gastroenterology | Jakkampudi A.,Asian Health Care Foundation | Kota R.,Asian Health Care Foundation | And 5 more authors.
Journal of Clinical and Experimental Hepatology | Year: 2013

Background: High mobility group box1 (HMGB1) and poly(ADP-ribose) polymerase1 (PARP1) proteins repair cellular DNA damage. Reduced expression of the corresponding genes can lead to an impaired DNA damage repair mechanism. Intracellular replication of hepatitis B virus (HBV) in such conditions can favor the integration of viral DNA into host genome leading to the development of hepatocellular carcinoma (HCC). Objective: This study was performed to assess the expression of HMGB1 and PARP1 mRNAs in conjunction with the estimation of HBV replication intermediate pregenomic RNA (PgRNA) in various phases of HBV infection. Materials: Eighty eight patients and 26 voluntary blood donors as controls were included in the study. Patients were grouped in to acute (AHB; n=15), inactive carriers (IC; n=36), cirrhosis (Cirr; n=25) and hepatocellular carcinoma (HCC; n=12). Serum HBV DNA was quantified by real time polymerase chain reaction (PCR) assay. Expression of HMGB1, PARP1 and PgRNA were evaluated using peripheral blood mononuclear cells (PBMCs) derived RNA by reverse transcription PCR (RT-PCR) and densitometry. Results: Significant reduction of HMGB1 and PARP1 gene expressions (P<0.05) were observed in patients than controls with more explicit decline of PARP1 (P=0.0002). Both genes were significantly downregulated (P<0.001) in ICs than controls. In ICs, HMGB1 was significantly lowered than cirrhosis (P=0.002) and HCC (P=0.0006) while PARP1 declined significantly (P=0.04) than HCC. Level of PgRNA was comparable in all the disease categories. Conclusion: In conclusion, our findings indicate impaired DNA damage repair mechanisms in HBV infected cells of ICs. This, along with low viral load but higher level of PgRNA in this group is suggestive of the diversion of HBV replication pathway that might facilitate viral DNA integration in to host genome. Intrusion of HBV PgRNA reverse transcription in early stage of infection might appear advantageous to thwart the development of HCC. © 2013 INASL. Source

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