Vemula M.H.,University of Hyderabad |
Ganji R.,University of Hyderabad |
Sivangala R.,Bhagwan Mahavir Medical Research Center |
Jakkala K.,University of Hyderabad |
And 4 more authors.
Frontiers in Microbiology | Year: 2016
Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis, the tuberculosis (TB) causing bacilli in human is cleared by cell-mediated immunity (CMI) with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI) is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches toward vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M. tuberculosis Zinc metalloprotease-1 (Zmp1), a secretory protein essential for intracellular survival and pathogenesis of M. tuberculosis. We observed that Zmp1 was secreted by in vitro grown M. tuberculosis under granuloma-like stress conditions (acidic, oxidative, iron deficiency, and nutrient deprivation) and generated Th2 cytokine microenvironment upon exogenous treatment of peripheral blood mononulear cells PBMCs with recombinant Zmp1 (rZmp1). This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n = 121) as against healthy control (n = 62), household contacts (n = 89) and non-specific infection controls (n = 23). A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL) to paucibacillary smear-negative pulmonary tuberculosis (PTB) cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can be explored as antigen candidates for prime-boost vaccination strategies or extrapolated as markers for disease detection and progression. © 2016 Vemula, Ganji, Sivangala, Jakkala, Gaddam, Penmetsa and Banerjee.
PubMed | Bhagwan Mahavir Medical Research Center, Mahavir Hospital and Research Center and Osmania University
Type: | Journal: International journal of cardiology | Year: 2016
Genetic factors play a significant role in pathogenesis of most diseases of heart. The present study was undertaken to correlate coronary artery disease with demographical, biochemical alterations, SNPs, gene expression and chromosomal abnormalities and for further enlightening the investigation in this field.150 patients taking clopidogrel drug were selected and single nucleotide polymorphism was done by PCR-RFLP techniques. With the same patients cytogenetic analysis was carried out on leukocyte cultures by karyotyping. Gene expression studies for 20 CAD patients and normal controls were done by RT-PCR techniques.In this study of patients with coronary artery disease the frequencies of the Extreme Metabolizers, Intermediate Metabolizers in CYP2C19*2 (rs4244285) were present in 90% and 10% but no Poor Metabolizers were found in this allele. The frequencies of Extreme Metabolizer, Intermediate Metabolizer and Poor Metabolizer in CYP2C19*3 (rs4986893) were present in 41%, 50% and 9% respectively. Among 20 CAD samples, 13 of 20 (65%) showed CYP2C19 gene over expression in CAD patients and all controls showed normal expression. Among the 150 CAD patients, 145 had normal karyotype, only five patients showed change in normal karyogram carried out by leukocyte culture.Genetic testing of CYP2C19 may help in prescribing a dose according to genetic makeup and represent the initial steps towards the development of diagnostic tests and therapeutic strategies that will substantially improve human health. This study highlights the progress that has been made in using pharmacogenomic and gene expression analysis, cardiovascular genomic research and the potential for applying these findings in clinical medicine.
Ansari M.S.S.,Mahavir Hospital and Research Center |
Hussain M.H.,Mahavir Hospital and Research Center
Biology and Medicine | Year: 2012
Allergy is considered to be the most damaging factor for the causation of bronchial asthma. An attempt was made to identify the allergens and the risk factors, and their correlation with IgE levels and spirometry-the measuring of breath which is the most common of the pulmonary function. The study group consisted of 139 patients suffering from asthma from South India, visiting Mahavir Hospital. Screening and clinical investigations were performed for all cases. Intradermal skin test was done for the identification of allergens. Patients with respiratory allergy were in the age group of 20-39 years. About 55.4% were males and 44.6%females and 59.7%were from urban areas. The disease conditions prevalent among these patients were asthma and rhinitis in 64%, asthma in 29.5%, asthma, urticaria and rhinitis in 4.3%, and asthma and urticaria in 2.2%; some of the male patients were cigarette smokers. Most individuals used LPG as fuel (96%) and few individuals used kerosene and cow dung as fuel. The percentage of patients positive for various fungal and pollen allergens was identified. Comparative studies with spirometry showed FEV1, FVC, and FEV1/FVC were >80%. IgE levels were more than 100 IU in 87%of individuals. 40%of patients had family history of allergy and 10%had history of pets at home. Higher prevalence of asthma was among men. Maximum population was from urban areas. Allergic symptoms co-existed and skin testing reflected the behavior of disease. Patients with allergen sensitivity showed obstructive airways. It is concluded that the identification of allergens can allow early intervention of ongoing disease and modification of subsequent natural history of disease.
Ehtesham N.Z.,University of Hyderabad |
Ehtesham N.Z.,National Institute of Nutrition |
Nasiruddin M.,National Institute of Nutrition |
Alvi A.,University of Hyderabad |
And 7 more authors.
Tuberculosis | Year: 2011
Treatment of tuberculosis (TB), which takes one human life every 15 s, globally, requires a prolonged (>6 months) antitubercular treatment (ATT) which, is known to have hepatotoxic side effects. This study was designed to explore the utility of human resistin, a proinflammatory hormone, as a sensitive biomarker to determine TB treatment end points. Patients for pulmonary tuberculosis enrolled under the directly observed treatment, short-course (DOTS) program were followed-up for six months and were monitored by sputum analysis, body weight and ELISA-based serum resistin and C-reactive protein (CRP) levels at 0, 2, 4 and 6 months, along with close family contacts of TB patients and healthy controls. The mean circulating resistin levels were found to be significantly higher (P < 0.001) in patients (n = 48, 25.74 ± 9.45 ng/ml) reporting for the first time for treatment (T0) as compared to healthy subjects (n = 45, 7.18 ± 2.40 ng/ml). Resistin levels in contacts (n = 48, 19.61 ± 7.88 ng/ml) also were found to be significantly (P < 0.001) elevated as compared to healthy controls. Significant increase in body weight after four months (P = 0.006) and at 6 months (P < 0.001) of treatment inversely correlated with resistin levels. Our data suggest resistin could be a surrogate marker for TB treatment in addition to its utility as an early prognostic biomarker for monitoring TB disease onset. © 2011 Elsevier Ltd. All rights reserved.
Sultana Shaik A.,King Saud University |
Shaik A.P.,King Saud University |
Jamil K.,Mahavir Hospital and Research Center |
Alsaeed A.H.,King Saud University
Toxicology Mechanisms and Methods | Year: 2016
The cytotoxicity and genotoxicity of pesticide mixtures viz. endosulfan + chlorpyrifos, chlorpyrifos + profenofos, and endosulfan + profenofos were evaluated on cultured human peripheral blood lymphocytes using assays for cell viability, and genotoxicity using chromosomal aberrations test and comet assay. The LC50 values for cytotoxicity were 3.50 μM, 4.18 μM, and 10.5 μM for profenofos, endosulfan, and chlorpyrifos respectively. When combined in equimolar concentrations, the LC50 values for cytotoxicity were 1.4 μM, 1.8 μM, and 2.0 μM for endosulfan + chlorpyrifos, chlorpyrifos + profenofos, and endosulfan + profenofos, respectively. Higher concentrations of individual pesticides (0.5–4.0 μM) but very low concentrations of pesticide mixtures caused significant DNA damage. Additive index values indicated a synergistic effect of toxicity for endosulfan + chlorpyrifos combination (1.12 TTU). The binary mixture of chlorpyrifos + profenofos showed an additive toxicity (0.46 TTU) while an antagonistic effect was observed for endosulfan + profenofos combination. Synergism could be due to these complementary pesticides simultaneously acting in different ways, magnifying their efficacy, whereas an additive interaction would imply that the chemicals are acting by the same mechanism and at the same target. Analysis of toxicity of pesticide mixtures may serve as important biomarker for occupational and household exposure to pesticides, with different modes of action. © 2016 Informa UK Limited, trading as Taylor & Francis Group
Hasan T.N.,Bharathiar University |
Leena Grace B.,Vinayaka Missions University |
Shafi G.,Hospital for Genetic Diseases |
Syed R.,Mahavir Hospital and Research Center
Clinical and Translational Oncology | Year: 2013
Objective: Breast cancer is the most common cancer and the main cause of cancer morbidity for women worldwide and is manifestation of abnormal genetic as well as epigenetic changes. Therefore, our aim was to study the association of BRCA1 promoter methylation with rs11655505 (c.-2265C/T) variants and gene expression in sporadic breast cancer. Methods: Twenty-nine sporadic breast cancer tissues and 26 normal biopsies were used for this study. Genomic DNA and total RNA were extracted from paraffin-embedded tissue and SNP analysis performed. Methylation status of the BRCA1 promoter region was determined by methylation-specific PCR after sodium bisulfite modification of DNA. Results: Among all clinical-pathological parameters only estrogen receptor -ve and +ve samples were significantly different for methylation status (P = 0.04). The genotypic (CC, CT and TT), allelic frequencies and methylation status had not been found to be significantly different from that of healthy controls (P = 0.67, 0.71 and 0.17, respectively). Similarly, methylated BRCA1 promoter was not found to be significantly different in different genotypes from unmethylated promoters between patients and controls. Interestingly, only heterozygous (CT) genotypes with low and normal expression of BRCA1 were significantly different for the differential expression of BRCA1 compared to controls (P = 0.004). However, in tumor samples decreased expression of gene is associated with methylated state of BRCA1 promoter [OR (95 % CI) = 25.09 (2.17-29.75); P = 0.01]. Conclusions: Our data suggest that both single nucleotide variations rs11655505 (c.-2265C/T) and the methylation status of BRCA1 are not associated significantly with the occurrence of sporadic breast cancer in studied population. However, decreased expression of gene is associated with the CT genotypes and the disease. But, in case of tumor samples, an association of methylation of the promoter to the decreased expression of BRCA1 gene suggests the possible role of methylation in gene silencing. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).
Chava S.,Mahavir Hospital and Research Center |
Chava S.,Vasavi Medical and Research Center |
Mohan V.,Tapadia Diagnostics Services |
Shetty P.J.,Vasavi Medical and Research Center |
And 10 more authors.
Diseases of the Esophagus | Year: 2012
The aim of the study was to evaluate the expression of tumor suppressor genes p53, fragile histidine triad gene (FHIT), and an oncogene insulin-like growth factor 2 (IGF2) as prognostic markers in the etiology of esophageal cancer. Immunohistochemistry (IHC) was performed in 39 archival tissue samples of different esophageal pathologies for the three genes. Abnormal p53 expression was maximum in all the cases of squamous cell carcinoma, while IGF2 expression was enhanced in squamous cell carcinoma (81%), adenocarcinoma (100%), and dysplasia of squamous epithelium (75%) samples when compared with normals (50%). To our surprise, 75% of normal tissues did not show FHIT expression, which was also not seen in 40% of dysplasias of squamous epithelium, 33.3% of adenocarcinoma, and 41% of squamous cell carcinoma. To the best of our knowledge, this is the first study evaluating IGF2 by IHC, as well as, correlating it with the expression of the two tumor suppressor genes, p53 and FHIT, in esophageal tissue. p53 expression was threefold higher than normal in dysplasias of squamous epithelium and adenocarcinoma, while it was eightfold higher in squamous cell carcinoma. IGF2 expression was low in normal and dysplasia tissue but was increased 1.97-fold in both types of malignancy. FHIT and p53 expression were well correlated in squamous cell carcinoma, supporting the observation that FHIT regulates and stabilizes p53. Altered/lowered FHIT levels may be a result of exposure to various exogenous agents; however, this could not be assessed in the present study as it was carried out on archival samples. A larger prospective study is warranted to establish the role of exogenous factors in FHIT expression. © 2011 the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.
Alam K.,DNA Diagnostics Center |
Ghousunnissa S.,DNA Diagnostics Center |
Nair S.,DNA Diagnostics Center |
Valluriand V.L.,Mahavir Hospital and Research Center |
Mukhopadhyay S.,DNA Diagnostics Center
Journal of Immunology | Year: 2010
The glutathione-redox balance, expressed as the ratio of intracellular reduced glutathione (GSH) and oxidized glutathione, plays an important role in regulating cellular immune responses. In the current study, we demonstrate that alteration of glutathione-redox balance in macrophages by GSH donors like cell-permeable glutathione ethyl ester reduced or N-acetyl-L-cysteine (NAC) can differentially regulate production of IL-12 cytokine in macrophages. A low concentration of NAC increased IL-12 p40/p70 production, whereas at high concentration, IL-12 production was inhibited due to increased calmodulin expression that binds and sequesters c-rel in the cytoplasm. Although NAC treatment increased the IκBα phosphorylation, it failed to increase TNF-α levels due to enhanced expression of suppressor of cytokine signaling 1, which specifically prevented nuclear translocation of p65 NF-κB. We demonstrate that NAC at 3 mM concentration could increase bacillus Calmette-Guérin-induced IFN-γ production by PBMCs from patients with active tuberculosis and shifts the anti-bacillus Calmette-Guérin immune response toward the protective Th1 type. Our results indicate that redox balance of glutathione plays a critical role in regulating IL-12 induction in native macrophages, and NAC can be used in tailoring macrophages to induce enhanced Th1 response that may be helpful to control tuberculosis and other pathophysiological disorders. Copyright © 2010 by The American Association of Immunologists, Inc.
Deeba F.,Osmania University |
Syed R.,Mahavir Hospital and Research Center |
Quareen J.,Central Research Institute of Unani Medicine |
Waheed M.,Central Research Institute of Unani Medicine |
And 2 more authors.
Indian Journal of Dermatology | Year: 2010
Background: Vitiligo or leukoderma is a chronic skin condition that causes loss of pigment due to destruction of melanocytes, resulting in irregular pale patches of skin. Vitiligo is a polygenic disease and is associated with autoimmunity with an unknown etiology. Aims: One of the candidate genes which has a strong association with several autoimmune diseases is ctla0 -4 gene located in chromosome 2q33 region. We investigated the possible association between ctla0 -4 gene polymorphism in exon 1 (A49G) and vitiligo in patients from South India and compared the distribution of this polymorphism to matched control groups. Patients and Methods: The polymorphism was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in 175 patients and 180 normal, age/ethnicity matched individuals. Consistency of genotype frequencies with the Hardy-Weinberg equilibrium was tested using a 2 test. Results: There was no significant difference between the genotype (P=0.93) and allele (P=0.615) frequencies of CTLA-4 A49G polymorphism in patients and normal healthy individuals. However there was significant association of the CTLA-4 genotype ( P=0.02) and allelic frequency ( P=0.008) between the segmental and non-segmental sub groups within vitiligo. Conclusion: Our results indicate that there is no association between CTLA-4 A49G gene polymorphism and vitiligo in southern Indian population.
PubMed | Mahavir Hospital and Research Center, Transimmun Transplantation Immunology and Research Center and Krishna Institute of Medical science
Type: Journal Article | Journal: Immunologic research | Year: 2016
Achievement of an immunosuppression-free condition defined as clinical operational tolerance is an ideal goal. We hereby report a case of clinical operational tolerance in a patient whose allograft is functioning normally, without immunosuppression, for more than 3years. The patient withdrew from immunosuppression in 2011 following which his serum creatinine was 1.34mg/dl and proteinuria was 178mg/24h. Flowcytometric studies showed an elevated number of B lymphocytes and NK cells. IL-10 cytokine levels had increased, whereas those of IFN- decreased, suggesting that both B lymphocytes and NK cells, with their immunoregulatory function, contribute to the maintenance of long-term graft function. Consequently, further studies in understanding the interactions of NK cells and B lymphocytes may give us a better insight into the underlying mechanisms that underpin organ tolerance.