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1.  Characterization of the Protective HIV-1 CTL Epitopes and the Corresponding HLA Class I Alleles: A Step towards Designing CTL Based HIV-1 Vaccine 
Advances in Virology  2014;2014:321974.
Human immunodeficiency virus (HIV) possesses a major threat to the human life largely due to the unavailability of an efficacious vaccine and poor access to the antiretroviral drugs against this deadly virus. High mutation rate in the viral genome underlying the antigenic variability of the viral proteome is the major hindrance as far as the antibody based vaccine development is concerned. Although the exact mechanism by which CTL epitopes and the restricting HLA alleles mediate their action towards slow disease progression is still not clear, the important CTL restricted epitopes for controlling viral infections can be utilized in future vaccine design. This study was designed for the characterization the HIV-1 optimal CTL epitopes and their corresponding HLA alleles. CTL epitope cluster distribution analysis revealed only two HIV-1 proteins, namely, Nef and Gag, which have significant cluster forming capacity. We have found the role of specific HLA supertypes such as HLA B∗07, HLA B∗58, and HLA A∗03 in selecting the hydrophobic and conserved amino acid positions within Nef and Gag proteins, to be presented as epitopes. The analyses revealed that the clusters of optimal epitopes for Nef and p24 proteins of HIV-1 could potentially serve as a source of vaccine.
doi:10.1155/2014/321974
PMCID: PMC3976937  PMID: 24744786
2.  The difficulties in cancer treatment 
ecancermedicalscience  2012;6:ed16.
Cancer is clearly the most deadly disease in the developed world as one in three people develop cancer during their lifetime. The cure for cancer is like the Holy Grail since most of the existing treatments are not effective enough to provide full protection from this disease. In recent years the burgeoning of sophisticated genomic, proteomic and bioinformatics techniques has made it possible for us to get a glimpse of the intricate interplay of numerous cellular genes and regulatory genetic elements that are responsible for the manifestation of cancerous phenotypes. With the use of modern genomic technologies we are now beginning to understand the enormous complexity of cancer. However there are few success stories as far as the treatment of cancer is concerned. For instance the treatments of leukemia and lymphoma have been established and proved to be satisfactory. Despite occasional successes the treatment for most cancers is still a long way from reality. In this editorial, we have addressed several reasons for the difficulties in cancer treatment.
doi:10.3332/ecancer.2012.ed16
PMCID: PMC4024849  PMID: 24883085
3.  Pattern of β-Thalassemia and Other Haemoglobinopathies: A Cross-Sectional Study in Bangladesh 
ISRN Hematology  2012;2012:659191.
Thalassemia and other structural haemoglobinopathies are the major erythrocyte formation disorder prevalent in certain parts of the world including Bangladesh. We investigated 600 cases of anaemic patients referred from various parts of the country for diagnosis and counselling during 3 months (April to June 2011) of time. The most common form of haemoglobin (Hb) formation disorder observed in 600 subjects studied was β-thalassemia minor (21.3%). Two other conditions, such as E-β-Thalassemia and HbE trait, were also fairly common (13.5 and 12.1%, resp.) in the total subjects studied. Other forms of haemoglobin formation disorders observed were HbE disease (9.2%), Hb D/S trait (0.7%), β-thalassemia major (0.5%), and δ-β-thalassemia (0.5%). The majority of the haemoglobinopathies belonged to neonatal to childhood period (0–15 years), followed by reproductive age group (16–45 years). Few old-age (46+ years) cases were also detected in course of clinical complications.
doi:10.5402/2012/659191
PMCID: PMC3384890  PMID: 22778980
4.  Correlation of Oxidative Stress with Serum Trace Element Levels and Antioxidant Enzyme Status in Beta Thalassemia Major Patients: A Review of the Literature 
Anemia  2012;2012:270923.
Beta thalassemia major is an inherited disease resulting from reduction or total lack of beta globin chains. Patients with this disease need repeated blood transfusion for survival. This may cause oxidative stress and tissue injury due to iron overload, altered antioxidant enzymes, and other essential trace element levels. The aim of this review is to scrutinize the relationship between oxidative stress and serum trace elements, degree of damage caused by oxidative stress, and the role of antioxidant enzymes in beta thalassemia major patients. The findings indicate that oxidative stress in patients with beta thalassemia major is mainly caused by tissue injury due to over production of free radical by secondary iron overload, alteration in serum trace elements and antioxidant enzymes level. The role of trace elements like selenium, copper, iron, and zinc in beta thalassemia major patients reveals a significant change of these trace elements. Studies published on the status of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione S-transferase in beta thalassemia patients also showed variable results. The administration of selective antioxidants along with essential trace elements and minerals to reduce the extent of oxidative damage and related complications in beta thalassemia major still need further evaluation.
doi:10.1155/2012/270923
PMCID: PMC3357501  PMID: 22645668
5.  Repeated Topical Application of para-Phenylenediamine Induces Renal Histopathological Changes in Rats 
Toxicology International  2012;19(2):132-137.
Hemolytic anemia and rhabdomyolysis have been often reported to be an adverse effect of drug- and chemical-induced toxicity both in experimental and real-life scenario. para-Phenylenediamine (PPD) is a derivative of para-nitroaniline and has been found as an ingredient of almost all hair dye formulations in varying concentrations from 2% to 4% w/v. Earlier studies have reported that the accidental oral ingestion of PPD in humans can lead to acute renal failure because of rhabdomyolysis. In the present investigation, we have tested the chronic topical application of PPD and its effect on the renal histology of Sprague-Dawley rats. The experiment provides clear evidence that topically applied PPD induces hemolytic anemia as evident from the decrease in the total RBC count, packed cell volume, and hemoglobin content apart from rhabdomyolysis which subsequently causes acute renal failure in rats.
doi:10.4103/0971-6580.97206
PMCID: PMC3388756  PMID: 22778510
Hemolysis; para-phenylenediamine; renal dysfunction; rhabdomyolysis; topical
6.  Vibrio cholerae O1 Infection Induces Proinflammatory CD4+ T-Cell Responses in Blood and Intestinal Mucosa of Infected Humans▿† 
Vibrio cholerae O1 is a noninvasive enteric pathogen and serves as a model for studies of mucosal immunity. Although symptomatic V. cholerae infection induces durable protection against subsequent disease, vaccination with oral killed whole-cell V. cholerae stimulates less long-lasting protection against cholera. In this study, we demonstrated that cholera induces an early proinflammatory cellular immune response that results in priming of Th1- and Th17-type cytokine responses to ex vivo antigenic stimulation and an increase in the ratio of Th1 to Th2 CD4+ T-cell responses. Comparable priming of Th1 and Th17 responses, with an increased ratio of Th1 to Th2 CD4+ T-cell responses, was not observed in subjects who received two doses of the oral cholera vaccine Dukoral (a whole-cell cholera toxin B subunit containing [WC-CTB] vaccine). These findings suggest that natural V. cholerae infection induces an early, proinflammatory cellular immune response, despite the apparent lack of clinical signs of inflammation. The failure of the WC-CTB vaccine to activate equivalent, CD4+ T-cell responses is a potential explanation for the shorter duration of protection following immunization with this vaccine. Additional studies are needed to determine whether these early T-cell-mediated events predict the subsequent duration of immunologic memory.
doi:10.1128/CVI.05088-11
PMCID: PMC3147337  PMID: 21697339
7.  Interferon-γ and Proliferation Responses to Salmonella enterica Serotype Typhi Proteins in Patients with S. Typhi Bacteremia in Dhaka, Bangladesh 
Background
Salmonella enterica serotype Typhi is a human-restricted intracellular pathogen and the cause of typhoid fever. Cellular immune responses are required to control and clear Salmonella infection. Despite this, there are limited data on cellular immune responses in humans infected with wild type S. Typhi.
Methodology/Principal Findings
For this work, we used an automated approach to purify a subset of S. Typhi proteins identified in previous antibody-based immuno-affinity screens and antigens known to be expressed in vivo, including StaF-putative fimbrial protein-STY0202, StbB-fimbrial chaperone-STY0372, CsgF-involved in curli production-STY1177, CsgD- putative regulatory protein-STY1179, OppA-periplasmic oligopeptide binding protein precursor-STY1304, PagC-outer membrane invasion protein-STY1878, and conserved hypothetical protein-STY2195; we also generated and analyzed a crude membrane preparation of S. Typhi (MP). In comparison to samples collected from uninfected Bangladeshi and North American participants, we detected significant interferon-γ responses in PBMCs stimulated with MP, StaF, StbB, CsgF, CsgD, OppA, STY2195, and PagC in patients bacteremic with S. Typhi in Bangladesh. The majority of interferon-γ expressing T cells were CD4 cells, although CD8 responses also occurred. We also assessed cellular proliferation responses in bacteremic patients, and confirmed increased responses in infected individuals to MP, StaF, STY2195, and PagC in convalescent compared to acute phase samples and compared to controls. StaF is a fimbrial protein homologous to E. coli YadK, and contains a Pfam motif thought to be involved in cellular adhesion. PagC is expressed in vivo under the control of the virulence-associated PhoP-regulon required for intra-macrophage survival of Salmonella. STY2195 is a conserved hypothetical protein of unknown function.
Conclusion/Significance
This is the first analysis of cellular immune responses to purified S. Typhi antigens in patients with typhoid fever. These results indicate that patients generate significant CD4 and CD8 interferon-γ responses to specific S. Typhi antigens during typhoid fever, and that these responses are elevated at the time of clinical presentation. These observations suggest that an interferon-γ based detection system could be used to diagnose individuals with typhoid fever during the acute stage of illness.
Author Summary
Salmonella enterica serotype Typhi infection is a significant global public health problem and the cause of typhoid fever. Salmonella are intracellular pathogens, and cellular immune responses are required to control and clear Salmonella infections. Despite this, there are limited data on cellular immune responses during wild type S. Typhi infection in humans. Here we report the assessment of cellular immune responses in humans with S. Typhi bacteremia through a screening approach that permitted us to evaluate interferon-γ and proliferation responses to a number of S. Typhi antigens. We detected significant interferon-γ CD4 and CD8 responses, as well as proliferative responses, to a number of recombinantly purified S. Typhi proteins as well as membrane preparation in infected patients. Antigen-specific interferon-γ responses were present at the time of clinical presentation in patients and absent in healthy controls. These observations could assist in the development of interferon-γ-based diagnostic assays for typhoid fever.
doi:10.1371/journal.pntd.0001193
PMCID: PMC3110156  PMID: 21666798

Results 1-7 (7)