National Institute of Immunohaematology

Mumbai, India

National Institute of Immunohaematology

Mumbai, India

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Kalathil S.G.,Roswell Park Cancer Institute | Lugade A.A.,Roswell Park Cancer Institute | Pradhan V.,Roswell Park Cancer Institute | Pradhan V.,National Institute of Immunohaematology | And 6 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2014

Rationale: Previous studies from our laboratory have shown that peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD) prone to exacerbations with nontypeable Haemophilus influenzae have impaired responses to lipoprotein P6. We hypothesized that an underlying immunosuppressive network could be responsible for the defective antibacterial immunity observed in these patients. We evaluated T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC), and exhausted T effector cells (programmed death 1 [PD-1]+) in patients with COPD, because these cells are known to play a pivotal role in suppressing immune responses. Objectives: We performed an in-depth characterization of Tregs, T effector cells, and MDSC in COPD and correlated their levels and function with disease severity. Methods: Treg, effector T cell, and MDSC frequency from patients with COPD and healthy subjects' PBMCs were analyzed by flow cytometry. Treg immunosuppressive capacity was measured by in vitro suppression assay. The frequency of interferon-γ producing T cells and T-cell proliferation were measured after blocking CTLA-4 and PD-1. Plasma proinflammatory and immunosuppressive cytokine levels were measured. Measurements and Main Results: Significantly increased levels of Tregs, MDSC, and PD-1+ exhausted effector T cells were present in patients with COPD compared with healthy subjects. Tregs from patients with COPD suppressed P6-specific T-cell proliferation to a greater extent than Tregs from healthy subjects. Plasma levels of Treg-generated cytokines, IL-10, and transforming growth factor-β were elevated. Blockade of CTLA-4 resulted in significant augmentation of T-cell IFN-γ production in patients with COPD. Conclusions: Functionally suppressive Tregs, MDSCs, and exhausted PD-1+ T cells contribute to effector T-cell dysfunction in COPD. Copyright © 2014 by the American Thoracic Society.


Colah R.,National Institute of Immunohaematology | Chattopadhyay S.,Bhabha Atomic Research Center
Free Radical Research | Year: 2013

The protecting ability of the Piper betle leaves-derived phenol, allylpyrocatechol (APC) against AAPH-induced membrane damage of human red blood cells (RBCs) was investigated. Compared to control, AAPH (50 mM) treatment resulted in significant hemolysis (55%, p < 0.01), associated with increased malondialdehyde (MDA) (2.9-fold, p < 0.001) and methemoglobin (6.1-fold, p < 0.001) levels. The structural deformation due to membrane damage was confirmed from scanning electron microscopy (SEM) images and Heinz bodies formation, while the cell permeability was evident from the K+ efflux (28.7%, p < 0.05) and increased intracellular Na+ concentration (8%, p < 0.05). The membrane damage, due to the reduction of the cholesterol/phospholipids ratio and depletion (p < 0.001) of ATP, 2,3-DPG by ̃44-54% and Na+-K+ ATPase activity (43.7%), indicated loss of RBC functionality. The adverse effects of AAPH on all these biochemical parameters and the resultant oxidative hemolysis of RBCs were significantly reduced by pretreating the cells with APC (7 μM) or α-tocopherol (50 μM) for 1 h, prior to incubation with AAPH. © 2013 Informa UK, Ltd.


Joshi S.R.,Institute of Health science | Vasantha K.,National Institute of Immunohaematology
Asian Journal of Transfusion Science | Year: 2012

From transfusion point of view, a rare blood is the one which lacks a high-frequency antigen as well as the one who lacks multiple common antigens and such blood donations help in transfusion to those recipients having alloantibodies to corresponding antigens. In India, we have about four such kinds of phenotypes potential enough to pose problems in providing blood to the recipients having these phenotypes. Besides, there are other four kinds of rare bloods that pose seldom problems in blood supply, though some of these may cause problems in interpretation of results on assigning proper blood groups for a person.


Marvin J.,Northwestern University | Swaminathan S.,Northwestern University | Swaminathan S.,National Institute of Immunohaematology | Kraker G.,Northwestern University | And 3 more authors.
Blood | Year: 2011

Molecular and cytogenetic alterations are involved in virtually every facet of acute myeloid leukemia (AML), including dysregulation of major signal-transduction pathways. The present study examines 5 phosphoproteins (pErk, pAkt, pS6, pStat3, and pStat5) in response to 5 cytokine/growth factors (stem cell factor [SCF], Flt-3/Flk-2 ligand [FL], granulocyte/macrophage-colony stimulating factor [GM-CSF], interleukin-3 [IL-3], and granulocyte-CSF [G-CSF]) within 7 immunophenotypically defined populations, spanning progenitor to mature myeloid/myelomonocytic cells in normal bone marrows with further comparison to AML samples. The normal cohort showed pathway-specific responses related to lineage, maturation, and stimulus. Heterogeneous-signaling responses were seen in homogeneous immunophenotypic subsets emphasizing the additive information of signaling. These profiles provided a critical baseline for detection of dysregulated signaling in AML falling into 4 broad categories, viz lack of response, increased activation, altered constitutive expression, and dysregulated response kinetics, easily identified in 10 of 12 AMLs. These studies clearly show robust and reproducible flow cytometry phosphoprotein analyses capable of detecting abnormal signal-transduction responses in AML potentially contributing to definitive reliable identification of abnormal cells. As functional correlates of underlying genetic abnormalities, signal-transduction abnormalities may provide more stable indicators of abnormal cells than immunophenotyping which frequently changes after therapy and disease recurrence. © 2011 by The American Society of Hematology.


Patil A.S.,University of Mumbai | Pawar A.S.,National Institute of Immunohaematology
International Journal of Pharma and Bio Sciences | Year: 2015

Transfusion transmitted infections (TTI) create a significant burden on health care system. Donor selection is of paramount importance because infected individuals serve as an asymptomatic reservoir and a potential source of transmission. The present study was carried out to find out the prevalence of Transfusion transmitted Infections (TTI) in blood donors of Maharashtra region. A retrospective study was carried out in healthy blood donors of NACO assisted blood banks in Maharashtra over a period of seven years from January 2008 to December 2014, to determine the prevalence of HIV, HBV, HCV, syphilis and malaria in blood donors. The prevalence of TTIs among the total collected blood was 20271(0.40) for HIV1 and 2, 75266(1.48%) for HBsAg, 19022 (0.37%) for HCV, 5651 (0.11%) for Syphilis and 838 (0.02%) for malaria. The HBsAg percentage of TTI positivity detected in blood donors of Maharashtra is high. That may be due to the stringent follow up of testing or may be due to compromised testing quality.


Warang P.P.,National Institute of Immunohaematology | Kedar P.S.,National Institute of Immunohaematology | Shanmukaiah C.,Kem Hospital | Ghosh K.,National Institute of Immunohaematology | Colah R.B.,National Institute of Immunohaematology
Clinical Genetics | Year: 2015

We report the clinical features and molecular characterization of 23 patients with cyanosis due to NADH-cytochrome b5 reductase (NADH-CYB5R) deficiency from India. The patients with type I recessive congenital methemoglobinemia (RCM) presented with mild to severe cyanosis only whereas patients with type II RCM had cyanosis associated with severe neurological impairment. Thirteen mutations were identified which included 11 missense mutations causing single amino acid changes (p.Arg49Trp, p.Arg58Gln, p.Pro145Ser, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, p.Ala179Thr, p.Thr238Met, and p.Val253Met), one stop codon mutation (p.Trp236X) and one splice-site mutation (p.Gly76Ser). Seven of these mutations (p.Arg50Trp, p.Gly155Glu, p.Arg160Pro, p.Met177Ile, p.Met177Val, p.Ile178Thr, and p.Thr238Met) were novel. Two mutations (p.Gly76Ser and p.Trp236X) were identified for the first time in the homozygous state globally causing type II RCM. We used the three-dimensional (3D) structure of human erythrocyte NADH-CYB5R to evaluate the protein structural context of the affected residues. Our data provides a rationale for the observed enzyme deficiency and contributes to a better understanding of the genotype-phenotype correlation in NADH-CYB5R deficiency. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Madkaikar M.R.,National Institute of Immunohaematology
BMJ case reports | Year: 2011

The authors report a case of purine nucleoside phosphorylase (PNP) deficiency for the first time from India. The case presented with recurrent severe infections, developmental delays, seizures and progressive neurological deterioration. The diagnosis of primary immunodeficiency disorder was delayed in spite of recurrent infection due to predominant neurological symptoms. Sequencing of the PNP gene revealed a novel mutation resulting in a premature stop codon.


Italia K.,National Institute of Immunohaematology | Colah R.,National Institute of Immunohaematology | Ghosh K.,National Institute of Immunohaematology
PLoS ONE | Year: 2013

Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination. © 2013 Italia et al.


Warang P.,National Institute of Immunohaematology | Kedar P.,National Institute of Immunohaematology | Ghosh K.,National Institute of Immunohaematology | Colah R.B.,National Institute of Immunohaematology
International Journal of Laboratory Hematology | Year: 2012

Introduction: Pyrimidine 5′ nucleotidase type I (P5′N-1) deficiency is the most frequent abnormality of cell nucleotide metabolism causing hereditary non spherocytic hemolytic anemia (HNSHA). The aim of this study was to develop a simple method of determination of P5′N-1 activity in human erythrocytes using an ELISA reader Methods: Determination of P5′N-1 activity is based on the liberation of inorganic phosphorus (Pi) after incubation with uridine monophosphate/cytidine monophosphate. Inorganic phosphorus (Pi), a product of the enzymatic reaction is directly quantitated from its ultraviolet absorbance. Purine/Pyrimidine nucleotides ratio (OD 260: OD 280) was also measured Results: P5′N-1 deficient patients showed reduction in P5′N-1 activity (Mean±SD; 4.06±0.66 using an ELISA reader & 6.25±1.37 using a spectrophotometer) as compared to the normal control group (ELISA reader: 13.24±3.42 & Spectrophotometer: 18.25±3.20). Heterozygotes showed intermediate activity (ELISA reader: 6.06±0.48 & Spectrophotometer: 8.06±1.28), however they would have been missed on screening using the Purine/Pyrimidine nucleotides ratio Conclusion: Determination of P5′N-1 activity by using an ELISA reader is a new, simple, less time consuming and reliable method. It also avoids the use of radioactive material or HPLC which is a significant advantage. © 2011 Blackwell Publishing Ltd.


Italia K.,National Institute of Immunohaematology | Colah R.,National Institute of Immunohaematology | Ghosh K.,National Institute of Immunohaematology
Blood Cells, Molecules, and Diseases | Year: 2015

The disorders of iron overload due to primary or secondary cause are one of the important human diseases leading to high mortality if untreated. To understand this, an animal model has been extensively studied. The source of iron administered to the mode of iron administration that can mimic the iron overload in humans has been studied. A safe and orally active iron chelator is still needed as many of the existing compounds have different types of complications and toxicity associated. Hence having a simple animal model which can be availed quickly and can be used to study various compounds for its iron chelating activity would likely to have immense utility for pharmacological studies. In this review we have shown how, using a simple procedure, a large number of small iron overloaded animals can be produced easily for various studies. © 2015.

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