Browsing by Author "Ghosh, Kanjaksha"

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    Additional markers for genetic diagnosis of type 3 von Willebrand disease in Indian population.
    (2015-12) Kasatkar, Priyanka; Ghosh, Kanjaksha; Shetty, Shrimati
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    Alternate strategies for carrier detection and antenatal diagnosis in haemophilias in developing countries.
    (2003-01) Shetty, Shrimati; Ghosh, Kanjaksha; Mohanty, Dipika
    Carrier detection and prenatal diagnosis constitute an important component of haemophilia management . Recent advances in molecular biology allows us to use the tools of molecular biology to give such a diagnosis early in the pregnancy with a much higher confidence. Because of lyonisation, diagnosis of a carrier by factor assay is imperfect and hence lacks sensitivity. Molecular diagnosis in such cases is robust.There are several techniques by which this diagnosis can be made.Though the preferred method is to do direct mutation studies, yet the complexities of factor VIII and factor IX genes may not make this approach easy or cost effective. Hence depending on the capability of the laboratory, education status of the family, availability of data through several generations and economic situation of the country, a combination of these techniques need to be adopted for optimum results. These techniques are broadly classified as indirect techniques through linkage analysis or direct detection of affected genes by a combination of screening and sequencing techniques. Occasionally in our country even all the gene based techniques may prove inadequate and we may have to give prenatal diagnosis by antigen and clotting activity assay of the defective factor by cordocentesis between 17-20 weeks of gestation. For any prenatal diagnosis of haemophilia, prior detection of fetal sex either by USG or by molecular technique is necessary to decide whether any further work up is necessary or not? The present article describes various algorithms of carrier detection prenatal diagnosis of haemophilia that was found suitable in our country.
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    Annoucement.
    (2012-09) Ghosh, Kanjaksha
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    Anti-nucleosome antibodies as a disease marker in systemic lupus erythematosus and its correlation with disease activity and other autoantibodies.
    (2010-03) Pradhan, Vandana D; Patwardhan, Manisha M; Ghosh, Kanjaksha
    Background: Detection of anti-nucleosome antibodies (anti-nuc) in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. Aims: The aim of this study is to evaluate the incidence of anti-nuc antibodies and to correlate them with disease activity and its association with other autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), as well as autoantibodies to histone subfractions like H1, (H2A-H4) complex, H2B, and H3. Methods: This cross-sectional study included 100 SLE patients referred from the Rheumatology, Dermatology, and Nephrology Departments. SLE disease activity was evaluated by using SLE-Disease Activity Index (SLEDAI) score. A patient was defined as having active SLE when the SLEDAI score was more than 5.0. Fifty normal controls were also tested as a healthy control group. Anti-nuc antibodies, anti-dsDNA, and AHA were tested by Enzyme-Linked Immunosorbent Assay (ELISA) and ANA was detected by an indirect immunofluorescence test. Results: All patients studied were in an active stage of disease and were untreated, of which 44 patients had renal biopsy-proven kidney involvement, which was categorized as lupus nephritis (LN) and 56 patients did not show any renal manifestations (SLE without LN). Anti-nuc antibodies were positive in 88%, anti-dsDNA in 80%, and AHA in 38% of the cases. ANA was positive in all SLE patients studied. None of the normal controls was found to be positive for these antibodies. Although a slightly higher incidence of autoantibodies were noted in LN, there was no statistical difference noted between LN and SLE without LN groups for anti-nuc and anti-dsDNA antibodies (p > 0.05). A higher incidence of autoantibodies to ANA specificities were noted in anti-nuc positive cases, but there was no statistical difference between anti-nuc positive and anti-nuc negative cases for ANA specificities among LN and SLE without nephritis groups (p > 0.05). Conclusions: Anti-nuc antibody detection could be a better tool for the diagnosis of SLE. Although there was no significant difference in LN and SLE without LN groups, this study suggests that anti-nuc detection can be useful as an additional disease activity marker to other laboratory tests.
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    Antiplatelet antibodies in cases of Glanzmann's thrombasthenia with and without a history of multiple platelet transfusion.
    (2009-01) Ghosh, Kanjaksha; Kulkarni, B; Shetty, S; Nair, S
    Antiplatelet antibodies are known to be present in a wide spectrum of patients, which include chronic Idiopathic Thrombocytopenic Purpura (ITP), infections, etc., including Glanzmann's thrombasthenia (GT) patients who receive multiple platelet transfusions. The presence of natural antibodies to platelet receptors is not studied in cases of GT. We studied the antiplatelet antibodies in 23 patients with GT, 15 of which had received multiple transfusions and eight that had not received transfusions, along with 50 cases of chronic ITP. The prevalence and specificity of platelet-bound antibodies were detected by inhibition assays using O-group platelets on flow cytometry. The mean antiplatelet antibodies in 15 patients of GT who had not received transfusions and eight patients with multiple transfusions was 8427 + 2131.88 and 9038 + 2856 antibodies/platelet, respectively, while in case of the 50 ITP patients studied, it was 22166 + 5616 antibodies/platelet (Normal Range 1500–3200 antibodies/platelet). We conclude that GT patients who have not received transfusions may develop antiplatelet antibodies to the missing/abnormal receptor. Whether this is due to a molecular mimicry or due to some other mechanism needs to be explored.
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    Bacteriological infections during the first hundred days of allogenic bone marrow transplantation--experience from Oman.
    (2002-07-20) Ghosh, Kanjaksha; Shenoy, A K; Al-Mahrooqi, Zahra
    BACKGROUND: Allogeneic bone marrow transplantation (ABMT) produces severe neutropenia lasting for days. During the first 100 days of allogeneic BMT bacterial infection is a major cause of mortality and morbidity. This is specially so till the patient engrafts with good neutrophil count (> 500/microl). Nature of bacterial infection and its sensitivity pattern partly reflects the patient's own flora, hospital flora and the antibiotic usage pattern in the hospital and the community. Hence although we know quite a lot about the nature of bacterial sepsis following ABMT quite well, its details vary from centre to centre. Hence the present study was undertaken at a newly developed BMT unit at Muscat, Oman. MATERIAL AND METHODS: Twenty one patients receiving allogeneic BMT for different indications were included in this study. These patients had blood culture from central and peripheral line whenever they developed fever > 38 degrees C lasting more than two hours and the relevant investigators like X-ray chest, USG, CRP levels, urine culture was done as and when required. RESULTS: All patients in BMT unit developed fever > 38 degrees C during first 100 days but only nine patients showed positive blood culture on 12 occasions. 42% of these isolates were gram-positive organisms. No fungal infections were noticed. Twenty percent of the gram-negative isolates from adjoining pardiatric oncology ward were resistant to ciprofloxacin though this is a reserved drug in this hospital. One out of 21 BMT patient in the present study died due to sepsis with resistant Klebsiella organism. Imipenem as a single drug did not cover all the organisms isolated. Listeria monocytogenes was an unusual organism in our BMT patient. CONCLUSION: The present result of less than 5% mortality in the ABMT patients due to sepsis is excellent and this is related to early marrow recovery and efficient microbiological surveillance in this centre. Cautions should be exercised while using imipenem as a single antibiotic in ABMT situations. Though ciprofloxacin is a reserved drug in this hospital, increased incidence of resistance to this antibiotic probably represents its wide usage in the community.
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    Bombay phenotype in Orissa: What could we make out of it.
    (2007-09) Ghosh, Kanjaksha; Vasantha, K
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    Chimeric Fusion Karyotypes in Childhood B-cell Acute Lymphoblastic Leukemia.
    (2014-02) Kerketta, Lily S; Rao, Vundinti Babu; Ghosh, Kanjaksha
    Cytogenetics study using combination of conventional cytogenetics and fluorescent insitu hybridization was carried out in 171 pediatric acute lymphoblastic leukemia patients subgrouped to B-ALL (n=126) and T-ALL (n=45) by bone marrow morphology and immunophenotype. The chromosomal aberration frequency in B-ALL and T-ALL was 79% and 71%, respectively. TEL/AML1 translocation was detected in 28% of patients.
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    Chromosomal breakage in myelodysplatic syndrome.
    (2008-01-29) Korgaonkar, Seema; Babu, V Rao; Kerketta, Lily; Ghosh, Kanjaksha
    The myelodysplastic syndrome (MDS) represents a group of clonal hematological disorders characterized by progressive cytopenia reflecting defects in erythroid, myeloid and mega karyocytic maturation. The incidence of MDS is greter in older age groups. Detailed studies on MDS from India are not available. Cytogenetic study using GTG-banding and FISH revealed 54.5% clonal chromosomal abnormalities. We have carried out chromosomal breakage study from peripheral blood cultures induced with mitomycin C, in karyotypically normal MDS (49) and 15 (30.6%) showed significant (p < 0.001) increase in chromosome damage compared to controls. Among 22 occupationally exposed MDS, 6 (27.3%) showed a high frequency of chromosome breakage while in the non-exposure (n=27) group, high chromosome breakage was noted in 9 (33.3% ) MDS patients. Our results suggest that the high chromosome damage may be due to acquired Fanconi anemia which leads to multiple defects in chromosomes and clonal chromosome anomalies.
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    Chromosomal instability and cancer: An insight into the rhythm of life.
    (2009-01) Vundinti, Babu Rao; Ghosh, Kanjaksha
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    Clinical, hematologic and molecular variability of sickle cell-β thalassemia in western India.
    (2010-09) Mukherjee, Malay B; Nadkarni, Anita H; Gorakshakar, Ajit C; Ghosh, Kanjaksha; Mohanty, Dipika; Colah, Roshan B
    BACKGROUND: Sickle cell-β thalassemia (HbS-β thalassemia) is a sickling disorder of varying severity, which results from compound heterozygosity for sickle cell trait and β thalassemia trait. The present study was undertaken to determine the genetic factors responsible for the clinical variability of HbS-β thalassemia patients from western India. MATERIALS AND METHODS: Twenty-one HbS-β thalassemia cases with variable clinical manifestations were investigated. The α and β globin gene clusters were studied by molecular analysis. RESULTS: Thirteen patients showed milder clinical presentation as against eight patients who had severe clinical manifestations. Four β thalassemia mutations were identified: IVS 1-5 (G→C), codon 15 (G→A), codon 30 (G→C) and codon 8/9 (+G). α thalassemia and XmnI polymorphism in homozygous condition (+/+) were found to be common among the milder cases. The βS chromosomes were linked to the typical Arab-Indian haplotype (#31). Framework (FW) linkage studies showed that four β thalassemia mutations were associated with different β globin gene frameworks. Linkage of codon 15 (G→A) mutation to FW2 is being observed for the first time. CONCLUSION: The phenotypic expression of HbS-β thalassemia is not uniformly mild and α thalassemia and XmnI polymorphism in homozygous condition (+/+) are additional genetic factors modulating the severity of the disease in the Indian subcontinent.
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    Coagulation disorders seen through the window of molecular biology.
    (2007-09) Ghosh, Kanjaksha
    Coagulation disorders have been traditionally worked up by their clinical phenotypes and coagulation factor assays which are dependent on APTT- and PT-based techniques. Development of chromogenic substrates in the late seventies and early eighties allowed coagulation factors to be measured like enzymes. There was still a major lacuna in the understanding of the biology of different coagulation disorders. Modern molecular biology - which developed as an unique synthesis of biochemistry, immunology, cell biology, and genetics - allowed us to have a more comprehensive understanding of the pathobiology of many of these coagulation disorders. This overview presents several examples which show how we have enriched our understanding about the varied clinical phenotypes of different coagulation disorders.
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    Combination of thrombophilia markers in acute myocardial infarction of the young.
    (2004-09-08) Khare, Amit; Ghosh, Kanjaksha; Shetty, Shrimati; Kulkarni, Bipin; Mohanty, Dipika
    BACKGROUND: The pathogenesis of arterial thrombotic disease involves multiple genetic and environmental factors related to atherosclerosis and thrombosis. But, there have been very few studies in India which have investigated some of the thrombophilia markers. AIM: To look for combined thrombophilia in MI patients. SETTINGS AND DESIGN: One hundred twenty patients of myocardial infarction (age below 40 yrs.) were recruited 8-10 weeks after stabilization. Hundred age and sex-matched healthy controls were also recruited in the present study. METHODS AND MATERIAL: Following thrombophilia markers were screened in these patients--plasma fibrinogen, protein C, protein S, antithrombin III, factor V Leiden, PT G20210A polymorphism, MTHFR C677T, homocysteine, fibrinogen b448 Arg/Lys polymorphism and CBS T833C mutation. STATISTICAL ANALYSIS: Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 10.0, SPSS Inc., Chicago, USA. RESULTS AND CONCLUSION: Elevated fibrinogen levels, homocysteine (p< 0.001 and homocysteine with odds ratio 6.26) and factor V Leiden (p=0.038) were independently associated with MI in our patients. A total of 37 patients (42.5%) had the presence of more than one thrombophilia markers in combination. Out of these, 10 had the presence of three markers in combination and 1 had five thrombophilia markers in combination. Only 2 controls had prothrombotic markers in combination. Combined prothrombotic risk factors were significant in cases in comparison to controls (p< 0.001). Further larger studies on a nationwide basis recruiting a large number of young MI patients should be done to substantiate these findings.
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    Comparison of in-vitro and in-vivo response to fetal hemoglobin production and γ-mRNA expression by hydroxyurea in Hemoglobinopathies.
    (2013-04) Italia, Khushnooma; Jijina, Farah; Merchant, Rashid; Swaminathan, Suchitra; Nadkarni, Anita; Gupta, Maya; Ghosh, Kanjaksha; Colah, Roshan
    BACKGROUND: Hydroxyurea, which induces Fetal hemoglobin (HbF) synthesis, is the only drug widely used in different hemoglobinopathies; however, the response is very variable. We compared the efficacy of hydroxyurea in-vitro in erythroid cultures and in-vivo in the same patients with different hemoglobinopathies to induce HbF production and enhance γ-messenger RNA expression. MATERIALS AND METHODS: A total of 24-patients with different Hemoglobinopathies were given hydroxyurea and their response was studied in-vivo and in-vitro on mononuclear cells collected from them simultaneously. RESULTS: A total of 57.7% of patients (responders) showed no further crisis or transfusion requirements after hydroxyurea therapy with a mean increase in fetal cells (F-cells) of 63.8 ± 59.1% and γ-mRNA expression of 205.5 ± 120.8%. In-vitro results also showed a mean increase in F-cells of 27.2 ± 24.7% and γ-mRNA expression of 119.6% ± 65.4% among the treated cells. Nearly 19.0% of the partial-responders reduced their transfusion requirements by 50% with a mean increase in F-cells of 61.2 ± 25.0% and 28.4 ± 25.3% and γ-mRNA-expression of 21.0% ± 1.4% and 80.0% ± 14.1% in-vivo and in-vitro respectively. The non-responders (15.3%) showed no change in their clinical status and there was no significant increase in F-cells levels and γ-mRNA expression in-vivo or in-vitro. CONCLUSION: Thus, this method may help to predict the in-vivo response to hydroxyurea therapy; however, a much larger study is required.
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    Dandy-Walker malformations in a case of partial trisomy 9p (p12.1→pter) due to maternal translocation t(9;12)(p12.1;p13.3).
    (2007-01) Vundinti, Babu Rao; Kerketta, Lily; Korgaonkar, Seema; Ghosh, Kanjaksha
    We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in right scrotum in addition to typical trisomy 9p clinical features. Routine cytogenetic studies with GTG - banding showed 46,XY,der(12)t(9;12) (p12;q13.3),mat karyotype (trisomy 9p). Chromosomal analysis of the father was normal and phenotypically normal mother had 46,XX,t(9;12)(p12;q13) karyotype. Fluorescence in situ hybridization analysis with single copy probes bA5OIA2 (9p11.2), bA562M8 (12p12.1) and centromere probes (9) showed break point at 9p12.1 region. The gene dosage effect of Chromosome 9p along with environmental factors might be associated with Dandy- Walker malformations in the patient.
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    Deletion of ABL/BCR on der(9) associated with severe basophilia.
    (2011-05) Vaidya, Shantashri; Madkaikar, Manisha; Ghosh, Kanjaksha; Vundinti, Babu Rao
    Chronic basophilic leukemia is a rare form in chronic myeloid leukemia patients. Only limited number of reports are available. Herein, we describe a patient who presented with fatigue, weight loss, leucocytosis, prominent basophilia, and mild eosinophilia. On biopsy, bone marrow was hypercellular with marked basophils. The immunophenotype showed abnormal expression of CD7, which is suggestive of basophilic maturation. Chromosomal analysis from GTG-banded metaphases revealed Ph positivity, and fluorescence in situ hybridization (FISH) with BCR/ABL dual color, dual fusion probe showed single fusion on the der(22) chromosome and ABL/BCR fusion was deleted on the der(9) chromosome. The deletion (ABL/BCR) on der(9) may be associated with basophilia which may be also indicative of the transformation of CML to acute myeloid leukemia.
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    Efficacy of Fixed Low Dose Hydroxyurea in Indian Children with Sickle Cell Anemia: A Single Centre Experience.
    (2013-10) Jain, Dipti L; Apte, Mohini; Colah, Roshan; Sarathi, Vijaya; Desai, Saumil; Gokhale, Amruta; Bhandarwar, Amol; Jain, Harshwardhan L; Ghosh, Kanjaksha
    Introduction: Data on the efficacy of hydroxyurea (HU) in Indian children with sickle cell anaemia (SCA) is limited. Hence, we have evaluated the efficacy of fixed low dose HU in Indian children. Methods: The study cohort consisted of 144 children (<18 years of age) with SCA having severe manifestations (≥3 episodes of vasocclusive crisis or blood transfusions, or having ≥1 episode of acute chest syndrome or cerebrovascular stroke or sequestration crisis) who were started on fixed low dose HU (10 mg/kg/day). They were followed up for two years and monitored for the hematological and clinical efficacy and safety. Results: There was significant increase in the fetal hemoglobin level (HbF%), total hemoglobin and mean corpuscular volume. Vasoocclusive crises, blood transfusions, acute chest syndrome, sequestration crises and hospitalizations decreased significantly. Baseline HbF% had significant positive correlation with HbF% at 24 months. There was significant negative correlation between baseline HbF% and change in HbF% from baseline to 24 months. No significant correlation was found between HbF% at baseline and clinical event rates per year after HU. No major adverse events occurred during the study period. Conclusion: Fixed low dose HU is effective and safe in Indian children with SCA.
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