Roshan Colah - Academia.edu (original) (raw)

Papers by Roshan Colah

Indian Journal of Pediatrics, Jun 1, 2004

Glucose–6–phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in huma... more Glucose–6–phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance. It has been reported from India more than 30 years ago and the prevalence varies from 0–27% in different caste, ethnic and linguistic groups. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic non–spherocytic hemolytic anemia. Individuals with G6PD

Blood Cells Molecules and Diseases, Apr 1, 2014

Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of... more Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle hemoglobin polymer. Fetal hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBBlike gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers. (Blood. 2011;118(1):19-27) HbF and the retardation of HbS polymerization HbF is composed of 2 ␣-globin polypeptide chains and 2 ␥-globin chains. The ␥-globin chains are encoded by 2 nearly identical genes (HBG2 and HBG1) within the ␤-globin gene-like cluster on chromosome 11p that differ by a glycine or alanine residue at

Frontiers in Molecular Biosciences, Mar 19, 2021

Indian Journal of Medical Research, Jul 1, 2006

Blood, Dec 3, 2015

Objectives: To assess the clinical, haematological and molecular features of sickle cell disease ... more Objectives: To assess the clinical, haematological and molecular features of sickle cell disease in central India where the disease has been reported to be more severe than the mild clinical course usually observed in the Asian haplotype of homozygous sickle cell (SS) disease. Methods: A cross-sectional assessment of 91 consecutive patients with sickle cell disease attending clinics at the Akola Government Medical College, Akola, Maharastra State, India. Results: Of the 91 patients, who were predominantly of the scheduled caste community, 49 had SS disease, 6 had sickle cell-HbD Punjab, and 36 had sickle cell-beta thalassaemia. Of the patients with sickle cell-beta thalassaemia, the beta thalassemia mutation was IVS1-5 G>C mutation in 25 patients (69%) while the rest had one of seven other molecular mutations identified (Table1). Contrary to commonly held beliefs, alpha thalassaemia occurred in only 9/90 (10%) of subjects but fetal haemoglobin (HbF) levels were markedly elevated with mean and median levels of 24.4%. All except 3 SS disease patients had the Xmn1(+/+) polymorphism. These patients exhibited many of the severe manifestations of sickle cell disease. Comparison of SS disease and sickle cell-beta thalassaemia showed no differences in the prevalence of dactylitis, bone pain crisis, acute chest syndrome, haemoglobin level, reticulocyte counts or hydroxyurea usage but patients with sickle cell-beta thalassaemia had significantly more hospital admissions, blood transfusions, and greater frequencies of splenomegaly and hepatomegaly. Conclusions: Many of the patients with sickle cell disease in central India appear to have relatively severe manifestations. This appears to be due to much lower frequencies of alpha thalassaemia and more frequent sickle cell-beta thalassaemia. There is a need for assessment of the indications and policies for blood transfusion and for hydroxyurea. Table 1. Beta Thalassemia mutations associated with HbS/Beta Thalassemia in Akola Mutation Expression Number IVS 1-5 (G>C) severe b+ 22 IVS 1-1 (G>A) bo 3 Cd 15 (-T) bo 2 Cd 30…

Indian Journal of Medical Research, 2020

Background & objectives: Homozygous sickle cell (SS) disease in Central India runs a more sev... more Background & objectives: Homozygous sickle cell (SS) disease in Central India runs a more severe clinical course than reports from other areas of India. The current study was undertaken to compare the disease in Central India (Nagpur) with that in Jamaica, both populations defined by newborn screening. Methods: The Nagpur cohort included infants born to sickling-positive mothers from May 2008 to 2012, examined by high-pressure liquid chromatography and DNA analysis. The Jamaican cohort screened 100,000 consecutive non-operative deliveries between June 1973 and December 1981, analyzed by haemoglobin (Hb) electrophoresis and confirmed by family studies and compatible HbA2levels. Results: In Nagpur, 103 SS patients were detected, but only 78 (76%) were followed up. In Jamaica, 311 cases were followed from birth and compliance with follow up remained 100 per cent up to 45 years. In the Nagpur cohort all had the Asian haplotype, and 82 per cent of Jamaicans had at least one Benin chromosome; none had the Asian haplotype. Compared to Jamaica, Nagpur patients had higher foetal Hb, less alpha-thalassaemia, later development of splenomegaly and less dactylitis. There were also high admission rates for febrile illness and marked anaemia. Invasive pneumococcal disease occurred in 10 per cent of Jamaicans but was not seen in Nagpur. Interpretation & conclusions: There were many differences between the disease in Nagpur, Central India and the African form observed in Jamaica. The causes of severe anaemia in Nagpur require further study, and reticulocyte counts may be recommended as a routine parameter in the management of SS disease. The role of pneumococcal prophylaxis needs to be determined in Nagpur patients. Future studies in India must avoid high default rates.

Journal of Medical Screening, Sep 1, 2007

Mediterranean Journal of Hematology and Infectious Diseases, Jun 24, 2019

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is associated with in... more Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is associated with increased risk of complications and early mortality. Nowadays, with improved health care facilities, antibiotic prophylaxis, vaccination, and availability of drugs like hydroxyurea, the life expectancy of SCD patients has improved. More women are reaching reproductive age group and are expressing their desire to reproduce. Though SCD adversely affects pregnancy, leading to increased incidence of maternal and perinatal complications like pre-eclampsia, preterm labor, IUGR, abortions etc., adequate care throughout pregnancy ensures a better outcome. Also, recent advancements in the fields of prenatal diagnosis and preimplantation genetic diagnosis, help couples suffering from SCD to have a healthy baby. This paper focuses on the effects of SCD on pregnancy outcomes and effective management of complications during pregnancy, also comparing maternal and perinatal outcomes in studies conducted in different countries. The second part of the paper summarizes pregnancy management in SCD for better maternal and fetal outcomes.

Free Radical Research, Jul 27, 2016

In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radi... more In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radical scavenger and/or iron chelator in β-thalassemia patients with iron overload. Twenty-one β-thalassemia intermedia patients who presented between 3 and 17 years but later required regular blood transfusions were enrolled for hydroxyurea therapy for a year. Fourteen patients responded to the therapy with hemoglobin levels maintained above 7.5 g/dl without transfusions. Hydroxyurea was discontinued after 6 months in seven patients who did not respond to the therapy and had to be continued on regular blood transfusions. We observed a statistically significant decrease in serum ferritin levels from 4194 ± 4850 ng/ml to 2129 ± 2380 ng/ml among the responders and from 2955 ± 2909 ng/ml to 2040 ± 2432 ng/ml among the non-responders and statistically significant decrease in labile iron pool from 18678.7 ± 10067.4 mean fluorescence intensity (MFI) to 14888.5 ± 5284.0 MFI among responders and from 17986.3 ± 9079.8 MFI to 15634.8 ± 8976.9 MFI among the non-responders after therapy. Phosphatidylserine externalization also showed a statistically significant decrease from 44.2 ± 22.2 MFI to 16.6 ± 6.7 MFI among the responders and from 46.9 ± 33.1 MFI to 39.8 ± 7.4 MFI among the non-responders along with a statistically significant decrease in the levels of reactive oxygen species from 72.8 ± 35.5 MFI to 29.0 ± 8.3 MFI among the responders and from 80.9 ± 41.4 MFI to 40.5 ± 15.8 MFI among the non-responders after therapy. A statistically significant increase in reduced glutathione levels was also observed from 430.8 ± 201.1 MFI to 715.5 ± 292.4 MFI among the responders and from 359.6 ± 165.6 MFI to 450.3 ± 279.5 MFI among the non-responders after therapy. This suggests the possible additional role of hydroxyurea as a free radical scavenger and/or iron chelator but requires a larger study for substantiation.

Cytometry Part B-clinical Cytometry, Nov 1, 2014

Blood, May 15, 1997

A Novel b "-Thalassemia Mutation (Codon 10 GCC r GCA) and a Rare Transcriptional Mutation (Ï28A r... more A Novel b "-Thalassemia Mutation (Codon 10 GCC r GCA) and a Rare Transcriptional Mutation (Ï28A r G) in Indians To the Editor: been transfused. Globin biosynthesis in the next pregnancy showed that the 18-week-old fetus was normal. DGGE analysis showed the IVS I-5 G r C mutation in the mother Characterization of b-thalassemia mutations in different popula-(I-2), whereas the father (I-1) had another anomalous DGGE pattern tions has shown 180 mutant alleles. 1 So far, 25 mutations have been in fragment B. The DGGE pattern in the homozygous child (II-1) reported among Indians, 5 of which comprise more than 80% of the was different from that seen in the parents. mutant alleles. 2-4 Sequencing of this b-globin gene region using the forward primer We report two interesting Indian families showing a novel b /did not show any mutation. Sequencing with the reverse primer thalassemia mutation and a rare transcriptional mutation. They had showed a T r C change on the noncoding strand (Fig 2B). This come to us for second trimester prenatal diagnosis by globin biosynmutation was found in the daughter (II-1) as well, who also showed thesis. the presence of the IVS-I-5 G r C mutation. This A r G change The b-thalassemia mutations were characterized by denaturing in the upstream ATA box at position (028) is a transcriptional gradient gel electrophoresis (DGGE) analysis. 5 Both mutations were mutant reported among Chinese. 8 Nevertheless, it has not been redetected in fragment B of the b-globin gene spanning from the ported among Indians. upstream 064 nucleotide to IVS-I-nt61 containing the promoter These two new rare mutations could be added to the 25 different boxes and exon-1. DNA Sequencing was performed by the dideoxy b-thalassemic mutations that have been reported among Indians so method using Sequenase version 2.0 to identify the mutation. 6 far. Family I was from Madhya Pradesh in central India. Both parents ACKNOWLEDGEMENT (I-1) and (I-2) had classical b-thalassemia trait (Fig 1). Their 3year-old son (II-1) with severe homozygous b-thalassemia had been We thank S.R. Shirsat for preparation of the manuscript. diagnosed at 8 months of age and had been transfused every month. This child was not available for investigation. Fetal diagnosis at 18 weeks of gestation in the next pregnancy showed that the b/a biosynthetic ratio was 0.021, indicating that the fetus had homozygous b /-thalassemia (normal b/a ratio, ú0.03). DGGE analysis showed that the mother (I-2) had the IVS I-5 G

Thrombosis and Haemostasis, 2000

Blood Cells Molecules and Diseases, Oct 1, 2015

The disorders of iron overload due to primary or secondary cause are one of the important human d... more 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.

Indian Journal of Human Genetics, 2006

American Journal of Hematology, 2010

Journal of Fetal Medicine, Mar 1, 2015

Indian Journal of Medical Research, 2018

High prevalence of certain polymorphic alleles of erythrocytes in malaria endemic area has been l... more High prevalence of certain polymorphic alleles of erythrocytes in malaria endemic area has been linked to the resistance provided by these alleles against parasitic infestations. Numerous studies undertaken to demonstrate this correlation have generated conflicting results. This study was undertaken to investigate the abilities of various polymorphic erythrocytes to support in vitro growth of Plasmodium falciparum parasites. In this study under in vitro condition the ability of P. falciparum parasites to grow was assessed in the erythrocytes obtained from a total of 40 patients with various haemoglobinopathies, such as β-thalassaemia (β-Thal), sickle cell anaemia, erythroenzymopathy-like glucose-6-phosphate dehydrogenase deficiency and membranopathy-like hereditary spherocytosis. Significantly reduced in vitro invasion and growth of parasites was seen in the cultures containing abnormal erythrocytes than in control cultures containing normal erythrocytes (P< 0.05). The mean per cent parasitaemia comparison was also carried out among the three polymorphic erythrocyte groups, i.e. β-Thal, sickle cell anaemia and enzyme-membranopathies. Erythroenzymopathies and membranopathies were found to provide a more hostile environment for parasites, as the least parasitaemia was observed in these erythrocytes. The present in vitro study showed that P. falciparum did not grow well and did not invade well in erythrocytes obtained from common inherited red cell disorders.

PLOS ONE, Dec 9, 2013

Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea ... more 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.

Indian Journal of Pediatrics, Jun 1, 2004

Glucose–6–phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in huma... more Glucose–6–phosphate dehydrogenase (G6PD) deficiency is the commonest red cell enzymopathy in humans and has an X-linked inheritance. It has been reported from India more than 30 years ago and the prevalence varies from 0–27% in different caste, ethnic and linguistic groups. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic non–spherocytic hemolytic anemia. Individuals with G6PD

Blood Cells Molecules and Diseases, Apr 1, 2014

Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of... more Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle hemoglobin polymer. Fetal hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBBlike gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers. (Blood. 2011;118(1):19-27) HbF and the retardation of HbS polymerization HbF is composed of 2 ␣-globin polypeptide chains and 2 ␥-globin chains. The ␥-globin chains are encoded by 2 nearly identical genes (HBG2 and HBG1) within the ␤-globin gene-like cluster on chromosome 11p that differ by a glycine or alanine residue at

Frontiers in Molecular Biosciences, Mar 19, 2021

Indian Journal of Medical Research, Jul 1, 2006

Blood, Dec 3, 2015

Objectives: To assess the clinical, haematological and molecular features of sickle cell disease ... more Objectives: To assess the clinical, haematological and molecular features of sickle cell disease in central India where the disease has been reported to be more severe than the mild clinical course usually observed in the Asian haplotype of homozygous sickle cell (SS) disease. Methods: A cross-sectional assessment of 91 consecutive patients with sickle cell disease attending clinics at the Akola Government Medical College, Akola, Maharastra State, India. Results: Of the 91 patients, who were predominantly of the scheduled caste community, 49 had SS disease, 6 had sickle cell-HbD Punjab, and 36 had sickle cell-beta thalassaemia. Of the patients with sickle cell-beta thalassaemia, the beta thalassemia mutation was IVS1-5 G>C mutation in 25 patients (69%) while the rest had one of seven other molecular mutations identified (Table1). Contrary to commonly held beliefs, alpha thalassaemia occurred in only 9/90 (10%) of subjects but fetal haemoglobin (HbF) levels were markedly elevated with mean and median levels of 24.4%. All except 3 SS disease patients had the Xmn1(+/+) polymorphism. These patients exhibited many of the severe manifestations of sickle cell disease. Comparison of SS disease and sickle cell-beta thalassaemia showed no differences in the prevalence of dactylitis, bone pain crisis, acute chest syndrome, haemoglobin level, reticulocyte counts or hydroxyurea usage but patients with sickle cell-beta thalassaemia had significantly more hospital admissions, blood transfusions, and greater frequencies of splenomegaly and hepatomegaly. Conclusions: Many of the patients with sickle cell disease in central India appear to have relatively severe manifestations. This appears to be due to much lower frequencies of alpha thalassaemia and more frequent sickle cell-beta thalassaemia. There is a need for assessment of the indications and policies for blood transfusion and for hydroxyurea. Table 1. Beta Thalassemia mutations associated with HbS/Beta Thalassemia in Akola Mutation Expression Number IVS 1-5 (G>C) severe b+ 22 IVS 1-1 (G>A) bo 3 Cd 15 (-T) bo 2 Cd 30…

Indian Journal of Medical Research, 2020

Background & objectives: Homozygous sickle cell (SS) disease in Central India runs a more sev... more Background & objectives: Homozygous sickle cell (SS) disease in Central India runs a more severe clinical course than reports from other areas of India. The current study was undertaken to compare the disease in Central India (Nagpur) with that in Jamaica, both populations defined by newborn screening. Methods: The Nagpur cohort included infants born to sickling-positive mothers from May 2008 to 2012, examined by high-pressure liquid chromatography and DNA analysis. The Jamaican cohort screened 100,000 consecutive non-operative deliveries between June 1973 and December 1981, analyzed by haemoglobin (Hb) electrophoresis and confirmed by family studies and compatible HbA2levels. Results: In Nagpur, 103 SS patients were detected, but only 78 (76%) were followed up. In Jamaica, 311 cases were followed from birth and compliance with follow up remained 100 per cent up to 45 years. In the Nagpur cohort all had the Asian haplotype, and 82 per cent of Jamaicans had at least one Benin chromosome; none had the Asian haplotype. Compared to Jamaica, Nagpur patients had higher foetal Hb, less alpha-thalassaemia, later development of splenomegaly and less dactylitis. There were also high admission rates for febrile illness and marked anaemia. Invasive pneumococcal disease occurred in 10 per cent of Jamaicans but was not seen in Nagpur. Interpretation & conclusions: There were many differences between the disease in Nagpur, Central India and the African form observed in Jamaica. The causes of severe anaemia in Nagpur require further study, and reticulocyte counts may be recommended as a routine parameter in the management of SS disease. The role of pneumococcal prophylaxis needs to be determined in Nagpur patients. Future studies in India must avoid high default rates.

Journal of Medical Screening, Sep 1, 2007

Mediterranean Journal of Hematology and Infectious Diseases, Jun 24, 2019

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is associated with in... more Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is associated with increased risk of complications and early mortality. Nowadays, with improved health care facilities, antibiotic prophylaxis, vaccination, and availability of drugs like hydroxyurea, the life expectancy of SCD patients has improved. More women are reaching reproductive age group and are expressing their desire to reproduce. Though SCD adversely affects pregnancy, leading to increased incidence of maternal and perinatal complications like pre-eclampsia, preterm labor, IUGR, abortions etc., adequate care throughout pregnancy ensures a better outcome. Also, recent advancements in the fields of prenatal diagnosis and preimplantation genetic diagnosis, help couples suffering from SCD to have a healthy baby. This paper focuses on the effects of SCD on pregnancy outcomes and effective management of complications during pregnancy, also comparing maternal and perinatal outcomes in studies conducted in different countries. The second part of the paper summarizes pregnancy management in SCD for better maternal and fetal outcomes.

Free Radical Research, Jul 27, 2016

In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radi... more In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radical scavenger and/or iron chelator in β-thalassemia patients with iron overload. Twenty-one β-thalassemia intermedia patients who presented between 3 and 17 years but later required regular blood transfusions were enrolled for hydroxyurea therapy for a year. Fourteen patients responded to the therapy with hemoglobin levels maintained above 7.5 g/dl without transfusions. Hydroxyurea was discontinued after 6 months in seven patients who did not respond to the therapy and had to be continued on regular blood transfusions. We observed a statistically significant decrease in serum ferritin levels from 4194 ± 4850 ng/ml to 2129 ± 2380 ng/ml among the responders and from 2955 ± 2909 ng/ml to 2040 ± 2432 ng/ml among the non-responders and statistically significant decrease in labile iron pool from 18678.7 ± 10067.4 mean fluorescence intensity (MFI) to 14888.5 ± 5284.0 MFI among responders and from 17986.3 ± 9079.8 MFI to 15634.8 ± 8976.9 MFI among the non-responders after therapy. Phosphatidylserine externalization also showed a statistically significant decrease from 44.2 ± 22.2 MFI to 16.6 ± 6.7 MFI among the responders and from 46.9 ± 33.1 MFI to 39.8 ± 7.4 MFI among the non-responders along with a statistically significant decrease in the levels of reactive oxygen species from 72.8 ± 35.5 MFI to 29.0 ± 8.3 MFI among the responders and from 80.9 ± 41.4 MFI to 40.5 ± 15.8 MFI among the non-responders after therapy. A statistically significant increase in reduced glutathione levels was also observed from 430.8 ± 201.1 MFI to 715.5 ± 292.4 MFI among the responders and from 359.6 ± 165.6 MFI to 450.3 ± 279.5 MFI among the non-responders after therapy. This suggests the possible additional role of hydroxyurea as a free radical scavenger and/or iron chelator but requires a larger study for substantiation.

Cytometry Part B-clinical Cytometry, Nov 1, 2014

Blood, May 15, 1997

A Novel b "-Thalassemia Mutation (Codon 10 GCC r GCA) and a Rare Transcriptional Mutation (Ï28A r... more A Novel b "-Thalassemia Mutation (Codon 10 GCC r GCA) and a Rare Transcriptional Mutation (Ï28A r G) in Indians To the Editor: been transfused. Globin biosynthesis in the next pregnancy showed that the 18-week-old fetus was normal. DGGE analysis showed the IVS I-5 G r C mutation in the mother Characterization of b-thalassemia mutations in different popula-(I-2), whereas the father (I-1) had another anomalous DGGE pattern tions has shown 180 mutant alleles. 1 So far, 25 mutations have been in fragment B. The DGGE pattern in the homozygous child (II-1) reported among Indians, 5 of which comprise more than 80% of the was different from that seen in the parents. mutant alleles. 2-4 Sequencing of this b-globin gene region using the forward primer We report two interesting Indian families showing a novel b /did not show any mutation. Sequencing with the reverse primer thalassemia mutation and a rare transcriptional mutation. They had showed a T r C change on the noncoding strand (Fig 2B). This come to us for second trimester prenatal diagnosis by globin biosynmutation was found in the daughter (II-1) as well, who also showed thesis. the presence of the IVS-I-5 G r C mutation. This A r G change The b-thalassemia mutations were characterized by denaturing in the upstream ATA box at position (028) is a transcriptional gradient gel electrophoresis (DGGE) analysis. 5 Both mutations were mutant reported among Chinese. 8 Nevertheless, it has not been redetected in fragment B of the b-globin gene spanning from the ported among Indians. upstream 064 nucleotide to IVS-I-nt61 containing the promoter These two new rare mutations could be added to the 25 different boxes and exon-1. DNA Sequencing was performed by the dideoxy b-thalassemic mutations that have been reported among Indians so method using Sequenase version 2.0 to identify the mutation. 6 far. Family I was from Madhya Pradesh in central India. Both parents ACKNOWLEDGEMENT (I-1) and (I-2) had classical b-thalassemia trait (Fig 1). Their 3year-old son (II-1) with severe homozygous b-thalassemia had been We thank S.R. Shirsat for preparation of the manuscript. diagnosed at 8 months of age and had been transfused every month. This child was not available for investigation. Fetal diagnosis at 18 weeks of gestation in the next pregnancy showed that the b/a biosynthetic ratio was 0.021, indicating that the fetus had homozygous b /-thalassemia (normal b/a ratio, ú0.03). DGGE analysis showed that the mother (I-2) had the IVS I-5 G

Thrombosis and Haemostasis, 2000

Blood Cells Molecules and Diseases, Oct 1, 2015

The disorders of iron overload due to primary or secondary cause are one of the important human d... more 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.

Indian Journal of Human Genetics, 2006

American Journal of Hematology, 2010

Journal of Fetal Medicine, Mar 1, 2015

Indian Journal of Medical Research, 2018

High prevalence of certain polymorphic alleles of erythrocytes in malaria endemic area has been l... more High prevalence of certain polymorphic alleles of erythrocytes in malaria endemic area has been linked to the resistance provided by these alleles against parasitic infestations. Numerous studies undertaken to demonstrate this correlation have generated conflicting results. This study was undertaken to investigate the abilities of various polymorphic erythrocytes to support in vitro growth of Plasmodium falciparum parasites. In this study under in vitro condition the ability of P. falciparum parasites to grow was assessed in the erythrocytes obtained from a total of 40 patients with various haemoglobinopathies, such as β-thalassaemia (β-Thal), sickle cell anaemia, erythroenzymopathy-like glucose-6-phosphate dehydrogenase deficiency and membranopathy-like hereditary spherocytosis. Significantly reduced in vitro invasion and growth of parasites was seen in the cultures containing abnormal erythrocytes than in control cultures containing normal erythrocytes (P< 0.05). The mean per cent parasitaemia comparison was also carried out among the three polymorphic erythrocyte groups, i.e. β-Thal, sickle cell anaemia and enzyme-membranopathies. Erythroenzymopathies and membranopathies were found to provide a more hostile environment for parasites, as the least parasitaemia was observed in these erythrocytes. The present in vitro study showed that P. falciparum did not grow well and did not invade well in erythrocytes obtained from common inherited red cell disorders.

PLOS ONE, Dec 9, 2013

Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea ... more 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.