Publications by authors named "Sumana Chatterjee"

18 Publications

  • Page 1 of 1

Growth Hormone Receptor (GHR) 6Ω Pseudoexon Activation: a Novel Cause of Severe Growth Hormone Insensitivity.

J Clin Endocrinol Metab 2021 Jul 28. Epub 2021 Jul 28.

Centre for Endocrinology, William Harvey Research Institute: Barts and The London School of Medicine and Dentistry William Harvey Research Institute, London EC1M 6BQ, UK.

Context: Severe forms of growth hormone insensitivity (GHI) are characterized by extreme short stature, dysmorphism, and metabolic anomalies.

Objective: This work aims to identify the genetic cause of growth failure in 3 "classical" GHI individuals.

Methods: A novel intronic growth hormone receptor gene (GHR) variant was identified, and in vitro splicing assays confirmed aberrant splicing. A 6Ω pseudoexon GHR vector and patient fibroblast analysis assessed the consequences of the novel pseudoexon inclusion and the impact on GHR function.

Results: We identified a novel homozygous intronic GHR variant (g.5:42700940T > G, c.618+836T > G), 44 bp downstream of the previously recognized intronic 6Ψ GHR pseudoexon mutation in the index patient. Two siblings also harbored the novel intronic 6Ω pseudoexon GHR variant in compound heterozygosity with the known GHR c.181C > T (R43X) mutation. In vitro splicing analysis confirmed inclusion of a 151-bp mutant 6Ω pseudoexon not identified in wild-type constructs. Inclusion of the 6Ω pseudoexon causes a frameshift resulting in a nonfunctional truncated GHR lacking the transmembrane and intracellular domains. The truncated 6Ω pseudoexon protein demonstrated extracellular accumulation and diminished activation of STAT5B signaling following GH stimulation.

Conclusion: Novel GHR 6Ω pseudoexon inclusion results in loss of GHR function consistent with a severe GHI phenotype. This represents a novel mechanism of Laron syndrome and is the first deep intronic variant identified causing severe postnatal growth failure. The 2 kindreds originate from the same town in Campania, Southern Italy, implying common ancestry. Our findings highlight the importance of studying variation in deep intronic regions as a cause of monogenic disorders.
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http://dx.doi.org/10.1210/clinem/dgab550DOI Listing
July 2021

Growth Hormone Receptor (Ghr) 6ω Pseudoexon Activation: A Novel Cause Of Severe Growth Hormone Insensitivity (Ghi).

J Clin Endocrinol Metab 2021 Jul 28. Epub 2021 Jul 28.

Centre for Endocrinology, William Harvey Research Institute: Barts and The London School of Medicine and Dentistry William Harvey Research Institute.

Context: Severe forms of Growth Hormone Insensitivity (GHI) are characterized by extreme short stature, dysmorphism and metabolic anomalies.

Objective: Identification of the genetic cause of growth failure in 3 'classical' GHI subjects.

Design: A novel intronic GHR variant was identified, and in vitro splicing assays confirmed aberrant splicing. A 6Ω pseudoexon GHR vector and patient fibroblast analysis assessed the consequences of the novel pseudoexon inclusion and the impact on GHR function.

Results: We identified a novel homozygous intronic GHR variant (g.5:42700940T>G, c.618 + 836T> G), 44bp downstream of the previously recognized intronic 6Ψ GHR pseudoexon mutation in the index patient. Two siblings also harbored the novel intronic 6Ω pseudoexon GHR variant in compound heterozygosity with the known GHR c.181C>T (R43X) mutation. In vitro splicing analysis confirmed inclusion of a 151bp mutant 6Ω pseudoexon not identified in wild-type constructs. Inclusion of the 6Ω pseudoexon causes a frameshift resulting in a non-functional truncated GHR lacking the transmembrane and intracellular domains. The truncated 6Ω pseudoexon protein demonstrated extracellular accumulation and diminished activation of STAT5B signaling following growth hormone stimulation.

Conclusion: Novel GHR 6Ω pseudoexon inclusion results in loss of GHR function consistent with a severe GHI phenotype. This represents a novel mechanism of Laron syndrome and is the first deep intronic variant identified causing severe postnatal growth failure. The 2 kindreds originate from the same town in Campania, Southern Italy, implying common ancestry. Our findings highlight the importance of studying variation in deep intronic regions as a cause of monogenic disorders.
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http://dx.doi.org/10.1210/clinem/dgab550DOI Listing
July 2021

Genetic characterization of short stature patients with overlapping features of growth hormone insensitivity syndromes.

J Clin Endocrinol Metab 2021 Jun 16. Epub 2021 Jun 16.

Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Context And Objective: Growth hormone insensitivity (GHI) in children is characterized by short stature, functional IGF-I deficiency and normal or elevated serum GH concentrations. The clinical and genetic etiology of GHI is expanding. We undertook genetic characterization of short stature patients referred with suspected GHI and features which overlapped with known GH-IGF-I axis defects.

Design And Methods: Between 2008 and 2020, our center received 149 GHI referrals for genetic testing. Genetic analysis utilized a combination of candidate gene sequencing (CGS), whole exome sequencing (WES), array comparative genomic hybridization (aCGH) and a targeted whole genome short stature gene panel.

Results: Genetic diagnoses were identified in 80/149 subjects (54%) with 45/80 (56%) having known GH-IGF-I axis defects (GHR n=40, IGFALS n=4, IGFIR n=1). The remaining 35/80 (44%) had diagnoses of 3M syndrome (n=10) (OBSL1 n=7, CUL7 n=2 and CCDC8 n=1), Noonan syndrome (n=4) (PTPN11 n=2, SOS1 n=1 and SOS2 n=1), Silver-Russell syndrome (n=2) (Loss of methylation on chromosome 11p15 and uniparental disomy for chromosome 7), Class 3-5 copy number variations (n=10) and disorders not previously associated with GHI (n=9) (Barth syndrome, Autoimmune lymphoproliferative syndrome, Microcephalic osteodysplastic primordial dwarfism Type II, Achondroplasia, Glycogen storage disease Type IXb, Lysinuric protein intolerance, Multiminicore Disease, MACS syndrome and Bloom syndrome).

Conclusion: We report the wide range of diagnoses in 149 patients referred with suspected GHI, which emphasizes the need to recognize GHI as a spectrum of clinical entities in undiagnosed short stature patients. Detailed clinical and genetic assessment may identify a diagnosis and inform clinical management.
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http://dx.doi.org/10.1210/clinem/dgab437DOI Listing
June 2021

Rare CNVs provide novel insights into the molecular basis of GH and IGF-1 insensitivity.

Eur J Endocrinol 2020 Dec;183(6):581-595

Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.

Objective: Copy number variation (CNV) has been associated with idiopathic short stature, small for gestational age and Silver-Russell syndrome (SRS). It has not been extensively investigated in growth hormone insensitivity (GHI; short stature, IGF-1 deficiency and normal/high GH) or previously in IGF-1 insensitivity (short stature, high/normal GH and IGF-1).

Design And Methods: Array comparative genomic hybridisation was performed with ~60 000 probe oligonucleotide array in GHI (n = 53) and IGF-1 insensitivity (n = 10) subjects. Published literature, mouse models, DECIPHER CNV tracks, growth associated GWAS loci and pathway enrichment analyses were used to identify key biological pathways/novel candidate growth genes within the CNV regions.

Results: Both cohorts were enriched for class 3-5 CNVs (7/53 (13%) GHI and 3/10 (30%) IGF-1 insensitivity patients). Interestingly, 6/10 (60%) CNV subjects had diagnostic/associated clinical features of SRS. 5/10 subjects (50%) had CNVs previously reported in suspected SRS: 1q21 (n = 2), 12q14 (n = 1) deletions and Xp22 (n = 1), Xq26 (n = 1) duplications. A novel 15q11 deletion, previously associated with growth failure but not SRS/GHI was identified. Bioinformatic analysis identified 45 novel candidate growth genes, 15 being associated with growth in GWAS. The WNT canonical pathway was enriched in the GHI cohort and CLOCK was identified as an upstream regulator in the IGF-1 insensitivity cohorts.

Conclusions: Our cohort was enriched for low frequency CNVs. Our study emphasises the importance of CNV testing in GHI and IGF-1 insensitivity patients, particularly GHI subjects with SRS features. Functional experimental evidence is now required to validate the novel candidate growth genes, interactions and biological pathways identified.
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http://dx.doi.org/10.1530/EJE-20-0474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592635PMC
December 2020

Severe acute onset dry eye following presumed Epstein.Barr viral infection.

Indian J Ophthalmol 2020 04;68(4):642-644

Cornea and Anterior Segment, Sunayan Advanced Eye Institute, Tamluk, West Bengal, India.

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http://dx.doi.org/10.4103/ijo.IJO_1212_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210863PMC
April 2020

GHR gene transcript heterogeneity may explain phenotypic variability in GHR pseudoexon (6Ψ) patients.

Endocr Connect 2020 Feb 1. Epub 2020 Feb 1.

H Storr, Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, EC1M 6BQ, United Kingdom of Great Britain and Northern Ireland.

Objectives: The homozygous GH receptor (GHR) pseudoexon (6Ψ) mutation leads to growth hormone insensitivity (GHI) with clinical and biochemical heterogeneity. We investigated whether transcript heterogeneity (6Ψ-GHR to WT-GHR transcript ratio) and/or concurrent defects in other short stature (SS) genes contribute to this.

Methods: 6Ψ-GHR and WT-GHR mRNA transcripts of 4 6Ψ patient (height SDS -4.2 to -3.1) and 1 control fibroblasts were investigated by RT-PCR. Transcripts were quantified by qRT-PCR and delta delta CT analysis and compared using ANOVA with Bonferroni correction. In eleven 6Ψ patients, 40 genes known to cause GHI/SS were analysed by targeted next generation sequencing.

Results: RT-PCR confirmed 6Ψ-GHR transcript in the 6Ψ patients but not control. 6Ψ-GHR transcript levels were comparable in patients 1 and 3 but significantly different among all other patients. The mean 6Ψ:WT transcript ratios ranged from 29-71:1 for patients 1-4 and correlated negatively with height SDS (R=-0.85; p<0.001). Eight deleterious variants in 6 genes were detected but the number of gene hits did not correlate with the degree of SS in individual 6Ψ patients.

Conclusion: Variable amounts of 6Ψ- and WT-GHR transcripts were identified in 6Ψ patients but no 6Ψ transcript was present in the control. Higher 6Ψ:WT GHR transcript ratio correlated with SS severity and may explain the phenotypic variability. Analysis of known SS genes suggested that phenotypic variation is independent of the genetic background. This is the first report of transcript heterogeneity producing a spectrum of clinical phenotypes in different individuals harbouring an identical homozygous genetic mutation.
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http://dx.doi.org/10.1530/EC-20-0026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077524PMC
February 2020

Arcuate keratotomy infiltration following uneventful femtosecond laser assisted cataract surgery.

Indian J Ophthalmol 2019 10;67(10):1742-1744

Ophthalmology Resident, Dr. D Y Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India.

An 84-year-old gentleman underwent uneventful femtolaser-assisted cataract surgery (FLACS) with an arcuate keratotomy (AK) in the left eye. On the 18 post-operative day, a corneal infiltrate developed involving the AK. Staphylococcus epidermidis was the organism isolated on culture. The infiltrate resolved with topical fortified vancomycin and amikacin eyedrops, and the patient regained a visual acuity of 6/6 after 12 weeks. This is the first case from south-east Asia reported in the literature of an infective infiltrate along a femtosecond laser AK. We propose strict peri-operative recommendations to be followed to prevent and treat such infections.
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http://dx.doi.org/10.4103/ijo.IJO_72_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786192PMC
October 2019

Nonclassical GH Insensitivity: Characterization of Mild Abnormalities of GH Action.

Endocr Rev 2019 04;40(2):476-505

Division of Endocrinology, Cincinnati Center for Growth Disorders, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.

GH insensitivity (GHI) presents in childhood with growth failure and in its severe form is associated with extreme short stature and dysmorphic and metabolic abnormalities. In recent years, the clinical, biochemical, and genetic characteristics of GHI and other overlapping short stature syndromes have rapidly expanded. This can be attributed to advancing genetic techniques and a greater awareness of this group of disorders. We review this important spectrum of defects, which present with phenotypes at the milder end of the GHI continuum. We discuss their clinical, biochemical, and genetic characteristics. The objective of this review is to clarify the definition, identification, and investigation of this clinically relevant group of growth defects. We also review the therapeutic challenges of mild GHI.
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http://dx.doi.org/10.1210/er.2018-00146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607971PMC
April 2019

Phenotypic spectrum and responses to recombinant human IGF1 (rhIGF1) therapy in patients with homozygous intronic pseudoexon growth hormone receptor mutation.

Eur J Endocrinol 2018 May 2;178(5):481-489. Epub 2018 Mar 2.

Centre for EndocrinologyWilliam Harvey Research Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK

Background: Patients with homozygous intronic pseudoexon GH receptor () mutations (6Ψ) have growth hormone insensitivity (GHI) (growth failure, IGF1 deficiency and normal/elevated serum GH). We report 9 patients in addition to previously described 11 6Ψ patients and their responses to rhIGF1 therapy.

Methods: 20 patients (12 males, 11 families, mean age 4.0 ± 2.2 years) were diagnosed genetically in our centre. Phenotypic data and responses to rhIGF1 treatment were provided by referring clinicians. Continuous parametric variables were compared using Student -test or ANOVA.

Results: 10/20 (50%) had typical facial features of GHI, 19/20 (95%) from consanguineous families and 18/20 (90%) of Pakistani origin. At diagnosis, mean height SDS: -4.1 ± 0.95, IGF1 SDS: -2.8 ± 1.4; IGFBP3 SDS: -3.0 ± 2.1 and mean basal and peak GH levels: 11.9 µg/L and 32.9 µg/L, respectively. 1/12 who had IGF1 generation test, responded (IGF1: 132-255 ng/mL). 15/20 (75%; 11M) received rhIGF1 (mean dose: 114 µg/kg twice daily, mean duration: 5.3 ± 2.5 years). Mean baseline height velocity of 4.7 ± 1.1 cm/year increased to 7.4 ± 1.8 cm/year ( = 0.001) during year 1 of therapy. Year 3 mean height SDS (-3.2 ± 1.0) was higher than pre-treatment height SDS (-4.3 ± 0.8) ( = 0.03). Mean cumulative increase in height SDS after year 5 was 1.4 ± 0.9. Difference between target height (TH) SDS and adult or latest height SDS was less than that of TH SDS and pre-treatment height SDS (2.1 ± 1.2 vs 3.0 ± 0.8;  = 0.02).

Conclusion: In addition to phenotypic heterogeneity in the cohort, there was mismatch between clinical and biochemical features in individual patients with 6Ψ mutations. rhIGF1 treatment improved height outcomes.
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http://dx.doi.org/10.1530/EJE-18-0042DOI Listing
May 2018

Kisspeptin Is a Novel Regulator of Human Fetal Adrenocortical Development and Function: A Finding With Important Implications for the Human Fetoplacental Unit.

J Clin Endocrinol Metab 2017 09;102(9):3349-3359

Centre for Endocrinology, William Harvey Research Institute, London, EC1M 6BQ, United Kingdom.

Context: The human fetal adrenal (HFA) is an integral component of the fetoplacental unit and important for the maintenance of pregnancy. Low kisspeptin levels during pregnancy are associated with miscarriage, and kisspeptin and its receptor are expressed in the HFA. However, the role of kisspeptin in fetal adrenal function remains unknown.

Objective: To determine the role of kisspeptin in the developing HFA.

Design: Experiments using H295R and primary HFA cells as in vitro models of the fetal adrenal. Association of plasma kisspeptin levels with HFA size in a longitudinal clinical study.

Setting: Academic research center and tertiary fetal medicine unit.

Participants: Thirty-three healthy pregnant women were recruited at their 12-week routine antenatal ultrasound scan.

Main Outcome Measures: The spatiotemporal expression of Kiss1R in the HFA. The production of dehydroepiandrosterone sulfate (DHEAS) from HFA cells after kisspeptin treatment, alone or in combination with adrenocorticotropic hormone or corticotropin-releasing hormone. Fetal adrenal volume (FAV) and kisspeptin levels at four antenatal visits (∼20, 28, 34, and 38 weeks' gestation).

Results: Expression of Kiss1R was present in the HFA from 8 weeks after conception to term and was shown in the inner fetal zone. Kisspeptin significantly increased DHEAS production in H295R and second-trimester HFA cells. Serial measurements of kisspeptin confirmed a correlation with FAV growth in the second trimester, independent of sex or estimated fetal weight.

Conclusions: Kisspeptin plays a key role in the regulation of the HFA and thus the fetoplacental unit, particularly in the second trimester of pregnancy.
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http://dx.doi.org/10.1210/jc.2017-00763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587078PMC
September 2017

Whole-exome sequencing gives additional benefits compared to candidate gene sequencing in the molecular diagnosis of children with growth hormone or IGF-1 insensitivity.

Eur J Endocrinol 2017 Dec 4;177(6):485-501. Epub 2017 Sep 4.

Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Background: GH insensitivity (GHI) is characterised by short stature, IGF-1 deficiency and normal/elevated serum GH. IGF-1 insensitivity results in pre- and post-natal growth failure with normal/high IGF-1 levels. The prevalence of genetic defects is unknown.

Objective: To identify the underlying genetic diagnoses in a paediatric cohort with GH or IGF-1 insensitivity using candidate gene (CGS) and whole-exome sequencing (WES) and assess factors associated with the discovery of a genetic defect.

Methods: We undertook a prospective study of 132 patients with short stature and suspected GH or IGF-1 insensitivity referred to our centre for genetic analysis. 107 (96 GHI, 88 probands; 11 IGF-1 insensitivity, 9 probands) underwent CGS. WES was performed in those with no defined genetic aetiology following CGS.

Results: A genetic diagnosis was discovered 38/107 (36%) patients (32% probands) by CGS. WES revealed 11 patients with genetic variants in genes known to cause short stature. A further 2 patients had hypomethylation in the H19/IGF2 region or mUPD7 consistent with Silver-Russell Syndrome (total with genetic diagnosis 51/107, 48% or 41/97, 42% probands). WES also identified homozygous putative variants in and in 2 patients. Low height SDS and consanguinity were highly predictive for identifying a genetic defect.

Conclusions: Comprehensive genetic testing confirms the genetic heterogeneity of GH/IGF-1 insensitivity and successfully identified the genetic aetiology in a significant proportion of cases. WES is rapid and may isolate genetic variants that have been missed by traditional clinically driven genetic testing. This emphasises the benefits of specialist diagnostic centres.
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http://dx.doi.org/10.1530/EJE-17-0453DOI Listing
December 2017

Polymorphisms of CYP1A1, GSTM1 and GSTT1 Loci as the Genetic Predispositions of Oral Cancers and Other Oral Pathologies: Tobacco and Alcohol as Risk Modifiers.

Indian J Clin Biochem 2010 Jul 25;25(3):260-72. Epub 2010 Aug 25.

Polycyclic aromatic hydrocarbons of tobacco require activation by phase I enzymes, such as cytochrome-P4501A1 (CYP1A1) to become an ultimate carcinogen, which are subjected to detoxification by phase II enzymes, especially glutathione S-transferases (GSTs). A study was designed to find whether genetic predisposition are risk modifiers of oral pathologies. The study included 102 cases with Oral Cancers (OCs), 68 cases with nonmalignant pathologies, 100 cases as control group. GSTM1 null genotype was associated with increased risk of OCs but not with benign pathologies. Deleted GSTT1 was associated with all pathologies. Both m1m2 and m2m2 polymorphisms of CYP1A1 were associated with oral pathologies.
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http://dx.doi.org/10.1007/s12291-010-0057-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001838PMC
July 2010

Polymorphisms of methylenetetrahydrofolate reductase gene as the genetic predispositions of coronary artery diseases in eastern India.

J Cardiovasc Dis Res 2010 Jul;1(3):152-7

Thalassemia Research Unit, Vivekananda Institute of Medical Sciences 99, Sarat Bose Road, Kolkata - 700 026, West Bengal, India.

Background: Gene-environment interaction is an important aspect in the development of coronary artery disease (CAD). The mutation (677C-T) of methylenetetrahydrofolate reductase (MTHFR) gene results in a decrease of the enzyme activity that leads to mild hyperhomocysteinemia. Elevated plasma level of homocysteine has been recognized as an independent risk factor for cardiovascular disease. A case-control study was designed to assess whether the prevalence of some MTHFR gene polymorphisms have any role in the development of CAD.

Materials And Methods: The study included unrelated 217 cases with CAD and 255 healthy controls. DNA was extracted from peripheral blood. MTHFR genotypes were identified by seeing the presence or absence of 677C→T mutation obtained by PCR followed by Hinf1 restriction digestion. Multiple logistic regression analysis was carried out to find association between studied genotypes and lifestyle as well as biochemical risk factors.

Results: The T allele was found to be associated with the disease. Significant associations were found with smoking, hypertension, diabetes, and family history of CAD.

Conclusion: The results indicate that MTHFR 677C-T polymorphism has significant association with CADs in the population of eastern India.
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http://dx.doi.org/10.4103/0975-3583.70922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982204PMC
July 2010

Cytogenetic monitoring in human oral cancers and other oral pathology: the micronucleus test in exfoliated buccal cells.

Toxicol Mech Methods 2009 Sep;19(6-7):427-33

Thalassaemia Research Unit, Ramakrishna Mission Seva Pratishthan, Vivekananda Institute of Medical Sciences, Kolkata, West Bengal, India.

Oral cancer is a lifestyle-related cancer, with tobacco as a primary factor. Progression of oral cancer develops over several years from the stage of leukoplakia, erythroplakia, etc. A micronucleus test was applied to oral mucosal cells, considering them as the target site for carcinogens and cytogenetic damage. The test has been established as a reliable biomarker for differential prevalence of MN indices among oral cancers, pre-cancers, non-malignant oral pathologies, and healthy controls for the first time. Buccal scrapings were collected from 63 patients with cancer and pre-cancerous lesions, 42 with non-malignant oral problems, and 100 healthy controls. The analysis revealed that MN frequencies in cancer and pre-cancerous cases were 4-fold elevated (p < 0.001) and 3.87-fold (p < 0.002) elevated for other non-malignant pathologies. Significant associations between use of tobacco in various forms and development of oral pathologies are also established. The relative cancer risk for smoking healthy controls with a definite MN frequency was also found to be significant. The results indicate the validity of the MN test as a cytogenetic marker for the development of several oral pathologies.
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http://dx.doi.org/10.1080/15376510903127530DOI Listing
September 2009

Prevalence of CYP1A1 and GST polymorphisms in the population of northeastern India and susceptibility of oral cancer.

Oncol Res 2009 ;17(9):397-403

Thalassaemia Research Unit, Vivekananda Institute of Medical Sciences, Ramakrishna Mission Seva Pratishthan, West Bengal, India.

Individual cancer susceptibility is the result of several host factors, including differences in lifestyle habits and genetic susceptibility. There is a correlation between CYP1A1 polymorphism (MspI) and oral cancer susceptibility. Individuals carrying the deletions of GSTM1 and GSTT1 are at high risk of developing oral cancers. In the present study on healthy tribal and nontribal individuals of Assam, we found that the genetic variation of GSST polymorphisms is evident (p = 0.20) with differential dose of toxic exposure. Prevalence of different polymorphic alleles of CYP1A1 also proves the same result. A mini-case-control study with very small sample size showed no marked increase in the risk of developing oral cancer as the frequencies of the studied GST genotypes did not show any statistical significance. But GSTT1-null genotypes were found to have higher risk of developing leukoplakia (OR 1.94, 95% CI 2.61-18.54). CYP1A1 genotype m2 allele was also not found to be associated with the risk of developing leukoplakias in the population.
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http://dx.doi.org/10.3727/096504009788912499DOI Listing
October 2009

Isolation and identification of poly beta hydroxybutyric acid accumulating bacteria of Staphylococcal sp. and characterization of biodegradable polyester.

Indian J Exp Biol 2009 Apr;47(4):250-6

Dr B C Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019.

Staphylococcus sp. strain BP/SU1, capable of degrading the biopolymer and utilize it as a source of carbon and energy, was isolated from activated sludge using METABOLIX (MBX D411G). It was found that this strain was capable of accumulating poly(3-hydroxybutyric acid) P(3-HB), as granule poly (3-hydroxybutyric acid), p(3-HB), inclusion bodies when grown under suitable nutrient conditions. These strains could sustain cell growth up to a dry mass of 9.24 g/l with a doubling time of 8 to 10 hr and could accumulate P(3-HB) as granular inclusion bodies to a cell dry weight of more than 12%. P(3-HB) accumulated by this organism was isolated and characterized through NMR, FT-IR spectroscopy, UV Spectroscopy, Mass spectroscopy and Differential Scanning Calorimetry. P(3-HB) granules so isolated showed physical and chemical properties that should be possessed by a superior quality thermoplastic biopolymer.
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April 2009

Ligand specificity and ligand-induced conformational change in gal repressor.

Proteins 2002 Dec;49(4):554-9

Department of Biophysics, Bose Institute, P-1/12 C.I.T. Scheme VII M, Calcutta, India.

Gal repressor (GalR) binds D-galactose, which is responsible for lifting of repression of the gal operon. Proton T1 measurements of alpha- and beta-anomers of galactose as a function of gal repressor show preferential binding of the beta-anomer. The beta-anomer was isolated by high-performance liquid chromatography and was shown to bind tightly to GalR. Calorimetry was used to determine enthalpy changes at several temperatures. Heat capacity change was found to be positive, indicating that a significant amount of hydrophobic surface area was exposed upon galactose binding. Bis-ANS binding to GalR is significantly enhanced in the presence of a saturating amount of galactose, indicating additional exposure of hydrophobic surfaces. We propose that the galactose-induced conformational change involves the opening of the two subdomains, which may disrupt protein-protein interactions responsible for repression.
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http://dx.doi.org/10.1002/prot.10236DOI Listing
December 2002
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