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B Mittal

Publications and source records attributed to B Mittal.

At least 19 recordsLinked to original sources
PubMed2006

Association of APOE-C1 gene cluster polymorphisms with gallstone disease.

BACKGROUND: Genetic polymorphisms in apolipoprotein genes may be associated with alteration in lipid profile and susceptibility to gallstone disease. AIM: To find out the association of APOE HhaI and APOC1 HpaI polymorphisms with gallstone disease. SUBJECTS: HhaI polymorphism of APOE and HpaI polymorphism of APOC1 were analysed in DNA samples of 214 gallstone patients and 322 age- and sex-matched healthy controls. METHODS: For genotyping DNA samples of all study subjects were amplified using polymerase chain reaction, followed by restriction digestion. All statistical analyses were done using SPSS v11.5 and ARLEQUIN v2.0 softwares. RESULT: APOC1 HpaI polymorphism was found to be significantly associated with gallstone disease. Frequency of H2H2 was significantly higher (P = 0.017) in patients than in controls and it was imposing very high risk (OR 9.416, 95% CI 1.125-78.786) for gallstone disease. When data were stratified in male and female, H2H2 was associated (P = 0.011) with disease in females only. Analysis at allele level revealed no association. APOE HhaI polymorphism and APOE-C1 haplotypes showed no association with gallstone disease. CONCLUSION: APOC1 HpaI polymorphism is associated with gallstone disease and shows gender-specific differences. APOE HhaI polymorphism may not be associated with gallstone disease.

Adult↗
PubMed2006

The role of mast cells and eosinophils in chronic gastritis.

The role of mast cells and eosinophils in influencing the pathology of chronic gastritis remains unclear. We attempted to study the relationship between endoscopy and the mast cell and eosinophil infiltrate. We also studied the role of gene polymorphisms, Helicobacter pylori density and the CagA antibody status in influencing the mast cell and eosinophil infiltrate. One hundred and twenty consecutive patients were studied. Endoscopic evaluation was done and 3 antral biopsies were taken from each patient and were assessed for eosinophilic and mast cell infiltration, H. pylori density and the density of the other inflammatory cells as per the revised Sydney system. Cytokine gene polymorphisms (IL-1beta, IL-1RA and TNF-alpha) were done on the DNA extracted from the peripheral blood by PCR-RFLP. ELISA was done on the patients' serum for the anti-CagA antibody titres. Nodularity is strongly associated with the presence and density of eosinophils on biopsy (P < 0.05). Eosinophil density is strongly associated with the density of H. pylori, neutrophils, lymphocytes, plasma cells, atrophy, ulceration, foveolitis and lymphoid follicles. The mast cell density is not associated with any of the other histopathological variables. Gene polymorphisms and the CagA antibody titres have no relationship to the mast cell and eosinophil density. Eighty-one patients showed positive anti-CagA antibody titres but there was no association with the eosinophilic or the mast cell infiltrate. It is likely that eosinophilic infiltration is influenced by the H. pylori density but the CagA protein has no role to play in influencing the grade of the eosinophilic infiltrate in the Indian context. Cytokine gene proinflammatory polymorphisms have no role to play in influencing the eosinophilic or the mast cell response. It is likely that other mediators are involved in the inflammatory cell responses.

Adolescent↗
PubMed2005

A clinical, magnetic resonance imaging, and survival motor neuron gene deletion study of Hirayama disease.

BACKGROUND: Hirayama disease (HD) is a segmental nonprogressive spinal muscular atrophy found in male patients. OBJECTIVE: To report the results of a comprehensive evaluation of clinical, magnetic resonance imaging (MRI), electromyography (EMG), and survival motor neuron (SMN) gene analysis of HD. DESIGN: Clinical, MRI, and SMN gene deletion study. SETTING: Tertiary care teaching hospital. PATIENTS: Patients with HD diagnosed according to defined criteria were included in the study. INTERVENTIONS: Patients underwent a neurologic evaluation and pedigree charting. Concentric needle EMG was performed on a number of muscles. Motor nerve conduction study of the median, ulnar, and peroneal nerves and sensory conduction study of the median, ulnar, and sural nerves were also performed. Spinal MRI of the cervical region was performed with the 2-T scanner operating at 1.5 T. Gene deletion study of SMN1 and SMN2 was performed in all patients. MAIN OUTCOME MEASURES: History of trauma, occupation, exercise, associated medical disease, and cold paresis and muscle wasting, power, reflex changes, and tone. RESULTS: Fifteen male patients with HD from 14 families participated in the study (mean age at the onset of disease, 18 years; range, 15-23 years). Muscle weakness and wasting were noted in the right upper limb in 12 and the left upper limb in 3, which became bilateral in 8 patients. Cold paresis was present in 6 patients and polyminimyoclonus in all patients. The EMG revealed fibrillations in 10, fasciculations in 15, and neurogenic motor unit potentials in C7, C8, and T1 myotomes in all patients. The EMG abnormalities were unilateral in 5, bilateral in 10, and subclinical in 2 patients. Spinal MRI revealed cord atrophy in 3 of 11 patients. Although family history was present in 1 brother only, the results of both SMN1 and SMN2 gene deletion studies were negative in all patients. CONCLUSIONS: The SMN gene deletion is not found in HD. Exclusive occurrence in male patients and the presence of this disease in 2 brothers suggest a possible role of the X chromosome, which needs further evaluation.

Adolescent↗
PubMed2004

Molecular diagnosis and genetic counseling for fragile X mental retardation.

The fragile X syndrome is the most frequent cause of inherited mental retardation. It is caused by a dynamic mutation: the progressive expansion of polymorphic (CGG)n trinucleotide repeats located in the promoter region of the FMRI gene at Xq27.3. The cloning of the FMRI gene and the elucidation of the molecular basis of the fragile X syndrome is of great importance for the diagnosis and understanding of this unusual type of mutation. Although extensively studied, the mechanism behind the transition from stable normal (CGG)n alleles to the carrier state (an unstable premutation) and from premutation to mutation is partially understood. The clinical diagnosis of fragile X mental retardation (FXMR) is not possible as dysmorphic features are subtle. Molecular diagnosis by Southern Blot is the confirmatory test that makes carrier detection and prenatal diagnosis possible. As the risk of recurrence of FXMR is high in the family and carrier relatives, an identification of fragile X positive children, and offering carrier detection and prenatal diagnosis to the families is very important. It is possible by screening mentally retarded children and adults even if there is no family history of mental retardation or typical behavioral or physical features associated with the fragile X phenotype. In this review we have discussed the method for the diagnosis and counseling of the families. The complexities due to premutation and the variable severity of manifestations in carrier females need to be understood while counseling fragile X families.

Animals↗
PubMed2003

Re-evaluation of reading frame-shift hypothesis in Duchenne and Becker muscular dystrophy.

The reading frame hypothesis has been proposed to explain the molecular basis of two allelic forms of muscular dystrophies, Duchenne/Becker muscular dystrophy (D/BMD). To evaluate the hypothesis in Indian D/BMD patients, we analyzed deletion of dystrophin exons in 147 DMD and 19 BMD patients. Our studies showed deviation of more than 30% from the reading frame hypothesis in DMD patients (47/147). The present results implicate a need to reevaluate the reading frame hypothesis.

Child↗
PubMed2002

Autoantibodies against cytoskeletal proteins in rheumatoid arthritis.

We determined the prevalence and antigenic specificity of autoantibodies against cytoskeletal proteins in patients affected with various autoimmune diseases. Sera collected from patients with rheumatoid arthritis, systemic lupus erythematosus or progressive systemic sclerosis, and normal volunteers, were examined for the presence of autoantibodies against cytoskeletal proteins by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Patients with rheumatoid arthritis had the highest reactivity to cytoskeletal antigens on immunofluorescence assays using isolated muscle myofibrils (41/50) and L929 cells (37/50). Antigen-specific ELISA revealed significant immunoreactivity against actin (11/50) and myosin (15/50). In nine patients, immunoreactivity was seen against multiple cytoskeletal antigens. We concluded that the prevalence of IgG autoantibodies against cytoskeletal antigens, especially myofibrillar components actin and myosin, is elevated in patients with rheumatoid arthritis.

Animals↗
PubMed2002

Molecular screening of FRAXA and FRAXE in Indian patients with unexplained mental retardation.

Fragile-X mental retardation is the commonest form of inherited mental retardation. We have studied 146 Indian patients (174 X chromosomes) with unexplained mental retardation by molecular methods. All study subjects were unrelated. Three of the 118 males were found to have the FMR1 full mutation. None of the patients tested were positive for the FMR2 full mutation. The Fragile X prevalence was 2.5% among males, which is lower than previously reported in Indian mentally retarded patients. Screening for Fragile X among patients with nonspecific mental retardation is important, even if there is no family history of mental retardation or typical behavioral or physical features associated with the Fragile-X phenotype. Identification of positive cases is also very important for the families, because of the high recurrence risk of the disease. Large multicenter screening programs with uniform criteria would be worthwhile to determine the prevalence of Fragile-X mental retardation in the Indian population.

Female↗
PubMed2002

Clinical and molecular diagnosis of spinal muscular atrophy.

The spinal muscular atrophies are a group of disorders characterized by flaccid limb weakness. It is necessary to differentiate these from other causes and identify the SMA variants. In classical SMA, majority of the patients shows homozygous deletion of the telomeric SMN gene (SMN1) on chromosome 5q. The availability of DNA analysis has allowed proper genetic counseling and prenatal diagnosis in the affected families. Application of newer techniques has enabled more accurate carrier detection. Our objective is to stress the variability in the clinical features and recent advances in the molecular diagnosis for SMA.

Genetic Carrier Screening↗
PubMed2002

DNA mismatch repair, microsatellite instability and cancer.

Mismatch (MMR) repair system plays a significant role in restoration of stability in the genome. Mutations in mismatch repair genes hamper their activity thus bring about a defect in mismatch repair (MMR) mechanism thereby conferring instability in the microsatellite sequences of both the coding and non-coding regions of the genome. Mutated mismatch repair genes result in the expansion or contraction of microsatellite sequence and confer microsatellite unstable or replication error positive phenotype. Hypermethylation of promoter regions of some of the MMR genes also causes inactivation of these genes and thus contribute to MSI. Microsatellite instability is an indicator of MMR deficiency and is a prime cause of varied tumorogenesis.

Animals↗
PubMed2001

Point mutation and polymorphism in Duchenne/Becker muscular dystrophy (D/BMD) patients.

Duchenne and Becker muscular dystrophies (D/BMD) are caused by mutations in the dystrophin gene. Two-thirds of patients have large intragenic deletions or duplications and the remaining one-third have point mutations, small deletions or insertions. Point mutations are more difficult to detect due to the enormous size (2.4 Mb) of the gene and its large transcript (14 kb). In the present study, a total of 50 DNA samples from unrelated D/BMD (38 DMD and 12 BMD) patients who did not show intragenic deletions by multiplex PCR, were analyzed for detection of point mutations. Single stranded conformation analysis and heteroduplex analysis observed electrophoretic mobility shifts in one (BMD) and two (DMD and BMD) patients, respectively. The mobility shift and heteroduplexes were observed in exon 17 in all of the three patients. Sequencing of the amplified PCR products revealed a nucleotide change (-37 g to t) in the intronic region in two of the patients while a C2268T substitution in the exonic region in one. Mutation database search for D/BMD mutations showed the nucleotide substitution in the exonic region as a novel change in the human dystrophin gene, which was not reported earlier. It resulted in an amino acid transition from threonine to methionine in the 687th position of the dystrophin protein. This novel substitution has been included in the mutation database of Leiden muscular dystrophy pages (http://www.dmd.nl) in the rare polymorphism/mutation category. The substituted nucleotide segregated with the disease phenotype in the family suggesting that it can be directly used for carrier detection and prenatal diagnosis without identification of disease causing mutation.

Amino Acid Sequence↗
PubMed2001

SMN2-deletion in childhood-onset spinal muscular atrophy.

The human genome has two homologous survival motor neuron genes, SMN1 and SMN2. Although deletions of SMN1 are frequently reported in childhood-onset spinal muscular atrophy (SMA), SMN2 have been found to be intact in patients with the disorder. We report on a 5-year-old boy with childhood-onset SMA who has a homozygous deletion of SMN2. He had wasting, weakness, and hyporeflexia, predominantly in the distal muscles. The muscles involved showed chronic neurogenic changes on electromyogram. There was no sensory involvement. A nerve conduction study showed near normal conduction velocity with reduction in the amplitude of the compound muscle action potential. Analysis of polymerase chain reaction-restriction fragment length polymorphism as well as single-strand conformation polymorphism on exons 7 and 8 of the SMN genes revealed the SMN2-deletion. Base sequencing and densitometric analysis of the critical region (exon 7) did not show any microdeletion or duplication of SMN1, but confirmed the deletion of SMN2. We conclude that a deletion of SMN2 may also result in the SMA phenotype.

Child↗
PubMed2001

Effects of xerostomia on perception and performance of swallow function.

BACKGROUND: Head and neck cancer treatment with high-dose chemoradiation may cause xerostomia and affect the patient's perception of swallowing ability. METHOD: Whole saliva production was measured in 36 patients with advanced-stage cancer of the oropharynx before treatment and 3 months after treatment by weighing a 4 x 4 inch gauze before and after a 2-minute chewing period. Presence of multiple eating difficulties was measured by patient interview. Swallowing was examined videofluorographically (VFG). RESULTS: Saliva weight decreased from a mean (SEM) of 5.1 (0.5) g pretreatment to 1.4 (0.5) g after treatment (p<.0001). At 3 months, significantly more patients perceived difficulty swallowing, dry mouth, needing water while eating, food stuck in the mouth or throat, and change in taste. Saliva weight was not correlated with VFG measures of bolus transit or observations of residue. CONCLUSIONS: Chemoradiation treatment results in xerostomia and a significant increase in patient perception of swallowing difficulties. Saliva weight in patients who perceive swallowing problems was lower. Xerostomia did not affect the physiologic aspects of bolus transport. Xerostomia affected the sensory process and comfort of eating more than bolus transport.

Adult↗
PubMed2001

Sequential induction chemotherapy and concomitant chemoradiotherapy in the management of locoregionally advanced laryngeal cancer.

PURPOSE: To determine overall survival, progression-free survival, rate of voice preservation, and patterns of failure in locoregionally advanced laryngeal cancer treated with induction chemotherapy with or without surgery followed by concomitant chemoradiation. BACKGROUND: Locoregionally advanced laryngeal cancer has been conventionally treated with either surgery and adjuvant radiotherapy or radiotherapy alone, and clinical and functional outcomes have been poor. Chemoradiotherapy has been demonstrated to improve functional outcome and disease control over conventional treatment in recent randomized head and neck trials. PATIENTS AND METHODS: Advanced head and neck cancer patients were enrolled onto two consecutive phase II studies. Induction treatment consisted of three cycles of cisplatin, 5-fluorouracil (5-FU), leucovorin, and interferon-alpha 2b (PFL-IFN) followed by surgery for residual disease. Surgical intent was to spare the larynx when possible. All patients then proceeded to concomitant chemoradiation consisting of seven or eight cycles of 5-FU, hydroxyurea, and a planned total radiotherapy dose of 7000 cGy (FHX). RESULTS: A subset of thirty-two laryngeal cancer patients with predominantly stage IV disease comprises the study group for this report. Clinical CR was observed in 59% of patients following induction therapy. The median follow-up was 63.0 months for surviving patients and 44.5 months for all patients. At five years, overall survival is 47%, progression-free survival is 78%, and locoregional control is 78%. No distant failures were observed. Voice preservation with disease control was 75% at five years. Only two total laryngectomies were performed during the course of treatment and follow-up. Treatment-related toxicity accounted for two deaths. CONCLUSIONS: The addition of concomitant chemoradiotherapy to induction chemotherapy for locoregionally advanced laryngeal cancer appears to increase locoregional control and survival rates. PFL-IFN-FHX resulted in high rates of disease cure and voice preservation in a group of patients that has traditionally fared poorly in both clinical and functional outcome.

Aged↗
PubMed2001

Carrier detection in non-deletional Duchenne/Becker muscular dystrophy families using polymorphic dinucleotide (CA) repeat loci of dystrophin gene.

BACKGROUND & OBJECTIVES: Carrier detection and prenatal diagnosis is of great importance for families with one or more sons affected with Duchenne/Becker muscular dystrophy (D/BMD). In about 35-40 per cent of these patients, the causative mutation does not involve gross rearrangement in the structure of dystrophin gene. In these non-deletional families, genetic counselling can be provided only by linkage analysis. The aim of the present study was to determine the carrier status of female relatives in north Indian families with non-deletional D/BMD using highly polymorphic intragenic dinucleotide (CA) repeat markers. METHODS: Six short tandem repeats (STRs) spanning 5' (1), central (4) and 3' regions of the dystrophin gene were used to analyse 14 unrelated families comprising 68 individuals with 12 female siblings at risk of being carriers. RESULTS: Five female siblings inherited at risk STR haplotype, six inherited normal haplotype and one had meiotic recombination. The intragenic recombinations were observed in three families at the central region STR loci and in one family between the proximal and central regions of the gene. INTERPRETATION & CONCLUSIONS: Our study suggested that at least 6 STR markers spanning 5', central and 3' regions of the dystrophin gene are essential to ascertain one or more informative loci and to rule out recombinations in non-deletional D/BMD families for carrier analysis.

Dinucleotide Repeats↗
PubMed2001

Internet resources for the human geneticist.

The Internet is a massive expanding body of information, which is likely to play a significant role for clinicians and researchers across the world. Since its inception in December 1969 the Internet has grown rapidly and is anticipated to expand 1,000% in the coming next few years. Various useful databases on human genetics are already in 'the Net' and many more are being added constantly. The future of human geneticist is in handling of information. In this review of Internet and compilation of important web site addresses we expect to stimulate and instruct human geneticists in navigating the Net. The list of web sites provided in this article is expected to facilitate their search.

Databases, Genetic↗
PubMed2000

Targeting of cardiac muscle titin fragments to the Z-bands and dense bodies of living muscle and non-muscle cells.

A 6.5-kb N-terminal region of embryonic chick cardiac titin, including the region previously reported as part of the protein zeugmatin, has been sequenced, further demonstrating that zeugmatin is part of the N-terminal region of titin, and not a separate Z-band protein. This Z-band region of cardiac titin, from both 7- and 19-day embryos as well as from adult animals, was found to contain six different small motifs, termed z-repeats [Gautel et al., 1996: J. Cell Sci. 109:2747-2754], of approximately 45 amino acids each sandwiched between flanking regions containing Ig domains. Fragments of Z-band titin, linked to GFP, were expressed in cultured cardiomyocytes to determine which regions were responsible for Z-band targeting. Transfections of primary cultures of embryonic chick cardiomyocytes demonstrated that the z-repeats play the major role in targeting titin fragments to the Z-band. Similar transfections of skeletal myotubes and non-muscle cells lead to the localization of these cardiac z-repeats in the Z-bands of the myofibrils and the dense bodies of the stress fibers. Over-expression of these z-repeat constructs in either muscle or non-muscle cells lead to the loss of the myofibrils or stress fibers, respectively. The transfection experiments also indicated that small domains of a protein, 40 to 50 amino acids, can be studied for their localization properties in living cells if a suitable linker is placed between these small domains and the much larger 28 kDa GFP protein.

Amino Acid Sequence↗