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Biomedical subjects

D Kumari

Publications and source records attributed to D Kumari.

12 recordsLinked to original sources
PubMed2006

Sensitization to blackgram in patients with bronchial asthma and rhinitis: clinical evaluation and characterization of allergens.

BACKGROUND: Legumes are important causative agents of type I hypersensitivity in south Asia and Europe but such studies are lacking in Indian population. The present study investigates blackgram sensitization in asthma and rhinitis patients and identifies immunoglobulin E (IgE)-binding proteins. METHODS: Respiratory allergy patients were evaluated using standard questionnaire and skin prick tests (SPT) with common foods and aeroallergens. Blackgram-specific IgE level was estimated by enzyme-linked immunosorbent assay (ELISA) and sensitization was established by a double-blind, placebo-controlled food challenge (DBPCFC). The cross-reactivity of blackgram with other legumes was studied by immunobiochemical methods. RESULT: Of 816 patients, 35 gave history of blackgram hypersensitivity. From these, 16 patients were SPT positive and 14 showed elevated specific IgE (three times of negative control) to blackgram. DBPCFC established blackgram sensitivity in four of 14 patients. Immunoblotting with individual patient's sera recognized eight most prevalent allergens of 78, 56, 47, 43, 40, 30, 28 and 16 kDa. Roasted blackgram showed six major allergens whereas 47, 43 and 28 kDa proteins retained IgE reactivity upon boiling. Blackgram extract required 14 ng of self protein for 50% ELISA inhibition whereas roasted and boiled blackgram required 16 and 120 ng protein. ELISA and immunoblot inhibition show partial inhibition to blackgram proteins by lentil, limabean and pea. CONCLUSION: Blackgram induces IgE-mediated reactions in 1.7% of asthma and rhinitis patients and contains eight major IgE-binding components, of which six retained IgE reactivity after roasting. Blackgram shares allergenicity with lentil and limabean.

Adolescent↗
PubMed2003

Transcription defects induced by repeat expansion: fragile X syndrome, FRAXE mental retardation, progressive myoclonus epilepsy type 1, and Friedreich ataxia.

Fragile X mental retardation syndrome, FRAXE mental retardation, Progressive myoclonus epilepsy Type I, and Friedreich ataxia are members of a larger group of genetic disorders known as the Repeat Expansion Diseases. Unlike other members of this group, these four disorders all result from a primary defect in the initiation or elongation of transcription. In this review, we discuss current models for the relationship between the expanded repeat and the disease symptoms.

Base Sequence↗
PubMed2003

Instability of the fragile X syndrome repeat in mice: the effect of age, diet and mutations in genes that affect DNA replication, recombination and repair proficiency.

Repeat expansion diseases such as fragile X syndrome (FXS) result from increases in the size of a specific tandem repeat array. In addition to large expansions, small changes in repeat number and deletions are frequently seen in FXS pedigrees. No mouse model accurately recapitulates all aspects of this instability, particularly the occurrence of large expansions. This may be due to differences between mice and humans in CIS and/or TRANS-acting factors that affect repeat stability. The identification of such factors may help reveal the expansion mechanism and allow the development of suitable animal models for these disorders. We have examined the effect of age, dietary folate, and mutations in the Werner's syndrome helicase (WRN) and TRP53 genes on FXS repeat instability in mice. WRN facilitates replication of the FXS repeat and enhances Okazaki fragment processing, thereby reducing the incidence of processes that have been suggested to lead to expansion. p53 is a protein involved in DNA damage surveillance and repair. We find two types of repeat instability in these mice, small changes in repeat number that are seen at frequencies approaching 100%, and large deletions which occur at a frequency of about 10%. The frequency of these events was independent of WRN, p53, parental age, or folate levels. The large deletions occur at the same frequency in mice homozygous and heterozygous for the repeat suggesting that they are not the result of an interallelic recombination event. In addition, no evidence of large expansions was seen. Our data thus show that the absence of repeat expansions in mice is not due to a more efficient WRN protein or p53-mediated error correction mechanism, and suggest that these proteins, or the pathways in which they are active, may not be involved in expansion in humans either. Moreover, the fact that contractions occur in the absence of expansions suggests that these processes occur by different mechanisms.

Age Factors↗
PubMed2003

Deletion analysis of the dystrophin gene in Duchenne and Becker muscular dystrophy patients: use in carrier diagnosis.

The dystrophin gene was analyzed in 8 Duchenne muscular dystrophy (DMD) and 10 Becker muscular dystrophy (BMD) unrelated families (22 subjects: 18 index cases and 4 sibs) for the presence of deletions by multiplex polymerase chain reaction (mPCR; 27 exons) and Southern hybridization using 8 cDMD probes. Deletions were identified in 5 DMD and 7 BMD patients (6 index cases and 1 sib). The concordance between the clinical phenotype and "reading frame hypothesis" was observed in 11/12 patients (92%). The female relatives of DMD/BMD patients with identifiable deletions were examined by quantitative mPCR. Carriers were identified in 7 families. We also describe a variation in the HindIII pattern with cDNA probe 8 and 11-14. Molecular characterization of the dystrophin gene in this study has been helpful in advising the patients concerning the inheritance of the condition, and carrier diagnosis of female relatives, and should also prove useful for prenatal diagnosis.

Adolescent↗
PubMed2000

Interaction of the transcription factors USF1, USF2, and alpha -Pal/Nrf-1 with the FMR1 promoter. Implications for Fragile X mental retardation syndrome.

Hypermethylation of the FMR1 promoter reduces its transcriptional activity, resulting in the mental retardation and macroorchidism characteristic of Fragile X syndrome. How exactly methylation causes transcriptional silencing is not known but is relevant if current attempts to reactivate the gene are to be successful. Understanding the effect of methylation requires a better understanding of the factors responsible for FMR1 gene expression. To this end we have identified five evolutionarily conserved transcription factor binding sites in this promoter and shown that four of them are important for transcriptional activity in neuronally derived cells. We have also shown that USF1, USF2, and alpha-Pal/Nrf-1 are the major transcription factors that bind the promoter in brain and testis extracts and suggest that elevated levels of these factors account in part for elevated FMR1 expression in these organs. We also show that methylation abolishes alpha-Pal/Nrf-1 binding to the promoter and affects binding of USF1 and USF2 to a lesser degree. Methylation may therefore inhibit FMR1 transcription not only by recruiting histone deacetylases but also by blocking transcription factor binding. This suggests that for efficient reactivation of the FMR1 promoter, significant demethylation must occur and that current approaches to gene reactivation using histone deacetylase inhibitors alone may therefore have limited effect.

Animals↗
PubMed2000

Detection of deletion in the dystrophin gene of a patient with quadriceps myopathy.

A 43 year old male presented with slowly progressive weakness of limbs and hypertrophy of triceps, brachioradialis and calf muscles for four years. There was thinning of quadriceps muscles in both thighs. Histological study was compatible with Becker muscular dystrophy (BMD). Genomic DNA analysis showed a deletion of the Hind III fragments, spanning exons 45-47. A junction fragment of 11.0 kb was observed along with a deletion of a 3.4 kb PstI fragment containing exon 51 in the patient, and in one of his two sisters. The clinical and laboratory characteristics in this patient are in keeping with what has been described 'quadriceps myopathy' and fall within the phenotypic variants of BMD as has been shown by others.

Adult↗
PubMed1998

Molecular characterisation of Duchenne muscular dystrophy and phenotypic correlation.

Dystrophin gene was analysed in 32 unrelated DMD families (46 subjects: 32 index cases and 14 sibs) for the presence of deletions by mPCR for 27 exons and cDNA probes for the entire gene. Deletions were identified in 32 patients (25 index cases and seven sibs) from 25 families. The concordance between the clinical phenotype and 'reading frame' hypothesis was observed in 24 (75%) cases. Of these, nine patients were wheelchair bound between 8-12 years of age, nine (age range 5-10 years) showed progressive difficulty in walking and six (age range 1.6-4 years) had onset of muscle weakness. One patient (CH), who was wheelchair bound at 12 years, the effect of mutation on the ORF could not be ascertained due to the presence of a junction fragment. Seven patients had inframe deletions of which four were wheelchair bound by the age of 13 years, and three (age range 5-7 years) although, ambulatory had difficulty in walking. There were eight patients who showed no deletion, of which four became wheelchair bound by the age of 12 years, four, though still ambulatory, were unable to run and tired easily. Correlation between phenotype and genotype of these DMD patients demonstrates that genetic studies of lymphocyte DNA may not always reflect the situation in the tissue involved in dystrophin, i.e. muscle. We describe a common dystrophin gene polymorphism in the Indian population with cDNA 11-14 that alters the Hind III restriction sites. Novel RFLPs were observed in 26 patients and their family members. Whether this is a polymorphism or, related to the diseased phenotype needs confirmation.

Adolescent↗
PubMed1994

Effect of retinol on ochratoxin-produced genotoxicity in mice.

Ochratoxin (1 microgram/kg body weight/day), when administered orally daily to albino Swiss mice for 14 continuous days, increased the incidence of abnormalities in mitotic and meiotic metaphase chromosomes, and the gross morphology of the sperm head; the sperm count per unit volume of caput epididymal suspension also decreased. These genotoxic effects were substantially reduced by concurrent oral administration of retinol at double the clinically therapeutic dose. It is possible that the electrophilic metabolites of ochratoxin form adducts with DNA or produce replacement-type mutations. Retinol may achieve its antigenotoxic effect by means of blocks and shunts in the ochratoxin metabolic pathway. Vitamin A-mediated cellular repair and scavenging of the mutagenic radicals can also take place. The vitamin itself has some genotoxic potential.

Animals↗
PubMedDate not supplied

Fragile X syndrome and Friedreich's ataxia: two different paradigms for repeat induced transcript insufficiency.

DNA repeat expansion is the genetic basis for a growing number of neurological disorders. While the largest subset of these diseases results in an increase in the length of a polyglutamine tract in the protein encoded by the affected gene, the most common form of inherited mental retardation, fragile X syndrome, and the most common inherited ataxia, Friedreich's ataxia, are both caused by expansions that are transcribed but not translated. These expansions both decrease expression of the gene in which the expanded repeat is located, but they do so by quite different mechanisms. In fragile X syndrome, CGG. CCG expansion in the 5' untranslated region of the FMR1 gene leads to hypermethylation of the repeats and the adjacent CpG-rich promoter. Methylation prevents the binding of the transcription factor alpha-Pal/NRF-1, and may indirectly affect the binding of other factors via the formation of transcriptionally silent chromatin. In Friedreich's ataxia, GAA. TTC expansion in an intron of the FRDA gene reduces expression by interfering with transcription elongation. The model that best describes the available data is transcription-driven formation of a transient purine. purine. pyrimidine DNA triplex behind an advancing RNA polymerase. This structure lassoes the RNA polymerase that caused it, trapping the enzyme on the template.

DNA Methylation↗