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N Sodha

Publications and source records attributed to N Sodha.

8 recordsLinked to original sources
PubMed2002

CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours.

We have recently shown that the CHEK2*1100delC mutation acts as a low penetrance breast cancer susceptibility allele. To investigate if other CHEK2 variants confer an increased risk of breast cancer, we have screened an affected individual with breast cancer from 68 breast cancer families. Five of these individuals were found to harbour germline variants in CHEK2. Three carried the 1100delC variant (4%). One of these three individuals also carried the missense variant, Arg180His. In the other two individuals, missense variants, Arg117Gly and Arg137Gln, were identified. These two missense variants reside within the Forkhead-associated domain of CHEK2, which is important for the function of the expressed protein. None of these missense variants were present in 300 healthy controls. Microdissected tumours with a germline mutation showed loss of the mutant allele suggesting a mechanism for tumorigenesis other than a loss of the wild type allele. This study provides further evidence that sequence variation in CHEK2 is associated with an increased risk of breast cancer, and implies that tumorigenesis in association with CHEK2 mutations does not involve loss of the wild type allele.

Adult↗
PubMed2000

The value of rapid functional assays of germline p53 status in LFS and LFL families.

We have tested two rapid assays of p53 function, namely the apoptotic assay and the FASAY as means of detecting germline p53 mutations in members of Li-Fraumeni and Li-Fraumeni-like families. Results of the functional assays have been compared with direct sequencing of all 11 exons of the p53 gene. The results show good agreement between the two functional assays and between them and sequencing. No false-positives or negatives were seen with either functional assay although the apoptotic assay gave one borderline result for an individual without a mutation. As an initial screen the apoptotic assay is not only rapid but inexpensive and very simple to perform. It would be expected to detect any germline defect that leads to loss of p53 function. The apoptotic assay could be ideal as a means of prescreening large numbers of samples and identifying those that require further investigation. The FASAY detects mutations in exons 4-10, is rapid and distinguishes between functionally important and silent mutations.

Apoptosis↗
PubMed1999

Analysis of Li-Fraumeni syndrome and Li-Fraumeni-like families for germline mutations in Bcl10.

The Li-Fraumeni syndrome (LFS) is a dominant disease whose hallmark is an increased risk of breast cancers, brain tumours, sarcomas, leukaemia and adrenal carcinoma. Some, but not all LFS and Li-Fraumeni-like (LFL) families are caused by TP53 mutations. Bcl10 is a recently identified tumour suppressor reported to be commonly mutated in a wide range of cancers. To investigate the possibility that Bcl10 is a susceptibility gene for LFS and LFL we have analysed 27 LFS/LFL families. No mutations were observed. This indicates that Bcl10 is unlikely to act as a susceptibility gene for LFS and LFL.

Adaptor Proteins, Signal Transducing↗
PubMed1994

On genetic and environmental factors in Menière's disease.

The etiology of Menière's disease (MD) remains obscure. Previous studies have shown a highly significant association between sporadic MD and one of the human leukocyte antigen, HLA-C genotypes, whereas disease activity has been related to the detection of enterovirus-specific viral protein (VP1) in the peripheral circulation. This present research extends the HLA association of sporadic cases to the study of families with more than one living member with unequivocal MD. Since the sporadic HLA associations point to chromosome 6 being a candidate region of a possible MD mutation, this area of the human genome has been investigated first; DNA suitable for study by other markers has been stored. The presence or absence of VP1 in the familial MD patients has been measured and related to disease activity at the time of sample collection. The association, in both sporadic and familial cases, of MD and partial HLA class I haplotypes points to a likely MD locus lying between the HLA-C and HLA-A loci on the short arm of chromosome 6. The significant relation between disease activity and circulating VP1 has been confirmed. It is likely that the predisposition to familial MD is attributable to a mutation on chromosome 6, which has been designated M1.

Antigens, Viral↗
PubMed1989

Calcium, magnesium and phosphorus status of elderly inpatients: dietary intake, metabolic balance studies and biochemical status.

The calcium, magnesium and phosphorus status of a group of elderly inpatients was studied by use of duplicate meal analysis over a 5 d period and biochemical indices in twenty-one patients, and metabolic balance (5 d) in six of these. Mean daily Ca intake was lower than that of apparently healthy elderly subjects in metabolic equilibrium, although commensurate with present UK recommendations. Metabolic balance was negative for Ca. Mean daily Mg intake was approximately half the US recommendation, and half the intake at which metabolic balance has been observed in healthy elderly people. The five patients studied were in metabolic balance for Mg. Mean daily P intake was close to the UK recommendation, but negative metabolic balance was observed. The disparity between official recommendations for Ca-intake, factors contributing to suboptimal Ca status, and measures that may improve Ca status in this group are discussed.

Aged↗
PubMed1988

Energy, protein, zinc and copper status of twenty-one elderly inpatients: analysed dietary intake and biochemical indices.

1. Duplicate diet analysis for energy, protein, zinc and copper with estimates of biochemical status for Zn and Cu were undertaken in twenty-one elderly long-stay inpatients (mean age 82 (range 63-89) years) consuming their customary hospital diet and in a stable medical condition. Fourteen patients had a long-standing and significant healing problem, either a leg ulcer or pressure sore. 2. Mean daily intakes of energy (5.2 MJ), protein (45 g), Zn (85 mumol) and Cu (14 mumol) were low in comparison with both official recommendations and levels of intake at which metabolic equilibrium was observed in healthy elderly people studied by the same methods (Bunker et al. 1984a). 3. Mean leucocyte Zn (9 pmol/10(6) cells) and Cu (7.5 pmol/10(6) cells) were low in comparison with results from healthy elderly people (Bunker et al. 1984a), implying suboptimal status for these elements. Those patients with healing problems tended to have the lower values within the range. 4. Recommendations are made with respect to improving nutritional status in this disadvantaged group of people.

Aged↗