Search PubMed⌕ Search

Biomedical subjects

A Sahota

Publications and source records attributed to A Sahota.

At least 37 records · Page 2Linked to original sources
PubMed1997

The association between Apo E genotype and depressive symptoms in elderly African-American subjects.

In this study of 138 elderly subjects (112 without and 26 with dementia) obtained from a community sample of elderly African-American subjects, there were no significant differences in mean Geriatric Depression Scale scores by Apo E epsilon 4 status for dementia or nondementia subjects. Three subjects received a diagnosis of major depressive disorder. None of these subjects were Apo E epsilon 4-positive. These results do not support an association between depressive symptoms and Apo E allele status in this elderly African-American population.

Aged↗
PubMed1997

The role of cell migration and microchimerism in the induction of tolerance after solid organ transplantation.

A new hypothesis has been proposed which states that microchimerism is the basis for the clinical tolerance seen in long-term survivors of solid organ transplants. Efforts to enhance microchimerism include simultaneous infusion of bone marrow of donor origin and transplantation of a solid organ. Studies are in progress to verify the phenomenon of microchimerism and its role in clinical tolerance.

Bone Marrow Transplantation↗
PubMed1997

Loss of heterozygosity analysis in a human fibrosarcoma cell line.

Loss of heterozygosity (LOH) is an important event in tumor formation. We have used polymorphic microsatellite repeat markers to identify and characterize LOH in spontaneous mutants of a human cell line, MR12-1, that is heterozygous for the adenine phosphoribosyltransferase gene (APRT+/-) located on chromosome 16q24.3. Initially, clones without extensive LOH (which are likely derived as a consequence of intragenic point mutations) and clones with multilocus LOH (which are likely due to major chromosome alterations) were identified. Clones with major regions of LOH were further characterized by assaying additional informative microsatellite markers. Analysis of 20 spontaneously-arising, independent APRT-/- clones from MR12-1 demonstrated that nine of the mutants retained both copies of APRT and 11 had undergone multilocus genetic alterations. The nature of LOH in four of the latter clones has been examined in detail by karyotype and fluorescence in situ hybridization analysis (Shao et al., 1996). These data demonstrate that LOH of chromosome 16 may be due to mitotic recombination, interstitial or partial deletion, or to more complex mechanisms. LOH in these clones may be a consequence of events similar to those observed in many tumors.

Adenine Phosphoribosyltransferase↗
PubMed1996

Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis.

Adenine phosphoribosyltransferase (APRT) deficiency in humans is an autosomal recessive syndrome characterized by the urinary excretion of adenine and the highly insoluble compound 2,8-dihydroxyadenine (DHA) that can produce kidney stones or renal failure. Targeted homologous recombination in embryonic stem cells was used to produce mice that lack APRT. Mice homozygous for a null Aprt allele excrete adenine and DHA crystals in the urine. Renal histopathology showed extensive tubular dilation, inflammation, necrosis, and fibrosis that varied in severity between different mouse backgrounds. Thus, biochemical and histological changes in these mice mimic the human disease and provide a suitable model of human hereditary nephrolithiasis.

Adenine↗
PubMed1996

Polymorphisms in the human apolipoprotein-J/clusterin gene: ethnic variation and distribution in Alzheimer's disease.

Apolipoprotein-J/clusterin (APOJ/CLI) shares many biological properties with apolipoprotein-E (APOE) including, but not limited to, avid binding with beta-amyloid peptide. Thus, APOJ/CLI warrants scrutiny as a candidate Alzheimer's disease (AD) susceptibility gene. We identified seven nucleotide sequence polymorphisms in APOJ/ CLI, two of which, in exon 7, after the predicted amino acid sequence. The JVIIB variant is an asparagine-to-histidine substitution, which deletes a glycosylation signal at amino acid 317; the JVIIC variant is an aspartate-to-asparagine substitution, which forms a new glycosylation signal at position 328. Both of these coding variants, as well as two neutral polymorphisms in exon 2, were more frequent in African-Americans than Hispanics and were rare in Caucasians. However, no individual coding or noncoding variant was consistently associated with AD. At the population level, APOJ/CLI polymorphisms are frequent among persons of African descent, but probably do not alter susceptibility to AD.

Black or African American↗
PubMed1996

HPRT-APRT-deficient mice are not a model for lesch-nyhan syndrome.

Complete hypoxanthine-guanine phosphoribosyl-transferase (HPRT) deficiency in humans results in the Lesch-Nyhan syndrome which is characterized, among other features, by compulsive self-injurious behavior. HPRT-deficient mice generated using mouse embryonic stem cells exhibit none of the behavioral symptoms associated with the Lesch-Nyhan syndrome. Administration of drugs that inhibit adenine phosphoribosyltransferase (APRT) in HPRT-deficient mice has produced the suggestion that deficiency of APRT in combination with HPRT-deficiency in mice may lead to self-mutilation behavior [C.L. Wu and D.W. Melton (1993) Nature Genet. 3, 235-240]. To test this proposition, we bred HPRT-APRT-deficient mice. Although the doubly-deficient mice excrete adenine and its highly insoluble derivative, 2,8-dihydroxyadenine, which are also associated with human APRT deficiency, additional abnormalities or any self-injurious behavior were not detected. Thus, APRT-HPRT-deficient mice, which are devoid of any purine salvage pathways, show no novel phenotype and are not a model for the behavioral abnormalities associated with the Lesch-Nyhan syndrome as previously suggested.

Adenine Phosphoribosyltransferase↗
PubMed1996

Complex chromosomal mechanisms lead to APRT loss of heterozygosity in heteroploid cells.

Loss of the wild-type allele of a tumor suppressor gene, or loss of heterozygosity (LOH), is one of the most important mechanisms of carcinogenesis. Adenine phosphoribosyltransferase (APRT) has been used as a surrogate marker for tumor suppressor genes. We have previously shown that APRT deficiency in an APRT heterozygous human cell line, MR12-1, was predominantly caused by the loss of the remaining wild-type allele. Here we report the characterization of the chromosomal pathways leading to LOH in four clones derived from this heteroploid cell line. We performed karyotype analysis, chromosome 16-specific painting, and fluorescence in situ hybridization with an APRT-containing cosmid on these clones and their heteroploid parental cells. Our findings suggest that LOH occurs in tetraploid as well as diploid cells, and that diploid cells with LOH may undergo endoreduplication to attain tetraploidy. Our results also suggest that, in addition to LOH being caused by a single event (such as mitotic recombination or deletion), LOH may be caused by a combination of sequential events, such as mitotic recombination or translocation followed by chromosome loss. The instability of the genomes of the parental cells may have provided a greater diversity of options for genetic evolution. Similar karyotypic evolution may occur at late stages of carcinogenesis in vivo.

Adenine Phosphoribosyltransferase↗
PubMed1996

Association of the epsilon 4 allele of apolipoprotein E with poor performance on a dementia screen in African Americans.

In a community-based study of Alzheimer's disease in African Americans age 65 and over, subjects were classified into three levels of performance based on their scores as measured by the Community Screening Instrument for Dementia (CSI"D"), consisting of cognitive and functioning components. In a subset of 268 subjects with apolipoprotein E (APOE) genotype data, we found that the epsilon 4 allele of APOE was associated with intermediate/poor performance (single copy epsilon 4 odds ratio 1.51, 95% CI 1.18 to 1.92; double copy epsilon 4 odds ratio 3.42, 95% CI 2.18 to 5.43). From these data, we believe it would be possible to conduct population screening for the effects of possession of the APOE-epsilon 4 allele using information derived from the CSI"D".

Aged↗
PubMed1995

Cloning and characterization of the adenine phosphoribosyltransferase-encoding gene (APT1) from Saccharomyces cerevisiae.

We have cloned, sequenced and characterized the APT1 (adenine phosphoribosyltransferase) gene from Saccharomyces cerevisiae. The APT1 sequence includes an open reading frame encoding 221 amino acids and is contained within a 1322-bp insert that complements APRT-deficient mutants to wild-type levels of enzyme activity. Analysis by primer extension revealed multiple transcription start points (tsp) and a major tsp 21-bp upstream from the ATG start codon. A transcript initiated at the major tsp would yield a 700-nt mRNA which is in agreement with the size observed by Northern analysis. Sequence comparison indicates that the yeast enzyme shares strong similarities with other known APRT of bacterial, invertebrate, plant and mammalian origins.

Adenine Phosphoribosyltransferase↗
PubMed1995

Apolipoprotein E genotypes and Alzheimer's disease in a community study of elderly African Americans.

As part of a community-based study of Alzheimer's disease (AD) in the African-American population age 65 and over, we have determined apolipoprotein E (Apo E) genotypes in 85 subjects (31 AD patients and 54 controls). The epsilon 4 allele of Apo E was strongly associated with AD in this population sample. The epsilon 4 allele frequency in AD patients was 40.3% compared with 13.9% in the control group, and 22.6% of the AD patients were homozygous for this allele compared with 3.7% of the control subjects (p = 0.01). This study extends the association of Apo E-epsilon 4 and AD to nonwhite populations and provides further evidence that the observed allelic association is biologically relevant.

Black or African American↗
PubMed1995

Lack of an association between apolipoprotein E epsilon 4 and Alzheimer's disease in elderly Nigerians.

As part of a community-based study of Alzheimer's Disease (AD) in a Nigerian population aged 65 years and over, we have determined apolipoprotein E (APOE) genotypes on 56 subjects (39 controls and 17 subjects with dementia, including 12 with AD). The epsilon 4 allele of APOE was not associated with AD or dementia in this community-based sample. The epsilon 4 allele frequency was 17.6% in demented patients and 16.7% in AD patients compared with 20.5% in the control subjects. These findings are in marked contrast to the strong association between the epsilon 4 allele and AD in our previously reported study with African Americans.

Aged↗