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P Charmley

Publications and source records attributed to P Charmley.

41 records · Page 3Linked to original sources
PubMed1989

The germline repertoire of T cell receptor beta-chain genes in patients with chronic progressive multiple sclerosis.

The T cell receptor (TcR) beta-chain germline gene repertoire of multiple sclerosis (MS) patients was compared to that of 100 normal individuals. No differences in the number of gene segments defined by probes representing 14 different human V beta subfamilies and the constant region genes were found. The distribution of haplotypes defined by restriction fragment length polymorphism (RFLP) alleles detected with V beta 8, V beta 11, and C beta probes in the MS patients was significantly different from that found in normal individuals. Because 84% of the MS patients were DR2+, the findings in these patients were compared to a second group of 43 normals who were DR2+. The distribution of TcR haplotypes in MS patients was also significantly different from that in the DR2+ normals. The data suggest that an MS susceptibility gene(s) may be located in the region of the TcR beta-chain gene complex.

Alleles↗
PubMed1989

The germline repertoire of T-cell receptor beta-chain genes in patients with multiple sclerosis.

The T-cell receptor (TCR) beta-chain gene repertoire of 40 multiple sclerosis (MS) patients was compared to that of 100 normal individuals. V-beta probes that represent 14 different V-beta subfamilies plus a C-beta probe were used to identify 53 separate beta-chain gene segments. No duplication or deletion of any of these 53 gene segments was found in the MS patients. Restriction fragment length polymorphism (RFLP) alleles detected by V-beta 8, V-beta 11 and C-beta probes defined 8 different beta-chain haplotypes. The distribution of these haplotypes in Caucasian MS patients and normal individuals was significantly different (p = 0.012). Comparison of the DR2+ subset of MS patients (n = 32) to a second group of 43 Caucasian DR2+ normal individuals revealed that the distribution of these beta-chain haplotypes was significantly different in these two populations (p = 0.015). These results suggest that an MS susceptibility gene(s) may be located in the region of the TCR/beta-chain gene complex.

Alleles↗
PubMed1988

Localization of an ataxia-telangiectasia gene to chromosome 11q22-23.

Ataxia-telangiectasia (AT) is a human autosomal recessive disorder of childhood characterized by: (1) progressive cerebellar ataxia with degeneration of Purkinje cells; (2) hypersensitivity of fibroblasts and lymphocytes to ionizing radiation; (3) a 61-fold and 184-fold increased cancer incidence in white and black patients, respectively; (4) non-random chromosomal rearrangements in lymphocytes; (5) thymic hypoplasia with cellular and humoral (IgA and IgG2) immunodeficiencies; (6) elevated serum level of alphafetoprotein; (7) premature ageing; and (8) endocrine disorders, such as insulin-resistant diabetes mellitus. A DNA processing or repair protein is the suspected common denominator in this pathology. Heterozygotes are generally healthy; however, the sensitivity of their cultured cells to ionizing radiation is intermediate between normal individuals and that of affected homozygotes. Furthermore, heterozygous females are at an increased risk of breast cancer. These findings, when coupled with an estimated carrier frequency of 0.5-5.0%, suggest that (1) as many as one in five women with breast cancer may carry the AT gene and that (2) the increased radiation sensitivity of AT heterozygotes may be causing radiation therapists to reduce the doses of radiation used for treating cancer in all patients. To identify the genetic defect responsible for this multifaceted disorder, and to provide effective carrier detection, we performed a genetic linkage analysis of 31 families with AT-affected members. This has allowed us to localize a gene for AT to chromosomal region 11q22-23.

Ataxia Telangiectasia↗