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Biomedical subjects

C M Steel

Publications and source records attributed to C M Steel.

At least 109 records · Page 6Linked to original sources
PubMed1990

p53 gene mRNA expression and chromosome 17p allele loss in breast cancer.

p53 messenger RNA expression was examined using a cDNA probe in 76 fresh primary breast tumour specimens, 15 of which came from patients treated with toxoxifen prior to surgery. A 2.8 kb mRNA for p53 was expressed in 43 of the 76 specimens. In 19 tumours the levels were similar to those seen in non-malignant (reduction mammoplasty) breast tissue, but in 24 tumours over-expression of mRNA for p53, approaching that seen in three breast cancer cell lines, was found. The cell lines MCF-7, T-47D and MDA-MB-231 expressed three p53 mRNA species of about 2.8 kb and a forth of 1.6 kb. Increased mRNA expression for p53 correlated (P less than 0.05) with loss of genetic material from the short arm of chromosome 17 as demonstrated by allele loss with the VNTR probe YNZ 22.1. There was also statistically significant correlation between increased p53 mRNA expression and low oestrogen receptor protein content in the tumours (P less than 0.05), but not with other clinical parameters. The findings support the view that p53 is involved in breast tumour biology, and suggest that its role may be complex.

Alleles↗
PubMed1990

Gene expression in oestrogen-dependent human breast cancer xenograft tumours.

Xenograft tumours from an oestrogen-dependent human breast cancer cell line MCF-7 have been established and characterised in thymectomised, irradiated female CBA strain mice. There was evidence for selection in xenografts of a subpopulation of MCF-7 cells with an altered pattern of gene expression as measured by mRNA levels compared with the original cells in vitro. Tumorigenicity increased significantly on repeated animal passage but oestrogen dependence was retained. Following injection of the mice with oestrogen, mitosis was induced in the tumour cells with associated increases in thymidine uptake and percentage of cells in S-phase. In accord with these changes, c-myc and p53 expression were increased and TGF-beta was suppressed. Thereafter the expression of the c-myc and p53 genes fell whilst that of the TGF-beta gene was induced as the oestrogenic-stimulus declined. The oestrogen-regulated mRNA pS2 showed a biphasic response to oestrogen and levels declined as the serum oestrogen fell to undetectable levels. This xenograft system demonstrates that changes in transcription of oncogenes, growth factor and oestrogen-regulated genes can be detected in vivo in response to oestrogen. It thus provides an in vivo model for studies of the biochemical and molecular basis for therapeutic manipulation of hormone-sensitive human breast cancer.

Animals↗
PubMed1990

Genetic linkage map of six polymorphic DNA markers around the gene for familial adenomatous polyposis on chromosome 5.

A genetic linkage map of six polymorphic DNA markers close to the gene (APC) for familial adenomatous polyposis (FAP) on chromosome 5q is reported. One hundred fifty-five typed members of nine FAP kindred provided more than 90 meioses for linkage analysis. A number of crucial recombination events have been identified which are informative at three or more loci, allowing confident ordering of parts of the map. There was no evidence of genetic heterogeneity, with all families showing linkage of at least one chromosome 5 marker to the gene. Recombination data and two-point linkage analysis support a locus order of centromere-pi 227-C11P11-ECB27-L5.62-APC-EF5.44-YN5.48-telomer e, although EF5.44 could lie in the interval L5.62-APC or ECB27-L5.62. No recombinants were identified between APC and either EF5.44 or YN5.48, but published deletion mapping in colorectal carcinomas and linkage analysis in FAP suggest that YN5.48 is 1-3 cM from APC. The present study suggests that YN5.48 and L5.62 delineate a small region of chromosome 5 within which the EF5.44 locus lies very close to the APC gene. These data not only allow use of flanking markers for presymptomatic diagnosis of FAP but also provide a high-density map of the region for isolation of the APC gene itself and for further assessment of the role of chromosome 5 deletions in the biology of sporadic colorectal cancer.

Adenomatous Polyposis Coli↗
PubMed1990

Allele losses on chromosome 17 in human epithelial ovarian carcinoma.

16 epithelial ovarian carcinomas (12 serous, 2 mucinous and 2 endometrioid) and 2 benign ovarian adenomas were studied using recombinant DNA technology to compare loci on chromosome 17 in germ-line and tumour DNA. Four polymorphic probes mapping to 17p and one mapping to 17q were used. There was a high frequency of allele loss on 17q/(77%) and a slightly lower frequency on 17p (69%). These findings probably indicate loss of tumour suppressor genes which are of fundamental importance in the genesis or progression of epithelial ovarian carcinomas.

Adenoma↗
PubMed1989

Linkage analysis in familial adenomatous polyposis: order of C11P11 (D5S71) and pi 227 (D5S37) loci at the apc gene.

Linkage analysis with DNA probes C11P11 and pi 227 is reported in six Scottish families with familial adenomatous polyposis. Two families were informative for C11P11 and all six were at least partly informative for pi 227. Two C11P11-apc and two pi 227-apc recombinants were identified and one of these was recombinant for both C11P11-apc and pi 227-apc. A further possible combined C11P11-apc and pi 227-apc recombination event was also identified. Peak lod score for linkage of C11P11 to apc was 5.80 at a recombination fraction (theta) of 0.069 (95% probability limits 0.012-0.191) and for linkage of pi 227 to apc was 3.19 at theta = 0.110 (95% probability limits 0.023-0.286). Peak lod score for linkage of C11P11 to pi 227 was 1.79 at theta = 0.00. The data support a gene order of pi 227-C11P11-apc.

Chromosomes, Human, Pair 5↗
PubMed1989

Human immunodeficiency virus detection: correlation with clinical progression in the Edinburgh haemophiliac cohort.

HIV p24 antigenaemia and virus detection in cultures of peripheral blood lymphocytes were examined in 16 of 18 haemophiliacs infected with HIV by a single batch of Scottish National Blood Transfusion Service factor VIII concentrate. Six (38%) had p24 antigenaemia and 11 (69%) had positive lymphocyte cultures. All seven patients with serious HIV disease (CDC group IV) had positive lymphocyte cultures whereas four (57%) had p24 antigenaemia. Four of nine (44%) patients with asymptomatic HIV disease (CDC groups II and III) had positive cultures and two (22%) had p24 antigenaemia. Twenty-eight of 36 samples from the symptomatic group were HIV culture positive compared with nine of 30 samples from the asymptomatic group (P less than 0.001). None of 14 antibody negative haemophiliacs who also received the implicated batch of factor VIII had p24 antigenaemia or positive HIV cultures. The ability to detect HIV in cultured lymphocytes correlates with the clinical severity of HIV disease in this cohort.

AIDS Serodiagnosis↗
PubMed1989

Vertical transmission of HIV: a prospective study.

Forty nine infants of HIV seropositive women were followed up for a median of 24 months, together with 24 controls. The infection status of 11 index children under 18 months of age was indeterminate; 34 were presumed uninfected while four showed clinical and laboratory evidence of HIV disease. Based on current definitions of HIV infection and excluding children under 18 months old as well as those who had not been studied from birth, two out of 28 children were infected. The estimated rate of maternofetal transmission was therefore 7.1%. In children with proved infection, sequential laboratory data showed that hypergammaglobulinaemia was noted as early as 6 months and often predated clinical signs. This observation, in the presence of non-specific clinical findings, was helpful in alerting the paediatrician to a diagnosis of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Suppression of malignancy in human lymphoid cell hybrids: the role of differentiation.

Human somatic cell hybrids were generated from fusions between a tumorigenic B-cell line, and mononuclear cells from a patient with low-grade B-cell lymphoma in which the neoplastic cells largely corresponded to cells at an intermediate stage of differentiation. The resulting hybrids and the parent cells were immunophenotyped, karyotyped and genotyped in an effort to determine whether the stage of B-cell development of the fusion partners was important in the suppression of malignancy. The majority of hybrids demonstrated suppression of tumorigenicity as measured in immunodeprived mice. Chromosome markers and immunoglobulin gene rearrangements found in the patient's neoplastic cells were also present in several of the hybrids. One of the tumorigenic hybrids retained specific chromosomes also found in the non-tumorigenic hybrids, but demonstrated an immunophenotype and genotype possibly associated with a subset of early B-cells. In the non-tumorigenic hybrids that retained most of the chromosomes from both parents there was evidence of plasmacytoid differentiation. These results suggest that the ability of B-lymphocytes to suppress malignancy in human lymphoid hybrids may be dependent on the corresponding stage of normal B-cell ontogeny, and that suppression is associated with differentiation.

B-Lymphocytes↗
PubMed1989

High frequency of APC loss in sporadic colorectal carcinoma due to breaks clustered in 5q21-22.

Familial adenomatous polyposis is transmitted by a gene (APC) located within 5q21-22. Hemizygous loss of at least a part of 5q has been reported in 19-36% of sporadic colorectal carcinomas. This suggests that an anti-oncogene is located on that chromosome arm, but the probes used previously gave little information on the status of APC in the tumours. Using DNA probes homologous to polymorphic sequences flanking and close to the APC locus we show that more than half of a large series of carcinomas had lost at least one flanking allele. Mapping of allele losses provides data that imply clustering of breakpoints in a 10-15 megabase region around APC. The commonest chromosome defect responsible for APC loss was interstitial deletion. Mitotic recombination or partial arm loss were less frequent mechanisms. Whole chromosome loss was rare. This pattern contrasts with that reported in acquired homozygosity at other anti-oncogene loci in sporadic tumours and implies that APC loss is an early event in colorectal carcinogenesis. This view is also supported by the observations that 5q21-22 loss occurs with similar frequency in DNA diploid and DNA aneuploid tumours, and also in tumours at all clinical stages of progression.

Adenoma↗
PubMed1988

Allele loss on short arm of chromosome 17 in breast cancers.

Tumour and blood leucocyte DNA from a consecutive series of patients with primary breast cancer was probed to detect deletions at six polymorphic loci in tumour tissue. The highest frequency of allele loss (61%) was found with the probe YNZ22, which detects a sequence on the short arm of chromosome 17 (at p13.3). The previously reported loss of alleles at the Harvey ras locus (11p14) in about 20% of breast tumours was confirmed. The putative breast tumour suppressor gene on 17p may be the same as that already noted for colon and lung cancers and it is suggested that deletion of this gene is one of a cumulative series of lesions involving genetic changes in the evolution of breast cancer. The findings identify chromosome 17p as a candidate region for linkage studies in breast cancer families.

Alleles↗
PubMed1988

HLA haplotype A1 B8 DR3 as a risk factor for HIV-related disease.

Of 32 patients exposed to a single batch of factor VIII contaminated with human immunodeficiency virus (HIV), 18 became antibody positive. Serial T cell subset analyses over the succeeding four years have shown a progressive decline in circulating T4 cells in those 18 but no change in the 14 who remain seronegative. 2 of the seroconverters have died and a further 7 have symptoms attributable to HIV infection. In the group as a whole, the HLA haplotype A1 B8 DR3 was weakly associated with an increased risk of seroconversion on exposure to the virus while, in those who seroconverted, it was strongly associated with a rapid decline in T4 cells and development of HIV-related symptoms within four years of infection.

Adult↗