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P Chapman

Publications and source records attributed to P Chapman.

At least 55 records · Page 3Linked to original sources
PubMed1994

Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system. The MSH2 genomic locus has been cloned and shown to cover approximately 73 kb of genomic DNA and to contain 16 exons. The sequence of all the intron-exon junctions has been determined and used to develop methods for analyzing each MSH2 exon for mutations. These methods have been used to analyze two large HNPCC kindreds exhibiting features of the Muir-Torre syndrome and demonstrate that cancer susceptibility is due to the inheritance of a frameshift mutation in the MSH2 gene in one family and a nonsense mutation in the MSH2 gene in the other family.

Amino Acid Sequence↗
PubMed1994

Genetic linkage in Muir-Torre syndrome to the same chromosomal region as cancer family syndrome.

The Muir-Torre syndrome, in which sebaceous gland tumours occur in association with internal malignancy, is inherited as an autosomal dominant disorder. Many features of the syndrome are similar to those of the Lynch II cancer family syndrome, and thus the two disorders might share a common genetic basis. We typed two large families with DNA markers on chromosome 2p around D2S123, a site recently shown to be linked to the Lynch II syndrome. LOD scores at this locus demonstrated significant and tight linkage to D2S123, suggesting that defects in the same gene might give rise to both syndromes.

Adult↗
PubMed1994

Regionally clustered APC mutations are associated with a severe phenotype and occur at a high frequency in new mutation cases of adenomatous polyposis coli.

Germline mutation in APC at 5q21-22 results in the dominantly inherited syndrome adenomatous polyposis coli (APC). Somatic mutation in this gene is an early event in colorectal tumourigenesis. Both types of mutation are concentrated in the 5' half of exon 15. We have used single strand conformational polymorphism (SSCP) and heteroduplex analysis to screen for variants in this region of the gene in a total of 45 affected but unrelated individuals. Eighteen patients had no family history of the disease; of these 11 were classified as having a severe phenotype, based on an early age at presentation or cancer development. This compared with 6 of 27 familial cases. A 5 bp deletion at codon 1309 reported to occur in 10-15% of unselected APC patients worldwide, was found in 5 of the 18 new mutation cases and 4 of the 27 familial cases: all nine were classed as severe. A further 3 new mutations and 1 familial mutation were located downstream from codon 1309, these individuals similarly being classed as phenotypically severe. In contrast all of the APC mutations detected in affected individuals with an average phenotype were located prior to codon 1309. The frequent association of a severe phenotype with fresh mutation may explain the apparent conflict of a high mutation rate (20-30%) in a condition, which on average, is lethal at a post-reproductive age.

Adenomatous Polyposis Coli↗
PubMed1993

Germline rearrangement of MCC and APC detected by pulsed field gel electrophoresis and fluorescent in situ hybridization.

Pulsed field gel electrophoresis was carried out on lymphocyte DNA obtained from ten patients with the inherited premalignant condition adenomatous polyposis coli and a similar number of control samples to search for large scale molecular rearrangements in the vicinity of the APC locus. DNA from one patient showed a rearranged pattern which was interpreted as evidence for an inversion of approximately 150 kb, changing the transcriptional orientation of the neighbouring MCC gene and bringing it closer to APC. Such an interpretation was supported by fluorescent in situ hybridization data.

Adenomatous Polyposis Coli↗
PubMed1992

Training--have your cake and eat it.

Training programmes which take staff away from the workplace for long periods are unpopular with managers. In this special report we look at developments in on-the-job training: how open learning has become the main growth area in staff development; why national vocational qualifications aren't yet living up to the ideal; how Cornwall providers have replaced 'sitting beside Nellie' with more effective IT training.

Inservice Training↗
PubMed1992

An intrachromosomal insertion causing 5q22 deletion and familial adenomatous polyposis coli in two generations.

We report familial adenomatous polyposis coli (FAPC) with epidermoid cysts, osteomata, and areas of congenital hypertrophy of the retinal pigment epithelium (CHRPEs) in a male patient and his maternal aunt, both of whom suffered a mild to moderate degree of mental handicap. Both had an interstitial deletion of the long arm of chromosome 5 (del(5)(q22q23.2)). Two other normal family members had the underlying direct insertion of chromosome 5(dir ins(5)(q31.3q22q23.2)). Molecular genetic and fluorescent hybridisation studies have shown that loci D5S37 and D5S98 are outside the deletion whereas loci detected by probes EF5.44 and YN5.48 are lost. As expected, the molecular analyses indicate loss of one allele at the MCC and APC loci. The APC gene is located within band 5q22. Familial direct insertions should be considered as a cause of recurrent microdeletion syndromes.

Adenomatous Polyposis Coli↗
PubMed1991

Is iliac node clearance necessary for stage II melanoma?

In a retrospective review (1970-1983), survival following block dissection of the groin was compared in two groups with clinical stage II melanoma. Twenty patients under one surgeon had ilioinguinal (high) block dissection, and 22 patients under another surgeon had inguinal (low) block dissection. The high block 5-year survival was 40 percent, and the low block 5-year survival was 35 percent. There was no statistical difference between groups on life-table or log-rank test analysis. It is concluded that the extent of groin dissection has no effect on survival of stage II melanoma.

Female↗
PubMed1991

Linkage analysis in adenomatous polyposis coli: the use of four closely linked DNA probes in 20 UK families.

Linkage analysis was carried out on 20 unselected UK families segregating for adenomatous polyposis coli (APC) using four closely linked DNA probes. Significant lod scores were obtained between APC and three markers: pi 227 (D5S37) theta = 0.16; C11p11 (D5S71) theta = 0.10; and YN5.48 (D5S81) theta = 0.00. The fourth, ECB27 (D5S98), gave low lod scores. The APC gene showed linkage with at least one of the probes used in all families, which is in agreement with previous publications. Combined lod scores are now sufficiently high to allow the use of these probes in presymptomatic diagnosis. Despite the fact that 61% of persons at risk were informative for at least one DNA marker, only 15% were informative with flanking probes. One prenatal diagnosis was performed where the initial request had been for sterilisation.

Adenomatous Polyposis Coli↗
PubMed1991

The UK Northern region genetic register for familial adenomatous polyposis coli: use of age of onset, congenital hypertrophy of the retinal pigment epithelium, and DNA markers in risk calculations.

A polyposis register has been established in the Northern Region of England. A total of 48 families with 71 living affected subjects has been identified during the first three years of operation, a prevalence of 2.29 x 10(-5). Indirect ophthalmoscopy identifies the majority of gene carriers by showing multiple areas of congenital hypertrophy of the retinal pigment epithelium (CHRPE). The absence of this sign in families limits its value where a relative with CHRPE has not been identified. Combining eye examination with data on age of onset and linked DNA markers is highly effective in carrier exclusion; 38% of 528 first, second, and third degree relatives had their carrier risk reduced to less than 1 in 1000. Even with such assurance many subjects will request continued bowel screening at a reduced frequency. Little interest has been shown in prenatal diagnosis. The principal value of a genetic register with domiciliary nurse visiting is the reduction in early mortality among unrecognised gene carriers.

Adenomatous Polyposis Coli↗
PubMed1990

Tissue expansion: a unit review of non-scalp, non-breast expansion.

The results in 76 tissue expansions of sites other than the breast and scalp in 56 patients are presented. The overall failure rate was 12%, being particularly high in the arm (31%) and low in the leg (0%). Details of the technique used and their relevance to success are discussed.

Adolescent↗
PubMed1990

Biochemical analysis of normal articular cartilage in horses.

Articular cartilage specimens from the distal articular surface of 32 radiocarpal bones from 24 2- to 5-year-old horses were analyzed. The total collagen content was determined on the basis of the 4-hydroxyproline content, using a colorimetric method. A method for estimating the proportions of types-I and -II collagen by measuring spectrophotometric densities of specific cyanogen bromide peptide bands from mixtures of types-I and -II collagen on sodium dodecyl sulfate-polyacrylamide gels was used. The cyanogen bromide peptides representative of each collagen types-I and -II were identified. The peptide ratios were then computed for each of several standards of type-I and -II mixtures. A standard curve was derived from the correlation between these ratios and the corresponding proportions of type-II collagen in standard mixtures. Galactosamine and glucosamine content (hexosamines) were measured by ion chromatography. The galactosamine-to-glucosamine ratio, chondroitin sulfate and keratan sulfate values, and total glycosaminoglycan content were derived from the measured hexosamine content. The total collagen content averaged 556 mg/g (55.6 mg/100 mg) of tissue (dry weight, [dw]). Type-II collagen was the major collagen type in normal articular cartilage specimens. The ratio of the area under the alpha 1 (II)CB10 peak to the area under the alpha 1 (I)CB 7,8 + alpha 1 (II)CB11 peak was a second-order polynomial function of the proportion of type-II collagen in the specimens. The mean galactosamine and glucosamine content were 20.6 mg/g and 7.9 mg/g (dw), respectively. The mean galactosamine-to-glucosamine ratio was 3.74 +/- 0.62.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗