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M Parkes

Publications and source records attributed to M Parkes.

15 recordsLinked to original sources
PubMed1996

Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12.

Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200/100,000 (ref. 1). Epidemiological studies, particularly concordance rates in twin pairs and siblings, strongly implicate genetic susceptibility in the pathogenesis of CIBD. In fact, the relative contribution of genetic factors to the pathogenesis of CD may be greater than in schizophrenia, asthma or hypertension, and at least equivalent to that in insulin-dependent diabetes. Systematic screening of the entire human genome now provides a strategy for the identification of susceptibility genes in complex polygenic disorders. We undertook a two-stage genome search for susceptibility genes in inflammatory bowel disease involving 186 affected sibling pairs from 160 nuclear families. We provide strong evidence for the presence of susceptibility loci for both CD and UC on chromosome 3, 7 and 12. We obtained the highest lod score (5.47; P = 2.66 x 10(-7) with the marker D12S83 and lod scores of 3.08 and 2.69 for D7S669 and D3S1573, respectively. Our data suggest that CD and UC are closely related, but distinct, polygenic disorders that share some, but not all, susceptibility genes.

Chromosome Mapping↗
PubMed1996

Cytokine gene polymorphisms in inflammatory bowel disease.

BACKGROUND: Concordance rates in siblings and twins provide strong evidence that genetic susceptibility is important in the pathogenesis of inflammatory bowel disease. The number and identity of susceptibility genes is largely uncertain. Cytokine genes are attractive candidate loci. AIMS: To study allelic frequencies of polymorphisms of the interleukin-1 receptor antagonist (IL-1RA) gene and the tumour necrosis factor alpha gene in patients with inflammatory bowel disease. SUBJECTS: One hundred and twenty nine North European caucasoid patients with ulcerative colitis, 120 patients with Crohn's disease, and 89 healthy controls. METHODS: Genotyping was performed by polymerase chain reaction. A variable number of tandem repeats (VNTR) in the IL-1RA gene and a single base pair polymorphism in the TNF alpha gene promoter region (TNF-308) were analysed. RESULTS: No significant differences in IL-1RA VNTR allelic frequencies were noted between Crohn's disease (allele 1: 72.6%, allele 2: 24.7%, allele 3: 2.6%), ulcerative colitis (72.6%, 24.3%, 3.1%, respectively), and controls (76.9%, 20.8% and 2.3%). Some 42.4% of patients with ulcerative colitis and 43.4% patients with Crohn's disease were carriers of allele 2, compared with 34.8% healthy subjects. The TNF2 allele was modestly reduced in Crohn's disease (13.2%), compared with healthy subjects (21.3%; p = 0.04), and ulcerative colitis (21.6%). CONCLUSIONS: The associations demonstrated are modest: these polymorphisms are unlikely to be important determinants of overall disease susceptibility.

Adult↗
PubMed1992

A comparison of the clearance of ovine and human corticotrophin-releasing hormone (CRH) in man and sheep: a possible role for CRH-binding protein.

A specific binding protein for human corticotrophin-releasing hormone (hCRH), which does not bind to the ovine hormone (oCRH), has recently been demonstrated in human plasma. No such binding protein has been found in sheep plasma. We have investigated the half-life of human and ovine CRH in man and in sheep. Peptides were measured directly in plasma with two-site immunoradiometric assays, as these assays are unaffected by the presence of inactivated peptide fragments. In man, the half-life of hCRH (30.5 +/- 3.3 min; mean +/- S.E.M.) was significantly (P less than 0.001) less than that of oCRH (42.8 +/- 6.4 min). In sheep, there was no significant difference between the half-life of hCRH (46.5 +/- 7.2 min) and that of oCRH (39.8 +/- 10.1 min); these half-lives were also significantly (P less than 0.001) longer than that of hCRH in man. One possible explanation for the shorter half-life of hCRH in man is that the clearance of hCRH is enhanced by CRH-binding protein, although other binding proteins often have the opposite effect. Peak ACTH and cortisol responses occurred earlier in sheep than in man, although no differences were found in the response times to oCRH or hCRH within either species. The responses were more sustained in sheep than in man, and the previously reported biphasic response was only seen in some of the sheep and not in man. Absolute responses to either peptide were greater in sheep than in man; however, in man an 8.1-fold rise in ACTH was measured in response to oCRH, while hCRH gave a significantly (P = 0.043) smaller 4.4-fold response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1980

The intervention of a modulator with learning disabled children.

Tested the role of a child modulator, an investigator, and coordinator of services for learning disabled children. Ninety regular third- and fourth- grade children with average intelligence were selected from a population of 1,030 children on the basis of low scores on the Pupil Rating Scale and at least one of four Metropolitan Achievement subtests and were assigned randomly to one of three groups. The first group received the services of the modulator for a 6-month period, while the respective schools were informed of the teachers' ratings and achievement test scores for the second group, and the third group was an untreated control. In addition to the selection procedures, school grades, the Piers-Harris Self-Concept Scale and the Connors Parents Questionnaire were completed before and after treatment. The results showed teacher ratings and achievement score changes for all groups with the modulation group superior only in teacher ratings of Personal-Social behavior. Follow-up testing 18 months later between the modulated and school informed group within the Piers-Harris Scale and ratings by unbiased teachers reflected numerous differences, which suggests a growing self-confidence in the modulated Ss. The positive usefulness of this form of intervention in meeting the general needs of the child and in treating the concomitants of school failure are discussed.

Canada↗
PubMed1977

Hair element content in learning disabled children.

Hair samples from 31 learning disabled and 22 normal children were analyzed for content of 14 elements. Significant group differences were determined and a discriminant function was completed which separated the groups with 98 per cent accuracy. Elevated lead and cadmium content in the learning disabled group is viewed as being of particular importance.

Cadmium↗
PubMed1976

Further experience with the pinch technique for repair of eyelid deformities.

The pinch technique has been found to be useful in repairing cosmetic eyelid deformities. However, the local anesthetic containing hyaluronidase must be injected only in small amounts and only into the subcutaneous space. Scar tissue and skin that is firmly adherent to underlying muscle do not yield a satisfactory ridge, and therefore, the pinch technique should not be used. Ectropion can be predicted by the observation of eversion of the lid margin when even only minimal skin is pinched, and impending ectropion can be discovered by our "lean forward and look up" maneuver. An ectropion repair can then be combined with the blepharoplasty surgical operation. The pinch technique has also been found useful when upper and lower blepharoplasties are joined laterally to elevate the lateral canthus and eliminate "crow's feet." One component of a repair of trichiasis also involves the use of the pinch technique.

Anesthesia, Local↗