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H J Thomas

Publications and source records attributed to H J Thomas.

At least 19 recordsLinked to original sources
PubMed2002

[Evaluation of olfactory stimuli by depressed patients].

Anhedonia, a cardinal sign of depression, is discussed to originate from a transmitter dysbalance in the central dopaminergic reward system. This system involves neuroanatomically many structures of the olfactory system. Hence the question arises whether anhedonia can be quantified when depressive patients judge smells hedonically. Sensory evaluation of olfactory stimuli by 16 depressive patients was compared that of an age-matched control group. In the group comparison, mono- and birhinal sensory thresholds as well as judgment of intensity were not significantly different. For four of the eight smells, the hedonic judgements were found to be identical between the group of depressives and controls, with the remaining smells not significantly different. There were no differences in the consistency of ranking of smells. In a longitudinal (test-retest) assessment there were again no differences in intensity, familiarity, and hedonic quality of the smells. The findings suggest that changes in the dopaminergic transmitter balance during the state of depression causing anhedonia affect neither olfactory perception nor the hedonic judgement of smells. Contrary to the clinical picture, anhedonia thus seems not to arise at the level of sensory perception yet but should be considered a more complex construct of disturbed central processing.

Adult↗
PubMed2001

Review article: the prevention of colorectal cancer.

Colorectal cancer is a leading cause of cancer mortality in the industrialized world. Survival remains poor because most cases are diagnosed at an advanced stage. It is a preventable disease as colorectal cancers usually develop slowly from an identifiable precursor lesion, the adenoma. The existing strategies for colorectal cancer prevention include dietary prevention, chemoprevention and endoscopic intervention. The exact relationship between diet, particularly fibre, and colorectal cancer remains unclear, with the most recent studies suggesting that dietary fibre may not decrease colorectal cancer risk as previously thought. Non-steroidal anti-inflammatory drugs have been shown to have a protective effect against colorectal cancer, but the adverse effect profile of the non COX-2 selective drugs, particularly the risk of gastrointestinal haemorrhage, precludes their widespread use. There is increasing evidence that colorectal cancer incidence and mortality can be decreased from endoscopic polypectomy and early detection of cancer. Faecal occult blood testing in the general population ('average-risk') has been shown in randomized trials to decrease mortality from colorectal cancer by 15--33%. Long-term results of randomized trials of the effectiveness of flexible sigmoidoscopy and colonoscopy screening in the general population are awaited. Targeting high risk individuals may also be an effective and efficient way to decrease the colorectal cancer burden. As many as 15--30% of colorectal cases may be due to hereditary factors. Individuals with one or two direct relatives affected are at moderate risk for colorectal cancer (empirical lifetime mortality from colorectal cancer approximately 10%) and approximately 2--3% of cases arise in individuals harbouring highly penetrant autosomal dominant mutations, which puts them at high-risk for colorectal cancer. Surveillance colonoscopy is offered to individuals at moderate and high risk for colorectal cancer.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

HLA-B polymorphism affects interactions with multiple endoplasmic reticulum proteins.

To explore the nature of amino acid substitutions that influence association with TAP, we compared a site-directed mutant of HLA-B*0702 (Y116D) to unmutated HLA-B7 in regard to TAP interaction. We found that the mutant had stronger association with TAP, and, in addition, with tapasin and calreticulin. These data confirm the importance of position 116 for TAP association, and indicate that (1) an aspartic acid at the 116 position can facilitate the interaction, and (2) association with tapasin and calreticulin is affected along with TAP. Furthermore, we tested three natural subtypes of HLA-B15, and found that a B15 subtype with a tyrosine at position 116 (B*1510) was strongly associated not only with TAP, but also with tapasin and calreticulin. In contrast, two B15 subtypes with a serine at position 116 (B*1518 and B*1501) exhibited very little or no association with any of these proteins. Thus, very closely related HLA-B subtypes can differ in regard to interaction with the entire assembly complex. Interestingly, when their surface expression was tested by flow cytometry, the HLA-B15 subtypes with little to no detectable intracellular assembly complex association had a slightly, yet consistently, higher level of the open heavy chain form than did the B15 subtype with intracellular assembly complex association. These data suggest that the relatively low strength or short length of interaction between endoplasmic reticulum proteins and natural HLA class I molecules can decrease their surface stability.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Inherited susceptibility to colorectal adenomas and carcinomas: evidence for a new predisposition gene on 15q14-q22.

BACKGROUND & AIMS: The aim of this study was to evaluate the role of known colorectal adenoma and carcinoma susceptibility genes and to locate a novel susceptibility gene in an Ashkenazi family (SM1311) with dominantly inherited predisposition to colorectal adenomas and carcinomas. METHODS: Clinicopathologic and family history data were collected. Genetic linkage and mutational analyses were used to investigate the genetic basis of the family's disease. RESULTS: Affected members of SM1311 develop multiple tubular, villous, tubulovillous, and/or serrated colorectal adenomas throughout the large bowel, and some develop colon carcinoma. There are no extracolonic features clearly associated with disease in SM1311. We have shown that the family's phenotype does not result from APC mutations (including the I1307K variant) or from genetic changes in the other known genes that predispose to colon cancer. Using genetic linkage analysis, supplemented by allele loss in tumors, we have provided evidence for a new colorectal cancer susceptibility gene, CRAC1 (colorectal adenoma and carcinoma), mapping to chromosome 15q14-q22. CONCLUSIONS: We provide evidence for a novel colorectal adenoma and carcinoma susceptibility gene on chromosome 15q14-q22. Further studies are needed to confirm this localization and to evaluate the contribution of CRAC1 to this disease.

Adenoma↗
PubMed1999

Microsatellite instability in benign skin lesions in hereditary non-polyposis colorectal cancer syndrome.

The coexistence of cutaneous and extra-cutaneous malignancies within one family could be explained by shared genetic mechanisms such as common tumor suppressor gene mutations or oncogene activation, as well as mutations in DNA repair genes. Hereditary non-polyposis colorectal cancer syndrome (HNPCC) and its variant Muir-Torre syndrome (MTS) are caused by germline DNA mismatch repair gene mutations. Colonic and endometrial tumors from HNPCC patients exhibit microsatellite instability (MSI), as do sebaceous lesions in MTS. We recruited individuals from cancer prone families to determine if MSI is found in benign and malignant skin lesions and to assess whether MSI in the skin is predictive of genomic instability with susceptibility to tumors characteristic of HNPCC. One hundred and fifteen benign, dysplastic, and malignant skin lesions from 39 cancer prone families were analyzed. Thirteen benign skin lesions from three individuals belonging to two HNPCC pedigrees showed MSI. No mutations in hMSH2 and hMLH1 were found in two of the three individuals with RER + skin lesions. We found MSI in non-sebaceous non-dysplastic skin lesions in HNPCC pedigrees. MSI was not found in skin lesions within other family cancer syndromes. These results have important clinical implications as the detection of MSI in prevalent readily accessible skin lesions could form the basis of noninvasive screening for HNPCC families. It may also be a valuable tool in the search for new mismatch repair genes.

Adenoma↗
PubMed1999

Grapes to wine.

Explore the source record for details and available documents.

Forecasting↗
PubMed1998

The APC variants I1307K and E1317Q are associated with colorectal tumors, but not always with a family history.

Classical familial adenomatous polyposis (FAP) is a high-penetrance autosomal dominant disease that predisposes to hundreds or thousands of colorectal adenomas and carcinoma and that results from truncating mutations in the APC gene. A variant of FAP is attenuated adenomatous polyposis coli, which results from germ-line mutations in the 5' and 3' regions of the APC gene. Attenuated adenomatous polyposis coli patients have "multiple" colorectal adenomas (typically fewer than 100) without the florid phenotype of classical FAP. Another group of patients with multiple adenomas has no mutations in the APC gene, and their phenotype probably results from variation at a locus, or loci, elsewhere in the genome. Recently, however, a missense variant of APC (I1307K) was described that confers an increased risk of colorectal tumors, including multiple adenomas, in Ashkenazim. We have studied a set of 164 patients with multiple colorectal adenomas and/or carcinoma and analyzed codons 1263-1377 (exon 15G) of the APC gene for germ-line variants. Three patients with the I1307K allele were detected, each of Ashkenazi descent. Four patients had a germ-line E1317Q missense variant of APC that was not present in controls; one of these individuals had an unusually large number of metaplastic polyps of the colorectum. There is increasing evidence that there exist germ-line variants of the APC gene that predispose to the development of multiple colorectal adenomas and carcinoma, but without the florid phenotype of classical FAP, and possibly with importance for colorectal cancer risk in the general population.

Adult↗
PubMed1997

Absence of toxicity of oats in patients with dermatitis herpetiformis.

BACKGROUND: People with gluten sensitivity should avoid foods containing wheat, rye, and barley, but there has been debate about whether they should avoid oats. Although patients with celiac disease have recently been shown to tolerate oats, less is known about the effects of oats on patients with dermatitis herpetiformis. METHODS: We studied seven men and three women (mean age, 58 years) with biopsy-confirmed dermatitis herpetiformis. They had followed a strict gluten-free diet for a mean of 15.8 years, which controlled their rash and enteropathy. The patients added oats that were not contaminated with gluten to their diets for 12 weeks (mean [+/-SD] daily intake, 62.5+/-10.8 g). RESULTS: None of the patients had any adverse effects. Serologic tests for antigliadin, antireticulin, and antiendomysial antibodies were negative before oats were introduced into the diet and after they were discontinued. Villous architecture remained normal: the mean (+/-SE) ratio of the height of villi to the depth of crypts was 3.59+/-0.11 before the diet and 3.71+/-0.09 afterward (normal, 3 to 5), and the mean enterocyte heights were 31.36+/-0.58 microm and 31.75+/-44 microm, respectively (normal range, 29 to 34). Duodenal intraepithelial lymphocyte counts all remained within normal limits (mean, 13.8+/-1.03 per 100 enterocytes before the diet and 14.2+/-1.2 per 100 enterocytes afterward; normal range, 10 to 30). Dermal IgA showed no significant changes. CONCLUSIONS: Patients with dermatitis herpetiformis can include moderate amounts of oats in their gluten-free diets without deleterious effects to the skin or intestine.

Adult↗
PubMed1997

Clinical and molecular features of the hereditary mixed polyposis syndrome.

BACKGROUND & AIMS: Various inherited syndromes predispose to the development of colonic juvenile polyps and colorectal cancer, with potential importance for sporadic tumorigenesis. This study describes features of a possibly new syndrome of atypical juvenile polyps and other colonic tumors and compares these features with those of known gastrointestinal tumor syndromes. METHODS: A large family, St. Mark's family 96, with a tendency to develop colonic polyps of mixed histological types is described. Genetic linkage to known polyposis syndromes has been tested. RESULTS: Adenomatous and hyperplastic polyps occur in affected members of the family, although the characteristic lesion is an atypical juvenile polyp. Some affected individuals have developed polyps of more than one type, and individual polyps may contain features of more than one histological type. Polyps can undergo malignant change. Typically, fewer than 15 polyps are found at colonoscopy and there is no extracolonic disease associated with the development of polyps. The family's polyps seem to be inherited in an autosomal-dominant fashion, but the disease is probably unlinked to candidate loci with importance in colorectal tumorigenesis, such as APC, hMSH2, and hMLH1. CONCLUSIONS: We term this family's disease hereditary mixed polyposis syndrome (HMPS). Although mutations in the putative HMPS gene may be responsible for syndromes such as juvenile and Peutz-Jeghers polyposes, HMPS may also be a distinct disease.

Adenomatous Polyposis Coli↗
PubMed1996

Genetic mapping of hereditary mixed polyposis syndrome to chromosome 6q.

Hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas. HMPS appears to be inherited in an autosomal dominant manner. Genetic linkage analysis has been performed on a large family with HMPS. Data did not support linkage to the APC locus or to any of the loci for hereditary nonpolyposis colorectal cancer. Evidence that the HMPS locus lies on chromosome 6q was, however, provided by significant two-point LOD scores for linkage between HMPS and the D6S283 locus. Analysis of recombinants and multipoint linkage analysis suggested that the HMPS locus lies in a 4-cM interval containing the D6S283 locus and flanked by markers D6S468 and D6S301.

Adenoma↗
PubMed1994

Structure-based design of inhibitors of purine nucleoside phosphorylase. 4. A study of phosphate mimics.

9-(3,3-Dimethyl-5-phosphonopentyl)guanine was synthesized and found to be a potent inhibitor of purine nucleoside phosphorylase (PNP) (IC50 = 44 nM). A number of other functional end groups were investigated as phosphate mimics attached to the 9-position of guanine by this same alkyl side chain, which provided a sensitive method for the detection of any interaction of these groups with the phosphate binding site of PNP. Both the sulfonic acid (compound 13) and the carboxylic acid (compound 15) end groups interact significantly with the phosphate binding site, but in different ways, as determined by X-ray crystallographic analysis of the complexes. The sulfonic acid of 13, which binds about one-fourth as tightly as the phosphonate 12, binds in the phosphate subsite much like the phosphonic acid. The carboxylic acid, the interaction of which is much weaker, turns away from the center of the phosphate binding site to form hydrogen bonds with Ser 200 and Met 219. Thus, the only phosphate mimics that bind like phosphate itself are themselves highly ionic, probably with limited ability to penetrate cell membranes.

Binding Sites↗
PubMed1993

A long-range restriction map of human chromosome 5q21-q23.

A long-range restriction map encompassing the APC (adenomatous polyposis coli) gene has been constructed. The map includes 35 DNA markers and consists of two segments of 10 and 2.5 Mb. Published genetic markers have been connected using additional, nonpolymorphic DNA probes. The map clarifies marker order and allows comparison of physical and genetic data.

Adenomatous Polyposis Coli↗
PubMed1992

Yeast artificial chromosomes for the molecular analysis of the familial polyposis APC gene region.

Two yeast artificial chromosomes (YACs) spanning a total distance of 1.1 megabase pairs of DNA around the MCC (for mutated in colorectal carcinoma) and APC (for adenomatous polyposis coli) genes at 5q21 have been isolated and characterized. Starting from the MCC gene, a strategy was undertaken to identify constitutional submicroscopic deletions in familial adenomatous polyposis patients that might considerably narrow down the position of the APC gene. To this end, YACs identified by the MCC gene were screened across a chromosome 5-specific cosmid library to provide a source of DNA probes for genomic scanning. The cosmids isolated from these experiments were used to screen a panel of somatic cell hybrids containing chromosome 5 segregated from patients suspected to carry putative interstitial deletions. This screening approach led to the confirmation of a small heterozygous deletion in a polyposis patient that overlaps one of the two isolated YACs. This YAC has been shown to contain the entire APC gene, in addition to a significant portion of DNA flanking the 5' end of the gene, and should therefore prove a valuable resource for functional studies by transfer to colorectal tumor-derived cell lines.

Adenomatous Polyposis Coli↗
PubMed1991

The genetics and molecular biology of colorectal cancer.

Progress has continued in explicating the genetics of inherited predispositions to colorectal cancer and the molecular events that lead to tumorigenesis. New polymorphic DNA markers have been described for the presymptomatic diagnosis of familial adenomatous polyposis and a candidate gene has been characterized. Pedigree studies have suggested that there may be an inherited predisposition to many apparently nonfamilial colorectal cancers and a genetic model of tumorigenesis in common colorectal cancer has been proposed that includes the activation of dominantly acting oncogenes and the inactivation of growth suppressor genes. Two features of colorectal cancer make it a particularly good model for studying neoplasia. There are several well-defined rare inherited syndromes that predispose to the development of colorectal cancer in an autosomal dominant manner, and the majority of carcinomas are thought to arise from preexisting benign adenomatous polyps, allowing the analysis of genetic changes during tumorigenesis.

Adenomatous Polyposis Coli↗