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Biomedical subjects

C D Evans

Publications and source records attributed to C D Evans.

At least 19 recordsLinked to original sources
PubMed1996

The dysmorphic human-mouse homology database (DHMHD): an interactive World-Wide Web resource for gene mapping.

Genetic mapping and the examination of "candidate genes" for isolating loci associated with clinical syndromes can be greatly accelerated if there is information about where in the genome a particular locus might be situated. Such clues can come from homology to mouse mutants that have been mapped and knowledge of homology between mouse and human chromosomal segments. Further clues can come from chromosome aberrations giving a similar phenotype. However, these clues are often scattered widely in published reports, and even if they are collected together in catalogues or databases there is no rapid way of moving from one data type to another. The Dysmorphic Human and Mouse Homology Database (DHMHD) is designed to ease this data transition. DHMHD comprises detailed information from four separate sources and enables cross referencing through phenotypic and chromosome homology. The DHMHD system is a prototype which is now available online through the World-Wide Web.

Animals↗
PubMed1995

Immunophenotypic analysis of childhood Burkitt's lymphoma in the West Midlands 1957-1986.

AIMS: To analyse the immunophenotype of a large number of non-endemic Burkitt's lymphomas to determine whether a B cell phenotype is consistently recognisable using formalin fixed, paraffin wax embedded archival material and a standard panel of commercially available antibodies. METHODS: Archival material was obtained from 30 cases of childhood Burkitt's lymphoma registered with the West Midlands Regional Children's Tumour Research Group. These were analysed by a standard avidin biotin complex immunoperoxidase method using antibodies to CD45, CD43, CD30, CD20, CD15, and immunoglobulin heavy and light chains. RESULTS: There was a high incidence of the CD45RB and CD20 immunophenotypes, with a clearly recognisable B cell lineage even in archival material. IgM was identifiable in 13 of the 23 (56.5%) cases tested. Only three of 17 (18%) cases expressed CD30. Positive membrane staining with CD45RO was observed in two (6.7%) cases. CONCLUSIONS: A B cell lineage can be identified in Burkitt's lymphoma in formalin fixed, paraffin wax embedded material, even in archival tissue. There was a low incidence of membrane staining with CD45RO which is a potential source of diagnostic confusion.

Adolescent↗
PubMed1995

Computer systems in dysmorphology.

A number of computer systems have been dedicated to some aspect of dysmorphology. These systems have generally been developed in isolation and demonstrate much variation in their design. Some systems are purely database applications designed to take advantage of computer technology in order to provide up to date syndrome compendia. Conversely, a number of research projects have endeavoured to build an intelligent system that can formulate a diagnosis, either through its own knowledge-base, or through interaction with an expert user. This report reviews computer systems in dysmorphology with reference to these two alternative design methodologies. The London Dysmorphology Database and POSSUM provide case studies in a standard database approach. The Skeletal Dysplasia Diagnostician (SDD) is described in order to demonstrate how an expert system might operate in dysmorphology. Other work in the field is reviewed in terms of the common and distinctive aspects of their design with respect to the three aforenamed systems.

Databases, Factual↗
PubMed1994

Reduced levels of topoisomerase II alpha and II beta in a multidrug-resistant lung-cancer cell line.

We have previously shown that the doxorubicin-selected multidrug-resistant small-cell lung-cancer cell line H69AR is resistant to VP-16-induced single-strand DNA breaks as compared with its parental H69 cell line. Levels of immunoreactive topoisomerase II alpha are also reduced in H69AR cells. In the present study, we found that cleaved complex formation in the presence of VP-16 was decreased in H69AR cells as compared with H69 cells. In addition, the resistant cells contained lower levels of both topoisomerase II alpha and topoisomerase II beta protein and mRNA. However, these changes were not accompanied by a decrease in the P4-unknotting (strand-passing) activity of 0.67 M NaCl nuclear extracts of H69AR cells, nor was there any difference in VP-16 inhibition of unknotting activity in the H69 and H69AR nuclear extracts. These data suggest that reduced levels of topoisomerase II alpha and II beta may contribute to the resistance of H69AR cells to VP-16 and other drugs that target these isoenzymes.

Blotting, Northern↗
PubMed1994

Resistance of the hamster to amiodarone-induced pulmonary toxicity following repeated intraperitoneal administration.

Amiodarone is an effective antidysrhythmic agent, restricted in use by the development of pulmonary toxicity. Several in vivo animal models have been used to study amiodarone-induced pulmonary toxicity. Intratracheal administration of amiodarone to the hamster has been used as a model for the critical amiodarone-induced pulmonary fibrosis (AIPF). In order to investigate the cellular mechanism of human AIPF, which occurs following oral or intravenous administration, an animal model of AIPF resulting from systemic administration of the drug would appear to be preferable. We have evaluated pulmonary toxicity following repeated intraperitoneal amiodarone administration to the hamster. Intraperitoneal treatment of hamsters for 1, 4, or 7 weeks with amiodarone (100 mg/kg/day) did not lead to pulmonary toxicity based on wet lung weight, hydroxyproline content, or histological examination. Furthermore, when comparing 1- and 7-week treatment groups, there was no pulmonary accumulation of either amiodarone or desethylamiodarone beyond levels found at 1 week. Therefore, failure to develop pulmonary toxicity may be due to an inability to accumulate sufficient amiodarone and/or desethylamiodarone. Intratracheal administration of amiodarone to rodents remains the only in vivo animal model for studying the mechanism(s) of AIPF.

Amiodarone↗
PubMed1994

Validation of a food-repertory grid with a diabetic population.

The application of a psychology tool, the repertory grid, was explored. A diabetic sample was used to evaluate this new assessment tool. The grid measures attitudes about food and was created by determining elements (food items) and constructs (adjectival phrases) as identified by diabetic participants and dietitians. The grid was administered twice to 17 diabetic participants to determine applicability. The interindividual correlation coefficients ranged from 0.24 to 0.54 for elements and from 0.24 to 0.61 for constructs. The most stable components can be used for a grid designed to help dietitians with counseling. Clients would fill out a grid so that problem areas in the way of attitudes about food could be pinpointed. Because many diabetic persons fail to comply with their diets, a new and innovative tool is needed. The possibilities for grid development are abundant among other clinical populations for whom dietary management is important.

Attitude↗
PubMed1994

Death of a classified worker probably caused by overexposure to gamma radiation.

This paper describes the case of an industrial radiographer who was seriously overexposed to gamma radiation. The exact circumstances of this exposure were not established but it was concluded that he was repeatedly irradiated probably to a total average whole body dose of at least 10 Gy over several years. Also, a much larger dose to a hand required its partial amputation. He developed myelodysplasia, which progressed to acute myeloid leukaemia from which he died. Karyotypic examination of the leukaemic blasts showed changes very similar to those associated with secondary leukaemia that may develop after radio or chemotherapy. The paper describes his medical case history, the investigation of his workplace, and the attempts to estimate his radiation dose by chromosomal analysis of blood lymphocytes and electron spin resonance of dental enamel and bone.

Acute Disease↗
PubMed1993

Altered topoisomerase II alpha in a drug-resistant small cell lung cancer cell line selected in VP-16.

The H209/V6 cell line was derived from the H209 small cell lung cancer cell line by selection in etoposide (VP-16). Cytogenetic analysis indicates that the sensitive and resistant cell lines share 20 marker chromosomes and thus are clearly related. However, the H209/V6 cell line has four additional structurally altered chromosomes and a 2 N-modal chromosome number, while the H209 cell line is hypotetraploid (4 N-). H209/V6 cells are cross-resistant to some drugs that interact with topoisomerase II but not mitoxantrone. H209/V6 cells are also not cross-resistant to vincristine, trimetrexate, or cisplatin. The rates of VP-16 efflux are the same in the resistant and sensitive cell lines, which is consistent with the observation that P-glycoprotein mRNA is not detectable in either cell line. Fewer VP-16-induced DNA-protein complexes are observed in H209/V6 cells, and immunoblot analysis shows that levels of topoisomerase II alpha are reduced in H209/V6 cells compared to the sensitive H209 cells. Furthermore, the topoisomerase II alpha-related protein in H209/V6 cells has an increased electrophoretic mobility, with an apparent M(r) of 160,000. The levels of the topoisomerase II alpha 6.1-kilobase mRNA in H209/V6 cells are reduced > 10-fold. In addition, a second topoisomerase II alpha-related mRNA of approximately 4.8 kilobases is observed in H209/V6 cells but not in H209 cells. The quantity and electrophoretic mobility of the M(r) 180,000 topoisomerase II beta protein and its 6.1-kilobase mRNA are the same in the sensitive and resistant cell lines. The topoisomerase II strand-passing activity in H209/V6 nuclear extracts is reduced about 2-fold, but this activity is not more resistant to inhibition by VP-16 than the activity in H209 cells. However, band depletion immunoblot experiments show that the topoisomerase II alpha-related M(r) 160,000 protein in H209/V6 cells is not bound to DNA in the presence of concentrations of VP-16 that deplete the M(r) 170,000 topoisomerase II alpha in H209 cells and the M(r) 180,000 topoisomerase II beta in both the resistant and sensitive cells. We conclude that quantitative and qualitative alterations in topoisomerase II alpha have occurred in H209/V6 cells and are likely to contribute to its resistance phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men.

Isoprene is a normal constituent of human breath and may be derived from the cholesterol synthetic pathway. Acute and chronic lovastatin and a cholesterol-supplemented diet were used to determine whether a mechanistic link exists between isoprene and cholesterol biosynthesis in vivo in humans. The acute effects of lovastatin, a competitive inhibitor of the rate-limiting step of cholesterol biosynthesis, on breath isoprene excretion was determined by administering a single 20, 40 or 80 mg dose of this drug to five healthy male subjects at 8 p.m. and measuring their breath isoprene levels every 4 h for one 24 h cycle before and after treatment. When compared to the baseline cycle, all three doses of lovastatin significantly reduced breath isoprene levels at 6 and 10 h post-drug treatment. Chronic lovastatin therapy (40 mg b.i.d. for 6 wk) reduced 6 a.m. breath isoprene levels (time of maximum baseline value) by 27 +/- 9% (SEM) and cholesterol synthesis measured in freshly isolated mononuclear leukocytes (ML) by 12 +/- 6%. A cholesterol-supplemented diet (1070 mg, total) ingested for 6 wk reduced breath isoprene excretion and ML sterol synthesis by 16 +/- 5 and 19 +/- 4%, respectively. The parallel decreases in isoprene excretion and cholesterol synthesis caused by these pharmacologic and dietary means suggest that breath isoprene is derived from the cholesterol synthesis pathway.

Adolescent↗
PubMed1992

The local lymph node assay: results of a final inter-laboratory validation under field conditions.

The local lymph node assay (LLNA) assesses the sensitizing activity of chemicals by measurement of primary lymphocyte proliferation in lymph nodes draining the site of application. In this final inter-laboratory study the consistency of LLNA results between laboratories and with guinea pig maximization test (GPMT) data was examined under 'field' conditions. Nine chemicals were evaluated independently by each laboratory according to guidelines for test concentration and vehicle selection developed during previous validation studies to ensure assay optimization. Equivalent predictions of sensitization potential were obtained by all laboratories for eight chemicals. Five of seven chemicals identified as sensitizers in the GPMT were correctly identified in the LLNA--four by all laboratories and 1 (4-chloroaniline) by one laboratory only--although in this latter case, two other laboratories obtained clear dose responses, suggestive of sensitization. The LLNA identified correctly those chemicals predicted to be extreme or strong sensitizers in the GPMT. The remaining two chemicals were non-sensitizers in the guinea pig and failed to elicit positive proliferative responses in the LLNA. These data demonstrate that sensitivity and reliability of the LLNA is retained when chemicals are evaluated independently, and that it provides a reliable pre-screen for the identification of chemicals with significant sensitization potential.

Animals↗
PubMed1992

Sulphanilic acid: divergent results in the guinea pig maximization test and the local lymph node assay.

The guinea pig maximization test (GPMT) has proven to be a valuable tool for the identification of the skin sensitization potential of chemicals. The method identifies a hazard which can lead in the EC to compulsory labelling of that chemical. In the present study, data on sulphanilic acid derived from the GPMT has been compared with results from a second guinea pig assay (the cumulative contact enhancement test) and the murine local lymph node assay, both of which require only topical application of chemical. Except for the GPMT, no test identified any sensitizing activity associated with exposure to sulphanilic acid. These latter results are consistent with the experience gained from substantial human exposure in an occupational setting and from which no cases of allergic contact dermatitis to sulphanilic acid have arisen over a 20-year period. In consequence, it is questioned which test protocol in practice has given the more accurate identification of sensitization hazard relevant to man.

Administration, Topical↗
PubMed1992

Thyroid hormone differentially augments biliary sterol secretion in the rat. I. The isolated-perfused liver model.

Thyroid hormone lowers serum cholesterol and alters sterol metabolic processes. This laboratory has previously reported increased biliary lipid secretion as an early effect of triiodothyronine (T3) in the rat. To evaluate whether the bile lipid action of T3 is a primary or secondary effect, the isolated-perfused rat liver model was used. Red blood cells in lipid-free buffer were used to perfuse livers of euthyroid and methimazole-hypothyroid rats, as well as hypothyroid rats given T3 at intervals before perfusion. Bile flow was maintained by taurocholate perfusion. Hypothyroid rats had elevated pre-perfusion serum cholesterol compared to euthyroid (107 +/- 4 vs. 65 +/- 2 mg/dl) and decreased biliary cholesterol (0.016 +/- 0.001 vs. 0.031 +/- 0.004 mumol/g liver/h) secretion. Serum cholesterol decreased to euthyroid levels by 18 h after T3, an effect that was prevented by bile duct ligation. Bile cholesterol secretion doubled by 18 h, and reached levels twice euthyroid by 42 h, while phospholipid secretion doubled to levels just above euthyroid. The fourfold increase in biliary cholesterol secretion occurred with lipid-free perfusion and unchanging bile acid uptake or output. It occurred without a fall in hepatic lipoprotein cholesterol secretion. Blockade of cholesterol synthesis with lovastatin failed to alter T3-augmented bile cholesterol secretion. We conclude that T3 induces biliary cholesterol secretion concomitantly with the fall in serum cholesterol. This augmented biliary secretion did not appear to depend upon lipoprotein uptake, increased bile acid transport, or cholesterol synthesis. It did not occur at the expense of hepatic lipoprotein secretion. Facilitated biliary lipid secretion may be a primary effect of T3.

Animals↗
PubMed1992

Evidence for a common biliary cholesterol and VLDL cholesterol precursor pool in rat liver.

Hepatic free cholesterol levels are influenced by cholesterol synthesis and ester formation, which, in turn, might regulate cholesterol secretion into bile and plasma. We manipulated the rates of hepatic cholesterol synthesis and esterification and measured biliary and very low density lipoprotein (VLDL) cholesterol secretion, and bile acid synthesis. Mevalonate decreased HMG CoA reductase by 80%, increased acyl coenzyme A: cholesterol acyltransferase (ACAT) by 60% and increased [3H]oleate incorporation into microsomal and VLDL cholesteryl esters by 174% and 122%, respectively. Microsomal and biliary free cholesterol remained constant at the expense of increased microsomal and VLDL cholesteryl ester content. Mevalonate did not change bile acid synthesis. 25-OH cholesterol decreased HMG-CoA reductase by 39%, increased ACAT by 24%, but did not effect 7 alpha-hydroxylase. 25-OH cholesterol increased [3H]oleate in microsomal and VLDL cholesterol esters by 71% and 120%. Biliary cholesterol decreased by 40% and VLDL cholesteryl esters increased by 83%. A small and unsustained decrease in bile acid synthesis (14CO2 release) occurred after 25-OH cholesterol. After orotic acid feeding, HMG-CoA reductase increased 352%, and [3H]oleate in microsomal and VLDL cholesteryl esters decreased by 43% and 89%. Orotic acid decreased all VLDL components including free cholesterol (68%) and cholesteryl esters (55%), and increased biliary cholesterol by 160%. No change in bile acid synthesis occurred. Hepatic cholesterol synthesis and esterification appear to regulate a cholesterol pool available for both biliary and VLDL secretion. Changing cholesterol synthesis and esterification did not alter bile acid synthesis, suggesting that either this common bile/VLDL secretory pool is functionally distinct from the cholesterol pool used for bile salt synthesis, or that free cholesterol availability in this precursor pool is not a major determinant of bile acid synthesis.

Animals↗
PubMed1991

Assessment of the relative skin sensitizing potency of 3 biocides using the murine local lymph node assay.

The relative skin-sensitizing potency of 3 biocides, 5-chloro-2-methyl-4-isothiazolin-3-one (the major active ingredient in Kathon CG), 1,2-benzisothiazolin-3-one and 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, was assessed using the murine local lymph node assay. Potency was ranked according to the lowest dose of material which, following epicutaneous exposure, induced a significant proliferation of T lymphocytes in the draining lymph nodes. The results showed that 5-chloro-2-methyl-4-isothiazolin-3-one was able to induce proliferative activity at significantly lower dose levels than the other 2 biocides and that it may therefore be a more potent skin sensitizer.

Animals↗
PubMed1991

Some meanings of body and self in eating-disordered and comparison subjects.

A new repertory grid was used to compare a group of 27 eating-disordered women (EDS) with a group of 20 women of normal weight without eating disorders (NWC) on contrasts from theories which link abnormalities in the perception of body and self to the eating disorders. No evidence was found for greater polarization of either self or body images in the EDS. A negative connotation of the body at normal weight and overweight was specific to EDS, but the underweight body did not have a more positive connotation. Negative connotation of normal weight is shown to be more specific for EDS than is negative connotation of the overweight body. There was no evidence for specific implications of weight for sexuality nor for family pressures against sexuality or femininity in EDS although they did construe themselves as less sexual than the NWC.

Adult↗