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Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 235 records · Page 13Linked to original sources
PubMed1989

Distress associated with radiotherapy for malignant disease: a quantitative analysis based on patients perceptions.

Distress associated with attendance at a radiotherapy department was assessed in 80 consecutive patients. All patients were interviewed within 24 h of their first fraction of radiotherapy; 31 patients were also interviewed at the end of treatment. The problem identified at first interview as causing the most distress was worry about the effects of disease and its treatment upon the patient's family. At second interview the dominant complaint was of not being allowed to wash. Psychological problems, including anxiety and sleep disturbances, caused more overall distress than did physical symptoms. The method used in this study for eliciting information on the side-effects of therapy is straightforward and has yielded data that are provocative and suggest interesting avenues for further investigation.

Adolescent↗
PubMed1989

Mutations induced by aminofluorene-DNA adducts during replication in human cells.

To gain insight into the mechanisms by which carcinogens induce mutations in human cells, we treated a shuttle vector, pZ189, carrying the supF gene as the target for mutations with N-acetoxy-N-trifluoroacetyl-2-aminofluorene (N-AcO-TFA-AF). The plasmids were allowed to replicate in human cell line 293, and the progeny plasmids were examined for the frequency and kinds of mutations induced in supF, as well as their specific location in the sequence of the supF gene. The plasmids were reacted with N-AcO-TFA-AF so as to obtain the deacetylated adduct N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF), the principal adduct formed in DNA when mammalian cells are exposed to reactive derivatives of 2-acetylaminofluorene (AAF), including N-acetoxy-2-acetylaminofluorene. The results showed there was a linear relationship between the number of dG-C8-AF adducts per plasmid and the frequency of supF mutants induced. DNA sequencing of 47 independent mutants obtained from doses of N-AcO-TFA-AF that increased the frequency of mutants 9-15 times the background frequency and three independent mutants from lower doses showed that 92% contained point mutations, i.e. changes affecting one, or two, or three nearby bases, and that all of these point mutations involved G.C base pairs. Ninety eight percent of the point mutations were base substitutions, predominantly G.C----T.A transversions. 46% of these mutations occurred at four out of the 85 bp in the target gene (hot spots). The most prominent mutation hot spot was also the most prominent hot spot for adduct formation as judged by the frequency of termination of in vitro polymerization by the Klenow fragment on N-AcO-TFA-AF-treated plasmids.

2-Acetylaminofluorene↗
PubMed1989

A randomized controlled trial of the provision of a social support service during pregnancy: the South Manchester Family Worker Project.

A pilot scheme was introduced in Manchester to provide additional social support to pregnant women at above average risk of giving birth to a low-birthweight baby. The help of lay workers, known as family workers, was made available to eligible women. The effect on infant birthweight of offering the help of a family worker was assessed by a randomized controlled trial. No significant differences were observed between the experimental and control group, but on a number of grounds the interpretation of this finding is not straightforward, and further research is recommended.

Allied Health Personnel↗
PubMed1989

Chronic cough in a hospital population; its relationship to atopy and defects in host defence.

The background and aetiology of chronic cough were investigated by comparing 60 children under 6 years with simple cough, 60 children with asthma, and 60 controls. Both cough and asthma were more common in boys and associated with a history of eczema, chest deformity, and skin reactivity to inhaled allergens, but these findings were more prevalent in asthma than cough. House dust mite sensitivity was found in 34 (57%) children with cough, 45 (75%) with asthma, and six (10%) controls. Tests of immunological function showed some high concentrations of IgM in groups with both cough and asthma, but high IgE concentrations, eosinophilia, and lymphocytosis were significant only in asthma. IgG1 and IgG2 concentrations were raised in some children with cough or asthma, but the only low subclass concentrations were of IgG3 observed in the group with cough. Children with simple cough represented a heterogeneous population but many showed evidence of atopy. Major defects of immunity were not observed.

Asthma↗
PubMed1989

Substance abuse/mental illness: diagnostic issues.

"Dual diagnoses" of substance abuse and mental illness disorders are common both in psychiatric and substance abuse treatment settings. Recent studies have demonstrated that specific diagnostic categories of mental illness have implications for treatment outcomes of dually disordered patients, but a diagnostic standard has not emerged. The present study compared lay-administered DIS diagnoses with clinical diagnoses of patients in a state hospital treatment program for "dual diagnoses" patients. Categories of DIS diagnoses showed weak association with categories of clinical diagnoses. Several frequent DIS diagnoses were not made clinically and vice versa. Implications for choice of diagnostic instruments to use with this patient population are discussed, as is the potential value of structured assessments in supplementing clinical data.

Adolescent↗
PubMed1989

Risk of aluminium intoxication in long-term acetate Redy dialysis.

Closed-circuit dialysis using the Redy sorbent cartridge to regenerate the dialysate has been incriminated in previous reports as a cause of severe fracturing osteomalacia and fatal encephalopathy in several patients treated with this procedure for 15-36 months. In a retrospective study, we compared 15 unselected patients who had received Redy dialysis for 66 +/- 14 months with 15 control patients dialysed with single passage of dialysate. Redy and control patients were matched for age, sex, and duration of dialysis. They belonged to two dialysis centres, situated in the same geographical area and having a common water supply. Mean serum and bone aluminium concentrations were slightly greater in the Redy group but the differences were not significant. Pathological fractures had occurred in two Redy patients and in one control, but could not be attributed to aluminium-induced bone disease. Although the histochemical staining for aluminium in bone was positive in six patients, diagnosis of aluminium-induced bone disease was made in one case only. The results of bone histomorphometry did not differ significantly between the two groups. Our findings may be explained by the strict application of the measures required to avoid aluminium contamination of the Redy dialysate, i.e. sufficient rinsing before dialysis, use of almost aluminium-free water, and of acetate-buffered dialysate.

Adult↗
PubMed1989

Genetic analysis of colorectal cancer.

Adenomatous polyposis, mainly of the colon, (APC) is a rare dominantly inherited susceptibility to colon cancer in which individuals develop hundreds of polyps mainly in their large bowel. The APC gene has been localised to chromosome 5q21 by following up a case report of an individual with an interstitial deletion on chromosome 5q who had multiple developmental abnormalities together with adenomatous polyposis. A DNA marker (D5S71) was found to be closely linked to APC in family studies and localised to 5q21 by in situ annealing. Material from further patients with deletions in this region of chromosome 5 has been used, by a combination of somatic cell hybrid and long-range DNA analysis, to identify new DNA markers close to the APC gene. These and other markers now provide the basis for genetic counselling of nearly all families with APC. These studies are being extended, together with other approaches for analysing DNA clones around the APC gene, in the search for the gene itself. Allele loss in tumour as compared to normal tissue from sporadic cases of colorectal carcinomas has clearly implicated the APC gene in at least 25 to 40% of all cases of colorectal carcinomas. Similar studies by Vogelstein and others as well as ourselves have further implicated recessive changes on chromosomes 17 and 18 in the development of colorectal carcinomas. Following the demonstration by Vogelstein of the role of p53 mutations in connection with the chromosome 17 changes, we have now shown, using monoclonal antibodies to the mutant p53 products and by other approaches, that changes in the p53 gene may occur in up to 50% or more of colorectal carcinomas. Frequent mutations of the K-ras dominant oncogene, as well as changes in the expression of human leucocyte antigen (HLA)-A, B, C determinants, are further genetic changes that appear commonly to be involved in the progression of colorectal carcinomas. The latter have important implications for T cell immune response to tumours and its manipulation for treatment and even prevention of colorectal cancer. We may soon be approaching a situation when it will become possible to identify all the genetic steps and their sequence during tumour progression, as well as their functional significance largely through the induction of inappropriate growth and the suppression of differentiation.

Adenomatous Polyposis Coli↗
PubMed1988

Isozymes of fructose 6-phosphate,2-kinase:fructose-2,6-bisphosphatase in rat and bovine heart, liver, and skeletal muscle.

The distribution of Fructose 6-P,2-kinase:Fructose 2,6-bisphosphatase in rat and bovine heart, liver, and skeletal muscle tissues was examined. With DEAE-cellulose chromatography, two peaks (I and II) of Fru 6-P,2-kinase activity were detected in all tissue extracts. Peak I was the predominant form both in rat and bovine heart tissue, while peak II was the major form in liver and skeletal muscle. Antibodies to heart enzyme reacted specifically with peak I, and antibodies to liver enzyme reacted with peak II from both liver and skeletal muscle. All the isozymes were bifunctional. All the tissues examined contained other isozymes in minor amounts.

Animals↗
PubMed1988

Human liver cytosolic epoxide hydrolases.

Human liver epoxide hydrolases were characterized by several criteria and a cytosolic cis-stilbene oxide hydrolase (cEHCSO) was purified to apparent homogeneity. Styrene oxide and five phenylmethyloxiranes were tested as substrates for human liver epoxide hydrolases. With microsomes activity was highest with trans-2-methylstyrene oxide, followed by styrene 7,8-oxide, cis-2-methylstyrene oxide, cis-1,2-dimethylstyrene oxide, trans-1,2-dimethylstyrene oxide and 2,2-dimethylstyrene oxide. With cytosol the same order was obtained for the first three substrates, whereas activity with 2,2-dimethylstyrene oxide was higher than with cis-1,2-dimethylstyrene oxide and no hydrolysis occurred with trans-1,2-dimethylstyrene oxide. Generally, activities were lower with cytosol than with microsomes. The isoelectric point for both microsomal styrene 7,8-oxide and cis-stilbene oxide hydrolyzing activity was 7.0, whereas cEHCSO had an isoelectric point of 9.2 and cytosolic trans-stilbene oxide hydrolase (cEHTSO) of 5.7. The cytosolic epoxide hydrolases could be separated by anion-exchange chromatography and gel filtration. The latter technique revealed a higher molecular mass for cEHCSO than for cEHTSO. Both cytosolic epoxide hydrolases showed higher activities at pH 7.4 than at pH 9.0, whereas the opposite was true for microsomal epoxide hydrolase. The effects of ethanol, methanol, tetrahydrofuran, acetonitrile, acetone and dimethylsulfoxide on microsomal epoxide hydrolase depended on the substrate tested, whereas both cytosolic enzymes were not at all, or only slightly, affected by these solvents. Effects of different enzyme modulators on microsomal epoxide hydrolase also depended on the substrates used. Trichloropropene oxide and styrene 7,8-oxide strongly inhibited cEHCSO whereas cEHTSO was moderately affected by these compounds. Immunochemical investigations revealed a close relationship between cEHCSO and rat liver microsomal, but not cytosolic, epoxide hydrolase. Interestingly, cEHTSO has no immunological relationship to rat microsomal, nor to rat cytosolic epoxide hydrolase. cEHTSO from human liver differed also from its counterpart in the rat in that it was only moderately affected by tetrahydrofuran, acetonitrile and trichloropropene oxide. Five steps were necessary to purify cEHCSO. The enzyme has a molecular mass (49 kDa) identical to that of rat liver microsomal epoxide hydrolase.

Adult↗
PubMed1988

Purification and characterization of rat-liver cytosolic epoxide hydrolase.

Rat liver cytosolic epoxide hydrolase has been purified and characterized. The enzyme was purified from tiadenol-induced rat liver 540-fold with respect to trans-stilbene oxide as a substrate. Similar purification was obtained with the substrates trans-beta-ethyl styrene oxide and styrene 7,8-oxide, the specific activities decreasing in the order trans-beta-ethyl styrene oxide greater than styrene 7,8-oxide greater than trans-stilbene oxide. The enzyme exerts highest activity at pH 7.4 Km and Vmax of the pure enzyme for trans-stilbene oxide were 1.7 microM and 205 nmol x min-1 x mg protein-1 respectively. With trans-stilbene oxide as a substrate, the inhibition by organic solvents (2.5% by vol.) increased in the order ethanol less than methanol less than acetone less than isopropanol = N,N-dimethyl formamide less than acetonitrile less than tetrahydrofuran. The native enzyme, with a molecular mass of 120 kDa, consists of two 61-kDa subunits. Digestion of rat liver cytosolic and microsomal epoxide hydrolase by three proteases resulted in markedly different peptide maps. Western-blot analysis with antiserum against rat liver cytosolic epoxide hydrolase revealed a single band with the purified enzyme, and with liver cytosol from control and clofibrate-induced rats. No cross-reactivity was observed with purified rat microsomal epoxide hydrolase or microsomes. A positive reaction at the same molecular mass was obtained with liver cytosol of mouse, guinea pig, Syrian hamster and New Zealand white rabbit but not with that of green monkey.

Animals↗
PubMed1988

Cytosolic epoxide hydrolase in humans: development and tissue distribution.

Cytosolic epoxide hydrolase activity was measured towards trans-stilbene oxide in 41 human adult livers, in 40 fetal livers, in 17 placentas and in fetal and adult lungs, kidneys and gut. The cytosolic epoxide hydrolase activity was measurable in all specimens investigated. The rate of formation of trans-stilbene glycol (pmol/min per mg protein, mean +/- SD) was 55.2 +/- 89.6 (fetal liver). 303.2 +/- 73.2 (adult liver) and 18.8 +/- 13.1 (placenta) In the fetal extrahepatic tissues, the cytosolic epoxide hydrolase activity was 70.0 +/- 9.4 (adrenals), 47.6 +/- 7.2 (gut), 69.4 +/- 22.5 (kidneys) and 43.2 +/- 19.2 (lungs) pmol/min per mg protein, whereas in the adult tissues it was 131.2 +/- 63.1 (kidneys), 27.8 +/- 20.3 (intestine), 8.5 +/- 2.8 (lungs) and 7.2 +/- 4.2 (urinary bladder) pmol/min per mg protein.

Adult↗