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Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 19 recordsLinked to original sources
PubMed1992

Dihydrodiol dehydrogenase activities of rabbit liver are associated with hydroxysteroid dehydrogenases and aldo-keto reductases.

1. Dihydrodiol dehydrogenase activities were investigated in rabbit liver. Using a five-step purification scheme, eight isoenzymes of dihydrodiol dehydrogenase with isoelectric points of 5.55-9.3 and promoter molecular masses of 34-35 kDa were purified to apparent homogeneity and designated CF-1 to CF-6, CM-1 and CM-2. 2. CF-1 and CF-2 had near-neutral isoelectric points of 7.4 and 6.8 and molecular masses of about 125 kDa in the native state. Both enzymes readily accepted NAD+ as well as NADP+ as coenzymes, had relatively low Km values of 0.33 mM and 0.47 mM for benzene dihydrodiol and resembled previously described carbonyl reductases in their substrate specificity towards ketones and quinones. 3. CF-5 and CF-6 had acidic isoelectric points of 5.9 and 5.55 and native molecular masses of approximately 60 kDa. They displayed a strong preference for NADP(H) as coenzyme and had high Km and Vmax with benzene dihydrodiol. Since these enzymes reduced p-nitrobenzaldehyde and glucuronic acid efficiently, they appeared to be closely related to aldehyde reductase. 4. CF-4 had a high 3 alpha-hydroxysteroid dehydrogenase activity for the diagnostic substrate androsterone, a moderate activity for other 3 alpha-hydroxysteroids as well as 17 alpha-hydroxysteroids, and relatively low activities for 3 beta-hydroxysteroids and 17 beta-hydroxysteroids. CF-5 and CM-1 had high 17 beta-hydroxysteroid dehydrogenase activity for the diagnostic substrate 5 alpha-dihydrotestosterone, and low to moderate activities for other 17 beta-hydroxysteroids as well as 3 alpha-hydroxysteroids. 5. The isoenzyme CM-2 had an isoelectric point of 9.3 and was a very active quinone reductase with phenanthrene-9,10-quinone as substrate. It was potently inhibited by phenobarbital. 6. We conclude that the dihydrodiol dehydrogenase activities of rabbit liver are associated with aldehyde and carbonyl reductase and with 3 alpha-hydroxysteroid and 17 beta-hydroxysteroid dehydrogenases.

Alcohol Oxidoreductases↗
PubMed1992

Interaction of valproic acid and some analogues with microsomal epoxide hydrolase.

Valproic acid (VPA) and its analogues valpromide (VPM), valproyl-Coenzyme A (VP-CoA) and valproyl-ethylester (VPE) were examined as potential inhibitors of microsomal epoxide hydrolase (mEHb) using styrene-7,8-oxide (STO) and benzo(a)pyrene-4,5-oxide (BPO) as enzyme substrates. The effect of each potential inhibitor was examined using mEHb from rat liver, human livers (from a child, woman and man) and from human placenta. Of the compounds tested, only VPM (2 mM) expressed significant inhibition of mEHb activity with a maximum inhibition of 49%, 48%, 35% and 33% for liver microsomes from the child, woman, man and rat, respectively, using STO (2 mM) as substrate. Human placenta mEHb was inhibited 59% under the same conditions. The inhibition was found to be competitive, with closely related KI values of 0.11, 0.16, 0.28, 0.27 and 0.31 mM for mEHb obtained from rat liver, human placenta, child, female and male liver, respectively. VPA demonstrated only a slight inhibition (maximum 16%) of mEHb at high concentrations (10 mM), and VP-CoA was found to activate STO hydrolysis slightly at concentrations between 1 and 5 mM. VPE caused a moderate concentration-dependent activation of mEHb in all microsomal preparations examined. The inhibitory or activating properties of each compound were independent of the substrate and influenced slightly by the pH used in the incubation medium. The lack of inhibition of mEHb by VPA and its analogues other than VPM shows that neither masking of the carboxyl function of VPA nor the introduction of higher lipophilicity are sufficient to account for the inhibitory properties of VPM for mEHb. A molecular mechanism for the inhibition of mEHb by VPM is discussed.

Adult↗
PubMed1992

The effect of cyclosporin A on cationized bovine serum albumin-induced nephropathy in NZW rabbits.

The effect of cyclosporin A (CyA) was studied on the morphology and protein excretion of a rabbit chronic serum sickness nephritis using cationized bovine serum albumin (cBSA). One group of rabbits was given intravenous (i.v.) immunizing doses of cBSA and Escherichia coli endotoxin. One week later, these animals began a 6-week i.v. injection schedule of cBSA only. A second group followed the same injection protocol, but was given intramuscular (i.m.) CyA for 3 days prior to the immunizing dose of cBSA/endotoxin and throughout the subsequent cBSA schedule. A third group was given i.m. CyA only. Regular blood samples for CyA levels were taken from animals given the drug. Two 24-h urine samples were obtained from all animals in the study. Analysis of the blood samples showed that immunosuppressive levels of CyA were achieved after two i.m. doses of CyA. These levels were maintained during the course of the schedule. Morphologically, all rabbits completing the cBSA only injection schedule showed evidence of an immune-mediated glomerulopathy with variably severe membranous and endocapillary proliferative change. Less than half the rabbits in the cBSA/CyA group showed any evidence of membranous change. The glomeruli of animals given CyA only were normal. No morphological evidence of CyA toxicity was seen in any animal given the drug. The proteinuria profiles, however, suggested that as well as reducing protein excretion in rabbits given cBSA, CyA may interact with the immunizing dose of cBSA to produce an early, reversible, nephrotoxic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Sequential interleukin-2 and alpha interferon for renal cell carcinoma and melanoma.

There is a theoretical basis for the synergy of interleukin-2 (IL-2) with other cytokines. We have investigated sequential treatment with IL-2 and alpha interferon. 1 of 22 patients with metastatic renal cell carcinoma had a partial response and one a minimal response to continuous infusion IL-2 but none of the 9 patients with melanoma responded. 16 of 17 patients with renal cell cancer, and 8 with melanoma, were then treated with alpha interferon. 2 patients with renal cell cancer responded to alpha interferon with sustained remissions of 30 and 40 months; both had responded to IL-2. The investigation of combination therapy with other cytokines is suggested, by these unusually long responses to alpha interferon.

Adolescent↗
PubMed1992

A rational approach to shift work in emergency medicine.

As the only medical specialists who routinely provide continuous 24-hour daily coverage, emergency physicians are all too familiar with the demands of shift work. Although shift work has a pervasive effect on the practice of emergency medicine and is regarded as a major stressor, it has received little attention per se in our literature and in our residency training programs. We review the principles of circadian rhythms and their effects on sleep and alertness, and recommend ways by which emergency physicians can better schedule themselves to mitigate the negative consequences of working shifts.

Circadian Rhythm↗
PubMed1992

Droperidol versus haloperidol for chemical restraint of agitated and combative patients.

STUDY OBJECTIVE: To compare two related pharmacological agents used for the chemical restraint of agitated and combative patients. DESIGN AND SETTING: A randomized, double-blind, prospective study was carried out in patients requiring physical restraint in a university hospital emergency department. PARTICIPANTS: Sixty-eight violent or agitated adult patients whom the attending physician believed would benefit from chemical restraint to protect the patient and staff and to expedite evaluation. INTERVENTION: Twenty-one participants were administered 5 mg haloperidol IM; 26 were administered 5 mg droperidol IM; 12 were administered haloperidol IV; and nine were administered 5 mg droperidol IV. RESULTS: All patients were rated on a five-point combativeness scale at five, ten, 15, 30, and 60 minutes after the study drug was given. Vital signs also were recorded at these times. IM droperidol decreased combativeness significantly more than IM haloperidol at ten (P = .006), 15 (P = .01), and 30 (P = .04) minutes. There was no significant difference between the two drugs when given by the IV route (beta at the 5% confidence level, P = .78). CONCLUSION: In equal IM doses (5 mg), droperidol results in more rapid control of agitated patients than haloperidol, without any increase in undesirable side effects.

Adult↗
PubMed1992

Solitary cerebral metastases from gynaecological malignancy: the case for radical therapy.

Three cases of solitary cerebral metastases from gynaecological malignancy are reported. Each was treated with surgical resection followed by radical radiotherapy resulting in prolonged disease-free survival. The reasons for the increasing incidence of cerebral metastases in these malignancies is discussed, the case for radical treatment made and the literature reviewed.

Brain Neoplasms↗
PubMed1992

What proportion of isotope injected does the child receive in dynamic renal scanning?

Because of significant difficulties encountered in the manipulation of data from 99Tcm-DTPA and 99Tcm-mercaptoacetyltriglycine (MAG3) renogram studies, it was decided to try to improve the percentage dose of radioisotope injected and thus the number of counts obtained by using a minimum dose volume of 1 ml for all injections. This resulted in an improvement in the percentage dose injected. However, difficulties were still encountered in the younger children. 18.7% of children aged less than 3 months, received less than 50% of the injected dose, showing little or no improvement using the newer method. The difficulty of injecting small babies seems the most obvious reason. During the interpretation of the findings in paediatric radioisotope studies, it is important to remember that not all children may have received an adequate percentage dose to constitute a reliably diagnostic study.

Child↗
PubMed1992

Integration of hepatitis B virus DNA through a mutational hot spot within the cohesive region in a case of hepatocellular carcinoma.

Integrated hepatitis B virus (HBV) DNA previously cloned from a hepatocellular carcinoma genomic library derived from a Japanese patient was characterized further. Sequence analysis of restriction fragments bearing the virus-host junctions defined 3125 nucleotides of essentially un-rearranged HBV DNA of the adr subtype with the right junction mapping within the cohesive region at position 1970 and the left within the pre-core at position 1886. The right viral-host junction contains a 7 bp repeat (TGTAGGC) and a possible 2 bp inversion. The integrated HBV DNA includes the complete open reading frames for core, pre-S, S and polymerase and a 3' truncated X gene, and lacks most of the pre-core. Integration has occurred at a mutational hot spot of the viral genome and appears to be located in a region of semi-repetitive genomic DNA 3' to the beta-globin gene cluster.

Base Sequence↗
PubMed1992

Cloning and sequencing of the structural region and expression of putative core gene of hepatitis C virus from a British case of chronic sporadic hepatitis.

We report the cloning and sequencing of the putative structural region of the hepatitis C virus (HCV) genome (2229 nucleotides) from an isolate derived from a British case of chronic sporadic non-A, non-B hepatitis. The overall sequence shows a higher similarity with one type of HCV, HCV1 (92%), than with HCV2 (80%), is very highly conserved at the 5' end (99%) preceding the long open reading frame, is well conserved also in the putative core region (90 to 97%), but shows marked variation in the putative envelope region, particularly in the envelope 2/non-structural 1 region (70%). The putative core gene was cloned in pJ3 omega under the early simian virus 40 promoter and expressed in human hepatoma cells. A predominantly cytoplasmic 22K polypeptide was expressed which was antigenically reactive with serum from chronically infected HCV patients.

Amino Acid Sequence↗
PubMed1992

Xenobiotic-metabolizing enzyme activities in hybrid cell lines established by fusion of primary rat liver parenchymal cells with hepatoma cells.

1. The activities of xenobiotic-metabolizing enzymes were determined in hybrid cell lines (hepatocytoma, HPCT) which have been established by fusion of liver parenchymal cells from adult rat (PC) with cells from a Reuber hepatoma cell line (FAO). 2. Cytochrome P450 was not measurable spectrophotometrically in FAO and HPCT. P450-dependent conversion of testosterone was below the detection limit in FAO and only marginally present in HPCT. 3. Microsomal and cytosolic epoxide hydrolase, glutathione S-transferase and phenol sulphotranserase were low or even below detection limit in FAO. These enzyme activities were significantly higher in HPCT and correspond to about 1-10% the activities measured in PC. 4. 1-Naphthol UPD-glucuronosyl transferase activity was about 20% in FAO and about 100% in HPCT compared to PC. 5. Metabolic conversion of benzo[a]pyrene was low in FAO, high in PC, and intermediate in HPCT. The presented data, however, do not allow the conclusion whether this intermediate rate is catalyzed by similar P450 isoenzymes as in PC. 6. Due to the easily measurable phase II-metabolizing enzyme activities HPCT may, however, be useful for in vitro enzyme induction or repression studies.

Animals↗
PubMed1992

Scurvy in a nonalcoholic person in the United States.

Scurvy is rarely diagnosed in our society today. The authors describe the case of a 31-year-old man with weakness, gingival pain, and a rash over the lower extremities. He had a history of poor nutritional intake, no alcohol consumption, and a 13 pack-year history of cigarette smoking. Laboratory studies revealed an extremely deficient serum ascorbic acid level. Treatment was begun with oral ascorbic acid tablets and, within 3 days after discharge, all clinical symptoms of scurvy had resolved. Scurvy is an easily treated disease and should be considered when there is an appropriate history and classic clinical findings. Because vitamin C deficiency can be seen in many chronic disease states, it is important to recognize some of the early features and clinical manifestations of such nutritional deficiencies.

Adult↗
PubMed1991

An impaired peroxisomal targeting sequence leading to an unusual bicompartmental distribution of cytosolic epoxide hydrolase.

To gain an understanding of the mechanism by which the subcellular distribution of cytosolic epoxide hydrolase (cEH) is directed, we have analyzed the carboxy terminal region of rat liver cEH by means of cDNA cloning to define the structure of its possible peroxisomal targeting sequence (PTS). Purified cEH was subjected to peptide analysis following endoproteinase Glu-C digestion and HPLC-separation of the fragments. The obtained sequence information was used to perform PCR experiments resulting in the isolation of a 680 bp cDNA clone encoding the carboxy terminus of cEH. The deduced amino acid sequence displays a terminal tripeptide Ser-Lys-Ile which is highly homologous to the PTS (Ser-Lys-Leu) found in other peroxisomal enzymes. This slight difference appears to be sufficient to convert the signal sequence into an impaired and therefore ambivalent PTS, directing the enzyme partly to the peroxisomes and allowing part to reside in the cytosol.

Amino Acid Sequence↗
PubMed1991

Fine mapping of probes in the adenomatous polyposis coli region of chromosome 5 by in situ hybridization.

The gene for adenomatous polyposis coli has been localized to 5q21-22. We have mapped six probes from this region using isotopic or nonisotopic in situ hybridization. Using tritium-labeled probes we localized II227 (D5S37) to 5q14-15 and ECB27 (D5S98) to 5q21. Following hybridization with biotin-labeled probes, the positions of signals along the chromosomes were measured as fractional length relative to the length of the chromosome arm from centromere to qter (FLcen-qter). Ninety-five percent confidence limits, compared with standard karyotypes, provided the corresponding band localization. By this method we localized Cllpll (D5S71) to FLcen-qter 0.407-0.452 (5q21.1-21.3), ECB27 to FLcen-qter 0.426-0.473 (5q21.3), YN5.48 (D5S81) to FLcen-qter 0.459-0.496 (5q21.3-22.2), and ECB134 (D5S97) to FLcen-qter 0.509-0.533 (5q22.3-23.1). ECB220 had three sites of hybridization, a major site at FLcen-qter 0.460-0.492 (5q21.3-22.1) and minor sites at FLcen-qter 0.299-0.339 (5q14.3-15) and FLcen-qter 0.629-0.691 (5q23.3-31.2). We have shown that the chromosome 5 breakpoint in a t(5;15) translocation from a patient with Gardner's syndrome (GM03314) is between Cllpll and ECB27. Linkage data are presented suggesting that ECB27 is located on the same side of the APC locus as II227. These and published results including data on several constitutional deletions (M, SD, and brothers PW and ND) give a probable order of [cen] - [II227, proximal SD breakpoint] - [Cllpll] - [proximal PW/ND, M breakpoint(s), GM03314 breakpoint] - [ECB27] - [APC] - [YN5.48] - [distal PW/ND breakpoint] - [ECB134] - [distal M breakpoint] - [qter]. The major site of ECB220 appears to be between ECB27 and the distal PW/ND breakpoint; the distal SD breakpoint is distal to YN5.48.

Adenomatous Polyposis Coli↗