Search PubMed⌕ Search

Biomedical subjects

H Thomas

Publications and source records attributed to H Thomas.

At least 163 records · Page 9Linked to original sources
PubMed1993

Immunoelectron microscopic localization of cytochrome P-450 isoenzyme CYP4A1 in liver, ileum and kidney of nafenopin treated male rats.

A monoclonal antibody raised against and specific for cytochrome P-450 isoenzyme CYP4A1 was used to investigate the subcellular distribution of this enzyme in the liver, kidney and ileum of nafenopin treated rats by means of immunoelectron microscopy. In the liver and kidney, labelling was restricted to peroxisomes and mitochondria of hepatocytes and proximal tubular epithelial cells whereas in ileum, immunolabelling was exclusively detected in mitochondria of absorptive cells.

Animals↗
PubMed1993

Benzene metabolism by reconstituted cytochromes P450 2B1 and 2E1 and its modulation by cytochrome b5, microsomal epoxide hydrolase, and glutathione transferases: evidence for an important role of microsomal epoxide hydrolase in the formation of hydroquinone.

Benzene metabolism was investigated using two purified rat hepatic MFO systems containing either cytochrome P450 2B1 or cytochrome P450 2E1. Studies performed over a wide substrate concentration range indicate that cytochrome P450 2B1 represents a relatively low-affinity form of cytochrome P450 with respect to benzene metabolism while cytochrome P450 2E1 is substantially more efficient at low benzene concentrations (apparent Km value 0.17 mM). Cytochrome b5 stimulated benzene metabolism by both cytochromes P450 2B1 and P450 2E1. With cytochrome P450 2E1 the stimulation of benzene metabolism by cytochrome b5 was very pronounced (up to 6-fold) at low concentrations of benzene and was most effective (up to 15-fold) with respect to formation of hydroquinone. The metabolites observed in these studies were phenol and hydroquinone. Cytochrome P450 2E1 metabolized phenol with an affinity and capacity comparable to those of benzene. Hydroquinone was the major product formed at all substrate concentrations, while some catechol was formed at all substrate concentrations, while some catechol was formed at higher concentrations of phenol. Phenol metabolism was also stimulated by cytochrome b5. The metabolism of benzene by cytochrome P450 2E1 in the presence of the major microsomal epoxide hydrolase, mEHb, yielded phenol, hydroquinone, and benzene dihydrodiol. Interestingly, the addition of mEHb did not lead to a decrease of the toxicologically important metabolite hydroquinone as might be expected from sequestration of the intermediate benzene oxide to the vicinal dihydrodiol pathway but rather led to a marked (more than 4-fold) increase in the formation of hydroquinone, suggesting catalysis by mEHb of a predominant attack at the homoallylic position rather than at a carbon atom which forms the epoxide ring of benzene oxide. The addition of glutathione transferases plus glutathione did not yield GSH conjugates during benzene metabolism. However, metabolism of phenol by cytochrome P450 2E1 in the presence of glutathione yielded a nonenzymatically formed glutathione conjugate derived from hydroquinone or from an oxidative product of hydroquinone.

Animals↗
PubMed1993

Demonstration of highly specific and sensitive antibodies to a naturally occurring tetrahydroisoquinoline alkaloid, salsolidine.

1. We report for the first time on the production and characterization of antibodies against a naturally occurring tetrahydroisoquinoline, namely salsolidine (6,7-dimethoxy-1-methyl-1,2,3,4-tetrahydroisoquinoline). 2. Immunogen synthesis was carried out by coupling the hapten salsolidine to bovine serum albumin (BSA) as carrier protein on the basis of reductive amination. 3. By immunization of rabbits with salsolidine-BSA conjugate antisalsolidine antibodies were produced. 4. At a final dilution of 1:1700 the highest-titre antiserum bound 35% of 0.21 pmol [3H]salsolidine. This antiserum was used to develop a radioimmunoassay for salsolidine. 5. Cross-reactivity studies revealed a high specificity of the antiserum to the hapten. 6. The antibodies had a high affinity to salsolidine (Ka = 1.5 x 10(9) M-1). 7. Standard curves covered a measuring range of 0.5-70 pmol/tube and the detection limit was found to be 0.27 pmol/tube.

Animals↗
PubMed1993

Calf vessel preservation in peripheral vascular disease--angiography versus pulse generated run-off.

Previous angiographic and radiological studies have suggested that the peroneal artery is the best preserved of the calf vessels in peripheral vascular disease and should be a site of preference for a femorodistal bypass graft. Calf vessel run-off assessed by pulse generated run-off (PGR) provides a more accurate prediction of graft success or failure than angiography and may therefore give a better functional picture of vessel patency than angiography. This study compares the presence and degree of preservation of the three calf vessels in patients with severe peripheral vascular disease using both intra-arterial digital subtraction angiography (IADSA) and PGR. Thirty-four limbs in patients with either ischaemic rest pain, ulceration or gangrene were studied and the results were scored according to the extent and severity of disease in the peroneal, posterior tibial and anterior tibial arteries. On IADSA, the peroneal artery was patent significantly more often (79%) than the posterior tibial artery (47%) or the anterior tibial artery (38%). Conversely, PGR examination showed no difference in patency between the three vessels (peroneal 91%, posterior tibial 88%, anterior tibial 79%). The peroneal artery was also significantly better preserved on IADSA (65%) compared to the posterior tibial artery (38%) and the anterior tibial artery (23%). PGR studies again showed no difference in the best preserved vessel between peroneal (47%), posterior tibial (50%) and anterior tibial (50%) arteries. Thus, the peroneal artery appears the better preserved vessel on angiography but this appearance may be misleading because the more functional PGR studies show no significant difference in the patency or degree of preservation of the three calf vessels.

Angiography, Digital Subtraction↗
PubMed1993

Genotoxicity characteristics of reverse diol-epoxides of chrysene.

Trans-3,4-dihydroxy-3,4-dihydrochrysene (chrysene-3,4-diol), a major metabolite of chrysene, is further metabolized by rat liver enzymes to products which effectively revert the his- Salmonella typhimurium strain TA98 to histidine prototrophy, but are only weakly mutagenic in strain TA100 and in Chinese hamster V79 cells (acquisition of resistance to 6-thioguanine). The liver enzyme mediated mutagenicity of chrysene-3,4-diol is substantially enhanced in the presence of 1,1,1-trichloropropene 2,3-oxide, an inhibitor of microsomal epoxide hydrolase. The predominant metabolites of chrysene-3,4-diol, namely the anti- and syn-isomers of its 1,2-oxide (termed reverse diol-epoxides), proved to be extraordinarily effective mutagens in S.typhimurium strain TA98, but were only moderately active in strains TA100 and TA104, and in the SOS induction in Escherichia coli PQ37. These genotoxicity spectra in bacteria are completely different from those observed with the bay-region diol-epoxides of chrysene and 3-hydroxychrysene. In V79 cells, the reverse diol-epoxides formed low levels of DNA adducts and were very weak inducers of gene mutations. In M2 mouse prostate cells, however, high numbers of transformed foci were induced by chrysene-3,4-diol and its diastereomeric 1,2-oxides. Chrysene-3,4-diol was somewhat more potent than chrysene-1,2-diol. The potency of both reverse diol-epoxides was similar to that of the syn-diastereomers of the bay-region diol-epoxides of chrysene and 3-hydroxychrysene, but lower than that of their anti-diastereomers. The reverse diol-epoxides of chrysene, unlike the bay-region diol-epoxides, were inactivated by purified microsomal epoxide hydrolase. Noteworthy findings were also made with regard to the chemical stability of the diol-epoxides in buffer, determined from the decline in mutagenicity after preincubation in the absence of the target cells. Despite its lower delta Edeloc/beta value for the formation of the benzylic carbocation, anti-chrysene-3,4-diol 1,2-oxide was shorter-lived (t1/2 = 46 min) than anti-chrysene-1,2-diol 3,4-oxide (t1/2 = 74 min). Unlike other investigated diastereomeric pairs of diol-epoxides, it was also shorter-lived than its syn-diastereomer (t1/2 = 340 min).

Animals↗
PubMed1993

Postoperative pulmonary complications. Epidural analgesia using bupivacaine and opioids versus parenteral opioids.

BACKGROUND: Different types of analgesia have been proposed for the prevention of postoperative respiratory complications. The aim of this prospective, double-blind randomized study was to compare the impact of epidural bupivacaine and opioids versus parenteral opioids on respiratory complications in patients who had undergone major abdominal surgery. METHODS: One hundred fifty-three patients undergoing abdominal surgery for cancer were randomly allocated to receive either general anesthesia with intravenous fentanyl and postoperative analgesia with subcutaneous morphine (SC group) or general anesthesia combined with epidural bupivacaine and epidural bupivacaine plus morphine for postoperative pain relief (EP group). Analgesia was tested on a visual analog pain scale. Pulmonary complications were evaluated according to clinical complications, chest radiographs, arterial blood gas analysis, and pulmonary function tests. The evaluation was carried out on the day before the operation and on the first 5 postoperative days. Particular attention also was paid to the episodes of arterial hypotension and hemoglobin oxygen desaturation during the 1st postoperative night. RESULTS: Pain relief was significantly better in the EP group than in the SC group (P < 0.05) especially during recovery and on the 1st and 2nd postoperative days. In the EP group, vital capacity decreased less on the 1st postoperative day (P < 0.05) and arterial oxygen tension was greater in the recovery room (P < 0.05). However, no statistically significant difference was observed between the SC and EP groups in the incidence of clinical pulmonary complications (31% and 27%, respectively) and radiographic chest abnormalities (52% and 46%, respectively). The EP group recovered intestinal function earlier (P < 0.05), but significantly more patients in this group had episodes of systolic hypotension (21% vs. 8%; P < 0.05) during the 1st postoperative night. The length of the hospital stay was similar in both groups of treatment. CONCLUSIONS: Epidural analgesia with a combination of local anesthetic and opioid improves patient comfort. However, this type of analgesia does not decrease the incidence of postoperative pulmonary complications, does not reduce the length of the hospital stay, and carries the risk of complications from episodic systemic hypotension.

Abdomen↗
PubMed1993

Structural comparison and epitope analysis of outer-membrane protein PIA from strains of Neisseria gonorrhoeae with differing serovar specificities.

The sequences of the por genes, encoding outer-membrane protein PI, have been obtained from a number of strains of Neisseria gonorrhoeae that express PIA molecules with differing serovar specificities. The inferred amino acid sequences of the mature proteins each comprise 308 residues and show considerable homology, with the degree of sequence variation between PIA molecules being considerably less than seen previously with PIB, but more evenly distributed throughout the molecule. The positions of sequence variation are largely confined to the regions predicted to form one of eight surface-exposed loops, suggesting a more widespread distribution of potential antigenic diversity. The deduced amino acid sequences were used to synthesize peptides for epitope mapping experiments. Some epitopes responsible for serovar specificity or recognized by bactericidal monoclonal antibodies could be identified on the basis of their reactivity with simple linear peptides, whilst others recognized conformational epitopes. By comparison of sequence differences with mAb reactivity it was possible to identify regions that appear to contribute to such determinants, including separated regions of the molecule which together were required for the formation of the conformational epitopes. All the epitopes identified lie at or close to the apices of the predicted surface-exposed loops 1, 3, 6, or 8, focusing attention on these regions as accessible targets for immune attack.

Amino Acid Sequence↗
PubMed1993

Psychiatric symptoms in cannabis users.

The usual phenomena of cannabis intoxication include experiences which in a non-intoxicated state would be considered as psychiatric symptoms. These can be distinguished from adverse reactions to cannabis, the commonest of which is an acute anxiety state. Acute psychotic episodes can also follow ingestion of the drug but are infrequent. These can be classified as acute confusional states and episodes occurring in clear consciousness. Neither presentation consistently shows enough specific features to warrant the diagnosis of 'cannabis psychosis' as a distinct clinical entity. The evidence that cannabis has a causative role in chronic psychotic or affective disorders is not convincing, although the drug may modify the course of an already established illness. Further controlled studies would be required to clarify the aetiological significance of the drug in these conditions.

Anxiety↗
PubMed1993

Modeling growth and individual differences in spatial tasks.

The goal of the present research is to understand individual differences and growth of children's and adolescents' performance on two spatial tasks through a formal model framework. In Study 1, 579 subjects aged 7-16 years old drew lines to represent their water-level task predictions for eight tilted rectangular vessels. In the verticality task, called the "van task," subjects drew lines representing their predictions concerning the orientation of a plumb line suspended from the ceiling of a van parked on eight different inclines. In Study 2, 185 subjects aged 9-16 years were presented with video displays on a computer monitor and were instructed to adjust lines on the screen to indicate their predictions for the same stimuli used in Study 1. Later, they responded to a multiple-choice verbal analogies test and answered interview questions concerning their task performance strategies for the van and water-level tasks. In both studies, responses on the van and water-level tasks were scored as correct or incorrect on the basis of empirically derived scoring criteria that varied with age. The number of correct responses for each subject on the van and water-level tasks was modeled as a binomial random variable. Individual differences, growth differences, and sex differences in task performance were modeled as mixtures of binomial distributions, a model that may be viewed as a latent class model. Data for Study 1 subjects 11 years and older were combined so that the joint structure of the water-level and van tasks could be studied. This structure was modeled as a mixture of bivariate binomial distributions. On the basis of their task performance, subjects in Study 1 were assigned to their corresponding latent classes. Once classified, the original response distributions of subjects within each latent class were explored in an effort to understand their various response strategies. Additionally, the correspondence between verbal explanations and van and water-level task performance was investigated in Study 2. Results include the following: 1. A two-component binomial mixture distribution fit well the van and water-level task data for each age and sex group; each binomial component may be viewed as a different latent class. Variance accounted for under the model often exceeded 90%. One binomial component (latent class) modeled the poor performers with poor task success rates, and the second component modeled the remaining good performers who consistently performed well.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
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↗