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Biomedical subjects

H M Thomas

Publications and source records attributed to H M Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1995

A double-blind, placebo-controlled study of nortriptyline and bromocriptine in male alcoholics subtyped by comorbid psychiatric disorders.

This double-blind, placebo-controlled, 6-month follow-up treatment study investigated the efficacy of bromocriptine and nortriptyline in attenuating drinking behavior and psychiatric symptoms in 216 male alcoholic patients subtyped by comorbid psychiatric disorder(s). Three well-defined subtypes were examined: alcoholism only, alcoholism + affective/anxiety disorder, and alcoholism + antisocial personality disorder. It was hypothesized that both medications would relieve negative affective symptoms associated with alcohol use and would be particularly effective for the affective/anxiety subgroup. Contrary to our predictions, the only significant effects found were with the antisocial personality disorder patients who were receiving nortriptyline. One interpretation of the results was that nortriptyline may have reduced impulsive drinking in the antisocial personality disorder subgroup by actions on serotonergic neurotransmission.

Adult↗
PubMed1994

SPECT regional cerebral blood flow alterations in naltrexone-precipitated withdrawal from buprenorphine.

The effects of naltrexone-precipitated withdrawal from buprenorphine on behavior and regional cerebral blood flow (rCBF) were studied in 11 opiate-dependent patients. Patients initially received buprenorphine, 2 mg sublingually, every day for 7 days. They were then challenged sequentially with placebo and naltrexone, 25 mg orally, before single photon emission computed tomography with technetium-99m-d,l-hexamethyl-propylene amine oxime as tracer. Behavioral ratings of withdrawal severity were made before and after naltrexone/placebo administration. Naltrexone produced significantly greater signs and symptoms of opiate withdrawal than placebo. Analysis of variance revealed no significant regionally specific effect of naltrexone on rCBF ratios. Severity of withdrawal, however, showed a significant negative correlation with rCBF in the anterior cingulate cortex following naltrexone. These results are interesting as the anterior cingulate region has been implicated in the emotional component of pain and in opiate-induced analgesia.

Adult↗
PubMed1994

Recurrence of Pallister-Hall syndrome in two sibs.

We report the first definite sib recurrence of Pallister-Hall syndrome in a family without a cytogenetically visible chromosome abnormality. The father of these two sibs was born with nearly identical digital abnormalities and could represent either mild expression or gonosomal mosaicism for a dominant gene.

Abnormalities, Multiple↗
PubMed1994

Impact of desipramine or carbamazepine on patient retention in outpatient cocaine treatment: preliminary findings.

This is a preliminary report of a double-blind comparison of desipramine or carbamazepine to placebo among subjects participating in an outpatient cocaine treatment program. Sixty-five subjects were randomly assigned to one of the active drugs or placebo and followed until treatment completion or drop-out to determine if either drug enhanced retention in treatment and/or increased cocaine abstinence. There was no significant difference between carbamazepine or desipramine and placebo on either outcome measure in this preliminary analysis. While this is a preliminary report and does not take into account the heterogeneity of the patients in cocaine treatment, the results are consistent with those of other investigators and suggest that use of desipramine or carbamazepine may not offer any advantage in retaining cocaine-dependent patients in treatment.

Ambulatory Care↗
PubMed1993

Kinetic analysis of the liver-type (GLUT2) and brain-type (GLUT3) glucose transporters in Xenopus oocytes: substrate specificities and effects of transport inhibitors.

We have expressed the human isoforms of the liver-type (GLUT2) and brain-type (GLUT3) facilitative glucose transporters in oocytes from Xenopus laevis via injection of in vitro transcribed mRNA. As reported previously [Gould, Thomas, Jess and Bell (1991) Biochemistry 30, 5139-5145], GLUT2 mediates the transport of fructose and galactose, and GLUT3 mediates the transport of galactose. We have examined the effects of D-glucose, D-fructose and maltose on deoxyglucose transport in oocytes expressing GLUT2, and D-glucose, D-galactose and maltose on deoxyglucose transport in oocytes expressing GLUT3, and show that each sugar is a competitive inhibitor of transport. Moreover, D-glucose and maltose competitively inhibit fructose transport by GLUT2 and galactose transport by GLUT3, indicating that the transport of the alternative substrates for these transporters is likely to be mediated by the same outward-facing sugar-binding site used by glucose. Cytochalasin B is a non-competitive inhibitor of glucose transport by the well-characterized GLUT1 isoform. We show here that cytochalasin B is also a non-competitive inhibitor of the transport of deoxyglucose and alternative substrates by GLUT2 and GLUT3 expressed in oocytes. Km and Ki values for each substrate and inhibitor are presented for each isoform, together with further analysis of the binding sites for alternative substrates for these transporter isoforms.

Animals↗
PubMed1993

Differential targeting of glucose transporter isoforms heterologously expressed in Xenopus oocytes.

We have examined the subcellular distribution of three members of the human glucose transporter family expressed in oocytes from Xenopus laevis. Following injection of in vitro-transcribed mRNA encoding the transporter isoform to be studied, we have determined the subcellular localization of the expressed protein by immunofluorescence and by subcellular fractionation coupled with immunoblotting using specific anti-peptide antibodies. We have shown that both the liver-type (GLUT 2) and brain-type (GLUT 3) glucose transporters are expressed predominantly in the plasma membranes of oocytes, and in both cases high levels of glucose transport activity are exhibited. In contrast, the insulin-regulatable glucose transporter (GLUT 4) is localized predominantly to an intracellular membrane pool, and the levels of transport activity recorded in oocytes expressing GLUT 4 are correspondingly lower. The localization of the different transporter isoforms to distinct subcellular fractions mirrors the situation observed in their native cell type and thus demonstrates that oocytes may prove to be a useful system with which to study the targeting signals for this important class of membrane proteins. In addition, the determination of the amounts of the transporters expressed per oocyte together with a knowledge of their Km values has allowed us to estimate the turnover numbers of these transporters. Insulin was without effect on glucose transport in oocytes expressing any of these transporter isoforms. Microinjection of guanosine 5'-[gamma-thio]triphosphate into oocytes expressing GLUT 4 was also without effect on the transport rate.

Animals↗
PubMed1993

Pancreatic beta-cells express a low affinity glucose transporter: functional consequences in normal and diabetic states.

The application of molecular biology to the study of membrane transport proteins has led to a rapid advance in our understanding of the mechanisms behind the regulation of blood glucose levels. Moreover the demonstration of lesions in the expression of GLUT2 in the islets from diabetic models has provided a focus for research efforts aimed at addressing the defects responsible for the development and onset of both type I and perhaps type II diabetes. The recent demonstration that an 'artificial beta-cell' can be engineered from anterior pituitary-derived cell lines by transfection with both the insulin cDNA and the cDNA encoding GLUT2 represents a significant advance in the development of potential therapies for type I diabetes [24].

Animals↗
PubMed1992

Analysis of the glucose transporter content of islet cell lines: implications for glucose-stimulated insulin release.

Glucose transport across the plasma membrane of mammalian cells is mediated by a family of homologous proteins. Each glucose transporter isoform has a specific tissue distribution which relates to that tissue's demand for glucose. The beta-cells of pancreatic islets are known to express a distinct glucose transporter isoform, termed GLUT 2, which has a high Km for glucose. In this study, we examined the glucose transporter content of normal rat islets and three beta cell lines, beta-TC, HIT and RIN cells. We show that at the protein level, GLUT 2 is the only detectable transporter isoform in normal islets, and that all three cell lines also express detectable GLUT 2. In contrast, all three cell lines expressed high levels of GLUT 1, but this isoform was not detected in normal islets. Neither the native islets nor any of the cell lines expressed GLUT 3. The insulin-responsive glucose transporter GLUT 4 was detected at very low levels in beta-TC cells; to our knowledge, this is the only non-muscle or adipose cell line which expresses this isoform. We propose that the elevated level of GLUT 1 expression, together with a reduced expression of the high Km transporter GLUT 2, may account for the characteristic aberrant patterns of glucose-stimulated insulin release in cell lines derived from beta-cells.

Amino Acid Sequence↗
PubMed1991

Expression of human glucose transporters in Xenopus oocytes: kinetic characterization and substrate specificities of the erythrocyte, liver, and brain isoforms.

We describe the functional expression of three members of the family of human facilitative glucose transporters, the erythrocyte-type transporter (GLUT 1), the liver-type transporter (GLUT 2), and the brain-type transporter (GLUT 3), by microinjection of their corresponding mRNAs into Xenopus oocytes. Expression was determined by the appearance of transport activity, as measured by the transport of 3-O-methyl-D-glucose or 2-deoxy-D-glucose. We have measured the Km for 3-O-methyl-D-glucose of GLUTs 1, 2, and 3, and the results are discussed in light of the possible roles for these different transporters in the regulation of blood glucose. The substrate specificity of these transporter isoforms has also been examined. We show that, for all transporters, the transport of 2-deoxy-D-glucose is inhibited by D-but not by L-glucose. In addition, both D-galactose and D-mannose are transported by GLUTs 1-3 at significant rates; furthermore, GLUT 2 is capable of transporting D-fructose. The nature of the glucose binding sites of GLUTs 1-3 was investigated by using hexose inhibition of 2-deoxy-D-glucose uptake. We show that the characteristics of this inhibition are different for each transporter isoform.

Animals↗
PubMed1990

Cardiovascular screening in Army personnel over age 40 in the State of Hawaii.

A cardiovascular screening protocol was applied prospectively to 1,900 soldiers over 40 years of age to identify individuals with latent coronary artery disease. Primary screening included a cardiovascular history, physical examination, electrocardiogram, serum cholesterol and serum glucose determinations, and calculated Framingham risk index. Seven hundred ninety-six individuals required secondary screening, consisting of stress testing and cardiac fluoroscopy. The screening process led to coronary angiography in 43 individuals; of these, 17 had obstructive coronary artery disease, ten had nonobstructive coronary artery disease, and 16 had normal coronary arteries. Application of primary screening before exercise testing increased the posttest probability of obstructive coronary artery disease to 50% in the individuals with a positive treadmill test. This is four times the expected value of 11% calculated using Bayes' theorem. The combination of a positive treadmill test and the finding of coronary artery calcification on fluoroscopy was an excellent predictor of obstructive coronary artery disease.

Adult↗