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Biomedical subjects

T Thomas

Publications and source records attributed to T Thomas.

At least 271 records · Page 15Linked to original sources
PubMed1990

GABAB agonists modulate a transient potassium current in cultured mammalian hippocampal neurons.

Depolarization of voltage-clamped cultured rat hippocampal neurons from holding potentials more negative than -60 mV produced a transient outward current with the characteristics of an A-current: it was 50% inactivated at a holding potential of -85 mV and blocked by 4-aminopyridine (1 mM). In the presence of GABA or baclofen (50-200 microM), with or without bicuculline, inactivation of this current was shifted to more positive potentials so that there was little inactivation at -70 mV. Activation of the A-current was also shifted to more positive potentials by these agonists, but the voltage dependence of activation of the sodium current was unaffected. If A-currents with similar properties can influence the time course of action potentials in presynaptic terminals. GABAB agonists could make action potentials briefer by potentiating the A-current and hence depress transmitter release.

4-Aminopyridine↗
PubMed1990

Increase in glomerular filtration rate in patients with insulin-dependent diabetes and elevated erythrocyte sodium-lithium countertransport.

Increased sodium-lithium countertransport in erythrocytes is found in patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy. To determine whether such an increase precedes the onset of nephropathy and, if so, whether it is associated with changes in renal function, we measured erythrocyte sodium-lithium countertransport in 52 patients with IDDM but not nephropathy or hypertension and in 32 control subjects. Seventeen of the 52 patients with IDDM (33 percent) had sodium-lithium countertransport activity that exceeded the maximal activity in the control subjects (0.39 mmol of lithium per hour per liter of cells). Eighteen of the 52 patients with IDDM were studied in more detail. The 7 patients with raised sodium-lithium countertransport values had glomerular filtration rates (median, 159 ml per minute per 1.73 m2 of body-surface area; range, 134 to 197) that were significantly higher (P less than 0.01) than those in the remaining 11 patients with IDDM and normal sodium-lithium countertransport (median, 126 ml per minute per 1.73 m2; range, 110 to 176) or in the 10 control subjects (median, 128 ml per minute per 1.73 m2; range, 93 to 151). In the seven patients with elevated sodium-lithium countertransport, the filtration fraction (median, 0.27; range, 0.22 to 0.37) was also greater (P less than 0.01) than that in control subjects (median, 0.22; range, 0.18 to 0.28). There were no differences in renal function between the patients with IDDM and normal sodium-lithium countertransport and the control subjects. We conclude that sodium-lithium countertransport is increased in patients with IDDM before the onset of nephropathy and is associated with hyperfiltration. Thus, elevated sodium-lithium countertransport activity may be an early marker of diabetic nephropathy.

Adult↗
PubMed1990

Acute, chronic, and interactive effects of type I and II corticosteroid receptor stimulation on feeding and weight gain.

Type I (aldosterone) and/or type II (dexamethasone or RU28362) corticosterone receptor agonists were continuously infused in adrenalectomized Sprague-Dawley rats for 28 days at doses of 3.4, 17.2, or 86.2 nmol/day. Additional groups received combined agonist infusions, blank infusions, or sham operations. The type I agonist stimulated body weight gain, and the type II agonists were both suppressive, differing mainly in degree. Although there were a few early effects of these hormones (usually a stage of exaggerated activity), once passed, chronic stimulation was marked by steady or slightly increasing steroid influence on body weight. Throughout the chronic phase of this study there was no departure from a simple opponent model of type I and II ligand actions, and their combination approximated an arithmetic summation of the two separate agonists. This was generally true of feeding as well, although steroid effects on intake were always less pronounced. In contrast to chronic administration, acute combinations of these agonists were highly interactive, producing slight losses than large gains for the aldosterone and RU28362 combinations, but a large gain then small loss for the aldosterone and dexamethasone combination. These results imply that RU28362 and dexamethasone differ in more respects than potency. Because normal endogenous type II stimulation is acute and occurs against a background of type I receptor occupation, mixed agonist interactions are probably the rule for everyday physiological activity, not the exception.

Aldosterone↗
PubMed1990

Regulation of polyamine biosynthesis by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

We have examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on tissue polyamine concentrations in CD1 mice. Two days after a low dose treatment with TCDD, polyamine content of the liver and thymus of treated mice showed a 49-82% decrease, but that of spleen was not affected. Based on this finding, we examined the role of alterations in polyamine levels in the toxicity of TCDD. We administered the polyamine biosynthetic inhibitor difluoromethylornithine (DFMO) to animals treated with a toxic dose of TCDD. DFMO dramatically increased the toxicity of TCDD as measured by mortality, ascites and changes in organ weights. In addition, administration of the polyamine putrescine was able to reduce the toxicity of TCDD. These results suggest that a decrease in polyamine concentrations in critical organs may play an important role in the toxic effects of TCDD.

Animals↗
PubMed1990

Ethanol predominantly alters sodium influx in human leucocytes.

1. Although ethanol appears to alter cellular sodium transport, the exact nature of its effects has not been clearly defined. We have studied the effects of different concentrations of ethanol on human leucocyte sodium content, and on the rise in leucocyte sodium content which occurs during sodium pump blockade with ouabain. 2. Sodium content was significantly reduced after a 20 min incubation with ethanol at concentrations between 17 and 170 mmol/l. 3. The rise in sodium content during a 20 min incubation with ouabain was significantly less in the presence of 170 mmol/l ethanol as compared with 17 mmol/l ethanol. 4. These results suggest that the effect of ethanol on intracellular sodium content is independent of sodium pump activity, i.e. it is mediated through reduced sodium influx.

Biological Transport↗
PubMed1990

A new radioimmunoassay for human alpha atrial natriuretic peptide and its physiological validation.

A new sensitive, specific radioimmunoassay for human alpha atrial natriuretic peptide (hANP) and a novel extraction method for hANP have been developed. Antiserum to hANP (Keq = 1.923 x 10(11) l/mol) showed no cross-reactivity with related analogues. Displacement of 50% bound 125I-hANP occurred at 4.7 +/- 0.1 fmol/tube (n = 15). The limit of detection of plasma hANP after extraction of 2 ml plasma with Florisil was 1.2 pmol hANP/litre plasma. The recovery of synthetic hANP from plasma over the range 6.5-162.5 pmol/l was 71.2 +/- 1.9%. Inter- and intra-assay coefficients of variation were 13.1% and 10.1% respectively. Extracted plasma was stored at -80 degrees C without loss in immunoreactivity. The radioimmunoassay was physiologically validated in man by measuring plasma hANP following central volume expansion - (a) plasma hANP rose from 2.5 +/- 0.5 to 4.1 +/- 0.6 pmol/l in 9 normal volunteers after postural change from seated to lying (b) infusion of normal saline (2 litre/2 hour) increased hANP from 1.6 to 4.3 pmol/l (n = 2). Infusion of hANP (2 pmol/kg/min) increased plasma hANP to 19.9 +/- 3.4 pmol/l (n = 6).

Animals↗
PubMed1990

Conformational transitions of polynucleotides in the presence of rhodium complexes.

We studied the effects of hexammine and tris(ethylene diamine) complexes of rhodium on the conformation of poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) using spectroscopic techniques and an enzyme immunoassay. Circular dichroism spectroscopic measurements showed that Rh(NH3)6(3+) provoked a B-DNA----Z-DNA----psi-DNA conformational transition in poly(dG-dC).poly(dG-dC). Using the enzyme immunoassay technique with a monoclonal anti-Z-DNA antibody, we found that the left-handedness of the polynucleotide was maintained in the psi-DNA form. In addition, we compared the efficacy of Rh(NH3)6(3+) and Rh(en)3(3+) to provoke the Z-DNA conformation in poly(dG-dC).poly(dG-dC) and poly(dG-m5dC.poly(dG-m5dC). The concentrations of Rh(NH3)6(3+) and Rh(en)3(3+) at the midpoint B-DNA----Z-DNA transition of poly(dG-dC).poly(dG-dC) were 48 +/- 2 and 238 +/- 2 microM, respectively. The psi-DNA form of poly(dG-dC).poly(dG-dC) was stabilized at 500 microM Rh(NH3)6(3+). With poly(dG-m5dC).poly(dg-m5dC), both counterions provoked the Z-DNA form at approximately 5 microM and stabilized the polynucleotide in this form up to 1000 microM concentration. These results show that trivalent complexes of Rh have a profound influence on the conformation of poly(dG-dC).poly(dG-dC) and its methylated derivative. Furthermore, the Rh complexes are capable of maintaining the Z-DNA form at concentration ranges far higher than that of other trivalent complexes. Our results also demonstrate that the efficacy of trivalent inorganic complexes to induce the B-DNA to Z-DNA transition of poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) is dependent on the nature of the ligand as well as the polynucleotide modification. Differences in charge density and hydration levels of counterions or base sequence- and counterion-dependent specific interactions between DNA and metal complexes might be possible mechanisms for the observed effects.

Antibodies, Monoclonal↗
PubMed1990

Potassium supplementation in the treatment of idiopathic postural hypotension.

We studied the effects of potassium supplementation (60 mmol/day) and matching placebo on the postural blood-pressure fall in ten elderly patients with symptomatic idiopathic postural hypotension in a double-blind, randomized cross-over trial. There was a significant decrease in the orthostatic fall in systolic blood pressure (SBP 33 +/- 5 mmHg to 16 +/- 9 mmHg, p less than 0.01) and in supine SBP (162 +/- 7 to 150 +/- 7 mmHg, p less than 0.01) between placebo and potassium phases. Supine diastolic and erect blood pressures were unchanged, though pulse rate showed a greater orthostatic increase (7 +/- 3 beats/min to 14 +/- 2 beats/min, p less than 0.05) following potassium therapy. No significant changes were seen in intracellular electrolytes, plasma renin activity, aldosterone levels or body weight. Seven patients reported symptomatic improvement with potassium, but none during the placebo phase. Potassium therapy was well tolerated and may be a successful and safe method of treating idiopathic postural hypotension.

Aged↗
PubMed1990

Sodium content and transport of white and red blood cells in undialysed uraemic and continuous ambulatory peritoneal dialysis patients.

Leukocyte cation content and sodium pump transport were measured in 14 undialysed uraemic and 15 CAPD patients and compared with results from healthy controls. Sodium content was elevated in the undialysed group compared with the CAPD group (P = 0.05) or the healthy controls (P less than 0.001), but this abnormality could not be clearly attributed to increased sodium influx or reduced sodium pumping. Sodium content correlated with plasma urea (rs = 0.69, P = 0.005) and creatinine (rs = 0.56, P = 0.031) concentrations in the CAPD group only. In subgroups of 12 undialysed and ten CAPD patients, erythrocyte sodium content and pump transport were measured at the same time as the leukocyte studies. Erythrocyte sodium was less in the undialysed group (P less than 0.01) and again there was no evidence of significant sodium-pump inhibition. The abnormalities in sodium content in undialysed patients were therefore in opposite directions in the two cell types, and were significantly less in both cell types in CAPD patients. These results emphasise the dangers of assuming that abnormalities of sodium transport seen in a single cell type can be taken as evidence of a generalised abnormality.

Adolescent↗
PubMed1990

The haemodynamic effects of correction of anaemia in haemodialysis patients using recombinant human erythropoietin.

STUDY OBJECTIVE: To evaluate the acute and long-term haemodynamic response to recombinant human erythropoietin (rHuEpo) correction of chronic anaemia in haemodialysis-supported patients. DESIGN: Prospective analysis of randomly chosen patients undergoing the multicentre phase III clinical recombinant erythropoietin trial. SETTING: Chronic haemodialysis patients supported in one of two dialysis centres of a large urban tertiary referral centre. PATIENTS: Thirteen of the 59 patients who met the criterion for participation in the multicentre clinical phase III trial of recombinant erythropoietin were randomly chosen. Mean age (42.6 years), and time on dialysis (3.4 years) was representative of the study population. Ten patients were receiving antihypertensive therapy, which remained unchanged throughout the study. INTERVENTIONS: Haemodynamic testing was done in a fasting state, in the supine position, utilising radionuclide angiocardiography. Plasma volume was determined by 125I-labelled serum albumin. Echocardiographic and hormonal evaluations were also performed at each haemodynamic evaluation. All testing was done immediately prior to first dose of drug, upon reaching target haematocrit, and at 6 months and 1 year of continued non-anaemia. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure did not seem to change at any of the study periods, while total peripheral resistance did drop at target (34 +/- 2.5 vs 27.2 +/- 3.2 microns2, P = 0.05). Cardiac output (5.6 +/- 0.5 vs 7.6 +/- 0.8 l/min, P = 0.005) and stroke volume (77 +/- 9.6 vs 116 +/- 15.4 ml, P = 0.005) also rose at this same period but returned to baseline during later periods. Ejection fraction increased over baseline at both target and 1 year study points (50 +/- 2.7 vs 57.7 +/- 3 vs 63 +/- 4.3, P = 0.05) while the haematocrit was increased at target (21.8 +/- 0.9 vs 35.6 +/- 1.0, P less than 0.0005), and maintained at this new level throughout the study. Total blood volume (118 +/- 6.7 vs 100.4 +/- 8.1 ml/cm, P less than 0.05) and plasma volume (150 +/- 8.2 vs 108.5 +/- 9.4 ml/cm, P less than 0.001) decreased at 1 year. CONCLUSION: Recombinant human erythropoietin is effective in correcting the anaemia of chronic renal failure. Any haemodynamic changes which may be induced seem to occur early in the course of therapy, are different from those changes induced by blood transfusions, and tend to return to baseline with continued treatment.

Adolescent↗
PubMed1990

Gene expression in regenerating and acute-phase rat liver.

The integration of growth and the acute-phase response is investigated by comparing the mRNA levels in rat liver during acute inflammation with those after partial hepatectomy. Northern analysis is carried out for the mRNAs for thiostatin, alpha 2-macroglobulin, alpha 1-antitrypsin, inter-alpha-trypsin inhibitor subunit 1, haptoglobin, ceruloplasmin, transferrin, vitamin D-binding protein, alpha 1-acid glycoprotein, beta-fibrinogen, apolipoproteins A-IV and E, albumin, transthyretin, alpha 2-HS-glycoprotein, retinol-binding protein, beta-tubulin, c-myc protooncogene, glyceraldehyde-3-phosphate dehydrogenase, phosphoenolpyruvate carboxykinase, ornithine transcarbamylase, and alcohol dehydrogenase. The acute-phase response dominates during the first 18 h. Changes in mRNA levels related to growth of the liver become important thereafter, and the capacity for an acute-phase response of plasma protein synthesis becomes greatly reduced. The early increase in the level of ceruloplasmin mRNA observed during inflammation is abolished during regeneration, and that of vitamin D-binding protein mRNA is converted into a decrease. The mRNAs levels of glyceraldehyde-3-phosphate dehydrogenase increase, and those for phosphoenolpyruvate carboxykinase decrease during regeneration. Ornithine transcarbamylase mRNA levels are found to exhibit negative acute-phase regulation. The pattern of transcriptional regulation is similar during inflammation and regeneration.

Acute-Phase Proteins↗