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Biomedical subjects

B O'Neill

Publications and source records attributed to B O'Neill.

At least 19 recordsLinked to original sources
PubMed1992

ATP-dependent bile-salt transport in canalicular rat liver plasma-membrane vesicles.

The present study identifies and characterizes a novel ATP-dependent bile-salt transport system in isolated canalicular rat liver plasma-membrane (cLPM) vesicles. ATP (1-5 mM) stimulated taurocholate uptake into cLPM vesicles between 6- and 8-fold above equilibrium uptake values (overshoot) and above values for incubations in the absence of ATP. The ATP-dependent portion of taurocholate uptake was 2-fold higher in the presence of equilibrated KNO3 as compared with potassium gluconate, indicating that the stimulatory effect of ATP was not due to the generation of an intravesicular positive membrane potential. Saturation kinetics revealed a very high affinity (Km approximately 2.1 microM) of the system for taurocholate. The system could only minimally be stimulated by nucleotides other than ATP. Furthermore, it was preferentially inhibited by conjugated univalent bile salts. Further strong inhibitory effects were observed with valinomycin, oligomycin, 4,4'-di-isothiocyano-2,2'-stilbene disulphonate, sulphobromophthalein, leukotriene C4 and N-ethylmaleimide, whereas nigericin, vanadate, GSH, GSSG and daunomycin exerted only weak inhibitory effects or none at all. These results indicate the presence of a high-affinity primary ATP-dependent bile-salt transport system in cLPM vesicles. This transport system might be regulated in vivo by the number of carriers present at the perspective transport site(s), which, in addition to the canalicular membrane, might also include pericanalicular membrane vesicles.

Adenosine Triphosphate↗
PubMed1992

Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease.

In order to clarify the relationship between coronary artery disease (including myocardial infarction) and image contrast in gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced MRI it was decided to model the myocardial tissue distribution and clearance of Gd-DTPA using the modified Kety equation. Using a canine model, myocardial tissue Gd-DTPA concentrations ([Gd-DTPA]m) were measured 1 or 5 min after a bolus injection of Gd-DTPA or immediately after the end of a constant infusion of Gd-DTPA in a total of 35 dogs. It was found that within 5 min of a bolus injection [Gd-DTPA]m is determined primarily by myocardial blood flow (MBF) and after about 10 min primarily by myocardial extracellular volumes (MECV). This study suggests that repeat, rapid (every 2-4 s) measurements of myocardial T1 relaxation rates following the bolus injection of Gd-DTPA are required to calculate MBF (i.e., myocardial tissue perfusion) and MECV.

Animals↗
PubMed1992

Identification of sodium-dependent and sodium-independent dicarboxylate transport systems in rat liver basolateral membrane vesicles.

The mechanisms involved in the hepatocellular uptake of Krebs-cycle intermediates were investigated in isolated basolateral (sinusoidal and lateral) rat liver plasma membrane (blLPM) vesicles. An inwardly directed Na+ gradient markedly stimulated uptake of 2-oxoglutarate and succinate into voltage- and pH-clamped blLPM vesicles. This Na(+)-dependent portion of the dicarboxylate uptake was characterized by (a) saturability with increasing substrate concentrations (Km = 6.4-10 mM; Vmax approximately 0.2 nmol min-1 mg protein-1), (b) cis-inhibition by lithium (10 mM), other Krebs-cycle dicarboxylates (1 mM) and DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid; 1 mM) but not by sulphate, monocarboxylates, oxalate, acidic amino acids, bile salts and probenecid, (c) stimulation by an intravesicular negative K(+)-diffusion potential indicating electrogenic [(Na+)n greater than 2-succinate] cotransport, and (d) a pH optimum for transport between 7.0 and 7.5. In the absence of Na+, an inside alkaline pH gradient also markedly stimulated 2-oxoglutarate uptake. This pH-gradient-driven 2-oxoglutarate uptake was insensitive to lithium, but could also be inhibited by DIDS and succinate. Furthermore, saturation kinetics demonstrated Km (approximately 34 mM) and Vmax (approximately 0.8 nmol min-1 mg protein-1) values that were clearly different from those of the Na(+)-dependent uptake system. These results indicate the occurrence of two separate dicarboxylate transport systems along the sinusoidal border of hepatocytes, one being a Na(+)-dicarboxylate symporter and the other representing an anion-exchange system.

Animals↗
PubMed1990

Abnormal zymosan-induced neutrophil chemiluminescence as a marker of depression.

Preliminary studies have shown that polymorphonuclear neutrophil (PMN) activity is decreased in a state-dependent manner in patients with endogenous depression. The present study investigates this finding in a larger group of psychiatric patients and attempts to determine the identification of the factor responsible for the abnormal neutrophil function. Chemiluminescence responses of PMNs from patients with diagnoses of endogenous depression, panic disorder, anxiety, schizophrenia and alcoholism were assessed concurrently with age- and sex-matched control subjects. The reduction in PMN activity was observed in panic disorder patients as well as during depression but remained normal in schizophrenia, alcoholism and generalised anxiety. The defect in PMN function appears to be related to an abnormal factor in the serum of the patient which is corrected on clinical recovery. Aspirin-inhibited prostaglandin synthesis resulted in an enhancement of PMN activity in healthy subjects, suggesting a possible role for prostaglandins in the abnormal PMN response.

Alcoholism↗
PubMed1988

County mapping of injury mortality.

Death rates for injuries were mapped by county in order to identify high-risk geographic areas. Overall rates of unintentional injury death were high in rural areas, especially in the West, and in low-income southern counties. Homicides, primarily due to firearms, had high rates throughout the South; elsewhere, homicide rates were high in large cities but not in suburban counties. Southern counties also had high rates of housefire mortality. Drowning rates for young children were high on the West Coast and in Florida, and were high for the population as a whole in the Mississippi Delta. Mapping by county is a potentially powerful tool for identifying high-risk areas and developing preventive measures.

Adolescent↗
PubMed1987

The biosynthesis of intestinal sucrase-isomaltase in human embryo is most likely controlled at the level of transcription.

Although sucrase-isomaltase appears in the small intestine at quite different stages of development in man as compared with most mammals, we find that in human embryo also the appearance of sucrase-isomaltase mRNA closely parallels that of sucrase and isomaltase activities, as we have previously found to be the case in baby rabbits. Also, in the proximal-distal gradient of human embryonic intestine (proximal small intestine greater than distal small intestine greater than colon) the levels of these enzyme activities and those of the corresponding mRNA correlate closely. Finally, glucocorticosteroid treatment of a human colon carcinoma cell line (Caco-2) in vitro or of baby rabbits in vivo leads to a parallel increase of both sucrase and isomaltase activities and of sucrase-isomaltase mRNA. We conclude that in man also, in spite of the different timing in development, the biosynthesis of sucrase-isomaltase is most likely to be controlled at the level of transcription or perhaps of the mRNA stability.

Animals↗
PubMed1987

Geographic variations in mortality from motor vehicle crashes.

Using a new technique to study the mortality associated with motor vehicle crashes, we calculated population-based death rates of occupants of motor vehicles during the period 1979 through 1981 and mapped them according to county for the 48 contiguous states of the United States. Mortality was highest in counties of low population density (r = 0.57; P less than 0.0001) and was also inversely correlated with per capita income (r = 0.23; P less than 0.0001). Death rates varied more than 100-fold; for example, Esmeralda County, Nevada, with 0.2 residents per square mile (2.6 km2), had a death rate of 558 per 100,000 population, as compared with Manhattan, New York, with 64,000 residents per square mile and a death rate of 2.5 per 100,000. Differences in road characteristics, travel speeds, seat-belt use, types of vehicles, and availability of emergency care may have been major contributors to these relations.

Accidents, Traffic↗
PubMed1987

The electrogenic, Na+-dependent I- transport system in plasma membrane vesicles from thyroid glands.

Using vesicles from the plasma membrane of hog thyroid, we have characterized its Na+-dependent I- transport system. We have found it to be totally Na+ dependent; K+ cannot substitute and Li+ can partially substitute for Na+; the Na+:I- flux ratio is larger than one; the system is electrogenic, being stimulated by a delta psi negative inside the vesicles. A number of large, lipophilic anions are fully-competitive inhibitors of Na+-dependent I- uptake; the closer their atomic radii are to that of iodine, the smaller their Ki values.

Animals↗
PubMed1987

Nonmetric test of the minimax theory of two-person zerosum games.

As an experimental test of the minimax theory for two-person zerosum games, subjects played a game that was especially easy for them to understand and whose minimax-prescribed solution did not depend on quantitative assumptions about their utilities for money. Players' average relative frequencies for the moves and their proportions of wins were almost exactly as predicted by minimax, but subject-to-subject variability was too high. These results suggest that people can deviate somewhat from minimax play since their opponents have limited information-processing ability and are imperfect record keepers, but they do not stray so far that the difference will be noticed and their own payoffs will be diminished.

Game Theory↗
PubMed1986

Ethanol selectively affects Na+-gradient dependent intestinal transport systems.

Moderate concentrations of ethanol reduce the velocity of uptake of three representative Na+-symport systems (D-glucose, L-alanine, L-ascorbate), whether electrogenic (the first two) or electroneutral (L-ascorbate). This 'inhibition' is observed only if these transport systems are tested in the presence of an initial Na+ gradient (out greater than in); no inhibition is found in tracer-equilibrium exchange measurements. A representative Na+-independent system (D-fructose) is not inhibited by ethanol. 'Passive diffusion' (measured as uptake of L-glucose) is increased somewhat by alcohol. All these observations can be rationalized [as suggested by Tillotson et al. (1981) Arch. Biochem. Biophys. 207, 360-370] by an effect of ethanol on passive diffusion, which leads to a faster collapse of the Na+ gradient, with the resulting reduction of the uptake velocities of Na+-dependent transport systems when tested with the added driving force of an Na+ out----in gradient.

Alanine↗
PubMed1986

Perceived risks and driving behavior.

Claims have been made that safer cars result in drivers who take more risks. However, there are two basic design changes that make cars safer: the first reduces the likelihood of a crash; the second reduces the chance of injury during a crash. Because design changes that reduce the likelihood of a crash also often provide direct and immediate feedback, drivers may change their behavior, although there is no evidence that the change offsets the benefits of the increased crash avoidance capability. Design changes that increase occupant protection usually provide no direct and immediate feedback and, therefore, should have no effect on driving behavior. The data are consistent with this hypothesis and contradict the hypothesis of risk compensation.

Accidents, Traffic↗
PubMed1985

A prospective study between carbamazepine, phenytoin and sodium valproate as monotherapy in previously untreated and recently diagnosed patients with epilepsy.

One hundred and eighty one patients with previously untreated epilepsy were randomised to sodium valproate, phenytoin or carbamazepine as monotherapy and followed up for a median period which ranged from 14 to 24 months. All three drugs were highly effective in the control of generalised seizures but less effective for partial seizures. Excellent or good control was achieved with therapeutic levels of sodium valproate and carbamazepine, but with subtherapeutic levels of phenytoin.

Adolescent↗