Biomedical subjects

A Baron

Publications and source records attributed to A Baron.

At least 73 records · Page 4Linked to original sources

PubMed1996

Temporal control by progressive-interval schedules of reinforcement.

Progressive-interval performances are described using measures that have proven to be successful in the analysis of fixed-interval responding. Five rats were trained with schedules in which the durations of consecutive intervals increased arithmetically as each interval was completed (either 6-s or 12-s steps for different subjects). The response patterns that emerged with extended training (90 sessions) indicated that performances had come under temporal control. Postreinforcement pausing increased as a function of the interval duration, the pauses were proportional to the prevailing duration, and the likelihood of the first response within an interval increased as the interval elapsed. To assess the resistance of these patterns to disruption, subjects were trained with a schedule that generated high response rates and short pauses (variable ratio). When the progressive-interval schedule was reinstated, pausing was attenuated and rates were elevated, but performances reverted to earlier patterns with continued exposure. The results indicated that temporal control by progressive-interval schedules, although slow to develop, is similar in many respects to that for fixed-interval schedules.

Animals↗

PubMed1996

[Dynamic MR colpocystorectography. A new methods for evaluating pelvic floor descent and genital prolapse].

AIM: Introduction of a new method for the dynamic evaluation of genital prolapse by using fast magnetic resonance imaging. METHODS: Dynamic fast magnetic resonance imaging with pelvic floor contraction, relaxation and straining manoeuvres were performed with volunteers and patients presenting with pelvic descent. The urethra, bladder, vagina and rectum were opacified by using a water or Magnevist enteral solution. RESULTS: Delineation and movement of the urethra, bladder, uterus, vagina, rectum and small bowel can be shown in a reliable manner. In comparison to dynamic fluoroscopy an equal or superior diagnosis has been achieved in all cases. CONCLUSION: In comparison to dynamic fluoroscopy MR-Colpocystorectography is a promising new method in assessing pelvic floor descent and prolapse in women. Further studies will have to focus on standardisation and clinical implication.

Aged↗

PubMed1995

Mechanisms of enhanced insulin sensitivity in endurance-trained athletes: effects on blood flow and differential expression of GLUT 4 in skeletal muscles.

Exercise is associated with increased insulin sensitivity. To better understand mechanisms that could be responsible for this association, we studied seven controls and seven endurance-trained athletes. A 600 mU/m2.min hyperinsulinemic euglycemic glucose clamp with the limb balance technique assessed insulin sensitivity as whole body glucose uptake (WBGU) and leg glucose uptake (LGU). Indirect calorimetry and hemodynamic measurements, such as leg blood flow (LBF) and cardiac output, were performed at baseline and maximal insulin stimulation. The content of the glucose transporter GLUT 4 and muscle fiber type were evaluated in three muscle groups: vastus lateralis, gastrocnemius, and biceps. Athletes exhibited 35% higher WBGU and 30% higher LGU than controls. Basal LBF (liters per min) was higher in athletes, but the difference was not statistically significant. After insulin stimulation, LBF was 31% higher in athletes than controls (P = 0.05). Indirect calorimetry revealed that athletes had a 44% higher rate of nonoxidative glucose metabolism than controls (P = 0.01). GLUT 4 levels in vastus were 90% (P < 0.05) greater in athletes, whereas smaller differences were noted between athletes and controls in biceps and gastrocnemius. Importantly, the vastus lateralis GLUT 4 content was correlated with WBGU (r = 0.60; P < 0.05) and LGU (r = 0.62; P < 0.05). Relative numbers of oxidative fibers were increased in vastus from athletes and were positively correlated with maximal oxygen consumption (VO2 max), but GLUT 4 content could not be correlated with oxidative fiber content in individual controls or athletes. We conclude that in humans 1) endurance training enhances insulin's ability to increase LBF; 2) GLUT 4 is differentially expressed as a function of muscle group and is up-regulated by exercise in a muscle-specific manner; 3) in vastus lateralis, GLUT 4 levels are well correlated with insulin-stimulated rates of both WBGU and LGU; and 4) GLUT 4 content and in vivo insulin sensitivity do not vary as a function of fiber type composition. Thus, blood flow and GLUT 4 expression in muscle are important mechanisms that mediate greater insulin sensitivity in athletes.

Adult↗

PubMed1995

Effects of a variable-ratio conditioning history on sensitivity to fixed-interval contingencies in rats.

We investigated the possibility that human-like fixed-interval performances would appear in rats given a variable-ratio history (Wanchisen, Tatham, & Mooney, 1989). Nine rats were trained under single or compound variable-ratio schedules and then under a fixed-interval 30-s schedule. The histories produced high fixed-interval rates that declined slowly over 90 sessions; differences as a function of the particular history were absent. Nine control animals given only fixed-interval training responded at lower levels initially, but rates increased with training. Despite differences in absolute rates, rates within the intervals and postreinforcement pauses indicated equivalent development of the accelerated response patterns suggestive of sensitivity to fixed-interval contingencies. The finding that the histories elevated rates without retarding development of differentiated patterns suggests that the effective response unit was a burst of several lever presses and that the fixed-interval contingencies acted on these units in the same way as for single responses. Regardless of history, the rats did not manifest the persistent, undifferentiated responding reported for humans under comparable schedules. We concluded that the shortcomings of animal models of human fixed-interval performances cannot be easily remedied by including a variable-ratio conditioning history within the model.

Animals↗

PubMed1994

Role of coreceptors in positive selection and lineage commitment.

Recent experiments have re-awakened interest in a stochastic/selective model of positive selection of T lymphocytes. A revised version of the model has been proposed whereby commitment of double-positive thymocytes to either the CD4 or CD8 lineage requires two engagements with MHC molecules: the first, initiating the differentiation program, signals down-regulation of one or the other coreceptor, regardless of the T cell receptor's specificity for MHC class I or II molecules; the second, leading to terminal differentiation, screens the choice of coreceptor by permitting only those cells with matched receptors and coreceptors to proceed. Here we explore the role of coreceptors in the two stages of positive selection by manipulating CD8 expression in MHC class II-deficient mice, crossing them with either CD8-negative animals or animals carrying combinations of CD8 alpha and CD8 beta transgenes. We find that coreceptors are required at both stages of positive selection and that artificial expression of the down-modulated CD8 molecule can quite efficiently rescue cells that have made a 'mistake' in their choice of coreceptor. We also establish that commitment to the CD4 pathway and to the helper phenotype can be linked.

Animals↗

PubMed1994

Inhibition of L-type Ca2+ channels in portal vein myocytes by the enantiomers of oxodipine.

We studied the effects of the enantiomers of the dihydropyridine derivative, 4-(2,3 methylenedioxyphenyl)-1,4-dihydro-2,6-dimethyl-3 carboxyethyl-5-carboxymethyl-pyridine (oxodipine), on voltage-dependent Ca2+ channels of rat portal vein myocytes by combining electrophysiological techniques and binding studies. (+)- and (-)-oxodipine depressed the L-type Ca2+ current in a concentration-dependent manner, with similar IC50 values (around 10 nM) but had no appreciable effect on the intracellular Ca2+ stores. The steady-state inactivation curve for the Ca2+ current was shifted along the voltage axis to negative membrane potentials indicating that the block of the Ca2+ current by oxodipine enantiomers increased with depolarization. The voltage-dependent inhibitory property of oxodipine was related to an increase in [3H](+)-4-(benzo-2-oxa-1,3-diazol-4-yl)-1,4-dihydro-2,6-dimethy lpy ridine- 3,5-dicarboxylic acid 3-isopropyl, 5-methyl ester (isradipine) binding affinity without change in binding capacity. In normally polarized intact strips, interactions of (+)- and (-)-oxodipine with [3H](+)-isradipine binding indicated a stimulation of the radioligand binding at low concentrations of (-)-oxodipine while the (+) enantiomer seemed to act as a competitive ligand. Depolarization of intact strips with 135 mM K(+)-solutions increased the apparent affinity of the enantiomers of oxodipine, and abolished the stimulating effect of (-)-oxodipine on the binding of [3H](+)-isradipine. Inhibition of Ca2+ current was increased in the simultaneous presence of 1 nM of (+)- and (-)-oxodipine when compared to the inhibitions induced by 2 nM of each enantiomer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Thymic selection of CD8+ single positive cells with a class II major histocompatibility complex-restricted receptor.

We describe mice that express a transgenic T cell receptor alpha/beta (TCR-alpha/beta) specific for peptide 111-119 from influenza hemagglutinin presented by I-Ed class II major histocompatibility complex (MHC) molecules. The transgenic TCR is expressed on CD4+8- as well as CD4-8+ mature T cells even in mice that are deficient in rearrangement or do not express endogenous TCR-alpha genes. The CD4-8+ T cells require I-Ed class II MHC molecules for positive selection and can be activated to proliferate and to kill by I-Ed molecules presenting the relevant peptide. Full maturation of these cells, however, also requires the presence of class I MHC molecules. The results are compatible with the notion that T cell maturation requires multiple receptor-ligand interactions and establish an exception to the rule that class II-restricted TCRs are exclusively expressed by mature CD4+8- cells.

Animals↗

PubMed1994

A human CD4 transgene rescues CD4-CD8+ cells in beta 2-microglobulin-deficient mice.

The specificity of the alpha beta T cell receptor for class I or class II major histocompatibility complex (MHC) molecules determines whether a mature T cell will be of the CD4-CD8+ or CD4+CD8- phenotype, respectively. We show here that a human CD4 transgene can rescue a significant fraction of CD4-CD8+ T cells in beta 2-microglobulin-deficient mice. Cells with this phenotype could be induced to become potent killers of targets expressing allogeneic MHC antigens, indicating that lineage commitment can precede the rescue of developing cells by the T cell receptor for antigen and the CD4 coreceptor.

Animals↗

PubMed1994

Coordinate suppression of mutations caused by Robertson's mutator transposons in maize.

Transposable elements from the Robertson's Mutator family are highly active insertional mutagens in maize. However, mutations caused by the insertion of responder (non-autonomous) elements frequently depend on the presence of active regulator (autonomous) elements for their phenotypic effects. The hcf106::Mu1 mutation has been previously shown to depend on Mu activity in this way. The dominant Lesion-mimic 28 mutation also requires Mu activity for its phenotypic effects. We have used double mutants to show that the loss of Mu activity results in the coordinate suppression of both mutant phenotypes. This loss can occur somatically resulting in large clones of cells that have a wild-type phenotype. Autonomous and non-autonomous Mutator elements within these clones are insensitive to digestion with methylation-sensitive enzymes, suggesting extensive methylation of CG and non-CG cytosine residues. Our data are consistent with the sectors being caused by the cycling of MuDR regulatory elements between active and inactive phases. The pattern of sectors suggests that they are clonal and that they are derived from the apical cells of the vegetative shoot meristem. We propose that these cells are more likely to undergo epigenetic loss of Mu activity because of their longer cell division cycle during shoot growth. Coordinate suppression of unlinked mutations can be used to perform mosaic analysis in maize.

Base Sequence↗

PubMed1994

Ectopic Hoxa-1 induces rhombomere transformation in mouse hindbrain.

Homeobox genes are expressed with a specific spatial and temporal order, which is essential for pattern formation during the early development of both invertebrates and vertebrates. Here we show that widespread ectopic expression of the Hoxa-1 (Hox 1.6) gene directed by a human beta-actin promoter in transgenic mice is embryolethal and produces abnormal phenotypes in a subset of domains primarily located in anterior regions. Interestingly, this abnormal development in the Hoxa-1 transgenic mice is associated with ectopic expression of the Hoxb-1 (Hox 2.9) gene in select hindbrain regions. At gestation day 9.5, two domains of strong Hoxb-1 expression are found in the anterior region of the hindbrains of Hoxa-1 transgenic embryos. One region represents the normal pattern of Hoxb-1 expression in rhombomere 4 and its associated migrating neural crest cells, while another major domain of Hoxb-1 expression consistently appears in rhombomere 2. Similar ectopic domains of beta-galactosidase activity are detected in dual transgenic embryos containing both beta-actin/Hoxa-1 transgene and a Hoxb-1/lacZ reporter construct. Expression of another lacZ reporter gene that directs beta-galactosidase activity predominantly in rhombomere 2 is suppressed in the Hoxa-1 transgenic embryos. We have also detected weaker and variable ectopic Hoxb-1 expression in rhombomeres 1, 3 and 6. No ectopic Hoxb-1 expression is detected in rhombomere 5 and the expression of Hoxa-3 and Krox-20 in this region is unchanged in the Hoxa-1 transgenic embryos. While no obvious change in the morphology of the trigeminal or facial-acoustic ganglia is evident, phenotypic changes do occur in neurons that emanate from rhombomeres 2 and 3 in the Hoxa-1 transgenic embryos. Additionally, alterations in the pattern of Hoxa-2 and Hoxb-1 expression in a subpopulation of neural crest cells migrating from the rhombomere 2 region are detected in these transgenics. Taken together, these data suggest that ectopic Hoxa-1 expression can reorganize select regions of the developing hindbrain by inducing partial transformations of several rhombomeres into a rhombomere-4-like identity.

Actins↗

PubMed1994

Molecular and molar analyses of fixed-interval performance.

Fixed-interval performances of rats were described either in terms of the individual intervals of the session or in terms of a single average interval constructed for the entire session. Responding in the individual intervals usually followed break-and-run and single response patterns rather than the scalloped pattern that emerged when the results were averaged. There was, however, a reasonable correspondence between the quarter-life values calculated from individual intervals and those calculated from the averages. According to the pattern exhibited by the average interval, the probability of a response increased as the interval elapsed. The same conclusion was indicated by more molecular analyses of the conditional probabilities of pause terminations. The results showed that descriptions of fixed-interval data in terms of overall averages reveal aspects of performance that are not immediately apparent within individual intervals.

Animals↗

PubMed1993

Dual effect of thrombin on voltage-dependent Ca2+ channels of portal vein smooth muscle cells.

Thrombin induces a number of physiological responses in several types of cells. To determine the action of thrombin in the vein, the electrophysiological and mechanical effects of thrombin were studied in rat portal vein smooth muscle cells. Ca2+ channel currents were recorded using the whole-cell patch-clamp technique. Thrombin had both inhibitory and stimulatory effects on the Ca2+ channel current. The inhibitory effect was reversed on washout of thrombin, whereas the stimulatory effect was maintained after thrombin was removed. Thrombin (1 unit/ml) produced a reversible decrease of 27.3 +/- 3.3% (n = 12) in the current amplitude and a sustained increase of 71.2 +/- 12.9% (n = 20). The thrombin-induced inhibition of Ca2+ channel current was blocked by the thrombin inhibitor hirudin and by the protease inhibitor leupeptin. The stimulatory effect of thrombin was inhibited by hirudin, by intracellular application of guanosine 5'-O-(beta-thio)diphosphate, and by antiphophatidylinositide antibodies but not by pertussis toxin. The thrombin-induced enhancement of the Ca2+ channel current amplitude was not observed when the current was previously stimulated by phorbol 12,13-dibutyrate. This suggests that the inhibitory effect of thrombin was related to its proteolytic activity and that the stimulatory effect involved activation of a pertussis toxin-insensitive GTP-binding protein, phosphatidylinositide hydrolysis, and protein kinase C activation. Both thrombin effects occurred in the same concentration range (0.001-10 units/ml). The thrombin-induced contraction of portal vein strips was completely inhibited by isradipine, and thrombin did not produce an increase in cytosolic [Ca2+], measured by indo-1 fluorescence in cells clamped at -50 mV, sufficient to activate Ca(2+)-dependent chloride current.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Autoanti-phosphatidylinositide antibodies specifically inhibit noradrenaline effects on Ca2+ and Cl- channels in rat portal vein myocytes.

High levels of circulating autoantibodies (auto-Ab) directed against phosphatidylinositides have been identified in the sera of patients with malignant tumors. These polyclonal autoantibodies had higher avidity and specificity for phosphatidylinositol (PtdIns) than for the other phosphatidylinositides. Effects of the auto-Ab were studied in smooth muscle myocytes in the PtdIns-involving transduction mechanism triggered by activation of alpha 1-adrenoceptors. Noradrenaline activated a Ca(2+)-dependent Cl- current through the Ca(2+)-releasing action of inositol 1,4,5-trisphosphate (InsP3) and enhanced the Ca2+ channel current through a diacylglycerol and protein kinase C-dependent mechanism. External applications of auto-Ab (0.03-0.3 mg/ml) were without effect on noradrenaline-induced responses whereas intracellular applications (0.0004-0.012 mg/ml) inhibited both Cl- current activation and Ca2+ channel current stimulation. Intracellular applications of IgG from healthy donors had no effect on noradrenaline-induced responses. When anti-PtdIns Ab were preincubated with PtdIns the inhibition of the noradrenaline-induced responses on Ca2+ and Cl- channels was not observed. Autoanti-PtdIns Ab inhibited also the acetylcholine-activated Cl- current, confirming that the acetylcholine response was mediated through the phosphatidylinositol breakdown. In contrast, the autoanti-PtdIns Ab were ineffective against the transduction pathway after beta-adrenoceptor activation. Therefore, these results suggest that the biological effect of autoanti-PtdIns Ab results from a specific binding to membrane PtdIns or PtdIns metabolites and thereby prevented InsP3 and diacylglycerol production. These autoanti-PtdIns Ab appear to be a new specific tool to identify the role of phosphatidylinositides in intracellular transduction processes.

Acetylcholine↗

PubMed1992

Phenotypic changes accompanying positive selection of CD4+CD8+ thymocytes.

We know little about the way mature CD4 (helper) and CD8 (killer) T cells develop from thymic CD4+CD8+ precursors. Here we show that small but not large CD4+CD8+ cells with high levels of the alpha beta T cell receptor (TcRhigh) result from positive selection. Neither CD4+CD8+ cells with low TcR levels nor large CD4+CD8+ thymocytes with high TcR levels differentiate in vitro. However, small CD4+CD8+ cells with high TcR levels develop in vitro into mature cells by gradually decreasing the surface levels of one or the other co-receptor and acquiring the potential to respond with proliferation to ligation of the TcR. Small CD4+CD8+ cells with high levels of a major histocompatibility complex (MHC) class I-restricted transgenic TcR develop in vitro exclusively into CD4-CD8+ cells while small CD4+CD8+ TcRhigh cells with heterogeneous TcR from various mice yield both CD4 and CD8 T cells. While these experiments are consistent with an instructive model of CD4/CD8 lineage commitment they do not rule out other mechanisms which require multiple TcR-MHC ligand interactions in the generation of mature alpha beta T cells.

Animals↗

PubMed1992

T cell receptor (TCR) beta chain homodimers on the surface of immature but not mature alpha, gamma, delta chain deficient T cell lines.

Transfected T cell receptor (TCR) beta chain genes are expressed as homodimers on the surface of immature (Sci/ET27F) but not on mature (58 alpha-beta-) T cell lines which lack TCR alpha, gamma and delta chains. The homodimer on Sci/ET27F cells is tightly bound to CD3 delta and CD3 epsilon while the association with CD3 gamma and CD3 zeta proteins is rather weak. Crosslinking of the TCR beta homodimers resulted in a strong and rapid calcium flux. In 58 alpha-beta- T cells the beta TCR chain could be easily visualized intracellularly but was not transported to the cell surface. The Scid cell lines considerably facilitate the molecular analysis of early differentiation events in the thymus which are likely to be regulated by the beta TCR homodimer.

Animals↗

PubMed1992

Fetal gender differences in preterm birth: findings in a North American cohort.

A higher incidence of preterm birth (PTB) and premature rupture of membranes (PROM) has been observed among women delivering male newborns compared with female newborns in different populations. Some authors have speculated that this higher incidence of PTB may be related to the relatively greater weight at lower gestational age of male newborns compared with female newborns. Others have suggested that the greater incidence of PTB and PROM is caused by an increased vulnerability to infection in women carrying males. To understand possible pathogenic factors leading to PTB further, we examined the association between PTB and infant gender in a cohort of North American women. In addition, incidences of PROM, chorioamnionitis, and postpartum endometritis were analyzed for women delivering males versus females. Overall, males were more likely than females to deliver at 33 to 36 weeks' gestation (OR = 1.21; 95% CI: 1.02-1.42). This increase in PTB among males was not accompanied by an increased number of males with low birthweight; rather, males were less likely than females to weigh between 2000 and 2499 gm (OR = 0.71; 95% CI: 0.60-0.84). The difference in PTB by gender could not be explained by an increased occurrence of PROM, chorioamnionitis, endometritis, or other infection-linked processes. Our findings suggest that shorter gestation in males in this population may be related to their relatively increased size and birthweight. Male gender-associated factors that predispose to infection-mediated preterm birth may play greater roles in populations at higher risk for reproductive tract infection during pregnancy.

Adolescent↗

PubMed1992

Hypertension during chronic exposure to cold: comparison between Sprague-Dawley and Long-Evans strains.

It is now well established that chronic exposure of rats to cold (5-6 degrees C) induces an elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy within 3 weeks. Since rats of the Long-Evans (LE) strain are known to be resistant to the induction of deoxycorticosterone salt induced hypertension, their cardiovascular responses to chronic exposure to cold were compared with those of rats of the Sprague-Dawley (SD) strain. The results of these studies revealed clear differences between the LE and SD strains of rats. Thus, rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine and epinephrine; a significantly greater dipsogenic responsiveness to acute administration of angiotensin II, and significant increases in weights of the heart, kidneys, adrenals, and brown adipose tissue compared with their warm-adapted controls. All of these changes are characteristic of rats acclimated to cold. In contrast, rats of the LE strain appear to be less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level. Furthermore, urinary outputs of norepinephrine and epinephrine were significantly lower in cold-treated rats of the LE strain compared with cold-treated rats of the SD strain, but dipsogenic responsiveness to angiotensin II was unchanged. Although increases in the weight of the previously mentioned organs were also observed in cold-treated rats of the LE strain compared with their warm-adapted controls, weights of the heart and interscapular brown adipose tissue of both groups were significantly less than those of counterparts of the SD strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Reinforcement magnitude and pausing on progressive-ratio schedules.

Rats responded under progressive-ratio schedules for sweetened milk reinforcers; each session ended when responding ceased for 10 min. Experiment 1 varied the concentration of milk and the duration of postreinforcement timeouts. Postreinforcement pausing increased as a positively accelerated function of the size of the ratio, and the rate of increase was reduced as a function of concentration and by timeouts of 10 s or longer. Experiment 2 varied reinforcement magnitude within sessions (number of dipper operations per reinforcer) in conjunction with stimuli correlated with the upcoming magnitude. In the absence of discriminative stimuli, pausing was longer following a large reinforcer than following a small one. Pauses were reduced by a stimulus signaling a large upcoming reinforcer, particularly at the highest ratios, and the animals tended to quit responding when the past reinforcer was large and the stimulus signaled that the next one would be small. Results of both experiments revealed parallels between responding under progressive-ratio schedules and other schedules containing ratio contingencies. Relationships between pausing and magnitude suggest that ratio pausing is under the joint control of inhibitory properties of the past reinforcer and excitatory properties of stimuli correlated with the upcoming reinforcer, rather than under the exclusive control of either factor alone.

Journal Article↗