Specificity of practice: the case of powerlifting.
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Biomedical subjects
Publications and source records attributed to L Tremblay.
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Rewards constitute important goals for voluntary behavior. This study aimed to investigate how expected rewards influence behavior-related neuronal activity in the anterior striatum. In a delayed go-nogo task, monkeys executed or withheld a reaching movement and obtained liquid or sound as reinforcement. An initial instruction picture indicated the behavioral reaction to be performed and the reinforcer to be obtained after a subsequent trigger stimulus. Movements varied according to the reinforcers predicted by the instructions, suggesting that animals differentially expected the two outcomes. About 250 of nearly 1,500 neurons in anterior parts of caudate nucleus, putamen, and ventral striatum showed typical task-related activations that reflected the expectation of instructions and trigger, and the preparation, initiation, and execution of behavioral reactions. Strikingly, most task-related activations occurred only when liquid reward was delivered at trial end, rather than the reinforcing sound. Activations close to the time of reward showed similar preferences for liquid reward over the reinforcing sound, suggesting a relationship to the expectation or detection of the motivational outcome of the trial rather than to a "correct" or "end-of-trial" signal. By contrast, relatively few activations in the present task occurred irrespective of the type of reinforcement. In conclusion, many of the behavior-related neurons investigated in the anterior striatum were influenced by an upcoming primary liquid reward and did not appear to code behavioral acts in a motivationally neutral manner. Rather, these neurons incorporated information about the expected outcome into their behavior-related activity. The activations influenced by reward several seconds before its occurrence may constitute a neuronal basis for the retrograde effects of rewards on behavioral reactions.
This study investigated neuronal activity in the anterior striatum while monkeys repeatedly learned to associate new instruction stimuli with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or not. During learning, new instruction pictures were presented, and animals guessed and performed one of the trial types according to a trial-and-error strategy. Learning of a large number of pictures resulted in a learning set in which learning took place in a few trials and correct performance exceeded 80% in the first 60-90 trials. About 200 task-related striatal neurons studied in both familiar and learning conditions showed three forms of changes during learning. Activations related to the preparation and execution of behavioral reactions and the expectation of reward were maintained in many neurons but occurred in inappropriate trial types when behavioral errors were made. The activations became appropriate for individual trial types when the animals' behavior adapted to the new task contingencies. In particular, reward expectation-related activations occurred initially in both rewarded and unrewarded movement trials and became subsequently restricted to rewarded trials. These changes occurred in parallel with the visible adaptation of reward expectations by the animals. The second learning change consisted in decreases of task-related activations that were either restricted to the initial trials of new learning problems or persisted during the subsequent consolidation phase. They probably reflected reductions in the expectation and preparation of upcoming task events, including reward. The third learning change consisted in transient or sustained increases of activations. These might reflect the increased attention accompanying learning and serve to induce synaptic changes underlying the behavioral adaptations. Both decreases and increases often induced changes in the trial selective occurrence of activations. In conclusion, neurons in anterior striatum showed changes related to adaptations or reductions of expectations in new task situations and displayed activations that might serve to induce structural changes during learning.
Acute allograft rejection in animals and humans has been associated with increased nitric oxide production in the graft. Exhaled nitric oxide (ENO) measurement is a noninvasive method of assessing inflammation in airway diseases, e.g., asthma, which might be applicable to lung transplant recipients. Over 12 months, ENO of lower respiratory origin was measured in 108 lung transplant recipients with a mean time after transplant of 1,083 d. ENO (mean +/- SEM; ppb) in stable patients (19.5 +/- 1.1; p < 0.001) was not different from that of healthy controls (23.8 +/- 3.2). ENO was significantly higher in episodes of clinical acute rejection (51.1 +/- 6.3) compared with stable patients but not elevated in bronchiolitis obliterans syndrome (18.6 +/- 1.5) or pulmonary infection (25.9 +/- 4.0). A retrospective analysis of bronchoscopy findings and concurrent ENO (n = 99) showed that ENO did not vary according to histological findings (normal, acute rejection grade I, nonspecific inflammatory change) or with a positive BAL culture. ENO was not correlated with differential lymphocyte and neutrophil counts. ENO appears to be a valid marker of clinical acute rejection in human lung transplantation as distinct from infection or bronchiolitis obliterans. Furthermore, bronchoscopic findings in the absence of a clinical illness were not associated with a rise in ENO.
Bombesin-like peptides, including the mammalian homologue gastrin-releasing peptides, are highly expressed and secreted by neuroendocrine cells in prostate carcinoma (PCa) tissues and are likely to be related to the progression of this disease. In the present study, we show that bombesin enhances the migration of androgen-independent PCa cells (PC-3) in vitro, while not affecting their adhesion to extracellular matrix proteins. The bombesin-increased motility of PC-3 cells occurs through its receptor, and, as shown with inhibitors, it likely requires activation of both protein tyrosine kinases (PTKs) and protein kinases C (PKCs). Because the focal adhesion kinase pp125FAK plays a key role in adhesion/motility and is highly expressed in advanced PCa, we examined whether in PC-3 cells bombesin signal transduction triggers the tyrosine phosphorylation of this PTK and of associated integrins and signaling proteins likely to be present in focal adhesion plaques. pp125FAK tyrosine phosphorylation was stimulated by bombesin and mimicked by PKC activation with the tumor-promotor phorbol 12-myristate-13-acetate (PMA). Moreover, this effect of bombesin on pp125FAK tyrosine phosphorylation requires the presence of both active PKC and cytoskeleton integrity since this signal was abolished by down-regulating PKCs induced by prolonged PMA treatment or by PKC inhibition with GF 109203X, as well as by disruption of the cytoskeleton with cytochalasin D. We also show that bombesin increases the tyrosine phosphorylation of a 95-kDa protein (pp95) which was co-immunoprecipitated with the alpha v and beta (3 and 5) subunits, forming integrin receptors with alpha v in PC-3 cells. The protein pp95 is distinct from the endogenously tyrosine-phosphorylated beta3 subunit. In addition, upon bombesin treatment, the beta1, beta3 and beta5 integrin subunits co-immunoprecipitated with pp125FAK and major phosphotyrosine (pY)-containing proteins of 125 and 68-70 kDa, likely corresponding to pp125FAK and paxillin. Together our data suggest that, in addition to PKC activation, tyrosine phosphorylation of pp125FAK and integrin-associated proteins may play an important role in bombesin signaling, triggering the processes of PCa cell motility and invasion.
We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (Vt) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), Vt = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), Vt = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), Vt = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFalpha, IL-1beta, IL-6, IL-10, MIP-2, and IFNgamma were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNFalpha versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three-fold increase in TNFalpha, whereas MVZP produced a six-fold increase in lavage TNFalpha. Northern blot analysis revealed a similar pattern (C, MVHP < MVZP < HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.
pp125FAK, a protein tyrosine kinase (PTK) co-localized with integrins in focal adhesion plaques, is known to transduce signals involved in the regulation of cell adhesion and motility as well as the anchorage-independent growth of transformed cells. We investigated whether pp125FAK could be part of a signalling pathway that contributes to the progression of human prostate carcinoma (PCa). Up-regulation of pp125FAK expression, its activation by phosphorylation on tyrosine and its association with paxillin and p50csk were preferentially observed in PCa tissues from patients with metastases, whereas normal and hyperplastic prostates and localized PCa tissues showed undetectable or low levels of both FAK mRNA and protein and an absence of pp125FAK signalling complexes. The increase in expression and activation of pp125FAK in metastatic PCa tissues was also corroborated by our findings in human PCa cell lines. Indeed, higher levels of pp125FAK and FAK mRNA were observed in highly tumorigenic PC-3 cells as was the presence of activated pp125FAK, as opposed to an inactive form in LNCaP cells, which have a lower tumorigenic ability. In addition, pp125FAK formed signalling complexes with both paxillin and p50csk in PC-3 cells as in metastatic PCa tissues. Together, our results show that an increase in FAK mRNA and protein, as well as pp125FAK activation and association with signalling proteins, correlates with progression and invasion in human PCa tissues and cells.
Two separate, independent experiments were conducted to evaluate the effect of 60 Hz linearly polarized, sinusoidal, continuous-wave magnetic fields (MFs) on immune system performances in rats born and raised under these fields. Each experiment lasted for 6 weeks. A total of 96 animals, divided into groups of eight animals each, was exposed for 20 h/day to MFs of different intensities, i.e., sham (< 0.02 microT) and 2, 20, 200, and 2000 microT. Another group of animals, which was housed in a separate room, served as cage controls (CC). These animals were exposed to ambient MFs of < 0.02 microT. The following immune responses were evaluated in both experiments total T and B cells; CD4+ and CD8+ subpopulation and natural killer (NK) cell activity in splenic lymphocytes; hydrogen peroxide (H2O2), nitrous oxide (NO), and tumor necrosis factor (TNF) production by peritoneal macrophages. Our results show that a 6 week exposure to MFs induced a significant decrease in the number of CD5+, CD4+, and CD8+ populations. These changes were even more significant in rats that were exposed to fields of 2000 microT. A lower, although significant, decrease in the CD5+ population was also observed in animals that were exposed to fields of 200 microT. Linear regression analysis demonstrated a dose effect with MF intensity. B lymphocyte (Ig+ cell) populations also showed a 12% decrease (P < .05) in the groups that were exposed to fields of 20 and 200 microT. However, these results were not significant, and no relation with MF intensities could be demonstrated. In contrast, evaluation of splenic NK cell activity revealed a 50% increase (P < .05) in animals that were exposed to fields of 2000 microT. No significant results were obtained from the evaluation of TNF activity and NO secretion in peritoneal macrophages. Phorbol 12-myristate 13-acetate (PMA)-stimulated and net H2O2 productions for a minor subpopulation of peritoneal cells showed positive dose-response correlations by linear regression analysis. Taken together, our results suggest that an in vivo exposure of rats for 6 weeks to 60 Hz MFs can induce significant immunological perturbations on effector cells of both natural and adaptive immunity in a dose-dependent fashion.
Isolated perfused lung systems are commonly used to assess lung function in experimental studies. Assessment of hemodynamics and gas-exchange function in these systems is limited by the availability of venous blood. This study describes and validates a rat lung perfusion circuit in which a double-lung block ventilated with a hypoxic gas mixture [inspired O2 fraction (FIO2) 0.04; inspired CO2 fraction 0.08; deoxygenator (Deoxy) block] is used to provide blood with blood gases that are similar to mixed venous values to perfuse a study lung (FIO2 0.21; left lung only). This allows extended assessment of hemodynamics and gas exchange. Fifty adult male Wistar rats (300-400 g) were used as double-lung donors. Twenty-five perfusions (of both Deoxy and study lungs) were performed in four protocols (groups 1-5; n = 5). In protocol 1 (group 1), we tested whether exposure to room air affects the gas composition of the blood in the system. We found that the gas composition of the venous reservoir blood was identical to that of the blood entering the study block. In protocol 2, the effect of perfusion time and perfusion flow rate on the stability of the system was assessed. Lungs were perfused at 4 and 12 ml/min (groups 2 and 3, respectively), and the procedure was discontinued if edema or a marked decline in hemodynamics or gas-exchange function was observed. Pulmonary function was excellent and remained stable for 3 (at 12 ml/min) and 5 h (at 4 ml/min). In protocol 3, we examined whether hypoxic ventilation in the Deoxy lungs affects the stability of the system. Despite the low FIO2 used in the Deoxy lungs, the mean pulmonary arterial pressure-to-blood flow relationships in the study and Deoxy lungs were similar. Finally, in protocol 4, perfusion of a damaged study lung did not impair the function of the system. We conclude that this model permits reliable assessment of pulmonary function in rats under controlled ventilation and perfusion conditions. The use of a Deoxy double-lung block simplifies the perfusion apparatus and eliminates the main cause of instability of other systems that use an anesthetized host animal to provide venous blood.
Focal adhesion kinase (pp125FAK) is a nonreceptor protein tyrosine kinase transducing signals initiated through integrin activation triggered by cell/extracellular matrix (ECM) interactions. To examine its role in epithelial cell adhesion, proliferation, and differentiation, we have studied pp125FAK expression, activity, and association with paxillin in two canine prostate models in which these functions can be selectively regulated: in vitro by vitronectin (VN) and serum factors, and in vivo by sex steroids. Kinetic studies revealed that the adhesion and spreading of prostatic epithelial cells in primary culture was regulated by serum VN and a natural ECM containing VN produced by prostate cells. While barely detectable in freshly isolated prostate cells, proliferating cells, after 72 h in culture, expressed higher levels of FAK mRNA (8-fold), pp125FAK (50-fold), and paxillin (50-fold). In prostate cells with a reduced growth rate after 2 weeks in culture, we observed a decrease in pp125FAK (4-fold) and its transcript (3-fold), but no change in paxillin. In vivo, both proteins were undetectable in normal and hyperplastic glands composed of a well differentiated epithelium, and in prostates restored by androgen supplementation. In contrast, pp125FAK and paxillin were up-regulated by androgen deprivation (castration) and further increased by estrogen treatment, which yielded metaplastic prostates mostly composed of proliferating basal epithelial cells. Moreover, both proteins were constitutively phosphorylated on tyrosine in the metaplastic prostate, as well as in proliferating cultured cells. Together, these results demonstrate that pp125FAK expression is regulated at the protein and mRNA levels and forms active signaling complexes with paxillin when epithelial cells in contact with ECM proteins are induced to proliferate in vivo and in vitro.
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The present study was undertaken to determine whether dyskinesia, resulting from injection of the GABA antagonist bicuculline into the external globus pallidus of intact monkeys, is induced by hyperactivity of local external pallidal neurons and ensuing hypoactivity of neurons in the internal globus pallidus, at the output of the basal ganglia. Accordingly, 86% of responding external pallidal neurons increased and 56% of internal pallidal neurons decreased their activity, either exclusively or within biphasic responses. Whereas 29% of external pallidal neurons decreased and as much as 85% of internal pallidal neurons increased their activity. The latter unpredicted responses may be explained by diffusion of bicuculline from the external to the internal pallidum and by lateral monosynaptic inhibition within the external and its mirror image in the internal pallidum. With respect to individual injection sites, the hypoactive neurons in the internal pallidum tended to be grouped together and surrounded by hyperactive or unresponsive neurons. The changes occurred before and persisted during dyskinesia, suggesting that they were required to induce and maintain the dyskinesia. There were also changes in firing patterns, comprising long periods of silence, especially in external pallidal neurons close to the injection site. The periods of silence did not appear to result from depolarization block but rather from activation of receptors of inhibitory neurotransmission other than type A GABA. Dyskinesia therefore does not appear to result exclusively from a simple imbalance of activity between the pallidal segments, with hyperactivity in the external and hypoactivity in the internal segment, but also from imbalances within each pallidal segment, possibly with a center-surround organization.
The present study was performed to establish the intrinsic frequency of the slow waves in different regions of the cat stomach, to define the propagation velocity of the slow wave along the stomach, and to determine whether endogenous prostaglandins can affect the slow wave frequency. In 20 cats, electrical activity was recorded from the anterior wall of the intact stomach in vivo and in vitro, and in vitro after cutting the stomach into 16 pieces to isolate each pair of electrodes. In vivo, slow waves (4.1 +/- 0.5 cpm) were seen only from mid corpus to pylorus, the apparent propagation velocity decreasing towards the antrum. In vitro: (a) after cutting, the slow wave frequency increased, to a maximum in 1 h (12 +/- 1.8 cpm; range 10.2-17.3), with the highest frequency always in the mid or orad corpus, usually on the greater curvature (GC), (b) with indomethacin (10(-5) M) the increase in slow wave frequency was prevented or reversed, and there was a frequency gradient with the highest frequency (4.4 +/- 1.2 cpm) uniformly located in the most proximal active site on the GC, and (c) slow waves on the GC were more stable, regular and continuous than on the lesser curvature (LC), the difference being most evident in the corpus. The results suggest that the cat stomach behaves as a system of electrically coupled oscillators of different frequencies. The dominant oscillator of highest frequency is situated in the proximal corpus of the GC, with the remainder of the distal stomach entrained at this frequency. All gastric slow wave oscillators can be driven to higher frequencies by endogenous prostaglandins. The decreasing velocity of slow wave propagation distally suggests that oscillator properties and/or coupling among oscillators differs in the cat.
Nursing students at the college level must master specific techniques related to their profession. Some techniques, including those associated with intravenous (I.V.) therapy, present unique learning challenges because of their complexity. This article offers a teaching strategy based on the main scientific principles of I.V. therapy. The authors recommend a systems-based approach that was successfully tested by nursing students during the theoretical portion of their studies. This strategy relies on the use of concepts, experimental learning, simulation and role playing. The theory portion uses diagrams to establish links between the various subjects and concepts initially learned by the student. Then, based on the individual's learning processes, more specific information is added during the motivation, acquisition and performance phases. The article elaborates on the development of this strategy.
The Quebec Patient Smart Card Project is a Provincial Government initiative under the responsibility of the Rgie de l'assurance-maladie du Québec (Quebec Health Insurance Board). Development, implementation, and assessment duties were assigned to a team from Université Laval, which in turn joined a group from the Direction de la santé publique du Bas-St-Laurent in Rimouski, where the experiment is taking place. The pilot project seeks to evaluate the use and acceptance of a microprocessor card as a way to improve the exchange of clinical information between card users and various health professionals. The card can be best described as a résumé containing information pertinent to an individual's health history. It is not a complete medical file; rather, it is a summary to be used as a starting point for a discussion between health professionals and patients. The target population is composed of persons 60 years and over, pregnant women, infants under 18 months, and the residents of a small town located in the target area, St-Fabien, regardless of age. The health professionals involved are general practitioners, specialists, pharmacists, nurses, and ambulance personnel. Participation in the project is on a voluntary basis. Each health care provider participating in the project has a personal identification number (PIN) and must use both an access card and a user card to access information. This prevents unauthorized access to a patient's card and allows the staff to sign and date information entered onto the patient card. To test the microprocessor card, we developed software based on a problem-oriented approach integrating diagnosis, investigations, treatments, and referrals. This software is not an expert system that constrains the clinician to a particular decisional algorithm. Instead, the software supports the physician in decision making. The software was developed with a graphical interface (Windows 3.1) to maximize its user friendliness. A version of the software was developed for each of the four groups of health care providers involved. In addition we designed an application to interface with existing pharmaceutical software. For practical reasons and to make it possible to differentiate between the different access profiles, the information stored on the card is divided in several blocks: Identification, Emergency, History (personal and family), Screening Tests, Vaccinations, Drug Profile, General follow-up, and some Specific follow-ups (Pregnancy, Ophthalmology, Kidney failure, Cardiology, Pediatrics, Diabetes, Pneumology, Specific parameters). Over 14,000 diagnoses and symptoms are classified with four levels of precision, the codification being based on the ICPC (International Classification for Primary Care). The software contains different applications to assist the clinician in decision making. A "Drug Advisor" helps the prescriber by detecting possible interactions between drugs, giving indications (doses) and contraindications, cautions, potential side-effects and therapeutic alternatives. There is also a prevention module providing recommendations for vaccination and periodic examinations based on the patient's age and sex. The pharmaceutical, vaccination, and screening tests data banks are updated every six months. These sections of the software are accessible to access card holders at any times, even without a patient card, and constitute in themselves an interesting clinical tool. We developed a software server (SCAM) allowing the different applications to access the data in a memory card regardless of the type of memory card used. Using a single high level command language, this server provides a standardized utilization of memory cards from various manufacturers. It ensures the compatibility of the applications using the card as a storage medium. (abstract truncated)
The effect of inhibition of nitric oxide synthase on nonadrenergic, noncholinergic nerve-mediated responses in circular smooth muscle of the human esophageal body and lower esophageal sphincter (LES) was examined in vitro. Tissues were obtained from 10 patients (eight esophageal resection for cancer, two transplant donors). Muscle strips from the LES developed significant spontaneous tension (11.6 +/- 2.1 mN/mm2, N = 6) and relaxed in response to electrical stimulation. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine (NNA), at 10(-5) M, inhibited the relaxation, but had no significant effect on the spontaneous tension (13.0 +/- 2.6 mN/mm2, P = 0.07). Esophageal body strips developed little spontaneous tension, demonstrated an "off" contraction following the cessation of the electrical stimulus, and when contracted with 10(-5) M carbachol, relaxed during electrical stimulation. NNA (10(-5) M) inhibited the off contraction and the relaxation seen after carbachol and unmasked a prominent intrastimulus contraction. This intrastimulus contraction was enhanced by eserine and inhibited by atropine and tetrodotoxin. NNA showed similar potency in the esophageal body and LES and its effects were reversed by L-arginine, but not D-arginine. The results indicate that nitric oxide is an important mediator for nonadrenergic, noncholinergic nerve effects in the human esophagus and lower esophageal sphincter.
BACKGROUND/AIMS: The lower esophageal sphincter (LES) pressure in humans is asymmetric; the highest pressure and the most significant cholinergic contribution occurs toward the left. The basis of this asymmetry was examined using the cat as a model. METHODS: The LES pressure profile was determined using a manometry catheter with four ports oriented at right angles. The LES was dissected into right and left halves with the latter including a contribution from the oblique gastric sling fibers. Isometric tension responses were studied in vitro. RESULTS: In vivo, both the initial LES pressure (31.8 +/- 4.0 mm Hg) and the decrease (79.9% +/- 6.4%) after intravenous atropine (100 micrograms/kg) were greatest in the leftward direction. In vitro, both halves of the LES developed similar spontaneous tension, but the increase in tension to carbachol was twofold greater on the left than the right. Eserine increased and atropine decreased initial tension by 25%-30% in both. Strips from either side relaxed in response to electrical stimulation but the response was more complete in strips from the right, whereas sodium nitroprusside produced similar relaxation in both. CONCLUSIONS: Regional differences in the LES pressure and its cholinergic component can be accounted for by differences in the in vitro properties of the LES muscle fiber groups.
1. Exogenous and endogenous tyrosine protein phosphorylation activities were examined in soluble and particulate fractions from various normal tissues by using poly-[Glu-80Na, Tyr20] and a monoclonal antibody specific for phosphotyrosine. 2. Phosphorylation of the exogenous substrate by the particulate forms of TPKs was 2- to 10-fold higher than by soluble forms. The activities of particulate and soluble enzymes decreased in the following order: spleen > (thymus = kidney) > testes > or = (pancreas = liver = brain) > heart. 3. The level of endogenous phosphorylation in the tissues decreased respectively in the following order: thymus > brain > or = (pancreas = liver) > spleen > testes > kidney > heart for the particulate fractions, and spleen > thymus > brain > pancreas > or = liver > testes > kidney > heart for the soluble fractions. 4. A large number of phosphotyrosine-containing proteins were detected. In addition, several phosphotyrosine-containing proteins of similar molecular weight were found in different tissues and fractions.