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Biomedical subjects

T Abel

Publications and source records attributed to T Abel.

At least 19 recordsLinked to original sources
PubMed2007

Biochemical, molecular and behavioral phenotypes of Rab3A mutations in the mouse.

Ras-associated binding (Rab) protein 3A is a neuronal guanosine triphosphate (GTP)-binding protein that binds synaptic vesicles and regulates synaptic transmission. A mouse mutant, earlybird (Ebd), with a point mutation in the GTP-binding domain of Rab3A (D77G), exhibits anomalies in circadian behavior and homeostatic response to sleep loss. Here, we show that the D77G substitution in the Ebd allele causes reduced GTP and GDP binding, whereas GTPase activity remains intact, leading to reduced protein levels of both Rab3A and rabphilin3A. Expression profiling of the cortex and hippocampus of Ebd and Rab3a-deficient mice revealed subtle differences between wild-type and mutant mice. Although mice were backcrossed for three generations to a C57BL/6J background, the most robust changes at the transcriptional level between Rab3a(-/-) and Rab3a(+/+) mice were represented by genes from the 129/Sv-derived chromosomal region surrounding the Rab3a gene. These results showed that differences in genetic background have a stronger effect on gene expression than the mutations in the Rab3a gene. In behavioral tests, the Ebd/Ebd mice showed a more pronounced mutant phenotype than the null mice; Ebd/Ebd have reduced anxiety-like behavior in the elevated zero-maze test, reduced response to stress in the forced swim test and a deficit in cued fear conditioning (FC), whereas Rab3a(-/-) showed only a deficit in cued FC. Our data implicate Rab3A in learning and memory as well as in the regulation of emotion. A combination of forward and reverse genetics has provided multiple alleles of the Rab3a gene; our studies illustrate the power and complexities of the parallel analysis of these alleles at the biochemical, molecular and behavioral levels.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Rolipram: a specific phosphodiesterase 4 inhibitor with potential antipsychotic activity.

Currently available antipsychotic medications work primarily by antagonizing D2 dopamine receptors, thus raising intracellular cAMP levels. We hypothesized that intracellular stimulation of cAMP levels in the CNS would have similar effects to treatment with antipsychotic medication. To test this hypothesis, we studied the effect of an acute treatment of rolipram, an inhibitor of type 4 phosphodiesterases that degrade cAMP, on acoustic startle and prepulse inhibition (PPI) of the acoustic startle response in C57BL/6J mice known to exhibit poor PPI. PPI is disrupted in schizophrenia patients, and the ability of a drug to increase PPI in mice is predictive of antipsychotic efficacy. We show here that acute treatment with rolipram significantly increases PPI at doses that do not alter the acoustic startle response (lowest effective dose 0.66 mg/kg). In addition, rolipram (0.66 mg/kg) blocks the disruptive effects of amphetamine (10 mg/kg) on PPI. At a slightly higher dose (1.0 mg/kg), rolipram also induces catalepsy. Thus, phosphodiesterase-4 (PDE4) inhibition has many of the same behavioral effects as traditional antipsychotic medications. In contrast to traditional antipsychotics, these effects are achieved through alteration of an intracellular second messenger system rather than antagonism of neurotransmitter receptors. Given previous reports showing rolipram improves cognition, we conclude that PDE4 represents an important novel target for further antipsychotic drug development.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Mice expressing constitutively active Gsalpha exhibit stimulus encoding deficits similar to those observed in schizophrenia patients.

People with schizophrenia display sensory encoding deficits across a broad range of electrophysiological and behavioral measures, suggesting fundamental impairments in the ability to transduce the external environment into coherent neural representations. This inability to create basic components of complex stimuli interferes with a high fidelity representation of the world and likely contributes to cognitive deficits. The current study evaluates the effects of constitutive forebrain activation of the G(s)alpha G-protein subunit on auditory threshold and gain using acoustic brainstem responses and cortically generated N40 event-related potentials to assess the role of cyclic AMP signaling in sensory encoding. Additionally, we examine the ability of pharmacological treatments that mimic (amphetamine) or ameliorate (haloperidol) positive symptoms of schizophrenia to test the hypothesis that the encoding deficits observed in G(s)alpha transgenic mice can be normalized with treatment. We find that G(s)alpha transgenic mice have decreased amplitude of cortically generated N40 but normal acoustic brainstem response amplitude, consistent with forebrain transgene expression and a schizophrenia endophenotype. Transgenic mice also display decreased stimulus intensity response (gain) in both acoustic brainstem response and N40, indicating corticofugal influence on regions that lack transgene expression. N40 deficits in transgenic animals were ameliorated with low dose haloperidol and reversed with higher dose, suggesting dopamine D2 receptor-linked Gi activity contributes to the impairment. Consistent with this hypothesis, we recreated the G(s)alpha transgenic deficit in wild type animals using the indirect dopamine agonist amphetamine. This transgenic model of sensory encoding deficits provides a foundation for identifying biochemical contributions to sensory processing impairments associated with schizophrenia.

Acoustic Stimulation↗
PubMed2006

Aerobic capacity and peak power output of elite quadriplegic games players.

BACKGROUND: Participation in wheelchair sports such as tennis and rugby enables people with quadriplegia to compete both individually and as a team at the highest level. Both sports are dominated by frequent, intermittent, short term power demands superimposed on a background of aerobic activity. OBJECTIVE: To gain physiological profiles of highly trained British quadriplegic athletes, and to examine the relation between aerobic and sprint capacity. METHODS: Eight male quadriplegic athletes performed an arm crank exercise using an ergometer fitted with a Schoberer Rad Messtechnik (SRM) powermeter. The sprint test consisted of three maximum-effort sprints of five seconds duration against a resistance of 2%, 3%, and 4% of body mass. The highest power output obtained was recorded (PPO). Peak oxygen consumption (V(O2peak)), peak heart rate (HR(peak)), and maximal power output (PO(aer)) were determined. RESULTS: Mean PO(aer) was 67.7 (16.2) W, mean V(O2peak) was 0.96 (0.17) litres/min, and HR(peak) was 134 (19) beats/min for the group. There was high variability among subjects. Peak power over the five second sprint for the group was 220 (62) W. There was a significant correlation between V(O2peak) (litres/min) and PO(aer) (W) (r = 0.74, p<0.05). CONCLUSIONS: These British quadriplegic athletes have relatively high aerobic fitness when compared with the available literature. Moreover, the anaerobic capacity of these athletes appeared to be relatively high compared with paraplegic participants.

Adult↗
PubMed2006

Performance diagnostics in handbiking during competition.

STUDY DESIGN: Case study in handbiking under competition conditions. OBJECTIVE: To investigate exercise-induced, metabolic, pulmonary, cardiovascular and energetic reactions of a paraplegic athlete during a city marathon. SETTING: City marathon Cologne, Germany. SUBJECT: We tested a 27-year-old male athlete from the German national team. The handicap of the athlete was a complete traumatic spinal cord injury ASIA/IMSOP Grade A at the level of the fourth thoratic vertebra (Th4). METHOD: In the competition, the athlete used his own race handbike whose crank system had been exchanged for a power measurement system with registering option. For measuring ventilatory gas parameters during exercise, a portable spirometric system was used. The athlete managed to finish the marathon race in 1:48:54 h. RESULTS: The mean oxygen uptake (VO2) during the marathon was 1580 ml/min, with a maximum value of 2535 ml/min. The mean heart frequency was 137 bpm with a maximum of 157 bpm. During the race the mean energy consumption was 463 kcal/h with a maximum of 758 kcal/h. Prior to the race, the blood lactate value was 2.9 mmol/l; after 10 km 4.4 mmol/l; after 20 km 2.9 mmol/l, and after 30 km 2.9 mmol/l. CONCLUSION: Competition-oriented handbikers should concentrate on exercise units of long duration at low intensities--like marathon runners or cyclists--in order to improve their aerobic performance capacity. However, it has to be pointed out that paraplegic athletes develop relatively high metabolic intensities in competition and that the variability of their physiological parameters is considerably high.

Adult↗
PubMed2005

Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - a randomized, double-blind, placebo-controlled study.

The intake of arginine aspartate has been shown to increase anabolic hormones like human growth hormone (hGH) and glucagon. The aim of our study was to investigate whether daily intake of two different dosages of arginine asparate during four weeks affects selected parameters of overtraining syndrome like performance, metabolic and endocrine parameters. Thirty male endurance-trained athletes were included in a randomized, double-blind, placebo-controlled study and divided into three groups. During four weeks, they ingested either arginine aspartate with a high concentration (H) of 5.7 g arginine and 8.7 g aspartate, with a low concentration (L) of 2.8 g arginine and 2.2 g aspartate or placebo (P).VO(2)peak and time to exhaustion were determined on a cycling ergometer in an incremental exercise test before and after supplementation. Before and after each incremental exercise test, concentrations of hGH, glucagon, testosterone, cortisol, ferritine, lactate, and urea were measured. Compared to placebo, no significant differences on endurance performance (VO(2)peak, time to exhaustion), endocrine (concentration of hGH, glucagon, cortisol, and testosterone) and metabolic parameters (concentration of lactate, ferritine, and urea) were found after chronic arginine aspartate supplementation. The chronic intake of arginine asparate during four weeks by male endurance athletes showed independent of dosage no influence on performance, selected metabolic or endocrine parameters. Consequently, there seems to be no apparent reason why the supplementation of arginine aspartate should be an effective ergogenic aid. The practice of using arginine aspartate as potential ergogenics should be critically reevaluated. Further investigations with higher dosage and extended supplementation periods should be performed.

Adult↗
PubMed2004

Phosphodiesterase inhibitors: a novel mechanism for receptor-independent antipsychotic medications.

OVERVIEW: All current antipsychotic medications work by binding to Gi-coupled dopamine (DA) D2 receptors. Such medications are thought to affect cellular function primarily by decreasing DA-mediated regulation of intracellular cyclic adenosine monophosphate (cAMP).However, several studies indicate that cAMP signal transduction abnormalities in schizophrenia may not be limited to D2-containing cells. The current study examines the potential of using non-receptor-based agents that modify intracellular signal transduction as potential antipsychotic medications. METHODS: The indirect DA agonist amphetamine has been used to model the auditory sensory processing deficits in schizophrenia. Such pharmacologically induced abnormalities are reversed by current antipsychotic treatments. This study examines the ability of the phosphodiesterase-4 inhibitor, rolipram, to reverse amphetamine-induced abnormalities in auditory-evoked potentials that are characteristic of schizophrenia. RESULTS: Rolipram reverses amphetamine-induced reductions in auditory-evoked potentials. CONCLUSION: This finding could lead to novel approaches to receptor-independent treatments for schizophrenia.

Amphetamine↗
PubMed2002

Behavioral analysis of CREB alphadelta mutation on a B6/129 F1 hybrid background.

The cyclic AMP (cAMP)-response element binding protein (CREB) is an activity-dependent transcription factor that plays a role in synaptic plasticity and memory storage in Aplysia, Drosophila, and rodents. Mice with targeted deletions of two CREB isoforms (alpha and delta; CREB alphadelta mice) have been characterized on a mixed genetic background of C57BL/6 (B6) and 129/SvEv (129), as well as on a defined F1 hybrid of B6 and FVB/N, and these results suggest that the phenotype of CREB alphadelta mice depends critically on genetic background. In an examination of the hypothesis that the role of CREB in learning and memory can be influenced by strain differences, we analyzed mice with the CREB alphadelta mutation on an F1 hybrid background of B6 and 129 strains. CREB alphadelta mice on this background had impaired short-term and long-term cued and contextual fear conditioning and normal spatial learning in the Morris water maze. Our results suggest that at least some aspects of hippocampal function are normal in CREB alphadelta mice, and that CREB alphadelta mice on the B6/129 F1 background have alterations in amygdala function. These studies underscore the importance of controlling for genetic background in the behavioral analysis of knockout and transgenic mice.

Animals↗
PubMed2001

Different requirements for protein synthesis in acquisition and extinction of spatial preferences and context-evoked fear.

Many molecular accounts of long-term memory storage postulate that the synthesis of new proteins is necessary for long-term changes in neuronal function. These experiments generally have examined the learning that occurs as associations are acquired between neutral and biologically important stimuli. Little is known about the importance of protein synthesis in the establishment of memories for extinction, which occurs as the relations established during acquisition are severed. Extinction appears to be an active learning process that results in the formation of new memories rather than in the simple erasure or forgetting of memories from acquisition. Furthermore, under certain circumstances, extinction can result in long-term changes in behavior lasting for days to weeks. Here we show that although memories for the acquisition of spatial and contextual learning required protein synthesis, memories for extinction formed in the absence of protein synthesis. These results suggest that acquisition and extinction are mediated by distinct molecular mechanisms and that long-term memories can form in the absence of protein synthesis.

Animals↗
PubMed2001

The cAMP-protein kinase A signal transduction pathway modulates ethanol consumption and sedative effects of ethanol.

Ethanol and other drugs of abuse modulate cAMP-PKA signaling within the mesolimbic reward pathway. To understand the role of the cAMP-PKA signal transduction in mediating the effects of ethanol, we have studied ethanol consumption and the sedative effects of ethanol in three lines of genetically modified mice. We report that mice with the targeted disruption of one Gsalpha allele as well as mice with reduced neuronal PKA activity have decreased alcohol consumption compared with their wild-type littermates. Genetic reduction of cAMP-PKA signaling also makes mice more sensitive to the sedative effects of ethanol, although plasma ethanol concentrations are unaffected. In contrast, mice with increased adenylyl cyclase activity resulting from the transgenic expression of a constitutively active form of Gsalpha in neurons within the forebrain are less sensitive to the sedative effects of ethanol. Thus, the cAMP-PKA signal transduction pathway is critical in modulating sensitivity to the sedative effects of ethanol as well as influencing alcohol consumption.

Adenylyl Cyclases↗
PubMed2001

Receptor polymorphisms and diseases.

The aim of our review is to summarize common genetic variations of some receptors associated with clinical consequences, which were not outlined in the previous special issue of this journal. Because of the multiple pathomechanisms of diseases, a set of genetic variation can play a role in the development of pathological conditions. From the data available three articles would merit a greater interest. In systemic lupus erythematosus the associations related to some polymorphisms of Fc-, tumor necrosis factor (TNF) alpha- and interferon receptor may explore new autoimmunological and inflammatorical pathomechanisms. In the endocrinology, the androgen receptor repeat polymorphism will exert significant aspects in the development of prostate cancer. The pleoitropic responsibility of vitamin D3 receptor polymorphism in the pathogenesis of immunological disorders (primary biliary cirrhosis, inflammatory bowel disease, type 1 diabetes mellitus) and of malignancies (malignant melanoma, breast cancer) shed light on the importance of common nuclear receptors. Nevertheless, in the future studies a more consistent approach minimizing requirement bias in the selection of patients will approve our understanding the role of genetic influence on the pathogenesis of diseases.

Antigens, CD↗
PubMed2001

[Health promotion by sports and physical activity: politics, behavior and infrastructures in a European comparison].

OBJECTIVES: The focus of physical activity promotion is moving from measures to increase health-enhancing physical activity on the individual level to higher-level strategies including policy and environmental approaches. Scientific evidence, traditionally related to individual-based strategies, calls for adaptation and refinement when environmental and policy changes become more relevant. METHODS: This paper investigates differences in physical activity promotion and public policy among six European countries. Data from a European study on public health promotion policy and health behaviours (MAREPS) is analysed to study behaviour, community-based opportunities for physical activity, and populations' perception of the effectiveness of their national policies in promoting physical activity. RESULTS: Analyses show significant differences in both involvement in and perceived opportunities for physical activity among the investigated countries. Populations in Finland, Switzerland, and The Netherlands show comparably higher participation and, at the same time, perceive better opportunities for physical activity within the residential environment than people in East Germany, Belgium, and Spain. Moreover, respondents from the former group of nations report considerably greater contribution of health policy in their country to the promotion of physical activity than respondents from the latter group. CONCLUSIONS: In conclusion, the results provide empirical support for the significance of environmental and policy approaches with regard to physical activity. Opportunities created by implementing such approaches may enable populations to develop more active lifestyles conducive to health. Further research employing longitudinal designs could be especially helpful to explore the causalities of the relationship between policy, environment and physical activity.

Adolescent↗
PubMed2001

Quality of life in children and adolescents: a European public health perspective.

OBJECTIVES: The measurement of health-related quality of life (HRQOL) is increasingly important as a means of monitoring population health status over time, of detecting sub-groups within the general population with poor HRQOL, and of assessing the impact of public health interventions within a given population. At present, no standardised instrument exists which can be applied with equal relevance in pediatric populations in different European populations. The collaborative European KIDSCREEN project aims to develop a standardised screening instrument for children's quality of life which will be used in representative national and European health surveys. Participants of the project are centres from Austria, France, Germany, Netherlands, Spain, Switzerland, and United Kingdom. By including the instrument in health services research and health reporting, it also aims at identifying children at risk in terms of their subjective health, thereby allowing the possibility of early intervention. METHODS: Instrument development will be based on constructing a psychometrically sound HRQOL instrument taking into account the existing state of the art. Development will centre on literature searches, expert consultation (Delphi Methods) and focus groups with children and adolescents (8-17 years). According to international guidelines, items will be translated into the languages of the seven participating countries for a pilot test with 2,100 children and their parents in Europe. The final instrument will be used in representative mail and telephone surveys of HRQOL in 1,800 children and their parents per country (total n = 25,200) and normative data will be produced. The potential for implementing the measurement tool in health services and health reporting will also be evaluated in several different research and public health settings. The final analysis will involve national and cross cultural-analysis of the instrument. RESULTS: The international, collaborative nature of the KIDSCREEN project means it is likely to provide many challenges in terms of producing an instrument which is conceptually and linguistically appropriate for use in many different countries, but it will also provide the opportunity to develop, test and implement the first truly cross-national HRQOL instrument developed for use in children and adolescents. This will help to contribute to a better understanding of perceived health in children and adolescents and to identify populations at risk.

Adolescent↗
PubMed2001

Gender bias in the assessment of physical activity in population studies.

OBJECTIVES: Despite their generally more health promoting behaviours, women are found to participate less in physical activity than men. This study explores possible gender bias in measurement of physical activity in population studies. METHODS: Data collected by telephone (CATI) from the Berne Lifestyle Panel in 1996 is utilised. A representative samples of the population of the city of Berne comprised N = 1119 cases. Gender differences are assessed for the weekly frequency of three measurements of physical activities. RESULTS: An indicator of sport and exercise showed higher physical activity among men, while the indicator of habitual physical activity showed higher rates of daily walking and biking among women. A combined indicator of general physical activity showed no significant gender differences. CONCLUSIONS: The results provide empirical evidence on potential risk of underestimation of physical activity among women and of misclassification with respect to high or low risk behaviour patterns.

Aged↗
PubMed2001

Sleep and memory: a molecular perspective.

This review synthesizes data from behavioral studies examining the role of sleep in memory storage with what is known about the molecular mechanisms of memory consolidation. There are striking similarities in the effects on memory storage of post-training pharmacological manipulations and post-training manipulations of sleep. For example, inhibition of protein synthesis is most effective if it occurs at a time post-training when rapid eye movement (REM) sleep is required for memory consolidation. The neurochemical changes that occur across sleep/wake states, especially the cholinergic changes that occur in the hippocampus during REM sleep, might provide a mechanism by which sleep modulates specific cellular signaling pathways involved in hippocampus-dependent memory storage.

Acetylcholine↗
PubMed2001

The importance of the social environment for physically active lifestyle--results from an international study.

Physically active lifestyles are regularly associated with improved health and quality of life. Differences in lifestyles in society can partly be understood through the differences in the social and physical environment. This study examines the relationships between reported physical activity, and the extent of perceived support for physical activity in the physical and policy environment (e.g. facilities, programmes and other opportunities), and in the social environment. The data for the study come from a cross-cultural health policy study called MAREPS. In total, 3342 adults, 18 years or older, from six countries (Belgium, Finland, Germany, The Netherlands, Spain, Switzerland) were interviewed via telephone. Respondents were categorised as active or inactive according to self-reported physical activity. Social environmental factors and physical and policy environmental factors were also assessed. The analysis of the data was informed by social cognitive theory, although the study was not originally designed for this purpose. Sixty-eight percent of females and 70% of males were active. The proportions of active and inactive varied by countries to a great extent. The strongest independent predictor of being physically active was social environment. Those who perceived low social support from their personal environment (i.e. family, friends, school and workplace) were more than twice as likely to be sedentary compared to those who reported high social support from their personal environment. Specific knowledge of the programmes and actions for physical activity and sport was also a strong predictor of being active. A supportive physical and policy environment was not associated with participation in physical activity as strongly as had been anticipated. The variation between countries was stronger predictor of being active than the physical and policy environment variables. This study generates the hypotheses and raises the questions that in a preliminary way, there appears to be some relationships between aspects of physical and social environment and physical activity participation. However, future research is needed to refine and clarify this.

Adolescent↗
PubMed2001

Molecular mechanisms of memory acquisition, consolidation and retrieval.

Memory is often considered to be a process that has several stages, including acquisition, consolidation and retrieval. Memory can be modified further through reconsolidation and performance can change during extinction trials while the original memory remains intact. Recent studies of the molecular basis of these processes have found that many signaling molecules are involved in several stages of memory but, in some cases, molecular pathways may be selectively recruited only during certain stages of memory.

Animals↗