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C Cyr

Publications and source records attributed to C Cyr.

7 recordsLinked to original sources
PubMed2001

Canadian guidelines for cardiac rehabilitation and atherosclerotic heart disease prevention: a summary.

Atherosclerotic heart disease (AHD) is the leading cause of death in Canadian women and men. Cardiac rehabilitation has been repeatedly shown to reduce cardiac morbidity and mortality significantly among patients with documented AHD. The Canadian Association of Cardiac Rehabilitation (CACR) has defined cardiac rehabilitation as "the enhancement and maintenance of cardiovascular health through individualized programs designed to optimize physical, psychological, social, vocational and emotional status. This process includes the facilitation and delivery of secondary prevention through heart hazard (risk factor) identification and modification in an effort to prevent disease progression and the recurrence of cardiac events". This summary presents a limited amount of background information and the majority of clinical practice recommendations contained within the previously published CACR Guidelines. These evidence-based clinical recommendations are intended as guidelines to good clinical practice rather than as standards of care. The key focus of this summary is the need for complete and targeted intervention of all heart hazards in patients at high or very high risk for, or with documented, AHD. To achieve this goal, the CACR Guidelines and this summary present risk stratification strategies designed to determine unambiguously a patient's risk of exercise-related cardiac events (short term absolute risk or disease prognosis) and their risk of recurrent AHD events (long term absolute risk from disease progression). The establishment of the short term and long term absolute AHD risks can then be used to determine heart hazard targets and the type of exercise program prescribed for patients with AHD. Despite the use of evidence-based medical practices, none of the recommendations presented in this document can replace the expert judgment of properly trained and experienced cardiac rehabilitation professionals. Health care providers must always be free to choose where and when clinical practice guidelines are applied, modified or superceded, depending on individual patient circumstances.

Canada↗
PubMed1999

Activation of the endothelin receptor inhibits the G protein-coupled inwardly rectifying potassium channel by a phospholipase A2-mediated mechanism.

To develop a malleable system to model the well-described, physiological interactions between Gq/11 - coupled receptor and Gi/o-coupled receptor signaling, we coexpressed the endothelin A receptor, the mu-opioid receptor, and the G protein-coupled inwardly rectifying potassium channel (Kir 3) heteromultimers in Xenopus laevis oocytes. Activation of the Gi/o-coupled mu-opioid receptor strongly increased Kir 3 channel current, whereas activation of the Gq/11-coupled endothelin A receptor inhibited the Kir 3 response evoked by mu-opioid receptor activation. The magnitude of the inhibition of Kir 3 was channel subtype specific; heteromultimers composed of Kir 3.1 and Kir 3.2 or Kir 3.1 and Kir 3.4 were significantly more sensitive to the effects of endothelin-1 than heteromultimers composed of Kir 3.1 and Kir 3.5. The difference in sensitivity of the heteromultimers suggests that the endothelin-induced inhibition of the opioid- activated current was caused by an effect at the channel rather than at the opioid receptor. The endothelin-1-mediated inhibition was mimicked by arachidonic acid and blocked by the phospholipase A2 inhibitor arachidonoyl trifluoromethyl ketone. Consistent with a possible phospholipase A2-mediated mechanism, the endothelin-1 effect was blocked by calcium chelation with BAPTA-AM and was not affected by kinase inhibition by either staurosporine or genistein. The data suggest the hypothesis that Gq/11-coupled receptor activation may interfere with Gi/o-coupled receptor signaling by the activation of phospholipase A2 and subsequent inhibition of effector function by a direct effect of an eicosanoid on the channel.

Analgesics, Opioid↗
PubMed1996

Thr353, located within the COOH-terminal tail of the delta opiate receptor, is involved in receptor down-regulation.

Prolonged exposure to abused drugs such as opiates causes decreased response to the drug; this reduced sensitivity is thought to be due to the loss of receptors, or down-regulation. The molecular mechanism of the opiate receptor down-regulation is not known. In order to address this, we generated a number of mutants of the delta opiate receptor COOH-terminal tail. When expressed in the Chinese hamster ovary cells, both the wild type and the receptor with a deletion of 37 COOH-terminal residues bind diprenorphine with comparable affinities and show similar decreases in cAMP levels in response to D-Ala2, D-Leu5, enkephalin (DADLE). However, the truncated receptor does not show down-regulation from the cell surface upon prolonged exposure (2-48 h) to DADLE. In contrast, both the wild type receptor and the receptor with the deletion of only 15 COOH-terminal residues show substantial down-regulation upon long term DADLE treatment. These results suggest that the region located between 15 and 37 residues from the COOH terminus is involved in the receptor down-regulation. In order to identify residues that play a key role in down-regulation, point mutations of residues within this region were examined for their ability to modulate receptor down-regulation. The receptor with a mutation of Thr353 to Ala does not down-regulate, whereas the receptor with a mutation of Ser344 to Gly down-regulates with a time course similar to that of the wild type receptor. Taken together, these results suggest that the COOH-terminal tail is not essential for functional coupling but is necessary for down-regulation and that Thr353 is critical for the agonist-mediated down-regulation of the delta opiate receptor.

Alanine↗
PubMed1993

Desensitization of human endothelin A receptor.

The response of G-protein-coupled receptors is modulated by homologous desensitization. Because endothelin A receptor (ETA) plays a part in vasoconstriction, the extent of desensitization and resensitization of endothelin responsiveness was studied. A cDNA clone encoding human ETA receptor was isolated based on similarities to bovine endothelin A receptor. Xenopus laevis oocytes injected with cloned mRNA transcripts were used as a model system for analyzing desensitization. Human neurokinin A (NKA) receptor was used for comparison with ETA receptor in desensitization experiments. Xenopus laevis oocytes injected with the two receptor mRNAs show homologous desensitization but variable rates of recovery. Human NKA receptors desensitize within 5 min and resensitize after 20-30 min. Human ETA receptors also desensitize within 5 min but have a prolonged resensitization period lasting 1.5-2 h. Such a prolonged recovery period is unique to this class of receptors and may serve to regulate some of the deleterious effects mediated by the ETA receptor. The mechanism of differential desensitization is being investigated using genetically engineered mutants of human ETA receptor.

Animals↗
PubMed1991

Cloning and chromosomal localization of a human endothelin ETA receptor.

A cDNA clone encoding a human endothelin receptor was isolated from a placenta cDNA library. The deduced amino acid sequence of the clone is 94% identical to the bovine endothelin ETA receptor and represents the human homologue. The human endothelin ETA receptor gene was localized to chromosome 4 by analysis of its segregation pattern in rodent-human hybrids.

Amino Acid Sequence↗
PubMed1981

[Not Available].

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Canada↗