Examining Social Influences on Why We Drink: Perceived Drinking Motives in the Social Network Impact Individuals' Own Drinking Motives and Alcohol Use.

Introduction: A significant body of research has investigated the impacts of social influence and social selection on binge drinking and risk factors for binge drinking in emerging adults; however, one risk factor for binge drinking that has yet to be thoroughly investigated in this regard is drinking motives. Preliminary research suggests the motives of others may impact emerging adults' own alcohol use indirectly through their own motives (i.e., social influence). While these are important findings, research to date has been only conducted with adolescents or dyads and has not examined selection (i.e., selecting social network members with similar motives). We filled these gaps with a longitudinal egocentric social network design. Methods: Emerging adults (N = 177) completed measures on their alcohol use, drinking motives, and social networks at baseline (T1) and four-month follow-up (T2). Results: A cross-lagged panel model indicated T1 perceived network drinking motives predicted T2 participant drinking motives (for all motives but social), but T1 participant drinking motives did not predict T2 perceived network drinking motives. Path analysis indicated T1 perceived network drinking motives predicted T2 participant binge drinking frequency indirectly through T2 participant drinking motives for enhancement, coping-with-anxiety, and conformity, but not social or coping-with-depression, motives. Discussion: Results suggests drinking motives of those around emerging adults impact their own drinking motives, and indirectly, their own alcohol use. We found evidence of social influence, but not social selection. Conclusion: It appears that those around emerging adults have the capacity to influence their drinking behaviors and drinking motives.

[Vocal fatigue as an indicator of complex voice disorders-a diagnostic and therapeutic challenge]. / Vocal Fatigue als Indikator für komplexe Stimmstörungen ­ eine diagnostische und therapeutische Herausforderung.

Vocal fatigue is increasingly observed among professional voice users (e.g., teachers). This pathologic state is associated with restrictions in everyday life and is considered to be an indicator of complex voice disorders. Since there are few systematic studies on the phenomenon, there is currently no uniform definition or diagnostic workup. Based on the case study of a professional speaker, possibilities for a structured vocal fatigue assessment are presented. These are discussed with regard to their laryngoscopic, instrumental acoustic ("performance fatigue") and subjective symptom-related characteristics ("perceived fatigue"). In addition, a differentiation from the vocal effort, vocal demand, and vocal demand response models according to Hunter et al. (2020) is made.

[Teaching during the COVID-19 pandemic: how do medical students evaluate interactive video-based distance bedside teaching in otorhinolaryngology?] / Ausbildung in COVID-19-Pandemie-Zeiten: Wie bewerten Medizinstudierende einen interaktiven, videobasierten Distanzunterricht am Patienten im Fach Hals-Nasen-Ohren-Heilkunde?

BACKGROUND: The first wave of the SARS-CoV­2 pandemic required substantial changes in the teaching of medical students, with strict avoidance of direct contact between students and patients. Therefore, the teaching format "bedside teaching" was implemented and conducted as an interactive video-based distance bedside teaching. OBJECTIVE: The objective of this study was to analyze a students' evaluation of this teaching concept in otorhinolaryngology. MATERIALS AND METHODS: From an ENT examination room, the situation was transmitted live to the students in a lecture hall, who could interact with the patients through a video connection. Macro-, micro-, and endoscopic images were transmitted into the lecture hall in real time. Evaluation was performed by means of an online questionnaire with 13 questions (Likert scale) as well as by free-text feedback. RESULTS: The response rate was 16.8% (42 of 250 students). Overall, 85.7% had a positive impression, and it was generally considered that the concept was well implemented in light of the special situation. However, students would rather not renounce direct patient contact, even if a certain compensation by video transmission was reported. Overall, this teaching concept was considered as educative, and students could imagine using such a teaching concept more often in the future. CONCLUSION: This teaching model cannot replace classical bedside teaching, but represents a good alternative-particularly in otorhinolaryngology-if classical bedside teaching is not possible due to the pandemic situation. Aspects of the interactive video-based distance bedside teaching could be implemented into classical teaching concepts in the future.

[Functional results after soft palate reconstruction in oropharyngeal cancer patients]. / Funktionelle Ergebnisse nach Rekonstruktion des weichen Gaumens bei Patienten mit Oropharynxkarzinom.

BACKGROUND: Surgery of the soft palate in patients with oropharyngeal cancer can result in functional deficiencies of swallowing and speech. Reconstruction of the resected structures can contribute to regaining sufficient functionality after therapy. OBJECTIVE: The current study used frequency analysis to evaluate the change in speech characteristics after resection and reconstruction of the soft palate during post-therapeutic follow-up. MATERIALS AND METHODS: In 18 patients with oropharyngeal carcinoma and involvement of the soft palate, resection and reconstruction by free radial forearm graft (FRFG) and adjuvant chemoradiotherapy was conducted. The spoken German numbers "eins", "zwei", "drei", "vier", "fünf" were recorded during follow-up and objectively assessed by frequency analysis. Additionally, food intake status and the necessity of a tracheostomy were evaluated. RESULTS: The maximum peak frequencies of the numbers analysed increased from 150-300 Hz before up to 1000 Hz after therapy. Two years post therapy, the peak frequencies again declined to levels comparable to those before tumour therapy. One year after therapy, complete oral nutrition was possible in two thirds of patients and the tracheostomy was closed in 80%. CONCLUSION: Reconstruction of the soft palate by FRFG during the course of oropharyngeal cancer treatment allows function to be regained with respect to speech and swallowing. In the majority of patients, it is possible to reach a level of function comparable to the state before tumour treatment.

Self-isolation: A significant contributor to cannabis use during the COVID-19 pandemic.

BACKGROUND: Emerging research suggests the COVID-19 pandemic has resulted in a significant increase in self-reported isolation and loneliness in a large proportion of the population. This is particularly concerning given that isolation and loneliness are associated with increased cannabis use, as well as using cannabis to cope with negative affect. Objective: We investigated whether self-isolation due to COVID-19 and using cannabis to cope with depression were unique and/or interactive predictors of cannabis use during the pandemic, after controlling for pre-pandemic levels of cannabis use. Method: A sample of 70 emerging adults (mean age = 23.03; 34.3% male) who used both alcohol and cannabis pre-pandemic completed measures of cannabis use (i.e., quantity x frequency) and a novel COVID-19 questionnaire between March 23 and June 15, 2020. Pre-pandemic cannabis use levels had been collected four months earlier. Results: Linear regressions indicated self-isolation and coping with depression motives for cannabis use during the pandemic were significant predictors of pandemic cannabis use levels after accounting for pre-pandemic use levels. There was no interaction between coping with depression motives and self-isolation on cannabis use during the pandemic. Conclusions: Those who engaged in self-isolation were found to use 20% more cannabis during the pandemic than those who did not. Our results suggest that self-isolation is a unique risk factor for escalating cannabis use levels during the pandemic. Thus, self-isolation may inadvertently lead to adverse public health consequences in the form of increased cannabis use.

Influences of environmental bacteria and their metabolites on allergies, asthma, and host microbiota.

The prevalence of allergic diseases and asthma has dramatically increased over the last decades, resulting in a high burden for patients and healthcare systems. Thus, there is an unmet need to develop preventative strategies for these diseases. Epidemiological studies show that reduced exposure to environmental bacteria in early life (eg, birth by cesarean section, being formula-fed, growing up in an urban environment or with less contact to various persons) is associated with an increased risk to develop allergies and asthma later in life. Conversely, a reduced risk for asthma is consistently found in children growing up on traditional farms, thereby being exposed to a wide spectrum of microbes. However, clinical studies with bacteria to prevent allergic diseases are still rare and to some extent contradicting. A detailed mechanistic understanding of how environmental microbes influence the development of the human microbiome and the immune system is important to enable the development of novel preventative approaches that are based on the early modulation of the host microbiota and immunity. In this mini-review, we summarize current knowledge and experimental evidence for the potential of bacteria and their metabolites to be used for the prevention of asthma and allergic diseases.

Identification of a plasma miRNA biomarker signature for allergic asthma: A translational approach.

BACKGROUND: Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there is a high clinical need for molecular disease biomarkers to aid in differentiating these distinct phenotypes. As MicroRNAs (miRNAs), that regulate gene expression at the post-transcriptional level, are altered in experimental and human asthma, circulating miRNAs are attractive candidates for the identification of novel biomarkers. This study aimed to identify plasmatic miRNA-based biomarkers of asthma, through a translational approach. METHODS: We prescreened miRNAs in plasma samples from two different murine models of experimental asthma (ovalbumin and house dust mite); miRNAs deregulated in both models were further tested in a human training cohort of 20 asthma patients and 9 healthy controls. Candidate miRNAs were then validated in a second, independent group of 26 asthma patients and 12 healthy controls. RESULTS: Ten miRNA ratios consisting of 13 miRNAs were differentially regulated in both murine models. Measuring these miRNAs in the training cohort identified a biomarker signature consisting of five miRNA ratios (7 miRNAs). This signature showed a good sensitivity and specificity in the test cohort with an area under the receiver operating characteristic curve (AUC) of 0.92. Correlation of miRNA ratios with clinical characteristics further revealed associations with FVC % predicted, and oral corticosteroid or antileukotriene use. CONCLUSION: Distinct plasma miRNAs are differentially regulated both in murine and in human allergic asthma and were associated with clinical characteristics of patients. Thus, we suggest that miRNA levels in plasma might have future potential to subphenotype patients with asthma.

[Individual and Contextual Reasons for Drop-outs in Vocational Retraining]. / Individuelle und kontextbezogene Ursachen von Abbrüchen beruflicher Qualifizierungsmaßnahmen.

BACKGROUND AND AIMS: The study focusses on the explanation of the individual, process-driven, and institutional factors and their interplay, and on the subjective accounts for the high drop-out rates in vocational retraining which are reported by the German statutory pension insurance scheme. METHODS: 454 participants of 2-year lasting vocational retraining schemes in 3 vocational promotion centers and 3 education providers took part in the questionnaire survey. Furthermore, experts, dropouts and participants were interviewed and group discussions with experts and participants were conducted. RESULTS: Drop-out is not a definite term. Instead, it consists of different dimensions. 3 personal factors for predicting a drop-out could be identified: suffering from depression, negative health assessment and lack of social support. Generally speaking, drop-out of vocational retraining is a complex and mainly situational process which can hardly be predicted by personal factors, job-biographies or foregoing unemployment.

[Improved outcome quality following total knee and hip arthroplasty in an integrated care setting: results of a controlled study]. / Verbesserte Behandlungsqualität durch integrierte Versorgung bei Knie- und Hüftgelenkersatz: Ergebnisse einer kontrollierten Studie.

OBJECTIVE: In Germany, the introduction of the Law on integrated care (IC) (§ 140 a-d SGB V) opened up the possibility of cross-sectional health care settings and new forms of remuneration, and improved the conditions for a closer cooperation between health care providers. Patients awaiting a hip or knee arthroplasty expect a higher benefit from such an intensified cooperation of operating hospital and rehabilitation centre. However, to date there is no study that investigated the anticipated effects on functional outcomes. Therefore, the aim of our study was the efficacy evaluation of an arthroplastic IC model in comparison with usual care. METHODS: The controlled multicentre trial included pensioners who received an arthroplasty following gonarthrosis or coxarthrosis. Implantation of the arthroplasty was accomplished in 11 hospitals. Participants of the intervention group (IG; 3 hospitals) were treated within an IC model, participants of the control group (CG; 8 hospitals) were treated within conventional care. Primary outcome were the functional complaints measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: 481 patients attended the study (IG: n = 249; KG: n = 232). Response at end of treatment was 85.9% (n = 413), response after 4 months was 89.4% (n = 430) and after 1 year 85.9% (n = 413). Multivariate analyses confirmed a reduction of treatment time by 4 days (b = -3.964; 95% CI: -5.833 to -2.094; p < 0.001) and improved functional outcomes on the WOMAC (4 months: b = -7.219; 95% CI: -11.184 to -3.254; p < 0.001; 12 months: b = -8.070; 95% CI: -12.101 to -4.039; p < 0.001). Patients of the IG rated the process better (e. g. cooperation between hospital and rehabilitation centre: b = 0.672; 95% CI: 0.401 to 0.943; p < 0.001); reported a better self-rated health after 1 year (b = 4.418; 95% CI: 0.050 to 8.786; p = 0.047), and were physically more active (b = 1.603; 95% CI: 0.655 to 2.551; p = 0.001). CONCLUSION: The IC setting improved coordination and communication at the interface between hospital and rehabilitation centre (internal patient orientation). Higher patient satisfaction and better outcome quality (external patient orientation) are not only achievable by improved medical devices but also by innovative communicative and organisational structures bringing along an improved process quality.

[Factors of successful integrated care settings for total knee and hip arthroplasty: findings of a qualitative process analysis]. / Erfolgsfaktoren integrierter Versorgungsprozesse in der Endoprothetik: Ergebnisse einer qualitativen Prozessanalyse.

AIMS: In Germany, introduction of the law on Integrated Health Care (IC) (section sign 140a-d SGB V) opened up the possibility of cross-sectoral health care settings and new forms of remuneration, and improved the conditions for a closer cooperation between health care providers. However, cross-institutional and interdisciplinary work contexts demand new organizational structures in order to assure the coordination of different competences, resources and interests. This study aims at identifying factors of successful integrated care settings for total hip and knee arthroplasty. Using the example of an integrated care setting between an orthopaedic hospital and a rehabilitation clinic it will be examined which factors lead to successful implementation of the services and measures designed. METHOD: A qualitative research design was developed comprising different methods of data assessment (participant observation, guided expert interviews, document analyses) enabling a comprehensive exploration. Overall, data were derived from six consultations with patients, two integrated care information sessions and various documents (17 patient files, information material, patient lists, etc.). RESULTS: First of all, the different phases of development and implementation of integrated care settings were described. In this context, clearly defined aims, structures and appropriate measures seem to be crucial for an ideal long-term cooperation. Furthermore, the staff perspective on the effects of the IC programme on their daily routines proved an essential basis for process reconstruction. The staff members pointed out four main aspects regarding IC settings, i. e., improved image, increased knowledge, intensity of relationship, and less and more work effort. Against this background, factors of successful IC settings could be generated such as the need for central coordination, a regular staff information systems as well as accompanying process monitoring. CONCLUSION: Several key factors of successful integrated care settings in arthroplasty could be generated which provide important clues for shaping future interdisciplinary and cross-sectoral cooperation settings in health care services in general.

Classification of Orthorexia Nervosa: Further evidence for placement within the eating disorders spectrum.

PURPOSE: Orthorexia Nervosa (ON) may belong on the eating disorder (ED) or obsessive-compulsive (OC) spectrum. We sought to provide additional evidence regarding the working classification of ON as an ED. METHODS: 512 individuals completed a measure of ON symptoms (rBOT), ED symptoms (Eating Disorder Examination Questionnaire), OC symptoms (Obsessive-Compulsive Inventory Revised), food choice motives (Food Choice Questionnaire), and perfectionism (Multidimensional Perfectionism Scale). RESULTS: ON symptoms were more strongly linked to ED symptoms than to OC symptoms. ON symptoms were related to body weight and shape concerns, and with prioritizing weight above health with respect to food selection. Both ED and ON symptoms were moderately related to perfectionism, while OC symptoms were strongly related to perfectionism. CONCLUSION: Our results support ON being classified on the ED spectrum; however, whether ON represents a precursor to an ED, an ED with added health concerns, or a disorder that evolves from an ED is not certain. Future longitudinal research is necessary to test these alternate possibilities.

Both beta(2)- and beta(1)-adrenergic receptors mediate hastened relaxation and phosphorylation of phospholamban and troponin I in ventricular myocardium of Fallot infants, consistent with selective coupling of beta(2)-adrenergic receptors to G(s)-protein.

BACKGROUND: In adult human heart, both beta(1)- and beta(2)-adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of beta(1)- and beta(2)-adrenergic receptors on relaxation and phosphorylation of phospholamban and troponin I in ventricle obtained from infants with tetralogy of Fallot. METHODS AND RESULTS: Myocardium dissected from the right ventricular outflow tract of 27 infants (age range 21/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of beta(1)-adrenergic receptors with (-)-norepinephrine (NE) and beta(2)-adrenergic receptors with (-)-epinephrine (EPI) evoked phosphorylation of phospholamban (at serine-16 and threonine-17) and troponin I and caused concentration-dependent increases in contractile force (-log EC(50) [mol/L] NE 5.5+/-0.1, n=12; EPI 5.6+/-0.1, n=13 patients), hastening of the time to reach peak force (-log EC(50) [mol/L] NE 5.8+/-0.2; EPI 5.8+/-0.2) and 50% relaxation (-log EC(50) [mol/L] NE 5.7+/-0.2; EPI 5.8+/-0.1). Ventricular membranes from Fallot infants, labeled with (-)-[(125)I]-cyanopindolol, revealed a greater percentage of beta(1)- (71%) than beta(2)-adrenergic receptors (29%). Binding of (-)-epinephrine to beta(2)-receptors underwent greater GTP shifts than binding of (-)-norepinephrine to beta(1)-receptors. CONCLUSIONS: Despite their low density, beta(2)-adrenergic receptors are nearly as effective as beta(1)-adrenergic receptors of infant Fallot ventricle in enhancing contraction, relaxation, and phosphorylation of phospholamban and troponin I, consistent with selective coupling to G(s)-protein.

beta2-adrenergic cAMP signaling is uncoupled from phosphorylation of cytoplasmic proteins in canine heart.

BACKGROUND: Recent studies of beta-adrenergic receptor (beta-AR) subtype signaling in in vitro preparations have raised doubts as to whether the cAMP/protein kinase A (PKA) signaling is activated in the same manner in response to beta2-AR versus beta1-AR stimulation. METHODS AND RESULTS: The present study compared, in the intact dog, the magnitude and characteristics of chronotropic, inotropic, and lusitropic effects of cAMP accumulation, PKA activation, and PKA-dependent phosphorylation of key effector proteins in response to beta-AR subtype stimulation. In addition, many of these parameters and L-type Ca2+ current (ICa) were also measured in single canine ventricular myocytes. The results indicate that although the cAMP/PKA-dependent phosphorylation cascade activated by beta1-AR stimulation could explain the resultant modulation of cardiac function, substantial beta2-AR-mediated chronotropic, inotropic, and lusitropic responses occurred in the absence of PKA activation and phosphorylation of nonsarcolemmal proteins, including phospholamban, troponin I, C protein, and glycogen phosphorylase kinase. However, in single canine myocytes, we found that beta2-AR-stimulated increases in both ICa and contraction were abolished by PKA inhibition. Thus, the beta2-AR-directed cAMP/PKA signaling modulates sarcolemmal L-type Ca2+ channels but does not regulate PKA-dependent phosphorylation of cytoplasmic proteins. CONCLUSIONS: These results indicate that the dissociation of beta2-AR signaling from cAMP regulatory systems is only apparent and that beta2-AR-stimulated cAMP/PKA signaling is uncoupled from phosphorylation of nonsarcolemmal regulatory proteins involved in excitation-contraction coupling.

Soluble substances released from postischemic reperfused rat hearts reduce calcium transient and contractility by blocking the L-type calcium channel.

OBJECTIVES: This study was designed to investigate the effects of cardiodepressant substances released from postischemic myocardial tissue on myocardial calcium-regulating pathways. BACKGROUND: We have recently reported that new cardiodepressant substances are released from isolated hearts during reperfusion after myocardial ischemia. METHODS: After 10 min of global ischemia, isolated rat hearts were reperfused, and the coronary effluent was collected for 30 s. We tested the effects of the postischemic coronary effluent on cell contraction, Ca2+ transients and Ca2+ currents of isolated rat cardiomyocytes by applying fluorescence microscopy and the whole-cell, voltage-clamp technique. Changes in intracellular phosphorylation mechanisms were studied by measuring tissue concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), as well as activities of cAMP-dependent protein kinase (cAMP-dPK) and protein kinase C (PKC). RESULTS: The postischemic coronary effluent, diluted with experimental buffer, caused a concentration-dependent reduction of cell shortening and Ca2+ transient in the field-stimulated isolated cardiomyocytes of rats, as well as a reduction in peak L-type Ca2+ current in voltage-clamped cardiomyocytes. The current reduction resulted from reduced maximal conductance--not from changes in voltage- and time-dependent gating of the L-type Ca2+ channel. The postischemic coronary effluent modified neither the tissue concentrations of cAMP or cGMP nor the activities of cAMP-dPK and PKC. However, the effluent completely eliminated the activation of glycogen phosphorylase after beta-adrenergic stimulation. CONCLUSIONS: Negative inotropic substances released from isolated postischemic hearts reduce Ca2+ transient and cell contraction through cAMP-independent and cGMP-independent blockage of L-type Ca2+ channels.

A phase I and pharmacokinetic study of a new camptothecin derivative, 9-aminocamptothecin.

Camptothecins are the only available antitumor agents which target the nuclear enzyme topoisomerase I. 9-Aminocamptothecin (9-AC) is a water-insoluble derivative of camptothecin which has demonstrated impressive antitumor activity in preclinical models. While two other water-soluble derivatives, CPT-11 and topotecan, have successfully completed Phase I and Phase II testing, biochemical and tissue culture studies suggest that camptothecin analogues differ in characteristics which may be important in determining antitumor activity. We performed a Phase I trial of 9-AC to determine the pharmacokinetics, dose-limiting toxicity, and maximum tolerated dose of this agent when administered as a 72-h continuous i.v. infusion. Thirty-one patients with resistant solid cancers received 5-60 microgram/m2/h 9-AC for 72 h, repeated at 3-week intervals. The drug was administered in a vehicle containing dimethylacetamide, polyethylene glycol, and phosphoric acid. Blood samples were collected and the lactone (closed ring) form of 9-AC was quantitated. The maximum tolerated dose of 9-AC was determined to be 45 microgram/m2/h. Dose-limiting toxicity consisted of neutropenia. Thrombocytopenia was also prominent. There were no significant nonhematological toxicities. Minimal responses were seen in patients with gastric, colon, and non-small cell lung cancer. Although significant interpatient variation in plasma 9-AC lactone levels was observed, pooled data were fit to a two-compartment model, with a terminal half-life of 36 h. Analyses of topoisomerase protein levels in peripheral blood cells indicated decreases in topoisomerase I accompanied by increases in topoisomerase II in two of three patients. 9-AC is an active antitumor agent and may be administered safely as a 72-h infusion in patients with cancer. Although Phase II trials with a 72-h infusion of 9-AC are warranted, alternate schedules should be evaluated given the dramatic preclinical activity seen with more prolonged administrations.

Protein phosphorylation and cardiac function: cholinergic-adrenergic interaction.

OBJECTIVE: The muscarinic inhibition of cyclic AMP (cAMP) mediated contractile effects may not only be the result of a reduction in cAMP levels, but may also involve cAMP linked protein phosphorylation in the heart. To show that a cholinergic agonist may antagonise the effects of agents that induce the cAMP signalling sequence at the level of protein phosphorylation, the effect of carbachol was investigated on the in vivo phosphorylation of phospholamban, troponin I, and a 15 kDa protein during positive inotropic intervention with isoprenaline, forskolin, and a phosphodiesterase inhibitor in the isolated rat heart. METHODS: The contractile activity of the heart was monitored during drug administration, and the hearts were freeze clamped for assay of protein phosphorylation and metabolites [cAMP, cyclic guanosine monophosphase (cGMP), cAMP dependent protein kinase (cA-PK), and phosphorylase a]. For estimation of the amount of in vivo phosphorylation, a "back phosphorylation" method was used. RESULTS: Carbachol attenuated in vivo phosphorylation, induced by cAMP increasing drugs, of all the phosphoproteins studied, whereas the accumulation of cAMP was not affected or was decreased to 61% after exposure to isoprenaline alone. In addition, the cAMP mediated phosphorylase a activation was completely reversed by carbachol. similarly, sodium nitroprusside reduced phosphorylation as well as the contractile force of the investigated phosphoproteins. CONCLUSIONS: These data confirm the reduction of cAMP mediated cardiac protein phosphorylation by carbachol. The cholinergic antagonism may primarily involve cellular target systems distal to sites of cAMP generation. The observed similarity in the cardiac response to carbachol and sodium nitroprusside indicates a role of cGMP in the antiadrenergic action of carbachol in the myocardium.

The endogenous cardiac sarcoplasmic reticulum Ca2+/calmodulin-dependent kinase is activated in response to beta-adrenergic stimulation and becomes Ca2+-independent in intact beating hearts.

We investigated the effects of beta-adrenergic stimulation on the activity of the endogenous cardiac sarcoplasmic reticulum Ca2+/calmodulin-dependent protein kinase (SRCaM kinase) in Langendorff-perfused rat hearts. We found that isoproterenol induced generation of autonomous (Ca2+-independent) SRCaM kinase activity to 28 +/- 4.4% of the total activity. Moreover, dephosphorylation of the autonomous SRCaM kinase with protein phosphatase 2A resulted in an enzyme that was again dependent on Ca2+ and calmodulin for its activity. Activation of SRCaM kinase was coupled to phospholamban phosphorylation and activation of the cAMP-signaling system. Our results suggest that the cardiac SRCaM kinase is activated in response to beta-adrenoceptor stimulation. This activation stimulates autophosphorylation at its regulatory domain and converts it to an active Ca2+-independent species that may be the basis for potentiation of Ca2+ transients in the heart.