Insights from defining nurses' career success: An integrative review.

AIMS: To review the literature and identify factors that make sense of and influence nurses' career success. We sought to provide insights into achieving nurses' career success. DESIGN: An integrative review conducted in May 2022 using Whittemore and Knafl's methodology of integrative review. METHODS: The databases searched were PubMed, Web of Science, Scopus, and CINAHL. Search criteria included the keywords "nurs*" and "career success" in the title and abstract. The quality of the reviewed papers was assessed using the JBI Critical Appraisal Tool for cross-sectional studies and qualitative research. We extracted five types of information from quantitative studies: the definition of career success, factors of career success instruments, reliability or validity of career success instruments, and factors influencing nursing career success. Furthermore, we extracted two types of information from qualitative studies: themes that imply career success and factors that influence nurses' career success. Primary data were categorized into two perspectives: (1) what nurses' career success means and (2) what influences nurses' career success. Categorized data were unified into similar contents. Themes were developed from unified subgroups. RESULTS: Fourteen studies were included in the analysis. Seven themes were integrated into the factors that make sense of nurses' career success: satisfaction, positive attitude towards work, quality work in nursing, continuation of career and professional development, positive interaction at work, person-organization fit, and enrichment of an individual's life. Three themes were integrated into the factors influencing nursing career success: personal resources, positive behavior toward nursing work and research, and job resources and environment. NO PATIENT OR PUBLIC CONTRIBUTION: Patients or members of the public were not involved in this review.

The moderating role of work-to-family spillover in the association between nurses' work values and work engagement: A cross-sectional study.

AIM: Although researchers have emphasized the importance of enhancing work engagement in nurses to ensure work-related well-being, the underlying mechanisms of the influencing factors of work engagement remain unclear. This study aimed to elucidate whether work-to-family spillover moderates the relationship between nurses' work values and work engagement. METHODS: In total, 2600 nurses from 52 hospitals in the Tohoku region of Japan were recruited, and 1587 nurses participated. The questionnaire included items on demographic characteristics, the Nurses' Work Values Scale, the Japanese version of the Work-life Balance Scale, and the Work Engagement Scale. Data were analyzed using hierarchical multiple regression. RESULTS: The interaction terms of negative work-to-family spillover with extrinsic work values and prestige work values were significantly associated with work engagement. The interaction terms of nurses' work values and positive work-to-family spillovers did not show a significant association. CONCLUSIONS: Nurses who emphasized extrinsic work values and those who did not emphasize prestige work values had the lowest work engagement in settings with high negative work-to-family spillover. To ensure nurses' work-related well-being and engagement, nursing managers could provide support for nurses in tackling work-related negative events, so that these do not carry over to family settings.

Development and psychometric evaluation of the nurses' Work Values Scale.

AIM: This study aimed to develop the nurses' Work Values Scale (WVS) to determine how important certain values are for nurses and to psychometrically test the scale. DESIGN: Instrument development and validation study. METHOD: A two-phase scale development process comprising item generation, scale improvement and psychometric property evaluation was used. In the first phase, scale items were identified. In the second phase, item and exploratory factor analyses were performed in Study 1, and confirmatory factor analysis, validity verification and reliability verification of the nurses' WVS were performed in Study 2. RESULTS: As a result of the analysis, a scale of 30 items with four subdomains was developed. In convergent validity and reliability verification, it was shown that the nurses' WVS has acceptable validity and reliability. NO PATIENT OR PUBLIC CONTRIBUTION: Patients or members of the public were not involved in this study.

Classification by Nurses' Work Values and Their Characteristics: Latent Profile Analysis of Nurses Working in Japanese Hospitals.

This study aimed to classify nurses with similar work values into subgroups by examining their intrinsic, extrinsic, social, and prestige work values. Additionally, we clarified the characteristics of the obtained subgroups using personal attributes, work engagement, and life satisfaction. Using a cross-sectional observational study design, we randomly sampled 52 hospitals in the Tohoku region of Japan and conducted a self-administered questionnaire survey with 2600 nurses. Latent profile analysis was performed to identify the number of subgroups. Of the 1627 collected questionnaires, 1587 were regarded as valid. The latent profile analysis revealed the following five subgroups with strong statistical significance: (1) self-oriented, (2) low, (3) medium-low, (4) medium-high, and (5) high types. The means of work engagement and life satisfaction gradually increased from the (2) low- to (5) high-type subgroups. There were significant differences among the subgroups in terms of marital status, child status, and job title. The (5) high-type subgroup had many nurses with job titles, high work engagement, and high life satisfaction. The (2) low-type subgroup included many nurses who were young, had few years of experience, were married, had children, and had low levels of work engagement and life satisfaction. Preregistration: This study was not registered.

A concept analysis of shame in the field of nursing.

AIM: The study aimed to conceptually define "shame" within the field of nursing. BACKGROUND: Many nurses sometimes experience and struggle with shame in their professional lives. It reduces their sense of self-worth and hampers emotional well-being and efficacy at work. DESIGN: The conceptual analysis was performed using Walker and Avant's method. DATA SOURCES: We searched using Academic Search Complete, CINAHL, PsycINFO, MEDLINE, and Psychology and Behavioral Sciences Collection databases for literature published between 1980 and 2020. REVIEW METHODS: We searched for keywords "shame," "nurse," and "nursing," with the condition that the keywords must be included in the title or abstract. RESULTS: Shame in the nursing field was defined as a negative emotion, an experience of self-blame and anger, an emotion accompanied by social anxiety, loneliness, and influenced by society and culture. Shame in the nursing field has three antecedents: negative evaluation, the involvement of others, and social and affiliated-group norms. Consequences of shame in nursing include decreased senses of self-esteem and self-efficacy, escape through defense mechanisms, depressive states, and alleviation of distress through reaffirmation of self-promotion and reflection leading to personal growth. CONCLUSIONS: We clarified the significance of self, others, others' evaluations, and differences in socio-cultural contexts while defining shame.

Psychometric properties of the Japanese version of the career competencies questionnaire for nurses: a cross-sectional study.

BACKGROUND: Career competencies, which are the knowledge, skills, and abilities essential for career development, have been shown to facilitate career success, fulfilling both work and life goals. In dynamically changing healthcare settings, nurses' career competencies are key for successfully navigating their careers and improving their nursing practice abilities. However, limited studies have examined career competencies in the nursing profession. In particular, no research has been conducted on career competencies among Japanese nurses, which remains a major challenge as voluntary effort is the main factor promoting career and professional development. Therefore, the purpose of this study was to evaluate the validity and reliability of the Japanese version of the Career Competencies Questionnaire (CCQ-J). METHODS: In this cross-sectional study conducted between June 2020 and August 2021, the English CCQ was translated into Japanese using back and forward translation. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted on separate samples. In the first step, item analysis and EFA were conducted with 276 nurses from one hospital. In the second step, CFA was conducted and concurrent validity and reliability were evaluated with 522 nurses from hospitals in the Tohoku region. RESULTS: Content validity was confirmed by the back-translation report, an expert panel, and a pilot test. The EFA showed that the CCQ-J consisted of a three-factor structure that explained 66.69% of the variance. The CFA revealed that all the fit indices were acceptable [chi-square value (CMIN) = 432.26, degree of freedom (df) = 153, chi-square fit statistic/degree of freedom (CMIN/df) = 2.83, goodness-of-fit index (GFI) = 0.93, adjusted goodness of fit index (AGFI) = 0.89, comparative fix index (CFI) = 0.96, and root mean square error of approximation (RMSEA) = 0.06]. Cronbach's α for the 21-item CCQ-J and its subscales ranged from 0.85 to 0.95. Concurrent validity was demonstrated via the positive correlation between work engagement, life satisfaction, and the CCQ-J. CONCLUSIONS: The CCQ-J is a valid and reliable instrument to assess the career competencies of Japanese nurses. We hope that the findings presented in this study will contribute to a better understanding of nurses' career competencies and their successful career and professional development in the future.

Impact of Intrinsic and Extrinsic Motivation on Work Engagement: A Cross-Sectional Study of Nurses Working in Long-Term Care Facilities.

Nurses' work motivation impacts their job satisfaction and work engagement, affecting their quality of care. Work motivation, a personal resource, can be categorized into intrinsic and extrinsic motivation, each of which may function differently in the job demands-resources (JD-R) model. To study the effect of nurses' intrinsic and extrinsic work motivation on work engagement in long-term care (LTC) facilities, we randomly selected 1200 facilities from 6055 LTC facilities in eastern Japan. Two nurses from each facility completed a self-report questionnaire-newly developed for this study for evaluating intrinsic and extrinsic work motivation-to assess their work engagement, job satisfaction, and work motivation. Multiple regression analysis of 561 valid questionnaires investigated the relationship between work motivation and work engagement, indicating that intrinsic work motivation, job satisfaction, and age had a significant positive effect on work engagement, while extrinsic work motivation had no significant effect. However, half the nurses chose to work because of extrinsic work motivation, explaining the high turnover rate of nursing staff in LTC facilities. Findings indicate the importance of measures to foster nurses' intrinsic motivation to improve work engagement. Further research should investigate how to improve the intrinsic motivation of nurses working in LTC facilities.

Nurses Working in Nursing Homes: A Mediation Model for Work Engagement Based on Job Demands-Resources Theory.

This study examined the impact that the attractiveness of working in nursing homes and autonomous clinical judgment have on affective occupational commitment, and whether work engagement mediates these relationships. This analysis was based on the job demands-resources theory. The study setting was 1200 nursing homes (including long-term care welfare facilities and long-term care health facilities) in eastern Japan. An anonymous, self-report questionnaire survey was administered to two nurses from each facility, resulting in a prospective sample of 2400 participants. Overall, 552 questionnaires were analyzed, in which structural equation modeling and mediation analysis using the bootstrap method were performed. The results showed that the attractiveness of working in nursing homes does not directly affect affective occupational commitment; work engagement fully mediates the impact of attractiveness of working in nursing homes on affective occupational commitment. Additionally, autonomous clinical judgment showed a direct impact on both work engagement and affective occupational commitment, indicating that work engagement partially mediates the impact on affective occupational commitment. To increase the affective occupational commitment of nurses working in nursing homes, managers should help nurses recognize the attractiveness of working in nursing homes, and then provide appropriate support to help such nurses work in a motivated manner.

Japanese nurse practitioners' legal liability ambiguity regarding their medical practice: a qualitative study.

BACKGROUND: Nurse practitioners' role is always expanding. The Japanese Nurse Practitioner (JNP) system was initiated in 2015 to shift some aspects of doctors' work to various other healthcare professionals, including nurses. JNPs' fulfillment of their roles was shown to have a certain degree of efficacy and provide positive outcomes for patients (e.g., shortening hospitalization period). Nurse practitioners are considered legally liable for their medical practices because they are performed on doctors' behalf; however, in real life, there is ambiguity regarding such practice. It is necessary to clarify nurse practitioners' legal liability in order to ensure the safety of their medical practice and protect them in medical procedures performed on physicians' behalf. This study aimed to clarify how JNPs understand their own legal liability in medical practice. METHODS: A qualitative, inductive research design was adopted to record participants' opinions. The survey was conducted from October 2017 to February 2018. Participants were nurses working as JNPs at general hospitals in eastern Japan. We recruited participants via snowball sampling. RESULTS: With regard to JNPs' legal liability in their medical practice, three themes understanding were observed: "determining whether the JNP has the ability to perform the assigned medical procedure," "exercising caution when performing medical procedures on a doctor's behalf" and "an urge to follow up with appropriate medical practice until the end of care." CONCLUSIONS: We demonstrated that JNPs recognized their own legal liability in medical practice. They had to protect themselves because their legal position was ambiguous. Furthermore, JNPs accepted that diagnosis and drug prescription could be performed on behalf of doctors if trusting relationships had been previously established.

Interaction of scaffolding adaptor protein Gab1 with tyrosine phosphatase SHP2 negatively regulates IGF-I-dependent myogenic differentiation via the ERK1/2 signaling pathway.

Grb2-associated binder 1 (Gab1) coordinates various receptor tyrosine kinase signaling pathways. Although skeletal muscle differentiation is regulated by some growth factors, it remains elusive whether Gab1 coordinates myogenic signals. Here, we examined the molecular mechanism of insulin-like growth factor-I (IGF-I)-mediated myogenic differentiation, focusing on Gab1 and its downstream signaling. Gab1 underwent tyrosine phosphorylation and subsequent complex formation with protein-tyrosine phosphatase SHP2 upon IGF-I stimulation in C2C12 myoblasts. On the other hand, Gab1 constitutively associated with phosphatidylinositol 3-kinase regulatory subunit p85. To delineate the role of Gab1 in IGF-I-dependent signaling, we examined the effect of adenovirus-mediated forced expression of wild-type Gab1 (Gab1(WT)), mutated Gab1 that is unable to bind SHP2 (Gab1(DeltaSHP2)), or mutated Gab1 that is unable to bind p85 (Gab1(Deltap85)), on the differentiation of C2C12 myoblasts. IGF-I-induced myogenic differentiation was enhanced in myoblasts overexpressing Gab1(DeltaSHP2), but inhibited in those overexpressing either Gab1(WT) or Gab1(Deltap85). Conversely, IGF-I-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation was significantly repressed in myoblasts overexpressing Gab1(DeltaSHP2) but enhanced in those overexpressing either Gab1(WT) or Gab1(Deltap85). Furthermore, small interference RNA-mediated Gab1 knockdown enhanced myogenic differentiation. Overexpression of catalytic-inactive SHP2 modulated IGF-I-induced myogenic differentiation and ERK1/2 activation similarly to that of Gab1(DeltaSHP2), suggesting that Gab1-SHP2 complex inhibits IGF-I-dependent myogenesis through ERK1/2. Consistently, the blockade of ERK1/2 pathway reversed the inhibitory effect of Gab1(WT) overexpression on myogenic differentiation, and constitutive activation of the ERK1/2 pathway suppressed the enhanced myogenic differentiation by overexpression of Gab1(DeltaSHP2). Collectively, these data suggest that the Gab1-SHP2-ERK1/2 signaling pathway comprises an inhibitory axis for IGF-I-dependent myogenic differentiation.

Carbacyclin induces carnitine palmitoyltransferase-1 in cardiomyocytes via peroxisome proliferator-activated receptor (PPAR) delta independent of the IP receptor signaling pathway.

Prostacyclin (PGI2) and its analogues exert cardioprotective effects via the rhodopsin type membrane PGI2 receptor, IP. Peroxisome proliferator-activated receptor (PPAR) delta is a nuclear receptor abundantly expressed in cardiomyocytes and plays a pivotal role in maintaining constitutive mitochondrial fatty acid beta-oxidation (FAO). Recently, a novel signaling pathway of PGI2 via PPARdelta has been demonstrated in non-cardiac tissues. We therefore examined whether carbacyclin (cPGI2), a PGI2 analogue, up-regulates transcriptional expression of carnitine palmitoyltransferase-1 (CPT-1), the rate-limiting enzyme in mitochondrial FAO, via PPARdelta in cardiomyocytes. Intraperitoneal injection of cPGI2 increased CPT-1 mRNA expression in murine hearts. Transcriptional activity was evaluated by PPAR responsive element (PPRE)-luciferase reporter gene assay in cultured neonatal rat cardiomyocytes. CPT-1 mRNA expression and PPRE promoter activity were significantly increased by cPGI2 in a concentration-dependent manner, where PPRE has been mapped to the promoter region of the CPT-1 gene. Moreover, the elevation of CPT-1 mRNA expression and PPRE promoter activity by cPGI2 was not abolished by H-89, a potent protein kinase A inhibitor, but was significantly inhibited in cardiomyocytes over-expressing a dominant-negative type of PPARdelta. Furthermore, electrophoretic mobility shift assays demonstrated that binding of PPARdelta to PPRE in the CPT-1 gene promoter is enhanced in response to cPGI2 stimulation. In addition, down-regulation of CPT-1 mRNA expression in cardiomyocytes subjected to hypoxia was attenuated by cPGI2. These results indicate that cPGI2 induces CPT-1 mRNA expression through PPARdelta, independent of the IP receptor signaling pathway, suggesting a possibility that cPGI2 modulates cardiac energy metabolism by activating FAO via PPARdelta.

Effect of bosentan on plasma endothelin-1 concentration in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease with high mortality. An orally active dual endothelin (ET) receptor antagonist, bosentan, has been reported to improve exercise capacity and survival in patients with PAH. Plasma ET-1 concentration is known to be increased in PAH patients; however, the effect of bosentan on ET-1 concentration has not yet been investigated. METHODS AND RESULTS: The concentration of ET-1 after bosentan administration was examined in 7 PAH patients, including 2 primary and 5 secondary cases. They were clinically assessed by pulmonary artery pressure (PAP), 6-min walk distance (6MWD) and plasma brain natriuretic peptide (BNP) concentration. Baseline ET-1 concentration was significantly higher in patients with PAH than in normal individuals (2.19+/-0.71 pg/ml vs 1.45+/-0.10 pg/ml, p<0.05) and was significantly correlated with 6MWD and BNP. A single dose of 62.5 mg bosentan in patients with PAH significantly increased plasma ET-1 concentration to 2.04 times the basal concentration (p<0.01) with a peak at 8.1 h. The peak to base ratio of ET-1 after bosentan administration correlated negatively with severity of PAH as assessed by PAP. CONCLUSIONS: The present study is the first study to show that bosentan administration increases plasma ET-1 in patients with PAH. The response of plasma ET-1 to bosentan administration might be useful for determining the severity of PAH.

Haplotype of thrombomodulin gene associated with plasma thrombomodulin level and deep vein thrombosis in the Japanese population.

INTRODUCTION: Thrombomodulin (TM) is an essential cofactor in protein C activation by thrombin. Here, we evaluated the contribution of genetic variations in the TM gene to soluble TM (sTM) level and deep vein thrombosis (DVT) in Japanese. PATIENTS AND METHODS: We sequenced the TM putative promoter, exon, and 3'-untranslated region in DVT patients (n=118). Among 17 genetic variations we identified, two missense mutations (R385K, D468Y) and three common single nucleotide polymorphisms (-202G>A, 2487A>T, 2729A>C) were genotyped in a general population of 2247 subjects (1032 men and 1215 women) whose sTM levels were measured. We then compared the frequency of these mutations in DVT patients with that in the age, body mass index-adjusted population-based controls. RESULTS: We identified one neutral mutation (H381) and three missense mutations (R385K; n=2, A455V; n=53 heterozygous, n=14 homozygous, D468Y; n=2) of TM in the DVT patients. Age-adjusted mean values of sTM were lower in C-allele carriers of 2729A>C than in noncarriers in the Japanese general population (women: 16.7+/-0.3 U/ml vs. 17.9+/-0.2 U/ml, p<0.01, men: 19.4+/-0.3 U/ml vs. 20.4+/-0.3 U/ml, p=0.03). Additionally, the CC genotype of this mutation was more common in the male DVT patients than in the male individuals of the general population (odds ratio=2.76, 95% confidence interval=1.14-6.67; p=0.02). This mutation was in linkage disequilibrium (r-square>0.9) with A455V mutation. CONCLUSIONS: TM mutations, especially those with a haplotype consisting of 2729A>C and A455V missense mutation, affect sTM levels, and may be associated with DVT in Japanese.

Sildenafil as adjunct therapy to high-dose epoprostenol in a patient with pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease is refractory to medical treatment and is generally associated with a poor prognosis. Treatment with vasodilators, such as prostacyclin, of patients with PVOD is controversial because of concerns regarding hemodynamic deterioration. Although a preferential pulmonary vasodilatory effect of a specific phosphodiesterase-5 inhibitor, sildenafil, has recently been reported in patients with primary pulmonary hypertension, little information is available regarding the effect of sildenafil on patients with pulmonary veno-occlusive disease. In the present case, remarkable improvement of hemodynamics and of clinical course was produced by adjunctive use of oral sildenafil in association with intravenous high-dose epoprostenol. These findings suggest that sildenafil may be a therapeutic option in the medical treatment of pulmonary veno-occlusive disease.

Cross-talk between bone morphogenetic protein 2 and leukemia inhibitory factor through ERK 1/2 and Smad1 in protection against doxorubicin-induced injury of cardiomyocytes.

The survival of cardiomyocytes is regulated by growth factors and cytokines such as bone morphogenetic protein (BMP) 2 and leukemia inhibitory factor (LIF). BMP2 and LIF induce distinct signal transduction pathways that each activate a different transcription factor [Smad1 and signal transducing activating transcriptional factor (Stat) 3, respectively] and common signal pathway [mitogen-activated protein kinase (MAPK)]. We previously demonstrated that BMP2 and LIF protect cardiomyocytes via Smad1 and STAT3 signaling pathways, respectively. On the other hand, these signals are known to act in synergy via synergistic integration of signaling pathways. Here, we examined interaction between BMP2 and LIF in primary cultured neonatal rat cardiomyocytes. LIF sustained phosphorylation/activation of Smad1 by BMP2. The role of extracellular signal-regulated kinase (ERK) 1/2 cascade activated by LIF was highlighted by the use of a MAPK/ERK kinase (MEK) 1/2 inhibitor, U0126, or overexpression of dominant-negative form of MEK1 that abolished sustained phosphorylation of Smad1 and cell survival effect induced by co-stimulation of LIF with BMP2, while BMP2 alone did not activate ERK1/2. Conversely, overexpression of the constitutive-active form of MEK1 increased BMP2-induced phosphoration of Smad1 without additional LIF. Moreover, BMP2 and LIF synergistically induced bcl-xL mRNA in doxorubicin (DOX)-injured cardiomyocytes. These findings suggest that the ERK1/2 pathway downstream of LIF is involved in sustained phosphorylation/activation of Smad1 by BMP2 and provide a possible mechanism for cooperation between intracellular signals activated by LIF and BMP2 in protection against DOX-induced injury of cardiomyocytes.

AMP-activated protein kinase protects cardiomyocytes against hypoxic injury through attenuation of endoplasmic reticulum stress.

Oxygen deprivation leads to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), causing ER stress. Under conditions of ER stress, inhibition of protein synthesis and up-regulation of ER chaperone expression reduce the misfolded proteins in the ER. AMP-activated protein kinase (AMPK) is a key regulatory enzyme involved in energy homeostasis during hypoxia. It has been shown that AMPK activation is associated with inhibition of protein synthesis via phosphorylation of elongation factor 2 (eEF2) in cardiomyocytes. We therefore examined whether AMPK attenuates hypoxia-induced ER stress in neonatal rat cardiomyocytes. We found that hypoxia induced ER stress, as assessed by the expression of CHOP and BiP and cleavage of caspase 12. Knockdown of CHOP or caspase 12 through small interfering RNA (siRNA) resulted in decreased expression of cleaved poly(ADP-ribose) polymerase following exposure to hypoxia. We also found that hypoxia-induced CHOP expression and cleavage of caspase 12 were significantly inhibited by pretreatment with 5-aminoimidazole-4-carboxyamide-1-beta-D-ribofuranoside (AICAR), a pharmacological activator of AMPK. In parallel, adenovirus expressing dominant-negative AMPK significantly attenuated the cardioprotective effects of AICAR. Knockdown of eEF2 phosphorylation using eEF2 kinase siRNA abolished these cardioprotective effects of AICAR. Taken together, these findings demonstrate that activation of AMPK contributes to protection of the heart against hypoxic injury through attenuation of ER stress and that attenuation of protein synthesis via eEF2 inactivation may be the mechanism of cardioprotection by AMPK.

Smad1 protects cardiomyocytes from ischemia-reperfusion injury.

BACKGROUND: We previously reported that bone morphogenetic protein 2 (BMP2) protected against apoptosis of serum-deprived cardiomyocytes via induction of Bcl-xL through the Smad1 pathway. To investigate whether Smad1 signaling promotes cell survival in the adult heart, we subjected transgenic mice with cardiac-specific overexpression of smad1 gene (Smad1TG) to ischemia-reperfusion (I/R) injury. METHODS AND RESULTS: The effects of BMP2 or adenovirus-mediated transfection of smad1 on cardiomyocyte survival in hypoxia-reoxygenation were examined using rat neonatal cardiomyocytes. BMP2 and Smad1 each significantly promoted survival and diminished apoptotic death of cardiomyocytes during hypoxia-reoxygenation. Interestingly, Smad1 was found to be activated during I/R in normal mouse heart. To examine physiological and pathological roles of Smad1 in I/R, we generated Smad1TG using the alpha-myosin heavy chain gene promoter. Phosphorylation of Smad1 was found in all smad1 transgene-positive mouse hearts. To examine whether Smad1 prevents injury of cardiomyocytes in vivo, we subjected Smad1TG and age-matched wild-type mice (WT) to I/R injury induced by 1 hour of ligation of the left coronary artery and 1 hour of reperfusion. TUNEL and DNA ladder analyses showed that Smad1TG had significantly smaller myocardial infarctions and fewer apoptotic deaths of cardiomyocytes than did WT. Interestingly, increased expression of Bcl-xL and beta-catenin was more remarkable whereas caspase3 was less activated in Smad1TG heart than in that of WT. CONCLUSIONS: These findings suggest that the Smad1 signaling pathway plays a role in cardioprotection against I/R injury.

Circulating interleukin-6 family cytokines and their receptors in patients with congestive heart failure.

gp130 is a common signal-transducing receptor subunit for the interleukin (IL)-6 cytokine family. Studies in genetically engineered animal models have demonstrated a critical role for the gp130-dependent cardiomyocyte survival pathway in the transition to heart failure. In the present study, we examined plasma levels of the IL-6 family of cytokines and the soluble form of their receptors in patients with congestive heart failure (CHF). Circulating levels of the IL-6 family of cytokines, soluble IL-6 receptor (sIL-6R), and soluble gp130 (sgp130) were examined in 48 patients with various degrees of CHF, including dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), and valvular cardiomyopathy (VCM). Circulating levels of IL-6, leukemia inhibitory factor (LIF), and sgp130 significantly increased in association with the severity of CHF. No significant difference was observed in the circulating levels of sIL-6R and IL-11 among these patients. Interestingly, DCM patients showed higher circulating sgp130 levels than patients with ICM or VCM. Our findings suggest that gp130 expression in the heart is likely to be dynamic, and that the IL-6 family of cytokines and their common receptor gp130 participates in the pathogenesis of CHF, especially in DCM.

Novel insertional mutation in the bone morphogenetic protein receptor type II associated with sporadic primary pulmonary hypertension.

Primary pulmonary hypertension (PPH), which results from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene (BMPR2), a component of the transforming growth factor- beta (TGF-beta) family, which plays a key role in cell growth, have recently been identified as causing familial and sporadic PPH. The first case of BMPR2 mutation found in Japan is reported here in a 19-year-old woman with a clinical diagnosis of PPH and no identifiable family history of pulmonary hypertension. Direct sequencing of the entire coding region and intron/exon boundaries of BMPR2 revealed a frameshift mutation predicted to alter the cell signaling response to specific ligands. A molecular classification of PPH, based upon the presence or absence of BMPR2 mutations, might have important implications for patient management and screening of relatives.

Solitary right ventricle metastasis by renal cell carcinoma.

A 57-year-old man with a history of renal cell carcinoma presented with presyncope. He underwent nephrectomy years earlier followed by HLA-matched allogeneic peripheral-blood stem-cell transplantation. Echocardiographic investigation revealed a solitary right ventricle mass without contiguous vena caval or right atrial involvement. The mass was pathologically confirmed to be metastatic carcinoma in the right ventricular cavity. This case highlights the need to consider an underlying neoplastic syndrome in patients presenting isolated right ventricle mass by echocardiography.