Cardiopulmonary Exercise Testing as a Tool for Diagnosing Pulmonary Hypertension in Patients with Dilated Cardiomyopathy.

Background: Recently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly threatening result of left-sided heart disease. However, there have been few investigations of the impact of cardiopulmonary exercise testing (CPX) variables on PH in dilated cardiomyopathy (DCM). We evaluated the usefulness of crucial CPX variables for detecting elevated pulmonary arterial pressure (PAP) in patients with DCM.

Lifetime of Ionic Vacancy Created in Redox Electrode Reaction Measured by Cyclotron MHD Electrode.

The lifetimes of ionic vacancies created in ferricyanide-ferrocyanide redox reaction have been first measured by means of cyclotron magnetohydrodynamic electrode, which is composed of coaxial cylinders partly exposed as electrodes and placed vertically in an electrolytic solution under a vertical magnetic field, so that induced Lorentz force makes ionic vacancies circulate together with the solution along the circumferences. At low magnetic fields, due to low velocities, ionic vacancies once created become extinct on the way of returning, whereas at high magnetic fields, in enhanced velocities, they can come back to their initial birthplaces. Detecting the difference between these two states, we can measure the lifetime of ionic vacancy.

Quantitative Proteomics-Based Reconstruction and Identification of Metabolic Pathways and Membrane Transport Proteins Related to Sugar Accumulation in Developing Fruits of Pear (Pyrus communis).

During their 6 month development, pear (Pyrus communis) fruits undergo drastic changes in their morphology and their chemical composition. To gain a better understanding of the metabolic pathways and transport processes active during fruit development, we performed a time-course analysis using mass spectrometry (MS)-based protein identification and quantification of fruit flesh tissues. After pre-fractionation of the samples, 2,841 proteins were identified.

Intratumoral heterogeneity of steroidogenesis in aldosterone-producing adenoma revealed by intensive double- and triple-immunostaining for CYP11B2/B1 and CYP17.

Introduction: Cytochrome P450 11B2 (CYP11B2) plays a pivotal role in aldosterone synthesis, while cytochrome P450 11B1 (CYP11B1) and cytochrome P450 17A1 (CYP17) are involved in cortisol synthesis in normal human adrenal glands. However, their detailed distribution in aldosterone-producing adenoma (APA) remains incompletely settled.

Materials And Methods: We examined the status of CYP11B1/CYP11B2 and CYP11B2/CYP17A1 expressions in 27 APA (double staining) cases and 21 APA (triple staining) cases by using immunofluorescence staining and semi-quantitative evaluation.

Clinical Management and Outcomes of Adrenal Hemorrhage Following Adrenal Vein Sampling in Primary Aldosteronism.

Aldosterone-producing adenoma and bilateral adrenal hyperplasia account for >90% of all primary aldosteronism cases. Distinguishing between bilateral and unilateral disease is of fundamental importance because it allows targeted therapy. Adrenal vein sampling (AVS) is the only reliable means to preoperatively differentiate between unilateral and bilateral subtypes.

A case of bilateral aldosterone-producing adenomas differentiated by segmental adrenal venous sampling for bilateral adrenal sparing surgery.

Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules.

Impact of abdominal aortic calcification on long-term cardiovascular outcomes in patients with chronic kidney disease.

Background: The presence of abdominal aortic calcification (AAC) can predict cardiovascular (CV) outcomes in hemodialysis patients. However, little is known about the predictive value of AAC for CV outcomes in chronic kidney disease (CKD) patients without hemodialysis. The aim of this study was to investigate the prevalence and the predictive value of AAC in asymptomatic CKD patients.

Implications of an inverted duplication in the wheat KN1-type homeobox gene Wknox1 for theorigin of Persian wheat.

Introgression between related species with different ploidy levels has played important roles in wheat subspecies differentiation. Persian wheat, a cultivated tetraploid wheat subspecies (Triticum turgidum subsp. carthlicum), is postulated to have evolved through interploidy hybridization between tetraploid and hexaploid wheats.

Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease.

Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and reduced aggregation using a Caenorhabditis elegans model of mutant ataxin 3-induced neurotoxicity.

Cost-Effectiveness Analysis of the Diagnosis and Treatment of Primary Aldosteronism in Japan.

Approximately 10% of cases of hypertension in Japan are caused by primary aldosteronism (PA), amounting to about 4 million patients in total. Primary aldosteronism due to unilateral aldosterone hypersecretion is potentially curable by adrenalectomy. The clinical benefits of identifying and treating PA have been reported internationally, but its cost-effectiveness is unclear.

Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation.

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states. Healthy metazoan cells effectively eliminate intracellular protein aggregates, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro.

Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments.

The cellular proteostasis network integrates the protein folding and clearance machineries in multiple sub-cellular compartments of the eukaryotic cell. The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. A distinctive feature of the ER is its tightly controlled redox homeostasis necessary for the formation of inter- and intra-molecular disulphide bonds.

Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction.

The heat shock response (HSR) is essential for proteostasis and cellular health. In metazoans, aging is associated with a decline in quality control, thus increasing the risk for protein conformational disease. Here, we show that in C.

Childhood-Onset Anti-Ku Antibody-Positive Generalized Morphea with Polymyositis: A Japanese Case Study.

We report a 16-year-old Japanese girl with anti-Ku antibody-positive generalized morphea and polymyositis who, at the age of 7 years, developed multiple brownish plaques on her left forearm that gradually extended to her upper arm, back, and left thigh, which a skin biopsy revealed as morphea. Laboratory testing was positive for antinuclear antibody and a high serum creatine kinase level. Although there were no clinical signs of muscular involvement, magnetic resonance imaging revealed findings consistent with myositis.

Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism?

Objective And Design: Adrenal venous sampling (AVS) is critical to determine the subtype of primary aldosteronism (PA). Central AVS (C-AVS)--that is, the collection of effluents from bilateral adrenal central veins (CV)--sometimes does not allow differentiation between bilateral aldosterone-producing adenomas (APA) and idiopathic hyperaldosteronism. To establish the best treatment course, we have developed segmental AVS (S-AVS); that is, we collect effluents from the tributaries of CV to determine the intra-adrenal sources of aldosterone overproduction.

Tertiary Amine Pyrazolones and Their Salts as Inhibitors of Mutant Superoxide Dismutase 1-Dependent Protein Aggregation for the Treatment of Amyotrophic Lateral Sclerosis.

Pyrazolone derivatives have previously been found to be inhibitors of Cu/Zn superoxide dismutase 1 (SOD1)-dependent protein aggregation, which extended survival of an amyotrophic lateral sclerosis (ALS) mouse model. On the basis of ADME analysis, we describe herein a new series of tertiary amine-containing pyrazolones and their structure-activity relationships. Further conversion to the conjugate salts greatly improved their solubility.

Relationship between abdominal aortic and coronary artery calcification as detected by computed tomography in chronic kidney disease patients.

The purpose of this study was to investigate the relationship between abdominal aortic calcification (AAC) and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients. We evaluated 126 asymptomatic CKD patients (mean estimated glomerular filtration rate: 36.1 ± 14.

Intra-adrenal Aldosterone Secretion: Segmental Adrenal Venous Sampling for Localization.

Purpose: To use segmental adrenal venous sampling (AVS) (S-AVS) of effluent tributaries (a version of AVS that, in addition to helping identify aldosterone hypersecretion, also enables the evaluation of intra-adrenal hormone distribution) to detect and localize intra-adrenal aldosterone secretion.

Materials And Methods: The institutional review board approved this study, and all patients provided informed consent. S-AVS was performed in 65 patients with primary aldosteronism (34 men; mean age, 50.

Dynamic multidetector CT and non-contrast-enhanced MR for right adrenal vein imaging: comparison with catheter venography in adrenal venous sampling.

Objectives: To evaluate visualization of the right adrenal vein (RAV) with multidetector CT and non-contrast-enhanced MR imaging in patients with primary aldosteronism.

Methods: A total of 125 patients (67 men) scheduled for adrenal venous sampling (AVS) were included. Dynamic 64-detector-row CT and balanced steady-state free precession-based non-contrast-enhanced 3-T MR imaging were performed.

Adrenocortical carcinoma: review of the pathologic features, production of adrenal steroids, and molecular pathogenesis.

Adrenocortical carcinoma (ACC) is a malignant neoplasm often associated with an aggressive biological behavior. The histologic differentiation between ACC and adrenocortical adenoma (ACA) is largely determined by employing the Weiss criteria, although this classification may not apply to all the cases. Additionally, various genomic features of ACC could be an auxiliary mode to establish the diagnosis of ACC.

The Chemical Biology of Molecular Chaperones--Implications for Modulation of Proteostasis.

Protein homeostasis (proteostasis) is inextricably tied to cellular health and organismal lifespan. Aging, exposure to physiological and environmental stress, and expression of mutant and metastable proteins can cause an imbalance in the protein-folding landscape, which results in the formation of non-native protein aggregates that challenge the capacity of the proteostasis network (PN), increasing the risk for diseases associated with misfolding, aggregation, and aberrant regulation of cell stress responses. Molecular chaperones have central roles in each of the arms of the PN (protein synthesis, folding, disaggregation, and degradation), leading to the proposal that modulation of chaperone function could have therapeutic benefits for the large and growing family of diseases of protein conformation including neurodegeneration, metabolic diseases, and cancer.

Widespread Proteome Remodeling and Aggregation in Aging C. elegans.

Aging has been associated with a progressive decline of proteostasis, but how this process affects proteome composition remains largely unexplored. Here, we profiled more than 5,000 proteins along the lifespan of the nematode C. elegans.

A petal-specific InMYB1 promoter from Japanese morning glory: a useful tool for molecular breeding of floricultural crops.

Production of novel transgenic floricultural crops with altered petal properties requires transgenes that confer a useful trait and petal-specific promoters. Several promoters have been shown to control transgenes in petals. However, all suffer from inherent drawbacks such as low petal specificity and restricted activity during the flowering stage.