Red Blood Cell Dysfunction Induced by High-Fat Diet: Potential Implications for Obesity-Related Atherosclerosis.

Background: High-fat diet (HFD) promotes endothelial dysfunction and proinflammatory monocyte activation, which contribute to atherosclerosis in obesity. We investigated whether HFD also induces the dysfunction of red blood cells (RBCs), which serve as a reservoir for chemokines via binding to Duffy antigen receptor for chemokines (DARC).

Methods And Results: A 60% HFD for 12 weeks, which produced only minor changes in lipid profile in C57/BL6 mice, markedly augmented the levels of monocyte chemoattractant protein-1 bound to RBCs, which in turn stimulated macrophage migration through an endothelial monolayer.

Placental lactogen is expressed but is not translated into protein in breast cancer.

Introduction: Several studies reported that the pregnancy-specific hormone placental lactogen (hPL) is expressed at both mRNA and protein levels in breast cancer. The overall objective was to establish hPL, the product of the CSH1 and CSH2 genes, as a biomarker for breast cancer.

Methods: CSH expression was determined at the mRNA level in breast cancer cell lines (BCC) and primary carcinomas by real-time and conventional PCR and the products verified as CSH1 by sequencing.

HDAC9 knockout mice are protected from adipose tissue dysfunction and systemic metabolic disease during high-fat feeding.

During chronic caloric excess, adipose tissue expands primarily by enlargement of individual adipocytes, which become stressed with lipid overloading, thereby contributing to obesity-related disease. Although adipose tissue contains numerous preadipocytes, differentiation into functionally competent adipocytes is insufficient to accommodate the chronic caloric excess and prevent adipocyte overloading. We report for the first time that a chronic high-fat diet (HFD) impairs adipogenic differentiation, leading to accumulation of inefficiently differentiated adipocytes with blunted expression of adipogenic differentiation-specific genes.

Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis.

Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs.

Heart rate decrease during crizotinib treatment and potential correlation to clinical response.

Background: Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC). Sinus bradycardia (SB) is a side effect listed in its package insert. We investigated the frequency and timing of SB, patient characteristics associated with SB during crizotinib treatment, and potential correlation between heart rate (HR) changes and clinical response to crizotinib.

Nitric oxide bioavailability and adiponectin production in chronic systolic heart failure: relation to severity of cardiac dysfunction.

Adiponectin is an anti-inflammatory, antiatherogenic adipokine elevated in heart failure (HF) that may protect against endothelial dysfunction by influencing underlying nitric oxide bioavailability. In this study, we examine the relationship between plasma adiponectin levels and measures of nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association class I to IV), we measured plasma levels of adiponectin, asymmetric dimethylarginine (ADMA), and global arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance.

Progressive rise in red cell distribution width is associated with disease progression in ambulatory patients with chronic heart failure.

Background: Single red cell distribution width (RDW) assessment is a consistent prognostic marker of poor outcomes in heart failure as well as in other patient cohorts. The objective of this study was to determine the prognostic value of sequential RDW assessment in ambulatory patients with chronic heart failure.

Methods And Results: We reviewed 6,159 consecutive ambulatory patients with chronic heart failure between 2001-2006 and examined changes in RDW values from baseline to 1-year follow-up.

Right atrial volume index in chronic systolic heart failure and prognosis.

Objectives: The aim of this study was to determine the relationship between right atrial volume index (RAVI) and right ventricular (RV) systolic and diastolic function, as well as long-term prognosis in patients with chronic systolic heart failure (HF).

Background: RV dysfunction is associated with poor prognosis in patients with HF, although echocardiographic assessment of RV systolic and diastolic dysfunction is challenging. The ability to visualize the RA allows a quantitative, highly reproducible assessment of the RA volume that can be indexed to body surface area.

Measuring impedance in congestive heart failure: current options and clinical applications.

Measurement of impedance is becoming increasingly available in the clinical setting as a tool for assessing hemodynamics and volume status in patients with heart failure. The 2 major categories of impedance assessment are the band electrode method and the implanted device lead method. The exact sources of the impedance signal are complex and can be influenced by physiologic effects such as blood volume, fluid, and positioning.

Relation of mechanical dyssynchrony with underlying cardiac structure and performance in chronic systolic heart failure: implications on clinical response to cardiac resynchronization.

Aims: The aim of this study is to describe the relationship between ventricular mechanical dyssynchrony (VMD) and echocardiographic indices of cardiac remodelling.

Methods And Results: We evaluated 219 ambulatory patients with chronic systolic heart failure [left ventricular ejection fraction (LVEF) 40 ms and/or inter-VMD > 38 ms).

Differential effects of arginine methylation on diastolic dysfunction and disease progression in patients with chronic systolic heart failure.

Aims: To investigate the association of arginine methylation with myocardial function and prognosis in chronic systolic heart failure patients.

Methods And Results: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), as well as N-mono-methylarginine (MMA) and methyl-lysine, were simultaneously measured by tandem mass spectrometry in 132 patients with chronic systolic heart failure with echocardiographic evaluation and follow-up. Increasing ADMA and SDMA levels were associated with elevated natriuretic peptide levels (both P < 0.

Impact of myocardial function on cystatin C measurements in chronic systolic heart failure.

Background: The influence of myocardial function on plasma levels of cystatin C (CysC), a sensitive marker of renal function, in chronic systolic heart failure (HF) has not been well established.

Methods: We prospectively identified 139 subjects with stable, chronic HF (left ventricular ejection fraction < or = 35%) and measured plasma levels of CysC. We prospectively tracked patients' long-term adverse clinical outcomes (death, cardiac transplantation, and HF hospitalizations).

Evaluation and long-term prognosis of new-onset, transient, and persistent anemia in ambulatory patients with chronic heart failure.

Objectives: This study sought to determine the characteristics and long-term prognosis of anemia in ambulatory patients with chronic heart failure.

Background: Anemia is prevalent in heart failure, and may portend poor outcomes.

Methods: We reviewed 6,159 consecutive outpatients with chronic stable heart failure at baseline, short-term (3-month) follow-up, and long-term (6-month) follow-up between 2001 and 2006.

Prognostic value and echocardiographic determinants of plasma myeloperoxidase levels in chronic heart failure.

Objectives: The purpose of this study was to explore the relationship between myeloperoxidase (MPO) and cardiac structure, performance, and prognosis.

Background: Myeloperoxidase is an inflammatory marker that is elevated in patients with heart failure (HF) and cardiac dysfunction, with mechanistic links to plaque vulnerability and left ventricular (LV) remodeling.

Methods: We evaluated plasma MPO levels (CardioMPO, PrognostiX, Inc.

Plasma myeloperoxidase levels in patients with chronic heart failure.

Increased oxidative stress and endothelial dysfunction are commonly observed in patients with chronic heart failure (HF). The relation between myeloperoxidase (MPO), an inflammatory marker with mechanistic links to plaque vulnerability and abnormal ventricular remodeling, and degrees of severity in chronic HF has not been reported. Plasma MPO levels were measured in 105 normal controls (no history of HF or left ventricular dysfunction) and 102 patients with chronic systolic HF (left ventricular ejection fraction <50%), and the relations among plasma MPO levels, plasma B-type natriuretic peptide levels, and the left ventricular ejection fraction were examined.

Nonreciprocity of counterpropagating signals in a monolithically integrated Sagnac interferometer.

We demonstrate nonlinearly induced nonreciprocity of counterpropagating waves in a monolithically integrated Sagnac interferometer that employs a semiconductor optical amplifier as the nonlinear element. We show that the dependence of the linewidth enhancement factor on charge injection can influence the third-order nonlinearity in the semiconductor gain medium to a surprisingly large degree. This effect is utilized to control the phases of the counterpropagating signals in the interferometer.

A novel fast optical switch based on two cascaded Terahertz Optical Asymmetric Demultiplexers (TOAD).

A novel optical switch based on cascading two terahertz optical asymmetric demultiplexers (TOAD) is presented. By utilizing the sharp edge of the asymmetric TOAD switching window profile, two TOAD switching windows are overlapped to produce a narrower aggregate switching window, not limited by the pulse propagation time in the SOA of the TOAD. Simulations of the cascaded TOAD switching window show relatively constant window amplitude for different window sizes.