Objectives Left ventricular systolic dyssynchrony is the most important determinant of response to cardiac resynchronization therapy (CRT), playing a vital role to predict improvement of systolic function or LV reverse remodeling. CardioGRAF is a novel programmer based on the ECG gated single photon emission computed tomography (G-SPECT) imaging to detect LV systolic and diastolic dyssynchrony simultaneously. This study was to investigate the prevalence of systolic and diastolic left ventricular (LV) dyssynchrony in patients with heart failure. Methods We retrospectively studied 69 patients with heart disease, including 31 patients who had symptoms of heart failure (NYHA class Ⅱ-Ⅲ), and 38 patients who had no symptoms of heart failure (NYHA class Ⅰ). G-SPECT data were analyzed by cardiaGRAF, and measurements included the time to end systole (TES), the time to peak ejection (TPE), the time to peak filling (TPF), TES+TPF and maximal difference (MD) of each parameters were obtained, using the 95th percentile of the control group as a cutoffof 150 ms for MD-TES, 139 ms for MD-TPE, 345 ms for MD-TPF and 315 ms for MD-TES+TPF. Results The prevalence of LV systolic dyssynchrony was significantly higher in heart failure patients with reduced LV ejection fraction (LVEF)<45% (72% for MD-TES; 64% for MD-TPE) compared with heart failure patients with preserved LVEF=45% (14% for both MD-TES and MD-TPE; P=0.002, P=0.005, respectively); The prevalence of MD-TES<150 ms was higher in NYHA class Ⅲ patients (64%) compared with NYHA class Ⅱ patients (27%, P=0.049). However, the prevalence of the LV diastolic dyssynchrony were high but not difference between NYHA class Ⅲ(47% for both MD-TPF and MD-TES+TPF) and class Ⅲ(63% for MD-TPF; 69% for MD-TES+TPF; P=NS) patients as well as between patients with preserved LVEF (43% for both MD-TPF and MD-TES+TPF) and patients with reduced LVEF(64% for MD-TPF; 72% for MD-TES+TPF; P=NS). Conclusions The prevalence of LV systolic dyssynchrony was high in heart failure patients with reduced LVEF. Diastolic dyssynchrony was common in patients with heart failure. CardioGRAF maybe a useful method to detect LV dyssynchrony.

From April 1983 through March 1993, 10, 767 women underwent health examinations at the Health Care Center in Obihiro Kosei Hospital. Cervical smears were taken from theuterine cervix for cervical cancer screening. One hundred and six women had abnormal results, greater than class III. Those patients who were diagnosed as having carcinoma numbered 10 (0.09%). Of the cervical carcinomas found, 1 was frankly invasive (adenocarcinoma Ib); 3, microinvasive (2; squamous cell carcinoma and 1; co-existence of adenocarcinoma and squamous cell carcinoma); and 6, carcinomas in situ (squamous cell carcinoma).

LR11, also known as SorLA or SORL1, is a type-I membrane protein from which a large extracellular part, soluble LR11 (sLR11), is released by proteolytic shedding on cleavage with a disintegrin and metalloproteinase 17 (ADAM17). A shedding mechanism is presumed to have a key role in the functions of LR11, but the evidence for this has not yet been demonstrated. Tetraspanin CD9 has been recently shown to regulate the ADAM17-mediated shedding of tumor necrosis factor-alpha and intercellular adhesion molecule-1 on the cell surface. Here, we investigated the role of CD9 on the shedding of LR11 in leukocytes. LR11 was not expressed in THP-1 monocytes, but it was expressed and released in phorbol 12-myristate 13-acetate (PMA)-induced THP-1 macrophages (PMA/THP-1). Confocal microscopy showed colocalization of LR11 and CD9 proteins on the cell surface of PMA/THP-1. Ectopic neo-expression of CD9 in CCRF-SB cells, which are LR11-positive and CD9-negative, reduced the amount of sLR11 released from the cells. In contrast, incubation of LR11-transfected THP-1 cells with neutralizing anti-CD9 monoclonal antibodies increased the amount of sLR11 released from the cells. Likewise, the PMA-stimulated release of sLR11 increased in THP-1 cells transfected with CD9-targeted shRNAs, which was negated by treatment with the metalloproteinase inhibitor GM6001. These results suggest that the tetraspanin CD9 modulates the ADAM17-mediated shedding of LR11 in various leukemia cell lines and that the association between LR11 and CD9 on the cell surface has an important role in the ADAM17-mediated shedding mechanism.
ADAM Proteins/*metabolism ; Antigens, CD9/genetics/*metabolism ; Cell Line, Tumor ; Humans ; LDL-Receptor Related Proteins/genetics/*metabolism ; Leukocytes/*metabolism ; Macrophages/metabolism ; Membrane Transport Proteins/genetics/*metabolism ; Proteolysis