Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells

Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells. Adrenomedullin (AM), a potent vasorelaxant and natriuretic peptide isolated from human pheochromocytoma, is present in the kidney and secreted from endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the functional role of AM is still unclear. To clarify the significance of AM as a local regulator, we investigated its secretion and action in cultured cells, and examined the effects of neutralization using a specific monoclonal antibody against AM. The prepared antibody directed against the ring structure showed a high affinity for human and rat AM. Using radioimmunoassay with this antibody, we found significant secretion from cultured rat mesangial cells (MC) of a 6-kDa mature form of AM as seen from EC and VSMC. The addition of AM into cultured cells dose-dependently increased cAMP production and potently inhibited PDGF-stimulated thymidine incorporation. Pretreatment with the monoclonal antibody completely abolished cAMP increase induced by exogenous AM. Moreover, antibody neutralization of endogenously secreted AM in cultured EC, but not in MC or VSMC, markedly (by ∼70%) reduced basal cAMP production and significantly (1.7-fold) enhanced DNA synthesis. These results indicate that AM, acting as an autocrine/paracrine regulator, exerts an antiproliferative action on EC and MC, and suggest its role as a local modulator of endothelial and mesangial function

Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells

Autocrine/paracrine role of adrenomedullin in cultured endothelial and mesangial cells. Adrenomedullin (AM), a potent vasorelaxant and natriuretic peptide isolated from human pheochromocytoma, is present in the kidney and secreted from endothelial cells (EC) and vascular smooth muscle cells (VSMC), but the functional role of AM is still unclear. To clarify the significance of AM as a local regulator, we investigated its secretion and action in cultured cells, and examined the effects of neutralization using a specific monoclonal antibody against AM. The prepared antibody directed against the ring structure showed a high affinity for human and rat AM. Using radioimmunoassay with this antibody, we found significant secretion from cultured rat mesangial cells (MC) of a 6-kDa mature form of AM as seen from EC and VSMC. The addition of AM into cultured cells dose-dependently increased cAMP production and potently inhibited PDGF-stimulated thymidine incorporation. Pretreatment with the monoclonal antibody completely abolished cAMP increase induced by exogenous AM. Moreover, antibody neutralization of endogenously secreted AM in cultured EC, but not in MC or VSMC, markedly (by ∼70%) reduced basal cAMP production and significantly (1.7-fold) enhanced DNA synthesis. These results indicate that AM, acting as an autocrine/paracrine regulator, exerts an antiproliferative action on EC and MC, and suggest its role as a local modulator of endothelial and mesangial function

Community Trial on Heat Related-Illness Prevention Behaviors and Knowledge for the Elderly

This study aims to explore whether broadcasting heat health warnings (HHWs), to every household and whether the additional home delivery of bottled water labeled with messages will be effective in improving the behaviors and knowledge of elderly people to prevent heat-related illness. A community trial on heat-related-illness-prevention behaviors and knowledge for people aged between 65 and 84 years was conducted in Nagasaki, Japan. Five hundred eight subjects were selected randomly from three groups: heat health warning (HHW), HHW and water delivery (HHW+W), and control groups. Baseline and follow-up questionnaires were conducted in June and September 2012, respectively. Of the 1524 selected subjects, the 1072 that completed both questionnaires were analyzed. The HHW+W group showed improvements in nighttime AC use (p = 0.047), water intake (p = 0.003), cooling body (p = 0.002) and reduced activities in heat (p = 0.047) compared with the control, while the HHW group improved hat or parasol use (p = 0.008). An additional effect of household water delivery was observed in water intake (p = 0.067) and cooling body (p = 0.095) behaviors. HHW and household bottled water delivery improved heat-related-illness-prevention behaviors. The results indicate that home water delivery in addition to a HHW may be needed to raise awareness of the elderly

Knowledge, experience, and potential risks of dating violence among Japanese university students: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The Domestic Violence Prevention Act came into effect in Japan in 2001, but covers only marriage partner violence and post-divorce partner violence, and does not recognize intimate partner violence (IPV). The present study was performed to determine the experience of harassment, both toward and from an intimate partner, and recognition of harassment as IPV among Japanese university students.</p> <p>Methods</p> <p>A self-administered questionnaire survey regarding the experience of harassment involving an intimate partner was conducted as a cross-sectional study among freshman students in a prefectural capital city in Japan.</p> <p>Results</p> <p>A total of 274 students participated in the present study. About half of the subjects (both male and female students) had experience of at least one episode of harassment toward or had been the recipient of harassment from an intimate partner. However, the study participants did not recognize verbal harassment, controlling activities of an intimate partner, and unprotected sexual intercourse as violence. Experience of attending a lecture/seminar about domestic violence and dating violence did not contribute to appropriate help-seeking behavior.</p> <p>Conclusions</p> <p>An educational program regarding harassment and violence prevention and appropriate help-seeking behavior should be provided in early adolescence to avoid IPV among youth.</p

Evaluation of efficacy and safety of lascufloxacin for nursing and healthcare associated pneumonia: single-arm, open-label clinical trial: A study protocol

Background: Lascufloxacin hydrochloride (LSFX) is a quinolone antibiotic that inhibits DNA gyrase and topoisomerase IV of bacteria, it is anticipated to minimize antibiotic resistance in bacteria. It exhibits antibacterial activity against a relatively wide range of bacterial species, including anaerobic bacteria, and its efficacy and safety against community-acquired pneumonia have been shown; however, its efficacy and safety against nursing and healthcare associated pneumonia (NHCAP) have not been verified.Methods/Design: Here, a single-arm, open-label, uncontrolled study was conducted in which LSFX was administered to patients with NHCAP at 24 facilities. The research subjects (77 cases) were orally administered 75 mg of LSFX once a day for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC) (TOC; 5–10 days after the end of LSFX administration), while the secondary endpoints were the efficacy at the time of end of treatment, early clinical efficacy, microbiological efficacy at the time of TOC and end of treatment, and safety evaluation of LSFX.Discussion: NHCAP is a common pneumonia in clinical settings and a notable pneumonia whose mortality is high compared to community-acquired pneumonia. The present study showed the efficacy and safety of LSFX against NHCAP, which could lead to a larger number of therapeutic options for NHCAP

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

The status of DECIGO

DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) is the planned Japanese space gravitational wave antenna, aiming to detect gravitational waves from astrophysically and cosmologically significant sources mainly between 0.1 Hz and 10 Hz and thus to open a new window for gravitational wave astronomy and for the universe. DECIGO will consists of three drag-free spacecraft arranged in an equilateral triangle with 1000 km arm lengths whose relative displacements are measured by a differential Fabry-Perot interferometer, and four units of triangular Fabry-Perot interferometers are arranged on heliocentric orbit around the sun. DECIGO is vary ambitious mission, we plan to launch DECIGO in era of 2030s after precursor satellite mission, B-DECIGO. B-DECIGO is essentially smaller version of DECIGO: B-DECIGO consists of three spacecraft arranged in an triangle with 100 km arm lengths orbiting 2000 km above the surface of the earth. It is hoped that the launch date will be late 2020s for the present