Roles of the mitochondrial Na+-Ca2+ exchanger, NCLX, in B lymphocyte chemotaxis

Lymphocyte chemotaxis plays important roles in immunological reactions, although the mechanism of its regulation is still unclear. We found that the cytosolic Na+-dependent mitochondrial Ca2+ efflux transporter, NCLX, regulates B lymphocyte chemotaxis. Inhibiting or silencing NCLX in A20 and DT40 B lymphocytes markedly increased random migration and suppressed the chemotactic response to CXCL12. In contrast to control cells, cytosolic Ca2+ was higher and was not increased further by CXCL12 in NCLX-knockdown A20 B lymphocytes. Chelating intracellular Ca2+ with BAPTA-AM disturbed CXCL12-induced chemotaxis, suggesting that modulation of cytosolic Ca2+ via NCLX, and thereby Rac1 activation and F-actin polymerization, is essential for B lymphocyte motility and chemotaxis. Mitochondrial polarization, which is necessary for directional movement, was unaltered in NCLX-knockdown cells, although CXCL12 application failed to induce enhancement of mitochondrial polarization, in contrast to control cells. Mouse spleen B lymphocytes were similar to the cell lines, in that pharmacological inhibition of NCLX by CGP-37157 diminished CXCL12-induced chemotaxis. Unexpectedly, spleen T lymphocyte chemotaxis was unaffected by CGP-37157 treatment, indicating that NCLX-mediated regulation of chemotaxis is B lymphocyte-specific, and mitochondria-endoplasmic reticulum Ca2+ dynamics are more important in B lymphocytes than in T lymphocytes. We conclude that NCLX is pivotal for B lymphocyte motility and chemotaxis

Desirable Way to Support for Guardians and Cooperation among Nursery Teachers in Case Study

　子どもの健やかな成長と発達のためには，保育士と保護者が円滑な関係にあることが望ましい。経験年数の短い若手保育士と中堅・熟練保育士では，保護者対応に違いはあるのだろうか。本論では，経験年数別に保護者対応について聴き取り調査を行った。さらに，中堅・熟練保育士自身が若手保育士だった頃の振り返りから，現在の保護者対応を比較し検討した。その結果，保護者対応には経験の蓄積と先輩保育士の助言・指導等が必要であることが分かった

Importance of Fatty Acid Compositions in Patients with Peripheral Arterial Disease

Objective: Importance of fatty acid components and imbalances has emerged in coronary heart disease. In this study, we analyzed fatty acids and ankle-brachial index (ABI) in a Japanese cohort. Methods: Peripheral arterial disease (PAD) was diagnosed in 101 patients by ABI <= 0.90 and/or by angiography. Traditional cardiovascular risk factors and components of serum fatty acids were examined in all patients (mean age 73.2 +/- 0.9 years; 81 males), and compared with those in 373 age- and sex-matched control subjects with no evidence of PAD. Results: The presence of PAD (mean ABI: 0.71 +/- 0.02) was independently associated with low levels of gamma-linolenic acid (GLA) (OR: 0.90; 95% CI: 0.85-0.96; P = 0.002), eicosapentaenoic acid: arachidonic acid (EPA: AA) ratio (OR: 0.38; 95% CI: 0.17-0.86; P = 0.021), and estimated glomerular filtration rate (OR: 0.97; 95% CI: 0.96-0.98; P<0.0001), and with a high hemoglobin A1c level (OR: 1.34; 95% CI: 1.06-1.69; P = 0.013). Individuals with lower levels of GLA (<= 7.95 mu g/mL) and a lower EPA: AA ratio (<= 0.55) had the lowest ABI (0.96 +/- 0.02, N = 90), while the highest ABI (1.12 +/- 0.01, N = 78) was observed in individuals with higher values of both GLA and EPA: AA ratio (P<0.0001). Conclusion: A low level of GLA and a low EPA: AA ratio are independently associated with the presence of PAD. Specific fatty acid abnormalities and imbalances could lead to new strategies for risk stratification and prevention in PAD patients.ArticlePLOS ONE. 9(9):e107003 (2014)journal articl

Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila

Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity), we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of Drosophila. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of Drosophila olfactory receptor neurons (ORNs), Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.This work was supported by grants from the Japan Society for the Promotion of Science and the Japan Ministry of Education, Culture, Sports, Science and Technology to TC and MMi, from the Uehara memorial foundation to TC, from NIH to JWW (DK092640), and from NIH to RLD (2R37 NS19904-30). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

イソプロテレノール誘導肥大心においてNHE-1阻害薬は、ラット左心室の筋スライスのCa2+トランジェントを正常化する

We previously reported that left ventricular (LV) slices from isoproterenol (ISO)-induced hypertrophied rat hearts showed an increase of energy expenditure due to remodeling of Ca2+ handling in excitation–contraction coupling, i.e., suppressed SERCA2a activity and enhanced Na+/Ca2+exchanger-1 (NCX-1) activity. Na+/H+ exchanger-1 (NHE-1) inhibitor (NHEI) has been demonstrated to exert beneficial effects in the development of cardiac remodeling. We hypothesized that a novel NHE-1 selective inhibitor, BIIB723 prevents remodeling of Ca2+ handling in LV slices of ISO-induced hypertrophied rat hearts mediated by inhibiting NCX-1 activity. The significant shortening in duration of multi-cellular Ca2+ transient in ISO group was normalized in ISO + BIIB723 group. The significant increase in amplitude of multi-cellular Ca2+ waves (CaW) generated at high [Ca2+]o of LV slices in ISO group was also normalized in ISO + BIIB723 group. However, the enhanced NCX-1 activity was not antagonized by BIIB723. We recently reported that ISO-induced down-regulation of a Ca2+ handling protein, SERCA2a, was normalized by BIIB723. Therefore, it seems likely that BIIB723 normalized shortened multi-cellular Ca2+ transient duration and increased CaW amplitude in LV slices mediated via normalization of SERCA2a activity. Furthermore, the results presented here suggest the multi-cellular Ca2+ transient duration and CaW amplitude in LV slices might be better indices reflecting SERCA2a activity than SERCA2a protein expression level.博士（医学）・甲618号・平成26年3月17

Chemotherapy with low-dose capecitabine as palliative treatment in a patient with metastatic breast cancer: a case report

Chemotherapeutic agents are rarely used for symptom management in patients under palliative care setting. This is because chemotherapeutic agents not only have limited efficacy in palliative treatment but are also known to exert severe adverse effects. We describe our experience with a patient with metastatic breast cancer who was successfully treated with low-dose capecitabine, without the development of any severe toxicities and with significant improvement in activities of daily living (ADL) and quality of life (QOL)

Catheter ablation of non-inducible atrial tachycardia after surgical repair of heart disease

We present a patient with non-inducible atrial tachycardia (AT) after atriotomy for surgical repair of heart disease who underwent ablation successfully. Using a 3-D mapping system, we presumed the atriotomy site on the lateral right atrial wall by searching for linear double potentials (DP) during sinus/paced rhythm from the coronary sinus, but it was evaluated incompletely. We could verify the edges of the atriotomy scar precisely by pacing from close to the linear DP lesion and the opposite site. After ablation between the presumed atriotomy scar and the inferior vena cava and cavotricuspid isthmus, no AT recurred without anti-arrhythmic drugs.ArticleHEART AND VESSELS. 27(1):114-118 (2012)journal articl