http://hdl.handle.net/10271/3 RSSチャネルの検索 検索 http://hikumano.hama-med.ac.jp/dspace/simple-search http://hdl.handle.net/10271/1898 タイトル: Local control of mitochondrial membrane potential, permeability transition pore and reactive oxygen species by calcium and calmodulin in rat ventricular myocytes <br/> <br/>著者: Odagiri, Keiichi; Katoh, Hideki; Kawashima, Hirotaka; Tanaka, Takamitsu; Ohtani, Hayato; Saotome, Masao; Urushida, Tsuyoshi; Satoh, Hiroshi; Hayashi, Hideharu <br/> <br/>抄録: Calmodulin (CaM) and Ca2+/CaM-dependent protein kinase II (CaMKII) play important roles in the development of heart failure. In this study, we evaluated the effects of CaM on mitochondrial membrane potential (ΔΨm), permeability transition pore (mPTP) and the production of reactive oxygen species (ROS) in permeabilized myocytes; our findings are as follows. (1) CaM depolarized ΔΨm dose-dependently, but this was prevented by an inhibitor of CaM (W-7) or CaMKII (autocamtide 2-related inhibitory peptide (AIP)). (2) CaM accelerated calcein leakage from mitochondria, indicating the opening of mPTP, however this was prevented by AIP. (3) Cyclosporin A (an inhibitor of the mPTP) inhibited both CaM-induced ΔΨm depolarization and calcein leakage. (4) CaM increased mitochondrial ROS, which was related to ΔΨm depolarization and the opening of mPTP. (5) Chelating of cytosolic Ca2+ by BAPTA, the depletion of SR Ca2+ by thapsigargin (an inhibitor of SERCA) and the inhibition of mitochondrial Ca2+ uniporter by Ru360 attenuated the effects of CaM on mitochondrial function. (6) CaM accelerated Ca2+ extrusion from mitochondria. We conclude that CaM/CaMKII depolarized ΔΨm and opened mPTP by increasing ROS production, and these effects were strictly regulated by the local increase in cytosolic Ca2+ concentration, initiated by Ca2+ releases from the SR. In addition, CaM was involved in the regulation of mitochondrial Ca2+ homeostasis. <br/> <br/>記述: 浜松医科大学学位論文　医博第550号(平成２１年３月１８日） http://hdl.handle.net/10271/1895 タイトル: Cytokine responses of intraepithelial lymphocytes are regulated by histamine H2 receptor <br/> <br/>著者: Takagaki, Kosuke; Osawa, Satoshi; Horio, Yoshiaki; Yamada, Takanori; Hamaya, Yasushi; Takayanagi, Yasuhiro; Furuta, Takahisa; Hishida, Akira; Ikuma, Mutsuhiro <br/> <br/>抄録: Backgrounds. Histamine participates in the immune regulation of several gastrointestinal diseases. However, the effect of histamine on intestinal intraepithelial lymphocytes (IELs), the front line of intestinal mucosal immune system, is not well-understood. We examined whether histamine has a direct effect on cytokine production by IELs and the involvement of histamine receptor subtypes.　Methods. Murine IELs were activated by PMA plus ionomycin with/without histamine. Secreted cytokines were measured and compared with those of splenocytes. Intracellular cytokines were detected by flow cytometory. Expression of histamine receptor subtypes in IELs was examined by RT-PCR. Results. Histamine H1 receptor (H1R), H2R, and H4R, but not H3R mRNA were expressed on IELs. Histamine significantly decreased Th1-cytokine (IFN-γ, TNF-α, and IL-2) and also IL-4 production in IELs as well as splenocytes. The selective H2R antagonist famotidine, but not the H1R antagonist pyrilamine nor the H3R/H4R antagonist thioperamide, competes with the inhibitory effect of histamine on these cytokine production in IELs. These suppressive effects of histamine were mimicked by a selective H2R/H4R agonist dimaprit. Further, these suppressive effects of histamine for Th1-cytokine and IL-4 did not accompany with the enhancement of IL-10 production nor IL-10 mRNA level in IELs. Intracellular cytokine analysis revealed that the number of IFN-γ-producingαβ T cells was significantly reduced by histamine in IELs.　Conclusions. Histamine has a direct suppressive effect on IEL-derived cytokines via H2R, which would have a crucial role in the suppression of local immunoregulation in the intestinal epithelium. <br/> <br/>記述: 浜松医科大学学位論文　医博第549号(平成２１年３月１８日） http://hdl.handle.net/10271/1799 タイトル: Left Ventricular Diastolic Performance in Neonates <br/> <br/>著者: Iwashima, Satoru; Seguchi, Masashi; Ohzeki, Takehiko <br/> <br/>抄録: Background The left ventricular (LV) diastolic performance of infants who were in a stable post-treatment condition in the neonatal intensive care unit was evaluated using echocardiography. Methods and Results The study group comprised 55 infants (Stable infant group, SI) and the parameters of LV performance were: LV propagation velocity (Vp) by color M-mode Doppler echocardiography (CMD), peak E wave, peak A wave, and the E/A ratio of transmitral flow. In a second set of measurements, a subset of 10 infants (patent ductus arteriosus (PDA) infant group, PI) were evaluated for LV diastolic performance during closure of PDA. The mean Vp in the SI was 27.2±7.3 cm/s and a positive correlation was observed between Vp and gestational age (r=0.477, p=0.0002). In the PI, Vp did not change significantly during closure of the PDA (from 23.3±8.2 cm/s to 27.5±8.4 cm/s); however, the E/Vp ratio decreased significantly with closure (from 3.14±0.83 to 2.12±0.68, p=0.0051). Conclusion The measurement of Vp by CMD can be considered a parameter for the evaluation of LV diastolic performance, even in the neonatal period. The LV diastolic performance of the infant is maintained from immediately after birth to spontaneous closure of the PDA. <br/> <br/>記述: rights:社団法人日本循環器学会; rights:本文データは学協会の許諾に基づきCiNiiから複製したものである; relation：isVersionOf:http://ci.nii.ac.jp/naid/110002703846; 浜松医科大学学位論文　医博論第459号(平成２０年１１月２１日） http://hdl.handle.net/10271/1798 タイトル: Antimalarial activity of methanolic extracts from plants used in Kenyan ethnomedicine and their interactions with chloroquine (CQ) against a CQ-tolerant rodent parasite, in mice. <br/> <br/>著者: Muregi, Francis Wamakima; Ishih, Akira; Miyase, Toshio; Suzuki, Tohru; Kino, Hideto; Amano, Teruaki; Mkoji, Gerald M.; Terada, Mamoru <br/> <br/>抄録: Methanolic extracts from 15 medicinal plants representing 11 families, used traditionally for malaria treatment in Kenya were screened for their in vivo antimalarial activity in mice against a chloroquine (CQ)-tolerant Plasmodium berghei NK65, either alone or in combination with CQ. The plant parts used ranged from leaves (L), stem bark (SB), root bark (RB), seeds (S) and whole plant (W). When used alone, extracts from 7 plants, Clerodendrum myricoides (RB), Ficus sur (L/SB/RB), Maytenus acuminata (L/RB), Rhamnus prinoides (L/RB), R. staddo (RB), Toddalia asiatica (RB) and Vernonia lasiopus (RB) had statistically significant parasitaemia suppressions of 31.7-59.3%. In combination with CQ, methanolic extracts of Albizia gummifera (SB), F. sur (RB), R. prinoides and R. staddo (L/RB), Caesalpinia volkensii (L), Maytenus senegalensis (L/RB), Withania somnifera (RB), Ekebergia capensis (L/SB), T. asiatica (L/RB) and V. lasiopus (L/SB/RB) gave statistically significant and improved suppressions which ranged from 45.5-85.1%. The fact that these activities were up to 5-fold higher than that of extract alone may suggest synergistic interactions. Remarkable parasitaemia suppression by the extracts, either alone or in combination with CQ mostly resulted into longer mouse survival relative to the controls, in some cases by a further 2 weeks. Plants, which showed significant antimalarial activity including V. lasiopus, T. asiatica, F. sur, R. prinoides and R. staddo warrant further evaluation in the search for novel antimalarial agents against drug-resistant malaria. <br/> <br/>記述: 浜松医科大学学位論文　医博第546号(平成２１年３月１８日）