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91.
Toshiki MORIYAMA Chen XIA Akiko MIYAI Yoshitaka AKAGI Yoshitaka ISAKA Tetsuya KANEKO Noritaka KAWADA Naohiko UEDA Atsushi YAMAUCHI Masaru HORIO Akio O Enyu IMAI Masatsugu HORI 《Nephrology (Carlton, Vic.)》1997,3(6):443-453
Summary: Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is encoded by the mitogen-inducible gene 3CH 134. MKP-1 has recently been shown to be a dual specificity (serine/threonine, tyrosine) protein phosphatase, which dephosphorylates and inactivates MAP kinases in vitro and in vivo. to seek the role of MKP-1 in growth regulation of mesangial cells, expression of MKP-1 mRNA in cultured mesangial cells and in glomeruli isolated from anti-Thy 1.1 mesangial proliferative glomerulonephritis rats was studied. the effect of inhibition of endogenous MKP-1 by use of antisense-DNA technology on the regulation of MAP kinase activity and the growth regulation of rat cultured inesangial cells was also studied. By northern blot analysis, it was demonstrated that in mesangial cells, MKP-1 mRNA expression was rapidly induced after the stimulation by serum, growth factors and vasoactive peptides. Maximal signals were found in 30-60 min in all growth factors tested. Fetal calf serum (FCS) was the most potent stimulus of MKP-1 mRNA expression, followed by platelet-derived growth factor (PDGF)-B and arginine vasopressin. to elucidate a possible involvement of MKP-1 in disease development of mesangial proliferative glomerulonephritis, MKP-1 mRNA expression was examined in rat anti-Thy 1.1 glomerulonephritis model. A marked increase in MKP-1 mRNA level in isolated glomeruli was observed at day 3 after disease induction (4.3-fold over control). In situ hybridization of MKP-1 mRNA in Thy 1.1 glomerulonephritius rats confirmed the enhanced glomerular expression of MKP-1. to study the role of MKP-1 in mesangial cell growth regulation, phosphorothioate oligodeoxynucleotide (ODN) were used to modulate MKP-1 expression. an antisense ODN targeting the translation initiation site of MKP-1 mRNA inhibited stimulated (by FCS, or PDGF-B) DNA synthesis and FCS- or PDGF-induced mitogenesis in mesangial cells. Sense ODN or mismatched ODN had no effect on the DNA synthesis or mitogenic response of mesangial cells. These results suggest that MKP-1 is an immediately early gene in rat mesangial cells and it plays a critical role in growth regulation of mesangial cells in vitro. 相似文献
92.
Kunihide IMAI Kennichi YAMAGUCHI Mayumi WATANABE Eisuke KAINUMA Naohumi HIKAKE Shizuka SAITOH Masaharu TANAKA Masahiro MORITA Toru SUNAYAMA Miyoshi NOMURA Tetsuo KOZAKAI Shigetsugu WADA Ken UEKI Reiko KIMURA 《Psychogeriatrics》2007,7(2):58-63
Objective: It is suggested that thalami, basal ganglia, putamina and caudate heads play a crucial role in strong emotion such as the fear of serious earthquake. The aim of this study was to elucidate the radiographic findings (mainly the lacunae) in these regions, mental abilities and the extent of the activities of daily livings (ADL) of moderately demented patients who could recognize the Niigata Ken (prefecture) Chuetsu earthquake 2004 Japan. Methods: In patients with moderate dementia, mainly Alzheimer’s disease, who could recognize the Niigata Ken (prefecture) Chuetsu earthquake 2004 in Niigata prefecture in Japan, their radiographic findings regarding thalami, basal ganglia, putamina and caudate heads were investigated by counting the numbers of lacunae using magnetic resonance imaging. In addition, their mental abilities were examined by Mini‐Mental Examination Score and Hasegawa Dementia Scale–Revised. Their activities of daily living were also assessed. Results: The patients who could recognize the earthquake have statistically fewer lacunae in the thalami, basal ganglia, putamina and caudate heads, than those who could not (P < 0.01 by Student’s t‐test). This analysis revealed that the patients who could recognize the earthquake have statistically significant higher scores in both Mini‐Mental Examination Score, Hasegawa Dementia Scale–Revised (P < 0.05 by Student’s t‐test) and activities of daily living (P < 0.01 by Student’s t‐test). However, statistical significance was not obtained regarding education between two groups. Conclusion: Thalami and the structures around them such as basal ganglia, putamina and caudate heads play an important role in emotion and cognition. Therefore, we concluded that numbers of lacunae might be a valuable marker in evaluating the cognitive abilities of the demented patients. 相似文献
93.
HIROSHI NIINAMI M.D. YASUHARU IMAI M.D. KAZUO SAWATARI M.D. MASATSUGU TERADA M.D. TOSHIHARU SHINOKA M.D. YOSHITAKA SUGIYAMA M.D. 《Journal of cardiac surgery》1992,7(4):351-355
A right coronary artery originating from the left coronary sinus and traversing anteriorly is thought to be one of the contraindications for a Konno aortoventriculoplasty in congenital aortic stenosis because this procedure necessitates incision of the right ventricular outflow tract. The case of a 5-year-old girl with congenital aortic stenosis associated with a single coronary artery, successfully treated surgically by the Konno procedure and right coronary artery reimplantation, is reported. Preoperatively there was a pressure gradient between the left ventricle and the ascending aorta of 109 mmHg, which disappeared postoperatively. A postoperative angiography showed a patent right coronary artery. 相似文献
94.
CHRISTINE ACKLIN KENDALL STONEY ROBERT A. ROSENFELD JAMES A. MILLER MICHAEL F. ROHDE MITSURU HANIU 《Chemical biology & drug design》1993,41(6):548-552
Three disulfide linkages of recombinant human brain-derived neurotrophic factor (BDNF) were determined by peptide sequence analysis and characterized by mass spectrometry. The three disulfide bonds for BDNF expressed in Chinese hamster ovary cells include Cys-13-Cys-80, Cys-58-Cys-109 and Cys-68-Cys-111, and the disulfide structure was homologous to that of nerve growth factor. 相似文献
95.
KEN ISEKI TAKESHI HIRANO KAORI TSUJI SHOZO MIYAZAKI MASAHIRO TAKADA MICHIYA KOBAYASHI MITSURU SUGAWARA KATSUMI MIYAZAKI 《The Journal of pharmacy and pharmacology》1998,50(6):627-634
The mechanism of uptake of sparfloxacin, a new quinolone, by intestinal brush-border membrane vesicles was investigated to clarify whether there is a common transport process for new quinolones mediated by the diffusion potential across the intestinal membrane bilayer. Sparfloxacin was taken up pH-dependently by rat intestinal brush-border membrane vesicles, behaviour analogous to that of organic cations including enoxacin and ciprofloxacin. Transient overshooting uptake of this quinolone was observed in the presence of an outward H+ gradient. Momentary dissipation of the H+ gradient by addition of carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone did not affect the uptake of sparfloxacin, and a marked but incomplete reduction in the H+-sensitive overshooting uptake of sparfloxacin was apparent in the voltage-clamped brush-border membrane vesicles. Furthermore, a valinomycin-induced K+-diffusion potential (interior negative) and an inward Cl—-diffusion potential stimulated the initial uptake of Sparfloxacin at pH 5.5. Sparfloxacin uptake was inhibited by tetracaine and imipramine. The inhibitory effect of these cations correlated well with changes in membrane surface charges induced by the presence of tetracaine or imipramine. These results indicate that sparfloxacin transport across the brush-border membrane depends upon the inside-negative ionic diffusion potential, that the H+- or K+-diffusion-potential-dependent uptake of sparfloxacin by intestinal brush-border membrane vesicles is affected by the membrane surface potential and that inhibition of sparfloxacin uptake originates from changes in the membrane surface potential caused by the organic cations. 相似文献
96.
MOHAMMED SHAMEEM TERUKO IMAI MASAKI OTAGIRI 《The Journal of pharmacy and pharmacology》1993,45(4):246-252
Abstract— A series of ester prodrugs of propranolol was synthesized by incorporating substituents (straight alkyl, branched alkyl, acyloxyalkyl and cycloalkyl) into the β-hydroxy function of propranolol with the aim of protecting the drug against first-pass metabolism following oral administration. The in-vitro hydrolysis rates of the prodrugs were, in increasing order, liver homogenate ? plasma > buffers. The pH-rate profile of the prodrugs showed maximum stability around pH 4·0; the hydrolysis rates were drastically increased over pH 6·8. QSAR analysis revealed hydrophobic (π) and electronic (σ) effects of the substituents play the main roles for prodrug hydrolysis in buffers and plasma, while hydrolysis in liver homogenate could not be well explained by any of these parameters. Four prodrugs (O-acetyl-, O-butyryl-, O-isovaleryl- and O-cyclopropanoyl-propranolol) were selected for oral administration based on their hydrolysis in-vitro. Following oral administration of prodrugs to beagle dogs the absolute bioavailabilities (F) of propranolol were about 2–4-fold that after an equivalent dose of propranolol. The prodrugs were rapidly absorbed and regenerated propranolol to attain peak plasma levels at 0–0·5 h. Intact prodrug levels were also observed, which varied depending on their respective stabilities in in-vitro media. A linear relationship between F of propranolol and log P was obtained. F further appeared to be parabolically dependent on the observed hydrolysis rates of prodrugs in liver homogenate suggesting optimal design manipulation. The overall in-vitro and in-vivo results showed that lipophilic prodrugs having higher chemical and enzymatic stability in buffers and plasma, but susceptible to hydrolysis in the liver homogenate, to be the most promising prodrugs for improving oral bioavailability of propranolol. 相似文献
97.
KENICHI AKAJI NOBUTAKA FUJII HARUAKI YAJIMA MOTOYUKI MORIGA MITSURU AONO ATSUSHI TAKAGI 《Chemical biology & drug design》1981,18(2):180-194
The heptacosapeptide amide corresponding to the entire amino acid sequence of gastrin-releasing peptide (GRP) was synthesized by assembling seven peptide fragments followed by deprotection with a new reagent system, IM trifluoro-methanesulfonic acid-thioanisole in TFA. The deprotected peptide was purified by ion-exchange chromatography on CM-cellulose followed by partition chromatography on Sephadex G-25. The latter was found to remove effectively the Met (O) derivative of GRP. The highly purified synthetic GRP was active as synthetic bombesin on the molar basis. A new carboxyl-activating reagent, thiazoline-2-thione, was employed for preparation of the necessary fragments. 相似文献
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