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81.
Tomoko Yoshinari Yoshikazu Iwasawa Keiko Miura Ikuko S. Takahashi Takahiro Fukuroda Kunio Suzuki Akira Okura 《Cancer chemotherapy and pharmacology》1989,24(6):367-370
Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-3H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists. 相似文献
82.
Jun Ishigooka Mitsukuni Murasaki Hirobumi Wakatabe Sadanori Miura Kozo Hikida Masahiro Shibata 《Psychopharmacology》1989,97(3):303-308
The pharmacokinetic properties of the iminodibenzyl antipsychotic drugs clocapramine (CCP, 3-chloro-5-[3-(4-carbamoyl-4-piperidino piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) and Y-516 (3-chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo [1,2-a] pyridine-3-spiro-4-piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) were investigated in dog and man. Dogs were administered CCP and Y-516 intravenously, intraperitoneally, and orally, and the concentrations of the parent drugs and their metabolites in the plasma and urine were determined. Half-life (t1/2) was approximately the same by all three administration routes, being approximately 5 h for CCP and 3 h for Y-516. Bioavailability following oral administration was 0.16±0.01 (mean ± SD, n=3) for CCP and 0.29±0.07 for Y-516. The fractions of dose absorbed following oral administration were 0.43±0.07 and 0.79±0.24, and the fractions of dose metabolized in the liver due to the first-pass effect were 0.63±0.05 and 0.63±0.04 for CCP and Y-516, respectively. Y-516 was detected in the plasma after intraperitoneal and oral administration of CCP. The ratio of the AUC of Y-516 to that of CCP was 0.06 following intraperitoneal administration and 0.40 following oral administration. This indicated that while the metabolism of CCP into Y-516 may occur partly in the liver due to the first-pass effect, it occurs mostly within the gastrointestinal tract itself or its mucosa. When CCP and Y-516 were given orally to man, the plasma concentrations of both parent drugs increased in a dose-dependent manner. The t1/2 of CCP at a dose of 50 mg was 46±6 h (n=3) while that of Y-516 at a dose of 25 mg was 15±2 h (n=5), so that elimination from the circulation was slower than in the dog in both cases. As in the dog, Y-516 was detected in the plasma following administration of CCP, but its concentration was approximately one fifth that of CCP and lower than that found in the dog. From the ratios of Y-516 produced upon oral administration of CCP in dog and man, we concluded that Y-516 is involved to a considerable degree in the pharmacological action of CCP in the dog and, though to a lesser degree, in man as well. 相似文献
83.
Suzuki Hisamitsu; Ota Kazuo; Ohno Ryuzo; Masaoka Toru; Shibata Hirotoshi; Kimura Ikuro; Amaki Ichita; Miura Yasusada; Uzuka Yoshiro; Kawato Masafumi; Shirakawa Shigeru; Hirota Yutaka; Maekawa Tadashi; lmai Kuniyuki; Takaku Fumimaro; Shimoyama Masanori; Kitahara Takeshi; Oguro Masao; Kozuru Mitsuo; Kawagoe Hiroya; Nakamura Toru; Yamada Kazumasa 《Japanese journal of clinical oncology》1989,19(4):338-347
Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 19711975 to 62.3%during 19811985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 19711975and 69.7% during 19811985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 3740 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe. 相似文献
84.
Kitajima T Kanbayashi T Saito Y Takahashi Y Ogawa Y Sugiyama T Kaneko Y Aizawa R Shimizu T 《Neuroscience letters》2004,355(1-2):77-80
It is known that benzodiazepines have a hypotensive effect, but the mechanism has not been well elucidated yet. To clarify whether this effect is due to central or peripheral mechanism, we administered 5 mg of diazepam or saline intravenously to healthy volunteers and assessed the change in blood pressure, heart rate, muscle sympathetic nerve activity and heart rate variability. After diazepam administration, systolic and mean blood pressure decreased significantly. Muscle sympathetic nerve activity was also significantly reduced but heart rate did not change, whereas the variables of spectral analysis of heart rate variability did not show significant change. We concluded that the hypotensive effect of diazepam in human is mainly due to the central mechanism. 相似文献
85.
Yozo Miura Yuzo Morimoto Masayoshi Kinoshita 《Macromolecular chemistry and physics.》1974,175(12):3487-3493
2,4,6-Triphenyl-3,4-dihydro-s-tetrazin-1(2H)-yl ( 1 ) (1,3,5-triphenylverdazyl) was allowed to react with ethyl- and butyllithium, ethyl-, isopropyl-, and butylmagnesium bromide, as well as benzylmagnesium chloride to give the coupling products 2a–d . These results indicate that structures corresponding to 2 are present in the polymers resulting from vinyl monomers containing the verdazyl structure, if they are initiated with alkyllithium or a Grignard reagent. A reaction mechanism is discussed. 相似文献
86.
Koichiro Yuji Shigesaburo Miyakoshi Daisuke Kato Yuji Miura Tomohiro Myojo Naoko Murashige Yukiko Kishi Kazuhiro Kobayashi Eiji Kusumi Hiroto Narimatsu Tamae Hamaki Tomoko Matsumura Masahiro Kami Takahiro Fukuda Shigeru Masuo Kazuhiro Masuoka Atsushi Wake Junichi Ueyama Akiko Yoneyama Ko Miyamoto Haruhisa Nagoshi Michio Matsuzaki Shinichi Morinaga Yoshitomo Muto Yoichi Takeue Shuichi Taniguchi 《Biology of blood and marrow transplantation》2005,11(4):314-318
We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor. 相似文献
87.
Morita Y Ujike H Tanaka Y Uchida N Nomura A Ohtani K Kishimoto M Morio A Imamura T Sakai A Inada T Harano M Komiyama T Yamada M Sekine Y Iwata N Iyo M Sora I Ozaki N Kuroda S 《Neuroscience letters》2005,376(3):182-187
Genetic contributions to the etiology of substance abuse and dependence are topics of major interest. Acute and chronic cannabis use can produce drug-induced psychosis resembling schizophrenia and worsen positive symptoms of schizophrenia. The endocannabinoid system is one of the most important neural signaling pathways implicated in substance abuse and dependence. The fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme of endocannabinoids. To clarify a possible involvement of FAAH in the etiology of methamphetamine dependence/psychosis or schizophrenia, we examined the genetic association of a nonsynonymous polymorphism of the FAAH gene (Pro129Thr) by a case-control study. We found no significant association in allele and genotype frequencies of the polymorphism with either disorder. Because the Pro129Thr polymorphism reduces enzyme instability, it is unlikely that dysfunction of FAAH and enhanced endocannabinoid system induce susceptibility to either methamphetamine dependence/psychosis or schizophrenia. 相似文献
88.
Kohno R Toyono T Seta Y Kataoka S Yamaguchi K Toyoshima K 《Archives of histology and cytology》2005,68(4):235-241
Synapses between taste receptor cells and primary sensory afferent fibers transmit the output signal from taste buds to the central nervous system. The synaptic vesicle cycle at the synapses involves vesicle docking, priming, fusion, endocytosis, and recycling. Many kinds of synaptic vesicle proteins participate in synaptic vesicle cycles. One of these, synaptotagmin 1, binds Ca(2+) phospholipids with high affinity and plays a role in Ca(2+) regulated neurotransmitter release in the central and peripheral nervous systems. However, the expression patterns of synaptotagmin 1 in rat taste tissues have not been determined. We therefore examined the expression patterns of synaptotagmin 1 and several cell specific markers of type II and III cells in rat taste buds. RT-PCR assay showed that synaptotagmin 1 mRNA was expressed in circumvallate papillae. In fungiform, foliate, and circumvallate papillae, the antibody against synaptotagmin 1 yielded the labeling of a subset of taste bud cells and intra- and subgemmal nerve processes. Double labeled experiments showed that synaptotagmin 1 positive cells co-expressed type III cell markers, PGP 9.5, and NCAM. Intragemmal nerve processes positive for synaptotagmin 1 co-expressed PGP 9.5. Conversely, all synaptotagmin 1 expressing cells did not co-expressed type II cell markers, PLCbeta2, or gustducin. These results show that synaptotagmin 1 may play some regulatory roles in vesicle membrane fusion events with the plasma membrane at the synapses of type III cells in rat taste buds. 相似文献
89.
Polycystic ovarian syndrome was induced in adult rats by treatment with continuous illumination to study follicular atresia.
Granulosa cells of regressing antral follicles showed characteristic features of apoptosis ultrastructurally: condensed nuclei,
apoptotic bodies, and phagocytosis of the apoptotic cells and their fragments by neighboring cells. In this study, moreover,
it was observed that an intact granulosa cell was able to ingest another granulosa cell of normal appearance, presumably indicating
an early stage of follicular atresia. The phagocytosing granulosa cell surrounded another granulosa cell to be phagocytosed
by elongated cell processes. Gap junctions developed between the phagocytic cell and the phagocytosed cell. The phagocytic
cell possessed abundant free ribosomes, well-developed rough endoplasmic reticulum and mitochondria, but few lysosomes. The
ingested cell was similar in appearance to the phagocytic cell. In addition, granulosa cells were also observed ingesting
karyopyknotic cells and degenerative organelles, both displayed in large vacuoles filled with fragments of nuclei and organelles.
These findings suggest a process of apoptosis in the granulosa cells during follicular atresia.
This study was presented at the 20th Annual Meeting of the Clinical Electron Microscopy Society of Japan, Fukuoka, September
1–3, 1988. 相似文献
90.
Fumihiko Sasaki Yuji Ichikawa Shoji Yamauchi 《Anatomical record (Hoboken, N.J. : 2007)》1992,233(1):135-142
Adenohypophyses of porcine fetuses from 25 to 110 days of gestation were studied by immunohistochemical staining to ascertain the ontogeny of specific cell types and their spatial distribution in the pars distalis. No hormonecontaining cells were found before 30 days of gestation. ACTH cells were observed first at 40 days, while GH and LH cells appeared first at 60 days. PRL cells were initially detected at 105 days. ACTH immunoreactive cells were also observed in the pars intermedia at 40 days. Blood capillaries were interposed between cell cords of the pars distalis after 40 days of gestation. ACTH cells were evenly distribution in all areas of the pars distalis except the rostal area (sex zone). GH cells were densely distributed in lateral wings of the pars distalis and immediately anterior to Rathke's lumen. PRL cells resembled GH cells in their distribution pattern, but PRL cells were fewer in number. LH cells were scattered in the sex zone of the pars distalis from 60 to 80 days of gestation. After 90 days, they became scattered throughout the pars distalis but were more numerous in the sex zone than in other areas. The inductive elements of adenohypophysial cells from Rathke's pouch epithelia are discussed. We hypothesize that cell cords of specific areas facing Rathke's lumen may differentiate into specific cell types of the pars distalis during fetal life. © 1992 Wiley-Liss, Inc. 相似文献