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Mitsumasa Iwata Shunji Izuta Motoshi Suzuki Kiyohide Kojima Yoshihito Furuhashi Yutaka Tomoda Shonen Yoshida 《Cancer science》1991,82(4):433-439
We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (-)-( R )-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis- diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP. 相似文献
5.
Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384) on learning and memory in rats 总被引:1,自引:0,他引:1
Effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384) on learning and memory were studied using four different experimental rat models. In electroconvulsive shock- or scopolamine-induced amnesia in the step-through passive avoidance task, DM-9384 improved both types of amnesia when administered before the training trial. Aniracetam also showed similar but somewhat weaker effects. Furthermore, in the scopolamine amnesia model, an improvement was confirmed with arecoline. The dose-response curves for these compounds were bell-shaped. In the shuttle box active avoidance task, DM-9384 administered daily 1 hr before each training session facilitated the acquisition process of the avoidance response. In addition, the experiment of light-dark discrimination task with positive reinforcement showed that this compound administered daily after each session slightly accelerated the acquisition process of the correct response. These results suggest an ability of DM-9384 to enhance cognitive functions. 相似文献
6.
K Tamazawa H Arima T Kojima Y Isomura M Okada S Fujita T Furuya T Takenaka O Inagaki M Terai 《Journal of medicinal chemistry》1986,29(12):2504-2511
Four enantiomers (3a-d) of the title compound, YM-09730 (3), were synthesized by the reaction of (-)- or (+)-5-(methoxycarbonyl)-2, 6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (1a or 1b) with (S)- or (R)-1-benzyl-3-pyrrolidinol (2a or 2b). [3H]Nitrendipine binding affinity and coronary vasodilating activity of these compounds were evaluated. The absolute configuration of the most potent enantiomer (3a) with the longest duration was unequivocally determined to be (S)-1,4-dihydropyridine-C4 and (S)-pyrrolidine-C3 (S,S) by X-ray crystallographic study on 3a X HBr as well as 3a X HCl. The configuration of 1a corresponds to R, and the other enantiomers of 3 were respectively determined by chemical correlation. The potency order of the four enantiomers was (S,S)-3a greater than (S,R)-3b greater than (R,R)-3d greater than (R,S)-3c. Latent chiral characters of nifedipine derivatives with the identical ester groups were assigned by comparison of their puckering modes of 1,4-dihydropyridine (DHP) rings with those found in 3a X HCl or 3a X HBr. On the basis of the assignment, it has been revealed that the (S)-DHP nifedipine derivatives possess the synperiplanar carbonyl group at C5. The conformational restriction may be a factor causing stereoselectivity of antagonism. 相似文献
7.
K. Arima Minako Nakamura Nobuhiko Sunohara Masafumi Ogawa Midori Anno Yoko Izumiyama Shigeo Hirai Kazuhiko Ikeda 《Acta neuropathologica》1997,93(6):558-566
Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive
supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This
report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five
PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were
the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules
were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the
inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised,
at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation
of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia
of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there
are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases.
Received: 4 October 1996 / Accepted: 6 December 1996 相似文献
8.
Yoshihiro Wakayama Masahiko Inoue Makoto Murahashi Seiji Shibuya Takahiro Jimi Hiroko Kojima Hiroaki Oniki 《Annals of neurology》1996,39(2):217-223
The ultrastructural localization of adhalin and its relations to dystrophin, β-dystroglycan, and β-spectrin were studied in normal murine skeletal myofibers. The C-terminal peptides of adhalin and β-dystroglycan were synthesized based on their cDNAs, and the affinity-purified antibodies against these peptides were produced. Single-immunolabeling electron microscopy showed that the adhalin was located just inside the muscle plasma membrane or inside the myofiber a short distance from the plasma membrane. The adhalin signal was also noted at the sarcoplasmic side of plasmalemmd invaginations or at vesicular structures in subsarcolemmal areas. Double-immunogold-labeling electron microscopy disclosed a similar localization of dystrophin, β-dystroglycan, and β-spectrin. The close association of adhalin with dystrophin or β-dystroglycan was demonstrated by formation of doublets by signals of antibodies of adhalin with those of dystrophin or β-dystroglycan and was confirmed by statistical analyses. This study demonstrated that the location of adhalin is close to that of dystrophin and β-dystroglycan at the muscle plasma membrane. 相似文献
9.
Kazumasa Miyake Atsushi Tatsuguchi Mikiko Tachibana Masanobu Kusunoki Yoko Shinji Kei Shinoki Tetsuro Hiratsuka Kazuhiro Nagata Hitoshi Nishigaki Seiji Futagami Ken Wada Taku Tsukui Toshiro Yoshiyuki Akira Tokunaga Takashi Tajiri Choitsu Sakamoto 《Digestive endoscopy》2004,16(2):172-175
A 52‐year‐old Japanese woman who presented with gastrointestinal (GI) bleeding underwent a proximal gastrectomy for a gastrointestinal stromal tumor (GIST) with a foveolar hyperplasia at the apex of the tumor, 4.5 cm in size, located in the upper body of the stomach. Although GIST are often asymptomatic and are found only incidentally, clinical symptoms such as bleeding, abdominal pain, or obstruction, occasionally lead to a premorbid diagnosis. When submucosal tumors present GI bleeding, the source of the bleeding usually is an ulceration of the mucosa over the tumor. However, in the present study, it was thought that the bleeding originated from the region of foveolar hyperplasia. 相似文献
10.
Kunihiro Ichinose Mitsuru Nakamura Kenji Takezawa Ichiro Masutomi Yoichi Shima Yoko Hirayama Kahoko Sorimachi Teruhiko Shimizu Hiroyo Ishikawa Namiko Kaji Sayaka Nakajima Michiko Wataru Shiho Nishigaki Hiroshi Suwa Yosuke Toyama Masaki Okumura Yoshikazu Ishitsuka Ken Shimizu Kazuya Kokubo Kenji Sasaki Shodai Saito 《Seishin shinkeigaku zasshi》2006,108(9):945-954