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41.
Tomoaki Yuhi Akihiko Wada Ryuichi Yamamoto Masanobu Urabe Hiromi Niina Futoshi Izumi Toshihiko Yanagital 《Naunyn-Schmiedeberg's archives of pharmacology》1994,350(2):209-212
We have previously reported that in bovine adrenal chromaffin cells Ptychodiscus brevis toxin-3 (PbTx-3) does not alter the veratridine-induced 22Na influx when given alone, but increases the influx of 22Na when co-applied with either - or -scorpion venom (Wada et al. 1992). In the present study, we characterized [3H]PbTx-3 binding in bovine adrenal chromaffin cells. [3H]PbTx-3 binding was saturable, reversible and of high-affinity with an equilibrium dissociation constant (Kd) of 32.0±4.9 nmol/1 and a maximum binding capacity Bmax of 6.2 ± 1.2 pmol/4 × 106 cells (4.5 ± 0.9 pmol/mg cell protein). A Hill plot revealed the lack of cooperative interaction among the binding sites. Unlabelled PbTx-3 inhibited [3H]PbTx-3 binding with an IC50 of 31 nmol/l. However, tetrodotoxin, veratridine, - and -scorpion venom, or veratridine in combination with either - or -scorpion venom did not alter [3H]PbTx-3 binding. All these results suggest that PbTx-3 binds to a site (site 5) distinct from the previously known four toxin binding sites, which does not gate voltage-dependent Na channels by itself, but is specifically involved in the allosteric modulation of Na channels in adrenal medullary cells.
Correspondence to: A. Wada at the above address 相似文献
42.
The ultrastructure of parapapillary chorioretinal atrophy in eyes with secondary angle closure glaucoma 总被引:4,自引:0,他引:4
Toshiaki Kubota Ursula M. Schlötzer-Schrehardt Gottfried O. H. Naumann Toshihiko Kohno Hajime Inomata 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1996,234(6):351-358
Background: The present study was performed to investigate the ultrastructure of deep retinal layers and choroid corresponding to the parapapillary chorioretinal atrophy in eyes with secondary angle-closure glaucoma. Methods: The glaucomatous eyes included two eyes enucleated due to iris ring melanoma with high intraocular pressure and one eye with neovascular glaucoma enucleated due to ocular pain. The control eyes included one eye enucleated due to choroidal malignant melanoma with normal intraocular pressure and one eye enucleated during surgery for supramandibular carcinoma. These eyes were studied with light and electron microscopy. Results: In the region of parapapillary chorioretinal atrophy of glaucomatous eyes, the retinal pigment epithelial cells showed degenerative changes, such as loss of basal in foldings and microvilli, degenerated mitochondria, vacuolar degeneration and irregular distribution of melanin granules. The photoreceptors were decreased in number in this area of glaucomatous eyes. The lumen of the choriocapillary vessels adjacent to the optic nerve was collapsed. Conclusion: These results elucidate the fine structures of deep retina and choroid in the region of parapapillary chorioretinal atrophy of glaucomatous eyes, and suggest that the reduced choroidal perfusion might be the pathogenetic mechanism of glaucomatous parapapillary chorioretinal atrophy. 相似文献
43.
Tohru Ozaki Toshihiko Uematsu Satoru Nagashima Masahiko Nishimoto Mitsuyoshi Nakashima 《Naunyn-Schmiedeberg's archives of pharmacology》1991,344(4):478-487
Summary DPI 201-106 (DPI), a novel and potent cardiotonic agent, exhibits its effects by prolonging the open state of Na+ channels, resulting in an increase in action potential duration, and thus, is supposed to share the class III antiarrhythmic activity. The effects of DPI on the hemodynamics, intraventricular conduction and refractoriness of heart, and the incidence of arrhythmias induced by programmed electrical ventricular stimulation (PES) were compared with (±)-dobutamine. Dogs which survived for 5 to 7 days after the induction of myocardial infarction were used as the model. The presence of sub-acute myocardial infarction caused by occluding the left anterior descending coronary artery elicited a mild left ventricular dysfunction represented by a significant decrease in peak LV dp/dt by about 20%.Both i.v. bolus injection of DPI (1, 3 and 5 mg/kg) and i. v. continuous infusion of dobutamine (3, 5 and 10 g/kg/min), which were administered in a cumulative manner, dose-dependently improved the hemodynamic parameters. At the higher doses of both DPI (3 and 5 mg/kg) and dobutamine (5 and 10 g/kg/min) the control values were reached or even exceeded. DPI dose-dependently increased the effective refractory period (ERP) of both non-infarcted and infarcted ventricular myocardia to a similar degree, but the conduction time showed a frequency-dependent increase in the infarcted myocardium to a greater degree than in the non-infarcted myocardium after DPI. In contrast, dobutamine decreased the ERP in both non-infarcted and infarcted myocardia, and slightly increased the difference of refractoriness between the non-infarcted and infarcted zones with no effect on the intraventricular conduction. In the PES study, DPI (3 and 5 mg/kg) produced a significant decrease in the incidence of ventricular tachycardia, whereas dobutamine (5 and 10 g/kg/min) tended to worsen the arrhythmias. These findings suggest that cardiotonic agents with a class III antiarrhythmic property such as DPI may be potentially useful for the management of heart failure accompanied by ischemic heart disease.Abbreviations DPI, DPI 201-106; PES
programmed electrical ventricular stimulation
- LV dp/dt
the rate of rise of left ventricular pressure
- ERP
effective refractory period
- RVOT
right ventricular outflow tract
- VT
ventricular tachycardia
- LAD
left anterior discending coronary artery
Send offprint requests to T. Uematsu at the above address 相似文献
44.
Toshihiko Kotake Tsuneharu Miki Hideyuki Akaza Yoshinobu Kubota Yasunori Nishio Yosuke Matsumura Kazuo Ota Nobuya Ogawa 《Cancer chemotherapy and pharmacology》1991,27(4):253-257
Summary The effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 g/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period. 相似文献
45.
Kazuhiko Ogawa Takafumi Toita Yasumasa Kakinohana Keiichiro Yamaguchi Koichi Miyagi Toshihiko Kinjyo Katsumi Yamashiro Satoshi Sawada 《International journal of clinical oncology / Japan Society of Clinical Oncology》1997,2(2):67-72
Background This retrospective study analyzed the outcome in patients with intracranial germ-cell tumors to determine whether tumor response
during radiation therapy can predict achievement of primary local control with radiation therapy alone.
Methods Between 1983 and 1993, 22 patients with untreated primary intracranial germ cell tumors received a total whole brain radiation
dose of between 18 Gy and 45 Gy (mean 31.3 Gy) with or without a localized field of 10 to 36.4 Gy (mean, 22.4 Gy), or local
irradiation only (1 patient). In 10 patients with pineal tumor only, who were treated first with radiation therapy, tumor
response to radiation therapy was evaluated using computed tomography (CT) (at baseline, and approximately 20 Gy and 50 Gy).
Areas of calcification in the tumor were subtracted from total tumor volume. Follow-up time ranged from 2 to 12 years.
Results Five-year actuarial survival rates for patients with germinoma were 71%, 100% for patients with a teratoma component, and
100% for patients without histologic verification. Patients with germinomas or tumors suspected of being germinomas who were
given more than 50 Gy had no local relapse. There was no correlation between primary local control by radiation therapy alone
and initial tumor volume. The rate of tumor volume response to irradiation assesed by CT was significantly different in those
patients who relapsed compared to those who did not relapse
Conclusion Tumor response during radiation therapy using CT was considered to be predictive of primary local control with radiation therapy
alone. 相似文献
46.
Akio Hiraki Hiroshi Ueoka Toshihiko Matsuo Tomio Nakagawa Tadashi Yoshino Katsuyuki Kiura Masahiro Tabata Katsuyoshi Sakae Yuji Ohtsuki Yoshio Hiraki Mine Harada 《International journal of clinical oncology / Japan Society of Clinical Oncology》1998,3(3):186-190
A 72-year-old Japanese woman, suffering from squamous cell lung cancer with brain metastasis, underwent 2 courses of combination
chemotherapy, consisting of cisplatin and vindesine. Although both the primary tumor and the brain metastasis regressed markedly,
she developed left ocular pain with blurred vision. An abnormal mass was found in the left iris, and cytologic examination
of the aqueous aspirate revealed a few malignant cells, which, when examined by electron microscopy, were considered to be
derived from squamous cell carcinoma of the lung. 相似文献
47.
Antitumor Immunity Induction by Intracellular Hyperthermia Using Magnetite Cationic Liposomes 总被引:10,自引:0,他引:10
Mitsugu Yanase Masashige Shinkai Hiroyuki Honda Toshihiko Wakabayashi Jun Yoshida Takeshi Kobayashi 《Cancer science》1998,89(7):775-782
Induction of antitumor immunity to T-9 rat glioma by intracellular hyperthermia using functional magnetic particles was investigated. Magnetite cationic liposomes (MCLs), which have a positive surface charge, were used as heating mediators for intracellular hyperthermia. Solid T-9 glioma tissues were formed subcutaneously on both femurs of female F344 rats, and MCLs were injected via a needle only into the left solid tumors (treatment side). The rats were then divided into two groups, which received no irradiation, or irradiation for 30 min given three times at 24-h intervals with an alternating magnetic field (118 kHz, 384 Oe). On the treatment side, the tumor tissue disappeared completely in many rats exposed to the magnetic field. The tumor tissue on the opposite side also disappeared completely, even though MCLs were not injected into the right solid tumors. To examine whether a long-lasting and tumor-specific immunity could be generated, the rats that had been cured by the hyperthermia treatment were rechallenged with T-9 cells 3 months later. After a period of transient growth, all tumors disappeared. Furthermore, immuno-cytochemical assay revealed that the immune response induced by the hyperthermia treatment was mediated by both CD8+ and CD4+ T cells and accompanied by a marked augmentation of tumor-selective cytotoxic T lymphocyte activity. These results suggest that our magnetic particles are potentially effective tools for hyperthermic treatment of solid tumors, because in addition to killing of the tumor cells by heat, a host immune response is induced. 相似文献
48.
Ohno Ken; Araki Naohiro; Yanase Toshihiko; Nawata Hajime; Iida Mitsuru 《Toxicological sciences》2005,83(2):406
The following sentences should have read: Results, Reproducibility 相似文献
49.
Dihydropyrimidine dehydrogenase activity in 150 healthy Japanese volunteers and identification of novel mutations. 总被引:4,自引:0,他引:4
50.
Satoshi Gando Atsushi Shiraishi Takeshi Wada Kazuma Yamakawa Seitaro Fujishima Daizoh Saitoh Shigeki Kushimoto Hiroshi Ogura Toshikazu Abe Toshihiko Mayumi Junichi Sasaki Joji Kotani Naoshi Takeyama Ryosuke Tsuruta Kiyotsugu Takuma Shin-ichiro Shiraishi Yasukazu Shiino Taka-aki Nakada Kohji Okamoto Yuichiro Sakamoto Akiyoshi Hagiwara Satoshi Fujimi Yutaka Umemura Yasuhiro Otomo 《Medicine》2022,101(32)
Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified. 相似文献