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Noda, Akihiro ; Takamatsu, Hiroyuki ; Murakami, Yoshihiro ; Yajima, Kazuyoshi ; Tatsumi, Mitsuyoshi ; Ichise, Rikiya ; Nishimura, Shintaro
概要:
金沢大学大学院医学系研究科<br />This study used PET to measure the time course of the brain concentration of 18F-labeled N-(4-acetyl-
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1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a novel antidementia drug, after oral administration to conscious rhesus monkeys. Methods: Three young-adult male rhesus monkeys were tested. FK960 (0.1 mg/kg) containing about 370 MBq of 18F-FK960 was administered orally to each monkey. Dynamic PET images were acquired for 4 h from 5 min after the administration. Arterial blood samples were withdrawn during PET scanning and were analyzed by an automatic well γ-counter and thin-layer chromatography to determine the time course of authentic 18F-FK960 activity concentration in plasma. FK960 concentrations in brain and plasma were calculated in units of mol/L using the specific activity of FK960 preparations. Results: 18F-FK960 penetrated the blood-brain barrier and underwent perfusion-dependent distribution in the entire brain. Maximal concentrations in the brain and plasma were 1.11 ± 0.30 x 10-7 mol/L (at 3.0 ± 0.6 h after administration) and 4.04 ± 1.29 x 10-7 mol/L (at 2.0 ± 1.1 h after administration), respectively. Conclusion: We succeeded in measuring the FK960 concentration in the brains of conscious monkeys and in plasma after oral administration at a dose of 0.1 mg/kg. The results suggested that this method can measure the FK960 concentration in the human brain, and a potential use of the PET technique in drug development was demonstrated.
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| 2.
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Takamatsu, Hiroyuki ; Honda, Sumihisa ; Miyamoto, Toshihiro ; Yokoyama, Kenji ; Hagiwara, Shotaro ; Ito, Toshiro ; Tomita, Naoto ; Iida, Shinsuke ; Iwasaki, Toshihiro ; Sakamaki, Hisashi ; Suzuki, Ritsuro ; Sunami, Kazutaka
概要:
We evaluated the clinical significance of prognostic factors including the International Staging System (ISS) and modifi
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ed European Group for Blood and Marrow Transplantation response criteria in 1650 Japanese patients with multiple myeloma (MM) who underwent upfront single autologous stem cell transplantation (ASCT). We categorized patients into two treatment cohorts: pre-novel agent era (1995-2006) and novel agent era (2008-2011). The combined percentage of pre-ASCT complete response and very good partial response cases (463 of 988, 47%) significantly increased during the novel agent era compared with the pre-novel agent era (164 of 527, 31%; P < 0.0001). The 2-year overall survival (OS) rate of 87% during the novel agent era was a significant improvement relative to that of 82% during the pre-novel agent era (P = 0.019). Although significant differences in OS were found among ISS stages during the pre-novel agent era, no significant difference was observed between ISS I and II (P = 0.107) during the novel agent era. The factors independently associated with a superior OS were female gender (P = 0.002), a good performance status (P = 0.024), lower ISS (P < 0.001), pre-ASCT response at least partial response (P < 0.001) and ASCT during the novel agent era (P = 0.017). These results indicate that the response rate and OS were significantly improved, and the ISS could not clearly stratify the prognoses of Japanese patients with MM who underwent upfront single ASCT during the novel agent era. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
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| 3.
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Takamatsu, Hiroyuki ; Araki, Raita ; Nishimura, Ryosei ; Yachie, Akihiro ; Espinoza, J. Luis ; Okumura, Hirokazu ; Yoshida, Takashi ; Kuzushima, Kiyotaka ; Nakao, Shinji
概要:
Leukemic Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative diseases (PTLD) following allogeneic he
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matopoietic stem cell transplantation are extremely rare. We can successfully treat an EBV-associated leukemic lymphoma patient with rituximab, cidofovir, and donor lymphocyte infusion (DLI). In the present case, EBV-specific T cells that were present in the peripheral blood before rituximab administration treatment rapidly increased after DLI in association with a decrease in the EBV-DNA load. © 2016 Elsevier B.V.<br />Embargo Period 12 months
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| 4.
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Takamatsu, Hiroyuki ; Yagasaki, Hiroshi ; Takahashi, Yoshiyuki ; Hama, Asahito ; Saikawa, Yutaka ; Yachie, Akihiro ; Koizumi, Shoichi ; Kojima, Seiji ; Nakao, Shinji
概要:
金沢大学医薬保健研究域医学系<br />A 1-yr-old Japanese male infant developed hepatitis-associated aplastic anemia (AA), and anti-thymoc
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yte globulin (ATG) plus cyclosporine A (CsA) was administered without any appreciable effects. Laboratory examination of the patient's serum obtained before therapy revealed various autoantibodies, such as PA-IgG, anti-platelets, anti-single-stranded DNA (ssDNA), and anti-double-stranded DNA (dsDNA) antibodies (Abs) in addition to anti-DRS-1 Abs and anti-moesin Abs, both of which are known to be detectable in approximately 40% of all patients presenting with AA. He was therefore treated with 17.5mg/kg/d rituximab 5.5months after ATG/CsA therapy. The same rituximab therapy was repeated three times once a month thereafter. His neutrophil counts started to increase 50d after the first rituximab therapy and he achieved a complete remission at 16months after the last rituximab administration. All of the autoantibodies including anti-ssDNA, dsDNA, DRS-1, and moesin became undetectable when he attained the remission. Anti-CD20 monoclonal antibody therapy may be effective in a subset of patients with AA characterized by the presence of autoantibodies. © 2011 John Wiley & Sons A/S.
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| 5.
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論文
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Takamatsu, Hiroyuki ; Honda, Sumihisa ; Miyamoto, Toshihiro ; Yokoyama, Kenji ; Hagiwara, Shotaro ; Ito, Toshiro ; Tomita, Naoto ; Iida, Shinsuke ; Iwasaaki, Toshihiro ; Sakamaki, Hisashi ; Suzuki, Ritsuro ; Sunami, Kazutaka
概要:
We evaluated the clinical significance of prognostic factors including the International Staging System (ISS) and modifi
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ed European Group for Blood and Marrow Transplantation response criteria in 1650 Japanese patients with multiple myeloma (MM) who underwent upfront single autologous stem cell transplantation (ASCT). We categorized patients into two treatment cohorts: pre-novel agent era (1995-2006) and novel agent era (2008-2011). The combined percentage of pre-ASCT complete response and very good partial response cases (463 of 988, 47%) significantly increased during the novel agent era compared with the pre-novel agent era (164 of 527, 31%; P < 0.0001). The 2-year overall survival (OS) rate of 87% during the novel agent era was a significant improvement relative to that of 82% during the pre-novel agent era (P = 0.019). Although significant differences in OS were found among ISS stages during the pre-novel agent era, no significant difference was observed between ISS I and II (P = 0.107) during the novel agent era. The factors independently associated with a superior OS were female gender (P = 0.002), a good performance status (P = 0.024), lower ISS (P < 0.001), pre-ASCT response at least partial response (P < 0.001) and ASCT during the novel agent era (P = 0.017). These results indicate that the response rate and OS were significantly improved, and the ISS could not clearly stratify the prognoses of Japanese patients with MM who underwent upfront single ASCT during the novel agent era. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
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