177 results on '"Kohshi Ohishi"'
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2. Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway
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Kensuke Hachiya, Masahiro Masuya, Naoki Kuroda, Misao Yoneda, Junya Tsuboi, Keiki Nagaharu, Komei Nishimura, Takuya Shiotani, Kohshi Ohishi, Isao Tawara, and Naoyuki Katayama
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Medicine ,Science - Abstract
Abstract The introduction of anti-inflammatory therapies has enabled substantial improvement of disease activity in patients with inflammatory bowel diseases (IBD). However, IBD can lead to serious complications such as intestinal fibrosis and colorectal cancer. Therefore, novel therapies reducing the development of these complications are needed. Angiotensin II (Ang II) promotes tissue inflammation by stimulating the production of monocyte chemoattractant protein-1 (MCP-1) or proinflammatory cytokines. It plays a pivotal role in IBD progression. Although blockade of Ang II has been reported to ameliorate experimental colitis and reduce colorectal cancer risk, the cellular and molecular mechanisms remain poorly understood. Our previous work showed that irbesartan, an Ang II type 1 receptor blocker, reduced the number of C–C chemokine receptor 2-positive (CCR2+) monocytic cells in the inflamed pancreas. This study aimed to investigate the possible antifibrotic and antitumour effects of irbesartan using the azoxymethane/dextran sodium sulphate mouse model. Irbesartan suppressed MCP-1 production and the accumulation of Ly6C+CCR2+ monocytes and fibrocytes in the inflamed colon, downregulated the expression of type 1 collagen and matrix metalloproteinase 9 and inhibited the development of intestinal fibrosis and tumours. Our observations suggest that blocking the MCP-1/CCR2 pathway using irbesartan might be beneficial in preventing colitis-associated colon tumours.
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- 2021
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3. Impact of physician−pharmacist collaborative protocol-based pharmacotherapy management for HIV outpatients: a retrospective cohort study
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Kimihiko Urano, Miki Ishibashi, Takeshi Matsumoto, Kohshi Ohishi, Yuichi Muraki, Takuya Iwamoto, Junichi Kunimasa, and Masahiro Okuda
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HIV ,AIDS ,PBPM ,Pharmacist ,Therapeutics. Pharmacology ,RM1-950 ,Pharmacy and materia medica ,RS1-441 - Abstract
Abstract Background Effective treatment for human immunodeficiency virus (HIV) infection requires close cooperation among healthcare professionals. This is because maintaining continuity with treatment regimens is important in anti-HIV therapy. In addition, explaining medication use is more important than that for other diseases. Since 2010, pharmacists at the Mie University Hospital have been interviewing patients, selecting drugs, and formulating medication plans for HIV-positive patients. In August 2011, we established the physician and pharmacist-led collaborative Protocol-based Pharmacotherapy Management (PBPM) to increase the efficacy and safety of treatment, while reducing the burden on physicians. In the present study, we evaluated the outcomes associated with PBPM for HIV pharmacotherapy. Methods We prepared protocols for drug selection, timing of interventions, and methods of intervention according to various guidelines. This study included 40 HIV-positive patients receiving outpatient care between January 2009 and February 2017. Of these patients, 17 received treatment before implementing PBPM and 23 patients received treatment afterward. We compared the intervention parameters between before and after the implementation of PBPM. Results The proportion of patients receiving prescription proposals from pharmacists was markedly higher after introducing PBPM (6 out of 17 patients vs. 23 out of 23 patients). All prescription proposals were accepted by physicians before and after PBPM. The number of interviews before antiretroviral therapy (ART) initiation (median [range]) decreased from 2 [1–5] to 1 [1–3] after PBPM introduction, suggesting the time to introduction of treatment has been shortened. Before the introduction of PBPM, nine patients required a change in their ART prescriptions and four patients were hospitalized (one patient was hospitalized due to an error in the self-administration of anti-HIV medicines, two patients were hospitalized due to interruptions in medication, and one patient was hospitalized for the treatment of other diseases). Only one patient was hospitalized after PBPM, and was unrelated to drug adherence. The proportion of patients with a reduced HIV-RNA load increased from 71 to 100%. Furthermore, the proportion of patients who maintained levels below the limit of quantitation increased from 59 to 91% after implementing PBPM. Conclusion The implementation of PBPM for HIV outpatients improves the efficacy and safety of HIV pharmacotherapy.
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- 2020
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4. Usefulness of the APTT waveform for the diagnosis of DIC and prediction of the outcome or bleeding risk
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Kei Suzuki, Hideo Wada, Takeshi Matsumoto, Makoto Ikejiri, Kohshi Ohishi, Yoshiki Yamashita, Hiroshi Imai, Toshiaki Iba, and Naoyuki Katayama
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APTT waveform ,Hypofibrinogenemia ,Bleeding ,Outcome ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Background The usefulness of the activated partial thromboplastin time (APTT) waveform has been reported in hemophilia, acquired hemophilia and monitoring for anticoagulants. Material and methods The APTT waveform was examined in patients suspected of having disseminated intravascular coagulation (DIC) to analyze its usefulness for the diagnosis of DIC or the prediction of the outcome or bleeding risk. Results DIC with fibrinogen
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- 2019
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5. The Evaluation of APTT Reagents in Reference Plasma, Recombinant FVIII Products; Kovaltry® and Jivi® Using CWA, Including sTF/7FIX Assay
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Hideo Wada MD, PhD, Katsuya Shiraki MD, PhD, Takeshi Matsumoto MD, PhD, Kohshi Ohishi MD, PhD, Hideto Shimpo MD, PhD, Yumi Sakano Mrs, Hiroko Nishii Mrs, and Motomu Shimaoka MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The FVIII activity in patients treated with several extended half-life FVIII (EHL-FVIII) agents different when various activated partial thromboplastin time (APTT) reagents were used. The present study examined the difference in clot waveform analysis (CWA) findings and FVIII activity when various APTT reagents and CWA were used. The CWA including FVIII activity was measured using 12 APTT reagents, and the FIX activation based on a small amount of tissue factor assay (sTF/FIX) were examined in reference plasma (RP), EHL-FVIII (Jivi ® ) and Kovaltry ® . The 3 APTT reagents were associated with high variation in the peak time and height in the CWA when analyzing low concentrations of FVIII. The peak time and height could not be measured with one APTT reagent, and there were marked differences in the CWA findings between Jivi ® and Kovaltry ® among APTT reagents. Several APTT reagents showed a markedly lower FVIII activity with Jivi ® than with Kovaltry ® . In the FVIII assay, the peak time measured with sTF/FIX did not differ markedly between Jivi ® and Kovaltry ® ; however, the FVIII activity in Jivi ® (as measured by the peak height) tended to be higher than in Kovaltry ® . The CWA findings for monitoring Jivi ® varied for monitoring Jivi ® depending on the APTT reagents used, and sTF/FIX assay may be able to measure the EHL-FVIII.
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- 2021
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6. Platelet-Rich Plasma-Releasate (PRPr) for the Treatment of Discogenic Low Back Pain Patients: Long-Term Follow-Up Survey
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Koji Akeda, Norihiko Takegami, Junichi Yamada, Tatsuhiko Fujiwara, Kohshi Ohishi, Satoshi Tamaru, and Akihiro Sudo
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low back pain ,disc degeneration ,platelet-rich plasma ,Medicine (General) ,R5-920 - Abstract
Background and Objectives: Clinical studies of platelet-rich plasma (PRP) for the treatment of low back pain (LBP) have been reported; however, less is known about its long-term efficiency. Materials and Methods: This study was a long-term follow-up of a previous prospective clinical feasibility study for the use of PRP releasate (PRPr) to treat discogenic LBP patients. Among 14 patients, 11 patients were evaluated for a long-term survey. The efficacy was assessed by a visual analogue scale (VAS) for LBP intensity and the Roland-Morris Disability Questionnaire (RDQ) for LBP-related disability. Radiographic disc height was evaluated for seven patients. Results: Improvements in VAS and RDQ were sustained at an average of 5.9 years after the intradiscal injection of PRPr (p < 0.01 vs. baseline, respectively). Clinically meaningful improvements (more than 30% decrease from baseline) in VAS and RDQ were identified in 91% of patients at final survey. The radiographic measurement of disc height of PRPr-injected discs showed a mild decrease (13.8% decrease compared to baseline) during the average 5.9 years. Conclusions: The results of this study with a small number of patients suggest that the intradiscal injection of PRPr has a safe and efficacious effect on LBP improvement for more than 5 years after treatment. Further large-scale studies would be needed to confirm the clinical evidence for the use of PRPr for the treatment of patients with discogenic LBP.
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- 2022
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7. Platelet-Rich Plasma Releasate versus Corticosteroid for the Treatment of Discogenic Low Back Pain: A Double-Blind Randomized Controlled Trial
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Koji Akeda, Kohshi Ohishi, Norihiko Takegami, Takao Sudo, Junichi Yamada, Tatsuhiko Fujiwara, Rui Niimi, Takeshi Matsumoto, Yuki Nishimura, Toru Ogura, Satoshi Tamaru, and Akihiro Sudo
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intervertebral disc degeneration ,platelet-rich plasma ,corticosteroid ,low back pain ,Medicine - Abstract
Clinical application of platelet-rich plasma is gaining popularity in treating low back pain (LBP). This study investigated the efficacy and safety of platelet-rich plasma releasate (PRPr) injection into degenerated discs of patients with discogenic LBP. A randomized, double-blind, active-controlled clinical trial was conducted. Sixteen patients with discogenic LBP received an intradiscal injection of either autologous PRPr or corticosteroid (CS). Patients in both groups who wished to have PRPr treatment received an optional injection of PRPr eight weeks later. The primary outcome was change in VAS from baseline at eight weeks. Secondary outcomes were pain, disability, quality of life (QOL), image analyses of disc degeneration, and safety for up to 60 weeks. The VAS change at eight weeks did not significantly differ between the two groups. Fifteen patients received the optional injection. Compared to the CS group, the PRPr group had a significantly improved disability score at 26 weeks and walking ability scores at four and eight weeks. Radiographic disc height and MRI grading score were unchanged from baseline. PRPr caused no clinically important adverse events. PRPr injection showed clinically significant improvements in LBP intensity equal to that of CS. PRPr treatment relieved pain, and improved disability and QOL during 60 weeks of observation.
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- 2022
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8. Update on the Clot Waveform Analysis
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Hideo Wada MD, PhD, Takeshi Matsumoto MD, PhD, Kohshi Ohishi MD, PhD, Katsuya Shiraki MD, PhD, and Motomu Shimaoka MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The activated partial thromboplastin time (APTT)–clot waveform analysis (CWA) was previously reported to be associated with the early detection of disseminated intravascular coagulation and was also reported to be able to measure very low levels of coagulation factor VIII activity. The software program for the analysis for the APTT-CWA allows the associated first and second derivative curves (first and second DCs) to be displayed. The first and second DC reflect the velocity and acceleration, respectively. The height of the first DC reflects the “thrombin burst” and bleeding risk, while that of the second DC is useful for detecting any coagulation factor deficiency and abnormal enhancement of coagulation by phospholipids. Activated partial thromboplastin time-CWA aids in making a differential diagnosis which is difficult to do using only the routine APTT. The CWA is currently used for many applications in the clinical setting, including the monitoring of hemophilia patients and patients receiving anticoagulant therapy and the differential diagnosis of diseases.
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- 2020
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9. Intradiscal Injection of Autologous Platelet-Rich Plasma Releasate to Treat Discogenic Low Back Pain: A Preliminary Clinical Trial
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Koji Akeda, Kohshi Ohishi, Koichi Masuda, Won C. Bae, Norihiko Takegami, Junichi Yamada, Tomoki Nakamura, Toshihiko Sakakibara, Yuichi Kasai, and Akihiro Sudo
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Intervertebral disc degeneration ,Platelet-rich plasma ,Low back pain ,Clinical trial ,Medicine - Abstract
Study DesignPreliminary clinical trial.PurposeTo determine the safety and initial efficacy of intradiscal injection of autologous platelet-rich plasma (PRP) releasate in patients with discogenic low back pain.Overview of LiteraturePRP, which is comprised of autologous growth factors and cytokines, has been widely used in the clinical setting for tissue regeneration and repair. PRP has been shown in vitro and in vivo to potentially stimulate intervertebral disc matrix metabolism.MethodsInclusion criteria for this study included chronic low back pain without leg pain for more than 3 months; one or more lumbar discs (L3/L4 to L5/S1) with evidence of degeneration, as indicated via magnetic resonance imaging (MRI); and at least one symptomatic disc, confirmed using standardized provocative discography. PRP releasate, isolated from clotted PRP, was injected into the center of the nucleus pulposus. Outcome measures included the use of a visual analog scale (VAS) and the Roland-Morris Disability Questionnaire (RDQ), as well as X-ray and MRI (T2-quantification).ResultsData were analyzed from 14 patients (8 men and 6 women; mean age, 33.8 years). The average follow-up period was 10 months. Following treatment, no patient experienced adverse events or significant narrowing of disc height. The mean pain scores before treatment (VAS, 7.5±1.3; RDQ, 12.6±4.1) were significantly decreased at one month, and this was generally sustained throughout the observation period (6 months after treatment: VAS, 3.2±2.4, RDQ; 3.6±4.5 and 12 months: VAS, 2.9±2.8; RDQ, 2.8±3.9; p
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- 2017
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10. Comments to: An Evaluation of Hemostatic Abnormalities in Patients With Hemophilia by APTT Waveform, Peak Heights of APTT Waveform Are Useful for Diagnosing Hemophilia or Inhibitor
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Takeshi Matsumoto MD, PhD, Hideo Wada MD, PhD, Kohshi Ohishi MD, PhD, Yoshiki Yamashita MD, PhD, Makoto Ikejiri PhD, and Naoyuki Katayama MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2019
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11. Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan
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Naoto Takahashi, Kaichi Nishiwaki, Chiaki Nakaseko, Nobuyuki Aotsuka, Koji Sano, Chikako Ohwada, Jun Kuroki, Hideo Kimura, Michihide Tokuhira, Kinuko Mitani, Kazuhisa Fujikawa, Osamu Iwase, Kohshi Ohishi, Fumihiko Kimura, Tetsuya Fukuda, Sakae Tanosaki, Saori Takahashi, Yoshihiro Kameoka, Hiroyoshi Nishikawa, and Hisashi Wakita
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
The purpose of this trial was to evaluate the efficacy of 2-year consolidation therapy with nilotinib, at a dose of 300 mg twice daily, for achieving treatment-free remission in chronic myeloid leukemia patients with a deep molecular response (BCR-ABL1IS ≤0.0032%). Successful treatment-free remission was defined as no confirmed loss of deep molecular response. We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4–78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achieving a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free survival, 75.6 versus 48.6%, respectively; P=0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor-withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib. This study was registered with UMIN-CTR (UMIN000005904).
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- 2018
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12. Expression of CD25 fluctuates in the leukemia-initiating cell population of CD25-positive AML.
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Yuki Kageyama, Hiroshi Miwa, Rino Arakawa, Isao Tawara, Kohshi Ohishi, Masahiro Masuya, Kazunori Nakase, and Naoyuki Katayama
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Medicine ,Science - Abstract
CD25 is expressed on leukemic cells in 10-20% cases of acute myeloid leukemia (AML), and its expression is associated with poor prognosis. We reevaluated the relationship between CD25 expression and the leukemia-initiating cell (LIC) properties of AML using a patient-derived xenograft model. We divided lineage marker-negative (Lin-) CD34+CD38- or Lin-CD34+ cells from CD25-positive AML into CD25-positive and -negative populations, and then transplanted each population into NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz mice. Leukemic engraftment was observed with both CD25-positive and -negative populations from three of nine CD25-positive AML patients. In two of those three patients, CD25-positive and -negative Lin-CD34+ cells engrafted at the primary transplantation led to leukemic engraftment at the secondary transplantation, in which engrafted cells contained both CD25-positive and -negative Lin-CD34+ AML cells. In an in vitro culture system, expression of CD25 was considerably induced in the CD25-negative population of Lin-CD34+ cells from two cases of CD25-positive AML. In one case, CD25-positive Lin-CD34+ cells gave rise to CD25-negative as well as -positive CD34+ cells. These observations suggest that there exist CD25-positive and -negative populations that can reconstitute CD25-positive AML in a patient-derived xenograft model, and that CD25 expression fluctuates in the LICs of AML.
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- 2018
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13. Monocytes infiltrate the pancreas via the MCP-1/CCR2 pathway and differentiate into stellate cells.
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Kazuko Ino, Masahiro Masuya, Isao Tawara, Eri Miyata, Keiko Oda, Yoshiki Nakamori, Kei Suzuki, Kohshi Ohishi, and Naoyuki Katayama
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Medicine ,Science - Abstract
Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP)(+)CD45(-) cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4). Because the vast majority of EGFP(+)CD45(-) cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs). EGFP(+) PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1) and angiotensin II (Ang II) increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2) and Ang II type 1 receptor (AT1R), were expressed on Ly6C(high) monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP(+)F4/80(+)CCR2(+) monocytic cells and EGFP(+) PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP(+) bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP(+) PaSCs in injured mice. We propose that CCR2(+) monocytes migrate into the pancreas possibly via the MCP-1/CCR2 pathway and give rise to PaSCs.
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- 2014
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14. The experience of flow cytometry for specific antibody against cisplatin‐treated red blood cells: A case report
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Kazutaka Suzuki, Keiki Nagaharu, Mitsuko Maruyama, Takeshi Matsumoto, Kohshi Ohishi, and Isao Tawara
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Immunology ,Immunology and Allergy ,Hematology - Published
- 2023
15. Clinical Utility of Flow Cytometry for Detection of Anti-Jkb IgM in Acute Haemolytic Transfusion Reaction.
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Keiki Nagaharu, Takuya Izumi, Mitsuko Maruyama, Yuka Sugimoto, Kohshi Ohishi, Isao Tawara, Eiji Usui, and Shigehisa Tamaki
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- 2024
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16. Efficacy and safety of ropeginterferon alfa-2b in Japanese patients with polycythemia vera: an open-label, single-arm, phase 2 study
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Yoko, Edahiro, Kohshi, Ohishi, Akihiko, Gotoh, Katsuto, Takenaka, Hirohiko, Shibayama, Takayuki, Shimizu, Kensuke, Usuki, Kazuya, Shimoda, Masafumi, Ito, Scott A, VanWart, Oleh, Zagrijtschuk, Albert, Qin, Hiroaki, Kawase, Narihisa, Miyachi, Toshiaki, Sato, Norio, Komatsu, and Keita, Kirito
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Treatment Outcome ,Japan ,Humans ,Hematology ,Interferon alpha-2 ,Polycythemia Vera ,Alleles ,Recombinant Proteins - Abstract
Ropeginterferon alfa-2b is a novel, site-selective, monopegylated recombinant human interferon alfa-2b. Safety and efficacy of ropeginterferon alfa-2b for the treatment of polycythemia vera were demonstrated in clinical studies conducted in European countries, but clinical studies in Japanese patients are lacking. This phase 2, open-label, multicenter, single-arm study investigated the safety and efficacy of ropeginterferon alfa-2b in 29 Japanese patients with polycythemia vera including young patients and patients with low thrombosis risk who are difficult to receive guideline-based standard treatments. The primary outcome of durable complete hematologic response without phlebotomy at months 9 and 12 was achieved by 8/29 (27.6%) patients. The fastest complete hematologic response was observed at week 12. A corresponding reduction in the JAK2 V617F allele burden from baseline to 52 weeks was also observed (mean ± standard deviation = - 19.2% ± 22.6%). No new safety concerns were identified in Japanese patients when compared with previous studies of ropeginterferon alfa-2b in European populations; the most common treatment-related adverse events were alopecia (55.2%), fatigue (27.6%) and influenza-like illness (27.6%). Most treatment-related adverse events were mild or moderate, with none of grade ≥ 3. Ropeginterferon alfa-2b is a safe and efficacious treatment option in Japanese patients with polycythemia vera.
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- 2022
17. Supplementary Figure Legend from Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer
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Hiroshi Shiku, Naoyuki Katayama, Kazutoh Takesako, Junichi Mineno, Ikuei Nukaya, Daisuke Tomura, Hirofumi Yoshioka, Tomohide Kidokoro, Masashige Tanabe, Naoki Inoue, Taizo Shiraishi, Kohshi Ohishi, Hiroaki Naota, Satoshi Kokura, Takeshi Ishikawa, Shugo Ueda, Sahoko Sugino, Kanako Saito, Mikiya Ishihara, Naoko Imai, Yoshihiro Miyahara, Hiroaki Ikeda, and Shinichi Kageyama
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Adoptive transfer of MAGE-A4 T-cell receptor gene−transduced lymphocytes in patients with recurrent esophageal cancer.
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- 2023
18. Supplementary Figure S6 from Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer
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Hiroshi Shiku, Naoyuki Katayama, Kazutoh Takesako, Junichi Mineno, Ikuei Nukaya, Daisuke Tomura, Hirofumi Yoshioka, Tomohide Kidokoro, Masashige Tanabe, Naoki Inoue, Taizo Shiraishi, Kohshi Ohishi, Hiroaki Naota, Satoshi Kokura, Takeshi Ishikawa, Shugo Ueda, Sahoko Sugino, Kanako Saito, Mikiya Ishihara, Naoko Imai, Yoshihiro Miyahara, Hiroaki Ikeda, and Shinichi Kageyama
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Disease progression and overall survival of 10 patients who received transfer of TCR-transduced lymphocytes.
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- 2023
19. Data from Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer
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Hiroshi Shiku, Naoyuki Katayama, Kazutoh Takesako, Junichi Mineno, Ikuei Nukaya, Daisuke Tomura, Hirofumi Yoshioka, Tomohide Kidokoro, Masashige Tanabe, Naoki Inoue, Taizo Shiraishi, Kohshi Ohishi, Hiroaki Naota, Satoshi Kokura, Takeshi Ishikawa, Shugo Ueda, Sahoko Sugino, Kanako Saito, Mikiya Ishihara, Naoko Imai, Yoshihiro Miyahara, Hiroaki Ikeda, and Shinichi Kageyama
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Purpose: Preparative lymphodepletion, the temporal ablation of the immune system, has been reported to promote persistence of transferred cells along with increased rates of tumor regression in patients treated with adoptive T-cell therapy. However, it remains unclear whether lymphodepletion is indispensable for immunotherapy with T-cell receptor (TCR) gene–engineered T cells.Experimental Design: We conducted a first-in-man clinical trial of TCR gene-transduced T-cell transfer in patients with recurrent MAGE-A4–expressing esophageal cancer. The patients were given sequential MAGE-A4 peptide vaccinations. The regimen included neither lymphocyte-depleting conditioning nor administration of IL2. Ten patients, divided into 3 dose cohorts, received T-cell transfer.Results: TCR-transduced cells were detected in the peripheral blood for 1 month at levels proportional to the dose administered, and in 5 patients they persisted for more than 5 months. The persisting cells maintained ex vivo antigen-specific tumor reactivity. Despite the long persistence of the transferred T cells, 7 patients exhibited tumor progression within 2 months after the treatment. Three patients who had minimal tumor lesions at baseline survived for more than 27 months.Conclusions: These results suggest that TCR-engineered T cells created by relatively short-duration in vitro culture of polyclonal lymphocytes in peripheral blood retained the capacity to survive in a host. The discordance between T-cell survival and tumor regression suggests that multiple mechanisms underlie the benefits of preparative lymphodepletion in adoptive T-cell therapy. Clin Cancer Res; 21(10); 2268–77. ©2015 AACR.
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- 2023
20. Supplementary Table S1 from Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer
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Hiroshi Shiku, Naoyuki Katayama, Kazutoh Takesako, Junichi Mineno, Ikuei Nukaya, Daisuke Tomura, Hirofumi Yoshioka, Tomohide Kidokoro, Masashige Tanabe, Naoki Inoue, Taizo Shiraishi, Kohshi Ohishi, Hiroaki Naota, Satoshi Kokura, Takeshi Ishikawa, Shugo Ueda, Sahoko Sugino, Kanako Saito, Mikiya Ishihara, Naoko Imai, Yoshihiro Miyahara, Hiroaki Ikeda, and Shinichi Kageyama
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Peptides which have homologue sequences with MAGE-A4143-151 peptide.
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- 2023
21. Clinical utility of oral management in allogeneic hematopoietic stem cell transplantation recipients: microbiological evidence based on molecular analysis of oral bacteria
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Jouji Nomura, Naoyuki Katayama, Atsushi Fujieda, Kazunori Nakase, Naoya Arai, Akiko Nakamura, Kohshi Ohishi, Jumpei Kawajiri, Kokoro Nagata, and Kazuko Ino
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Periodontitis ,medicine.medical_specialty ,Evidence-based practice ,biology ,business.industry ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,medicine.disease ,biology.organism_classification ,Oral hygiene ,Molecular analysis ,Transplantation ,stomatognathic diseases ,Oncology ,Internal medicine ,Mucositis ,Medicine ,business ,Bacteria - Abstract
This study aimed to clarify the clinical utility of oral management to prevent bloodstream infections by oral bacteria microbiologically in patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT). Ten consecutive patients with hematological malignancies undergoing ASCT were enrolled in this study. We implemented dental treatments before transplantation, if required, and carried out oral hygiene instructions and oral management every other day after transplantation. Molecular analysis of bacterial DNA for seven oral species using a polymerase chain reaction (PCR) assay was performed for oral samples and peripheral blood once a week for 3 weeks after transplantation. Periodontitis was found in all 10 patients (mild grade in 3 and middle grade in 7) for whom basic periodontal therapy was conducted. Necessary dental procedures, including tooth extraction were performed in 5 patients. After transplantation, oral mucositis occurred in 10 patients (grade 1 in 3, grade 2 in 2, and grade 3 in 5) for whom oral hygiene instruction and oral care were continued every other day. PCR-identified three to six bacterial species in oral samples from nine patients, but none in peripheral blood from any patient during the observation period. Our study suggests that oral management could prevent bloodstream infections by oral bacteria in ASCT recipients despite the existence of periodontitis or oral mucositis. Its utility was confirmed by microbiological evidence based on molecular data.
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- 2021
22. Unveiling Highly Fluctuating Single-Cell Transcriptome Dynamics at a Novel Bifurcation Point in a Human Lymphoid Pathway
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Keiki Nagaharu, Yasuhiro Kojima, Yuki Kageyama, Yuka Sugimoto, Masahiro Masuya, Shigeru Nii, Masahide Seki, Yutaka Suzuki, Isao Tawara, Teppei Shimamura, Naoyuki Katayama, and Kohshi Ohishi
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
23. MPL exon 10 mutations other than canonical MPL W515L/K mutations identified by in-house MPL exon 10 direct sequencing in essential thrombocythemia
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Isao Tawara, Maki Nakamura, Kaname Nakatani, Ikeda T, Yuka Sugimoto, Shigehisa Tamaki, Naoyuki Katayama, Keiki Nagaharu, Kohshi Ohishi, Minoru Mizutani, and Makoto Ikejiri
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Mutation ,medicine.medical_specialty ,Hematology ,Direct sequencing ,Essential thrombocythemia ,Biology ,medicine.disease_cause ,medicine.disease ,Molecular biology ,Exon ,Internal medicine ,medicine ,Mutation testing ,In patient ,Myelofibrosis - Abstract
MPL exon 10 mutations are one of the driver mutations in essential thrombocythemia (ET) or myelofibrosis (MF). We have established an in-house MPL mutation analysis system, covering the entire region of MPL exon 10 by direct sequencing. Since 2009, MPL exon 10 mutation analysis has been performed for diagnosis of myeloproliferative neoplasms (MPN) without JAK2 V617F or CALR exon 9 mutations. So far, 11 cases of MPL exon 10 mutation have been found in 51 patients with suspected MPN. In patients with ET, we detected five non-canonical MPL mutations including one novel mutation, MPL R514_P518delinsK, and one canonical MPL W515L mutation. Notably, three ET patients without canonical MPL mutations had thrombotic events. Meanwhile, in primary or secondary MF, only canonical MPL W515L/K mutations were found. Further cases need to be examined to elucidate the full MPL mutation profile in MPN. However, our data indicate that analysis of the whole of MPL exon 10 is warranted for the diagnosis of MPL mutations, especially in ET, and that the use of Japanese commercial laboratory tests that only detect canonical MPL W515L/K mutations may miss a significant percentage of MPL exon 10 mutations, which could delay the administration of anti-thrombotic therapy.
- Published
- 2021
24. Correction to: Efficacy and safety of ropeginterferon alfa-2b in Japanese patients with polycythemia vera: an open-label, single-arm, phase 2 study
- Author
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Yoko Edahiro, Kohshi Ohishi, Akihiko Gotoh, Katsuto Takenaka, Hirohiko Shibayama, Takayuki Shimizu, Kensuke Usuki, Kazuya Shimoda, Masafumi Ito, Scott A. VanWart, Oleh Zagrijtschuk, Albert Qin, Hiroaki Kawase, Narihisa Miyachi, Toshiaki Sato, Norio Komatsu, and Keita Kirito
- Subjects
Hematology - Published
- 2022
25. Evaluation of Medication Adherence and Pharmacokinetics of Dasatinib for Earlier Molecular Response in Japanese Patients With Newly Diagnosed Chronic Myeloid Leukemia: A Pilot Study
- Author
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Kei Suzuki, Koji Oka, Takao Sekine, Masahiro Okuda, Naoyuki Katayama, Akira Umino, Keiki Kawakami, Fumihiko Monma, Takuya Iwamoto, and Kohshi Ohishi
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Dasatinib ,Fusion Proteins, bcr-abl ,Pilot Projects ,030226 pharmacology & pharmacy ,Medication Adherence ,03 medical and health sciences ,Myelogenous ,0302 clinical medicine ,Asian People ,Pharmacokinetics ,Tandem Mass Spectrometry ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Adverse effect ,Prospective cohort study ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,Pharmacology ,business.industry ,Myeloid leukemia ,Middle Aged ,medicine.disease ,Leukemia ,Female ,business ,Tyrosine kinase ,Chromatography, Liquid ,medicine.drug - Abstract
Tyrosine kinase inhibitors markedly improve the survival for patients with chronic myeloid leukemia (CML). However, a decrease in adherence leads to undesired therapeutic outcomes. In this study, the relationships among adherence, pharmacokinetics, response, and adverse effects for dasatinib treatment were prospectively investigated.This study was a prospective cohort study of patients with newly diagnosed CML at 4 general hospitals and 1 university hospital. Patients started to receive dasatinib 100 mg once daily. A Medication Event Monitoring System was used to assess medication adherence and the medication possession ratio during the 12 months. Plasma concentrations of dasatinib were measured using liquid chromatograph-tandem mass spectrometry (LC-MS/MS), and therapy responses were assessed at 3, 6, and 12 months after treatment.Ten patients were included. An extremely high medication adherence for dasatinib was observed; the median medication possession ratio was 99.4%. All 9 CML patients with breakpoints in the major BCR-ABL achieved major molecular response (MMR; major BCR-ABL transcript level below 0.1% on the International Scale) within 12 months, and 5 achieved MMR within 6 months. The receiver operating characteristic curve analysis revealed that the cutoff value for the dasatinib area under the concentration-time curve was 336.1 ng × h/mL (accuracy 88.9%, sensitivity 80.0%, specificity 100%, and receiver operating characteristic curve-area under the concentration-time curve 0.800) for achieving MMR within 6 months. Two patients had interrupted dasatinib treatment because of pleural effusion and diarrhea with intestinal edema, respectively. These edematous adverse events developed after plasma dasatinib Cmin surpassed 3.0 ng/mL.A Medication Event Monitoring System was applied for the direct evaluation of oral dasatinib adherence for the first time, and the clinical effect of dasatinib was investigated under the strict monitoring of patient adherence. Although this study had a small sample size, the plasma concentration monitoring of dasatinib is considered to be useful to predict an earlier molecular response with fewer edematous adverse events.
- Published
- 2019
26. Irbesartan, an angiotensin II type 1 receptor blocker, inhibits colitis-associated tumourigenesis by blocking the MCP-1/CCR2 pathway
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Komei Nishimura, Isao Tawara, Takuya Shiotani, Kohshi Ohishi, Junya Tsuboi, Naoki Kuroda, Masahiro Masuya, Naoyuki Katayama, Kensuke Hachiya, Keiki Nagaharu, and Misao Yoneda
- Subjects
CCR2 ,Carcinogenesis ,Receptors, CCR2 ,Science ,Azoxymethane ,Article ,Proinflammatory cytokine ,chemistry.chemical_compound ,Chemokine receptor ,Irbesartan ,medicine ,Animals ,Gastrointestinal models ,Colitis ,Chemokine CCL2 ,Multidisciplinary ,business.industry ,Monocyte ,Dextran Sulfate ,Gastroenterology ,medicine.disease ,Angiotensin II ,Mice, Inbred C57BL ,medicine.anatomical_structure ,chemistry ,Colonic Neoplasms ,Cancer research ,Medicine ,business ,Angiotensin II Type 1 Receptor Blockers ,medicine.drug - Abstract
The introduction of anti-inflammatory therapies has enabled substantial improvement of disease activity in patients with inflammatory bowel diseases (IBD). However, IBD can lead to serious complications such as intestinal fibrosis and colorectal cancer. Therefore, novel therapies reducing the development of these complications are needed. Angiotensin II (Ang II) promotes tissue inflammation by stimulating the production of monocyte chemoattractant protein-1 (MCP-1) or proinflammatory cytokines. It plays a pivotal role in IBD progression. Although blockade of Ang II has been reported to ameliorate experimental colitis and reduce colorectal cancer risk, the cellular and molecular mechanisms remain poorly understood. Our previous work showed that irbesartan, an Ang II type 1 receptor blocker, reduced the number of C–C chemokine receptor 2-positive (CCR2+) monocytic cells in the inflamed pancreas. This study aimed to investigate the possible antifibrotic and antitumour effects of irbesartan using the azoxymethane/dextran sodium sulphate mouse model. Irbesartan suppressed MCP-1 production and the accumulation of Ly6C+CCR2+ monocytes and fibrocytes in the inflamed colon, downregulated the expression of type 1 collagen and matrix metalloproteinase 9 and inhibited the development of intestinal fibrosis and tumours. Our observations suggest that blocking the MCP-1/CCR2 pathway using irbesartan might be beneficial in preventing colitis-associated colon tumours.
- Published
- 2021
27. A bifurcation concept for B-lymphoid/plasmacytoid dendritic cells with largely fluctuating transcriptome dynamics
- Author
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Keiki Nagaharu, Yasuhiro Kojima, Haruka Hirose, Kodai Minoura, Kunihiko Hinohara, Hirohito Minami, Yuki Kageyama, Yuka Sugimoto, Masahiro Masuya, Shigeru Nii, Masahide Seki, Yutaka Suzuki, Isao Tawara, Teppei Shimamura, Naoyuki Katayama, Hiroyoshi Nishikawa, and Kohshi Ohishi
- Subjects
Humans ,Cell Differentiation ,Dendritic Cells ,Transcriptome ,Lymphocyte Function-Associated Antigen-1 ,General Biochemistry, Genetics and Molecular Biology ,Hematopoiesis - Abstract
Hematopoiesis was considered a hierarchical stepwise process but was revised to a continuous process following single-cell RNA sequencing. However, the uncertainty or fluctuation of single-cell transcriptome dynamics during differentiation was not considered, and the dendritic cell (DC) pathway in the lymphoid context remains unclear. Here, we identify human B-plasmacytoid DC (pDC) bifurcation as large fluctuating transcriptome dynamics in the putative B/NK progenitor region by dry and wet methods. By converting splicing kinetics into diffusion dynamics in a deep generative model, our original computational methodology reveals strong fluctuation at B/pDC bifurcation in IL-7Rα
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- 2022
28. Acquisition of JAK2 V617F to CALR ‐mutated clones accelerates disease progression and might enhance growth capacity
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Misa Nishimura, Yuka Sugimoto, Takao Sekine, Isao Tawara, Kohshi Ohishi, Minoru Mizutani, Makoto Ikejiri, Ryota Sasao, Keiki Nagaharu, and Eiko Ohya
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Disease progression ,Cancer research ,medicine ,Myeloproliferative disease ,Hematology ,Biology ,Myelofibrosis ,medicine.disease ,JAK2 V617F - Published
- 2021
29. A population of CD20+CD27+CD43+CD38lo/int B1 cells in PNH are missing GPI-anchored proteins and harbor PIGA mutations
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Isao Tawara, Hiroshi Miwa, Naoyuki Katayama, Kohshi Ohishi, Masahiro Masuya, and Yuki Kageyama
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0301 basic medicine ,CD20 ,CD43 ,education.field_of_study ,Mutation ,biology ,Immunology ,Population ,Cell Biology ,Hematology ,CD38 ,medicine.disease_cause ,Biochemistry ,Molecular biology ,Phenotype ,B-1 cell ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immunoglobulin M ,biology.protein ,medicine ,education ,030215 immunology - Abstract
TO THE EDITOR: B1 cells were first described in 1983 as a rare B-lymphocyte subpopulation that spontaneously secreted immunoglobulin M (IgM) and appeared to be distinguished from B2 cells.[1][1] The functional properties, phenotype, and ontogeny of B1 cells differ from those of B2 cells.[2][2] In
- Published
- 2019
30. GUIDELINE FOR THE MANAGEMENT OF ADVERSE EVENTS OF TRANSFUSION BASED ON SCIENTIFIC EVIDENCES
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Hitoshi Okazaki, Hidefumi Kato, Isao Hamaguchi, Masanori Matsumoto, Kohshi Ohishi, Tadashi Matsushita, Toshiyuki Ikeda, and Yasuhiko Fujii
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medicine.medical_specialty ,business.industry ,Medicine ,Guideline ,business ,Intensive care medicine ,Adverse effect - Published
- 2019
31. PROTOCOL FOR THE IN-HOUSE PRODUCTION OF FFP-LR240-DERIVED CRYOPRECIPITATE
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Hidefumi Kato, Shigeki Miyata, Yumi Tanaka, Shigeyoshi Makino, Noriaki Iwao, Takeshi Matsumoto, Kohei Otsuka, Chiaki Yamada, Koji Yamamoto, Keiko Mori, Junko Ikemoto, Shigehisa Tamaki, Satoshi Fujii, Akihiro Takeshita, Kohshi Ohishi, Kenichi Miyazaki, Yoshihiro Fujimori, and Koji Hoshino
- Subjects
Protocol (science) ,medicine.medical_specialty ,business.industry ,Cryoprecipitate ,medicine ,Production (economics) ,Intensive care medicine ,business - Published
- 2019
32. Clinical Utility of Molecular Diagnosis of Blood Stream Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Hematologic Malignancies
- Author
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Akiko Nakamura, Atsushi Fujieda, Masahiro Masuya, Kazunori Nakase, Fumihiko Monma, Naoyuki Katayama, Kohshi Ohishi, and Yuka Sugimoto
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biology ,medicine.diagnostic_test ,Microbial DNA ,business.industry ,medicine.medical_treatment ,General Medicine ,Hematopoietic stem cell transplantation ,Antimicrobial ,biology.organism_classification ,law.invention ,chemistry.chemical_compound ,chemistry ,law ,Immunology ,Medicine ,Blood culture ,business ,Blood stream ,Polymerase chain reaction ,Bacteria ,DNA - Abstract
Blood stream infections (BSIs) are a serious problem in patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (ASCT). We evaluated the clinical utility of molecular diagnosis for the management of BSIs in such patients. We prospectively performed a polymerase chain reaction (PCR) analysis of microbial DNA in blood samples from 10 consecutive patients with hematological malignancies at least once a week for one month after ASCT. In total, 51 and 54 samples were analyzed by bacterial and fungal PCR assays, respectively. Bacteria were detected in 24 samples from 8 patients by PCR, but in only 2 samples from one patient by blood culture. Notably, the bacteria detected in at least half of the 24 samples were considered to have originated from the oral cavity. Fungi were detected in 5 samples from 3 patients by PCR, but not by blood culture. Most cases with positive PCR results were manageable with empirical antimicrobial therapy without disclosure of DNA data. Our DNA analyses did not directly contribute to management of BSIs, but did provide valuable microbiological evidence for the patients. Additionally, oral management appears to require a critical re-evaluation to reduce the occurrence of BSIs in ASCT recipients.
- Published
- 2019
33. GUIDELINE FOR THE USE OF RED BLOOD CELL PRODUCTS BASED ON SCIENTIFIC EVIDENCE (REVISION 2ND EDITION)
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Eiichi Inada, Takashi Sonoki, Yasunori Ueda, Kazuhiro Nagai, Midori Kumakawa, Eizaburo Sueoka, Naohito Fujishima, Takahiko Kubo, Tadashi Matsushita, Masanori Matsumoto, Yuji Yonemura, and Kohshi Ohishi
- Subjects
Cultural Studies ,Red blood cell ,medicine.medical_specialty ,medicine.anatomical_structure ,business.industry ,medicine ,Guideline ,Intensive care medicine ,business ,Education ,Scientific evidence - Published
- 2018
34. Tyrosine kinase inhibitor therapy prescribed for non‐urologic diseases can modify PSA titers in urology patients
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Omar E. Franco, Naoto Takahashi, Susan E. Crawford, Naoyuki Katayama, Yana Filipovich, Kohshi Ohishi, Simon W. Hayward, Kenichiro Ishii, Takeshi Sasaki, and Yoshiki Sugimura
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,medicine.drug_class ,Urology ,Prostatic Hyperplasia ,urologic and male genital diseases ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Cell Line, Tumor ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,medicine ,Humans ,RNA, Messenger ,Protein Kinase Inhibitors ,Aged ,Cell Proliferation ,business.industry ,Prostatic Neoplasms ,Imatinib ,Prostate-Specific Antigen ,medicine.disease ,Dasatinib ,Prostate-specific antigen ,Pyrimidines ,030104 developmental biology ,Oncology ,Nilotinib ,Receptors, Androgen ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Kallikreins ,business ,Tyrosine kinase ,medicine.drug ,Chronic myelogenous leukemia - Abstract
Background The tyrosine kinase inhibitors (TKI), imatinib and nilotinib, are used to treat chronic myelogenous leukemia (CML). In three CML patients being monitored for urologic diseases, we observed that switching of TKI therapy affected prostate-specific antigen (PSA) titers. Urologists and other medical professionals need to be aware of the potential side-effects of drugs that patients may be receiving for other indications to modify this important prostate diseases indicator. TKIs may affect PSA titers independent of prostate growth or volume. Materials and methods We followed PSA levels in urology patients who were also undergoing TKI treatment for CML. We determined the effects of nilotinib and imatinib on proliferation, AR and PSA expression in the LNCaP and 22Rv1 prostate cancer (PCa) cell lines using real-time PCR and Western blotting. Results Clinically, nilotinib and dasatinib reversibly reduced PSA titers compared to imatinib. At high doses nilotinib and imatinib both demonstrated antiproliferative effects in the PCa cells. At low doses expression of AR and PSA was decreased by both drugs, at mRNA and protein levels. Nilotinib exerted greater effects at lower doses than imatinib. Conclusions Nilotinib down-regulates serum PSA in patients being treated for non-urological indications, potentially masking a clinical useful marker, we cannot exclude a similar but smaller effect of imatinib. Nilotinib and imatinib both decreased AR and PSA expression in PCa cell lines with the nilotinib effect evident at lower doses. Urologists must appreciate the effects of drugs provided for other diseases on PSA titers and be aware that sudden changes may not reflect underlying prostatic disease.
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- 2018
35. Clinical utility of oral management in allogeneic hematopoietic stem cell transplantation recipients: microbiological evidence based on molecular analysis of oral bacteria
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Jumpei Kawajiri, Kokoro Nagata, Akiko Nakamura, Atsushi Fujieda, Kazuko Ino, Jouji Nomura, Naoya Arai, Kohshi Ohishi, Naoyuki Katayama, and Kazunori Nakase
- Subjects
stomatognathic diseases ,Stomatitis ,Bacteria ,Hematopoietic Stem Cell Transplantation ,Administration, Oral ,Humans ,Periodontitis - Abstract
Purpose: This study aimed to clarify the clinical utility of oral management to prevent bloodstream infections by oral bacteria microbiologically in patients undergoing allogeneic hematopoietic stem cell transplantation (ASCT). Methods: Ten consecutive patients with hematological malignancies undergoing ASCT were enrolled in this study. We implemented dental treatments before transplantation, if required, and carried out oral hygiene instructions and oral management every other day after transplantation. Molecular analysis of bacterial DNA for seven oral species using a polymerase chain reaction (PCR) assay was performed for oral samples and peripheral blood once a week for 3 weeks after transplantation. Results: Periodontitis was found in all 10 patients (mild grade in 3 and middle grade in 7) for whom basic periodontal therapy was conducted. Necessary dental procedures, including tooth extraction of the tooth were performed in 5 patients. After transplantation, oral mucositis occurred in 10 patients (grade 1 in 3, grade 2 in 2, and grade 3 in 5) for whom oral hygiene instruction and oral care were continued every other day. PCR-identified three to six bacterial species in oral samples from nine patients, but none in peripheral blood from any patient during the observation period. Conclusions: Oral management prevented blood stream infections by oral bacteria in ASCT recipients despite the existence of periodontitis or oral mucositis. Its utility was confirmed by microbiological evidence based on molecular data.
- Published
- 2021
36. Supplemental Material, sj-pdf-1-cat-10.1177_1076029620976913 - The Evaluation of APTT Reagents in Reference Plasma, Recombinant FVIII Products; Kovaltry® and Jivi® Using CWA, Including sTF/7FIX Assay
- Author
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Wada, Hideo, Shiraki, Katsuya, Matsumoto, Takeshi, Kohshi Ohishi, Shimpo, Hideto, Sakano, Yumi, Nishii, Hiroko, and Motomu Shimaoka
- Subjects
FOS: Clinical medicine ,Cardiology ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified - Abstract
Supplemental Material, sj-pdf-1-cat-10.1177_1076029620976913 for The Evaluation of APTT Reagents in Reference Plasma, Recombinant FVIII Products; Kovaltry® and Jivi® Using CWA, Including sTF/7FIX Assay by Hideo Wada, Katsuya Shiraki, Takeshi Matsumoto, Kohshi Ohishi, Hideto Shimpo, Yumi Sakano, Hiroko Nishii and Motomu Shimaoka in Clinical and Applied Thrombosis/Hemostasis
- Published
- 2021
- Full Text
- View/download PDF
37. MPL exon 10 mutations other than canonical MPL W515L/K mutations identified by in-house MPL exon 10 direct sequencing in essential thrombocythemia
- Author
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Yuka, Sugimoto, Keiki, Nagaharu, Kohshi, Ohishi, Maki, Nakamura, Makoto, Ikejiri, Kaname, Nakatani, Minoru, Mizutani, Shigehisa, Tamaki, Takeshi, Ikeda, Isao, Tawara, and Naoyuki, Katayama
- Subjects
Adult ,Aged, 80 and over ,Male ,DNA Mutational Analysis ,Mutation ,Humans ,Female ,Exons ,Middle Aged ,Receptors, Thrombopoietin ,Aged ,Thrombocythemia, Essential - Abstract
MPL exon 10 mutations are one of the driver mutations in essential thrombocythemia (ET) or myelofibrosis (MF). We have established an in-house MPL mutation analysis system, covering the entire region of MPL exon 10 by direct sequencing. Since 2009, MPL exon 10 mutation analysis has been performed for diagnosis of myeloproliferative neoplasms (MPN) without JAK2 V617F or CALR exon 9 mutations. So far, 11 cases of MPL exon 10 mutation have been found in 51 patients with suspected MPN. In patients with ET, we detected five non-canonical MPL mutations including one novel mutation, MPL R514_P518delinsK, and one canonical MPL W515L mutation. Notably, three ET patients without canonical MPL mutations had thrombotic events. Meanwhile, in primary or secondary MF, only canonical MPL W515L/K mutations were found. Further cases need to be examined to elucidate the full MPL mutation profile in MPN. However, our data indicate that analysis of the whole of MPL exon 10 is warranted for the diagnosis of MPL mutations, especially in ET, and that the use of Japanese commercial laboratory tests that only detect canonical MPL W515L/K mutations may miss a significant percentage of MPL exon 10 mutations, which could delay the administration of anti-thrombotic therapy.
- Published
- 2020
38. Effects of platelet and phospholipids on clot formation activated by a small amount of tissue factor
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Katsuya Shiraki, Hideto Shimpo, Kohshi Ohishi, Motomu Shimaoka, Takeshi Matsumoto, and Hideo Wada
- Subjects
Blood Platelets ,medicine.medical_specialty ,Phospholipid ,030204 cardiovascular system & hematology ,law.invention ,Thromboplastin ,03 medical and health sciences ,chemistry.chemical_compound ,Tissue factor ,0302 clinical medicine ,law ,Internal medicine ,medicine ,Humans ,Platelet ,Blood Coagulation ,Phospholipids ,Lupus anticoagulant ,Hematology ,Coagulation Factor IX ,medicine.disease ,Thrombocytopenic purpura ,Endocrinology ,Coagulation ,chemistry ,030220 oncology & carcinogenesis ,Recombinant DNA ,Blood Coagulation Tests - Abstract
Introduction Physiological coagulation is considered to activate coagulation factor IX (FIX) by a small amount of tissue factor (TF) and activated coagulation factor VII (FVIIa) with the presence of platelets. A Clot waveform analysis (CWA) may be useful for evaluating physiological coagulation. Material and methods A CWA using a small amount of TF (CWA/sTF) was performed in platelet-rich plasma (PRP), platelet-poor plasma (PPP), several phospholipids (PLs) and patients with lupus anticoagulant (LA), idiopathic thrombocytopenic purpura (ITP) or inhibitor for FVIII. Results The CWA/sTF without PLs showed a shorter peak time and higher peak height in PRP than in PPP. The effect of PRP on the CWA/sTF depended on the platelet count, and PLs showed a similar effect on the CWA/sTF results in PPP. The peak time of the CWA/sTF in PRP was prolonged in patient with ITP. The CWA/sTF in PRP showed a prolonged peak time and decreased peak height of the second derivative in patient with LA. Both a shortened peak time and elevated peak height were observed in the CWA/sTF of patient with inhibitor after treatment with activated recombinant human FVII. Conclusion A CWA can be conducted using a small amount of TF and platelets or PL without contact activation and may be able to detect not only hemostatic abnormalities but also changes in platelet counts.
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- 2020
39. Update on the Clot Waveform Analysis
- Author
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Kohshi Ohishi, Hideo Wada, Takeshi Matsumoto, Motomu Shimaoka, and Katsuya Shiraki
- Subjects
Male ,CWA ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Coagulation Factor Deficiency ,APTT ,Review ,030204 cardiovascular system & hematology ,Hemophilia A ,DIC ,03 medical and health sciences ,0302 clinical medicine ,Thrombin ,hemophilia ,Internal medicine ,medicine ,Humans ,Thromboplastin ,Blood Coagulation ,Disseminated intravascular coagulation ,medicine.diagnostic_test ,business.industry ,Thrombosis ,Hematology ,General Medicine ,medicine.disease ,Coagulation ,Waveform analysis ,lcsh:RC666-701 ,Cardiology ,Female ,Differential diagnosis ,business ,030215 immunology ,Partial thromboplastin time ,medicine.drug ,circulatory and respiratory physiology - Abstract
The activated partial thromboplastin time (APTT)–clot waveform analysis (CWA) was previously reported to be associated with the early detection of disseminated intravascular coagulation and was also reported to be able to measure very low levels of coagulation factor VIII activity. The software program for the analysis for the APTT-CWA allows the associated first and second derivative curves (first and second DCs) to be displayed. The first and second DC reflect the velocity and acceleration, respectively. The height of the first DC reflects the “thrombin burst” and bleeding risk, while that of the second DC is useful for detecting any coagulation factor deficiency and abnormal enhancement of coagulation by phospholipids. Activated partial thromboplastin time-CWA aids in making a differential diagnosis which is difficult to do using only the routine APTT. The CWA is currently used for many applications in the clinical setting, including the monitoring of hemophilia patients and patients receiving anticoagulant therapy and the differential diagnosis of diseases.
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- 2020
40. Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells
- Author
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Shimon Sakaguchi, Hiroyoshi Nishikawa, Yuka Maeda, Yoshiko Takeuchi, Toshio Kitawaki, Elke Jäger, Fumihiko Monma, Danbee Ha, Yoshihiro Kameoka, Atsushi Tanaka, Naoto Takahashi, Naoyuki Katayama, Kohshi Ohishi, Shinsuke Noguchi, Yoshinori Shinohara, Kenichi Sawada, Keiko Iwaisako, Julia Karbach, Hiromasa Morikawa, Takuro Saito, Daisuke Sugiyama, and Naoya Shigeta
- Subjects
medicine.drug_class ,Immunology ,Fusion Proteins, bcr-abl ,Receptors, Antigen, T-Cell ,Apoptosis ,Mice, Transgenic ,chemical and pharmacologic phenomena ,Mice, SCID ,CD8-Positive T-Lymphocytes ,T-Lymphocytes, Regulatory ,Article ,Tyrosine-kinase inhibitor ,Mice ,Immune system ,Antigen ,Blood cell depletion therapy ,Cell Line, Tumor ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Immunology and Allergy ,Protein Kinase Inhibitors ,neoplasms ,Research Articles ,Mice, Inbred BALB C ,Chemistry ,Immunity ,hemic and immune systems ,Imatinib ,medicine.disease ,Disease Models, Animal ,Treatment Outcome ,Imatinib mesylate ,Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ,Colonic Neoplasms ,Imatinib Mesylate ,Cancer research ,Female ,CD8 ,medicine.drug ,Chronic myelogenous leukemia - Abstract
As a novel type of anticancer reagent, imatinib inhibits not only BCR-ABL oncogenic protein but also LCK in T cells as an off-target, being able to selectively deplete mature T reg cells and thereby evoke effective immune responses to various cancers., This report addresses whether small molecules can deplete FoxP3-expressing regulatory T (T reg) cells, thereby augmenting antitumor immunity. Imatinib, a tyrosine kinase inhibitor of oncogenic BCR-ABL protein expressed by chronic myelogenous leukemia (CML) cells, possesses off-targets including LCK expressed in T cells. We showed that imatinib-treated CML patients in complete molecular remission (CMR) exhibited selective depletion of effector T reg (eT reg) cells and significant increase in effector/memory CD8+ T cells while non-CMR patients did not. Imatinib at CML-therapeutic concentrations indeed induced apoptosis specifically in eT reg cells and expanded tumor antigen–specific CD8+ T cells in vitro in healthy individuals and melanoma patients, and suppressed colon tumor growth in vivo in mice. Mechanistically, because of FoxP3-dependent much lower expression of LCK and ZAP-70 in T reg cells compared with other T cells, imatinib inhibition of LCK further reduced their TCR signal intensity, rendering them selectively susceptible to signal-deprived apoptotis. Taken together, eT reg cell depletion by imatinib is instrumental in evoking effective immune responses to various cancers.
- Published
- 2019
41. Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan
- Author
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Michihide Tokuhira, Jun Kuroki, Osamu Iwase, Fumihiko Kimura, Tetsuya Fukuda, Naoto Takahashi, Koji Sano, Kaichi Nishiwaki, Kinuko Mitani, Kohshi Ohishi, Sakae Tanosaki, Hisashi Wakita, Saori Takahashi, Chikako Ohwada, Kazuhisa Fujikawa, Hiroyoshi Nishikawa, Chiaki Nakaseko, Yoshihiro Kameoka, Nobuyuki Aotsuka, and Hideo Kimura
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,medicine.drug_class ,Chronic Myeloid Leukemia ,Gastroenterology ,Disease-Free Survival ,Article ,Tyrosine-kinase inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,Humans ,Medicine ,Survival rate ,Survival analysis ,Aged ,Aged, 80 and over ,business.industry ,Remission Induction ,Myeloid leukemia ,Consolidation Chemotherapy ,Hematology ,Middle Aged ,medicine.disease ,Survival Rate ,Leukemia ,Pyrimidines ,030104 developmental biology ,Nilotinib ,030220 oncology & carcinogenesis ,Molecular Response ,Female ,business ,medicine.drug - Abstract
The purpose of this trial was to evaluate the efficacy of 2-year consolidation therapy with nilotinib, at a dose of 300 mg twice daily, for achieving treatment-free remission in chronic myeloid leukemia patients with a deep molecular response (BCR-ABL1IS ≤0.0032%). Successful treatment-free remission was defined as no confirmed loss of deep molecular response. We recruited 96 Japanese patients, of whom 78 sustained a deep molecular response during the consolidation phase and were therefore eligible to discontinue nilotinib in the treatment-free remission phase; of these, 53 patients (67.9%; 95% confidence interval: 56.4–78.1%) remained free from molecular recurrence in the first 12 months. The estimated 3-year treatment-free survival was 62.8%. Nilotinib was readministered to all patients (n=29) who experienced a molecular recurrence during the treatment-free remission phase. After restarting treatment, rapid deep molecular response returned in 25 patients (86.2%), with 50% of patients achieving a deep molecular response within 3.5 months. Tyrosine kinase inhibitor withdrawal syndrome was reported in 11/78 patients during the early treatment-free remission phase. The treatment-free survival curve was significantly better in patients with undetectable molecular residual disease than in patients without (3-year treatment-free survival, 75.6 versus 48.6%, respectively; P=0.0126 by the log-rank test). There were no significant differences in treatment-free survival between subgroups based on tyrosine kinase inhibitor treatment before the nilotinib consolidation phase, tyrosine kinase inhibitor-withdrawal syndrome, or absolute number of natural killer cells. The results of this study indicate that it is safe and feasible to stop tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia who have achieved a sustained deep molecular response with 2 years of treatment with nilotinib. This study was registered with UMIN-CTR (UMIN000005904).
- Published
- 2018
42. Congenital Thrombophilia in Patients With Superior Mesenteric Venous Thrombosis or Portal Vein Thrombosis
- Author
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Hidekazu Tomimoto, Hideo Wada, Kaname Nakatani, Ikejiri Makoto, Takeshi Matsumoto, Shuji Isaji, Masanobu Usui, Yoshiki Yamashita, Shigehisa Tamaki, Kohshi Ohishi, and Akihiro Shindo
- Subjects
Adult ,Male ,medicine.medical_specialty ,genetic structures ,030204 cardiovascular system & hematology ,Gene mutation ,medicine.disease_cause ,Thrombophilia ,behavioral disciplines and activities ,Gastroenterology ,Protein S ,superior mesenteric vein thrombosis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,mental disorders ,medicine ,Humans ,portal vein thrombosis ,Vein ,Aged ,Aged, 80 and over ,Venous Thrombosis ,Mutation ,biology ,Portal Vein ,business.industry ,Antithrombin ,Original Articles ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Portal vein thrombosis ,medicine.anatomical_structure ,biology.protein ,Female ,030211 gastroenterology & hepatology ,business ,Protein C ,medicine.drug - Abstract
We explored the relationship between abdominal vein thromboses, including portal vein thrombosis (PVT) and superior mesenteric vein thrombosis (SMVT), and thrombophilia. The frequency of thrombophilia, such as antithrombin (AT), protein C (PC), or protein S (PS) gene mutations, was examined in 21 patients with PVT, 6 patients with SMVT, and 6 patients with both PVT and SMVT. Low levels of AT, PC, or PS were frequently detected in patients with PVT or mesenteric vein thrombosis, and 4 mutations in the PS gene, 3 mutations in the PC gene, and 2 mutations in AT the gene were detected. Protein S Tokushima was detected in 3 of 4 patients with a PS gene mutation and was associated with 2 other PS gene mutations. The onset of PVT or SMVT was almost idiopathic in patients with congenital thrombophilia. Both PVT and SMVT were frequently caused by an AT, a PC, or a PS mutation, and the onset of these thromboses due to thrombophilia was frequently idiopathic.
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- 2018
43. An Evaluation of Hemostatic Abnormalities in Patients With Hemophilia According to the Activated Partial Thromboplastin Time Waveform
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Kohshi Ohishi, Makoto Ikejiri, Naoki Fujimoto, Takeshi Matsumoto, Hideo Wada, Naoyuki Katayama, Haruna Katayama, Koji Habe, Yasunori Abe, Junki Toyoda, and Yoshiki Yamashita
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Adult ,Male ,Fviii activity ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,APTT ,030204 cardiovascular system & hematology ,Hemophilia A ,Hemostatics ,Fibrin ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,biphasic waveform ,hemophilia ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Waveform ,In patient ,Aged ,Lupus anticoagulant ,medicine.diagnostic_test ,biology ,business.industry ,Original Articles ,Hematology ,General Medicine ,Biphasic waveform ,Middle Aged ,medicine.disease ,waveform ,lupus anticoagulant ,biology.protein ,Cardiology ,Female ,Partial Thromboplastin Time ,business ,circulatory and respiratory physiology ,030215 immunology ,Partial thromboplastin time - Abstract
The usefulness of the waveform of activated partial thromboplastin time (APTT) in various diseases has been evaluated in recent years. The APTT waveform was examined in patients with hemophilia and patients positive for lupus anticoagulant (LA). The correlation with the FVIII activity was highest for the height of acceleration peak. The peak time of acceleration, velocity, and ½ fibrin formation, and the width of acceleration and velocity were significantly long and the height of acceleration was significantly low in patients with hemophilia. The height of velocity was significantly low in patients with hemophilia with inhibitor. There were no significant differences in the APTT waveform between patients with hemophilia and patients with LA, but the peak of acceleration and ½ fibrin formation were significantly longer and the height of acceleration and velocity were significantly lower in patients with hemophilia with inhibitor than in the patients with LA. Wave changes in the APTT were observed in all 22 patients positive for LA, while a biphasic waveform was observed in patients with hemophilia with FVIII activity
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- 2018
44. Effect of ruxolitinib therapy on the quality-of-life of Japanese patients with myelofibrosis
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Taro Amagasaki, Katsuto Takenaka, Hikaru Okada, Hiroshi Handa, Keita Kirito, Shinichiro Okamoto, Kenji Oritani, Shiho Wakase, Norio Komatsu, Kazuya Shimoda, Koichi Akashi, Shigeki Saito, Tetsuzo Tauchi, Kohshi Ohishi, and Kojiro Shimozuma
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Adult ,Male ,Oncology ,Ruxolitinib ,medicine.medical_specialty ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,Nitriles ,medicine ,Humans ,Myelofibrosis ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,business.industry ,Symptom burden ,General Medicine ,Janus Kinase 2 ,Middle Aged ,medicine.disease ,Pyrimidines ,Treatment Outcome ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Quality of Life ,Pyrazoles ,Female ,business ,030215 immunology ,medicine.drug - Abstract
Myelofibrosis (MF) is associated with a significant symptom burden that severely impacts patient quality-of-life (QoL). Ruxolitinib, a potent Janus kinase 1 (JAK1)/JAK2 inhibitor, led to substantial improvements in splenomegaly, MF-associated symptoms, and QoL in the phase 3 COMFORT studies, proving superior to placebo and best available therapy. This study evaluated the effect of ruxolitinib on symptoms and QoL in Japanese patients with MF.A pooled analysis of studies A2202 (NCT01392443) and AJP01 (NCT02087059) of ruxolitinib in Japanese patients with MF (n = 81) was conducted. Changes in total symptom score (TSS) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were summarized.Most patients received a starting dose of 15 or 20 mg twice daily (BID) and had a final titrated dose of ≥10 mg BID. Overall, 67.7% (44/65) achieved a ≥50% reduction from baseline in TSS at week 24. Reductions in TSS were seen in every dose group; the greatest reductions occurred in patients with a final titrated dose of 20 or 25 mg BID. Improvements in QoL were seen in patients who achieved a ≥50% reduction in TSS. Generally, improvements in TSS and individual symptoms correlated with reductions in spleen size, with those having a ≥35% reduction in spleen volume having the greatest improvements.Consistent with COMFORT-I, ruxolitinib provided substantial improvements in symptoms and QoL in Japanese patients with MF, with higher doses of ruxolitinib associated with better responses.
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- 2018
45. The Plasma Levels of ADAMTS-13, von Willebrand Factor, VWFpp, and Fibrin-Related Markers in Patients With Systemic Sclerosis Having Thrombosis
- Author
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Tomoko Akeda, Hideo Wada, Masato Kakeda, Koji Habe, Takeshi Matsumoto, Hitoshi Mizutani, Kenshiro Tsuda, Keiichi Yamanaka, Ayaka Higashiyama, Naoyuki Katayama, Kohshi Ohishi, and Ryoko Mori
- Subjects
Male ,medicine.medical_specialty ,systemic sclerosis ,ADAMTS13 Protein ,Connective tissue ,030204 cardiovascular system & hematology ,Gastroenterology ,Fibrin ,Fibrin Fibrinogen Degradation Products ,03 medical and health sciences ,soluble fibrin ,0302 clinical medicine ,Von Willebrand factor ,Internal medicine ,von Willebrand Factor ,D-dimer ,medicine ,VWF ,Humans ,ADAMTS-13 ,skin and connective tissue diseases ,d-dimer ,Aged ,030203 arthritis & rheumatology ,Thrombospondin ,Scleroderma, Systemic ,integumentary system ,biology ,business.industry ,ADAMTS ,Interstitial lung disease ,Thrombosis ,Original Articles ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,VWFpp ,medicine.anatomical_structure ,Acute Disease ,biology.protein ,Female ,business ,Biomarkers - Abstract
This study aimed to examine the hemostatic abnormalities in patients with systemic sclerosis (SSc) and the relationship between these abnormalities and thrombotic events (THEs), focusing on the difference in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). The plasma levels of ADAMTS-13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13), von Willebrand factor (VWF), VWF propeptide (VWFpp), d-dimer, and soluble fibrin (SF) were measured in 233 patients with SSc. The relationship between their levels and organ involvement, including THEs and interstitial lung disease (ILD), was evaluated. The plasma levels of VWF and VWFpp were significantly elevated and ADAMTS-13 activity was significantly decreased in patients with SSc compared to healthy participants. The VWFpp in dcSSc was significantly higher than in lcSSc. Twelve patients with SSc were complicated with acute THE, and 25 patients with SSc were complicated with past THE. The plasma levels of d-dimer and SF were significantly elevated in patients with SSc having THE. The plasma levels of VWF and VWFpp were significantly elevated in patients with SSc having ILD. The plasma levels of d-dimer were elevated in patients with SSc having other connective tissue diseases (CTDs). The plasma levels of ADAMTS-13 were significantly decreased and VWF, VWFpp, and SF were increased in patients with a d-dimer level of ≥1 μg/mL. Systemic sclerosis carries a high risk of THE, especially in patients with other CTDs. Plasma hemostasis-related markers are closely related to ILD and THE. These markers are important as markers of organ involvement as well as THE.
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- 2017
46. CXCL12–CXCR4 Axis Is Required for Contact-Mediated Human B Lymphoid and Plasmacytoid Dendritic Cell Differentiation but Not T Lymphoid Generation
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Naoyuki Katayama, Kohshi Ohishi, Masahiro Masuya, Isao Tawara, Hiroshi Miwa, Takeshi Matsumoto, Yuka Sugimoto, Naoshi Shimojo, Yoshiki Nakamori, Keiki Nagaharu, Hirohito Minami, and Yuki Kageyama
- Subjects
0301 basic medicine ,Receptors, CXCR4 ,Stromal cell ,T-Lymphocytes ,Antigens, CD19 ,Immunology ,CD34 ,Antigens, CD34 ,Bone Marrow Cells ,chemical and pharmacologic phenomena ,CD38 ,CD19 ,Immunophenotyping ,03 medical and health sciences ,immune system diseases ,hemic and lymphatic diseases ,Precursor cell ,Humans ,Immunology and Allergy ,Cell Lineage ,Lymphocytes ,Plasmacytoid dendritic cell differentiation ,B-Lymphocytes ,biology ,Chemistry ,Cell Differentiation ,hemic and immune systems ,Dendritic Cells ,Chemokine CXCL12 ,Coculture Techniques ,Hematopoiesis ,Cell biology ,Haematopoiesis ,030104 developmental biology ,Culture Media, Conditioned ,biology.protein ,Stromal Cells ,Signal Transduction - Abstract
We investigated the involvement of CXCL12–CXCR4 interactions in human lymphohematopoiesis by coculture with telomerized human stromal cells. CXCR4 expression was low in CD34+CD38−CD45RA−CD10−CD7−CD19− immature hematopoietic stem/precursor cells (HSPCs) but higher in CD34+CD38−CD45RA+CD10+CD7+/−CD19− early lymphoid precursors and even higher in CD34+CD38+CD45RA+CD10+CD7−CD19+ pro-B cells. Inhibition of the effect of stromal cell–produced CXCL12 by an anti-CXCR4–blocking Ab suppressed the generation of CD45RA+CD10−CD7+CD19− early T lymphoid precursors (ETPs) and CD45RA+CD10+CD7−CD19+/− B lymphoid precursors on stromal cells, but it did not affect the generation of ETPs in conditioned medium of stromal cell cultures. Replating assays showed that contact with stromal cells was critical for HSPC-derived CD45RA+CD10+CD7−CD19− B lineage–biased precursors to differentiate into CD19+ pro-B cells, which was suppressed by the anti-CXCR4 Ab. Conversely, HSPC-derived ETPs possessed T and B lymphoid and monocytic differentiation potential; stromal cell contact was not required for their growth but rather promoted B lymphoid differentiation. The anti-CXCR4 Ab did not affect the growth of ETPs in conditioned medium, but it suppressed their B lymphoid differentiation on stromal cells. CD14−CD11c−HLA-DR+CD123highCD303+ plasmacytoid dendritic cells developed from HSPCs and ETPs exclusively in contact with stromal cells, which was suppressed by the anti-CXCR4 Ab. These data indicate that CXCL12 plays an essential role in stromal cell contact–mediated B lymphoid and plasmacytoid dendritic cell differentiation from immature hematopoietic and early T lymphoid precursors with a multilineage differentiation potential, but it does not participate in contact-independent generation of early T lymphoid precursors.
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- 2017
47. Attempt to Harvest a Sufficient Number of Mononuclear Cells in an Appropriate Blood Product Volume By Modification of the Default Apheresis Setting
- Author
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Yumi Tanaka, Naoyuki Katayama, Hideo Wada, Shinichi Kageyama, Hiroshi Shiku, Hitoshi Iwasaki, Toshiki Sawai, Takashi Tanigawa, Masahiro Masuya, Takeshi Matsumoto, Kohshi Ohishi, and Masaaki Ito
- Subjects
business.industry ,T cell ,Hematology ,Cell concentration ,030204 cardiovascular system & hematology ,Peripheral blood mononuclear cell ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Cobe spectra ,Nephrology ,Blood product ,030220 oncology & carcinogenesis ,Immunology ,medicine ,Therapeutic angiogenesis ,business - Abstract
To harvest for T cell therapy, a 1.6-fold higher number of CD3+ T cells was collected with MNC mode (N = 10) compared with Auto PBSC mode (N = 5) in COBE Spectra cell separator, but the blood product volume was increased by 3.5-fold. For therapeutic angiogenesis therapy, apheresis was initially performed using Auto PBSC mode (N = 4) to fine tune the blood product volume to omit cell concentration, but the collected number of mononuclear cells was lower than expected. However, an increase of the harvest cycle number from 3.8 ± 0.5 to 7.4 ± 2.0 cycles (N = 19) resulted in a 2.1-fold higher number of collected mononuclear cells (8.7 ± 4.1 × 109 vs. 4.1 ± 1.0 × 109 cells, P
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- 2017
48. Intradiscal Injection of Autologous Platelet-Rich Plasma Releasate to Treat Discogenic Low Back Pain: A Preliminary Clinical Trial
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Won C. Bae, Akihiro Sudo, Koji Akeda, Yuichi Kasai, Kohshi Ohishi, Koichi Masuda, Tomoki Nakamura, Toshihiko Sakakibara, Norihiko Takegami, and Junichi Yamada
- Subjects
medicine.medical_specialty ,Visual analogue scale ,lcsh:Medicine ,03 medical and health sciences ,0302 clinical medicine ,Lumbar ,Platelet-rich plasma ,medicine ,Orthopedics and Sports Medicine ,Low back pain ,030212 general & internal medicine ,medicine.diagnostic_test ,business.industry ,lcsh:R ,Intervertebral disc ,Magnetic resonance imaging ,Surgery ,Clinical trial ,medicine.anatomical_structure ,Anesthesia ,Orthopedic surgery ,Clinical Study ,medicine.symptom ,Intervertebral disc degeneration ,business ,030217 neurology & neurosurgery - Abstract
Study DesignPreliminary clinical trial.PurposeTo determine the safety and initial efficacy of intradiscal injection of autologous platelet-rich plasma (PRP) releasate in patients with discogenic low back pain.Overview of LiteraturePRP, which is comprised of autologous growth factors and cytokines, has been widely used in the clinical setting for tissue regeneration and repair. PRP has been shown in vitro and in vivo to potentially stimulate intervertebral disc matrix metabolism.MethodsInclusion criteria for this study included chronic low back pain without leg pain for more than 3 months; one or more lumbar discs (L3/L4 to L5/S1) with evidence of degeneration, as indicated via magnetic resonance imaging (MRI); and at least one symptomatic disc, confirmed using standardized provocative discography. PRP releasate, isolated from clotted PRP, was injected into the center of the nucleus pulposus. Outcome measures included the use of a visual analog scale (VAS) and the Roland-Morris Disability Questionnaire (RDQ), as well as X-ray and MRI (T2-quantification).ResultsData were analyzed from 14 patients (8 men and 6 women; mean age, 33.8 years). The average follow-up period was 10 months. Following treatment, no patient experienced adverse events or significant narrowing of disc height. The mean pain scores before treatment (VAS, 7.5±1.3; RDQ, 12.6±4.1) were significantly decreased at one month, and this was generally sustained throughout the observation period (6 months after treatment: VAS, 3.2±2.4, RDQ; 3.6±4.5 and 12 months: VAS, 2.9±2.8; RDQ, 2.8±3.9; pConclusionsWe demonstrated that intradiscal injection of autologous PRP releasate in patients with low back pain was safe, with no adverse events observed during follow-up. Future randomized controlled clinical studies should be performed to systematically evaluate the effects of this therapy.
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- 2017
49. Persistent symptomatic parvovirus B19 infection with severe thrombocytopenia transmitted by red blood cell transfusion containing low parvovirus B19 DNA levels
- Author
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Takanori Yamaguchi, Keiji Matsubayashi, Kohshi Ohishi, Yuka Sugimoto, Keiki Kawakami, Ryugo Ito, Yuji Hoshi, and Keiki Nagaharu
- Subjects
0301 basic medicine ,Anemia ,medicine.medical_treatment ,Immunology ,030204 cardiovascular system & hematology ,Virus ,Diabetic nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,medicine ,Immunology and Allergy ,biology ,Parvovirus ,business.industry ,Infectious dose ,Hematology ,medicine.disease ,biology.organism_classification ,Virology ,030104 developmental biology ,biology.protein ,Hemodialysis ,Antibody ,business - Abstract
BACKGROUND Transfusion-mediated human parvovirus B19 (PVB19) infection is rare but often causes severe hematologic disorders. In Japan, routine blood donor screening for PVB19 antigen (detection sensitivity, 106.4 IU/mL) using a chemiluminescent enzyme immunoassay (CLEIA) was introduced in 2008. However, there is no consensus on the minimal infectious dose of PVB19 permissible for red blood cells (RBCs). CASE REPORT A 64-year-old man, who had received hemodialysis for diabetic nephropathy for 5 years, underwent an RBC transfusion for anemia caused by hemorrhagic enterocolitis. He developed persistent high fever and progressive thrombocytopenia. He was diagnosed with PVB19 infection when a marrow examination showed giant erythroblasts, and his serum was positive for PVB19 DNA. His serum was negative for PVB19 immunoglobulin (Ig)M and IgG before transfusion, but positive for both after transfusion. This PVB19 infection was deemed to be transmitted by the RBC transfusion because low levels of PVB19 DNA (1.10 × 104 IU/mL) were detected in one of the blood donors. A DNA homology test of PVB19 showed complete genomic identity between the virus in the donor and our patient. CONCLUSION We report a patient who developed persistent PVB19 infection from an RBC transfusion containing low levels of PVB19. This is the second case of transfusion-mediated PVB19 infection since the introduction of CLEIA in 2008. Transmission may occur in immunocompromised patients lacking PVB19-neutralizing antibodies. The report of further such cases will allow the establishment of minimal threshold values and more effective screening tests for PBV19 transmission through RBC products.
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- 2017
50. Management of Pulmonary Mucormycosis Based on a Polymerase Chain Reaction (PCR) Diagnosis in Patients with Hematologic Malignancies: A Report of Four Cases
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Kohshi Ohishi, Naoyuki Katayama, Akiko Nakamura, Kana Miyazaki, Atsushi Fujieda, Yoshiki Nakamori, Kazuko Ino, Yuka Sugimoto, Kazunori Nakase, Fumihiko Monma, Masahiro Masuya, and Yumiko Sugawara
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,Antifungal Agents ,polymerase chain reaction ,medicine.medical_treatment ,030106 microbiology ,Case Report ,Gastroenterology ,Targeted therapy ,law.invention ,Diagnostic modalities ,Absidia species ,03 medical and health sciences ,0302 clinical medicine ,law ,Amphotericin B ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Mucormycosis ,In patient ,Pulmonary mucormycosis ,Cunninghamella ,Polymerase chain reaction ,Aged ,Pcr diagnosis ,Lung Diseases, Fungal ,business.industry ,pulmonary mucormycosis ,General Medicine ,Middle Aged ,Peripheral blood ,Hematologic Neoplasms ,hematologic malignancy ,Female ,business ,030215 immunology - Abstract
Pulmonary mucormycosis (PM) is a life-threatening fungal infection in patients with hematologic malignancies, and early and accurate diagnostic modalities are urgently needed. We conducted a polymerase chain reaction (PCR) assay targeting these fungi in peripheral blood from four patients with hematologic malignancies who were strongly suspected of having PM. In these four patients, the Rhizopus species was identified in two patients, and the Cunninghamella and Absidia species in one each. Based on these molecular findings, all of the patients were successfully treated via targeted therapy with liposomal amphotericin B. In this report, a PCR analysis proved very useful for managing PM in patients with hematologic malignancies.
- Published
- 2017
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