論文 - 永田 賢治
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Tamura H, Ozono Y, Uchiyama N, Hatada H, Nakamura K, Iwakiri H, Hasuike S, Nagata K, Kawakami H
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 120 ( 6 ) 500 - 507 2023年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般財団法人 日本消化器病学会
症例は82歳，女性．両眼の視力低下を認め，近医眼科より当院紹介となった．精査により発症4日目に<i>Klebsiella pneumoniae</i>による侵襲性肝膿瘍症候群，両側眼内炎と診断した．抗菌薬の全身投与と硝子体内注射を行い，肝膿瘍は改善したが，両眼失明に至った．侵襲性肝膿瘍症候群は発熱を初発症状とする報告が多いが，本例では眼症状発症時に発熱がなく，診断が遅れ，視力予後が不良となった．
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Komaki Y., Ozono Y., Nakamura K., Iwakiri H., Hasuike S., Sueta M., Miike T., Yamamoto S., Uto H., Kusumoto K., Ochiai T., Kato J., Komada N., Kuroki K., Eto T., Shigehira M., Hirono S., Nagata K., Kawakami H.
BMC Gastroenterology 22 ( 1 ) 210 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：BMC Gastroenterology
Background: It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years. Methods: This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group. Results: In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups. Conclusions: Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment.
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Trends in hepatocellular carcinoma incident cases in Japan between 1996 and 2019 査読あり
Nakano M., Yatsuhashi H., Bekki S., Takami Y., Tanaka Y., Yoshimaru Y., Honda K., Komorizono Y., Harada M., Shibata M., Sakisaka S., Shakado S., Nagata K., Yoshizumi T., Itoh S., Sohda T., Oeda S., Nakao K., Sasaki R., Yamashita T., Ido A., Mawatari S., Nakamuta M., Aratake Y., Matsumoto S., Maeshiro T., Goto T., Torimura T.
Scientific Reports 12 ( 1 ) 1517 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996–2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60–69 years, 70–79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease.
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Uchida K., Ozono Y., Uchiyama N., Hatada H., Nakamura K., Komaki Y., Iwakiri H., Hasuike S., Nagata K., Sato Y., Kawakami H.
Medicine United States 101 ( 35 ) e30486 2022年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Medicine United States
Rationale: Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally. Since 2020, combination treatment with atezolizumab and bevacizumab were approved in patients with unresectable HCC in Japan, and atezolizumab plus bevacizumab is the first-line treatment for unresectable HCC. Patient concerns: A 73-year-old Japanese man diagnosed with a large HCC was treated with atezolizumab plus bevacizumab. After 2 cycles, he had fever and fatigue and was admitted to the hospital. Diagnosis: Abdominal contrast-enhanced computed tomography revealed tumor necrosis in HCC with gas formation in the necrotic area. Laboratory examination revealed a white blood cell (WBC) count of 16,340/μL and C-reactive protein (CRP) level of 33.0 mg/dL. Based on the above findings, he was diagnosed with a liver abscess. Interventions: Percutaneous transhepatic liver abscess drainage and broad-spectrum antibiotics treatment were performed. Outcomes: Despite liver abscess drainage, persistent fever and no improvement in the WBC count or CRP level was observed. The patient's respiratory condition and renal function gradually worsened; The patient's general condition did not improve despite the ventilator support and continuous hemodiafiltration, and he died on day 37. Lessons: We report the first case of liver abscess after atezolizumab plus bevacizumab treatment for unresectable HCC.
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大園 芳範, 中村 憲一, 岩切 久芳, 蓮池 悟, 末田 光恵, 三池 忠, 山本 章二朗, 永田 賢治, 河上 洋
BMC Gastroenterology 22 ( 1 ) 210 2022年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Springer Nature
Background
It is estimated that approximately 50% of patients with hepatitis C virus (HCV) infection in Japan are currently over 75 years old. However, patients aged ≥ 75 years are typically underrepresented in clinical trials of direct-acting antivirals. This study aimed to evaluate the efficacy and safety of glecaprevir and pibrentasvir (G/P) treatment in Japanese patients with HCV infection aged ≥ 75 years.
Methods
This multicenter, retrospective study included 271 Japanese patients with HCV infection from 12 centers in Miyazaki Prefecture, Japan. Demographic, clinical, virological, and adverse events (AEs) data obtained during and after G/P treatment were collected from medical records. The patients were divided into two groups: younger (n = 199, aged < 75 years) and older (n = 72, aged ≥ 75 years). Virological data and AEs were analyzed according to the age group.
Results
In intention-to-treat (ITT) and per-protocol analyses, the overall sustained virological response 12 (SVR12) rates were 93% and 98.8%, respectively. Two patients in the older group and 14 patients in the younger group dropped out before SVR12 assessment. Although patients in the older group tended to have liver cirrhosis, 95.8% in the older group and 92% in the younger group achieved SVR12 in the ITT analysis (P = 0.404). In total, 48 (17.7%) patients experienced treatment-related AEs. Common AEs during treatment included pruritus, headache, and fatigue. The AEs were not significantly different between the two groups.
Conclusions
Compared with younger patients, older patients showed similar virological response and tolerance to G/P treatment. -
NAKAMURA K., KUSUMOTO K., OZONO Y., KUROKI K., MATSUURA Y., MUKUDA T., OCHIAI T., TSUCHIMOCHI M., IWAKIRI H., HASUIKE S., SHIMODA K., NAGATA K.
Anticancer Research 41 ( 8 ) 4127 - 4131 2021年8月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Anticancer Research
Background/Aim: Direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection deliver higher cure rates and lower frequencies of adverse events than existing therapies, though DAA treatment costs $45,000-64,000 in Japan. The prognosis of patients who require new long-term care insurance (LTCI) certification is inferior to that of patients who do not. Here, we clarify the factors associated with new LTCI certification in elderly patients with HCV infection who undergo DAA therapy. Patients and Methods: We retrospectively surveyed 53 patients aged ≥70 years who were treated with DAAs, and evaluated the factors associated with new LTCI certification. Results: Of 53 patients, 10 required new LTCI certification. Age ≥85 years and a modified Japanese Cardiovascular Health Study index ≥2 were independently associated with new LTCI certification. Conclusion: In elderly HCV patients, poor frailty status strongly predicted new LTCI certification after DAA therapy.
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Ozono Y., Shide K., Kameda T., Kamiunten A., Tahira Y., Sekine M., Akizuki K., Nakamura K., Iwakiri H., Sueta M., Hidaka T., Kubuki Y., Yamamoto S., Hasuike S., Sawaguchi A., Nagata K., Shimoda K.
Leukemia 35 ( 2 ) 454 - 467 2021年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-β1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. In this study, we showed that the vast majority of collagen- and fibronectin-producing cells in the BM and spleens of Jak2V617F-induced myelofibrosis (MF) mice were fibrocytes derived from neoplastic hematopoietic cells. Neoplastic monocyte depletion eliminated collagen- and fibronectin-producing fibrocytes in BM and spleen, and ameliorated most characteristic MF features in Jak2V617F transgenic mice, including BM fibrosis, anemia, and splenomegaly, while had little effect on the elevated numbers of megakaryocytes and stem cells in BM, and leukothrombocytosis in peripheral blood. TGF-β1, which was produced by hematopoietic cells including fibrocytes, promoted the differentiation of neoplastic monocytes to fibrocytes, and elevated plasma TGF-β1 levels were normalized by monocyte depletion. Collectively, our data suggest that neoplastic fibrocytes are the major contributor to BM fibrosis in PMF, and TGF-β1 is required for their differentiation.
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肝疾患診療連携拠点病院における肝炎医療コーディネーターの現状 査読あり
Enomoto M., Hidaka I., Inoue T., Isoda H., Ide T., Arao Y., Uchida Y., Inoue T., Ikegami T., Kakizaki S., Setoyama H., Shimakami T., Ogawa K., Suetsugu A., Inoue J., Endo M., Nagata K., Korenaga M.
肝臓 62 ( 2 ) 96 - 98 2021年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Acta Hepatologica Japonica
In Japan, each prefecture in collaboration with regional core centers is required to train hepatitis medical care coordinators (HMCCs). In this study, we sur-veyed the present status of HMCCs in 17 of the 71 regional core centers. The findings indicated that the number of HMCCs varied from 8 to 77 per regional core center. The proportion of HMCCs who actively contributed to hepatitis patient care also varied from 7.9% to 100%. Among the HMCCs, 50% were nurses, 11% clinical laboratory technicians, 8.0% pharmacists, 8.0% registered dietitians, and 3.5% doctors. The results of the survey show that, in each regional core center, there is a substantial variety in the present status of HMCCs.
DOI： 10.2957/kanzo.62.96
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Shide K., Kameda T., Kamiunten A., Ozono Y., Tahira Y., Yokomizo-Nakano T., Kubota S., Ono M., Ikeda K., Sekine M., Akizuki K., Nakamura K., Hidaka T., Kubuki Y., Iwakiri H., Hasuike S., Nagata K., Sashida G., Shimoda K.
Blood 136 ( 1 ) 106 - 118 2020年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Blood
Mutations in JAK2, myeloproliferative leukemia virus (MPL), or calreticulin (CALR) occur in hematopoietic stem cells (HSCs) and are detected in more than 80% of patients with myeloproliferative neoplasms (MPNs). They are thought to play a driver role in MPN pathogenesis via autosomal activation of the JAK-STAT signaling cascade. Mutant CALR binds to MPL, activates downstream MPL signaling cascades, and induces essential thrombocythemia in mice. However, embryonic lethality of Calr-deficient mice precludes determination of a role for CALR in hematopoiesis. To clarify the role of CALR in normal hematopoiesis and MPN pathogenesis, we generated hematopoietic cell-specific Calr-deficient mice. CALR deficiency had little effect on the leukocyte count, hemoglobin levels, or platelet count in peripheral blood. However, Calr-deficient mice showed some hematopoietic properties of MPN, including decreased erythropoiesis and increased myeloid progenitor cells in the bone marrow and extramedullary hematopoiesis in the spleen. Transplantation experiments revealed that Calr haploinsufficiency promoted the self-renewal capacity of HSCs. We generated CALRdel52 mutant transgenic mice with Calr haploinsufficiency as a model that mimics human MPN patients and found that Calr haploinsufficiency restored the self-renewal capacity of HSCs damaged by CALR mutations. Only recipient mice transplanted with Lineage−Sca1+c-kit+ cells harboring both CALR mutation and Calr haploinsufficiency developed MPN in competitive conditions, showing that CALR haploinsufficiency was necessary for the onset of CALR-mutated MPNs. Key Points: • Calr deficiency induces reduction of erythropoiesis in the bone marrow and extramedullary hematopoiesis in the spleen. • CALR haploinsufficiency restores the self-renewal capacity of HSCs damaged by CALR del52 and is required for the development of MPN.
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Yamaji T, Shide K, Kameda T, Sekine M, Kamiunten A, Hidaka T, Kubuki Y, Shimoda H, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Shimoda K
Anticancer Research 37 ( 7 ) 3841 - 3847 2017年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Anticancer Research
Background/Aim: In myeloproliferative neoplasms (MPN), Janus kinase 2 (JAK2) is activated by mutations including JAK2V617F (JAK2VF). It is unclear whether JAK kinases [i.e. JAK1, JAK2, JAK3, or tyrosine kinase 2 (TYK2)] other than JAK2 have cooperative actions such as enhancement or suppression of JAK2. If other kinases enhance activation, therapies that co-target them could have a therapeutic efficacy. We examined the role of TYK2 in Jak2VF-induced murine MPN. Materials and Methods: We crossed Jak2VF transgenic mice and Tyk2-knockout (Tyk2KO) mice to generate Jak2VF/Tyk2KO mice. The disease severity and treatment effect with a JAK2 inhibitor was compared between Jak2VF and Jak2VF/Tyk2KO mice. Results: Both types of mice developed MPN, and there were no differences in peripheral blood counts, spleen weight, or survival period. Upon JAK2 inhibitor therapy, both types of mice had equally improved leukocytosis and splenomegaly. Conclusion: TYK2 does not have cooperative effects with JAK2VF upon MPN onset nor in the presence of a JAK2 inhibitor.
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Prediction of Sustained Virological Response to Telaprevir/Simeprevir-Based Triple Therapy in Patients with Genotype 1 Hepatitis C Virus Using Super-Early Viral Response within 2 Weeks. 査読あり
Ozono Y, Takaishi Y, Tsuchimochi M, Nakamura K, Abe H, Miike T, Kusumoto K, Iwakiri H, Sueta M, Tahara Y, Yamamoto S, Hasuike S, Nagata K, Shimoda K
Journal of Liver. 6 ( 6 ) 1 - 6 2017年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Shide K., Kameda T., Yamaji T., Sekine M., Inada N., Kamiunten A., Akizuki K., Nakamura K., Hidaka T., Kubuki Y., Shimoda H., Kitanaka A., Honda A., Sawaguchi A., Abe H., Miike T., Iwakiri H., Tahara Y., Sueta M., Hasuike S., Yamamoto S., Nagata K., Shimoda K.
Leukemia 31 ( 5 ) 1136 - 1144 2017年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Leukemia
© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Mutations of calreticulin (CALR) are detected in 25-30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal tr ansducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation. Transgenic mice expressing a human CALR mutation with a 52 bp deletion (CALRdel52-transgenic mice (TG)) developed ET, with an increase in platelet count, but not hemoglobin level or white blood cell count, in association with an increase in bone marrow (BM) mature megakaryocytes. CALRdel52 BM cells did not drive away wild-type (WT) BM cells in in vivo competitive serial transplantation assays, suggesting that the self-renewal capacity of CALRdel52 hematopoietic stem cells (HSCs) was comparable to that of WT HSCs. Therapy with the Janus kinase (JAK) inhibitor ruxolitinib ameliorated the thrombocytosis in TG mice and attenuated the increase in number of BM megakaryocytes and HSCs. Taken together, our study provides a model showing that the C-terminal of mutant CALR activated JAK-STAT signaling specifically downstream of MPL and may have a central role in CALR-induced myeloproliferative neoplasms.
DOI： 10.1038/leu.2016.308
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TET2 mutation in diffuse large B-cell lymphoma. 査読あり
Kubuki Y, Yamaji T, Hidaka T, Kameda T, Shide K, Sekine M, Kamiunten A, Akizuki K, Shimoda H, Tahira Y, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Kitanaka A, Shimoda K
Journal of clinical and experimental hematopathology 56 ( 3 ) 145 - 149 2017年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：日本リンパ網内系学会
<i>Ten-eleven translocation-2 (TET2)</i> mutation is frequently observed in myeloid malignancies, and loss-of-function of TET2 is essential for the initiation of malignant hematopoiesis. <i>TET2</i> mutation presents across disease entities and was reported in lymphoid malignancies. We investigated <i>TET2</i> mutations in 27 diffuse large B-cell lymphoma (DLBCL) patients and found a frameshift mutation in 1 case (3.7%). <i>TET2</i> mutation occurred in some populations of DLBCL patients and was likely involved in the pathogenesis of their malignancies.
DOI： 10.3960/jslrt.56.145
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Ito K., Yotsuyanagi H., Sugiyama M., Yatsuhashi H., Karino Y., Takikawa Y., Saito T., Arase Y., Imazeki F., Kurosaki M., Umemura T., Ichida T., Toyoda H., Yoneda M., Tanaka Y., Mita E., Yamamoto K., Michitaka K., Maeshiro T., Tanuma J., Korenaga M., Murata K., Masaki N., Koike K., Mizokami M., Imai Y., Yamada N., Takahashi H., Ishii K., Nomura H., Nishida J., Mikami S., Kitamura T., Tsubota A., Shimada N., Ishikawa T., Ueno Y., Ohno T., Orito E., Suzuki M., Kakizaki S., Takagi H., Tomita E., Takashi K., Mizuta T., Mine T., Kang J., Hirano K., Tsubouchi H., Nozaki A., Sakai A., Nishiguchi S., Tamori A., Hagiwara S., Nakazawa T., Sata M., Kamoshida T., Takahashi A., Kobayashi Y., Sasaki S., Ikegami T., Hiasa Y., Nagata K., Kubota T., Mitsui H., Yamamoto N., Tsuge M., Sato S., Ito Y., Sato W., Uchida S., Tada Y., Mizuochi T., Furusho N., Hige S., Yoshiyasu Karino, Kobayashi M., Hosho K., Yamagiwa S., Sakaida I., Nakane K.
Journal of Gastroenterology and Hepatology (Australia) 31 ( 1 ) 180 - 189 2016年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Gastroenterology and Hepatology (Australia)
© 2016 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd. Background and Aims: The prevalence of sexually transmitted acute infections of the genotype A hepatitis B virus (HBV) has been increasing in Japan. Genotype A HBV is associated with an increased risk of HBV progression to chronic infection after acute hepatitis B (AHB) in adults. A nationwide survey was conducted to evaluate the geographic distribution, clinical, and virologic characteristics of genotype A AHB and chronic hepatitis B (CHB) in Japan. Methods: Five hundred seventy AHB patients were recruited between 2005 and 2010, and 3682 CHB patients were recruited between 2010 and 2011. HBV genotypes were determined for 552 and 3619 AHB and CHB patients, respectively. Clinical characteristics were compared among different genotypes in AHB and CHB patients. Genomic characteristics of HBV genotype A were examined by molecular evolutionary analysis. Results: Hepatitis B virus genotype A was the predominant genotype for AHB between 2005 and 2010. Phylogenetic analysis showed that all strains in the AHB patients with genotype A were classified into subtype Ae. Among CHB patients, the occurrence of genotype A was 4.1%, and genotype A was spreading in young adults. In genotype A CHB patients, early stage liver diseases were predominant, although liver diseases progressed to cirrhosis or hepatocellular carcinoma in some patients. Conclusions: The distribution of HBV genotypes is quite different between AHB and CHB in Japanese patients. Genotype A infection is spreading in young adults of Japanese CHB patients. Sequences derived from Japanese AHB patients were identical to or closely resembled the sequences derived from other Japanese AHB patients.
DOI： 10.1111/jgh.13030
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Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer.
Miike T, Yamamoto S, Miyata Y, Hirata T, Noda Y, Noda T, Suzuki S, Takeda S, Natsuda S, Sakaguchi M, Maemura K, Hashimoto K, Yamaji T, Abe H, Iwakiri H, Tahara Y, Hasuike S, Nagata K, Kitanaka A, Shimoda K
Gastroenterology research and practice 2016 6527653 2016年
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Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer. (共著) 査読あり
Miike T, Yamamoto S, Miyata Y, Hirata T, Noda Y, Noda T, Suzuki Sho, Takeda S, Natsuda S, Sakaguchi M, Maemura K, Hashimoto K, Yamaji T, Abe H, Iwakiri H, Tahara Y, Hasuike S, Nagata K, Kitanaka A, Shimoda K:
Gastroenterology Research and Practice. 2015年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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TET2 Mutation in Adult T-Cell Leukemia/Lymphoma. (共著) 査読あり
Shimoda K, Shide K, Kameda T, Hidaka T, Kubuki Y, Kamiunten A, Sekine M, Akizuki K, Shimoda H, Yamaji T, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Kitanaka A:
J Clin Exp Hematop. 2015年12月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Kameda T., Shide K., Yamaji T., Kamiunten A., Sekine M., Taniguchi Y., Hidaka T., Kubuki Y., Shimoda H., Marutsuka K., Sashida G., Aoyama K., Yoshimitsu M., Harada T., Abe H., Miike T., Iwakiri H., Tahara Y., Sueta M., Yamamoto S., Hasuike S., Nagata K., Iwama A., Kitanaka A., Shimoda K.
Blood 125 ( 2 ) 304 - 315 2015年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Blood
© 2015 by The American Society of Hematology Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs).We examined the individual and cooperative effects of these mutations onMPN development. Recipients of JAK2V617F cells developed primary myelofibrosis-like features; the addition of loss of TET2 worsened this JAK2V617F-induced disease, causing prolonged leukocytosis, splenomegaly, extramedullary hematopoiesis, and modestly shorter survival. Double-mutant (JAK2V617F plus loss of TET2) myeloid cells were more likely to be in a proliferative state than JAK2V617F single-mutant myeloid cells. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the second recipients, which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and loss of TET2 developed and maintained MPNs in the second recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. In-vitro sequential colony formation assays also supported the observation that JAK2V617F did not maintain HSC functioning over the long-term, but concurrent loss of TET2 mutation restored it. Transcriptional profiling revealed that loss of TET2 affected the expression of many HSC signature genes. We conclude that loss of TET2 has two different roles in MPNs: disease accelerator and disease initiator and sustainer in combination with JAK2V617F.
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Nakamura M., Kusumoto K., Ochiai T., Kawagoe T., Tai H., Matsuoka H., Nakano T., Nagata K., Shimoda K., Okamoto H.
Journal of Japanese Society of Gastroenterology 112 ( 8 ) 1533 - 1541 2015年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Japanese Society of Gastroenterology
We experienced two cases of acute hepatitis E in Miyazaki Prefecture in the same period. The patients were unknown to each other and did not have any clear causes or common risk factors of hepatitis E virus (HEV) infection. Nucleotide sequences of the HEV isolates revealed that the two isolates were closely related but with different HEV genotype 3 strains. The two cases appeared to be infected from unknown and different sources. Molecular phylogenetic analysis indicated that the strains were probably descendants of the strains which had been isolated from swine herd in Miyazaki Prefecture 12 years previously. This result indicates that the strains persisted in pig farms, in wild life, or in the natural environment in this region. The source should be identified, and efforts should be made to prevent of the spread of the infection. One of the cases had acute facial paralysis, which might be an extra-hepatic manifestation of HEV infection.
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12年前から宮崎県に存続している遺伝子型3型E型肝炎ウイルスによるE型急性肝炎の2症例 1例での急性末梢性顔面神経麻痺の合併(共著) 査読あり
Nakamura M, Kusumoto K, Ochiai T, Kawagoe T, Tai H, Matsuoka H, Nakano T, Nagata K, Shimoda K, Okamoto H:
日本消化器病学会雑誌 2015年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌）