Papers - UMEKITA Kunihiko
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全身性強皮症と関節リウマチで治療中の患者に生じた尖圭コンジローマ，bowenoid papulosisの合併例 Reviewed
西元順子、 成田幸代、梅北邦彦、天野 正宏
皮膚病診療 44 ( 4 ) 334 - 337 2022.4
Publishing type：Case report
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宮崎県内で初めて人工呼吸器管理を要した重症新型コロナウイルス感染症. Reviewed
工藤理紗, 高城一郎, 力武雄輝, 岩尾浩昭, 力武真央, 相澤彩子, 仮屋裕美, 川口剛, 松田基弘, 宮内俊一, 梅北邦彦, 高城佳人子, 川名遼, 森定淳, 松元信弘, 谷口正彦, 落合秀信, 岡山昭彦.
宮崎県医師会医学会誌 45 ( 1 ) 44 - 49 2021.3
Publishing type：Research paper (scientific journal)
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TNF阻害療法経過中に肺 Mycobacterium avium complex 感染症を発症したHTLV-1陽性関節リウマチ患者への生物学的製剤治療経験. Reviewed
木村賢俊, 梅北邦彦, 工藤理紗, 岩尾千紘, 力武雄幹, 力武真央, 岩尾浩昭, 相澤彩子, 川口剛, 仮屋裕美, 松田基弘, 宮内俊一, 高城佳人子, 高城一郎, 岡山昭彦.
九州リウマチ 40 ( 1 ) 34 - 40 2020.3
Language：Japanese Publishing type：Research paper (scientific journal)
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HTLV-1 Infection and Rheumatic Diseases
Umekita K., Okayama A.
Frontiers in Microbiology 11 152 2020.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Frontiers in Microbiology
Some major research and clinical questions about human T-cell leukemia virus type 1 (HTLV-1) infection and rheumatic diseases remain: (1) Does HTLV-1 infection cause rheumatic diseases? (2) Do patients with rheumatic diseases display different responses to treatment with anti-rheumatic agents when they are HTLV-1 carriers? (3) Is adult T-cell leukemia/lymphoma (ATL) or HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) more prevalent in HTLV-1 carriers with rheumatic diseases who are treated with anti-rheumatic agents? These questions are important because increasing numbers of patients with rheumatic diseases are currently receiving treatment with aggressive medicines such as immunosuppressants and biologics. Studies on HTLV-1 gene-transgenic mice have shown manifestations resembling rheumatic diseases. Epidemiological studies have shown a high incidence of HTLV-1 infection in patients with rheumatic diseases including rheumatoid arthritis (RA), Sjogren’s syndrome, and polymyositis. HTLV-1-positive and HTLV-1-negative patients with RA have displayed similar immunological features including the seroprevalence of anti-citrullinated peptide antibodies. Conversely, attenuated effectiveness of tumor necrosis factor inhibitors for HTLV-1-positive patients with RA in Japan has been reported. Therefore, although no direct evidence has shown that HTLV-1 infection alone causes rheumatic diseases, HTLV-1 may affect the inflammation of RA. Although the incidence of ATL or HAM/TSP among patients with rheumatic diseases has not been investigated in large-scale studies, ATL or HAM/TSP has developed among HTLV-1-positive patients with rheumatic diseases. HTLV-1 infection may affect the clinical course of patients with rheumatic diseases, particularly after receiving anti-rheumatic agents. Because studies on these issues are limited, further investigation with large sample sizes is necessary.
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抗HTLV-1抗体陽性関節リウマチにおける非TNF阻害薬の臨床効果と安全性
遠藤 友志郎, 中村 英樹, 梅北 邦彦, 岡田 覚丈, 藤川 敬太, 荒牧 俊幸, 松岡 直樹, 植木 幸孝, 日高 利彦, 川上 純
日本内科学会雑誌 109 ( Suppl. ) 254 - 254 2020.2
Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本内科学会
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Umekita K., Miyauchi S., Nomura H., Umeki K., Okayama A.
Clinical and experimental rheumatology 37 ( 5 ) 834 - 841 2019.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Clinical and experimental rheumatology
OBJECTIVES: Damage-associated molecular patterns (DAMPs) are proposed to drive aberrant stimulation of Toll-like receptors (TLRs) in rheumatoid arthritis (RA) inflamed joints. In the current study we investigated the role of the neutrophil-derived lactoferrin (LTF), as an endogenous ligand for TLR4 in the inflammatory response of RA synovial fibroblasts (RASFs). METHODS: RASFs were stimulated with LTF, and the expressions of inflammatory cytokines in RASFs were measured. To clarify the TLR4 signalling pathway associated with LTF stimulation, a small molecular inhibitor of TLR4 (TAK242) and NF-κB inhibitor were used. The role of nuclear factor of activated T cells 5 (NFAT5) was identified using small interfering RNA. To reveal the interaction between NF-κB and NFAT5, cerulenin, which disrupts their interaction, was used. RESULTS: Stimulation of RASFs with LTF significantly increased the expressions of inflammatory cytokines and chemokines, such as IL-6, CCL20 and IL-8, in RASFs. LTF enhanced the mRNA expressions of these cytokines in RASFs stimulated by TNF-α. TAK242 almost completely inhibited the expressions of inflammatory cytokines and chemokines in RASFs stimulated by LTF. The NF-κB inhibitor partially repressed the expressions of IL-6 and IL-8 mRNAs induced by LTF, but not CCL20 mRNA expression. On the other hand, NFAT5 silencing decreased the expressions of CCL20 and IL-8 mRNAs induced by LTF, but not IL-6 mRNA expression. Cerulenin repressed the expressions of IL-6, CCL20 and IL-8 in RASFs stimulated by LTF. CONCLUSIONS: Neutrophil-derived LTF may play a role as an endogenous ligand for TLR4 expressed on RASFs. NFAT5-NF-κB enhanceosome might regulate the expressions of LTF-TLR4-responsive genes in RASFs.
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Peliosis Hepatis Due to Corticosteroid in Systemic Lupus Erythematosus Reviewed
Kimura Masatoshi, Aizawa Ayako, Miyauchi Shunichi, Hasuike Satoru, Umekita Kunihiko
Internal Medicine 58 ( 11 ) 1663 - 1664 2019.6
Language：English Publishing type：Research paper (scientific journal) Publisher：一般社団法人 日本内科学会
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Insight of diagnostic performance using B-cell epitope antigens derived from triple P44-related proteins of Anaplasma phagocytophilum Reviewed
Su H., Ito K., Kawarasaki Y., Morita H., Nose H., Ikeda K., Nakadouzono F., Gokuden M., Kamiyama S., Tokaji A., Rikitake Y., Kawaguchi T., Umekita K., Oishi S., Abe F., Kanda T., Kawabata H., Ando S., Ohashi N.
Diagnostic Microbiology and Infectious Disease 95 ( 2 ) 125 - 130 2019.5
Language：English Publishing type：Research paper (scientific journal) Publisher：Diagnostic Microbiology and Infectious Disease
© 2019 Elsevier Inc. Human granulocytic anaplasmosis (HGA) is caused by Anaplasma phagocytophilum. Indirect immunofluorescence assay (IFA) is generally used for HGA serodiagnosis. A. phagocytophilum immunodominant P44 major outer membrane proteins are encoded by p44/msp2 multigene family, responsible for IFA reactivity. However, because multiple P44-related proteins may involve immunoreactivity in IFA, the available diagnostic antigens remain obscure. In this study, we identified 12 B-cell epitopes on triple P44-related proteins using peptide array that reacted with 4 HGA patients' sera. Then, peptide spot immunoassay using 14 synthetic peptides derived from those 12 epitopes as antigens was applied for the detection of antibody to A. phagocytophilum from patients with fever of unknown origin. The sensitivities and diagnostic efficiencies of this immunoassay were higher than those of Western blot analysis using 3 recombinant proteins previously developed. Thus, the immunoassay using our epitope-derived antigens, which has higher diagnostic performances, may have significant benefit for HGA serodiagnosis.
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Diversity of cell phenotypes among MT-2 cell lines affects the growth of U937 cells and cytokine production. Reviewed
Nomura H, Umekita K, Hashikura Y, Umeki K, Yamamoto I, Aratake Y, Saito M, Hasegawa H, Yanagihara K, Okayama A
Human cell 32 ( 2 ) 185 - 192 2019.4
Language：English Publishing type：Research paper (scientific journal)
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IgG4関連涙腺・唾液腺炎に認められた回腸末端部の隆起性病変. Reviewed
岩尾浩昭, 梅北邦彦, 岩尾千紘, 力武雄幹, 力武真央, 相澤彩子, 川口剛, 松田基弘, 宮内俊一, 高城一郎, 長安真由美, 秋山裕, 片岡寛章, 前川和也, 浅田祐士郎, 岡山昭彦.
九州リウマチ 39 ( 1 ) 40 - 48 2019.3
Language：Japanese Publishing type：Research paper (scientific journal)
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Yamada A, Umeki K, Saeki Y, Hashikura Y, Nomura H, Yamamoto I, Umekita K, Takajo I, Koshimoto C, Okayama A.
Journal of Microbiological Methods 155 42 - 48 2018.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Microbiological Methods
© 2018 Elsevier B.V. Although isolation and identification of bacteria in a clinical specimen constitute essential steps for the diagnosis of bacterial infection, positive results of the bacterial culture are not always attained, despite observing the bacteria by Gram staining. As bacteria phagocytosed by the leukocytes are considered as the causative agents of infectious diseases, this study aims to introduce a new approach for the collection of only bacteria phagocytosed by the neutrophils in an animal model using laser capture microdissection (LCM) followed by the DNA identification using polymerase chain reaction (PCR). We inoculated representative bacteria (Escherichia coli and Staphylococcus aureus) into the abdominal cavities of specific pathogen-free C57BL/6 J mice. After 6 h inoculation, we collected the fluid samples from the peritoneal cavities of mice and demonstrated peritonitis by the increase of neutrophils. Then, we smeared the neutrophils on the membrane slides and collected single-cell phagocytosing bacteria by LCM. The supernatant of the cell lysate was supplied for the PCR reaction to amplify the 16S rRNA gene, and we validated the DNA sequences specific for the inoculated bacteria. In addition, PCR using specific primers for E. coli and S. aureus identified each species of bacteria. Hence, this study suggests that the combination of LCM and PCR could be a novel approach to determine bacteria in infectious diseases. Nevertheless, further investigation is warranted to test various additional bacterial taxa to demonstrate the general applicability of this method to clinical samples.
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Takajo, I., Yamada, A., Umeki, K., Saeki, Y., Hashikura, Y., Yamamoto, I., Umekita, K., Urayama-Kawano, M., Yamasaki, S., Taniguchi, T., Misawa, N., Okayama, A.
Journal of Microbiological Methods 144 22 - 28 2018.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Microbiological Methods
© 2017 Elsevier B.V. Vibrio furnissii and V. fluvialis are closely related, the discrimination of which by conventional biochemical assay remains a challenge. Investigation of the sequence of the 16S rRNA genes in a clinical isolate of V. furnissii by visual inspection of a sequencing electropherogram revealed two sites of single-nucleotide polymorphisms (SNPs; positions 460 A/G and 1261 A/G) in these genes. A test of 12 strains each of V. fluvialis and V. furnissii revealed these SNPs to be common in V. furnissii but not in V. fluvialis. Divergence of SNP frequency was observed among the strains of V. furnissii tested. Because the SNPs described in V. furnissii produce a difference in the target sequence of restriction enzymes, a combination of polymerase chain reaction (PCR) of the 16S rRNA genes using conventional primers and restriction fragment length polymorphism analysis using Eco RV and Eae I was shown to discriminate between V. fluvialis and V. furnissii. This method is simple and alleviates the need for expensive equipment or primer sets specific to these bacteria. Therefore, we believe that this method can be useful, alongside specific PCR and mass spectrometry, when there is a need to discriminate between V. fluvialis and V. furnissii.
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Infliximab as an alternative therapy for refractory adult onset Kawasaki disease A case report Reviewed
Kawaguchi T., Rikitake Y., Tsuruda T., Kawata C., Rikitake M., Iwao K., Aizawa A., Kariya Y., Matsuda M., Miyauchi S., Umekita K., Takajo I., Okayama A.
Medicine (United States) 97 ( 40 ) e12720 - e12720 2018.10
Language：English Publishing type：Research paper (scientific journal) Publisher：Medicine (United States)
Copyright © 2018 the Author(s). Rationale: Kawasaki disease (KD) is an acute febrile illness predominantly affecting children less than 5 years of age and characterized by systemic inflammation in all medium-sized arteries. Adult-onset KD (AKD) is rare with only 105 case reports published. Recently, the efficacy of infliximab (IFX) for patients with refractory KD has been demonstrated. Patient concerns: A previously healthy 24-year-old man was admitted because of a persistent fever, and elevated serum level of AST, ALT, LDH, and CRP. Diagnosis: The patients met the diagnostic criteria for KD based on the findings of persistent fever, polymorphous exanthema, unilateral cervical lymphadenopathy, non-purulent palpebral conjunctivitis and membranous desquamation. Echocardiogram revealed the dilatation at the proximal sites of the right coronary artery (7.9 mm) and left anterior descending artery (5 mm). The patient was treated with high-dose intravenous immunoglobulin (1 g/kg/day for 2 days) and ASA (100 mg daily). However, his fever and arthralgia persisted. Interventions: He was administered single 5 mg/kg doses of IFX. Outcomes: He became afebrile the next day and his arthralgia improved. Lessons: We report the first case of administration of IFX in a patient with AKD refractory to intravenous immunoglobulin (IVIG), and successful reduction of systemic inflammation. However, the effectiveness of IFX in the regression of coronary artery aneurysm remains to be determined.
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多発脳梗塞を来した治療抵抗性巨細胞性動脈炎の1例. Reviewed
力武真央, 梅北邦彦, 楠元規生, 岩尾浩昭, 相澤彩子, 松田基弘, 久保和義, 仮屋裕美, 宮内俊一, 高城一郎, 長友安弘, 岡山昭彦.
九州リウマチ. 37 ( 2 ) 125 - 131 2017.9
Language：Japanese Publishing type：Research paper (scientific journal)
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Infection of defective human T-lymphotropic virus type 1 Reviewed
Hashikura Y., Umeki K., Umekita K., Nomura H., Yamada A., Yamamoto I., Hasegawa H., Yanagihara K., Okayama A.
Human Cell 30 ( 2 ) 117 - 123 2017.4
Language：English Publishing type：Research paper (scientific journal) Publisher：Human Cell
© 2017, Japan Human Cell Society and Springer Japan. In a previous study, we reported that an identical defective provirus had integrated into multiple sites of the genome of a representative human T-lymphotropic virus type 1 (HTLV-1) cell line, MT-2. A possible explanation for this may be the repeated infection of this defective provirus to a cell. Therefore, we attempted to determine whether a defective provirus could transmit during the co-culture of HTLV-1 uninfected human T-cell line, Jurkat, with MT-2 cells treated with mitomycin C. As a result, we established not only a cell line with the integration of one complete provirus, but also a cell line with the integration of one defective provirus. The rearrangement of the T-cell receptor -γ gene of these cell lines showed them to be derived from Jurkat cells. Both HTLV-1 Tax/Rex and HBZ RNA were detected in the cell line, which harbors a complete provirus. On the other hand, HBZ RNA and transcriptional product specific for the defective provirus were detected in the cell line, which harbors a defective HTLV-1 provirus only. These results suggested that a defective HTLV-1 provirus with large depletion of internal sequence could transmit to other cells. Moreover, the defective provirus can be transcriptionally active. This suggested the possibility that the defective HTLV-1 provirus found in the lymphocytes of HTLV-1 carriers and patients with adult T-cell leukemia may transmit to other T-cells in vivo. The results also suggested that defective provirus in HTLV-1 carriers could be functional and may play a role in leukemogenesis.
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関節リウマチ治療中に発症したウエステルマン肺吸虫症.
小村真央, 宮内俊一, 岩尾浩昭, 河野彩子, 松田基弘, 久保和義, 梅北邦彦, 高城一郎, 長友安弘, 岡山昭彦, 丸山治彦.
宮崎県内科医会誌. ( 91 ) 11 - 15 2017.3
Language：Japanese Publishing type：Research paper (scientific journal)
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筋ジストロフィーとの鑑別を要し、経口ステロイドおよびタクロリムス併用療法が奏功した抗SRP抗体陽性ミオパチーの2例. Reviewed
河野彩子, 梅北邦彦, 小村真央, 岩尾浩昭, 松田基弘, 久保和義, 宮内俊一, 高城一郎, 長友安弘, 塩見一剛, 西野一三, 岡山昭彦.
九州リウマチ. 37 ( 1 ) 72 - 79 2017.3
Language：Japanese Publishing type：Research paper (scientific journal)
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Kato H., Yamagishi T., Shimada T., Matsui T., Shimojima M., Saijo M., Oishi K., Abe M., Wada M., Umekita K., Kamekou M., Tanioka D., Sanada I., Kuwai T., Tanaka Y., Shigetou K., Homma Y., Yamamoto C., Yamauchi M., Hayashi S., Watanabe S., Kitao A., Takatsu H., Nakanishi Y., Koguro K., Watanabe M., Uehara N., Kaneko M., Yamanaka A., Murakami Y., Konishi T., Sakamoto A., Harada M., Yamamoto K., Hayashi T., Kondo N., Suemori K., Ogawa T., Nakazawa R., Yamamoto Y., Miyahara M., Senba T., Maruhashi T., Fukushi S., Tani H., Yoshikawa T., Morikawa S.
PLoS ONE 11 ( 10 ) 2016.10
Language：English Publishing type：Research paper (scientific journal) Publisher：PLoS ONE
© 2016 Kato et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these casepatients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients.
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Kawaguchi T, Matsuda M, Takajo I, Kawano A, Kariya Y, Kubo K, Miyauchi S, Umekita K, Nagatomo Y, Yano T, Yano K, Okayama A.
Journal of Infection and Chemotherapy. 22 ( 9 ) 633 - 637 2016.9
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier.
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The diversity of the structure and genomic integration sites of HTLV-1 provirus in MT-2 cell lines Reviewed
Hashikura Y., Umeki K., Umekita K., Nomura H., Yamamoto I., Hasegawa H., Yanagihara K., Okayama A.
Human Cell 29 ( 3 ) 122 - 129 2016.7
Language：English Publishing type：Research paper (scientific journal) Publisher：Human Cell
© 2016, Japan Human Cell Society and Springer Japan. A human T-lymphotropic virus Type 1 (HTLV-1) positive cell line, MT-2, derived from human cord leukocytes co-culturing with adult T cell leukemia/lymphoma (ATL) cells is commonly used in HTLV-1 research; however, the details of provirus integrated in MT-2 genome have not yet been characterized. In this study, five types of HTLV-1 proviral sequences were detected in 11 different sites of the genome in a reference MT-2 cell line. The five types of HTLV-1 proviral sequences were one complete proviral genome, two types of proviruses with deletion of large internal viral sequences (5.3 and 3.9 kB), one provirus with a large deletion (6.2 kB) from 5′LTR to position 6257, and one provirus of LTR only. The provirus with identical deletion of large internal viral sequence (5.3 kB) was found to be integrated into six different sites (chromosomes). A complete provirus and three of four types of defective provirus were consistently detected in two other MT-2 cell lines cultured in different laboratories. Not only Tax/Rex RNA and HBZ RNA, but also the transcriptional product for a specific defective provirus, were detectable in all three MT-2 cell lines. Because it has been reported that defective provirus is frequently detected in ATL cells, these results may be important in understanding the mechanism of HTLV-1 proviral polymorphism, which may be related to leukemogenesis. In addition, the large variation in integrated HTLV-1 proviruses makes it important for researchers to exercise caution in their assessment and interpretation of results using MT-2 cell lines.