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4. Pulmonary Hypertension With Interstitial Pneumonia: Initial Treatment Effectiveness and Severity in a Japan Registry

Author

Tanabe, Nobuhiro, Kumamaru, Hiraku, Tamura, Yuichi, Kondoh, Yasuhiro, Nakayama, Kazuhiko, Kinukawa, Naoko, Kimura, Tomoki, Nishiyama, Osamu, Tsujino, Ichizo, Shigeta, Ayako, Morio, Yoshiteru, Inoue, Yoshikazu, Kuraishi, Hiroshi, Hirata, Ken-ichi, Tanaka, Kensuke, Kuwana, Masataka, Nagaoka, Tetsutaro, Handa, Tomohiro, Sugimura, Koichiro, Sakamaki, Fumio, Naito, Akira, Taniguchi, Yu, Matsubara, Hiromi, Hanaoka, Masayuki, Inami, Takumi, Hayama, Naoki, Nishimura, Yoshihiro, Kimura, Hiroshi, Miyata, Hiroaki, and Tatsumi, Koichiro

Published
2024
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5. Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH Registry

Author

Guth, Stefan, D'Armini, Andrea M, Delcroix, Marion, Nakayama, Kazuhiko, Fadel, Elie, Hoole, Stephen P, Jenkins, David P, Kiely, David G, Kim, Nick H, Lang, Irene M, Madani, Michael M, Matsubara, Hiromi, Ogawa, Aiko, Ota-Arakaki, Jaquelina S, Quarck, Rozenn, Sadushi-Kolici, Roela, Simonneau, Gérald, Wiedenroth, Christoph B, Yildizeli, Bedrettin, Mayer, Eckhard, and Pepke-Zaba, Joanna

Subjects
Rare Diseases, Lung, Cardiovascular
Abstract

Pulmonary endarterectomy (PEA), pulmonary arterial hypertension (PAH) therapy and balloon pulmonary angioplasty (BPA) are currently accepted therapies for chronic thromboembolic pulmonary hypertension (CTEPH). This international CTEPH Registry identifies clinical characteristics of patients, diagnostic algorithms and treatment decisions in a global context. 1010 newly diagnosed consecutive patients were included in the registry between February 2015 and September 2016. Diagnosis was confirmed by right heart catheterisation, ventilation-perfusion lung scan, computerised pulmonary angiography and/or invasive pulmonary angiography after at least 3 months on anticoagulation. Overall, 649 patients (64.3%) were considered for PEA, 193 (19.1%) for BPA, 20 (2.0%) for both PEA and BPA, and 148 (14.7%) for PAH therapy only. Reasons for PEA inoperability were technical inaccessibility (n=235), comorbidities (n=63) and patient refusal (n=44). In Europe and America and other countries (AAO), 72% of patients were deemed suitable for PEA, whereas in Japan, 70% of patients were offered BPA as first choice. Sex was evenly balanced, except in Japan where 75% of patients were female. A history of acute pulmonary embolism was reported for 65.6% of patients. At least one PAH therapy was initiated in 35.8% of patients (26.2% of PEA candidates, 54.5% of BPA candidates and 54.1% of those not eligible for either PEA or BPA). At the time of analysis, 39 patients (3.9%) had died of pulmonary hypertension-related causes (3.5% after PEA and 1.8% after BPA). The registry revealed noticeable differences in patient characteristics (rates of pulmonary embolism and sex) and therapeutic approaches in Japan compared with Europe and AAO.

Published
2021

12. Predictive model of bosentan-induced liver toxicity in Japanese patients with pulmonary arterial hypertension

Author

Yorifuji, Kennosuke, Uemura, Yuko, Horibata, Shinji, Tsuji, Goh, Suzuki, Yoko, Nakayama, Kazuhiko, Hatae, Takashi, Kumagai, Shunichi, and Emoto, Noriaki

Subjects
Endothelin -- Physiological aspects -- Analysis, Single nucleotide polymorphisms -- Physiological aspects -- Analysis, Liver -- Analysis -- Physiological aspects, Enzymes -- Physiological aspects -- Analysis, Liver diseases -- Care and treatment, Antihypertensive drugs -- Analysis -- Physiological aspects, Pulmonary hypertension -- Care and treatment, Pharmacogenetics -- Analysis -- Physiological aspects, Biological sciences
Abstract

Bosentan, an endothelin receptor antagonist, has been widely used as a first-line medication for the treatment of pulmonary arterial hypertension (PAH). It has been shown to improve symptoms of hypertension, exercise capacity, and hemodynamics and prolong time to clinical worsening. However, liver dysfunction is a major side effect of bosentan treatment that could hamper the optimal management of patients with PAH. Previously, we demonstrated, using drug metabolism enzymes and transporters analysis, that the carbohydrate sulfotransferase 3 (CHST3) and CHST13 alleles are significantly more frequent in patients with elevated aminotransferases during therapy with bosentan than they are in patients without liver toxicity. In addition, we constructed a pharmacogenomics model to predict bosentan-induced liver injury in patients with PAH using two single-nucleotide polymorphisms and two nongenetic factors. The purpose of the present study was to externally validate the predictive model of bosentan-induced liver toxicity in Japanese patients. We evaluated five cases of patients treated with bosentan, and one presented with liver dysfunction. We applied mutation alleles of CHST3 and CHST13, serum creatinine, and age to our model to predict liver dysfunction. The sensitivity and specificity were calculated as 100% and 50%, respectively. Considering that PAH is a rare disease, multicenter collaboration would be necessary to validate our model. Key words: bosentan, pulmonary arterial hypertension, pharmacogenomics, CHST3, CHST13. Le bosentan, un antagoniste des recepteurs de l'endotheline, est un medicament qui a ete largement utilise en premiere ligne dans le traitement de l'hypertension arterielle pulmonaire (HAP). On a montre qu'il permet d'attenuer les symptomes de l'hypertension ainsi que d'ameliorer la capacite a l'effort physique et les parametres hemodynamiques, avec une augmentation du temps ecoule avant de presenter une aggravation sur le plan clinique. Cependant, le dysfonctionnement hepatique represente un effet indesirable majeur du bosentan qui pourrait nuire a la prise en charge optimale des patients atteints d'HAP. Anterieurement, a l'aide de l'etude des enzymes et des transporteurs de la biotransformation des medicaments, nous avons montre que les alleles de la sulfotransferase carbohydrique 3 (CHST3) et CHST13 sont nettement plus frequents chez les patients presentant une hausse des aminotransferases au cours du traitement par le bosentan que chez ceux qui ne presentaient pas de toxicite hepatique. De plus, nous avons construit un modele pharmacogenomique en vue de predire la presence de lesions hepatiques engendrees par le bosentan chez les patients atteints d'HAP a l'aide de deux polymorphismes mononucleotidiques et de deux facteurs non genetiques. La presente etude avait pour but de valider exterieurement le modele predictif de toxicite hepatique engendree par le bosentan chez des patients japonais. Nous avons evalue cinq cas de patients traites par le bosentan, dont l'un d'entre eux presentait un dysfonctionnement hepatique. En vue de predire le dysfonctionnement hepatique, nous avons applique a notre modele des alleles de mutation de CHST3 et de CHST13, la creatinine serique et l'age. Nous avons calcule une sensibilite et une specificite de 100 % et de 50 %, respectivement. Etant donne que l'HAP est une maladie rare, une collaboration multicentrique serait necessaire pour valider notre modele. [Traduit par la Redaction] Mots-cles: bosentan, hypertension arterielle pulmonaire, pharmacogenomique, CHST3, CHST13., Introduction Pulmonary arterial hypertension (PAH) is a rare disease with a high mortality rate (Galie et al. 2016). Treatment options have improved in the last two decades including prostanoids, phosphodiesterase-5 [...]

Published
2020
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23. Methylobacteriumsp. isolated from the midgut of Anopheles stephensiinhibits egg maturation in host ovary

Author

Hakozaki, Jun, Nonogaki, Yusuke, Tanabe, Taishi, Nishiyama, Keita, Nakayama, Kazuhiko, Haraguchi, Asako, Nakamura, Sakure, Kusakisako, Kodai, and Ikadai, Hiromi

Abstract

The gut bacteria of insects are associated with digestion, nutrition, and reproduction. The midgut bacteria of Anophelesmosquitoes have been examined predominantly for their effects on the transmission of Plasmodiumparasites. However, the effects of midgut bacteria on Anophelesmosquitoes have not been studied. In this study, we investigated the effects of midgut bacteria on adult female An. stephensimosquitoes.These mosquitoes were fed antibiotics mixed with 10% sucrose for 2 weeks to alter the composition of their midgut bacteria. The results showed that the mosquitoes fed with streptomycin (ST) or kanamycin (KM) showed inhibited egg maturation 2 days after blood feeding. Methylobacteriumsp. was the predominant bacterium in the midgut of mosquitoes fed KM or ST for 2 weeks (ST/2 weeks). Mosquitoes that were fed suspensions of Methylobacteriumsp. isolated from the midgut of ST/2 weeks after blood feeding for 3 days showed inhibited egg maturation. Furthermore, egg maturation was inhibited in mosquitoes that were fed supernatant and precipitate obtained by boiling and centrifuging Methylobacteriumsp. suspension. Thus, this study demonstrated that Methylobacteriumsp. isolated from the midgut of An. stephensimosquitoes after blood feeding inhibited egg maturation.

Published
2023
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30. Basic design of the Hot Laboratory exhaust stack

Author

Morita, Hisashi, Daigo, Fumihisa, Sayato, Natsuki, Watahiki, Shunsuke, Kojima, Kazuki, Nakayama, Kazuhiko, and Ide, Hiroshi

Abstract

平成27年1月にJMTRホットラボ建家において雨漏れ補修を行っていたところ、ホットラボ排気筒の基礎部アンカーボルト1本に減肉が確認された。その後の排気筒における詳細調査により、複数のアンカーボルトの減肉及びフランジプレートとアンカーボルトのナットに間隙が確認されたことを受け、排気筒の倒壊が否定できない状態であると判断されたため、排気筒の撤去を行った。そのため、早急に当該排気筒の取替えを行う必要が生じた。新たな排気筒の設計を行うにあたり、詳細調査により判明したアンカーボルトの減肉等の原因である基礎部への雨水の浸入への対策に加え、東京電力福島第一原子力発電所の事故後に策定された新規制基準への対応を踏まえた設計とした。また、建築確認を受けなければならない建築物及び工作物に該当することから、建築基準法及び煙突構造設計指針に基づく地震力や風荷重に対する排気筒の健全性の評価を行った。本報告書はホットラボ排気筒の基本設計についてまとめたものである。, When the roof of the JMTR Hot Laboratory (HL) building was repaired for rain leaks in January, 2015, thinning was found at one of the anchor bolts on base of the HL exhaust stack. Moreover, the thinning of some anchor bolts and gaps between the anchor bolt nuts and flange plate was found in the later investigation for the exhaust stack. Since the possibility of the exhaust stack collapsing cannot be denied, it was removed. Therefore, it became necessary to rebuild a new exhaust stack as soon as possible. The design of the new exhaust stack was based on the measures to prevent rainwater intrusion into the base, which was the cause of the thinning of the anchor bolts found in the investigation, and on the new regulatory standards established after the accident at the Fukushima Daiichi Nuclear Power Station. Furthermore, since the new exhaust stack corresponds to buildings and structures that must undergo building confirmation, the soundness of the new exhaust stack against seismic force and wind load was evaluated based on the Building Standards Law and the Stack Structure Design Guideline. This report described the basic design of the new exhaust stack.

Published
2022

34. Additional file 2 of Plasmodium berghei Brca2 is required for normal development and differentiation in mice and mosquitoes

Author

Yoshikawa, Yasunaga, Kimura, Shunta, Soga, Akira, Sugiyama, Makoto, Ueno, Aki, Kondo, Hiroki, Zhu, Zida, Ochiai, Kazuhiko, Nakayama, Kazuhiko, Hakozaki, Jun, Kusakisako, Kodai, Haraguchi, Asako, Kitano, Taisuke, Orino, Koichi, Fukumoto, Shinya, and Ikadai, Hiromi

Abstract

Additional file 2: Figure S2. Three-dimensional structure of DNA-binding domains in Plasmodium berghei Brca2. A Three-dimensional structures of OB, tower, and DNA-binding domains in P. berghei Brca2 were predicted with AlphaFold2 and compared against human BRCA2 domains (PDB ID 1MIU). B Three-dimensional structures of OB and tower domains in P. berghei Brca2 were compared against the typical OB domain of human replication protein A1 (PDB ID 4O0A).

Published
2022
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35. Additional file 1 of Plasmodium berghei Brca2 is required for normal development and differentiation in mice and mosquitoes

Author

Yoshikawa, Yasunaga, Kimura, Shunta, Soga, Akira, Sugiyama, Makoto, Ueno, Aki, Kondo, Hiroki, Zhu, Zida, Ochiai, Kazuhiko, Nakayama, Kazuhiko, Hakozaki, Jun, Kusakisako, Kodai, Haraguchi, Asako, Kitano, Taisuke, Orino, Koichi, Fukumoto, Shinya, and Ikadai, Hiromi

Subjects
endocrine system diseases, fungi, parasitic diseases, skin and connective tissue diseases
Abstract

Additional file 1: Figure S1. Alignment of Brca2 amino acid sequence among Plasmodium spp. Alignment of Plasmodium berghei, Plasmodium yoelii, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi Brca2. Red and blue boxes indicate BRC repeats and OB and tower domains in P. berghei Brca2, respectively.

Published
2022
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36. Additional file 3 of Plasmodium berghei Brca2 is required for normal development and differentiation in mice and mosquitoes

Author

Yoshikawa, Yasunaga, Kimura, Shunta, Soga, Akira, Sugiyama, Makoto, Ueno, Aki, Kondo, Hiroki, Zhu, Zida, Ochiai, Kazuhiko, Nakayama, Kazuhiko, Hakozaki, Jun, Kusakisako, Kodai, Haraguchi, Asako, Kitano, Taisuke, Orino, Koichi, Fukumoto, Shinya, and Ikadai, Hiromi

Subjects
enzymes and coenzymes (carbohydrates), genetic processes, health occupations, biological phenomena, cell phenomena, and immunity
Abstract

Additional file 3: Figure S3. A human and P. berghei Rad51 alignment. Red characters indicate amino acid residues interacting with vital phenylalanine residues F1524 and F1546 in BRC repeat 4 in human Rad51. Blue characters in P. berghei Rad51 indicate the amino acid residues that differ from the human Rad51 amino acid residues required for interaction with F1524 and F154 in BRC repeat 4.

Published
2022
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40. Plasmodium berghei Brca2 Is Required for Normal Development and Differentiation in Mice and Mosquitoes

Author

Yoshikawa, Yasunaga, primary, Kimura, Shunta, additional, Soga, Akira, additional, Sugiyama, Makoto, additional, Ueno, Aki, additional, Kondo, Hiroki, additional, Zhu, Zida, additional, Ochiai, Kazuhiko, additional, Nakayama, Kazuhiko, additional, Hakozaki, Jun, additional, Kusakisako, Kodai, additional, Haraguchi, Asako, additional, Kitano, Taisuke, additional, Orino, Koichi, additional, Fukumoto, Shinya, additional, and Ikadai, Hiromi, additional

Published
2022
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43. Morphological and molecular phylogenetical identification of Tricodectes pinguis from Japanese black bears (Ursus thibetanus japonicus) in Aomori Prefecture, Japan

Author

KUSAKISAKO, Kodai, primary, NIIYAMA, Hikaru, additional, ASANO, Erika, additional, HARAGUCHI, Asako, additional, HAKOZAKI, Jun, additional, NAKAYAMA, Kazuhiko, additional, NAKAMURA, Sakure, additional, SHINDO, Junji, additional, KUDO, Noboru, additional, and IKADAI, Hiromi, additional

Published
2022
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49. Sequence Comparison Applied to Correction and Markup of Multi-Word Responses.

Author

Nesbit, John C. and Nakayama, Kazuhiko

Abstract

A sequence comparison procedure, referred to as the edit distance procedure, has been shown to be particularly accurate for recognizing misspelled responses in second-language computer-assisted instruction. Experience with real dictation responses indicates that this technique reliably obtains markups that appear natural for users. (Author/VWL)

Published
1990

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