南須原 康行 (ナスハラ ヤスユキ)
| 北海道大学病院 医療安全管理部 | 教授 |
Last Updated :2025/06/13
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- Associations of COVID-19 symptoms with omicron subvariants BA.2 and BA.5, host status, and clinical outcomes in Japan: a registry-based observational study.
Sho Nakakubo, Naoki Kishida, Kenichi Okuda, Keisuke Kamada, Masami Iwama, Masaru Suzuki, Isao Yokota, Yoichi M Ito, Yasuyuki Nasuhara, Richard C Boucher, Satoshi Konno
The Lancet. Infectious diseases, 2023年06月30日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Previous SARS-CoV-2 infection and vaccination, coupled with the rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We aimed to characterise the clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. METHODS: In this registry-based observational study, individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Eligibility criteria included symptomatic individuals who tested positive for SARS-CoV-2 (PCR or antigen test), and individuals who were not tested for SARS-CoV-2 but developed new symptoms after a household member tested positive for SARS-CoV-2. Symptom prevalence, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. FINDINGS: Data were collected and analysed between April 25 and Sept 25, 2022. For 157 861 omicron-infected symptomatic individuals, cough was the most common symptom (99 032 [62·7%] patients), followed by sore throat (95 838 [60·7%] patients), nasal discharge (69 968 [44·3%] patients), and fever (61 218 [38·8%] patients). Omicron BA.5 infection was associated with a higher prevalence of systemic symptoms than BA.2 in vaccinated and unvaccinated individuals (adjusted odds ratio [OR] for fever: 2·18 [95% CI 2·12-2·25]). Omicron breakthrough-infected individuals with three or more vaccinations or previous infection were less likely to exhibit systemic symptoms (fever 0·50 [0·49-0·51]), but more likely to exhibit upper respiratory symptoms (sore throat 1·33 [1·29-1·36]; nasal discharge 1·84 [1·80-1·89]). Infected older individuals (≥65 years) had lower odds for all symptoms. However, when symptoms were manifest, systemic symptoms were associated with increased odds for severe disease (dyspnoea 3·01 [1·84-4·91]; fever 2·93 [1·89-4·52]), whereas upper respiratory symptoms were associated with decreased odds (sore throat 0·38 [0·24-0·63]; nasal discharge 0·48 [0·28-0·81]). INTERPRETATION: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a higher systemic symptom prevalence than BA.2. Vaccination and previous infection reduced systemic symptom prevalence and improved outcomes but increased upper respiratory tract symptom prevalence. Systemic, but not upper respiratory, symptoms in older people heralded severe disease. Our findings could serve as a practical guide to use COVID-19 symptoms to appropriately modify health-care strategies and predict clinical outcomes for older patients with omicron infections. FUNDING: Japan Agency for Medical Research and Development. - Associations of COVID-19 Symptoms with Omicron Subvariants BA.2 and BA.5, Host Status, and Clinical Outcomes: A Registry-Based Observational Study in Sapporo, Japan.
Sho Nakakubo, Naoki Kishida, Kenichi Okuda, Keisuke Kamada, Masami Iwama, Masaru Suzuki, Isao Yokota, Yoichi M Ito, Yasuyuki Nasuhara, Richard C Boucher, Satoshi Konno
medRxiv : the preprint server for health sciences, 2023年02月07日, ［国際誌］
英語, BACKGROUND: Previous SARS-CoV-2 infection and vaccination, coupled to rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We characterized clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. METHODS: Individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Symptom frequencies, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. RESULTS: For all omicron-infected individuals, cough was the most common symptom (62.7%), followed by sore throat (60.7%), nasal discharge (44.3%), and fever (38.8%). Omicron BA.5 infection was associated with a higher symptom burden than BA.2 in vaccinated and unvaccinated individuals. Omicron breakthrough-infected individuals with ≥ 3 vaccinations or previous infection were less likely to exhibit systemic symptoms, but more likely to exhibit upper respiratory symptoms. Infected elderly individuals had lower odds for all symptoms, but, when symptoms were manifest, systemic symptoms were associated with an increased risk, whereas upper respiratory symptoms with a decreased risk, of severe disease. CONCLUSION: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a greater symptom burden than BA.2. Vaccination and prior infection mitigated systemic symptoms and improved outcomes, but increased upper respiratory tract symptom burden. Systemic, but not upper respiratory, symptoms in the elderly heralded severe disease. - C-reactive protein level predicts need for medical intervention in pregnant women with SARS-CoV2 infection: A retrospective study.
Ryutaro Yamamoto, Hiroshi Asano, Takeshi Umazume, Masato Takaoka, Kiwamu Noshiro, Yoshihiro Saito, Kinuko Nakagawa, Kentaro Chiba, Sho Nakakubo, Yasuyuki Nasuhara, Satoshi Konno, Hidemichi Watari
The journal of obstetrics and gynaecology research, 48, 4, 938, 945, 2022年04月, ［国際誌］
英語, 研究論文（学術雑誌）, AIM: To make effective use of the limited available hospital space during the Coronavirus disease 2019 (COVID-19) pandemic, we conducted this study to investigate the laboratory indices that identify pregnant women with SARS-CoV2 infection who require medical intervention. METHODS: We carried out a retrospective analysis of pregnant women positive for COVID-19 who were admitted to Hokkaido University Hospital from September 2020 to June 2021. Medical interventions included oxygen supplementation, systemic corticosteroids, or supplemental liquids to treat infection-related symptoms. RESULTS: Forty-two infected pregnant patients were admitted to the hospital, half of whom required medical intervention (n = 21). Fever, C-reactive protein (CRP), and platelet count are all associated with need for medical intervention. Of the 32 patients with a fever of ≥37.5°C on days 0-3 after onset of syndromes, 22 (69%) continued to have a fever on days 4-6, of which 19 (86.4%) required medical intervention. CRP level on days 4-6 predicted the presence or absence of medical intervention (area under the receiver operating characteristic curve = 0.913), with a sensitivity of 81% and specificity of 100% at a CRP cutoff of 1.28 mg/dL. CONCLUSIONS: The need for medical intervention in pregnant patients can be predicted with high accuracy using a CRP cutoff of 1.28 mg/dL on days 4-6 after onset of syndromes. The presence of fever also may be an easy marker for selecting subjects who need or will need therapeutic intervention. These could be an effective triage method to determine appropriate indications for the hospitalization of pregnant women in future outbreaks. - Characteristics of COVID-19 patients admitted into two hospitals in sapporo, Japan: Analyses and insights from two outbreak waves.
Takeshi Hattori, Atsushi Saito, Hirofumi Chiba, Koji Kuronuma, Masaru Amishima, Daisuke Morinaga, Yasuo Shichinohe, Yasuyuki Nasuhara, Satoshi Konno
Respiratory investigation, 59, 2, 180, 186, 2021年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Coronavirus disease (COVID-19) emerged in January 2020 in Sapporo city, and the outbreak has shown two peaks. METHODS: A total of 260 COVID-19 patients were enrolled and categorized into three groups according to the pandemic pattern, jobs and situation, and disease severity. We compared clinical characteristics according to these categories. RESULTS: We found two pandemic peaks, and the proportion of patients and health providers who were infected in other hospitals had increased in the latter two periods (period 2: 49.6%, period 3: 32.7%). Particularly, the proportion of infected health providers was 27% in period 2, and they tended to be younger females with a mild condition. Severity of the disease (requirement of oxygen and/or mechanical ventilation) was associated with advanced age, and all the patients who died during admission were over 60 years old. CONCLUSIONS: We reported the temporal dynamics and characteristics of the COVID-19 pandemic in Sapporo city, Japan. This survey from the viewpoint of the hospital provides a new insight into and a better guide for the further management of the COVID-19 pandemic. - Implementation Status of Liver Function Tests for Monitoring Benzbromarone-Induced Hepatotoxicity: An Epidemiological Survey Using the Japanese Claims Database.
Shungo Imai, Yasuyuki Nasuhara, Kenji Momo, Hiromitsu Oki, Hitoshi Kashiwagi, Yuki Sato, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma
Biological & pharmaceutical bulletin, 44, 10, 1499, 1505, 2021年, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, A major adverse effect of benzbromarone is hepatotoxicity. Therefore, periodic liver function tests are required at least for the first 6 months of benzbromarone administration. However, it is not clear whether the relevant blood tests are implemented appropriately. Here, we performed a cross-sectional survey of the implementation status of liver function tests in patients who were newly prescribed benzbromarone, using the Japanese large claims database. Male patients who were newly prescribed benzbromarone from January 2010 to December 2016 were included. We targeted patients who continued benzbromarone during the observation period (up to 180 d from the start of administration). The primary endpoint was the proportion of patients in whom periodic liver function tests were implemented. A periodic liver function test was defined as one or more liver function tests performed during both 1-90 and 91-180 d of initial benzbromarone administration. We labeled the tests as a "periodic test" or "non-periodic test" based on whether periodic liver function tests were performed or not, respectively. Furthermore, factors influencing non-periodic test were analyzed. Periodic testing was implemented only in 28.7% of patients. Additionally, factors such as number of hospital beds ≤19 (compared to 100-199 beds) and duration of the first prescription of benzbromarone were associated with non-periodic testing. Our study revealed that periodic liver function tests are not performed sufficiently in Japan. Thus, clinicians prescribing benzbromarone should be educated about the test. Our blood-test-based approach should be applied to other drugs and countries in future research. - Proposal of COVID-19 Clinical Risk Score for the management of suspected COVID-19 cases: a case control study.
Sho Nakakubo, Masaru Suzuki, Keisuke Kamada, Yu Yamashita, Junichi Nakamura, Hiroshi Horii, Kazuki Sato, Munehiro Matsumoto, Yuki Abe, Kosuke Tsuji, Nobuhisa Ishiguro, Yasuyuki Nasuhara, Satoshi Konno
BMC infectious diseases, 20, 1, 858, 858, 2020年11月18日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: No clinical scoring system has yet been established to estimate the likelihood of coronavirus disease (COVID-19) and determine the suitability of diagnostic testing in suspected COVID-19 patients. METHODS: This was a single-center, retrospective, observational study of patients with suspected COVID-19 and confirmed COVID-19. Patient background, clinical course, laboratory and computed tomography (CT) findings, and the presence of alternative diagnoses were evaluated. Clinical risk scores were developed based on clinical differences between patients with and without COVID-19. RESULTS: Among 110 patients suspected of having COVID-19, 60.9% underwent polymerase chain reaction (PCR) testing based on the judgment of physicians. Two patients were found to have COVID-19. The clinical characteristics of 108 non-COVID-19 patients were compared with those of 23 confirmed COVID-19 patients. Patients with COVID-19 were more likely to have a history of high-risk exposures and an abnormal sense of taste and smell. The COVID-19 group had significantly higher rates of subnormal white blood cell counts, lower eosinophil counts, and lower procalcitonin levels than the non-COVID-19 group. When blood test results, CT findings, and the presence of alternative diagnoses were scored on an 11-point scale (i.e., "COVID-19 Clinical Risk Score"), the COVID-19 group scored significantly higher than the non-COVID-19 group, more than four points in the COVID-19 group. All non-COVID patients who did not undergo PCR had a score of 4 or less. CONCLUSIONS: The COVID-19 Clinical Risk Score may enable the risk classification of patients suspected of having COVID-19 and can help in decision-making in clinical practice, including appropriateness of diagnostic testing. Further studies and prospective validation with an increased sample size are required. - Older age is associated with sustained detection of SARS-CoV-2 in nasopharyngeal swab samples.
Takeshi Hattori, Masaru Amishima, Daisuke Morinaga, Keisuke Kamada, Sho Nakakubo, Yu Yamashita, Yasuo Shichinohe, Shinichi Fujisawa, Mutsumi Nishida, Yasuyuki Nasuhara, Takanori Teshima, Satoshi Konno
The Journal of infection, 82, 1, 159, 198, 2020年06月21日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - Analysis of the Implementation of Blood Tests Specified in the Package Insert After Prescription of Thiamazole.
Yasuyuki Nasuhara, Ken Sakushima, Hiromitsu Oki, Takehiro Yamada, Ken Iseki, Reona Umeki, Akira Endoh
Journal of patient safety, 16, 1, 24, 29, 2020年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The antithyroid drug thiamazole has long been known to cause the serious adverse effect of agranulocytosis, and performing regular blood tests is listed among the warnings on the package insert. We conducted a retrospective survey of how often doctors conducted blood tests in accordance with the package insert when thiamazole was prescribed at our hospital. METHODS: The subjects were patients to whom thiamazole was newly prescribed at our hospital between April 2004 and March 2012. During the target period, thiamazole was newly prescribed to 438 patients. RESULTS: We found that blood tests after prescription of thiamazole as listed in the warning section on the package insert are not performed sufficiently. The rate at which white blood cell counts were obtained decreased over time. The rate at which differential leukocyte counts were obtained was approximately 80% of white blood cell counts at all observational time points. In contrast, the percentage of subjects whose white blood cell counts were measured increased according to a time-trend analysis. CONCLUSIONS: This study revealed that blood tests after prescription of thiamazole as listed in the warning section on the package insert are not performed sufficiently at our hospital. The rate at which differential leukocyte counts were obtained was approximately 80% of white blood cell counts at all observational periods. Physician education should be more rigorously performed than presently done, and automatic generation of warnings that urge blood tests and patient education regarding the importance of blood tests is also important. - Rapidly progressive organizing pneumonia associated with COVID-19.
Hiroshi Horii, Keisuke Kamada, Sho Nakakubo, Yu Yamashita, Junichi Nakamura, Yasuyuki Nasuhara, Satoshi Konno
Respiratory medicine case reports, 31, 101295, 101295, 2020年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We report a case of clinically diagnosed secondary organizing pneumonia (SOP) associated with coronavirus disease 2019 (COVID-19). A 70-year-old woman who had been diagnosed with COVID-19 was admitted to Hokkaido University Hospital. Although her fever, cough, dyspnea, and serum C-reactive protein levels improved, she developed rapidly progressive respiratory failure and computed tomography revealed the development of bilateral lung consolidation. Her dyspnea was relieved, and her oxygenation levels and radiological findings improved after commencing corticosteroid treatment. Blood biomarkers for interstitial lung disease, Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), showed different responses during the clinical course of her disease. Evaluation of serial changes in levels of KL-6 and SP-D may help diagnose and monitor COVID-19-associated organizing pneumonia (OP). Clinicians should be aware that SOP can develop in response to COVID-19 and that these patients may benefit from the use of steroids. - Unique Mortality Profile in Japanese Patients with COPD: An Analysis from the Hokkaido COPD Cohort Study.
Hironi Makita, Masaru Suzuki, Satoshi Konno, Kaoruko Shimizu, Yasuyuki Nasuhara, Katsura Nagai, Yasushi Akiyama, Satoshi Fuke, Hiroshi Saito, Takeshi Igarashi, Kimihiro Takeyabu, Masaharu Nishimura
International journal of chronic obstructive pulmonary disease, 15, 2081, 2090, 2020年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: Causes of death may be unique and different in Japanese patients with COPD because they are generally older, thinner, experience fewer exacerbations, and live longer than those in other countries. We investigated the detailed mortality profile in the Hokkaido COPD cohort study, which completed a 10-year follow-up with a very low dropout rate. Patients and Methods: We prospectively examined the 10-year natural history in 279 Japanese patients with COPD (GOLD 1, 26%; GOLD 2, 45%; GOLD 3, 24%; and GOLD 4, 5%). The majority of patients were male, and the average age at baseline was 69 years old. About 95% of all patients had accurate mortality data. The risk factors for mortality were also analyzed. Results: During the 10 years, 112 patients (40%) died. Their median survival time was 6.1 years (interquartile range: 4.7-7.9 years), and age at death was 79 ± 6 years old (mean ± SD). Respiratory diseases, including pneumonia, were the leading causes of death in 45 (40%), followed by lung cancer in 24 (21%), other cancers in 18 (16%), and cardiovascular diseases in 12 (11%). In particular, lung cancer-related death was equally distributed across all COPD stages, with a higher proportion of lung cancer in the relatively younger generation (<64 years old). Older age at baseline, lower BMI, and severer emphysema were significant risk factors for all-cause mortality. Conclusion: The unique mortality profile observed in this study should be considered when designing strategies for the management of patients with COPD in any geographic region. - Venipuncture Nerve Injuries in the Upper Extremity From More Than 1 Million Procedures.
Yukinori Tsukuda, Tadanao Funakoshi, Yasuyuki Nasuhara, Yusuke Nagano, Chikara Shimizu, Norimasa Iwasaki
Journal of patient safety, 15, 4, 299, 301, 2019年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The purpose of this study was to investigate the nerve injury rate for 1 million venipunctures and the efficacy of attempts to avoid severe nerve injury. METHODS: We collected data for outpatients from whom a venipuncture blood sample was obtained in our hospital from 2005 to 2014. Every venipuncture procedure for outpatients was performed by a trained nurse or clinical technologist at the center for blood sampling in our hospital. In addition, a series of lectures by a specialist is held in our hospital at various times. All complaints related to venipuncture blood sampling were reported to our division of hospital safety management and were followed up using the guidelines for injuries related to the venipuncture. RESULTS: The number of venipuncture-related complications was 293 (0.027%, 1/3700) of 1,082,053 during the 10 years. A total of 40 of the 1,082,053 venipunctures were referred to the department of orthopedic surgery, and 16 (0.0015%, 1/67,000) were diagnosed with obvious nerve injuries. The average duration of the treatment was 46.4 days (range, 1-126 days); 69% of the patients recovered within 5 weeks, and all patients recovered within 18 weeks. CONCLUSIONS: Although it is impossible to completely prevent venipuncture-related complications, appropriate venipuncture skills and risk management decrease the incidence of chronic or permanent nerve injury risk after venipuncture. - Annual change in FEV1 in elderly 10-year survivors with established chronic obstructive pulmonary disease.
Suzuki M, Makita H, Konno S, Shimizu K, Nasuhara Y, Nagai K, Akiyama Y, Fuke S, Saito H, Igarashi T, Takeyabu K, Nishimura M
Scientific reports, 9, 1, 2073, 2073, 2019年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Long-term decline in lung function is generally considered to be progressive in individuals with established chronic obstructive pulmonary disease (COPD), despite the presence of intersubject variation. We hypothesized that the annualized rate of decline in forced expiratory volume in 1 second (FEV1) would not be constant among different time periods in the natural history of established COPD. We compared the annual change rates in FEV1 during the first 5 years and the last 5 years, estimated separately using a linear mixed-effects model in 10-year survivors (n = 110). The subjects were classified into three FEV1 decline groups, based on the 25th and 75th percentile values in each time period. The rates of FEV1 changes, calculated from the first 5 years and the last 5 years, did not correlate with each other among 10-year survivors; the subjects of each FEV1 decline group during the first 5 years did not consistently remain in the same FEV1 decline group during the last 5 years. Smoking status and exacerbation frequency were not associated with decline in FEV1. In conclusion, the disease activity, which is often expressed as annualized change in FEV1, might be changeable either way over years in patients with established COPD. - A Semiquantitative Computed Tomographic Grading System for Evaluating Therapeutic Response in Pulmonary Alveolar Proteinosis.
Sayoko Tokura, Masanori Akira, Tomohisa Okuma, Ryushi Tazawa, Toru Arai, Chikatoshi Sugimoto, Akiko Matsumuro, Masaki Hirose, Toshinori Takada, Koh Nakata, Haruyuki Ishii, Yasunori Kasahara, Masayuki Hojo, Shinya Ohkouchi, Yoshiko Tsuchihashi, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Takahito Nei, Konosuke Morimoto, Yasuyuki Nasuhara, Masahito Ebina, Toshio Ichiwata, Koichiro Tatsumi, Etsuro Yamaguchi, Yoshikazu Inoue
Annals of the American Thoracic Society, 14, 9, 1403, 1411, 2017年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, RATIONALE: A useful semiquantitative method of using computed tomographic (CT) images to evaluate therapeutic response in pulmonary alveolar proteinosis (PAP) has not been established, although the extent score or grading score of ground-glass opacities has been used. OBJECTIVES: The purpose of this study was to establish a semiquantitative method for evaluating therapeutic response in PAP. METHODS: CT scans were obtained within 1 month before and after therapy from 32 patients with PAP who participated in a multicenter phase II trial of granulocyte-macrophage colony-stimulating factor inhalation therapy. The scans were evaluated by two chest radiologists independently. Increased parenchymal opacity was evaluated on the basis of its intensity and extent (CT grade), and the severity scores were compared with CT scores based on the extent alone (CT extent), as well as on the basis of physiological and serological results. RESULTS: CT grade score and CT extent score had significant correlation with diffusing capacity of the lung for carbon monoxide percent predicted (%DlCO), PaO2, VC percent predicted (%VC), Krebs von den Lungen (KL)-6, and surfactant protein D. The change in CT grade score between pre- and post-treatment examinations (ΔCT grade) correlated better with difference of PaO2 between pre- and post-treatment examinations (ΔPaO2) than ΔCT extent (difference of CT extent score between pre- and post-treatment examinations). In univariate analysis, ΔCT grade, ΔCT extent, ΔKL-6, Δ%DlCO, Δ%VC, and change in surfactant protein D correlated significantly with ΔPaO2. In multivariate analysis, ΔCT grade and ΔKL-6 correlated more closely with ΔPaO2. CONCLUSIONS: Although a number of CT variables were collected, the currently proposed grading system that correlates well with PaO2 should be viewed as a retrospective scoring system that needs future validation with another PAP cohort. - Characteristics of Medical Adverse Events/Near Misses Associated With Laparoscopic/Thoracoscopic Surgery: A Retrospective Study Based on the Japanese National Database of Medical Adverse Events.
Abe T, Murai S, Nasuhara Y, Shinohara N
Journal of patient safety, 15, 4, 343, 351, 2017年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The aim of this study was to clarify the characteristics of adverse events/near misses during laparoscopic/thoracoscopic surgery. METHODS: Using relevant key words for minimally invasive surgeries, 540 records were identified in the database of the Japan Council for Quality Health Care. After data review and the classification of adverse events, 746 events associated with laparoscopic (laparo group) and/or thoracoscopic (thoraco group) surgery were identified. We calculated the frequency of each event, compared the frequency regarding recurrent events, and evaluated the types of event that had resulted in deaths between the 2 groups. RESULTS: There were 582 events in the laparo group, 159 in the thoraco group, and 5 in those undergoing combined surgery. Overall, injury of other organs (11.4%, 85/746), retention of a foreign body (9.1%, 68/746), breakage/failure of medical equipment or devices (6.2%, 46/746), massive bleeding (5.9%, 44/746), misperception of anatomy (5.6%, 42/746), and vascular injury (4.8%, 36/746) were frequently reported. There were marked differences in the frequency of injury of other organs (laparo group: 13.4%, 78/582; thoraco group: 4.4%, 7/159), massive bleeding (laparo group: 3.4%, 20/582; thoraco group: 14.5%, 23/159), and vascular injury (laparo group: 2.6%, 15/582; thoraco group: 12.6%, 20/159) between the 2 groups. Among the 56 patient-death reports, 132 adverse events were identified. In the thoraco group, bleeding events were frequently observed, whereas in the laparo group, various categories of events were noted. CONCLUSIONS: We observed recurrent incidents and differences in the frequency between the 2 groups. Surgeons should keep in mind these characteristics. Retention of a foreign body and the breakage/malfunctioning of instruments might be reduced by the introduction of specialized checklists. - Erratum to: Physicians' responses to computerized drug interaction alerts with password overrides.
Yasuyuki Nasuhara, Ken Sakushima, Akira Endoh, Reona Umeki, Hiromitsu Oki, Takehiro Yamada, Ken Iseki, Makoto Ishikawa
BMC medical informatics and decision making, 16, 1, 108, 108, 2016年08月10日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌） - Three-day regimen of oseltamivir for postexposure prophylaxis of influenza in wards
Ishiguro N., Oyamada R., Nasuhara Y., Yamada T., Miyamoto T., Imai S., Akizawa K., Fukumoto T., Iwasaki S., Iijima H., Ono K.
Journal of Hospital Infection, 94, 2, 150, 153, Elsevier, 2016年, ［査読有り］
英語, 研究論文（学術雑誌）, Inpatients who had been in close contact with patients with influenza were given oseltamivir [75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children] for three days as postexposure prophylaxis (PEP). The index patients with influenza were prescribed a neuraminidase inhibitor and were discharged immediately or transferred to isolation rooms. The protective efficacy of oseltamivir for three days was 93% overall [95% confidence interval (CI) 53-99%; P = 0.023] and 94% for influenza A (95% CI 61-99%; P = 0.017), which is comparable to that of seven- to 10-day regimens of oseltamivir as PEP. - Physicians' responses to computerized drug interaction alerts with password overrides.
Yasuyuki Nasuhara, Ken Sakushima, Akira Endoh, Reona Umeki, Hiromitsu Oki, Takehiro Yamada, Ken Iseki, Makoto Ishikawa
BMC medical informatics and decision making, 15, 74, 74, 2015年08月28日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Although evidence has suggested that computerized drug-drug interaction alert systems may reduce the occurrence of drug-drug interactions, the numerous reminders and alerts generated by such systems could represent an excessive burden for clinicians, resulting in a high override rate of not only unimportant, but also important alerts. METHODS: We analyzed physicians' responses to alerts of relative contraindications and contraindications for coadministration in a computerized drug-drug interaction alert system at Hokkaido University Hospital. In this system, the physician must enter a password to override an alert and continue an order. All of the drug-drug interaction alerts generated between December 2011 and November 2012 at Hokkaido University Hospital were included in this study. RESULTS: The system generated a total of 170 alerts of relative contraindications and contraindication for coadministration; 59 (34.7 %) of the corresponding orders were cancelled after the alert was accepted, and 111 (65.3 %) were overridden. The most frequent contraindication alert was for the combination of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors and fibrates. No incidents involving drug-drug interactions were reported among patients who were prescribed contraindicated drug pairs after an override. CONCLUSIONS: Although computerized drug-drug interaction alert systems that require password overrides appear useful for promoting medication safety, having to enter passwords to override alerts may represent an excessive burden for the prescribing physician. Therefore, both patient safety and physicians' workloads should be taken into consideration in future designs of computerized drug-drug interaction alert systems. - Time trend of injection drug errors before and after implementation of bar-code verification system.
Ken Sakushima, Reona Umeki, Akira Endoh, Yoichi M Ito, Yasuyuki Nasuhara
Technology and health care : official journal of the European Society for Engineering and Medicine, 23, 3, 267, 74, 2015年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Bar-code technology, used for verification of patients and their medication, could prevent medication errors in clinical practice. OBJECTIVE: Retrospective analysis of electronically stored medical error reports was conducted in a university hospital. METHODS: The number of reported medication errors of injected drugs, including wrong drug administration and administration to the wrong patient, was compared before and after implementation of the bar-code verification system for inpatient care. RESULTS: A total of 2867 error reports associated with injection drugs were extracted. Wrong patient errors decreased significantly after implementation of the bar-code verification system (17.4/year vs. 4.5/year, p< 0.05), although wrong drug errors did not decrease sufficiently (24.2/year vs. 20.3/year). The source of medication errors due to wrong drugs was drug preparation in hospital wards. CONCLUSION: Bar-code medication administration is effective for prevention of wrong patient errors. However, ordinary bar-code verification systems are limited in their ability to prevent incorrect drug preparation in hospital wards. - Analysis of the implementation of blood tests specified in the drug package insert after prescription of thiamazole
NASUHARA Yasuyuki
Journal of Patient Safety, Epub, 2015年, ［査読有り］
英語, 研究論文（学術雑誌） - Duration of benefit in patients with autoimmune pulmonary alveolar proteinosis after inhaled granulocyte-macrophage colony-stimulating factor therapy.
Ryushi Tazawa, Yoshikazu Inoue, Toru Arai, Toshinori Takada, Yasunori Kasahara, Masayuki Hojo, Shinya Ohkouchi, Yoshiko Tsuchihashi, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Haruyuki Ishii, Takahito Nei, Konosuke Morimoto, Yasuyuki Nasuhara, Masahito Ebina, Masanori Akira, Toshio Ichiwata, Koichiro Tatsumi, Etsuro Yamaguchi, Koh Nakata
Chest, 145, 4, 729, 737, 2014年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by subcutaneous injection or inhaled therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been demonstrated to be safe and efficacious in several reports. However, some reports of subcutaneous injection described transient benefit in most instances. The durability of response to inhaled GM-CSF therapy is not well characterized. METHODS: To elucidate the risk factors for recurrence of aPAP after GM-CSF inhalation, 35 patients were followed up, monitoring for the use of any additional PAP therapies and disease severity score every 6 months. Physiologic, serologic, and radiologic features of the patients were analyzed for the findings of 30-month observation after the end of inhalation therapy. RESULTS: During the observation, 23 patients remained free from additional treatments, and twelve patients required additional treatments. There were no significant differences in age, sex, symptoms, oxygenation indexes, or anti-GM-CSF antibody levels at the beginning of treatment between the two groups. Baseline vital capacity (% predicted, %VC) were higher among those who required additional treatment (P<.01). Those patients not requiring additional treatment maintained the improved disease severity score initially achieved. A significant difference in the time to additional treatment between the high %VC group (%VC≥80.5) and the low %VC group was seen by a Kaplan-Meier analysis and a log-rank test (P<.0005). CONCLUSIONS: These results demonstrate that inhaled GM-CSF therapy sustained remission of aPAP in more than one-half of cases, and baseline %VC might be a prognostic factor for disease recurrence. TRIAL REGISTRY: ISRCTN Register and JMACCT Clinical Trial Registry; No.: ISRCTN18931678 and JMAIIA00013; URL: http://www.isrctn.org and http://www.jmacct.med.or.jp. - Serum KL-6 concentrations are associated with molecular sizes and efflux behavior of KL-6/MUC1 in healthy subjects.
Shigemura M, Konno S, Nasuhara Y, Shijubo N, Shimizu C, Nishimura M
Clinica chimica acta; international journal of clinical chemistry, 424, 148, 152, 2013年09月, ［査読有り］
英語, 研究論文（学術雑誌） - Occupational and environmental impact on the clinical course of autoimmune pulmonary alveolar proteinosis
Yoshikazu Inoue, Koh Nakata, Toru Arai, Etsuro Yamaguchi, Toshio Ichiwata, Masahito Ebina, Ryushi Tazawa, Haruyuki Ishii, Yasuhiro Setoguchi, Masanori Kitaichi, Masanori Akira, Koichiro Tatsumi, Yasuyuki Nasuhara, Kazutoshi Cho, Yoshiko Tsuchihashi, Kanji Uchida, Toshinori Takada, Hideaki Nakayama, Keisuke Tomii, Chikatoshi Sugimoto, Yasuo Kohashi, Shinya Ohkouchi, Yasunori Kasahara, Kohnosuke Morimoto, Naoko Sakamoto
EUROPEAN RESPIRATORY JOURNAL, 40, 2012年09月, ［査読有り］
英語 - Impact of asthmatic control status on serum cystatin C concentrations.
Shigemura M, Konno S, Nasuhara Y, Shimizu C, Matsuno K, Nishimura M
Clinical chemistry and laboratory medicine : CCLM / FESCC, 50, 1367, 1371, 8, 2012年08月, ［査読有り］ - Effects of molecular structural variants on serum Krebs von den Lungen-6 levels in sarcoidosis.
Shigemura M, Nasuhara Y, Konno S, Shimizu C, Matsuno K, Yamguchi E, Nishimura M
Journal of translational medicine, 10, 111, 111, BioMed Central, 2012年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Serum Krebs von den Lungen-6 (KL-6), which is classified as human mucin-1 (MUC1), is used as a marker of sarcoidosis and other interstitial lung diseases. However, there remain some limitations due to a lack of information on the factors contributing to increased levels of serum KL-6. This study was designed to investigate the factors contributing to increased levels of serum KL-6 by molecular analysis. Methods: Western blot analysis using anti-KL-6 antibody was performed simultaneously on the bronchoalveolar lavage fluid (BALF) and serum obtained from 128 subjects with sarcoidosis. Results: KL-6/MUC1 in BALF showed three bands and five band patterns. These band patterns were associated with the MUC1 genotype and the KL-6 levels. KL-6/MUC1 band patterns in serum were dependent on molecular size class in BALF. Significantly increased levels of serum KL-6, serum/BALF KL-6 ratio and serum soluble interleukin 2 receptor were observed in the subjects with influx of high molecular size KL-6/MUC1 from the alveoli to blood circulation. The multivariate linear regression analysis involving potentially relevant variables such as age, gender, smoking status, lung parenchymal involvement based on radiographical stage and molecular size of KL-6/MUC1 in serum showed that the molecular size of KL-6/MUC1 in serum was significant independent determinant of serum KL-6 levels. Conclusions: The molecular structural variants of KL-6/MUC1 and its leakage behavior affect serum levels of KL-6 in sarcoidosis. This information may assist in the interpretation of serum KL-6 levels in sarcoidosis. - Reduced GM-CSF autoantibody in improved lung of autoimmune pulmonary alveolar proteinosis
K. Ohashi, A. Sato, T. Takada, T. Arai, Y. Kasahara, M. Hojo, T. Nei, H. Nakayama, N. Motoi, S. Urano, R. Eda, M. Yokoba, Y. Tsuchihashi, Y. Nasuhara, H. Ishii, M. Ebina, E. Yamaguchi, Y. Inoue, K. Nakata, R. Tazawa
European Respiratory Journal, 39, 3, 777, 780, European Respiratory Society, 2012年03月01日, ［査読有り］
英語 - Endobronchial ultrasonography with a guide sheath in the diagnosis of benign peripheral diseases.
Shinagawa N, Nakano K, Asahina H, Kikuchi E, Ito T, Matsuno Y, Oizumi S, Nasuhara Y, Nishimura M
The Annals of thoracic surgery, 93, 3, 951, 957, 2012年03月, ［査読有り］
英語, 研究論文（学術雑誌） - Direct evidence that GM-CSF inhalation improves lung clearance in pulmonary alveolar proteinosis.
Kazumasa Ohashi, Atsuyasu Sato, Toshinori Takada, Toru Arai, Takahito Nei, Yasunori Kasahara, Natsuki Motoi, Masayuki Hojo, Shinya Urano, Haruyuki Ishii, Masanori Yokoba, Ryosuke Eda, Hideaki Nakayama, Yasuyuki Nasuhara, Yoshiko Tsuchihashi, Chinatsu Kaneko, Hiroko Kanazawa, Masahito Ebina, Etsuro Yamaguchi, Jacqueline Kirchner, Yoshikazu Inoue, Koh Nakata, Ryushi Tazawa
Respiratory medicine, 106, 2, 284, 93, 2012年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is caused by granulocyte/macrophage-colony stimulating factor (GM-CSF) autoantibodies in the lung. Previously, we reported that GM-CSF inhalation therapy improved alveolar-arterial oxygen difference and serum biomarkers of disease severity in these patients. It is plausible that inhaled GM-CSF improves the dysfunction of alveolar macrophages and promotes the clearance of the surfactant. However, effect of the therapy on components in bronchoalveolar lavage fluid (BALF) remains unclear. OBJECTIVES: To figure out changes in surfactant clearance during GM-CSF inhalation therapy. METHODS: We performed retrospective analyses of BALF obtained under a standardized protocol from the same bronchus in each of 19 aPAP patients before and after GM-CSF inhalation therapy (ISRCTN18931678, JMA-IIA00013; total dose 10.5-21 mg, duration 12-24 weeks). For evaluation, the participants were divided into two groups, high responders with improvement in alveolar-arterial oxygen difference ≥13 mmHg (n = 10) and low responders with that < 13 mmHg (n = 9). RESULTS: Counts of both total cells and alveolar macrophages in BALF did not increase during the therapy. However, total protein and surfactant protein-A (SP-A) were significantly decreased in high responders, but not in low responders, suggesting that clearance of surfactant materials is correlated with the efficacy of the therapy. Among 94 biomarkers screened in bronchoalveolar lavage fluid, we found that the concentration of interleukin-17 and cancer antigen-125 were significantly increased after GM-CSF inhalation treatment. CONCLUSIONS: GM-CSF inhalation decreased the concentration of total protein and SP-A in BALF, and increase interleukin-17 and cancer antigen-125 in improved lung of autoimmune pulmonary alveolar proteinosis. - Annual change in pulmonary function and clinical phenotype in chronic obstructive pulmonary disease.
Nishimura M, Makita H, Nagai K, Konno S, Nasuhara Y, Hasegawa M, Shimizu K, Betsuyaku T, Ito YM, Fuke S, Igarashi T, Akiyama Y, Ogura S, Hokkaido COPD Cohort, Study Investigators
American journal of respiratory and critical care medicine, 185, 1, 44, 52, 1, 2012年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, RATIONALE: Although the rate of annual decline in FEV1 is one of the most important outcome measures in chronic obstructive pulmonary disease (COPD), little is known about intersubject variability based on clinical phenotypes. OBJECTIVES: To examine the intersubject variability in a 5-year observational cohort study, particularly focusing on emphysema severity. METHODS: A total of 279 eligible patients with COPD (stages I-IV: 26, 45, 24, and 5%) participated. We conducted a detailed assessment of pulmonary function and computed tomography (CT) at baseline, and performed spirometry every 6 months before and after inhalation of bronchodilator. Smoking status, exacerbation, and pharmacotherapy were carefully monitored. Emphysema severity was evaluated by CT and annual measurements of carbon monoxide transfer coefficient. MEASUREMENTS AND MAIN RESULTS: Using mixed effects model analysis, the annual decline in post-bronchodilator FEV1 was -32±24 (SD) ml/yr (n=261). We classified the subjects of less than the 25th percentile as Rapid decliners, the 25th to 75th percentile as Slow decliners, and greater than the 75th percentile as Sustainers (-63±2, -31±1, and -2±1 [SE] ml/yr). Emphysema severity, but not %FEV1, showed significant differences among the three groups. Multiple logistic regression analysis demonstrated that the Rapid decliners were independently associated with emphysema severity assessed either by CT or carbon monoxide transfer coefficient. The Sustainers displayed less emphysema and higher levels of circulating eosinophils. CONCLUSIONS: Emphysema severity is independently associated with a rapid annual decline in FEV1 in COPD. Sustainers and Rapid decliners warrant specific attention in clinical practice. - [A case of multifocal micronodular pneumocyte hyperplasia without clinical findings of tuberous sclerosis].
Natsuko Taniguchi, Satoshi Konno, Yasuyuki Nasuhara, Yoshihiro Matsuno, Teruaki Oka, Masaharu Nishimura
Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society, 49, 5, 355, 9, 2011年05月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, A 30-year-old woman was referred because of multiple ground-glass opacities (GGOs) on chest CT examination. Lung biopsy was performed. Histologically, multifocal well-demarcated nodular lesions comprising proliferation of type II pneumocytes with mild fibrous thickening of the alveolar septa were observed in the lung tissue. We made a histopathologic diagnosis of multifocal micronodular pneumocyte hyperplasia (MMPH). Neither the clinical findings nor the family history of the patient suggested tuberous sclerosis (TSC). MMPH is a pulmonary manifestation of tuberous sclerosis, together with lymphangioleiomyomatosis (LAM). MMPH should be considered as a differential diagnosis of multiple GGOs in the lung even when findings of TSC and LAM are not recognized. - Inhaled granulocyte/macrophage-colony stimulating factor as therapy for pulmonary alveolar proteinosis.
Tazawa R, Trapnell BC, Inoue Y, Arai T, Takada T, Nasuhara Y, Hizawa N, Kasahara Y, Tatsumi K, Hojo M, Ishii H, Yokoba M, Tanaka N, Yamaguchi E, Eda R, Tsuchihashi Y, Morimoto K, Akira M, Terada M, Otsuka J, Ebina M, Kaneko C, Nukiwa T, Krischer JP, Akazawa K, Nakata K
American journal of respiratory and critical care medicine, 181, 12, 1345, 1354, 12, 2010年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, RATIONALE: Inhaled granulocyte/macrophage-colony stimulating factor (GM-CSF) is a promising therapy for pulmonary alveolar proteinosis (PAP) but has not been adequately studied. OBJECTIVES: To evaluate safety and efficacy of inhaled GM-CSF in patients with unremitting or progressive PAP. METHODS: We conducted a national, multicenter, self-controlled, phase II trial at nine pulmonary centers throughout Japan. Patients who had lung biopsy or cytology findings diagnostic of PAP, an elevated serum GM-CSF antibody level, and a Pa(O(2)) of less than 75 mm Hg entered a 12-week observation period. Those who improved (i.e., alveolar-arterial oxygen difference [A-aDO(2)] decreased by 10 mm Hg) during observation were excluded. The rest entered sequential periods of high-dose therapy (250 microg Days 1-8, none Days 9-14; x six cycles; 12 wk); low-dose therapy (125 microg Days 1-4, none Days 5-14; x six cycles; 12 wk), and follow-up (52 wk). MEASUREMENTS AND MAIN RESULTS: Fifty patients with PAP were enrolled in the study. During observation, nine improved and two withdrew; all of these were excluded. Of 35 patients completing the high- and low-dose therapy, 24 improved, resulting in an overall response rate of 62% (24/39; intention-to-treat analysis) and reduction in A-aDO(2) of 12.3 mm Hg (95% confidence interval, 8.4-16.2; n = 35, P < 0.001). No serious adverse events occurred, and serum GM-CSF autoantibody levels were unchanged. A treatment-emergent correlation occurred between A-aDO(2) and diffusing capacity of the lung, and high-resolution CT revealed improvement of ground-glass opacity. Twenty-nine of 35 patients remained stable without further therapy for 1 year. CONCLUSIONS: Inhaled GM-CSF therapy is safe, effective, and provides a sustained therapeutic effect in autoimmune PAP. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN18931678), www.jmacct.med.or.jp/english (JMA-IIA00013). - [Intravascular large B-cell lymphoma with massive pulmonary lesions].
Asumi Higashiyama, Satoshi Hashino, Masahiro Onozawa, Mutsumi Takahata, Kohei Okada, Kaoru Kahata, Natsuko Taniguchi, Yasuyuki Nasuhara, Kanako Kubota, Nozomu Fujimoto, Yoshihiro Matsuno, Masahiro Nishimura, Masahiro Asaka
[Rinsho ketsueki] The Japanese journal of clinical hematology, 51, 5, 353, 6, 2010年05月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, A 61-year-old man was admitted to our hospital with dyspnea on effort. Neither computed tomography scan nor chest X-ray film detected any specific findings that could explain hypoxemia. Since (67)Ga scintigraphy showed abnormal uptake in the bilateral lungs, transbronchial lung biopsy (TBLB) was performed. The TBLB specimen was diagnosed as intravascular large B-cell lymphoma (IVLBCL). There was no involvement of any other organ considered typical of IVLBCL. In cases showing clinical findings such as hypoxia despite mild pulmonary radiographic changes, a definitive diagnosis should be made using methods such as TBLB with consideration given to the possibility of IVLBCL. - Levels of transferrin in bronchoalveolar lavage fluid in sarcoidosis.
Shigemura M, Nasuhara Y, Konno S, Hattori T, Shimizu C, Matsuno K, Nishimura M
Lung, 188, 2, 151, 157, 2, 2010年04月, ［査読有り］
英語, There has been only one report showing high levels of transferrin (Tf) in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. The aim of this study is to assess the levels of Tf in both BALF and serum and to examine the relationship between the levels of Tf and other disease markers in sarcoidosis. Subjects were 64 sarcoidosis and 10 healthy controls. Tf in BALF and serum was measured by nephelometric assay. Median Tf levels in BALF from sarcoidosis was 0.70 mg/dl (range, 0.00-3.97), which was significantly higher when compared with controls (0.36 mg/dl; range, 0.00-1.02) (p = 0.005). In contrast, median Tf levels in serum from sarcoidosis was 258 mg/dl (range, 171-383), which was significantly lower when compared with controls (322 mg/dl; range, 234-356) (p = 0.003). Tf levels in BALF were significantly correlated with both the percentage of lymphocytes (r = 0.617, p = 0.001) and serum angiotensin-converting enzyme activity (r = 0.363, p = 0.003) and serum soluble interleukin-2 receptor (r = 0.450, p = 0.001) in sarcoidosis. Levels of Tf in BALF from patients with sarcoidosis were not influenced by smoking status. The levels of Tf in sarcoidosis are high in BALF, but low in serum. Increased levels of Tf in BALF may reflect the disease activity. - Aging enhances susceptibility to cigarette smoke-induced inflammation through bronchiolar chemokines.
Chinatsu Moriyama, Tomoko Betsuyaku, Yoko Ito, Ichiro Hamamura, Junko Hata, Hiroshi Takahashi, Yasuyuki Nasuhara, Masaharu Nishimura
American journal of respiratory cell and molecular biology, 42, 3, 304, 11, 2010年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Cigarette smoking and aging are major risk factors for chronic obstructive pulmonary disease. An unsolved question is whether elderly lungs are particularly vulnerable to cigarette smoke (CS) exposure. In this study, we used a mouse model to test the hypothesis that aging increases the susceptibility to CS-induced pulmonary inflammation. We subjected 9-week-old and 69-week-old C57BL/6J mice to CS (whole-body exposure, 90 min/d), and evaluated neutrophil infiltration in the lungs, the levels of keratinocyte-derived chemokine (KC) and macrophage inflammatory protein (MIP)-2 in bronchoalveolar lavage fluid, and mRNA expression in bronchiolar epithelium retrieved by laser capture microdissection. The 69-week-old mice showed a greater number of neutrophils and higher levels of bronchiolar KC and MIP-2 expression than 9-week-old mice after 9 days of CS exposure. Furthermore, single CS exposure induced the rapid up-regulation of KC and MIP-2 in bronchiolar epithelium in both 9-week-old and 69-week-old mice, and the much higher levels in 69-week-old mice were associated with greater nuclear translocation of NF-kappaB. In contrast, no age-related differences were observed in the bronchiolar expression of NF-E2-related factor 2-regulated antioxidant and detoxification genes, heme oxygenase-1, reduced nicotinamide adenine dinucleotide phosphate quinone reductase 1, and glutamate-cysteine ligase, modifier unit, or antioxidant activity in bronchoalveolar lavage fluid, regardless of CS exposure. In summary, aging increases susceptibility to CS-induced inflammation in a mouse model, and robust mRNA up-regulation and nuclear translocation of NF-kappaB in bronchiolar epithelium may be involved. - [Flow-volume curve as an aid to diagnosis in double aortic arch masquerading as asthma in a young adult].
Takayuki Yoshida, Satoshi Konno, Ayumu Takahashi, Yasuyuki Nasuhara, Tomoko Betsuyaku, Masaharu Nishimura
Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society, 48, 3, 229, 34, 2010年03月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, We describe a young adult with double aortic arch who for several years had experienced stridor during exercise. He had been given a diagnosis of exercise-induced asthma, also known as hyperventilation syndrome. Antiasthmatic drugs, including inhaled corticosteroids and a short-acting bronchodilator, in addition to antidepressants, did not improve his symptoms. He had a history of allergic rhinitis and a familial history of asthma, but no signs of asthma as assessed by expectorated sputum and airway responsiveness (Dmin). However, flow-volume curves demonstrated a pattern consistent with upper airway constriction. Computed tomography confirmed severe tracheal narrowing caused by a double aortic arch. Compressive tracheal narrowing was also evaluated by fiber-optic tracheobronchoscopy. A treadmill exercise study induced respiratory distress with audible stridor that resolved itself without intervention. He underwent surgical division of the left aortic arch, which relieved the stridor during exercise. The flow-volume curve improved but constriction was still indicated even at 1.5 years after surgery. Double aortic arch should be considered in the differential diagnosis of drug-resistant stridor. This case re-emphasizes the value of flow-volume curves for diagnosing upper-airway obstruction. - Endobronchial actinomycosis associated with a foreign body--successful short-term treatment with antibiotics--.
Maki K, Shinagawa N, Nasuhara Y, Oizumi S, Domen H, Haga H, Nishimura M
Internal medicine (Tokyo, Japan), 49, 13, 1293, 1296, The Japanese Society of Internal Medicine, 2010年, ［査読有り］
英語, Primary endobronchial actinomycosis is a very rare condition. We report herein the case of a healthy 66-year-old woman who presented with right lower lobe endobronchial actinomycosis associated with aspiration of a foreign body, which was presumed to be a fish bone swallowed 28 months previously. The patient achieved complete clinical and radiological recovery after removal of the foreign body and 1-month antibiotic therapy of oral amoxycillin. Our experience in the management of this patient should help clinicians to realize the importance of bronchoscopic investigation and the management of this rare but treatable condition. - [Usefulness of fluorodeoxyglucose-positron emission tomography in a case of pleural sarcoidosis].
Takeshi Hattori, Satoshi Konno, Takashi Inomata, Yasuyuki Nasuhara, Tomoko Betsuyaku, Masaharu Nishimura
Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society, 47, 7, 658, 62, 2009年07月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, BACKGROUND: Pleural sarcoidosis is not a rare disease, and some patients with sarcoidosis experience chest pain, although the cause is often unknown. Various studies have indicated that fluorodeoxyglucose-positron emission tomography (FDG-PET) is useful for diagnosing and monitoring sarcoidosis. CASE: A 62-year-old man noted left-side dominant chest and back pain, although chest computed tomography (CT) revealed no abnormalities. Two months later, chest and back pain rapidly increased in severity and blurred vision appeared. In addition to uveitis, renal dysfunction was observed and chest CT on admission revealed enlargement of bilateral hilar/mediastinal lymph nodes and diffuse small nodular opacities and subpleural nodules, mainly in the segment of the left upper lobe (S1+2). FDG-PET revealed intense FDG uptake in bilateral peripheral lung parenchyma, spread widely along the subpleura and right inguinal lymph nodes with high uptake in the hilar and mediastinal lymph nodes. Sarcoidosis was diagnosed by transbronchial lung biopsy and renal biopsy. Oral corticosteroid treatment was performed due to persistent chest and back pain and rapid progression of renal dysfunction. Chest and back pain immediately disappeared and renal function improved. Follow-up FDG-PET performed 2 months after corticosteroid treatment revealed no areas of intense FDG uptake. - [Efficacy of leukotriene receptor antagonists in asthma treatment and analysis of background factors evaluated by a questionnaire survey among physicians].
Yoshinobu Fukui, Nobuyuki Hizawa, Daisuke Takahashi, Yukiko Maeda, Motoko Kobayashi, Yasuyuki Nasuhara, Masaharu Nishimura
Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society, 46, 12, 972, 80, 2008年12月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, The efficacy of leukotriene receptor antagonists (LTRAs) in the treatment of asthma and the involvement of various patient background factors were investigated. A questionnaire was used to survey the physicians of 1,600 asthma patients regarding the use of LTRAs, whether treatment was being continued or had been discontinued, and reasons for continuation or discontinuation. The results showed that 797 patients had used an LTRA, with 468 having used pranlukast (P), 294 having used montelukast (M) and 25 having used zafirlukast. For the remaining 10 patients, either the drug name was unknown or multiple LTRAs had been used. The P Group was slightly younger in age (median: P, 55 years, M, 57 years) and had a higher frequency of mild, intermittent disease (P: 20.3%; M:11.2%). The P Group also had a higher percentage of patients who continued taking an LTRA because the drug was "clearly effective" (P: 34.6%; M: 17.3%), and a lower percentage of patients who discontinued the drug because the drug was "ineffective" (P: 2.6%; M:19.0%). Logistic regression analysis showed the following as independent factors contributing to efficacy of the LTRA in the treatment of the asthma (R2 = 0.19): P as the drug used (p < 0.01); allergic rhinitis not present as a complication (p < 0.01); and mild severity of asthma (p = 0.02). Further, the present findings indicate that LTRAs are highly effective for patients who have mild asthma without complication by allergic rhinitis. Further investigation is necessary to determine differences in efficacy among different LTRAs. - the Hokkaido COPD Cohort Study Group Functional SNPs of the CCL5 gene and non-emphysematous phenotype in patients with COPD.
Hizawa, N, Makita H, Nasuhara Y, Hasegawa M, Nagai K, Ito Y, Betsuyaku T, Konno S, Nishimura M
Eur Respir J., 32, 2, 372-378, 2008年01月, ［査読有り］
英語, 研究論文（学術雑誌） - beta(2)-Adrenergic receptor genetic Polymorphisms and short-term bronchodilator responses in patients with COPD
Hizawa, Nobuyuki, Makita, Hironi, Nasuhara, Yasuyuki, Betsuyaku, Tomoko, Roh, Yoko, Nagai, Katsura, Hasegawa, Masant, Nishimura, Masaham
CHEST, 132, 5, 1485, 1492, AMER COLL CHEST PHYSICIANS, 2007年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: COPD is characterized by a persistent airflow limitation that is not fully reversible; thus, the reversibility of airflow limitations in response to a bronchodilator is an important component of COPD. Several studies have established that two common nonsynonymous polymorphisms in the beta2-adrenergic receptor gene (ADRB2), Arg16Gly and Gln27Glu, have important effects in modulating responses to beta2-agonists; however, the effects of these polymorphisms on responses to beta2-agonists in patients with COPD is unknown. OBJECTIVE: To examine whether different genotypes at these two polymorphisms are related to differential responses to inhaled beta2-agonists in patients with COPD. DESIGN AND PARTICIPANTS: A total of 246 patients with COPD who were participants in a longitudinal study of COPD (ie, the Hokkaido COPD cohort study) were studied. We compared short-term bronchodilator responses (BDRs) to salbutamol according to ADRB2 genotypes at codons 16 and 27. RESULTS: The presence of the Arg16 allele was associated with lower BDRs to beta2-agonist inhalation. The mean (+/-SD) log (postbronchodilator FEV1-prebronchodilator FEV1) values of Gly16 homozygotes (n=65), Arg16Gly16 heterozygotes (n=106), and Arg16 homozygotes (n=75) were 2.19+/-0.43, 2.09+/-0.42, and 2.01+/-0.42, respectively (p<0.05). The genetic effects of the Arg16Gly polymorphism were independent of the severity of airflow limitation, age, and smoking status. The most common Arg16-Gln27 haplotype was also significantly associated with decreased BDRs to salbutamol (p<0.01). CONCLUSION: The genetic effects of ADRB2 gene polymorphisms may explain some of the variability in response to therapeutic doses of a short-acting beta2-agonists in patients with COPD. - Lipopolysaccaride-induced neutrophilic inflammation in the lungs differs with age
Yoko Ito, Tomoko Betsuyaku, Yasuyuki Nasuhara, Masaharu Nishimura
EXPERIMENTAL LUNG RESEARCH, 33, 7, 375, 384, 2007年, ［査読有り］
英語, 研究論文（学術雑誌） - [Cibenzoline succinate induced pneumonitis].
Hasegawa M, Nasuhara Y, Maki N, Miura T, Betsuyaku T, Hizawa N, Nishimura M, Onozuka H, Tsutsui H
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 95, 7, 1362, 1364, 7, 2006年07月, ［査読有り］
日本語, 症例は70歳男性. 発作性心房細動に対し, コハク酸シベンゾリン (シベノール®) の服用を開始したところ, 15日目ごろより労作時呼吸困難を自覚し, 25日目に胸部異常陰影を指摘された. 抗生剤投与にて改善がみられないため, 我々はコハク酸シベンゾリンによる薬剤性肺炎も疑い, 同剤を中止した上でステロイド治療を施行した. 肺炎の改善を認めたが発作性心房細動が再発したため, 慎重な観察の下同剤を再開したところ肺炎の再増悪を認めた. 以上よりコハク酸シベンゾリンによる薬剤性肺炎と診断した. - Long term smoking with age builds up excessive oxidative stress in bronchoalveolar lavage fluid
K. Nagai, T. Betsuyaku, T. Kondo, Y. Nasuhara, M. Nishimura
Thorax, 61, 6, 496, 502, 2006年06月
英語, 研究論文（学術雑誌） - Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats
M. Kobayashi, Y. Nasuhara, A. Kamachi, Y. Tanino, T. Betsuyaku, E. Yamaguchi, J. Nishihira, M. Nishimura
European Respiratory Journal, 27, 4, 726, 734, 2006年04月
英語, 研究論文（学術雑誌） - Decrease of vascular endothelial growth factor in macrophages from long-term smokers
K Nagal, T Betsuyaku, Y Ito, Y Nasuhara, M Nishimura
EUROPEAN RESPIRATORY JOURNAL, 25, 4, 626, 633, 2005年04月, ［査読有り］
英語, 研究論文（学術雑誌） - Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid
Tomoko Betsuyaku, Y. Kuroki, K. Nagai, Y. Nasuhara, M. Nishimura
European Respiratory Journal, 24, 6, 964, 970, 2004年12月
英語, 研究論文（学術雑誌） - Chemokines in bronchiolar epithelium in the development of chronic obstructive pulmonary disease
S Fuke, T Betsuyaku, Y Nasuhara, T Morikawa, H Katoh, M Nishimura
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 31, 4, 405, 412, 2004年10月, ［査読有り］
英語, 研究論文（学術雑誌） - Effect of low-dose theophylline on airway inflammation in COPD
Motoko Kobayashi, Yasuyuki Nasuhara, Tomoko Betsuyaku, Eiji Shibuya, Yoshinori Tanino, Mishie Tanino, Kei Takamura, Katsura Nagai, Takeshi Hosokawa, Masaharu Nishimura
Respirology, 9, 2, 249, 254, 2004年06月
英語, 研究論文（学術雑誌） - Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line
K Takamura, Y Nasuhara, M Kobayashi, T Betsuyaku, Y Tanino, Kinoshita, I, E Yamaguchi, S Matsukura, RP Schleimer, M Nishimura
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 286, 4, L777, L785, 2004年04月, ［査読有り］
英語, 研究論文（学術雑誌） - [A case of paclitaxel-induced pneumonitis].
Taniguchi N, Shinagawa N, Kinoshita I, Nasuhara Y, Yamazaki K, Yamaguchi E, Akita H, Nishimura M
Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society, 42, 158, 163, 2, 2004年02月, ［査読有り］ - Studies on airway hyperresponsiveness by the astograph® method in asthmatics and young adult non-asthmatic asymptomatics
Yoshinobu Fukui, Etsuro Yamaguchi, Nobuyuki Hizawa, Yukiko Maeda, Daisuke Takahashi, Satoshi Konno, Motoko Kobayashi, Takeshi Hosokawa, Eisei Jinushi, Kei Takamura, Yasuyuki Nasuhara, Masaharu Nishimura
Japanese Journal of Allergology, 53, 6, 565, 574, 2004年, ［査読有り］
日本語, 研究論文（学術雑誌） - Extracellular matrix metalloproteinase inducer is increased in smokers' bronchoalveolar lavage fluid
T Betsuyaku, M Tanino, K Nagai, Y Nasuhara, M Nishimura, RM Senior
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 168, 2, 222, 227, 2003年07月, ［査読有り］
英語, 研究論文（学術雑誌） - Dissociation between airway responsiveness to methacholine and responsiveness to antigen
A. Kamachi, Y. Nasuhara, M. Nishimura, T. Takahashi, Y. Homma, Y. Ohtsuka, M. Munakata
European Respiratory Journal, 19, 1, 76, 83, 2002年
英語, 研究論文（学術雑誌） - Inhibition of ozone-induced lung neutrophilia and nuclear factor-kappa B binding activity by vitamin A in rat
T Hisada, IM Adcock, Y Nasuhara, M Salmon, TJ Huang, PJ Barnes, KF Chung
EUROPEAN JOURNAL OF PHARMACOLOGY, 377, 1, 63, 68, 1999年07月
英語, 研究論文（学術雑誌） - Role of cysteinyl-leukotrienes in eotaxin-induced bronchial hyperresponsiveness and eosinophil migration in IL-5 transgenic mice
T Hisada, M Salmon, Y Nasuhara, KF Chung
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 159, 3, A404, A404, 1999年03月
英語 - Intravascular lymphomatosis diagnosed by transbronchial lung biopsy
K. Takamura, Y. Nasuhara, T. Mishina, T. Matsuda, M. Nishimura, Y. Kawakami, M. Fujita, C. Mikuni, K. Yamashiro
European Respiratory Journal, 10, 4, 955, 957, European Respiratory Society, 1997年
英語, 研究論文（学術雑誌） - Meanings of the clinical parameters of airway hyperresponsiveness
M. Munakata, Y. Nasuhara, A. Sato, T. Takahashi, R. Sato, Y. Homma, Y. Kawakami
Japanese Journal of Thoracic Diseases, 34, 42, 47, 1996年
日本語, 研究論文（国際会議プロシーディングス）
その他活動・業績
- 人工呼吸器安全管理体制の構築 人工呼吸器点検パトロールの充実
渋谷 かをり, 大井 睦美, 沖 洋充, 石川 誠, 南須原 康行, 医療の質・安全学会誌, 9, Suppl., 223, 223, 2014年10月
(一社)医療の質・安全学会, 日本語 - パネル展示による医療者と患者・家族との医療安全に関する情報共有
大井 睦美, 渋谷 かをり, 沖 洋充, 石川 誠, 南須原 康行, 医療の質・安全学会誌, 9, Suppl., 294, 294, 2014年10月
(一社)医療の質・安全学会, 日本語 - 投稿受領(No.923)転倒・転落防止対策および対応に関する看護師の意識調査
南須原 康行, 佐久嶋 研, 奥原 芳子, 臨床看護, 39, 11, 1589, 1592, 2013年10月
へるす出版, 日本語 - 7対1看護導入がインシデント報告件数に与えた影響について 新人看護職数の増加に着目して
南須原 康行, 佐久嶋 研, 奥原 芳子, 渋谷 かをり, 伊藤 陽一, 石川 誠, 宝金 清博, 日本医療マネジメント学会雑誌, 14, 1, 25, 30, 2013年05月
(NPO)日本医療マネジメント学会, 日本語 - 肺胞蛋白症のGM‐CSF吸入治療の予後と肺活量
田澤立之, 新井徹, 笠原靖紀, 放生雅章, 大河内眞也, 江田良輔, 横場正典, 土橋佳子, 中山秀章, 石井晴之, 森本浩之輔, 南須原康行, 高田俊範, 海老名雅仁, 山口悦郎, 井上義一, 中田光, 日本呼吸器学会誌, 2, 増刊, 223, 223, 2013年03月10日
(一社)日本呼吸器学会, 日本語 - Vital Capacity And Recurrence After Granulocyte-Macrophage Colony Stimulating Factor (gm-Csf) Inhalation Therapy For Pulmonary Alveolar ProteINOSis
R. Tazawa, T. Arai, Y. Kasahara, M. Hojo, S. Ohkouchi, R. Eda, M. Yokoba, Y. Tsuchihashi, T. Nei, H. Nakayama, H. Ishii, K. Morimoto, Y. Nasuhara, T. Takada, M. Ebina, E. Yamaguchi, Y. Inoue, K. Nakata, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 187, 2013年
英語, 研究発表ペーパー・要旨（国際会議） - 医療安全管理部と診療録管理室協働による診療録監査の取り組み
初山 貴, 勝谷 剛, 佐々木 綾香, 横山 瑠奈, 齊藤 恵里佳, 渋谷 かをり, 奥原 芳子, 石川 誠, 南須原 康行, 寶金 清博, 診療情報管理 : 日本診療情報管理学会誌 = Health information management, 24, 3, 68, 71, 2012年12月25日
日本診療情報管理学会, 日本語 - 転倒・転落防止及び対応に関する看護師の意識調査
南須原 康行, 佐久嶋 研, 奥原 芳子, 渋谷 かをり, 石川 誠, 伊藤 陽一, 宝金 清博, 医療の質・安全学会誌, 7, Suppl., 205, 205, 2012年10月
(一社)医療の質・安全学会, 日本語 - 国立大学附属病院におけるGRM業務への医師・歯科医師参画の現状 医師GRMアンケートの結果より
南須原 康行, 石川 誠, 兼児 敏浩, 久田 友治, 福井 康三, 藤盛 啓成, 本間 覚, 宮本 智行, 国立大学附属病院医療安全管理協議会医師GRMアンケートプロジェクトチーム, 医療の質・安全学会誌, 7, 2, 133, 141, 2012年06月
(一社)医療の質・安全学会, 日本語 - Beta2-adrenergic receptor polymorphisms as a determinant of preferential bronchodilator responses to beta 2-agonist and anticholinergic agents in Japanese patients with chronic obstructive pulmonary disease
Satoshi Konno, Hironi Makita, Masaru Hasegawa, Yasuyuki Nasuhara, Katsura Nagai, Tomoko Betsuyaku, Nobuyuki Hizawa, Masaharu Nishimura, PHARMACOGENETICS AND GENOMICS, 21, 11, 687, 693, 2011年11月, ［査読有り］
英語 - 当院における成人用転倒・転落アセスメントシートの妥当性についての検討
南須原 康行, 佐久嶋 研, 伊藤 陽一, 奥原 芳子, 渋谷 かをり, 石川 誠, 寶金 清博, 医療の質・安全学会誌, 6, Suppl., 176, 176, 2011年10月
(一社)医療の質・安全学会, 日本語 - Comparison of airway remodelling assessed by computed tomography in asthma and COPD
Kaoruko Shimizu, Masaru Hasegawa, Hironi Makita, Yasuyuki Nasuhara, Satoshi Konno, Masaharu Nishimura, RESPIRATORY MEDICINE, 105, 9, 1275, 1283, 2011年09月, ［査読有り］
英語 - Effect Of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Inhalation On Bronchoalveolar Lavage Fluid And Serum In Pulmonary Alveolar ProteINOSis
R. Tazawa, K. Ohashi, A. Sato, T. Arai, Y. Kasahara, M. Hojo, M. Yokoba, Y. Tsuchihashi, H. Ishii, Y. Nasuhara, M. Ebina, T. Takada, E. Yamaguchi, Y. Inoue, K. Nakata, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 183, 2011年
英語, 研究発表ペーパー・要旨（国際会議） - Two Atypical Cases Of Hard Metal Lung Disease
T. Hosokawa, H. Terui, T. Ogi, C. Moriyama, A. Isada, K. Nagai, S. Konno, Y. Nasuhara, M. Nishimura, K. Kubota, Y. Matsuno, A. Morioka, I. Nakano, K. Kimura, K. Okamoto, M. Uo, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 183, 2011年, ［査読有り］
英語, 研究発表ペーパー・要旨（国際会議） - 結節性硬化症病変を伴わないmultifocal micronodular pneumocyte hyperplasia の1例
日本呼吸器学会雑誌, 49, 5, 355, 359, 2011年
速報，短報，研究ノート等（学術雑誌） - A Case of Follicular Bronchiolitis Associated with Asthma, Eosinophilia, and Increased Immunoglobulin E
Kaoruko Shimizu, Satoshi Konno, Yasuyuki Nasuhara, Mishie Tanino, Yoshihiro Matsuno, Masaharu Nishimura, JOURNAL OF ASTHMA, 47, 10, 1161, 1164, 2010年12月, ［査読有り］
英語, 速報，短報，研究ノート等（学術雑誌） - Airflow limitation and airway dimensions assessed per bronchial generation in older asthmatics
Kaoruko Shimizu, Masaru Hasegawa, Hironi Makita, Yasuyuki Nasuhara, Satoshi Konno, Masaharu Nishimura, RESPIRATORY MEDICINE, 104, 12, 1809, 1816, 2010年12月, ［査読有り］
英語, 速報，短報，研究ノート等（学術雑誌） - 国立大学附属病院における医師・歯科医師GRMの業務・役割の現状
南須原 康行, 石川 誠, 兼児 敏浩, 久田 友治, 福井 康三, 藤盛 啓成, 本間 覚, 宮本 智行, 医療の質・安全学会誌, 5, Suppl., 157, 157, 2010年11月
(一社)医療の質・安全学会, 日本語 - O14-3 肺CT3次元気道解析を用いた気管支喘息とCOPDにおける気道病変の比較(O14 喘息画像解析,口演,第60回日本アレルギー学会秋季学術大会)
清水 薫子, 長谷川 大, 牧田 比呂仁, 南須原 康行, 今野 哲, 西村 正治, アレルギー, 59, 9, 1384, 1384, 2010年10月30日
一般社団法人日本アレルギー学会, 日本語 - 喘息として加療されフローボリューム子九千が発見の契機となった成人重複大動脈弓の1例
日本呼吸器学会雑誌, 48, 3, 229, 234, 2010年
速報，短報，研究ノート等（学術雑誌） - 当院における死因分析 医療安全調査委員会設置後に向けて
南須原 康行, 佐竹 惠美子, 石川 誠, 奥原 芳子, 玉木 長良, 医療の質・安全学会誌, 4, Suppl., 131, 131, 2009年11月
(一社)医療の質・安全学会, 日本語 - MPO-ANCA陽性であったが糸球体腎炎や血管炎は確認されず、間質性肺炎に感染症を合併して死亡した症例
石津 明洋, 岩崎 沙理, 外丸 詩野, 武田 広子, 大塚 紀幸, 富居 一範, 笠原 正典, 清水 健一, 南須原 康行, 西村 正治, 北海道医学雑誌, 84, 5, 403, 403, 2009年09月
北海道医学会, 日本語 - Comparison of the Pharmacodynamics of Biapenem in Bronchial Epithelial Lining Fluid in Healthy Volunteers Given Half-Hour and Three-Hour Intravenous Infusions
Eiki Kikuchi, Junko Kikuchi, Yasuyuki Nasuhara, Satoshi Oizumi, Akitoshi Ishizaka, Masaharu Nishimura, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 53, 7, 2799, 2803, 2009年07月, ［査読有り］
英語 - Relationship between improved airflow limitation and changes in airway calibre induced by inhaled anticholinergic agents in COPD
M. Hasegawa, H. Makita, Y. Nasuhara, N. Odajima, K. Nagai, Y. Ito, T. Betsuyaku, M. Nishimura, THORAX, 64, 4, 332, 338, 2009年04月, ［査読有り］
英語 - Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice
Masaru Suzuki, Tomoko Betsuyaku, Yoko Ito, Katsura Nagai, Nao Odajima, Chinatsu Moriyama, Yasuyuki Nasuhara, Masaharu Nishimura, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 296, 4, L614, L623, 2009年04月
英語 - Aging affects lipopolysaccharide-induced upregulation of heme oxygenase-1 in the lungs and alveolar macrophages
Yoko Ito, Tomoko Betsuyaku, Chinatsu Moriyama, Yasuyuki Nasuhara, Masaharu Nishimura, BIOGERONTOLOGY, 10, 2, 173, 180, 2009年04月, ［査読有り］
英語 - 関節リウマチ患者における肺病変の検討
藤枝 雄一郎, 渥美 達也, 加藤 将, 大友 耕太郎, 橋本 陶子, 奥 健志, 古崎 章, 片岡 浩, 堀田 哲也, 保田 晋助, 南須原 康行, 小池 隆夫, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 53回・18回, 314, 314, 2009年03月
(一社)日本リウマチ学会, 日本語 - Aerosolized GM-CSF Therapy of Pulmonary Alveolar Proteinosis (PAP).
R. Tazawa, Y. Inoue, T. Takada, T. Arai, Y. Nasuhara, N. Hizawa, Y. Kasahara, K. Tatsumi, M. Hojo, M. Yokoba, N. Tanaka, E. Yamaguchi, R. Eda, Y. Tsuchihashi, K. Oishi, M. Terada, C. Kaneko, T. Nukiwa, J. P. Krischer, B. C. Trapnell, K. Nakata, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 179, 2009年
英語, 研究発表ペーパー・要旨（国際会議） - Catalase Expression in Pulmonary Macrophages of Smokers and Chronic Obstructive Pulmonary Disease (COPD) Patients.
T. Inomata, T. Betsuyaku, Y. Ito, Y. Nasuhara, M. Nishimura, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 179, 2009年, ［査読有り］
英語, 研究発表ペーパー・要旨（国際会議） - 胸痛を呈し、胸膜病変の診断と病勢評価にFDG-PET (fluorodeoxyglucose-positron emission tomography) が有用であったサルコイドーシスの1例
日本呼吸器学会雑誌, 47, 7, 658, 662, 2009年
速報，短報，研究ノート等（学術雑誌） - Matrix metalloproteinases in blood from patients with LAM
Nao Odajima, Tomoko Betsuyaku, Yasuyuki Nasuhara, Hiromasa Inoue, Kuniaki Seyama, Masaharu Nishimura, RESPIRATORY MEDICINE, 103, 1, 124, 129, 2009年01月, ［査読有り］
英語 - Down-Regulated NF-E2-Related Factor 2 in Pulmonary Macrophages of Aged Smokers and Patients with Chronic Obstructive Pulmonary Disease
Masaru Suzuki, Tomoko Betsuyaku, Yoko Ito, Katsura Nagai, Yasuyuki Nasuhara, Kichizo Kaga, Satoshi Kondo, Masaharu Nishimura, AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 39, 6, 673, 682, 2008年12月, ［査読有り］
英語 - Diversity of protein carbonylation in allergic airway inflammation
Katsura Nagai, Tomoko Betsuyaku, Satoshi Konno, Yoko Ito, Yasuyuki Nasuhara, Nobuyuki Hizawa, Takahito Kondo, Masaharu Nishimura, FREE RADICAL RESEARCH, 42, 11-12, 921, 929, 2008年11月, ［査読有り］
英語 - 肺限局型MPO-ANCA関連血管炎と考えられた一剖検例
外丸 詩野, 武田 広子, 岩崎 沙理, 大塚 紀幸, 富居 一範, 笠原 正典, 清水 健一, 南須原 康行, 西村 正治, 石津 明洋, 日本病理学会会誌, 97, 2, 33, 33, 2008年09月
(一社)日本病理学会, 日本語, 速報，短報，研究ノート等（学術雑誌） - Functional single nucleotide polymorphisms of the CCL5 gene and nonemphysernatous phenotype in COPD patients
N. Hizawa, H. Makita, Y. Nasuhara, M. Hasegawa, K. Nagai, Y. Ito, T. Betsuyaku, S. Konno, M. Nishimura, EUROPEAN RESPIRATORY JOURNAL, 32, 2, 372, 378, 2008年08月, ［査読有り］
英語 - ビアペネム30分点滴静注と3時間点滴静注における気管支上皮被覆液中薬物動態の解析
菊地英毅, 山崎浩一, 菊地順子, 石坂彰敏, 南須原康行, 西村正治, 日本呼吸器学会雑誌, 46, 155, 2008年05月10日
日本語 - 関節リウマチ患者における肺合併症の検討
藤枝 雄一郎, 古崎 章, 堀田 哲也, 笠原 郁美, 吉田 修也, 加藤 将, 大友 耕太郎, 片岡 浩, 保田 晋助, 渥美 達也, 小池 隆夫, 南須原 康行, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 52回・17回, 302, 302, 2008年04月
(一社)日本リウマチ学会, 日本語 - Role of basement membrane in EMMPRIN/CD147 induction in rat tracheal epithelial cells
Takeshi Hosokawa, Tomoko Betsuyaku, Nao Odajima, Masaru Suzuki, Katsumi Mochitate, Yasuyuki Nasuhara, Masaharu Nishimura, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 368, 2, 426, 432, 2008年04月, ［査読有り］
英語 - Dual oxidase 1 and 2 expression in airway epithelium of smokers and patients with mild/moderate chronic obstructive pulmonary disease
Katsura Nagai, Tomoko Betsuyaku, Masaru Suzuki, Yasuyuki Nasuhara, Kichizo Kaga, Satoshi Kondo, Masaharu Nishimura, ANTIOXIDANTS & REDOX SIGNALING, 10, 4, 705, 714, 2008年04月, ［査読有り］
英語 - 呼吸器内科医による成人喘息診断の実態―アンケート調査の結果―
日本呼吸器学会雑誌, 46, 8, 601, 607, 2008年 - Decreased airway expression of vascular endothelial growth factor in cigarette smoke-induced emphysema in mice and COPD patients
Masaru Suzuki, Tomoko Betsuyaku, Katsura Nagai, Satoshi Fuke, Yasuyuki Nasuhara, Kichizo Kaga, Satoshi Kondo, Ichiro Hamamura, Junko Hata, Hiroshi Takahashi, Masaharu Nishimura, INHALATION TOXICOLOGY, 20, 3, 349, 359, 2008年, ［査読有り］
英語 - 慢性閉塞性肺疾患と中高年発症喫煙者喘息における血清総ＩｇＥ値、末梢血好酸球数およびアトピー素因の比較
清水 健一, 檜澤 伸之, 牧田 比呂仁, 今野 哲, 南須原 康行, 別役 智子, 西村 正治, 日本医師会雑誌, 137, 2, 326, 331, 2008年
(公社)日本医師会, 日本語 - The realities of clinical asthma diagnosis from questionnaire results
Yoshinobu Fukui, Nobuyuki Hizawa, Daisuke Takahashi, Yukiko Maeda, Motoko Kobayashi, Yasuyuki Nasuhara, Masaharu Nishimura, Nihon Kokyuki Gakkai Zasshi, 46, 8, 601, 607, 2008年, ［国内誌］
We investigated the basis on which respiratory physicians establish a diagnosis of asthma in clinical practice. A questionnaire survey was conducted on physicians in charge of 1,600 asthma patients receiving outpatient treatment at the Hokkaido University General Hospital or its affiliated hospitals or clinics. The bases for diagnosis were ranked as follows: 1) recurrent paroxysmal dyspnea or symptoms such as wheezing and cough (86%); 2) detection of wheezing on auscultation (78%); 3) improvement in symptoms or auscultation findings after using bronchodilators (56%); 4) improvement in symptoms or auscultation findings after using inhaled corticosteroids (55%); 5) diagnosis of asthma by another physician (46%); and 6) spirometry findings (31%). The performance rates of each examination were as follows. Spirometry at initial visit, 47%; sputum eosinophils, 25%; improvements in FEV1 measured after inhalation of bronchodilator or after treatment as asthma, 12%; measurements of airway responsiveness, 5% and variability in peak expiratory flow, 2%. Asthma is often diagnosed by respiratory physicians based on symptoms, physical examinations and improvement in symptoms or physical findings after treatment for asthma in medical practice. The performance rates of tests used to diagnose asthma were low., 日本語 - Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease
Hironi Makita, Yasuyuki Nasuhara, Katsura Nagai, Yoko Ito, Masaru Hasegawa, Tomoko Betsuyaku, Yuya Onodera, Nobuyuki Hizawa, Masaharu Nishimura, THORAX, 62, 11, 932, 937, 2007年11月, ［査読有り］
英語 - Loss of caveolin-1 in bronchiolization in lung fibrosis
Nao Odajima, Tomoko Betsuyaku, Yasuyuki Nasuhara, Masaharu Nishimura, JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 55, 9, 899, 909, 2007年09月
英語 - Increase in soluble CD138 in bronchoalveolar lavage fluid of multicentric Castleman's disease
Masaru Hasegawa, Tomoko Betsuyaku, Nobuya Yoshida, Yasuyuki Nasuhara, Ichiro Kinoshita, Satoshi Ohta, Tomoo Itoh, Pyong Woo Park, Masaharu Nishimura, RESPIROLOGY, 12, 1, 140, 143, 2007年01月, ［査読有り］
英語 - リウマチ性多発筋痛症寛解後非特異的間質性肺炎, 自己免疫性溶血性貧血を合併した1例
中舘 恵, 南須原 康行, 濱田 邦夫, 西村 正治, 日本呼吸器学会雑誌 = The journal of the Japanese Respiratory Society, 44, 11, 864, 868, 2006年11月10日
日本語 - Airflow limitation and airway dimensions in chronic obstructive pulmonary disease
M Hasegawa, Y Nasuhara, Y Onodera, H Makita, K Nagai, S Fuke, Y Ito, T Betsuyaku, M Nishimura, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 173, 12, 1309, 1315, 2006年06月, ［査読有り］
英語 - 【抗菌薬サイクリングvsミキシング 耐性菌対策としての抗菌薬使用への介入】 ICUにおける抗菌薬サイクリング
松田 直之, 秋沢 宏次, 南須原 康行, 石黒 信久, 奥 直子, 早川 峰司, 澤村 淳, 石川 岳彦, 亀上 隆, 西村 正治, 丸藤 哲, Progress in Medicine, 25, 9, 2329, 2336, 2005年09月
(株)ライフ・サイエンス, 日本語 - 「Q熱に伴う器質化肺炎の1例」
小野 江和之, 南須原 康行, 笠原 郁美, 檜澤 伸之, 西村 正治, 上野 弘志, 村松 康和, 森田 千春, 田村 豊, 『日内会誌』, 94, 5, 961, 963, 2005年
症例は69歳女性.特発性器質化肺炎としてステロイド治療を開始し,自他覚所見は速やかに改善した.しかし,経過中行った検索にてCoxiella burnetiiに対する血清抗体価上昇,血液PCR陽性であったため, Q熱が器質化肺炎の原因と考えられた. Q熱については,診断法が一般的でなく市中肺炎の原因としても見逃されていることが多いとされており,特発性器質化肺炎と診断されている症例の中に, Q熱によって引き起こされている症例が少なからず存在する可能性がある., The Japanese Society of Internal Medicine, 日本語, 速報，短報，研究ノート等（学術雑誌） - 「気管支肺胞洗浄所見の変化を追跡したgefitinibによる間質性肺炎の1例」
『日呼吸会誌』, 43, 466, 470, 2005年
速報，短報，研究ノート等（学術雑誌） - 「咳喘息に対する吸入ステロイド単独療法とプロカテロール併用療法の比較」
『呼吸』, 24, 65, 70, 2005年 - Nagai K，Betsuyaku T，Ito Y，Nasuhara Y，Nishimura M．： “Decrease of vascular endothelial growth factor in macrophages from long-team smokers” ，Eur Respir J，25：626-633 (2005)*
2005年, ［査読有り］ - Ito Y，Betsuyaku T，Nagai K，Nasuhara Y，Nishimura M．： “Expression of pulmonary VEGF family declines with age and is further down-regulated in lipopolysaccharide（LPS）-induced lung injury” ，Exp Gerontol，40：315-323 (2005)
Y Ito, T Betsuyaku, K Nagai, Y Nasuhara, M Nishimura, EXPERIMENTAL GERONTOLOGY, 40, 4, 315, 323, 2005年, ［査読有り］
英語 - A case of paclitaxel-induced pneumonitis
Natsuko Taniguchi, Naofumi Shinagawa, Ichiro Kinoshita, Yasuyuki Nasuhara, Koichi Yamazaki, Etsuro Yamaguchi, Hirotoshi Akita, Masaharu Nishimura, Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society, 42, 2, 158, 163, 2004年
日本語, 書評論文,書評,文献紹介等 - 「パクリタキセル投与との関連が示唆された薬剤性肺炎の1例」
『日呼吸会誌』, 42, 158, 163, 2004年
速報，短報，研究ノート等（学術雑誌） - 「気管支喘息患者と若年成人無症候者におけるアストグラフ法による気道過敏性の検討」
『アレルギー』, 53, 565, 574, 2004年 - Kobayashi M，Nasuhara Y，Betsuyaku T，Shibuya E，Tanino Y，Tanino M，Takamura K，Nagai K，Hosokawa T，Nishimura M．：“Effect of low-dose theophylline on airway inflammation in COPD”，Respirology，9：249-254 (2004)*
2004年, ［査読有り］ - Takamura K，Nasuhara Y，Kobayashi M，Betsuyaku T，Tanino Y，Kinoshita I，Yamaguchi E，Matsukura S，Schleimer RP，Nishimura M．：“Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line”，Am J Physiol Lung Cell Mol ・・・
2004年, ［査読有り］
Takamura K，Nasuhara Y，Kobayashi M，Betsuyaku T，Tanino Y，Kinoshita I，Yamaguchi E，Matsukura S，Schleimer RP，Nishimura M．：“Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line”，Am J Physiol Lung Cell Mol Physiol，286：777-785 (2004)* - Fuke S，Betsuyaku T，Nasuhara Y，Morikawa T，Katoh H，Nishimura M．：“Chemokines in Bronchiolar Epithelium in the Development of Chronic Obstructive Pulmonary Disease”，Am J Respir Cell Mol Biol，31：405-412 (2004)*
2004年, ［査読有り］ - Catley MC，Cambridge LM，Nasuhara Y，Itoh K，Chivers JE，Beaton A，Holden NS，Bergmann MW，Barnes PJ，Newton R．：“Inhibitors of Protein Kinase C (PKC) Prevent Activated Transcription；Role of events down stream of NF-κB DNA binding”，J Biol Chem，279：18457-18466 (2・・・
2004年, ［査読有り］
Catley MC，Cambridge LM，Nasuhara Y，Itoh K，Chivers JE，Beaton A，Holden NS，Bergmann MW，Barnes PJ，Newton R．：“Inhibitors of Protein Kinase C (PKC) Prevent Activated Transcription；Role of events down stream of NF-κB DNA binding”，J Biol Chem，279：18457-18466 (2004)* - Betsuyaku T，Kuroki Y，Nagai K，Nasuhara Y，Nishimura M．：“Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid”，Eur Respir J，24：964-970 (2004)*
2004年, ［査読有り］ - 「喘息におけるβ刺激薬」
『International Review of Asthma』, 6, 30, 36, 2004年
記事・総説・解説・論説等（学術雑誌） - 6. RS_3PE症候群に肺扁平上皮癌を合併した1例(第29回日本肺癌学会北海道支部会)(支部活動)
菅 正之, 山崎 浩一, 木下 一郎, 濱田 邦夫, 南須原 康行, 西村 正治, 天崎 吉晴, 秋田 弘俊, 肺癌, 43, 7, 1047, 1047, 2003年12月30日
日本肺癌学会, 日本語 - 上肺の線維化に合併したアスペルギルス感染と血中, BAL液中SP-A, SP-Dの経過
福家 聡, 別役 智子, 大泉 聡史, 南須原 康行, 斉藤 拓志, 山口 悦郎, 西村 正治, 日本呼吸器学会雑誌 = The journal of the Japanese Respiratory Society, 41, 3, 196, 201, 2003年03月10日
日本語 - Betsuyaku T, Tanino M, Nagai K, Nasuhara Y, Nishimura M, Senior RM. Related Articles, Links Extracellular matrix metalloproteinase inducer is increased in smokers' bronchoalveolar lavage fluid. Am J Respir Crit Care Med. 2003 Jul 15;168(2):222-7.*
2003年, ［査読有り］ - Elevated serum KL-6 concentrations in patients with diabetes mellitus
T Takahashi, K Takamura, S Sakaue, J Ishii, H Yokouchi, Y Nasuhara, JOURNAL OF DIABETES AND ITS COMPLICATIONS, 16, 5, 352, 358, 2002年09月
英語 - Q&A COPDと気管支喘息との病態の相違について教えてください (特集 プライマリケアのための慢性閉塞性肺疾患(COPD)の管理)
南須原 康行, 西村 正治, 治療, 84, 9, 2310, 2312, 2002年09月
南山堂, 日本語 - Expression and alteration of ras and p53 proteins in patients with lung carcinoma accompanied by idiopathic pulmonary fibrosis
T Takahashi, M Munakata, Y Ohtsuka, H Nisihara, Y Nasuhara, A Kamachi-Satoh, H Dosaka-Akita, Y Homma, Y Kawakami, CANCER, 95, 3, 624, 633, 2002年08月
英語 - Takahashi, T., Ohtsuka, Y., Munakata, Y., Nasuhara, Y., Kamachi-Satoh, A., Homma, Y., Kawakami Y.:"Occurence of Farmer's Lung Disease is relevant to meteorological conditions: A 20-year follow-up field survey analysis", Am J Ind Med, 41:506-513(2002)*
2002年, ［査読有り］ - Kamachi, A., Nasuhara, Y., Nishimura, M., Takahashi, T., Homma, Y., Ohtsuka, Y., Munakata, M.: "Dissociation between airway responsiveness to methacholine and responsiveness to antigen", Eur Respir J, 19:76-83 (2002)*
2002年, ［査読有り］ - Enhancement of goblet cell hyperplasia and airway hyperresponsiveness by salbutamol in a rat model of atopic asthma
A Kamachi, M Munakata, Y Nasuhara, M Nishimura, Y Ohtsuka, M Amishima, T Takahashi, Y Homma, Y Kawakami, THORAX, 56, 1, 19, 24, 2001年01月
英語 - Effect of an oral β2-adrenoceptor agonist in a patient with idiopathic interstitial pneumonia
T. Takahashi, Y. Nasuhara, K. Takamura, Y. Kawakami, Allergology International, 50, 1, 109, 111, 2001年, ［査読有り］
Blackwell Publishing, 英語 - Kamachi,A., Munakata,M., Nasuhara,Y., Nishimura,M., Ohtsuka,Y., Kawakami,Y.:"Enhancement of gblet cell hyperplasia and airway hypereponsiveness by salbutamol in a rat model of atopic asthma", Thorax,56:19-24(2001)*
2001年, ［査読有り］ - Meja,KK., Seldon,PM., Nasuhara,Y., Ito,K., Barnes,PJ., Lindsay,MA., Giembycz,MA. "p38 MAP kinase and MKK-1 co-operate in the generation of GM-CSF from LPS-stimulated human monocytes by an NF-kappaB-independent mechanism", Br J Pharmacol, 131:1143-1153(・・・
KK Meja, PM Seldon, Y Nasuhara, K Ito, PJ Barnes, MA Lindsay, MA Giembycz, BRITISH JOURNAL OF PHARMACOLOGY, 131, 6, 1143, 1153, 2000年11月, ［査読有り］
英語 - Extracellular signal-regulated kinase 1/2 control Ca2+-independent force development in histamine-stimulated bovine tracheal smooth muscle
A Koch, Y Nasuhara, PJ Barnes, MA Lindsay, MA Giembycz, BRITISH JOURNAL OF PHARMACOLOGY, 131, 5, 981, 989, 2000年11月, ［査読有り］
英語 - Hisada,T., Salmon,M., Nasuhara,Y., Chung,KF. "Involvement of haemooxygenase-1 in ozone-induced airway inflammation and hyperresponsiveness",Eur J Pharmacol, 399:229-234(2000)*
2000年, ［査読有り］
英語 - Cysteinyl-leukotrienes partly mediate eotaxin-induced bronchial hyperresponsiveness and eosinophilia in IL-5 transgenic mice
T Hisada, M Salmon, Y Nasuhara, KF Chung, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 160, 2, 571, 575, 1999年08月, ［査読有り］
英語 - Adcock,I.M., Nasuhara,Y., Stevens,D.A., Barnes,P.J.: "Ligand-induced differentiation of glucocorticoid receptor (GR) transrepression and transactivation: preferential targetting of NF-kB and lack of I-kB involvement", Br.J.Pharmacol., 127:1003-1011 (19・・・
IM Adcock, Y Nasuhara, DA Stevens, PJ Barnes, BRITISH JOURNAL OF PHARMACOLOGY, 127, 4, 1003, 1011, 1999年06月, ［査読有り］
英語 - Hisada,T., Adcock,I.M., Nasuhara,Y., Salmon,M., Huang,T.J., Chung,K.F.: "Inhibition of ozone-induced lung neutrophilia and nuclear factor-kappa B binding activity by vitamin A in rat", Eur.J.Pharmacol., 377:63-68 (1999)*
1999年, ［査読有り］
英語 - Nasuhara,Y., Adcock,I.M., Catley,M., Barnes,P.J., Newton,R.: "Differential IkB kinase activation and IkBa degradation by interleukin-1b and tumor necrosis factor-a in human U937 monocytic cells", J.Biol.Chem., 274:571-575 (1999)*
1999年 - 吸入誘発で診断したウサギ毛抗原によるPIE症候群の1例
本村 文宏, 棟方 充, 土肥 勇, 南須原 康行, 川上 義和, 日本胸部疾患学会雑誌 = The Japanese journal of thoracic diseases, 35, 4, 455, 460, 1997年04月25日
日本語 - 特発性間質性肺炎の急性増悪に対するステロイドパルス療法施行例の予後
高橋 亨, 棟方 充, 大塚 義紀, 南須原 康行, 蒲池 敦子, 佐藤 利佳, 本間 行彦, 川上 義和, 日本胸部疾患学会雑誌 = The Japanese journal of thoracic diseases, 35, 1, 9, 15, 1997年01月25日
日本語 - 気管支喘息患者における抗原吸入後気道反応パターンと関連因子の検討
佐藤 敦子, 棟方 充, 網島 優, 南須原 康行, 本間 行彦, 川上 義和, 日本胸部疾患学会雑誌 = The Japanese journal of thoracic diseases, 33, 6, 612, 617, 1995年06月25日
日本語
共同研究・競争的資金等の研究課題
- 医療機関内の医療事故の機能的な報告体制の構築のための研究
厚生労働行政推進調査事業費補助金 地域医療基盤開発推進研究事業
2023年04月 - 2025年03月
木村壮介, 宮田哲郎, 後信, 南須原康行, 秋元菜穂子
厚生労働省, 医療事故の機能的な報告体制の構築, 一般社団法人 日本医療安全調査機構, 研究分担者, 22IA1004 - 院内の医療安全管理体制を定量的に評価する指標の確立と実装を行う研究
厚生労働行政推進調査事業補助金 地域医療基盤開発推進研究事業
2022年04月 - 2024年03月
長尾能雅, 大川淳, 遠山信幸, 南須原康行, 兼児敏浩, 浦松雅史, 平松真理子, 梅村朋, 植村政和
厚生労働省, これまでの研究成果を基に医療安全評価指標を確立し、試験的な導入を経て本格的な社会実装に向けた検証を行う, 名古屋大学医学部附属病院, 研究分担者, 22IA002 - 人工知能技術を利用した医用画像診断支援システムの倫理リスクマネジメント手法の研究
科学研究費助成事業
2020年04月01日 - 2021年03月31日
平田 雄一, 平田 健司, 南須原 康行, 白土 博樹
本研究は、将来的に重要性が増すと予想される人工知能技術を利用した医用画像診断支援システムの倫理リスクを具体化するための新しいリスクマネジメント手法の構築を試み、人工知能技術を利用した医用画像診断支援システムの倫理リスクの低減策の検討を詳細に深く行えるようにすることを目的とした。
具体的には、本研究では、医学物理学の放射線治療分野や放射線安全管理分野において、既に活用されている複雑なシステムを、システムの要素(コンポーネント)間の入力と出力により決定される制御関係の安全性に着目して解析する安全解析手法であるSTAMP(System Theoretic Accident Model and Processes)を、人工知能技術を利用した医用画像診断支援システムの倫理リスクのリスクマネジメントに応用した。
2020年度は、新しい倫理リスク・マネジメント・モデルを、医用画像に関する倫理リスク事項のネットワークを高速に処理するために本研究で購入した高速データ処理が可能な高性能ワークステーション上に実装されたSTAMPのモデリングツールであるSTAMP Workbenchを基盤とした新しい倫理リスク・モデリング・システムにより構築した。
その結果、本研究で構築した、STAMP Workbenchを基盤とした、人工知能技術を利用した医用画像診断支援システムの新しい倫理リスクマネジメント手法は、放射線治療における事故防止のための強力なツールとなりえることが明らかになった。
そして、日本放射線腫瘍学会第33回学術大会において、本研究の分担者全員と共同して上記研究結果を発表した。
日本学術振興会, 基盤研究(C), 北海道大学, 20K12708 - 高信頼性内視鏡外科医育成のための継続的教育モデルの構築
科学研究費助成事業
2017年04月01日 - 2020年03月31日
安部 崇重, 南須原 康行, 篠原 信雄
ブタ臓器を用いた腹腔鏡手術手技トレーニングモデルを開発した。参加者は3つのタスク(1: 大動脈周囲の組織剥離, 2: 腎動脈の剥離とヘモロックを用いた血管処理, 3: 腎実質縫合)を行い、トレーニングの録画動画を2名の技術認定医が評価した。医師40名、医学生14名のデータに関して開発したモデルの良好なconstruct validityを確認した。またVirtual reality (VR)シミュレーターを用いて、腹腔鏡下左腎摘除術シナリオのvalidation studyを行った。33名が参加し、VRシミュレーターの良好なconstruct validityを確認した。
日本学術振興会, 基盤研究(C), 北海道大学, 17K08897 - 医療安全管理体制の可視化と人材育成のための研究
厚生労働科学研究補助金 地域医療基盤開発推進研究事業
2018年04月 - 2020年03月
長尾能雅, 遠山信幸, 南須原康行, 兼児敏浩, 新井有美, 浦松雅史, 田辺公一, 深見達弥, 植村政和, 梅村朋
厚生労働省, 名古屋大学医学部附属病院, 研究分担者 - インシデント報告、ニアミス報告を利用した高信頼性手術チームの醸成に関する研究
科学研究費助成事業
2014年04月01日 - 2017年03月31日
安部 崇重, 南須原 康行, 篠原 信雄
公益財団法人日本医療機能評価機構医療事故情報収集等事業による公開データに関して、腹腔鏡/胸腔鏡手術関連の報告540件から、746件のインシデントを抽出した。術式別の比較では、腹腔鏡/腹腔鏡補助手術(L群)582件、胸腔鏡/胸腔鏡補助手術(T群)159件、腹腔鏡+胸腔鏡手術5件のインシデントを認めた。他臓器損傷、異物遺残、医療機器の不良/故障、大量出血、血管等の誤認、血管損傷の報告が多かった。L群/T群の比較では、他臓器損傷, 大量出血, 血管損傷で差を認めた。
日本学術振興会, 基盤研究(C), 北海道大学, 26460853 - 気管支喘息、ＣＯＰＤの病態における組織因子（ＴＦ）、第７因子（Ｆ７）の関与
科学研究費助成事業
2011年 - 2013年
今野 哲, 伊佐田 朗, 南須原 康行
2種類のマウス喘息モデルにおいて、気管支肺胞洗浄液(BALF)中、全肺組織において、組織因子(TF)、第VII因子の発現が亢進していることを確認した。更には、同モデルにおいて、TF-第VII因子阻害作用を有するFVIIaiを腹腔内投与したところ、BALF中の好酸球細胞数の減少、OVA特異的IgE抗体の低下、及び気道過敏性の改善を確認した。以上の結果は、FVIIaiの気管支喘息の新たな治療法の可能性を示唆するものと考えられた。
遺伝子多型研究においては、症例（喘息）-対象研究において、凝固系カスケードに関連する種々の遺伝子(TF,F2R,CC16,CAT)に存在するのSNPsと気管支喘息との関連を見出した。
日本学術振興会, 基盤研究(C), 北海道大学, 23591110 - 難治性喘息に対する創薬への挑戦-新規NF-kB阻害薬(DHMEQ)の可能性-
科学研究費助成事業
2009年 - 2011年
西村 正治, 藤堂 省, 南須原 康行, 今野 哲
新規NF-kB阻害薬であるDHMEQは、種々の慢性炎症性疾患モデルにおける効果が報告されている。本研究では、マウス喘息モデルにおいて、DHMEQは、好酸球性気道炎症、気道線維化を有意に抑制することが見出された。更には、in vitroを用いた系において、気道上皮細胞からのケモカインの抑制、Th2細胞からのサイトカイン産生を抑制することが示された。DHMEQは、気管支喘息における新規治療薬となる可能性が示唆された。
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 21659206 - 大規模コホート研究による難治性気道疾患の病態解明と個別化治療への展開
科学研究費助成事業
2009年 - 2011年
西村 正治, 今野 哲, 南須原 康行, 牧田 比呂仁
慢性閉塞性肺疾患(COPD)患者における1秒量の経年変化は、必ずしもすべての症例で進行性ではなく、5年間にわたり1秒量経年変化が維持される症例も認め、症例により様々である。この結果は、COPDが常に進行性であるという、疾患概念を覆すものであり、治療の重要性を示す。
また、1秒量経年変化が急速に低下する群では、気腫病変の重症度が、気流閉塞の重症度とは独立した寄与因子であった。この結果は、今後の臨床研究において新しい病型分類に基づいた評価、解析が必要性を示している。
日本学術振興会, 基盤研究(B), 北海道大学, 21390253 - 慢性喫煙と加齢が肺胞マクロファージのアポトーシス細胞貪食能に与える影響
科学研究費助成事業
2008年 - 2010年
南須原 康行, 伊藤 洋子, 別役 智子
マクロファージの細胞表面に発現するアポトーシス細胞の認識/貪食に関わる受容体が、喫煙や加齢の影響でどのように修飾を受けるのかを検討した。非喫煙者では加齢により、肺胞マクロファージ(AM)のhosphatidylserine receptor(PSR)やscavenger receptor A(SR-A)の発現は上昇したが、中高年では喫煙者のPSR, SR-A発現は同年齢の非喫煙者と比較し低値であった。また、分化誘導したマクロファージ様の単球系細胞U937において、タバコ抽出液曝露にてPSRの発現が増強することを示した。このPSR発現はVascular endothelial growth factor(VEGF)receptor blockerであるSU5416により濃度依存性に抑制された。このことはマクロファージのアポトーシス細胞貪食能にVEGFがPSR発現を介して間接的に関与していることを示唆する。
日本学術振興会, 基盤研究(C), 北海道大学, 20590890 - 難治性気道疾患への新たな挑戦-病態、診断、治療へのアプローチ-
科学研究費助成事業
2007年 - 2008年
西村 正治, 桧澤 伸之, 別役 智子, 南須原 康行
難治性の気道疾患という観点から慢性閉塞性肺疾患(Chronic obstructive pulmonary disease : COPD)と気管支喘息をとらえ、その克服をめざしたものである。近年、酸化ストレスが、COPD、気管支喘息の病態に様々な形で関与すると考えられており、具体的には1)治療標的の特定を目指す病態の解明、2)低侵襲的気道病態の評価法の開発(新規酸化ストレスバイオマーカー・3次元的気道画像解析)、3)抗酸化剤治療介入へ向けての基礎的研究、4)北海道COPDコホート研究という4つのプロジェクトからなる。
日本学術振興会, 基盤研究(B), 北海道大学, 19390221 - 3次元CTによる気腫・気道病変の評価と慢性閉塞性肺疾患病態解析への応用
科学研究費助成事業
2005年 - 2006年
西村 正治, 南須原 康行, 小野寺 裕也
今年度は、3次元画像解析を用いて、以下の3つの検討を行い結果を得た。1)以前から検討してきた右上葉肺尖枝B1と下葉前下行枝B8の2本の気管支に加えて、各部位より複数の枝(上葉3本、中葉2本、下葉3本)を測定し、COPD患者における気道病変の均一性の検討を行った。測定評価については、昨年度と同様に3次から6次分枝にかけて中枢から末梢にかけて気道の壁面積比(WA%)を検討した。多くの気管支を調べた結果、末梢の6次では中枢の3次に比べてlobeによるばらつきが少なく、我々が今まで検討していたB1,8の2本が特に末梢の6次に関しては他の気管支の6次の病変を十分に反映しているものと考えられた。2)-950HUを閾値にして気腫病変を立体的に定量評価し、さらに気腫病変を上肺、中肺、下肺と分割することにより、COPDにおける局所における気腫病変と気流制限および気道病変の関係について検討を行った。気流制限の程度は、上肺の気腫とは全く相関は見られなかったが、下肺の気腫とは強い相関が見られた。一方、上肺の気腫は同じく上肺の気道病変とは相関が見られなかったが、下肺の気腫と下肺の末梢気道病変に相関が見られ、下肺の気腫病変の進展と末梢気道病変の進行は、パラレルに進むことが考えられた。3)COPDにおける、気管支拡張薬(チオトロピウム)の気道への影響を3次元画像解析にて検討した。吸入による気流制限の改善の程度は、全体として気道内腔面積の改善の程度と相関し、その関係は3次、4次よりも5次、6次といったより末梢の気道内腔面積の改善と強い相関が見られた。
日本学術振興会, 萌芽研究, 北海道大学, 17659242 - 肺上皮障害・再生におけるbasigin/EMMPRINの役割とMMP誘導機序
科学研究費助成事業
2005年 - 2006年
別役 智子, 南須原 康行
線維化肺、肺がんにおけるbasigin/EMMPRINの役割を中心に検討した。当該施設にて肺がんと診断され手術を施行された患者、臨床的に間質性肺炎の診断がなされ、病理診断目的に胸腔鏡下肺生検を受けた患者を対象に。手術摘出された肺組織のホルマリン固定・パラフィン包埋薄切標本をmicrowave法で抗原賦活化後、抗ヒトEMMPRIN抗体(CHEMICON社,1000倍希釈)を1次抗体とし、Catalyzed Signal Amplification(CSA)法(DAKO社)を用いて免疫染色を施行した。basigin/EMMPRINによる誘導が報告されているMMP-1,-2,3-,-9についても連続切片で同様に免疫染色を施行した。また、以前、我々が作成したBAL液を用いた系を参考に、修正を加え測定方法を新たに確立し、同患者の血清やBAL液を用いて、basigin/EMMPRINの濃度をELISA法にて定量した。臨床的背景とその濃度との関係、病理組織上の免疫組織学的検討が可能である検体については、染色性との関係を明らかにした。以上の結果は、平成18年5月、米国胸部疾患学会にて報告し、Hum Patholに学術論文として掲載された。また、名古屋大学との共同研究において、basigin/EMMPRINのノックアウトマウスの供与を受け、気管支喘息モデルを作成している。ノックアウトマウスにおける気道炎症の程度、各種マトリックスメタロプロテアーゼの発現の有無を詳細に現在分析中である。本結果は、平成19年5月に米国胸部疾患学会にて発表予定である。一方、ラット肺気道上皮細胞を用いてbasigin/EMMPRIN遺伝子の誘導機序に関する検討を行った。基底膜構成成分のひとつであるlaminin-1がその誘導能を有することを明らかにした。一連の成果については、平成19年5月日本呼吸器学会におけるシンポジウム、ミニシンポジウム、また同年5月サンフランシスコで開かれる米国胸部疾患学会において多数の演題を発表予定である。
日本学術振興会, 基盤研究(C), 北海道大学, 17590772 - 慢性閉塞性肺疾患(COPD)の病因、病態、病型別自然歴に関する統合的研究
科学研究費助成事業
2005年 - 2006年
西村 正治, 檜澤 伸之, 別役 智子, 南須原 康行, 小野寺 裕也
本研究について、第二年度として、一定の成果をあげることができた。短期、長期喫煙暴露による肺障害マウスモデルを作成し、細気管支上皮における遺伝子発現のin vivoにおける経時的変化を定量することができた。特に、抗酸化能、解毒機構に関与する遺伝子群について、それらの網羅的解析による発現プロファイルと、DNA酸化、転写機構に関する知見を得た。我々は、喫煙の急性効果と慢性効果の気道上皮の反応性の違いを明らかにし、その機序を解明する研究に取り組んでいる。ヒトの手術肺を用いて、我々はCOPD病変に及ぼす加齢と喫煙の相補的影響を明らかにした。ヒトの肺検体から、laser capture microdissection (LCM)法を用いて、細気管支上皮を選択的に採取する方法を用いて、COPD患者において選択的に上昇・低下する遺伝子をスクリーニングした。細胞内過酸化水素に対して抗酸化機構に関与するカタラーゼ遺伝子に注目し、COPD患者の細気管支上皮、およびマクロファージにおいては、カタラーゼ遺伝子、蛋白の発現が低下していることを明らかにした。気管支鏡を用いて採取した末梢気道上皮細胞を用いる研究については、中枢気道上皮に発現するNADPH系oxidaseに注目した。喫煙刺激に対してDuox1hは低下し、逆にDuox2の発現が低下することを明らかにした。ex vivo環境下での機能保持、分化に及ぼす基底膜の立体構造の影響について研究中である。
また、北海道COPDコホート調査として307名の登録を行った。その中で、52名のCOPD患者を対象として、気道の評価を行った。対象とした気管支は、右肺尖枝のB1と右前肺底枝のB8で、それぞれ3次分岐から6次分岐までの気道内腔面積(Ai)と気道の外周で囲まれた気道の総断面積に対する気道壁の割合(WA%)を測定した。B1の一部を除いて、Ai、WA%とも、対標準1秒量と有意な相関を示した(WA%は逆相関)。さらに、Ai、WA%とも、末梢の気管支ほど相関係数が大きかった。一連の成果については、平成19年5月日本呼吸器学会におけるシンポジウム、ミニシンポジウム、また同年5月サンフランシスコで開かれる米国胸部疾患学会において多数の演題を発表予定である。
日本学術振興会, 基盤研究(B), 北海道大学, 17390239 - 炎症性呼吸器疾患の内因に関する研究
科学研究費助成事業
2002年 - 2004年
南須原 康行, 山口 悦郎, 檜澤 伸之, 別役 智子, 西村 正治, 南須原 康行
・本研究では、日本人において喘息発症に影響を与える遺伝因子を検討するために、包括的遺伝子発現解析から喘息病態との関連が大きいと考えられるいくつかの候補遺伝子に着目し、それらの遺伝子に存在する機能的な遺伝子変異の喘息発症における意義を検討した。検討した遺伝子は高親和性IgE受容体β鎖遺伝子(FCER1B、11q13)、プラスミノーゲンアクチベーターインヒビター遺伝子(PAI1、7q21)である。気管支喘息患者(約400名)、健常人(約400名)を対象とした。FCER1B遺伝子の-109C/T多型は喘息患者における血清総IgE値に遺伝的な影響を与えていた。FCER1B遺伝子とPAI1遺伝子いずれの多型も単独では気管支喘息との間に関連を認めなかったが、FCER1B遺伝子がTT型の場合にはPAI1遺伝子5G5G型が4G型を有する遺伝子型(4G4G or 4G5G)に比べ有意に喘息発症のリスクが小さかった。これらの一連の研究結果は、検討したそれぞれの分子の喘息病態における重要性を遺伝疫学的な手法で確認したことに加え、FCER1BとPAI1との交互作用の存在から、これらの分子を内包した共通のpasswayの存在と、それらの喘息病態における重要性を示したことに意義がある。
・肺気腫に関しては、laser capture microdissection (LCM)法とRT-PCR法を用いて末梢気道上皮細胞および肺内マクロファージにおける3種類のケモカインの発現を定量し、喫煙、COPDの病態との関連を検討した。対象は肺癌にて肺葉切除術を受けた喫煙歴のない患者10名、喫煙歴があるが閉塞性障害や気腫病変を有さない患者10名。喫煙歴があり閉塞性障害あるいはCT上気腫性病変を有する患者10名。非癌部肺組織の凍結標本からLCMにて末梢気道上皮細胞およびマクロファージを選択的に採取した。閉塞性障害あるいはCT上気腫性病変を有する患者では、末梢気道上皮細胞におけるIL-8,MIP-1α,MCP-1の発現が他の2群に比べ有意に高かった。肺内マクロファージにおいては喫煙歴や疾患によるケモカイン発現に差は認められなかった。末梢気道上皮における炎症性ケモカインの産生亢進が、肺気腫の病態に関与している可能性を示唆する。
日本学術振興会, 基盤研究(B), 北海道大学, 14370193 - 難治性気管支喘息の病因解明と抗マクロファージ遊走阻止因子抗体による治療の試み
科学研究費助成事業
2000年 - 2001年
西村 正治, 南須原 康行, 西平 順
・抗MIF抗体のアトピー型気管支喘息モデルに対する効果
昨年度は,BNラットを卵白アルブミンで感作したアトピー型気管支喘息モデルにおいて,1)吸入誘発後の肺胞洗浄液中のMIF濃度は,未処置群に比して有意に上昇していた,2)坑MIF抗体は卵白アルブミンによる特異的気道収縮を著明に抑制した.3)抗MIF抗体は肺胞洗浄液中の総細胞数はを有意に減少した,その分画の検討において,この減少は主に好酸球と好中球の減少によることが判明した,4)感作ラットでは卵白アルブミンに対する特異的IgGが上昇するが,抗MIF抗体はその上昇には影響を与えなかった,との結果を得た.これらの結果より,抗MIF抗体はアトピー型喘息モデルにおいて,特異的IgEの産生には影響を与えないが,特異的気道収縮および気道炎症を抑制することが示唆された.
今年度はさらに,
1)抗MIF抗体は,メサコリンに対する気道反応つまり非特異的気道収縮を抑制した.
2)吸入後の肺組織を用いて,定量的real time PCR法により,好酸球の走化因子であるエオタキシンの発現を検討した結果,抗MIF抗体はエオタキシンの発現を抑制した.
との結果を得た.現在,好中球の走化因子であるCINCについて肺胞洗浄液を用いて,抗MIF抗体の効果を検討中である.さらに,今後は肺組織標本を用いて,MIF発現部位,時間的推移などについて更なる検討を加える予定である.
日本学術振興会, 萌芽的研究, 北海道大学, 12877091 - 染色体5q31および11q13のIgE高反応性遺伝子の同定
科学研究費助成事業
1998年 - 2000年
山口 悦朗, 川上 義和, 南須原 康行, 伊藤 昭英, 山口 悦郎, 棟方 充
(1)我々は高親和性IgEFc受容体遺伝子(FceRIb)のプロモーター領域-109の位置に新たにCからTへの1塩基置換を発見した。この多型の分布は喘息と健常人の両群で特に有意な差は認められなかったが、喘息群において対立遺伝子Tをホモで有する喘息患者は、それ以外の遺伝子型(TCまたはCC)を有する喘息患者に比べて有意に血清総IgEが高い値を示した(p=0.0015)。また喘息の発症年齢を考慮して同様の検討を行うと、遺伝子多型の総IgE値への影響がより明瞭に認められた(p=0.0004)。
(2)我々はまたIL-4非翻訳部位に新たな多型(+33C/T)を発見した。T対立遺伝子頻度は喘息患者で0.675、健常者で0.671と両群に有意差を認めなかった。一方、遺伝子型(CT+TT)はCCに比して、検討対象者全員および喘息群において、性、年齢で補正しても有意に血清総IgE値が高かった。
(3)上記二つの1塩基多型(SNP)について、血清総IgE値におよぼす相互作用を検討した。その結果、喘息患者において両SNPが、血清総IgE値に及ぼす影響は、お互いの遺伝子型に依存する可能性が示唆された。
(4)アトピー性皮膚炎群での上記二つのSNP頻度は健常群と比べ有意差は認められず、これらの遺伝子多型はアトピー性皮膚炎の発症に寄与していないと考えられた。また両SNPはアトピー性皮膚炎での血清総IgE値と相関を示さなかった。したがって、アトピー性皮膚炎のIgE上昇の個体差には、高親和性IgE受容体β鎖遺伝子やIL-4遺伝子より、むしろ他の遺伝子多型あるいは環境因子の関与が大きいと考えられた。
(5)ムスカリンM1受容体遺伝子の翻訳開始部位からそれぞれ287bpと1353bp下流の位置にアミノ酸置換を伴わない1塩基多型を発見した。同多型に関する症例対照研究では、健常対照群に比べ喘息群では遺伝子型CCの頻度が有意に高く、M1受容体遺伝子はアトピーとは独立して喘息の発症に影響を与えている可能性がある。
日本学術振興会, 基盤研究(A), 北海道大学, 10307013 - 特発性間質性肺炎の進展予防
競争的資金
