Shu Hashimoto

Nihon University, Edo, Tōkyō, Japan

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Publications (88)184.64 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent epidemiological studies have documented that depression is associated with short sleep duration, which may be interpreted as a consequence of comorbid insomnia and/or that of curtailment of time in bed (TIB). However, none of the studies examined association between depression and TIB. Here, we study TIB, short sleep duration and depression in the Japanese general adult population. Cross-sectional surveys with a face-to-face interview were conducted in 2009 as part of the Nihon University Sleep and Mental Health Epidemiology Project (NUSMEP). Data from 2532 individuals were analyzed. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess the prevalence of depression with a cut-off point of 16. Sleep habits and sleep problems during the previous month, including bed time, getting up time, sleep duration, insomnia symptoms, and hypnotic medication use were evaluated. TIB was calculated from bed time and getting up time. The prevalence of depression identified with CES-D was 6.0% in total samples, 5.1% in men and 6.7% in women. Multiple logistic regression analysis revealed that both short sleep duration (<6 h) and short TIB (<6 h) were significantly associated with CES-D depression after adjusting for the confounding effects of sociodemographic variables, insomnia symptoms, and hypnotic medication use. We postulate that TIB, a modifiable sleep habit, may be an important target for improvement of sleep hygiene as a means of preventing depression.
    Sleep and Biological Rhythms 04/2015; 13(2):136-145. DOI:10.1111/sbr.12096 · 0.76 Impact Factor
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    ABSTRACT: To establish a system for the early diagnosis of respiratory diseases, we developed a method for analyzing RNA sequence data obtained by next-generation sequencer identify genes showing altered expression as biomarkers of respiratory tract infection. The respiratory tracts of mice were exposed to lipopolysaccharide to establish a model of respiratory disease. Twenty-five genes exhibited significantly altered RNA expression following exposure. We identified non-coding RNAs in five regions that could be candidate biomarkers of respiratory diseases.
    Journal of Computer Chemistry Japan 01/2015; 13(6):332-334. DOI:10.2477/jccj.2014-0054
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    ABSTRACT: The pathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear, but involves loss of alveolar surface area (emphysema) and airway inflammation (bronchitis) as the consequence of cigarette smoke (CS) exposure. Previously, we demonstrated that autophagy proteins promote lung epithelial cell death, airway dysfunction, and emphysema in response to CS; however, the underlying mechanisms have yet to be elucidated. Here, using cultured pulmonary epithelial cells and murine models, we demonstrated that CS causes mitochondrial dysfunction that is associated with a reduction of mitochondrial membrane potential. CS induced mitophagy, the autophagy-dependent elimination of mitochondria, through stabilization of the mitophagy regulator PINK1. CS caused cell death, which was reduced by administration of necrosis or necroptosis inhibitors. Genetic deficiency of PINK1 and the mitochondrial division/mitophagy inhibitor Mdivi-1 protected against CS-induced cell death and mitochondrial dysfunction in vitro and reduced the phosphorylation of MLKL, a substrate for RIP3 in the necroptosis pathway. Moreover, Pink1-/- mice were protected against mitochondrial dysfunction, airspace enlargement, and mucociliary clearance (MCC) disruption during CS exposure. Mdivi-1 treatment also ameliorated CS-induced MCC disruption in CS-exposed mice. In human COPD, lung epithelial cells displayed increased expression of PINK1 and RIP3. These findings implicate mitophagy-dependent necroptosis in lung emphysematous changes in response to CS exposure, suggesting that this pathway is a therapeutic target for COPD.
    Journal of Clinical Investigation 08/2014; 124(9). DOI:10.1172/JCI74985 · 13.77 Impact Factor
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    ABSTRACT: Background: Omalizumab, a monoclonal anti-IgE antibody, is currently indicated for the treatment of moderate-to-severe allergic asthma. To measure active IgE levels in sera from patients treated with omalizumab, the IgE subfraction in complex with omalizumab should be eliminated from total IgE, and free IgE levels can then be determined. With the aim of therapeutic monitoring for anti-IgE therapy, we developed a new ELISA for free IgE. Methods: We used recombinant human soluble FcεRIα as a capture antigen and a biotinylated polyclonal anti-IgE antibody for detection. Using the newly developed ELISA, we measured the serum free IgE levels weekly in four asthmatic patients after their first omalizumab injection. We also measured the serum free IgE levels in 54 patients treated with omalizumab for over 4 weeks. Results: This assay was technically robust, the mean recovery rate in serum was 93.16% ± 5.34%. For all patients, omalizumab treatment significantly reduced serum free IgE levels prior to the second omalizumab injection. To maintain the benefit of omalizumab, serum free IgE concentrations should be <50ng/ml. However, in 14 of 54 patients treated with omalizumab for over 4 weeks, serum free IgE concentrations measured by our ELISA were >50ng/ml. Conclusions: Our data suggest that the measurement of free IgE levels using our newly developed ELISA would be useful for monitoring serum free IgE levels during omalizumab therapy.
    Allergology International 05/2014; 63 Suppl 1(Supplement.1):37-47. DOI:10.2332/allergolint.13-OA-0643
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    ABSTRACT: Simulated patient/standardized patient (SP) training between the School of Medicine/Dentistry and the College of Art at Nihon University was retrospectively investigated to determine what the practical considerations should be in future. There were 63 participants (18 males; 45 females) from the Nihon University College of Art. There were a total of 162 students enrolled for practical medical interview training and the Objective Structured Clinical Examination (OSCE) of the Common Achievement Tests Organization at the School of Medicine. At the department of dentistry 12 participants (male 5: female 7) attended the practical medical interview training and the OSCE. A total of 23 students were enrolled for the diagnostic practical training and OSCE at the School of Dentistry. SP certification was issued to 10 participants (male 3: female 7) from the SP approval committee of the Nihon University School of Medicine in June 2013. Future issues highlighted in our study include the following: (1) remuneration for Nihon University College of Art graduates acting as SP trainers, (2) Nihon University general certification for SP training.
    Nichidai igaku zasshi 01/2014; 73(1):26-30. DOI:10.4264/numa.73.26
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    ABSTRACT: Next-generation sequencers (NGS) have made it possible to analyze entire genome sequence. NGS can be used for the identification of genes associated with a wide variety of diseases. We investigate RNAs encoded by intergenic regions to identify novel genes that are involved in respiratory diseases. The respiratory tracts of mice were exposed to lipopolysaccharide to establish a model of respiratory disease. RNA expression levels in the mouse exosome were analyzed by NGS to identify genes involved in the development of respiratory diseases. Several disease-related regions exhibited altered expression levels of intergenic RNAs.
    Journal of Computer Chemistry Japan 01/2014; 13(6):310-311. DOI:10.2477/jccj.2014-0058
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    ABSTRACT: A 57-year-old man presented to a local clinic with gradually progressive wheezing and was referred to our hospital. Chest computed tomography revealed atelectasis in the lingular segment of the left lung and a polypoid lesion in the left main bronchus. Endoscopic resection of the endobronchial tumour was performed with a high-frequency electrosurgical snare under general anaesthesia. Based on histological examination of the resected specimen, an endobronchial cartilaginous hamartoma was diagnosed. This approach may be an alternative for resection of selected benign endobronchial tumours. After 2 years of follow up, the patient remains free of disease. While endobronchial hamartoma is relatively rare, this diagnosis should be considered in a patient with respiratory complaints, such as gradual progression of wheezing and persistent cough.
    Nichidai igaku zasshi 01/2014; 73(6):254-258. DOI:10.4264/numa.73.254
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    ABSTRACT: Diffuse alveolar hemorrhage (DAH) has a varied etiology, including anticoagulation drugs. There is conflicting evidence whether low molecular weight heparin (LMWH) has a low risk of bleeding complications compared to unfractionated heparin. We report here a case of DAH in a 74-year-old woman who was administered enoxaparin, a LMWH, after bilateral total knee arthroplasty. Although congestive heart failure after blood transfusion and fluid infusion could in part be associated with the bleeding, LMWH may be a major cause of DAH since the patient quickly recovered after its cessation. DAH should be of concern when acute respiratory failure with ground-glass shadow develops in both lungs during anticoagulation therapy with LMWH.
    08/2013; 1(1). DOI:10.1002/rcr2.3
  • Yasuhiro Gon, Shu Hashimoto
    Nihon Naika Gakkai Zasshi 06/2013; 102(6):1370-7.
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    ABSTRACT: Advanced lung cancer is primarily treated with platinum combination chemotherapy, however, its prognosis remains poor. The aim of this study was to examine the correlation between the expression of thymidylate synthase (TS) in cancer tissues and the efficacy of chemotherapy in patients with advanced lung cancer in order to clarify the role of TS in the overall response. In total, 120 patients diagnosed with lung cancer between June 2004 and December 2010 at Nihon University Hospital, Tokyo, Japan, were included in this study. Cancer tissue specimens were obtained from the included patients by surgery or bronchofiberscopy prior to treatment. The expression of TS protein was evaluated using specimens immunostained with anti-TS antibody and H-scoring. TS protein expression tended to be higher in smokers compared with non-smokers. Overall survival (OS) (median value) was significantly prolonged in the low TS expression group compared with the high TS expression group. More favorable therapeutic effects were observed in the high TS expression group compared with the low TS expression group, when carboplatin + paclitaxel combined chemotherapy (CbPac therapy) was used. When the therapeutic effects were compared between CbPac therapy and carboplatin + pemetrexed combined chemotherapy (CbPem therapy) in the high TS expression group, prolongation of OS (median value) was observed with CbPac therapy. The present study suggests that TS protein expression is a critical factor in determining the efficacy of CbPac therapy in lung cancer. CbPac therapy is more effective when TS protein is highly expressed in lung cancer tissue.
    Molecular and Clinical Oncology 05/2013; 1(3):411-417. DOI:10.3892/mco.2013.94
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    ABSTRACT: In patients with inoperable advanced non-small cell lung carcinomas (NSCLCs), histological subtyping using small-mount biopsy specimens was often required to decide the indications for drug treatment. The aim of this study was to assess the utility of highly sensitive mRNA quantitation for the subtyping of advanced NSCLC using small formalin fixing and paraffin embedding (FFPE) biopsy samples. Cytokeratin (CK) 6, CK7, CK14, CK18, and thyroid transcription factor (TTF)-1 mRNA expression levels were measured using semi-nested real-time quantitative (snq) reverse-transcribed polymerase chain reaction (RT-PCR) in microdissected tumor cells collected from 52 lung biopsies. Our results using the present snqRT-PCR method showed an improvement in mRNA quantitation from small FFPE samples, and the mRNA expression level using snqRT-PCR was correlated with the immunohistochemical protein expression level. CK7, CK18, and TTF-1 mRNA were expressed at significantly higher levels (P<0.05) in adenocarcinoma (AD) than in squamous cell carcinoma (SQ), while CK6 and CK14 mRNA expression was significantly higher (P<0.05) in SQ than in AD. Each histology-specific CK, particularly CK18 in AD and CK6 in SQ, were shown to be correlated with a poor prognosis (P=0.02, 0.02, respectively). Our results demonstrated that a quantitative CK subtype mRNA analysis from lung biopsy samples can be useful for predicting the histology subtype and prognosis of advanced NSCLC.
    Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry 04/2013; 46(2):85-96. DOI:10.1267/ahc.12024 · 1.22 Impact Factor
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    ABSTRACT: Background: Cysteinyl leukotriene (LT) induces bronchoconstriction as well as airway inflammation and remodeling. Heparin-binding EGF-like growth factor (HB-EGF) is associated with remodeling in airway smooth muscle (ASM) cells in bronchial asthma. A disintegrin and metalloproteinase (ADAM) 12 is an enzyme implicated in the ectodomain shedding of membrane-anchored proHB-EGF and release of HB-EGF. Objective: To determine the role of LTD4 in HB-EGF and ADAM12 expression and the regulatory mechanism in human ASM cells, we analyzed a functioning signaling molecule in LTD4-induced HB-EGF and ADAM12 expression in human ASM cells by focusing on the role of mitogen-activated protein kinase (MAPK) cascades. Method: Human ASM cells were stimulated LTD4 in a time-dependent manner. We observed phosphorylation of MAPK by western blot analysis and the expression of HB-EGF and ADAM12 by quantitative PCR analysis of mRNA. Furthermore, we pretreated with specific inhibitors of MAPK and LTD4. Results: LTD4 induced an extracellular-signal regulated kinase (ERK), p38 MAPK and c-Jun-NH2-terminal kinase (JNK) phosphorylation in human ASM cells. LTD4 induced HB-EGF and ADAM12 mRNA expression. Furthermore, the regulation of LTD4-induced HB-EGF and ADAM12 mRNA expression is associated with ERK and p38 MAPK, not but JNK. Conclusion: we conclude that p38 MAPK and ERK are capable of regulating LTD4-induced HB-EGF and ADAM12 expression in human ASM cells. In bronchial asthma, the specific inhibitor of p38 MAPK and ERK may produce beneficial effects in controlling airway remodeling and inflammation.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 03/2013; 31(1):58-66. · 1.26 Impact Factor
  • Yasuhiro Gon, Shu Hashimoto
    Nihon Naika Gakkai Zasshi 01/2013; 102(6):1370-1377. DOI:10.2169/naika.102.1370
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    ABSTRACT: A 44-year-old woman was hospitalized with a 2-day history of cough, sputum, and fever. There was no history of atopic dermatitis or asthma. On admission, the chest X-ray revealed scattered infiltration in the left upper lung fields. Further examination revealed peripheral blood and bronchoalveolar lavage fluid eosinophilia. Transbronchial lung biopsy revealed eosinophilic pneumonia, with eosinophil infiltration of the alveoli, destroyed basal lumina, and connecting intraluminal fibrosis of the alveolar walls. Based on the findings, we made the diagnosis of chronic eosinophilic pneumonia. Treatment with prednisolone at 60 mg/day resulted in dramatic improvement of both the symptoms and the radiologic abnormalities.
    Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 12/2012; 30(4):321-5. · 1.26 Impact Factor
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    ABSTRACT: Pemetrexed inhibits three key folate enzymes: thymidylate synthetase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). The relationship between the clinical efficacy of pemetrexed and the expression of folate enzymes in lung cancer cells is unknown. The purpose of this study was to determine whether TYMS, DHFR, and GARFT expression affect the therapeutic efficacy of pemetrexed. Participants (n=50) were patients with advanced non-small cell lung cancer (NSCLC) treated with pemetrexed. Samples were obtained by tumor biopsy before treatment. We isolated cancer cells from formalin-fixed paraffin-embedded tissues using laser microdissection, and mRNA levels were analyzed using real-time reverse transcription polymerase chain reaction. Protein expression was evaluated using immunohistochemistry. We assessed the association between TYMS, DHFR, and GARFT expression and the therapeutic efficacy of pemetrexed. The median age was 66.8 years. Compared to healthy tissues, the relative TYMS mRNA expression ranged from 0.001 to 41.613 (mean 4.638±1.357), and was significantly lower in responders compared to non-responders (1.671±0.844 versus 5.978±1.895, p=0.0142). Progression-free survival was prolonged in patients with lower TYMS mRNA expression compared to those with higher TYMS mRNA expression, but the difference was not statistically significant (18.0 versus 13.3 weeks, p=0.3001). DHFR and GARFT mRNA expression did not correlate with the efficacy of pemetrexed. We specifically analyzed TYMS, DHFR, and GARFT mRNA expression levels in lung cancer cells from biopsy specimens using laser microdissection. TYMS mRNA expression affected the therapeutic efficacy of pemetrexed and could therefore constitute a useful predictive biomarker for NSCLC patients receiving pemetrexed.
    Anticancer research 10/2012; 32(10):4589-96. · 1.87 Impact Factor
  • Tomoko Kobayashi, Shu Hashimoto
    Nippon rinsho. Japanese journal of clinical medicine 08/2012; 70 Suppl 6:543-7.
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    ABSTRACT: Sleep problems in humans have been reported to impact seriously on daily function and to have a close association with well-being. To examine the effects of individual sleep problems on physical and mental health, we conducted a nationwide epidemiological survey and examined the associations between sleep problems and perceived health status. Cross-sectional surveys with a face-to-face interview were conducted in August and September, 2009, as part of the Nihon University Sleep and Mental Health Epidemiology Project (NUSMEP). Data from 2559 people aged 20 years or older were analyzed (response rate 54.0%). Participants completed a questionnaire on perceived physical and mental health statuses, and sleep problems including the presence or absence of insomnia symptoms (i.e., difficulty initiating sleep [DIS], difficulty maintaining sleep [DMS], and early morning awakening [EMA]), excessive daytime sleepiness (EDS), poor sleep quality (PSQ), short sleep duration (SSD), and long sleep duration (LSD). The prevalence of DIS, DMS, and EMA was 14.9%, 26.6%, and 11.7%, respectively, and 32.7% of the sample reported at least one of them. At the complaint level, the prevalence of EDS, PSQ, SSD, and LSD was 1.4%, 21.7%, 4.0%, and 3.2%, respectively. Multiple logistic regression analyses revealed that DMS, PSQ, SSD, and LSD were independently associated with poor perceived physical health status; DIS, EDS, and PSQ were independently associated with poor perceived mental health status. This study has demonstrated that sleep problems have individual significance with regard to perceived physical or mental health status.
    Sleep Medicine 05/2012; 13(7):831-7. DOI:10.1016/j.sleep.2012.03.011 · 3.10 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • 01/2012; 32(1):171-178. DOI:10.7878/jjsogd.32.171

Publication Stats

1k Citations
184.64 Total Impact Points


  • 1996–2014
    • Nihon University
      • • Department of Internal Medicine II
      • • School of Medicine
      Edo, Tōkyō, Japan
  • 1995
    • Kyoto University
      Kioto, Kyōto, Japan