Publications by authors named "Junko Suzuki"

147 Publications

Kawasaki Disease Shock Syndrome in Japan and Comparison With Multisystem Inflammatory Syndrome in Children in European countries.

Front Pediatr 2021 19;9:625456. Epub 2021 Mar 19.

Department of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Chiba, Japan.

Multisystem inflammatory syndrome in children (MIS-C) is a severe Kawasaki-like illness that was first linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in European countries in the spring of 2020 and has been suggested to have overlap with Kawasaki disease shock syndrome (KDSS). There are few reports of MIS-C from Asia. This observational study aimed to identify the clinical features in children presenting with KDSS in Japan over a 5-year period and to summarize similarities and differences between KDSS and MIS-C. We retrospectively collected data on patient characteristics, clinical signs and symptoms, treatment, and prognosis including coronary artery abnormalities (CAAs), which were compared with data of patients with KDSS worldwide and patients with MIS-C from a review. KDSS was identified in 6 (1.1%) of 552 patients with Kawasaki disease (KD) treated at a single institution in Japan between 2015 and 2020 (1 in 2020). In patients with KDSS in Japan or worldwide vs. patients with MIS-C, KDSS was more likely to have a diagnosis of complete KD (100, 70 vs. 6.3%), a higher incidence of CAAs (50, 65 vs. 11%), and a greater requirement for vasoactive agonists (67, 67 vs. 43%) because of circulatory shock (100, 50 vs. 26%). Both KDSS and MIS-C had good prognosis (mortality 0, 6.7 vs. 1.7%). Although KDSS in Japan and MIS-C show some overlap in clinical symptoms, they are unlikely to be the same disease entity. KDSS is more likely to have a cardiovascular phenotype with CAAs and requires treatment with cardiovascular agents.
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http://dx.doi.org/10.3389/fped.2021.625456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017212PMC
March 2021

Prognostic factors of chronic pulmonary aspergillosis: A retrospective cohort of 264 patients from Japan.

PLoS One 2021 1;16(4):e0249455. Epub 2021 Apr 1.

Center for Pulmonary Diseases, Department of Respiratory Medicine, National Hospital Organization Tokyo National Hospital, Tokyo, Japan.

Background: Chronic pulmonary aspergillosis (CPA) develops in various underlying pulmonary conditions. There is scarce data evaluating interstitial lung disease (ILD)/abnormalities (ILA) as such conditions, and it has not been explored much whether non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a prognostic factor for mortality in CPA patients. Few reports had investigated prognostic factors of CPA including underlying pulmonary conditions.

Objectives: To explore prognostic factors of CPA including pulmonary conditions.

Methods: We conducted a retrospective cohort study of 264 CPA patients from a center for pulmonary aspergillosis in Japan.

Results: Survival rates were 78.7%, 61.0%, and 47.4% at 1, 3, and 5 years, respectively. Of 264 patients, 53 (20.1%) and 87 (33.1%) were complicated with ILA and NTM-PD. Several independent prognostic factors were identified by multivariate Cox proportional analysis: ILA (HR 1.76, 95%CI 1.06-2.92, p = 0.029), age (1.05, 1.02-1.08, p<0.001), male sex (2.48, 1.34-4.59, p = 0.004), body mass index of <18.5 kg/m2 (1,87, 1.20-2.90, p = 0.005), presence of aspergilloma (1.59, 1.04-2.45, p = 0.033), and lower serum albumin (0.56, 0.38-0.83, p = 0.004). NTM-PD was not associated with higher mortality (0.85, 0.52-1.38, p = 0.51).

Conclusions: The poor prognosis of CPA and several prognostic factors were revealed. Early diagnosis and intervention is required with reference to such factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249455PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016288PMC
April 2021

[Clinical Application of Gemcitabine plus Cisplatin plus Bevacizumab Combination Chemotherapy for Ovarian Clear Cell Carcinoma].

Gan To Kagaku Ryoho 2021 Mar;48(3):375-378

Dept. of Obstetrics and Gynecology, Kansai Rosai Hospital.

Ovarian clear cell carcinoma(OCCC)shows a poor response to standard chemotherapy, and it is often difficult to choose a regimen for patients with recurrent OCCC. Several reports have suggested a synergistic effect between gemcitabine and cisplatin; another report suggested that gemcitabine, platinum, and bevacizumab are efficacious against recurrent ovarian cancer. We treated patients with OCCC using a combination chemotherapy regimen consisting of gemcitabine(1,000 mg/ m2)and cisplatin(40 mg/m2)on days 1 and 15, and bevacizumab(15 mg/kg)on day 1, with the cycle repeated every 4 weeks. Six patients received this therapy after informed consent, and 2 evaluable patients showed a partial response. Adverse events were mild, with Grade 3 anemia, leukopenia, and neutropenia occurring in 67%, 33%, and 17% of cases, respectively. No Grade 4 events were observed, including hematological or non-hematological toxicities. This suggests that a regimen of combined gemcitabine, platinum, and bevacizumab can be efficacious and feasible for the treatment of OCCC.
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March 2021

Prolonged onset and duration of action of rocuronium after accidental subcutaneous injection in a patient with chronic renal failure-a case report.

JA Clin Rep 2021 Feb 27;7(1):18. Epub 2021 Feb 27.

Department of Anesthesiology, Nihon University, School of Medicine, 30-1, Oyaguchi, Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.

Background: Drugs administered subcutaneously have delayed onset and prolonged duration of action versus those given intravenously. Since the duration of action of rocuronium is prolonged in patients with renal dysfunction, subcutaneous administration of rocuronium to such patients might significantly prolong its effect.

Case Presentation: A 51-year-old female with chronic renal failure was accidentally administered 1.04 mg/kg rocuronium subcutaneously. Marked prolongation of onset and duration of action of rocuronium were detected on acceleromyography. Slow development of the neuromuscular block was still observed at 100 min after injection. Administration of 4.5 mg/kg sugammadex at 140 min after rocuronium injection facilitated recovery from a train-of-four (TOF) count of 2 to a TOF ratio of 100% within 5 min. No symptoms of postoperative recurarization and upper airway obstruction were observed.

Conclusion: Neuromuscular monitoring is necessary to evaluate the progress and depth of neuromuscular block, particularly when rocuronium is inadvertently administered subcutaneously.
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http://dx.doi.org/10.1186/s40981-021-00421-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914319PMC
February 2021

Mitochondrial sorting and assembly machinery operates by β-barrel switching.

Nature 2021 02 6;590(7844):163-169. Epub 2021 Jan 6.

Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-motoyama, Kyoto, Japan.

The mitochondrial outer membrane contains so-called β-barrel proteins, which allow communication between the cytosol and the mitochondrial interior. Insertion of β-barrel proteins into the outer membrane is mediated by the multisubunit mitochondrial sorting and assembly machinery (SAM, also known as TOB). Here we use cryo-electron microscopy to determine the structures of two different forms of the yeast SAM complex at a resolution of 2.8-3.2 Å. The dimeric complex contains two copies of the β-barrel channel protein Sam50-Sam50a and Sam50b-with partially open lateral gates. The peripheral membrane proteins Sam35 and Sam37 cap the Sam50 channels from the cytosolic side, and are crucial for the structural and functional integrity of the dimeric complex. In the second complex, Sam50b is replaced by the β-barrel protein Mdm10. In cooperation with Sam50a, Sam37 recruits and traps Mdm10 by penetrating the interior of its laterally closed β-barrel from the cytosolic side. The substrate-loaded SAM complex contains one each of Sam50, Sam35 and Sam37, but neither Mdm10 nor a second Sam50, suggesting that Mdm10 and Sam50b function as placeholders for a β-barrel substrate released from Sam50a. Our proposed mechanism for dynamic switching of β-barrel subunits and substrate explains how entire precursor proteins can fold in association with the mitochondrial machinery for β-barrel assembly.
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http://dx.doi.org/10.1038/s41586-020-03113-7DOI Listing
February 2021

IL-1RA in the supernatant of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus is useful for discriminating active tuberculosis from latent infection.

J Infect Chemother 2021 Apr 11;27(4):617-624. Epub 2020 Dec 11.

Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, Tokyo, Japan.

Introduction: The new-generation QuantiFERON (QFT)-TB Gold Plus (QFT-Plus) is expected to be useful because it includes a new peptide that is supposed to induce a CD8 T cell response. There is a need for a new marker with sensitivity higher than that of the conventional IFN-γ release assays owing to false-negative results in the latter. This study aimed to compare cytokines in QFT-plus and QuantiFERON-Gold In-Tube (QFT-GIT) supernatants to discriminate between active tuberculosis and latent tuberculosis infection (LTBI).

Methods: A cross-sectional study was conducted at Tokyo National Hospital, wherein 21 LTBI patients and age and sex-matched active TB patients were randomly selected. The levels of various cytokines were measured and compared using the MAGPIX System, and receiver operating characteristic (ROC) curves were generated.

Results: IL-1RA, IFN-γ, CXCL10/IP-10, and CCL4/MIP-1β levels were higher in the active TB group than in the LTBI group in QFT-GIT antigen (GIT Ag) tubes. In QFT-plus tubes, IL-1RA was higher in TB1 and TB2 tubes, while CCL2/MCP-1 was higher only in TB2 tubes. In Nil tubes, CCL5/RANTES, TNF-α, PDGF-BB, and IL-2 levels were significantly higher in the active TB group. IL-1RA in GIT Ag tubes showed the highest area under the curve of 0.8367. The sensitivity and specificity of IL-1RA were 66.7% (95% confidence interval [CI]: 43.0-85.4) and 90.5% (95% CI: 69.6-98.8), respectively, which were the highest among the cytokines.

Conclusions: IL-1RA level in the QFT-GIT supernatant can be a good marker for discriminating active TB from LTBI.
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http://dx.doi.org/10.1016/j.jiac.2020.11.023DOI Listing
April 2021

[Design of Teaching Materials for Pharmaceutical Law Education].

Yakugaku Zasshi 2020 ;140(11):1389-1396

School of Pharmacy, Kitasato University.

A questionnaire survey was conducted with pharmacy students to obtain useful information for preparing teaching materials in the field of pharmaceutical laws. We conducted a customer satisfaction (CS) analysis by asking pharmacy students to evaluate whether the teaching materials used in the Pharmaceutical Laws class at Kitasato University were effective in promoting learning and understanding. In addition, we asked them about their impressions of attending the Pharmaceutical Laws class and analyzed their freely described answers. The CS analysis suggested teaching materials that included case studies of pharmaceutical law judgments and violations may have been useful for learning this subject. Furthermore, the text analysis showed many of the participants believed the contents of the teaching materials were difficult. Therefore, it is necessary to redesign the contents so that learning can progress step by step from the basic items. In addition, since some students recognized that the subject could be memorized, it is possible they can convey only what they remember and not what they had learned or what knowledge they could use in other contexts and situations. Therefore, it is necessary to clearly present the learning objectives for each item in lesson's teaching materials.
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http://dx.doi.org/10.1248/yakushi.19-00212DOI Listing
November 2020

Migrated coil expectorated 12 years after embolization of pulmonary arteriovenous malformation, due probably to abscess formation around the coil.

Respir Med Case Rep 2020 3;31:101245. Epub 2020 Oct 3.

Center for Pulmonary Disease, National Hospital Organization Tokyo Hospital, 3-1-1 Takeoka, Kiyose, Tokyo, 204-8585, Japan.

Pulmonary arteriovenous malformations (PAVMs) are rare vascular structures providing direct capillary-free communications between pulmonary arteries and veins. Embolotherapy is indicated as a front-line therapy. We report an unusual long-term complication of coil embolization for a 44-year-old woman with hereditary hemorrhagic telangiectasia (HHT) who had repeatedly undergone the procedures for her PAVMs. She expectorated the coil which had been placed 12 years earlier and migrated to the bronchus according to the chest radiogram and bronchoscopy. Histology of the resected lung segment suggested the cavity communicating with the bronchus was the consequence of abscess formation around the coils. Even after technically successful embolization to PAVMs, long term follow-up should be necessary paying attention to the symptoms and imaging to avoid massive hemoptysis and subsequent emergency surgery.
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http://dx.doi.org/10.1016/j.rmcr.2020.101245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554207PMC
October 2020

CD64 expression on neutrophils reflects the activity of nontuberculous mycobacterial lung disease.

Respir Investig 2021 Jan 10;59(1):155-156. Epub 2020 Oct 10.

National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo, 204-8585, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.resinv.2020.08.008DOI Listing
January 2021

New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation.

J Allergy Clin Immunol 2021 Apr 10;147(4):1261-1268.e5. Epub 2020 Sep 10.

Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.

Background: There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) are currently available.

Objective: This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods.

Methods: Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n = 37), chronic eosinophilic pneumonia (n = 64), Aspergillus-sensitized severe asthma (n = 26), or chronic pulmonary aspergillosis (n = 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey.

Results: The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively.

Conclusions: The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.
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http://dx.doi.org/10.1016/j.jaci.2020.08.029DOI Listing
April 2021

High-dose rocuronium-induced paralysis of the adductor pollicis muscle facilitates detection of the timing for tracheal intubation in elderly patients: a randomized double-blind study.

J Anesth 2020 12 23;34(6):876-880. Epub 2020 Jul 23.

Department of Anesthesiology, Nihon University School of Medicine, 30-1, Oyaguchi-Kamicho, Itabashi-Ku, Tokyo, 173-8610, Japan.

Purpose: To prevent coughing related to tracheal intubation and the resultant exposure of intubating staff to the patients' expiratory aerosols, the timing of tracheal intubation needs to be precisely predicted. The aim of this study was to evaluate the hypothesis that the timing for safe tracheal intubation in elderly patients can be determined by acceleromyographically monitoring paralysis of the adductor pollicis muscle when high-dose rocuronium, given to block the respiratory muscles, is administered.

Methods: Forty elderly (65-92 years) patients were enrolled in this study and randomly assigned to two groups, to receive rocuronium 0.6 mg/kg or 1 mg/kg. After induction of anesthesia and observing acceleromyographic train-of-four (TOF) responses of the adductor pollicis muscle to ulnar nerve stimulation, the patients randomly received either dose of rocuronium. The onset times from rocuronium administration to TOF counts of 0 were measured. Soon thereafter, a single anesthesiologist who was blinded to the allocated dose of rocuronium performed laryngoscopy and tracheal intubation, and assessed intubating conditions. Data were analyzed by the unpaired t-test and Chi-squared test.

Results: The averaged [SD] onset time of neuromuscular blockade was significantly shorter with 1 mg/kg than 0.6 mg/kg rocuronium (104.3 [30.1] s vs. 186.8 [37.5] s, p < 0.001). Patients who received 0.6 mg/kg rocuronium variously showed either poor (n = 9) or good (n = 11) intubating conditions. However, all patients who received 1 mg/kg rocuronium had excellent intubating conditions.

Conclusions: If 1 mg/kg rocuronium is administered, a TOF count of 0 acceleromyographically observed at the adductor pollicis muscle can reveal the adequate timing for tracheal intubation.
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http://dx.doi.org/10.1007/s00540-020-02831-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377532PMC
December 2020

Comparison of QuantiFERON-TB Gold Plus, QuantiFERON-TB Gold In-Tube, and T-SPOT.TB among patients with tuberculosis.

J Infect Chemother 2020 Nov 19;26(11):1205-1212. Epub 2020 Jul 19.

Asthma Allergy and Rheumatology Center, National Hospital Organization Tokyo National Hospital. Electronic address:

Objectives: This study evaluated the efficacy of the following interferon (IFN)-γ release assays (IGRAs): QuantiFERON-TB Gold Plus (QFT-Plus), QFT-Gold In-Tube (QFT-GIT), and T-SPOT. TB (T-SPOT) with the quantitative values of IFN-γ response.

Methods: Blood samples were collected from patients with active tuberculosis (TB), latent TB infection (LTBI), individuals with previous TB infection, and healthy volunteers enrolled between May 2017 and June 2018.

Results: IGRAs results were analyzed in 175 subjects (76 had active TB, 14 had LTBI, 35 had prior TB infection, and 50 were healthy). QFT-Plus and QFT-GIT revealed equal efficacy for IFN-γ values, and the IFN-γ response in QFTs tended to increase with the spot counts in T-SPOT, with similar high sensitivities (approximately 90%) in the active TB group. The test concordance of two of three IGRAs was optimal among all subjects (κ coefficients: 0.82-0.96). Additionally, the median quantitative values of IFN-γ with QFT-Plus and QFT-GIT were higher in the active TB group than in the LTBI and previous TB groups.

Conclusion: Three IGRAs showed equivalent efficacy with high sensitivities and higher IFN-γ response in active TB group than that in non-active TB group.
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http://dx.doi.org/10.1016/j.jiac.2020.06.019DOI Listing
November 2020

High detection rate of azole-resistant Aspergillus fumigatus after treatment with azole antifungal drugs among patients with chronic pulmonary aspergillosis in a single hospital setting with low azole resistance.

Med Mycol 2021 Apr;59(4):327-334

Division of Clinical Research, Medical Mycology Research Centre, Chiba University, Chiba, Japan.

The prevalence of azole-resistant Aspergillus fumigatus (ARAF) among chronic pulmonary aspergillosis (CPA) patients treated with azoles in Japan is unknown. The aim of this study was to determine the detection rate of ARAF in isolates from CPA patients who were treated with azoles for varying durations. The potential mechanism of acquiring resistance was examined by sequencing cyp51A and hmg1, two genes associated with ARAF. A. fumigatus isolates (n = 120) were collected from CPA patients (n = 104) between February 2012 and February 2019, at National Hospital Organization Tokyo National Hospital. The isolates were tested for susceptibility to the azole drugs itraconazole (ITCZ) and voriconazole (VRCZ). The detection rate of ARAF among all isolates was 8.3% (n = 10). Of the 10 resistant isolates, eight were ITCZ-resistant and five were VRCZ-resistant. Among 47 isolates obtained from 36 CPA patients who were treated with ITCZ (for an average of 256 days) and/or VRCZ (for an average of 29 days), the resistance rates were 17.0% and 10.6%, respectively. In addition, 46.2% of 13 isolates obtained from CPA patients with ongoing azole treatment at the time of antifungal therapy failure were resistant to azoles. Among the 10 ARAF isolates, a point mutation was detected in cyp51A in seven isolates and in hmg1 in two isolates. ARAF was detected at a high rate in CPA patients, particularly in those with ongoing long-term azole treatment, at the time of azole antifungal therapy failure.
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http://dx.doi.org/10.1093/mmy/myaa052DOI Listing
April 2021

Effects of Evening-Only Low-Carbohydrate Meal on Healthy Volunteers.

J Nutr Sci Vitaminol (Tokyo) 2020 ;66(3):229-236

Graduate School of Nursing and Nutrition, Tenshi College.

We performed a pre/post-interventional study with participants as self-controls to evaluate the effects of consuming an evening-only low-carbohydrate meal (LCM) at 1800 h on biochemical measures of glucose and lipid metabolism. Study participants comprised 14 healthy men (age range, 20-29 y) who, consumed standard test meals (STMs) or LCM at 1800 h. Blood samples were collected at fasting, and at 60-, 120-, and 240 min after the start of the meals. The 60-min postprandial levels and the area under the curve (AUC) 0-120 min for plasma glucose were significantly lower after the LCM than after the STMs. The 60- and 120-min postprandial levels and the AUC for plasma insulin were significantly lower after the LCM than after the STMs (p<0.01). Postprandial triglyceride (TG) levels at 120- and 240 min and the AUC were significantly higher after the LCM than after the STMs (p<0.05, p<0.01, and p<0.05, respectively). The interleukin-6 levels were significantly higher 240 min after the STMs than before the meals (p<0.05), but not after the LCM. In these healthy volunteers, consuming an LCM at 1800 h suppressed postprandial hyperglycemia and insulin secretion; however, postprandial TG increased. Consuming an LCM at 1800 h was beneficial as it inhibited elevation of blood glucose; however, it may also increase the risk of arteriosclerosis through increasing TG levels.
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http://dx.doi.org/10.3177/jnsv.66.229DOI Listing
April 2021

[Analysis of Learner Characteristics Affecting Learning Outcomes in the Field of Pharmaceutical Law].

Yakugaku Zasshi 2020 ;140(7):949-953

Kitasato University School of Pharmacy.

To contribute to research on the effective practice of pharmaceutical law, we analyzed the learner characteristics that influence learning outcomes in this field at Kitasato University School of Pharmacy. Specifically, we conducted a forced entry multiple regression analysis. The explanatory variables were the learner's gender, course, university entrance examination format, course year progression, completion of related subjects, and submission of class quizzes, while examination performance in pharmaceutical law was the response variable. The learners' course of study and submission of class quizzes were found to have a significant influence on the examination results. The examination performance of students enrolled in a four-year course was 14.4% lower than students enrolled in a six-year course, while students with records of not submitting the class quizzes scored 8.4% lower than those who submitted all the quizzes. It is probable that there was a fundamental difference between the academic ability of the students enrolled in the two courses that affected the examination results. The fact that the submission of class quizzes had an effect on the examination results may be useful in developing a learning guide for the students. To further enhance the evidence of the analysis of learner characteristics in this field, obtaining the results of joint research with other universities is necessary.
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http://dx.doi.org/10.1248/yakushi.19-00209DOI Listing
September 2020

Evaluation of cytokine levels using QuantiFERON-TB Gold Plus in patients with active tuberculosis.

J Infect 2020 05 22;80(5):547-553. Epub 2020 Feb 22.

Clinical Research Center, National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose-City, Tokyo 204-8585, Japan.

Objectives: A recently released new QuantiFERON (QFT) product, QFT TB Gold plus (QFT-plus), is optimized for both CD4 and CD8 responses and reported to have higher sensitivity compared to the former QFT-3 G. Previously, using supernatants of QFT-3 G, we and others have demonstrated that cytokines other than IFN-γ may be useful in diagnosing tuberculosis. The present study aimed to identify cytokines that are useful for accurately diagnosing active tuberculosis by using QFT-plus and compared the data to those with QFT-3 G.

Methods: Eighty-three active tuberculosis patients and 70 healthy control subjects who were examined by QFT at Tokyo National Hospital from June 2017 to July 2018 were enrolled. QFT-3 G and QFT-plus were performed according to the manufacturer's instructions. At the same time, blood cell culture supernatants were collected and assayed for their cytokine levels using R&D Systems Luminex Assay and MAGPIX System. The levels of cytokines were compared between different antigen-containing tubes (3 G Ag, TB1 and TB2 tubes), as well as between the patients and the control subjects. ROC curves were drawn, and the AUCs were calculated.

Results: Five cytokines, i.e., IL-2, IL-6, IL-8, IP-10 and MIP-1β, produced by human blood cells in three independent tubes containing different tuberculosis antigens were higher in the 3 G Ag tube compared to both the TB1 and TB2 tubes. Further, when the TB1 and TB2 tubes were compared, TB2 showed greater production of only PDGF-BB, and less production of IL-6 and TNF-α. For diagnosing active tuberculosis, the levels of IP-10 were superior to the level of IFN-γ based on showing a larger AUC for ROC curves in our present study setting. Finally, the levels of IFN-γ, IL-1RA, IL-2, IP-10, MCP-1 and MIP-1β were distinctly different between the active tuberculosis patients and healthy controls.

Conclusions: In summary, there was no cytokine that was higher in the tubes of QFT-plus compared to the tube of QFT-3 G, suggesting inferiority of QFT-plus antigens to 3 G Ag in terms of elicitation of cytokine production. Our results also suggest the usefulness of cytokines that showed a significant difference between the active tuberculosis patients and the healthy controls-namely, IFN-γ, IL-1RA, IL-2, IP-10, MCP-1 and MIP-1β-for diagnosing tuberculosis, but the roles of these cytokines in the pathogenesis of tuberculosis need to be elucidated (UMIN000035253).
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http://dx.doi.org/10.1016/j.jinf.2020.02.007DOI Listing
May 2020

Structure of the mitochondrial import gate reveals distinct preprotein paths.

Nature 2019 11 10;575(7782):395-401. Epub 2019 Oct 10.

Faculty of Life Sciences, Kyoto Sangyo University, Kyoto, Japan.

The translocase of the outer mitochondrial membrane (TOM) is the main entry gate for proteins. Here we use cryo-electron microscopy to report the structure of the yeast TOM core complex at 3.8-Å resolution. The structure reveals the high-resolution architecture of the translocator consisting of two Tom40 β-barrel channels and α-helical transmembrane subunits, providing insight into critical features that are conserved in all eukaryotes. Each Tom40 β-barrel is surrounded by small TOM subunits, and tethered by two Tom22 subunits and one phospholipid. The N-terminal extension of Tom40 forms a helix inside the channel; mutational analysis reveals its dual role in early and late steps in the biogenesis of intermembrane-space proteins in cooperation with Tom5. Each Tom40 channel possesses two precursor exit sites. Tom22, Tom40 and Tom7 guide presequence-containing preproteins to the exit in the middle of the dimer, whereas Tom5 and the Tom40 N extension guide preproteins lacking a presequence to the exit at the periphery of the dimer.
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http://dx.doi.org/10.1038/s41586-019-1680-7DOI Listing
November 2019

The study of metabolic improvement by nutritional intervention controlling endogenous GIP (Mini Egg study): a randomized, cross-over study.

Nutr J 2019 09 2;18(1):52. Epub 2019 Sep 2.

Biological Science Research, Kao Corporation, 2606 Akabane, Ichikai-machi, Haga-gun, Tochigi, 321-3497, Japan.

Background: Given the major role of glucose-dependent insulinotropic polypeptide (GIP) in the regulation of adiposity, this study examined the effects induced by a diet based on the Japanese tradition (SMART WASHOKU) on the visceral fat area (VFA) and GIP secretions.

Methods: Overweight/obese men (n = 21; mean age, 41.0 ± 9.0 years; mean BMI, 25.2 ± 2.0 kg/m) without diabetes were placed on either a SMART WASHOKU or control meal for 2 weeks, in a randomized, cross-over setup with a four-week washout period.

Results: For the meal tolerance test, blood samples were collected at 0, 30, 60, 120, 180, and 240 min post-meal, followed by measuring blood glucose, insulin, GIP, and glucagon-like peptide-1 (GLP-1) levels. Relative to a control meal, SMART WASHOKU meal yielded significantly lower plasma postprandial GIP concentrations (AUC: 700.0 ± 208.0 vs. 1117.0 ± 351.4 pmol/L・4 h, P < 0.05); however, between meals, there was no significant difference in the levels of GLP-1, peptide YY, and ghrelin. Compared to the control meal, SMART WASHOKU intervention significantly reduced VFA and the levels of LDL-cholesterol, triglyceride, and HbA1c after the chronic meal intervention.

Conclusions: In conclusion, a SMART WASHOKU meal may decrease VFA and improve metabolic parameters in overweight/obese men, possibly via suppressing GIP secretion.
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http://dx.doi.org/10.1186/s12937-019-0472-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720405PMC
September 2019

Species identification, antifungal susceptibility, and clinical feature association of Aspergillus section Nigri isolates from the lower respiratory tract.

Med Mycol 2020 Apr;58(3):310-314

Division of Clinical Research, Medical Mycology Research Center, Chiba University, Chiba, Japan.

Species of Aspergillus section Nigri are generally identified by molecular genetics approaches, whereas in clinical practice, they are classified as A. niger by their morphological characteristics. This study aimed to investigate whether the species of Aspergillus section Nigri isolated from the respiratory tract vary depending on clinical diagnosis. Forty-four Aspergillus section Nigri isolates isolated from the lower respiratory tracts of 43 patients were collected from February 2012 to January 2017 at the National Hospital Organization (NHO) Tokyo National Hospital. Species identification was carried out based on β-tubulin gene analysis. Drug susceptibility tests were performed according to the Clinical and Laboratory Standards Institute (CLSI) M38 3rd edition, and the clinical characteristics were retrospectively reviewed. A. welwitschiae was isolated most frequently, followed by A. tubingensis. More than half of the A. tubingensis isolates exhibited low susceptibility to azoles in contrast to only one A. welwitschiae isolate. Approximately three quarters of the patients from whom A. welwitschiae was isolated were diagnosed with colonization, whereas more than half the patients from whom A. tubingensis was isolated were diagnosed with chronic pulmonary aspergillosis (CPA). More attention needs to be given to the drug choice for patients with CPA with Aspergillus section Nigri infection because A. tubingensis, which was found to be frequently azole-resistant, was the most prevalent in these patients.
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http://dx.doi.org/10.1093/mmy/myz072DOI Listing
April 2020

A case of Mycobacterium tuberculosis laboratory cross-contamination.

J Infect Chemother 2019 Aug 11;25(8):610-614. Epub 2019 Apr 11.

Department of Mycobacterium Reference and Research, The Research Institute of Tuberculosis, Japan; Department of Basic Mycobacteriology, Graduate School of Biomedical Science, Nagasaki University, Japan. Electronic address:

Setting: A laboratory cross-contamination event was suspected because Mycobacterium tuberculosis was unexpectedly detected at a high incidence in the cultures of several clinical specimens at the National Hospital Organization, Tokyo National Hospital, Japan.

Objective: To describe a case of Mycobacterium tuberculosis laboratory cross-contamination.

Design: We reviewed the medical records of 20 patients whose clinical specimens were suspected to have been contaminated by Mycobacterium tuberculosis. Variable number of tandem repeat analysis with 15 loci, the Japan Anti-Tuberculosis Association-12, and three additional hyper-variable loci, was performed to identify the cross-contamination event.

Results: The clinical, laboratory, and variable number of tandem repeat data revealed that the cross-contamination had possibly originated from one strongly positive specimen, resulting in false-positive results in 11 other specimens, including a case treated with anti-tuberculosis drugs.

Conclusion: Clinical and laboratory data must be re-evaluated when cross-contamination is suspected and variable number of tandem repeat analysis should be used to confirm cross-contamination. Furthermore, original isolates should be stored appropriately, without sub-culturing and genotyping should be performed at the earliest possible for better utilization of variable number of tandem repeat for the identification of cross-contamination.
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http://dx.doi.org/10.1016/j.jiac.2019.03.012DOI Listing
August 2019

Exacerbation of chronic pulmonary aspergillosis was associated with a high rebleeding rate after bronchial artery embolization.

Respir Investig 2019 May 25;57(3):260-267. Epub 2019 Jan 25.

Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-8585, Japan. Electronic address:

Background: Hemoptysis is a common symptom associated with chronic pulmonary aspergillosis (CPA). While surgery is the primary choice to manage hemoptysis, it is often avoided because patients with CPA are more likely to have complications such as respiratory insufficiency and low pulmonary function. Bronchial artery embolization (BAE) may be considered one of the treatments of massive and persistent hemoptysis for such patients.

Methods: We retrospectively reviewed medical records of 41 patients, admitted to National Hospital Organization Tokyo National Hospital, Tokyo, Japan with hemoptysis arising from CPA between January 2011 to December 2016, who were considered inoperable and had undergone BAE.

Results: Out of the 41 cases analyzed in this study, 21 (51.2%) developed rebleeding after BAE within the mean follow-up duration of 24 months. The non-rebleeding rate of patients after BAE was 92.7% within a month and 65.8% within a year. Patients who developed rebleeding had significantly more non-bronchial systemic arteries responsible for the bleeding compared with patients who did not develop rebleeding (mean of 2.55 vs. 4.86, respectively, P = 0.011). Patients with stable or improved radiological findings demonstrated significantly lower rebleeding rates than those with radiological deterioration (P < 0.001). The non-rebleeding patients had significantly better survival than those with rebleeding (79.7% vs. 39.9% over 5 years, P = 0.046).

Conclusions: Bronchial artery embolization was effective in controlling hemoptysis in patients with CPA, especially those who could not undergo surgical resection. However, disease control of CPA was important to prevent rebleeding over the long term and to improve survival after BAE.
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http://dx.doi.org/10.1016/j.resinv.2018.12.009DOI Listing
May 2019

Species-specific detection of medically important aspergilli by a loop-mediated isothermal amplification method in chronic pulmonary aspergillosis.

Med Mycol 2019 Aug;57(6):703-709

Graduate School of Medicine, Teikyo University, Tokyo, Japan.

Chronic pulmonary aspergillosis (CPA) is a common subtype of pulmonary aspergillosis and a life-threatening disease. However, its diagnosis remains difficult due to the lack of specific clinical features and radiologic findings, as well as the difficulty of isolating Aspergillus spp. We developed a novel species-specific detection method of medically important aspergilli using a loop-mediated isothermal amplification (LAMP) for CPA. Specific LAMP primer sets for Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus terreus, and Aspergillus nidulans were designed. The use of the LAMP assay was validated using respiratory specimens (CPA cases, n = 21; nonaspergillosis cases, n = 23). A total of 15 cases were positive in the CPA group (A. fumigatus, n = 5; A. flavus, n = 1; A. niger, n = 1; A. terreus, n = 7; A. nidulans, n = 1), but only three in the non-CPA group (A. niger, n = 2; A. terreus n = 1). The sensitivity and specificity of the diagnosis of CPA by the LAMP system were 71.4% and 87.0%, respectively. In conclusion, we developed a species-specific detection approach for five medically important aspergilli using the LAMP method. The system showed high sensitivity and specificity for diagnosis of CPA.
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http://dx.doi.org/10.1093/mmy/myy128DOI Listing
August 2019

Induction of Hepatic Metabolic Functions by a Novel Variant of Hepatocyte Nuclear Factor 4γ.

Mol Cell Biol 2018 12 28;38(24). Epub 2018 Nov 28.

Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu, Gunma, Japan

Hepatocyte nuclear factor 4α (HNF4α) is a critical factor for hepatocyte differentiation. HNF4α expression is decreased in hepatocellular carcinoma (HCC), which suggests a role in repression of hepatocyte dedifferentiation. In the present study, hepatic expression of HNF4γ was increased in liver-specific -null mice. The HNF4γ whose expression was increased contained two variants, a known short variant, designated HNF4γ1, and a novel long variant, designated HNF4γ2. mRNA was highly expressed in small intestine, and the transactivation potential of HNF4γ2 was the strongest among these variants, but the potential of HNF4γ1 was the lowest. Cotransfection experiments revealed that HNF4γ1 repressed HNF4α- and HNF4γ2-dependent transactivation, while HNF4γ2 promoted HNF4α-dependent transactivation. HNF4γ1 and HNF4γ2 were able to bind to the HNF4α binding sites with an affinity similar to that of HNF4α. Furthermore, HNF4γ2, but not HNF4γ1, robustly induced the expression of typical HNF4α target genes to a greater degree than HNF4α. Additionally, HNF4γ2 suppressed proliferation of hepatoma cells as well as HNF4α and HNF4γ1 did, and HNF4γ2 induced critical hepatic functions, such as glucose and urea production, and cytochrome P450 1A2 activity more strongly than HNF4α and HNF4γ1 did. These results indicate that HNF4γ2 has potential for redifferentiation of HCC and thus may be explored as a target for HCC therapy.
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http://dx.doi.org/10.1128/MCB.00213-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275183PMC
December 2018

[Paradigm Shift in the Quality of Regional Medical Care: Cooperative Treatment of Onychomycosis].

Yakugaku Zasshi 2018 ;138(5):621-628

Japan Home Care institute of Education and Research, Inc.

 In a superaging society, the medical paradigm should include both less coverage of medical-care work flow by human resources and high-quality care for patients. Strategies such as establishing medical-care teams and community medicine systems mainly for home medical care should be implemented. However, a well-organized system for home-based medical treatment of elderly patients is not yet in place, as evidenced by the lack of care, problems with long-term polypharmacy resulting from visits to multiple healthcare providers, and declines in their physical strength. It is assumed that care might not be provided in association with treatment because planning based on the paradigm of "home medical care" has not been fully established. Therefore, in this study, we aimed to determine the "paradigm shift in home medical care" based on the treatment of onychomycosis. We also hoped to identify the types of medical support required to improve the general well-being of individuals and what needs to be done to ensure a high quality of life for patients. All those (including patients themselves) involved in patient care should together formulate a protocol for medical treatment and cooperate based on the role each can play. Although it may be difficult to maintain cooperation among healthcare workers, improvements in the medical quality of an entire region can be achieved by planning a life design including medical treatment for each patient.
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http://dx.doi.org/10.1248/yakushi.17-00118-5DOI Listing
August 2018

[Role of Pharmacists in Topical Therapy for Onychomycosis in the Home-care Setting].

Yakugaku Zasshi 2018 ;138(5):615-619

Kitasato University School of Pharmacy.

 There is an urgent need to promote home medical care in Japan because of the country's superaging society. Community pharmacists are expected to play an important role as part of home medical care teams. The prevalence of nail ringworm is high among home-care patients and can cause decreases in the quality of life, including difficulty in walking due to pain caused by nail deformation and inflammation around infected nails. Nail ringworm is typically treated with oral medication. However, the condition is left untreated in many elderly patients because of the risk of drug-drug interactions or concerns about severe liver damage. Efinaconazole, a novel triazole antifungal agent, has recently become available in Japan, enabling patients with nail ringworm to be treated with a topical medication. In topical treatment, the method of application is important because of its major impact on the therapeutic effect. Therefore, pharmacists should take special care to instruct patients and caregivers on the proper use of topical efinaconazole. Adherence to oral medication can be easily monitored by checking the number of tablets or capsules remaining, but adherence to topical medication regimens is more difficult to assess because the remaining amount cannot be determined precisely by checking the outer appearance of the container. The aim of this study was to determine and improve home-care patients' adherence to topical efinaconazole treatment regimens by measuring amounts remaining in the containers using a portable electronic scale. We found that this method is useful for determining the status of topical efinaconazole use.
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http://dx.doi.org/10.1248/yakushi.17-00118-4DOI Listing
August 2018

[Study of Home-based Ringworm Treatment and Follow-up by Visiting Nurses and Physicians: Interventional Effects].

Yakugaku Zasshi 2018 ;138(5):611-613

Kitasato University School of Pharmacy.

 The aim of this study was to assess the effects of cooperation by visiting nurses and physicians experienced in general patient care, dermatology, and podiatry for the treatment of ringworm. Questionnaires were delivered to 1184 patients receiving home-based care by one of 14 participating visiting nursing establishments with a combined capacity of 3273 patients throughout five wards of the Tokyo metropolitan area. Responses were obtained from 691 patients (participation rate, 60.2%; average age, 80.2 years). The onychomycosis morbidity rate among home care patients was 22.7%. The results showed a significant reduction in the incidence of ringworm in the intervention group, from 79.5% to 54.5% (p=0.022), and in the incidence of "foot skin infection", from 100.0% to 31.6% (p<0.001). Although the level of care deteriorated in the control group (p=0.008), there was no significant change in the intervention group. The incidence of leg pain also remained unchanged in the control group (p=0.285) but decreased in the intervention group (p=0.003). While the "degree of satisfaction with foot cleanliness" did not change significantly in the control group (p=0.260), patients in the intervention group were generally satisfied with foot cleanliness. It is necessary to take into account foot care and the effect of onychomycosis treatment vearsusu no treatment and to ensure that visiting nurses and caregivers master foot care-related treatment regimens. We suggest the need to improve the maintenance of foot care and ringworm intervention/treatment performed by physicians, nurses, and caregivers.
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http://dx.doi.org/10.1248/yakushi.17-00118-3DOI Listing
August 2018

[Current Status of Onychomycosis Topical Therapy Conducted at Home].

Yakugaku Zasshi 2018 ;138(5):607-609

Kitasato University School of Pharmacy.

 Patients usually consult a dermatologist for the treatment of onychomycosis. However, in the case of home care, visiting nurses may assist with bathing, which offers the opportunity to observe patients' feet for possible signs of onychomycosis without causing anxiety. It is estimated that more than 30% of patients receiving home care have onychomycosis. Before the approval of efinaconazole, healthcare personnel hesitated to treat onychomycosis because of: 1) possible side effects, especially liver dysfunction and pain due to repeated blood collection, as a major goal of home care is to minimize pain; and 2) the questionable efficacy of previously available antifungal medications. In addition, many patients report fear of "transmitting athlete's foot to others" and "do not want to show my dirty toenails". On the other hand, caregivers reportedly worry about "athlete's foot being transmitted to them".
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http://dx.doi.org/10.1248/yakushi.17-00118-2DOI Listing
August 2018