Publications by authors named "Kazuya Tone"

16 Publications

  • Page 1 of 1

New aspects of fundamental pathology and environmental control: Important issues in allergic bronchopulmonary mycosis.

J Allergy Clin Immunol Pract 2021 Mar;9(3):1420

Department of Environmental and Preventive Medicine, Kanazawa University, Ishikawa, Japan.

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http://dx.doi.org/10.1016/j.jaip.2020.12.056DOI Listing
March 2021

Investigation of Filamentous Basidiomycetes in the Airway Is the Third Unmet Need in the Management of Unexplained Chronic Cough in Adults.

Biomed Hub 2020 May-Aug;5(2):196-199. Epub 2020 Aug 5.

Laboratory of Space and Environmental Medicine, Teikyo University, Tokyo, Japan.

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http://dx.doi.org/10.1159/000508611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841723PMC
August 2020

Endobronchial neurogenic tumor consisting of the features of a solitary circumscribed neuroma.

J Thorac Dis 2020 Dec;12(12):7498-7500

Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

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http://dx.doi.org/10.21037/jtd-20-2365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797859PMC
December 2020

Mucus plugs and bronchial wall thickening on three-dimensional computed tomography in patients with unexplained chronic cough whose sputum yielded filamentous Basidiomycetes.

Eur Radiol 2020 Jun 11;30(6):3268-3276. Epub 2020 Feb 11.

Department of Radiology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.

Objectives: This study was conducted in order to identify imaging features on three-dimensional computed tomography (CT) of unexplained chronic cough (UCC) patients with positive sputum cultures for filamentous Basidiomycetes (f-BM).

Methods: UCC outpatients who had been given various questionnaires for cough, pulmonary function tests, and fungal cultures of sputum were evaluated. Multidetector row CT (MDCT) was performed for three-dimensional CT analysis of the lungs. Retrospective analysis was carried out with three groups: f-BM culture-positive group, other fungal culture-positive group, and culture-negative group. The Kruskal-Wallis test, analysis of variance, Fischer exact test, χ test, Student's t test, Mann-Whitney U test, Spearman's correlation coefficient, and Dunn-Bonferroni post hoc method were used for statistical analysis.

Results: Of the 50 patients, 3 were excluded and the remaining 47 were included in the analysis. There were no significant differences in respiratory function or clinical characteristics among the three groups. The common features on high-resolution CT (HRCT) included tree-in-bud (TIB) pattern, multiple centrilobular nodules, and bronchial wall thickening. Bronchiolar mucus plugs were detected in 7 (15%) of 47 cases. Bronchiole wall thickness and %FEV appeared to be slightly correlated (p = 0.033, r = 0.357). The bronchiole walls were significantly thicker when mucus plugs were found (p = 0.010). Bronchiolar walls were the thickest and the score of mucus plugs was the highest in patients with f-BM culture-positive sputum (p = 0.008).

Conclusions: Imaging findings for identifying f-BM culture-positive fungus-associated chronic cough (FACC) patients include high mucus plug scores and bronchiolar wall thickening on three-dimensional CT.

Key Points: • Three-dimensional computed tomography helps clinicians assess patients with unexplained chronic cough and identify those with fungus-associated chronic cough. • A retrospective single-center study showed that computed tomography images in patients with filamentous Basidiomycetes cultured from sputum had mucus plugs and bronchiolar wall thickening. • UCC patients with sputum cultures positive for filamentous Basidiomycetes may have fine airway lesions that could not be detected without three-dimensional computed tomography.
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http://dx.doi.org/10.1007/s00330-020-06664-5DOI Listing
June 2020

C-type lectin receptors of the Dectin-1 cluster: Physiological roles and involvement in disease.

Eur J Immunol 2019 12 13;49(12):2127-2133. Epub 2019 Nov 13.

Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Aberdeen, Scotland.

C-type lectin receptors (CLRs) are essential for multicellular existence, having diverse functions ranging from embryonic development to immune function. One subgroup of CLRs is the Dectin-1 cluster, comprising of seven receptors including MICL, CLEC-2, CLEC-12B, CLEC-9A, MelLec, Dectin-1, and LOX-1. Reflecting the larger CLR family, the Dectin-1 cluster of receptors has a broad range of ligands and functions, but importantly, is involved in numerous pathophysiological processes that regulate health and disease. Indeed, these receptors have been implicated in development, infection, regulation of inflammation, allergy, transplantation tolerance, cancer, cardiovascular disease, arthritis, and other autoimmune diseases. In this mini-review, we discuss the latest advancements in elucidating the function(s) of each of the Dectin-1 cluster CLRs, focussing on their physiological roles and involvement in disease.
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http://dx.doi.org/10.1002/eji.201847536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916577PMC
December 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

Real-Time PCR Detection of the Basidiomycetous Fungus Bjerkandera adusta: A Tool to Identify Itraconazole Responder Patients with Unexplained Chronic Cough.

Respiration 2019;97(1):84-91. Epub 2018 Oct 19.

Graduate School of Medicine, Teikyo University, Tokyo,

Background: Filamentous basidiomycetes (f-BMs) are involved in some unexplained chronic cough (UCC) cases that can be improved by the administration of antifungal agents. The disease concept was termed fungus-associated chronic cough (FACC). The current diagnostic criteria warrant environmental fungi isolation from respiratory specimens, which is hardly conceivable for such fungi.

Objectives: This study aimed to detect the f-BMs Bjerkandera adusta, the most common pathogen in FACC, from respiratory specimens of patients with UCC using real-time polymerase chain reaction (PCR). It also evaluated the applicability of the PCR system to detect antifungal agent responders among patients with unexplained cough.

Methods: The PCR system specific to B. adusta was developed and its utility was evaluated using sputum samples from 23 patients with chronic cough.

Results: B. adusta was detected in 10 out of 14 patients with UCC (71.4%), in contrast to only 2 out of 9 patients with non-UCC (22.2%; p < 0.05 with the Fisher's exact test). The copy number of the samples correlated with the therapeutic impact score for cough symptoms following the oral administration of itraconazole.

Conclusion: Development of the real-time PCR system enabled us to demonstrate that many patients with UCC might be influenced by B. adusta, a fact evidenced by the improvement of symptoms with itraconazole administration in most PCR-positive patients. This method would help in detecting itraconazole responders among patients with UCC when the isolation of f-BMs is not achievable.
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http://dx.doi.org/10.1159/000492118DOI Listing
April 2020

Central suppressant therapies in unexplained chronic cough patients whose sputum cultures yielded Bjerkandera adusta.

Allergol Int 2019 Jan 23;68(1):125-126. Epub 2018 Aug 23.

Laboratory of Space and Environmental Medicine, Teikyo University, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.alit.2018.07.009DOI Listing
January 2019

Epidural abscess caused by Schizophyllum commune: A rare case of rhinogenic cranial complication by a filamentous basidiomycete.

Mycoses 2018 Mar 5;61(3):213-217. Epub 2017 Dec 5.

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

Central nervous system (CNS) infections due to filamentous basidiomycetes are extremely rare. We encountered a case of epidural abscess due to Schizophyllum commune that extended from sinusitis. A 53-year-old Japanese man presented at our hospital with a headache. Computed tomography (CT) of the cranium and sinuses showed ethmoid and sphenoid sinusitis with no intracranial abnormalities. The patient was diagnosed with acute sinusitis and underwent antibiotic treatment. However, the symptoms deteriorated, and the patient came to our hospital again with consciousness disturbance. CT scan of the cranium and sinuses showed no improvement of sinusitis after antibiotic therapy and an epidural abscess emerged in the middle cranial fossa. Therefore, emergency craniotomy and endoscopic sinus fenestration were performed. Filamentous fungal elements were observed in both rhinorrhoea and epidural abscess. The symptoms improved after the operation and administration of liposomal amphotericin B. The clinical isolate was identified as S. commune by a molecular-based method. To our knowledge, this is the first report of epidural abscess due to this fungus. Although rare, clinicians should be aware that S. commune could be a causative agent of CNS infections.
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http://dx.doi.org/10.1111/myc.12729DOI Listing
March 2018

Detection of Fungi from an Indoor Environment using Loop-mediated Isothermal Amplification (LAMP) Method.

Biocontrol Sci 2017 ;22(2):97-104

Division of Clinical Laboratory Medicine, Graduate School of Medical Care and Technology.

 Loop-mediated isothermal amplification (LAMP) is a useful DNA detection method with high specificity and sensitivity. The LAMP reaction is carried out within a short time at a constant temperature without the need for thermal cycling. We developed a LAMP primer set for detecting a wide range of fungi by aligning the sequences of the large subunit ribosomal RNA gene of Candida albicans (Ascomycota), Cryptococcus neoformans (Basidiomycota), and Mucor racemosus (Mucorales). The threshold of C. albicans rDNA as template with our LAMP primer set was in the range of 10-100 copies per a reaction. In this study, we evaluated the correlation between colony forming units (CFU) and LAMP detection rate using the LAMP method for environmental fungi. The LAMP method should be a useful means of detecting fungi in indoor environments, disaster areas, or even in confined manned spacecraft to prevent allergies or infections caused by fungi.
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http://dx.doi.org/10.4265/bio.22.97DOI Listing
January 2018

Enhancing melting curve analysis for the discrimination of loop-mediated isothermal amplification products from four pathogenic molds: Use of inorganic pyrophosphatase and its effect in reducing the variance in melting temperature values.

J Microbiol Methods 2017 01 27;132:41-45. Epub 2016 Oct 27.

Graduate School of Medicine, Teikyo University, Tokyo 173-8605, Japan; Teikyo University Institute of Medical Mycology, 539 Otsuka, Hachioji, Tokyo 192-0395, Japan; General Medical Education and Research Center, Teikyo University, Tokyo, Japan. Electronic address:

Loop-mediated isothermal amplification (LAMP) is widely used for differentiating causative agents in infectious diseases. Melting curve analysis (MCA) in conjunction with the LAMP method reduces both the labor required to conduct an assay and contamination of the products. However, two factors influence the melting temperature (Tm) of LAMP products: an inconsistent concentration of Mg ion due to the precipitation of MgPO, and the guanine-cytosine (GC) content of the starting dumbbell-like structure. In this study, we investigated the influence of inorganic pyrophosphatase (PPase), an enzyme that inhibits the production of MgPO, on the Tm of LAMP products, and examined the correlation between the above factors and the Tm value using MCA. A set of LAMP primers that amplify the ribosomal DNA of the large subunit of Aspergillus fumigatus, Penicillium expansum, Penicillium marneffei, and Histoplasma capsulatum was designed, and the LAMP reaction was performed using serial concentrations of these fungal genomic DNAs as templates in the presence and absence of PPase. We compared the Tm values obtained from the PPase-free group and the PPase-containing group, and the relationship between the GC content of the theoretical starting dumbbell-like structure and the Tm values of the LAMP product from each fungus was analyzed. The range of Tm values obtained for several fungi overlapped in the PPase-free group. In contrast, in the PPase-containing group, the variance in Tm values was smaller and there was no overlap in the Tm values obtained for all fungi tested: the LAMP product of each fungus had a specific Tm value, and the average Tm value increased as the GC% of the starting dumbbell-like structure increased. The use of PPase therefore reduced the variance in the Tm value and allowed the differentiation of these pathogenic fungi using the MCA method.
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http://dx.doi.org/10.1016/j.mimet.2016.10.020DOI Listing
January 2017

Cross-reactivity in Cryptococcus antigen latex agglutination test in two commercial kits.

Med Mycol 2016 May 27;54(4):439-43. Epub 2016 Feb 27.

Laboratory of Space and Environmental Medicine, Graduate School of Medicine, Teikyo University, Tokyo 173-8605, Japan Teikyo University Institute of Medical Mycology, 539 Otsuka, Hachioji, Tokyo 192-0395, Japan

This article presents an examination of the cross-reactivity of pathogenic fungi with Cryptococcus neoformans in two commercial Cryptococcus antigen latex agglutination tests performed across 39 fungal strains. Some fungi were newly indicated as Cryptococcus cross-reactive, and the two kits showed differences in cross-reactive fungi.
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http://dx.doi.org/10.1093/mmy/myv115DOI Listing
May 2016

Fatal Cyberlindnera fabianii fungemia in a patient with mixed phenotype acute leukemia after umbilical cord blood transplantation.

Int J Hematol 2016 May 15;103(5):592-5. Epub 2016 Feb 15.

Laboratory of Space and Environmental Medicine, Graduate School of Medicine, Teikyo University, Tokyo, Japan.

We report a case of Cyberlindnera fabianii fungemia after umbilical cord blood transplantation (CBT). A 69-year-old woman was diagnosed as having mixed phenotype acute leukemia. The patient received CBT for primary refractory disease. After preconditioning chemotherapy, the patient's condition deteriorated, leading to acute respiratory failure from capillary leak syndrome and consequent admittance to the intensive care unit. The patient recovered temporarily following the administration of noninvasive positive pressure ventilation and continuous hemodiafiltration, but died of fungemia with the presence of yeast-like cells 15 days post-CBT. The yeast-like cells were analyzed by sequencing of the D1/D2 domain of the large subunit and the internal transcribed spacer domain, and were identified as C. fabianii. This case shows that molecular genetic-based methods may be effective for detecting undetermined invasive fungal infections in stem cell transplantation settings.
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http://dx.doi.org/10.1007/s12185-016-1953-yDOI Listing
May 2016

Morgagni hernia with respiratory failure aggravated by noninvasive positive pressure ventilation: a case report and overview of the literature.

Respir Investig 2014 May 18;52(3):203-8. Epub 2014 Jan 18.

Department of Internal Medicine, Respiratory Division, Jikei University School of Medicine, Tokyo, Japan. Electronic address:

An elderly woman diagnosed with multiple myeloma (MM) in 2007 had improved with chemotherapy. She had severe kyphosis and a diaphragmatic hernia (DH), but no respiratory symptoms. In 2011, because of thoracic deformity and emaciation, we advised her to continue the previously prescribed domiciliary noninvasive positive pressure ventilation (NPPV) therapy for chronic type II respiratory failure. However, she refused to continue NPPV. She was later admitted for deterioration in respiratory status and carbon dioxide (CO2) narcosis. We believed her low adherence to domiciliary NPPV caused CO2 narcosis; hence, we advised her to continue domiciliary NPPV and she complied. In May 2012, the now 79-year-old patient was admitted for acute exacerbation of chronic respiratory failure and CO2 narcosis. Chest imaging suggested that DH had caused a deterioration of her status. She underwent laparoscopic diaphragmatic hernia repair. Operative findings revealed a retrosternal hernia sac, and she was diagnosed as having a Morgagni hernia (MH). Her respiratory status subsequently improved. We hypothesize that NPPV increased intra-abdominal pressure, thereby worsening the MH and exacerbating respiratory failure. We believe that clinicians should be cautious when prescribing NPPV for MH patients.
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http://dx.doi.org/10.1016/j.resinv.2013.11.001DOI Listing
May 2014

[A case of tuberculous pleurisy developing contralateral effusion during anti-tuberculosis chemotherapy].

Kekkaku 2011 Jul;86(7):723-7

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

A 55-year-old woman was admitted to our hospital because of chest pain, fever, and right pleural effusion that was exudative and lymphocyte-dominant with a high level of adenosine deaminase (ADA). Since her blood QuantiFERON-TB 3G test (QFT) was positive, she was diagnosed with tuberculous pleurisy. After initiation of anti-tuberculosis chemotherapy with isoniazid, rifampicin, ethambutol, and pyrazinamide, her symptoms improved. Later, liquid culture of the pleural effusion turned positive for Mycobacterium tuberculosis. On the 18th day of treatment, her chest X-ray and computed tomography exhibited pleural effusion in a moderate amount in the left thorax, with subsiding pleural effusion in the right thorax. Thoracocentesis demonstrated that the left thorax effusion was also exudative and lymphocyte-dominant, with elevated QFT response and high ADA concentration, suggesting tuberculous pleurisy. Mycobacterium tuberculosis was detected in the culture of a left pleural biopsy specimen obtained by thoracoscopy. We assumed that the left pleural effusion was due to paradoxical worsening because (1) on admission no effusion or lung parenchymal lesion was detected in the left hemithorax, (2) on the 14th day of treatment she was afebrile without pleural effusion on both sides, and (3) the bacilli were sensitive to the drugs she had been taking regularly. We performed drainage of the left effusion and continued the same anti-tuberculosis drugs, which led to the elimination of all her symptoms and of the pleural effusion on both sides. In conclusion, paradoxical worsening should be included in the differential diagnosis when contralateral pleural effusion is detected during the treatment of tuberculosis.
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July 2011