Takayuki Honda

Shinshu University, Shonai, Nagano, Japan

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Publications (246)556.57 Total impact

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    ABSTRACT: Reverse transcription (RT)-nested polymerase chain reaction (PCR) is a time-consuming procedure because it has several handling steps and is associated with the risk of cross-contamination during each step. Therefore, a rapid and sensitive one-step RT-nested PCR was developed that could be performed in a single tube using a droplet-PCR machine. The K562 BCR-ABL mRNA-positive cell line as well as bone marrow aspirates from 5 patients with chronic myelogenous leukemia (CML) and 5 controls without CML were used. We evaluated one-step RT-nested PCR using the droplet-PCR machine. One-step RT-nested PCR performed in a single tube using the droplet-PCR machine enabled the detection of BCR-ABL mRNA within 40 min, which was 10(3)-fold superior to conventional RT nested PCR using three steps in separate tubes. The sensitivity of the one-step RT-nested PCR was 0.001%, with sample reactivity comparable to that of the conventional assay. One-step RT-nested PCR was developed using the droplet-PCR machine, which enabled all reactions to be performed in a single tube accurately and rapidly and with high sensitivity. This one-step RT-nested PCR may be applicable to a wide spectrum of genetic tests in clinical laboratories. Copyright © 2015. Published by Elsevier B.V.
    Clinica chimica acta; international journal of clinical chemistry 07/2015; 448. DOI:10.1016/j.cca.2015.07.003 · 2.76 Impact Factor
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    ABSTRACT: We report a case of vulval extramammary Paget disease (EMPD) with dermal invasion showing mucinous carcinoma (MC). An 80-year-old woman presented with vulvar itching and pain. A physical examination showed a pigmented vulvar, perianal erythematous plague, and a subcutaneous nodule in the left major labia. No internal malignancy, such as colorectal or genitourinary carcinoma, was identified in any of the clinical examinations. A histological examination of the resected specimen revealed Pagetoid tumor cells that had spread widely through the epidermis and invaded the dermis forming a solid nest with mucous lake-like MC. Immunohistochemical examination revealed that the tumor cells in the epidermis and dermis were positive for CK7, CEA, GCDFP-15, MUC5AC, and MUC2, but negative for CK20, MUC6, and CDX2. Only the invasive component showed overexpression of p53. A diagnosis of primary EMPD with dermal invasion showing MC of the vulva was made. This is an extremely rare diagnosis, and we suggest that immunohistochemical evaluations in addition to systemic work-ups are helpful in distinguishing between these cases and those involving vulvar or perianal skin invasion of underlying colorectal or genitourinary carcinomas, which are referred to as secondary EMPD.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 04/2015; 34(4). DOI:10.1097/PGP.0000000000000169 · 1.63 Impact Factor
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    ABSTRACT: Chimerism analysis is important for evaluation of engraftment and predicting relapse following hematopoietic stem cell transplantation (HSCT). We developed a chimerism analysis for single nucleotide polymorphisms (SNPs), including rapid screening of the discriminable donor/recipient alleles using droplet allele-specific PCR (droplet-AS-PCR) pre-HSCT and quantitation of recipient DNA using AS-quantitative PCR (AS-qPCR) following HSCT. SNP genotyping of 20 donor/recipient pairs via droplet-AS-PCR and the evaluation of the informativity of 5 SNP markers for chimerism analysis were performed. Samples from six follow-up patients were analyzed to assess the chimerism via AS-qPCR. These results were compared with that determined by short tandem repeat PCR (STR-PCR). Droplet-AS-PCR could determine genotypes within 8 min. The total informativity using all 5 loci was 95% (19/20). AS-qPCR provided the percentage of recipient DNA in all 6 follow-up patients without influence of the stutter peak or the amplification efficacy, which affected the STR-PCR results. The droplet-AS-PCR had an advantage over STR-PCR in terms of rapidity and simplicity for screening before HSCT. Furthermore, AS-qPCR had better accuracy than STR-PCR for quantification of recipient DNA following HSCT. The present chimerism assay compensates for the disadvantages of STR-PCR and is readily performable in clinical laboratories. Copyright © 2015. Published by Elsevier B.V.
    Clinica chimica acta; international journal of clinical chemistry 03/2015; 445. DOI:10.1016/j.cca.2015.03.018 · 2.76 Impact Factor
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    ABSTRACT: Small-colony variants (SCVs) are slow-growing subpopulations of various auxotrophic bacterial strains. Thymidine-dependent SCVs (TD-SCVs) are unable to synthesize thymidine; hence, these variants fail to grow in a medium without thymidine. In this study, we used 10 TD-SCVs of Staphylococcus aureus, of which four strains possessed mecA. We compared the efficacy of a newly modified medium containing thymidine for the detection of TD-SCVs of methicillin-resistant S. aureus (MRSA) to the efficacy of routinely used laboratory media. We observed that none of the 10 TD-SCVs of S. aureus grew in Mueller-Hinton agar, and four TD-SCVs of MRSA failed to grow on all MRSA screening media, except for the ChromID™ MRSA medium. Laboratory tests conducted using medium with thymidine incorporated showed that thymidine did not affect the minimum inhibitory concentrations of oxacillin and cefoxitin for clinical isolates of S. aureus, and was able to detect MRSA, including TD-SCVs. These findings showed that thymidine-incorporated media are able to detect TD-SCVs of MRSA without altering the properties of other clinically isolated MRSA strains. Copyright © 2015. Published by Elsevier B.V.
    Journal of Microbiological Methods 01/2015; 110. DOI:10.1016/j.mimet.2015.01.007 · 2.10 Impact Factor
  • Kazuyuki Matsuda · Takayuki Honda
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    ABSTRACT: Single nucleotide alternations such as single nucleotide polymorphisms (SNPs) or single nucleotide mutations are useful genetic markers for molecular diagnosis, prognosis, drug response, and predisposition to diseases. Rapid identification of SNPs or mutations is clinically important, especially for determining drug responses and selection of molecular-targeted therapy. Here, we describe a rapid genotyping assay based on the allele-specific polymerase chain reaction (AS-PCR) by using our droplet-PCR machine (droplet-AS-PCR).
    Methods in molecular biology (Clifton, N.J.) 01/2015; 1310:29-35. DOI:10.1007/978-1-4939-2690-9_3 · 1.29 Impact Factor
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    ABSTRACT: A 49-year-old man was admitted to a hospital with chest pain and polyarthralgia. Chest radiography showed abnormal findings, and chest computed tomography showed a mass in the right lung. A transbronchial lung biopsy led to a diagnosis of anaplastic lymphoma kinase (ALK)-positive adenocarcinoma. Bone scintigraphy revealed bilateral symmetrical accumulations of (99m)Technetium complexes in the long bones, suggesting co-existing hypertrophic pulmonary osteoarthropathy (HPO). The patient underwent four courses of chemotherapy with cisplatin plus pemetrexed, which led to decreased (99m)Technetium accumulations in the long bones. To the best of our knowledge, this is the first reported case of HPO associated with ALK-positive lung cancer.
    Internal Medicine 01/2015; 54(16):2045-9. DOI:10.2169/internalmedicine.54.4452 · 0.97 Impact Factor
  • Hiroya Hidaka · Takayuki Honda
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    ABSTRACT: Serum lipids have a variety of molecular frameworks and fatty acid side chains, and these molecules include various metabolites and derivatives. Lipid molecules influence the physicochemical properties of the plasma membrane and intracellular transport, and their metabolites are often bioactive substances. Fatty acid molecules are also precursors of lipid mediators, and are involved in the regulation of inflammatory reactions. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is used in various fields in the clinical laboratory. Serum phosphatidylcholine (PC), lysoPCGSphingomyelin, triglycerides, cholesterol ester, sulfatide, phosphatidylethanolamine, and phosphatidylglycerol can be analyzed by MALDI-TOF MS. We devised an analytical procedure for serum ceramide and glycolipids from partially purified serum lipids. Investigation of lipid molecular species is used for the characterization of disorders of lipid metabolism. MS methods for use in routine laboratory tests require both precise and accurate measurement, and sample preparation procedures should be both simple and quick. (Review).
    Rinsho byori. The Japanese journal of clinical pathology 12/2014; 62(12):1236-42.
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    ABSTRACT: Epithelial-mesenchymal transition (EMT) is associated with pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF). In this study, we investigated EMT of human pulmonary epithelial-derived cells (A549). A549 cells was either cultured by itself or co-cultured with THP-1 macrophages under normoxic (21% O2) and hypoxic (2% O2) conditions. We evaluated the presence of EMT by determining the expression of EMT markers, E-cadherin, vimentin, and fibronectin. To determine the role of TGF-β1 and IL-1β in EMT of the A549 cells, we analyzed the effects of blocking their activity with TGF-β1 inhibitor or IL-1β neutralizing antibody respectively. The A549 cells presented EMT when they were co-cultured with THP-1 macrophages. The EMT of the A549 cells co-cultured with THP-1 macrophages was exacerbated under hypoxia. In addition, the EMT were prevented by the addition of TGF-β1 type I receptor kinase inhibitor. The hypoxic condition increased the mRNA levels of TGF-β1 in A549 cells and THP-1 macrophages and that of IL-1β in THP-1 macrophages when each cells were co-cultured. Anti-IL-1β neutralizing antibody attenuated TGF-β1 secretion in co-culture media under hypoxic conditions. Thus, the IL-1β from THP-1 macrophages up-regulated the TGF-β1 from A549 cells and THP-1 macrophages, and then the TGF-β1 from both cells induced and promoted the EMT of A549 cells when they were co-cultured under hypoxia. Together, these results demonstrate that the interaction between type II pneumocytes and macrophages under hypoxia is necessary for the development of pulmonary fibrosis.
    Biochemical and Biophysical Research Communications 10/2014; 453(4). DOI:10.1016/j.bbrc.2014.10.022 · 2.28 Impact Factor
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    ABSTRACT: The morphological mechanism of alveolar wall destruction during pulmonary emphysema has not been clarified. The aim of this study was to elucidate this process three‐dimensionally. Lung specimens from five patients with pulmonary emphysema were used, and five controls with normal alveolar structure were also examined. Sections 150 μm thick were stained with hematoxylin and eosin, elastica, and silver impregnation, and immunostained with selected antibodies. We examined these sections three‐dimensionally using a laser confocal microscope and a light microscope. There were only a few Kohn's pores and no fenestrae in the normal alveoli from the controls. In the lungs of the emphysema patients a small rupture appeared in the extremely thin alveolar wall among the alveolar capillaries. This rupture enlarged to form a circle surrounded by the capillaries, which was called an alveolar fenestra. Two neighboring fenestrae fused by breakdown of the collapsed or cord‐like capillary between them to form a large fenestra. The large fenestrae fused repeatedly to become larger, and these were bordered by thick elastic fibers constructing an alveolar framework. Alveolar wall destruction during emphysema could start from small ruptures of the alveolar wall that become fenestrae surrounded by capillaries, which fuse repeatedly to become larger fenestrae rimmed with elastic fibers. The alveolar capillary network could initially prevent enlargement of the fenestrae, and the thick elastic fibers constituting the alveolar framework could secondarily prevent destruction of the alveolar wall structure. Clin. Anat., 2014. © 2014 Wiley Periodicals, Inc.
    Clinical Anatomy 09/2014; 28(2). DOI:10.1002/ca.22463 · 1.16 Impact Factor
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    ABSTRACT: It is an important role of a clinical laboratory to provide accurate results of examinations promptly when a physician requires them, and this may be generally achieved. What more can technologists do to improve the medical service? It is more helpful for other medical staff to report crude laboratory data with adequate comments, which can be easily and promptly used in medical treatment. In this reversed clinicopathological conference, the admission periods of patients were divided into several phases: the admission day, from the 1st to 7th days, and from the 1st to 15th days. We closely analyzed routine laboratory data in each phase, and commented on what might be useful for the medical staff to the grasp the pathological state of patients in each phase. If comments from the laboratory become commonly acceptable, clinical laboratories will come to play a more valuable role in medical practice.
    Rinsho byori. The Japanese journal of clinical pathology 08/2014; 62(8):802-10.
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    ABSTRACT: Background The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is a recently described entity associating upper-lobe emphysema and lower-lobe fibrosis. We sought to evaluate differences in pulmonary function between CPFE patients with and without airflow obstruction. Subjects and methods Thirty-one CPFE patients were divided into two groups according to the presence or absence of irreversible airflow obstruction based on spirometry (forced expiratory volume in 1 second/forced vital capacity <70% following inhalation of a β2-agonist) as follows: CPFE patients with airflow obstruction (CPFE OB+ group, n=11), and CPFE patients without airflow obstruction (CPFE OB− group, n=20). Pulmonary function, including respiratory impedance evaluated using impulse oscillometry and dynamic hyperinflation following metronome-paced incremental hyperventilation, was retrospectively analyzed in comparison with that observed in 49 chronic obstructive pulmonary disease (COPD) patients (n=49). Results In imaging findings, low-attenuation-area scores on chest high-resolution computed tomography, representing the degree of emphysema, were significantly lower in the CPFE OB− group than in the CPFE OB+ and COPD groups. In contrast, the severity of pulmonary fibrosis was greater in the CPFE OB− group than in the CPFE OB+ group. In pulmonary function, lung hyperinflation was not apparent in the CPFE OB− group. Impairment of diffusion capacity was severe in both the CPFE OB− and CPFE OB+ groups. Impulse oscillometry showed that respiratory resistance was not apparent in the CPFE OB− group compared with the COPD group, and that easy collapsibility of small airways during expiration of tidal breath was not apparent in the CPFE OB+ group compared with the COPD group. Dynamic hyperinflation following metronome-paced incremental hyperventilation was significantly greater in the COPD group than in the CPFE OB− group, and also tended to be greater in the CPFE OB+ group than in the CPFE OB− group. Conclusion The mechanisms underlying impairment of physiological function may differ among CPFE OB+ patients, CPFE OB− patients, and COPD patients. CPFE is a heterogeneous disease, and may have distinct phenotypes physiologically and radiologically.
    International Journal of COPD 07/2014; 9:805-11. DOI:10.2147/COPD.S65621
  • Mikiko Kobayashi · Naoko Asano · Mana Fukushima · Takayuki Honda
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    ABSTRACT: We report a rare case in which Epstein-Barr virus (EBV)-negative polymorphic B-cell post-transplant lymphoproliferative disorder (PTLD) and EBV-negative monomorphic T-cell PTLD [anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL)] were observed simultaneously in the same cervical lymph node, 34 months after liver transplantation for hepatitis C liver cirrhosis. Although hepatitis C recurred after 2 months, he had no other complications until PTLD occurred 34 months post-transplantation. The patient underwent reduction of the immunosuppressive drug and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, and he was considered to have achieved complete remission. However, PTLD recurred, and he died 6 months after the initial diagnosis. Autopsy revealed only EBV-negative monomorphic T-cell PTLD (ALK-negative ALCL) that involved the liver, spleen, bilateral kidneys, stomach, bladder, heart, bone marrow, right ureter, and pons. Thus, recurrent PTLD may show a different histological type from the primary disorder, as PTLD has a multiclonal potentiality that causes various types of lymphomas. Therefore, it may be difficult to predict PTLD-related prognosis from the initial PTLD histological identification.
    International Journal of Hematology 05/2014; 100(3). DOI:10.1007/s12185-014-1599-6 · 1.68 Impact Factor
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    ABSTRACT: Mucormycosis is a fatal complication in immunocompromised patients, and is additionally difficult to diagnose due to the lack of useful serum biomarkers. Using a quantitative PCR approach, we retrospectively analyzed Mucorales DNA load in sera collected serially from a 3-year-old patient with chronic granulomatous disease, who died of multi-organ failure probably due to dissemination of Rhizomucor pusillus, which was detected from necropsy specimens. Mucorales DNA load was below the detection limit on days 9, 2, and 4 after unrelated bone marrow transplantation. Rhizomucor DNA was first detected on day 14 (1.6 × 10(3) copies/mL), and subsequently fluctuated between 1.3 × 10(3) and 37.2 × 10(3) copies/mL until day 43. Rhizomucor achieved a peak value of 940.0 × 10(3) copies/mL on day 48 the day before death. The detection or fluctuation of Rhizomucor DNA appeared to be associated with corticosteroid dosages or C-reactive protein levels. This specific, noninvasive, and highly quantitative assay may be useful for the early diagnosis of mucormycosis and prediction of disease progression.
    International Journal of Hematology 05/2014; 100(2). DOI:10.1007/s12185-014-1597-8 · 1.68 Impact Factor
  • Diagnostic Cytopathology 03/2014; DOI:10.1002/dc.23147 · 1.52 Impact Factor
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    ABSTRACT: Abstract A high homocysteine (Hcy) level is a risk factor for atherosclerosis. Hcy can be added to proteins through a process known as N-homocysteinylation. This is thought to be a potential cause of atherosclerosis induction. We previously reported that N-homocysteinylated apolipoprotein A-I (N-Hcy-apoA-I) was identified in normal human plasma. In this study, the effect of N-homocysteinylation on the functions of apoA-I was examined. A kinetic study using dimyristoyl phosphatidylcholine (DMPC) liposomes indicated that N-Hcy-apoA-I showed increased lipid-binding activity compared to wild-type apoA-I. Two reconstituted high-density lipoprotein (rHDL) particles of different sizes (approximately 8.2 nm and 7.6 nm in diameter) were produced by mixing apoA-I and 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). However, an increased ratio of large to small particles was found in rHDL prepared with N-Hcy-apoA-I. The normal apoA-I antioxidant ability, estimated by the suppression of conjugated diene formation in low-density lipoprotein (LDL) induced by copper sulfate oxidation, was considerably impaired when using N-Hcy-apoA-I. Although N-Hcy-apoA-I functioned as an oxidant, no significant difference was observed in the cholesterol efflux capacity from THP-1 macrophages between wild-type apoA-I and N-Hcy-apoA-I. These results suggest that N-Hcy-apoA-I might be proatherogenic due to its oxidative behavior but not an attenuation of cholesterol efflux capacity.
    Biological Chemistry 02/2014; 395(6). DOI:10.1515/hsz-2013-0262 · 2.69 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2014; 28(7). DOI:10.1038/leu.2014.58 · 9.38 Impact Factor
  • Japanese journal of infectious diseases 01/2014; 67(3):232-3. DOI:10.7883/yoken.67.232 · 1.20 Impact Factor
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    ABSTRACT: Objectives. To assess the utility of low-dose spiral chest CT (LDCT) screening for detecting lung cancer at the early stage and to examine the tumor volume doubling time (TVDT) according to the smoking status and age. Methods. A total of 295 patients who participated in an LDCT screening program for citizens of Nagano, Japan between 2000 and 2010 were examined with respect to the incidence, prognosis-related features (tumor size, proportion of clinical stage I tumors and histopathology) and TVDT of the lesions. Results. 1) The prevalence rate of lung cancer was similarly high in all smoking categories (504 per 100,000 subjects for the entire group), especially high in the elderly subjects (>50 years) and low in the patients in their 40&apos;s, seen only in non-smokers. The annual incidence was 84 in all subjects, being particularly low in the non-smokers and zero in the 40-year-old group. 2) The ratio of the prevalence cancer/annual repeat cancer was 6.0 (504/84), with 4.1 for smokers and 11.0 for non-smokers. 3) The prognosis-related features were significantly different between the smokers and non-smokers, with smokers having a larger tumor size and lower proportion of c-stage I lesions. 4) The mean TVDT for all 69 analyzed lesions was 459 days, with 364 days for smokers and 606 days for non-smokers. The TVDT values were shorter in the elderly smokers but longer in the elderly non-smokers, and varied widely in the current and non-smokers, while remaining within narrow limits in the ex- and passive smokers. 5) The rate of possible over-diagnosis (TVDT >400 days) was 17% in smokers and 44% in non-smokers. Summary and Conclusions. 1) Compared with the findings of US studies, the rate of detection of lung cancer was lower in the Japanese smokers, while the prognosis-related features were similar in the two populations, although more favorable features were identified in the Japanese non-smokers. 2) The high rate of prevalence cancer, irrespective of the smoking status, with nearly 45% of patients having tumors >14 mm, stresses the importance of prevalence CT screening for both smokers and non-smokers. The prevalence of lung cancer was fairly high in the subjects >50 years of age, thus justifying the use of cost-effective screening. The detection of lung cancer in 40-year-old patients among the non-smoking subjects only requires further examinations. 3) For non-smokers, the lower incidence with more favorable prognosis-related features/TVDT of lung cancer stresses the importance of performing repeat scans at an inter-screening interval of >1 year. 4) Hence, in general, annual repeat screening for smokers and biennial screening for non-smokers appear to be appropriate for detecting the majority of lung cancers measuring <14 mm. However, based on the TVDT results obtained in this study, the detection of lung cancer measuring <14 mm is expected to fail in some proportion of 60- and 70-year-old smokers on annual repeat screening and 60-year-old non-smokers on biennial repeat screening, and it is necessary to identify specific risk factors rationally supporting the more frequent use of CT scans in these patients in order to avoid detecting cancer in the late stage. In contrast, no failure to detect lesions <14 mm is expected using triennial and quadrennial scans in 70- and 50-year-old non-smokers, respectively (although the number of 50-year-old patients in this study was limited), and triennial repeat screening appears to be appropriate for these subgroups. 5) The variety of TVDT values observed according to the smoking status/age should be taken into account when planning chest CT screening in the community and performing work-up studies to estimate the degree of tumor growth in the hospital.
    Haigan 01/2014; 54(7):937-946. DOI:10.2482/haigan.54.937
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    ABSTRACT: The polymerase chain reaction (PCR) has been widely used for diagnosis of infectious diseases of domestic animals. Rapid detection of respiratory pathogens of cattle is useful for making therapeutic decisions. Therefore, we developed a new genetic-based method called droplet-real-time PCR, which can detect bovine respiratory syncytial virus (BRSV) within 10 min. Our droplet-real-time PCR markedly reduced the reaction time of reverse transcription-PCR while maintaining the same sensitivity as conventional real-time PCR, and it can be used as a rapid assay for detection of BRSV. Furthermore, our method is potentially applicable for rapid diagnosis of almost all infectious diseases, including highly pathogenic avian influenza virus.
    Journal of Veterinary Medical Science 11/2013; 76(3). DOI:10.1292/jvms.13-0357 · 0.88 Impact Factor
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    ABSTRACT: Abstract Background: Oxidative stress is implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Analysis of the expired breath condensate (EBC) has been suggested to provide non-invasive inflammatory markers that reflect oxidative stress in the airways. Objective: The present study attempts to elucidate whether the hydrogen peroxide (H2O2) levels and pH values in EBC may be useful as biomarkers of the activity or severity of asthma and COPD. Methods: We measured the H2O2 levels and pH values using a derivatives of reactive oxygen metabolites exhalation test kit (Diacron) and a pH analyser, respectively, in EBC obtained using an EcoScreen from 29 patients with asthma, 33 with COPD, and 33 healthy individuals (all non-smokers). We then examined the relationships among oxidative stress and the asthma control test (ACT) or COPD assessment test (CAT) scores, pulmonary function, fractional exhaled nitric oxide (FeNO), and the extent of low attenuation areas on HRCT. Results: The H2O2 levels were elevated and pH was lower in both asthma (H2O2; 8.75 ± 0.88 μM, p < 0.01, pH; 7.14 ± 0.07, p < 0.05) and COPD (H2O2; 7.44 ± 0.89 μM, p < 0.01, pH; 6.87 ± 0.10, p < 0.01) compared with control subjects (H2O2; 3.42 ± 0.66 μM, pH; 7.35 ± 0.04). Neither the H2O2 levels nor pH correlated with the ACT scores and FeNO in asthma patients. Neither the H2O2 levels nor pH significantly correlated with the pulmonary function in asthma and COPD. However, the CAT scores significantly correlated with the H2O2 levels in patients with COPD (r = 0.52, p < 0.01). Conclusions: These findings suggest that oxidative stress is involved in the pathogenesis of asthma and COPD and that the H2O2 levels in EBC might reflect the health status in COPD.
    COPD Journal of Chronic Obstructive Pulmonary Disease 10/2013; 11(1). DOI:10.3109/15412555.2013.830094 · 2.62 Impact Factor

Publication Stats

3k Citations
556.57 Total Impact Points

Institutions

  • 1985–2015
    • Shinshu University
      • • Department of Laboratory Medicine
      • • Department of Biomedical Laboratory Sciences
      • • Department of Internal Medicine I
      • • Department of Clinical Laboratory Sciences
      • • Department of Medicine
      • • Department of Legal Medicine
      Shonai, Nagano, Japan
  • 2011
    • Keio University
      Edo, Tōkyō, Japan
  • 1996
    • Matsumoto University
      Shonai, Nagano, Japan
  • 1991
    • Tokai University
      • School of Medicine
      Hiratsuka, Kanagawa-ken, Japan