Language：English   Publishing type：Research paper (scientific journal)   Publisher：IWA PUBLISHING  

We previously demonstrated the colonization of Mycobacterium avium complex in bathrooms by the conventional culture method. In the present study, we aimed to directly detect M. avium organisms in the environment using loop-mediated isothermal amplification (LAMP), and to demonstrate the efficacy of LAMP by comparing the results with those obtained by culture. Our data showed that LAMP analysis has detection limits of 100 fg DNA/reaction for M. avium. Using an FTA (R) elute card,DNA templates were extracted from environmental samples from bathrooms in the residences of 29 patients with pulmonary M. avium disease. Of the 162 environmental samples examined, 143 (88%) showed identical results by both methods; 20 (12%) and 123 (76%) samples were positive and negative, respectively, for M. avium. Of the remaining 19 samples (12%), seven (5%) and 12 (7%) samples were positive by the LAMP and culture methods, respectively. All samples that contained over 20 colony forming units/primary isolation plate, as measured by the culture method, were also positive by the LAMP method. Our data demonstrate that the combination of the FTA elute card and LAMP can facilitate prompt detection of M. avium in the environment.

DOI： 10.2166/wh.2013.007

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: The aim of this substudy of the ghrelin treatment, multicenter, randomized, double-blind, placebo-controlled trial was to investigate the effects of ghrelin administration on exercise capacity and the underlying mechanisms in underweight patients with chronic obstructive pulmonary disease (COPD) using cardiopulmonary exercise testing.
Methods: Twenty underweight COPD patients were randomized to pulmonary rehabilitation with intravenous ghrelin (2 mu g/kg, n = 10) or placebo (n = 10) twice daily for 3 weeks in a double-blind fashion. The primary outcome was changes in peak oxygen uptake ((V) over dot O-2). Secondary outcomes included changes in exertional cardio-respiratory functions: O-2-pulse, physiologic dead space/tidal volume-ratio (V-D/V-T), ventilatory equivalent for oxygen ((V) over dot(E)/(V) over dotO(2)), and ventilatory equivalent for carbon dioxide ((V) over dot(E)//(V) over dotCO(2)).
Results: With incremental exercise, at peak exercise, there was a significant difference in the mean difference (ghrelin minus placebo), i.e., treatment effect in: i) peak (V) over dotO(2) (1.2 mL/kg/min, 95% CI: 0.2-2.3 mL/kg/min, between-group p = 0.025); ii) (V) over dot(E)/(V) over dotO(2) (-4.2, 95% CI: -7.9 to -0.5, between-group p = 0.030); iii) (V) over dot(E)/(V) over dotCO(2) (-4.1, 95% CI: -8.2 to -0.1, between-group p = 0.045); iv) V-D/V-T (-0.04, 95% CI: -0.08 to -0.00, between-group p = 0.041); and v) O-2-pulse (0.7 mL/beat, 95% CI: 0.3 to 1.2 mL/beat, between-group p = 0.003). Additionally, repeated-measures analysis of variance (ANOVA) indicated a significant time-course effect of ghrelin versus placebo in the peak (V) over dotO(2) (p = 0.025).
Conclusion: Ghrelin administration was associated with improved exertional capacity and improvements in ventilatory-cardiac parameters.

DOI： 10.1186/1471-2466-13-37

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

To understand the mechanism of exertional dyspnea, we postulated that, despite hyperoxia during exercise, patients with idiopathic pulmonary fibrosis (IPF) might not regulate exertional acidosis by ventilatory compensation to stop exercise. The exercise responses during 30% O(2) or compressed air (CA) were examined in 13 patients with IPF. The PaO(2), PaCO(2), and HCO(3)(-) levels were higher during exercise with hyperoxia than with CA. At peak exercise, hyperoxia reduced the plasma lactate level. The dyspnea-ratio (%) of the ΔV(O(2)) (peak minus resting oxygen uptake) curve reached a break point that occurred at a similar exercise point with hyperoxia and CA, preceded by a break point in the breathing frequency-ratio of the ΔV(O(2)). Accordingly, the dyspnea score and pH each reached similar levels with hyperoxia and CA to stop exercise. Regardless of breathing CA or 30% O(2), IPF patients did not regulate exertional acidosis by ventilatory compensation to stop exercise, resulting in reaching a specific pH.

DOI： 10.1016/j.resp.2012.11.008

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Development of accurate methods for predicting progression of tuberculosis (TB) from the latent state is recognized as vitally important in controlling TB, because a majority of cases develop from latent infections. Past TB that has never been treated has a higher risk of progressing than does latent Mycobacterium tuberculosis infection in patients who have previously received treatment. Antibody responses against 23 kinds of M. tuberculosis proteins in individuals with past TB who had not been medicated were evaluated. These individuals had significantly higher concentrations of antibodies against Antigen 85A and mycobacterial DNA-binding protein 1 (MDP1) than did those with active TB and uninfected controls. In addition, immunohistochemistry revealed colocalization of tubercle bacilli, antigen 85 and MDP1 inside tuberculous granuloma lesions in an asymptomatic subject, showing that M. tuberculosis in lesions expresses both antigen 85 and MDP1. Our study suggests the potential usefulness of measuring antibody responses to antigen 85A and MDP1 for assessing the risk of TB progression.

DOI： 10.1111/j.1348-0421.2012.12005.x

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1128/genomeA.00608-13

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.4187/respcare.02201

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Society for Microbiology  

We report the draft genome sequence of Mycobacterium tuberculosis Beijing strain OM-V02_005, which exhibits possible hypertransmissible characteristics among the population of patients with multidrug-resistant tuberculosis in Osaka Prefecture, the largest urban area in western Japan.

DOI： 10.1128/genomeA.00608-13

Scopus

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

We report herein the draft genome sequence of Mycobacterium intracellulare clinical strain M.i.198, which consistently exhibits hypervirulence in human patients, human macrophages in vitro, and immunocompetent mice.

DOI： 10.1128/JB.01439-12

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Tuberculosis remains one of the most deadly infectious diseases worldwide and is a leading public health problem. Although isoniazid (INH) is a key drug for the treatment of tuberculosis, tolerance to INH necessitates prolonged treatment, which is a concern for effective tuberculosis chemotherapy. INH is a prodrug that is activated by the mycobacterial enzyme, KatG. Here, we show that mycobacterial DNA-binding protein 1 (MDP1), which is a histone-like protein conserved in mycobacteria, negatively regulates katG transcription and leads to phenotypic tolerance to INH in mycobacteria. Mycobacterium smegmatis deficient for MDP1 exhibited increased expression of KatG and showed enhanced INH activation compared with the wild-type strain. Expression of MDP1 was increased in the stationary phase and conferred growth phase-dependent tolerance to INH in M. smegmatis. Regulation of KatG expression is conserved between M. smegmatis and Mycobacterium tuberculosis complex. Artificial reduction of MDP1 in Mycobacterium bovis BCG was shown to lead to increased KatG expression and susceptibility to INH. These data suggest a mechanism by which phenotypic tolerance to INH is acquired in mycobacteria.

DOI： 10.1074/jbc.M111.333385

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Background: Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated.
Methodology/Principal Findings: In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 mg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated.
Conclusions/Significance: In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD.

DOI： 10.1371/journal.pone.0035708

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Background and objective: The results of studies on the oxygen response in patients with COPD should provide important clues to the pathophysiology of exertional dyspnoea. We investigated the exercise responses to hyperoxia in relation to dyspnoea profile, as well as cardiopulmonary, acidotic and sympathetic parameters in 35 patients with stable COPD (mean FEV1 46% predicted).
Methods: This was a single-blind trial, in which patients breathed 24% O-2 or compressed air (CA) in random order during two incremental cycle exercise tests.
Results: PaO2 and PaCO2 were higher (P < 0.0001 and P < 0.05, respectively) at each exercise point while patients were breathing 24% O-2 compared with CA. At a standardized time point near peak exercise, use of O-2 resulted in reduced plasma lactate and plasma noradrenaline concentrations (P < 0.01). Peak minute ventilation/indirect maximum voluntary ventilation was similar while breathing 24% O-2 and CA. At peak exercise, the dyspnoea score, pH and plasma noradrenaline concentrations were similar while breathing 24% O-2 and CA. The dyspnoea-ratio (%) of Delta oxygen uptake (peak minus resting oxygen uptake) curve reached a break point that occurred at a similar exercise point while breathing 24% O-2 or CA.
Conclusions: Regardless of whether they breathed CA or 24% O-2, patients with COPD did not develop ventilatory compensation for exertional acidosis, and the pH values measured were similar. Hyperoxia during a standardized exercise protocol did not alter the pattern of exertional dyspnoea in these patients, compared with breathing CA, although hyperoxia resulted in miscellaneous effects.

DOI： 10.1111/j.1440-1843.2011.02086.x

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER COLL CHEST PHYSICIANS  

DOI： 10.1378/chest.10-0248

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

The objective of this study was to investigate whether exertional dyspnea correlates with exercise responses, especially arterial blood pH and plasma norepinephrine (NE) changes, in patients with sequelae of tuberculosis (TBsq). Cardiopulmonary exercise testings were performed in 49 TBsq patients and 9 controls. Each group had a break point in the dyspnea, plasma lactate, and plasma NE changes during exercise, all of which occurred at a similar exercise point. In TBsq patients in both exercise phases before and after the dyspnea break point, the dyspnea-slope (a dagger Borg scale/a dagger minute ventilation) correlated with the pH-slope (a dagger pH/a dagger oxygen uptake) (r = -0.616, p < 0.0001; r = -0.629, p < 0.0001, respectively, before and after the break point) and with the NE-slope (a dagger NE/a dagger oxygen uptake) (r = 0.443, p = 0.0012; r = 0.643, p < 0.0001, respectively, before and after the break point). In TBsq patients during exercise, increases in circulating NE levels and exertional acidosis were correlated with exertional dyspnea.

DOI： 10.1007/s12576-009-0083-1

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

CD4(+)CD25(+) regulatory T (Treg) cells cause immune suppression by inhibiting T cell effector functions and play pivotal roles not only in self-tolerance but also in immune response to parasitic microbial pathogens. Mycobacteria are major parasitic bacterial pathogens, but the role of CD4(+)CD25(+) Treg cells in mycobacterial infection is not yet defined. In this study we found that, at the early stage of infection, depletion of CD25(+) cells reduced both bacterial load and granuloma formation in mice infected with Mycobacterium tuberculosis strains, such as M. tuberculosis Erdman or M. tuberculosis Kurono. However, at a later stage of infection, bacterial burden and histopathology were similar regardless of depletion of CD25(+) cells. Severe combined immunodeficient (SCID) mice reconstituted with CD4(+)CD25(-) T cells alone or a combination of CD4(+)CD25(+) and CD4(+)CD25(-) T cells showed similar bacterial loads and survival kinetics after infection with M. tuberculosis Erdman. Consistent with in vivo data, in vitro studies revealed that mycobacterial antigens, purified protein derivative of tuberculin (PPD), failed to induce the suppressive function of CD4(+)CD25(+) Treg cells to CD4(+)CD25(-) effector T cells, as demonstrated by the lack of response of CD4(+)CD25(+) T cells to PPD, in mice chronically infected with Mycobacterium bovis bacillus Calmette-Guerin and M. tuberculosis. Our data show that CD4(+)CD25(+) Treg cells have a transient effect at the early stage of mycobacterial infection but, contrary to the expectation, have little impact on the overall course of infection.

DOI： 10.1093/intimm/dxp126

Web of Science

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

Background and objective: Exertional dyspnoea limits patients with IPF in their activities of daily living. The mechanism, however, has not been elucidated. This study tested the hypothesis in IPF that exertional dyspnoea correlates with cardiopulmonary exercise responses, specifically changes in arterial blood pH and plasma norepinephrine (NE).
Methods: Cardiopulmonary exercise testing with measurements of dyspnoea (Borg scale), plasma NE, plasma lactate and arterial blood gases were performed in 29 patients with IPF and in nine controls.
Results: Both groups showed obvious break points in dyspnoea changes during exercise. In IPF, an abrupt change in the Borg scale, pH, PaCO(2) and plasma NE occurred in the late exercise phase after the 'break point'. Compared with controls, patients with IPF had significantly higher HCO(3)(-) levels and physiologic dead space/tidal volume during exercise. In IPF, during both exercise phases, the dyspnoea slope (Delta Borg scale/Delta minute ventilation) correlated with the pH slope (Delta pH/Delta oxygen uptake) (before the break point: r = -0.537, P = 0.0022; r = -0.886, P < 0.0001, after the break point) and the NE slope (Delta NE/Delta oxygen uptake) (before the break point: r = 0.481, P = 0.0075; R = 0.784, P < 0.0001, after the break point).
Conclusions: In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.

DOI： 10.1111/j.1440-1843.2009.01607.x

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD  

Mycobacterium avium complex (MAC) disease has been increasing worldwide not only in immunocompromised but also in immunocompetent humans. However, the relationship between mycobacterial strain virulence and disease progression in immunocompetent humans is unclear. In this study, we isolated 6 strains from patients with pulmonary MAC disease. To explore the virulence, we examined the growth in human THP-1 macrophages and pathogenicity in C57BL/6 mice. We found that one strain, designated 198, which was isolated from a patient showing the most progressive disease, persisted in THP-1 cells. In addition, strain 198 grew to a high bacterial load with strong inflammation in mouse lungs and spleens 16 weeks after infection. To our knowledge, strain 198 is the first isolated MAC strain that exhibits hypervirulence consistently for the human patient, human macrophages in vitro, and even for immunocompetent mice. Other strains showed limited survival and weak virulence both in macrophages and in mice, uncorrelated to disease progression in human patients. We demonstrated that there is a hypervirulent clinical MAC strain whose experimental virulence corresponds to the serious disease progression in the patients. The existence of such strain suggests the involvement of bacterial virulence in the pathogenesis of pulmonary MAC disease in immunocompetent status. (c) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.micpath.2008.10.007

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Osaka City University  

CiNii Article

CiNii Books

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

CiNii Article

CiNii Books

researchmap

Language：English   Publishing type：Thesis (other)  

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

researchmap

Language：Japanese   Publishing type：Research paper (scientific journal)  

CiNii Article

CiNii Books

researchmap