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ABSTRACT: 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 Pa(O2), Pa(CO2), and H(CO3-) 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.
Respiratory Physiology & Neurobiology 12/2012; · 2.24 Impact Factor
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Mayuko Osada-Oka,
Yoshitaka Tateishi,
Yukio Hirayama,
Yuriko Ozeki,
Mamiko Niki,
Seigo Kitada, Ryoji Maekura,
Kunio Tsujimura,
Yukio Koide,
Naoya Ohara,
Taro Yamamoto,
Kazuo Kobayashi,
Sohkichi Matsumoto
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ABSTRACT: Development of accurate methods for predicting progression of tuberculosis (TB) from the latent state has been recognized as being vitally important in controlling TB, because a majority of cases develop from latent infections. Past TB without medication has a higher risk of progressing than latent Mycobacterium tuberculosis infection alone. We evaluated antibody responses against 23 kinds of M. tuberculosis proteins in individuals with past TB who had not been medicated. The group showed significantly higher levels of antibodies against Antigen 85A, and mycobacterial DNA-binding protein 1 (MDP1) compared to those with active TB and uninfected controls. Besides, immunohistochemistry revealed colocalization of tubercle bacilli, Antigen 85 and MDP1 inside tuberculous granuloma lesions in an asymptomatic subject, showing that M. tuberculosis in the lesion 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.
Microbiology and Immunology 11/2012; · 1.30 Impact Factor
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Yoshitaka Tateishi,
Seigo Kitada,
Keisuke Miki, Ryoji Maekura,
Yoshitoshi Ogura,
Yuriko Ozeki,
Yukiko Nishiuchi,
Mamiko Niki,
Tetsuya Hayashi,
Kazuto Hirata,
Kazuo Kobayashi,
Sohkichi Matsumoto
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ABSTRACT: 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.
Journal of bacteriology 11/2012; 194(22):6336. · 3.94 Impact Factor
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ABSTRACT: Background: The features of pulmonary disease caused by rapidly growing mycobacteria (RGM) have not been sufficiently documented. Objectives: To establish these features, we retrospectively evaluated 44 patients. Methods: We screened respiratory isolates at the National Toneyama Hospital (Osaka, Japan) between 2003 and 2007. Diagnosis was based on the latest guidelines of the American Thoracic Society. The patients were classified into 3 types according to their radiographic findings: fibrocavitary, nodular bronchiectatic and unclassified variant. Results: We obtained 1,348 nontuberculous mycobacteria respiratory isolates from 1,187 patients, including 119 RGM isolates from 100 patients. Forty-four of these 100 patients were definitively diagnosed with respiratory disease due to RGM. The most common pathogen was Mycobacteriumabscessus, which accounted for 65.9% of cases, followed by Mycobacterium fortuitum at 20.5%. There was a statistically significant difference in smoking history between patients infected with these 4 RGM species (excluding those with an unknown smoking history; p = 0.039). The overall evaluation of radiographic findings revealed 18.2% as fibrocavitary, 43.2% as nodular bronchiectatic and 38.6% as unclassified variants in these 44 patients. There was a significant difference in radiographic findings between the 4 RGM species (p = 0.002). There was also a significant difference in radiographic findings between M. abscessus and M. fortuitum infected patients (p = 0.022). Conclusions: Patients with M. abscessus seem to have less of a smoking history and more frequent nodular bronchiectatic radiographic patterns than patients with M. fortuitum. In contrast, fibrocavitary patterns might be more frequent with M. fortuitum infection.
Respiration 08/2012; · 2.26 Impact Factor
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Aki Tamaru,
Chie Nakajima,
Takayuki Wada,
Yajun Wang,
Manabu Inoue,
Ryuji Kawahara, Ryoji Maekura,
Yuriko Ozeki,
Hisashi Ogura,
Kazuo Kobayashi,
Yasuhiko Suzuki,
Sohkichi Matsumoto
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ABSTRACT: Infection and transmission of multidrug-resistant Mycobacterium tuberculosis (MDR-Mtb) and extensively drug-resistant M. tuberculosis (XDR-Mtb) is a serious health problem. We analyzed a total of 1,110 Mtb isolates in Osaka Prefecture and neighboring areas from April 2000 to March 2009. A total of 89 MDR-Mtb were identified, 36 (48.5%) of which were determined to be XDR-Mtb. Among the 89 MDR-Mtb isolates, 24 (27.0%) phylogenetically distributed into six clusters based on mycobacterial interspersed repetitive units-various number of tandem repeats (MIRU-VNTR) typing. Among these six clusters, the MIRU-VNTR patterns of four (OM-V02, OM-V03, OM-V04, and OM-V06) were only found for MDR-Mtb. Further analysis revealed that all isolates belonging to OM-V02 and OM-V03, and two isolates from OM-V04 were clonal. Importantly such genotypes were not observed for drug-sensitive isolates. These suggest that few but transmissible clones can transmit after acquiring multidrug resistance and colonize even in a country with a developed, well-organized healthcare system.
PLoS ONE 01/2012; 7(8):e42505. · 4.09 Impact Factor
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ABSTRACT: The objective of the present study was to evaluate the effects of inhaled tiotropium on pulmonary function and left ventricular diastolic function in chronic obstructive pulmonary disease patients ≥ 1 year after pulmonary resection for lung cancer.
This prospective single-arm analysis involved 21 chronic obstructive pulmonary disease patients who underwent pulmonary resection for lung cancer at least one year earlier. Blood pressures, heart rate, spirometry, transthoracic echocardiography including tissue Doppler imaging, and quality of life were evaluated prior to and after 3 months of inhaled tiotropium treatment. B-type natriuretic peptide, white blood cell counts, and C-reactive protein levels before and after inhaled tiotropium treatment were also examined.
There were no significant differences between before and after treatment in forced vital capacity and left ventricular ejection fraction. Forced expiratory volume in 1 second and early transmitral velocity/tissue Doppler mitral annular early diastolic velocity values improved from 1.60 ± 0.5 L and 8.97 ± 1.6, respectively, before treatment, to 1.84 ± 0.5 L and 7.59 ± 1.4, respectively, 3 months after treatment (P <0.001).
Treatment with inhaled tiotropium may be effective in improving not only pulmonary function but also left ventricular diastolic function of patients with chronic obstructive pulmonary disease in the chronic phase after pulmonary resection.
Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 01/2012; 18(3):206-11.
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ABSTRACT: Tiotropium partially relieves exertional dyspnea and reduces the risk of congestive heart failure in chronic obstructive pulmonary disease (COPD) patients. However, its effect on the sympathetic activation response to exercise is unknown.
This study aimed to determine whether tiotropium use results in a sustained reduction in sympathetic activation during exercise.
We conducted a 12-week, open-label (treatments: tiotropium 18 μg or oxitropium 0.2 mg × 3 mg), crossover study in 17 COPD patients. Treatment order was randomized across subjects. The subjects underwent a pulmonary function test and two modes of cardiopulmonary exercise (constant work rate and incremental exercise) testing using a cycle ergometer, with measurement of arterial catecholamines after each treatment period.
Forced expiratory volume in 1 second and forced vital capacity were significantly larger in the tiotropium treatment group. In constant exercise testing, exercise endurance time was longer, with improvement in dyspnea during exercise and reduction in dynamic hyperinflation in the tiotropium treatment group. Similarly, in incremental exercise testing, exercise time, carbon dioxide production, and minute ventilation at peak exercise were significantly higher in the tiotropium treatment group. Plasma norepinephrine concentrations and dyspnea intensity were also lower during submaximal isotime exercise and throughout the incremental workload exercise in the tiotropium treatment group.
Tiotropium suppressed the increase of sympathetic activation during exercise at the end of the 6-week treatment, as compared with the effect of oxipropium. This effect might be attributed to improvement in lung function and exercise capacity and reduction in exertional dyspnea, which were associated with decreases in respiratory frequency and heart rate and reduced progression of arterial acidosis.
International Journal of COPD 01/2012; 7:109-17.
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Keisuke Miki, Ryoji Maekura,
Noritoshi Nagaya,
Masamitsu Nakazato,
Hiroshi Kimura,
Shinsuke Murakami,
Shunsuke Ohnishi,
Toru Hiraga,
Mari Miki,
Seigo Kitada,
Kenji Yoshimura,
Yoshitaka Tateishi,
Yasuji Arimura,
Nobuhiro Matsumoto,
Masanori Yoshikawa,
Kenichi Yamahara,
Kenji Kangawa
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ABSTRACT: 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.
In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/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.
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.
UMIN Clinical Trial Registry C000000061.
PLoS ONE 01/2012; 7(5):e35708. · 4.09 Impact Factor
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ABSTRACT: 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 FEV(1) 46% predicted).
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.
PaO(2) and PaCO(2) 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 Δoxygen 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.
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.
Respirology 01/2012; 17(1):149-54. · 2.42 Impact Factor
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ABSTRACT: Postoperative atrial fibrillation is the most common complication encountered during the early postoperative period following a pulmonary resection procedure. Landiolol is a newly developed, ultrashortacting, β-adrenoceptor antagonist. The objective of the present study was to evaluate the efficacy and safety of low-dose landiolol for postoperative atrial fibrillation in patients undergoing pulmonary resection for lung cancer.
Of 553 patients who underwent an elective pulmonary resection procedure for lung cancer at National Toneyama Hospital from January 2005 to December 2009, this analysis involved 30 consecutive patients who developed atrial fibrillation after surgery and needed treatment. These patients were divided into two groups: the landiolol group (n = 15) and the historical control group (treated with a combination of verapamil and digoxin, n = 15). Hemodynamic changes before and 30 min, 2 h, and 12 h after medication, the time required to restore sinus rhythm, and adverse events were evaluated.
There were no significant differences between the two groups regarding blood pressure before and after medication. Heart rate was reduced immediately in both groups after medication and was significantly lower in the landiolol group than in the control group. The time to restore sinus rhythm was significantly shorter in the landiolol group than in the control group (8.1 ± 11.0 h vs. 23.0 ± 26.0 h, P < 0.05). In none of the subjects with the landiolol infusion was it discontinued because of side effects.
Low-dose landiolol can be effective quickly and used safely in patients who develop atrial fibrillation after pulmonary resection for lung cancer.
General Thoracic and Cardiovascular Surgery 12/2011; 59(12):799-805.
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ABSTRACT: Smoking has been determined as a cause of chronic obstructive pulmonary disease (COPD) in most patients. Smoking cessation should be stressed above everything else for COPD patients under all conditions. A smoking habit is determined not as a preference but as a dependency on tobacco; therefore, smoking cessation is difficult solely based on one's motivation. Smoking cessation therapy is employed with cessation aids. Now, we can use nicotine-containing gum, patches, and the nicotine-receptor partial agonist varenicline. First, nicotine from tobacco is replaced with a nicotin patch, or a nicotine-free condition is induced by varenicline. Subsequently, the drugs are gradually reduced. In Japan, smoking cessation therapy is covered by public health insurance as definite requirements.
Nippon rinsho. Japanese journal of clinical medicine 10/2011; 69(10):1831-5.
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Masahide Mori,
Kazutaka Izawa,
Takeya Fujikawa,
Takeshi Uenami,
Teppei Sugano,
Sin-ichi Kagami,
Yoshinobu Namba,
Yukihiro Yano,
Tsutomu Yoneda,
Seigo Kitada,
Hiromi Kimura,
Toshihiko Yamaguchi,
Soichiro Yokota, Ryoji Maekura
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ABSTRACT: A 49-year-old-woman was diagnosed with tuberculosis of the left humerus. She had received treatment, including rifampicin, for tuberculosis 17 years previously. Treatment was begun with isoniazid, rifampicin, ethambutol, and pyrazinamide, but these were discontinued because of mild neutropenia and thrombocytopenia 2 weeks posttreatment. Rifampicin and ethambutol were readministered after a 4-day interruption; however, generalized purpura appeared several hours later. By the next day, her platelet count was reduced from 160 × 10(3) to 3 × 10(3)/μl. The patient improved rapidly after platelet transfusion and steroid treatment. Readministration of drugs other than rifampicin did not induce thrombocytopenia; therefore, thrombocytopenia was likely due to rifampicin.
Journal of Infection and Chemotherapy 04/2011; 17(2):288-90. · 1.80 Impact Factor
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ABSTRACT: We investigated the susceptibility to conventional and newer antimycobacterial agents including rifabutin (RBT) and novel fluoroquinolones (NFQs) among 48 clinical Mycobacterium avium complex (MAC) isolates from patients with sputum culture-positive MAC disease who were undergoing standard chemotherapy. RBT and NFQs were superior to conventional agents because of higher rates of susceptibility and lower minimum inhibitory concentration. NFQs showed cross-resistance among quinolones. In contrast, RBT did not show cross-resistance to RFP. Most clarithromycin-resistant or rifampicin-resistant cases were susceptible to RBT and NFQs. In conclusion, RBT and NFQs possess good in vitro antimicrobial activity among clinical isolates of culture-positive pulmonary MAC disease, which suggests that a combination of such microbiologically active agents may improve clinical effectiveness more than standard chemotherapy regimens.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 11/2010; 48(11):797-802.
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ABSTRACT: The objective of the present study was to evaluate the utility of tissue Doppler imaging for predicting the development of postoperative atrial fibrillation.
In this prospective observational study, we evaluated 126 patients with lung cancer who underwent a lobectomy during the 18-month period from August 2007 to January 2009. Preoperative evaluations for all patients included tissue Doppler imaging in addition to conventional echocardiographic analysis. The study end point was the development of postoperative atrial fibrillation.
Postoperative atrial fibrillation was identified in 29 (23%) patients, in whom significantly higher early transmitral velocity/tissue Doppler mitral annular early diastolic velocity values were noted compared with those seen in patients without atrial fibrillation (9.76 ± 2.3 vs 7.14 ± 1.7, P < .0001). The area under the receiver operating characteristic curve for early transmitral velocity/tissue Doppler mitral annular early diastolic velocity to predict postoperative atrial fibrillation after pulmonary resection for lung cancer was 0.83 (95% confidence interval, 0.74-0.92; P < .001). An early transmitral velocity/tissue Doppler mitral annular early diastolic velocity value of greater than 8 had a sensitivity of 90% and a specificity of 73% for predicting postoperative atrial fibrillation.
Postoperative atrial fibrillation after pulmonary resection might be associated with left ventricular diastolic dysfunction before surgical intervention revealed by using tissue Doppler imaging. Additional studies to establish the significance of tissue Doppler imaging as a tool to predict postoperative atrial fibrillation could contribute to improvements in lung cancer treatments.
The Journal of thoracic and cardiovascular surgery 10/2010; 140(4):764-8. · 3.41 Impact Factor
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Seigo Kitada,
Kazuo Kobayashi,
Yukiko Nishiuchi,
Kenji Fushitani,
Kenji Yoshimura,
Yoshitaka Tateishi,
Keisuke Miki,
Mari Miki,
Hisako Hashimoto,
Masaharu Motone,
Takeya Fujikawa,
Toru Hiraga, Ryoji Maekura
Chest 07/2010; 138(1):236-7. · 5.25 Impact Factor
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ABSTRACT: 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 (DeltaBorg scale/Deltaminute ventilation) correlated with the pH-slope (DeltapH/Deltaoxygen 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 (DeltaNE/Deltaoxygen 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.
The Journal of Physiological Sciences 05/2010; 60(3):187-93. · 1.61 Impact Factor
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ABSTRACT: To evaluate the usefulness of atrial natriuretic peptide (ANP) and brain B-type natriuretic peptide (BNP) for predicting postoperative atrial fibrillation (AF), we determined the changes in perioperative ANP and BNP levels in patients undergoing pulmonary resection for lung cancer.
This prospective observational study was conducted during the 10-month period from July 2007 to April 2008. Eighty patients with lung cancer underwent lobectomy, segmentectomy or wedge resection. Preoperative evaluations included spirometry and examinations of plasma ANP and BNP-levels, which were also determined on postoperative days 1, 3 and 7.
Postoperative AF was identified in 22 (28%) of the patients, and those had significantly higher preoperative ANP and BNP levels as compared with patients without AF. During the postoperative course, patients with postoperative AF also had significantly higher ANP and BNP-levels. The area under the receiver-operating characteristic curve for BNP to predict postoperative AF following pulmonary resection for lung cancer was 0.90 (95% confidence interval (CI), 0.82-0.98; p<0.001). A BNP value of 30pgml(-1) had a sensitivity of 77% and a specificity of 93% for predicting postoperative AF following pulmonary resection for lung cancer.
Preoperative BNP level seems to be an appropriate predictor of AF after pulmonary resection.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 11/2009; 37(4):787-91. · 2.40 Impact Factor
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ABSTRACT: 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).
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.
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 (DeltaBorg scale/Deltaminute ventilation) correlated with the pH slope (DeltapH/Deltaoxygen 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 (DeltaNE/Deltaoxygen uptake) (before the break point: r = 0.481, P = 0.0075; R = 0.784, P < 0.0001, after the break point).
In patients with IPF, exercise-induced acidosis and increases in circulating NE levels were associated with intensity of exertional dyspnoea.
Respirology 09/2009; 14(7):1020-6. · 2.42 Impact Factor
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Yukiko Nishiuchi,
Aki Tamura,
Seigo Kitada,
Takahiro Taguri,
Sohkichi Matsumoto,
Yoshitaka Tateishi,
Mamiko Yoshimura,
Yuriko Ozeki,
Narumi Matsumura,
Hisashi Ogura, Ryoji Maekura
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ABSTRACT: Medical treatment of pulmonary Mycobacterium avium complex (MAC) disease does not always provide curative effects and is frequently hampered by recurrence. This suggests the presence of a reservoir for MAC in the environment surrounding patients. We previously reported the recovery of MAC isolates from the residential bathrooms of outpatients. In the present study, to ascertain the colonizing sites and the possibility of an MAC reservoir in the bathrooms of patients, we tested the recovery and the genetic diversity of MAC isolates from 6 sites of specimens, including 2 additional sampling sites, inside the showerhead and the bathtub inlet, in the residential bathrooms of patients with pulmonary MAC disease. MAC isolates were recovered from 15 out of the 29 bathrooms (52%), including specimens from 14 bathtub inlets and 3 showerheads. Nearly half of these bathrooms (7/15) contained MAC strains that were identical or similar to their respective clinical isolates Additionally, in 5 out of 15 bathrooms, polyclonal colonization was revealed by pulsed-field gel electrophoresis. The results imply that colonization of MAC organisms in the bathrooms of MAC patients occurs predominantly in the bathtub inlets, and there is thus a risk of infection and/or reinfection for patients via use of the bathtub and other sites in the bathroom.
Japanese journal of infectious diseases 06/2009; 62(3):182-6. · 1.49 Impact Factor
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Yoshitaka Tateishi,
Yukio Hirayama,
Yuriko Ozeki,
Yukiko Nishiuchi,
Mamiko Yoshimura,
Jing Kang,
Atsushi Shibata,
Kazuto Hirata,
Seigo Kitada, Ryoji Maekura,
Hisashi Ogura,
Kazuo Kobayashi,
Sohkichi Matsumoto
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ABSTRACT: 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.
Microbial Pathogenesis 12/2008; 46(1):6-12. · 1.94 Impact Factor
