[Show abstract][Hide abstract] ABSTRACT: Factors that can interfere with the successful treatment of Mycobacterium avium lung infection have been inadequately studied. To identify a potent predictor of therapeutic responses of M. avium lung infection, we analyzed variable number tandem repeats (VNTR) at 16 minisatellite loci of M. avium clinical isolates. Associations between the VNTR profiling data and a therapeutic response were evaluated in 59 subjects with M. avium lung infection. M. avium lung infection of 30 subjects in whom clarithromycin-containing regimens produced microbiological and radiographic improvement was defined as responsive disease, while that of the remaining 29 subjects was defined as refractory disease. In phylogenetic analysis using the genotypic distance aggregated from 16-dimensional VNTR data, 59 M. avium isolates were divided into three clusters, which showed a nearly significant association with therapeutic responses (p 0.06). We then subjected the raw 16-dimensional VNTR data directly to principal component analysis, and identified the genetic features that were significantly associated with the therapeutic response (p <0.05). By further analysis of logistic regression with a stepwise variable-selection, we constructed the highest likelihood multivariate model, adjusted for age, to predict a therapeutic response, using VNTR data from only four minisatellite loci. In conclusion, we identified four mycobacterial minisatellite loci that together were associated with the therapeutic response of M. avium lung infections.
Clinical Microbiology and Infection 05/2013; · 4.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mycobacteria are among the most common causes of hypersensitivity pneumonitis (HP), but controversy persists with regard to the involvement of the infectious potency of the organism in mycobacterial HP (hot tub lung). This study aimed to establish a mouse model of hot tub lung to clarify its pathophysiology. Mice were exposed intranasally to formalin-killed Mycobacterium avium from a patient with hot tub lung (HP strain) or chronic pulmonary infection (non-HP strain), and bronchoalveolar lavage fluids and lung tissues were evaluated for allergic inflammation. Dead M. avium HP strain, but not non-HP strain, elicited marked HP-like pulmonary inflammation in wild-type mice. Although the inflammation was induced in mice lacking CD4 or CD8, the induction of HP-like responses was prevented in mice lacking myeloid differentiation factor (MyD)88 or Toll-like receptor (TLR)9. Cultured lung CD11c+ cells responded to M. avium in a TLR9-dependent manner, and reconstitution of TLR9-/- mice with lung CD11c+ cells from wild-type mice restored the inflammatory responses. Further investigation revealed that pulmonary exposure to M. avium HP strain increased the number of lung CD11b+ CD11c+ cells (dendritic cells) through TLR9 signalling. Our results provide evidence that hot tub lung develops via the mycobacterial engagement of TLR9-MyD88 signalling in lung CD11b+ dendritic cells independent of the mycobacterial infectious capacity.
European Respiratory Journal 01/2011; 38(3):688-701. · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In animal models and human trials, Lactobacillus gasseri OLL2716 (LG21) strain suppressed Helicobacter pylori colonization in the stomach. The aim of the present study was to clarify whether orally administered LG21 strain can enter the gastric mucus layer. Biopsy samples were taken from the gastric antrum and corpus of two healthy volunteers (H. pylori infected and non-infected) who drank yogurt supplemented with LG21 strains. DNA of LG21 and H. pylori in the mucus layer was detected using the laser-assisted microdissection and non-contact pressure catapulting (LMPC) method and the semi-nested PCR method with primer sets of RNA helicases of superfamily II gene-Insertion sequence for LG21 strain and those of ureA gene for H. pylori. In the volunteer with H. pylori infection, DNA fragments of LG21- and H. pylori-specific regions from both antrum and corpus were amplified, whereas in a non-infected volunteer, only the LG21 DNA from the antrum was amplified. The present study demonstrated that LG21 strains administered through a yogurt drink can enter into the gastric mucus layer. Our novel method may be useful in studying gastric probiotics for H. pylori infection.
Letters in Applied Microbiology 12/2006; 43(5):578-81. · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The major transmission route of Helicobacter pylori remains unclear. In this study, we examined H. pylori in the environmental waters in Japan.
A total of 24 water samples were collected from the upper, middle and downstream reaches of four Japanese rivers. Helicobacter pylori-specific DNA was examined using nested PCR. In addition, 224 children who lived near one river were studied by the stool antigen test for H. pylori prevalence. Helicobacter pylori DNA was detected in the water from the middle and downstream reaches of all four rivers, but not in the upper reaches. Helicobacter pylori was not found in cultured water samples with positive PCR results. Helicobacter pylori prevalence in the children examined was 9.8% for those living near the middle reaches and 23.8% nearby downstream, both of which were higher than the value in an area distant from the river (0%) (both, P < 0.01).
Difference in H. pylori prevalence in the children may be related to the presence of H. pylori in the river. The results of this study showed that H. pylori DNA is frequently present in river water from the middle and downstream reaches in which the human biosphere is embedded.
It is suggested that river water in the natural environment could be a risk factor for H. pylori transmission.
Letters in Applied Microbiology 02/2004; 38(6):517-21. · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the existence of Helicobacter pylori in cow's milk as one of the foods which most Japanese children eat.
Detection of H. pylori was demonstrated by the semi-nested polymerase chain reaction (PCR), a culture method and electron microscopy. Semi-nested PCR demonstrated the ureA gene of H. pylori in 13 of 18 (72.2%) raw milk samples and in 11 of 20 (55%) commercial pasteurized milk samples. Helicobacter pylori binding immunomagnetic beads with H. pylori-specific goat anti-H. pylori antibody was shown by electron microscopy in both raw and pasteurized milk positive for the ureA gene. Helicobacter pylori was cultured in one raw milk sample, whereas it was not cultured in pasteurized milk samples.
There is a possibility that cow's milk is a transmission vehicle in childhood H. pylori infection, although we failed to confirm the survival of H. pylori in pasteurized milk.
Letters in Applied Microbiology 02/2002; 35(6):504-7. · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the antibacterial activity of 12 antibiotics, inclusive of four carbapenems, against 167 strains of respiratory pathogens isolated between 1999 and 2000. Thirty strains of methicillin-susceptible Staphylococcus aureus (MSSA), 28 strains of methicillin-resistant S. aureus (MRSA), 11 strains of penicillin-susceptible Streptococcus pneumoniae (PSSP), 29 strains of penicillin-resistant S. pneumoniae (PRSP), 30 strains of Pseudomonas aeruginosa, 14 strains of Moraxella catarrhalis, and 25 strains of Haemophilus influenzae were examined. The minimum inhibitory concentration (MICs)50/90 (microg/ml) of imipenem, panipenem, meropenem, and biapenem against the clinical isolates obtained between 1999 and 2000 were: 0.06/0.25, 0.12/0.25, 0.12/0.25, and 0.12/0.25, respectively, against MSSA; 16/32, 16/32, 16/32, and 8/32 against MRSA; < or = 0.015/0.06, < or = 0.015/0.03, 0.03/0.12, and < or = 0.015/0.06 against PSSP; 0.12/0.25, 0.03/0.06, 0.25/0.5, and 0.12/0.25 against PRSP; 1/8, 2/8, 0.5/2, and 2/16 against P. aeruginosa; 0.06/0.06, 0.03/0.06, < or = 0.015/0.06, and 0.06/0.12 against M. catarrhalis; and 1/4, 1/4, 0.12/0.25, and 2/4 against H. influenzae. A comparison of the antibacterial activity of the four carbapenems with that found in our previous studies showed no significant difference in the susceptibility of clinical isolates, except for a slight decrease in the susceptibility of MSSA. Carbapenems have remained effective for severe infections. The MIC data showed that imipenem and panipenem were more active than meropenem and biapenem against gram-positive bacteria, and that meropenem and biapenem were more active than imipenem and panipenem against gram-negative bacteria. As only meropenem had an MIC90 below the breakpoint of pneumonia against all species except MRSA, meropenem was considered to be the most potent of the four carbapenems studied.
Journal of Infection and Chemotherapy 01/2002; 7(4):267-71. · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 60-year-old female, diagnosed as scleroderma, was referred to our hospital because of symptoms of common cold and abnormal findings on a chest X-ray. The chest X-ray and CT scan revealed a mass in the left upper field, suspected to invade left anterior chest wall. Moreover, fibrotic changes were observed in the lung field. Cytology by bronchofiberscopy showed squamous cell carcinoma. Evaluation of pulmonary function, including unilateral pulmonary artery occlusion test (UPAO), revealed possibility of lung resection. Subsequently, pneumonectomy with combined resection of left 1st rib was performed. Postoperative course was uneventful and she was discharged. She was admitted again four months after the operation with appetite loss and body weight loss. Further examinations revealed arrhythmia, renal failure, pancreatitis and liver metastasis. Her general conditions grew worse and she died five months after the operation. In conclusion, UPAO was a useful method to determine the functional lung resectability for the case with scleroderma. However, effects of surgical stress for the development of scleroderma remain to be elucidated.
Kyobu geka. The Japanese journal of thoracic surgery 08/2001; 54(7):606-9.
[Show abstract][Hide abstract] ABSTRACT: A 70-year-old female was operated on for extradural spinal cord tumor in 1982. Microscopic examination revealed the tumor as paraganglioma. Tumor recurred at paravertebral twice in 1985 and 1989, and they were also resected. In 1995, her chest X-ray film showed round tumor in the right upper field. Exploratory open lung biopsy was performed in 1996, and right upper lobectomy was performed according to for malignant lung tumor because intra-operative microscopic findings showed carcinoid or lung metastasis of paraganglioma. Chest wall tumor at paravertebral was resected at the same time. Postoperative microscopic examination revealed the tumors were same as operated paraganglioma. The 2nd thoracotomy was done in 1999, and two chest wall tumors and a pulmonary nodule in right S8 segment were resected. They were recurrence and pulmonary metastasis of paraganglioma. Now 18 years after initial operation, she is out of hospital in tumor free.
Kyobu geka. The Japanese journal of thoracic surgery 08/2001; 54(7):610-3.
[Show abstract][Hide abstract] ABSTRACT: Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy associated with pulmonary vascular remodeling. Because hypoxia might promote generation of oxidative stress in vivo, we hypothesized that oxidative stress may play a role in the hypoxia-induced cardiopulmonary changes and examined the effect of treatment with the antioxidant N-acetylcysteine (NAC) in rats. NAC reduced hypoxia-induced cardiopulmonary alterations at 3 wk of hypoxia. Lung phosphatidylcholine hydroperoxide (PCOOH) increased at days 1 and 7 of the hypoxic exposure, and NAC attenuated the increase in lung PCOOH. Lung xanthine oxidase (XO) activity was elevated from day 1 through day 21, especially during the initial 3 days of the hypoxic exposure. The XO inhibitor allopurinol significantly inhibited the hypoxia-induced increase in lung PCOOH and pulmonary hypertension, and allopurinol treatment only for the initial 3 days also reduced the hypoxia-induced right ventricular hypertrophy and pulmonary vascular thickening. These results suggest that oxidative stress produced by activated XO in the induction phase of hypoxic exposure contributes to the development of chronic hypoxic pulmonary hypertension.
Journal of Applied Physiology 05/2001; 90(4):1299-306. · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is a RNA-binding protein of Mr 37,000. We previously reported that hnRNP B1 was specifically overexpressed in the nuclei of human lung cancer cells, particularly in squamous cell carcinoma (E. Sueoka et al., Cancer Res., 59: 1404-1407, 1999). We extended this study to determine whether hnRNP BL was overexpressed in roentgenographically occult cancers of the lungs and premalignant lesions of squamous cell carcinomas, such as bronchial dysplasia. The additional object of our study was to examine the usefulness of hnRNP B1 as a potential diagnostic marker for squamous cell carcinoma of various organs, such as the oral cavity and esophagus in humans. Surgically resected specimens of bronchial dysplasia, lung cancers, and various human squamous cell carcinomas, collected at two hospitals in Japan, were subjected to immunohistochemical staining with anti-hnRNP B1 antibody. Overexpression of hnRNP B1 protein was observed in 100% of stage I lung cancer tissues, but it was not found in normal bronchial epithelium. Squamous cell carcinoma of the lungs showed stronger staining than other histological types, and elevation of hnRNP B1 was found in both roentgenographically occult lung cancers and bronchial dysplasia. Furthermore, cytological examination with anti-hnRNP B1 antibody detected cancer cells in sputum, suggesting the potential of hnRNP B1 protein as a new biomarker for the very early stage of lung cancer in humans. Because strong staining of hnRNP B1 was also observed in various squamous cell carcinomas of oral and esophageal tissues as shown in our recent reports, overexpression of hnRNP B1 seems to be a common event in the carcinogenic processes of squamous cell carcinoma. These results suggest that hnRNP B1 protein could be a useful diagnostic biomarker for both the very early stages of lung cancer and various squamous cell carcinomas in humans.
Cancer Research 04/2001; 61(5):1896-902. · 8.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The number of patients with lung cancer is increasing. This study was undertaken to realize the probability, fate and management of acute fatal postoperative complications. Since interstitial pneumonia was one of the most fatal postoperative complications, to know its incidence and fate is very important.
A total of 2667 patients who underwent thoracotomy caused by malignant tumors during the past 17 years were reviewed and studied. We performed investigations on medical records, chest X-rays, whole-body CT films, operative records and pathological specimens for all inpatients.
Nineteen patients died in hospital 30 days after thoracotomy (operative death). Nine patients died in hospital more than 31 days after thoracotomy (hospital death). Eight cases out of 28 patients (operative and hospital deaths) developed and finally died by interstitial pneumonia. Each case was treated with steroids, neutrophil-elastase inhibitor, and/or immunosuppressive agents. These patients could not be selected by any preoperative laboratory examination, such as preoperative pulmonary function tests, serum biochemistry tests, and chest X-ray or CT films. Interstitial pneumonia as a complication of postoperative stage, was fatal and once developed, it was very difficult to save their lives.
Since we reported the cases who died from acute postoperative complications, especially interstitial pneumonia, we could not present effective management. However, in this report, several therapeutic trials that may solve the problems of acute postoperative interstitial pneumonia were proposed.
The Journal of cardiovascular surgery 03/2001; 42(1):125-9. · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiopulmonary bypass (CPB) and diseased lung ventilation were presented as new methods of oxygenation during carinal reconstruction. Two cases of left sleeve pneumonectomy (SP) were performed for bronchial gland carcinoma through clamshell incisions. Adequate oxygenation and excellent operative fields were provided by CPB in both patients. The postoperative courses of these patients were uneventful, although they developed temporary pulmonary edema that needed mechanical ventilation and appropriate diuretics for several days. One case of patient with squamous cell carcinoma after chemotherapy was successfully treated by right SP through midline sternotomy. Adequate oxygenation and excellent operative fields was obtained by diseased right lung ventilation in this patient. The postoperative course of the patient was uneventful without mechanical ventilation support. These procedures of oxygenation in this paper are considered to be safe and effective methods for carinal reconstruction.
Kyobu geka. The Japanese journal of thoracic surgery 02/2001; 54(1):24-30.
[Show abstract][Hide abstract] ABSTRACT: Reconstruction of chest wall using myocutaneous flap has been performed in 2 cases. A 72-year-old female referred to our hospital for locally recurrent left breast cancer without any distant metastases. The other patient was a 77-year-old female, having locally recurrent liposarcoma of the left lateral chest wall. Chest wall was resected with wide margin of normal tissue, and myocutaneous flaps of latissimus dorsi were used for reconstruction of skin defect (13 x 8 cm and 14 x 10 cm) in both cases. Although additional split-thickness skin graft was required for one of them, myocutaneous flaps were useful for the reconstruction of widely defected chest wall. By using this technique, wider margin can be obtained, which could decrease the risk for local recurrence of malignant tumor.
Kyobu geka. The Japanese journal of thoracic surgery 01/2001; 53(13):1081-4.
[Show abstract][Hide abstract] ABSTRACT: Although a few reports indicated some benefit to survival, the effect of adjuvant therapy for the patients with resected lung cancer was still controversial. The aim of our study was to evaluate survival advantage of CDDP-based adjuvant therapy compared with short-term immunochemotherapy.
Experimental design: prospective randomized trial. Patients: from 1990 through 1994, 94 patients were registered. Forty-seven patients were randomly assigned to each group, i.e., CDDP-based therapy group (CB Group, CDDP+VDS+tegafur+OK-432 or CDDP+OK-432+mediastinal irradiation) or immunochemotherapy group (IC Group, tegafur+OK-432). Patients in both groups were followed at 4-month intervals with the routine follow-up program of our department.
No significant difference was observed between the patients' characteristics of two groups. Compliance of the regimen in each group was 79% in CB Group and 85% in IC Group. No treatment-related death was observed. Five-year survival rates of CB Group and IC Group were 49% and 51%, and 5-year disease-free survival rates were 46% and 44%, respectively. There were no statistical differences between the two groups. Furthermore, no survival differences could be found between CB Group and IC Group in any subgroup of patients.
Both of these regimens were feasible. However, we have not observed any survival benefit in the CB Group in any subgroup, so far. Induction therapy, new chemotherapeutic agents, or anti-angiogenetic a agents may improve the survival of surgically treated lung cancer patients.
The Journal of cardiovascular surgery 01/2001; 41(6):935-9. · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 21-year-old female was admitted to our hospital because of high fever, neck swelling, and dyspnea. She was diagnosed as descending necrotizing mediastinitis (DNM) extended from odontogenic infection. On the day of admission, she underwent cervical drainage. Next day, the CT scan showed an abscess below the tracheal bifurcation and bilateral pleural effusion. Mediastinal drainage was performed through a right thoracotomy, and a left thoracic tube was inserted. Anaerobic Peptostreptococcus was found with bacteriological culture. After the mediastinal drainage, bilateral thoracic irrigation was performed through the thoracic tubes. Left thoracic tube was removed on the 8th day and right one was removed on the 20th day after the thoracotomy. She was discharged on the 42nd day. DNM is relatively rare, but it is lethal disease with high mortality. Immediate and sufficient mediastinal drainage is indispensable for the disease.
Kyobu geka. The Japanese journal of thoracic surgery 12/2000; 53(12):1058-61.
[Show abstract][Hide abstract] ABSTRACT: We investigated the indications for lung transplantation (LTx) in Japan and discussed questions regarding the current Japanese criteria of LTx. This study examined 37 patients referred to our institute for LTx. Among these patients, there were 11 cases of primary pulmonary hypertension (PPH), 6 of lymphoangiomyomatosis (LAM), 4 of Eisenmenger's syndrome, 3 of bronchiolitis obliterans, 2 each of bronchiectasis, idiopathic pulmonary fibrosis (IPF), and pneumoconiosis, and 7 of other diseases. The most frequent age group was 30-39 years (12 cases, 32.4%), and more than half of the patients were female (22 cases, 59.5%). The regions of residence of the patients were Tohoku (19 patients), Kanto (16), and Chubu (2). Patients were referred from all over eastern Japan. On evaluation, LTx was contraindicated in 5 cases, in 4 of which mechanical ventilation had been installed before consultation with us. Six patients died before registration on the Japan Organ Transplant Network (JOT). 6 transplant candidates were registered with JOT, but one (PPH) died after 6 months of waiting, and one (LAM) received a lung transplant from a brain dead cadaver donor. We propose to reform and clarify the Japanese criteria for LTx-both indications and contraindications, to include such indications as a survival probability of less than two years, and such contraindications as mechanical ventilation. Early consultation at LTx centers was hoped for, in accordance with the International Guidelines and a transplant window.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 12/2000; 38(11):839-43.
[Show abstract][Hide abstract] ABSTRACT: Poly (L-lactide) sternal coaptation pin has been developed as an assistant material for the fixation of sternum. We used the novel material to a patient who underwent median sternotomy. A 21-year-old male was suspected to have invasive thymoma in the anterior mediastinum. The median sternotomy was indicated as an approach for the resection of tumor. Tumor was completely resected and there was no invasion to sternum. For the fixation of sternum, three poly (L-lactide) sternal coaptation pins were inserted in the bone marrow of sternum and five stainless steel wires were used as conventional procedure. Sternum was adapted without slippage and no complication from the material was observed in the post-surgical period. The application of poly (L-lactide) sternal coaptation pin is a good option for ensuring the fixation of sternum.
Kyobu geka. The Japanese journal of thoracic surgery 12/2000; 53(12):1011-2.
[Show abstract][Hide abstract] ABSTRACT: The significance of limited resections, including wedge resection and segmentectomy, remains controversial because of their curability rates. In the current study, the objective was to determine a strategy for the treatment of patients with roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC) based on the pathologic findings from 184 patients with ROSCC who underwent resection.
In Miyagi Prefecture, 1422 patients with lung carcinoma were diagnosed during a mass screening program between 1982 and 1995. Among them, 236 patients had ROSCC, and 184 patients with ROSCC underwent pulmonary resection followed by systemic lymph node dissection.
Pathologically, only 0.9% of the ROSCCs that were within the range of endoscopic visibility were revealed to have lymph node involvement, whereas 13% of patients with extracartilage invasion had lymph node involvement. Early ROSCC, which means ROSCC that is limited within the cartilaginous layer and is without lymph node involvement, comprised 90% of ROSCCs that measured <10 mm in longitudinal extension, comprised 77% of ROSCCs that measured 10-29 mm in longitudinal extension, and comprised 33% of ROSCCs that measured >30 mm in longitudinal extension. Eighty-nine percent of the tumors with lymph node involvement had extracartilaginous invasion. The 3-year survival rate of patients after undergoing photodynamic therapy was 100% when their tumor was regarded as early ROSCC (i.e., within 10 mm in longitudinal extension and within the range of endoscopic visibility). To date, 18 patients with ROSCC underwent segmentectomy, and all of these patients are alive without tumor recurrence. The incidence rate of multiple lung carcinomas, including synchronous and metachronous tumors, in patients with ROSCC was 22%.
The authors concluded the following: 1) Patients with lesions that are within the range of endoscopic visibility and that measure <10 mm in longitudinal extension are candidates for photodynamic therapy. 2) Patients with lesions that are beyond the range of endoscopic visibility or that measure >10 mm in longitudinal extension are candidates for segmentectomy as long as intraoperative examination shows a tumor free bronchial stump and negative lymph nodes 11-13. 3) Patients with lesions that show bronchial obstruction or extrabronchial invasion should undergo standard resection.
Cancer 12/2000; 89(11 Suppl):2445-8. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the present condition of lung transplant candidates and the familiarity of doctors in eastern Japan by questionnaire. We shipped questionnaires to 614 hospitals in the Hokkaido district, the Tohoku district, the Kanto district and Niigata Prefecture, a received responses from 216 departments (200 hospitals). The percentage of respondents was 32.6%. There were 191 lung transplant candidates, 97 men and 94 women, in the past two years. Moreover, there were 45 patients with primary pulmonary hypertension (PPH), 38 with idiopathic pulmonary fibrosis, 23 with pulmonary emphysema, 20 with pulmonary lymphangiomyomatosis, among others. Currently, however, there are 88 patients who are lung transplant candidates, a large number, in eastern Japan. On the other hand, only 38 of 68 departments had informed their patients about lung transplantation. It was a lamentable result for transplant surgeons, and points urgently to the importance of giving information about lung transplantation.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 11/2000; 38(10):762-9.