Search

Copyright of Rigakuryoho Kagaku is the property of International Press Editing Center Incorporation and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A 62-year-old woman suffering from pulmonary Mycobacterium avium complex (MAC) disease was admitted to our hospital with fever, visual impairment, and lower limb weakness. MRI detected lesions in the optic chiasm and spinal cord extending the length of 6 vertebrae. The anti-aquaporin 4 (AQP4) antibody titer determined by ELISA was elevated to 8.3 IU/l. On the basis of these findings, the patient was diagnosed as having neuromyelitis optica (NMO), when chest CT also demonstrated exacerbation of pulmonary lesions. Methylprednisolone pulse therapy and double-filtered plasma exchange ameliorated the symptoms, and the EDSS score improved from 8.5 to 6.5. Six months later, visual impairment recurred, although ELISA showed that the anti-AQP4 antibody titer had become undetectable. Also, the CSF interleukin-6 (IL-6) level was elevated to 34.8 pg/ml. There have been few reports of NMO associated with pulmonary MAC disease. An increase of IL-6 is considered to exacerbate the clinical picture of NMO, whereas it may suppress progression of the pulmonary MAC disease. Exacerbation of the pulmonary MAC disease and the following internal counteraction with IL-6 may have resulted in a NMO relapse. The present patient was therefore administered eculizumab but not satralizumab, a humanized anti-IL-6 receptor antibody, for prevention of NMO recurrence.

Secondary spontaneous pneumothorax associated with pulmonary Mycobacterium avium complex (MAC) infection is often difficult to treat. Pneumothorax associated with pulmonary MAC is characterized by a large fistula with a cavity or bronchodilation, and pleural thickening due to pleurisy. Herein, we report two cases of pneumothorax with pulmonary MAC successfully treated by minimally invasive thoracoscopic intra-fistula filling with a suture closure method. At operation, after fully filling the fistula with a polyglycolic acid (PGA) sheet and fibrin glue, the fistula was sutured with covering the PGA sheet and fibrin glue. Postoperative course was uneventful and both patient could discharged from the hospital.

A man in his 70s was referred to our hospital for evaluation of low-grade fever, weight loss, and liver dysfunction. Serological tests for viral hepatitis or autoimmune diseases were negative. No significant findings were observed on whole-body computed tomography (CT). Histopathologic examination of a liver biopsy sample revealed a non-caseating granuloma with acid-fast bacillus using the Ziehl-Neelsen stain. Serum Mycobacterium avium complex (MAC) antibody was positive. We started treatment for pulmonary MAC disease. His clinical condition and liver function improved within two months. He was diagnosed with liver MAC disease.

The number of patients with nontuberculous mycobacterial (NTM) disease is reportedly increasing both in Japan and worldwide. NTM diseases are classified into disseminated and pulmonary diseases based on their clinical characteristics. These two types of NTM diseases are thought to be controlled by different mechanisms. Disseminated NTM disease is caused by a defect in signal transduction of Th1 cellular immune responses, including the IFN-γ/IL-12 axis. The precise molecular mechanisms of disseminated NTM disease are understood in detail. Pulmonary NTM disease progression is associated with both bacterial factors as well as host factors. Furthermore, it is suggested that some susceptibility genes for NTM diseases may also exist. A previous study on the susceptibility genes for pulmonary NTM disease was performed using Single Nucleotide Polymorphism (SNP) analysis and microsatellite marker analysis. However, a number of challenges remain in terms of the reproducibility. The emergence of next generation sequencing enables genome-wide analysis, and further studies on the susceptibility genes for pulmonary NTM disease are expected in the future.

A 45 year-old-man was admitted to our hospital because of discomfort in his left scrotum. He had a left testicular tumor. We performed high orchiectomy and pathological findings revealed testicular cancer. He was treated with bleomycin, etoposide and cisplatin. Computed tomography showed a new mass in the left lung after 3 cycles of the chemotherapy. Because of its rapid growth, the tumor was thought to be a metastasis lesion of testicular cancer or pulmonary infection. Transbronchial lung biopsy showed an invasion of multinucleated giant cells and granuloma. The culture and polymerase chain reaction of the bronchial sputum were positive for myobacterium avium-complex (MAC). From these findings, the left lung tumor was diagnosed as pulmonary MAC disease. He received partial resection of the left lung and the lesion was diagnosed as granuloma. There was no recurrence of testicular cancer or pulmonary disease after the surgery.

A 70-year-old woman was admitted to our hospital on suspicion of liver tumor on regular abdominal ultrasonography. The abdominal ultrasonography identified a solitary, low-echoic lesion measuring 17mm in diameter in S7. This lesion was not enhanced in any phase of contrast-enhanced computed tomography (CT), and thus we performed a liver biopsy. Histopathological examination revealed a caseating granuloma. The chest CT showed pulmonary nodules, and Mycobacterium intracellulare was cultured from the bronchoalveolar lavage fluid. We diagnosed the individual with a Mycobacterium avium complex infection, and suspected that this was the cause of the solitary liver lesion.

In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of. certain types of suppressor macrophage populations. During the course of infections due to pathogenic mycobacteria, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This review describes the immunological properties of M1- and M2-type macrophages generated in hosts with certain microbial infections including mycobacteriosis and those generated in tumor-bearing animals. Particularly, this paper highlights the immunological and molecular biological characteristics of M1 and M2 macrophage populations, which are induced by mycobacterial infections

Mycobacterium avium complex (MAC) were the most frequently isolated (about 80%) and most common cause of lung nontuberculosis. Its rate of infection is globally increasing, especially in Japan. In this situation, it is urgently needed to provide scientific evidences and develop therapeutic interventions in MAC infections. Recently, more and more patients are elderly women with no history of smoking, and they have reticulonodular infiltrates and patchy bilateral bronchiectasis. However the prognostic and intractable factors of MAC infections are poorly known. In this symposium, we address five novel strategies for MAC infection, concerning the more accurate incidence and prevalence rates compared with other countries, host defense associated with Th1/Th17 balance, route of MAC infection related soil exposure, MAC IgA antibody as a diagnosis maker, and improved chemotherapy including aminoglycoside or new quinolone. Appropriate clinical intervention may help to reduce the prolongation of MAC infection or enhance the activity of chemotherapy for the improved control of MAC. Below are the abstracts for each of the five speakers. 1. Review of current epidemiological study of pulmonary nontuberculous mycobacterial disease in Japan and the rest of the world: Kozo MORIMOTO (Respiratory Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association) The studies on pulmonary nontuberculous mycobacterial (NTM) disease prevalence were started in early 1970s in Japan by the Mycobacteriosis Research Group of National Chest Hospitals. They were followed by a questionnaire survey in 1990s, by the National Tuberculosis and NTM Survey in late 1990s, and recently by the questionnaire surveys conducted by the NTM Disease Research Committee. The latest data in Japan (from 2007) indicated a morbidity rate of 5.7 per 100,000 population. Deaths from NTM disease were reported for the first time in 1970 and showed a marked, steady increase until 2007, with 912 deaths in that year. We estimated NTM prevalence in our country in 2005 to be 33-65/100,000 using death number and the 1-2% fatality rate obtained from in our hospital. Epidemiologic study conducted by some regions, states and countries estimated the incidence or prevalence of NTM by unique methods in each. Although the microbiologic criteria of diagnosis is attractive to get information of prevalence, we think the most reliable method is to use the health insurance claims that should be done in future in Japan. 2. The elucidation of the pathogenesis of pulmonary MAC disease by using gene modified mice: Masashi MATSUYAMA, Yukio ISHII, Nobuyuki HIZAWA (Division of Respiratory Medicine, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba), Kenji OGAWA (Department of Clinical Research, National Hospital Organization Higashi Nagoya National Hospital) Thl immune responses are associated with protective immunity to intracellular pathogens. T-bet is the master regulator for Thl cell differentiation. We therefore investigated the role of T-bet in the host defense against pulmonary MAC infection using T-bet knockout (T-bet-/-) mice and T-bet overexpressing (T-bet tg/tg) mice. Pulmonary MAC infection was induced by intratracheal instillation with 1 X 10(7) CFU of Mycobacterium avium subsp. hominissuis. The degrees of pulmonary inflammation and the number of organisms were much enhanced in T-bet-/- mice than in wild-type mice and T-bet tg/tg mice after MAC infection. A significant decrease in Th1 cytokines and increase in Th17 cytokines were observed in the lungs of T-bett-/-mice, compared with wild-type mice and T-bet tg/tg mice. Interestingly, however, the level of Th2 cytokines was not different among mice genotypes in response to MAC. These findings indicate that T-bet plays a central role in controlling MAC disease progression, through the regulation of both Th1 and Th17, but not Th2 responses. 3. Route of infection in Mycobacterium avium-intracellulare complex disease: Yutaka ITO (Department of Respiratory Medicine, Department of Infection Control and Prevention, Kyoto University) Environmental exposure is considered to be the primary route for Mycobacterium avium-intracellulare complex (MAC) infection. MAC is isolated from drinking water distribution systems, bathroom and showerheads and the genetic relatedness of clinical isolates from MAC patients with water isolates have been reported. We reported that patients with pulmonary MAC disease had significantly more soil exposure (>2 per week) than noninfected control patients after adjustments for the potential confounding diseases and conditions in pulmonary MAC disease. Moreover, we found six pairs of clinical isolates and corresponding soil isolates with identical variable numbers of tandem repeats profiles among patients with high soil exposure, suggesting that residential soils are a likely source of pulmonary MAC infection. 4. Clinical data analysis of Mycobacterium avium complex serodiagnosis kit: Yuta HAYASHI (Department of Respiratory Medicine, National Hospital Organization Higashi Nagoya National Hospital), Taku NAKAGAWA, Kenji OGAWA (Department of Clinical Research, National Hospital Organization Higashi Nagoya National Hospital) Mycobacterium avium complex (MAC) serodiagnosis kit was covered by health insurance in August 2011 in Japan, but experience with this kit in daily clinical practice is still scarce. We analyzed the clinical data of MAC serum diagnostic kit in our hospital. Considering the high diagnostic performance of this kit (specificity 92.9%), that can also be incorporated into the diagnostic criteria. However it should be noted that there can be false-negative even in patients with active pulmonary MAC. Although this test is also expected usefulness as a marker of disease activity, at the present time should be kept for reference. 5. Clinical effect of combined chemotherapy containing aminoglycoside or new quinolone antibiotics for Mycobacterium avium complex disease: Yosihiro KOBASHI, Mikio OKA (Department of Respiratory Medicine, Kawasaki Medical School) Because it was possible to administrate CAM 800 mg/day for the treatment of Mycobacterium avium complex (MAC) disease after 2008, we compared the clinical effect of combined chemotherapy (RFP, EB, CAM 800 mg/day) containing aminoglycoside (SM) and combined chemotherapy (RFP, EB, CAM 400 mg/day or 600 mg/day) containing SM before 2007. Subsequently, the latter treatment was significantly better in the sputum conversion rate and clinical improvement such as clinical symptoms or radiological findings than the former treatment. Concerning the side effects or abnormal laboratory findings, although gastrointestinal symptoms were frequently appeared in the latter period, there was no significant difference between both periods.

Unlabelled: The presence of a cavitary lesion is important factor for pulmonary Mycobacterium avium complex (MAC) treatment., Purpose: Clarify the location of pulmonary MAC cavities and the changes of these cavities., Material & Methods: We observed the location of 56 cavities in 48 patients with pulmonary MAC on computed tomography (CT) images and evaluated the changes in the external diameter of these cavities before and after treatment with a regimen of rifampicin (RFP), ethambutol (EB), and clarithromycin (CAM)., Results: These pulmonary MAC cavities were significantly frequently located in segments S2, S3, S9, and S10, and their distribution was different from that of pulmonary tuberculosis at the patients' initial visit. Examination of the external diameters of these cavities after chemotherapy showed that 42.1% of cavities expanded, 0.2% were unchanged, and 56.1% shrank. The mean diameter of the cavities decreased significantly (by 3.1 mm) after chemotherapy. The mean size of the cavities in the upper lobe did not differ from the mean size of the cavities in the lower lobe before chemotherapy; however, the reduction in cavity size was significantly higher in the lower lobe cavities. In 14 cases, the cavities disappeared under the standard chemotherapy regimen in an average of 971 days, and there was a tendency for lower lobe cavities to disappear more rapidly.

A 76-year-old woman was admitted to our hospital in October 2007 because of fever and anorexia. Chest computed tomography demonstrated consolidation and reticular shadows in the right middle lobe and left lingula. Pulmonary nontuberculous mycobacteriosis was diagnosed based on isolation of Mycobacterium intracellulare from her sputum. Her symptoms, which included fever, were improved by chemotherapy with clarithromycin and ethambutol, but the treatment was halted due to adverse effects. Subsequently, she complained of lumbago from April 2008, and spinal osteomyelitis from the T-4 through T-5 vertebral bodies was suspected based on the findings of magnetic resonance imaging. Spinal osteomyelitis due to Mycobacterium intracellulare was diagnosed based on isolation of the bacteria from a tissue culture taken from the vertebral body. Surgery was performed after chemotherapy with clarithromycin, rifampicin and moxifloxacin. Spinal osteomyelitis caused by nontuberculous mycobacterium infection should be considered due to a worldwide increase in reported cases of pulmonary nontuberculous mycobacteriosis.

A 70-year-old man was admitted to our hospital for examination of an abnormal shadow found on a chest radiograph. Chest CT showed a nodular shadow in the left upper lobe S1+2. We diagnosed non-small cell lung cancer (squamous cell carcinoma) clinical stage T4N2M1. Chemotherapy consisting of carboplatin and weekly paclitaxel was begun. After the second course of chemotherapy, another nodular shadow with small cavities in the left lower lobe S6 was seen, and which then increased in size. Bronchial lavage revealed a diagnosis of non-tubercular mycobacteriosis (Mycobacterium intracellulare). Anti-NTM chemotherapy consisting of rifampicin, ethambutol and clarithromycin was started in addition to anticancer chemotherapy, without severe side effects. Although there are some reports of the co-occurrence of lung cancer and non-tuberculous mycobacteriosis, this apparently rare case involved the appearance of a solitary nodule with a cavity caused by pulmonary non-tuberculous mycobacteriosis during anticancer chemotherapy.

Mycobacterium avium complex (MAC) causes respiratory tract infections and develops granulomatous lesions in the alveolar areas and bronchioles in humans. In contrast with the above, the intestinal tract is the primary infection site of immunocompromised hosts, such as patients with acquired immune deficiency syndrome (AIDS), or animals, such as pigs. Recent studies have revealed that hosts with hereditary dysfunction of mediators in the Th-1 cascade as well as hosts with a high titer of auto-antibodies against interferon-gamma are susceptible to MAC, and such hosts facilitate dissemination of MAC. However, their disseminated lesions are formed mainly in the lung or in soft tissues, and the mechanism of development of MAC in such host may be different from that of AIDS-related MAC infection. In this review, we specifically discuss the development mechanism of disseminated MAC disease in recently-identified several pathological conditions.

Recently, the clinical importance of nontuberculous mycobacteria (especially, Mycobacterium avium complex [MAC] respiratory infection) has been increasing. In addition, an official ATS/IDSA statement about diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases has been published in February, 2007. In this review article, essence of this official statement will be introduced. In MAC respiratory infection, (i) primarily fibrocavitary disease, (ii) nodular/bronchiectatic disease, and (iii) hypersensitivity-like disease are identified, and (i) and (ii) are clinically important. Primarily fibrocavitary disease is characterized by cavitary lesions in upper lung fields in elderly subjects, smoking patients, or patients with pneumoconiosis. Nodular/bronchiectatic disease is characterized by centrilobular nodules and diffuse bronchiectases in the right middle lobe and the left lingula in middle-aged women. In addition, disseminated MAC disease in patients with acquired immunodeficiency syndrome should be considered. Further studies concerning transmission route as well as mechanism of MAC disease should be performed.

Mycobacterium avium complex (MAC) infection has been giving major impact on human health. MAC infection is also one of zoonosis transmittable from environmental reservoirs to domestic animal such as pig, and from wildlife to human. Although the relationship between pig MAC infection and human MAC infection has been suggested, it has not been clarified about difference of pathogens, differences in the pathogenesis of the disease, and differences in pathological findings between them. As one of zoonosis, hog farms suffer from the epidemic in pig population and it may causes huge economical loss. At the same time, from pig to human transmission of MAC has been worried. Therefore, the control of MAC infection among hog farms is a very important issue both for pig industries and for human public health. We have demonstrated that the specific MAC strains can spread through pig market in the main island of Okinawa. In pig MAC infection, pathogens are infected orally, and granulomatous lesions are formed in abdominal lymph nodes. Subsequently, it spreads lymphogenously or hematogenously and forms disseminated disease. Pathologically, calcified lesion was formed within several months. These findings are quite different from human MAC disease, in which the infection was caused by inhalation, and form granulomatous lesions in lungs, and rarely cause lymph node swellings. Since the pathogenesis of human MAC respiratory infection has not been well clarified, it may be very important to examine the mechanism of pig MAC infection to find out some clues to explain the mechanism of human MAC infection.

A 56-year-old man in whom reticulonodular shadows had been noted on a previous chest radiography study was admitted to our hospital with complaint of exertional dyspnea in March 2004. His thoracic computed tomography (CT) showed diffuse ground-glass opacities and multiple centrilobular small nodules in both lung fields. Lymphocytes occupied a high proportion in the cells recovered from the bronchoalveolar lavage fluid. These findings were compatible with those for hypersensitivity pneumonitis. Histopathological findings observed in the video-assisted thoracoscopic surgical biopsy specimens included necrotizing granulomas, organizing pneumonia associated with collective epithelioid cell granulomas without necrosis, and alveolar septal thickening with lymphocyte infiltration that showed a centrilobular distribution. These findings were also compatible with those for hot tub lung. Further information that supported the diagnosis were the identifications of Mycobacterium avium complex in his sputum by acid-fast bacteriological culture as well as positive for Mycobacterium avium polymerase chain reaction in lung specimen. He responded well to corticosteroid therapy, resulting in improvement in his clinical condition as well as in his chest radiographs. He was later put on an antituberculosis therapy, and the corticosteroid therapy was discontinued. This led to an exacerbation of his disease and corticosteroid therapy was restarted. It is not long time since the disease was first recognized, and thus few cases have been reported in Japan. Our report may provide valuable information on the disease in this country.

A 75-year-old woman with Mycobacterium avium complex (MAC) pulmonary disease who had been treated by drug therapy for 7 years was admitted on an emergency basis for hemoptysis. Through the previous 7 years, her sputum cultures had been positive for MAC, and her clinical symptoms and examinations, such as chest X-ray and computed tomography, revealed that her condition had worsened. The lesions spread over the right middle lobe, segment 3 (S3) in the right upper lobe, and segment 6 (S6) in the right lower lobe, however, no lesions were present in the left lung. Since we believed that the disease was localized unilaterally, surgical treatment was selected. The surgical procedures that were employed included right middle lobectomy, right S3 segmentectomy and partial resection of right S6 by thoracoscopy. Sixteen months postoperatively, the sputum culture is negative for MAC. Our procedure enabled the preservation of effective lung function and was successful in controlling MAC pulmonary disease. It is believed that surgery for MAC pulmonary disease should be evaluated in more patients to decide the appropriate surgical indication and procedure.

A case was 56 years old woman, and she did not have any subjective symptom. She received multiphasic health screening, and abnormal shadow was detected on her chest radiograph. Chest radiography revealed infiltrations in the middle lobe. Computed tomography (CT) of the thorax showed clusters of small nodules in the middle lobe. The bronchial washing specimen showed acid-fast bacilli identified as Mycobacterium intracellulare by DNA-DNA hybridization (DDH) method. This case was diagnosed as Mycobacterium intracellulare lung disease. The patient received combination therapy with rifampicin, ethambutol, and clarithromycin for one year with radiological improvement. CT findings were characteristic and useful for the early diagnosis of MAC infection, which led to cure of the disease by chemotherapy.

A 45-year-old woman with no immunodeficiency or clinical symptoms presented to our hospital for treatment of an enlarging spherical lung tumor in 4.0-cm-diameter. Chest radiography 8 years ago had shown a 1.5-cm-diameter tumor. Chest computed tomography (CT) showed the solitary tumor, located in the right apical segment, to have an irregular margin without satellite lesions or cavitations. Mycobacterium avium complex (MAC) was cultured in tumor specimens incised during transbronchial biopsy. Right upper lobectomy was performed because of resistance to 6-month antituberculosis treatment. Pathological findings showed a MAC-infected granuloma with caseous necrosis. Postoperative course was uneventful and she had no recurrence 3 years after surgery. These findings suggest that nontuberculous mycobacterial granuloma can enlarge without clinical manifestations or any satellite lesions and cavitations, leading to a misdiagnosis of lung cancer.

We retrospectively investigated the efficacy of regimens including clarithromycin (CAM) in 129 patients with Mycobacterium avium complex (MAC) pulmonary disease and their outcomes. None of the patients suffered from acquired immunodeficiency syndrome. All were observed for over 12 months. We studied the factors that may affect sputum conversion and fatal outcomes by logistic regression analysis. The results indicated that the presence of either cavitation or bronchiectasis was significantly correlated with persistent MAC-positive culture results in sputum (Odds ratio, 4.71, 95%; CL, 1.21-18.5; P<0.05). Regimens including antituberculous drugs and CAM were administered to 118 patients, 11 of whom received CAM alone because of the adverse events of antituberculous agents. There was no difference in sputum conversion or mortality between the two groups, suggesting that the pattern of drug combination should be further investigated.

A 76-year-old woman was admitted to our hospital because of an abnormal shadow on chest radiography and a suspected familial prevalence of pulmonary tuberculosis. Her son had previously been admitted to our hospital with pulmonary tuberculosis and tuberculous pleuritis. In the present case, a diagnosis of pulmonary tuberculosis and atypical pulmonary mycobacteriosis was made on the basis of detection of both Mycobacterium tuberculosis and M. intracellulare several times in a sputum culture of anti-fast bacilli. Restriction fragment length polymorphism (RFLP) analysis was then performed for both the woman and her son. The RFLP analysis revealed the same pattern in both mother and son, and confirmed that this was a case of mixed pulmonary infection passed from son to mother.

Studied were made on the profiles of the therapeutic efficacy of KRM-1648 (KRM) against Mycobacterium avium complex (MAC) infection, which was induced in mice at different challenge doses, in reducing bacterial growth in the visceral organs and altering the profiles of cytokine mRNA expression at the sites of infection. First, bacterial growth in the lungs of mice infected with either high or low challenge doses of MAC, was reduced due to KRM treatment. This effect was noted even in the early phase of infection (week 4) in mice, that were given a high-dose infection. Second, marked therapeutic efficacy of KRM was observed in mice, that were given low-dose MAC infection, in terms of the reduction in bacterial loads in the spleen. However, in mice given a high-dose bacterial challenge, KRM did not exhibit such an efficacy. Third, the expression of both proinflammatory cytokines (TNF-alpha, IFN-gamma) and anti-inflammatory cytokines (IL-10, TGF-beta) in mRNA levels were increased at 4 weeks after infection. Notably, all of the cytokines tested for the mRNA expression levels were higher in mice given a low-dose MAC infection as compared to those in mice given a high-dose infection. KRM treatment increased the mRNA levels of these cytokines at week 4, while TGF-beta mRNA expression at week 8 was conversely decreased by KRM treatment. These findings suggest that the profiles of the therapeutic efficacy of KRM vary in mice given low- or high-dose MAC infection.

We reported on a 79-year-old woman with pneumonia caused by Mycobacterium avium complex (MAC). She was admitted with fever, general fatigue, and cough. A chest X-ray film showed infiltrative shadows in the right lung field. In spite of administration of conventional antibiotics, the infiltrative shadows enlarged. A chest CT scan revealed areas of consolidation and ground glass opacities. Bronchoalveolar lavage (BAL) examination revealed an increased number of lymphocytes. Transbronchial lung biopsy revealed many granulomatous regions with giant cells. Mycobacterium intracellulare was found in the culture of BAL fluid and identified by PCR. Treatment was started with rifampicin, ethambutol, and clarithromycin. However, rifampicin and ethambutol were soon discontinued because of severe anorexia. Her symptoms and the radiographic appearance markedly improved following treatment of clarithromycin alone. Subsequently small doses of rifampicin and ethambutol were restarted because her general condition was much improved. These findings suggest that clarithromycin is an effective and tolerable agent for elderly patients with MAC.

An intratracheal infection method of experimental murine mycobacteriosis was developed for an in vivo study of antimycobacterial agents. Two models of intratracheal (IT) and intravenous (i.v.) routes of infection with mycobacteria of the same inoculum dose were compared in terms of the mean survival days of mice or bacterial loads in organs during the course of infection. IT model with either of M. bovis Ravenel, M. tuberculosis Kurono, M. tuberculosis H37Rv or M. intracellular N-256 exhibited a much more distinct lung-specific infection than i.v. model with the same dose of respective mycobacterial strains. The intratracheal infection method presented in this report does not require any special equipment and is a much safer method for the researcher than airborne infection. In this model, following slight anesthetizing of mice, bacillary suspension was injected quantitatively into lungs through the mouth and trachea by using a specially modified needle set with a short fine polyethylene tube. This IT model may be useful not only for the in vivo assessment of anti-mycobacterial agents but also for the comparison of virulence among various mycobacterial strains.

A 46-year-old man was admitted for evaluation of a solitary pulmonary cavity in the apey of the left lung. Because two transbronchial biopsies followed by brushing and washing and sputum cytology did not yield any diagnostic findings, the patient was treated with INH, RFP and SM under a tentative diagnosis of pulmonary tuberculosis. The shadow decreased over two months with combination therapy, but increased again after the dose of SM was decreased. We performed a left upper lobectomy to diagnose either multi-drug-resistant pulmonary tuberculosis or lung cancer. Pathological examination of the resected lung revealed epitheloid cell granulomas with areas of caseous necrosis. Smooth chromophoric colonies were isolated on an Ogawa egg medium, and were identified as M. avium by PCR and DDH. A diagnosis of pulmonary M. avium was made. A chest X-ray film taken two years later was normal. Pulmonary M. avium disease developed in this patient, who had no predisposing lung pathologies.

The patient was 71-year-old male with a history of sinobronchial syndrome since 8 years ago. He has been suffering from cough, sputum and upper abdominal discomfort since January 1994. He was diagnosed as an early gastric cancer by endoscopy, and his chest X-ray film showed an infiltrative shadow in the right upper lung field. A smear of the sputum specimen was positive for acid fast bacilli, which were later identified as Mycobacterium intracellulare. In this case, before the Mycobacterium intracellulare infection, it was confirmed that his mucociliary transport was severely impaired by using aerosol inhalation cine-scintigraphy. This case suggests that an impairment of the local defence mechanisms may play an important role in the pathogenesis of Mycobacterium intracellulare infection.

The interaction of LFA-1 on T lymphocytes with ICAM-1 on antigen presenting cells (APCs) is critical in determining conjugate formation between the APCs and T cells as well as activation of T cells. Recently, it was found that stimulation of THP-1 cells, a human monocyte M phi cell line, with Mycobacterium tuberculosis or its lipoarabinomannan, elicited the increase in the ICAM-1 expression. In addition, in cases of lepromatous leprosy patients with a serious defect in the M. leprae antigen-specific cellular immunity, keratinocytes in the leprosy lesions were lacking in the ICAM-1 expression. Therefore, ICAM-1 seems to participate in the host response to mycobacterial infections. Here, we studied the mode of the expression of ICAM-1 molecules on murine peritoneal M phis in response to stimulation with M. avium complex (MAC). In addition, the regulatory effect of some cytokines including TNF-alpha, IL-10, and transforming growth factor-beta (TGF-beta) on the ICAM-1 expression was studied. Monolayer cultures of peptone-starch induced murine peritoneal M phis were cultured in RPMI-1640 medium in the presence of MAC with or without test agents. At intervals, the M phis were stained with anti-ICAM-1 antibody (Ab) and then treated with alkaline phosphatase (Ap)-conjugated anti-1g Ab. After color development with NBT-BCIP substrate, percentage of the blue-stained (ICAM-1 positive) M phis was determined microscopically. The concentrations of TNF-alpha, IL-10, and TGF-beta in the M phi culture fluid was measured by ELISA using capture Ab, biotin-labelled capping Ab, and Ap-conjugated streptavidin. When M phis infected with MAC organisms were cultured in RPMI medium containing 10% fetal bovine serum or in serum-free GPI medium, a significant increase in their ICAM-1 expression was observed, reaching the peak at days 1 to 3, thereafter rapidly decreased and returned to the normal level by day 14. Further addition of TNF-alpha caused no significant change in the mode of the MAC-induced expression of ICAM-1. A transient increase in the IL-10 production of MAC-infected M phis was observed during the first 3-days cultivation, as in the case of TNF-alpha. On the other hand, TGF-beta production of the Mø population was initiated from day 3, and therafter increased gradually until day 14. ICAM-1 expression of the MAC-infected M phis was not influenced by the addition of IL-10, while anti-IL-10 Ab retarded the decline of ICAM-1 expression at day 7. On the other hand, the addition of TCF-beta attenuated the MAC infection-induced increase in the ICAM-1 expression significantly. In addition, anti-TGF-beta Ab significantly delayed the reduction of the ICAM-1 expression of MAC-infected M phis during days 3 to 7. These results indicate that, in the MAC-infected M phis. TGF-beta rather than IL-10 play important roles as a mediators for the late-phase down-regulation of ICAM-1 expression which had been transiently elevated by the action of TNF-alpha in the early phase of the Mø cultivation.

Six cases of pulmonary M. kansasii infection were studied. The ages of the patients ranged from 26 to 51, with a mean of 39.6 years. All the patients were male. None had any underlying systemic or lung diseases. On chest X-ray and CT scan, the majority of cases showed a solitary thin-walled cavitary lesion with little satellite or scattered lesions, which were predominantly located in S1 or S2. The strains of M. kansasii isolated from the 6 patients showed a certain pattern of antibiotic sensitivity being highly sensitive to TH, CS, EB and RFP. In 5 out of the 6 patients, chemotherapy with RFP combined with 2 or 3 other antituberculous drugs for 12 months was successful. In another patient, chemotherapy with RFP, EB and INH for 12 months was unsuccessful and surgical resection was required. Comparison of patients with M. kansasii (n = 6), M. tuberculosis (n = 112) and M. avium complex infection (n = 51) revealed that the former two had some common clinical features: predominance in males, younger age than the patients with M. avium complex infection, predominant involvement of S1, S2 and S6, and involving a single rather than multiple lung lobes. Even in cases clinically suspected of having M. tuberculosis infection, bacteriological examination should be carried out routinely to rule out M. kansasii infection.

On 397 patients with pulmonary disease due to nontuberculous mycobacteria (NTM) [102 due to M. kansasii (MK) and 295 due to M. avium complex (MAC)] observed at National Tokyo Chest Hospital, 191 patients with pulmonary disease (59 due to MK and 132 due to MAC) observed at Fukujuji Hospital of Antituberculosis Association and 257 patients from whose sputum MK (36) or MAC (221) were isolated in Byotai-Seiri Clinical Laboratory, the distribution of these patients by domicile in Tokyo area was analysed. The percentage of patients with MK disease among the whole patients with MK disease and MAC disease (MK ratio) in each community area was investigated. MK ratio was 30.9% in the 23 wards and 16.4% in Tama section of Tokyo in the patients observed at National Tokyo Chest Hospital. It was 37.0% in the 23 wards and 32.1% in Tama section in the patients observed at Fukujuji Hospital and was 17.7% in the 23 wards and 8.1% in Tama section in the patients observed at Byotai-Seiri Clinical Laboratory. MK ratio in Tokyo was considerably higher in the 23 wards that were densely populated industrial and commercial areas than in Tama section, a comparatively sparsely populated suburb. MK ratio in patients of Ota Hospital located in the 23 wards was higher (36.4%) than that of Tachikawa-Sogo Hospital located in Tama area (10.0%). Regional differences in MK ratio were remarkable in Tokyo area. A high MK ratio appeared to correlate with a high incidence rate of tuberculosis. From the results mentioned above, it was suggested that M.K. disease may be transmitted from person to person.