Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026916 (MAC)
 5,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted four genetic studies on the Mycobacterium avium complex (MAC). (1) M. avium genotyping: A total of 70 clinical isolates from patients with pulmonary MAC infections were typed by MATR-VNTR, IS1245-RFLP, and MIRU-VNTR analyses to compare discriminatory powers of these typing methods. To allow a comparison of discriminatory powers, the Hunter-Gaston discriminatory index (HGDI) was calculated, giving a HGDI of 0.960 for IS1245-RFLP, 0.949 for MIRU-VNTR, and 0.990 for MATR-VNTR, demonstrating that MATR-VNTR analysis is the best of the three genotyping methods. (2) Genetic characteristics of M. avium: Japanese clinical isolates of M. avium were subjected to insertion sequence (IS) analyses. First, an analysis of 81 isolates by heat shock protein 65 identified all isolates as belonging to the subspecies of M. avium subsp. hominissuis. Another analysis by IS901 identified about 70% of the isolates as IS901-carriers. IS901 had been thought to be carried by the subspecies that infect birds: M. avium subsp. avium and M. avium subsp. silvaticum. Studies have reported that most human isolates in the U.S. and Europe carry no IS901. The prevalence of IS901-carriers among Japanese clinical isolates of M. avium is thus a significant characteristic. A further analysis of the IS901 showed that compared with M. avium subsp. avium, the clinical isolates shared 60 point mutations of nucleotide sequence. This novel insertion sequence was designated "ISMav6". (3) The CAM-resistance gene in MAC: This study assessed the correlation between CAM-susceptibility and mutation of the gene involved in drug resistance (A DNA sequence analysis identified mutations at positions 2058 and 2059 in domain V of 23S-rRNA). Furthermore, a system was developed to rapidly detect the presence/absence of CAM resistance by ARMS-PCR, a procedure used to detect gene mutations. The utility of this new system was also evaluated. A total of 253 clinical isolates were tested for drug susceptibility, with 227 isolates identified as sensitive and 26 as resistant. Sequence analyses showed that all 28 strains randomly selected for testing from the sensitive strains were wild type, whereas 24 of the 26 resistant strains were mutant type. The rest of the 2 strains were subsequently confirmed to be mutant type after they were isolated from contaminations with sensitive strains. These results showed an association between drug susceptibility and drug-resistant gene mutation. In addition, ARMS-PCR provided a sensitivity of 84.6% (22/26) and a specificity of 100% (28/28) for the detection of gene mutations. The lower sensitive was probably attributable to the fact that every one of the 4 strains was a combination of wild type and mutant type. These results indicated that compared with drug-susceptibility tests, ARMS-PCR provides earlier results on the presence/absence of drug resistance and has the capability of rapid detection even when the specimen contains a mixture of sensitive and resistant strains. (4) Development of a VNTR analysis for M. intracellulare: Bioinformatics analyses were used to develop a VNTR analysis for M. intracellulare and to evaluate the utility of the VNTR analysis. First, the Tandem Repeat Finder (TRF) software was used to conduct a search of TR loci on the genomic data of M. intracellulare ATCC 13950 published in December 2007, resulting in the identification of 16 TR loci, which were used in VNTR analyses of 74 isolates from pulmonary MAC infections. The HGDI was 0.988, suggesting an excellent discriminatory power. Furthermore, a stability evaluation of the VNTR loci was conducted in isolates from patients with long-term bacilli discharge. The VNTR loci were stable without changes for up to 4 years in 14 such patients. These results indicated that this method is useful in M. intracellulare genotyping and in determining whether the cause of recurrence in recurred patients is endogenous from the remnant bacilli or exogenous from another infection of different bacilli, given that the VNTR loci have been confirmed to be stable.
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PMID:Genetic research about Mycobacterium avium complex. 2351 64

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.
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PMID:[Strategies for Mycobacterium avium complex infection control in Japan: how do they improve the present situation?]. 2367 76

A 78-year-old woman who had been treated for two years with ITCZ for chronic pulmonary aspergillosis associated with prior pulmonary tuberculosis was admitted to our hospital because of general fatigue and hemosputum along with deterioration of her chest radiographic findings. Mycobacterium abscessus had been isolated once from her sputum one year before admission. We performed fiberoptic bronchoscopy (FOB) in order to help establish a final diagnosis. Sputum aspirated from her bronchus on FOB stained positive for acid-fast bacilli and was negative for Tbc and MAC using PCR. From these results, we diagnosed the patient with pulmonary M. abscessus infection. Chemotherapy with AMK, IPM/cs, and CAM was initiated. Because her symptoms rapidly improved, we switched the chemotherapy to long-term oral CAM and LVFX, and she has been in a good condition at 12 months after the initiation of the therapy. Recently, subtypes of M. abscessus complex, such as M. massiliense, have been recognized, which are more sensitive to chemotherapy. Considering the good response to therapy, there is a possibility that is the patient in the current case had a M. massiliense infection.
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PMID:[A CASE OF PULMONARY MYCOBACTERIUM ABSCESSUS INFECTION SUCCESSFULLY TREATED WITH SHORT-TERM CAM, AMK, AND IPM/cs FOLLOWED BY LONG-TERM ORAL CAM AND LVFX]. 2648 57


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