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Sample records for avium complex paradigm

  1. The Mycobacterium avium complex.

    PubMed Central

    Inderlied, C B; Kemper, C A; Bermudez, L E

    1993-01-01

    Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing

  2. ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

    EPA Science Inventory

    The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms isolated from clinical and environmental sources were measured in 9.15 mM KH2PO4 buffered water. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V-1 ...

  3. ELECTROPHORETIC MOBILITY OF MYCOBACTERIUM AVIUM COMPLEX ORGANISMS

    EPA Science Inventory

    The electrophoretic mobilities (EPMs) of thirty Mycobacterium avium Complex (MAC) organisms were measured. The EPMs of fifteen clinical isolates ranged from -1.9 to -5.0 µm cm V-1s-1, and the EPMs of fifteen environmental isolates ranged from -1...

  4. Comparative Genomic Hybridizations Reveal Genetic Regions within the Mycobacterium avium Complex That Are Divergent from Mycobacterium avium subsp. paratuberculosis Isolates†

    PubMed Central

    Paustian, Michael L.; Kapur, Vivek; Bannantine, John P.

    2005-01-01

    Mycobacterium avium subsp. paratuberculosis is genetically similar to other members of the Mycobacterium avium complex (MAC), some of which are nonpathogenic and widespread in the environment. We have utilized an M. avium subsp. paratuberculosis whole-genome microarray representing over 95% of the predicted coding sequences to examine the genetic conservation among 10 M. avium subsp. paratuberculosis isolates, two isolates each of Mycobacterium avium subsp. silvaticum and Mycobacterium avium subsp. avium, and a single isolate each of both Mycobacterium intracellulare and Mycobacterium smegmatis. Genomic DNA from each isolate was competitively hybridized with DNA from M. avium subsp. paratuberculosis K10, and open reading frames (ORFs) were classified as present, divergent, or intermediate. None of the M. avium subsp. paratuberculosis isolates had ORFs classified as divergent. The two M. avium subsp. avium isolates had 210 and 135 divergent ORFs, while the two M. avium subsp. silvaticum isolates examined had 77 and 103 divergent ORFs. Similarly, 130 divergent ORFs were identified in M. intracellulare. A set of 97 ORFs were classified as divergent or intermediate in all of the nonparatuberculosis MAC isolates tested. Many of these ORFs are clustered together on the genome in regions with relatively low average GC content compared with the entire genome and contain mobile genetic elements. One of these regions of sequence divergence contained genes homologous to a mammalian cell entry (mce) operon. Our results indicate that closely related MAC mycobacteria can be distinguished from M. avium subsp. paratuberculosis by multiple clusters of divergent ORFs. PMID:15774884

  5. DETECTION,QUANTIFICATION AND CHARACTERIZATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS IN DRINKING WATER.

    EPA Science Inventory

    Bacteria belonging to the Mycobacterium avium complex (MAC), including Mycobacterium avium and M. intracellulare, are clinically relevant and cause a myriad of opportunistic infections. Children, the elderly, and persons with previous lung conditions or immune system dysfunction...

  6. GENETIC FINGERPRINTING OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS ISOLATED FROM HOSPITAL PATIENTS AND THE ENVIRONMENT

    EPA Science Inventory

    A particularly pathogenic group of mycobacteria belong to the Mycobacterium avium complex (MAC), which includes M. avium and M. intracellulare. MAC organisms cause disease in children, the elderly, and immuno-compromised individuals. A critical step in preventing MAC infections...

  7. REGIONAL ASSESSMENT OF EXPOSURE TO MYCOBACTERIUM AVIUM COMPLEX(MAC)

    EPA Science Inventory

    There is accumulating evidence that potable water is a source of Mycobacterium avium complex (MAC). The linkage of mycobacteriosis to drinking water has been shown in AIDS populations where up to 8% of deaths in this group is attributed to MAC. Infection with these organisms ha...

  8. Hemolysin as a Virulence Factor for Systemic Infection with Isolates of Mycobacterium avium Complex

    PubMed Central

    Maslow, Joel N.; Dawson, David; Carlin, Elizabeth A.; Holland, Steven M.

    1999-01-01

    Isolates of the Mycobacterium avium complex were examined for hemolysin expression. Only invasive isolates of M. avium were observed to be hemolytic (P < 0.001), with activity the greatest for isolates of serovars 4 and 8. Thus, M. avium hemolysin appears to represent a virulence factor necessary for invasive disease. PMID:9889239

  9. [Isolation of Mycobacterium avium complex from the "24-hour bath"].

    PubMed

    Saito, H; Murakami, K; Ishii, N; Kwon, H H

    2000-01-01

    The "24-HOUR BATH" is an apparatus which circulates the bath water, keeps it clean and warm, and makes it possible to take a bath at any time during the day or night. It consists of apparatus for cleaning (sponge or mesh filter and filter material), heating (ceramic heater), and sterilizing (UV lamp). Recently, three cases of skin disease due to M. avium infection in private homes, in which "24-HOUR BATH" water was suspected to be the source of infection, have been reported. We attempted to isolate M. avium complex from the water (32 specimens), sponge filter (29 specimens), and filter material (32 specimens) of the "24-HOUR BATH". One hundred-ml samples of bath water, and 50-ml samples of rinse from a sponge filter or filter material were centrifuged at 3000 rpm for 20 min. Sediment was suspended in distilled water and a smear was prepared, and then digested and decontaminated with 2% sodium hydroxide. The processed specimens were cultured on 2% Ogawa medium containing ofloxacin (1 microgram/ml) and ethambutol (2.5 micrograms/ml) for 8 weeks at 37 degrees C. Positive smears were 3 (9.4%), 25 (86.2%) and 25 (78.1%) specimens from the water, sponge and filter material, respectively. A few bacterial clumps were observed, especially in the sponge specimens. The number of positive culture was 5 (15.6%), 24 (82.8%) and 25 (78.1%) from the water, sponge and filter material, respectively. Among them the number of Runyon's Group III-positive cultures was 5 (100%), 22 (91.7%) and 20 (80%) in the water, sponge, and filter material specimens, respectively. In most cases, cultures were positive for both the sponge and filter material specimens. All of the Group III mycobacteria were smooth, grew at 28, 37, 42, and 45 degrees C, negative for niacin, nitrate reductase, semiquantitative catalase, urease and Tween80 hydrolysis, and positive for 68 degrees C catalase. All of the strains reacted with M. avium complex AccuProbe and M. avium AccuProbe, but none of the strains reacted

  10. Characterization of Mouse Models of Mycobacterium avium Complex Infection and Evaluation of Drug Combinations

    PubMed Central

    Almeida, Deepak V.; Tyagi, Sandeep; Converse, Paul J.; Ammerman, Nicole C.; Grosset, Jacques H.

    2015-01-01

    The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy. PMID:25624335

  11. Draft genome sequence of a Mycobacterium avium complex isolate from a broadbill bird

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report the draft genome sequences of ten Mycobacterium avium complex isolates obtained from diverse hosts. This collection includes isolates obtained from deer, pig, elephant, ruddy duck and Red-tailed hawk species. The type strain of Mycobacterium avium subspecies silvaticum (ATCC 49884) is also...

  12. AMPLIFIED FRAGMENT LENGTH POLYMORPHISM ANALYSIS OF MYCOBACTERIUM AVIUM COMPLEX ISOLATES RECOVERED FROM SOUTHERN CALIFORNIA

    EPA Science Inventory

    Fine-scale genotyping methods are necessary in order to identify possible sources of human exposure to opportunistic pathogens belonging to the Mycobacterium avium complex (MAC). In this study, amplified fragment length polymorphism (AFLP) analysis was evaluated for fingerprintin...

  13. Proposal to elevate Mycobacterium avium complex ITS sequevar MAC-Q to Mycobacterium vulneris sp. nov.

    PubMed

    van Ingen, J; Boeree, M J; Kösters, K; Wieland, A; Tortoli, E; Dekhuijzen, P N R; van Soolingen, D

    2009-09-01

    The Mycobacterium avium complex (MAC) consists of four recognized species, Mycobacterium avium, Mycobacterium colombiense, Mycobacterium intracellulare and Mycobacterium chimaera, and a variety of other strains that may be members of undescribed taxa. We report on two isolates of a scotochromogenic, slowly growing, non-tuberculous Mycobacterium species within the M. avium complex from a lymph node and an infected wound after a dogbite of separate patients in The Netherlands. The extrapulmonary infections in immunocompetent patients suggested a high level of virulence. These isolates were characterized by a unique nucleotide sequence in the 16S rRNA gene, 99% similar to Mycobacterium colombiense, and the MAC-Q 16S-23S internal transcribed spacer (ITS) sequence. Sequence analyses of the hsp65 gene revealed 97% similarity to M. avium. The rpoB gene sequence was 98% similar to M. colombiense. Phenotypically, the scotochromogenicity, positive semi-quantitative catalase and heat-stable catalase tests, negative tellurite reductase and urease tests and susceptibility to hydroxylamine and oleic acid set these isolates apart from related species. High-performance liquid chromatography analysis of cell-wall mycolic acid content revealed a unique pattern, related to that of M. avium and M. colombiense. Together, these findings supported a separate species status within the Mycobacterium avium complex. We propose elevation of scotochromogenic M. avium complex strains sharing this 16S gene and MAC-Q ITS sequence to separate species status, for which the name Mycobacterium vulneris sp. nov. is proposed. The type strain is NLA000700772T (=DSM 45247T=CIP 109859T). PMID:19620376

  14. Thioridazine as Chemotherapy for Mycobacterium avium Complex Diseases

    PubMed Central

    Deshpande, Devyani; Srivastava, Shashikant; Musuka, Sandirai

    2016-01-01

    Mycobacterium avium-intracellulare complex (MAC) causes an intractable intracellular infection that presents as chronic pulmonary disease. Currently, therapy consists of ethambutol and macrolides and takes several years to complete. The neuroleptic phenothiazine thioridazine kills mycobacteria by inhibiting the electron transport chain. In several experiments with bacterial populations of up to 1012 CFU/ml, we failed to isolate any bacteria resistant to 3 times the MIC of thioridazine, suggesting the absence of resistant mutants at bacterial burdens severalfold higher than those encountered in patients. In the hollow-fiber model of intracellular MAC (HFS-MAC), thioridazine achieved an extracellular half-life of 16.8 h and an intracellular half-life of 19.7 h. Thioridazine concentrations were >28,000-fold higher inside infected macrophages than in the HFS-MAC central compartment (equivalent to plasma). Thioridazine maximal kill was 5.20 ± 0.75 log10 CFU/ml on day 7 (r2 = 0.96) and 7.19 ± 0.31 log10 CFU/ml on day 14 (r2 = 0.99), the highest seen with any drug in the system. Dose fractionation studies revealed that thioridazine efficacy and acquired drug resistance were driven by the peak concentation-to-MIC ratio, with a 50% effective concentration (EC50) of 2.78 ± 0.44 for microbial killing. Acquired drug resistance was encountered by day 21 with suboptimal doses, demonstrating that fluctuating drug concentrations drive evolution faster than static concentrations in mutation frequency studies. However, the thioridazine EC50 changed 16.14-fold when the concentration of fetal bovine serum was changed from 0% to 50%, suggesting that intracellular potency could be heavily curtailed by protein binding. Efficacy in patients will depend on the balance between trapping of the drug in the pulmonary system and the massive intracellular concentrations versus very high protein binding of thioridazine. PMID:27216055

  15. Thioridazine as Chemotherapy for Mycobacterium avium Complex Diseases.

    PubMed

    Deshpande, Devyani; Srivastava, Shashikant; Musuka, Sandirai; Gumbo, Tawanda

    2016-08-01

    Mycobacterium avium-intracellulare complex (MAC) causes an intractable intracellular infection that presents as chronic pulmonary disease. Currently, therapy consists of ethambutol and macrolides and takes several years to complete. The neuroleptic phenothiazine thioridazine kills mycobacteria by inhibiting the electron transport chain. In several experiments with bacterial populations of up to 10(12) CFU/ml, we failed to isolate any bacteria resistant to 3 times the MIC of thioridazine, suggesting the absence of resistant mutants at bacterial burdens severalfold higher than those encountered in patients. In the hollow-fiber model of intracellular MAC (HFS-MAC), thioridazine achieved an extracellular half-life of 16.8 h and an intracellular half-life of 19.7 h. Thioridazine concentrations were >28,000-fold higher inside infected macrophages than in the HFS-MAC central compartment (equivalent to plasma). Thioridazine maximal kill was 5.20 ± 0.75 log10 CFU/ml on day 7 (r(2) = 0.96) and 7.19 ± 0.31 log10 CFU/ml on day 14 (r(2) = 0.99), the highest seen with any drug in the system. Dose fractionation studies revealed that thioridazine efficacy and acquired drug resistance were driven by the peak concentation-to-MIC ratio, with a 50% effective concentration (EC50) of 2.78 ± 0.44 for microbial killing. Acquired drug resistance was encountered by day 21 with suboptimal doses, demonstrating that fluctuating drug concentrations drive evolution faster than static concentrations in mutation frequency studies. However, the thioridazine EC50 changed 16.14-fold when the concentration of fetal bovine serum was changed from 0% to 50%, suggesting that intracellular potency could be heavily curtailed by protein binding. Efficacy in patients will depend on the balance between trapping of the drug in the pulmonary system and the massive intracellular concentrations versus very high protein binding of thioridazine. PMID:27216055

  16. Assessing the effectiveness of low-pressure ultraviolet light for inactivating Mycobacterium avium complex (MAC) micro-organisms

    EPA Science Inventory

    Aims: To assess low-pressure ultraviolet light (LP-UV) inactivation kinetics of Mycobacterium avium complex (MAC) strains in a water matrix using collimated beam apparatus. Methods and Results: Strains of M. avium (n = 3) and Mycobacterium intracellulare (n = 2) were exposed t...

  17. Characterization to species level of Mycobacterium avium complex strains from human immunodeficiency virus-positive and -negative patients.

    PubMed Central

    Kyriakopoulos, A M; Tassios, P T; Matsiota-Bernard, P; Marinis, E; Tsaousidou, S; Legakis, N J

    1997-01-01

    Forty human clinical Mycobacterium avium-M. intracellulare complex strains isolated in Greece were characterized to the species level by PCR with three sets of primers specific for one or both species. M. avium predominated in both human immunodeficiency virus-positive and -negative patients, but the frequency of M. intracellulare isolation appeared to be higher in the latter. PMID:9350780

  18. MYCOBACTERIUM AVIUM COMPLEX IN DRINKING WATER: DETECTION, DISTRIBUTION, AND ROUTES OF EXPOSURE

    EPA Science Inventory

    Organisms of the Mycobacterium avium complex (MAC) are an increasingly prevalent cause of clinical disease and are known to be widespread in drinking water supplies. However, there are significant gaps in our current knowledge. Available methods for the detection of MAC in wat...

  19. Envelope protein complexes of Mycobacterium avium subsp. paratuberculosis and their antigenicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, a chronic enteric disease of ruminant animals. In the present study, blue native PAGE electrophoresis and 2D SDS-PAGE were used to separate MAP envelope protein complexes, followed by mass spectrometry (MS) ...

  20. Polypoid bronchial lesions due to Scedosporium apiospermum in a patient with Mycobacterium avium complex pulmonary disease.

    PubMed

    Murayama, T; Amitani, R; Tsuyuguchi, K; Watanabe, I; Kimoto, T; Suzuki, K; Tanaka, E; Kamei, K; Nishimura, K

    1998-09-01

    A 69 yr old female was hospitalized for further examination of abnormal shadows on chest radiographs. She had a history of tuberculous pleurisy, rheumatoid arthritis and gold-induced interstitial pneumonia. On admission she still suffered from rheumatoid arthritis. A chest computed tomography scan on admission showed clusters of small nodules in subpleural regions of both lungs combined with bronchiectasis. Mycobacterium avium complex was cultured repeatedly from the sputum. Bronchoscopic examination disclosed white-yellow polypoid lesions in the orifice of the left B4 bronchus. Cultures of the brushing specimen of the polypoid lesions and bronchial aspirates from the B4 bronchus yielded smoky-grey mycelial colonies that were later identified as Scedosporium apiospermum. It was concluded that the polypoid bronchial lesions due to Scedosporium apiospermum were formed in the preexisting dilated bronchus caused by Mycobacterium avium complex pulmonary disease. PMID:9762808

  1. Experimental Reactivation of Pulmonary Mycobacterium avium Complex Infection in a Modified Cornell-Like Murine Model

    PubMed Central

    Kim, Woo Sik; Kim, Jong-Seok; Kim, Hong Min; Kwon, Kee Woong; Cho, Sang-Nae; Shin, Sung Jae; Koh, Won-Jung

    2015-01-01

    The latency and reactivation of Mycobacterium tuberculosis infection has been well studied. However, there have been few studies of the latency and reactivation of Mycobacterium avium complex (MAC), the most common etiological non-tuberculous Mycobacterium species next to M. tuberculosis in humans worldwide. We hypothesized that latent MAC infections can be reactivated following immunosuppression after combination chemotherapy with clarithromycin and rifampicin under experimental conditions. To this end, we employed a modified Cornell-like murine model of tuberculosis and investigated six strains consisting of two type strains and four clinical isolates of M. avium and M. intracellulare. After aerosol infection of each MAC strain, five to six mice per group were euthanized at 2, 4, 10, 18, 28 and 35 weeks post-infection, and lungs were sampled to analyze bacterial burden and histopathology. One strain of each species maintained a culture-negative state for 10 weeks after completion of 6 weeks of chemotherapy, but was reactivated after 5 weeks of immunosuppression in the lungs with dexamethasone (three out of six mice in M. avium infection) or sulfasalazine (four out of six mice in both M. avium and M. intracellulare infection). The four remaining MAC strains exhibited decreased bacterial loads in response to chemotherapy; however, they remained at detectable levels and underwent regrowth after immunosuppression. In addition, the exacerbated lung pathology demonstrated a correlation with bacterial burden after reactivation. In conclusion, our results suggest the possibility of MAC reactivation in an experimental mouse model, and experimentally demonstrate that a compromised immune status can induce reactivation and/or regrowth of MAC infection. PMID:26406237

  2. Mycobacterium avium complex-associated peritonitis with CAPD after unrelated bone marrow transplantation.

    PubMed

    Miyashita, Emiko; Yoshida, Hisao; Mori, Daisuke; Nakagawa, Natsuki; Miyamura, Takako; Ohta, Hideaki; Seki, Masafumi; Tomono, Kazunori; Hashii, Yoshiko; Ozono, Keiichi

    2014-12-01

    Peritonitis remains an important complication of peritoneal dialysis and is mostly caused by aerobic enteric bacteria. Non-tuberculous mycobacteria (NTM)-associated peritonitis is an unusual but serious infection, requiring special culture techniques to avoid delay in diagnosis. We report the case of an 11-year-old girl with aplastic anemia on ambulatory peritoneal dialysis who had Mycobacterium avium complex-associated peritonitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case emphasizes that we should be constantly cautious about NTM infection in allo-HSCT recipients, especially when standard cultures are negative and the infection is refractory to empirical antibiotic therapy. PMID:25521993

  3. HOST RESPONSES TO MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS: A COMPLEX ARSENAL

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The immune system is not always successful in recognizing and destroying pathogens it may encounter. Host immunity to mycobacteria is characterized by a very complex series of events, designed to clear the infection. The first line of defense is uptake and processing of the pathogen by macrophages...

  4. THE ISOLATION AND IDENTIFICATION OF MYCOBACTERIUM AVIUM COMPLEX (MAC) RECOVERED FROM LOS ANGELES POTABLE WATER, A POSSIBLE SOURCE OF INFECTION IN AIDS PATIENTS

    EPA Science Inventory

    Los Angeles water was investigated as a possible source of Mycobacterium avium complex (MAC) infection in patients with AIDS. MAC consists of M.avium (MA), M. intracellulare (MI) and Mycobacterium X (MX)(positive for MAC by DNA probe but not MA or MI). The study included 13 reser...

  5. [A case of pulmonary Mycobacterium avium complex disease, mimicking hot tub lung].

    PubMed

    Sato, Nagato; Kawabata, Yoshinori; Nagata, Makoto; Hagiwara, Koichi; Kanazawa, Minoru

    2006-12-01

    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. PMID:17233395

  6. Mycobacterium avium complex in day care hot water systems, and persistence of live cells and DNA in hot water pipes.

    PubMed

    Bukh, Annette S; Roslev, Peter

    2014-04-01

    The Mycobacterium avium complex (MAC) is a group of opportunistic human pathogens that may thrive in engineered water systems. MAC has been shown to occur in drinking water supplies based on surface water, but less is known about the occurrence and persistence of live cells and DNA in public hot water systems based on groundwater. In this study, we examined the occurrence of MAC in hot water systems of public day care centers and determined the persistence of live and dead M. avium cells and naked DNA in model systems with the modern plumbing material cross-linked polyethylene (PEX). The occurrence of MAC and co-occurrence of Legionella spp. and Legionella pneumophila were determined using cultivation and qPCR. Co-occurrences of MAC and Legionella were detected in water and/or biofilms in all hot water systems at temperatures between 40 and 54 °C. Moderate correlations were observed between abundance of culturable MAC and that of MAC genome copies, and between MAC and total eubacterial genome copies. No quantitative relationship was observed between occurrence of Legionella and that of MAC. Persistence in hot water of live and dead M. avium cells and naked DNA was studied using PEX laboratory model systems at 44 °C. Naked DNA and DNA in dead M. avium cells persisted for weeks. Live M. avium increased tenfold in water and biofilms on PEX. The results suggest that water and biofilms in groundwater-based hot water systems can constitute reservoirs of MAC, and that amplifiable naked DNA is relatively short-lived, whereas PEX plumbing material supports persistence and proliferation of M. avium. PMID:24272032

  7. [Rapid diagnosis of mycobacteria, especially Mycobacterium tuberculosis and Mycobacterium avium complex, using MB Check system].

    PubMed

    Saito, H; Tomioka, H; Sato, K; Inoue, K; Shigeto, E

    1992-07-01

    Fourty-five sputum specimens were subjected to isolation for mycobacteria either MB Check system (MB method; F. Hoffmann-La Roche Ltd., Basel, Switzerland) or 3% Ogawa egg medium (Ogawa method). Test sputum was treated with 4 volumes of 4% NaOH for 1-2 min and 0.1 ml of the resulting mixture was inoculated onto 3% Ogawa egg medium. The remaining portion of the mixture was neutralized with IN HCl, diluted with 1/15 M phosphate buffer (PB; pH 6.8), and subsequently centrifuged at 3,000 rpm for 20 min. The sediment was suspended in 1.5 ml of PB and 0.5 ml each was inoculated into MB Check M bottle (20 ml) supplemented with M supplement (1 ml). In MB method, bacterial growth was measured on Middlebrook 7H11 agar medium and Middlebrook 7H11 agar medium containing NAP (p-nitro-alpha-acetylamino-beta-hydroxy-propiophenone). Among 45 sputum specimens, the number of positive specimens for mycobacterial growth in the above two cultivation methods and time required for growth were as follows: 3% Ogawa egg medium; 12 specimens (26.7%) gave positive growth, including 7 of M. tuberculosis complex strains on 14-35 days (average 22 days) and 5 of M. avium complex strains on 14-21 days (average 18 days); MB method; 15 of specimens (33.3%) gave positive growth, including 8 of M. tuberculosis complex strains on 7-21 days (average 15 days), 6 of M. avium complex strains on 7-14 days (average 11 days) and 1 of M. scrofulaceum strain on 28 days. There was no specimen which was positive for mycobacterial growth on 3% Ogawa egg medium but negative on MB medium. PMID:1434318

  8. Detection of Mycobacterium tuberculosis and Mycobacterium avium Complexes by Real-Time PCR in Bovine Milk from Brazilian Dairy Farms.

    PubMed

    Bezerra, André Vinícius Andrade; Dos Reis, Emily Marques; Rodrigues, Rogério Oliveira; Cenci, Alexander; Cerva, Cristine; Mayer, Fabiana Quoos

    2015-05-01

    Foodborne diseases are a public health problem worldwide. The consumption of contaminated raw milk has been recognized as a major cause of transmission of bovine tuberculosis to humans. Other mycobacteria that may be present in raw milk and may cause diseases are those belonging to the Mycobacterium avium complex. In this study, molecular biology tools were applied to investigate raw milk contamination with Mycobacterium spp. in family dairy farms from Rio Grande do Sul, southern Brazil. Furthermore, different variables related to the source of the milk, herd characteristics, and management were evaluated for their effect on milk contamination. Five hundred and two samples were analyzed, of which 354 were from the Northwest region (102 farms with samples from 93 bulk tanks and 261 animals) and 148 from the South region of the state (22 farms with samples from 23 bulk tanks and 125 animals). Among them, 10 (1.99%) and 7 (1.39%) were positive for Mycobacterium tuberculosis (9 confirmed as Mycobacterium bovis) and M. avium complexes, respectively. There was no difference in the frequencies of positive samples between the regions or the sample sources. Of the positive samples, 4 were collected from a bulk tank (1 positive for M. avium and 3 for M. tuberculosis). Moreover, 1 sample was positive concomitantly for M. tuberculosis and M. avium complexes. On risk analysis, no variable was associated with raw milk contamination by M. tuberculosis complex species. However, washing the udders of all animals and drying them with paper towels were weakly classified as risk factors for M. avium contamination. Positive samples were obtained from both animals and bulk tanks, which emphasizes the importance of tuberculosis control programs and provides evidence that milk monitoring can be used as a control practice. Moreover, the findings of this study reinforce the need for awareness of the problems of raw milk consumption among the general population. PMID:25951404

  9. Major histocompatibility complex class II deficiency complicated by Mycobacterium avium complex in a boy of mixed ethnicity.

    PubMed

    Dimitrova, Dimana; Ong, Peck Y; O'Gorman, Maurice R G; Church, Joseph A

    2014-08-01

    Major histocompatibility complex class II (MHCII) deficiency represents a rare form of severe immunodeficiency associated with increased susceptibility to viral, bacterial, and fungal pathogens and commonly leads to failure to thrive and early death. This autosomal recessive disorder is caused by mutations in MHCII transcription regulator genes, resulting in impaired expression of MHCII, and it is usually seen in consanguineous populations. Our patient presented at age 15 months with a history of developmental delay, multiple respiratory infections and skin abscesses, and recently, at 5 years of age, he was found to have disseminated Mycobacterium avium complex. His mother is Mexican-American, and his father is Persian. Laboratory investigations showed hypogammaglobulinemia, modest T-lymphopenia, borderline mitogen responses, absent tetanus toxoid and candida antigen lymphoproliferative assays, and absent tetanus toxoid and Haemophilus influenzae type b antibody levels. Flow cytometry demonstrated absent HLA-DR antigen on monocytes and B-cells, and a diagnosis of MHCII deficiency was made. Genetic analysis yielded a homozygous pathogenic class II transactivator (CIITA) mutation. The same mutation was found in both parents. Coincidently, an Xq28 microduplication was identified and likely was the cause of the patient's developmental delay. This patient demonstrated some of the typical features of MHCII deficiency with the addition of several unique findings: disseminated M. avium complex, homozygosity in a CIITA mutation despite remarkably diverse parental ethnicity, and coincident Xq28 microdeletion with mild intellectual disability. PMID:24789686

  10. Clinical Evaluation of COBAS TaqMan PCR for the Detection of Mycobacterium tuberculosis and M. avium Complex

    PubMed Central

    Ikegame, Satoshi; Sakoda, Yoritake; Fujino, Nao; Taguchi, Kazuhito; Kawasaki, Masayuki; Kajiki, Akira

    2012-01-01

    A retrospective observational study was performed to determine the sensitivity and limitation of PCR test for the detection of Mycobacterium tuberculosis and M. avium complex. We obtained clinical specimens collected from the respiratory tract, cultured M. tuberculosis or M. avium complex, and performed PCR analysis. A total of 299 samples (M. tuberculosis, 177; M. avium, 35; M. intracellulare, 87) were analyzed by COBAS TaqMan PCR from April 2007 to March 2011. The PCR positivity rates were 50–55%, 70–100%, 88–98%, and 100% in smear-negative, smear 1+, 2+, and 3+ groups, respectively. The PCR positivity of tuberculosis in smear 1+ was 80.6%, which was statistically significantly (P < 0.001) lower than that of smear 2+ (97.3%). From January 2005 to March 2007, we collected an additional 138 samples (M. tuberculosis, 74; M. avium, 21; M. intracellulare, 43), which were analyzed by COBAS Amplicor PCR. The PCR positivity rates obtained using COBAS TaqMan PCR and COBAS Amplicor PCR were not significantly different. The sensitivity of PCR test for mycobacteria is not sufficient in case of smear 1+. Careful consideration must be given to the interpretation of negative PCR test results in smear 1+, because smear-positive tuberculosis is the criterion for isolation. PMID:23029612

  11. Disseminated mycobacterium avium complex as protein-losing enteropathy in a non-HIV patient.

    PubMed

    Konjeti, Venkata Rajesh; Paluri, Sravanthi

    2014-01-01

    Disseminated mycobacterium avium complex (MAC) causing protein-losing enteropathy (PLE) due to intestinal lymphangiectasia (IL) in a non-HIV immunocompromised state is extremely rare. We present a case of 56-year-old male who was evaluated for worsening dyspnea and found to have right-sided chylous pleural effusion as well as worsening abdominal and retroperitoneal lymphadenopathy. He had a history of psoriasis for which hewas on etanercept and alefacept which were stopped two years prior to the presentation. The evaluation revealed a MAC infection in his lymph nodes--a low CD4 count but negative for HIV. He was started on MAC therapy. He subsequently developed noninfectious diarrhea, Hypoalbuminemia, recurrentpleural effusions, ascites, and Pneumocystis jiroveci pneumonia (PJP). Despite appropriate antibiotics and management--including total parental nutrition (TPN) with a medium-chain triglyceride enriched low fat diet--the patient's clinical condition deteriorated rapidly resulting in death. PMID:25672059

  12. Mycobacterium avium Complex Osteomyelitis in Persons With Human Immunodeficiency Virus: Case Series and Literature Review

    PubMed Central

    Wood, Brian R.; Buitrago, Martha O.; Patel, Sugat; Hachey, David H.; Haneuse, Sebastien; Harrington, Robert D.

    2015-01-01

    In persons with advanced immunosuppression, Mycobacterium avium complex (MAC) typically causes disseminated disease with systemic symptoms. We report 2 cases in which MAC caused localized osteomyelitis in human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy with rising CD4 counts. We summarize 17 additional cases of HIV-associated MAC osteomyelitis from the literature and compare CD4 count at presentation for vertebral cases versus nonvertebral cases, which reveals a significantly higher CD4 at presentation for vertebral cases (median 251 cells/µL vs 50 cells/µL; P = .043; Mann–Whitney U test). The literature review demonstrates that the majority of cases of MAC osteomyelitis, especially vertebral, occurs in individuals with CD4 counts that have increased to above 100 cells/µL on antiretroviral therapy. Among HIV-infected individuals with osteomyelitis, MAC should be considered a possible etiology, particularly in the setting of immune reconstitution. PMID:26180837

  13. [Measurement of sitafloxacin MIC for Mycobacterium avium complex and application for treatment of pulmonary nontuberculous mycobacteriosis].

    PubMed

    Fujita, Masaki; Matsumoto, Takemasa; Hirano, Ryousuke; Harada, Eiji; Ikegame, Satoshi; Nakanishi, Yoichi; Watanabe, Kentaro

    2014-12-01

    Treatment for pulmonary nontuberculous mycobacteriosis is difficult. Since current treatment has limitation, new application is needed. Fluoroquinolone is one of candidates. We have investigated the feasibility of sitafloxacin (STFX). At first, the drug of MIC (minimum inhibitory concentration) was determined by the methods based on BrothMIC NTM. The MICs of STFX, moxifloxacin (MFLX), gatifloxacin (GFLX) were low. On contrast, the MICs of garenoxacin (GRNX) and tosufloxacin (TFLX) were high. Two cases of pulmonary Mycobacterium avium-intracellulare complex (MAC) disease were treated by STFX-contained regimen. In all cases of pulmonary MAC disease, improve of symptoms and chest CT images were attained. Adverse events were slight. These MIC studies and case reports suggest that STFX might have excellent in vitro and in vivo antimicrobial activities against MAC and is considered to be a candidate for the medication against pulmonary MAC disease. PMID:25796743

  14. Rapid susceptibility testing of Mycobacterium avium complex and Mycobacterium tuberculosis isolated from AIDS patients

    NASA Technical Reports Server (NTRS)

    Dhople, Arvind M.

    1994-01-01

    In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of HIV infection will continue to rise more rapidly worldwide than predicted earlier. The AIDS patients are susceptible to diseases called opportunistic infections of which tuberculosis and Mycobacterium avium complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, MD, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. We proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis.

  15. Opportunistic Pathogens Mycobacterium Avium Complex (MAC) and Legionella spp. Colonise Model Shower

    PubMed Central

    Whiley, Harriet; Giglio, Steven; Bentham, Richard

    2015-01-01

    Legionella spp. and Mycobacterium avium complex (MAC) are opportunistic pathogens of public health concern. Hot water systems, including showers, have been identified as a potential source of infection. This paper describes the colonization of Legionella and MAC on the flexible tubing within a model potable shower system, utilizing thermostatic mixing and a flexible shower head. A MAC qPCR method of enumeration was also developed. MAC and Legionella spp. were detected within the biofilm at maximum concentrations of 7.0 × 104 and 2.0 × 103 copies/cm2 PVC tubing respectively. No significant changes were observed between sample of the flexible shower tubing that dried between uses and those that remained filled with water. This suggested the “unhooking” showerheads and allowing them to dry is not an effective method to reduce the risk of Legionella or MAC colonisation. PMID:26213977

  16. Typing of Clinical Mycobacterium avium Complex Strains Cultured during a 2-Year Period in Denmark by Using IS1245

    PubMed Central

    Bauer, Jeanett; Andersen, Åse B.; Askgaard, Dorthe; Giese, Sten B.; Larsen, Birger

    1999-01-01

    In the present study restriction fragment length polymorphism analyses with the recently described insertion sequence IS1245 as a probe was performed with clinical Mycobacterium avium complex strains cultured in Denmark during a 2-year period. The overall aim of the study was to disclose potential routes of transmission of these microorganisms. As a first step, the genetic diversity among isolates from AIDS patients and non-human immunodeficiency virus (HIV)-infected patients was described. In addition, a number of isolates from nonhuman sources cultured during the same period were analyzed and compared to the human isolates. A total of 203 isolates from AIDS patients (n = 90), non-HIV-infected patients (n = 91), and nonhuman sources (n = 22) were analyzed. The presence of IS1245 was restricted to Mycobacterium avium subsp. avium isolates. The majority of human isolates had large numbers of IS1245 copies, while nonhuman isolates could be divided into a high-copy-number group and a low-copy-number group. Groups of identical strains were found to be geographically widespread, comprising strains from AIDS patients as well as strains from non-HIV-infected patients. Samples of peat (to be used as potting soil) and veterinary samples were found to contain viable M. avium isolates belonging to genotypes also found in humans. PMID:9986819

  17. Detection of Mycobacteria, Mycobacterium avium Subspecies, and Mycobacterium tuberculosis Complex by a Novel Tetraplex Real-Time PCR Assay

    PubMed Central

    Molina, Elena; Elguezabal, Natalia; Pérez, Valentín; Garrido, Joseba M.

    2015-01-01

    Mycobacterium tuberculosis complex, Mycobacterium avium, and many other nontuberculous mycobacteria are worldwide distributed microorganisms of major medical and veterinary importance. Considering the growing epidemiologic significance of wildlife-livestock-human interrelation, developing rapid detection tools of high specificity and sensitivity is vital to assess their presence and accelerate the process of diagnosing mycobacteriosis. Here we describe the development and evaluation of a novel tetraplex real-time PCR for simultaneous detection of Mycobacterium genus, M. avium subspecies, and M. tuberculosis complex in an internally monitored single assay. The method was evaluated using DNA from mycobacterial (n = 38) and nonmycobacterial (n = 28) strains, tissues spiked with different CFU amounts of three mycobacterial species (n = 57), archival clinical samples (n = 233), and strains isolated from various hosts (n = 147). The minimum detectable DNA amount per reaction was 50 fg for M. bovis BCG and M. kansasii and 5 fg for M. avium subsp. hominissuis. When spiked samples were analyzed, the method consistently detected as few as 100 to 1,000 mycobacterial CFU per gram. The sensitivity and specificity values for the panel of clinical samples were 97.5 and 100% using a verified culture-based method as the reference method. The assays performed on clinical isolates confirmed these results. This PCR was able to identify M. avium and M. tuberculosis complex in the same sample in one reaction. In conclusion, the tetraplex real-time PCR we designed represents a highly specific and sensitive tool for the detection and identification of mycobacteria in routine laboratory diagnosis with potential additional uses. PMID:25588660

  18. Rapid susceptibility testing of mycobacterium avium complex and mycobacterium tuberculosis isolated from AIDS patients

    NASA Technical Reports Server (NTRS)

    Dhople, Arvind M.

    1993-01-01

    In ominous projections issued by both U.S. Public Health Service and the World Health Organization, the epidemic of the Human Immunodeficiency Virus (HIV) infection will continue to rise more rapidly worldwide than predicted earlier. The Acquired Immunodeficiency Syndrome (AIDS) patients are susceptible to diseases called opportunistic infections of which tuberculosis and M. avium Complex (MAC) infection are most common. This has created an urgent need to uncover new drugs for the treatment of these infections. In the seventies, NASA scientists at Goddard Space Flight Center, Greenbelt, Maryland, had adopted a biochemical indicator, adenosine triphosphate (ATP), to detect presence of life in extraterrestrial space. Therefore, we proposed to develop ATP assay technique to determine sensitivity of antibacterial compounds against MAC and M. tuberculosis. The work was initiated in June 1992. In the last report, we described our efforts in developing ATP assay method using MAC. Studies were continued further, and during the period of this report, we established the relationship between colony forming units and ATP levels of these organisms during the growth cycle. Also, we evaluated the effects of standard antimycobacterial drugs using ATP assay technique and compared the results with those obtained with conventional tube dilution proportional method.

  19. Mycobacterium avium Complex Infection in a Patient with Sickle Cell Disease and Severe Iron Overload

    PubMed Central

    Jafferjee, Nasima; Thomas, David; Jacobs, Gretta; Meyerson, Howard J.

    2014-01-01

    A 34-year-old female with sickle cell anemia (hemoglobin SS disease) and severe iron overload presented to our institution with the subacute presentation of recurrent pain crisis, fever of unknown origin, pancytopenia, and weight loss. A CT scan demonstrated both lung and liver nodules concerning for granulomatous disease. Subsequent biopsies of the liver and bone marrow confirmed the presence of noncaseating granulomas and blood cultures isolated Mycobacterium avium complex MAC. Disseminated MAC is considered an opportunistic infection typically diagnosed in the immunocompromised and rarely in immunocompetent patients. An appreciable number of mycobacterial infection cases have been reported in sickle cell disease patients without immune dysfunction. It has been reported that iron overload is known to increase the risk for mycobacterial infection in vitro and in vivo studies. While iron overload is primarily known to cause end organ dysfunction, the clinical relationship with sickle cell disease and disseminated MAC infection has not been reported. Clinical iron overload is a common condition diagnosed in the sub-Saharan African population. High dietary iron, genetic defects in iron trafficking, as well as hemoglobinopathy are believed to be the etiologies for iron overload in this region. Patients with iron overload in this region were 17-fold more likely to die from Mycobacterium tuberculosis. Both experimental and clinical evidence suggest a possible link to iron overload and mycobacterial infections; however larger observational studies are necessary to determine true causality. PMID:25544913

  20. The Significance of Mycobacterium abscessus Subspecies abscessus Isolation During Mycobacterium avium Complex Lung Disease Therapy

    PubMed Central

    Philley, Julie V.; Brown-Elliott, Barbara A.; Benwill, Jeana L.; Shepherd, Sara; York, Deanna; Wallace, Richard J.

    2015-01-01

    BACKGROUND: Isolation of Mycobacterium abscessus subspecies abscessus (MAA) is common during Mycobacterium avium complex (MAC) lung disease therapy, but there is limited information about the clinical significance of the MAA isolates. METHODS: We identified 53 of 180 patients (29%) treated for MAC lung disease who had isolation of MAA during MAC lung disease therapy. Patients were divided into those without (group 1) and those with (group 2) MAA lung disease. RESULTS: There were no significant demographic differences between patients with and without MAA isolation or between groups 1 and 2. Group 1 and 2 patients had similar total sputum cultures obtained (P = .7; 95% CI, −13.4 to 8.6) and length of follow-up (P = .8; 95% CI, −21.5 to 16.1). Group 2 patients had significantly more total positive cultures for MAA (mean±SD, 15.0 ± 11.1 vs 1.2 ± 0.4; P < .0001; 95% CI, −17.7 to −9.9), were significantly more likely to develop new or enlarging cavitary lesions while on MAC therapy (P > .0001), and were significantly more likely to meet all three American Thoracic Society diagnostic criteria for nontuberculous mycobacterial disease (21 of 21 [100%] vs 0 of 32 [0%]; P < .0001) compared with group 1 patients. Group 1 patients were significantly more likely to have single, positive MAA cultures than group 2 patients (25 of 31 vs 0 of 21; P < .0001). CONCLUSIONS: Microbiologic and clinical follow-up after completion of MAC lung disease therapy is required to determine the significance of MAA isolated during MAC lung disease therapy. Single MAA isolates are not likely to be clinically significant. PMID:25357074

  1. Relationship Between Lung Cancer and Mycobacterium Avium Complex Isolated Using Bronchoscopy

    PubMed Central

    Tamura, Atsuhisa; Hebisawa, Akira; Kusaka, Kei; Hirose, Takashi; Suzuki, Junko; Yamane, Akira; Nagai, Hideaki; Fukami, Takeshi; Ohta, Ken; Takahashi, Fumiaki

    2016-01-01

    Introduction: The incidence of Mycobacterium avium complex (MAC)-positive respiratory specimen cultures and MAC lung disease (MACLD) is increasing worldwide. This retrospective study aimed to assess the association between MAC culture-positive bronchoscopy specimens and lung cancer. Materials and Methods: The medical records of 1382 untreated lung cancer patients between 2003 and 2011 were collected using our hospital database. Of them, records for 1258 that had undergone bronchoscopy together with sampling for mycobacterial culture were reviewed. Patient characteristics were compared between those with MAC-positive/other nontuberculous mycobacteria (NTM)-negative bronchial washings and those with MAC-negative/other NTM-negative bronchial washings. Patients with MAC-positive lung cancer were cross-sectionally divided into MACLD and non-MACLD groups, and their features were assessed. Follow-up data for patients with lung cancer but without MACLD were reviewed for subsequent development of MACLD. Results: Of the 1258 patients with lung cancer, 25 (2.0%) had MAC-positive/other NTM-negative bronchial washings. The proportion of women (52% vs 30%; P = 0.0274) and patient age (72 years vs 69 years; P = 0.0380) were significantly higher in the MAC-positive/other NTM-negative lung cancer group (n = 25) than in the MAC-negative/other NTM-negative lung cancer group (n = 1223). There were 10 patients with lung cancer and MACLD and 15 without MACLD; significant differences in patient characteristics were not found between the two groups, and none of the 15 patients without MACLD subsequently developed MACLD. Conclusion: MAC culture-positive bronchial washing is positively associated with lung cancer. Female sex and advanced age, but not lung cancer characteristics, were found to be associated with MAC infection in patients with lung cancer. PMID:27335625

  2. Isolation of Mycobacterium avium complex from water in the United States, Finland, Zaire, and Kenya.

    PubMed Central

    von Reyn, C F; Waddell, R D; Eaton, T; Arbeit, R D; Maslow, J N; Barber, T W; Brindle, R J; Gilks, C F; Lumio, J; Lähdevirta, J

    1993-01-01

    Disseminated infection with organisms of the Mycobacterium avium complex (MAC) is a common complication of AIDS in the United States and other developing countries, but it is rare or absent in sub-Saharan Africa. To assess the comparative likelihood of exposure to MAC in these geographic areas, we used a standard protocol to culture 91 water samples from environmental sites and piped water supply systems in the United States, Finland, Zaire, and Kenya. MAC was isolated from all geographic areas and from 22 of 91 (24%) samples. Isolation rates were 13 of 47 (28%) for environmental samples and 9 of 44 (20%) for water supply samples. Overall isolation rates were 18 of 52 (35%) samples in the United States and Finland, whereas they were 4 of 39 (10%) samples in Zaire and Kenya (P = 0.015). MAC isolation rates from water supply systems were 8 of 25 (32%) samples in the United States and Finland and 1 of 19 (5%) samples in Zaire and Kenya (P = 0.056). MAC was isolated from hospital water in the United States and Finland but not in hospital water in Zaire and Kenya. Serovar determinations showed that six of eight isolates from the United States were serovar 4 or 8. One MAC isolate from Zaire was identified as an "X" mycobacterium. These data suggest that exposure to MAC in water is likely in diverse areas of the world, but that the likelihood of human exposure to the organism in water may be slightly less in sub-Saharan Africa than in developed countries in the Northern Hemisphere. PMID:8308115

  3. THE EFFECT OF TEMPERATURE ON THE GROWTH OF MYCOBACTERIUM AVIUM COMPLEX (MAC) ORGANISMS

    EPA Science Inventory

    MAC organisms are able to grow, persist, and colonize in water distribution systems and may amplify in hospital hot water systems. This study examined the response of MAC organisms (M. avium, M. intracellulare, and MX) to a range of temperatures commonly associated with drinking...

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

    PubMed

    Ogawa, Kenji; Sano, Chiaki

    2013-03-01

    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

  5. Proteins as paradigms of complex systems.

    SciTech Connect

    Fenimore, P. W.; Frauenfelder, Hans,; Young, R. D.

    2003-03-26

    The science of complexity has moved to center stage within the past few decades. Complex systems range from glasses to the immune system and the brain. Glasses are too simple to possess all aspects of complexity; brains are too complex to expose common concepts and laws of complexity. Proteins, however, are systems where many concepts and laws of complexity can be explored experimentally, theoretically, and computationally. Such studies have elucidated crucial aspects. The energy landscape has emerged as one central concept; it describes the free energy of a system as a function of temperature and the coordinates of all relevant atoms. A second concept is that of fluctuations. Without fluctuations, proteins would be dead and life impossible. A third concept is slaving. Proteins are not isolated systems; they are embedded in cells and membranes. Slaving arises when the fluctuations in the surroundings of a protein dominate many of the motions of the protein proper.

  6. Distinctive western blot antibody patterns induced by infection of mice with individual strains of the Mycobacterium avium complex.

    PubMed Central

    Elsaghier, A; Nolan, A; Allen, B; Ivanyi, J

    1992-01-01

    Systemic infection of mice with organisms of the Mycobacterium avium complex (MAC) induced antibody responses, characteristic for each of the three tested individual strains. The influence of host genetic factors was reflected up to 3 months after infection by the finding of generally oligobanded and multibanded Western blot patterns in C57B1/6 and BALB/c mice, respectively. Nevertheless, more bands developed at 6 months in C57BL/6 mice. The response to three antigens of 18,000, 38,000 and 24,000 MW was analysed in greater detail. Antibodies to a protease-resistant 18,000 MW band produced only by BALB/c mice were either strain specific, following infection with M. avium, strain Maa-B2, or cross-reactive within MAC, following infection with M. avium strain Maa-A6 and M. paratuberculosis, strain Map-203. Another protease-resistant antigen of 38,000 MW was immunogenic only in Maa-B2 infected mice. This constituent was found to be related to the protease-sensitive antigen of corresponding molecular weight from M. tuberculosis. Two 24,000 MW proteins of M. paratuberculosis were separated by two-dimensional gel electrophoresis: antibodies to the anodic band were induced by Map-203 infection, whilst the cathodic band was revealed by heteroclitic antibodies from Maa-B2-infected mice. The latter antigen is apparently expressed during in vivo replication, but not during in vitro culture of Maa-B2 bacteria. We generally conclude, that the selective antibody patterns after live infection, could be attributed to differences in the release of native antigens within mycobacterial lesions. In view of a high degree of species specificity, some of the immunogenic constituents identified may also be useful for serodiagnostic application. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1526646

  7. Generation of monoclonal antibodies to the specific sugar epitopes of Mycobacterium avium complex serovars.

    PubMed Central

    Rivoire, B; Ranchoff, B J; Chatterjee, D; Gaylord, H; Tsang, A Y; Kolk, A H; Aspinall, G O; Brennan, P J

    1989-01-01

    Monoclonal antibodies have been generated to the unique distal sugar epitopes on the oligosaccharide haptens of the glycopeptidolipid antigens of clinically prominent members of the Mycobacterium avium serocomplex. Thus, antibodies are described that recognize the distal O-acetyl-alpha-L-rhamnopyranosyl residue of the specific glycopeptidolipid of M. avium serovar 1, the 4-O-acetyl-2,3-di-O-methyl-alpha-L-fucopyranose of serovar 2, the 4-O-methyl-alpha-L-rhamnopyranosyl-(1----4)-2-O-methyl-alpha-L- fucopyranosyl unit of serovar 4, the 4,6-(1'-carboxyethylidene)-3-O-methyl-beta-D-glucopyranosyl unit of serovar 8 [and the 4,6-(1'-carboxyethylidene)-beta-D-glucopyranosyl residue of serovar 21], and the 4-O-acetyl-2,3-di-O-methyl-alpha-L-fucopyranosyl-(1----4)-beta-D- glucuronopyranosyl unit of serovar 9. Epitope definition was arrived at through use of the pure, chemically defined glycopeptidolipid antigens and neoglycoproteins containing the chemically synthesized distal sugars of some select serovars. These monoclonal antibodies combined with the already published information on the structure of the antigen determinants and the tools used to arrive at these structures provide powerful means for fundamental studies on the role of these antigens in immunopathogenesis and for the precise mapping of the epidemiology of opportunistic infections caused by M. avium. Images PMID:2476400

  8. Complex Engineered Systems: A New Paradigm

    NASA Astrophysics Data System (ADS)

    Mina, Ali A.; Braha, Dan; Bar-Yam, Yaneer

    Human history is often seen as an inexorable march towards greater complexity — in ideas, artifacts, social, political and economic systems, technology, and in the structure of life itself. While we do not have detailed knowledge of ancient times, it is reasonable to conclude that the average resident of New York City today faces a world of much greater complexity than the average denizen of Carthage or Tikal. A careful consideration of this change, however, suggests that most of it has occurred recently, and has been driven primarily by the emergence of technology as a force in human life. In the 4000 years separating the Indus Valley Civilization from 18th century Europe, human transportation evolved from the bullock cart to the hansom, and the methods of communication used by George Washington did not differ significantly from those used by Alexander or Rameses. The world has moved radically towards greater complexity in the last two centuries. We have moved from buggies and letter couriers to airplanes and the Internet — an increase in capacity, and through its diversity also in complexity, orders of magnitude greater than that accumulated through the rest of human history. In addition to creating iconic artifacts — the airplane, the car, the computer, the television, etc. — this change has had a profound effect on the scope of experience by creating massive, connected and multiultra- level systems — traffic networks, power grids, markets, multinational corporations — that defy analytical understanding and seem to have a life of their own. This is where complexity truly enters our lives.

  9. Broncho-Pleural Fistula with Hydropneumothorax at CT: Diagnostic Implications in Mycobacterium avium Complex Lung Disease with Pleural Involvement

    PubMed Central

    Yoon, Hyun Jung; Chung, Myung Jin; Lee, Kyung Soo; Kim, Jung Soo; Park, Hye Yun

    2016-01-01

    Objective To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. Materials and Methods We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. Results The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410–100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. Conclusion In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion. PMID:26957917

  10. Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.

    PubMed

    Tomioka, Haruaki; Sano, Chiaki; Sato, Katsumasa; Shimizu, Toshiaki

    2002-02-01

    We studied the activities of clarithromycin and fluoroquinolones (gatifloxacin, sitafloxacin, levofloxacin) in combination with other antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex (MAC). Clarithromycin potentiated the activities of rifampicin and rifalazil against both extracellular and intramacrophage MAC. In contrast, all the test quinolones exhibited antagonistic effects against extracellular MAC when combined with either clarithromycin or rifamycins. Such an antagonism was not observed for the activity of these combinations against intramacrophage MAC. Combined effects were observed with combinations of these fluoroquinolones with either ethambutol or streptomycin. Similar profiles were seen for the activities of two-drug combinations of clarithromycin or fluoroquinolones with other drugs against intramacrophage MAC isolated from pulmonary and disseminated MAC infections. PMID:11850167

  11. The presence of opportunistic pathogens, Legionella spp., L. pneumophila and Mycobacterium avium complex, in South Australian reuse water distribution pipelines.

    PubMed

    Whiley, H; Keegan, A; Fallowfield, H; Bentham, R

    2015-06-01

    Water reuse has become increasingly important for sustainable water management. Currently, its application is primarily constrained by the potential health risks. Presently there is limited knowledge regarding the presence and fate of opportunistic pathogens along reuse water distribution pipelines. In this study opportunistic human pathogens Legionella spp., L. pneumophila and Mycobacterium avium complex were detected using real-time polymerase chain reaction along two South Australian reuse water distribution pipelines at maximum concentrations of 10⁵, 10³ and 10⁵ copies/mL, respectively. During the summer period of sampling the concentration of all three organisms significantly increased (P < 0.05) along the pipeline, suggesting multiplication and hence viability. No seasonality in the decrease in chlorine residual along the pipelines was observed. This suggests that the combination of reduced chlorine residual and increased water temperature promoted the presence of these opportunistic pathogens. PMID:26042986

  12. Antineutrophil Cytoplasmic Antibody-associated Vasculitis Superimposed on Infection-related Glomerulonephritis Secondary to Pulmonary Mycobacterium avium Complex Infection.

    PubMed

    Asano, Shuichi; Mizuno, Shige; Okachi, Shotaro; Aso, Hiromichi; Wakahara, Keiko; Hashimoto, Naozumi; Ito, Satoru; Kozaki, Yohei; Katsuno, Takayuki; Maruyama, Shoichi; Hasegawa, Yoshinori

    2016-01-01

    A 73-year-old woman was diagnosed with pulmonary Mycobacterium avium complex (MAC) infection and received no treatment. Disease progression was evident one year later with the development of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) titers and systemic symptoms of a fever, polyarthritis, purpura, and rapidly progressive glomerulonephritis. Her symptoms did not improve with antibiotic treatment. A renal biopsy revealed crescentic glomerulonephritis with immunodeposition. According to these findings, she was diagnosed with ANCA-associated vasculitis (AAV) superimposed on infection-related glomerulonephritis (IRGN). Although there was a risk of aggravating an underlying infection, the combination therapy of corticosteroid and antibiotics improved AAV, IRGN, and even the lung radiological findings. To the best of our knowledge, this is the first case of AAV and IRGN secondary to pulmonary MAC infection. PMID:27580547

  13. [The dimension of the paradigm of complexity in health systems].

    PubMed

    Fajardo-Ortiz, Guillermo; Fernández-Ortega, Miguel Ángel; Ortiz-Montalvo, Armando; Olivares-Santos, Roberto Antonio

    2015-01-01

    This article presents elements to better understand health systems from the complety paradigm, innovative perspective that offers other ways in the conception of the scientific knowledge prevalent away from linear, characterized by the arise of emerging dissociative and behaviors, based on the intra and trans-disciplinarity concepts such knowledges explain and understand in a different way what happens in the health systems with a view to efficiency and effectiveness. The complexity paradigm means another way of conceptualizing the knowledge, is different from the prevalent epistemology, is still under construction does not separate, not isolated, is not reductionist, or fixed, does not solve the problems, but gives other bases to know them and study them, is a different strategy, a perspective that has basis in the systems theory, informatics and cybernetics beyond traditional knowledge, the positive logics, the newtonian physics and symmetric mathematics, in which everything is centered and balanced, joint the "soft sciences and hard sciences", it has present the Social Determinants of Health and organizational culture. Under the complexity paradigm the health systems are identified with the following concepts: entropy, neguentropy, the thermodynamic second law, attractors, chaos theory, fractals, selfmanagement and self-organization, emerging behaviors, percolation, uncertainty, networks and robusteness; such expressions open new possibilities to improve the management and better understanding of the health systems, giving rise to consider health systems as complex adaptive systems. PMID:25982615

  14. Absence of Mycobacterium intracellulare and Presence of Mycobacterium chimaera in Household Water and Biofilm Samples of Patients in the United States with Mycobacterium avium Complex Respiratory Disease

    PubMed Central

    Iakhiaeva, Elena; Williams, Myra D.; Brown-Elliott, Barbara A.; Vasireddy, Sruthi; Vasireddy, Ravikiran; Lande, Leah; Peterson, Donald D.; Sawicki, Janet; Kwait, Rebecca; Tichenor, Wellington S.; Turenne, Christine; Falkinham, Joseph O.

    2013-01-01

    Recent studies have shown that respiratory isolates from pulmonary disease patients and household water/biofilm isolates of Mycobacterium avium could be matched by DNA fingerprinting. To determine if this is true for Mycobacterium intracellulare, household water sources for 36 patients with Mycobacterium avium complex (MAC) lung disease were evaluated. MAC household water isolates from three published studies that included 37 additional MAC respiratory disease patients were also evaluated. Species identification was done initially using nonsequencing methods with confirmation by internal transcribed spacer (ITS) and/or partial 16S rRNA gene sequencing. M. intracellulare was identified by nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm samples. By ITS sequencing, 49 (90.7%) respiratory isolates were M. intracellulare and 4 (7.4%) were Mycobacterium chimaera. In contrast, 30 (73%) household water samples were M. chimaera, 8 (20%) were other MAC X species (i.e., isolates positive with a MAC probe but negative with species-specific M. avium and M. intracellulare probes), and 3 (7%) were M. avium; none were M. intracellulare. In comparison, M. avium was recovered from 141 water/biofilm samples. These results indicate that M. intracellulare lung disease in the United States is acquired from environmental sources other than household water. Nonsequencing methods for identification of nontuberculous mycobacteria (including those of the MAC) might fail to distinguish closely related species (such as M. intracellulare and M. chimaera). This is the first report of M. chimaera recovery from household water. The study underscores the importance of taxonomy and distinguishing the many species and subspecies of the MAC. PMID:23536397

  15. Response to stimulation with recombinant cytokines and synthesis of cytokines by murine intestinal macrophages infected with the Mycobacterium avium complex.

    PubMed Central

    Hsu, N; Young, L S; Bermudez, L E

    1995-01-01

    Current evidence suggests that the gut is the chief portal of entry for organisms of the Mycobacterium avium complex (MAC) in AIDS patients. Bacterial invasion of intestinal mucosa presumably occurs through epithelial cells, and M cells in the Peyer's patches, where the bacteria have contact with immunocompetent cells such as macrophages and T and B lymphocytes. As mucosal macrophages are probably the first line of defense against MAC, we examined their ability to inhibit intracellular growth of MAC when properly stimulated. Mouse intestinal macrophages were purified, infected with MAC 101, serovar 1, and MAC 86-2686, serovar 16, and subsequently stimulated with recombinant tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), or macrophage colony-stimulating factor (M-CSF). Viable intracellular bacteria were quantitated at 24 h after infection and again after 4 days of infection. Stimulation with TNF-alpha, IFN-gamma, and GM-CSF, but not M-CSF, was associated with mycobacteriostatic and/or mycobactericidal activity in macrophages. Treatment with 10(3) U of TNF-alpha, GM-CSF, and IFN-gamma per ml at 24 h prior to infection with MAC resulted in a significant enhancement in killing of MAC at 4 days after infection, compared with that observed for macrophages exposed to cytokines after infection. When stimulated with lipopolysaccharide or live MAC, intestinal macrophages had produced significantly less TNF-alpha and transforming growth factor beta than had splenic and peritoneal macrophages, although the levels of production of interleukin 6 and interleukin 10 among the three populations of cells were similar. Intestinal macrophages can be stimulated with cytokines to inhibit the intracellular growth of MAC, but they have differentiated abilities to produce cytokines which can modulate the anti-MAC immune response. PMID:7822018

  16. Mycobacterium avium complex olecranon bursitis resolves without antimicrobials or surgical intervention: A case report and review of the literature

    PubMed Central

    Working, Selene; Tyser, Andrew; Levy, Dana

    2015-01-01

    Introduction Nontuberculous mycobacteria are an uncommon cause of septic olecranon bursitis, though cases have increasingly been described in both immunocompromised and immunocompetent hosts. Guidelines recommend a combination of surgical resection and antimicrobials for treatment. This case is the first reported case of nontuberculous mycobacterial olecranon bursitis that resolved without medical or surgical intervention. Case presentation A 67-year-old female developed a painless, fluctuant swelling of the olecranon bursa following blunt trauma to the elbow. Due to persistent bursal swelling, she underwent three separate therapeutic bursal aspirations, two involving intrabursal steroid injection. After the third aspiration, the bursa became erythematous and severely swollen, and bursal fluid grew Mycobacterium avium complex. Triple-drug antimycobacterial therapy was initiated, but discontinued abruptly due to a rash. Surgery was not performed. The patient was observed off antimicrobials, and gradually clinically improved with a compressive dressing. By 14 months after initial presentation, clinical exam revealed complete resolution of the previously erythematous bursal mass. Discussion This is the first reported case of nontuberculous mycobacterial olecranon bursitis managed successfully without surgery or antimicrobials. Musculoskeletal nontuberculous mycobacterial infections are challenging given the lack of clinical data about optimal duration and choice of antimicrobials or the role of surgery. Additionally, the potential toxicity and drug interactions of antimycobacterials are not insignificant and warrant close monitoring if treatment is pursued. Conclusion This case raises an important clinical question of whether close observation off antimicrobials is appropriate in select cases of immunocompetent patients with localized atypical mycobacterial disease of soft tissue and skeletal structures. PMID:26793457

  17. Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

    PubMed Central

    González-Pérez, Mónica; Mariño-Ramírez, Leonardo; Parra-López, Carlos Alberto; Murcia, Martha Isabel; Marquina, Brenda; Mata-Espinoza, Dulce; Rodriguez-Míguez, Yadira; Baay-Guzman, Guillermina J.; Huerta-Yepez, Sara

    2013-01-01

    The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue. PMID:23959717

  18. Spectrum of activity of levofloxacin against nontuberculous mycobacteria and its activity against the Mycobacterium avium complex in combination with ethambutol, rifampin, roxithromycin, amikacin, and clofazimine.

    PubMed Central

    Rastogi, N; Goh, K S; Bryskier, A; Devallois, A

    1996-01-01

    The spectrum of activity of levofloxacin was initially determined against 29 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs. Levofloxacin MICs were 1 to 2 dilutions lower compared with those obtained for ofloxacin and 8 to 64 dilutions lower compared with those obtained for its D-isomer. Levofloxacin MICs were below its peak level in serum (5.5 micrograms/ml following administration of a single oral dose of 350 mg) for 25 of 29 isolates tested. It possessed MICs below its peak level in serum for M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, M. kansasii, M. chelonei, M. abcessus, M. fortuitum, and M. peregrinum. Regarding the M. avium complex, the MICs of levofloxacin for 11 clinical isolates (7 from human immunodeficiency virus-positive patients and 4 from human immunodeficiency virus-negative patients) were 1 to 2 dilutions lower than those of ofloxacin. Among 20 isolates belonging to 12 pathogenic mycobacterial species, the MBC/MIC ratios varied from 1 to 4 for levofloxacin and 2 to 4 for ofloxacin. When drug combinations were screened by using the radiometric x/y quotient methodology against five M. avium complex isolates, levofloxacin activity against all five isolates was enhanced by ethambutol and activity against three isolates was enhanced by clofazimine. Screening of three-drug combinations showed that the combination levofloxacin-ethambutol with a third potential anti-M. avium drug (rifampin, roxithromycin, amikacin, or clofazimine) resulted in enhanced activity for all 20 drug combinations screened. PMID:8913450

  19. Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages.

    PubMed Central

    Rastogi, N; Labrousse, V; Goh, K S; De Sousa, J P

    1991-01-01

    The MICs and MBCs of the new difluorinated quinolone drug sparfloxacin against type strains belonging to 21 species of mycobacteria were screened. The MICs and MBCs were within the range of 0.1 to 2.0 and 0.1 to 4.0 micrograms/ml, respectively (with an MBC/MIC ratio of 1 to 2), and against 18 of the 21 species tested, the drug showed significant bactericidal activity (at least 99% killing or more of the initial inoculum added) at concentrations well within the reported peak concentrations in serum (Cmax) in humans. MICs of sparfloxacin for 7 of 10 Mycobacterium avium complex strains were below the Cmax, with MBC/MIC ratios within the range of 2 to 4. Enhancement of its activity by ethambutol, rifampin, amikacin, and clarithromycin (which were used at sublethal concentrations) assessed by using BACTEC radiometry revealed that its activity was further enhanced in 2 of 10 strains by rifampin and in 7 of 10 strains by ethambutol. The bactericidal effects of various drugs used alone as well as two-drug combinations used at Cmax levels were also screened against four strains of M. avium complex growing intracellularly in two different macrophage systems, namely, mouse bone marrow-derived macrophages and peripheral blood monocyte-derived human macrophages. Our results showed a satisfactory correlation between the extracellular and intracellular drug activity data. PMID:1667250

  20. The role of efflux pumps in macrolide resistance in Mycobacterium avium complex.

    PubMed

    Rodrigues, Liliana; Sampaio, Daniela; Couto, Isabel; Machado, Diana; Kern, Winfried V; Amaral, Leonard; Viveiros, Miguel

    2009-12-01

    Mycobacteriumavium complex (MAC) is clinically important since it can cause severe infections in acquired immune deficiency syndrome (AIDS) patients and other immunocompromised individuals. Use of the macrolides clarithromycin and azithromycin has improved the outcome of MAC infections, but therapeutic failure is still a major problem. In this work, we studied efflux pump activity in MAC clinical strains and evaluated the contribution of active efflux to macrolide resistance. Eighteen clinical strains isolated from AIDS patients were evaluated for macrolide resistance in the presence and absence of the efflux pump inhibitors (EPIs) thioridazine, chlorpromazine and verapamil. The efflux activity of these strains was then assessed by a semi-automated fluorometric method that detects extrusion of ethidium bromide (EtBr), a known efflux pump substrate. Resistance to clarithromycin was significantly reduced in the presence of thioridazine, chlorpromazine and verapamil. The same EPIs were effective in decreasing the efflux of EtBr from MAC cells. Moreover, increased retention of [(14)C]-erythromycin in the presence of these EPIs further demonstrated that active efflux contributes to MAC resistance to macrolides. This study demonstrates that efflux pumps play an important role in MAC resistance to antibiotics. PMID:19740629

  1. Mycobacterium Avium Complex (MAC)

    MedlinePlus

    ... MAC? The symptoms of MAC can include high fevers, chills, diarrhea , weight loss, stomach aches, fatigue, and anemia ( ... anemia. Many drug interactions. Rifampin (Rifampicin, Rifadin, Rimactane): fever, chills, muscle or bone pain; can turn urine, sweat, ...

  2. Polyclonal infections due to Mycobacterium avium complex in patients with AIDS detected by pulsed-field gel electrophoresis of sequential clinical isolates.

    PubMed Central

    Slutsky, A M; Arbeit, R D; Barber, T W; Rich, J; von Reyn, C F; Pieciak, W; Barlow, M A; Maslow, J N

    1994-01-01

    Invasive infection with organisms of the Mycobacterium avium complex (MAC) is common among patients with advanced human immunodeficiency virus infection. In previous studies, we analyzed multiple individual colonies of MAC isolated from specimens obtained at the same time and observed that 14 to 20% of patients are simultaneously infected with more than one strain. In this study, we examined sequential isolates from 12 patients with AIDS who had two or more MAC isolates available from clinical specimens collected more than 1 week apart; the intervals between the first and last specimens ranged from 8 to 192 (median, 46) days. For each isolate, restriction digests of genomic DNA were analyzed by pulsed-field gel electrophoresis; DNA was prepared by using a protocol, described here in detail, which had been optimized for conditions of bacterial growth and lysis. The pulsed-field gel electrophoresis analysis identified four patients (33%) infected with two different MAC strains. Both M. avium and M. intracellulare were cultured from blood specimens from two patients. In each of the four patients, the second strain was identified from a culture taken within 14 days of the initial study isolate, and in three of these patients, the first strain was detected again in a subsequent culture. These observations suggest that the presence of two different strains among isolates from sequential cultures may reflect ongoing polyclonal infection. We conclude that polyclonal infection with MAC is common among patients with AIDS. The identification of such infections may be critical in the development of effective treatments. Images PMID:7929773

  3. Complexity, Training Paradigm Design, and the Contribution of Memory Subsystems to Grammar Learning

    PubMed Central

    Ettlinger, Marc; Wong, Patrick C. M.

    2016-01-01

    Although there is variability in nonnative grammar learning outcomes, the contributions of training paradigm design and memory subsystems are not well understood. To examine this, we presented learners with an artificial grammar that formed words via simple and complex morphophonological rules. Across three experiments, we manipulated training paradigm design and measured subjects' declarative, procedural, and working memory subsystems. Experiment 1 demonstrated that passive, exposure-based training boosted learning of both simple and complex grammatical rules, relative to no training. Additionally, procedural memory correlated with simple rule learning, whereas declarative memory correlated with complex rule learning. Experiment 2 showed that presenting corrective feedback during the test phase did not improve learning. Experiment 3 revealed that structuring the order of training so that subjects are first exposed to the simple rule and then the complex improved learning. The cumulative findings shed light on the contributions of grammatical complexity, training paradigm design, and domain-general memory subsystems in determining grammar learning success. PMID:27391085

  4. Therapeutic Effects of Benzoxazinorifamycin KRM-1648 Administered Alone or in Combination with a Half-Sized Secretory Leukocyte Protease Inhibitor or the Nonsteroidal Anti-Inflammatory Drug Diclofenac Sodium against Mycobacterium avium Complex Infection in Mice

    PubMed Central

    Sano, Chiaki; Shimizu, Toshiaki; Sato, Katsumasa; Kawauchi, Hideyuki; Kawahara, Shin; Tomioka, Haruaki

    1999-01-01

    The effects of half-sized secretory leukocyte protease inhibitor or diclofenac sodium administered alone or in combination with the benzoxazinorifamycin KRM-1648 on the therapeutic efficacy of KRM-1648 against Mycobacterium avium complex (MAC) in mice were studied. Neither of the two anti-inflammatory drugs affected the efficacy of KRM-1648, while they exerted significant modulating effects on tumor necrosis factor alpha production by MAC-infected macrophages. PMID:9925533

  5. Advancing Clinical Proteomics via Analysis Based on Biological Complexes: A Tale of Five Paradigms.

    PubMed

    Goh, Wilson Wen Bin; Wong, Limsoon

    2016-09-01

    Despite advances in proteomic technologies, idiosyncratic data issues, for example, incomplete coverage and inconsistency, resulting in large data holes, persist. Moreover, because of naïve reliance on statistical testing and its accompanying p values, differential protein signatures identified from such proteomics data have little diagnostic power. Thus, deploying conventional analytics on proteomics data is insufficient for identifying novel drug targets or precise yet sensitive biomarkers. Complex-based analysis is a new analytical approach that has potential to resolve these issues but requires formalization. We categorize complex-based analysis into five method classes or paradigms and propose an even-handed yet comprehensive evaluation rubric based on both simulated and real data. The first four paradigms are well represented in the literature. The fifth and newest paradigm, the network-paired (NP) paradigm, represented by a method called Extremely Small SubNET (ESSNET), dominates in precision-recall and reproducibility, maintains strong performance in small sample sizes, and sensitively detects low-abundance complexes. In contrast, the commonly used over-representation analysis (ORA) and direct-group (DG) test paradigms maintain good overall precision but have severe reproducibility issues. The other two paradigms considered here are the hit-rate and rank-based network analysis paradigms; both of these have good precision-recall and reproducibility, but they do not consider low-abundance complexes. Therefore, given its strong performance, NP/ESSNET may prove to be a useful approach for improving the analytical resolution of proteomics data. Additionally, given its stability, it may also be a powerful new approach toward functional enrichment tests, much like its ORA and DG counterparts. PMID:27454466

  6. Toward a Complexity Paradigm for Understanding Gender Role Conflict

    ERIC Educational Resources Information Center

    Enns, Carolyn Zerbe

    2008-01-01

    The well-developed body of theory and research on men's gender role conflict provides an excellent foundation for developing increasingly complex models of men's gender-related concerns. Theorists and researchers are encouraged to incorporate themes related to social structural aspects of gender as well as to examine the ways in which men's…

  7. Two markers, IS901-IS902 and p40, identified by PCR and by using monoclonal antibodies in Mycobacterium avium strains.

    PubMed Central

    Ahrens, P; Giese, S B; Klausen, J; Inglis, N F

    1995-01-01

    The occurrence of two markers, a newly identified 40-kDa protein (p40) and the insertion sequence IS901-IS902, in strains of Mycobacterium avium subspp. was evaluated. Analysis of 184 type and field strains of the M. avium complex from human, animal, and environmental sources by PCR specific to IS901 and by a monoclonal antibody specific to p40 demonstrated the presence of the two molecular markers in all of the M. avium subsp. silvaticum strains examined and also in a number of M. avium subsp. avium strains (the latter isolated mainly from pigs). The appearance of the two markers was completely concurrent in all strains. Further, the marker-positive M. avium subsp. avium strains were mainly serotype 2, whereas M. avium complex strains of serotypes 4, 6, 8, 9, and 10 were marker negative. The M. avium subsp. avium type strains ATCC 25291 and approximately 50% of the M. avium subsp. avium field strains isolated from animals contained the markers, while only one strain of human origin was found to be marker positive. Therefore, IS901 and p40 appear to have substantial potential to differentiate among isolates of the M. avium complex. This observation raises new issues regarding classification of strains, since the presence of the markers was found to be inconsistent with the present taxonomic grouping of M. avium subspp. PMID:7615703

  8. Rapid Mycobacterial Liquid Culture-Screening Method for Mycobacterium avium Complex Based on Secreted Antigen-Capture Enzyme-Linked Immunosorbent Assay▿

    PubMed Central

    Shin, Sung Jae; Anklam, Kelly; Manning, Elizabeth J. B.; Collins, Michael T.

    2009-01-01

    Sensors in automated liquid culture systems for mycobacteria, such as MGIT, BacT/Alert 3D, and Trek ESP II, flag growth of any type of bacteria; a positive signal does not mean that the target mycobacteria are present. All signal-positive cultures thus require additional and often laborious testing. An immunoassay was developed to screen liquid mycobacterial cultures for evidence of Mycobacterium avium complex (MAC). The method, called the MAC-enzyme-linked immunosorbent assay (ELISA), relies on detection of MAC-specific secreted antigens in liquid culture. Secreted MAC antigens were captured by the MAC-ELISA with polyclonal anti- Mycobacterium avium subsp. paratuberculosis chicken immunoglobulin Y (IgY), detected using rabbit anti-MAC IgG, and then revealed using horseradish peroxidase-conjugated goat anti-rabbit IgG. When the MAC-ELISA was evaluated using pure cultures of known mycobacterial (n = 75) and nonmycobacterial (n = 17) organisms, no false-positive or false-negative MAC-ELISA results were found. By receiver operator characteristic (ROC) analysis of 1,275 previously identified clinical isolates, at the assay optimal cutoff the diagnostic sensitivity and specificity of the MAC-ELISA were 92.6% (95% confidence interval [95% CI], 90.3 to 94.5) and 99.9% (95% CI, 99.2 to 100), respectively, with an area under the ROC curve of 0.992. Prospective evaluation of the MAC-ELISA with an additional 652 clinical samples inoculated into MGIT ParaTB medium and signaling positive per the manufacturer's instructions found that the MAC-ELISA was effective in determining those cultures that actually contained MAC species and warranting the resources required to identify the organism by PCR. Of these 652 MGIT-positive cultures, the MAC-ELISA correctly identified 96.8% (of 219 MAC-ELISA-positive cultures) as truly containing MAC mycobacteria, based on PCR or high-performance liquid chromatography (HPLC) as reference tests. Only 6 of 433 MGIT signal-positive cultures (1

  9. Paradigms of Complexity in Modelling of Fluid and Kinetic Processes

    NASA Astrophysics Data System (ADS)

    Diamond, P. H.

    2006-10-01

    The need to discuss and compare a wide variety of models of fluid and kinetic processes is motivated by the astonishing wide variety of complex physical phenomena which occur in plasmas in nature. Such phenomena include, but are not limited to: turbulence, turbulent transport and mixing, reconnection and structure formation. In this talk, I will review how various fluid and kinetic models come to grips with the essential physics of these phenomena. For example, I will discuss how the idea of a turbulent cascade and the concept of an ``eddy'' are realized quite differently in fluid and Vlasov models. Attention will be placed primarily on physical processes, the physics content of various models, and the consequences of choices in model construction, rather than on the intrinsic mathematical structure of the theories. Examples will be chosen from fusion, laboratory, space and astrophysical plasmas.

  10. Descriptive analysis of the prevalence and the molecular epidemiology of Mycobacterium avium complex-infected pigs that were slaughtered on the main island of Okinawa.

    PubMed

    Hibiya, K; Kazumi, Y; Nishiuchi, Y; Sugawara, I; Miyagi, K; Oda, Y; Oda, E; Fujita, J

    2010-09-01

    Recent genetic studies have revealed that several epidemiological factors affect Mycobacterium avium complex (MAC) infection in pig populations. However, mechanisms underlying the spread of MAC infection among hog farms have not been clarified. In consideration of this situation, we cross-sectionally investigated the mechanisms underlying the spread of MAC on the island of Okinawa. Pigs slaughtered (n=706,763) and 331 hog farms on Okinawa were surveyed during the years 2002-2004. Two outbreaks of MAC infection were occurred in several farms during survey period. Bacteria were isolated from randomly selected pigs and genotype of isolates was determined by using genetic finger printing methods with the insertion sequence (IS) 1245 restriction fragment length polymorphism (RFLP). Most isolates had large numbers of IS1245 copies, while strains with low copy numbers of IS1245 and isolates without IS1245 were seen in few farms. MACs strains were repeatedly isolated from pigs of the affected farms during the survey period. Those farms with an identical pig rearing systems showed synchronic changes in the prevalence of MAC infection. An industrial farm without an outbreak had an independent pig flow, but maintained distinct MAC strains. Multivariate analysis did not reveal independent factors for the prevalence of the MAC infection. These findings suggest that there were three clusters distinguished genetically in the main island of Okinawa, which were potentially spread by common pig flow. However, the outbreaks occurred because of unspecified conditions on each farm environment. PMID:19443033

  11. Is Primary Mycobacterium avium Complex Prophylaxis Necessary in Patients with CD4 < 50 Cells/μL Who Are Virologically Suppressed on cART?

    PubMed Central

    Yangco, Bienvenido G.; Buchacz, Kate; Baker, Rose; Palella, Frank J.; Armon, Carl; Brooks, John T.

    2015-01-01

    We analyzed 369 patients with no prior Mycobacterium avium complex (MAC) infection and CD4 < 50 cells/ μL (baseline), while on combination antiretroviral therapy(cART), for incidence rates of primary MAC infection during the 6 months after baseline, by prophylaxis status. Of participants (median age, 40 years old), most were male (81%) and about half were non-white; at baseline, 81% of participants were on cART > 60 days and 19% had HIV RNA < 1000 copies/mL, whereas 65% had HIV RNA > 10,000 copies/mL. Eleven patients had MAC infection within 6 months baseline (rate = 0.6/100 person months): 4/175 on MAC prophylaxis vs. 7/194, no MAC prophylaxis (p = 0.64). Of the 11 patients, seven had HIV RNA > 10,000, and three > 1000–9999 copies/mL at baseline (one missing). Median time to MAC infection was 62 days (IQR 43–126, maximum 139 days). No MAC infection occurred among 71 (19%) patients virologically suppressed (HIV RNA < 1000 copies/mL) at baseline, including 41 patients with no MAC prophylaxis during follow-up. A small number of eligible virologically suppressed participants and the lack of data on cART/MAC prophylaxis adherence limited our observational nonrandomized study. Primary MAC prophylaxis may not be required for cART-virologically suppressed patients with CD4 < 50 cells/mL. PMID:24833016

  12. Is primary mycobacterium avium complex prophylaxis necessary in patients with CD4 <50 cells/μL who are virologically suppressed on cART?

    PubMed

    Yangco, Bienvenido G; Buchacz, Kate; Baker, Rose; Palella, Frank J; Armon, Carl; Brooks, John T

    2014-06-01

    We analyzed 369 patients with no prior Mycobacterium avium complex (MAC) infection and CD4 <50 cells/μL (baseline), while on combination antiretroviral therapy(cART), for incidence rates of primary MAC infection during the 6 months after baseline, by prophylaxis status. Of participants (median age, 40 years old), most were male (81%) and about half were non-white; at baseline, 81% of participants were on cART >60 days and 19% had HIV RNA <1000 copies/mL, whereas 65% had HIV RNA >10,000 copies/mL. Eleven patients had MAC infection within 6 months baseline (rate=0.6/100 person months): 4/175 on MAC prophylaxis vs. 7/194, no MAC prophylaxis (p=0.64). Of the 11 patients, seven had HIV RNA >10,000, and three >1000-9999 copies/mL at baseline (one missing). Median time to MAC infection was 62 days (IQR 43-126, maximum 139 days). No MAC infection occurred among 71 (19%) patients virologically suppressed (HIV RNA <1000 copies/mL) at baseline, including 41 patients with no MAC prophylaxis during follow-up. A small number of eligible virologically suppressed participants and the lack of data on cART/MAC prophylaxis adherence limited our observational nonrandomized study. Primary MAC prophylaxis may not be required for cART-virologically suppressed patients with CD4 <50 cells/mL. PMID:24833016

  13. Challenging the Limits of Critique in Education through Morin's Paradigm of Complexity

    ERIC Educational Resources Information Center

    Alhadeff-Jones, Michel

    2010-01-01

    The position adopted in this paper is inspired by Edgar Morin's paradigm of complexity and his critique of scientific and philosophical forms of reductionism. This paper is based on research focusing on the diversity of conceptions of critique developed in academic discourses. It aims to challenge the fragmentation and the reduction framing the…

  14. Complexity aided design. The FuturICT technological innovation paradigm

    NASA Astrophysics Data System (ADS)

    Carbone, A.; Ajmone-Marsan, M.; Axhausen, K. W.; Batty, M.; Masera, M.; Rome, E.

    2012-11-01

    "In the next century, planet earth will don an electronic skin. It will use the Internet as a scaffold to support and transmit its sensations. This skin is already being stitched together. It consists of millions of embedded electronic measuring devices: thermostats, pressure gauges, pollution detectors, cameras, microphones, glucose sensors, EKGs, electroencephalographs. These will probe and monitor cities and endangered species, the atmosphere, our ships, highways and fleets of trucks, our conversations, our bodies-even our dreams ....What will the earth's new skin permit us to feel? How will we use its surges of sensation? For several years-maybe for a decade-there will be no central nervous system to manage this vast signaling network. Certainly there will be no central intelligence...some qualities of self-awareness will emerge once the Net is sensually enhanced. Sensuality is only one force pushing the Net toward intelligence". These statements are quoted by an interview by Cherry Murray, Dean of the Harvard School of Engineering and Applied Sciences and Professor of Physics. It is interesting to outline the timeliness and highly predicting power of these statements. In particular, we would like to point to the relevance of the question "What will the earth's new skin permit us to feel?" to the work we are going to discuss in this paper. There are many additional compelling questions, as for example: "How can the electronic earth's skin be made more resilient?"; "How can the earth's electronic skin be improved to better satisfy the need of our society?";"What can the science of complex systems contribute to this endeavour?"

  15. An eye-tracking paradigm for analyzing the processing time of sentences with different linguistic complexities.

    PubMed

    Wendt, Dorothea; Brand, Thomas; Kollmeier, Birger

    2014-01-01

    An eye-tracking paradigm was developed for use in audiology in order to enable online analysis of the speech comprehension process. This paradigm should be useful in assessing impediments in speech processing. In this paradigm, two scenes, a target picture and a competitor picture, were presented simultaneously with an aurally presented sentence that corresponded to the target picture. At the same time, eye fixations were recorded using an eye-tracking device. The effect of linguistic complexity on language processing time was assessed from eye fixation information by systematically varying linguistic complexity. This was achieved with a sentence corpus containing seven German sentence structures. A novel data analysis method computed the average tendency to fixate the target picture as a function of time during sentence processing. This allowed identification of the point in time at which the participant understood the sentence, referred to as the decision moment. Systematic differences in processing time were observed as a function of linguistic complexity. These differences in processing time may be used to assess the efficiency of cognitive processes involved in resolving linguistic complexity. Thus, the proposed method enables a temporal analysis of the speech comprehension process and has potential applications in speech audiology and psychoacoustics. PMID:24950184

  16. An Eye-Tracking Paradigm for Analyzing the Processing Time of Sentences with Different Linguistic Complexities

    PubMed Central

    Wendt, Dorothea; Brand, Thomas; Kollmeier, Birger

    2014-01-01

    An eye-tracking paradigm was developed for use in audiology in order to enable online analysis of the speech comprehension process. This paradigm should be useful in assessing impediments in speech processing. In this paradigm, two scenes, a target picture and a competitor picture, were presented simultaneously with an aurally presented sentence that corresponded to the target picture. At the same time, eye fixations were recorded using an eye-tracking device. The effect of linguistic complexity on language processing time was assessed from eye fixation information by systematically varying linguistic complexity. This was achieved with a sentence corpus containing seven German sentence structures. A novel data analysis method computed the average tendency to fixate the target picture as a function of time during sentence processing. This allowed identification of the point in time at which the participant understood the sentence, referred to as the decision moment. Systematic differences in processing time were observed as a function of linguistic complexity. These differences in processing time may be used to assess the efficiency of cognitive processes involved in resolving linguistic complexity. Thus, the proposed method enables a temporal analysis of the speech comprehension process and has potential applications in speech audiology and psychoacoustics. PMID:24950184

  17. Diagnostic test accuracy of anti-glycopeptidolipid-core IgA antibodies for Mycobacterium avium complex pulmonary disease: systematic review and meta-analysis

    PubMed Central

    Shibata, Yuji; Horita, Nobuyuki; Yamamoto, Masaki; Tsukahara, Toshinori; Nagakura, Hideyuki; Tashiro, Ken; Watanabe, Hiroki; Nagai, Kenjiro; Nakashima, Kentaro; Ushio, Ryota; Ikeda, Misako; Narita, Atsuya; Kanai, Akinori; Sato, Takashi; Kaneko, Takeshi

    2016-01-01

    Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6–52.8, I2 = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837–0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621–0.761) and 0.906 (95% CI 0.836–0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1–13.8) and 0.34 (95% CI 0.26–0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value. PMID:27373718

  18. Diagnostic test accuracy of anti-glycopeptidolipid-core IgA antibodies for Mycobacterium avium complex pulmonary disease: systematic review and meta-analysis.

    PubMed

    Shibata, Yuji; Horita, Nobuyuki; Yamamoto, Masaki; Tsukahara, Toshinori; Nagakura, Hideyuki; Tashiro, Ken; Watanabe, Hiroki; Nagai, Kenjiro; Nakashima, Kentaro; Ushio, Ryota; Ikeda, Misako; Narita, Atsuya; Kanai, Akinori; Sato, Takashi; Kaneko, Takeshi

    2016-01-01

    Currently, an anti-glycopeptidolipid (GPL)-core IgA antibody assay kit for diagnosing Mycobacterium avium complex (MAC) is commercially available. We conducted this systematic review and meta-analysis to reveal the precise diagnostic accuracy of anti-GPL-core IgA antibodies for MAC pulmonary disease (MAC-PD). We systematically searched reports that could provide data for both sensitivity and specificity by anti-GPL-core IgA antibody for clinically diagnosed MAC-PD. Diagnostic test accuracy was estimated using the bivariate model. Of the 257 articles that we had found through primary search, we finally included 16 reports consisted of 1098 reference positive subjects and 2270 reference negative subjects. The diagnostic odds ratio was 24.8 (95% CI 11.6-52.8, I(2) = 5.5%) and the area under the hierarchical summary receiver operating characteristic curves was 0.873 (95% CI 0.837-0.913). With a cutoff value of 0.7 U/mL, the summary estimates of sensitivity and specificity were 0.696 (95% CI 0.621-0.761) and 0.906 (95% CI 0.836-0.951), respectively. The positive and negative likelihood ratios were 7.4 (95% CI 4.1-13.8) and 0.34 (95% CI 0.26-0.43), respectively. The demanding clinical diagnostic criteria may be a cause of false positive of the index test. The index test had good overall diagnostic accuracy and was useful to ruling in MAC-PD with the cutoff value. PMID:27373718

  19. Mycobacterium avium subspecies Paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genome sequence has now defined the complete catalog of genes that make Mycobacterium avium subsp paratuberculosis what it is. Although similarity searches and bioinformatics analyses have assigned potential function to hundreds of genes in this pathogen, the future challenge is to begin to sys...

  20. Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (Map) is the causative agent of Johne’s disease in cattle and other domesticated and wild ruminant species. The organism and disease were first described over a century ago, and despite the considerable morbidity and mortality associated with Map infection...

  1. Characterization of clinical and environmental Mycobacterium avium spp. isolates and their interaction with human macrophages

    EPA Science Inventory

    Members of the Mycobacterium avium complex (MAC) are naturally occurring bacteria in the environment. A link has been suggested between M. avium strains in drinking water and clinical isolates from infected individuals. There is a need to develop new screening methodologies tha...

  2. Differences in serological responses to specific glycopeptidolipid-core and common lipid antigens in patients with pulmonary disease due to Mycobacterium tuberculosis and Mycobacterium avium complex.

    PubMed

    Fujita, Yukiko; Doi, Takeshi; Maekura, Ryoji; Ito, Masami; Yano, Ikuya

    2006-02-01

    Disease due to the Mycobacterium avium complex (MAC) is one of the most important opportunistic pulmonary infections. Since the clinical features of MAC pulmonary disease and tuberculosis (TB) resemble each other, and the former is often difficult to treat with chemotherapy, early differential diagnosis is desirable. The humoral immune responses to both diseases were compared by a unique multiple-antigen ELISA using mycobacterial species-common and species-specific lipid antigens, including glycopeptidolipid (GPL)-core. The results were assessed for two patient groups hospitalized and diagnosed clinically as having TB or MAC pulmonary disease. Diverse IgG antibody responsiveness was demonstrated against five lipid antigens: (1) monoacyl phosphatidylinositol dimannoside (Ac-PIM2), (2) cord factor (trehalose 6,6'-dimycolate) (TDM-T) and (3) trehalose monomycolate from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) (TMM-T), and (4) trehalose monomycolate (TMM-M) and (5) GPL-core from MAC. Anti-GPL-core IgG antibody was critical, and detected only in the primary and the secondary MAC diseases with high positivity, up to 88.4 %. However, IgG antibodies against Ac-PIM2, TDM-T and TMM-T were elevated in both TB and MAC patients. Anti-TMM-M IgG antibody was also elevated in MAC disease preferentially, with a positive rate of 89.9 %, and therefore, it was also useful for the diagnosis of the disease. IgG antibody levels were increased at the early stages of the disease and declined in parallel to the decrease of bacterial burden to near the normal healthy control level, when the anti-mycobacterial chemotherapy was completed successfully. Unexpectedly, about 25 % of hospitalized TB patient sera were anti-GPL-core IgG antibody positive, although the specificity of GPL-core was sufficiently high (95.8 % negative in healthy controls), suggesting that a considerable number of cases of latent co-infection with MAC may exist in TB patients. Taken together, the combination of

  3. IS1311 and IS1245 Restriction Fragment Length Polymorphism Analyses, Serotypes, and Drug Susceptibilities of Mycobacterium avium Complex Isolates Obtained from a Human Immunodeficiency Virus-Negative Patient

    PubMed Central

    Dvorska, Lenka; Bartos, Milan; Ostadal, Oldrich; Kaustova, Jarmila; Matlova, Ludmila; Pavlik, Ivo

    2002-01-01

    Six isolates of Mycobacterium avium of genotype dnaJ+ IS901− IS1311+ IS1245+ and serotypes 6 (n = 1), 6/9, (n = 2), and 9 (n = 3) were obtained within a 5-month period from a human immunodeficiency virus-negative patient treated for tuberculosis. The isolates were identified with PvuII restriction fragment length polymorphism (RFLP) analysis as a single IS1311 RFLP type and six different IS1245 RFLP types. Six separate colonies/clones obtained by subculture from each of the six isolates were tested for MICs of a set of 10 drugs. This report documents the appearance of isolates that are resistant to antimycobacterial drugs as the duration of therapy increases. Because isolates recovered from the patient following longer duration of treatment were more likely to be resistant to more antimycobacterial drugs, we would conclude that there was selection for antimycobacterial drug-resistant isolates. Analyses of all 36 clones identified three IS1311 and 22 IS1245 types forming three clusters. Tests of 105 environmental samples collected in the home and the work place of the patient yielded 16 mycobacterial isolates, of which one M. avium from soil was of genotype dnaJ+ IS901+ IS1311+ IS1245+ and serotype 2, and the second M. avium from a vacuum cleaner was of genotype dnaJ+ IS901− IS1311+ IS1245+ and serotype 9. Overall analyses of the results did not reveal any relation between serotype, RFLP type, and drug susceptibility. Based on the course of the disease in the patient and different serotypes, IS1311 and IS1245 RFLP types of isolates of M. avium we suppose represent polyclonal infection. PMID:12354870

  4. Viewing Complex, Dynamic Scenes "Through the Eyes" of Another Person: The Gaze-Replay Paradigm.

    PubMed

    Bush, Jennifer Choe; Pantelis, Peter Christopher; Morin Duchesne, Xavier; Kagemann, Sebastian Alexander; Kennedy, Daniel Patrick

    2015-01-01

    We present a novel "Gaze-Replay" paradigm that allows the experimenter to directly test how particular patterns of visual input-generated from people's actual gaze patterns-influence the interpretation of the visual scene. Although this paradigm can potentially be applied across domains, here we applied it specifically to social comprehension. Participants viewed complex, dynamic scenes through a small window displaying only the foveal gaze pattern of a gaze "donor." This was intended to simulate the donor's visual selection, such that a participant could effectively view scenes "through the eyes" of another person. Throughout the presentation of scenes presented in this manner, participants completed a social comprehension task, assessing their abilities to recognize complex emotions. The primary aim of the study was to assess the viability of this novel approach by examining whether these Gaze-Replay windowed stimuli contain sufficient and meaningful social information for the viewer to complete this social perceptual and cognitive task. The results of the study suggested this to be the case; participants performed better in the Gaze-Replay condition compared to a temporally disrupted control condition, and compared to when they were provided with no visual input. This approach has great future potential for the exploration of experimental questions aiming to unpack the relationship between visual selection, perception, and cognition. PMID:26252493

  5. Paradigms in the structural biology of the mitogenic ternary complex FGF:FGFR:heparin.

    PubMed

    Pomin, Vitor H

    2016-08-01

    The main achievements regarding the molecular interaction involving fibroblast growth factors (FGFs), canonical receptors (FGFRs) and the glycosaminoglycans (GAGs) heparan sulfate (HS)/heparin (Hp) are overviewed. Despite the recent works concerning the subject, conflicting paradigms in the structural biology of the resultant ternary complex FGF:FGFR:HS/Hp seem to persist up to these days. The principal dilemma, centered on the functional intermolecular complex of mitogenesis and angiogenesis, has been lasting for approximately a decade and a half since the publications of the two contradicting crystal structures, the asymmetric 2:2:1 versus the symmetric 2:2:2 complex model. When the principal results regarding this ternary complex are analyzed as a whole and through an impartial manner, conclusion heavily and reliably supports the existence and activity of both complex models. Selection of each complex is driven by multiple factors of different degrees of impact. Specificity in protein-binding motifs in ligands (although the minimal binding sequences are yet controversial), slight differences on the structure of the GAG-binding sites of FGF and of FGFR isoforms as well as on the possible ligand-induced conformational changes of FGFR are examples of these factors. Here, the structural biology of the mitogenic FGF:FGFR:HS/Hp ternary complex is revisited. Discussion is focused on the major attributes of this intermolecular complex including the existing conflicts about the righter biologically active model and information regarding ligand structure, conformation and minimal length required for binding to the growth factors and receptors. This review is very timely in light of the 100(th) anniversary of the discovery of Hp. PMID:27263122

  6. Using Common Graphics Paradigms Implemented in a Java Applet to Represent Complex Scheduling Requirements

    NASA Technical Reports Server (NTRS)

    Jaap, John; Meyer, Patrick; Davis, Elizabeth

    1997-01-01

    The experiments planned for the International Space Station promise to be complex, lengthy and diverse. The scarcity of the space station resources will cause significant competition for resources between experiments. The scheduling job facing the Space Station mission planning software requires a concise and comprehensive description of the experiments' requirements (to ensure a valid schedule) and a good description of the experiments' flexibility (to effectively utilize available resources). In addition, the continuous operation of the station, the wide geographic dispersion of station users, and the budgetary pressure to reduce operations manpower make a low-cost solution mandatory. A graphical representation of the scheduling requirements for station payloads implemented via an Internet-based application promises to be an elegant solution that addresses all of these issues. The graphical representation of experiment requirements permits a station user to describe his experiment by defining "activities" and "sequences of activities". Activities define the resource requirements (with alternatives) and other quantitative constraints of tasks to be performed. Activities definitions use an "outline" graphics paradigm. Sequences define the time relationships between activities. Sequences may also define time relationships with activities of other payloads or space station systems. Sequences of activities are described by a "network" graphics paradigm. The bulk of this paper will describe the graphical approach to representing requirements and provide examples that show the ease and clarity with which complex requirements can be represented. A Java applet, to run in a web browser, is being developed to support the graphical representation of payload scheduling requirements. Implementing the entry and editing of requirements via the web solves the problems introduced by the geographic dispersion of users. Reducing manpower is accomplished by developing a concise

  7. Molecular characterization of Mycobacterium avium complex isolates giving discordant results in AccuProbe tests by PCR-restriction enzyme analysis, 16S rRNA gene sequencing, and DT1-DT6 PCR.

    PubMed Central

    Devallois, A; Picardeau, M; Paramasivan, C N; Vincent, V; Rastogi, N

    1997-01-01

    Based on cultural and biochemical tests, a total of 84 strains (72 clinical and 12 environmental isolates from the Caribbean Isles, Europe, and the Indian subcontinent) were identified as members of the Mycobacterium avium complex (MAC). They were further characterized with MAC, M. avium, and M. intracellulare probes of the AccuProbe system, and this was followed by selective amplification of DT6 and DT1 sequences. Seventy isolates gave concordant results; 63 were identified as M. avium, 5 were identified as M. intracellulare, and 24 remained untypeable by both methods. Fourteen isolates gave discrepant results, as they were DT1 positive but gave negative results by the M. intracellulare AccuProbe test. Consequently, a detailed molecular analysis of all DT1-positive isolates (14 discrepant strains plus 5 M. intracellulare strains) was performed by PCR-restriction analysis (PRA) of the hsp65 gene and 16S rRNA gene sequencing. The results confirmed the reported heterogeneity of M. intracellulare, as only 6 of 19 isolates (32%) gave PRA results compatible with published M. intracellulare profiles while the rest of the isolates were grouped in four previously unpublished profiles. 16S rRNA gene sequencing showed that only 8 of 19 isolates (42%) were related to M. intracellulare IWGMT 90247 (EMBL accession no. X88917), the rest being related to MCRO19 (EMBL accession no. X93030) and MIWGTMR10 (EMBL accession no. X88915). In conclusion, we have characterized a significant number of MAC isolates which were not identified by the AccuProbe test, PRA, or 16S rRNA sequencing. However, all of them were identifiable by DT1-DT6 PCR (they were DT6 negative and DT1 positive) and could be tentatively identified as M. intracellulare based on previously published observations. It is noteworthy that the majority of such isolates (14 of 19) were from the Indian subcontinent, with 12 of 14 being environmental isolates. Our study confirms the marked heterogeneity of M. intracellulare

  8. The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders.

    PubMed

    De Vilder, Eva Y G; Hosen, Mohammad Jakir; Vanakker, Olivier M

    2015-01-01

    The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as chronic kidney disease or cardiovascular disorders have been linked to the ABCC6 gene. While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them. To gain more insights, multiple approaches are being used including next-generation sequencing, computational methods, and various "omics" technologies. Much effort is made to place the vast amount of data that is gathered in an integrated system-biological network; the involvement of ABCC6 in common disorders provides a good view on the wide implications and potential of such a network. In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases. PMID:26356190

  9. The ABCC6 Transporter as a Paradigm for Networking from an Orphan Disease to Complex Disorders

    PubMed Central

    De Vilder, Eva Y. G.; Hosen, Mohammad Jakir; Vanakker, Olivier M.

    2015-01-01

    The knowledge on the genetic etiology of complex disorders largely results from the study of rare monogenic disorders. Often these common and rare diseases show phenotypic overlap, though monogenic diseases generally have a more extreme symptomatology. ABCC6, the gene responsible for pseudoxanthoma elasticum, an autosomal recessive ectopic mineralization disorder, can be considered a paradigm gene with relevance that reaches far beyond this enigmatic orphan disease. Indeed, common traits such as chronic kidney disease or cardiovascular disorders have been linked to the ABCC6 gene. While during the last decade the awareness of the wide ramifications of ABCC6 has increased significantly, the gene itself and the transmembrane transporter it encodes have not unveiled all of the mysteries that surround them. To gain more insights, multiple approaches are being used including next-generation sequencing, computational methods, and various “omics” technologies. Much effort is made to place the vast amount of data that is gathered in an integrated system-biological network; the involvement of ABCC6 in common disorders provides a good view on the wide implications and potential of such a network. In this review, we summarize the network approaches used to study ABCC6 and the role of this gene in several complex diseases. PMID:26356190

  10. Disparate Host Immunity to Mycobacterium avium subsp. paratuberculosis Antigens in Calves Inoculated with M. avium subsp. paratuberculosis, M. avium subsp. avium, M. kansasii, and M. bovis

    PubMed Central

    Waters, W. R.; Bannantine, J. P.; Palmer, M. V.

    2013-01-01

    The cross-reactivity of mycobacterial antigens in immune-based diagnostic assays has been a major concern and a criticism of the current tests that are used for the detection of paratuberculosis. In the present study, Mycobacterium avium subsp. paratuberculosis recombinant proteins were evaluated for antigenic specificity compared to a whole-cell sonicate preparation (MPS). Measures of cell-mediated immunity to M. avium subsp. paratuberculosis antigens were compared in calves inoculated with live M. avium subsp. paratuberculosis, M. avium subsp. avium (M. avium), Mycobacterium kansasii, or Mycobacterium bovis. Gamma interferon (IFN-γ) responses to MPS were observed in all calves that were exposed to mycobacteria compared to control calves at 4 months postinfection. Pooled recombinant M. avium subsp. paratuberculosis proteins also elicited nonspecific IFN-γ responses in inoculated calves, with the exception of calves infected with M. bovis. M. avium subsp. paratuberculosis proteins failed to elicit antigen-specific responses for the majority of immune measures; however, the expression of CD25 and CD26 was upregulated on CD4, CD8, gamma/delta (γδ) T, and B cells for the calves that were inoculated with either M. avium subsp. paratuberculosis or M. avium after antigen stimulation of the cells. Stimulation with MPS also resulted in the increased expression of CD26 on CD45RO+ CD25+ T cells from calves inoculated with M. avium subsp. paratuberculosis and M. avium. Although recombinant proteins failed to elicit specific responses for the calves inoculated with M. avium subsp. paratuberculosis, the differences in immune responses to M. avium subsp. paratuberculosis antigens were dependent upon mycobacterial exposure. The results demonstrated a close alignment in immune responses between calves inoculated with M. avium subsp. paratuberculosis and those inoculated with M. avium that were somewhat disparate from the responses in calves infected with M. bovis, suggesting

  11. Fluorescence In Situ Hybridization Using Peptide Nucleic Acid Probes for Rapid Detection of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. paratuberculosis in Potable-Water Biofilms

    PubMed Central

    Lehtola, Markku J.; Torvinen, Eila; Miettinen, Ilkka T.; Keevil, C. William

    2006-01-01

    Here, we present for the first time a high-affinity peptide nucleic acid (PNA) oligonucleotide sequence for detecting Mycobacterium avium bacteria, including the opportunistically pathogenic subspecies M. avium subsp. avium, M. avium subsp. paratuberculosis, and M. avium subsp. silvaticum, by the fluorescence in situ hybridization (FISH) method. There is evidence that M. avium subsp. avium especially is able to survive and grow in drinking-water biofilms and possibly transmit via drinking water. The designed PNA probe (MAV148) specificity was tested with several bacterial species, including other mycobacteria and mycolic acid-containing bacteria. From the range of bacterial strains tested, only M. avium subsp. avium and M. avium subsp. paratuberculosis strains were hybridized. The PNA FISH method was applied successfully to detect M. avium subsp. avium spiked in water samples and biofilm established within a Propella biofilm reactor fed with potable water from a distribution supply. PMID:16391126

  12. "To Give an Example Is a Complex Act": Agamben's Pedagogy of the Paradigm

    ERIC Educational Resources Information Center

    Meskin, Jacob; Shapiro, Harvey

    2014-01-01

    Agamben's notion of the "paradigm" has far-reaching implications for educational thinking, curriculum design and pedagogical conduct. In his approach, examples--or paradigms--deeply engage our powers of analogy, enabling us to discern previously unseen affinities among singular objects by stepping outside established systems of…

  13. Molecular analysis and MIRU-VNTR typing of Mycobacterium avium subsp. avium, 'hominissuis' and silvaticum strains of veterinary origin.

    PubMed

    Rónai, Zsuzsanna; Csivincsik, Ágnes; Dán, Ádám; Gyuranecz, Miklós

    2016-06-01

    Besides Mycobacterium avium subsp. paratuberculosis (MAP), M. avium subsp. avium (MAA), M. avium subsp. silvaticum (MAS), and 'M. avium subsp. hominissuis' (MAH) are equally important members of M. avium complex, with worldwide distribution and zoonotic potential. Genotypic discrimination is a prerequisite to epidemiological studies which can facilitate disease prevention through revealing infection sources and transmission routes. The primary aim of this study was to identify the genetic diversity within 135 MAA, 62 MAS, and 84 MAH strains isolated from wild and domestic mammals, reptiles and birds. Strains were tested for the presence of large sequence polymorphism LSP(A)17 and were submitted to Mycobacterial interspersed repetitive units-variable-number tandem repeat (MIRU-VNTR) analysis at 8 loci, including MIRU1, 2, 3, and 4, VNTR25, 32, and 259, and MATR9. In 12 strains hsp65 sequence code type was also determined. LSP(A)17 was present only in 19.9% of the strains. All LSP(A)17 positive strains belonged to subspecies MAH. The discriminatory power of the MIRU-VNTR loci set used reached 0.9228. Altogether 54 different genotypes were detected. Within MAH, MAA, and MAS strains 33, 16, and 5 different genotypes were observed. The described genotypes were not restricted to geographic regions or host species, but proved to be subspecies specific. Our knowledge about MAS is limited due to isolation and identification difficulties. This is the first study including a large number of MAS field strains. Our results demonstrate the high diversity of MAH and MAA strains and the relative uniformity of MAS strains. PMID:26964909

  14. Immunogenicity of Proteome-Determined Mycobacterium avium subsp. paratuberculosis-Specific Proteins in Sheep with Paratuberculosis▿

    PubMed Central

    Hughes, Valerie; Bannantine, John P.; Denham, Susan; Smith, Stuart; Garcia-Sanchez, Alfredo; Sales, Jill; Paustian, Michael L.; Mclean, Kevin; Stevenson, Karen

    2008-01-01

    Mycobacterium avium subsp. paratuberculosis causes paratuberculosis, a chronic granulomatous enteritis. Detecting animals with paratuberculosis infections is difficult because the currently available tools have low sensitivity and lack specificity; these tools are prone to generating spurious positive test results caused by exposure to environmental M. avium complex organisms. To generate candidate antigens for incorporation into a specific test for paratuberculosis, subspecies-specific proteins were determined by proteomic comparison of M. avium subsp. paratuberculosis and M. avium subsp. avium. Analysis was aimed at revealing proteins only expressed (or predominant) in the protein profile of M. avium subspecies paratuberculosis. Two-dimensional gel electrophoresis resolved approximately 1,000 protein spots from each subspecies. Proteome analysis identified protein spots whose expression profile appeared markedly increased in M. avium subsp. paratuberculosis, and 32 were identified by analysis of their tryptic peptide profile by matrix-assisted laser desorption ionization-time of flight analysis. Thirty of these proteins were cloned, and their recombinant proteins were expressed. Ovine paratuberculosis sera were used to assess their immunoreactivity by enzyme-linked immunosorbent assay (ELISA), Western blotting, and dot blot analysis. Seventeen proteins were detected in at least one of the immunoassays, and eleven proteins were detected by ELISA with an optical density in excess of the cutoff of 0.1 in four of six sera tested. The immunoreactivity of these proteins indicates their potential as unique diagnostic antigens for the development of a specific serological detection of paratuberculosis. PMID:18845834

  15. New probes used for IS1245 and IS1311 restriction fragment length polymorphism of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. hominissuis isolates of human and animal origin in Norway

    PubMed Central

    Johansen, Tone Bjordal; Olsen, Ingrid; Jensen, Merete Rusås; Dahle, Ulf R; Holstad, Gudmund; Djønne, Berit

    2007-01-01

    Background Mycobacterium avium is an environmental mycobacterium that can be divided into the subspecies avium, hominissuis, paratuberculosis and silvaticum. Some M. avium subspecies are opportunistic pathogens for animals and humans. They are ubiquitous in nature and can be isolated from natural sources of water, soil, plants and bedding material. Isolates of M. avium originating from humans (n = 37), pigs (n = 51) and wild birds (n = 10) in Norway were examined by IS1245 and IS1311 RFLP using new and specific probes and for the presence of IS901 and ISMpa1 by PCR. Analysis and generation of a dendrogram were performed with the software BioNumerics. Results IS1311 RFLP provided clear results that were easy to interpret, while IS1245 RFLP generated more complex patterns with a higher discriminatory power. The combination of the two methods gave additional discrimination between isolates. All avian isolates except one were M. avium subsp. avium with two copies of IS1311 and one copy of IS1245, while the isolates of human and porcine origin belonged to M. avium subsp.hominissuis. The isolates from human patients were distributed randomly among the clusters of porcine isolates. There were few identical isolates. However, one isolate from a human patient was identical to a porcine isolate. Regional differences were detected among the porcine isolates, while there was no clustering of human isolates according to type of clinical symptoms or geographical location of the patient's home addresses. Conclusion The results demonstrate that a wide range of M. avium subsp.hominissuis are present in pigs and humans in Norway, and that some of these isolates are very similar. It remains to be determined whether humans are infected from pigs or if they are infected from common environmental sources. PMID:17335590

  16. Binding of the 68-kilodalton protein of Mycobacterium avium to alpha(v)beta3 on human monocyte-derived macrophages enhances complement receptor type 3 expression.

    PubMed Central

    Hayashi, T; Rao, S P; Catanzaro, A

    1997-01-01

    this receptor mediated by M. avium-alpha(v)beta3 interaction indicates a complex mechanism of communication among different receptors that participate in M. avium attachment and uptake. These findings add to current understanding of the roles played by multiple receptor-ligand systems in uptake and pathogenesis of intracellular pathogens such as M. avium. PMID:9119453

  17. [Three cases of Mycobacterium avium lung disease in an iron foundry].

    PubMed

    Sato, K; Matsumoto, H; Ogasa, T; Takahashi, M; Takeda, A; Fujita, Y; Yamazaki, Y; Tobise, K

    2000-09-01

    We report three cases of M. avium lung disease, all occurring in the same iron foundry over a 5-year period. Case 1: A 38-year-old man was admitted to our hospital because of abnormal chest x-ray shadows observed during a routine checkup. M. avium complex was isolated from the sputum and a CT scan showed multiple nodular shadows with cavities. Case 2: A 63-year-old man presented with dyspnea. Chest CT showed nodular shadows in both upper lobes. M. avium complex was isolated from his sputum. Case 3: A 62-year-old man was hospitalized for treatment of diabetes mellitus. A nodular cavitary shadow* OK?* in the right upper lobe was observed in the radiograph. CT scanning demonstrated a nodular shadow with thick pleural indentation. M. avium was isolated from the sputum and gastric juices. There were similarities in the radiographic findings in all cases: nodular shadows with cavities in the upper lung fields. These findings differed from those in another M. avium infection in the lung which occurred in a middle-aged woman. We suspected inhalation of an aerosol contaminated by M. avium complex. There have hitherto been no reports of group infections in healthy persons. We suspected the same environmental source for the infection. PMID:11109808

  18. Lymphadenitis in children is caused by Mycobacterium avium hominissuis and not related to ‘bird tuberculosis’

    PubMed Central

    de Haas, P. E. W.; Lindeboom, J. A.; Kuijper, E. J.; van Soolingen, D.

    2008-01-01

    Mycobacterium avium is the most commonly encountered mycobacterium species among non-Mycobacterium tuberculosis complex (nontuberculous mycobacteria) isolates worldwide and frequently causes lymphadenitis in children. During a multi-centre study in The Netherlands that was performed to determine the optimal treatment for mycobacterial lymphadenitis, concern was expressed in the media about the possible role of birds as sources of these M. avium infections, referred to as ‘bird tuberculosis.’ To examine the involvement of birds in mycobacterial lymphadenitis, 34 M. avium isolates from lymphadenitis cases were subjected to IS1245 restriction fragment length polymorphism (RFLP) typing. This genotyping method enables the distinction of the subspecies M. avium subsp. hominissuis and the ‘bird-type’ M. avium spp. avium. Highly variable RFLP patterns were found among the lymphadenitis M. avium isolates, and all belonged to the M. avium hominissuis subspecies. A relation to pet birds in the etiology of mycobacterial lymphadenitis could not be established, and the source of the infections may be environmental. PMID:18320245

  19. Genotyping of Mycobacterium avium subsp. avium isolates from naturally infected lofts of domestic pigeons in Ahvaz by IS901 RFLP

    PubMed Central

    Parvandar-Asadollahi, Kaveh; Mosavari, Nader; Mayahi, Mansoor

    2015-01-01

    Background and Objectives: Avian tuberculosis is one of the most important infections affecting most species of birds. Mycobacterium avium can not only infect all species of birds, but also infect some domesticated mammals. The most crucial aspect of control and eradication scheme is identification of infection sources and transmission routs. Molecular techniques such as restriction fragment length polymorphism and pulse field gel electrophoresis have been shown to be much more discriminatory and suitable for use in the epidemiological study. Materials and Methods: Eighty suspected pigeons to avian tuberculosis based on their clinical signs, were subjected to the study. Forty Mycobacterium avium subsp. avium isolates out of a total of 51 identified isolates were subjected to the test. Results: IS901-RFLP using Pvu II was successfully conducted and produced 7 patterns. The majority of isolates (60%) were RFLP type PI.1. This type was the most similar type to standard strain. However, all the patterns obtained in this study were different from the standard strain. Conclusion: The result of this study indicate that these isolates probably are limited to Khuzestan region. We recommend DNA fingerprinting differentiation of non tuberculous Mycobacteria particularly Mycobacterium avium complex isolated from infected birds and human to possibly find source of infections. PMID:26719782

  20. Reducing human exposure to Mycobacterium avium.

    PubMed

    Falkinham, Joseph O

    2013-08-01

    In light of the increasing prevalence of Mycobacterium avium pulmonary disease and the challenges of treating patients with M. avium infection, consideration of measures to reduce exposure is warranted. Because M. avium inhabits water and soil, humans are surrounded by that opportunistic pathogen. Because infection has been linked to the presence of M. avium in household plumbing, increasing hot water temperature, reducing aerosol (mist) exposures in bathrooms and showers, and installing filters that prevent the passage of mycobacteria will likely reduce M. avium exposure. Granular activated carbon (charcoal) filters support the growth of M. avium and should be avoided. When gardening, avoid the inhalation of soil dusts by using a mask or wetting the soil because peat-rich potting soils have high numbers of mycobacteria. PMID:23952861

  1. Isolation of Mycobacterium avium from waterfowl with polycystic livers.

    USGS Publications Warehouse

    Roffe, Thomas J.

    1989-01-01

    An unusual gross appearance of avian tuberculosis, where fluid-filled thin-walled cysts are produced and grossly apparent in preference to granulomas, is presented. Histopathology confirmed the granulomatous nature of the lesions and the presence of intracellular acid-fast organisms. Mycobacterium avium complex was cultured from affected organs. The unusual gross presentation in these cases indicates the need to consider tuberculosis in the differential of cystic diseases of avian livers.

  2. Emergence and decline of scientific paradigms in a dynamic complex network

    NASA Astrophysics Data System (ADS)

    Yao, Chao; Zhang, Mei

    2013-01-01

    We study the idea spreading process by extending a recent model proposed by Bornholdt [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.106.058701 106, 058701 (2011)] to the population on a two-dimensional square area either in the presence of static topological randomness or in which agents are allowed to freely move. We find that the static topological randomness induced by the random distribution of agents in the square area disfavors the common pattern of scientific paradigms, which is characterized by quick rise and slow decline of an arbitrary dominant idea. However, the common pattern of scientific paradigms is recovered when the movement of agents is enabled. In addition, we find that, when the moving speed of agents is low, the average lifetime of a dominant idea displays an optimal behavior. In contrast, the evolution of the model is no more sensitive to the movement speed once it is high enough.

  3. Mycobacterium avium MAV_2941 mimics Phosphoinositol-3-Kinase to interfere with macrophage phagosome maturation

    PubMed Central

    Danelishvili, Lia; Bermudez, Luiz E.

    2015-01-01

    Mycobacterium avium subsp hominissuis (M. avium) is a pathogen that infects and survives in macrophages. Previously, we have identified the M. avium MAV_2941 gene encoding a 73 amino acid protein exported by the oligopeptide transporter OppA to the macrophage cytoplasm. Mutations in MAV_2941 were associated with significant impairment of M. avium growth in THP-1 macrophages. In this study, we investigated the molecular mechanism of MAV_2941 action and demonstrated that MAV_2941 interacts with the vesicle trafficking proteins syntaxin-8 (STX8), adaptor-related protein complex 3 (AP-3) complex subunit beta-1 (AP3B1) and Archain 1 (ARCN1) in mononuclear phagocytic cells. Sequencing analysis revealed that the binding site of MAV_2941 is structurally homologous to the human phosphatidylinositol 3-kinase (PI3K) chiefly in the region recognized by vesicle trafficking proteins. The β3A subunit of AP-3, encoded by AP3B1, is essential for trafficking cargo proteins, including lysosomal-associated membrane protein 1 (LAMP-1), to the phagosome and lysosome-related organelles. Here, we show that while the heat-killed M. avium when ingested by macrophages co-localizes with LAMP-1 protein, transfection of MAV_2941 in macrophages results in significant decrease of LAMP-1 co-localization with the heat-killed M. avium phagosomes. Mutated MAV_2941, where the amino acids homologous to the binding region of PI3K were changed, failed to interact with trafficking proteins. Inactivation of the AP3B1 gene led to alteration in the trafficking of LAMP-1. These results suggest that M. avium MAV_2941 interferes with the protein trafficking within macrophages altering the maturation of phagosome. PMID:26043821

  4. Mycobacterium avium MAV_2941 mimics phosphoinositol-3-kinase to interfere with macrophage phagosome maturation.

    PubMed

    Danelishvili, Lia; Bermudez, Luiz E

    2015-09-01

    Mycobacterium avium subsp hominissuis (M. avium) is a pathogen that infects and survives in macrophages. Previously, we have identified the M. avium MAV_2941 gene encoding a 73 amino acid protein exported by the oligopeptide transporter OppA to the macrophage cytoplasm. Mutations in MAV_2941 were associated with significant impairment of M. avium growth in THP-1 macrophages. In this study, we investigated the molecular mechanism of MAV_2941 action and demonstrated that MAV_2941 interacts with the vesicle trafficking proteins syntaxin-8 (STX8), adaptor-related protein complex 3 (AP-3) complex subunit beta-1 (AP3B1) and Archain 1 (ARCN1) in mononuclear phagocytic cells. Sequencing analysis revealed that the binding site of MAV_2941 is structurally homologous to the human phosphatidylinositol 3-kinase (PI3K) chiefly in the region recognized by vesicle trafficking proteins. The β3A subunit of AP-3, encoded by AP3B1, is essential for trafficking cargo proteins, including lysosomal-associated membrane protein 1 (LAMP-1), to the phagosome and lysosome-related organelles. Here, we show that while the heat-killed M. avium when ingested by macrophages co-localizes with LAMP-1 protein, transfection of MAV_2941 in macrophages results in significant decrease of LAMP-1 co-localization with the heat-killed M. avium phagosomes. Mutated MAV_2941, where the amino acids homologous to the binding region of PI3K were changed, failed to interact with trafficking proteins. Inactivation of the AP3B1 gene led to alteration in the trafficking of LAMP-1. These results suggest that M. avium MAV_2941 interferes with the protein trafficking within macrophages altering the maturation of phagosome. PMID:26043821

  5. Identification of Mycobacterium tuberculosis and M. avium complex directly from smear-positive sputum specimens and BACTEC 12B cultures by high-performance liquid chromatography with fluorescence detection and computer-driven pattern recognition models.

    PubMed

    Jost, K C; Dunbar, D F; Barth, S S; Headley, V L; Elliott, L B

    1995-05-01

    A high-performance liquid chromatography method that utilized fluorescence detection (HPLC-FL) of mycolic acid 6,7-dimethoxycoumarin esters was developed to identify Mycobacterium tuberculosis (MTB) and M. avium complex (MAC) directly from fluorochrome stain smear-positive sputum specimens and young BACTEC 12B cultures. HPLC-FL chromatograms from a training set that included 202 smear-positive clinical sputum specimens and 343 mycobacterial cultures were used to construct a calibrated peak-naming table and computer-based pattern recognition models for MTB and MAC. Pattern recognition model performance was measured with an evaluation set of samples that included 251 smear-positive clinical sputum specimens and 167 BACTEC 12B cultures. Evaluation sputum specimens were culture positive for MTB (n = 132) and MAC (n = 48). With evaluation sputa, the MTB and MAC models were 56.8 and 33.3% sensitive, respectively. Evaluation set BACTEC 12B cultures were culture positive for MTB (n = 97) and MAC (n = 53). The sensitivities of the MTB and MAC models for identification of BACTEC 12B cultures were 99.0 and 94.3%, respectively. The specificity of both models was 100% for both types of evaluation samples. The average times from BACTEC 12B inoculation to cell harvest were 10.2 and 7.4 days for MTB and MAC, respectively. HPLC-FL can identify MTB and MAC in 1 day from many smear-positive sputa. Rapid and sensitive identification of MTB and MAC from young BACTEC 12B cultures was achieved. PMID:7615740

  6. The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice

    PubMed Central

    Krueger-Burg, Dilja; Winkler, Daniela; Mitkovski, Mišo; Daher, Fernanda; Ronnenberg, Anja; Schlüter, Oliver M.; Dere, Ekrem; Ehrenreich, Hannelore

    2016-01-01

    Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID:27563287

  7. The SocioBox: A Novel Paradigm to Assess Complex Social Recognition in Male Mice.

    PubMed

    Krueger-Burg, Dilja; Winkler, Daniela; Mitkovski, Mišo; Daher, Fernanda; Ronnenberg, Anja; Schlüter, Oliver M; Dere, Ekrem; Ehrenreich, Hannelore

    2016-01-01

    Impairments in social skills are central to mental disease, and developing tools for their assessment in mouse models is essential. Here we present the SocioBox, a new behavioral paradigm to measure social recognition. Using this paradigm, we show that male wildtype mice of different strains can readily identify an unfamiliar mouse among 5 newly acquainted animals. In contrast, female mice exhibit lower locomotor activity during social exploration in the SocioBox compared to males and do not seem to discriminate between acquainted and unfamiliar mice, likely reflecting inherent differences in gender-specific territorial tasks. In addition to a simple quantification of social interaction time of mice grounded on predefined spatial zones (zone-based method), we developed a set of unbiased, data-driven analysis tools based on heat map representations and characterized by greater sensitivity. First proof-of-principle that the SocioBox allows diagnosis of social recognition deficits is provided using male PSD-95 heterozygous knockout mice, a mouse model related to psychiatric pathophysiology. PMID:27563287

  8. Bovine Immunoinhibitory Receptors Contribute to Suppression of Mycobacterium avium subsp. paratuberculosis-Specific T-Cell Responses

    PubMed Central

    Okagawa, Tomohiro; Konnai, Satoru; Nishimori, Asami; Ikebuchi, Ryoyo; Mizorogi, Seiko; Nagata, Reiko; Kawaji, Satoko; Tanaka, Shogo; Kagawa, Yumiko; Murata, Shiro; Mori, Yasuyuki

    2015-01-01

    Johne's disease (paratuberculosis) is a chronic enteritis in cattle that is caused by intracellular infection with Mycobacterium avium subsp. paratuberculosis. This infection is characterized by the functional exhaustion of T-cell responses to M. avium subsp. paratuberculosis antigens during late subclinical and clinical stages, presumably facilitating the persistence of this bacterium and the formation of clinical lesions. However, the mechanisms underlying T-cell exhaustion in Johne's disease are poorly understood. Thus, we performed expression and functional analyses of the immunoinhibitory molecules programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) and lymphocyte activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC-II) in M. avium subsp. paratuberculosis-infected cattle during the late subclinical stage. Flow cytometric analyses revealed the upregulation of PD-1 and LAG-3 in T cells in infected animals, which suffered progressive suppression of interferon gamma (IFN-γ) responses to the M. avium subsp. paratuberculosis antigen. In addition, PD-L1 and MHC-II were expressed on macrophages from infected animals, consistent with PD-1 and LAG-3 pathways contributing to the suppression of IFN-γ responses during the subclinical stages of M. avium subsp. paratuberculosis infection. Furthermore, dual blockade of PD-L1 and LAG-3 enhanced M. avium subsp. paratuberculosis-specific IFN-γ responses in blood from infected animals, and in vitro LAG-3 blockade enhanced IFN-γ production from M. avium subsp. paratuberculosis-specific CD4+ and CD8+ T cells. Taken together, the present data indicate that M. avium subsp. paratuberculosis-specific T-cell exhaustion is in part mediated by PD-1/PD-L1 and LAG-3/MHC-II interactions and that LAG-3 is a molecular target for the control of M. avium subsp. paratuberculosis-specific T-cell responses. PMID:26483406

  9. Divergent Immune Responses to Mycobacterium avium subsp. paratuberculosis Infection Correlate with Kinome Responses at the Site of Intestinal Infection

    PubMed Central

    Määttänen, Pekka; Trost, Brett; Scruten, Erin; Potter, Andrew; Kusalik, Anthony; Griebel, Philip

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease (JD) in cattle. M. avium subsp. paratuberculosis infects the gastrointestinal tract of calves, localizing and persisting primarily in the distal ileum. A high percentage of cattle exposed to M. avium subsp. paratuberculosis do not develop JD, but the mechanisms by which they resist infection are not understood. Here, we merge an established in vivo bovine intestinal segment model for M. avium subsp. paratuberculosis infection with bovine-specific peptide kinome arrays as a first step to understanding how infection influences host kinomic responses at the site of infection. Application of peptide arrays to in vivo tissue samples represents a critical and ambitious step in using this technology to understand host-pathogen interactions. Kinome analysis was performed on intestinal samples from 4 ileal segments subdivided into 10 separate compartments (6 M. avium subsp. paratuberculosis-infected compartments and 4 intra-animal controls) using bovine-specific peptide arrays. Kinome data sets clustered into two groups, suggesting unique binary responses to M. avium subsp. paratuberculosis. Similarly, two M. avium subsp. paratuberculosis-specific immune responses, characterized by different antibody, T cell proliferation, and gamma interferon (IFN-γ) responses, were also observed. Interestingly, the kinomic groupings segregated with the immune response groupings. Pathway and gene ontology analyses revealed that differences in innate immune and interleukin signaling and particular differences in the Wnt/β-catenin pathway distinguished the kinomic groupings. Collectively, kinome analysis of tissue samples offers insight into the complex cellular responses induced by M. avium subsp. paratuberculosis in the ileum and provides a novel method to understand mechanisms that alter the balance between cell-mediated and antibody responses to M. avium subsp. paratuberculosis infection. PMID

  10. Divergent immune responses to Mycobacterium avium subsp. paratuberculosis infection correlate with kinome responses at the site of intestinal infection.

    PubMed

    Määttänen, Pekka; Trost, Brett; Scruten, Erin; Potter, Andrew; Kusalik, Anthony; Griebel, Philip; Napper, Scott

    2013-08-01

    Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease (JD) in cattle. M. avium subsp. paratuberculosis infects the gastrointestinal tract of calves, localizing and persisting primarily in the distal ileum. A high percentage of cattle exposed to M. avium subsp. paratuberculosis do not develop JD, but the mechanisms by which they resist infection are not understood. Here, we merge an established in vivo bovine intestinal segment model for M. avium subsp. paratuberculosis infection with bovine-specific peptide kinome arrays as a first step to understanding how infection influences host kinomic responses at the site of infection. Application of peptide arrays to in vivo tissue samples represents a critical and ambitious step in using this technology to understand host-pathogen interactions. Kinome analysis was performed on intestinal samples from 4 ileal segments subdivided into 10 separate compartments (6 M. avium subsp. paratuberculosis-infected compartments and 4 intra-animal controls) using bovine-specific peptide arrays. Kinome data sets clustered into two groups, suggesting unique binary responses to M. avium subsp. paratuberculosis. Similarly, two M. avium subsp. paratuberculosis-specific immune responses, characterized by different antibody, T cell proliferation, and gamma interferon (IFN-γ) responses, were also observed. Interestingly, the kinomic groupings segregated with the immune response groupings. Pathway and gene ontology analyses revealed that differences in innate immune and interleukin signaling and particular differences in the Wnt/β-catenin pathway distinguished the kinomic groupings. Collectively, kinome analysis of tissue samples offers insight into the complex cellular responses induced by M. avium subsp. paratuberculosis in the ileum and provides a novel method to understand mechanisms that alter the balance between cell-mediated and antibody responses to M. avium subsp. paratuberculosis infection. PMID

  11. Palatal Actinomycosis and Kaposi Sarcoma in an HIV-Infected Subject with Disseminated Mycobacterium avium-intracellulare Infection

    PubMed Central

    Ablanedo-Terrazas, Yuria; Ormsby, Christopher E.; Reyes-Terán, Gustavo

    2012-01-01

    Actinomyces and Mycobacterium avium-intracellulare are facultative intracellular organisms, members of the bacterial order actinomycetales. Although Actinomyces can behave as copathogen when anatomic barriers are compromised, its coinfection with Mycobacterium avium-intracellulare has not previously been reported. We present the first reported case of palatal actinomycosis co-infection with disseminated MAC, in an HIV-infected subject with Kaposi sarcoma and diabetes. We discuss the pathogenesis of the complex condition of this subject. PMID:22481952

  12. Iron Acquisition in Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Wang, Joyce; Moolji, Jalal; Dufort, Alex; Staffa, Alfredo; Domenech, Pilar; Reed, Michael B.

    2015-01-01

    ABSTRACT Mycobacterium avium subsp. paratuberculosis is a host-adapted pathogen that evolved from the environmental bacterium M. avium subsp. hominissuis through gene loss and gene acquisition. Growth of M. avium subsp. paratuberculosis in the laboratory is enhanced by supplementation of the media with the iron-binding siderophore mycobactin J. Here we examined the production of mycobactins by related organisms and searched for an alternative iron uptake system in M. avium subsp. paratuberculosis. Through thin-layer chromatography and radiolabeled iron-uptake studies, we showed that M. avium subsp. paratuberculosis is impaired for both mycobactin synthesis and iron acquisition. Consistent with these observations, we identified several mutations, including deletions, in M. avium subsp. paratuberculosis genes coding for mycobactin synthesis. Using a transposon-mediated mutagenesis screen conditional on growth without myobactin, we identified a potential mycobactin-independent iron uptake system on a M. avium subsp. paratuberculosis-specific genomic island, LSPP15. We obtained a transposon (Tn) mutant with a disruption in the LSPP15 gene MAP3776c for targeted study. The mutant manifests increased iron uptake as well as intracellular iron content, with genes downstream of the transposon insertion (MAP3775c to MAP3772c [MAP3775-2c]) upregulated as the result of a polar effect. As an independent confirmation, we observed the same iron uptake phenotypes by overexpressing MAP3775-2c in wild-type M. avium subsp. paratuberculosis. These data indicate that the horizontally acquired LSPP15 genes contribute to iron acquisition by M. avium subsp. paratuberculosis, potentially allowing the subsequent loss of siderophore production by this pathogen. IMPORTANCE Many microbes are able to scavenge iron from their surroundings by producing iron-chelating siderophores. One exception is Mycobacterium avium subsp. paratuberculosis, a fastidious, slow-growing animal pathogen whose growth

  13. Mycobacterium avium-intracellulare brain abscess in HIV-positive patient

    PubMed Central

    Karne, Sampada S.; Sangle, Shashikala A.; Kiyawat, Dilip S.; Dharmashale, Sujata N.; Kadam, Dilip B.; Bhardwaj, Renu S.

    2012-01-01

    Mycobacterial opportunistic infections are a major cause of morbidity and mortality among patients living with HIV (PLHIV) worldwide. Nontuberculous mycobacterial (NTM) infection is one of the leading causes of opportunistic infection in patients with advanced acquired immunodeficiency syndrome i.e., with CD4 count less than 50/cu.mm. Mycobacterium avium complex (MAC) is among the most common opportunistic bacterial infections in those patients with advanced immunodeficiency apart from cryptococcal meningitis, progressive multifocal leukoencephalopathy, etc. Common presentations of mycobacterium avium complex are fever, lymphadenitis and respiratory disease. Immune reconstitution disease is also known to manifest with MAC infections in PLHIV on highly active antiretroviral therapy. Very few cases of central nervous system involvement due to NTM infection have been described. We are reporting a case of advanced acquired immunodeficiency who presented with brain abscess due to Mycobacterium avium intracellulare. PMID:22412276

  14. Complexity and Chaos Theories as Potential Paradigms for Understanding and Treating Dissociative Disorders.

    NASA Astrophysics Data System (ADS)

    Drinkard, Lynne Bradford

    1995-01-01

    Early systems theory was a precursor of complexity theory, a global theory that suggests that the universe is an open system interacting on many dimensions. Chaos theory, a subset of complexity theory, states that in seeming chaos there is an underlying order. Between chaos and order lies emergence, from which healthy growth and change occur. Twenty years ago, chaos theory did not have a name and dissociative disorders were largely written off as rare or more imaginative than real. After physicists and mathematicians explained chaos and complexity in language understood by those outside their fields, scientists and practitioners from disparate disciplines were struck by the potential for applying the theories to their respective fields. Complexity and chaos theory combine reductionistic and holistic approaches to explain phenomena. Many mental health practitioners have suggested that a systems framework based in complexity theory may lead to greater understanding of human nature and ultimately toward more effective treatment of different disorders. This paper proposes that complexity and chaos theories may offer insight into the efficacy of various treatments for dissociative disorders.

  15. Complex Glycan Catabolism by the Human Gut Microbiota: The Bacteroidetes Sus-like Paradigm*

    PubMed Central

    Martens, Eric C.; Koropatkin, Nicole M.; Smith, Thomas J.; Gordon, Jeffrey I.

    2009-01-01

    Trillions of microbes inhabit the distal gut of adult humans. They have evolved to compete efficiently for nutrients, including a wide array of chemically diverse, complex glycans present in our diets, secreted by our intestinal mucosa, and displayed on the surfaces of other gut microbes. Here, we review how members of the Bacteroidetes, one of two dominant gut-associated bacterial phyla, process complex glycans using a series of similarly patterned, cell envelope-associated multiprotein systems. These systems provide insights into how gut, as well as terrestrial and aquatic, Bacteroidetes survive in highly competitive ecosystems. PMID:19553672

  16. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system.

    PubMed

    Tieri, Paolo; Grignolio, Andrea; Zaikin, Alexey; Mishto, Michele; Remondini, Daniel; Castellani, Gastone C; Franceschi, Claudio

    2010-01-01

    Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information. PMID:20701759

  17. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system

    PubMed Central

    2010-01-01

    Recently, the network paradigm, an application of graph theory to biology, has proven to be a powerful approach to gaining insights into biological complexity, and has catalyzed the advancement of systems biology. In this perspective and focusing on the immune system, we propose here a more comprehensive view to go beyond the concept of network. We start from the concept of degeneracy, one of the most prominent characteristic of biological complexity, defined as the ability of structurally different elements to perform the same function, and we show that degeneracy is highly intertwined with another recently-proposed organizational principle, i.e. 'bow tie architecture'. The simultaneous consideration of concepts such as degeneracy, bow tie architecture and network results in a powerful new interpretative tool that takes into account the constructive role of noise (stochastic fluctuations) and is able to grasp the major characteristics of biological complexity, i.e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information. PMID:20701759

  18. Lateral magma flow in sill-complexes: towards a paradigm shift in volcanology

    NASA Astrophysics Data System (ADS)

    Magee, C.; Muirhead, J.; Karvelas, A.; Holford, S. P.; Jackson, C. A. L.; Bastow, I. D.; Schofield, N.; Stevenson, C.; McLean, C.; McCarthy, W.; Shtukert, O.

    2015-12-01

    The structure of magma plumbing systems controls the distribution of volcanism, thereby influencing continental break-up and passive margin evolution. However, delimiting the structure of entire plumbing systems is difficult because: (1) intrusion networks cannot be directly accessed at active volcanoes; (2) field outcrops are limited by exposure; and (3) the resolution of geophysical data imaging the sub-surface is restricted. As a result, models involving the vertical transfer of magma in dikes, which extend from a melt source to overlying reservoirs and eruption sites, dominate the volcanic literature. Whilst there is evidence supporting the existence of vertically stacked plumbing systems, we compile a series of field- and seismic reflection-based case studies documenting the importance of extensive lateral magma transport (up to 4100 km) within sill-complexes. Most of these sill-complexes are emplaced into sediment-filled rift basins (e.g., Rockall Basin, NE Atlantic; Ceduna Sub-basin, offshore southern Australia; Karoo Basin, South Africa). There is also evidence that some sill-complexes occur within crystalline, continental crust (e.g., in the Yilgarn Craton, Australia). The case studies presented demonstrate that sill-complex emplacement is largely controlled by host rock lithology and structure. Sill intrusion is accommodated through roof uplift or, alternatively, via non-brittle processes (e.g., porosity reduction induced by host rock fluidization) that may not deform the overburden. The full or partial accommodation of magma by space-making mechanisms other than roof uplift means that intruding magma volumes may be underestimated by or completely hidden from ground deformation analyses. We show that plumbing systems need not be vertically stacked. Magma can instead be transported within laterally extensive (up to 3 × 106 km2) sill-complexes, promoting the development of volcanoes that do not overlie the melt source.

  19. Dynamic self-organization phenomena in complex ionized gas systems: new paradigms and technological aspects

    NASA Astrophysics Data System (ADS)

    Vladimirov, S. V.; Ostrikov, K.

    2004-04-01

    An overview of dynamic self-organization phenomena in complex ionized gas systems, associated physical phenomena, and industrial applications is presented. The most recent experimental, theoretical, and modeling efforts to understand the growth mechanisms and dynamics of nano- and micron-sized particles, as well as the unique properties of the plasma-particle systems (colloidal, or complex plasmas) and the associated physical phenomena are reviewed and the major technological applications of micro- and nanoparticles are discussed. Until recently, such particles were considered mostly as a potential hazard for the microelectronic manufacturing and significant efforts were applied to remove them from the processing volume or suppress the gas-phase coagulation. Nowadays, fine clusters and particulates find numerous challenging applications in fundamental science as well as in nanotechnology and other leading high-tech industries.

  20. Fenestrated stent grafts for the treatment of complex aortic aneurysm disease: A mature treatment paradigm.

    PubMed

    Georgiadis, George S; van Herwaarden, Joost A; Antoniou, George A; Giannoukas, Athanasios D; Lazarides, Miltos K; Moll, Frans L

    2016-06-01

    The introduction of fenestrated stent grafts (SGs) to treat abdominal aortic aneurysms (AAAs) with short proximal necks began in 1999. Nowadays, the whole visceral aorta can be treated totally by endovascular means. The established use of fenestrated devices to treat complex AAAs as a first-line management option has been previously reported. An up-to-date evaluation of the literature was performed including all types of publications regarding the use of fenestrated technology to repair complex AAAs. Fenestrated repair is now an established alternative to hybrid/chimney/snorkel repairs. However, specific criteria and prerequisites are required for the use and improvement of this method. Multiple device morphologies have been used incorporating the visceral arteries in various combinations. This modular strategy connects different devices (bridging covered stents and bifurcated SGs) with the aortic main body, thus excluding the aneurysm from the circulation. Precise deployment of the fenestrated SG is mandatory for successful visceral vessel revascularization. Accurate SG sizing and customization, a high level of technical skill, and facilities with modern imaging techniques including 3D road mapping and dedicated hybrid rooms are required. Most experience has been with the custom-made Zenith Cook platform, although off-the-shelf devices have been recently implanted. More complex repairs have been performed over the last few years, but device complexity has also increased. Perioperative, mid-term, and a few recently reported long-term results are encouraging. Secondary interventions remain the main problem, similar to that observed after traditional endovascular abdominal aortic aneurysm repair (EVAR). PMID:27013644

  1. Nanobiology of the primary cilium--paradigm of a multifunctional nanomachine complex.

    PubMed

    Wheatley, Denys N

    2008-01-01

    Of all the organelles in the eukaryotic cells, it is argued that the primary cilium is a paradigm in terms of nanomachinery found in the living cell. The components that are brought together in this single structure endow it with an extraordinary range of receptor and signaling functions. This organelle is based on the centriole, which is itself a minute compact structure that has been conserved throughout evolution for well over a billion years. After more than a century of interest in the presence and structural features of the primary cilium, it became clear from the advent of the electron microscope that they were much more ubiquitous and had many more functions in situations other than the most obvious of cases, that is, the retinal rods and cones. However, these other functional activities were considered to be largely speculative by nonspecialists, until more recently. In the last decade, more has been learned about their molecular biology and function than in all the preceding years of research. The impetus came from a better understanding of the process of ciliogenesis at the macromolecular level, the discovery of wide range of receptors localized in the ciliary membrane, and the appropriate signaling mechanisms to relay messages to the cell internum. These are the three central themes of current investigations. The reason for the recent flurry of activity stemmed from work in the mid-1990s emphasizing the fact that the failure of cells to develop primary cilia in certain tissues and organs was directly correlated with some drastic pathological consequences, just as failure to develop the primary cilia that form the basis of retinal cells, observed now over a half a century ago by Sjöstrand, F. S. (Sjöstrand, F. S. (1953). The ultrastructure of the inner segments of the retinal rods of the guinea pig eye as revealed by electron microscopy long ago, so blatantly causes blindness. The medical implications did in due course prove to be of such magnitude

  2. Protein folding and misfolding: a paradigm of self-assembly and regulation in complex biological systems.

    PubMed

    Vendruscolo, Michele; Zurdo, Jesús; MacPhee, Cait E; Dobson, Christopher M

    2003-06-15

    Understanding biological complexity is one of the grand scientific challenges for the future. A living organism is a highly evolved system made up of a large number of interwoven molecular networks. These networks primarily involve proteins, the macromolecules that enable and control virtually every chemical process that takes place in the cell. Proteins are also key elements in the essential characteristic of living systems, their ability to function and replicate themselves through controlled molecular interactions. Recent progress in understanding the most fundamental aspect of polypeptide self-organization, the process by which proteins fold to attain their active conformations, provides a global platform to gain knowledge about the function of biological systems and the regulatory mechanisms that underpin their ability to adapt to changing conditions. In order to exploit such progress effectively, we are developing a variety of approaches, including procedures that use experimental data to restrain the properties of complex systems in computer simulations, to describe their behaviour under a wide variety of conditions. We believe that such approaches can lead to significant advances in understanding biological complexity, in general, and protein folding and misfolding in particular. These advances would contribute to: a more effective exploitation of the information from genome sequences; more rational therapeutic approaches to diseases, particularly those associated with ageing; the responsible control of our own evolution; and the development of new technologies based on mimicking the principles of biological self-assembly, for instance in nanotechnology. More fundamentally, we believe that this research will result in a more coherent understanding of the origin, evolution and functional properties of living systems. PMID:12816607

  3. Laser chimeras as a paradigm for multistable patterns in complex systems

    NASA Astrophysics Data System (ADS)

    Larger, Laurent; Penkovsky, Bogdan; Maistrenko, Yuri

    2015-07-01

    A chimera state is a rich and fascinating class of self-organized solutions developed in high-dimensional networks. Necessary features of the network for the emergence of such complex but structured motions are non-local and symmetry breaking coupling. An accurate understanding of chimera states is expected to bring important insights on deterministic mechanism occurring in many structurally similar high-dimensional dynamics such as living systems, brain operation principles and even turbulence in hydrodynamics. Here we report on a powerful and highly controllable experiment based on an optoelectronic delayed feedback applied to a wavelength tuneable semiconductor laser, with which a wide variety of chimera patterns can be accurately investigated and interpreted. We uncover a cascade of higher-order chimeras as a pattern transition from N to N+1 clusters of chaoticity. Finally, we follow visually, as the gain increases, how chimera state is gradually destroyed on the way to apparent turbulence-like system behaviour.

  4. Design and control strategies for CELSS - Integrating mechanistic paradigms and biological complexities

    NASA Technical Reports Server (NTRS)

    Moore, B., III; Kaufmann, R.; Reinhold, C.

    1981-01-01

    Systems analysis and control theory consideration are given to simulations of both individual components and total systems, in order to develop a reliable control strategy for a Controlled Ecological Life Support System (CELSS) which includes complex biological components. Because of the numerous nonlinearities and tight coupling within the biological component, classical control theory may be inadequate and the statistical analysis of factorial experiments more useful. The range in control characteristics of particular species may simplify the overall task by providing an appropriate balance of stability and controllability to match species function in the overall design. The ultimate goal of this research is the coordination of biological and mechanical subsystems in order to achieve a self-supporting environment.

  5. Laser chimeras as a paradigm for multistable patterns in complex systems

    PubMed Central

    Larger, Laurent; Penkovsky, Bogdan; Maistrenko, Yuri

    2015-01-01

    A chimera state is a rich and fascinating class of self-organized solutions developed in high-dimensional networks. Necessary features of the network for the emergence of such complex but structured motions are non-local and symmetry breaking coupling. An accurate understanding of chimera states is expected to bring important insights on deterministic mechanism occurring in many structurally similar high-dimensional dynamics such as living systems, brain operation principles and even turbulence in hydrodynamics. Here we report on a powerful and highly controllable experiment based on an optoelectronic delayed feedback applied to a wavelength tuneable semiconductor laser, with which a wide variety of chimera patterns can be accurately investigated and interpreted. We uncover a cascade of higher-order chimeras as a pattern transition from N to N+1 clusters of chaoticity. Finally, we follow visually, as the gain increases, how chimera state is gradually destroyed on the way to apparent turbulence-like system behaviour. PMID:26169585

  6. Genomics and Machine Learning for Taxonomy Consensus: The Mycobacterium tuberculosis Complex Paradigm

    PubMed Central

    Azé, Jérôme; Sola, Christophe; Zhang, Jian; Lafosse-Marin, Florian; Yasmin, Memona; Siddiqui, Rubina; Kremer, Kristin; van Soolingen, Dick; Refrégier, Guislaine

    2015-01-01

    Infra-species taxonomy is a prerequisite to compare features such as virulence in different pathogen lineages. Mycobacterium tuberculosis complex taxonomy has rapidly evolved in the last 20 years through intensive clinical isolation, advances in sequencing and in the description of fast-evolving loci (CRISPR and MIRU-VNTR). On-line tools to describe new isolates have been set up based on known diversity either on CRISPRs (also known as spoligotypes) or on MIRU-VNTR profiles. The underlying taxonomies are largely concordant but use different names and offer different depths. The objectives of this study were 1) to explicit the consensus that exists between the alternative taxonomies, and 2) to provide an on-line tool to ease classification of new isolates. Genotyping (24-VNTR, 43-spacers spoligotypes, IS6110-RFLP) was undertaken for 3,454 clinical isolates from the Netherlands (2004-2008). The resulting database was enlarged with African isolates to include most human tuberculosis diversity. Assignations were obtained using TB-Lineage, MIRU-VNTRPlus, SITVITWEB and an algorithm from Borile et al. By identifying the recurrent concordances between the alternative taxonomies, we proposed a consensus including 22 sublineages. Original and consensus assignations of the all isolates from the database were subsequently implemented into an ensemble learning approach based on Machine Learning tool Weka to derive a classification scheme. All assignations were reproduced with very good sensibilities and specificities. When applied to independent datasets, it was able to suggest new sublineages such as pseudo-Beijing. This Lineage Prediction tool, efficient on 15-MIRU, 24-VNTR and spoligotype data is available on the web interface “TBminer.” Another section of this website helps summarizing key molecular epidemiological data, easing tuberculosis surveillance. Altogether, we successfully used Machine Learning on a large dataset to set up and make available the first

  7. Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity.

    PubMed

    Cornell, R F; Kassim, A A

    2016-04-01

    The use of modern therapies such as thalidomide, bortezomib and lenalidomide coupled with upfront high-dose therapy and autologous stem cell transplant (ASCT) has resulted in improved survival in patients with newly diagnosed multiple myeloma (MM). However, patients with relapsed/refractory multiple myeloma (RRMM) often have poorer clinical outcomes and might benefit from novel therapeutic strategies. Emerging therapies, such as deacetylase inhibitors, monoclonal antibodies and new proteasome inhibitors, appear promising and may change the therapeutic landscape in RRMM. A limited number of studies has shown a benefit with salvage ASCT in patients with RRMM, although there remains ongoing debate about its timing and effectiveness. Improvement in transplant outcomes has re-ignited a debate on the timing and possible role for salvage ASCT and allogeneic stem cell transplant in RRMM. As the treatment options for management of patients with RRMM become increasingly complex, physicians must consider both disease- and patient-related factors in choosing the appropriate therapeutic approach, with the goal of improving efficacy while minimizing toxicity. PMID:26726946

  8. Deciphering the Complexities of Atopic Dermatitis: Shifting Paradigms in Treatment Approaches

    PubMed Central

    Leung, Donald Y. M.; Guttman-Yassky, Emma

    2014-01-01

    Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It often precedes the development of food allergy and asthma. Recent insights into AD reveal abnormalities in terminal differentiation of the epidermal epithelium leading to a defective stratum corneum, which allows enhanced allergen penetration and systemic IgE sensitization. Atopic skin is also predisposed to colonization or infection by pathogenic microbes, most notably Staphylococcus aureus and herpes simplex virus (HSV). Causes of this abnormal skin barrier are complex and driven by a combination of genetic, environmental and immunologic factors. These factors likely account for the heterogeneity of AD onset, severity and natural history of this skin disease. Recent studies suggest prevention of AD can be achieved by early interventions protecting the skin barrier. Onset of lesional AD requires effective control of local and systemic immune activation for optimal management. Early intervention may improve long term outcomes for AD and reduce the systemic allergen sensitization leading to associated allergic diseases in the gastrointestinal and respiratory tract. PMID:25282559

  9. Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity

    PubMed Central

    Cornell, R F; Kassim, A A

    2016-01-01

    The use of modern therapies such as thalidomide, bortezomib and lenalidomide coupled with upfront high-dose therapy and autologous stem cell transplant (ASCT) has resulted in improved survival in patients with newly diagnosed multiple myeloma (MM). However, patients with relapsed/refractory multiple myeloma (RRMM) often have poorer clinical outcomes and might benefit from novel therapeutic strategies. Emerging therapies, such as deacetylase inhibitors, monoclonal antibodies and new proteasome inhibitors, appear promising and may change the therapeutic landscape in RRMM. A limited number of studies has shown a benefit with salvage ASCT in patients with RRMM, although there remains ongoing debate about its timing and effectiveness. Improvement in transplant outcomes has re-ignited a debate on the timing and possible role for salvage ASCT and allogeneic stem cell transplant in RRMM. As the treatment options for management of patients with RRMM become increasingly complex, physicians must consider both disease- and patient-related factors in choosing the appropriate therapeutic approach, with the goal of improving efficacy while minimizing toxicity. PMID:26726946

  10. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches.

    PubMed

    Leung, Donald Y M; Guttman-Yassky, Emma

    2014-10-01

    Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. It often precedes the development of food allergy and asthma. Recent insights into AD reveal abnormalities in terminal differentiation of the epidermal epithelium leading to a defective stratum corneum, which allows enhanced allergen penetration and systemic IgE sensitization. Atopic skin is also predisposed to colonization or infection by pathogenic microbes, most notably Staphylococcus aureus and herpes simplex virus. Causes of this abnormal skin barrier are complex and driven by a combination of genetic, environmental, and immunologic factors. These factors likely account for the heterogeneity of AD onset and the severity and natural history of this skin disease. Recent studies suggest prevention of AD can be achieved through early interventions to protect the skin barrier. Onset of lesional AD requires effective control of local and systemic immune activation for optimal management. Early intervention might improve long-term outcomes for AD and reduce the systemic allergen sensitization that leads to associated allergic diseases in the gastrointestinal and respiratory tract. PMID:25282559

  11. MYCOBACTERIUM AVIUM AND DRINKING WATER WHAT ARE THE CONNECTIONS?

    EPA Science Inventory

    Background: Human Mycobacterium avium infections are only known to be acquired from environmental sources such as water and soil. We compared M. avium isolates from clinical and drinking water sources using molecular tools. Methods: M. avium was isolated from water samples colle...

  12. Keap1 regulates inflammatory signaling in Mycobacterium avium-infected human macrophages.

    PubMed

    Awuh, Jane Atesoh; Haug, Markus; Mildenberger, Jennifer; Marstad, Anne; Do, Chau Phuc Ngoc; Louet, Claire; Stenvik, Jørgen; Steigedal, Magnus; Damås, Jan Kristian; Halaas, Øyvind; Flo, Trude Helen

    2015-08-01

    Several mechanisms are involved in controlling intracellular survival of pathogenic mycobacteria in host macrophages, but how these mechanisms are regulated remains poorly understood. We report a role for Kelch-like ECH-associated protein 1 (Keap1), an oxidative stress sensor, in regulating inflammation induced by infection with Mycobacterium avium in human primary macrophages. By using confocal microscopy, we found that Keap1 associated with mycobacterial phagosomes in a time-dependent manner, whereas siRNA-mediated knockdown of Keap1 increased M. avium-induced expression of inflammatory cytokines and type I interferons (IFNs). We show evidence of a mechanism whereby Keap1, as part of an E3 ubiquitin ligase complex with Cul3 and Rbx1, facilitates ubiquitination and degradation of IκB kinase (IKK)-β thus terminating IKK activity. Keap1 knockdown led to increased nuclear translocation of transcription factors NF-κB, IFN regulatory factor (IRF) 1, and IRF5 driving the expression of inflammatory cytokines and IFN-β. Furthermore, knockdown of other members of the Cul3 ubiquitin ligase complex also led to increased cytokine expression, further implicating this ligase complex in the regulation of the IKK family. Finally, increased inflammatory responses in Keap1-silenced cells contributed to decreased intracellular growth of M. avium in primary human macrophages that was reconstituted with inhibitors of IKKβ or TANK-binding kinase 1 (TBK1). Taken together, we propose that Keap1 acts as a negative regulator for the control of inflammatory signaling in M. avium-infected human primary macrophages. Although this might be important to avoid sustained or overwhelming inflammation, our data suggest that a negative consequence could be facilitated growth of pathogens like M. avium inside macrophages. PMID:26195781

  13. Detection of Mycobacterium avium in pet birds

    PubMed Central

    Godoy, Silvia Neri; Sakamoto, Sidnei Miyoshi; de Paula, Cátia Dejuste; Catão-Dias, José Luiz; Matushima, Eliana Reiko

    2009-01-01

    The present study is a report on the presence of Mycobacterium avium in four birds of the psittaciform order kept as pets. Anatomopathological diagnosis showed lesions suggestive of the agent and presence of alcohol-acid resistant bacilli (AARB) shown by the Ziehl-Neelsen staining. The identification of Mycobacterium avium was performed by means of PRA (PCR Restriction Analysis). DNA was directly extracted from tissue of the lesions and blocked in paraffin. The role of this agent in pet bird infection is discussed, as well as its zoonotic potential. PMID:24031356

  14. Comparative evaluation of PCR and commercial DNA probes for detection and identification to species level of Mycobacterium avium and Mycobacterium intracellulare.

    PubMed Central

    Devallois, A; Picardeau, M; Goh, K S; Sola, C; Vincent, V; Rastogi, N

    1996-01-01

    Selective amplification of a 187-bp fragment within the DT6 sequence using the AV6 and AV7 primers for Mycobacterium avium and of a 666-bp fragment within the DT1 sequence of Mycobacterium intracellulare using the IN38 and IN41 primers was performed for 69 clinical isolates identified as M. avium complex by conventional methods. The results were compared in parallel with results with commercial M. avium and M. intracellulare probes. A positive response to either of the two PCRs or M. avium-M. intracellulare AccuProbes constituted positive detection as M. avium complex; this cumulative detection limit was 94.2% for PCR, compared with 90% for AccuProbe. Concordance, on the other hand, was considered an identical species identification using either DT1 PCR and the M. intracellulare probe or DT6 and DT1 PCRs are inexpensive and at least equally sensitive, in-house options to the AccuProbe system for species identification of M. avium and M. intracellulare. PMID:8897178

  15. Disparate host immunity to Mycobacterium avium subsp. paratuberculosis antigens in calves inoculated with M. avium subsp. paratuberculosis, M. avium subsp. avium, M. kansasii and M. bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cross-reactivity of mycobacterial antigens in immune-based diagnostic assays has been a major concern and criticism of current tests for the detection of paratuberculosis. In the present study, host immune responses to antigen preparations of Mycobacterium avium subsp. paratuberculosis (MAP), consis...

  16. Effects of Stop-Signal Probability in the Stop-Signal Paradigm: The N2/p3 Complex Further Validated

    ERIC Educational Resources Information Center

    Ramautar, J.R.; Kok, A.; Ridderinkhof, K.R.

    2004-01-01

    The aim of this study was to examine the effects of frequency of occurrence of stop signals in the stop-signal paradigm. Presenting stop signals less frequently resulted in faster reaction times to the go stimulus and a lower probability of inhibition. Also, go stimuli elicited larger and somewhat earlier P3 responses when stop signals occurred…

  17. Mycobacterium avium infection in HIV-1-infected subjects increases monokine secretion and is associated with enhanced viral load and diminished immune response to viral antigens.

    PubMed Central

    Denis, M; Ghadirian, E

    1994-01-01

    The complex interaction between HIV-1 infection and Mycobacterium avium was studied. Viral burden was assessed, as well as immune response to HIV-1 in the context of Myco. avium infections. We also examined serum cytokine levels and cytokine release by blood mononuclear cells in HIV-1-infected subjects, infected or not with Myco. avium. Undetectable serum levels of IL-1, tumour necrosis factor-alpha (TNF-alpha) and IL-6 were found in normal controls and in groups I, II and III of HIV-1-infected subjects. Moderate levels of TNF-alpha, IL-1 and IL-6 were found in the sera of group IV patients. When group IV was subdivided into subjects with and without Myco. avium infections, subjects with Myco, avium infections were shown to have higher serum levels of TNF-alpha, IL-1 beta and IL-6 than those with other infections. Blood mononuclear cells from controls and HIV subjects were stimulated with bacterial lipopolysaccharide, and cytokine levels assessed. Cells from group II patients were shown to secrete normal levels of TNF-alpha and IL-6, and lower levels of IL-1 beta; group III subjects released higher levels of IL-6. Patients in group IV had blood cells that released elevated levels of IL-6 and TNF-alpha, and lower levels of IL-1 beta. Group IV subjects with Myco. avium infections had blood cells that released higher levels of TNF-alpha, IL-6 and IL-1 than group IV subjects with other infections. Assessment of viral burden in cells of HIV-1-infected subjects revealed that Myco. avium-infected subjects had a higher level of virus burden and a lower level of lymphoproliferative response to an inactivated gp120-depleted HIV-1 antigen than AIDS subjects with other infections. These data suggest that Myco. avium infections in HIV-1-infected subjects hasten the progression of viral disease, enhance cytokine release and contribute to the anergy to viral antigens. PMID:8033423

  18. Identification of Two Novel Mycobacterium avium Allelic Variants in Pig and Human Isolates from Brazil by PCR-Restriction Enzyme Analysis

    PubMed Central

    Leão, Sylvia Cardoso; Briones, Marcelo R. S.; Sircili, Marcelo Palma; Balian, Simone Carvalho; Mores, Nelson; Ferreira-Neto, José Soares

    1999-01-01

    Mycobacterium avium complex (MAC) is composed of environmental mycobacteria found widely in soil, water, and aerosols that can cause disease in animals and humans, especially disseminated infections in AIDS patients. MAC consists of two closely related species, M. avium and M. intracellulare, and may also include other, less-defined groups. The precise differentiation of MAC species is a fundamental step in epidemiological studies and for the evaluation of possible reservoirs for MAC infection in humans and animals. In this study, which included 111 pig and 26 clinical MAC isolates, two novel allelic M. avium PCR-restriction enzyme analysis (PRA) variants were identified, differing from the M. avium PRA prototype in the HaeIII digestion pattern. Mutations in HaeIII sites were confirmed by DNA sequencing. Identification of these isolates as M. avium was confirmed by PCR with DT1-DT6 and IS1245 primers, nucleic acid hybridization with the AccuProbe system, 16S ribosomal DNA sequencing, and biochemical tests. The characterization of M. avium PRA variants can be useful in the elucidation of factors involved in mycobacterial virulence and routes of infection and also has diagnostic significance, since they can be misidentified as M. simiae II and M. kansasii I if the PRA method is used in the clinical laboratory for identification of mycobacteria. PMID:10405407

  19. Immunization with a DNA Vaccine Cocktail Induces a Th1 Response and Protects Mice Against Mycobacterium avium subsp. paratuberculosis Challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several novel antigens of Mycobacterium avium subsp. paratuberculosis have been studied as vaccine components and their immunogenicity has been evaluated. Previously, we reported that 85 antigen complex (85A, 85B, and 85C), superoxide dismutase (SOD), and 35kDa protein could induce significant lymph...

  20. Mycobacterium avium subsp. avium found in raptors exposed to infected domestic fowl.

    PubMed

    Kriz, Petr; Kaevska, Marija; Bartejsova, Iva; Pavlik, Ivo

    2013-09-01

    We report a case of a falcon breeding facility, where raptors (both diurnal and nocturnal) were raised in contact with domestic fowl (Gallus gallus f. domesticus) infected by Mycobacterium avium subsp. avium. Fecal and environmental samples from 20 raptors and four common ravens (Corvus corax) were collected. Mycobacterium a. avium DNA was detected in feces of four raptors (bald eagle [Haliaeetus leucocephalus], eagle owl [Bubo bubo], barn owl [Tyto alba], and little owl [Athene noctua]) using triplex quantitative real-time PCR. As both the flock of domestic fowl and one of the infected raptors had the same origin (zoological collection), they might have had a common source of colonization/infection. However, the detection of M. a. avium in feces of three other raptors may point at transmission of the agent between the birds in the facility. Contact of raptors with domestic fowl infected by M. a. avium may pose a risk for transmission of the infection for them; however, raptors from the falcon breeding facility seemed to be relatively resistant to the infection. PMID:24283140

  1. Experimental inoculation of BFDV-positive budgerigars (Melopsittacus undulatus) with two Mycobacterium avium subsp. avium isolates.

    PubMed

    Ledwoń, Aleksandra; Sapierzyński, Rafał; Augustynowicz-Kopeć, Ewa; Szeleszczuk, Piotr; Kozak, Marcin

    2014-01-01

    Beak and feather disease virus- (BFDV-) positive (naturally infected) but clinically healthy budgerigars (Melopsittacus undulatus) were inoculated with two isolates of Mycobacterium avium subsp. avium isolated from naturally infected golden pheasant (Chrysolophus pictus) and peafowl (Pavo cristatus). During a period of more than two months after inoculation, samples of cloacal and crop swabs, faeces, and blood were obtained for BFDV and Mycobacterium avium testing with PCR. Birds were euthanized nine weeks after inoculation. All infected budgerigars developed signs typical of mycobacteriosis, but more advanced clinical and pathological changes were visible in the group infected with the pheasant isolate. Only a few cloacal and crop swab samples were positive for Mycobacterium avium subsp. avium despite advanced pathological changes in the internal organs. In the groups infected with mycobacterium isolates the frequency of BFDV-positive samples was higher than in the control group. In the infected groups the frequency of BFDV was substantially higher in the cloacal swabs of birds inoculated with the pheasant isolate than in the peafowl-isolate-infected group. PMID:24738057

  2. Experimental Inoculation of BFDV-Positive Budgerigars (Melopsittacus undulatus) with Two Mycobacterium avium subsp. avium Isolates

    PubMed Central

    Sapierzyński, Rafał; Szeleszczuk, Piotr

    2014-01-01

    Beak and feather disease virus- (BFDV-) positive (naturally infected) but clinically healthy budgerigars (Melopsittacus undulatus) were inoculated with two isolates of Mycobacterium avium subsp. avium isolated from naturally infected golden pheasant (Chrysolophus pictus) and peafowl (Pavo cristatus). During a period of more than two months after inoculation, samples of cloacal and crop swabs, faeces, and blood were obtained for BFDV and Mycobacterium avium testing with PCR. Birds were euthanized nine weeks after inoculation. All infected budgerigars developed signs typical of mycobacteriosis, but more advanced clinical and pathological changes were visible in the group infected with the pheasant isolate. Only a few cloacal and crop swab samples were positive for Mycobacterium avium subsp. avium despite advanced pathological changes in the internal organs. In the groups infected with mycobacterium isolates the frequency of BFDV-positive samples was higher than in the control group. In the infected groups the frequency of BFDV was substantially higher in the cloacal swabs of birds inoculated with the pheasant isolate than in the peafowl-isolate-infected group. PMID:24738057

  3. Endobronchial avium mycobacteria infection in an immunocompetent child.

    PubMed

    Perisson, Caroline; Nathan, Nadia; Thierry, Briac; Corvol, Harriet

    2013-01-01

    A 12-month-old boy, with no medical history, was admitted for dyspnoea with no cough or fever. Chest auscultation revealed an expiratory wheezing with decreased right-sided breath sounds. Chest imaging revealed subcarinal adenopathy and a nodule in the right principal bronchus (RB). Bronchoscopy showed a major obstruction of the RB by a granuloma, and a smaller granuloma in the left principal bronchus. The granulation tissue was removed by laser section. Histological examination revealed a necrotising granulomatous inflammation, culture showed a Mycobacterium avium complex (MAC). Tests to rule out tuberculosis and immunodeficiency were negative. The diagnosis of an MAC endobronchial granuloma was ascertained and a multidrug therapy associating clarithromycin, rifampin and ethambutol was started. The clinical outcome was good after 3 months of treatment and the bronchoscopy normalised after 1 year. Although rare, the frequency of MAC respiratory infections in immunocompetent children can increase. Reporting these cases should help to optimise diagnosis and treatment. PMID:24252838

  4. Pulmonary Mycobacterium avium infection demonstrating unusual lobar caseous pneumonia.

    PubMed

    Okuzumi, Shinichi; Minematsu, Naoto; Sasaki, Mamoru; Ohsawa, Kazuma; Murakami, Marohito

    2016-09-01

    Mycobacterium avium complex (MAC) infection is a major medical concern in Japan because of its increased prevalence and associated mortality. A common radiological feature in pulmonary MAC infection is a mixture of two basic patterns: fibrocavitary and nodular bronchiectatic; however, lobar consolidation is rare. We report an 83-year-old man with lobar caseous pneumonia caused by pulmonary MAC infection. Radiological findings were predominantly composed of dense lobar consolidation and ground-glass opacity. A diagnosis was made in accordance with the clinical and microbiological criteria set by the American Thoracic Society. A histological examination of lung specimens obtained by using a bronchoscope revealed a caseous granulomatous inflammation with an appearance of Langhans cells. The patient was treated using combined mycobacterium chemotherapy with an initial positive response for 6 months; however, the disease progressed later. We suggest that an awareness of lobar pneumonic consolidation as a rare radiological finding in pulmonary MAC infection is important. PMID:27516892

  5. Infants with complex congenital heart diseases show poor short-term memory in the mobile paradigm at 3 months of age.

    PubMed

    Chen, Chao-Ying; Harrison, Tondi; Heathcock, Jill

    2015-08-01

    The purpose of this study was to examine learning, short-term memory and general development including cognitive, motor, and language domains in infants with Complex Congenital Heart Defects (CCDH). Ten infants with CCHD (4 males, 6 females) and 14 infants with typical development (TD) were examined at 3 months of age. The mobile paradigm, where an infant's leg is tethered to an overhead mobile, was used to evaluate learning and short-term memory. The Bayley Scales of Infant Development 3rd edition (Bayley-III) was used to evaluate general development in cognitive, motor, and language domains. Infants with CCHD and infants with TD both showed learning with significant increase in kicking rate (p<0.001) across periods of the mobile paradigm, but only infants with TD demonstrated short-term memory (p=0.017) in the mobile paradigm. There were no differences on cognitive, motor, and language development between infants with CCHD and infants with TD on the Bayley-III. Early assessment is necessary to guide targeted treatment in infants with CCHD. One-time assessment may fail to detect potential cognitive impairments during early infancy in infants with CCHD. Supportive intervention programs for infants with CCHD that focuses on enhancing short-term memory are recommended. PMID:25919428

  6. Loci of Mycobacterium avium ser2 gene cluster and their functions.

    PubMed Central

    Mills, J A; McNeil, M R; Belisle, J T; Jacobs, W R; Brennan, P J

    1994-01-01

    The highly antigenic glycopeptidolipids present on the surface of members of the Mycobacterium avium complex serve to distinguish these bacteria from all others and to define the various serovars that compose this complex. Previously, the genes responsible for the biosynthesis of the disaccharide hapten [2,3-di-O-methyl-alpha-L-fucopyranosyl-(1-->3)-alpha-L-rhamnopyranose] of serovar 2 of the M. avium complex were isolated, localized to a contiguous 22- to 27-kb fragment of the M. avium genome, and designated the ser2 gene cluster (J. T. Belisle, L. Pascopella, J. M. Inamine, P. J. Brennan, and W. R. Jacobs, Jr., J. Bacteriol. 173:6991-6997, 1991). In the present study, transposon saturation mutagenesis was used to map the specific genetic loci within the ser2 gene cluster required for expression of this disaccharide. Four essential loci, termed ser2A, -B, -C, and -D, constituting a total of 5.7 kb within the ser2 gene cluster, were defined. The ser2B and ser2D loci encode the methyltransferases required to methylate the fucose at the 3 and 2 positions, respectively. The rhamnosyltransferase was encoded by ser2A, whereas either ser2C or ser2D encoded the fucosyltransferase. The ser2C and ser2D loci are also apparently involved in the de novo synthesis of fucose. Isolation of the truncated versions of the hapten induced by the transposon insertions provides genetic evidence that the glycopeptidolipids of M. avium serovar 2 are synthesized by an initial transfer of the rhamnose unit to the peptide core followed by fucose and finally O methylation of the fucosyl unit. PMID:8050992

  7. Loci of Mycobacterium avium ser2 gene cluster and their functions.

    PubMed

    Mills, J A; McNeil, M R; Belisle, J T; Jacobs, W R; Brennan, P J

    1994-08-01

    The highly antigenic glycopeptidolipids present on the surface of members of the Mycobacterium avium complex serve to distinguish these bacteria from all others and to define the various serovars that compose this complex. Previously, the genes responsible for the biosynthesis of the disaccharide hapten [2,3-di-O-methyl-alpha-L-fucopyranosyl-(1-->3)-alpha-L-rhamnopyranose] of serovar 2 of the M. avium complex were isolated, localized to a contiguous 22- to 27-kb fragment of the M. avium genome, and designated the ser2 gene cluster (J. T. Belisle, L. Pascopella, J. M. Inamine, P. J. Brennan, and W. R. Jacobs, Jr., J. Bacteriol. 173:6991-6997, 1991). In the present study, transposon saturation mutagenesis was used to map the specific genetic loci within the ser2 gene cluster required for expression of this disaccharide. Four essential loci, termed ser2A, -B, -C, and -D, constituting a total of 5.7 kb within the ser2 gene cluster, were defined. The ser2B and ser2D loci encode the methyltransferases required to methylate the fucose at the 3 and 2 positions, respectively. The rhamnosyltransferase was encoded by ser2A, whereas either ser2C or ser2D encoded the fucosyltransferase. The ser2C and ser2D loci are also apparently involved in the de novo synthesis of fucose. Isolation of the truncated versions of the hapten induced by the transposon insertions provides genetic evidence that the glycopeptidolipids of M. avium serovar 2 are synthesized by an initial transfer of the rhamnose unit to the peptide core followed by fucose and finally O methylation of the fucosyl unit. PMID:8050992

  8. Genetic IS901 RFLP diversity among Mycobacterium avium subsp. avium isolates from four pheasant flocks.

    PubMed

    Moravkova, Monika; Lamka, Jiri; Slany, Michal; Pavlik, Ivo

    2013-01-01

    IS901 RFLP analysis of 36 Mycobacterium avium subsp. avium (MAA) isolates from 15 pheasants (Phasianus colchicus) and two goshawks (Accipiter gentilis) from four pheasant farms was performed. Using this method, six different IS901 RFLP types (E, F, G, M, Q, and V) were identified. The distribution of IS901 RFLP profiles was tightly linked to individual flocks. Matching IS901 RFLP profiles observed in the present study indicate MAA transmission between pheasants and goshawks in the same locality. In two flocks, different pheasants within a flock as well as in various organs of five individual pheasants were found to have two distinct IS901 RFLP profiles. PMID:23388436

  9. Identification of Mycobacterium avium subsp. hominissuis Isolated From Drinking Water

    EPA Science Inventory

    Mycobacterium avium (MA) is divided into four subspecies based primarily on host-range and consists of MA subsp. avium (birds), MA subsp. silvaticum (wood pigeons), MA subsp. paratuberculosis (broad, poorly-defined host range), and the recently described MA subsp. hominissuis (hu...

  10. Avian mycobacteriosis caused by Mycobacterium avium subspecies avium in four ornamental birds and in vitro drug sensitivity testing of isolates.

    PubMed

    Stepień-Pyśniak, Dagmara; Puk, Krzysztof; Guz, Leszek; Wawrzyniak, Agata; Marek, Agnieszka; Kosikowska, Urszula

    2016-01-01

    Avian tuberculosis, one of the most important diseases affecting various species of birds, is most often caused by Mycobacterium (M.) avium. This report describes cases of M. avium subsp. avium (MAA) infection in a white-crested Holland dwarf rooster, a male and a female golden pheasant and a male peacock. We also investigated the prevalence of mycobacteria in 60 other birds and 40 alpacas. Tissue samples of necropsied birds were cultured for mycobacteria. From non-necropsied 60 other birds and alpacas only faecal samples were collected. Clinical signs in the affected white-crested Holland cock included gradual loss of body weight and hoarse attempts at crowing during its last 3 weeks, with a dramatic loss of body condition and depression over the final week. Only slight weakening was observed in the peacock just before its death, and the golden pheasants died suddenly. Diagnosis was confirmed by microbiological, molecular and pathological results. Mycobacterium avium subsp. avium strains were isolated from the internal organs of the affected birds. Only one faecal sample from 60 other birds was culture- and PCR-positive for M. avium subsp. avium, while another one was only PCR-positive for M. chelonae. We did not isolate any Mycobacterium spp. from faecal samples of alpacas and all of them were PCR-negative. All 18 isolated M. avium strains were resistant to rifampicin, isoniazid, ethambutol, ethionamide, capreomycin and ofloxacin, and susceptible to cycloserine and streptomycin. PMID:26904899

  11. Intermittent azithromycin for treatment of Mycobacterium avium infection in beige mice.

    PubMed Central

    Klemens, S P; Cynamon, M H

    1994-01-01

    The activity of azithromycin (AZI) was evaluated in the beige mouse model of disseminated Mycobacterium avium infection. Mice were infected intravenously with approximately 10(7) viable avium ATCC 49601. AZI at 50, 100, or 200 mg/kg of body weight or clarithromycin (CLA) at 200 mg/kg was given by gavage 5 days per week for 4 weeks. Groups of treated mice were compared with untreated control animals. A dose-related reduction in cell counts in organs was observed with AZI treatment. AZI at 200 mg/kg was more active than CLA at 200 mg/kg against organisms in spleens. The activities of these two agents at 200 mg/kg were comparable against organisms in lungs. In a second study, AZI at 200 mg/kg was given daily for 5 days; this was followed by intermittent AZI treatment for the next 3 weeks. The activities of AZI given on a three-times- and five-times-per-week basis in the continuation phase were comparable. AZI given on a once-weekly basis was less active. The regimen of AZI given in combination with rifapentine on a once-weekly basis for 8 weeks showed promising activity. Clinical evaluation of AZI and rifapentine will help to define the roles of these agents in the treatment of disseminated M. avium complex infection. PMID:7986001

  12. Characterization of a Novel Plasmid, pMAH135, from Mycobacterium avium Subsp. hominissuis

    PubMed Central

    Uchiya, Kei-ichi; Takahashi, Hiroyasu; Nakagawa, Taku; Yagi, Tetsuya; Moriyama, Makoto; Inagaki, Takayuki; Ichikawa, Kazuya; Nikai, Toshiaki; Ogawa, Kenji

    2015-01-01

    Mycobacterium avium complex (MAC) causes mainly two types of disease. The first is disseminated disease in immunocompromised hosts, such as individuals infected by human immunodeficiency virus (HIV). The second is pulmonary disease in individuals without systemic immunosuppression, and the incidence of this type is increasing worldwide. M. avium subsp. hominissuis, a component of MAC, causes infection in pigs as well as in humans. Many aspects of the different modes of M. avium infection and its host specificity remain unclear. Here, we report the characteristics and complete sequence of a novel plasmid, designated pMAH135, derived from M. avium strain TH135 in an HIV-negative patient with pulmonary MAC disease. The pMAH135 plasmid consists of 194,711 nucleotides with an average G + C content of 66.5% and encodes 164 coding sequences (CDSs). This plasmid was unique in terms of its homology to other mycobacterial plasmids. Interestingly, it contains CDSs with sequence homology to mycobactin biosynthesis proteins and type VII secretion system-related proteins, which are involved in the pathogenicity of mycobacteria. It also contains putative conserved domains of the multidrug efflux transporter. Screening of isolates from humans and pigs for genes located on pMAH135 revealed that the detection rate of these genes was higher in clinical isolates from pulmonary MAC disease patients than in those from HIV-positive patients, whereas the genes were almost entirely absent in isolates from pigs. Moreover, variable number tandem repeats typing analysis showed that isolates carrying pMAH135 genes are grouped in a specific cluster. Collectively, the pMAH135 plasmid contains genes associated with M. avium’s pathogenicity and resistance to antimicrobial agents. The results of this study suggest that pMAH135 influence not only the pathological manifestations of MAC disease, but also the host specificity of MAC infection. PMID:25671431

  13. Interaction of Mycobacterium avium with environmental amoebae enhances virulence.

    PubMed Central

    Cirillo, J D; Falkow, S; Tompkins, L S; Bermudez, L E

    1997-01-01

    Environmental mycobacteria are a common cause of human infections. Recently, contaminated domestic water supplies have been suggested as a potential environmental source of several mycobacterial diseases. Since many of these mycobacterial species replicate best intracellularly, environmental hosts have been sought. In the present study, we examined the interaction of Mycobacterium avium with a potential protozoan host, the water-borne amoeba Acanthamoeba castellanii. We found that M. avium enters and replicates in A. castellanii. In addition, similar to that shown for mycobacteria within macrophages, M. avium inhibits lysosomal fusion and replicates in vacuoles that are tightly juxtaposed to the bacterial surfaces within amoebae. In order to determine whether growth of M. avium in amoebae plays a role in human infections, we tested the effects of this growth condition on virulence. We found that growth of M. avium in amoebae enhances both entry and intracellular replication compared to growth of bacteria in broth. Furthermore, amoeba-grown M. avium was also more virulent in the beige mouse model of infection. These data suggest a role for protozoa present in water environments as hosts for pathogenic mycobacteria, particularly M. avium. PMID:9284149

  14. Endophthalmitis due to Mycobacterium avium in a patient with AIDS.

    PubMed

    Cohen, J I; Saragas, S J

    1990-02-01

    A 27-year-old man with acquired immunodeficiency syndrome [AIDS] had endophthalmitis OS four years after a trabeculectomy was done. The patient had a history of disseminated infection with Mycobacterium avium. Examination showed an intact filtering bleb with inflammation and hypopyon formation in the anterior chamber OS. The M. avium was cultured from an anterior chamber paracentesis. The patient responded to treatment with gentamicin, cefazolin, and prednisolone. Infection with M. avium should be included in the differential diagnosis of endophthalmitis in patients with AIDS. PMID:2316950

  15. Rethinking the longitudinal stream temperature paradigm: region-wide comparison of thermal infrared imagery reveals unexpected complexity of river temperatures

    USGS Publications Warehouse

    Fullerton, Aimee H.; Torgersen, Christian; Lawler, Joshua J.; Faux, Russell N.; Steel, E. Ashley; Beechie, Timothy J.; Ebersole, Joseph L.; Leibowitz, Scott J.

    2015-01-01

    Prevailing theory suggests that stream temperature warms asymptotically in a downstream direction, beginning at the temperature of the source in the headwaters and leveling off downstream as it converges to match meteorological conditions. However, there have been few empirical examples of longitudinal patterns of temperature in large rivers due to a paucity of data. We constructed longitudinal thermal profiles (temperature versus distance) for 53 rivers in the Pacific Northwest (USA) using an extensive dataset of remotely sensed summertime river temperatures and classified each profile into one of five patterns of downstream warming: asymptotic (increasing then flattening), linear (increasing steadily), uniform (not changing), parabolic (increasing then decreasing), or complex (not fitting other classes). We evaluated (1) how frequently profiles warmed asymptotically downstream as expected, and (2) whether relationships between river temperature and common hydroclimatic variables differed by profile class. We found considerable diversity in profile shape, with 47% of rivers warming asymptotically, and 53% having alternative profile shapes. Water temperature did not warm substantially over the course of the river for coastal parabolic and uniform profiles, and for some linear and complex profiles. Profile classes showed no clear geographical trends. The degree of correlation between river temperature and hydroclimatic variables differed among profile classes, but there was overlap among classes. Water temperature in rivers with asymptotic or parabolic profiles was positively correlated with August air temperature, tributary temperature and velocity, and negatively correlated with elevation, August precipitation, gradient, and distance upstream. Conversely, associations were less apparent in rivers with linear, uniform, or complex profiles. Factors contributing to the unique shape of parabolic profiles differed for coastal and inland rivers, where downstream cooling

  16. Cryptosporidium avium n. sp. (Apicomplexa: Cryptosporidiidae) in birds.

    PubMed

    Holubová, Nikola; Sak, Bohumil; Horčičková, Michaela; Hlásková, Lenka; Květoňová, Dana; Menchaca, Sarah; McEvoy, John; Kváč, Martin

    2016-06-01

    The morphological, biological, and molecular characteristics of Cryptosporidium avian genotype V are described, and the species name Cryptosporidium avium is proposed to reflect its specificity for birds under natural and experimental conditions. Oocysts of C. avium measured 5.30-6.90 μm (mean = 6.26 μm) × 4.30-5.50 μm (mean = 4.86 μm) with a length to width ratio of 1.29 (1.14-1.47). Oocysts of C. avium obtained from four naturally infected red-crowned parakeets (Cyanoramphus novaezealandiae) were infectious for 6-month-old budgerigars (Melopsittacus undulatus) and hens (Gallus gallus f. domestica). The prepatent periods in both susceptible bird species was 11 days postinfection (DPI). The infection intensity of C. avium in budgerigars and hens was low, with a maximum intensity of 5000 oocysts per gram of feces. Oocysts of C. avium were microscopically detected at only 12-16 DPI in hens and 12 DPI in budgerigars, while PCR analyses revealed the presence of specific DNA in fecal samples from 11 to 30 DPI (the conclusion of the experiment). Cryptosporidium avium was not infectious for 8-week-old SCID and BALB/c mice (Mus musculus). Naturally or experimentally infected birds showed no clinical signs of cryptosporidiosis, and no pathology was detected. Developmental stages of C. avium were detected in the ileum and cecum using scanning electron microscopy. Phylogenetic analyses based on small subunit rRNA, actin, and heat shock protein 70 gene sequences revealed that C. avium is genetically distinct from previously described Cryptosporidium species. PMID:26905074

  17. Hyper-longevity, a late-modern paradigm for understanding longevity, ageing and their complexities in Western developed globalised countries.

    PubMed

    Alzetta, Roberto; Cesario, Alfredo; Fini, Massimo

    2014-01-01

    If longevity is a biological and demographic indicator to determine human lifetime extension, hyper-longevity notion can represent a heuristic tool to better disentangle the complex bio-psycho-social implications of ageing and elderly in Western developed globalised countries. Departing from the assumption of a holistic approach to human condition understanding, it is possible to reveal the grounds and patterns of a multilayered and multidimensional structuring of longevity and ageing in our societies that would lead to a form of hyper-longevity. Socio-cultural processes, underlying hyper-longevity notion, rise the question of transition from modern/ latemodern societies to post-modern ones and it offers room for a cultural analysis of concepts, such as space time compression, digital capitalism, knowledge and mass information society. These are relevant ideas that can contribute to reshape and rethink the boundaries and traits of ageing experience in 21(st) century societies. To better catch the point emerging social category of Baby Boomers is presented and used to provide a concrete context related example on how hyper-longevity can better explain complex social evidences in many cultural respects and social domains. As a conclusive step some preliminary reflections, largely centered on the relation between Baby Boomers, hyper-longevity and bio-medical sciences are presented and discussed to provide a starting point for further future analyses within a trans and inter-disciplinary framework. PMID:24641235

  18. Subspecies Identification and Significance of 257 Clinical Strains of Mycobacterium avium

    PubMed Central

    Tran, Quynh T.

    2014-01-01

    Mycobacterium avium is abundant in the environment. It has four subspecies of three types: the human or porcine type, M. avium subsp. hominissuis; the bird type, including M. avium subsp. avium serotype 1 and serotype 2, 3 (also M. avium subsp. silvaticum); and the ruminant type, M. avium subsp. paratuberculosis. We determined the subspecies of 257 M. avium strains isolated from patients at the M.D. Anderson Cancer Center from 2001 to 2010 and assessed their clinical significance. An assay of multiplex PCR was used for the typing. Results showed M. avium subsp. hominissuis to be most common (n = 238, 92.6%), followed by M. avium subsp. avium serotype 1 (n = 12, 4.7%) and serotype 2, 3 (n = 7, 2.7%). No strains of M. avium subsp. paratuberculosis were found. Of the 238 patients with M. avium subsp. hominissuis, 65 (27.3%) showed evidence of definite or probable infections, mostly in the respiratory tract, whereas the rest had weak evidence of infection. The bird-type subspecies, despite being infrequently isolated, caused relatively more definite and probable infections (10 of 19 strains, 52.6%). Overall, women of 50 years of age or older were more prone to M. avium infection than younger women or men of all ages were. We therefore conclude that M. avium subsp. hominissuis is the dominant M. avium subspecies clinically, that the two bird-type subspecies do cause human infections, and that M. avium infects mainly postmenopausal women. The lack of human clinical isolation of the ruminant type subspecies may need further investigation. PMID:24501026

  19. Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine

    PubMed Central

    Harris, N. Beth; Barletta, Raúl G.

    2001-01-01

    Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the etiologic agent of a severe gastroenteritis in ruminants known as Johne's disease. Economic losses to the cattle industry in the United States are staggering, reaching $1.5 billion annually. A potential pathogenic role in humans in the etiology of Crohn's disease is under investigation. In this article, we review the epidemiology, pathogenesis, diagnostics, and disease control measures of this important veterinary pathogen. We emphasize molecular genetic aspects including the description of markers used for strain identification, diagnostics, and phylogenetic analysis. Recent important advances in the development of animal models and genetic systems to study M. paratuberculosis virulence determinants are also discussed. We conclude with proposals for the applications of these models and recombinant technology to the development of diagnostic, control, and therapeutic measures. PMID:11432810

  20. Apoptosis of human monocytes and macrophages by Mycobacterium avium sonicate.

    PubMed Central

    Hayashi, T; Catanzaro, A; Rao, S P

    1997-01-01

    Mycobacterium avium is an intracellular organism which multiplies predominantly within human macrophages. This organism has previously been shown to induce apoptosis in human macrophages. With a view to identifying M. avium components that induce cell death in infected host cells, sonicated extracts of M. avium as well as individual components isolated from the M. avium sonicate were tested in various assays with a human monocytic cell line (THP-1). THP-1 cells incubated with M. avium sonicate showed significantly reduced viability after a 2-day exposure compared to control cells incubated with media alone. This effect was dose dependent, with only 6.6% +/- 5.2% and 48.8% +/- 10.3% of the cells being viable by trypan blue exclusion at 600 and 300 microg/ml, respectively. Control cells, on the other hand, exhibited a viability of 98.8% +/- 1.0%. In addition, an 80% ammonium sulfate fraction of the M. avium sonicate and the previously characterized 68-kDa protein were found to have similar effects on THP-1 cells. In both cases, the reduction in viability was due to apoptosis characterized by chromatin condensation, DNA fragmentation by agarose gel electrophoresis, or terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling (TUNEL) and release of nuclear matrix protein (NMP) into the culture medium. M. avium sonicate-induced apoptosis of THP-1 cells was completely inhibited by the commonly used antioxidants pyrrolidinedithiocarbamate (PDTC) and butylated hydroxyanisole (BHA), indicating that the generation of free oxygen radicals may be responsible for inducing cell death. M. avium sonicate was found to induce apoptosis of monocyte-derived macrophages (MDMs) as well. This effect was not reversed in the presence of PDTC and was not accompanied with DNA fragmentation when determined by agarose gel electrophoresis, as seen in the case of THP-1 cells. However, these MDMs were found to contain fragmented DNA by TUNEL. These findings suggest that the mechanism

  1. Comparative Genomic Analysis of Mycobacterium avium subspecies Obtained from Multiple Host Species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A comparative genomic approach was used to identify large sequence polymorphisms among Mycobacterium avium (M. avium) subspecies obtained from a variety of host animals. DNA microarrays were used as a platform for comparing mycobacterial isolates with the sequenced bovine isolate M. avium subsp. p...

  2. Toll-Like Receptor 9 Is Required for Full Host Resistance to Mycobacterium avium Infection but Plays No Role in Induction of Th1 Responses▿

    PubMed Central

    Carvalho, Natália B.; Oliveira, Fernanda S.; Durães, Fernanda V.; de Almeida, Leonardo A.; Flórido, Manuela; Prata, Luana O.; Caliari, Marcelo V.; Appelberg, Rui; Oliveira, Sérgio C.

    2011-01-01

    To investigate the role of Toll-like receptor 9 (TLR9) in innate immunity to Mycobacterium avium, TLR9, TLR2, and MyD88 knockout (KO) mice were infected with this bacterium. Bacterial burdens were higher in the spleens, livers, and lungs of infected TLR9 KO mice than in those of C57BL/6 mice, indicating that TLR9 is required for efficient control of M. avium infection. However, TLR9 KO or TLR2 KO spleen cells displayed normal M. avium-induced tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) responses. This finding was confirmed by determining the number of splenic CD4+ T cells producing IFN-γ by flow cytometry. Furthermore, TLR2 and MyD88, but not TLR9, played a major role in interleukin-12 and TNF-α production by M. avium-infected macrophages and dendritic cells (DCs). We also found that major histocompatibility complex class II molecule expression on DCs is regulated by TLR2 and MyD88 signaling but not by TLR9. Finally, lack of TLR9, TLR2, or MyD88 reduced the numbers of macrophages, epithelioid cells, and lymphocytes in M. avium-induced granulomas but only MyD88 deficiency affected the number of liver granulomas. In summary, our data demonstrated that the involvement of TLR9 in the control of M. avium infection is not related to the induction of Th1 responses. PMID:21300776

  3. A novel insertion element from Mycobacterium avium, IS1245, is a specific target for analysis of strain relatedness.

    PubMed Central

    Guerrero, C; Bernasconi, C; Burki, D; Bodmer, T; Telenti, A

    1995-01-01

    The insertion sequence IS1245 is a novel mycobacterial repetitive element identified in Mycobacterium avium. It encodes a transposase which exhibits a 64% amino acid similarity with IS1081, an insertion element present in the M. tuberculosis complex. The host range of IS1245 appears limited to M. avium as this element was not identified in M. intracellulare or in any other of 18 mycobacteria species tested. When IS1245 was used for restriction fragment length polymorphism (RFLP) analysis, human isolates characteristically presented a high number of copies (median, 16; range, 3 to 27) and a diversity of RFLP patterns comparable to that found by pulsed-field gel electrophoresis. Isolates from nonhuman sources differed both in number of copies and in RFLP pattern diversity: while swine isolates shared the characteristics of human strains, those from several avian sources exhibited a very low copy number of IS1245 and appeared clonal on the basis of RFLP. PMID:7714183

  4. Anxiolytic-like actions of the hexane extract from leaves of Annona cherimolia in two anxiety paradigms: possible involvement of the GABA/benzodiazepine receptor complex.

    PubMed

    López-Rubalcava, C; Piña-Medina, B; Estrada-Reyes, R; Heinze, G; Martínez-Vázquez, M

    2006-01-11

    A hexane extract of leaves of Annona cherimolia produced anxiolytic-like actions when administered to mice and tested in two animal models of anxiety: the mouse avoidance exploratory behavior and the burying behavior tests. In order to discard unspecific drug-actions on general activity, all treatments studied in the anxiety paradigms were also analyzed in the open field test. Results showed that A. cherimolia induced anxiolytic-like actions at the doses of 6.25, 12.5, 25.0 and 50.0 mg/kg. Picrotoxin (0.25 mg/kg), a GABA-gated chloride ion channel blocker, antagonized the anxiolytic-like actions of A. cherimolia, while a sub-effective dose of muscimol (0.5 mg/kg), a selective GABA(A) receptor agonist, facilitated the effects of a sub-optimal dose of A. cherimolia (3.12 mg/kg). Thus, the involvement of the GABA(A) receptor complex in the anxiolytic-like actions of A. cherimolia hexane extract is suggested. In addition the extract was also able to enhance the duration of sodium pentobarbital induced sleeping time. Taken together, results indicate that the hexane extract of A. cherimolia has depressant activity on the Central Nervous System and could interact with the GABA(A) receptor complex. On the other hand, the chromatographic separation of this extract led to the isolation of palmitone, and beta-sitosterol as major constituents. In addition a GC-MS study of some fractions revealed the presence of several compounds such beta-cariophyllene, beta-selinene, alpha-cubebene, and linalool that have been reported to show effects on behavior that could explain some of the extract effects. PMID:16122763

  5. Clarifying the Narrative Paradigm.

    ERIC Educational Resources Information Center

    Fisher, Walter R.

    1989-01-01

    Replies to Rowland's article (same issue) on Fisher's views of the narrative paradigm. Clarifies the narrative paradigm by discussing three senses in which "narration" can be understood, and by indicating what the narrative paradigm is not. (SR)

  6. Induction of Mycobacterium avium proteins upon infection of human macrophages.

    PubMed

    Brunori, Lara; Giannoni, Federico; Bini, Luca; Liberatori, Sabrina; Frota, Cristiane; Jenner, Peter; Thoresen, Ove Fredrik; Orefici, Graziella; Fattorini, Lanfranco

    2004-10-01

    Induction of Mycobacterium avium proteins labelled with [35S]methionine and mRNAs upon infection of the human macrophage cell line THP-1 was investigated by two-dimensional gel electrophoresis-mass spectrometry and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. M. avium overexpressed proteins within the macrophages that are involved in fatty acids metabolism (FadE2, FixA), cell wall synthesis (KasA), and protein synthesis (EF-tu). The correlation of differential protein and mRNA expression varied between good and no correlation. Overall, these four proteins may be involved in the adaptation and survival of M. avium within human macrophages. PMID:15378697

  7. High-Density Lipoprotein Binds to Mycobacterium avium and Affects the Infection of THP-1 Macrophages.

    PubMed

    Ichimura, Naoya; Sato, Megumi; Yoshimoto, Akira; Yano, Kouji; Ohkawa, Ryunosuke; Kasama, Takeshi; Tozuka, Minoru

    2016-01-01

    High-density lipoprotein (HDL) is involved in innate immunity toward various infectious diseases. Concerning bacteria, HDL is known to bind to lipopolysaccharide (LPS) and to neutralize its physiological activity. On the other hand, cholesterol is known to play an important role in mycobacterial entry into host cells and in survival in the intracellular environment. However, the pathogenicity of Mycobacterium avium (M. avium) infection, which tends to increase worldwide, remains poorly studied. Here we report that HDL indicated a stronger interaction with M. avium than that with other Gram-negative bacteria containing abundant LPS. A binding of apolipoprotein (apo) A-I, the main protein component of HDL, with a specific lipid of M. avium might participate in this interaction. HDL did not have a direct bactericidal activity toward M. avium but attenuated the engulfment of M. avium by THP-1 macrophages. HDL also did not affect bacterial killing after ingestion of live M. avium by THP-1 macrophage. Furthermore, HDL strongly promoted the formation of lipid droplets in M. avium-infected THP-1 macrophages. These observations provide new insights into the relationship between M. avium infection and host lipoproteins, especially HDL. Thus, HDL may help M. avium to escape from host innate immunity. PMID:27516907

  8. High-Density Lipoprotein Binds to Mycobacterium avium and Affects the Infection of THP-1 Macrophages

    PubMed Central

    Ichimura, Naoya; Sato, Megumi; Yoshimoto, Akira; Yano, Kouji; Ohkawa, Ryunosuke; Kasama, Takeshi

    2016-01-01

    High-density lipoprotein (HDL) is involved in innate immunity toward various infectious diseases. Concerning bacteria, HDL is known to bind to lipopolysaccharide (LPS) and to neutralize its physiological activity. On the other hand, cholesterol is known to play an important role in mycobacterial entry into host cells and in survival in the intracellular environment. However, the pathogenicity of Mycobacterium avium (M. avium) infection, which tends to increase worldwide, remains poorly studied. Here we report that HDL indicated a stronger interaction with M. avium than that with other Gram-negative bacteria containing abundant LPS. A binding of apolipoprotein (apo) A-I, the main protein component of HDL, with a specific lipid of M. avium might participate in this interaction. HDL did not have a direct bactericidal activity toward M. avium but attenuated the engulfment of M. avium by THP-1 macrophages. HDL also did not affect bacterial killing after ingestion of live M. avium by THP-1 macrophage. Furthermore, HDL strongly promoted the formation of lipid droplets in M. avium-infected THP-1 macrophages. These observations provide new insights into the relationship between M. avium infection and host lipoproteins, especially HDL. Thus, HDL may help M. avium to escape from host innate immunity. PMID:27516907

  9. Hidden Gems in the Mycobacterium avium subsp. paratuberculosis Genome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    If 4,350 genes annotated in the M. avium subsp paratuberculosis strain K-10 genome wasn’t already enough to study, more genes have recently been uncovered, hidden deep within this genome sequence. Genomic and proteomic studies, both published and unpublished, have revealed a handful of new genes mi...

  10. Cellular Interactions in Mycobacterium avium subsp. paratuberculosis Infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Noted as one of the more fastidious mycobacteria, infection with MAP is often chara...

  11. Methylation of GPLs in Mycobacterium smegmatis and Mycobacterium avium

    PubMed Central

    Jeevarajah, Dharshini; Patterson, John H.; Taig, Ellen; Sargeant, Tobias; McConville, Malcolm J.; Billman-Jacobe, Helen

    2004-01-01

    Several species of mycobacteria express abundant glycopeptidolipids (GPLs) on the surfaces of their cells. The GPLs are glycolipids that contain modified sugars including acetylated 6-deoxy-talose and methylated rhamnose. Four methyltransferases have been implicated in the synthesis of the GPLs of Mycobacterium smegmatis and Mycobacterium avium. A rhamnosyl 3-O-methytransferase and a fatty acid methyltransferase of M. smegmatis have been previously characterized. In this paper, we characterize the methyltransferases that are responsible for modifying the hydroxyl groups at positions 2 and 4 of rhamnose and propose the biosynthetic sequence of GPL trimethylrhamnose formation. The analysis of M. avium genes through the creation of specific mutants is technically difficult; therefore, an alternative approach to determine the function of putative methyltransferases of M. avium was undertaken. Complementation of M. smegmatis methyltransferase mutants with M. avium genes revealed that MtfC and MtfB of the latter species have 4-O-methyltransferase activity and that MtfD is a 3-O-methyltransferase which can modify rhamnose of GPLs in M. smegmatis. PMID:15466031

  12. Tuberculosis in Birds: Insights into the Mycobacterium avium Infections

    PubMed Central

    Dhama, Kuldeep; Mahendran, Mahesh; Tiwari, Ruchi; Dayal Singh, Shambhu; Kumar, Deepak; Singh, Shoorvir; Sawant, Pradeep Mahadev

    2011-01-01

    Tuberculosis, a List B disease of World Organization for Animal Health, caused by M. avium or M. genavense predominantly affects poultry and pet or captive birds. Clinical manifestations in birds include emaciation, depression and diarrhea along with marked atrophy of breast muscle. Unlike tuberculosis in animals and man, lesions in lungs are rare. Tubercular nodules can be seen in liver, spleen, intestine and bone marrow. Granulomatous lesion without calcification is a prominent feature. The disease is a rarity in organized poultry sector due to improved farm practices, but occurs in zoo aviaries. Molecular techniques like polymerase chain reaction combined with restriction fragment length polymorphism and gene probes aid in rapid identification and characterization of mycobacteria subspecies, and overcome disadvantages of conventional methods which are slow, labour intensive and may at times fail to produce precise results. M. avium subsp. avium with genotype IS901+ and IS1245+ causes infections in animals and human beings too. The bacterium causes sensitivity in cattle to the tuberculin test. The paper discusses in brief the M. avium infection in birds, its importance in a zoonotic perspective, and outlines conventional and novel strategies for its diagnosis, prevention and eradication in domestic/pet birds and humans alike. PMID:21776352

  13. Mycobacterium avium subsp. paratuberculosis infection, immunology and pathology of livestock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) infection in ruminants leads to a chronic and progressive enteric disease (Johne’s disease) that results in loss of intestinal function, poor body condition, and eventual death. Transmission is primarily through a fecal-oral route in neonates but con...

  14. Polyclonal Mycobacterium avium infections in patients with AIDS: variations in antimicrobial susceptibilities of different strains of M. avium isolated from the same patient.

    PubMed Central

    von Reyn, C F; Jacobs, N J; Arbeit, R D; Maslow, J N; Niemczyk, S

    1995-01-01

    Broth microdilution MICs were determined for pairs of strains isolated from five AIDS patients with polyclonal Mycobacterium avium infection. Four (80%) of the five patients were infected simultaneously with strains having different antimicrobial susceptibility patterns. These findings have implications for the interpretation of susceptibility data in M. avium prophylaxis and treatment trials. PMID:7790424

  15. Indices of onchocerciasis transmission by different members of the Simulium damnosum complex conflict with the paradigm of forest and savanna parasite strains.

    PubMed

    Cheke, Robert A; Garms, Rolf

    2013-01-01

    Onchocerciasis in savanna zones is generally more severe than in the forest and pathologies also differ geographically, differences often ascribed to the existence of two or more strains and incompatibilities between vectors and strains. However, flies in the forest transmit more infective larvae than their savanna counterparts, even in sympatry, contradicting expectations based on the forest and savanna strains paradigm. We analysed data on the numbers of Onchocerca volvulus larvae of different stages found in 10 different taxonomic categories of the Simulium damnosum complex derived from more than 48,800 dissections of flies from Sierra Leone in the west of Africa to Uganda in the east. The samples were collected before widespread ivermectin distribution and thus provide a baseline for evaluating control measures. Savanna species contained fewer larvae per infected or per infective fly than the forest species, even when biting and parous rates were accounted for. The highest transmission indices were found in the forest-dwelling Pra form of Simulium sanctipauli (616 L3/1000 parous flies) and the lowest in the savanna-inhabiting species S. damnosum/S. sirbanum (135) and S. kilibanum (65). Frequency distributions of numbers of L1-2 and L3 larvae found in parous S. damnosum/S. sirbanum, S. kilibanum, S. squamosum, S. yahense, S. sanctipauli, S. leonense and S. soubrense all conformed to the negative binomial distribution, with the mainly savanna-dwelling species (S. damnosum/S. sirbanum) having less overdispersed distributions than the mainly forest-dwelling species. These infection patterns were maintained even when forest and savanna forms were sympatric and biting the same human population. Furthermore, for the first time, levels of blindness were positively correlated with infection intensities of the forest vector S. yahense, consistent with relations previously reported for savanna zones. Another novel result was that conversion rates of L1-2 larvae to L3s

  16. Mannosylated Lipoarabinomannans from Mycobacterium Avium Subsp. Paratuberculosis Alters the Inflammatory Response by Bovine Macrophages and Suppresses Killing of Mycobacterium Avium Subsp. Avium Organisms

    PubMed Central

    Souza, Cleverson; Davis, William C.; Eckstein, Torsten M.; Sreevatsan, Srinand; Weiss, Douglas J.

    2013-01-01

    Analysis of the mechanisms through which pathogenic mycobacteria interfere with macrophage activation and phagosome maturation have shown that engagement of specific membrane receptors with bacterial ligands is the initiating event. Mannosylated lipoarabinomannan (Man-LAM) has been identified as one of the ligands that modulates macrophage function. We evaluated the effects of Man-LAM derived from Mycobacterium avium subsp. paratuberculosis (MAP) on bovine macrophages. Man-LAM induced a rapid and prolonged expression of IL-10 message as well as transient expression of TNF-α. Preincubation with Man-LAM for up to 16 h did not suppress expression of IL-12 in response to interferon-γ. Evaluation of the effect of Man-LAM on phagosome acidification, phagosome maturation, and killing of Mycobacterium avium subsp. avium (MAA) showed that preincubation of macrophages with Man-LAM before addition of MAA inhibited phagosome acidification, phagolysosome fusion, and reduced killing. Analysis of signaling pathways provided indirect evidence that inhibition of killing was associated with activation of the MAPK-p38 signaling pathway but not the pathway involved in regulation of expression of IL-10. These results support the hypothesis that MAP Man-LAM is one of the virulence factors facilitating survival of MAP in macrophages. PMID:24098744

  17. Rapid discrimination of Mycobacterium avium strains from AIDS patients by randomly amplified polymorphic DNA analysis.

    PubMed Central

    Matsiota-Bernard, P; Waser, S; Tassios, P T; Kyriakopoulos, A; Legakis, N J

    1997-01-01

    A randomly amplified polymorphic DNA (RAPD) analysis was performed for the molecular typing of Mycobacterium avium strains. This method was applied to epidemiologically unrelated M. avium strains isolated from the blood of 10 different AIDS patients and to strains that were considered epidemiologically related, as they had been isolated from the same patient but from different body locations (4 patients, 10 strains). Three oligonucleotide primers among the six tested were found to generate RAPD profiles with DNA from all M. avium strains and to successfully type them. This method for the typing of M. avium strains is rapid and easy to perform. PMID:9163488

  18. Utilization of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) to Identify environmental Strains of Mycobacterium Complex

    EPA Science Inventory

    Species within the Mycobacterium avium Complex (MAC) group are found to be both prevalent and persistent in drinking water distribution systems. The MAC is composed of two predominant species: M. avium and M. intracellulare. These species have the ability to survive drinking ...

  19. Beyond desertification: New paradigms for dryland landscapes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The dryland desertification paradigm focuses on losses of ecosystem services accompanying transitions from grasslands to systems dominated by bare ground or woody plants unpalatable for domestic livestock. However, recent studies reveal complex transitions across a range of environmental conditions ...

  20. Paradigms Past and Future.

    ERIC Educational Resources Information Center

    Oates, Maureen

    1980-01-01

    Evaluates past paradigms (conceptual frameworks) such as the belief in the unlimited resources of the earth for humanity's particular benefit and the paradigm of the infallibility of technology. Illustrates how we are generally moving toward the new paradigm that small and simple is not only beautiful, but also more efficient, reliable, practical,…

  1. The Generative Paradigm.

    ERIC Educational Resources Information Center

    Loynes, Chris

    2002-01-01

    The "algorithmic" model of outdoor experiential learning is based in military tradition and characterized by questionable scientific rationale, production line metaphor, and the notion of learning as marketable commodity. Alternatives are the moral paradigm; the ecological paradigm "friluftsliv"; and the emerging "generative" paradigm, which…

  2. Profiling Bovine Antibody Responses to Mycobacterium avium subsp. paratuberculosis Infection by Using Protein Arrays▿ †

    PubMed Central

    Bannantine, John P.; Paustian, Michael L.; Waters, W. Ray; Stabel, Judith R.; Palmer, Mitchell V.; Li, Lingling; Kapur, Vivek

    2008-01-01

    With the genome sequence of Mycobacterium avium subsp. paratuberculosis determined, technologies are now being developed for construction of protein arrays to detect the presence of antibodies against M. avium subsp. paratuberculosis in host serum. The power of this approach is that it enables a direct comparison of M. avium subsp. paratuberculosis proteins to each other in relation to their immunostimulatory capabilities. In this study, 93 recombinant proteins, produced in Escherichia coli, were arrayed and spotted onto nitrocellulose. These proteins include unknown hypothetical proteins and cell surface proteins as well as proteins encoded by large sequence polymorphisms present uniquely in M. avium subsp. paratuberculosis. Also included were previously reported or known M. avium subsp. paratuberculosis antigens to serve as a frame of reference. Sera from healthy control cattle (n = 3) and cattle infected with either M. avium subsp. avium and Mycobacterium bovis were exposed to the array to identify nonspecific or cross-reactive epitopes. These data demonstrated a degree of cross-reactivity with the M. avium subsp. avium proteins that was higher than the degree of cross-reactivity with the more distantly related M. bovis proteins. Finally, sera from naturally infected cattle (n = 3) as well as cattle experimentally infected with M. avium subsp. paratuberculosis (n = 3) were used to probe the array to identify antigens in the context of Johne's disease. Three membrane proteins were the most strongly detected in all serum samples, and they included an invasion protein, an ABC peptide transport permease, and a putative GTPase protein. This powerful combination of genomic information, molecular tools, and immunological assays has enabled the identification of previously unknown antigens of M. avium subsp. paratuberculosis. PMID:18039835

  3. AhpC, AhpD, and a secreted 14-kilodalton antigen from Mycobacterium avium subsp. paratuberculosis distinguish between paratuberculosis and bovine tuberculosis in an enzyme-linked immunosorbent assay.

    PubMed

    Olsen, I; Tryland, M; Wiker, H G; Reitan, L J

    2001-07-01

    Sera from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis (n = 56) and naturally (n = 4) and experimentally (n = 8) infected with Mycobacterium bovis were tested for the presence of antibodies against paratuberculosis antigens. An enzyme-linked immunosorbent assay (ELISA) was established based on absorption of M. avium subsp. paratuberculosis antigens on a hyperimmune antiserum against M. avium subsp. avium proteins in order to remove cross-reacting antigens. This absorbed-antigen ELISA recognized 66% of animals with paratuberculosis (37 of 56), while none of the animals with naturally occurring bovine tuberculosis (TB) had detectable antibodies. However, the animals with experimental bovine TB also responded in this ELISA. Similar results were found in a commercial ELISA, showing that neither of these tests was able to distinguish between paratuberculosis and bovine TB. The sera were further tested for antibody activities against purified AhpC and AhpD, which are proteins constitutively expressed by M. avium subsp. paratuberculosis, and against a secreted 14-kDa protein present in culture filtrates from the M. avium complex. Elevated antibody levels to AhpC, AhpD, and the 14-kDa antigen were found in 27% (13 of 48), 15% (7 of 48), and 27% (13 of 48), respectively, of the cattle with paratuberculosis. Together these ELISAs were positive with 35% (17 of 48) of the animals. None of the animals with bovine TB had detectable antibodies against any of the purified proteins despite their high levels of cross-reacting antibodies. These results show that purified specific antigens are needed to differentiate between paratuberculosis and bovine TB in ELISA. PMID:11427429

  4. Characterization of IS1245 for Strain Typing of Mycobacterium avium

    PubMed Central

    Pestel-Caron, Martine; Arbeit, Robert D.

    1998-01-01

    IS1245 is an insertion element widely prevalent among isolates of Mycobacterium avium. We used PvuII Southern blots to analyze IS1245 polymorphisms among 159 M. avium isolates (141 clinical isolates from 40 human immunodeficiency virus-infected patients plus 18 epidemiologically related environmental isolates) that represented 40 distinct M. avium strains, as resolved by previous studies by pulsed-field gel electrophoresis (PFGE). All 40 strains carried DNA homologous to IS1245 and thus were typeable. Twenty-five (63%) strains had ≥10 copies of the element, 6 (15%) had 4 to 9 copies, and 9 (23%) had only 1 to 3 copies. Among the last group of nine strains (each of which was distinct by PFGE analysis), IS1245 typing resolved only four patterns and thus provided poor discriminatory power. To evaluate the in vivo stability of IS1245, we analyzed 32 strains for which sets of 2 to 19 epidemiologically related isolates were available. For 19 (59%) of these sets, all isolates representing the same strain had indistinguishable IS1245 patterns. Within eight (25%) sets, one or more isolates had IS1245 patterns that differed by one or two fragments from the modal pattern for the isolates of that strain. Five (16%) sets included isolates whose patterns differed by three or more fragments; on the basis of IS1245 typing those isolates would have been designated distinct strains. IS1245 was stable during in vitro passage, suggesting that the variations observed represented natural translocations of the element. IS1245 provides a useful tool for molecular strain typing of M. avium but may have limitations for analyzing strains with low copy numbers or for resolving extended epidemiologic relationships. PMID:9650925

  5. A monoclonal antibody-based latex bead agglutination test for the detection of Bordetella avium.

    PubMed

    Suresh, P; Arp, L H

    1993-01-01

    The purpose of this study was to develop a rapid method to distinguish Bordetella avium from closely related Bordetella avium-like and B. bronchiseptica bacteria. A monoclonal antibody of the IgM isotype was produced in Balb/c mice against live B. avium strain 75. The monoclonal antibody, in the form of ascites fluid, was added to a bovine serum albumin-glycine buffer (pH 8.6) and adsorbed to 3.03-microns-diameter latex beads. Optimum concentrations of antibody, beads, and bacteria were determined. The latex bead conjugate was tested against 40 isolates of B. avium, 24 isolates of B. avium-like bacteria, 17 isolates of B. bronchiseptica, two isolates of Alcaligenes faecalis, and several other common genera. Strong agglutination occurred with all B. avium isolates and the two isolates of A. faecalis. Weak agglutination occurred with Staphylococcus aureus and two isolates of B. bronchiseptica. There was no agglutination with any of the B. avium-like isolates. The latex bead agglutination test may be useful as an aid in the identification of B. avium when used in conjunction with other criteria. PMID:8257369

  6. Development and Characterization of Monoclonal Antibodies and Aptamers Against Major Antigens of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Specific antibodies, available in unlimited quantities, have not been produced against Mycobacterium avium subsp. paratuberculosis, the bacterium that causes Johne’s disease (JD). To fill this gap in JD research, monoclonal antibodies (mAbs) against M. avium subsp. paratuberculosis were produced fr...

  7. Complete genome sequence of Mycobacterium avium subsp. paratuberculosis, isolated from human breast milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp paratuberculosis is the etiologic agent of Johne’s disease. We report the draft genome sequences of six M. avium subsp paratuberculosis isolates obtained from diverse hosts including bison, cattle and sheep. These sequences will deepen our understanding of host association ...

  8. First isolation of Mycobacterium avium subsp Paratuberculosis from commercial pasteurized milk in Argentina

    PubMed Central

    Paolicchi, Fernando; Cirone, Karina; Morsella, Claudia; Gioffré, Andrea

    2012-01-01

    Mycobacterium avium subsp paratuberculosis was isolated from two out of seventy samples (2.86 %) of pasteurized and ultra-pasteurized milk. The isolates were positives to IS900 PCR and showed a C17 RFLP pattern, the most prevalent in Argentina. The present study is the first report of Mycobacterium avium subsp paratuberculosis culture from pasteurized milk in Argentina. PMID:24031925

  9. Antigenic Profiles of Recombinant Proteins from Mycobacterium avium subsp paratuberculosis in Sheep with Johne's Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methods to improve the ELISA test to detect Mycobacterium avium subsp paratuberculosis have been explored over several years. Previously, selected recombinant proteins of M. avium subspecies paratuberculosis were found to be immunogenic in cattle with Johne’s disease. In the present study, antibo...

  10. Roles for Cell Wall Glycopeptidolipid in Surface Adherence and Planktonic Dispersal of Mycobacterium avium

    EPA Science Inventory

    The opportunistic pathogen Mycobacterium avium is a significant inhabitant of biofilms in drinking water distribution systems. M. avium expresses on its cell surface serovar-specific glycopeptidolipids (ssGPLs). Studies have implicated the core GPL in biofilm formation by M. aviu...

  11. Fabrication of a Novel Conductometric Biosensor for Detecting Mycobacterium avium subsp. paratuberculosis Antibodies

    PubMed Central

    Okafor, Chika; Grooms, Daniel; Alocilja, Evangelyn; Bolin, Steven

    2008-01-01

    Johne's disease (JD) is one of the most costly bacterial diseases in cattle. In the U.S., economic losses from the disease have been estimated to exceed $1,500,000,000 per year, mainly from the effects of reduced milk production. Current diagnostic tests for JD are laboratory based and many of those tests require specialized equipment and training. Development of rapid and inexpensive diagnostic assays, which are adapted for point-of-care applications, would aid in the control of JD. In this study, a polyaniline (Pani)-based conductometric biosensor, in an immunomigration format, was fabricated for the detection of serum antibody (IgG) against the causal organism of JD, Mycobacterium avium subsp. paratuberculosis (MAP). Immobilized Mycobacterium avium purified proteins in the capture membrane were used to detect MAP IgG, previously bound with Pani/anti-bovine IgG* conjugate in the conjugate membrane. After detection, the Pani in the sandwiched captured complex bridges an electrical circuit between the silver electrodes, flanking the capture membrane. The electrical conductance, caused by Pani, was measured as drop in electrical resistance. Testing of the biosensor with known JD positive and negative serum samples demonstrated a significant difference in the mean resistance observed between the groups. This proof-of-concept study demonstrated that a conductometric biosensor could detect MAP IgG in 2 minutes. The biosensor's speed of detection and the equipment involved would, among other things, support its application towards the various point-of-care opportunities aimed at JD management and control.

  12. Serodiagnostic Potential of Mycobacterium avium MAV2054 and MAV5183 Proteins

    PubMed Central

    Shin, A-Rum; Lee, Kil-Soo; Lee, Kang In; Shim, Tae Sun; Koh, Won-Jung; Jeon, Haet Sal; Son, Yeo-Jin; Shin, Sung-Jae

    2013-01-01

    The Mycobacterium avium-M. intracellulare complex (MAC) causes a pulmonary disease (PD) similar to tuberculosis (TB). Diagnosis of MAC-PD is complicated and time-consuming. In this study, the serodiagnostic potential of the newly identified MAV2054 and MAV5183 proteins was evaluated in subjects with MAC-PD, pulmonary TB, or latent TB and in noninfected healthy controls (HC), together with HspX and the 38-kDa antigen, well-known serodiagnostic M. tuberculosis antigens. All four antigens evoked significantly higher IgG responses in MAC-PD and active TB than in latent TB and HC subjects. Among the antigens, MAV2054 elicited the highest antibody responses in pulmonary TB and MAC-PD patients. IgG titers against MAV2054 and MAV5183 were significantly higher in MAC-PD than in pulmonary TB subjects. In addition, the levels of IgG against all antigens in the M. intracellulare and fibrocavitary forms were higher than those in the M. avium and nodular bronchiectatic forms, respectively. Based on sensitivity and receiver operator characteristic curve analysis, the best candidates for detection of MAC-PD and pulmonary TB were MAV2054 and the 38-kDa antigen, respectively. In total, 76.0% of MAC-PD and 65.0% of active TB patients were reactive to at least two antigens. In contrast, only 2.8% of HC subjects were reactive with two or more antigens. Our findings suggest that an enzyme-linked immunosorbent assay (ELISA) using the four antigens would be valuable for screening for mycobacterial lung disease, including MAC-PD and pulmonary TB, although it does not provide good discrimination of the disease-causing pathogens. PMID:23269416

  13. Assessing the Inactivation of Mycobacterium avium subsp. paratuberculosis during Composting of Livestock Carcasses

    PubMed Central

    Tkachuk, Victoria L.; Krause, Denis O.; McAllister, Tim A.; Buckley, Katherine E.; Reuter, Tim; Hendrick, Steve

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis causes Johne's disease (JD) in ruminants, with substantial economic impacts on the cattle industry. Johne's disease is known for its long latency period, and difficulties in diagnosis are due to insensitivities of current detection methods. Eradication is challenging as M. avium subsp. paratuberculosis can survive for extended periods within the environment, resulting in new infections in naïve animals (W. Xu et al., J. Environ. Qual. 38:437-450, 2009). This study explored the use of a biosecure, static composting structure to inactivate M. avium subsp. paratuberculosis. Mycobacterium smegmatis was also assessed as a surrogate for M. avium subsp. paratuberculosis. Two structures were constructed to hold three cattle carcasses each. Naturally infected tissues and ground beef inoculated with laboratory-cultured M. avium subsp. paratuberculosis and M. smegmatis were placed in nylon and plastic bags to determine effects of temperature and compost environment on viability over 250 days. After removal, samples were cultured and growth of both organisms was assessed after 12 weeks. After 250 days, M. avium subsp. paratuberculosis was still detectable by PCR, while M. smegmatis was not detected after 67 days of composting. Furthermore, M. avium subsp. paratuberculosis remained viable in both implanted nylon and plastic bags over the composting period. As the compost never reached a homogenous thermophilic (55 to 65°C) state throughout each structure, an in vitro experiment was conducted to examine viability of M. avium subsp. paratuberculosis after exposure to 80°C for 90 days. Naturally infected lymph tissues were mixed with and without compost. After 90 days, M. avium subsp. paratuberculosis remained viable despite exposure to temperatures typically higher than that achieved in compost. In conclusion, it is unlikely composting can be used as a means of inactivating M. avium subsp. paratuberculosis associated with cattle

  14. Assessing the inactivation of Mycobacterium avium subsp. paratuberculosis during composting of livestock carcasses.

    PubMed

    Tkachuk, Victoria L; Krause, Denis O; McAllister, Tim A; Buckley, Katherine E; Reuter, Tim; Hendrick, Steve; Ominski, Kim H

    2013-05-01

    Mycobacterium avium subsp. paratuberculosis causes Johne's disease (JD) in ruminants, with substantial economic impacts on the cattle industry. Johne's disease is known for its long latency period, and difficulties in diagnosis are due to insensitivities of current detection methods. Eradication is challenging as M. avium subsp. paratuberculosis can survive for extended periods within the environment, resulting in new infections in naïve animals (W. Xu et al., J. Environ. Qual. 38:437-450, 2009). This study explored the use of a biosecure, static composting structure to inactivate M. avium subsp. paratuberculosis. Mycobacterium smegmatis was also assessed as a surrogate for M. avium subsp. paratuberculosis. Two structures were constructed to hold three cattle carcasses each. Naturally infected tissues and ground beef inoculated with laboratory-cultured M. avium subsp. paratuberculosis and M. smegmatis were placed in nylon and plastic bags to determine effects of temperature and compost environment on viability over 250 days. After removal, samples were cultured and growth of both organisms was assessed after 12 weeks. After 250 days, M. avium subsp. paratuberculosis was still detectable by PCR, while M. smegmatis was not detected after 67 days of composting. Furthermore, M. avium subsp. paratuberculosis remained viable in both implanted nylon and plastic bags over the composting period. As the compost never reached a homogenous thermophilic (55 to 65°C) state throughout each structure, an in vitro experiment was conducted to examine viability of M. avium subsp. paratuberculosis after exposure to 80°C for 90 days. Naturally infected lymph tissues were mixed with and without compost. After 90 days, M. avium subsp. paratuberculosis remained viable despite exposure to temperatures typically higher than that achieved in compost. In conclusion, it is unlikely composting can be used as a means of inactivating M. avium subsp. paratuberculosis associated with cattle

  15. Alkyl Hydroperoxide Reductases C and D Are Major Antigens Constitutively Expressed by Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Olsen, Ingrid; Reitan, Liv J.; Holstad, Gudmund; Wiker, Harald G.

    2000-01-01

    Antigens characteristic for Mycobacterium avium subspecies paratuberculosis were identified by crossed immunoelectrophoresis (CIE) and by absorbing out cross-reactive antigens by using a polyclonal and polyvalent Mycobacterium avium subspecies avium antiserum. Two antigens were present in M. avium subsp. paratuberculosis and not detected in Mycobacterium avium subsp. avium. They were identified as antigens 17 and 20 in a CIE reference system for M. avium subsp. paratuberculosis antigens. Purified antigen 20 was identified as alkyl hydroperoxide reductase C (AhpC) while the N-terminal part of purified antigen 17 showed 80% homology with alkyl hydroperoxide reductase D (AhpD) of Mycobacterium tuberculosis. AhpC had a nonreduced mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis corresponding to a molecular mass of 45 kDa and is probably a homodimer linked with disulfide bridges in its native form. AhpD had a mobility corresponding to 19 kDa. Monospecific rabbit antiserum against AhpC and AhpD reacted with 9 strains of M. avium subsp. paratuberculosis but not with 20 other mycobacterial strains except for a Mycobacterium gordonae strain, against which a weak cross-reactive band was produced. Goats experimentally infected with M. avium subsp. paratuberculosis had strong gamma interferon (IFN-γ) responses toward both AhpC and AhpD, and they also had antibodies against AhpC. The ability of AhpC and AhpD to induce IFN-γ production shows that these proteins potentially could be used in future vaccines or in diagnostic assays. These results further show that AhpC and AhpD are immunologically important proteins which are constitutively and highly expressed in M. avium subsp. paratuberculosis without the bacteria being submitted to oxidative stress and that the specificities of antigens can be a matter of different levels of protein expression in various species as well as distinct structural differences. PMID:10639449

  16. Mycobacterium avium Genes MAV_5138 and MAV_3679 Are Transcriptional Regulators That Play a Role in Invasion of Epithelial Cells, in Part by Their Regulation of CipA, a Putative Surface Protein Interacting with Host Cell Signaling Pathways▿

    PubMed Central

    Harriff, Melanie J.; Danelishvili, Lia; Wu, Martin; Wilder, Cara; McNamara, Michael; Kent, Michael L.; Bermudez, Luiz E.

    2009-01-01

    The Mycobacterium avium complex (MAC) is an important group of opportunistic pathogens for birds, cattle, swine, and immunosuppressed humans. Although invasion of epithelial cells lining the intestine is the chief point of entry for these organisms, little is known about the mechanisms by which members of the MAC are taken up by these cells. Studies with M. avium have shown that cytoskeletal rearrangement via activation of the small G-protein Cdc42 is involved and that this activation is regulated in part by the M. avium fadD2 gene. The fadD2 gene indirectly regulates a number of genes upon exposure to HEp-2 cells, including transcriptional regulators, membrane proteins, and secreted proteins. Overexpression of two fadD2-associated regulators (MAV_5138 and MAV_3679) led to increased invasion of HEp-2 cells, as well as altered expression of other genes. The protein product of one of the regulated genes, named CipA, has domains that resemble the PXXP motif of human Piccolo proteins, which bind SH3 domains in proteins involved in the scaffold complex formed during cytoskeletal rearrangement. Although CipA was not detected in the cytoplasm of HEp-2 cells exposed to M. avium, the recombinant protein was shown to be potentially expressed on the surface of Mycobacterium smegmatis incubated with HEp-2 cells and, possibly, to interact with human Cdc42. The interaction was then confirmed by showing that CipA activates Cdc42. These results suggest that members of the M. avium complex have a novel mechanism for activating cytoskeletal rearrangement, prompting uptake by host epithelial cells, and that this mechanism is regulated in part by fadD2, MAV_5138, and MAV_3679. PMID:19060135

  17. Organizational Paradigm Shifts.

    ERIC Educational Resources Information Center

    National Association of College and University Business Officers, Washington, DC.

    This collection of essays explores a new paradigm of higher education. The first essay, "Beyond Re-engineering: Changing the Organizational Paradigm" (L. Edwin Coate), suggests a model of quality process management and a structure for managing organizational change. "Thinking About Consortia" (Mary Jo Maydew) discusses cooperative effort and…

  18. The Investment Paradigm

    ERIC Educational Resources Information Center

    Perna, Mark C.

    2005-01-01

    Is marketing an expense or an investment? Most accountants will claim that marketing is an expense, and clearly that seems true when cutting the checks to fund these efforts. When it is done properly, marketing is the best investment. A key principle to Smart Marketing is the Investment Paradigm. The Investment Paradigm is understanding that every…

  19. An Integrative Paradigm

    ERIC Educational Resources Information Center

    Hammack, Phillip L.

    2005-01-01

    Through the application of life course theory to the study of sexual orientation, this paper specifies a new paradigm for research on human sexual orientation that seeks to reconcile divisions among biological, social science, and humanistic paradigms. Recognizing the historical, social, and cultural relativity of human development, this paradigm…

  20. Mycobacterium avium genotype is associated with the therapeutic response to lung infection.

    PubMed

    Kikuchi, T; Kobashi, Y; Hirano, T; Tode, N; Santoso, A; Tamada, T; Fujimura, S; Mitsuhashi, Y; Honda, Y; Nukiwa, T; Kaku, M; Watanabe, A; Ichinose, M

    2014-03-01

    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. PMID:23829301

  1. A new paradigm and computational framework to estimate stop-signal reaction time distributions from the inhibition of complex motor sequences

    PubMed Central

    Teichert, Tobias; Ferrera, Vincent P.

    2015-01-01

    Inhibitory control is an important component of executive function that allows organisms to abort emerging behavioral plans or ongoing actions on the fly as new sensory information becomes available. Current models treat inhibitory control as a race between a Go- and a Stop process that may be mediated by partially distinct neural substrates, i.e., the direct and the hyper-direct pathway of the basal ganglia. The fact that finishing times of the Stop process (Stop-Signal Reaction Time, SSRT) cannot be observed directly has precluded a precise comparison of the functional properties that govern the initiation (GoRT) and inhibition (SSRT) of a motor response. To solve this problem, we modified an existing inhibitory paradigm and developed a non-parametric framework to measure the trial-by-trial variability of SSRT. A series of simulations verified that the non-parametric approach is on par with a parametric approach and yields accurate estimates of the entire SSRT distribution from as few as ~750 trials. Our results show that in identical settings, the distribution of SSRT is very similar to the distribution of GoRT albeit somewhat shorter, wider and significantly less right-skewed. The ability to measure the precise shapes of SSRT distributions opens new avenues for research into the functional properties of the hyper-direct pathway that is believed to mediate inhibitory control. PMID:26236226

  2. Modulation of the effector function of human monocytes for Mycobacterium avium by human immunodeficiency virus-1 envelope glycoprotein gp120.

    PubMed Central

    Shiratsuchi, H; Johnson, J L; Toossi, Z; Ellner, J J

    1994-01-01

    Disseminated Mycobacterium avium infection in AIDS is associated with high tissue burdens (10(9)-10(10) mycobacteria/g tissue) of organism. The basis for the extraordinary susceptibility of AIDS to M. avium infection is unclear. HIV or its constituents may alter mononuclear phagocyte functions resulting in enhanced intracellular M. avium growth. The effects of an envelope glycoprotein (gp120), a transmembrane protein (p121), and core proteins of HIV-1 on M. avium infection of human monocytes were examined. Preculturing monocytes with gp120 inhibited M. avium phagocytosis and consistently enhanced intracellular growth of six M. avium strains. Pretreatment with p121, gag5, or p24 did not inhibit phagocytosis nor enhance intracellular growth of M. avium. Incubation of gp120 with soluble CD4 before addition to monocyte cultures or pretreatment of monocytes with OKT4A abrogated gp120 effects on M. avium phagocytosis and intracellular growth. gp120 also augmented cytokine production by infected monocytes. These results suggest that gp120, but not p121 or core proteins, modulate monocyte phagocytosis and enhance intracellular growth of M. avium at least in part through monocyte CD4 receptors. Direct effects of HIV-1 products may, therefore, contribute to the diathesis of AIDS to develop disseminated M. avium infection and to the extensive replication of the organisms within tissue macrophages. Images PMID:8113420

  3. Stability of Insertion Sequence IS1245, a Marker for Differentiation of Mycobacterium avium Strains

    PubMed Central

    Bauer, Jeanett; Andersen, Åse Bengård

    1999-01-01

    Recently a novel insertion element, IS1245, has been described and suggested for use as a probe in restriction fragment length polymorphism studies of Mycobacterium avium strains. An important issue in this context is the stability of the insertion element. We analyzed single colonies of M. avium cultures and found frequent small one- to two-band changes. However, following repeated in vitro passages over 1 year, similar one- to two-band changes were observed in the IS1245 patterns of only six M. avium strains investigated. PMID:9889238

  4. Paradigms for machine learning

    NASA Technical Reports Server (NTRS)

    Schlimmer, Jeffrey C.; Langley, Pat

    1991-01-01

    Five paradigms are described for machine learning: connectionist (neural network) methods, genetic algorithms and classifier systems, empirical methods for inducing rules and decision trees, analytic learning methods, and case-based approaches. Some dimensions are considered along with these paradigms vary in their approach to learning, and the basic methods are reviewed that are used within each framework, together with open research issues. It is argued that the similarities among the paradigms are more important than their differences, and that future work should attempt to bridge the existing boundaries. Finally, some recent developments in the field of machine learning are discussed, and their impact on both research and applications is examined.

  5. Communication Policy at the Chalk Face in Scotland and Jamaica: Complexity as a New Paradigm for Understanding Language Policy Interpretation and Implementation.

    ERIC Educational Resources Information Center

    Cross, Beth

    2003-01-01

    Examples from upper primary classrooms in Scotland and Jamaica demonstrate the subtle ways in which teachers support or restrict the classroom use of community languages (Scots and Patwa) through their broad or narrow implementation of language policy. The metaphor of fractals, derived from complexity theory, can form a sensitive and appropriate…

  6. The fictionalist paradigm.

    PubMed

    Paley, John

    2011-01-01

    The fictionalist paradigm is introduced, and differentiated from other paradigms, using the Lincoln & Guba template. Following an initial overview, the axioms of fictionalism are delineated by reference to standard metaphysical categories: the nature of reality, the relationship between knower and known, the possibility of generalization, the possibility of causal linkages, and the role of values in inquiry. Although a paradigm's 'basic beliefs' are arbitrary and can be assumed for any reason, in this paper the fictionalist axioms are supported with philosophical considerations, and the key differences between fictionalism, positivism, and constructivism are briefly explained. Paradigm characteristics are then derived, focusing particularly on the methodological consequences. Towards the end of the paper, various objections and misunderstandings are discussed. PMID:21143578

  7. Composition and potency characterization of Mycobacterium avium subsp. paratuberculosis purified protein derivatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) purified protein derivatives (PPDs) are immunologic reagents prepared from cultured filtrates of the type strain ATCC 19698. Traditional production consists of floating culture incubation at 37oC, organism inactivation by autoclaving, coarse filtrat...

  8. No holes barred: Invasion of the intestinal mucosa by Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The infection biology of Mycobacterium avium subspecies paratuberculosis (MAP) has recently crystalized with added details surrounding intestinal invasion. The involvement of pathogen-derived effector proteins such as the major membrane protein, oxidoreductase and fibronectin attachment proteins hav...

  9. Epidemiology and Ecology of Opportunistic Premise Plumbing Pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa

    EPA Science Inventory

    BACKGROUND: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa are opportunistic premise plumbing pathogens (OPPPs) that persist and grow in household plumbing, habitats they share with humans. Infections caused by these OPPPs involve individuals with preexis...

  10. Clinical outbreak of Bordetella avium infection in two turkey breeder flocks.

    PubMed

    Kelly, B J; Ghazikhanian, G Y; Mayeda, B

    1986-01-01

    An acute upper respiratory disease was observed in two broad-breasted white (BBW) turkey primary breeder flocks. Associated clinical signs included sneezing, depression, and a deep dry cough originating from large conducting airways. Morbidity reached approximately 15-20% of the hens in an affected house. None of the turkeys died, and total feed consumption was not affected. A minimal effect upon egg production was noticed. Sera from an acutely affected flock exhibited a marked rise in titer to Bordetella avium compared with preinfection sera samples. In Case 1, B. avium was isolated in pure culture from affected birds. In Case 2, B. avium was diagnosed by serological results and clinical signs; bacteriological examination was not attempted. The findings presented here are consistent with an acute clinical outbreak of B. avium-induced turkey rhinotracheitis (turkey coryza) in BBW turkey breeder hens. PMID:3729868

  11. Development and Use of a Partial Mycobacterium avium subspecies paratuberculosis Protein Array

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As an initial step toward systematically characterizing all antigenic proteins produced by a significant veterinary pathogen, 43 recombinant Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) expression clones were constructed, cataloged and stored. Nitrocellulose filters were sp...

  12. Early Antibody Response Against Mycobacterium avium subspecies paratuberculosis Antigens in Subclinical Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abstract Background Our laboratories have previously reported on the experimental infection of cattle with Mycobacterium avium subsp paratuberculosis (M. paratuberculosis) using an intratonsillar infection model. In addition, we have recently developed a partial protein array representing 92 M. par...

  13. Experimental Paratuberculosis in Calves following Inoculation with a Rabbit Isolate of Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Beard, P. M.; Stevenson, K.; Pirie, A.; Rudge, K.; Buxton, D.; Rhind, S. M.; Sinclair, M. C.; Wildblood, L. A.; Jones, D. G.; Sharp, J. M.

    2001-01-01

    The role of wildlife species in the epidemiology of paratuberculosis has been the subject of increased research efforts following the discovery of natural paratuberculosis in free-living rabbits from farms in east Scotland. This paper describes the experimental inoculation of young calves with an isolate of Mycobacterium avium subsp. paratuberculosis recovered from a free-living rabbit. After a 6-month incubation period, all eight calves inoculated with the rabbit isolate had developed histopathological and/or microbiological evidence of M. avium subsp. paratuberculosis infection. Similar results were obtained from a group of calves infected with a bovine isolate of M. avium subsp. paratuberculosis. The virulence of the rabbit isolate for calves demonstrated in this study suggests that rabbits are capable of passing paratuberculosis to domestic ruminants and that wildlife reservoirs of M. avium subsp. paratuberculosis should therefore be considered when formulating control plans for the disease. PMID:11526132

  14. Resistance of Macrophages to Mycobacterium avium Is Induced by α2-Adrenergic Stimulation

    PubMed Central

    Weatherby, Kelly E.; Zwilling, Bruce S.; Lafuse, William P.

    2003-01-01

    The ability of macrophages to control the growth of microorganisms is increased by macrophage activation. Previously, it was shown that epinephrine activated mouse macrophages to resist the growth of Mycobacterium avium via α2-adrenergic stimulation. In the present study, we show that the α2-adrenergic agonist (α2-agonist) clonidine induced resistance to M. avium growth in the RAW264.7 mouse macrophage cell line. The ability of catecholamines to induce resistance to mycobacteria was specific to α2-adrenergic stimulation, as α1-, β1-, and β2-agonists had no effect. Receptor signaling through Gi proteins was required. A G-protein antagonist specific for the α subunits of the Go/Gi family blocked the increased resistance induced by clonidine, while a Gs-protein antagonist was without effect. Both nitric oxide (NO) production and superoxide (O2−) production were required for the increased resistance to M. avium growth induced by clonidine. Although NO production was required, clonidine did not increase the level of NO in M. avium-infected cells. Since NO and O2− interact to produce peroxynitrite (ONOO−), we examined whether ONOO− mediates the increased resistance to M. avium induced by clonidine. 5,10,15,20-Tetrakis(4-sulfonatophenyl)prophyrinato iron (III) chloride (FeTPPS), a specific scavenger of ONOO−, inhibited the effect of clonidine on M. avium growth. Clonidine also increased the production of ONOO− in M. avium-infected RAW264.7 cells, as measured by the oxidation of 123-dihydrorhodamine and the production of nitrated tyrosine residues. We therefore conclude that α2-adrenergic stimulation activates macrophages to resist the growth of M. avium by enhancing the production of ONOO−. PMID:12496145

  15. Flow Cytometric Detection of Mycobacterium avium subsp. paratuberculosis-Specific Antibodies in Experimentally Infected and Naturally Exposed Calves

    PubMed Central

    Bridger, P. S.; Bulun, H.; Fischer, M.; Akineden, Ö.; Seeger, T.; Barth, S.; Henrich, M.; Doll, K.; Bülte, M.; Menge, C.; Bauerfeind, R.

    2013-01-01

    A desirable test to diagnose infections with Mycobacterium avium subsp. paratuberculosis facilitates identification of infected cattle prior to the state of M. avium subsp. paratuberculosis shedding. This study aimed at adjusting a flow cytometry (FC)-based assay, using intact M. avium subsp. paratuberculosis bacteria as the antigen, for diagnosis of M. avium subsp. paratuberculosis infections in calves. Serum samples were collected from experimentally infected (n = 12) and naturally exposed (n = 32) calves. Samples from five calves from positive dams were analyzed to determine the dynamics of maternal antibodies. Samples from adult cattle with defined infection status served as the standard (18 M. avium subsp. paratuberculosis shedders, 22 M. avium subsp. paratuberculosis free). After preadsorption with Mycobacterium phlei, sera were incubated with M. avium subsp. paratuberculosis and M. avium subsp. avium bacterial suspensions, respectively, followed by the separate detection of bovine IgG, IgG1, IgG2, and IgM attached to the bacterial surface. M. avium subsp. paratuberculosis-specific sample/positive (S/P) ratios were compared to enzyme-linked immunosorbent assay (ELISA) S/P ratios. In adult cattle, the FC assay for IgG1 had a sensitivity of 78% at a specificity of 100%. Maternally acquired antibodies could be detected in calves up to 121 days of life. While all but two sera taken at day 100 ± 10 postnatum from naturally exposed calves tested negative, elevated S/P ratios (IgG and IgG1) became detectable from 44 and 46 weeks postinoculation onwards in two calves infected experimentally. Even with the optimized FC assay, M. avium subsp. paratuberculosis-specific antibodies can only occasionally be detected in infected calves less than 12 months of age. The failure to detect such antibodies apparently reflects the distinct immunobiology of M. avium subsp. paratuberculosis infections rather than methodological constraints. PMID:23885032

  16. Expression library immunization confers protection against Mycobacterium avium subsp. paratuberculosis infection.

    PubMed

    Huntley, J F; Stabel, J R; Paustian, M L; Reinhardt, T A; Bannantine, J P

    2005-10-01

    Currently, paratuberculosis vaccines are comprised of crude whole-cell preparations of Mycobacterium avium subsp. paratuberculosis. Although effective in reducing clinical disease and fecal shedding, these vaccines have severe disadvantages as well, including seroconversion of vaccinated animals and granulomatous lesions at the site of vaccination. DNA vaccines can offer an alternative approach that may be safer and elicit more protective responses. In an effort to identify protective M. avium subsp. paratuberculosis sequences, a genomic DNA expression library was generated and subdivided into pools of clones (approximately 1,500 clones/pool). The clone pools were evaluated to determine DNA vaccine efficacy by immunizing mice via gene gun delivery and challenging them with live, virulent M. avium subsp. paratuberculosis. Four clone pools resulted in a significant reduction in the amount of M. avium subsp. paratuberculosis recovered from mouse tissues compared to mice immunized with other clone pools and nonvaccinated, infected control mice. One of the protective clone pools was further partitioned into 10 clone arrays of 108 clones each, and four clone arrays provided significant protection from both spleen and mesenteric lymph node colonization by M. avium subsp. paratuberculosis. The nucleotide sequence of each clone present in the protective pools was determined, and coding region functions were predicted by computer analysis. Comparison of the protective clone array sequences implicated 26 antigens that may be responsible for protection in mice. This study is the first study to demonstrate protection against M. avium subsp. paratuberculosis infection with expression library immunization. PMID:16177367

  17. Mycobacterium avium Genes Associated with the Ability To Form a Biofilm

    PubMed Central

    Yamazaki, Yoshitaka; Danelishvili, Lia; Wu, Martin; MacNab, Molly; Bermudez, Luiz E.

    2006-01-01

    Mycobacterium avium is widely distributed in the environment, and it is chiefly found in water and soil. M. avium, as well as Mycobacterium smegmatis, has been recognized to produce a biofilm or biofilm-like structure. We screened an M. avium green fluorescent protein (GFP) promoter library in M. smegmatis for genes involved in biofilm formation on polyvinyl chloride (PVC) plates. Clones associated with increased GFP expression ≥2.0-fold over the baseline were sequenced. Seventeen genes, most encoding proteins of the tricarboxylic acid (TCA) cycle and GDP-mannose and fatty acid biosynthesis, were identified. Their regulation in M. avium was confirmed by examining the expression of a set of genes by real-time PCR after incubation on PVC plates. In addition, screening of 2,000 clones of a transposon mutant bank constructed using M. avium strain A5, a mycobacterial strain with the ability to produce large amounts of biofilm, revealed four mutants with an impaired ability to form biofilm. Genes interrupted by transposons were homologues of M. tuberculosis 6-oxodehydrogenase (sucA), enzymes of the TCA cycle, protein synthetase (pstB), enzymes of glycopeptidolipid (GPL) synthesis, and Rv1565c (a hypothetical membrane protein). In conclusion, it appears that GPL biosynthesis, including the GDP-mannose biosynthesis pathway, is the most important pathway involved in the production of M. avium biofilm. PMID:16391123

  18. Mycobacterium avium serovars 2 and 8 infections elicit unique activation of the host macrophage immune responses.

    PubMed

    Cebula, B R; Rocco, J M; Maslow, J N; Irani, V R

    2012-12-01

    Mycobacterium avium is an opportunistic pathogen whose pathogenesis is attributed to its serovar-specific glycopeptidolipid (ssGPL), which varies among its 31 serovars. To determine if the presence and type of ssGPLs contribute to M. avium pathogenesis, we infected murine macrophages (mφs) with two M. avium wild type (wt) serovars (2 and 8) and their serovar-null strains. We examined the influence of ssGPL (presence and type) on cytokine production in non-activated (-IFN-γ) and activated (+IFN-γ) mφs, and the bacterial intra-mφ survival over a 6-day infection process. Serovar-2 infections activated TNF-α production that increased over the 6 day period and was capable of controlling the intra-mφ serovar-2 null strain. In contrast, the serovar-8 infection stimulated a strong pro-inflammatory response, but was incapable of removing the invading pathogen, maybe through IL-10 production. It was clear that the intracellular growth of serovar-null in contrast to the wt M. avium strains was easily controlled. Based on our findings and the undisputed fact that M. avium ssGPL is key to its pathogenesis, we conclude that it is not appropriate to dissect the pathogenesis of one M. avium serovar and apply those findings to other serovars. PMID:22991047

  19. Paradigm Change in Political Science.

    ERIC Educational Resources Information Center

    Rodman, John

    1980-01-01

    Traces the shift of paradigms in the political science profession from the 1960s to 1980, examines the classical paradigm, compares it with modern paradigms, and reviews contemporary efforts to articulate a new paradigm which takes the ecological crisis into account. (Author/DB)

  20. [Paradigm errors in the old biomedical science].

    PubMed

    Skurvydas, Albertas

    2008-01-01

    The aim of this article was to review the basic drawbacks of the deterministic and reductionistic thinking in biomedical science and to provide ways for dealing with them. The present paradigm of research in biomedical science has not got rid of the errors of the old science yet, i.e. the errors of absolute determinism and reductionism. These errors restrict the view and thinking of scholars engaged in the studies of complex and dynamic phenomena and mechanisms. Recently, discussions on science paradigm aimed at spreading the new science paradigm that of complex dynamic systems as well as chaos theory are in progress all over the world. It is for the nearest future to show which of the two, the old or the new science, will be the winner. We have come to the main conclusion that deterministic and reductionistic thinking applied in improper way can cause substantial damage rather than prove benefits for biomedicine science. PMID:18541951

  1. Emphysematous pyometra secondary to Enterococcus avium infection in a dog.

    PubMed

    Chang, An-Chi; Cheng, Ching-Chang; Wang, Hsien-Chi; Lee, Wei-Ming; Shyu, Ching-Lin; Lin, Cheng-Chung; Chen, Kuan-Sheng

    2016-06-16

    A 5-year-old female intact Mastiff dog was presented with a history of vaginal discharge for 1 day. Physical examination revealed a sanguineo-purulent vaginal discharge and systemic inflammatory response syndrome. Abdominal radiographs showed several dilated and gas- filled tubular loops. The differential diagnoses included emphysematous pyometra or small intestinal mechanical ileus. Surgical exploration of the abdomen demonstrated a severely dilated and gas-filled uterus, and emphysematous pyometra was confirmed. The patient's clinical signs resolved after ovariohysterectomy. Histopathology revealed mild endometrial cystic hyperplasia with infiltration of inflammatory cells in the superficial endometrial epithelia. Enterococcus avium, an α-hemolytic gram-positive coccus, was isolated from the uterus. This paper highlights the radiographic features of emphysematous pyometra and a pathogen that has never been reported to be associated with canine pyometra previously. PMID:27111397

  2. [Isolation of Mycobacterium avium-intracellulare from a hepatic biopsy].

    PubMed

    Ruiz, Aroldo; Mederos, Lilian; Capó, Virginia

    2002-01-01

    A 64 years-old patient, who was a farmer suffering from chronic fever for two years, loss of weight and acute asthenia, was studied. He was admitted to "Pedro Kourí" Tropical Medicine Institute where the studies were conducted and revealed a globular sedimentation rate of 116 mm in 2 hours, and anemia of 9,8g% hemoglobin. The laparoscopic study indicated hepatic granulomatosis that was confirmed by hepatic biopsy in which a sample was taken from the liver to be microbiologically and cytologically examined. By microbiological methods, a non-pigmented slowly-growing strain was isolated, which was classified by conventional diagnostic techniques for the non-tuberculous mycobacteria classification and the alternative diagnosing technique known as bidimensional thin layer chromatography to confirm the previous classification and set the mycolic acid patterns. The isolated strain belonged to group III of Rynyon and was identified as Mycobacterium avium-intracellulare. PMID:15849945

  3. Ammonium Ion Requirement for the Cell Cycle of Mycobacterium avium

    PubMed Central

    McCarthy, Charlotte

    1978-01-01

    Mycobacterium avium has a defined cell cycle in which small cells elongate to about five times their original length and then divide by fragmentation. The nitrogen requirement for production of maximal number of colony-forming units was assessed by varying concentrations and kinds of nitrogen source in the medium. Ferric ammonium citrate at a concentration in 7H10 medium of 0.17 μmol/ml or ammonium chloride at 0.25 μmol/ml as the nitrogen source permitted the cells to elongate and to undergo limited division, with the final culture at 4 × 107 colony-forming units per ml. Ammonium chloride at 2.5 μmol/ml or glutamine at 1.37 μmol/ml supported completion of the cell cycle with final colony-forming units at about 5 × 108/ml. Other amino acids, including glutamic acid, at 2.5 μmol/ml did not support completion of the cell cycle, although in most cases an intermediate number of colony-forming units per milliliter were formed. Limited uptake of [14C]glutamic acid and uptake of [14C]glutamine were not detectable until cell fission began. Cells not limited for nitrogen took up five times as much 35S during fission as limited cells did during the same time. The nonlimited cells contained 10 times as much sulfolipid as the nitrogen-limited cells at the end of the cell cycle. These results demonstrate that rapidly dividing cells of M. avium utilize amino acids and sulfur and also synthesize sulfolipids in events that are apparently separable from metabolic functions of elongating cells. The results are contrasted with those found for other mycobacteria in which no cell cycle has been demonstrated. Images PMID:624592

  4. [A case of hypersensitivity pneumonitis caused by inhalation of Mycobacterium avium from a home bath with a circulating water system].

    PubMed

    Kenmotsu, Hirotsugu; Honda, Atsuro; Baba, Tomohisa; Matsumoto, Yutaka; Shichi, Izumi; Eto, Takashi; Arai, Kazumori

    2005-11-01

    A 26-year-old man presented with complaints of exertional dyspnea and cough. The patient has already been given corticosteroids at a previous hospital. Chest CT revealed small centrilobular nodules with diffuse ground-glass opacities in both lungs. Lung biopsy specimens at thoracoscopy revealed non-necrotizing granulomas, patchy foci of mononuclear cell infiltration and fibrous thickening of alveolar septa, and Masson's bodies in bronchioles. Sputum culture showed the growth of Mycobacterium avium complex (MAC). Culture of water from the bath tub of his home showed MAC. Administration of antituberculous drugs and corticosteroids, and avoidance of bathing at home resulted in the improvement of his symptoms and CT findings. We believe the case is hypersensitivity pneumonitis to MAC in an immunocompetent patient, simulating hot tub lung. Hypersensitivity pneumonitis caused by MAC is rare in Japan. PMID:16366369

  5. Changing the Paradigm of Air Pollution Monitoring

    EPA Science Inventory

    Historically, approaches for monitoring air pollution generally use expensive, complex, stationary equipment,1,2 which limits who collects data, why data are collected, and how data are accessed. This paradigm is changing with the materialization of lower-cost, easy-to...

  6. THE ABILITY OF MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS TO ENTER BOVINE EPITHELIAL CELLS IS INFLUENCED BY PREEXPOSURE TO A HYPEROSMOLAR ENVIRONMENT AND INTRACELLULAR PASSAGE IN BOVINE MAMMARY EPITHELIAL CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis is the cause of Johne’s disease in cattle and other ruminants. M. avium subsp. paratuberculosis infection of the bovine host is not well understood; however, it is assumed that crossing the bovine intestinal mucosa is important in order for M. avium subsp...

  7. Overexpression of RORγt Enhances Pulmonary Inflammation after Infection with Mycobacterium Avium.

    PubMed

    Matsuyama, Masashi; Ishii, Yukio; Sakurai, Hirofumi; Ano, Satoshi; Morishima, Yuko; Yoh, Keigyou; Takahashi, Satoru; Ogawa, Kenji; Hizawa, Nobuyuki

    2016-01-01

    Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial disease in humans. The role of Th17 immunity in the pathogenesis of intracellular bacteria, such as MAC, is not currently understood. Transcription factor RAR-related orphan receptor gamma t (RORγt) is known as the master regulator for Th17 cell development. Here, we investigated the role of RORγt in host responses against MAC infection. Wild-type (WT) mice and RORγt-overexpressing mice were infected with MAC via intratracheal inoculation. Systemic MAC growth was not different between WT mice and RORγt-overexpressing mice. However, neutrophilic pulmonary inflammation following MAC infection was enhanced in RORγt-overexpressing mice compared with that in WT mice. The cytokine expression shifted toward a Th17 phenotype in the lungs of RORγt-overexpressing mice following MAC infection; the levels of IL-6 and IL-17 were significantly higher in the lung of these mice than in WT mice. In addition to the increase in IL-17 single-positive T cells, T cells producing both IL-17 and interferon-γ were elevated in the lung of RORγt-overexpressing mice following MAC infection. These findings suggest that RORγt overexpression-mediated Th17 bias contributes to local inflammation rather than systemic responses, by regulating neutrophil recruitment into the sites of infection during MAC infection. PMID:26784959

  8. LAMP technology: Rapid identification of Brucella and Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Trangoni, Marcos D; Gioffré, Andrea K; Cerón Cucchi, María E; Caimi, Karina C; Ruybal, Paula; Zumárraga, Martín J; Cravero, Silvio L

    2015-06-01

    In this study, we developed new sets of primers to detect Brucella spp. and M. avium subsp. paratuberculosis (MAP) through isothermal amplification. We selected a previously well-characterized target gene, bscp31, specific for Brucella spp. and IS900 for MAP. The limits of detection using the loop-mediated isothermal amplification (LAMP) protocols described herein were similar to those of conventional PCR targeting the same sequences. Hydroxynaphtol blue and SYBR Green(TM) allowed direct naked-eye detection with identical sensitivity as agarose gel electrophoresis. We included the LAMP-based protocol in a rapid identification scheme of the respective pathogens, and all tested isolates were correctly identified within 2 to 3 h. In addition, both protocols were suitable for specifically identifying the respective pathogens; in the case of Brucella, it also allowed the identification of all the biovars tested. We conclude that LAMP is a suitable rapid molecular typing tool that could help to shorten the time required to identify insidious bacteria in low-complexity laboratories, mainly in developing countries. PMID:26273282

  9. Alternative Evaluation Research Paradigm.

    ERIC Educational Resources Information Center

    Patton, Michael Quinn

    This monograph is one of a continuing series initiated to provide materials for teachers, parents, school administrators, and governmental decision-makers that might encourage reexamination of a range of evaluation issues and perspectives about schools and schooling. This monograph is a description and analysis of two contrasting paradigms: one…

  10. Deconstructing Research: Paradigms Lost

    ERIC Educational Resources Information Center

    Trifonas, Peter Pericles

    2009-01-01

    In recent decades, proponents of naturalistic and/or critical modes of inquiry advocating the use of ethnographic techniques for the narrative-based study of phenomena within pedagogical contexts have challenged the central methodological paradigm of educational research: that is, the tendency among its practitioners to adhere to quantitative…

  11. Paradigms of School Change

    ERIC Educational Resources Information Center

    Wrigley, Terry

    2011-01-01

    This short paper points to some paradigm issues in the field of school development (leadership, effectiveness, improvement) and their relationship to social justice. It contextualises the dominant School Effectiveness and School Improvement models within neo-liberal marketisation, paying attention to their transformation through a "marriage of…

  12. The "New Environmental Paradigm"

    ERIC Educational Resources Information Center

    Dunlap, Riley E.; Van Liere, Kent D.

    2008-01-01

    The "New Environmental Paradigm" or NEP appears to have gained considerable popularity in academic and intellectual circles, as well as among many college students; however, very little is known concerning the degree to which the general public has come to accept the ideas embodied in it. Thus, although there have been dozens of studies of…

  13. Telemedicine: a new paradigm.

    PubMed

    Denton, I

    1993-11-01

    Technological innovations sometimes compel paradigm shifts. Two decades ago the CT scanner was one such phenomenon: It quickly and absolutely transformed medical practice. A marriage of medicine and telecommunications could engender a similar transformation. The timing surely is favorable, as pressing requirements of healthcare reform coincide with the flowering of telecommunications technologies. PMID:10130474

  14. Characterization of the fibronectin-attachment protein of Mycobacterium avium reveals a fibronectin-binding motif conserved among mycobacteria.

    PubMed

    Schorey, J S; Holsti, M A; Ratliff, T L; Allen, P M; Brown, E J

    1996-07-01

    Mycobacterium avium is an intracellular pathogen and a major opportunistic infectious agent observed in patients with acquired immune deficiency syndrome (AIDS). Evidence suggests that the initial portal of infection by M. avium is often the gastrointestinal tract. However, the mechanism by which the M. avium crosses the epithelial barrier is unclear. A possible mechanism is suggested by the ability of M. avium to bind fibronectin, an extracellular matrix protein that is a virulence factor for several extracellular pathogenic bacteria which bind to mucosal surfaces. To further characterize fibronectin binding by M. avium, we have cloned the M. avium fibronectin-attachment protein (FAP). The M. avium FAP (FAP-A) has an unusually large number of Pro and Ala residues (40% overall) and is 50% identical to FAP of both Mycobacterium leprae and Mycobacterium tuberculosis. Using recombinant FAP-A and FAP-A peptides, we show that two non-continuous regions in FAP-A bind fibronectin. Peptides from these regions and homologous sequences from M. leprae FAP inhibit fibronectin binding by both M. avium and Mycobacterium bovis Bacillus Calmette-Guerin (BCG). These regions have no homology to eukaryotic fibronectin-binding proteins and are only distantly related to fibronectin-binding peptides of Gram-positive bacteria. Nevertheless, these fibronectin-binding regions are highly conserved among the mycobacterial FAPs, suggesting an essential function for this interaction in mycobacteria infection of their metazoan hosts. PMID:8858587

  15. The persistence of Mycobacterium avium in a drinking water system, what is the risk to human health?

    EPA Science Inventory

    Drinking water is believed to be a major source of human exposure to nontuberculous mycobacteria (NTM) such as Mycobacterium avium. We monitored the prevalence of M. avium in a drinking water system during the addition of filtration treatment. Our goal was to determine if the pre...

  16. ISOLATION OF THE GENOME SEQUENCE STRAIN MYCOBACTERIUM AVIUM 104 FROM MULTIPLE PATIENTS OVER A 17-YEAR PERIOD

    EPA Science Inventory

    The genome sequence strain 104 of the opportunistic pathogen Mycobacterium avium was isolated form an adult AIDS patient in Southern California in 1983. Isolates of non-paratuberculosis M. avium from 207 other patients in Southern California and elsewhere were examined for genoty...

  17. Concomitant Mycobacterium avium infection and Hodgkin's disease in a lymph node from an HIV-negative child.

    PubMed

    de Armas, Yaxsier; Capó, Virginia; González, Ida; Mederos, Lilian; Díaz, Raúl; de Waard, Jacobus H; Rodríguez, Alberto; García, Yarmila; Cabanas, Ricardo

    2011-03-01

    We report a case of an immunocompetent child with simultaneously an infection with Mycobacterium avium and Hodgkin's disease in a cervical lymph node. A positive PCR result for M. avium on a biopsy of the lymph node directed the definitive diagnosis for both etiologies and avoided a possible dissemination of this infection after chemotherapy was started. PMID:20467849

  18. The Nature of Paradigms and Paradigm Shifts in Music Education

    ERIC Educational Resources Information Center

    Panaiotidi, Elvira

    2005-01-01

    In this paper, the author attempts to extend the paradigm approach into the philosophy of music education and to build upon this basis a model for structuring music education discourse. The author begins with an examination of Peter Abbs' account of paradigms and paradigm shifts in arts education. Then she turns to Kuhn's conception and to his…

  19. Monoclonal Antibodies Directed Against the Outer Membrane Protein of Bordetella avium

    PubMed Central

    Liu, Guanhua; Liang, Manfei; Zuo, Xuemei; Zhao, Xue; Guo, Fanxia; Yang, Shifa

    2013-01-01

    Bordetella avium is the etiologic agent of coryza and rhinotracheitis in poultry. This respiratory disease is responsible for substantial economic losses in the poultry industry. Monoclonal antibodies (MAbs) were produced against the outer membrane proteins (OMPs) of B. avium isolated from diseased chickens. BALB/c mice were immunized with the extracted B. avium OMPs. Then the splenocytes from immunized mice and SP2/0 myeloma cells were fused using PEG 4000. Three stable hybridoma clones (designated as 3G10, 4A3, and 4E8) were produced via indirect ELISA and three rounds of subcloning. The MAbs were classified as IgG1, and can recognize the 58 kDa OMP band by Western blot assays. No MAb cross-reactivity with chicken Proteus mirabilis, Escherichia coli, and Salmonella was observed. A double antibody sandwich ELISA (DAS-ELISA) was developed using the rabbit polyclonal antibodies as the capture antibody and MAb 4A3 as the detection antibody. Under the DAS-ELISA, the minimum detectable concentration of B. avium was 1×104 CFU/mL, and no cross-reactivity occurred with chicken Proteus mirabilis, Escherichia coli, and Salmonella. Results showed that the DAS-ELISA has good sensitivity and specificity. Clinical application showed the DAS-ELISA was more sensitive than the plate agglutination test. This study may be used to develop a quick and specific diagnostic kit, analyze epitopes, and establish systems for typing B. avium. PMID:23909425

  20. Adhesion of Campylobacter jejuni and Mycobacterium avium onto polyethylene terephtalate (PET) used for bottled waters.

    PubMed

    Tatchou-Nyamsi-König, Josiane-Aurore; Dague, Etienne; Mullet, Martine; Duval, Jérôme F L; Gaboriaud, Fabien; Block, Jean-Claude

    2008-12-01

    Adhesion of the bacteria Campylobacter jejuni and Mycobacterium avium onto polyethylene terephtalate (PET), a polymer widely used within the bottled water industry was measured in two different groundwater solutions. From this, it was found that whilst the percentage cell adhesion for a given strain did not change between groundwater types, substantial variation was obtained between the two bacterial species tested: M. avium (10-30% adhered cells) and C. jejuni (1-2%) and no major variations were measured as a function of groundwater composition for a given strain. To explain this, the interfacial electro-hydrodynamic properties of the bacteria were investigated by microelectrophoresis, with the resultant data analysed on the basis of electrokinetic theory for soft biocolloidal particles. The results obtained showed that M. avium carries a significant volume charge density and that its peripheral layer exhibits limited hydrodynamic flow permeation compared to that of C. jejuni. It was also demonstrated that steric hindrance to flow penetration and the degree of hydrophobicity within/of the outer bacterial interface are larger for M. avium cells. In line with this, the larger amount of M. avium cells deposited onto PET substrates as compared to that of C. jejuni can be explained by hydrophobic attraction and chemical binding between hydrophobic PET and outer soft surface layer of the bacteria. Hydrophobicity of PET was addressed by combining contact angle analyses and force spectroscopy using CH(3)-terminated AFM tip. PMID:18929388

  1. Complex networks: Patterns of complexity

    NASA Astrophysics Data System (ADS)

    Pastor-Satorras, Romualdo; Vespignani, Alessandro

    2010-07-01

    The Turing mechanism provides a paradigm for the spontaneous generation of patterns in reaction-diffusion systems. A framework that describes Turing-pattern formation in the context of complex networks should provide a new basis for studying the phenomenon.

  2. Peyer's Patch-Deficient Mice Demonstrate That Mycobacterium avium subsp. paratuberculosis Translocates across the Mucosal Barrier via both M Cells and Enterocytes but Has Inefficient Dissemination ▿

    PubMed Central

    Bermudez, Luiz E.; Petrofsky, Mary; Sommer, Sandra; Barletta, Raúl G.

    2010-01-01

    Mycobacterium avium subsp. paratuberculosis, the agent of Johne's disease, infects ruminant hosts by translocation through the intestinal mucosa. A number of studies have suggested that M. avium subsp. paratuberculosis interacts with M cells in the Peyer's patches of the small intestine. The invasion of the intestinal mucosa by M. avium subsp. paratuberculosis and Mycobacterium avium subsp. hominissuis, a pathogen known to interact with intestinal cells, was compared. M. avium subsp. paratuberculosis was capable of invading the mucosa, but it was significantly less efficient at dissemination than M. avium subsp. hominissuis. B-cell knockout (KO) mice, which lack Peyer's patches, were used to demonstrate that M. avium subsp. paratuberculosis enters the intestinal mucosa through enterocytes in the absence of M cells. In addition, the results indicated that M. avium subsp. paratuberculosis had equal abilities to cross the mucosa in both Peyer's patch and non-Peyer's patch segments of normal mice. M. avium subsp. paratuberculosis was also shown to interact with epithelial cells by an α5β1 integrin-independent pathway. Upon translocation, dendritic cells ingest M. avium subsp. paratuberculosis, but this process does not lead to efficient dissemination of the infection. In summary, M. avium subsp. paratuberculosis interacts with the intestinal mucosa by crossing both Peyer's patches and non-Peyer's patch areas but does not translocate or disseminate efficiently. PMID:20498259

  3. Development and Characterization of Monoclonal Antibodies and Aptamers against Major Antigens of Mycobacterium avium subsp. paratuberculosis▿

    PubMed Central

    Bannantine, John P.; Radosevich, Thomas J.; Stabel, Judith R.; Sreevatsan, Srinand; Kapur, Vivek; Paustian, Michael L.

    2007-01-01

    Specific antibodies, available in unlimited quantities, have not been produced against Mycobacterium avium subsp. paratuberculosis, the bacterium that causes Johne's disease (JD). To fill this gap in JD research, monoclonal antibodies (MAbs) against M. avium subsp. paratuberculosis were produced from BALB/c mice immunized with a whole-cell extract of M. avium subsp. paratuberculosis. A total of 10 hybridomas producing MAbs to proteins ranging from 25 to 85 kDa were obtained. All MAbs showed some degree of cross-reactivity when they were analyzed against a panel of whole-cell protein lysates comprising seven different mycobacterial species. The MAbs were characterized by several methods, which included isotype analysis, specificity analysis, epitope analysis, reactivity in immunoblot assays, and electron microscopy. The identities of the antigens that bound to two selected MAbs were determined by screening an M. avium subsp. paratuberculosis lambda phage expression library. This approach revealed that MAb 9G10 detects MAP1643 (isocitrate lyase) and that MAb 11G4 detects MAP3840 (a 70-kDa heat shock protein), two proteins present in high relative abundance in M. avium subsp. paratuberculosis. The epitopes for MAb 11G4 were mapped to the N-terminal half of MAP3840, whereas MAb 9G10 bound to the C-terminal half of MAP1643. Aptamers, nucleic acids that bind to specific protein sequences, against the hypothetical protein encoded by MAP0105c were also generated and tested for their binding to M. avium subsp. paratuberculosis as well as other mycobacteria. These detection reagents may be beneficial in many JD research applications. PMID:17344350

  4. Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence?

    PubMed Central

    Vogel, Thorsten U.; Friedrich, Thomas C.; O'Connor, David H.; Rehrauer, William; Dodds, Elizabeth J.; Hickman, Heather; Hildebrand, William; Sidney, John; Sette, Alessandro; Hughes, Austin; Horton, Helen; Vielhuber, Kathy; Rudersdorf, Richard; de Souza, Ivna P.; Reynolds, Matthew R.; Allen, Todd M.; Wilson, Nancy; Watkins, David I.

    2002-01-01

    It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag71-79 GY9), and one from the Nef protein (Nef159-167 YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two eptiopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef159-167 YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag71-79 GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat28-35 SL8, which reproducibly selects for escape variants during acute infection, and Gag181-189 CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection. PMID:12388723

  5. Mycobacterium avium in pygmy rabbits (Brachylagus idahoensis): 28 cases.

    PubMed

    Harrenstien, Lisa A; Finnegan, Mitchell V; Woodford, Nina L; Mansfield, Kristin G; Waters, W Ray; Bannantine, John P; Paustian, Michael L; Garner, Michael M; Bakke, Antony C; Peloquin, Charles A; Phillips, Terry M

    2006-12-01

    The Columbia basin subpopulation of pygmy rabbit Brachylagus idahoensis was listed as endangered by the United States Fish and Wildlife Service in November 2001, and no pygmy rabbits have been seen in the wild since spring 2002. Captive propagation efforts have attempted to increase population size in preparation for reintroduction of animals into central Washington. Disseminated mycobacteriosis due to Mycobacterium avium has been the most common cause of death of adult captive pygmy rabbits. Between June 2002 and September 2004, mycobacteriosis was diagnosed in 28 captive adult pygmy rabbits (representing 29% of the captive population), in contrast to 18 adult pygmy rabbits dying of all other causes in the same time period. Antemortem and postmortem medical records were evaluated retrospectively to describe the clinical course of mycobacteriosis in pygmy rabbits, physical examination findings, and diagnostic test results in the diagnosis of mycobacteriosis in pygmy rabbits. Various treatment protocols, possible risk factors for mortality, and recommendations for prevention of mycobacteriosis were evaluated also. Compromised cell-mediated immunity appears to be the best explanation at this time for the observed high morbidity and mortality from mycobacterial infections in pygmy rabbits. PMID:17315435

  6. Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection.

    PubMed

    Park, Hong-Tae; Yoo, Han Sang

    2016-07-01

    Johne's disease or paratuberculosis is a chronic debilitating disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease causes significant economic losses in livestock industries worldwide. There are no effective control measures to eradicate the disease because there are no appropriate diagnostic methods to detect subclinically infected animals. Therefore, it is very difficult to control the disease using only test and cull strategies. Vaccination against paratuberculosis has been considered as an alternative strategy to control the disease when combined with management interventions. Understanding host-pathogen interactions is extremely important to development of vaccines. It has long been known that Th1-mediated cellular immune responses are play a crucial role in protection against MAP infection. However, recent studies suggested that innate immune responses are more closely related to protective effects than adaptive immunity. Based on this understanding, several attempts have been made to develop vaccines against paratuberculosis. A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available. In this study, studies of the development of vaccines for MAP were reviewed and summarized. PMID:27489800

  7. Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection

    PubMed Central

    2016-01-01

    Johne's disease or paratuberculosis is a chronic debilitating disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease causes significant economic losses in livestock industries worldwide. There are no effective control measures to eradicate the disease because there are no appropriate diagnostic methods to detect subclinically infected animals. Therefore, it is very difficult to control the disease using only test and cull strategies. Vaccination against paratuberculosis has been considered as an alternative strategy to control the disease when combined with management interventions. Understanding host-pathogen interactions is extremely important to development of vaccines. It has long been known that Th1-mediated cellular immune responses are play a crucial role in protection against MAP infection. However, recent studies suggested that innate immune responses are more closely related to protective effects than adaptive immunity. Based on this understanding, several attempts have been made to develop vaccines against paratuberculosis. A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available. In this study, studies of the development of vaccines for MAP were reviewed and summarized. PMID:27489800

  8. Description of a novel adhesin of Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Viale, Mariana Noelia; Echeverria-Valencia, Gabriela; Romasanta, Pablo; Mon, María Laura; Fernandez, Marisa; Malchiodi, Emilio; Romano, María Isabel; Gioffré, Andrea Karina; Santangelo, María de la Paz

    2014-01-01

    The binding and ingestion of Mycobacterium avium subsp. paratuberculosis (MAP) by host cells are fibronectin (FN) dependent. In several species of mycobacteria, a specific family of proteins allows the attachment and internalization of these bacteria by epithelial cells through interaction with FN. Thus, the identification of adhesion molecules is essential to understand the pathogenesis of MAP. The aim of this study was to identify and characterize FN binding cell wall proteins of MAP. We searched for conserved adhesins within a large panel of surface immunogenic proteins of MAP and investigated a possible interaction with FN. For this purpose, a cell wall protein fraction was obtained and resolved by 2D electrophoresis. The immunoreactive spots were identified by MALDI-TOF MS and a homology search was performed. We selected elongation factor Tu (EF-Tu) as candidate for further studies. We demonstrated the FN-binding capability of EF-Tu using a ligand blot assay and also confirmed the interaction with FN in a dose-dependent manner by ELISA. The dissociation constant of EF-Tu was determined by surface plasmon resonance and displayed values within the μM range. These data support the hypothesis that this protein could be involved in the interaction of MAP with epithelial cells through FN binding. PMID:25136616

  9. Description of a Novel Adhesin of Mycobacterium avium Subsp. paratuberculosis

    PubMed Central

    Viale, Mariana Noelia; Echeverria-Valencia, Gabriela; Romasanta, Pablo; Mon, María Laura; Fernandez, Marisa; Malchiodi, Emilio; Romano, María Isabel; Gioffré, Andrea Karina; Santangelo, María de la Paz

    2014-01-01

    The binding and ingestion of Mycobacterium avium subsp. paratuberculosis (MAP) by host cells are fibronectin (FN) dependent. In several species of mycobacteria, a specific family of proteins allows the attachment and internalization of these bacteria by epithelial cells through interaction with FN. Thus, the identification of adhesion molecules is essential to understand the pathogenesis of MAP. The aim of this study was to identify and characterize FN binding cell wall proteins of MAP. We searched for conserved adhesins within a large panel of surface immunogenic proteins of MAP and investigated a possible interaction with FN. For this purpose, a cell wall protein fraction was obtained and resolved by 2D electrophoresis. The immunoreactive spots were identified by MALDI-TOF MS and a homology search was performed. We selected elongation factor Tu (EF-Tu) as candidate for further studies. We demonstrated the FN-binding capability of EF-Tu using a ligand blot assay and also confirmed the interaction with FN in a dose-dependent manner by ELISA. The dissociation constant of EF-Tu was determined by surface plasmon resonance and displayed values within the μM range. These data support the hypothesis that this protein could be involved in the interaction of MAP with epithelial cells through FN binding. PMID:25136616

  10. Mycobacterium avium subsp hominissuis biofilm is composed of distinct phenotypes and influenced by the presence of antimicrobials

    PubMed Central

    McNabe, Molly; Tennant, Rachel; Danelishvili, Lia; Young, Lowell; Bermudez, Luiz E.

    2010-01-01

    Mycobacterium avium subsp hominissuis, hereafter referred to as M. avium, forms biofilm, a property that, in mice, is associated with lung infection via aerosol. As M. avium might co-inhabit the respiratory tract with other pathogens, treatment of the co-pathogen-associated infections, such as in bronchiectasis, would expose M. avium to therapeutic compounds which may have their origin in other organisms sharing the natural environments. Incubation of M. avium with two compounds produced by environmental organisms, streptomycin and tetracycline in vitro at sub-inhibitory concentrations increased biofilm formation in a number of M. avium strains, although exposure to ampicillin, moxifloxacin, rifampin, and TMP/SMX had no effect on biofilm. No selection of genotypically resistant clones was observed. While bacteria incubation in presence of streptomycin upregulates the expression of biofilm-associated genes, the response to the antibiotics had no association with a regulation of a regulator (LysR) linked to the formation of biofilm in M. avium. Biofilms are made of planktonic and sessile bacteria. While planktonic M. avium is susceptible to clarithromycin and ethambutol (clinically used antimicrobials), sessile bacteria are at least 3- to 4-fold more resistant to antibiotics. The sessile phenotype, though, is reversible, and no selection of resistant clones was observed. Mice infected through the airway with both phenotypes were infected with a similar number of bacteria, demonstrating no phenotype advantage. M. avium biofilm formation is enhanced by commonly used compounds and, in the sessile bacterial phenotype, is resistant to clarithromycin and ethambutol, in a reversible manner. PMID:20636426

  11. Genome-Wide Sequence Variation among Mycobacterium avium Subspecies paratuberculosis Isolates: A Better Understanding of Johne's Disease Transmission Dynamics.

    PubMed

    Hsu, Chung-Yi; Wu, Chia-Wei; Talaat, Adel M

    2011-01-01

    Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne's disease, infects many farmed ruminants, wild-life animals, and recently isolated from humans. To better understand the molecular pathogenesis of these infections, we analyzed the whole-genome sequences of several M. ap and M. avium subspecies avium (M. avium) isolates to gain insights into genomic diversity associated with variable hosts and environments. Using Next-generation sequencing technology, all six M. ap isolates showed a high percentage of similarity (98%) to the reference genome sequence of M. ap K-10 isolated from cattle. However, two M. avium isolates (DT 78 and Env 77) showed significant sequence diversity (only 87 and 40% similarity, respectively) compared to the reference strain M. avium 104, a reflection of the wide environmental niches of this group of mycobacteria. Within the M. ap isolates, genomic rearrangements (insertions/deletions) were not detected, and only unique single nucleotide polymorphisms (SNPs) were observed among M. ap isolates. While more of the SNPs (~100) in M. ap genomes were non-synonymous, a total of ~6,000 SNPs were detected among M. avium genomes, most of them were synonymous suggesting a differential selective pressure between M. ap and M. avium isolates. In addition, SNPs-based phylo-genomics had a enough discriminatory power to differentiate between isolates from different hosts but yet suggesting a bovine source of infection to other animals examined in this study. Interestingly, the human isolate (M. ap 4B) was closely related to a M. ap isolate from a dairy facility, suggesting a common source of infection. Overall, the identified phylo-genomes further supported the idea of a common ancestor to both M. ap and M. avium isolates. Genome-wide analysis described here could provide a strong foundation for a population genetic structure that could be useful for the analysis of mycobacterial evolution and for the tracking of Johne

  12. In Vivo Volatile Organic Compound Signatures of Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Bergmann, Andreas; Trefz, Phillip; Fischer, Sina; Klepik, Klaus; Walter, Gudrun; Steffens, Markus; Ziller, Mario; Schubert, Jochen K.; Reinhold, Petra; Köhler, Heike; Miekisch, Wolfram

    2015-01-01

    Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of a chronic enteric disease of ruminants. Available diagnostic tests are complex and slow. In vitro, volatile organic compound (VOC) patterns emitted from MAP cultures mirrored bacterial growth and enabled distinction of different strains. This study was intended to determine VOCs in vivo in the controlled setting of an animal model. VOCs were pre-concentrated from breath and feces of 42 goats (16 controls and 26 MAP-inoculated animals) by means of needle trap microextraction (breath) and solid phase microextraction (feces) and analyzed by gas chromatography/ mass spectrometry. Analyses were performed 18, 29, 33, 41 and 48 weeks after inoculation. MAP-specific antibodies and MAP-specific interferon-γ-response were determined from blood. Identities of all marker-VOCs were confirmed through analysis of pure reference substances. Based on detection limits in the high pptV and linear ranges of two orders of magnitude more than 100 VOCs could be detected in breath and in headspace over feces. Twenty eight substances differed between inoculated and non-inoculated animals. Although patterns of most prominent substances such as furans, oxygenated substances and hydrocarbons changed in the course of infection, differences between inoculated and non-inoculated animals remained detectable at any time for 16 substances in feces and 3 VOCs in breath. Differences of VOC concentrations over feces reflected presence of MAP bacteria. Differences in VOC profiles from breath were linked to the host response in terms of interferon-γ-response. In a perspective in vivo analysis of VOCs may help to overcome limitations of established tests. PMID:25915653

  13. Association of ISMav6 with the Pattern of Antibiotic Resistance in Korean Mycobacterium avium Clinical Isolates but No Relevance between Their Genotypes and Clinical Features

    PubMed Central

    Kim, Su-Young; Jeong, Byeong-Ho; Park, Hye Yun; Jeon, Kyeongman; Han, Seung Jung; Shin, Sung Jae; Koh, Won-Jung

    2016-01-01

    The aim of this study was to genetically characterize clinical isolates from patients diagnosed with Mycobacterium avium lung disease and to investigate the clinical significance. Multi-locus sequencing analysis (MLSA) and pattern of insertion sequence analysis of M. avium isolates from 92 Korean patients revealed that all isolates were M. avium subspecies hominissuis. In hsp65 sequevar analysis, codes 2, 15, and 16 were most frequently found (88/92) with similar proportions among cases additionally two isolates belonging to code N2 and an unreported code were identified, respectively. In insertion element analysis, all isolates were IS1311 positive and IS900 negative. Four of the M. avium subsp. hominissuis isolates did not harbor IS1245 and 1 of the M. avium isolates intriguingly harbored DT1, which is thought to be a M. intracellulare-specific element. M. avium subsp. hominissuis harboring ISMav6 is prevalent in Korea. No significant association between clinical manifestation and treatment response has been found in patients with the hsp65 code type and ISMav6, indicating that no specific strain/genotype among M. avium subsp. hominissuis organisms was a major source of M. avium lung disease. Interestingly, the presence of ISMav6 was correlated with greater resistance to moxifloxacin. Conclusively, the genotype of Korean M. avium subsp. hominissuis isolates is not a disease determinant responsible for lung disease and specific virulent factors of M. avium subsp. hominissuis need to be investigated further. PMID:26859598

  14. Survival of Mycobacterium avium subsp. paratuberculosis in bovine monocyte-derived macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is a significant problem in many North American cattle herds. The efficacy of currently available vaccines is questionable. There is a need to develop efficacious vaccines and strains of Mycobacterium avium subsp. paratuberculosis (MAPTB) that could serve as potential candidates for ...

  15. Primary transcriptomes of Mycobacterium avium subsp. paratuberculosis reveal proprietary pathways in tissue and macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Mycobacterium avium subsp. paratuberculosis persistently infect intestines and mesenteric lymph nodes leading to a prolonged subclinical disease. We investigated the intracellular lifestyle of MAP in the intestines and lymph nodes to understand the MAP pathways that function to govern th...

  16. Unraveling the Host Response to Mycobacterium avium subsp. paratuberculosis: One Thread at a Time

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Improved tools for the measurement of immunologic responses in ruminant species, par...

  17. Transcriptional profiling of ileocecal valve of holstein dairy cows infected with mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advan...

  18. Optimization of hexadecylpyridinium chloride decontamination for culture of Mycobacterium avium subsp. paratuberculosis from milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cows in advanced stages of Johne’s disease shed Mycobacterium avium subsp. paratuberculosis (MAP) into both their milk and feces, allowing for transmission of the bacteria between animals. The objective of this study was to formulate an optimized protocol for the isolation of MAP from milk and colos...

  19. Beta2-adrenergic receptor stimulation inhibits nitric oxide generation by Mycobacterium avium infected macrophages.

    PubMed

    Boomershine, C S; Lafuse, W P; Zwilling, B S

    1999-11-01

    Catecholamine regulation of nitric oxide (NO) production by IFNgamma-primed macrophages infected with Mycobacterium avium was investigated. Epinephrine treatment of IFNgamma-primed macrophages at the time of M. avium infection inhibited the anti-mycobacterial activity of the cells. The anti-mycobacterial activity of macrophages correlated with NO production. Using specific adrenergic receptor agonists, the abrogation of mycobacterial killing and decreased NO production by catecholamines was shown to be mediated via the beta2-adrenergic receptor. Elevation of intracellular cAMP levels mimicked the catecholamine-mediated inhibition of NO in both M. avium infected and LPS stimulated macrophages. Specific inhibitors of both adenylate cyclase and protein kinase A prevented the beta2-adrenoceptor-mediated inhibition of nitric oxide production. Beta2-adrenoreceptor stimulation at the time of M. avium infection of IFNgamma-primed macrophages also inhibited expression of iNOS mRNA. These observations show that catecholamine hormones can affect the outcome of macrophage-pathogen interactions and suggest that one result of sympathetic nervous system activation is the suppression of the capacity of macrophages to produce anti-microbial effector molecules. PMID:10580815

  20. Environmental contamination with Mycobacterium avium subsp. paratuberculosis in endemically infected dairy herds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Environmental contamination with Mycobacterium avium subsp. paratuberculosis (MAP) is thought to be the primary source of infection for dairy cattle. The exact link between fecal shedding of MAP by individual cows and environmental contamination levels at the herd level was explored with a cross-se...

  1. Comparison of fecal DNA extraction kits for the detection of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fecal culture is considered the gold standard for the diagnosis of paratuberculosis, however, PCR for the detection of Mycobacterium avium subsp. paratuberculosis (MAP) in fecal material is widely used today, having demonstrated great sensitivity and specificity. To insure the most efficient and rep...

  2. Survival of Mycobacterium avium subsp. paratuberculosis in Biofilms on Livestock Watering Trough Materials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite the ubiquitous occurrence of Mycobacterium sp. in nature and the fact that Johne’s disease has been reported worldwide, little research has been done to assess the survival of Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) in agricultural environments. The goal of this stu...

  3. Shared Mycobacterium avium genotypes observed among unlinked clinical and environmental isolates

    EPA Science Inventory

    Our understanding of the sources of Mycobacterium avium infection is partially based on genotypic matching of pathogen isolates from cases and environmental sources. These approaches assume that genotypic identity is rare in isolates from unlinked cases or sources. To test this, ...

  4. Effect of Watering Trough Chlorination on Persistence of Mycobacterium avium subsp. Paratuberculosi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The continued global increase in the number of cases of Johne’s disease suggests that more information is needed to understand the mechanisms by which the causative agent Mycobacterium avium subsp. paratuberculosis (MAP) is spread among livestock on the farm site. Livestock watering troughs are freq...

  5. Detection of Mycobacterium avium subspecies paratuberculosis in Drinking Water and Biofilms Using Quantitative PCR

    EPA Science Inventory

    Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne’s disease in domestic animals and has been implicated in Crohn’s disease in humans. This bacterium is a slow growing, gram-positive, acid-fast organism which can be difficult to culture from the environment. For ...

  6. Immunlogic responses to Mycobacterium avium subsp. paratuberculosis protein cocktail vaccines in a mouse model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is a chronic granulomatous enteritis characterized by severe diarrhea, wasting, and a decline in milk production caused by the bacterium Mycobacterium avium subsp. paratuberculosis (MAP). The vaccine currently on the market has some limitations including a severe injection site react...

  7. Molecular Analysis of Mycobacterium avium Isolates by Using Pulsed-Field Gel Electrophoresis and PCR

    PubMed Central

    Pestel-Caron, Martine; Graff, Gabriel; Berthelot, Gilles; Pons, Jean-Louis; Lemeland, Jean-François

    1999-01-01

    Genetic relationships among 46 isolates of Mycobacterium avium recovered from 37 patients in a 2,500-bed hospital from 1993 to 1998 were assessed by pulsed-field gel electrophoresis (PFGE) and PCR amplification of genomic sequences located between the repetitive elements IS1245 and IS1311. Each technique enabled the identification of 27 to 32 different patterns among the 46 isolates, confirming that the genetic heterogeneity of M. avium strains is high in a given community. Furthermore, this retrospective analysis of sporadic isolates allowed us (i) to suggest the existence of two remanent strains in our region, (ii) to raise the question of the possibility of nosocomial acquisition of M. avium strains, and (iii) to document laboratory contamination. The methods applied in the present study were found to be useful for the typing of M. avium isolates. In general, both methods yielded similar results for both related and unrelated isolates. However, the isolates in five of the six PCR clusters were distributed among two to three PFGE patterns, suggesting that this PCR-based method may have limitations for the analysis of strains with low insertion sequence copy numbers or for resolution of extended epidemiologic relationships. PMID:10405383

  8. Monoclonal infection involving Mycobacterium avium presenting with three distinct colony morphotypes.

    PubMed Central

    Wright, E L; Zywno-van Ginkel, S; Rastogi, N; Barrow, W W

    1996-01-01

    Recent reports indicate that polyclonal infections may play an important role in multiple drug resistance in Mycobacterium avium infections. We report here on the isolation of a single M. avium strain that appeared to have smooth colony morphology upon initial isolation on a Lowenstein-Jensen slant. Primary subculture onto Middlebrook 7H10, however, revealed three distinct morphotypes representing smooth opaque (SmO), smooth transparent (SmT), and rough (Rg) colony morphologies. All three morphotypes were identified as M. avium by standard biochemical procedures, Genprobe analysis, and mycolic acid patterns. Subsequent restriction fragment length polymorphism analysis, using SalI- and PvuII-digested genomic DNA, revealed identical patterns for hybridization with the IS1245 probe. Thin-layer chromatographic analysis of lipids from the three morphotypes revealed that only the SmT morphotype possessed what appeared to be lipid components similar to, but unlike, previously described serovar-specific glycopeptidolipid antigens. Further analysis of internally radiolabeled deacylated lipids from the SmT morphotype, by high-performance liquid chromatography and thin-layer chromatography, disclosed that some of these components can be internally radiolabeled with [14C] phenylalanine and [14C]mannose. These results suggest that these components are structurally similar to previously described glycopeptidolipid antigens. This is apparently the first report of a monoclonal infection involving a single strain of M. avium presenting with all three colony morphotypes, SmO, SmT, and Rg. PMID:8880503

  9. Mycobacterium avium subspecies paratuberculosis recombinant proteins modulate antimycobacterial functions of bovine macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been shown that Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) activates the Mitogen Activated Protein Kinase (MAPK) p38 pathway, yet it is unclear which components of M. paratuberculosis are involved in the process. Therefore, a set of 42 M. paratuberculosis recombinan...

  10. Immunologic Responses to Mycobacterium avium subsp. paratuberculosis in Neonatal Calves After Oral or Intraperitoneal Experimental Infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infection models are useful for studying host responses to infection to aid in the development of diagnostic tools and vaccines. The majority of experimental models for ruminants have utilized an oral inoculation of live Mycobacterium avium subsp. paratuberculosis (MAP) in order to establish infecti...

  11. The Transport of Mycobacterium avium subsp. paratuberculosis through Saturated Aquifer Materials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) is the causative agent of Johne’s disease, a chronic enteric infection causing diarrhea and wasting in cattle, sheep, and other ruminants. Because Johne’s disease is spread by the ingestion of M. paratuberculosis, a good understanding...

  12. COMPARISON OF MYCOBACTERIUM AVIUM ISOLATES FROM DRINKING WATER AND FROM THE POPULATION SERVED BY THE SYSTEM

    EPA Science Inventory

    Background: Current evidence suggests that drinking water, soil, and produce are potential sources of Mycobacterium avium infections, a pathogen not known to be transmitted person-to-person.

    Methods: We sampled water during 2000 - 2002 from a large municipal drinking wate...

  13. Immunologic responses to Mycobacterium avium subsp. paratuberculois protein cocktail vaccines in a mouse model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is a chronic granulomatous enteritis characterized by severe diarrhea, wasting and a decline in milk production caused by the bacterium Mycobacterium avium subsp. paratuberculois (MAP). The vaccine currently on the market has some limitations including a severe injection site reactio...

  14. Detection of Mycobacterium avium subsp. paratuberculosis in Drinking Water and Biofilms Using Quantitative PCR

    EPA Science Inventory

    Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne’s disease in domestic animals and has been implicated in Crohn’s disease in humans. Cows infected with Johne’s disease shed large quantities of MAP into soil. Further, MAP has been isolated from surface water, is resi...

  15. Pathogenesis of Mycobacterium avium subsp. paratuberculosis in Neonatal Calves after Oral or Intraperitoneal Experimental Infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the infection process to Mycobacterium avium subsp. paratuberculosis is tantamount to the development of effective vaccines and therapeutics for the control of this disease in the field. The current study compared the effectiveness of oral and intraperitoneal methods of experimental in...

  16. Cytokine Secretion in Periparturient dairy cows naturally infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne's disease, cause by Mycobacterium avium subsp. paratuberculosis (MAP), has a devastating impact on the dairy industry. Cows typically are infected as neonates, and stressors, such as parturition, may induce the transition from the subclinical to a more clinical stage of disease. The objective ...

  17. Molecular Epidemiology of Mycobacterium avium subsp. paratuberculosis in a Longitudinal Study of Three Dairy Herds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to evaluate whether cows that were low shedders of Mycobacterium avium subsp. paratuberculosis (MAP) were passive shedding animals or whether they were truly infected with MAP. We also evaluated whether these MAP-infected animals could have been infected as adults by ...

  18. Osteopontin Expression in Periparturient Dairy Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease (JD), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is estimated to infect more than 22% of US dairy herds. Periods of immunosuppression, typically seen at parturition, may contribute to the transition from the subclinical, or asymptomatic, to the clinical stage of inf...

  19. Evaluation of Mycobacterium avium subsp. paratuberculosis Transport in Saturated Porous Media

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (Map) is the causative agent of Johne’s disease, a chronic enteric infection that affects ruminants. Eradication of Map from infected farms has been difficult and is likely due to long-term survival of the organism in the environment. The application of Ma...

  20. Parturition and Mycobacterium avium subsp. paratuberculosis: A Potential Interface for the Pathogenesis of Johne's Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne’s disease (JD), is estimated to infect more than 22% of US dairy herds and cost the industry $250 million annually. One major period of stress for dairy cows is the periparturient period, and field observations suggest ...

  1. Assessment of Food as a Source of Exposure to Mycobacterium avium Subspecies Paratuberculosis (MAP)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The National Advisory Committee on Microbiological Criteria for Foods (NACMCF or Committee) was asked to assess the importance of food as a source of exposure to Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne’s disease, which affects primarily the small intestin...

  2. From mouth to macrophage: mechanisms of innate immune subversion by Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease (JD) is a chronic enteric infection of cattle caused by Mycobacterium avium subsp. paratuberculosis (MAP). The high economic cost and potential zoonotic threat of JD have driven efforts to develop tools and approaches to effectively manage this disease within livestock herds. Efforts...

  3. Characteristics of an Extensive Mycobacterium avium subspecies paratuberculosis Recombinant Protein Set

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the first step of a comprehensive large-scale antigen discovery project, 651 Mycobacterium avium subspecies paratuberculosis proteins were produced in Escherichia coli. All of these were purified by affinity chromatography, dialyzed in phosphate buffered saline, and analyzed on SDS-PAGE gels. C...

  4. Production and Characterization of Monoclonal Antibodies Against a Major Membrane Protein of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Mycobacterium avium subsp. paratuberculosis 35-kDa major membrane protein (MMP) encoded by MAP2121c has been shown to play a role in invasion of epithelial cells and is an important membrane antigen recognized by cattle with Johne’s disease. In this study, purified recombinant MMP was used to p...

  5. Antibacterial Activities of Naturally occurring Compounds against Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibacterial activities of 19 naturally-occurring compounds (including essential oils and some of their isolated constituents, apple and green tea polyphenols and other plant extracts) against three strains of Mycobacterium avium subspecies paratuberculosis (Map), a bovine isolate NCTC 8578, a raw ...

  6. Comparison of fecal DNA extraction kits for the detection of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fecal culture is considered the gold standard for the diagnostics of paratuberculosis, however, PCR for the detection of Mycobacterium avium subsp. paratuberculosis (MAP) in fecal material is widely used today, having demonstrated great sensitivity and specificity. To insure the most efficient and r...

  7. Functional Characterization of Iron Dependent Regulator (IdeR) of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study we investigated an iron dependent regulator (IdeR) of Mycobacterium avium subsp. paratuberculosis (MAP). IdeR is a transcriptional factor that plays a global iron regulatory role in Mycobacterium tuberculosis (MTB) with a 19-bp recognition sequence. IdeR recognition sites within MAP ge...

  8. Survival of Mycobacterium avium subsp. paratuberculosis in Biofilms on Livestock Watering Trough Materials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) is the causative agent of Johne’s disease, a chronic enteric infection that affects ruminants. Despite the ubiquitous occurrence of Mycobacterium sp. in nature and the fact that Johne’s disease has been reported worldwide, little rese...

  9. Surface Proteome of “Mycobacterium avium subsp. hominissuis” during the Early Stages of Macrophage Infection

    PubMed Central

    McNamara, Michael; Tzeng, Shin-Cheng; Maier, Claudia; Zhang, Li

    2012-01-01

    “Mycobacterium avium subsp. hominissuis” is a robust and pervasive environmental bacterium that can cause opportunistic infections in humans. The bacterium overcomes the host immune response and is capable of surviving and replicating within host macrophages. Little is known about the bacterial mechanisms that facilitate these processes, but it can be expected that surface-exposed proteins play an important role. In this study, the selective biotinylation of surface-exposed proteins, streptavidin affinity purification, and shotgun mass spectrometry were used to characterize the surface-exposed proteome of M. avium subsp. hominissuis. This analysis detected more than 100 proteins exposed at the bacterial surface of M. avium subsp. hominissuis. Comparisons of surface-exposed proteins between conditions simulating early infection identified several groups of proteins whose presence on the bacterial surface was either constitutive or appeared to be unique to specific culture conditions. This proteomic profile facilitates an improved understanding of M. avium subsp. hominissuis and how it establishes infection. Additionally, surface-exposed proteins are excellent targets for the host adaptive immune system, and their identification can inform the development of novel treatments, diagnostic tools, and vaccines for mycobacterial disease. PMID:22392927

  10. Identification of Immune Parameters To Differentiate Disease States among Sheep Infected with Mycobacterium avium subsp. paratuberculosis▿

    PubMed Central

    Gillan, Sonia; O'Brien, Rory; Hughes, Alan D.; Griffin, J. Frank T.

    2010-01-01

    Johne's disease, a chronic enteritis of ruminants, is caused by infection with Mycobacterium avium subsp. paratuberculosis. Three distinct forms have been observed in sheep: paucibacillary disease (PB), multibacillary disease (MB), and asymptomatic infection (AS). In this study, immune parameters for animals naturally infected with M. avium subsp. paratuberculosis and identified postmortem as having PB, MB, or AS were compared to provide a further understanding of the immunological reactivity contributing to or resulting from these different disease states in sheep. PB was associated with strong ex vivo M. avium subsp. paratuberculosis antigen-stimulated gamma interferon responses, pronounced increases in CD25+ T-cell frequencies in circulation, antibody production, and a B-cell population that expanded significantly upon ex vivo antigenic stimulation. The MB group featured the highest antibody levels and a lack of cellular immune responsiveness to the M. avium subsp. paratuberculosis antigen. The AS group expressed an immunological phenotype intermediate between that for noninfected control animals and that for the PB group. The relationship between immune responses and disease severity within the PB group was investigated more closely; significant positive correlations were observed between disease severity and both the CD8+ population in the circulating blood and the expression of interleukin-4 mRNA in antigen-stimulated blood samples ex vivo. Together, these data point toward distinct immune profiles in sheep that correspond to different Johne's disease states, which can be determined from circulating blood and/or from localized intestinal tract tissue samples. PMID:19923568

  11. Mycobacterium simiae and Mycobacterium avium-M. intracellulare mixed infection in acquired immune deficiency syndrome.

    PubMed Central

    Lévy-Frébault, V; Pangon, B; Buré, A; Katlama, C; Marche, C; David, H L

    1987-01-01

    Acquired immune deficiency syndrome was diagnosed in a 43-year-old man, born and living in Congo. The patient presented a disseminated infection caused by mycobacteria which were recovered from blood, jejunal fluid, and duodenal and rectal biopsies. Identification, according to conventional tests and mycolate profile determination, showed that Mycobacterium avium-M. intracellulare and M. simiae were both involved. Images PMID:3793869

  12. The Peter Pan paradigm.

    PubMed

    Cohen, J Craig; Larson, Janet E

    2008-01-01

    Genetic and environmental agents that disrupt organogenesis are numerous and well described. Less well established, however, is the role of delay in the developmental processes that yield functionally immature tissues at birth. Evidence is mounting that organs do not continue to develop postnatally in the context of these organogenesis insults, condemning the patient to utilize under-developed tissues for adult processes. These poorly differentiated organs may appear histologically normal at birth but with age may deteriorate revealing progressive or adult-onset pathology. The genetic and molecular underpinning of the proposed paradigm reveals the need for a comprehensive systems biology approach to evaluate the role of maternal-fetal environment on organogenesis."You may delay, but time will not" Benjamin Franklin, USA Founding Father. PMID:18182112

  13. Paradigms for parasite conservation.

    PubMed

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  14. Isolation of Mycobacterium avium subsp. paratuberculosis from free-ranging birds and mammals on livestock premises.

    PubMed

    Corn, Joseph L; Manning, Elizabeth J B; Sreevatsan, Srinand; Fischer, John R

    2005-11-01

    Surveys for Mycobacterium avium subsp. paratuberculosis infection in free-ranging mammals and birds were conducted on nine dairy and beef cattle farms in Wisconsin and Georgia. Specimens were collected from 774 animals representing 25 mammalian and 22 avian species. Specimens of ileum, liver, intestinal lymph nodes, and feces were harvested from the larger mammals; a liver specimen and the gastrointestinal tract were harvested from birds and small mammals. Cultures were performed by using radiometric culture and acid-fast isolates were identified by 16S/IS900/IS1311 PCR and mycobactin dependency characteristics. M. avium subsp. paratuberculosis was cultured from tissues and feces from 39 samples from 30 animals representing nine mammalian and three avian species. The prevalence of infected wild animals by premises ranged from 2.7 to 8.3% in Wisconsin and from 0 to 6.0% in Georgia. Shedding was documented in seven (0.9%) animals: three raccoons, two armadillos, one opossum, and one feral cat. The use of two highly polymorphic short sequence repeat loci for analysis of 29 of the 39 strains identified 10 alleles. One allelic pattern broadly shared in domestic ruminants ("7,5") appeared in approximately one-third of the wildlife M. avium subsp. paratuberculosis isolates studied. Given the few cases of shedding by free-ranging animals compared to the volume of contaminated manure produced by infected domestic ruminant livestock, contamination of the farm environment by infected wildlife was negligible. Wildlife may, however, have epidemiological significance for farms where M. avium subsp. paratuberculosis recently has been eliminated or on farms free of M. avium subsp. paratuberculosis but located in the geographic vicinity of farms with infected livestock. PMID:16269731

  15. Isolation of Mycobacterium avium subsp. paratuberculosis from Free-Ranging Birds and Mammals on Livestock Premises

    PubMed Central

    Corn, Joseph L.; Manning, Elizabeth J. B.; Sreevatsan, Srinand; Fischer, John R.

    2005-01-01

    Surveys for Mycobacterium avium subsp. paratuberculosis infection in free-ranging mammals and birds were conducted on nine dairy and beef cattle farms in Wisconsin and Georgia. Specimens were collected from 774 animals representing 25 mammalian and 22 avian species. Specimens of ileum, liver, intestinal lymph nodes, and feces were harvested from the larger mammals; a liver specimen and the gastrointestinal tract were harvested from birds and small mammals. Cultures were performed by using radiometric culture and acid-fast isolates were identified by 16S/IS900/IS1311 PCR and mycobactin dependency characteristics. M. avium subsp. paratuberculosis was cultured from tissues and feces from 39 samples from 30 animals representing nine mammalian and three avian species. The prevalence of infected wild animals by premises ranged from 2.7 to 8.3% in Wisconsin and from 0 to 6.0% in Georgia. Shedding was documented in seven (0.9%) animals: three raccoons, two armadillos, one opossum, and one feral cat. The use of two highly polymorphic short sequence repeat loci for analysis of 29 of the 39 strains identified 10 alleles. One allelic pattern broadly shared in domestic ruminants (“7,5”) appeared in approximately one-third of the wildlife M. avium subsp. paratuberculosis isolates studied. Given the few cases of shedding by free-ranging animals compared to the volume of contaminated manure produced by infected domestic ruminant livestock, contamination of the farm environment by infected wildlife was negligible. Wildlife may, however, have epidemiological significance for farms where M. avium subsp. paratuberculosis recently has been eliminated or on farms free of M. avium subsp. paratuberculosis but located in the geographic vicinity of farms with infected livestock. PMID:16269731

  16. Evaluation of Control Points in Youngstock and Adult Dairy Cow Management to Control Transmission of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Complete a series of prospective controlled on-farm trials to critically evaluate the efficacy and cost-benefit of commonly recommended management practices for reducing the transmission of Mycobacterium avium subsp. paratuberculosis (Map) in youngstock in infected herds....

  17. Faecal bacterial composition in dairy cows shedding Mycobacterium avium subsp. paratuberculosis in faeces in comparison with nonshedding cows.

    PubMed

    Kaevska, Marija; Videnska, Petra; Sedlar, Karel; Bartejsova, Iva; Kralova, Alena; Slana, Iva

    2016-06-01

    The aim of this study was to determine possible differences in the faecal microbiota of dairy cows infected with Mycobacterium avium subsp. paratuberculosis (Johne's disease) in comparison with noninfected cows from the same herds. Faecal samples from cows in 4 herds were tested for M. avium subsp. paratuberculosis by real-time PCR, and faecal bacterial populations were analysed by 454 pyrosequencing of the 16S rRNA gene. The most notable differences between shedding and nonshedding cows were an increase in the genus Psychrobacter and a decrease in the genera Oscillospira, Ruminococcus, and Bifidobacterium in cows infected with M. avium subsp. paratuberculosis. The present study is the first to report the faecal microbial composition in dairy cows infected with M. avium subsp. paratuberculosis. PMID:27127920

  18. Osteopontin Immunoreactivity in the Ileum and Ileoceccal Lymph Node of Dairy Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteopontin (Opn), a highly acidic glycoprotein, promotes cellular adhesion and recruitment and has been shown to be upregulated in the granulomas of mycobacterial infections. Johne’s disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is associated with granulomatous enteritis. ...

  19. Osteopontin: A Novel Cytokine Involved in the Regulation of Mycobacterium avium subsp. paratuberculosis Infection in Periparturient Dairy Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteopontin (Opn), an important mediator of the cell-mediated immune response, enhances the host immune response against mycobacterial infections. Infections caused by the intracellular bacterium, Mycobacterium avium subsp. paratuberculosis (MAP), have a devastating impact on the dairy industry. ...

  20. Antigenicity of Recombinant Maltose Binding Protein-Mycobacterium avium subsp. paratuberculosis Fusion Proteins with and without Factor Xa Cleaving

    PubMed Central

    Begg, Douglas J.; Purdie, Auriol C.; Bannantine, John P.; Whittington, Richard J.

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis causes Johne's disease (JD) in ruminants. Proteomic studies have shown that M. avium subsp. paratuberculosis expresses certain proteins when exposed to in vitro physiological stress conditions similar to the conditions experienced within a host during natural infection. Such proteins are hypothesized to be expressed in vivo, are recognized by the host immune system, and may be of potential use in the diagnosis of JD. In this study, 50 recombinant maltose binding protein (MBP)-M. avium subsp. paratuberculosis fusion proteins were evaluated using serum samples from sheep infected with M. avium subsp. paratuberculosis, and 29 (58%) were found to be antigenic. Among 50 fusion proteins, 10 were evaluated in MBP fusion and factor Xa-cleaved forms. A total of 31 proteins (62%) were found to be antigenic in either MBP fusion or factor Xa-cleaved forms. Antigenicity after cleavage and removal of the MBP tag was marginally enhanced. PMID:24132604

  1. Naturalistic Inquiry: Paradigm and Method.

    ERIC Educational Resources Information Center

    Lotto, Linda S.

    Despite the rhetoric acclaiming it as a new paradigm, educational researchers have tended to treat naturalistic inquiry as a new or alternative method employed within the dominant, rationalistic paradigm. Spokespersons for naturalistic inquiry tend to concentrate on what one does differently rather than how one perceives what one is doing…

  2. Immune-Enhancing Effects of Taishan Pinus massoniana Pollen Polysaccharides on DNA Vaccine Expressing Bordetella avium ompA.

    PubMed

    Zhu, Fujie; Liu, Xiao; Sun, Zhenhong; Yu, Cuilian; Liu, Liping; Yang, Shifa; Li, Bing; Wei, Kai; Zhu, Ruiliang

    2016-01-01

    Bordetella avium is the causative agent of bordetellosis, which remains to be the cause of severe losses in the turkey industry. Given the lack of vaccines that can provide good protection, developing a novel vaccine against B. avium infection is crucial. In this study, we constructed a eukaryotic expression plasmid, which expressed the outer membrane protein A (ompA) of B. avium, to prepare a B. avium recombinant ompA-DNA vaccine. Three concentrations (low, middle, and high) of Taishan Pinus massoniana pollen polysaccharides (TPPPS), a known immunomodulator, were used as adjuvants, and their immune conditioning effects on the developed DNA vaccine were examined. The pure ompA-DNA vaccine, Freund's incomplete adjuvant ompA-DNA vaccine, and the empty plasmid served as the controls. The chickens in each group were separately inoculated with these vaccines three times at 1, 7, and 14 days old. Dynamic changes in antibody production, cytokine secretion, and lymphocyte count were then determined from 7 to 49 days after the first inoculation. Protective rates of the vaccines were also determined after the third inoculation. Results showed that the pure DNA vaccine obviously induced the production of antibodies, the secretion of cytokines, and the increase in CD(4+) and CD(8+) T lymphocyte counts in peripheral blood, as well as provided a protective rate of 50% to the B. avium-challenged chickens. The chickens inoculated with the TPPPS adjuvant ompA-DNA vaccine and Freund's adjuvant ompA-DNA vaccine demonstrated higher levels of immune responses than those inoculated with pure ompA-DNA vaccine, whereas only the ompA-DNA vaccine with 200 mg/mL TPPPS completely protected the chickens against B. avium infection. These findings indicate that the B. avium ompA-DNA vaccine combined with TPPPS is a potentially effective B. avium vaccine. PMID:26870023

  3. Immune-Enhancing Effects of Taishan Pinus massoniana Pollen Polysaccharides on DNA Vaccine Expressing Bordetella avium ompA

    PubMed Central

    Zhu, Fujie; Liu, Xiao; Sun, Zhenhong; Yu, Cuilian; Liu, Liping; Yang, Shifa; Li, Bing; Wei, Kai; Zhu, Ruiliang

    2016-01-01

    Bordetella avium is the causative agent of bordetellosis, which remains to be the cause of severe losses in the turkey industry. Given the lack of vaccines that can provide good protection, developing a novel vaccine against B. avium infection is crucial. In this study, we constructed a eukaryotic expression plasmid, which expressed the outer membrane protein A (ompA) of B. avium, to prepare a B. avium recombinant ompA-DNA vaccine. Three concentrations (low, middle, and high) of Taishan Pinus massoniana pollen polysaccharides (TPPPS), a known immunomodulator, were used as adjuvants, and their immune conditioning effects on the developed DNA vaccine were examined. The pure ompA-DNA vaccine, Freund’s incomplete adjuvant ompA-DNA vaccine, and the empty plasmid served as the controls. The chickens in each group were separately inoculated with these vaccines three times at 1, 7, and 14 days old. Dynamic changes in antibody production, cytokine secretion, and lymphocyte count were then determined from 7 to 49 days after the first inoculation. Protective rates of the vaccines were also determined after the third inoculation. Results showed that the pure DNA vaccine obviously induced the production of antibodies, the secretion of cytokines, and the increase in CD4+ and CD8+ T lymphocyte counts in peripheral blood, as well as provided a protective rate of 50% to the B. avium-challenged chickens. The chickens inoculated with the TPPPS adjuvant ompA-DNA vaccine and Freund’s adjuvant ompA-DNA vaccine demonstrated higher levels of immune responses than those inoculated with pure ompA-DNA vaccine, whereas only the ompA-DNA vaccine with 200 mg/mL TPPPS completely protected the chickens against B. avium infection. These findings indicate that the B. avium ompA-DNA vaccine combined with TPPPS is a potentially effective B. avium vaccine. PMID:26870023

  4. Human Nature and Research Paradigms: Theory Meets Physical Therapy Practice

    ERIC Educational Resources Information Center

    Plack, Margaret M.

    2005-01-01

    Human nature is a very complex phenomenon. In physical therapy this complexity is enhanced by the need to understand the intersection between the art and science of human behavior and patient care. A paradigm is a set of basic beliefs that represent a worldview, defines the nature of the world and the individual's place in it, and helps to…

  5. Virulence and Immunity Orchestrated by the Global Gene Regulator sigL in Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    Ghosh, Pallab; Steinberg, Howard

    2014-01-01

    Mycobacterium avium subsp. paratuberculosis causes Johne's disease in ruminants, a chronic enteric disease responsible for severe economic losses in the dairy industry. Global gene regulators, including sigma factors are important in regulating mycobacterial virulence. However, the biological significance of such regulators in M. avium subsp. paratuberculosis rremains elusive. To better decipher the role of sigma factors in M. avium subsp. paratuberculosis pathogenesis, we targeted a key sigma factor gene, sigL, activated in mycobacterium-infected macrophages. We interrogated an M. avium subsp. paratuberculosis ΔsigL mutant against a selected list of stressors that mimic the host microenvironments. Our data showed that sigL was important in maintaining bacterial survival under such stress conditions. Survival levels further reflected the inability of the ΔsigL mutant to persist inside the macrophage microenvironments. Additionally, mouse infection studies suggested a substantial role for sigL in M. avium subsp. paratuberculosis virulence, as indicated by the significant attenuation of the ΔsigL-deficient mutant compared to the parental strain. More importantly, when the sigL mutant was tested for its vaccine potential, protective immunity was generated in a vaccine/challenge model of murine paratuberculosis. Overall, our study highlights critical role of sigL in the pathogenesis and immunity of M. avium subsp. paratuberculosis infection, a potential role that could be shared by similar proteins in other intracellular pathogens. PMID:24799632

  6. A new paradigm for geosciences information management

    SciTech Connect

    Bolivar, Stephen L.; Nasser, K.; Dorries, A. M.; Canepa, Julie Ann

    2002-01-01

    Over the past two decades, geoscientists have been increasingly engaged in providing answers to complex environmental problems with significant societal, political, and economic consequences. Today, these scientists have to perform under increasingly greater visibility to stakeholders and the general public. Their activities are much more scrutinized with regards to economic pressure, litigation support and regulatory compliance than in the past. Their current work is built on decades of past work and in many cases will continue for decades to come. Stakeholders are increasingly evaluating raw data rather than just examining summaries in final reports. They also need assurance that proper data control and data quality procedures were followed. Geoscientists are now faced with a new paradigm, i.e. with the challenge of cost effectively collecting, managing, analyzing, and synthesizing enormous volumes of multidisciplinary and complex information. In addition, these data must be processed and disseminated in a way that allows the public to make informed and rational assessments on decisions that are proposed or have been made. The new paradigm is clear - client and stakeholder needs must be better met, and the systems used to store and generate data must meet these needs. This paper addresses the challenges and the implications of this new paradigm on geosciences information management in the 21st Century. It concludes with a case study for a successful implementation of the new paradigm in an environmental restoration project at the Los Alamos National Laboratory (LANL) that is operated by the Department of Energy (DOE). LANL is upgrading and reengineering its data and business processes to better address client, user and stakeholder issues regarding data accessibility, control and quality.

  7. Immunological and Molecular Characterization of Susceptibility in Relationship to Bacterial Strain Differences in Mycobacterium avium subsp. paratuberculosis Infection in the Red Deer (Cervus elaphus)

    PubMed Central

    O'Brien, R.; Mackintosh, C. G.; Bakker, D.; Kopecna, M.; Pavlik, I.; Griffin, J. F. T.

    2006-01-01

    Johne's disease (JD) infection, caused by Mycobacterium avium subsp. paratuberculosis, represents a major disease problem in farmed ruminants. Although JD has been well characterized in cattle and sheep, little is known of the infection dynamics or immunological response in deer. In this study, typing of M. avium subsp. paratuberculosis isolates from intestinal lymphatic tissues from 74 JD-infected animals showed that clinical isolates of M. avium subsp. paratuberculosis from New Zealand farmed red deer were exclusively of the bovine strain genotype. The susceptibility of deer to M. avium subsp. paratuberculosis was further investigated by experimental oral-route infection studies using defined isolates of virulent bovine and ovine M. avium subsp. paratuberculosis strains. Oral inoculation with high (109 CFU/animal) or medium (107 CFU/animal) doses of the bovine strain of M. avium subsp. paratuberculosis established 100% infection rates, compared to 69% infection following inoculation with a medium dose of the ovine strain. The high susceptibility of deer to the bovine strain of M. avium subsp. paratuberculosis was confirmed by a 50% infection rate following experimental inoculation with a low dose of bacteria (103 CFU/animal). This study is the first to report experimental M. avium subsp. paratuberculosis infection in red deer, and it outlines the strong infectivity of bovine-strain M. avium subsp. paratuberculosis isolates for cervines. PMID:16714585

  8. Clinical Significance and Epidemiologic Analyses of Mycobacterium avium and Mycobacterium intracellulare among Patients without AIDS

    PubMed Central

    Han, Xiang Y.; Tarrand, Jeffrey J.; Infante, Rosa; Jacobson, Kalen L.; Truong, Mylene

    2005-01-01

    The clinical significance and prevalence of Mycobacterium avium and Mycobacterium intracellulare were analyzed in a cohort of 7,472 patients who, from 1999 to 2003, sought care at the University of Texas M.D. Anderson Cancer Center, Houston, and had cultures performed for mycobacteria. Patients were stratified for age, sex, and underlying diseases, and bacteria were identified by 16S rRNA gene sequencing. M. avium was isolated in 62 (0.83%) of 7,472 patients and M. intracellulare in 65 (0.87%). Clinically, only 10 of the 62 (16.2%) patients with M. avium had probable to definite evidence of infection, whereas the majority (83.8%) had weak evidence of infection. Sex and age did not affect the isolation or infection of M. avium. Hematological tumors predisposed to M. avium colonization but not infection. In contrast, 41 of the 65 (63.1%) patients with M. intracellulare had probable to definite infection, a level much higher than those with M. avium (P < 0.001). M. intracellulare was more prevalent in women (1.33% of 3,311) than in men (0.50% of 4,161) (P < 0.001), and underlying diseases had no effect in women. Men with lung cancer had a higher prevalence (1.37%) than men without (0.34%) (4.0-fold; P < 0.001), but it was similar to that in women. A marked age trend for the isolation of M. intracellulare among women was noted: 0.27% (1-fold) for ages of <50 years, 0.85% (3.1-fold) for ages 50 to 59 years, 1.50% (5.6-fold) for ages 60 to 69 years, and 3.74% (13.9-fold) for ages ≥70 years (trend, P < 0.001). The combined rate for women ≥50 was 1.86% (95% confidence interval [1.30 to 2.42%]) (6.9-fold). Together, these results suggest that, among non-AIDS patients, M. intracellulare is more pathogenic and tends to infect women increasingly beyond menopause (age ≥50 years) regardless of underlying disease. The prevalence rate of 1.86% in postmenopausal women suggests the need to further investigate the public health significance of M. intracellulare. PMID:16145084

  9. Novel Feature of Mycobacterium avium subsp. paratuberculosis, Highlighted by Characterization of the Heparin-Binding Hemagglutinin Adhesin

    PubMed Central

    Lefrancois, Louise H.; Bodier, Christelle C.; Cochard, Thierry; Canepa, Sylvie; Raze, Dominique; Lanotte, Philippe; Sevilla, Iker A.; Stevenson, Karen; Behr, Marcel A.; Locht, Camille

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis comprises two genotypically defined groups, known as the cattle (C) and sheep (S) groups. Recent studies have reported phenotypic differences between M. avium subsp. paratuberculosis groups C and S, including growth rates, infectivity for macrophages, and iron metabolism. In this study, we investigated the genotypes and biological properties of the virulence factor heparin-binding hemagglutinin adhesin (HBHA) for both groups. In Mycobacterium tuberculosis, HBHA is a major adhesin involved in mycobacterium-host interactions and extrapulmonary dissemination of infection. To investigate HBHA in M. avium subsp. paratuberculosis, we studied hbhA polymorphisms by fragment analysis using the GeneMapper technology across a large collection of isolates genotyped by mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) and IS900 restriction fragment length polymorphism (RFLP-IS900) analyses. Furthermore, we analyzed the structure-function relationships of recombinant HBHA proteins of types C and S by heparin-Sepharose chromatography and surface plasmon resonance (SPR) analyses. In silico analysis revealed two forms of HBHA, corresponding to the prototype genomes for the C and S types of M. avium subsp. paratuberculosis. This observation was confirmed using GeneMapper on 85 M. avium subsp. paratuberculosis strains, including 67 strains of type C and 18 strains of type S. We found that HBHAs from all type C strains contain a short C-terminal domain, while those of type S present a long C-terminal domain, similar to that produced by Mycobacterium avium subsp. avium. The purification of recombinant HBHA from M. avium subsp. paratuberculosis of both types by heparin-Sepharose chromatography highlighted a correlation between their affinities for heparin and the lengths of their C-terminal domains, which was confirmed by SPR analysis. Thus, types C and S of M. avium subsp. paratuberculosis may be

  10. Biological robustness: paradigms, mechanisms, and systems principles.

    PubMed

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  11. Biological Robustness: Paradigms, Mechanisms, and Systems Principles

    PubMed Central

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  12. MIRU-VNTR genotype diversity and indications of homoplasy in M. avium strains isolated from humans and slaughter pigs in Latvia.

    PubMed

    Kalvisa, Adrija; Tsirogiannis, Constantinos; Silamikelis, Ivars; Skenders, Girts; Broka, Lonija; Zirnitis, Agris; Jansone, Inta; Ranka, Renate

    2016-09-01

    Diseases which are caused by non-tuberculous mycobacteria (NTM) are an increasing problem in the developed countries. In Latvia, one of the most clinically important members of NTM is Mycobacterium avium (M. avium), an opportunistic pathogen which has been isolated from several lung disease patients and tissue samples of slaughter pigs. This study was designed to characterize the genetic diversity of the M. avium isolates in Latvia and to compare the distribution of genotypic patterns among humans and pigs. Eleven (Hall and Salipante, 2010) clinical M. avium samples, isolated from patients of Center of Tuberculosis and Lung Diseases (years 2003-2010), and 32 isolates from pig necrotic mesenterial lymph nodes in different regions (years 2003-2007) were analyzed. The majority (42 of 43) of samples were identified as M. avium subsp. hominissuis; one porcine isolate belonged to M. avium subsp. avium. MIRU-VNTR genotyping revealed 13 distinct genotypes, among which nine genotype patterns, including M. avium subsp. avium isolate, were newly identified. IS1245 RFLP fingerprinting of 25 M. avium subsp. hominissuis samples yielded 17 different IS1245 RFLP patterns, allowing an efficient discrimination of isolates. Clusters of identical RFLP profiles were observed within host species, geographical locations and time frame of several years. Additional in silico analysis on simulated MIRU-VNTR genotype population datasets showed that the MIRU-VNTR pattern similarity could partly arise due to probabilistic increase of acquiring homoplasy among subpopulations, thus the similar MIRU-VNTR profiles of M. avium strains even in close geographical proximity should be interpreted with caution. PMID:27178993

  13. Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin-18

    PubMed Central

    Kim, S H; Cho, D; Kim, T S

    2001-01-01

    Interferon-gamma (IFN-γ) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) was known to strongly induce IFN-γ production by T cells and natural killer (NK) cells. In order to determine whether injection with DNA encoding IL-18 can stimulate the resistance to Mycobacterium avium complex (MAC) infection, the mature IL-18 cDNA with κ leader sequence was cloned under control of the cytomegalovirus (CMV) promoter (TcCMVIL-18) and its effect on MAC infection was investigated in genetically susceptible BALB/c mice. Injection with the TcCMVIL-18 DNA during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while injection with the TcCMV control DNA did not. Lung cells in mice injected with the TcCMVIL-18 DNA showed persistent production of IFN-γ throughout the 8-week period. Furthermore, immunization with the TcCMVIL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than immunization with the TcCMV control vector. This work suggests that IL-18 DNA vaccination may be useful in the immunotherapeutic or immunoprotection approaches of infections by intracellular parasites such as mycobacteria. PMID:11260329

  14. The Narrative Paradigm: Another Story.

    ERIC Educational Resources Information Center

    Warnick, Barbara

    1987-01-01

    Claims that the narrative paradigm recently proposed as a model for rhetorical criticism is problematic because of internal contradictions and inconsistencies. Argues that independent sources are lacking for judging the adequacy of a critic's claims about a text. (JD)

  15. Mycobacterium avium subsp. paratuberculosis PtpA Is an Endogenous Tyrosine Phosphatase Secreted during Infection▿

    PubMed Central

    Bach, Horacio; Sun, Jim; Hmama, Zakaria; Av-Gay, Yossef

    2006-01-01

    Adaptive gene expression in prokaryotes is mediated by protein kinases and phosphatases. These regulatory proteins mediate phosphorylation of histidine or aspartate in two-component systems and serine/threonine or tyrosine in eukaryotic and eukaryote-like protein kinase systems. The genome sequence of Mycobacterium avium subsp. paratuberculosis, the causative agent of Johne's disease, does not possess a defined tyrosine kinase. Nevertheless, it encodes for protein tyrosine phosphatases. Here, we report that Map1985, is a functional low-molecular tyrosine phosphatase that is secreted intracellularly upon macrophage infection. This finding suggests that Map1985 might contribute to the pathogenesis of Mycobacterium avium subsp. paratuberculosis by dephosphorylating essential macrophage signaling and/or adaptor molecules. PMID:16982836

  16. Disseminated mycobacteriosis manifesting as paraplegia in two Parma wallabies (Macropus parma) naturally exposed to Mycobacterium avium.

    PubMed

    Robveille, Cynthia; Albaric, Olivier; Gaide, Nicolas; Abadie, Jérome

    2015-11-01

    Two captive female Parma wallabies (Macropus parma) died after a history of flaccid paraplegia. On postmortem examination, granulomatous and suppurative osteomyelitis involving the left ischium and the lumbosacral region, with meningeal extension at the cauda equina, and caseonecrotic mastitis were the most significant changes. Multiple small nodules in the liver and spleen, and an enlargement of some lymph nodes with central caseous necrosis were also observed. Microscopically, a disseminated granulomatous inflammation with numerous multinucleate giant cells was seen. Numerous acid-fast bacilli were detected in macrophages, in multinucleated giant cells, and free in the central necrosis and suppurative exudate. After culture, polymerase chain reaction assays were carried out to detect the 65-kDa heat shock protein (Hsp65) and insertion sequences (IS)1245 and IS900. The causative agent was identified as Mycobacterium avium subsp. avium. PMID:26450834

  17. Lactase persistence, NOD2 status and Mycobacterium avium subsp. paratuberculosis infection associations to Inflammatory Bowel Disease

    PubMed Central

    2012-01-01

    Background Inflammatory Bowel Disease (IBD), which includes both Crohn’s disease (CD) and ulcerative colitis (UC), is caused by a complex interplay involving genetic predisposition, environmental factors and an infectious agent. Mycobacterium avium subsp. paratuberculosis (MAP) is a promising pathogen candidate since it produces a chronic intestinal inflammatory disease in ruminants that resembles CD in humans. MAP is a ubiquitous microorganism, although its presence in the food chain, especially in milk from infected animals, is what made us think that there could be an association between lactase persistence (LP) and IBD. The LCT mutation has brought adaptation to dairy farming which in turn would have increased exposure of the population to infection by MAP. NOD2 gene mutations are highly associated to CD. Methods In our study, CD and UC patients and controls from the North of Spain were genotyped for the lactase gene (LCT) and for three NOD-2 variants, R702W, G908R and Cins1007fs. MAP PCR was carried out in order to assess MAP infection status and these results were correlated with LCT and NOD2 genotypes. Results As for LP, no association was found with IBD, although UC patients were less likely to present the T/T−13910 variant compared to controls, showing a higher C-allele frequency and a tendency to lactase non-persistence (LNP). NOD2 mutations were associated to CD being the per-allele risk higher for the Cins1007fs variant. MAP infection was more extended among the healthy controls (45.2%) compared to CD patients (21.38%) and UC patients (19.04%) and this was attributed to therapy. The Asturian CD cohort presented higher levels of MAP prevalence (38.6%) compared to the Basque CD cohort (15.5%), differences also attributed to therapy. No interaction was found between MAP infection and LCT or NOD2 status. Conclusions We conclude that LP is not significantly associated with IBD, but that MAP infection and NOD2 do show not mutually interacting associations

  18. Iron-sparing Response of Mycobacterium avium subsp. paratuberculosis is strain dependent

    PubMed Central

    2010-01-01

    Background Two genotypically and microbiologically distinct strains of Mycobacterium avium subsp. paratuberculosis (MAP) exist - S and C MAP strains that primarily infect sheep and cattle, respectively. Concentration of iron in the cultivation medium has been suggested as one contributing factor for the observed microbiologic differences. We recently demonstrated that S strains have defective iron storage systems, leading us to propose that these strains might experience iron toxicity when excess iron is provided in the medium. To test this hypothesis, we carried out transcriptional and proteomic profiling of these MAP strains under iron-replete or -deplete conditions. Results We first complemented M. smegmatisΔideR with IdeR of C MAP or that derived from S MAP and compared their transcription profiles using M. smegmatis mc2155 microarrays. In the presence of iron, sIdeR repressed expression of bfrA and MAP2073c, a ferritin domain containing protein suggesting that transcriptional control of iron storage may be defective in S strain. We next performed transcriptional and proteomic profiling of the two strain types of MAP under iron-deplete and -replete conditions. Under iron-replete conditions, C strain upregulated iron storage (BfrA), virulence associated (Esx-5 and antigen85 complex), and ribosomal proteins. In striking contrast, S strain downregulated these proteins under iron-replete conditions. iTRAQ (isobaric tag for relative and absolute quantitation) based protein quantitation resulted in the identification of four unannotated proteins. Two of these were upregulated by a C MAP strain in response to iron supplementation. The iron-sparing response to iron limitation was unique to the C strain as evidenced by repression of non-essential iron utilization enzymes (aconitase and succinate dehydrogenase) and upregulation of proteins of essential function (iron transport, [Fe-S] cluster biogenesis and cell division). Conclusions Taken together, our study revealed

  19. Cathepsin L maturation and activity is impaired in macrophages harboring M. avium and M. tuberculosis.

    PubMed

    Nepal, Rajeev M; Mampe, Stephanie; Shaffer, Brian; Erickson, Ann H; Bryant, Paula

    2006-06-01

    Mycobacterium tuberculosis-infected macrophages demonstrate diminished capacity to present antigens via class II MHC molecules. Since successful class II MHC-restricted antigen presentation relies on the actions of endocytic proteases, we asked whether the activities of cathepsins (Cat) B, S and L-three major lysosomal cysteine proteases-are modulated in macrophages infected with pathogenic Mycobacterium spp. Infection of murine bone marrow-derived macrophages with either Mycobacterium avium or M. tuberculosis had no obvious effect on Cat B or Cat S activity. In contrast, the activity of Cat L was altered in infected cells. Specifically, whereas the 24-kDa two-chain mature form of active Cat L predominated in uninfected cells, we observed an increase in the steady-state activity of the precursor single-chain (30 kDa) and 25-kDa two-chain forms of the enzyme in cells infected with either M. avium or M. tuberculosis. Pulse-chase analyses revealed that maturation of nascent, single-chain Cat L into the 25-kDa two-chain form was impaired in infected macrophages, and that maturation into the 24-kDa two-chain form did not occur. Consistent with these data, M. avium infection inhibited the IFNgamma-induced secretion of active two-chain Cat L by macrophages. Viable bacilli were not required to disrupt Cat L maturation, suggesting that a constitutively expressed mycobacterial component was responsible. The absence of the major active form of lysosomal Cat L in M. avium- and M. tuberculosis-infected macrophages may influence the types of T cell epitopes generated in these antigen-presenting cells, and/or the rate of class II MHC peptide loading. PMID:16636015

  20. Illegitimate recombination: An efficient method for random mutagenesis in Mycobacterium avium subsp. hominissuis

    PubMed Central

    2012-01-01

    Background The genus Mycobacterium (M.) comprises highly pathogenic bacteria such as M. tuberculosis as well as environmental opportunistic bacteria called non-tuberculous mycobacteria (NTM). While the incidence of tuberculosis is declining in the developed world, infection rates by NTM are increasing. NTM are ubiquitous and have been isolated from soil, natural water sources, tap water, biofilms, aerosols, dust and sawdust. Lung infections as well as lymphadenitis are most often caused by M. avium subsp. hominissuis (MAH), which is considered to be among the clinically most important NTM. Only few virulence genes from M. avium have been defined among other things due to difficulties in generating M. avium mutants. More efforts in developing new methods for mutagenesis of M. avium and identification of virulence-associated genes are therefore needed. Results We developed a random mutagenesis method based on illegitimate recombination and integration of a Hygromycin-resistance marker. Screening for mutations possibly affecting virulence was performed by monitoring of pH resistance, colony morphology, cytokine induction in infected macrophages and intracellular persistence. Out of 50 randomly chosen Hygromycin-resistant colonies, four revealed to be affected in virulence-related traits. The mutated genes were MAV_4334 (nitroreductase family protein), MAV_5106 (phosphoenolpyruvate carboxykinase), MAV_1778 (GTP-binding protein LepA) and MAV_3128 (lysyl-tRNA synthetase LysS). Conclusions We established a random mutagenesis method for MAH that can be easily carried out and combined it with a set of phenotypic screening methods for the identification of virulence-associated mutants. By this method, four new MAH genes were identified that may be involved in virulence. PMID:22966811

  1. Survival and Dormancy of Mycobacterium avium subsp. paratuberculosis in the Environment

    PubMed Central

    Whittington, Richard J.; Marshall, D. Jeff; Nicholls, Paul J.; Marsh, Ian B.; Reddacliff, Leslie A.

    2004-01-01

    The survival of Mycobacterium avium subsp. paratuberculosis was studied by culture of fecal material sampled at intervals for up to 117 weeks from soil and grass in pasture plots and boxes. Survival for up to 55 weeks was observed in a dry fully shaded environment, with much shorter survival times in unshaded locations. Moisture and application of lime to soil did not affect survival. UV radiation was an unlikely factor, but infrared wavelengths leading to diurnal temperature flux may be the significant detrimental component that is correlated with lack of shade. The organism survived for up to 24 weeks on grass that germinated through infected fecal material applied to the soil surface in completely shaded boxes and for up to 9 weeks on grass in 70% shade. The observed patterns of recovery in three of four experiments and changes in viable counts were indicative of dormancy, a hitherto unreported property of this taxon. A dps-like genetic element and relA, which are involved in dormancy responses in other mycobacteria, are present in the M. avium subsp. paratuberculosis genome sequence, providing indirect evidence for the existence of physiological mechanisms enabling dormancy. However, survival of M. avium subsp. paratuberculosis in the environment is finite, consistent with its taxonomic description as an obligate parasite of animals. PMID:15128561

  2. Lymphoproliferative and Gamma Interferon Responses to Stress-Regulated Mycobacterium avium subsp. paratuberculosis Recombinant Proteins

    PubMed Central

    Gurung, Ratna B.; Begg, Douglas J.; Purdie, Auriol C.; de Silva, Kumudika; Bannantine, John P.

    2014-01-01

    Johne's disease in ruminants is a chronic infection of the intestines caused by Mycobacterium avium subsp. paratuberculosis. An important strategy to control disease is early detection, and a potentially efficient method for early detection is measurement of cell-mediated immune responses developed by the host in response to exposure or infection. One method is to measure lymphoproliferation and cytokine release from the host cells when exposed to the organism or parts of the organism. In this study, 10 recombinant M. avium subsp. paratuberculosis proteins known to be upregulated under in vitro stress conditions were evaluated by examining their ability to evoke memory as a result of exposure by vaccination or oral challenge with live Mycobacterium avium subsp. paratuberculosis. Out of 10 proteins, MAP2698c was found to induce higher cell-mediated immune responses in vaccinated and challenged sheep in comparison to healthy controls. The findings suggest that not all stress-regulated proteins have the diagnostic potential to detect cell-mediated immune responses in ovine paratuberculosis. PMID:24695774

  3. Complete Genome Sequence of Mycobacterium avium, Isolated from Commercial Domestic Pekin Ducks (Anas platyrhynchos domestica), Determined Using PacBio Single-Molecule Real-Time Technology.

    PubMed

    Song, Xiao-Heng; Chen, Hong-Xi; Zhou, Wang-Shu; Wang, Jiang-Bo; Liu, Ma-Feng; Wang, Ming-Shu; Cheng, An-Chun; Jia, Ren-Yong; Chen, Shun; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Chen, Xiao-Yue; Zhu, De-Kang

    2016-01-01

    Mycobacterium avium is an important pathogenic bacterium in birds and has never, to our knowledge, reported to be isolated from domestic ducks. We present here the complete genome sequence of a virulent strain of Mycobacterium avium, isolated from domestic Pekin ducks for the first time, which was determined by PacBio single-molecule real-time technology. PMID:27587804

  4. Complete Genome Sequence of Mycobacterium avium, Isolated from Commercial Domestic Pekin Ducks (Anas platyrhynchos domestica), Determined Using PacBio Single-Molecule Real-Time Technology

    PubMed Central

    Song, Xiao-Heng; Chen, Hong-Xi; Zhou, Wang-Shu; Wang, Jiang-Bo; Liu, Ma-Feng; Wang, Ming-Shu; Cheng, An-Chun; Jia, Ren-Yong; Chen, Shun; Sun, Kun-Feng; Yang, Qiao; Wu, Ying; Chen, Xiao-Yue

    2016-01-01

    Mycobacterium avium is an important pathogenic bacterium in birds and has never, to our knowledge, reported to be isolated from domestic ducks. We present here the complete genome sequence of a virulent strain of Mycobacterium avium, isolated from domestic Pekin ducks for the first time, which was determined by PacBio single-molecule real-time technology. PMID:27587804

  5. Modulation of Cytokine Gene Expression and Secretion During the Periparturient Period in Dairy Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Modulation of cytokine gene expression and secretion during the periparturient period in dairy cows naturally infected with Mycobacterium avium subsp. paratuberculosis Technical abstract Johne’s disease (JD), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is estimated to infect more t...

  6. Health Inequities: Evaluation of Two Paradigms

    ERIC Educational Resources Information Center

    Ashcroft, Rachelle

    2010-01-01

    Social work practice in health is shaped by underlying paradigms. To effectively target health inequities, practitioners need to consider appropriate paradigms. In this exploration of how six health paradigms shape theory and practice, the two health paradigms that most attended to health inequalities are social determinants of health and…

  7. Paradigms of Sulfotransferase Catalysis

    PubMed Central

    Wang, Ting; Cook, Ian; Falany, Charles N.; Leyh, Thomas S.

    2014-01-01

    Human cytosolic sulfotransferases (SULTs) regulate the activities of thousands of signaling small molecules via transfer of the sulfuryl moiety (-SO3) from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to the hydroxyls and primary amines of acceptors. Sulfonation controls the affinities of ligands for their targets, and thereby regulates numerous receptors, which, in turn, regulate complex cellular responses. Despite their biological and medical relevance, basic SULT mechanism issues remain unresolved. To settle these issues, and to create an in-depth model of SULT catalysis, the complete kinetic mechanism of a representative member of the human SULT family, SULT2A1, was determined. The mechanism is composed of eight enzyme forms that interconvert via 22 rate constants, each of which was determined independently. The result is a complete quantitative description of the mechanism that accurately predicts complex enzymatic behavior. This is the first description of a SULT mechanism at this resolution, and it reveals numerous principles of SULT catalysis and resolves previously ambiguous issues. The structures and catalytic behaviors SULTs are highly conserved; hence, the mechanism presented here should prove paradigmatic for the family. PMID:25056952

  8. Paradigms for environmentally conscious manufacturing

    NASA Astrophysics Data System (ADS)

    Edinbarough, Immanuel A.; Wells, Wayne E.

    2004-12-01

    There are several stories involving the industries that pledge themselves for the environmentally conscious manufacturing practices. Paradigms for environmentally conscious manufacturing are associated with one of the aspects of environmental quality, protection, resource management, commitment or sustainability. The engineering rules of thumb that can easily be adopted by aspiring companies need identification. The underlying thread that unifies the efforts of environmentally conscious manufacturing companies, in offering the environmentally safe products to the world, is grouped and presented in the paper as paradigms for successful practices. The various ways in which a start up company, that wants to excel in environmentally conscious manufacturing, can position itself based on the paradigms is also discussed in the paper.

  9. The Synthesis Paradigm in Genetics

    PubMed Central

    Rice, William R.

    2014-01-01

    Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics—and other fields of biology—are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous “-omics” data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time. PMID:24496401

  10. Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance

    PubMed Central

    Khare, Sangeeta; Lawhon, Sara D.; Drake, Kenneth L.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Everts, Robin E.; Lewin, Harris A.; Galindo, Cristi L.; Garner, Harold R.; Adams, Leslie Garry

    2012-01-01

    Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection), processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i) early (30 min and 1 hr post-infection), ii) intermediate (2, 4 and 8 hrs post-infection), and iii) late (12 hrs post-infection). We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence) that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed pathways

  11. Amplified Fragment Length Polymorphism Reveals Specific Epigenetic Distinctions between Mycobacterium avium Subspecies paratuberculosis Isolates of Various Isolation Types▿

    PubMed Central

    O'Shea, B.; Khare, S.; Klein, P.; Roussel, A.; Adams, L. G.; Ficht, T. A.; Rice-Ficht, A. C.

    2011-01-01

    Amplified fragment length polymorphism (AFLP) was employed as a genetic analysis tool for the study of the genetic relatedness of Mycobacterium avium subsp. paratuberculosis isolates harvested from bovine fecal samples and from bovine or human tissues. This analysis revealed genetic differences between these two isolate types that were confirmed through cluster analysis. Dendrogram analysis separated these two isolate types based on the isolation scheme (tissue-associated versus fecal M. avium subsp. paratuberculosis isolates). Further sequence analysis of unique genetic regions from each isolation type revealed no genetic sequence differences. However, Clustal DNA alignments identified AFLP restriction enzyme sites that were undigested in the tissue-associated isolates. AFLP analysis also disclosed that the same AFLP restriction sites were digested in all of the fecal isolates. Sequence analysis further revealed a consensus sequence upstream of the undigested restriction sites for possible methyltransferase recognition in the tissue-associated M. avium subsp. paratuberculosis isolates. PMID:21471350

  12. Emergence of life: Physical chemistry changes the paradigm.

    PubMed

    Spitzer, Jan; Pielak, Gary J; Poolman, Bert

    2015-01-01

    Origin of life research has been slow to advance not only because of its complex evolutionary nature (Franklin Harold: In Search of Cell History, 2014) but also because of the lack of agreement on fundamental concepts, including the question of 'what is life?'. To re-energize the research and define a new experimental paradigm, we advance four premises to better understand the physicochemical complexities of life's emergence: (1) Chemical and Darwinian (biological) evolutions are distinct, but become continuous with the appearance of heredity. (2) Earth's chemical evolution is driven by energies of cycling (diurnal) disequilibria and by energies of hydrothermal vents. (3) Earth's overall chemical complexity must be high at the origin of life for a subset of (complex) chemicals to phase separate and evolve into living states. (4) Macromolecular crowding in aqueous electrolytes under confined conditions enables evolution of molecular recognition and cellular self-organization. We discuss these premises in relation to current 'constructive' (non-evolutionary) paradigm of origins research - the process of complexification of chemical matter 'from the simple to the complex'. This paradigm artificially avoids planetary chemical complexity and the natural tendency of molecular compositions toward maximum disorder embodied in the second law of thermodynamics. Our four premises suggest an empirical program of experiments involving complex chemical compositions under cycling gradients of temperature, water activity and electromagnetic radiation. PMID:26059688

  13. Integrating Essential Components of Quality Improvement into a New Paradigm for Continuing Education

    ERIC Educational Resources Information Center

    Van Hoof, Thomas J.; Meehan, Thomas P.

    2011-01-01

    Continuing education (CE) that strives to improve patient care in a complex health care system requires a different paradigm than CE that seeks to improve clinician knowledge and competence in an educational setting. A new paradigm for CE is necessary in order to change clinician behavior and to improve patient outcomes in an increasingly…

  14. The Development of the Foundations of Modern Pedagogy: Paradigmal and Methodological Aspects of Research

    ERIC Educational Resources Information Center

    Dmitrenko, ?amara ?.; Lavryk, Tatjana V.; Yaresko, Ekaterina V.

    2015-01-01

    Changes in the various fields of knowledge influenced the pedagogical science. The article explains the structure of the foundations of modern pedagogy through paradigmal and methodological aspects. Bases of modern pedagogy include complex of paradigms, object and subject of science, general and specific principles, methods and technologies.…

  15. Immuno-enhancement of Taishan Pinus massoniana pollen polysaccharides on recombinant Bordetella avium ompA expressed in Pichia pastoris.

    PubMed

    Liu, Liping; Yu, Cuilian; Wang, Chuanwen; Shao, Mingxu; Yan, Zhengui; Jiang, Xiaodong; Chi, Shanshan; Wang, Zhen; Wei, Kai; Zhu, Ruiliang

    2016-06-01

    Bordetellosis, caused by Bordetella avium, continues to be an economic problem in the poultry industry of China. Vaccines with good protective ability are lacking. Thus, developing a novel vaccine against the B. avium infection is crucial. Here, we constructed a recombinant Pichia pastoris transformant capable of expressing the outer membrane protein A (ompA) of B. avium to prepare the recombinant ompA subunit vaccine and then evaluated its immune effects. To further investigate the immunomodulation effects of Taishan Pinus massoniana pollen polysaccharides (TPPPS) on this subunit vaccine, three concentrations (20, 40, and 60 mg/mL) of TPPPS were used as the adjuvants of the ompA subunit vaccine respectively. The conventional Freund's incomplete adjuvant served as the control of TPPPS. Chickens in different groups were separately vaccinated with these vaccines thrice. During the monitoring period, serum antibody titers, concentrations of serum IL-4, percentages of CD4(+) and CD8(+) T-lymphocytes in the peripheral blood, lymphocyte transformation rate, and protection rate were detected. Results showed that the pure ompA vaccine induced the production of anti-ompA antibody, the secretion of IL-4, the increase of CD4(+) T-lymphocytes counts and lymphocyte transformation rate in the peripheral blood. Moreover, the pure ompA vaccine provided a protection rate of 71.67% after the B. avium challenge. Notably, TPPPS adjuvant vaccines induced higher levels of immune responses than the pure ompA vaccine, and 60 mg/mL TPPPS adjuvant vaccine showed optimal immune effects and had a 91.67% protection rate. Our findings indicated that this recombinant B. avium ompA subunit vaccine combined with TPPPS had high immunostimulatory potential. Results provided a new perspective for B. avium subunit vaccine research. PMID:26975477

  16. High-Throughput Direct Fecal PCR Assay for Detection of Mycobacterium avium subsp. paratuberculosis in Sheep and Cattle

    PubMed Central

    Waldron, Anna M.; Galea, Francesca; Whittington, Ann-Michele; Saunders, Vanessa F.; Begg, Douglas J.; de Silva, Kumudika; Purdie, Auriol C.; Whittington, Richard J.

    2014-01-01

    Johne's disease (JD) is a chronic enteric disease caused by Mycobacterium avium subsp. paratuberculosis that affects ruminants. Transmission occurs by the fecal-oral route. A commonly used antemortem diagnostic test for the detection of M. avium subsp. paratuberculosis in feces is liquid culture; however, a major constraint is the 2- to 3-month incubation period needed for this method. Rapid methods for the detection of M. avium subsp. paratuberculosis based on PCR have been reported, but comprehensive validation data are lacking. We describe here a new test, the high-throughput-Johnes (HT-J), to detect M. avium subsp. paratuberculosis in feces. Its diagnostic accuracy was compared with that of liquid radiometric (Bactec) fecal culture using samples from cattle (1,330 samples from 23 herds) and sheep (596 samples from 16 flocks). The multistage protocol involves the recovery of M. avium subsp. paratuberculosis cells from a fecal suspension, cell rupture by bead beating, extraction of DNA using magnetic beads, and IS900 quantitative PCR. The limit of detection of the assay was 0.0005 pg, and the limit of quantification was 0.005 pg M. avium subsp. paratuberculosis genomic DNA. Only M. avium subsp. paratuberculosis was detected from a panel of 51 mycobacterial isolates, including 10 with IS900-like sequences. Of the 549 culture-negative fecal samples from unexposed herds and flocks, 99% were negative in the HT-J test, while 60% of the bovine- and 84% of the ovine-culture-positive samples were positive in the HT-J test. As similar total numbers of samples from M. avium subsp. paratuberculosis-exposed animals were positive in culture and HT-J tests in both species, and as the results of a McNemar's test were not significant, these methods probably have similar sensitivities, but the true diagnostic sensitivities of these tests are unknown. These validation data meet the consensus-based reporting standards for diagnostic test accuracy studies for paratuberculosis and

  17. Paradigms, Exemplars and Social Change

    ERIC Educational Resources Information Center

    Lawson, Hal A.

    2009-01-01

    Researchers' social-cultural organization influences the scope, quality, quantity, coherence, dissemination, utilization and impact of research-based, theoretically sound knowledge. Five concepts--paradigm, exemplar, segment, network and gatekeeper--are salient to research on researchers' organization. Autobiographical reflections signal these…

  18. Paradigms of Justice and Love.

    ERIC Educational Resources Information Center

    Byrne, Patick H.

    This paper examines the philosophy behind the Pulse Program of Boston College and its attempt at integrating theory and practice and transforming student's paradigms of justice and love. The basic idea of the program, begun in the fall of 1969, is that students receive academic credit for participation in off-campus field projects which have a…

  19. Alternative Paradigms of Teacher Education.

    ERIC Educational Resources Information Center

    Zeichner, Kenneth M.

    1983-01-01

    Four paradigms have dominated the debate on teacher education in recent years: (1) the "behavioristic" orientation; (2) the "personalistic" mode; (3) the "traditional-craft" approach; and (4) the "inquiry" orientation. A heuristic device for organizing discussion about desirable teacher education practices is presented, which permits consideration…

  20. [The female paradigm in psychoanalysis].

    PubMed

    Rohde-Dachser, C

    1990-01-01

    According to the author, the necessary change to a new psychoanalytic paradigm of femininity can only take place if the patriarchal discourse of psychoanalytic metatheory is systematically deconstructed. Only then can a reconstruction of this discourse occur with a view toward the emancipation of both genders. PMID:2406796

  1. Transplant rejection and paradigms lost

    PubMed Central

    Strom, Terry B.

    2013-01-01

    During transplant rejection, migrating T cells infiltrate the grafted organ, but the signals that direct this migration are incompletely understood. In this issue of the JCI, Walch et al. debunk two classical paradigms concerning transplant rejection, with important consequences for the design of antirejection therapeutics. PMID:23676457

  2. Multimission Software Reuse in an Environment of Large Paradigm Shifts

    NASA Technical Reports Server (NTRS)

    Wilson, Robert K.

    1996-01-01

    The ground data systems provided for NASA space mission support are discussed. As space missions expand, the ground systems requirements become more complex. Current ground data systems provide for telemetry, command, and uplink and downlink processing capabilities. The new millennium project (NMP) technology testbed for 21st century NASA missions is discussed. The program demonstrates spacecraft and ground system technologies. The paradigm shift from detailed ground sequencing to a goal oriented planning approach is considered. The work carried out to meet this paradigm for the Deep Space-1 (DS-1) mission is outlined.

  3. PRESENCE OF MYCOBACTERIUM AVIUM SUBSP. PARATUBERCULOSIS IN ALPACAS (LAMA PACOS) INHABITING THE CHILEAN ALTIPLANO.

    PubMed

    Salgado, Miguel; Sevilla, Iker; Rios, Carolina; Crossley, Jorge; Tejeda, Carlos; Manning, Elizabeth

    2016-03-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of paratuberculosis. The organism causes disease in both domestically managed and wild ruminant species. South American camelids have a long, shared history with indigenous people in the Andes. Over the last few decades, increasing numbers of alpacas were exported to numerous countries outside South America. No paratuberculosis surveillance has been reported for these source herds. In this study, individual fecal samples from 85 adult alpacas were collected from six separate herds in the Chilean Altiplano. A ParaTB mycobacterial growth indicator tube (MGIT) liquid culture of each individual fecal sample, followed by real-time polymerase chain reaction (PCR) protocol was used for confirmation. DNA extracts from a subset of confirmed MAP isolates were subjected to mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing. Fifteen alpaca were fecal culture test-positive. Five false-positive culture samples were negative on PCR analysis for Mycobacterium avium subsp. avium (MAA), Mycobacterium bovis (M. bovis), and the 16 S rDNA gene. Three MAP isolates subset-tested belonged to the same MIRU-VNTR type, showing four repeats for TR292 (locus 1) in contrast to the three repeats typical of the MAP reference strain K10. The number of repeats found in the remaining loci was identical to that of the K10 strain. It is not known how nor when MAP was introduced into the alpaca population in the Chilean Altiplano. The most plausible hypothesis to explain the presence of MAP in these indigenous populations is transmission by contact with infected domestic small ruminant species that may on occasion share pastures or range with alpacas. Isolation of this mycobacterial pathogen from such a remote region suggests that MAP has found its way beyond the confines of intensively managed domestic agriculture premises. PMID:27010259

  4. Early Immune Markers Associated with Mycobacterium avium subsp. paratuberculosis Infection in a Neonatal Calf Model ▿

    PubMed Central

    Stabel, J. R.; Robbe-Austerman, S.

    2011-01-01

    The objective of this study was to observe early markers of cell-mediated immunity in naïve calves infected with Mycobacterium avium subsp. paratuberculosis and how expression of these markers evolved over the 12-month period of infection. Groups for experimental infection included control (noninfected), oral (infected orally with M. avium subsp. paratuberculosis strain K-10), oral/DXM (pretreatment with dexamethasone before oral inoculation), intraperitoneal (i.p.) inoculation, and oral/M (oral inoculation with mucosal scrapings from a cow with clinical disease) groups. One of the earliest markers to emerge was antigen-specific gamma interferon (IFN-γ). Only i.p. inoculated calves had detectable antigen-specific IFN-γ responses at 7 days, with responses of the other infection groups becoming detectable at 90 and 120 days. All infection groups maintained robust IFN-γ responses for the remainder of the study. At 1 month, calves in the oral and oral/M groups had higher antigen-stimulated interleukin-10 (IL-10) levels than calves in the other treatment groups, but IL-10 secretion declined by 12 months for all calves. T-cell activation markers such as CD25, CD26, CD45RO, and CD5 were significantly upregulated in infected calves compared to noninfected controls. Oral inoculation of calves resulted in significantly increased antigen-specific lymphocyte proliferation at 9 and 12 months, as well as inducible nitric oxide synthase (iNOS) secretion at 6 and 12 months. These results demonstrate that infection of naïve calves with M. avium subsp. paratuberculosis invoked early immunologic responses characterized by robust antigen-specific IFN-γ responses and induction of CD25 and CD45RO expression on T-cell subsets. These were followed by antigen-specific lymphocyte proliferation, iNOS secretion, and expression of CD26 and CD5bright markers in the latter part of the 12-month study. PMID:21228140

  5. Achieving Operability via the Mission System Paradigm

    NASA Technical Reports Server (NTRS)

    Hammer, Fred J.; Kahr, Joseph R.

    2006-01-01

    In the past, flight and ground systems have been developed largely-independently, with the flight system taking the lead, and dominating the development process. Operability issues have been addressed poorly in planning, requirements, design, I&T, and system-contracting activities. In many cases, as documented in lessons-learned, this has resulted in significant avoidable increases in cost and risk. With complex missions and systems, operability is being recognized as an important end-to-end design issue. Never-the-less, lessons-learned and operability concepts remain, in many cases, poorly understood and sporadically applied. A key to effective application of operability concepts is adopting a 'mission system' paradigm. In this paradigm, flight and ground systems are treated, from an engineering and management perspective, as inter-related elements of a larger mission system. The mission system consists of flight hardware, flight software, telecom services, ground data system, testbeds, flight teams, science teams, flight operations processes, procedures, and facilities. The system is designed in functional layers, which span flight and ground. It is designed in response to project-level requirements, mission design and an operations concept, and is developed incrementally, with early and frequent integration of flight and ground components.

  6. Chemical Decontamination with N-Acetyl-l-Cysteine–Sodium Hydroxide Improves Recovery of Viable Mycobacterium avium subsp. paratuberculosis Organisms from Cultured Milk

    PubMed Central

    Bradner, L.; Robbe-Austerman, S.; Beitz, D. C.

    2013-01-01

    Mycobacterium avium subsp. paratuberculosis is shed into the milk and feces of cows with advanced Johne's disease, allowing the transmission of M. avium subsp. paratuberculosis between animals. The objective of this study was to formulate an optimized protocol for the isolation of M. avium subsp. paratuberculosis in milk. The parameters investigated included chemical decontamination with N-acetyl-l-cysteine–sodium hydroxide (NALC-NaOH), alone and in combination with antibiotics (vancomycin, amphotericin B, and nalidixic acid), and the efficacy of solid (Herrold's egg yolk medium [HEY]) and liquid (Bactec 12B and para-JEM) culture media. For each experiment, raw milk samples from a known noninfected cow were inoculated with 102 to 108 CFU/ml of live M. avium subsp. paratuberculosis organisms. The results indicate that an increased length of exposure to NALC-NaOH from 5 to 30 min and an increased concentration of NaOH from 0.5 to 2.0% did not affect the viability of M. avium subsp. paratuberculosis. Additional treatment of milk samples with the antibiotics following NALC-NaOH treatment decreased the recovery of viable M. avium subsp. paratuberculosis cells more than treatment with NALC-NaOH alone. The Bactec 12B medium was the superior medium of the three evaluated for the isolation of M. avium subsp. paratuberculosis from milk, as it achieved the lowest threshold of detection. The optimal conditions for NALC-NaOH decontamination were determined to be exposure to 1.50% NaOH for 15 min followed by culture in Bactec 12B medium. This study demonstrates that chemical decontamination with NALC-NaOH resulted in a greater recovery of viable M. avium subsp. paratuberculosis cells from milk than from samples treated with hexadecylpyridinium chloride (HPC). Therefore, it is important to optimize milk decontamination protocols to ensure that low concentrations of M. avium subsp. paratuberculosis can be detected. PMID:23637290

  7. Genome-Wide Sequence Variation among Mycobacterium avium Subspecies paratuberculosis Isolates: A Better Understanding of Johne’s Disease Transmission Dynamics

    PubMed Central

    Hsu, Chung-Yi; Wu, Chia-Wei; Talaat, Adel M.

    2011-01-01

    Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne’s disease, infects many farmed ruminants, wild-life animals, and recently isolated from humans. To better understand the molecular pathogenesis of these infections, we analyzed the whole-genome sequences of several M. ap and M. avium subspecies avium (M. avium) isolates to gain insights into genomic diversity associated with variable hosts and environments. Using Next-generation sequencing technology, all six M. ap isolates showed a high percentage of similarity (98%) to the reference genome sequence of M. ap K-10 isolated from cattle. However, two M. avium isolates (DT 78 and Env 77) showed significant sequence diversity (only 87 and 40% similarity, respectively) compared to the reference strain M. avium 104, a reflection of the wide environmental niches of this group of mycobacteria. Within the M. ap isolates, genomic rearrangements (insertions/deletions) were not detected, and only unique single nucleotide polymorphisms (SNPs) were observed among M. ap isolates. While more of the SNPs (~100) in M. ap genomes were non-synonymous, a total of ~6,000 SNPs were detected among M. avium genomes, most of them were synonymous suggesting a differential selective pressure between M. ap and M. avium isolates. In addition, SNPs-based phylo-genomics had a enough discriminatory power to differentiate between isolates from different hosts but yet suggesting a bovine source of infection to other animals examined in this study. Interestingly, the human isolate (M. ap 4B) was closely related to a M. ap isolate from a dairy facility, suggesting a common source of infection. Overall, the identified phylo-genomes further supported the idea of a common ancestor to both M. ap and M. avium isolates. Genome-wide analysis described here could provide a strong foundation for a population genetic structure that could be useful for the analysis of mycobacterial evolution and for the tracking of Johne

  8. Mycobacterium avium lung disease combined with a bronchogenic cyst in an immunocompetent young adult.

    PubMed

    Kwon, Yong Soo; Han, Joungho; Jung, Ki Hwan; Kim, Je Hyeong; Koh, Won-Jung

    2013-01-01

    We report a very rare case of a bronchogenic cyst combined with nontuberculous mycobacterial pulmonary disease in an immunocompetent patient. A 21-year-old male was referred to our institution because of a cough, fever, and worsening of abnormalities on his chest radiograph, despite anti-tuberculosis treatment. Computed tomography of the chest showed a large multi-cystic mass over the right-upper lobe. Pathological examination of the excised lobe showed a bronchogenic cyst combined with a destructive cavitary lesion with granulomatous inflammation. Microbiological culture of sputum and lung tissue yielded Mycobacterium avium. The patient was administered anti-mycobacterial treatment that included clarithromycin. PMID:23346002

  9. Facts, myths and hypotheses on the zoonotic nature of Mycobacterium avium subspecies paratuberculosis.

    PubMed

    Atreya, Raja; Bülte, Michael; Gerlach, Gerald-F; Goethe, Ralph; Hornef, Mathias W; Köhler, Heike; Meens, Jochen; Möbius, Petra; Roeb, Elke; Weiss, Siegfried

    2014-10-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of paratuberculosis (Johne's disease [JD]), a chronic granulomatous enteritis in ruminants. JD is one of the most widespread bacterial diseases of domestic animals with significant economic impact. The histopathological picture of JD resembles that of Crohn's disease (CD), a human chronic inflammatory bowel disease of still unresolved aetiology. An aetiological relevance of MAP for CD has been proposed. This and the ambiguity of other published epidemiological findings raise the question whether MAP represents a zoonotic agent. In this review, we will discuss evidence that MAP has zoonotic capacity. PMID:25128370

  10. Current perspectives on Mycobacterium avium subsp. paratuberculosis, Johne's disease, and Crohn's disease: a review.

    PubMed

    Over, Ken; Crandall, Philip G; O'Bryan, Corliss A; Ricke, Steven C

    2011-05-01

    Mycobacterium avium subsp. paratuberculosis (MAP) causes the disease of cattle, Johne's. The economic impact of this disease includes early culling of infected cattle, reduced milk yield, and weight loss of cattle sold for slaughter. There is a possible link between MAP and Crohn's disease, a human inflammatory bowel disease. MAP is also a potential human food borne pathogen because it survives current pasteurization treatments. We review the current knowledge of MAP, Johne's disease and Crohn's disease and note directions for future work with this organism including rapid and economical detection, effective management plans and preventative measures. PMID:21254832

  11. Cutaneous gallium uptake in patients with AIDS with mycobacterium avium-intracellulare septicemia

    SciTech Connect

    Allwright, S.J.; Chapman, P.R.; Antico, V.F.; Gruenewald, S.M.

    1988-07-01

    Gallium imaging is increasingly being used for the early detection of complications in patients with AIDS. A 26-year-old homosexual man who was HIV antibody positive underwent gallium imaging for investigation of possible Pneumocystis carinii pneumonia. Widespread cutaneous focal uptake was seen, which was subsequently shown to be due to mycobacterium avium-intracellulare (MAI) septicemia. This case demonstrates the importance of whole body imaging rather than imaging target areas only, the utility of gallium imaging in aiding the early detection of clinically unsuspected disease, and shows a new pattern of gallium uptake in disseminated MAI infection.

  12. Systemic infection of Mycobacterium avium subspecies hominissuis and fungus in a pet dog

    PubMed Central

    KIM, Myung-Chul; KIM, JaeMyung; KANG, WoonKi; JANG, Yunho; KIM, Yongbaek

    2015-01-01

    A 3-year-old neutered female poodle with a long history of dermatophytic skin disease was presented with lethargy, anorexia and progressive weight loss. Abdominal ultrasonography revealed markedly enlarged mesenteric lymph nodes and multiple hypoechoic foci in the spleen. Cytology of the mesenteric lymph nodes and spleen showed granulomatous inflammation with fungal organisms and negatively stained intracytoplasmic bacterial rods consistent with Mycobacteria spp. Based on culture, multiplex polymerase chain reaction and sequence analysis, the bacterium was identified as Mycobacterium avium subspecies hominissuis. Despite treatment with antibiotics, the dog’s condition deteriorated, and it died approximately 3 weeks after first presentation. PMID:26412202

  13. Systemic infection of Mycobacterium avium subspecies hominissuis and fungus in a pet dog.

    PubMed

    Kim, Myung-Chul; Kim, JaeMyung; Kang, WoonKi; Jang, Yunho; Kim, Yongbaek

    2016-02-01

    A 3-year-old neutered female poodle with a long history of dermatophytic skin disease was presented with lethargy, anorexia and progressive weight loss. Abdominal ultrasonography revealed markedly enlarged mesenteric lymph nodes and multiple hypoechoic foci in the spleen. Cytology of the mesenteric lymph nodes and spleen showed granulomatous inflammation with fungal organisms and negatively stained intracytoplasmic bacterial rods consistent with Mycobacteria spp. Based on culture, multiplex polymerase chain reaction and sequence analysis, the bacterium was identified as Mycobacterium avium subspecies hominissuis. Despite treatment with antibiotics, the dog's condition deteriorated, and it died approximately 3 weeks after first presentation. PMID:26412202

  14. [Rapid diagnosis of mycobacteria, especially Mycobacterium tuberculosis and Mycobacterium avium complex, using BACTEC 460 TB system].

    PubMed

    Saito, H; Sato, K; Tomioka, H; Inoue, K; Shigeto, E

    1992-02-01

    Fourty-five sputum specimens collected at the National Sanatorium Hiroshima Hospital were subjected to cultivation using either BACTEC 460 TB System (BACTEC method; Becton Dickinson Co., Towson, Md., U.S.A.) or 3% Ogawa egg medium. Test sputum was treated with four volumes of 4% NaOH for approximately two minutes, after which 0.1 ml of the treated sputum was immediately inoculated onto 3% Ogawa egg medium. After neutralizing the remaining pretreated sputum with 1N HCl, and diluting with 1/15 M phosphate buffer PB; pH 6.8), it was then centrifuged at 3,000 rpm for 20 min and the sediment was suspended in 1.5 ml of PB. Volumes of 0.5 ml each were inoculated into BACTEC 12B medium (4 ml), containing PANTA for prevention of contamination and POES for promoting the growth of mycobacteria. In the BBCTEC method, bacterial growth was measured in terms of increases in the Growth Index (GI) values which were determined by the amount of 14CO2 released from the 14C-labelled palmitate during cultivation at 37 degrees C (positive growth; GI greater than or equal to 50). Moreover, rho-nitro-alpha-acetylamino-beta-hydroxy-propiophenone (NAP)-sensitivity testing was done by transferring a part of the BACTEC 12B culture showing positive growth to a NAP vial, and thereafter subjected to further cultivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1552698

  15. Mycobacterium avium Complex Empyema in a Patient with Interferon Gamma Autoantibodies

    PubMed Central

    Chung, Heath H; Opal, Steven M; Dworkin, Jonathan D

    2014-01-01

    Interferon gamma (IFN-γ) autoantibodies are a relatively recently discovered clinical entity, which have been shown to be associated with disseminated non-tuberculous mycobacterial (NTM) infections and other opportunistic infections. Interestingly, isolated NTM infections (without disseminated NTM infection) have not been shown to be a good predictor of the presence of IFN-γ autoantibodies. This case describes an isolated NTM empyema in a patient with IFN-γ autoantibodies and makes the argument that the development of an NTM empyema in a patient with no known immunodeficiency should prompt consideration for IFN-γ testing. Additionally, this case underscores the importance for clinicians to recognize that an unusual infection without the typical cause of impairment in immunity should prompt a more thorough investigation of the patient's immune system. PMID:25285250

  16. Connecting traditional sciences with the OLAP and data mining paradigms

    NASA Astrophysics Data System (ADS)

    Guergachi, Aziz A.

    2003-03-01

    The paradigms of OLAP, multidimensional modeling and data mining have first emerged in the areas of market analysis and finance to address various needs of people working in these areas. Does this mean that they are useful and applicable in these areas only? Or, can they also be applicable in the other more traditional areas of science and engineering? What characterize the systems for which these paradigms are suitable? What are the goals of these paradigms? How do they relate to the traditional body of knowledge that has been developed throughout the centuries in the areas of mathematics, statistics, systems science and engineering? Where, how and to what extent can we leverage the conventional wisdom that has been accumulated in the aforementioned disciplines to develop a foundational basis for the above paradigms? The goal of this paper is to address these questions at the foundational level. We argue that the paradigms of OLAP, multidimensional modeling and data mining can also be applied successfully to complex engineering systems, such as membrane-based water/wastewater treatment plants, for example. We develop mathematically-based axiomatic definition of the concepts of 'dimension,' 'dimension level,' 'dimension hierarchy' and 'measure' using set theory and equivalence relations.

  17. e-Science Paradigm for Astroparticle Physics at KISTI

    NASA Astrophysics Data System (ADS)

    Cho, Kihyeon

    2016-03-01

    The Korea Institute of Science and Technology Information (KISTI) has been studying the e-Science paradigm. With its successful application to particle physics, we consider the application of the paradigm to astroparticle physics. The Standard Model of particle physics is still not considered perfect even though the Higgs boson has recently been discovered. Astrophysical evidence shows that dark matter exists in the universe, hinting at new physics beyond the Standard Model. Therefore, there are efforts to search for dark matter candidates using direct detection, indirect detection, and collider detection. There are also efforts to build theoretical models for dark matter. Current astroparticle physics involves big investments in theories and computing along with experiments. The complexity of such an area of research is explained within the framework of the e-Science paradigm. The idea of the e-Science paradigm is to unify experiment, theory, and computing. The purpose is to study astroparticle physics anytime and anywhere. In this paper, an example of the application of the paradigm to astrophysics is presented.

  18. An experimental paradigm for team decision processes

    NASA Technical Reports Server (NTRS)

    Serfaty, D.; Kleinman, D. L.

    1986-01-01

    The study of distributed information processing and decision making is presently hampered by two factors: (1) The inherent complexity of the mathematical formulation of decentralized problems has prevented the development of models that could be used to predict performance in a distributed environment; and (2) The lack of comprehensive scientific empirical data on human team decision making has hindered the development of significant descriptive models. As a part of a comprehensive effort to find a new framework for multihuman decision making problems, a novel experimental research paradigm was developed involving human terms in decision making tasks. Attempts to construct parts of an integrated model with ideas from queueing networks, team theory, distributed estimation and decentralized resource management are described.

  19. Two Essays on the Learning Paradigm.

    ERIC Educational Resources Information Center

    Doud, Robert E.

    This document contains two essays, both of which discuss the ascendancy of the learning paradigm over the teaching paradigm. "Philosophy and the Learning Paradigm" reviews the effects of post-modernism on student learning with regard to loss of authority in the classroom, lack of academic standards in writing, and perceptions of professors as…

  20. The Composition Curriculum: A Paradigm of Possibilities.

    ERIC Educational Resources Information Center

    Bloom, Lynn Z.

    The process paradigm for teaching writing has been the dominant curricular model for the past 20 years, but by anatomizing various dimensions of this paradigm, it becomes clear why it, like any other paradigmatic model, will not last forever. To be adopted and become normative, any new paradigm has to appeal to salient features of the prevailing…

  1. The Learner-Centered Paradigm of Education

    ERIC Educational Resources Information Center

    Watson, Sunnie Lee; Reigeluth, Charles M.

    2008-01-01

    This article, the third in a series of four installments, begins by discussing the need for paradigm change in education and for a critical systems approach to paradigm change, and examines current progress toward paradigm change. Then it explores what a learner-centered, Information-Age educational system should be like, including the APA…

  2. Poverty eradication: a new paradigm.

    PubMed

    Pethe, V P

    1998-08-01

    This article offers a new paradigm for eradicating poverty in India. It was assumed incorrectly by Mahatma Gandhi that a good society without mass poverty would follow after independence. India copied Western models of development and developed giant factories, big dams, and megacities. Agriculture did not expand the number of jobs for people. The Western paradigm failed in India because of the false assumption of "trickle down" of income to the masses. The targeted programs to the poor did not directly benefit enough of the poor. Mega-industrialization led to reduced employment and higher skill needs. The model failed mainly because it was a proxy and relied on indirect ways of reaching the poor. The models failed to be adapted to conditions in India. The Swadeshi paradigm is a direct model for addressing mass poverty. Poverty is affected by immediate, intermediate, and ultimate determinants. Poverty begets social and economic problems, such as ignorance, ill health, high fertility, unemployment, and crime. In India and developing countries, mass poverty results from under use of human resources; lack of equal opportunities; and an outdated non-egalitarian social structure, an unjust global economic order, human cruelty, and erosion of ethical values. Indians are squandering their precious resources mimicking Western consumerism. Poverty leads to rapid population growth. People become productive assets with universal literacy, compulsory and free education, health services and sanitation, vocational training, and work ethics. India needs people-oriented policies with less emphasis on capital accumulation. PMID:12294462

  3. COMPARISON OF MYCOBACTERIUM AVIUM ISOLATES FROM A DRINKING WATER DISTRIBUTION SYSTEM AND FROM THE POPULATION SERVED BY THE SYSTEM

    EPA Science Inventory

    Background: Current evidence suggests that drinking water, soil, and produce are potential sources of Mycobacterium avium infections, a pathogen not known to be transmitted person-to-person.

    Methods: We sampled water during 2000-2002 from a large municipal drinking water ...

  4. Identification and Functional Characterization of the Iron Dependent Regulator (IdeR) of Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease in cattle and sheep, has unique iron requirements in that it is mycobactin-dependent for cultivation in vitro. The iron-dependent regulator (IdeR) is a well-characterized global regulator responsible for ma...

  5. Prevention of Mycobacterium avium subsp. paratuberculosis (MAP) Infection in BALB/c Mice by Feeding Probiotic Lactobacillus acidophilus NP-51

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to examine effects of feeding Lactobacillus acidophilus strain NP51 to mice challenged with Mycobacterium avium subspecies paratuberculosis (MAP). Mice were randomized to ten treatment groups; sentinels, control, heat-killed MAP, viable MAP, heat-killed NP51, viable ...

  6. THE MYCOBACTERIUM AVIUM SUPSPECIES PARATUBERCULOSIS 35 KDA PROTEIN PLAYS A ROLE IN INVASION OF BOVINE EPITHELIAL CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) enters intestinal epithelial cells of cattle and other ruminants via a mechanism that remains to be fully elucidated. In this study, we observed that a gene encoding the M. paratuberculosis 35-kDa major membrane protein (MMP) is ...

  7. Antigenicity of recombinant maltose binding protein-Mycobacterium avium subsp. paratuberculosis fusion proteins with and without factor Xa cleaving

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp paratuberculosis (MAP) causes Johne’s disease (JD) in ruminants. Proteomic studies have shown that MAP expresses certain proteins when exposed to in vitro physiological stress conditions similar to the conditions experienced within a host during natural infection. Such prot...

  8. Analysis of Mycobacterium avium subsp. paratuberculosis mutant libraries reveals loci-dependent transcription biases and strategies to novel mutant discovery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of Johne’s disease in ruminants and it has been implicated as a cause of Crohn’s disease in humans. The generation of comprehensive random mutant banks by transposon mutagenesis is a fundamental wide genomic technology utilized...

  9. The effects of progressing and nonprogressing Mycobacterium avium ssp. paratuberculosis infection on milk production in dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Longitudinal data from three commercial dairy herds in the northeast United States, collected from 2004 to 2011, were analyzed to determine the effect of Johne’s disease status and path on milk production. Disease status, as indicated by Mycobacterium avium subsp. paratuberculosis test results, was ...

  10. Differences in intermittent and continuous fecal shedding patterns between natural and experimental Mycobacterium avium subspecies paratuberculosis infections in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this paper is to study shedding patterns of cows infected with Mycobacterium avium subsp. paratuberculosis (MAP). While multiple single farm studies of MAP dynamics were reported, there is not large-scale meta-analysis of both natural and experimental infections. Large difference...

  11. Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

  12. Persistence of Mycobacterium avium subsp. paratuberculosis in soil, crops, and ensiled feed following manure spreading on infected dairy farms

    PubMed Central

    Fecteau, Marie-Eve; Hovingh, Ernest; Whitlock, Robert H.; Sweeney, Raymond W.

    2013-01-01

    The goal of this study was to determine the persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in soil, crops, and ensiled feeds following manure spreading. This bacterium was often found in soil samples, but less frequently in harvested feeds and silage. Spreading of manure on fields used for crop harvest is preferred to spreading on grazing pastures. PMID:24179246

  13. Early Immune Markers Associated with Experimental Mycobacterium avium subsp. paratuberculosis (MAP) Infection in a Neonatal Calf Model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to observe early markers of cell-mediated immunity in naïve calves infected with Mycobacterium avium subsp. paratuberculosis (MAP) and how expression of these markers evolved over the 12-month period of infection. Methods of experimental infection included: Control (n...

  14. Evaluation of survival of Mycobacterium avium subsp. paratuberculosis (Map) in ciliates isolated from Johne’s positive cow.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Persistence of Mycobacterium avium subsp. paratuberculosis (Map) in farm environments is not well understood. Previously we examined the ability of amoebae from a cow’s watering trough to sequester and enhance growth of Map and found that one amoeba species released vesicles containin...

  15. Comparative Transcriptional Analysis of Human Macrophages Exposed to Animal and Human isolates of Mycobacterium avium subspecies paratuberculosis with Diverse Genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Interactions between Mycobacterium avium subsp. paratuberculosis and host macrophages represent critical early events in the pathogenesis of Johne’s disease. We present here a genome-wide characterization of the transcriptional changes within macrophages in responses to different genotypes of M. par...

  16. A Novel Cell Wall Lipopeptide Is Important for Biofilm Formation and Pathogenicity of Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biofilm formation by pathogenic bacteria plays a key role in their pathogenesis. Previously, the pstA gene was shown to be involved in the virulence of Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne's disease in cattle and a potential risk factor for Crohn's d...

  17. ZAP-70, CTLA-4, and proximal T cell receptor signaling in cows infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Paratuberculosis is a chronic intestinal disease of ruminant animals caused by Mycobacterium avium subsp. paratuberculosis (MAP). A hallmark of paratuberculosis is a transition from a cell-mediated Th1 type response to a humoral Th2 response with the progression of disease from a subclinical to clin...

  18. How does a Mycobacterium change its spots? Applying molecular tools to track diverse strains of Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Defining genetic diversity in the wake of the release of several Mycobacterium avium subsp. paratuberculosis (MAP) genome sequences has become a major emphasis in the molecular biology and epidemiology of Johne’s disease research. These data can now be used to define the extent of strain diversity ...

  19. Development and Evaluation of a Variable-number Tandem Repeat (VNTR) Method for Subtyping of Mycobacterium avium subspecies paratuberculosis Isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (Map) is the causative agent of Johne’s disease in cattle and other ruminants. Because of the apparent ease by which Map can spread to susceptible animals within a dairy herd, a better understanding of the epidemiology of Map infections is required. In thi...

  20. Prevention of Mycobacterium avium subsp. paratuberculosis (MAP) infection in BALB/c mice by feeding probiotic Lactobacillus acidophilus NP-51

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to examine effects of feeding Lactobacillus acidophilus strain NP51 to mice challenged with Mycobacterium avium subspecies paratuberculosis (MAP). Mice were randomized to ten treatment groups; sentinels, control, heat-killed MAP, viable MAP, heat-killed NP51, viable ...

  1. Optimization of methods for the detection of Mycobacterium avium subsp. paratuberculosis in milk and colostrum of naturally infected dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP) is primarily shed into the feces but it has also been isolated from the milk and colostrum of cows. Because of this, there exists concern about transfer of the organism from dam to calf and about the prevalence of MAP in the milk supply. The prevalen...

  2. Optimization of methods for the detection of Mycobacterium avium subsp. paratuberculosis in milk and colostrum of naturally infected dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two decontamination chemicals, hexadecylpyridinium choride (HPC) and N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH), were compared for their efficacy of reducing the growth of non-specific microorganisms in milk while minimally affecting the recovery of Mycobacterium avium subsp. paratuberculosis ...

  3. ZAP-70, CTLA-4 and proximal T cell receptor signaling in cows infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Paratuberculosis is a chronic intestinal disease of ruminant animals caused by Mycobacterium avium subsp. paratuberculosis (MAP). A hallmark of paratuberculosis is a transition from a cell-mediated Th1 type response to a humoral Th2 response with the progression of disease from a subclinical to clin...

  4. Immunogenicity and protective efficacy of the Mycobacterium avium subsp. paratuberculosis attenuated mutants against challenge in a mouse model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease (JD), caused by Mycobacterium avium subsp. paratuberculosis (MAP), results in serious economic losses worldwide especially in cattle, sheep and goats. To control the impact of JD on the animal industry, an effective vaccine with minimal adverse effects is urgently required. In order ...

  5. Divergent cellular responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Infection of the host with Mycobacterium avium subsp. paratuberculosis (MAP) results in a chronic and progressive enteritis that traverses both subclinical and clinical stages. The mechanism(s) for the shift from asymptomatic subclinical disease state to advanced clinical disease are not fully under...

  6. A 38-kilobase pathogenicity island specific for Mycobacterium avium subsp. paratuberculosis encodes cell surface proteins expressed in the host.

    PubMed

    Stratmann, Janin; Strommenger, Birgit; Goethe, Ralph; Dohmann, Karen; Gerlach, Gerald-F; Stevenson, Karen; Li, Ling-Ling; Zhang, Qing; Kapur, Vivek; Bull, Tim J

    2004-03-01

    We have used representational difference analysis to identify a novel Mycobacterium avium subsp. paratuberculosis-specific ABC transporter operon (mpt), which comprises six open reading frames designated mptA to -F and is immediately preceded by two putative Fur boxes. Functional genomics revealed that the mpt operon is flanked on one end by a fep cluster encoding proteins involved in the uptake of Fe(3+) and on the other end by a sid cluster encoding non-ribosome-dependent heterocyclic siderophore synthases. Together these genes form a 38-kb M. avium subsp. paratuberculosis-specific locus flanked by an insertion sequence similar to IS1110. Expression studies using Western blot analyses showed that MptC is present in the envelope fraction of M. avium subsp. paratuberculosis. The MptD protein was shown to be surface exposed, using a specific phage (fMptD) isolated from a phage-peptide library, by differential screening of Mycobacterium smegmatis transformants. The phage fMptD-derived peptide could be used in a peptide-mediated capture PCR with milk from infected dairy herds, thereby showing surface-exposed expression of the MptD protein in the host. Together, these data suggest that the 38-kb locus constitutes an M. avium subsp. paratuberculosis pathogenicity island. PMID:14977927

  7. Analysis of Mycobacterium avium subspecies paratuberculosis mutant libraries reveals loci-dependent transposition biases and strategies to novel mutant discovery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of Johne’s disease, is one of the most important bacterial pathogens in ruminants. The lack of efficacious control measures demands a thorough understanding of MAP pathogenesis to develop new vaccines and diagnostic tests. The ge...

  8. Parturition invokes Changes in Peripheral Blood Mononuclear Cell Populations in Holstein Dairy Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Twenty-one multiparous and two primiparous Holstein cows were grouped according to infection status with Mycobacterium avium subsp. paratuberculosis (MAP), the causative microorganism for Johne’s disease (JD). The effect of parturition and infection on the percentages of CD4+, CD8+, and T-cells, B-...

  9. Accumulation of γ-aminobutyric acid by Enterococcus avium 9184 in scallop solution in a two-stage fermentation strategy.

    PubMed

    Yang, Haoyue; Xing, Ronge; Hu, Linfeng; Liu, Song; Li, Pengcheng

    2016-07-01

    In this study, a new bacterial strain having a high ability to produce γ-aminobutyric acid (GABA) was isolated from naturally fermented scallop solution and was identified as Enterococcus avium. To the best of our knowledge, this is the first study to prove that E. avium possesses glutamate decarboxylase activity. The strain was then mutagenized with UV radiation and was designated as E. avium 9184. Scallop solution was used as the culture medium to produce GABA. A two-stage fermentation strategy was applied to accumulate GABA. In the first stage, cell growth was regulated. Optimum conditions for cell growth were pH, 6.5; temperature, 37°C; and glucose concentration, 10 g·L(-1) . This produced a maximum dry cell mass of 2.10 g·L(-1) . In the second stage, GABA formation was regulated. GABA concentration reached 3.71 g·L(-1) at 96 h pH 6.0, 37°C and initial l-monosodium glutamate concentration of 10 g·L(-1) . Thus, compared with traditional one-stage fermentation, the two-stage fermentation significantly increased GABA accumulation. These results provide preliminary data to produce GABA using E. avium and also provide a new approach to process and utilize shellfish. PMID:26200650

  10. Comparison of fecal DNA extraction kits for the detection of Mycobacterium avium subsp. paratuberculosis by polymerase chain reaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Culture of Mycobacterium avium subsp. paratuberculosis (MAP) from feces has been considered the gold standard for the diagnosis of paratuberculosis for many years. However, direct fecal PCR is becoming more widely used today, demonstrating similar sensitivity and specificity to culture. To ensure ef...

  11. Survival of the Causative Agent of Johne’s Disease (Mycobacterium avium subsp. paratuberculosis) in Biofilms on Trough Materials

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The continued global increase in the number of cases of Johne’s disease among dairy cattle suggests that there remain hidden sources of contamination in the farm environment where susceptible animals may be routinely exposed to Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent o...

  12. Parturition Invokes Changes in Peripheral blood Mononuclear Cell Populations in Holstein Dairy Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is estimated to infect more than 22% of US dairy herds. Once infected, cows may remain in the asymptomatic subclinical state until a period of stress, such as parturition. Parturition has a major impact on the number of ...

  13. Prevention of Mycobacterium avium subsp. paratuberculosis (MAP) Infection in Balb/c Mice by Feeding Probiotic Lactobacillus acidophilus NP-51

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to examine effects of feeding Lactobacillus acidophilus strain NP51 to mice challenged with Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne’s disease. We hypothesized that feeding NP51 would increase Th-1 responses and decrease prog...

  14. Longitudinal data collection of Mycobacterium avium subspecies Paratuberculosis infections in dairy herds. Collection and use of observational data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Longitudinal infection data on Mycobacterium avium subspecies paratuberculosis (MAP) was collected on three dairy farms in Northeastern United States during approximately 10 years. Precise data on animal characteristics and animal location within farm were collected on these farms. Cows were followe...

  15. Prevention of Mycobacterium avium subsp. paratuberculosis Infection in BALB/c Mice by Feeding Lactobacillus acidophilus Strain NP-51

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The immune responses of 390 BALB/c mice fed the probiotic Lactobacillus acidophilus strain NP51® and infected with Mycobacterium avium subspecies paratuberculosis (MAP) were evaluated in a 6-month trial. Mice were randomized to nine treatment groups fed either viable- or heat-killed NP51 and inocula...

  16. Isolation of Mycobacterium avium subspecies paratuberculosis Reactive T-cells from Intestinal Biopsies of Crohn's Disease Patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crohn’s disease (CD) is a chronic granulomatous inflammation of the intestine. The etiology is still unknown. One hypothesis is that CD is caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP) in genetically predisposed individuals. MAP causes a similar disease in ruminants,...

  17. CD4 T Cells From Intestinal Biopsies of Crohn's Disease Patients React to Mycobacterium avium subspecies paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of Mycobacterium avium subspecies paratuberculosis (MAP) in Crohn’s disease (CD) remains controversial. One issue that has been raised is the lack of data showing a cellular immune response to MAP. Earlier studies have mostly focused on responses in peripheral blood which have several limit...

  18. Shedding of Mycobacterium avium subsp. paratuberculosis into milk and colostrum of naturally infected dairy cows over complete lactation cycles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The primary mode of transmission of Mycobacterium avium subsp. paratuberculosis (MAP) is fecal-oral. However, MAP is also shed into the milk and colostrum of infected cows. The objective of this study was to identify if an association exists between stage of MAP infection and days in lactation with ...

  19. Mediation of host immune responses after immunization of neonatal calves with a heat-killed Mycobacterium avium subsp. paratuberculosis vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major drawback of current whole-cell vaccines for Mycobacterium avium subsp. paratuberculosis(MAP) is the interference with diagnostic tests for bovine tuberculosis and paratuberculosis. The current study was designed to explore effects of immunization with a heat-killed whole cell vaccine (Mycop...

  20. Characterization of the inflammatory phenotype of Mycobacterium avium subspecies paratuberculosis using a novel cell culture passage model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the pathogenic mechanisms and host responses to Johne’s disease, a chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), is complicated by the multifaceted disease progression, late-onset host reaction, and the lack of ex vivo infection models ...

  1. Macrophage Transcriptional Response to Species-Adapted Mycobacterium avium subsp. Paratuberculosis Isolates: The Role of Pathogen Genotype in Host Response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The transcriptional response of human and bovine macrophages to Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) isolates from cattle and sheep were examined using DNA microarrays. M. paratuberculosis is the etiologic agent of Johne’s Disease, a chronic infection of ruminant anima...

  2. Identification and Functional Characterization of the Iron-dependent Regulator (IdeR) of Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mycobacterium avium subsp. paratuberculosis (MAP), a ruminant pathogen, has unique iron requirements based on the observation that it is mycobactin dependent for successful cultivation in vitro. Thus an elucidation of iron regulation in MAP is expected to provide an understanding of its survival in ...

  3. Proteome and Differential Expression Analysis of Membrane and Cytosolic Proteins from Mycobacterium avium subsp. paratuberculosis Strains K-10 and 187.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known of the protein expression in Mycobacterium avium subspecies paratuberculosis (MAP) and how this contributes to pathogenesis. In the present study, proteins from both outer membranes and cytosol were prepared from two strains of MAP; a laboratory-adapted strain K-10 and a recent isola...

  4. NlpC/P60 domain-containing proteins of Mycobacterium avium subspecies paratuberculosis that differentially bind and hydrolyze peptidoglycan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While intense research is being conducted to develop faster and more reliable methods for diagnosis of Johne’s disease, there are still significant knowledge gaps concerning the molecular function of Mycobacterium avium subspecies paratuberculosis proteins. Therefore, we describe atomic resolution ...

  5. Prevention of Mycobacterium avium subsp. paratuberculosis (MAP) infection in Balb/c mice by feeding probiotic Lactobacillus acidophilus NP-51

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to examine effects of feeding Lactobacillus acidophilus strain NP51 to mice challenged with Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne’s disease. We hypothesized that feeding NP51 would increase Th-1 responses and decrease prog...

  6. Evaluation of eight live attenuated vaccine candidates for protection against challenge with virulent Mycobacterium avium subspecies paratuberculosis in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is caused by Mycobacterium avium subsp. paratuberculosis (MAP), which results in serious economic losses worldwide in farmed livestock such as cattle, sheep and goats. To control this disease, an effective vaccine with minimal adverse effects is needed. In order to identify a live va...

  7. Immune Responses in Mice to Mycobacterium avium subsp. paratuberculosis Following Vaccination with a Novel 74F Recombinant Polyprotein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s Disease (JD) is a chronic infectious disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Here, we report the cloning and expression of a 74kDa recombinant polyprotein (Map74F) and its protective efficacy against MAP infection in mice. Map74F was generated by th...

  8. Results of Multiple Diagnostic Tests for Mycobacterium avium subsp. paratuberculosis in Patients with Inflammatory Bowel Disease and in Controls

    PubMed Central

    Collins, Michael T.; Lisby, Gorm; Moser, Claus; Chicks, Debra; Christensen, Steen; Reichelderfer, Mark; Høiby, Niels; Harms, Bruce A.; Thomsen, Ole Ø.; Skibsted, Ulrik; Binder, Vibeke

    2000-01-01

    Mycobacterium avium subsp. paratuberculosis has been incriminated as a cause of Crohn's disease (CD); however, studies to date have been relatively small and generally only used a single diagnostic assay. The objective of the study was to reexamine the association of M. avium subsp. paratuberculosis and CD using multiple diagnostic tests. Five methods were used to detect M. avium subsp. paratuberculosis infections in 439 inflammatory bowel disease (IBD) patients and 324 control subjects in the United States and Denmark. Most assays were adaptations of diagnostic tests for this infection performed routinely on animals. PCR for IS900, a genetic element unique to M. avium subsp. paratuberculosis, was positive significantly more often on resected bowel and lymph node tissues from CD patients (19.0%) and ulcerative colitis (UC) patients (26.2%) than from controls (6.3%) (P < 0.05). Positive IS900 PCR results occurred more often in U.S. than in Danish IBD patients, 32.0 versus 13.3% (P = 0.025). The majority of Danish patients were bacillus Calmette-Guérin (Mycobacterium bovis BCG) vaccinated (CD, 77.5%; UC, 86.6%; controls, 83.0%) whereas none of the U.S. patients with IBD and only 2% of U.S. controls were vaccinated. Among Danish IBD patients, positive PCR findings were four times more common among subjects who were not BCG vaccinated (33.3%) than among BCG vaccinates (8.8%, P = 0.02). Culture of the same tissues tested by PCR using modified BACTEC 12B medium failed to grow M. avium subsp. paratuberculosis from patients or controls. U.S. CD patients had the highest serological evidence (enzyme-linked immunosorbent assay [ELISA] for serum antibodies) of M. avium subsp. paratuberculosis infection (20.7% of patients positive) which was higher than for all UC patients studied (6.1%) or healthy controls (3.8%, P < 0.005). Among Danish patients alone, however, no significant differences in rates of ELISA-positive results among CD, UC, or control patients were found. For 181

  9. Shared Mycobacterium avium Genotypes Observed among Unlinked Clinical and Environmental Isolates

    PubMed Central

    Weigel, Kris M.; Yakrus, Mitchell A.; Becker, Annie L.; Chen, Hui-Ling; Fridley, Gina; Sikora, Arthur; Speake, Cate; Hilborn, Elizabeth D.; Pfaller, Stacy

    2013-01-01

    Our understanding of the sources of Mycobacterium avium infection is partially based on genotypic matching of pathogen isolates from cases and environmental sources. These approaches assume that genotypic identity is rare in isolates from unlinked cases or sources. To test this assumption, a high-resolution PCR-based genotyping approach, large-sequence polymorphism (LSP)-mycobacterial interspersed repetitive unit–variable-number tandem repeat (MIRU-VNTR), was selected and used to analyze clinical and environmental isolates of M. avium from geographically diverse sources. Among 127 clinical isolates from seven locations in North America, South America, and Europe, 42 genotypes were observed. Among 12 of these genotypes, matches were seen in isolates from apparently unlinked patients in two or more geographic locations. Six of the 12 were also observed in environmental isolates. A subset of these isolates was further analyzed by alternative strain genotyping methods, pulsed-field gel electrophoresis and MIRU-VNTR, which confirmed the existence of geographically dispersed strain genotypes. These results suggest that caution should be exercised in interpreting high-resolution genotypic matches as evidence for an acquisition event. PMID:23851084

  10. Relatedness of Mycobacterium avium subspecies hominissuis clinical isolates of human and porcine origins assessed by MLVA.

    PubMed

    Leão, Célia; Canto, Ana; Machado, Diana; Sanches, Ilda Santos; Couto, Isabel; Viveiros, Miguel; Inácio, João; Botelho, Ana

    2014-09-17

    Mycobacterium avium subsp. hominissuis (MAH) is an important opportunistic pathogen, infecting humans and animals, notably pigs. Several methods have been used to characterize MAH strains. RFLP and PFGE typing techniques have been used as standard methods but are technically demanding. In contrast, the analysis of VNTR loci is a simpler, affordable and highly reliable PCR-based technique, allowing a numerical and reproductive digitalization of typing data. In this study, the analysis of Mycobacterium avium tandem repeats (MATRs) loci was adapted to evaluate the genetic diversity of epidemiological unrelated MAH clinical strains of human (n=28) and porcine (n=69) origins, collected from diverse geographical regions across mainland Portugal. These MAH isolates were found to be genetically diverse and genotypes are randomly distributed across the country. Some of the human strains shared identical VNTR profiles with porcine isolates. Our study shows that the VNTR genotyping using selected MATR loci is a useful analysis technique for assessing the genetic diversity of MAH isolates from Portugal. This typing method could be successfully applied in other countries toward the implementation of a worldwide open-access database of MATR-VNTR profiles of MAH isolates, allowing a better assessment of the global epidemiology traits of this important pathogenic species. PMID:25085520

  11. Detection of Mycobacterium avium subsp. paratuberculosis in Infected Tissues by New Species-Specific Immunohistological Procedures

    PubMed Central

    Coetsier, Christophe; Havaux, Xavier; Mattelard, Francois; Sadatte, Sanaa; Cormont, Francoise; Buergelt, Klaus; Limbourg, Bernard; Latinne, Dominique; Bazin, Herve; Denef, Jean-Francois; Cocito, Carlo

    1998-01-01

    We have previously described the cloning and sequencing of a gene portion coding for the terminal part of a 34-kDa protein of Mycobacterium avium subsp. paratuberculosis, the etiological agent of Johne’s disease (P. Gilot, M. De Kesel, L. Machtelinckx, M. Coene, and C. Cocito, J. Bacteriol. 175:4930–4935, 1993). The recombinant polypeptide (a362) carries species-specific B-cell epitopes which do not cross-react with other mycobacterial pathogens (M. De Kesel, P. Gilot, M.-C. Misonne, M. Coene, and C. Cocito, J. Clin. Microbiol. 31:947–954, 1993). The present work describes the preparation of polyclonal and monoclonal antibodies directed against a362 and the use of these immunoglobulins for histopathological diagnosis of Johne’s disease. The new immunohistological procedures herewith detailed proved to be able to identify M. avium subsp. paratuberculosis antigens in the intestinal tissues and lymph nodes of cattle affected by either the paucibacillary or pluribacillary form of the disease. They yielded negative responses not only with healthy animals but also with those affected by tuberculosis (Mycobacterium bovis). Both immunohistological procedures proved to be as sensitive as or more sensitive than Ziehl-Neelsen staining and, in addition, to be endowed with species specificity. PMID:9665946

  12. Differential Immune Responses of Red Deer (Cervus elaphus) following Experimental Challenge with Mycobacterium avium subsp. paratuberculosis▿

    PubMed Central

    Robinson, Mark; O'Brien, Rory; Mackintosh, Colin; Griffin, Frank

    2008-01-01

    Immune responses of red deer (Cervus elaphus) that presented with different levels of paucibacillary pathology were profiled to detail immune changes during the progression of Johne's disease. Immune responses were monitored using an immunoglobulin G1 (IgG1) antibody enzyme-linked immunosorbent assay (ELISA), a gamma interferon (IFN-γ) ELISA, and flow cytometry. Animals in the study were divided into outcome groups postmortem according to disease severity. All animals mounted IgG1 antibody and IFN-γ responses to both the vaccination and experimental challenges. The Mycobacterium avium subsp. paratuberculosis-specific IgG1 antibody responses in the challenged group showed marked differences between infected and severely diseased animals. Slightly higher IFN-γ responses were seen in infected animals compared with severely diseased animals. No significant changes were seen in the phenotype of lymphocyte populations investigated. Vaccination with killed M. avium subsp. paratuberculosis in mineral oil adjuvant reduced the level of severe disease; however, it obscured immunological differences between the infected and severely diseased groups. This suggests protection is not exclusively mediated via the presence of a type 1 response and, furthermore, the presence of a type 2 response is compatible with protection. These profiles provide information on the different immune processes in Johne's disease progression. PMID:18400974

  13. Environmental Survival of Mycobacterium avium subsp. paratuberculosis in Different Climatic Zones of Eastern Australia

    PubMed Central

    Begg, Douglas J.; Dhand, Navneet K.; Watt, Bruce; Whittington, Richard J.

    2014-01-01

    The duration of survival of both the S and C strains of Mycobacterium avium subsp. paratuberculosis in feces was quantified in contrasting climatic zones of New South Wales, Australia, and detailed environmental temperature data were collected. Known concentrations of S and C strains in feces placed on soil in polystyrene boxes were exposed to the environment with or without the provision of shade (70%) at Bathurst, Armidale, Condobolin, and Broken Hill, and subsamples taken every 2 weeks were cultured for the presence of M. avium subsp. paratuberculosis. The duration of survival ranged from a minimum of 1 week to a maximum of 16 weeks, and the provision of 70% shade was the most important factor in extending the survival time. The hazard of death for exposed compared to shaded samples was 20 and 9 times higher for the S and C strains, respectively. Site did not affect the survival of the C strain, but for the S strain, the hazard of death was 2.3 times higher at the two arid zone sites (Broken Hill and Condobolin) than at the two temperate zone sites (Bathurst and Armidale). Temperature measurements revealed maximum temperatures exceeding 60°C and large daily temperature ranges at the soil surface, particularly in exposed boxes. PMID:24463974

  14. About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.

    PubMed

    Kaellis, Eugene

    2006-01-01

    Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non

  15. Suspicion of Mycobacterium avium subsp. paratuberculosis transmission between cattle and wild-living red deer (Cervus elaphus) by multitarget genotyping.

    PubMed

    Fritsch, Isabel; Luyven, Gabriele; Köhler, Heike; Lutz, Walburga; Möbius, Petra

    2012-02-01

    Multitarget genotyping of the etiologic agent Mycobacterium avium subsp. paratuberculosis is necessary for epidemiological tracing of paratuberculosis (Johne's disease). The study was undertaken to assess the informative value of different typing techniques and individual genome markers by investigation of M. avium subsp. paratuberculosis transmission between wild-living red deer and farmed cattle with known shared habitats. Fifty-three M. avium subsp. paratuberculosis type II isolates were differentiated by short sequence repeat analysis (SSR; 4 loci), mycobacterial interspersed repetitive-unit-variable-number tandem-repeat analysis (MIRU-VNTR; 8 loci), and restriction fragment length polymorphism analysis based on IS900 (IS900-RFLP) using BstEII and PstI digestion. Isolates originated from free-living red deer (Cervus elaphus) from Eifel National Park (n = 13), six cattle herds living in the area of this park (n = 23), and five cattle herds without any contact with these red deer (n = 17). Data based on individual herds and genotypes verified that SSR G2 repeats did not exhibit sufficient stability for epidemiological studies. Two common SSR profiles (without G2 repeats), nine MIRU-VNTR patterns, and nine IS900-RFLP patterns were detected, resulting in 17 genotypes when combined. A high genetic variability was found for red deer and cattle isolates within and outside Eifel National Park, but it was revealed only by combination of different typing techniques. Results imply that within this restricted area, wild-living and farmed animals maintain a reservoir for specific M. avium subsp. paratuberculosis genotypes. No host relation of genotypes was obtained. Results suggested that four genotypes had been transmitted between and within species and that one genotype had been transmitted between cattle herds only. Use of multitarget genotyping for M. avium subsp. paratuberculosis type II strains and sufficiently stable genetic markers is essential for reliable

  16. Suspicion of Mycobacterium avium subsp. paratuberculosis Transmission between Cattle and Wild-Living Red Deer (Cervus elaphus) by Multitarget Genotyping

    PubMed Central

    Fritsch, Isabel; Luyven, Gabriele; Köhler, Heike; Lutz, Walburga

    2012-01-01

    Multitarget genotyping of the etiologic agent Mycobacterium avium subsp. paratuberculosis is necessary for epidemiological tracing of paratuberculosis (Johne's disease). The study was undertaken to assess the informative value of different typing techniques and individual genome markers by investigation of M. avium subsp. paratuberculosis transmission between wild-living red deer and farmed cattle with known shared habitats. Fifty-three M. avium subsp. paratuberculosis type II isolates were differentiated by short sequence repeat analysis (SSR; 4 loci), mycobacterial interspersed repetitive-unit–variable-number tandem-repeat analysis (MIRU-VNTR; 8 loci), and restriction fragment length polymorphism analysis based on IS900 (IS900-RFLP) using BstEII and PstI digestion. Isolates originated from free-living red deer (Cervus elaphus) from Eifel National Park (n = 13), six cattle herds living in the area of this park (n = 23), and five cattle herds without any contact with these red deer (n = 17). Data based on individual herds and genotypes verified that SSR G2 repeats did not exhibit sufficient stability for epidemiological studies. Two common SSR profiles (without G2 repeats), nine MIRU-VNTR patterns, and nine IS900-RFLP patterns were detected, resulting in 17 genotypes when combined. A high genetic variability was found for red deer and cattle isolates within and outside Eifel National Park, but it was revealed only by combination of different typing techniques. Results imply that within this restricted area, wild-living and farmed animals maintain a reservoir for specific M. avium subsp. paratuberculosis genotypes. No host relation of genotypes was obtained. Results suggested that four genotypes had been transmitted between and within species and that one genotype had been transmitted between cattle herds only. Use of multitarget genotyping for M. avium subsp. paratuberculosis type II strains and sufficiently stable genetic markers is essential for reliable

  17. Infection with Mycobacterium avium subsp. paratuberculosis Results in Rapid Interleukin-1β Release and Macrophage Transepithelial Migration

    PubMed Central

    Lamont, Elise A.; O'Grady, Scott M.; Davis, William C.; Eckstein, Torsten

    2012-01-01

    Pathogen processing by the intestinal epithelium involves a dynamic innate immune response initiated by pathogen-epithelial cell cross talk. Interactions between epithelium and Mycobacterium avium subsp. paratuberculosis have not been intensively studied, and it is currently unknown how the bacterium-epithelial cell cross talk contributes to the course of infection. We hypothesized that M. avium subsp. paratuberculosis harnesses host responses to recruit macrophages to the site of infection to ensure its survival and dissemination. We investigated macrophage recruitment in response to M. avium subsp. paratuberculosis using a MAC-T bovine macrophage coculture system. We show that M. avium subsp. paratuberculosis infection led to phagosome acidification within bovine epithelial (MAC-T) cells as early as 10 min, which resulted in upregulation of interleukin-1β (IL-1β) at transcript and protein levels. Within 10 min of infection, macrophages were recruited to the apical side of MAC-T cells. Inhibition of phagosome acidification or IL-1β abrogated this response, while MCP-1/CCL-2 blocking had no effect. IL-1β processing was dependent upon Ca2+ uptake from the extracellular medium and intracellular Ca2+ oscillations, as determined by EGTA and BAPTA-AM [1,2-bis(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetrakis (acetoxymethyl ester)] treatments. Thus, M. avium subsp. paratuberculosis is an opportunist that takes advantage of extracellular Ca2+-dependent phagosome acidification and IL-1β processing in order to efficiently transverse the epithelium and enter its niche—the macrophage. PMID:22778093

  18. Induction of B Cell Responses upon Experimental Infection of Neonatal Calves with Mycobacterium avium subsp. paratuberculosis ▿

    PubMed Central

    Stabel, J. R.; Bannantine, J. P.; Eda, Shigetoshi; Robbe-Austerman, S.

    2011-01-01

    The objective of this study was to determine if experimental infection of neonatal calves with Mycobacterium avium subsp. paratuberculosis would invoke changes in the percentages of total B cells in the peripheral blood mononuclear cell population and of subpopulations of B cells as determined by CD5, CD25, and CD45RO markers during a 12-month period. Experimental infection groups included control (noninfected), oral (infected with M. avium subsp. paratuberculosis strain K-10), oral/DXM (pretreatment with dexamethasone before oral inoculation), i.p. (intraperitoneal inoculation), and oral/M (oral inoculation with mucosal scrapings from a cow with clinical disease) groups. Over the course of the study, the percentages of total B cells in nonstimulated and antigen-stimulated cell cultures increased for oral and i.p. group calves, with the highest percentages noted at 3 and 6 months. Oral/M group calves had increased percentages of activated B cells, as determined by CD5dim and CD5bright markers, at 9 and 12 months. Experimental infection by all methods resulted in increased expression of CD25+ and CD45RO+ B cells early in the study, but the most significant results were observed at 12 months for oral/DXM and oral/M group calves. Immunoblot analyses with a whole-cell sonicate of M. avium subsp. paratuberculosis demonstrated the most reactivity with sera from i.p. group calves and the least reactivity with sera from oral group calves. Further evidence of M. avium subsp. paratuberculosis-specific antibody responses in the i.p. group calves was demonstrated using the ethanol vortex enzyme-linked immunosorbent assay (EvELISA) method. In summary, an induction of B cell responses was noted after experimental infection with M. avium subsp. paratuberculosis, with differences in responses noted according to the method of experimental inoculation. PMID:21543587

  19. Effect of Feeding Heat-Treated Colostrum on Preweaning Health, Economics and Transmission of Mycobacterium avium subsp. paratuberculosis in Dairy Calves: Phase I

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction and Objectives Colostrum provides protective immunoglobulins (Ig) and nutrients essential for calf health and performance. However, colostrum may also represent an early source of pathogen exposure including Mycobacterium avium subsp. paratuberculosis (MAP). Pilot studies have suggest...

  20. Genome Sequences of Four Strains of Mycobacterium avium subsp. hominissuis, Isolated from Swine and Humans, Differing in Virulence in a Murine Intranasal Infection Model.

    PubMed

    Bruffaerts, N; Vluggen, C; Duytschaever, L; Mathys, V; Saegerman, C; Chapeira, O; Huygen, K

    2016-01-01

    This paper announces the genome sequences of four strains of Mycobacterium avium subsp. hominissuis, isolated from cases of lymphadenopathy in swine and humans, differing in virulence in a murine intranasal infection model. PMID:27313293

  1. Modulation of Cytokine Expression and Lymphocyte Subsets During the Periparturient Period in Dairy Cows Naturally Infected with Mycobacterium avium subsp. paratuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    On-farm observations suggest that dairy cows infected with Mycobacterium avium subsp. paratuberculosis (MAP) may demonstrate increased signs of clinical disease during the weeks following parturition. To date, limited research is available characterizing host immunity in periparturient dairy cows ...

  2. Genome Sequences of Four Strains of Mycobacterium avium subsp. hominissuis, Isolated from Swine and Humans, Differing in Virulence in a Murine Intranasal Infection Model

    PubMed Central

    Bruffaerts, N.; Vluggen, C.; Duytschaever, L.; Mathys, V.; Saegerman, C.; Chapeira, O.

    2016-01-01

    This paper announces the genome sequences of four strains of Mycobacterium avium subsp. hominissuis, isolated from cases of lymphadenopathy in swine and humans, differing in virulence in a murine intranasal infection model. PMID:27313293

  3. Treatment with antibiotics is detrimental to the recovery of viable Mycobacterium avium subsp. paratuberculosis cultured from milk and colostrum of dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic cocktails are frequently used as secondary decontaminants prior to the culture of Mycobacterium avium subsp. paratuberculosis (MAP). This study investigated whether secondary incubation with an antibiotic cocktail containing vancomycin, nalidixic acid, and amphotericin B after primary exp...

  4. Enabling a New Planning and Scheduling Paradigm

    NASA Technical Reports Server (NTRS)

    Jaap, John; Davis, Elizabeth

    2004-01-01

    without the intervention of a scheduling expert. The algorithm is tuned for the constraint hierarchies and the complex temporal relationships provided by the modeling schema. It has an extensive search algorithm which can exploit timing flexibilities and constraint and relationship options. (3) A web-based architecture allows multiple remote users to simultaneously model science and technology requirements and other users to model vehicle and hardware characteristics. The architecture allows the users to submit scheduling requests directly to the scheduling engine and immediately see the results. These three components are integrated so that science and technology experts with no knowledge of the vehicle or hardware subsystems and no knowledge of the internal workings of the scheduling engine have the ability to build and submit scheduling requests and see the results. The immediate feedback will hone the users' modeling skills and ultimately enable them to produce the desired timeline. This paper summarizes the three components of the enabling technology and describes how this technology would make a new paradigm possible.

  5. Bayesian evidence and predictivity of the inflationary paradigm

    NASA Astrophysics Data System (ADS)

    Gubitosi, Giulia; Lagos, Macarena; Magueijo, João; Allison, Rupert

    2016-06-01

    In this paper we consider the issue of paradigm evaluation by applying Bayes' theorem along the following nested hierarchy of progressively more complex structures: i) parameter estimation (within a model), ii) model selection and comparison (within a paradigm), iii) paradigm evaluation. In such a hierarchy the Bayesian evidence works both as the posterior's normalization at a given level and as the likelihood function at the next level up. Whilst raising no objections to the standard application of the procedure at the two lowest levels, we argue that it should receive a considerable modification when evaluating paradigms, when testability and fitting data are equally important. By considering toy models we illustrate how models and paradigms that are difficult to falsify are always favoured by the Bayes factor. We argue that the evidence for a paradigm should not only be high for a given dataset, but exceptional with respect to what it would have been, had the data been different. With this motivation we propose a measure which we term predictivity, as well as a prior to be incorporated into the Bayesian framework, penalising unpredictivity as much as not fitting data. We apply this measure to inflation seen as a whole, and to a scenario where a specific inflationary model is hypothetically deemed as the only one viable as a result of information alien to cosmology (e.g. Solar System gravity experiments, or particle physics input). We conclude that cosmic inflation is currently hard to falsify, but that this could change were external/additional information to cosmology to select one of its many models. We also compare this state of affairs to bimetric varying speed of light cosmology.

  6. A new paradigm in optimal missile guidance

    NASA Astrophysics Data System (ADS)

    Morgan, Robert W.

    2007-12-01

    This dissertation investigates advanced concepts in terminal missile guidance. The terminal phase of missile guidance usually lasts less than ten seconds and calls for very accurate maneuvering to ensure intercept. Technological advancements have produced increasingly sophisticated threats that greatly reduce the effectiveness of traditional approaches to missile guidance. Because of this, terminal missile guidance is, and will remain, an important and active area of research. The complexity of the problem and the desire for an optimal solution has resulted in researchers focusing on simplistic, usually linear, models. The fruit of these endeavors has resulted in some of the world's most advanced weapons systems. Even so, the resulting guidance schemes cannot possibly counter the evolving threats that will push the system outside the linear envelope for which they were designed. The research done in this dissertation greatly extends previous research in the area of optimal missile guidance. Herein it is shown that optimal missile guidance is fundamentally a pairing of an optimal guidance strategy and an optimal control strategy. The optimal guidance strategy is determined from a missile's information constraints, which are themselves largely determined from the missile's sensors. The optimal control strategy is determined by the missile's control constraints, and works to achieve a specified guidance strategy. This dichotomy of missile guidance is demonstrated by showing that missiles having different control constraints utilize the same guidance strategy so long as the information constraints are the same. This concept has hitherto been unrecognized because of the difficulty in developing an optimal control for the nonlinear set of equations that result from control constraints. Having overcome this difficulty by indirect means, evidence of the guidance strategy paradigm emerged. The guidance strategy paradigm is used to develop two advanced guidance laws. The new

  7. Testing paradigms of ecosystem change under climate warming in Antarctica.

    PubMed

    Melbourne-Thomas, Jessica; Constable, Andrew; Wotherspoon, Simon; Raymond, Ben

    2013-01-01

    Antarctic marine ecosystems have undergone significant changes as a result of human activities in the past and are now responding in varied and often complicated ways to climate change impacts. Recent years have seen the emergence of large-scale mechanistic explanations-or "paradigms of change"-that attempt to synthesize our understanding of past and current changes. In many cases, these paradigms are based on observations that are spatially and temporally patchy. The West Antarctic Peninsula (WAP), one of Earth's most rapidly changing regions, has been an area of particular research focus. A recently proposed mechanistic explanation for observed changes in the WAP region relates changes in penguin populations to variability in krill biomass and regional warming. While this scheme is attractive for its simplicity and chronology, it may not account for complex spatio-temporal processes that drive ecosystem dynamics in the region. It might also be difficult to apply to other Antarctic regions that are experiencing some, though not all, of the changes documented for the WAP. We use qualitative network models of differing levels of complexity to test paradigms of change for the WAP ecosystem. Importantly, our approach captures the emergent effects of feedback processes in complex ecological networks and provides a means to identify and incorporate uncertain linkages between network elements. Our findings highlight key areas of uncertainty in the drivers of documented trends, and suggest that a greater level of model complexity is needed in devising explanations for ecosystem change in the Southern Ocean. We suggest that our network approach to evaluating a recent and widely cited paradigm of change for the Antarctic region could be broadly applied in hypothesis testing for other regions and research fields. PMID:23405116

  8. Production and proteomic characterisation of purified protein derivative from Mycobacterium avium subsp. paratuberculosis

    PubMed Central

    2012-01-01

    Background Effective diagnosis of Johne's disease (JD), particularly at the stage of early subclinical infection, remains one of the greatest challenges for the control of JD worldwide. The IFN-γ test of cell mediated immunity is currently one of the most suitable diagnostics for subclinical infections, however a major limitation of this test is the lack of a standardised purified protein derivative (PPD) antigen (also referred to as Johnin PPD or PPDj). While attempting to replace PPDj with more specific individual antigens is an attractive proposition, bacterial culture derived PPDj remains the most effective antigen preparation for the diagnosis of subclinical JD. It may be possible to increase the reproducibility and specificity of PPDj preparations by further characterising and standardising the PPDj production. Results Using a standardised protocol, five in-house preparations of PPDj were prepared from cultures of Mycobacterium avium subsp. paratuberculosis (MAP). Compared to PPDs obtained from other institutes/laboratories, these preparations appeared to perform similarly well in the IFN-γ test. Although the broad proteomic composition of all PPDj preparations was remarkably similar, the absolute abundance of individual proteins varied markedly between preparations. All PPDj preparations contained common immunogenic proteins which were also observed in PPD preparations from Mycobacterium avium subsp. avium (PPDa) and Mycobacterium bovis (PPDb). Temporal difference in protein secretion of in vitro cultured MAP was observed between 20 and 34 weeks suggesting that the age of MAP culture used for PPDj preparations may markedly influence PPDj composition. Conclusions This study describes a protocol for the production of PPDj and its subsequent proteomic characterisation. The broad proteomic composition of different preparations of PPDj was, for the most part, highly similar. Compositional differences between PPDj preparations were found to be a direct

  9. Innate defensive behaviour and panic-like reactions evoked by rodents during aggressive encounters with Brazilian constrictor snakes in a complex labyrinth: behavioural validation of a new model to study affective and agonistic reactions in a prey versus predator paradigm.

    PubMed

    Guimarães-Costa, Raquel; Guimarães-Costa, Maria Beatriz; Pippa-Gadioli, Leonardo; Weltson, Alfredo; Ubiali, Walter Adriano; Paschoalin-Maurin, Tatiana; Felippotti, Tatiana Tocchini; Elias-Filho, Daoud Hibrahim; Laure, Carlos Júlio; Coimbra, Norberto Cysne

    2007-09-15

    Defensive behaviour has been extensively studied, and non-invasive methodologies may be interesting approaches to analyzing the limbic system function as a whole. Using experimental models of animals in the state of anxiety has been fundamental in the search for new anxiolytic and antipanic compounds. The aim of this present work is to examine a new model for the study of affective behaviour, using a complex labyrinth consisting of an arena and galleries forming a maze. Furthermore, it aims to compare the defensive behaviour of Wistar rats, Mongolian gerbils and golden hamsters in a complex labyrinth, as well as the defensive behaviour of Meriones unguiculatus in aggressive encounters with either Epicrates cenchria assisi or Boa constrictor amarali in this same model. Among species presently studied, the Mongolian gerbils showed better performance in the exploration of both arena and galleries of the labyrinth, also demonstrating less latency in finding exits of the galleries. This increases the possibility of survival, as well as optimizes the events of encounter with the predator. The duration of alertness and freezing increased during confrontation with living Epicrates, as well as the duration of exploratory behaviour in the labyrinth. There was an increase in the number of freezing and alertness behaviours, as well as in duration of alertness during confrontations involving E.c. assisi, compared with behavioural reactions elicited by jirds in presence of B.c. amarali. Interestingly, the aggressive behaviour of Mongolian gerbils was more prominent against B.c. amarali compared with the other Boidae snake. E.c. assisi elicited more offensive attacks and exhibited a greater time period of body movement than B.c. amarali, which spent more time in the arena and in defensive immobility than the E.c. assisi. Considering that jirds evoked more fear-like reaction in contact with E.c. assisi, a fixed E.c. assisi kept in a hermetically closed acrylic box was used as

  10. Differential Paradigms in Animal Models of Sepsis.

    PubMed

    Kingsley, S Manoj Kumar; Bhat, B Vishnu

    2016-09-01

    Sepsis is a serious clinical problem involving complex mechanisms which requires better understanding and insight. Animal models of sepsis have played a major role in providing insight into the complex pathophysiology of sepsis. There have been various animal models of sepsis with different paradigms. Endotoxin, bacterial infusion, cecal ligation and puncture, and colon ascendens stent peritonitis models are the commonly practiced methods at present. Each of these models has their own advantages and also confounding factors. We have discussed the underlying mechanisms regulating each of these models along with possible reasons why each model failed to translate into the clinic. In animal models, the timing of development of the hemodynamic phases and the varied cytokine patterns could not accurately resemble the progression of clinical sepsis. More often, the exuberant and transient pro-inflammatory cytokine response is only focused in most models. Immunosuppression and apoptosis in the later phase of sepsis have been found to cause more damage than the initial acute phase of sepsis. Likewise, better understanding of the existing models of sepsis could help us create a more relevant model which could provide solution to the currently failed clinical trials in sepsis. PMID:27432263

  11. Think globally, research locally: paradigms and place in agroecological research.

    PubMed

    Reynolds, Heather L; Smith, Alex A; Farmer, James R

    2014-10-01

    Conducting science for practical ends implicates scientists, whether they wish it or not, as agents in social-ecological systems, raising ethical, economic, environmental, and political issues. Considering these issues helps scientists to increase the relevance and sustainability of research outcomes. As we rise to the worthy call to connect basic research with food production, scientists have the opportunity to evaluate alternative food production paradigms and consider how our research funds and efforts are best employed. In this contribution, we review some of the problems produced by science conducted in service of industrial agriculture and its associated economic growth paradigm. We discuss whether the new concept of "ecological intensification" can rescue the industrial agriculture/growth paradigm and present an emerging alternative paradigm of decentralized, localized, biodiversity-promoting agriculture for a steady-state economy. This "custom fit" agriculture engages constructively with complex and highly localized ecosystems, and we draw from examples of published work to demonstrate how ecologists can contribute by using approaches that acknowledge local agricultural practices and draw on community participation. PMID:25326612

  12. Evidence for a Novel Gene Expression Program in Peripheral Blood Mononuclear Cells from Mycobacterium avium subsp. paratuberculosis-Infected Cattle

    PubMed Central

    Coussens, Paul M.; Colvin, Christopher J.; Rosa, Guilherme J. M.; Perez Laspiur, Juliana; Elftman, Michael D.

    2003-01-01

    A bovine-specific cDNA microarray system was used to compare gene expression profiles of peripheral blood mononuclear cells (PBMCs) from control uninfected (n = 4) and Johne's disease-positive (n = 6) Holstein cows. Microarray experiments were designed so that for each animal, a direct comparison was made between PBMCs stimulated in vitro with Mycobacterium avium subsp. paratuberculosis and PBMCs stimulated with phosphate-buffered saline (nil-stimulated PBMCs). As expected, M. avium subsp. paratuberculosis stimulation of infected cow PBMCs enhanced expression of gamma interferon transcripts. In addition, expression of 15 other genes was significantly affected (>1.25-fold change; P < 0.05) by in vitro stimulation with M. avium subsp. paratuberculosis. Similar treatment of control cow PBMCs with M. avium subsp. paratuberculosis resulted in significant changes in expression of 13 genes, only 2 of which were also affected in PBMCs from the infected cow PBMCs. To compare gene expression patterns in the two cow infection groups (infected cows and uninfected cows), a mixed-model analysis was performed with the microarray data. This analysis indicated that there were major differences in the gene expression patterns between cells isolated from the two groups of cows, regardless of in vitro stimulation. A total of 86 genes were significantly differentially expressed (P < 0.01) in M. avium subsp. paratuberculosis-stimulated PBMCs from infected cows compared to expression in similarly treated PBMCs from control cows. Surprisingly, a larger number of genes (110 genes) were also found to be significantly differentially expressed (P < 0.01) in nil-stimulated cells from the two infection groups. The expression patterns of selected genes were substantiated by quantitative real-time reverse transcriptase PCR. Flow cytometric analysis indicated that there were no gross differences in the relative populations of major immune cell types in PBMCs from infected and control cows. Thus

  13. [Possible association between Mycobacterium avium subsp paratuberculosis infection and Crohn's disease].

    PubMed

    Retamal, Patricio; Beltrán, Caroll; Abalos, Pedro; Quera, Rodrigo; Hermoso, Marcela

    2011-06-01

    Paratuberculosis is a chronic intestinal disease of animals caused by Mycobacterium avium subsp. paratuberculosis (MAP), which has some pathological features similar to Crohn's disease (CD) in humans. The presence of MAP in food for human consumption and in affected tissues of patients with CD has been detected. Therefore, a causal association between this microorganism and the disease in humans, has been postulated. However, several related studies have failed to confirm this hypothesis and the scientific acceptance of MAP as a zoonotic agent remains controversial. This review presents the main findings related to this issue, contrasting evidences for and against an association between MAP and CD. The need to promote national studies focusing on this area is suggested. PMID:22051762

  14. Mycobacterium avium ss paratuberculosis-associated diseases: piecing the Crohn's puzzle together.

    PubMed

    Gitlin, Laura; Borody, Thomas Julius; Chamberlin, William; Campbell, Jordana

    2012-09-01

    The relation of Mycobacterium avium ss paratuberculosis (MAP) to Crohn's Disease (CD) and other MAP-associated conditions remains controversial. New data, coupled with the analogous Helicobacter pylori (H. pylori) story, has permitted us to piece together the MAP puzzle and move forward with a more scientific way of treating inflammatory bowel disease, particularly CD. As infection moves centre stage in inflammatory bowel disease, the dated "aberrant reaction" etiology has lost scientific credibility. Now, our growing understanding of MAP-associated diseases demands review and articulation. We focus here on (1) the concept of MAP-associated diseases; (2) causality, Johne Disease, the "aberrant reaction" hypothesis; and (3) responses to published misconceptions questioning MAP as a pathogen in CD. PMID:22858515

  15. Mycobacterium avium subsp. paratuberculosis sheep strains isolated from Cyprus sheep and goats.

    PubMed

    Liapi, M; Botsaris, G; Slana, I; Moravkova, M; Babak, V; Avraam, M; Di Provvido, A; Georgiadou, S; Pavlik, I

    2015-04-01

    Paratuberculosis, caused by Mycobacterium avium subsp. paratuberculosis (Map), is a chronic incurable infection of intestinal tract of animals. Molecular characterization of Map isolates classifies them into two major groups, 'Cattle' or Type II and 'Sheep' or Type I/III with a different phenotype, epidemiology, virulence and pathogenesis. The aim of this study was to examine 192 Map ELISA-positive sheep and goats from Cyprus using faecal culture and genotype Map isolates using IS1311 PCR and restriction endonuclease analysis (IS1311 PCR-REA) with HinfI restriction enzyme. Map was isolated from only four (4.6%) faecal samples out of 88 sheep and 15 (14.4%) faecal samples out of 104 goats. Genotyping of the isolates using IS1311 PCR-REA revealed that sheep and goat populations on the island are infected primarily by 'Sheep' strains. Only three Map isolates from goats originated from one farm were characterized as 'Cattle' strains. PMID:23683358

  16. Genotype profiles of Mycobacterium avium subspecies paratuberculosis recovered from suspected and Crohn's disease patients in India.

    PubMed

    Singh, A V; Singh, S V; Sohal, J S; Singh, P K

    2010-06-01

    Present study aimed to genotype Mycobacterium avium subspecies paratuberculosis (MAP) recovered from suspected and Crohn' s disease patients. A total of 32 MAP and DNA (directly from clinical samples) recovered from human origin were genotyped using IS 1311 PCR-REA. Isolates were cultured from stool, biopsies and blood clots of Crohn's disease patients, and stool samples of suspected (animal attendants, lab workers etc). Of the 32 MAP isolates belonging to 28 human beings, majority (84.3%) were genotyped as 'Bison type', while 21.7% were of 'cattle' and none was 'sheep' genotype. Study first time reports distribution of 'Cattle' and 'Bison type' 'genotypes in suspected and Crohn's patients on pilot scale in India. 'Bison type' genotype was predominant in the surveyed human population. PMID:22471168

  17. Association between cattle herd Mycobacterium avium subsp. paratuberculosis (MAP) infection and infection of a hare population.

    PubMed

    Salgado, Miguel; Monti, Gustavo; Sevilla, Iker; Manning, Elizabeth

    2014-10-01

    Paratuberculosis has long been considered a disease of domestic and wild ruminants only. The known host range of Mycobacterium avium subsp. paratuberculosis (MAP) was recently extended to include non-ruminant wildlife species believed to be exposed to spillover of MAP from infected domestic cattle herds. The aim of the present study was to assess the association between cattle herd MAP infection pressure level and the infection level of a hare population in two dairy farms of southern Chile. Fifty hares from a herd A and 42 hares from herd B were captured and sampled for MAP culture. The results showed a statistically significant association between the cattle herds' infection prevalence and the hare infection prevalence. PMID:25030465

  18. Detection of Mycobacterium avium subsp. paratuberculosis by a Direct In Situ PCR Method

    PubMed Central

    Delgado, Fernando; Aguilar, Diana; Garbaccio, Sergio; Francinelli, Gladys; Hernández-Pando, R.; Romano, María Isabel

    2011-01-01

    In situ detection of Mycobacterium avium subsp. paratuberculosis is useful for diagnosis and research of paratuberculosis. The aim of this paper was to detect this agent in formalin-fixed, paraffin-embedded tissue samples by a direct in situ PCR. The technique was performed on ileum or ileocaecal lymph node samples from 8 naturally infected cattle and 1 healthy calf, by using p89 and p92 primers for amplification of IS900 sequence. Moderate positive signal was detected in all positive samples and not in negative control, but tissues resulted were affected in many cases due to the enzymatic treatment and the high temperature exposition. Although the technique was useful for Map detection, the signal was lower than immunohistochemistry probably because of the fixation process. In one case, signal was higher, which might be due to the detection of spheroplasts. Thus, the described method should be recommended when others resulted negative or for spheroplasts detection. PMID:21772965

  19. Utilization of a ts-sacB selection system for the generation of a Mycobacterium avium serovar-8 specific glycopeptidolipid allelic exchange mutant

    PubMed Central

    Irani, Vida R; Lee, Sun-Hwa; Eckstein, Torsten M; Inamine, Julia M; Belisle, John T; Maslow, Joel N

    2004-01-01

    Background Mycobacterium avium are ubiquitous environmental organisms and a cause of disseminated infection in patients with end-stage AIDS. The glycopeptidolipids (GPL) of M. avium are proposed to participate in the pathogenesis of this organism, however, establishment of a clear role for GPL in disease production has been limited by the inability to genetically manipulate M. avium. Methods To be able to study the role of the GPL in M. avium pathogenesis, a ts-sacB selection system, not previously used in M. avium, was employed as a means to achieve homologous recombination for the rhamnosyltransferase (rtfA) gene of a pathogenic serovar 8 strain of M. avium to prevent addition of serovar-specific sugars to rhamnose of the fatty acyl-peptide backbone of GPL. The genotype of the resultant rtfA mutant was confirmed by polymerase chain reaction and southern hybridization. Disruption in the proximal sugar of the haptenic oligosaccharide resulted in the loss of serovar specific GPL with no change in the pattern of non-serovar specific GPL moieties as shown by thin layer chromatography and gas chromatography/mass spectrometry. Complementation of wild type (wt) rtfA in trans through an integrative plasmid restored serovar-8 specific GPL expression identical to wt serovar 8 parent strain. Results In this study, we affirm our results that rtfA encodes an enzyme responsible for the transfer of Rha to 6d-Tal and provide evidence of a second allelic exchange mutagenesis system suitable for M. avium. Conclusion We report the second allelic exchange system for M. avium utilizing ts-sacB as double-negative and xylE as positive counter-selection markers, respectively. This system of allelic exchange would be especially useful for M. avium strains that demonstrate significant isoniazid (INH) resistance despite transformation with katG. Through the construction of mutants in GPL or other mycobacterial components, their roles in M. avium pathogenesis, biosynthesis, or drug

  20. Induction of murine macrophage TNF-alpha synthesis by Mycobacterium avium is modulated through complement-dependent interaction via complement receptors 3 and 4 in relation to M. avium glycopeptidolipid.

    PubMed

    Irani, Vida R; Maslow, Joel N

    2005-05-15

    We studied whether complement receptor (CR) mediated Mycobacterium avium interaction modulated macrophage TNF-alpha expression. Compared to control conditions, infections performed with C3-depletion yielded significantly higher TNF-alpha levels. Blockage of the CR4 iC3b site yielded increases in TNF-alpha for all morphotypic variants of a virulent serovar-8 strain (smooth transparent (SmT), smooth opaque (SmO), serovar-specific glycopeptidolipid (ssGPL) deficient knockout mutant) whereas CR3 blockage increased TNF-alpha only for SmT and ssGPL-deficient strains. Thus, complement-mediated binding of M. avium to CR3 and CR4 was shown to modulate TNF-alpha expression. The differential activation of morphotypic and isogenic variants of a single strain provides an excellent model system to delineate signaling pathways. PMID:15899409

  1. Host responses to the pathogen Mycobacterium avium subsp. paratuberculosis and beneficial microbes exhibit host sex specificity.

    PubMed

    Karunasena, Enusha; McMahon, K Wyatt; Chang, David; Brashears, Mindy M

    2014-08-01

    Differences between microbial pathogenesis in male and female hosts are well characterized in disease conditions connected to sexual transmission. However, limited biological insight is available on variances attributed to sex specificity in host-microbe interactions, and it is most often a minimized variable outside these transmission events. In this work, we studied two gut microbes-a pathogen, Mycobacterium avium subsp. paratuberculosis, and a probiotic, Lactobacillus animalis NP-51-and the interaction between each agent and the male and female gastrointestinal systems. This trial was conducted in BALB/c mice (n=5 per experimental group and per sex at a given time point), with analysis at four time points over 180 days. Host responses to M.avium subsp. paratuberculosis and L. animalis were sensitive to sex. Cytokines that were significantly different (P ≤ 0.05) betweenthe sexes included interleukin-1α/β (IL-1α/β), IL-17, IL-6, IL-10, IL-12, and gamma interferon (IFN-) and were dependent on experimental conditions. However, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and IL-13/23 showed no sex specificity. A metabolomics study indicated a 0.5- to 2.0-fold (log2 scale) increase in short-chain fatty acids (butyrate and acetate) in males and greater increases in o-phosphocholine or histidine from female colon tissues; variances distinct to each sex were observed with age or long-term probiotic consumption. Two genera, Staphylococcus and Roseburia, were consistently overrepresented in females compared to males; other species were specific to one sex but fluctuated depending on experimental conditions. The differences observed suggest that male and female gut tissues and microbiota respond to newly introduced microorganisms differently and that gut-associated microorganisms with host immune system responses and metabolic activity are supported by biology distinct to the host sex. PMID:24814797

  2. Superoxide dismutase activity of Mycobacterium avium, M. intracellulare, and M. scrofulaceum.

    PubMed Central

    Mayer, B K; Falkinham, J O

    1986-01-01

    Superoxide dismutase (EC 1.15.1.1) (SOD) activity has been detected in crude cell extracts of representative strains of the Mycobacterium avium, M. intracellulare, and M. scrofulaceum (MAIS) group. Polyacrylamide gel electrophoresis demonstrated a single SOD activity band for each of the MAIS strains, though there were differences in mobility. All M. avium and M. intracellulare and two of five M. scrofulaceum strains demonstrated a single activity band of identical mobility (Rf = 0.83), while the SOD activity band for the three remaining M. scrofulaceum strains migrated farther (Rf = 0.85). The differences in mobility correlated with differences in sensitivity to NaN3 and H2O2. The SOD activities of the majority of the MAIS strains which displayed the slower-migrating activity band were inhibited 22 to 81% after 15 min of exposure to 5 mM H2O2, suggesting that both iron and manganese may be present in a single enzyme. The SOD activities of the three M. scrofulaceum strains which had the faster-migrating activity band were inhibited 100% after only 5 min of exposure to 5 mM H2O2 and exhibited greater sensitivity to 5 and 10 mM NaN3, characteristics of an iron-containing SOD. A concentration of 1 mM KCN did not cause inhibition of enzyme activity in any of the MAIS strains tested. Extracellular SOD activity was detected in four of six MAIS strains and was shown to be identical in mobility to the SOD activity of the crude extracts. Images PMID:3744555

  3. GENETIC DIVERSITY OF SOME IRANIAN SWEET CHERRY (PRUNUS AVIUM) CULTIVARS USING MICROSATELLITE MARKERS AND MORPHOLOGICAL TRAITS.

    PubMed

    Farsad, A; Esna-Ashari, M

    2016-01-01

    The aim of this study was to characterize 23 important Iranian sweet cherry (Prunus avium) cultivars collected from different provinces of Iran and 1 foreign cultivar, which was used as control, considered for breeding programs by using 21 microsatellite markers and 27 morphological traits. In sweet cherry (Prunus avium) accessions, leaf, fruit, and stone morphological characters were evaluated during two consecutive years. The study revealed a high variability in the set of evaluated sweet cherry accessions. The majority of important correlations were determined among variables representing fruit and leaf size and variables related to color. Cluster analysis distinguished sweet cherry accessions into two distinct groups. Principal component analysis (PCA) of qualitative and quantitative morphological parameters explained over 86.59% of total variability in the first seven axes. In PCA, leaf traits such as leaf length and width, and fruit traits such as length, width, and weight, and fruit flesh and juice color were predominant in the first two components, indicating that they were useful for the assessment of sweet cherry germplasm characterization. Out of 21 SSR markers, 16 were polymorphic, producing 177 alleles that varied from 4 to 16 alleles (9.35 on average) with a mean heterozygosity value of 0.82 that produced successful amplifications and revealed DNA polymorphisms. Allele size varied from 95 to 290 bp. Cluster analyses showed that the studied sweet cherry genotypes were classified intofive main groups based mainly on their species characteristics and SSR data. In general, our results did not show a clear structuring of genetic variability within the Iranian diffusion area of sweet cherry, so it was not possible to draw any indications on regions of provenance delimitation. The results of this study contribute to a better understanding of sweet cherry genetic variations in Iran, thus making for more efficient programs aimed at preserving biodiversity and

  4. Monensin causes dose dependent inhibition of Mycobacterium avium subspecies paratuberculosis in radiometric culture

    PubMed Central

    Greenstein, Robert J; Su, Liya; Whitlock, Robert H; Brown, Sheldon T

    2009-01-01

    Background Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic wasting diarrheal disease in ruminants called Johne's disease, that is evocative of human inflammatory bowel disease (IBD). Agents used to treat IBD, called "anti-inflammatories", immuno-modulators" and "immuno-suppressants" inhibit MAP growth in culture. We concluded that, unknowingly, the medical profession has been treating MAP since sulfasalazine's introduction in 1942. Monensin, called a "Growth Enhancer" in cattle, ameliorates Johne's disease without a documented mechanism of action. We hypothesized that Monensin would inhibit MAP in culture. Methods Using the radiometric 14CO2 Bactec® system, that expresses mycobacterial growth in arbitrary growth index (GI) units, we studied the effect of Monensin on the growth kinetic of MAP isolated from humans with IBD ("Dominic", "Ben" & UCF-4) and cattle with Johne's disease (303 & ATCC 19698.) Results are expressed as percent inhibition of cumulative GI (%–ΔcGI). Results The positive control Clofazimine inhibits every strain tested. The negative controls Cycloheximide & Phthalimide, have no inhibition on any MAP strain. Monensin has dose dependent inhibition on every MAP strain tested. The most susceptible human isolate was UCF-4 (73% – ΔcGI at 1 μg/ml) and bovine isolate was 303 (73% – ΔcGI at 4 μg/ml.) Monensin additionally inhibits M. avium ATCC 25291 (87% – ΔcGI at 64 μg/ml) & BCG (92% – ΔcGI at 16 μg/ml). Discussion We show that in radiometric culture the "Growth Enhancer" Monensin causes dose dependent inhibition of mycobacteria including MAP. We posit that the "Growth Enhancer" effect of Monensin may, at least in part, be due to inhibition of MAP in clinical or sub-clinical Johne's disease. PMID:19338684

  5. Host Responses to the Pathogen Mycobacterium avium subsp. paratuberculosis and Beneficial Microbes Exhibit Host Sex Specificity

    PubMed Central

    McMahon, K. Wyatt; Chang, David; Brashears, Mindy M.

    2014-01-01

    Differences between microbial pathogenesis in male and female hosts are well characterized in disease conditions connected to sexual transmission. However, limited biological insight is available on variances attributed to sex specificity in host-microbe interactions, and it is most often a minimized variable outside these transmission events. In this work, we studied two gut microbes—a pathogen, Mycobacterium avium subsp. paratuberculosis, and a probiotic, Lactobacillus animalis NP-51—and the interaction between each agent and the male and female gastrointestinal systems. This trial was conducted in BALB/c mice (n = 5 per experimental group and per sex at a given time point), with analysis at four time points over 180 days. Host responses to M. avium subsp. paratuberculosis and L. animalis were sensitive to sex. Cytokines that were significantly different (P ≤ 0.05) between the sexes included interleukin-1α/β (IL-1α/β), IL-17, IL-6, IL-10, IL-12, and gamma interferon (IFN-γ) and were dependent on experimental conditions. However, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and IL-13/23 showed no sex specificity. A metabolomics study indicated a 0.5- to 2.0-fold (log2 scale) increase in short-chain fatty acids (butyrate and acetate) in males and greater increases in o-phosphocholine or histidine from female colon tissues; variances distinct to each sex were observed with age or long-term probiotic consumption. Two genera, Staphylococcus and Roseburia, were consistently overrepresented in females compared to males; other species were specific to one sex but fluctuated depending on experimental conditions. The differences observed suggest that male and female gut tissues and microbiota respond to newly introduced microorganisms differently and that gut-associated microorganisms with host immune system responses and metabolic activity are supported by biology distinct to the host sex. PMID:24814797

  6. Mycobacterium avium Subspecies paratuberculosis Recombinant Proteins Modulate Antimycobacterial Functions of Bovine Macrophages.

    PubMed

    Bannantine, John P; Stabel, Judith R; Laws, Elizabeth; D Cardieri, Maria Clara; Souza, Cleverson D

    2015-01-01

    It has been shown that Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) activates the Mitogen Activated Protein Kinase (MAPK) p38 pathway, yet it is unclear which components of M. paratuberculosis are involved in the process. Therefore, a set of 42 M. paratuberculosis recombinant proteins expressed from coding sequences annotated as lipoproteins were screened for their ability to induce IL-10 expression, an indicator of MAPKp38 activation, in bovine monocyte-derived macrophages. A recombinant lipoprotein, designated as MAP3837c, was among a group of 6 proteins that strongly induced IL-10 gene transcription in bovine macrophages, averaging a 3.1-fold increase compared to non-stimulated macrophages. However, a parallel increase in expression of IL-12 and TNF-α was only observed in macrophages exposed to a subset of these 6 proteins. Selected recombinant proteins were further analyzed for their ability to enhance survival of M. avium within bovine macrophages as measured by recovered viable bacteria and nitrite production. All 6 IL-10 inducing MAP recombinant proteins along with M. paratuberculosis cells significantly enhanced phosphorylation of MAPK-p38 in bovine macrophages. Although these proteins are likely not post translationally lipidated in E. coli and thus is a limitation in this study, these results form the foundation of how the protein component of the lipoprotein interacts with the immune system. Collectively, these data reveal M. paratuberculosis proteins that might play a role in MAPK-p38 pathway activation and hence in survival of this organism within bovine macrophages. PMID:26076028

  7. Mycobacterium avium Possesses Extracellular DNA that Contributes to Biofilm Formation, Structural Integrity, and Tolerance to Antibiotics

    PubMed Central

    Rose, Sasha J.; Babrak, Lmar M.; Bermudez, Luiz E.

    2015-01-01

    Mycobacterium avium subsp. hominissuis is an opportunistic pathogen that is associated with biofilm-related infections of the respiratory tract and is difficult to treat. In recent years, extracellular DNA (eDNA) has been found to be a major component of bacterial biofilms, including many pathogens involved in biofilm-associated infections. To date, eDNA has not been described as a component of mycobacterial biofilms. In this study, we identified and characterized eDNA in a high biofilm-producing strain of Mycobacterium avium subsp. hominissuis (MAH). In addition, we surveyed for presence of eDNA in various MAH strains and other nontuberculous mycobacteria. Biofilms of MAH A5 (high biofilm-producing strain) and MAH 104 (reference strain) were established at 22°C and 37°C on abiotic surfaces. Acellular biofilm matrix and supernatant from MAH A5 7 day-old biofilms both possess abundant eDNA, however very little eDNA was found in MAH 104 biofilms. A survey of MAH clinical isolates and other clinically relevant nontuberculous mycobacterial species revealed many species and strains that also produce eDNA. RAPD analysis demonstrated that eDNA resembles genomic DNA. Treatment with DNase I reduced the biomass of MAH A5 biofilms when added upon biofilm formation or to an already established biofilm both on abiotic surfaces and on top of human pharyngeal epithelial cells. Furthermore, co-treatment of an established biofilm with DNase 1 and either moxifloxacin or clarithromycin significantly increased the susceptibility of the bacteria within the biofilm to these clinically used antimicrobials. Collectively, our results describe an additional matrix component of mycobacterial biofilms and a potential new target to help treat biofilm-associated nontuberculous mycobacterial infections. PMID:26010725

  8. Biomedicine's Electronic Publishing Paradigm Shift

    PubMed Central

    Markovitz, Barry P.

    2000-01-01

    Biomedical publishing stands at a crossroads. The traditional print, peer-reviewed, subscription journal has served science well but is now being called into question. Because of spiraling print journal costs and the worldwide acceptance of the Internet as a valid publication medium, there is a compelling opportunity to re-examine our current paradigm and future options. This report illustrates the conflicts and restrictions inherent in the current publishing model and examines how the single act of permitting authors to retain copyright of their scholarly manuscripts may preserve the quality-control function of the current journal system while allowing PubMed Central, the Internet archiving system recently proposed by the director of the National Institutes of Health, to simplify and liberate access to the world's biomedical literature. PMID:10833158

  9. Contesting the paradigm of chirality

    NASA Astrophysics Data System (ADS)

    Efrati, Efi

    2012-02-01

    In 1893 Lord Kelvin coined the term chirality, and stated what is to become the elementary paradigm of chirality: 'I call any geometrical figure, or any group of points, chiral, and say it has chirality, if its image in a plane mirror , ideally realized cannot be brought to coincide with itself'. While the notion of chirality has greatly advanced our understanding of the structures of molecules and crystals, it has been shown to be inconsistent with every pseudo-scalar quantification. In this talk I will present a tabletop demonstration of a chiral structure which is constructed through the achiral summation of identical elementary units which are symmetric under reflection. The seeming contradiction to the definition of chirality is reconciled by proposing an alternative definition, relying on the physicist interpretation of the right hand rule.

  10. Paradigm change in evolutionary microbiology.

    PubMed

    O'Malley, Maureen A; Boucher, Yan

    2005-03-01

    Thomas Kuhn had little to say about scientific change in biological science, and biologists are ambivalent about how applicable his framework is for their disciplines. We apply Kuhn's account of paradigm change to evolutionary microbiology, where key Darwinian tenets are being challenged by two decades of findings from molecular phylogenetics. The chief culprit is lateral gene transfer, which undermines the role of vertical descent and the representation of evolutionary history as a tree of life. To assess Kuhn's relevance to this controversy, we add a social analysis of the scientists involved to the historical and philosophical debates. We conclude that while Kuhn's account may capture aspects of the pattern (or outcome) of an episode of scientific change, he has little to say about how the process of generating new understandings is occurring in evolutionary microbiology. Once Kuhn's application is limited to that of an initial investigative probe into how scientific problem-solving occurs, his disciplinary scope becomes broader. PMID:16120264

  11. Datacubes as a Service Paradigm

    NASA Astrophysics Data System (ADS)

    Rossi, Angelo Pio; Baumann, Peter

    2016-04-01

    Spatio-temporal data sets often can be represented conveniently through datacubes as a common unifying paradigm. Flexible, scalable services can be offered based on the concept of a datacube query language while hiding the technicalities, thereby allowing user-friendly visual data interaction. One of today's most influential initiatives in Big Geo Data is EarthServer which is paving the way for flexible, scalable datacube services based on innovative NewSQL technology (Fig. 1). Researchers from Europe, the US and recently Australia have teamed up to rigorously materialize the datacube paradigm for Earth Observation, ocean, meteorological, and planetary science. EarthServer has established client and server technology for such spatio-temporal datacubes strictly based on the open datacube standards, OGC WCS and WPCS. The underlying scalable array engine, rasdaman, enables direct interaction, including 3-D visualization, what-if scenarios, common EO data processing, and general analytics on regular and irregular grids. Integration of datacube and metadata retrieval, together with advanced visualization based on NASA WorldWind, are geared towards an effective, user-friendly access and analysis. Conversely, EarthServer is significantly shaping the ISO, OGC, and INSPIRE Big Data standards landscape by being specification editor. Phase 1 of EarthServer has advanced scalable array data¬base technology into 100+ TB services; in phase 2, a federation of Petabyte datacubes is being built in Europe and Australia to perform ad-hoc querying and merging. Phase 1 reviewers have attested rasdaman to "significantly transform the way that scientists in different areas of Earth Science will be able to access and use data in a way that hitherto was not possible". Altogether, these large-scale deployments prove that datacubes are a convenient model for presenting users with a simple, consolidated view on the massive amount of data files gathered - "a cube tells more than a million

  12. Methodological issues in the psychology of religion: toward another paradigm?

    PubMed

    Belzen, Jacob A; Hood, Ralph W

    2006-01-01

    Recent evaluations have identified the psychology of religion as a field in crisis and have called for a new multilevel interdisciplinary paradigm. However, a critical meta-perspective on methods reveals a broad range of methodologies, each appropriate for particular levels of complexity in the psychology of religion. No single methodology is appropriate for every level, nor can higher levels of complexity be explained by data from lower levels. The authors identify the different types of research practiced in the psychology of religion and critically discuss philosophical presuppositions involved in two major methodological traditions, the empiricist-analytical and the hermeneutical, often identified as quantitative and qualitative traditions, respectively. PMID:16619941

  13. Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium.

    PubMed

    Gentry-Weeks, C R; Hultsch, A L; Kelly, S M; Keith, J M; Curtiss, R

    1992-12-01

    Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the

  14. Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium.

    PubMed Central

    Gentry-Weeks, C R; Hultsch, A L; Kelly, S M; Keith, J M; Curtiss, R

    1992-01-01

    Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the

  15. Cloning and sequencing of the gene for alpha antigen from Mycobacterium avium and mapping of B-cell epitopes.

    PubMed Central

    Ohara, N; Matsuo, K; Yamaguchi, R; Yamazaki, A; Tasaka, H; Yamada, T

    1993-01-01

    The complete nucleotide sequence of alpha antigen secreted from Mycobacterium avium (A-alpha) was determined. The gene encodes 330 amino acids, including 40 amino acids for the signal peptide, followed by 290 amino acids for the mature protein with a molecular mass of 30,811 Da. This is the first sequence of A-alpha. Comparisons between A-alpha and alpha antigens of Mycobacterium leprae, Mycobacterium bovis BCG, and Mycobacterium kansasii showed highly homologous regions which suggested a conserved functional domain and two less-homologous regions. Serological analysis of recombinant A-alpha, expressed by a series of deletion constructs, indicated the possibility that A-alpha carries at least six B-cell epitopes. The three antigenic determinants were common to Mycobacterium tuberculosis, M. kansasii, and M. avium. The results also suggested the possibility that there are three species-specific epitopes. Images PMID:7681039

  16. Short communication: Heritability estimates for susceptibility to Mycobacterium avium subspecies paratuberculosis infection defined by ELISA and fecal culture test results in Jersey cattle.

    PubMed

    Zare, Y; Shook, G E; Collins, M T; Kirkpatrick, B W

    2014-07-01

    Paratuberculosis (Johne's disease), an enteric disorder in ruminants caused by Mycobacterium avium ssp. paratuberculosis, causes economic losses in excess of $200 million annually to the US dairy industry. Costly diagnostic testing, cumbersome control programs, incurability, and ineffective vaccination all make M. avium ssp. paratuberculosis susceptibility a good candidate for genetic studies and genetic selection a potentially useful adjunct to management-based control programs. No report has been published for heritability of susceptibility to M. avium ssp. paratuberculosis infection in Jersey cattle. The objective of this study was to estimate variance components and heritability for susceptibility to M. avium ssp. paratuberculosis infection in US Jersey cattle. Data consisted of complete serum ELISA and partial fecal culture results on a total of 2,861 Jersey cows from 23 commercial herds throughout the United States after editing. Four M. avium ssp. paratuberculosis susceptibility phenotypes were defined using (1) ELISA sample-to-positive ratios as a continuous trait, (2) ELISA results as a binary trait (positive=1, negative=0), (3) ELISA results as an ordered categorical trait, and (4) a combined test in which ELISA and fecal culture results were both taken into account in a binary analysis. Three statistical models, including linear, binary threshold, and ordered threshold sire models, were used to analyze the data. All analyses were executed using the restricted maximum likelihood method in ASReml 3 software. The heritability estimates were low to moderate and ranged from 0.08 (±0.03) to 0.27 (±0.11) based on different trait definitions. The nonzero heritability indicates that susceptibility to M. avium ssp. paratuberculosis infection in Jersey cattle is influenced by genetic factors. Therefore, selection of the least susceptible animals could decrease genetic predisposition to M. avium ssp. paratuberculosis infection in Jersey populations in future

  17. Typing of Human Mycobacterium avium Isolates in Italy by IS1245-Based Restriction Fragment Length Polymorphism Analysis

    PubMed Central

    Lari, Nicoletta; Cavallini, Michela; Rindi, Laura; Iona, Elisabetta; Fattorini, Lanfranco; Garzelli, Carlo

    1998-01-01

    All but 2 of 63 Mycobacterium avium isolates from distinct geographic areas of Italy exhibited markedly polymorphic, multibanded IS1245 restriction fragment length polymorphism (RFLP) patterns; 2 isolates showed the low-number banding pattern typical of bird isolates. By computer analysis, 41 distinct IS1245 patterns and 10 clusters of essentially identical strains were detected; 40% of the 63 isolates showed genetic relatedness, suggesting the existence of a predominant AIDS-associated IS1245 RFLP pattern. PMID:9817900

  18. Is Mycobacterium avium subsp. paratuberculosis, the cause of Johne's disease in animals, a good candidate for Crohn's disease in man?

    PubMed

    Singh, A V; Singh, S V; Singh, P K; Sohal, J S

    2010-03-01

    Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease or paratuberculosis, a gastro intestinal inflammatory condition in ruminants and other animals, which is similar to Crohn's disease (CD) that occurs in man. The role of MAP in the causation of CD has been under intense investigation in the last few decades. This review summarizes the status of MAP in animals and the food chain and its association with CD in man. PMID:20443099

  19. Implication of phagosome-lysosome fusion in restriction of Mycobacterium avium growth in bone marrow macrophages from genetically resistant mice.

    PubMed Central

    de Chastellier, C; Fréhel, C; Offredo, C; Skamene, E

    1993-01-01

    The ability of the host to resist infection to a variety of intracellular pathogens, including mycobacteria, is strongly dependent upon the expression of the Bcg gene. Mouse strains which express the resistance phenotype (Bcgr) restrict bacterial growth, whereas susceptible strains (Bcgs) allow bacterial growth. Expression of the Bcg allele is known to influence the priming of host macrophages (M phi s) for bactericidal function. In the present work, bone marrow-derived M phi s from congenic BALB/c (Bcgs) and C.D2 (BALB/c.Bcgr) mice were infected with the virulent strain Mycobacterium avium TMC 724 to define the mechanism involved in growth restriction of M. avium. By combining CFU measurements and ultrastructural analyses, we show that growth of this bacterium is restricted in marrow M phi s from resistant mice. Using acid phosphatase as a lysosomal marker, we provide evidence that the hydrolytic activity of M phi s, as measured by the capacity of lysosomes to fuse with and transfer active hydrolytic enzymes to phagosomes in which M. avium resides, is an expression of the Bcg gene and that this phenomenon is a key antibacterial activity responsible for growth restriction of M. avium: (i) the percentage of phagosome-lysosome fusions was twice as high in Bcgr M phi s as in Bcgs M phi s, and (ii) the percentage of intact viable bacteria residing in acid phosphatase-negative phagosomes was twice as low in Bcgr M phi s as in the Bcgs counterparts. These differences are not due to a lower activity of the enzyme in Bcgr M phi s. The mechanism by which the Bcg gene exerts control over the phagolysosomal fusion is discussed. Images PMID:8359899

  20. Indoleamine 2,3-Dioxygenase, Tryptophan Catabolism, and Mycobacterium avium subsp. paratuberculosis: a Model for Chronic Mycobacterial Infections ▿ †

    PubMed Central

    Plain, Karren M.; de Silva, Kumudika; Earl, John; Begg, Douglas J.; Purdie, Auriol C.; Whittington, Richard J.

    2011-01-01

    Virulent mycobacterial infections progress slowly, with a latent period that leads to clinical disease in a proportion of cases. Mycobacterium avium subsp. paratuberculosis is an intracellular pathogen that causes paratuberculosis or Johne's disease (JD), a chronic intestinal disease of ruminants. Indoleamine 2,3-dioxygenase (IDO), an enzyme that regulates tryptophan metabolism, was originally reported to have a role in intracellular pathogen killing and has since been shown to have an important immunoregulatory role in chronic immune diseases. Here we demonstrate an association between increased IDO levels and progression to clinical mycobacterial disease in a natural host, characterizing gene expression, protein localization, and functional effects. IDO mRNA levels were significantly increased in M. avium subsp. paratuberculosis-infected monocytic cells. Levels of both IDO gene and protein expression were significantly upregulated within the affected tissues of sheep with JD, particularly at the site of primary infection, the ileum, of animals with severe multibacillary disease. Lesion severity was correlated with the level of IDO gene expression. IDO gene expression was also increased in the peripheral blood cells of M. avium subsp. paratuberculosis-exposed sheep and cattle. IDO breaks down tryptophan, and systemic increases were functional, as shown by decreased plasma tryptophan levels, which correlated with the onset of clinical signs, a stage well known to be associated with Th1 immunosuppression. IDO may be involved in downregulating immune responses to M. avium subsp. paratuberculosis and other virulent mycobacteria, which may be an example of the pathogen harnessing host immunoregulatory pathways to aid survival. These findings raise new questions about the host-mycobacterium interactions in the progression from latent to clinical disease. PMID:21730087

  1. Shifting Paradigms: From Flexner to Competencies.

    ERIC Educational Resources Information Center

    Carraccio, Carol; Wolfsthal, Susan D.; Englander, Robert; Ferentz, Kevin; Martin, Christine

    2002-01-01

    Reviewed the literature on competency-based medical education to: (1) understand the evolution of this educational paradigm; (2) assess the evidence to date of the efficacy of competency-based education; and (3) provide practical insights into how to accomplish full implementation and evaluation of the paradigm shift. (EV)

  2. Is This the Paradigm Shift We Need?

    ERIC Educational Resources Information Center

    Mirvis, Jonathan

    2012-01-01

    Dr. Woocher's essay, states Mirvis, is seminal in the field of Jewish education. It proposes a new paradigm for Jewish education in North America. This proposed paradigm is supported by a comprehensive multi-disciplinary research drawing on literature from education, philosophy, history, sociology, psychology, and economics. The essay reflects a…

  3. Narrative: Mode of Discourse or Paradigm?

    ERIC Educational Resources Information Center

    Rowland, Robert C.

    1987-01-01

    Analyzes Walter Fisher's work on the "narrative paradigm." Considers Fisher's definition of narrative too broad and advocates a more limited definition. Rejects Fisher's view that there is an independent standard of narrative rationality distinguishable from the "rational world paradigm," and his idea that the role of the expert in the public…

  4. Paradigm Lost: The Human Chromosome Story.

    ERIC Educational Resources Information Center

    Unger, Lawrence; Blystone, Robert V.

    1996-01-01

    Discusses whether the discovery in 1956 that humans have a chromosome number of 46, as opposed to 47 or 48 as previously thought, fits into a paradigm shift of the Kuhnian type. Concludes that Kuhn probably would not have considered the chromosome number shift to be large enough to be a focus for one of his paradigms. (AIM)

  5. Genotyping and strain distribution of Mycobacterium avium subspecies hominissuis isolated from humans and pigs in Belgium, 2011-2013.

    PubMed

    Vluggen, Christelle; Soetaert, Karine; Duytschaever, Lucille; Denoël, Joseph; Fauville-Dufaux, Maryse; Smeets, François; Bruffaerts, Nicolas; Huygen, Kris; Fretin, David; Rigouts, Leen; Saegerman, Claude; Mathys, Vanessa

    2016-01-01

    Mycobacterium avium represents a health concern for both humans and pigs. The characterisation of its subspecies is an important step improving the understanding of the epidemiology and the control of this pathogen. Ninety-two human M. avium strains were selected for a retrospective study. Subspecies determination by rpoB sequencing and IS1245/IS901 analysis showed that 98.9% of Belgian human M. avium strains belong to the subspecies hominissuis (MAH). Some of these MAH strains present particular IS1245/IS901 profiles (absence of IS1245 and false IS901 detection provoked by the presence of ISMav6). In addition, 54 MAH strains isolated from submandibular lymph nodes of Belgian pigs with lymphadenitis were included in this study. Genotyping of human and porcine isolates was performed using multispacer sequence typing (MST). In total, 49 different MST types were identified among pig (n = 11) and human (n = 43) MA isolates, with only five shared by both hosts. Among these MST types, 34 were newly identified. Our findings demonstrate the extensive genetic diversity among MAH isolates. Some genotypes were more prevalent in human or pigs but no correlation was observed between MST type and place of residence or the farm of origin for human and porcine isolates respectively, suggesting an environmental source of infection. PMID:26835872

  6. Killing of Mycobacterium avium by Lactoferricin Peptides: Improved Activity of Arginine- and d-Amino-Acid-Containing Molecules

    PubMed Central

    Silva, Tânia; Magalhães, Bárbara; Maia, Sílvia; Gomes, Paula; Nazmi, Kamran; Bolscher, Jan G. M.; Rodrigues, Pedro N.; Bastos, Margarida

    2014-01-01

    Mycobacterium avium causes respiratory disease in susceptible individuals, as well as disseminated infections in immunocompromised hosts, being an important cause of morbidity and mortality among these populations. Current therapies consist of a combination of antibiotics taken for at least 6 months, with no more than 60% overall clinical success. Furthermore, mycobacterial antibiotic resistance is increasing worldwide, urging the need to develop novel classes of antimicrobial drugs. One potential and interesting alternative strategy is the use of antimicrobial peptides (AMP). These are present in almost all living organisms as part of their immune system, acting as a first barrier against invading pathogens. In this context, we investigated the effect of several lactoferrin-derived AMP against M. avium. Short peptide sequences from both human and bovine lactoferricins, namely, hLFcin1-11 and LFcin17-30, as well as variants obtained by specific amino acid substitutions, were evaluated. All tested peptides significantly inhibited the axenic growth of M. avium, the bovine peptides being more active than the human. Arginine residues were found to be crucial for the display of antimycobacterial activity, whereas the all-d-amino-acid analogue of the bovine sequence displayed the highest mycobactericidal activity. These findings reveal the promising potential of lactoferricins against mycobacteria, thus opening the way for further research on their development and use as a new weapon against mycobacterial infections. PMID:24709266

  7. Antigen-Specific B-Cell Unresponsiveness Induced by Chronic Mycobacterium avium subsp. paratuberculosis Infection of Cattle

    PubMed Central

    Waters, W. R.; Stabel, J. R.; Sacco, R. E.; Harp, J. A.; Pesch, B. A.; Wannemuehler, M. J.

    1999-01-01

    Mycobacterium avium subsp. paratuberculosis infection of cattle results in a chronic granulomatous enteritis. Clinical disease (i.e., cachexia, diarrhea, and high fecal bacterial counts) is preceded by a lengthy subclinical stage of disease. The immunologic mechanisms associated with the progression of infected cattle from subclinical to clinical disease are unclear. In this study, a cell proliferation assay was used in combination with flow cytometry to compare peripheral blood lymphocyte responses of cattle with subclinical paratuberculosis to responses of cattle with clinical paratuberculosis. B cells from cattle with subclinical disease proliferated vigorously upon stimulation with M. avium subsp. paratuberculosis antigen, with up to 12.4% of the total B cells responding. However, B cells from cattle with clinical disease did not proliferate upon antigen stimulation despite good proliferation in response to concanavalin A stimulation. In addition, these animals had high percentages of peripheral blood B cells. B cells from noninfected animals did not proliferate upon M. avium subsp. paratuberculosis antigen stimulation. Thus, it appears that B-cell proliferation is a sensitive indicator of subclinical Johne’s disease. Furthermore, the immunologic mechanisms responsible for the antigen-specific unresponsiveness of peripheral blood B cells may be significant in the eventual progression from subclinical to clinical Johne’s disease in cattle. PMID:10084991

  8. Alpha-1 Antitrypsin Deficiency: Beyond the Protease/Antiprotease Paradigm.

    PubMed

    Cosio, Manuel G; Bazzan, Erica; Rigobello, Chiara; Tinè, Mariaenrica; Turato, Graziella; Baraldo, Simonetta; Saetta, Marina

    2016-08-01

    From the discovery that alpha-1 antitrypsin (AAT) was an effective inhibitor of neutrophil elastase originated the classic paradigm of protease/antiprotease imbalance, linking lung destruction to the unopposed effect of proteases in patients with the deficiency. Notwithstanding its importance as an antiprotease, it has become evident that alpha-1 antitrypsin has important antiinflammatory and immune-regulatory activities, which may be critically involved in lung destruction. We review here recent evidence showing that, indeed, an important adaptive immune reaction is present in lungs with AAT deficiency, similar to the one seen in severe chronic obstructive pulmonary disease with normal AAT. On the basis of recent evidence from epidemiological, clinical, and pathogenetic studies, it is likely time to move on from the original protease/antiprotease hypothesis for the production of emphysema toward a more complex paradigm, involving the antiinflammatory and immune modulating functions of AAT. PMID:27564665

  9. Mercury biogeochemistry: Paradigm shifts, outstanding issues and research needs

    NASA Astrophysics Data System (ADS)

    Sonke, Jeroen E.; Heimbürger, Lars-Eric; Dommergue, Aurélien

    2013-05-01

    Half a century of mercury research has provided scientists and policy makers with a detailed understanding of mercury toxicology, biogeochemical cycling and past and future impacts on human exposure. The complexity of the global biogeochemical mercury cycle has led to repeated and ongoing paradigm shifts in numerous mercury-related disciplines and outstanding questions remain. In this review, we highlight some of the paradigm shifts and questions on mercury toxicity, the risks and benefits of seafood consumption, the source of mercury in seafood, and the Arctic mercury cycle. We see a continued need for research on mercury toxicology and epidemiology, for marine mercury dynamics and ecology, and for a closer collaboration between observational mercury science and mercury modeling in general. As anthropogenic mercury emissions are closely tied to the energy cycle (in particular coal combustion), mercury exposure to humans and wildlife are likely to persist unless drastic emission reductions are put in place.

  10. Inflationary paradigm in trouble after Planck2013

    NASA Astrophysics Data System (ADS)

    Ijjas, Anna; Steinhardt, Paul J.; Loeb, Abraham

    2013-06-01

    Recent results from the Planck satellite combined with earlier observations from WMAP, ACT, SPT and other experiments eliminate a wide spectrum of more complex inflationary models and favor models with a single scalar field, as reported by the Planck Collaboration. More important, though, is that all the simplest inflaton models are disfavored statistically relative to those with plateau-like potentials. We discuss how a restriction to plateau-like models has three independent serious drawbacks: it exacerbates both the initial conditions problem and the multiverse-unpredictability problem and it creates a new difficulty that we call the inflationary "unlikeliness problem." Finally, we comment on problems reconciling inflation with a standard model Higgs, as suggested by recent LHC results. In sum, we find that recent experimental data disfavors all the best-motivated inflationary scenarios and introduces new, serious difficulties that cut to the core of the inflationary paradigm. Forthcoming searches for B-modes, non-Gaussianity and new particles should be decisive.

  11. Dealing with a Paradigm Shift

    PubMed Central

    Pack, Allan I.

    2015-01-01

    Recent changes in policies by insurance companies with respect to mandating home sleep apnea testing rather than in-laboratory studies have a large impact on the financial viability of clinical sleep centers. Coping with this disruptive change requires forward planning. First, it is important to be well positioned with respect to facilities so that these can be quickly downsized to control costs. There is also a need to develop, in advance, an accredited home sleep study program so that centers can respond to the rapidly changing environment. Following the change there is a need to control costs by rapidly downsizing the technology workforce. Technologists can be retrained for other essential roles. Centralizing the precertification process with knowledgeable, well-trained staff and a robust auditing process is an essential component. The approach taken at the University of Pennsylvania to this change is described as is how one can ensure continued financial viability of a comprehensive sleep center program in a major academic medical center. Citation: Pack AI. Dealing with a paradigm shift. J Clin Sleep Med 2015;11(8):925–929. PMID:26094918

  12. Antiphospholipid antibodies: Paradigm in transition

    PubMed Central

    Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Ahn, Yeon S; Kelley, Roger E; Zivadinov, Robert; Maghzi, Amir H; Etemadifar, Masoud; Mousavi, Seyed Ali; Minagar, Alireza

    2009-01-01

    Objectives This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP. Organization After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed. Conclusion The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology. PMID:19154576

  13. Monsoon-Enso Relationships: A New Paradigm

    NASA Technical Reports Server (NTRS)

    Lau, K. M.; Einaudi, Franco (Technical Monitor)

    2000-01-01

    This article is partly a review and partly a new research paper on monsoon-ENSO relationship. The paper begins with a discussion of the basic relationship between the Indian monsoon and ENSO dating back to the work of Sir Gilbert Walker up to research results in more recent years. Various factors that may affect the monsoon-ENSO, relationship, including regional coupled ocean-atmosphere processes, Eurasian snow cover, land-atmosphere hydrologic feedback, intraseasonal oscillation, biennial variability and inter-decadal variations, are discussed. The extreme complex and highly nonlinear nature of the monsoon-ENSO relationship is stressed. We find that for regional impacts on the monsoon, El Nino and La Nina are far from simply mirror images of each other. These two polarities of ENSO can have strong or no impacts on monsoon anomalies depending on the strength of the intraseasonal oscillations and the phases of the inter-decadal variations. For the Asian-Australian monsoon (AAM) as a whole, the ENSO impact is effected through a east-west shift in the Walker Circulation. For rainfall anomalies over specific monsoon areas, regional processes play important roles in addition to the shift in the Walker Circulation. One of the key regional processes identified for the boreal summer monsoon is the anomalous West Pacific Anticyclone (WPA). This regional feature has similar signatures in interannual and intraseasonal time scales and appears to determine whether the monsoon-ENSO relationship is strong or weak in a given year. Another important regional feature includes a rainfall and SST dipole across the Indian Ocean, which may have strong impact on the austral summer monsoon. Results are shown indicating that monsoon surface wind forcings may induce a strong biennial signal in ENSO and that strong monsoon-ENSO coupling may translate into pronounced biennial variability in ENSO. Finally, a new paradigm is proposed for the study of monsoon variability. This paradigm provides

  14. Ostracism Online: A social media ostracism paradigm.

    PubMed

    Wolf, Wouter; Levordashka, Ana; Ruff, Johanna R; Kraaijeveld, Steven; Lueckmann, Jan-Matthis; Williams, Kipling D

    2015-06-01

    We describe Ostracism Online, a novel, social media-based ostracism paradigm designed to (1) keep social interaction experimentally controlled, (2) provide researchers with the flexibility to manipulate the properties of the social situation to fit their research purposes, (3) be suitable for online data collection, (4) be convenient for studying subsequent within-group behavior, and (5) be ecologically valid. After collecting data online, we compared the Ostracism Online paradigm with the Cyberball paradigm (Williams & Jarvis Behavior Research Methods, 38, 174-180, 2006) on need-threat and mood questionnaire scores (van Beest & Williams Journal of Personality and Social Psychology 91, 918-928, 2006). We also examined whether ostracized targets of either paradigm would be more likely to conform to their group members than if they had been included. Using a Bayesian analysis of variance to examine the individual effects of the different paradigms and to compare these effects across paradigms, we found analogous effects on need-threat and mood. Perhaps because we examined conformity to the ostracizers (rather than neutral sources), neither paradigm showed effects of ostracism on conformity. We conclude that Ostracism Online is a cost-effective, easy to use, and ecologically valid research tool for studying the psychological and behavioral effects of ostracism. PMID:24878596

  15. Leprosy: too complex a disease for a simple elimination paradigm.

    PubMed Central

    Lockwood, Diana N. J.; Suneetha, Sujai

    2005-01-01

    Can leprosy be eliminated? This paper considers the question against the background of the WHO programme to eliminate leprosy. In 1991 the World Health Assembly set a target of eliminating leprosy as a public health problem by 2000. Elimination was defined as reaching a prevalence of < 1 case per 10 000 people. The elimination programme has been successful in delivering highly effective antibiotic therapy worldwide. However, despite this advance, new-case detection rates remain stable in countries with the highest rates of endemic leprosy, such as Brazil and India. This suggests that infection has not been adequately controlled by antibiotics alone. Leprosy is perhaps more appropriately classed as a chronic stable disease than as an acute infectious disease responsive to elimination strategies. In many countries activities to control and treat leprosy are being integrated into the general health-care system. This reduces the stigma associated with leprosy. However, leprosy causes long-term immunological complications, disability and deformity. The health-care activities of treating and preventing disabilities need to be provided in an integrated setting. Detecting new cases and monitoring disability caused by leprosy will be a challenge. One solution is to implement long-term surveillance in selected countries with the highest rates of endemic disease so that an accurate estimate of the burden of leprosy can be determined. It is also critical that broad-based research into this challenging disease continues until the problems are truly solved. PMID:15798849

  16. Fuzzy Hybrid Deliberative/Reactive Paradigm (FHDRP)

    NASA Technical Reports Server (NTRS)

    Sarmadi, Hengameth

    2004-01-01

    This work aims to introduce a new concept for incorporating fuzzy sets in hybrid deliberative/reactive paradigm. After a brief review on basic issues of hybrid paradigm the definition of agent-based fuzzy hybrid paradigm, which enables the agents to proceed and extract their behavior through quantitative numerical and qualitative knowledge and to impose their decision making procedure via fuzzy rule bank, is discussed. Next an example performs a more applied platform for the developed approach and finally an overview of the corresponding agents architecture enhances agents logical framework.

  17. Contemporary Treatment Paradigms in Keratoconus.

    PubMed

    McGhee, Charles N J; Kim, Bia Z; Wilson, Peter J

    2015-10-01

    The past 20 years have witnessed an explosion in our knowledge of keratoconus, accompanied by a radical transformation of management options. A 2-hit hypothesis proposes an underlying genetic predisposition coupled with external environmental factors, including eye rubbing and atopy. The variable prevalence and natural history have been better defined including significant cone progression in middle age. Therefore, current management must include early diagnosis, regular monitoring, and treatment of environmental cofactors. Spectacles and contact lenses remain fundamental to the optical management of keratoconus. Intrastromal corneal ring segments have been increasingly used, providing improvement in the corneal shape, corrected visual acuity, and contact lens wear. However, like contact lenses, intrastromal corneal ring segments do not treat the underlying disease process. Therefore, current approaches must also consider treatments to minimize keratoconus progression. Fortunately, there is increasing evidence that corneal collagen crosslinking will halt or slow progression in most cases. Until relatively recently, penetrating keratoplasty was the preferred intervention for advanced keratoconus, with long-term success in the region of 90%; however, the greatest risk of failure remains endothelial allograft rejection. Deep anterior lamellar keratoplasty has emerged in the new millennium as a preferred approach to conserve the host endothelium and avoid rejection. Nonetheless, the overall superiority of deep anterior lamellar keratoplasty compared with penetrating keratoplasty, in terms of optical and survival benefits, is still debated. This perspective provides an overview of our current knowledge of keratoconus and current management options. A step-ladder approach to managing keratoconus is outlined to provide the practitioner with a contemporary management paradigm. PMID:26114829

  18. SN & GRB in Spinar paradigm

    NASA Astrophysics Data System (ADS)

    Lipunov, Vladimir

    A spinar is a collapsing object in quasi-equilibrium state. Its equilibrium is maintained by the balance of centrifugal and gravitational forces and its evolution is determined by its magnetic field. A model of spinar quasi-equilibrium has been discussed in the context of an extralong X-ray plateau in a gamma-ray burst. The differences between SN (we are talking about SN II) and long soft GRB is due to differences in specific angular momentum of the collapsing part of the pre supernova star or binary relativistic stars. There is the simple non-stationary three-parameter collapse model with the determining role of rotation and magnetic field (Lipunov V.M., Gorbovskoy E.S. "Spinar paradigm and the central engine of gamma-ray bursts", MNRAS, 383, 1397, 2008). The input parameters of the model are the mass, angular momentum and magnetic field of the collapsar. This model includes an approximate description of the following effects: the centrifugal force, the relativistic effects of the Kerr metrics, the pressure of nuclear matter, the dissipation of angular momentum as a result of the magnetic field, the decrease of the dipole magnetic moment as a result of compression and general-relativity effects (the black hole has no hair), neutrino cooling, time dilatation and gravitational redshift. The model describes the temporal behaviour of the central engine and demonstrates the qualitative variety of the types of such behaviour in nature. We apply our approach to an explanation of the observed features of all types of gamma-ray bursts. In particular, the model allows the unification of the phenomena of precursors, X-ray and optical flares, and the appearance of a plateau on the time-scale of several thousand seconds.

  19. Epidemiology and Ecology of Opportunistic Premise Plumbing Pathogens: Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa

    PubMed Central

    Hilborn, Elizabeth D.; Arduino, Matthew J.; Pruden, Amy; Edwards, Marc A.

    2015-01-01

    Background Legionella pneumophila, Mycobacterium avium, and Pseudomonas aeruginosa are opportunistic premise plumbing pathogens (OPPPs) that persist and grow in household plumbing, habitats they share with humans. Infections caused by these OPPPs involve individuals with preexisting risk factors and frequently require hospitalization. Objectives The objectives of this report are to alert professionals of the impact of OPPPs, the fact that 30% of the population may be exposed to OPPPs, and the need to develop means to reduce OPPP exposure. We herein present a review of the epidemiology and ecology of these three bacterial OPPPs, specifically to identify common and unique features. Methods A Water Research Foundation–sponsored workshop gathered experts from across the United States to review the characteristics of OPPPs, identify problems, and develop a list of research priorities to address critical knowledge gaps with respect to increasing OPPP-associated disease. Discussion OPPPs share the common characteristics of disinfectant resistance and growth in biofilms in water distribution systems or premise plumbing. Thus, they share a number of habitats with humans (e.g., showers) that can lead to exposure and infection. The frequency of OPPP-infected individuals is rising and will likely continue to rise as the number of at-risk individuals is increasing. Improved reporting of OPPP disease and increased understanding of the genetic, physiologic, and structural characteristics governing the persistence and growth of OPPPs in drinking water distribution systems and premise plumbing is needed. Conclusions Because broadly effective community-level engineering interventions for the control of OPPPs have yet to be identified, and because the number of at-risk individuals will continue to rise, it is likely that OPPP-related infections will continue to increase. However, it is possible that individuals can take measures (e.g., raise hot water heater temperatures and filter

  20. Selecting appropriate designs and comparison conditions in repetition paradigms.

    PubMed

    Feuerriegel, Daniel

    2016-07-01

    The studies described by Vogels (this issue) demonstrate the complexity of repetition effects in the visual processing stream. In addition to signal suppression, findings of inherited effects from earlier processing, and discrepancies between the stimulus selectivity of cells before and after repetition, have informed the inferences that can be drawn from measures over larger scales such as functional magnetic resonance imaging (fMRI) or electroencephalography (EEG). This work also demonstrates that integration of evidence across recording methods is vital for understanding repetition effects in the brain. It is however difficult to integrate evidence across different recording methods and repetition paradigms. At the crux of this difficulty is the selection of comparison or unrepeated stimulus conditions within paradigms, which influence the observed strength, selectivity and even direction of repetition effects. This viewpoint highlights prevalent methodological issues with regard to repeated-unrepeated stimulus comparisons: inherited adaptation, stimulus specific expectations, concurrent memory retrieval, stimulus novelty and familiarity, attention, and changes in neuronal selectivity with repetition. The extent to which current conflicting and uncertain findings are due to selection of unrepeated stimulus conditions is unknown, but needs to be addressed to develop models of repetition spanning recording methods and repetition paradigms. PMID:26654854

  1. Comparison of Large Restriction Fragments of Mycobacterium avium Isolates Recovered from AIDS and Non-AIDS Patients with Those of Isolates from Potable Water

    PubMed Central

    Aronson, T.; Holtzman, A.; Glover, N.; Boian, M.; Froman, S.; Berlin, O. G. W.; Hill, H.; Stelma, G.

    1999-01-01

    We examined potable water in Los Angeles, California, as a possible source of infection in AIDS and non-AIDS patients. Nontuberculous mycobacteria were recovered from 12 (92%) of 13 reservoirs, 45 (82%) of 55 homes, 31 (100%) of 31 commercial buildings, and 15 (100%) of 15 hospitals. Large-restriction-fragment (LRF) pattern analyses were done with AseI. The LRF patterns of Mycobacterium avium isolates recovered from potable water in three homes, two commercial buildings, one reservoir, and eight hospitals had varying degrees of relatedness to 19 clinical isolates recovered from 17 patients. The high number of M. avium isolates recovered from hospital water and their close relationship with clinical isolates suggests the potential threat of nosocomial spread. This study supports the possibility that potable water is a source for the acquisition of M. avium infections. PMID:10074518

  2. The safety implications of emerging software paradigms

    SciTech Connect

    Suski, G.J.; Persons, W.L.; Johnson, G.L.

    1994-10-01

    This paper addresses some of the emerging software paradigms that may be used in developing safety-critical software applications. Paradigms considered in this paper include knowledge-based systems, neural networks, genetic algorithms, and fuzzy systems. It presents one view of the software verification and validation activities that should be associated with each paradigm. The paper begins with a discussion of the historical evolution of software verification and validation. Next, a comparison is made between the verification and validation processes used for conventional and emerging software systems. Several verification and validation issues for the emerging paradigms are discussed and some specific research topics are identified. This work is relevant for monitoring and control at nuclear power plants.

  3. MICROHABITAT REVIEWED: ANALYSIS OF A PARADIGM

    EPA Science Inventory

    Small mammal microhabitat partitioning research has greatly influenced vertebrate community ecologists. It is not a stretch to assert that there exists a 'microhabitat paradigm' among small mammal specialists; sympatry among small mammal species is enabled by differential use of...

  4. A new paradigm for solar filament eruptions

    NASA Astrophysics Data System (ADS)

    Rust, David M.

    2001-11-01

    This article discusses the formation, magnetic structure, and eruption of solar filaments in terms of two contrasting paradigms. The standard paradigm is that filaments are formed by condensation of plasma on coronal magnetic fields that are twisted or dimpled as a result of photospheric motions. According to this paradigm, filaments erupt when photospheric motions shear the fields, increasing their energy and decreasing their stability. According to a new paradigm, subsurface motions generate toroidal magnetic flux ropes, and after these flux ropes emerge to form active regions, the most twisted parts migrate into the corona to form filaments. Filaments become unstable and are ejected after a sufficient accumulation of twist (i.e., magnetic helicity). Various proposed mechanisms for producing the needed helicity are reviewed, and several observational tests are proposed to differentiate among the possible mechanisms.

  5. The Emerging Paradigm in Black Studies.

    ERIC Educational Resources Information Center

    Kershaw, Terry

    1989-01-01

    Argues that traditional sociology has treated Black studies as peripheral to the study of human behavior. Proposes a paradigm that includes an emphasis on Afrocentric perspective and a methodology that combines positivist and critical methodologies. (FMW)

  6. Engineering paradigms and anthropogenic global change

    NASA Astrophysics Data System (ADS)

    Bohle, Martin

    2016-04-01

    This essay discusses 'paradigms' as means to conceive anthropogenic global change. Humankind alters earth-systems because of the number of people, the patterns of consumption of resources, and the alterations of environments. This process of anthropogenic global change is a composite consisting of societal (in the 'noosphere') and natural (in the 'bio-geosphere') features. Engineering intercedes these features; e.g. observing stratospheric ozone depletion has led to understanding it as a collateral artefact of a particular set of engineering choices. Beyond any specific use-case, engineering works have a common function; e.g. civil-engineering intersects economic activity and geosphere. People conceive their actions in the noosphere including giving purpose to their engineering. The 'noosphere' is the ensemble of social, cultural or political concepts ('shared subjective mental insights') of people. Among people's concepts are the paradigms how to shape environments, production systems and consumption patterns given their societal preferences. In that context, engineering is a means to implement a given development path. Four paradigms currently are distinguishable how to make anthropogenic global change happening. Among the 'engineering paradigms' for anthropogenic global change, 'adaptation' is a paradigm for a business-as-usual scenario and steady development paths of societies. Applying this paradigm implies to forecast the change to come, to appropriately design engineering works, and to maintain as far as possible the current production and consumption patterns. An alternative would be to adjust incrementally development paths of societies, namely to 'dovetail' anthropogenic and natural fluxes of matter and energy. To apply that paradigm research has to identify 'natural boundaries', how to modify production and consumption patterns, and how to tackle process in the noosphere to render alterations of common development paths acceptable. A further alternative

  7. The Environment of “Mycobacterium avium subsp. hominissuis” Microaggregates Induces Synthesis of Small Proteins Associated with Efficient Infection of Respiratory Epithelial Cells

    PubMed Central

    Babrak, Lmar; Danelishvili, Lia; Rose, Sasha J.; Kornberg, Tiffany

    2014-01-01

    “Mycobacterium avium subsp. hominissuis” is an opportunistic environmental pathogen that causes respiratory illness in immunocompromised patients, such as those with cystic fibrosis as well as other chronic respiratory diseases. Currently, there is no efficient approach to prevent or treat M. avium subsp. hominissuis infection in the lungs. During initial colonization of the airways, M. avium subsp. hominissuis forms microaggregates composed of 3 to 20 bacteria on human respiratory epithelial cells, which provides an environment for phenotypic changes leading to efficient mucosal invasion in vitro and in vivo. DNA microarray analysis was employed to identify genes associated with the microaggregate phenotype. The gene encoding microaggregate-binding protein 1 (MBP-1) (MAV_3013) is highly expressed during microaggregate formation. When expressed in noninvasive Mycobacterium smegmatis, MBP-1 increased the ability of the bacteria to bind to HEp-2 epithelial cells. Using anti-MBP-1 immune serum, microaggregate binding to HEp-2 cells was significantly reduced. By far-Western blotting, and verified by coimmunoprecipitation, we observed that MBP-1 interacts with the host cytoskeletal protein vimentin. As visualized by confocal microscopy, microaggregates, as well as MBP-1, induced vimentin polymerization at the site of bacterium-host cell contact. Binding of microaggregates to HEp-2 cells was inhibited by treatment with an antivimentin antibody, suggesting that MBP-1 expression is important for M. avium subsp. hominissuis adherence to the host cell. MBP-1 immune serum significantly inhibited M. avium subsp. hominissuis infection throughout the respiratory tracts of mice. This study characterizes a pathogenic mechanism utilized by M. avium subsp. hominissuis to bind and invade the host respiratory epithelium, suggesting new potential targets for the development of antivirulence therapy. PMID:25422262

  8. The environment of "Mycobacterium avium subsp. hominissuis" microaggregates induces synthesis of small proteins associated with efficient infection of respiratory epithelial cells.

    PubMed

    Babrak, Lmar; Danelishvili, Lia; Rose, Sasha J; Kornberg, Tiffany; Bermudez, Luiz E

    2015-02-01

    "Mycobacterium avium subsp. hominissuis" is an opportunistic environmental pathogen that causes respiratory illness in immunocompromised patients, such as those with cystic fibrosis as well as other chronic respiratory diseases. Currently, there is no efficient approach to prevent or treat M. avium subsp. hominissuis infection in the lungs. During initial colonization of the airways, M. avium subsp. hominissuis forms microaggregates composed of 3 to 20 bacteria on human respiratory epithelial cells, which provides an environment for phenotypic changes leading to efficient mucosal invasion in vitro and in vivo. DNA microarray analysis was employed to identify genes associated with the microaggregate phenotype. The gene encoding microaggregate-binding protein 1 (MBP-1) (MAV_3013) is highly expressed during microaggregate formation. When expressed in noninvasive Mycobacterium smegmatis, MBP-1 increased the ability of the bacteria to bind to HEp-2 epithelial cells. Using anti-MBP-1 immune serum, microaggregate binding to HEp-2 cells was significantly reduced. By far-Western blotting, and verified by coimmunoprecipitation, we observed that MBP-1 interacts with the host cytoskeletal protein vimentin. As visualized by confocal microscopy, microaggregates, as well as MBP-1, induced vimentin polymerization at the site of bacterium-host cell contact. Binding of microaggregates to HEp-2 cells was inhibited by treatment with an antivimentin antibody, suggesting that MBP-1 expression is important for M. avium subsp. hominissuis adherence to the host cell. MBP-1 immune serum significantly inhibited M. avium subsp. hominissuis infection throughout the respiratory tracts of mice. This study characterizes a pathogenic mechanism utilized by M. avium subsp. hominissuis to bind and invade the host respiratory epithelium, suggesting new potential targets for the development of antivirulence therapy. PMID:25422262

  9. Identification of Mycobacterium avium Genotypes with Distinctive Traits by Combination of IS1245-Based Restriction Fragment Length Polymorphism and Restriction Analysis of hsp65

    PubMed Central

    Oliveira, R. S.; Sircili, M. P.; Oliveira, E. M. D.; Balian, S. C.; Ferreira-Neto, J. S.; Leão, S. C.

    2003-01-01

    One-hundred eight Mycobacterium avium isolates from pigs, humans, birds, and bovines were typed by the IS1245-based restriction fragment length polymorphism (RFLP) method and PCR-restriction enzyme analysis (PRA) of hsp65. Nine clusters of isolates showing more than 80% similarity in their RFLP profiles were detected. The largest cluster (cluster B) included 32 of 79 pig isolates (40.5%), 3 of 25 human isolates (12%), and 1 of 2 bovine isolates, comprising 33% of all isolates. The second largest cluster (cluster A) included 18 pig isolates (22.8%) and 6 human isolates (24%). Six smaller clusters included six pig isolates (clusters C and D), four and two human isolates (clusters E and F, respectively), two pig isolates (cluster I), and two pig isolates plus one bovine isolate and the avian purified protein derivative strain (cluster H). Cluster G represented the “bird-type” profile and included the bird isolate in this series, one pig isolate, plus reference strain R13. PRA revealed four allelic variants. Seventy-seven isolates were identified as M. avium PRA variant I, 24 were identified as M. avium PRA variant II, 6 were identified as M. avium PRA variant III, and 1 was identified as M. avium PRA variant IV. Except for three isolates from cluster B, each of the RFLP clusters was associated with a single PRA pattern. Isolates with unique (nonclustered) RFLP profiles were distributed between PRA variants I and II, and there was one unique isolate of PRA variant IV. These observations are consistent with divergent evolution within M. avium, resulting in the emergence of distinct lineages with particular competence to infect animals and humans. PMID:12517823

  10. Genetic Structure of Mycobacterium avium subsp. paratuberculosis Population in Cattle Herds in Quebec as Revealed by Using a Combination of Multilocus Genomic Analyses

    PubMed Central

    Sohal, Jagdip Singh; Arsenault, Julie; Labrecque, Olivia; Fairbrother, Julie-Hélène; Roy, Jean-Philippe; Fecteau, Gilles

    2014-01-01

    Mycobacterium avium subsp. paratuberculosis is the etiological agent of paratuberculosis, a granulomatous enteritis affecting a wide range of domestic and wild ruminants worldwide. A variety of molecular typing tools are used to distinguish M. avium subsp. paratuberculosis strains, contributing to a better understanding of M. avium subsp. paratuberculosis epidemiology. In the present study, PCR-based typing methods, including mycobacterial interspersed repetitive units/variable-number tandem repeats (MIRU-VNTR) and small sequence repeats (SSR) in addition to IS1311 PCR-restriction enzyme analysis (PCR-REA), were used to investigate the genetic heterogeneity of 200 M. avium subsp. paratuberculosis strains from dairy herds located in the province of Quebec, Canada. The majority of strains were of the “cattle type,” or type II, although 3 strains were of the “bison type.” A total of 38 genotypes, including a novel one, were identified using a combination of 17 genetic markers, which generated a Simpson's index of genetic diversity of 0.876. Additional analyses revealed no differences in genetic diversity between environmental and individual strains. Of note, a spatial and spatiotemporal cluster was evidenced regarding the distribution of one of the most common genotypes. The population had an overall homogeneous genetic structure, although a few strains stemmed out of the consensus cluster, including the bison-type strains. The genetic structure of M. avium subsp. paratuberculosis populations within most herds suggested intraherd dissemination and microevolution, although evidence of interherd contamination was also revealed. The level of genetic diversity obtained by combining MIRU-VNTR and SSR markers shows a promising avenue for molecular epidemiology investigations of M. avium subsp. paratuberculosis transmission patterns. PMID:24829229

  11. Proteome and Differential Expression Analysis of Membrane and Cytosolic Proteins from Mycobacterium avium subsp. paratuberculosis Strains K-10 and 187▿†

    PubMed Central

    Radosevich, Thomas J.; Reinhardt, Timothy A.; Lippolis, John D.; Bannantine, John P.; Stabel, Judith R.

    2007-01-01

    Little is known of protein expression in Mycobacterium avium subsp. paratuberculosis and how this contributes to pathogenesis. In the present study, proteins from both membranes and cytosol were prepared from two strains of M. avium subsp. paratuberculosis, i.e., laboratory-adapted strain K-10 and a recent isolate, strain 187, obtained from a cow exhibiting clinical signs of Johne's disease. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cytosol and membrane proteins from K-10 and 187 showed marked differences in protein expression. Relative levels of protein expression from both M. avium subsp. paratuberculosis strains were measured by using amine-reactive isobaric tagging reagents (iTRAQ) and tandem mass spectroscopy. Protein identification and relative expression data were obtained for 874 membrane and cytosolic proteins from the M. avium subsp. paratuberculosis proteome. These data showed a number of significant differences in protein expression between strain K-10 and clinical isolate 187. Examples of proteins expressed at higher levels in clinical isolate 187 compared to strain K-10 are AtpC, RpoA, and several proteins involved in fatty acid biosynthesis. In contrast, proteins such as AhpC and several proteins involved in nitrogen metabolism were expressed at higher levels in strain K-10 compared to strain 187. These data may provide insights into the proteins whose expression is important in natural infection but are modified once M. avium subsp. paratuberculosis is adapted to laboratory cultivation. Results from these studies will provide tools for developing a better understanding of M. avium subsp. paratuberculosis infection in the host and offer potential as diagnostic reagents and vaccine candidates. PMID:17142399

  12. Managing Balloon Projects - A Changing Paradigm: A Retrospective Look

    NASA Astrophysics Data System (ADS)

    Black, R. K.; Smith, I. S.

    With the advent of the Ultra-Long Duration Balloon (ULDB) capability and balloons being offered as a carrier for NASA Explorer class missions, a fundamental shift in the way balloon mission projects are managed will be required. This shift will ensure the performance and reliability of the science instrument, balloon vehicle, flight system, and ground control center to support a science mission of up to 100 days in duration. The current ``design to capability'' paradigm, with minimal management oversight, has traditionally worked well for many years in flying scientific instruments on balloons at low cost with medium to high risk. Newer, more complex science instruments and missions, such as those developed under NASA's Explorers Program, will require a radical shift to a much more formal ``design to requirements'' management paradigm. This paper will attempt to take a retrospective look at the formality imposed by the Explorers Program and determine what management elements are needed to assure the success of the current ``design to capability'' missions without increasing significant cost. This paradigm shift is intended to support the successful accomplishment of balloon missions on schedule, within budget, and lower risk, while enhancing and satisfying the success criteria and requirements of the primary customer, the Principal Investigator. This shift to a ``Explorer-like'' formality paradigm will require development of a cohesive mission management organization, organizing an effective system engineering process that links science requirements to instrument and flight system performance, implementing a cost effective performance assurance program, and exerting cost control over all aspects of the mission. All of these elements need to be addressed within a context of a strong commitment to meeting schedule within the constrained budgets.

  13. Adaptive Systems Engineering: A Medical Paradigm for Practicing Systems Engineering

    SciTech Connect

    R. Douglas Hamelin; Ron D. Klingler; Christopher Dieckmann

    2011-06-01

    From its inception in the defense and aerospace industries, SE has applied holistic, interdisciplinary tools and work-process to improve the design and management of 'large, complex engineering projects.' The traditional scope of engineering in general embraces the design, development, production, and operation of physical systems, and SE, as originally conceived, falls within that scope. While this 'traditional' view has expanded over the years to embrace wider, more holistic applications, much of the literature and training currently available is still directed almost entirely at addressing the large, complex, NASA and defense-sized systems wherein the 'ideal' practice of SE provides the cradle-to-grave foundation for system development and deployment. Under such scenarios, systems engineers are viewed as an integral part of the system and project life-cycle from conception to decommissioning. In far less 'ideal' applications, SE principles are equally applicable to a growing number of complex systems and projects that need to be 'rescued' from overwhelming challenges that threaten imminent failure. The medical profession provides a unique analogy for this latter concept and offers a useful paradigm for tailoring our 'practice' of SE to address the unexpected dynamics of applying SE in the real world. In short, we can be much more effective as systems engineers as we change some of the paradigms under which we teach and 'practice' SE.

  14. [Paradigm shift in higher education].

    PubMed

    Csóka, Mária

    2009-08-30

    The fast changes that took place in the last quarter of the 20th century made the professionals dealing with pedagogy realize that our school system followed the economical changes in terms of training supply and the matter of education very slowly, if at all; let alone the educational methods. We had to realize that the maintaining of this conservative system is not rational, education has become the most important part of the globalisational competition and the key to the 21st century is learning. Accordingly, the spatial and temporal expenditure of education has become a new trend, namely lifelong learning (LLL). The social needs on education have increased, the expectations of economy and employers have changed: knowledge has become the fund of competitiveness. In this process, universities have got an accentuated role: in addition to being the place of undergraduate training they have become the site of postgraduate courses for the increasing graduate adult masses. Therefore, reform processes have started in a number of European countries in the nineties. The Bologna Declaration signed on 19th June 1999 set a common direction for these reforms, with its signatories aiming to establish a standard European Higher Education Area with harmonized and comparable educational systems by 2010. However, the administrative change itself is not enough to reach the goals; a formal innovation has to be followed by a reform of the contents which means reformation of higher education. In recent years, Hungarian colleges and universities have worked out their educational programs that are suitable for the new structure; it is only the new educational programs that started from 1st September 2006. The author determines the most important parts of the reform of the training system of Semmelweis University Faculty of Health Sciences, which are the following: redrawing of the training philosophy and paradigm, the reform of the training structure of macro level (cognition

  15. New Indivisible Planetary Science Paradigm: Consequence of Questioning Popular Paradigms

    NASA Astrophysics Data System (ADS)

    Marvin Herndon, J.

    2014-05-01

    Progress in science involves replacing less precise understanding with more precise understanding. In science and in science education one should always question popular ideas; ask "What's wrong with this picture?" Finding limitations, conflicts or circumstances that require special ad hoc consideration sometimes is the key to making important discoveries. For example, from thermodynamic considerations, I found that the 'standard model of solar system formation' leads to insufficiently massive planetary cores. That understanding led me to discover a new indivisible planetary science paradigm. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures, accumulating heterogeneously on the basis of volatility with liquid core-formation preceding mantle-formation; the interior states of oxidation resemble that of the Abee enstatite chondrite. Core-composition was established during condensation based upon the relative solubilities of elements, including uranium, in liquid iron in equilibrium with an atmosphere of solar composition at high pressures and high temperatures. Uranium settled to the central region and formed planetary nuclear fission reactors, producing heat and planetary magnetic fields. Earth's complete condensation included a ~300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions, associated with the thermonuclear ignition of the Sun, stripped the gases away from the Earth and the inner planets. The T-Tauri outbursts stripped a portion of Mercury's incompletely condensed protoplanet and transported it to the region between Mars and Jupiter where it fused with in-falling oxidized condensate from the outer regions of the Solar System, forming the parent matter of ordinary chondrite meteorites, the main-Belt asteroids, and veneer for the inner planets, especially Mars. With its massive gas/ice shell

  16. The Underlying Social Dynamics of Paradigm Shifts

    PubMed Central

    Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm. PMID:26418255

  17. FurA contributes to the oxidative stress response regulation of Mycobacterium avium ssp. paratuberculosis

    PubMed Central

    Eckelt, Elke; Meißner, Thorsten; Meens, Jochen; Laarmann, Kristin; Nerlich, Andreas; Jarek, Michael; Weiss, Siegfried; Gerlach, Gerald-F.; Goethe, Ralph

    2015-01-01

    The ferric uptake regulator A (FurA) is known to be involved in iron homeostasis and stress response in many bacteria. In mycobacteria the precise role of FurA is still unclear. In the presented study, we addressed the functional role of FurA in the ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) by construction of a furA deletion strain (MAPΔfurA). RNA deep sequencing revealed that the FurA regulon consists of repressed and activated genes associated to stress response or intracellular survival. Not a single gene related to metal homeostasis was affected by furA deletion. A decisive role of FurA during intracellular survival in macrophages was shown by significantly enhanced survival of MAPΔfurA compared to the wildtype, indicating that a principal task of mycobacterial FurA is oxidative stress response regulation in macrophages. This resistance was not associated with altered survival of mice after long term infection with MAP. Our results demonstrate for the first time, that mycobacterial FurA is not involved in the regulation of iron homeostasis. However, they provide strong evidence that FurA contributes to intracellular survival as an oxidative stress sensing regulator. PMID:25705205

  18. Structure determination of lipopeptides from Mycobacterium avium subspecies paratuberculosis and identification of antigenic lipopeptide probes.

    PubMed

    Mitachi, Katsuhiko; Sharma Gautam, Lekh Nath; Rice, Jeffrey H; Eda, Keiko; Wadhwa, Ashutosh; Momotani, Eiichi; Hlopak, Joseph P; Eda, Shigetoshi; Kurosu, Michio

    2016-07-15

    Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic illnesses mostly in ruminants. MAP infection of intestinal tissue triggers a fatal inflammatory disorder, Johne's disease (paratuberculosis). Development of fast and reliable diagnostic methods for Johne's disease in clinically suspected ruminants requires the discovery of MAP-specific antigens that induce immune responses. Despite a longtime interest in finding such antigens that can detect serum antibody responses with high sensitivity, the antigens currently used for a diagnosis of the MAP infections are the crude extracts from the whole cell. We performed the serum antibody response assay-guided purification of the ethanol extract from MAP isolated from an infected cow. With the results of extensive fractionations and in vitro assays, we identified that arachidyl-d-Phe-N-Me-l-Val-l-Ile-l-Phe-l-Ala-OH (named lipopeptide IIß, 3) exhibited the highest antibody binding activity in serum of a MAP-infected cattle compared with the other lipopeptides isolated from MAP. The absolute chemistry of 3 was determined unequivocally via our high-performance liquid chromatography (HPLC)-amino acid databases. α-Amino lipopeptide IIß and its fluorescent probes were synthesized and evaluated in serum antibody binding activity assays. Lipopeptide IIß-(2S)-NH2 (9) and its dansyl and fluorescein isothiocyanate (FITC) probes (10 and 11) exhibited antibody-mediated binding activity; thus, such MAP-specific lipopeptide probes can be potential biomarkers for the development of rapid and accurate diagnosis of Johne's disease. PMID:27114041

  19. Short communication: Viable Mycobacterium avium subspecies paratuberculosis in retail artisanal Coalho cheese from Northeastern Brazil.

    PubMed

    Faria, A C S; Schwarz, D G G; Carvalho, I A; Rocha, B B; De Carvalho Castro, K N; Silva, M R; Moreira, M A S

    2014-07-01

    Mycobacterium avium ssp. paratuberculosis (MAP) is the etiologic agent of paratuberculosis and it potentially plays a role in Crohn's disease. In humans, the main route of transmission of MAP might be the intake of contaminated milk and dairy products. Considering that MAP has already been detected in many types of cheese in different counties, and that Coalho cheese is an important dairy product in northeastern Brazil, the aim of this study was to report the first detection of MAP in retail Coalho cheese in Brazil by PCR and culture. Of 30 retail Coalho cheese samples, 3 (10%) amplified fragments of a similar size to that expected (626 bp) were obtained and viable MAP was recovered by culture from 1 (3.3%) sample. The DNA from the positive culture sample was sequenced and showed 99% identity with the insertion sequence IS900 deposited in GenBank. It was possible to identify the presence of MAP-specific DNA in the analyzed samples for the first time in Brazil, and to recover viable cells from retail Coalho cheese. PMID:24797534

  20. Genome-Wide Diversity and Phylogeography of Mycobacterium avium subsp. paratuberculosis in Canadian Dairy Cattle.

    PubMed

    Ahlstrom, Christina; Barkema, Herman W; Stevenson, Karen; Zadoks, Ruth N; Biek, Roman; Kao, Rowland; Trewby, Hannah; Haupstein, Deb; Kelton, David F; Fecteau, Gilles; Labrecque, Olivia; Keefe, Greg P; McKenna, Shawn L B; Tahlan, Kapil; De Buck, Jeroen

    2016-01-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative bacterium of Johne's disease (JD) in ruminants. The control of JD in the dairy industry is challenging, but can be improved with a better understanding of the diversity and distribution of MAP subtypes. Previously established molecular typing techniques used to differentiate MAP have not been sufficiently discriminatory and/or reliable to accurately assess the population structure. In this study, the genetic diversity of 182 MAP isolates representing all Canadian provinces was compared to the known global diversity, using single nucleotide polymorphisms identified through whole genome sequencing. MAP isolates from Canada represented a subset of the known global diversity, as there were global isolates intermingled with Canadian isolates, as well as multiple global subtypes that were not found in Canada. One Type III and six "Bison type" isolates were found in Canada as well as one Type II subtype that represented 86% of all Canadian isolates. Rarefaction estimated larger subtype richness in Québec than in other Canadian provinces using a strict definition of MAP subtypes and lower subtype richness in the Atlantic region using a relaxed definition. Significant phylogeographic clustering was observed at the inter-provincial but not at the intra-provincial level, although most major clades were found in all provinces. The large number of shared subtypes among provinces suggests that cattle movement is a major driver of MAP transmission at the herd level, which is further supported by the lack of spatial clustering on an intra-provincial scale. PMID:26871723