Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sarcoidosis, once thought to be a variant of tuberculosis, is currently listed as a disease of unknown etiology. The present study was initiated by unpublished observations that Schaumann bodies-the laminated inclusions often encountered in sarcoid granulomas-cross-reacted with commercial polyclonal antibodies to Mycobacterium bovis, Mycobacterium duvalii and Mycobacterium paratuberculosis. Given the broad cross-reactivity of many mycobacterial antigens, those findings lacked specificity but warranted in depth probing of the immunoprofile of the bodies, particularly for specific mycobacterial antigens. Formalin-fixed tissue from eight patients with an established diagnosis of sarcoidosis was studied with panels of antibodies against both common cytoplasmic proteins and various mycobacterial antigens, using a labeled streptavidin-biotin-alkaline phosphatase technique. Our findings indicate that Schaumann bodies are indeed residual bodies of heterophagic mycobacterial derivation. They immunostained intensely for the lysosomal proteins muramidase and CD68, variably for some cytoskeletal proteins (tubulin, desmin, vimentin) and not at all for cytokeratin, muscle actin, alpha-1-antichymotrypsin and ferritin. Both cross-reactive and species specific antigenic determinants of M. tuberculosis complex were shown to be present. Affinity absorption with killed intact bacilli H37 Rv resulted in virtually equal loss of binding by all polyclonal antimycobacterial antibodies to cross-reactive ligands in Schaumann bodies. In addition, the bodies were clearly labeled with the monoclonal antibodies TB68 and TB71, known to recognize species specific epitopes of Mycobacterium tuberculosis complex. Although obtained on a small number of cases, our findings uphold Schaumann's original postulate that the laminated calcific inclusions represent remnants of "transformed tubercle bacilli".
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PMID:Cross-reactive and species specific Mycobacterium tuberculosis antigens in the immunoprofile of Schaumann bodies: a major clue to the etiology of sarcoidosis. 872 Apr 56

As a result of damaging endothelial cells (ECs), Mycobacterium leprae triggers the production of antibodies (Abs). These anti-EC Abs (AECAs) can be divided into two types. The first type nonspecifically reacts with components of the cytosol (CY) and can be detected by enzyme-linked immunosorbent assay (ELISA). The second specifically reacts with the EC membrane (MB) and requires fluorescence-activated cell sorter (FACS) analysis to be detected. The presence of both types of AECAs was determined in 68 leprosy patients. The ELISA was positive for 35 of them but also for 30 of 34 malaria patients and 17 of 50 healthy African controls. However, whereas FACS analysis showed MB reactivity in only three malaria patients and four controls, this reactivity was found in 27 leprosy patients, more of those having the lepromatous than the tuberculoid form. Specificity for MB, which we failed to absorb by incubation with CY lysates, predominated over that for CY in leprosy, unlike malaria, where the EC reactivity was restricted to the CY. Western blot analysis and two-dimensional electrophoresis revealed that calreticulin, vimentin, tubulin, and heat shock protein 70 were targeted by AECAs from leprosy patients, but other proteins remained unidentified. These auto-Abs, but not those from malaria patients, did activate ECs, as indicated by the E-selectin and intercellular adhesion molecule 1 upregulation, and/or induced them into apoptosis, as documented by four different methods. Our findings suggest that, in some but not all leprosy patients, AECAs may play a role in pathogenesis.
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PMID:Effects of anti-endothelial cell antibodies in leprosy and malaria. 1468 9

We previously showed that human NK cells used the NKp46 receptor to lyse Mycobacterium tuberculosis H37Ra-infected monocytes. To identify ligands on H37Ra-infected human mononuclear phagocytes, we used anti-NKp46 to immunoprecipitate NKp46 from NK cells bound to its ligand(s) on H37Ra-infected monocytes. Mass spectrometry analysis identified a 57-kDa molecule, vimentin, as a putative ligand for NKp46. Vimentin expression was significantly up-regulated on the surface of infected monocytes, compared with uninfected cells, and this was confirmed by fluorescence microscopy. Anti-vimentin antiserum inhibited NK cell lysis of infected monocytes, whereas antiserum to actin, another filamentous protein, did not. CHO-K1 cells transfected with a vimentin construct were lysed much more efficiently by NK cells than cells transfected with a control plasmid. This lysis was inhibited by mAb-mediated masking of NKp46 (on NK cells) or vimentin (on infected monocytes). ELISA and Far Western blotting showed that recombinant vimentin bound to a NKp46 fusion protein. These results indicate that vimentin is involved in binding of NKp46 to M. tuberculosis H37Ra-infected mononuclear phagocytes.
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PMID:Vimentin expressed on Mycobacterium tuberculosis-infected human monocytes is involved in binding to the NKp46 receptor. 1705 48

We report a case of a splenic inflammatory pseudotumor (myofibroblastic tumor) in a 43-year-old man with a 5-year history of chronic bronchitis and sleep apnea syndrome. The patient was hospitalized because of a screen-detected splenic mass lesion. His sputum cultures revealed Mycobacterium avium complexes on only one occasion. Imaging studies revealed a 7 cm solitary tumorous lesion, and differential diagnoses of splenic hamartoma, hemangioma, lymphoma, and angiosarcoma were obtained from the radiologist. A splenectomy followed by pathological investigations was performed. By histology, the lesion contained fibroblastic or myofibroblastic spindle cell proliferations, accompanied by variable degrees of inflammatory cell infiltration. Ziehl-Neelsen staining did not reveal acid-fast bacteria. Immunohistochemically, the fibroblastic or myofibroblastic spindle cells were positive for vimentin, human smooth muscle actin, and muscle actin, but negative for desmin, CD8, CD21, CD23, CD35, p80, Epstein-Barr virus LMP, and human herpesvirus type 8. The infiltrating lymphoid cells demonstrated a nonneoplastic pattern. The results of in situ hybridization for Epstein-Barr virus encoded RNA were negative. The postoperative course was uneventful and he has had no recurrence in 22 months. His sleep apnea syndrome and chronic bronchitis have resolved spontaneously since the splenectomy.
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PMID:Splenic inflammatory pseudotumor (inflammatory myofibroblastic tumor). 1804 Jan 48

"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.
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PMID:The environment of "Mycobacterium avium subsp. hominissuis" microaggregates induces synthesis of small proteins associated with efficient infection of respiratory epithelial cells. 2542 62

Mycobacterium tuberculosis persists primarily in macrophages after infection and manipulates the host defence pathways in its favour. 2D gel electrophoresis results showed that vimentin, an intermediate filament protein, is downregulated in macrophages infected with live Mycobacterium tuberculosis H37Rv when compared to macrophages infected with heat- killed H37Rv. The downregulation was confirmed by Western blot and quantitative RT-PCR. Besides, the expression of vimentin in avirulent strain, Mycobacterium tuberculosis H37Ra- infected macrophages was similar to the expression in heat-killed H37Rv- infected macrophages. Increased expression of vimentin in H2O2- treated live H37Rv-infected macrophages and decreased expression of vimentin both in NAC and DPI- treated heat-killed H37Rv-infected macrophages showed that vimentin expression is positively regulated by ROS. Ectopic expression of ESAT-6 in macrophages decreased both the level of ROS and the expression of vimentin which implies that Mycobacterium tuberculosis-mediated downregulation of vimentin is at least in part due to the downregulation of ROS by the pathogen. Interestingly, the incubation of macrophages with anti-vimentin antibody increased the ROS production and decreased the survival of H37Rv. In addition, we also showed that the pattern of phosphorylation of vimentin in macrophages by PKA/PKC is different from monocytes, emphasizing a role for vimentin phosphorylation in macrophage differentiation.
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PMID:Downregulation of vimentin in macrophages infected with live Mycobacterium tuberculosis is mediated by Reactive Oxygen Species. 2687 31

BACKGROUND Extraskeletal osteosarcomas (ESOS) of the mediastinum are extremely rare and may present with concurrent nontuberculous mycobacteria infection. CASE REPORT We present the second documented case of high-grade anterior mediastinal extraskeletal osteosarcoma in a 59-year-old man with a history of treated, latent tuberculosis (TB). Sputum samples grew Mycoplasma avium complex and Mycobacterium fortuitum. Imaging showed a right-sided 7.6 cm mass with compression of the main bronchus. Subsequent biopsy with vimentin staining established the diagnosis of ESOS. Due to the patient's rapidly declining performance status, he was not deemed a candidate for surgery or chemotherapy. He subsequently expired within one month of presentation. CONCLUSIONS We present a unique case of high-grade anterior mediastinum ESOS and a review of the literature regarding all documented cases of ESOS to date. We suggest there is a possible link between mediastinal masses and nontuberculous mycobacteria infection.
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PMID:Concurrent Nontuberculous Mycobacteria Infection and High-Grade Anterior Mediastinal Extraskeletal Osteosarcoma (ESOS): Is There a Connection? 2753 18

Four red squirrels (Sciurus vulgaris) were subjected to necropsy examination over a 3-year period as part of a broader surveillance study. The squirrels presented with cutaneous, subcutaneous and/or internal swellings and nodules that consisted microscopically of sheets of atypical round cells and multinucleated giant cells. There was moderate anisokaryosis with rare mitoses. Nuclei ranged from oval to indented or C-shaped and some were bizarre, twisted or multilobulated. Many giant cells also had a bizarre morphology, with anisokaryosis within individual cells. Giant cell nuclei were often multilobulated, ring-shaped or segmented. Affected internal organs varied depending on the squirrel, but included lymph node, kidney, intestinal tract and lungs. Representative lesions from each of the four squirrels were negative for acid-fast organisms. Formalin-fixed tissues from all four squirrels and ethanol-fixed tissue from one animal were negative for Mycobacterium by polymerase chain reaction. Immunohistochemically, the majority of mononuclear and multinucleated giant cells in all four squirrels strongly expressed vimentin and class II molecules of the major histocompatibility complex. Otherwise, the atypical mononuclear and multinucleated cells were negative for CD3, Pax-5, Mac387, CD18 and E-cadherin. Based on the combination of cellular morphology, arrangement and immunophenotype, a novel form of atypical histiocytosis is considered most likely in these squirrels, although the exact origin and triggering factors remain uncertain.
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PMID:Atypical Histiocytosis in Red Squirrels (Sciurus vulgaris). 2832 May 32