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Robert L. Hunter - One of the best experts on this subject based on the ideXlab platform.
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Review: Multiple Roles of Cord Factor in the Pathogenesis of Primary, Secondary, and Cavitary Tuberculosis, Including a Revised Description of the Pathology of Secondary Disease
2015Co-Authors: Robert L. Hunter, Chinnaswamy Jagannath, Margaret R. Olsen, Jeffrey K. ActorAbstract:Abstract. Tuberculosis, once thought to have been controlled, is now resurgent in many parts of the world. Many gaps exist in understanding the pathogenesis of tuberculosis, especially secondary and cavitary disease. Evidence presented here suggests that cord factor (trehalose 6,6’-dimycolate, TDM) is a key driver of these processes. It is the most abundant Lipid released by virulent M. tuberculosis (MTB) and can switch between two sets of activities. On organisms, TDM is non-toxic and protects them from killing by macrophages. On Lipid surfaces, it becomes antigenic and highly toxic. Caseating granulomas, the hallmark of primary tuberculosis, develop from interaction of TDM with Lipid within granulomas. New evidence indicates that secondary tuberculosis begins as a Lipid Pneumonia that accumulates mycobacterial antigens and host Lipids in alveoli before developing conditions for activation of the toxicity and antigenicity of TDM. This rapidly produces caseation necrosis that leads to cavities. Finally, virulent MTB release large amounts of TDM during growth as a pellicle within cavities. We propose that such growth results in activation of the toxicity and antigenicity of TDM at the air interface and that presence of the activated TDM perpetuates the cavity
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doi:10.1155/2011/307631 Research Article Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in
2013Co-Authors: Cavitary Lesions, Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80 % of cases and nearly 100 % of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P<.05). Cavities contained significantly more T-regulatory cells (14.8%) than found in Lipid Pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis. 1
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Pathology of post primary tuberculosis of the lung: an illustrated critical review.
Tuberculosis (Edinburgh Scotland), 2011Co-Authors: Robert L. HunterAbstract:Post primary tuberculosis occurs in immunocompetent adults, is restricted to the lungs and accounts for 80% of all clinical cases and nearly 100% of transmission of infection. The supply of human tissues with post primary tuberculosis plummeted with the introduction of antibiotics decades before the flowering of research using molecular methods in animal models. Unfortunately, the paucity of human tissues prevented validation of the models. As a result, it is a paradigm of contemporary research that caseating granulomas are the characteristic lesion of all tuberculosis and that cavities form when they erode into bronchi. This differs from descriptions of the preantibiotic era when many investigators had access to thousands of cases. They reported that post primary tuberculosis begins as an exudative reaction: a tuberculous Lipid Pneumonia of foamy alveolar macrophages that undergoes caseation necrosis and fragmentation to produce cavities. Granulomas in post primary disease arise only in response to old caseous Pneumonia and produce fibrosis, not cavities. We confirmed and extended these observations with study of 104 cases of untreated tuberculosis. In addition, studies of the lungs of infants and immunosuppressed adults revealed a second type of tuberculous Pneumonia that seldom produces cavities. Since the concept that cavities arise from caseating granulomas was supported by studies of animals infected with Mycobacterium bovis, we investigated its pathology. We found that M. bovis does not produce post primary tuberculosis in any species. It only produces an aggressive primary tuberculosis that can develop small cavities by erosion of caseating granulomas. Consequently, a key unresolved question in the pathogenesis of tuberculosis is identification of the mechanisms by which Mycobacterium tuberculosis establish a localized safe haven in alveolar macrophages in an otherwise solidly immune host where it can develop conditions for formation of cavities and transmission to new hosts.
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Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in Cavitary Lesions
Hindawi Limited, 2011Co-Authors: Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P
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Immunopathology of postprimary tuberculosis: Increased T-regulatory cells and DEC-205-positive foamy macrophages in cavitary lesions
Clinical & developmental immunology, 2010Co-Authors: Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P < .05). Cavities contained significantly more T-regulatory cells (14.8%) than found in Lipid Pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis.
Jeffrey K. Actor - One of the best experts on this subject based on the ideXlab platform.
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Review: Multiple Roles of Cord Factor in the Pathogenesis of Primary, Secondary, and Cavitary Tuberculosis, Including a Revised Description of the Pathology of Secondary Disease
2015Co-Authors: Robert L. Hunter, Chinnaswamy Jagannath, Margaret R. Olsen, Jeffrey K. ActorAbstract:Abstract. Tuberculosis, once thought to have been controlled, is now resurgent in many parts of the world. Many gaps exist in understanding the pathogenesis of tuberculosis, especially secondary and cavitary disease. Evidence presented here suggests that cord factor (trehalose 6,6’-dimycolate, TDM) is a key driver of these processes. It is the most abundant Lipid released by virulent M. tuberculosis (MTB) and can switch between two sets of activities. On organisms, TDM is non-toxic and protects them from killing by macrophages. On Lipid surfaces, it becomes antigenic and highly toxic. Caseating granulomas, the hallmark of primary tuberculosis, develop from interaction of TDM with Lipid within granulomas. New evidence indicates that secondary tuberculosis begins as a Lipid Pneumonia that accumulates mycobacterial antigens and host Lipids in alveoli before developing conditions for activation of the toxicity and antigenicity of TDM. This rapidly produces caseation necrosis that leads to cavities. Finally, virulent MTB release large amounts of TDM during growth as a pellicle within cavities. We propose that such growth results in activation of the toxicity and antigenicity of TDM at the air interface and that presence of the activated TDM perpetuates the cavity
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doi:10.1155/2011/307631 Research Article Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in
2013Co-Authors: Cavitary Lesions, Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80 % of cases and nearly 100 % of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P<.05). Cavities contained significantly more T-regulatory cells (14.8%) than found in Lipid Pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis. 1
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Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in Cavitary Lesions
Hindawi Limited, 2011Co-Authors: Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P
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Immunopathology of postprimary tuberculosis: Increased T-regulatory cells and DEC-205-positive foamy macrophages in cavitary lesions
Clinical & developmental immunology, 2010Co-Authors: Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P < .05). Cavities contained significantly more T-regulatory cells (14.8%) than found in Lipid Pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis.
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multiple roles of cord factor in the pathogenesis of primary secondary and cavitary tuberculosis including a revised description of the pathology of secondary disease
Annals of Clinical and Laboratory Science, 2006Co-Authors: Robert L. Hunter, Margaret Olsen, Chinnaswamy Jagannath, Jeffrey K. ActorAbstract:Tuberculosis, once thought to have been controlled, is now resurgent in many parts of the world. Many gaps exist in understanding the pathogenesis of tuberculosis, especially secondary and cavitary disease. Evidence presented here suggests that cord factor (trehalose 6,6'-dimycolate, TDM) is a key driver of these processes. It is the most abundant Lipid released by virulent M. tuberculosis (MTB) and can switch between two sets of activities. On organisms, TDM is non-toxic and protects them from killing by macrophages. On Lipid surfaces, it becomes antigenic and highly toxic. Caseating granulomas, the hallmark of primary tuberculosis, develop from interaction of TDM with Lipid within granulomas. New evidence indicates that secondary tuberculosis begins as a Lipid Pneumonia that accumulates mycobacterial antigens and host Lipids in alveoli before developing conditions for activation of the toxicity and antigenicity of TDM. This rapidly produces caseation necrosis that leads to cavities. Finally, virulent MTB release large amounts of TDM during growth as a pellicle within cavities. We propose that such growth results in activation of the toxicity and antigenicity of TDM at the air interface and that presence of the activated TDM perpetuates the cavity.
Kerry J. Welsh - One of the best experts on this subject based on the ideXlab platform.
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doi:10.1155/2011/307631 Research Article Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in
2013Co-Authors: Cavitary Lesions, Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80 % of cases and nearly 100 % of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P<.05). Cavities contained significantly more T-regulatory cells (14.8%) than found in Lipid Pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis. 1
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Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in Cavitary Lesions
Hindawi Limited, 2011Co-Authors: Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P
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Immunopathology of postprimary tuberculosis: Increased T-regulatory cells and DEC-205-positive foamy macrophages in cavitary lesions
Clinical & developmental immunology, 2010Co-Authors: Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P < .05). Cavities contained significantly more T-regulatory cells (14.8%) than found in Lipid Pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis.
Semyon A. Risin - One of the best experts on this subject based on the ideXlab platform.
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doi:10.1155/2011/307631 Research Article Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in
2013Co-Authors: Cavitary Lesions, Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80 % of cases and nearly 100 % of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P<.05). Cavities contained significantly more T-regulatory cells (14.8%) than found in Lipid Pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis. 1
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Immunopathology of Postprimary Tuberculosis: Increased T-Regulatory Cells and DEC-205-Positive Foamy Macrophages in Cavitary Lesions
Hindawi Limited, 2011Co-Authors: Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P
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Immunopathology of postprimary tuberculosis: Increased T-regulatory cells and DEC-205-positive foamy macrophages in cavitary lesions
Clinical & developmental immunology, 2010Co-Authors: Kerry J. Welsh, Jeffrey K. Actor, Semyon A. Risin, Robert L. HunterAbstract:Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, Lipid Pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in Lipid Pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker DEC-205, compared to granulomas (9.0%, P < .05). Cavities contained significantly more T-regulatory cells (14.8%) than found in Lipid Pneumonia (5.2%) or granulomas (4.8%). Distribution of the immune cell types may contribute to the inability of the immune system to eradicate tuberculosis.
A Ramis - One of the best experts on this subject based on the ideXlab platform.
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endogenous Lipid Pneumonia in a ferret mustela putorius furo
Journal of Exotic Pet Medicine, 2011Co-Authors: David Perpinan, A RamisAbstract:A 1-year-old female ferret was presented with an acute history of severe respiratory distress. Abnormal clinical signs noted during the initial physical examination were hypothermia, dehydration, pale mucous membranes, tachypnea, and severe dyspnea. Thoracic radiographs revealed pleural effusion, an enlarged cardiac silhouette, and areas of lung consolidation. Both blood and thoracic fluid were hyperproteinemic and hypergammaglobulinemic. Antibiotic, corticosteroid, and diuretic supportive treatment provided temporary improvement. After the initial positive response to treatment, the ferret's condition progressively deteriorated until the owners decided to euthanize the patient 15 days after initial presentation. Gross necropsy results revealed 5 mL of serosanguinous fluid within the thoracic cavity, cardiomegaly, and consolidated lungs that had a patchy, pale golden tissue pattern. The histologic diagnosis was endogenous Lipid Pneumonia. Findings suggest that endogenous Lipid Pneumonia can be associated with severe respiratory disease in ferrets.
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identification of group 1 coronavirus antigen in multisystemic granulomatous lesions in ferrets mustela putorius furo
Journal of Comparative Pathology, 2008Co-Authors: J Martinez, D Perpiñán, M Reinacher, A RamisAbstract:Tissues from nine ferrets with granulomatous lesions similar to those seen in feline infectious peritonitis were examined histopathologically and immunohistochemically. Four main types of lesions were observed: diffuse granulomatous inflammation on serosal surfaces; granulomas with areas of necrosis; granulomas without necrosis; and granulomas with neutrophils. Other less commonly seen lesions were granulomatous necrotizing vasculitis and endogenous Lipid Pneumonia. FCV3-70 monoclonal antibody produced immunolabelling of group 1 coronavirus antigen in tissue samples from eight animals, the antigen being present in the cytoplasm of macrophages in the different types of granulomatous lesions.