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Journal articles on the topic 'Granuloma'
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1
Mattila, Joshua T., Victoria A. Gould, Beth A. Junecko, Michael C. Bellavia, H. Jacob Borish, Alexander G. White, Pauline Maiello, et al. "Bacteria load and hypoxia contribute to glucose uptake by macrophages and T cells in cynomolgus macaque granulomas." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 50.22. http://dx.doi.org/10.4049/jimmunol.208.supp.50.22.
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Abstract Granulomas form during tuberculosis (TB) and restrain bacterial dissemination but are also sites of mycobacterial replication and persistence. The immunometabolic state of cells in granulomas has immunologic and diagnostic relevance and PET-CT with the glucose analog FDG demonstrates that granuloma glucose uptake is dynamic and heterogenous within a host. Basic details on glucose uptake, including the cells responsible for FDG PET signal, have not been resolved and filling these gaps will improve interpretation of PET data in TB. Our objective was to identify relationships between glucose (FDG) uptake and granuloma composition and to identify factors that drive this process in M. tuberculosis-infected cynomolgus macaques. We used glucose transporter 1 (GLUT1) to identity cells that may be using glucose as an energy source in granulomas, and compared these data with the cell’s microenvironment, and the granuloma’s bacteria load and FDG PET data to determine how these factors influence GLUT1 expression. We found that GLUT1 was strongly expressed by myeloid cell subsets in specific granuloma microenvironments and this pattern was conserved in granulomas from different organs. We also identified macrophage subsets and T cells that may be important contributors to a granuloma’s potential glucose (FDG) uptake when their GLUT1 expression and population sizes were considered. We also correlated granuloma bacteria loads and hypoxia with GLUT1 expression, suggesting that bacterial antigens and hypoxic conditions drive a granuloma’s glucose uptake. Taken together, our data suggest that granuloma glycolysis and FDG uptake are driven, in part, by cell subset-specific responses to a granuloma’s microbial and microenvironmental milieu. This work was supported by NIH grants AI134183 and AI118195.
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Cardoso, Marcos S., Tânia M. Silva, Mariana Resende, Rui Appelberg, and Margarida Borges. "Lack of the Transcription Factor Hypoxia-Inducible Factor 1α (HIF-1α) in Macrophages Accelerates the Necrosis of Mycobacterium avium-Induced Granulomas." Infection and Immunity 83, no. 9 (June 22, 2015): 3534–44. http://dx.doi.org/10.1128/iai.00144-15.
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The establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology ofMycobacterium tuberculosis, using C57BL/6 mice infected intravenously with a low dose of a highly virulent strain ofMycobacterium avium. In this work, a mouse strain deleted of the hypoxia inducible factor 1α (HIF-1α) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1α in the caseation of granulomas. The genetic ablation of HIF-1α in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance againstM. aviuminfection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1α in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1α inactivation, accelerates granuloma necrosis.
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Hogan, Laura H., Wes Markofski, Anja Bock, Brittany Barger, James D. Morrissey, and Matyas Sandor. "Mycobacterium bovis BCG-Induced Granuloma Formation Depends on Gamma Interferon and CD40 Ligand but Does Not Require CD28." Infection and Immunity 69, no. 4 (April 1, 2001): 2596–603. http://dx.doi.org/10.1128/iai.69.4.2596-2603.2001.
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ABSTRACT Progressive granuloma formation is a hallmark of chronic mycobacterial infection. Granulomas are localized, protective inflammatory reactions initiated by CD4+ T cells, which contribute to control of bacterial growth and blockade of bacterial dissemination. In order to understand the costimulatory requirements that allow CD4+ T cells to directly or indirectly induce granulomas, we studied granuloma formation after 6 weeks inMycobacterium bovis BCG-infected CD28- and CD40 ligand (CD40L)-deficient mice and compared it to granuloma formation in infected wild-type inbred mice and infected cytokine-deficient mice. We characterized granulomas morphologically in liver sections, analyzed granuloma infiltrating cells by flow cytometry, and measured cytokine production by cultured granuloma cells. CD28-deficient mice have no defect at the local inflammatory site, inasmuch as they form protective granulomas and control bacterial growth. However, there are fewer activated T cells in the spleen compared to infected wild-type animals, and quantitative differences in the cellular composition of the granuloma are observed by flow cytometry. In CD40L-deficient mice, the granuloma phenotype is very similar to the phenotype in gamma interferon (IFN-γ)-deficient mice. Both IFN-γ-deficient and CD40L-deficient mice form granulomas which prevent bacterial dissemination, but control of bacterial growth is significantly impaired. The relative proportion of CD4+ T cells in granulomas from both CD28−/− and CD40L−/−mice is significantly decreased compared with wild-type animals. Both models demonstrate that the phenotype and activation stage of systemic T cells do not always correlate with the phenotype and activation stage of the localized granulomatous response.
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Fitzgerald, Liam E., Naiara Abendaño, Ramon A. Juste, and Marta Alonso-Hearn. "Three-DimensionalIn VitroModels of Granuloma to Study Bacteria-Host Interactions, Drug-Susceptibility, and Resuscitation of Dormant Mycobacteria." BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/623856.
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Mycobacterium tuberculosis,Mycobacterium leprae,Mycobacterium bovis,andMycobacterium aviumsubsp.paratuberculosiscan survive within host macrophages in a dormant state, encased within an organized aggregate of immune host cells called granuloma. Granulomas consist of uninfected macrophages, foamy macrophages, epithelioid cells, and T lymphocytes accumulated around infected macrophages. Within granulomas, activated macrophages can fuse to form multinucleated giant cells, also called giant Langhans cells. A rim of T lymphocytes surrounds the core, and a tight coat of fibroblast closes the structure. Severalin vivomodels have been used to study granuloma’s structure and function, but recently developedin vitromodels of granuloma show potential for closer observation of the early stages of host’s responses to live mycobacteria. This paper reviews culture conditions that resulted in three-dimensional granulomas, formed by the adhesion of cell populations in peripheral blood mononuclear cells infected with mycobacteria. The similarities of these models to granulomas encountered in clinical specimens include cellular composition, granulomas’ cytokine production, and cell surface antigens. A reliablein vitrodormancy model may serve as a useful platform to test whether drug candidates can kill dormant mycobacteria. Novel drugs that target dormancy-specific pathways may shorten the current long, difficult treatments necessary to cure mycobacterial diseases.
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Rumbley, Catherine A., S. Ali Zekavat, Hiroko Sugaya, Peter J. Perrin, Mohamad Ali Ramadan, and S. Michael Phillips. "The Schistosome Granuloma: Characterization of Lymphocyte Migration, Activation, and Cytokine Production." Journal of Immunology 161, no. 8 (October 15, 1998): 4129–37. http://dx.doi.org/10.4049/jimmunol.161.8.4129.
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Abstract Granuloma formation and its regulation are dependent on lymphocytes. Therefore, we compared the characteristics of lymphocytes derived from the spleens and granulomas of Schistosoma mansoni-infected mice during the course of their disease. We examined lymphocyte cell cycle kinetics, migration, expression of activation Ags (CD69 and IL-2R), cytokine production (IL-2, IL-4, IFN-γ), and apoptosis. Lymphocytes in the G2/M phase of the cell cycle and high levels of lymphocyte intracellular IL-2 were found in the spleen but not in the granuloma. Cell trafficking experiments showed Ag-specific recruitment of schistosomal egg Ag (SEA)-reactive lymphoblasts into granulomas in vivo, as well as recruitment to, residence within, and egress from granulomas in vitro. Granuloma-derived lymphocytes were more highly activated than splenic lymphocytes based on higher levels of CD69 and IL-2R expression. While the granuloma microenvironment was rich in Th2 cytokines, during peak granuloma formation, the lymphocytes per se from the spleen and granuloma did not exhibit a dominant Th1 or Th2 cytokine profile, producing low but similar levels of IL-4 and IFN-γ. The discrepancy between high IL-2R expression and low levels of IL-2 protein production by granuloma lymphocytes was associated with increased apoptosis in the granuloma compared with the spleen. These findings support the hypothesis that granulomas may play a role in the regulation of systemic pathology in schistosomiasis by adversely affecting the survival of SEA-reactive, immunopathogenic T lymphocytes.
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Herbath, Melinda, Jeffrey S. Harding, Sarah Marcus, George Hasko, Andras Nagy, Zsuzsanna Fabry, and Matyas Sandor. "Regulators of mycobacterial granuloma formation – CCL2 and VEGF-A." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 42.7. http://dx.doi.org/10.4049/jimmunol.200.supp.42.7.
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Abstract Granulomas are macrophage dominated lesions and are a central feature of mycobacterial infections. These cell aggregates are dynamically changing structures as the life span of the granuloma recruited effector cells is relatively short and the cells have to be replaced. CCL2 and VEGF-A are required for granuloma maintenance as blocking the action of these chemokines results in reduction of granuloma size and number after BCG or Mtb infections. We seek to elucidate the relevance of these two cytokines in the timeline of mycobacterial infections and their relative contribution to granuloma formation. CD11c+ cell immigration is impaired, costimulatory molecule expression is lower and granulomas are smaller while the bacterial burden is higher in the liver when CCR2KO mice are infected i.p. with M. bovis BCG. Similarly, in animals that are selectively deficient in macrophage VEGF-A production the granulomas are smaller. Granuloma cells produce VEGF-A. Caseating granulomas, like the ones induced in C3HeB/FeJ (Kramnik) mice are hypoxic and hypoxia is a strong inducer of VEGF-A production. Sarcoid lesions induced by BCG or Mtb in B6 mice are not hypoxic but we show that ATP released from dead cells induces VEGF-A in a subpopulation of macrophages in the granulomas. Additionally, VEGF production proved to be dependent on granuloma size: bigger granulomas produce larger quantities of VEGF-A while smaller lesions produce less or none. This finding suggests that unlike other chemokines such as CCL2, which is described to be involved in both granuloma initiation and maintenance, VEGF-A may support an increased lesion size in the late acute phase of infection. Regulating cellular recruitment may provide new therapies for granulomatous diseases.
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Dhakal, Mona, Om Prakash Dhakal, Mingma Sherpa, Amlan Gupta, and Dhurba Bhandari. "Large gastric ulcer: Result of foreign body-induced giant cell reaction." Journal of Digestive Endoscopy 04, no. 03 (July 2013): 078–81. http://dx.doi.org/10.4103/0976-5042.129974.
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AbstractA granuloma is an organized and compact mass of mature mononuclear phagocytes. Granulomas are reported to form in various organs and sites of the body. Granulomas in stomach are rarely encountered. Foreign body granulomas are formed as a result of reaction of the tissues to a foreign body which is immunologically inert. Food granuloma is type of foreign body granuloma which is formed in response to food particles like vegetable matters or cereals. These granulomas can be distinguished from other types of granulomas with ease because of their characteristic morphologic features. We report the case of a 29-year-old male who developed a large gastric ulcer as a result of foreign body–induced giant cell reaction, which was probably of vegetative origin. He was treated with the regimen for Helicobacter pylori, rabeprazole and sucralfate. This treatment resulted in partial healing of the ulcer with persistence of food granuloma; hence, the patient was referred for surgery.
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Metwali, A., D. Elliott, R. Mathew, A. Blum, and J. V. Weinstock. "IL-2 contributes to the IL-5 response in granulomas from mice infected with Schistosoma mansoni." Journal of Immunology 150, no. 2 (January 15, 1993): 536–42. http://dx.doi.org/10.4049/jimmunol.150.2.536.
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Abstract Th cells within the granulomas of murine schistosomiasis mansoni produce IL-5, which is essential for granuloma eosinophil growth and development. The mechanisms regulating granuloma IL-5 production are unknown. The granulomas also make IL-2 in small quantities. rIL-2 therapy stimulates eosinophilia and IL-5 synthesis. Therefore, we studied the effect of IL-2 on IL-5 production within the liver granulomas of murine Schistosoma mansoni. Dispersed granuloma cells and intact granulomas cultured in vitro released IL-5. Adding anti-IL-2 or anti-IL-2R to the cultures, to block IL-2 activity, significantly inhibited IL-5 production. However, supplementing the cultures with small quantities of rIL-2 markedly stimulated IL-5 release in a dose-dependent fashion. Blocking anti-IL-4 mAb had no effect. Also, granuloma T cells were isolated by FACS. These highly purified T cells produced IL-5 both in the presence and absence of plate-bound anti-CD3. Once again, the IL-5 production was dependent on IL-2. The requirement of IL-2 for normal IL-5 production was not dependent on an IL-2-induced expansion of the IL-5-producing, T lymphocyte population. Thus, IL-2 mediates T cell interactions within the granuloma that regulate granuloma IL-5 secretion.
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Talita Shofa Adestia. "In vitro Tuberculosis Granuloma Model in M. tuberculosis H37Rv." Jurnal Biosains Pascasarjana 25, no. 1 (June 30, 2023): 66–73. http://dx.doi.org/10.20473/jbp.v25i1.2023.66-73.
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M. tuberculosis is a bacterium that has many evasion mechanisms against the immune system, one of them is the formation of granulomas which is beneficial for the bacteria’s survival. The granuloma structure is useful for limiting the spread of M. tuberculosis and localizing infection, also considered as part of M. tuberculosis life cycle that successful fighting the body's immune system. This study aims to look at the formation of an in vitro tuberculous granuloma model. This study used the True Experiment type which began with blood sampling, PBMC isolation, macrophage isolation, MOI 10 making and granulomas making. Granulomas were observed on day 0, 1, 4, 7, 9, 10 and 14. Cells started to aggress on day 1 and giant cells were seen on day 4. The granuloma formed on day 9 and was maintained on day 10, however, the granuloma ruptured on day 14 which caused the cells to re-aggregate.
Keywords: Granuloma, M. tuberculosis, PBMC
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Rakasz, Eva, Arthur M. Blum, Ahmed Metwali, David E. Elliott, Jie Li, Zuhair K. Ballas, Khurram Qadir, Richard Lynch, and Joel V. Weinstock. "Localization and Regulation of IFN-γ Production Within the Granulomas of Murine Schistosomiasis in IL-4-Deficient and Control Mice." Journal of Immunology 160, no. 10 (May 15, 1998): 4994–99. http://dx.doi.org/10.4049/jimmunol.160.10.4994.
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Abstract Schistosome granulomas from normal or IL-4-deficient C57BL/6 mice make little IFN-γ and show no Th1 polarization. This could signify that these granulomas have few cells capable of IFN-γ synthesis or that such cells are under tight control. Granulomas can make IL-10 and TGF-β, which can regulate IFN-γ synthesis. Using FACS analysis and ELISA, we explored the origin and regulation of IFN-γ in schistosome granulomas from both IL-4−/− and IL-4+/+ mice. FACS analysis of intracytoplasmic IFN-γ staining showed that some granuloma Thy1.2+ T cells (CD8+ and CD4+) express IFN-γ. Granulomas had NK1.1+ cells, but they appeared to produce little or no IFN-γ. Purified granuloma Thy1.2+ cells made IFN-γ in vitro, whereas isolated NK1.1+ lymphocytes secreted little even with rIL-12 stimulation. Culture of granuloma cells with blocking anti-IL-10 or anti-TGF-β mAb or with rIL-12 substantially increased T cell IFN-γ synthesis, particularly in the IL-4−/− animals. Cultured granuloma cells depleted of Thy1.2+ lymphocytes by Ab and C released no IFN-γ. It is concluded that granuloma IFN-γ comes from T cells, not NK cells. Also, this T cell-derived IFN-γ is subject to IL-10 and TGF-β regulation, which is particularly evident in IL-4−/− mice. Thus, the Th2 granuloma of schistosomiasis has large numbers of activated Th1 or Th0 lymphocytes that are under tight restraint.
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Farwell, D. G., P. C. Belafsky, and C. J. Rees. "An endoscopic grading system for vocal process granuloma." Journal of Laryngology & Otology 122, no. 10 (March 3, 2008): 1092–95. http://dx.doi.org/10.1017/s0022215108001722.
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AbstractBackground:A reliable grading system allows the clinician to classify disease severity, monitor progress and evaluate treatment efficacy. There is no currently accepted grading system for vocal process granuloma of the larynx.Aim:To evaluate the reliability of a new grading system for vocal process granuloma.Methods:All vocal process granuloma images from a digital laryngeal image library were abstracted. Granulomas were graded on a one to four system, as follows: grade one, sessile, non-ulcerative granuloma limited to vocal process; grade two, pedunculated or ulcerated granuloma limited to vocal process; grade three, granuloma extending past vocal process but not crossing midline of airway in fully abducted position; and grade four, granuloma extending past vocal process and past the midline of the airway in the fully abducted position. The granulomas were additionally graded A if unilateral and B if bilateral. Two laryngologists and two otolaryngology residents rated the granulomas on two separate occasions. Intra- and inter-observer reliability was evaluated with the kappa (κ) test statistic.Results:Thirty-five vocal process granulomas were identified. The percentage intra-observer agreement for the two laryngologists was 97 and 100 per cent (κ = 0.94 and 1.00, respectively). The percentage inter-observer agreement between the two laryngologists was 91 per cent (κ = 0.83). The percentage intra-observer agreement for the two residents was 89 and 91 per cent (κ = 0.83 and 0.77, respectively). The percentage inter-observer agreement between the two residents was 83 per cent (κ = 0.67).Conclusions:The proposed grading system for vocal process granuloma displayed excellent intra- and inter-observer reliability among residents and experienced laryngologists.
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Volkman, Hannah E., Tamara Pozos, John Zheng, John F. Rawls, and Lalita Ramakrishnan. "The Mycobacterium marinum RD1 locus promotes virulence and macrophage aggregation into tuberculous granulomas by enhancing induction of host matrix metalloproteinase 9 in proximal epithelial cells (133.19)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 133.19. http://dx.doi.org/10.4049/jimmunol.182.supp.133.19.
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Abstract Granulomas are organized aggregates of differentiated macrophages and other immune cells that form in response to mycobacterial infection and other persistent stimuli. While the tuberculous granuloma has long been considered a host-protective structure, our recent work in the genetically tractable and optically transparent zebrafish embryo-Mycobacterium marinum model of tuberculosis, has suggested that the early granuloma actually benefits mycobacteria. The mycobacterial RD1 virulence locus, a specialized bacterial secretion system, enhances granuloma formation, which in turn, promotes bacterial expansion and dissemination. Here we present the molecular and cellular details of RD1-induced granuloma formation. RD1-secreted effectors induce host matrix metalloproteinase 9 (mmp9) in epithelial cells neighboring the infected macrophages. By specifically knocking down host mmp9, we have shown that its expression facilitates macrophage recruitment to form granulomas and bacterial expansion. Selective mmp9 induction in immotile epithelial cells neighboring infected macrophages may serve as a mechanism to fix and expand infection foci at optimal sites. Our results provide direct evidence that early granulomas benefit mycobacteria and suggest new tuberculosis therapeutic strategies that target granuloma-promoting host susceptibility determinants like mmp9.
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Herbath, Melinda, Jeffrey S. Harding, György Haskó, András Nagy, Zsuzsanna Fábry, and Mátyás Sándor. "Recruitment of myeloid cells into mycobacterial granulomas." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 65.18. http://dx.doi.org/10.4049/jimmunol.196.supp.65.18.
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Abstract Granuloma formation is a hallmark of mycobacterial infection. The dominant cell types in granuloma are the blood monocyte derived macrophages and inflammatory dendritic cells that represent up to 80% of cells in these lesions. Using granuloma transplantation we demonstrated that in a week more than the third of these cells are replaced. Innate and cognate immunity against the bacteria induces a battery of chemokines that are important in this recruitment and MCP1-CCR2 is one of the main representatives of these pathways. We have also shown that cell death and death-induced extracellular ATP through P2X7R promote VEGF production in a subpopulation of granuloma macrophages and that is also important for myeloid cell recruitment through VEGFR1 displayed by blood monocytes. These factors affect granuloma size, numbers and the number of extravasated monocytes in the tissue around granulomas. We further compare BCG-induced liver and Mtb-induced lung granulomas in wild type, hypoVEGF, macrophage VEGF production ablated, selective macrophage P2X7R deficient, and CCR2 deficient mice. Additionally to the size and frequency of granulomas we compare cell composition, the cytokines present and bacterial load in the lesions. These data clarify the role of immune response and cell death driven cell recruitment pathways in the granuloma maintenance.
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Metwali, Ahmed, Arthur Blum, David E. Elliott, and Joel V. Weinstock. "Interleukin-4 Receptor α Chain and STAT6 Signaling Inhibit Gamma Interferon but Not Th2 Cytokine Expression within Schistosome Granulomas." Infection and Immunity 70, no. 10 (October 2002): 5651–58. http://dx.doi.org/10.1128/iai.70.10.5651-5658.2002.
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ABSTRACT Compared to wild-type (WT) mice, schistosome granulomas in Stat6 knockout (KO) mice lacked eosinophils and had Th1 features. Interleukin-4 (IL-4) acts through Stat6 in assisting Th2 cell development. The importance of Stat6 for Th2-cell development within schistosome granulomas had not been explored. Therefore we studied gamma interferon (IFN-γ), IL-4, and IL-5 production in granulomas from Stat6 KO and WT mice. Dispersed granuloma cells from Stat6 KO and WT mice made similar amounts of IL-4 and IL-5. Only Stat6 KO granuloma cells released IFN-γ. Granuloma T cells contained most of the IL-4, IL-5, and IFN-γ mRNA and secreted these cytokines. In Stat6 KO mice, 16.6% of the granuloma cells were CD4+. Of these, 10.7% stained for IFN-γ and/or IL-4 by intracytoplasmic flow analysis. Few CD4− T cells stained positively. The IL-4-producing T cells did not stain for DX5 or with labeled α-GalCer CD1d tetramer, suggesting an absence of NK T cells. Thus, conventional Th cells in Stat6 KO granulomas produce IFN-γ and Th2 cytokines. Stat6 limits IFN-γ production but is unnecessary for Th2-cell development or localization within the granuloma.
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Taniguchi, Kazuto, Kazutaka Mizuta, and Kazuyasu Uemichi. "A Novel Strategy for Umbilical Granuloma Removal: Cutting off with a Nylon Suture Thread." Journal of Nepal Paediatric Society 42, no. 3 (December 31, 2022): 67–69. http://dx.doi.org/10.3126/jnps.v42i3.45499.
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Umbilical granuloma is a common umbilical problem in infants. Although various modalities are available for the treatment of umbilical granulomas, the best method remains controversial. A 7-week-old infant presented with umbilical granuloma followed by omphalitis. We treated the omphalitis first to prevent local inflammation. On the following day, the umbilical granuloma was successfully cut off with a nylon suture thread. No residue of the granuloma was left behind and no signs of local inflammation appeared. Umbilical granuloma can be successfully removed with a nylon suture thread. Treatment for omphalitis before granuloma removal may be useful to prevent local inflammation.
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Elliott, D. E., A. Metwali, A. M. Blum, M. Sandor, R. Lynch, and J. V. Weinstock. "T lymphocytes isolated from the hepatic granulomas of schistosome-infected mice express somatostatin receptor subtype II (SSTR2) messenger RNA." Journal of Immunology 153, no. 3 (August 1, 1994): 1180–86. http://dx.doi.org/10.4049/jimmunol.153.3.1180.
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Abstract Schistosomiasis mansoni is a disease characterized by liver and intestinal granulomas. Previous investigations in our laboratory showed that nylon wool-adherent CD4+ T lymphocytes isolated from murine hepatic schistosome granulomas express receptors for somatostatin 1-14. Moreover, somatostatin 1-14 substantially decreased IFN-gamma and IgG2a, but not IL-5 secretion by dispersed granuloma cells. This paper extends these observations by defining the somatostatin receptor (SSTR) isoform most likely expressed by granuloma inflammatory lymphocytes. Amplification of mRNA by reverse transcription PCR shows SSTR1, SSTR2, and SSTR3 mRNA in normal mouse brain and other tissues. Nevertheless, only the SSTR2 PCR product was amplified from granuloma cell RNA. The nucleotide sequence of the granuloma SSTR2 PCR product from inflammatory cells is identical to the CBA murine brain SSTR2 cDNA sequence. Granuloma-derived T cell lines, FACS-isolated granuloma CD4+ T cells, thymocytes, splenocytes, and cloned T cell lines all contain mRNA for SSTR2 by reverse transcription PCR. Moreover, both SSTR2A and the splice variant SSTR2B can be amplified from dispersed granuloma cells, granuloma T cell lines, thymocytes, and splenocytes. This is the first demonstration that inflammatory cells produce mRNA for an authentic somatostatin receptor. It is probable that the lymphocyte SSTR2 receptor mediates somatostatin-induced modulation of IFN-gamma secretion.
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Dykstra, M. J., and E. J. Noga. "A light and electron microscopic examination of novel features of fish granulomas." Proceedings, annual meeting, Electron Microscopy Society of America 45 (August 1987): 862–63. http://dx.doi.org/10.1017/s0424820100128596.
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A typical mammalian granuloma resulting from chronic inflammation is primarily composed of plasma cells, lymphocytes, macrophages, monocytes and giant cells. So-called epithelioid cells are usually found in granulomas of immunological origin and are derived from the mononuclear phagocyte series. Epithelioid cell granulomas are associated with a number of infectious diseases of man such as tuberculosis, schistosomiasis and fungal infections such as coccidioidomycosis.Tissues from Atlantic menhaden and Tilapia fish were fixed in 10% formalin and stained with hematoxylin and eosin (H&E) for light microscopy. Replicate samples were fixed with McDowell's and Trump's fixative, embedded in Spurr's resin, sectioned, stained with uranyl acetate and lead citrate and examined with a transmission electron microscope.Three fish granulomas were examined: 1) A granuloma of unknown origin in a menhaden spleen (Figs. 1,2); 2) A granuloma induced by fungal hyphae in a menhaden with ulcerative mycosis (Figs. 3,4); and 3) A granuloma due to mycobacteriosis in Tilapia (Figs. 5,6).
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Kobayashi, K., C. Allred, and T. Yoshida. "Mechanisms of suppressed cell-mediated immunity and impaired antigen-induced interleukin 2 production in granuloma-bearing mice." Journal of Immunology 135, no. 5 (November 1, 1985): 2996–3003. http://dx.doi.org/10.4049/jimmunol.135.5.2996.
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Abstract Pulmonary granulomas were induced in BALB/c mice immunized with methylated bovine serum albumin in complete Freund's adjuvant by the intratracheal injection of plain agarose beads or beads conjugated to specific antigen. Large hypersensitivity granulomas developed around antigen-coupled beads in immunized animals. Smaller but still prominent granulomatous reactions developed around plain beads in immunized mice. In nonimmunized animals, both plain and antigen conjugated beads produced very small granulomas. Granuloma formation in sensitized animals was associated with suppressed delayed-type hypersensitivity reactions induced by the footpad injection of specific and nonspecific antigens. Lymph node cells from sensitized granuloma-bearing mice with cutaneous anergy showed suppressed specific and nonspecific antigen-induced proliferative responses in vitro. These cells also showed suppressed interleukin 2 production in response to specific antigen. Although no soluble suppressive factor was detected in granuloma extracts, suppressor cells were found in lymph nodes of granuloma-bearing mice, which could inhibit antigen-induced production of interleukin 2 by lymph node cells from immunized mice. Antigen-specific immunoglobulin G antibody production was not suppressed in immunized granuloma-bearing mice. Previous studies from our laboratory have demonstrated migration inhibition factor and interleukin 1 activities in aqueous extracts prepared from granuloma-bearing lungs of immunized mice. These results and the findings reported here indicate that granuloma formation and the associated anergy observed in this system are primarily expressions of cell-mediated immunity; selective suppression of in vivo and in vitro expressions of cell-mediated immunity in granuloma-bearing mice may be due to impaired antigen-induced interleukin 2 production; and such impairment is caused by suppressor cells.
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Marino, Simeone, Nicholas Cilfone, Joshua Mattila, JoAnne Flynn, Jennifer Linderman, and Denise Kirschner. "Macrophage polarization drives granuloma outcome during Mycobacterium tuberculosis infection (IRC5P.475)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 125.24. http://dx.doi.org/10.4049/jimmunol.192.supp.125.24.
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Abstract Lung granulomas are the pathologic hallmark of tuberculosis (TB), where different immune cell types and bacteria co-localize. Macrophages are the most abundant cells in a granuloma. They are both critical effector and target cells for Mycobacterium tuberculosis (Mtb, the causative agent of TB) infection, and serve as regulators of inflammation and innate immune responses by producing a variety of pro- and anti-inflammatory cytokines. Overall, macrophage function, diversity and location within a granuloma environment are still poorly understood. In this study we used a systems biology approach to better characterize how macrophages are polarized by their microenvironment to mount either a pro- or an anti-inflammatory phenotype. We built on recently published experimental studies on non-human primates that suggest how a continuous dynamic balance between pro and anti-inflammatory signals is achieved to control pathology and restrain bacterial growth within a granuloma. Here we investigated how this balance translates into macrophage polarization and plasticity, and how the relative contribution of these macrophages, broadly classified as ‘M1’ and ‘M2’, evolves over time and leads to an effective immune response, at the granuloma scale. Our in silico granulomas suggest that temporal dynamics of granuloma polarization ratios can be predictive of granuloma outcome. We also find that a signature common to properly formed and functioning granulomas is increased NFkB degradation.
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Lukacs, N. W., S. L. Kunkel, R. M. Strieter, K. Warmington, and S. W. Chensue. "The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation." Journal of Experimental Medicine 177, no. 6 (June 1, 1993): 1551–59. http://dx.doi.org/10.1084/jem.177.6.1551.
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Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a 6-8-kD, lipopolysaccharide-inducible monocyte and neutrophil chemotactic protein that may be important in acute and chronic inflammation. The present study determined the sequential production, source, and in vivo contribution of murine MIP-1 alpha in synchronized Schistosoma mansoni egg pulmonary granuloma formation. Granulomas were examined under conditions of primary, secondary vigorous, and secondary immunomodulated immunity. Secreted MIP-1 alpha was measured in 24-h supernatants from intact granulomas (700/ml) cultured with or without soluble egg antigen (SEA). Primary granulomas isolated from naive mice over a 16-d period showed low spontaneous MIP-1 alpha production (< 1 ng/ml). However, when primary granulomas were challenged with SEA, significant MIP-1 alpha production was observed beginning at day 4 and peaking at day 16. Intact vigorous (isolated from 8-wk-infected mice) and modulated (isolated from 20-wk-infected mice) secondary pulmonary granulomas demonstrated comparable spontaneous MIP-1 alpha production. Addition of SEA to vigorous stage granulomas augmented expression of MIP-1 alpha at all time points, whereas stimulated modulated stage granulomas did not increase production. The latter observation is likely related to endogenous immunoregulatory mechanisms reported for modulated stage animals. Immunohistochemical localization of MIP-1 alpha in granuloma sections and cytocentrifuge preparations from vigorous lesions localized MIP-1 alpha production to macrophages within granulomas. Treatment of mice with rabbit anti-mouse MIP-1 alpha antibodies significantly decreased 8-d primary granuloma formation (> 40%) when compared with control mice. Anti-MIP-1 alpha sera also decreased vigorous (> 20%), but not modulated granuloma formation. These findings demonstrate that MIP-1 alpha contributes to cellular recruitment during schistosome egg granuloma formation.
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Lins, Romero Antunes Barreto, Carmelita Bezerra de Lima Cavalcanti, Jorge Luiz Silva Araújo-Filho, Mário Ribeiro de Melo-Júnior, and Maria Elizabeth Cavalcante Chaves. "A distribuição dos eosinófilos nas diferentes fases de evolução do granuloma hepático em camundongos infectados pelo Schistosoma mansoni." Revista da Sociedade Brasileira de Medicina Tropical 41, no. 2 (April 2008): 173–78. http://dx.doi.org/10.1590/s0037-86822008000200008.
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No presente estudo, avaliou-se a distribuição dos eosinófilos nas diferentes fases da formação do granuloma hepático de camundongos infectados pelo Schistosoma mansoni. A partir dos resultados obtidos sugerimos uma nova classificação para a evolução do granuloma hepático em camundongos montada a partir de fases descritas por outros autores. Em cada fase há um padrão diferente de distribuição dos eosinófilos. Na fase necrótico-exudativa os eosinófilos encontram-se concentrados na periferia e no centro do granuloma e na área de necrose eles são escassos; na "produtiva" os eosinófilos estão ainda distribuídos de maneira difusa por todo o granuloma; na de cura por fibrose se concentram na periferia e no centro do granuloma. Os eosinófilos estavam em contato direto com os ovos em todos os estágios de evolução dos granulomas. Conclui-se então que a dinâmica dos eosinófilos possui papel importante na formação da reação granulomatosa do hospedeiro e resolução do processo inflamatório causado pelo ovo do parasita, além de acrescentar novos dados na classificação dos granulomas hepáticos.
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Penar, Paul L., Jung Kim, Douglas Chyatte, and James K. Sabshin. "Intraventricular cryptococcal granuloma." Journal of Neurosurgery 68, no. 1 (January 1988): 145–48. http://dx.doi.org/10.3171/jns.1988.68.1.0145.
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✓ Infection by Cryptococcus neoformans, a budding nonmycelial yeast, involves the central nervous system in 70% of patients at the time of diagnosis. Meningitis and meningoencephalitis are common manifestations of infection; solid granulomas occur but are unusual, and intraventricular granulomas are distinctly rare. Two cases of intraventricular cryptococcal granuloma are reported. The diagnosis and treatment of mass lesions due to cryptococcal infection are discussed, with special reference to intraventricular granulomas.
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Evans, Stephanie, J. Russell Butler, Joshua T. Mattila, and Denise E. Kirschner. "Systems biology predicts that fibrosis in tuberculous granulomas may arise through macrophage-to-myofibroblast transformation." PLOS Computational Biology 16, no. 12 (December 28, 2020): e1008520. http://dx.doi.org/10.1371/journal.pcbi.1008520.
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Mycobacterium tuberculosis (Mtb) infection causes tuberculosis (TB), a disease characterized by development of granulomas. Granulomas consist of activated immune cells that cluster together to limit bacterial growth and restrict dissemination. Control of the TB epidemic has been limited by lengthy drug regimens, antibiotic resistance, and lack of a robustly efficacious vaccine. Fibrosis commonly occurs during treatment and is associated with both positive and negative disease outcomes in TB but little is known about the processes that initiate fibrosis in granulomas. Human and nonhuman primate granulomas undergoing fibrosis can have spindle-shaped macrophages with fibroblast-like morphologies suggesting a relationship between macrophages, fibroblasts, and granuloma fibrosis. This relationship has been difficult to investigate because of the limited availability of human pathology samples, the time scale involved in human TB, and overlap between fibroblast and myeloid cell markers in tissues. To better understand the origins of fibrosis in TB, we used a computational model of TB granuloma biology to identify factors that drive fibrosis over the course of local disease progression. We validated the model with granulomas from nonhuman primates to delineate myeloid cells and lung-resident fibroblasts. Our results suggest that peripheral granuloma fibrosis, which is commonly observed, can arise through macrophage-to-myofibroblast transformation (MMT). Further, we hypothesize that MMT is induced in M1 macrophages through a sequential combination of inflammatory and anti-inflammatory signaling in granuloma macrophages. We predict that MMT may be a mechanism underlying granuloma-associated fibrosis and warrants further investigation into myeloid cells as drivers of fibrotic disease.
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Marino, Simeone, Nicholas A. Cilfone, Joshua T. Mattila, Jennifer J. Linderman, JoAnne L. Flynn, and Denise E. Kirschner. "Macrophage Polarization Drives Granuloma Outcome during Mycobacterium tuberculosis Infection." Infection and Immunity 83, no. 1 (November 3, 2014): 324–38. http://dx.doi.org/10.1128/iai.02494-14.
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Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), induces formation of granulomas, structures in which immune cells and bacteria colocalize. Macrophages are among the most abundant cell types in granulomas and have been shown to serve as both critical bactericidal cells and targets forM. tuberculosisinfection and proliferation throughout the course of infection. Very little is known about how these processes are regulated, what controls macrophage microenvironment-specific polarization and plasticity, or why some granulomas control bacteria and others permit bacterial dissemination. We take a computational-biology approach to investigate mechanisms that drive macrophage polarization, function, and bacterial control in granulomas. We define a “macrophage polarization ratio” as a metric to understand how cytokine signaling translates into polarization of single macrophages in a granuloma, which in turn modulates cellular functions, including antimicrobial activity and cytokine production. Ultimately, we extend this macrophage ratio to the tissue scale and define a “granuloma polarization ratio” describing mean polarization measures for entire granulomas. Here we coupled experimental data from nonhuman primate TB granulomas to our computational model, and we predict two novel and testable hypotheses regarding macrophage profiles in TB outcomes. First, the temporal dynamics of granuloma polarization ratios are predictive of granuloma outcome. Second, stable necrotic granulomas with low CFU counts and limited inflammation are characterized by short NF-κB signal activation intervals. These results suggest that the dynamics of NF-κB signaling is a viable therapeutic target to promote M1polarization early during infection and to improve outcome.
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Ogburn, David, Sophia Bhalla, Nan Leffler, Arjun Mohan, Anagha Malur, Achut G. Malur, Matthew McPeek, Barbara P. Barna, and Mary Jane Thomassen. "The M2a Macrophage Phenotype Accompanies Pulmonary Granuloma Resolution in Mmp12 Knock-Out Mice Instilled with Multiwall Carbon Nanotubes." International Journal of Molecular Sciences 22, no. 20 (October 13, 2021): 11019. http://dx.doi.org/10.3390/ijms222011019.
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Sarcoidosis is a chronic disease with unknown etiology and pathophysiology, characterized by granuloma formation. Matrix Metalloproteinase-12 (MMP12) is an elastase implicated in active granulomatous sarcoidosis. Previously, we reported that oropharyngeal instillation of multiwall carbon nanotubes (MWCNT) into C57Bl/6 mice induced sarcoid-like granulomas and upregulation of MMP12. When Mmp12 knock-out (KO) mice were instilled with MWCNT, granuloma formation occurred 10 days post-instillation but subsequently resolved at 60 days. Thus, we concluded that MMP12 was essential to granuloma persistence. The aim of the current study was to identify potential mechanisms of granuloma resolution in Mmp12KO mice. Strikingly, an M2 macrophage phenotype was present in Mmp12KO but not in C57Bl/6 mice. Between 10 and 60 days, macrophage populations in MWCNT-instilled Mmp12KO mice demonstrated an M2c to M2a phenotypic shift, with elevations in levels of IL-13, an M2 subtype-regulating factor. Furthermore, the M2 inducer, Apolipoprotein E (ApoE), and Matrix Metalloproteinase-14 (MMP14), a promoter of collagen degradation, were upregulated in 60-day MWCNT-instilled Mmp12KO mice. In conclusion, alveolar macrophages express two M2 phenotypes in Mmp12KO mice: M2c at 10 days when granulomas form, and M2a at 60 days when granulomas are resolving. Findings suggest that granuloma resolution in 60-day Mmp12KO mice requires an M2a macrophage phenotype.
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Blum, Arthur M., Ahmed Metwali, Mindy Kim-Miller, Jie Li, Khurram Qadir, David E. Elliott, Bao Lu, Zsuzsa Fabry, Norma Gerard, and Joel V. Weinstock. "The Substance P Receptor Is Necessary for a Normal Granulomatous Response in Murine Schistosomiasis Mansoni." Journal of Immunology 162, no. 10 (May 15, 1999): 6080–85. http://dx.doi.org/10.4049/jimmunol.162.10.6080.
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Abstract Immune cells within the granulomas of murine schistosomiasis mansoni make the neuropeptide substance P (SP) and express neurokine 1 receptor, which is the specific receptor for substance P (SPr). It was determined if mice with deletion of the SPr (SPr−/−) would develop a normal granulomatous response to schistosome ova during the course of natural infection. Mean liver granuloma size was smaller in SPr−/− mice compared with that of wild-type control animals. Although flow analysis revealed little difference in the cellular composition of the granulomas, both splenocytes and granuloma cells from SPr−/− mice produced much less IFN-γ and IgG2a and less IgE. The expression of Th2 cytokines (IL-4/IL-5) and IgG1 was comparable to the wild-type control. The mouse with targeted disruption of its SPr had the nonmammalian gene encoding the enzyme β-galactosidase inserted in exon 1 of the SPr gene. There was β-galactosidase activity in many mononuclear cells scattered throughout the schistosome granulomas of SPr−/− mice. Also, a granuloma T cell line derived from this transgenic mouse produced β-galactosidase. These results provide further evidence that in murine schistosomiasis SPr is displayed commonly on granuloma inflammatory cells and is important for granuloma development and expression of IFN-γ circuitry in this natural infection.
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Evans, Stephanie, Eileen A. Wong, JoAnne L. Flynn, Joshua T. Mattila, and Denise Kirschner. "Unraveling the role of fibrosis in the TB Granuloma." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 182.86. http://dx.doi.org/10.4049/jimmunol.202.supp.182.86.
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Abstract Tuberculosis (TB), a deadly infectious disease caused by the bacterium Mycobacterium tuberculosis (Mtb). The disease is characterized by the development of granulomas consisting of immune cells that form a cluster around the bacteria to limit bacterial growth and disease outcomes. Control of the TB epidemic is limited by a complicated drug regimen, development of antibiotic resistance, and the lack of an effective vaccine against infection and disease. Fibrosis is common in older granulomas, and has been associated with both positive and negative disease outcomes. Little is known about fibrosis in TB, partly due to the fact that fibroblasts are difficult to identify using traditional antibody-based techniques. To provide insight into the role that fibrosis plays at a single granuloma scale, we have developed a computational, agent-based model of granuloma formation in the lung following infection with Mtb. In previously published work we have identified the mechanisms driving fibrosis within a granuloma i.e. how the granuloma environment effects fibrosis. Using immunohistochemistry, we have characterized fibroblasts and early collagen deposition in TB granulomas. Here we have extended this work to look at how fibrosis affects the ability of a granuloma to control bacteria, focusing on the role of both fibroblasts. Predictions show that early fibrosis alters the structure of the granuloma with few long-term effects on bacterial control, however late fibrosis decreases the promotability of bacterial dissemination. This work has implications on treatment options for TB that typically cause early fibrosis to occur.
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Jusuf Fantoni, Odelia Jovita, Inda Astri Aryani, Yuli Kurniawati, and Raden Pamudji. "Histopathological Features of Cutaneous Tuberculoid Granuloma Disorders." Bioscientia Medicina : Journal of Biomedicine and Translational Research 5, no. 9 (May 17, 2021): 825–36. http://dx.doi.org/10.32539/bsm.v5i9.347.
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Tuberculoid granulomas consist of epithelioid histiocytes, Langhans giant cells and rarely foreign bodies with lymphocytes, plasma cells and caseous necrosis. The granulomatous reaction pattern is defined as a typical inflammatory pattern that is characterized by granulomas. Various etiologies can lead to granulomatous reactions. The histopathological features of cutaneous disorders with tuberculoid granuloma include cutaneous tuberculosis, tuberculids, Morbus Hansen, syphilis and rosacea. There are various clinical manifestations of tuberculoid granuloma with similar appearances which makes it difficult to establish a definitive diagnosis. The histopathological features of cutaneous tuberculoid granuloma disorders can support the diagnosis. Therefore, the clinician can determine the appropriate treatment with the right diagnosis.
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Jusuf Fantoni, Odelia Jovita, Inda Astri Aryani, Yuli Kurniawati, and Raden Pamudji. "Histopathological Features of Cutaneous Tuberculoid Granuloma Disorders." Bioscientia Medicina : Journal of Biomedicine and Translational Research 5, no. 3 (May 17, 2021): 797–808. http://dx.doi.org/10.32539/bsm.v5i3.347.
Full textAbstract:
Tuberculoid granulomas consist of epithelioid histiocytes, Langhans giant cells and rarely foreign bodies with lymphocytes, plasma cells and caseous necrosis. The granulomatous reaction pattern is defined as a typical inflammatory pattern that is characterized by granulomas. Various etiologies can lead to granulomatous reactions. The histopathological features of cutaneous disorders with tuberculoid granuloma include cutaneous tuberculosis, tuberculids, Morbus Hansen, syphilis and rosacea. There are various clinical manifestations of tuberculoid granuloma with similar appearances which makes it difficult to establish a definitive diagnosis. The histopathological features of cutaneous tuberculoid granuloma disorders can support the diagnosis. Therefore, the clinician can determine the appropriate treatment with the right diagnosis.
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Haering, Moritz, Christian Saleh, Phillip Jaszczuk, Markus Koehler, and Margret Hund-Georgiadis. "Intrathecal pump catheter-tip granuloma recurrence with associated myelomalacia – How safe is intrathecal analgesic infusion therapy? A case report." Surgical Neurology International 10 (April 24, 2019): 62. http://dx.doi.org/10.25259/sni-33-2019.
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Background: A serious complication of intrathecal (IT) infusion therapy for pain management is catheter-tip-associated granuloma. Catheter-tip granulomas can lead to permanent severe neurological sequelae if not promptly detected. Case Description: We report a patient with a recurrence of a catheter-tip granuloma causing a high-grade paresis of the lower extremities and we review briefly the literature. Conclusion: Patients with IT pump therapy presenting new neurological findings need prompt imaging of the spinal axis to rule out a catheter-tip granuloma. In case of catheter-tip granuloma, early surgical decompression is important.
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Aga, Hitomi, Mitsuyoshi Hirokawa, Ayana Suzuki, Hisashi Ota, Maki Oshita, Takumi Kudo, Mitsuhiro Fukushima, Kaoru Kobayashi, and Akira Miyauchi. "Sonographic Evaluation of Nodules Newly Detected in the Neck After Thyroidectomy: Suture Granuloma Versus Recurrent Carcinoma." Ultrasound International Open 4, no. 04 (October 2018): E124—E130. http://dx.doi.org/10.1055/a-0749-8688.
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AbstractThis study aimed to clarify the sonographic features of suture granuloma and recurrent carcinoma newly detected after thyroidectomy.We retrospectively analyzed ultrasound reports with images of 25 cases of suture granuloma and 18 cases of recurrent carcinoma that newly appeared in the resected area after thyroidectomy in our institution. Both suture granulomas and recurrent carcinomas more frequently exhibited multiple lesions rather than solitary lesions. Suture granulomas tended to appear in the more superficial areas than the carotid artery, while recurrent carcinomas were more common between the trachea and carotid artery. A total of 10 of the 11 suture granulomas that we followed up decreased in size. Recurrent carcinomas showed irregular shape (55.6%), taller-than-wide shape (38.9%), low internal echogenicity (83.3%), and no punctate microcalcifications. By contrast, suture granulomas were fusiform in shape (56.0%) and showed linear internal echo parallel to the tissue plane on the longitudinal scan (64.0%). The vascular flow sign was mild to none in the majority of both lesions.Fusiform shape and linear internal echoes indicate suture granuloma, while irregular shape, taller-than-wide shape, and low echogenicity indicate recurrent carcinoma. Given that the clinical management of suture granuloma differs from that of recurrent carcinoma, it is important to distinguish between these two lesions.
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Ufimtseva, Elena. "Investigation of Functional Activity of Cells in Granulomatous Inflammatory Lesions from Mice with Latent Tuberculous Infection in the NewEx VivoModel." Clinical and Developmental Immunology 2013 (2013): 1–14. http://dx.doi.org/10.1155/2013/371249.
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The newex vivomodel system measuring functional input of individual granuloma cells to formation of granulomatous inflammatory lesions in mice with latent tuberculous infection has been developed and described in the current study. Monolayer cultures of cells that migrated from individual granulomas were established in the proposed culture settings for mouse spleen and lung granulomas induced byin vivoexposure to BCG vaccine. The cellular composition of individual granulomas was analyzed. The expression of the leukocyte surface markers such as phagocytic receptors CD11b, CD11c, CD14, and CD16/CD32 and the expression of the costimulatory molecules CD80, CD83, and CD86 were tested as well as the production of proinflammatory cytokines (IFNγand IL-1α) and growth factors (GM-CSF and FGFb) for cells of individual granulomas. The colocalization of the phagocytic receptors and costimulatory molecules in the surface microdomains of granuloma cells (with and without acid-fast BCG-mycobacteria) has also been detected. It was found that some part of cytokine macrophage producers have carried acid-fast mycobacteria. Detected modulation in dynamics of production of pro-inflammatory cytokines, growth factors, and leukocyte surface markers by granuloma cells has indicated continued processes of activation and deactivation of granuloma inflammation cells during the latent tuberculous infection progress in mice.
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Al-Dousary, Surayie. "Vocal Process Granuloma." Ear, Nose & Throat Journal 76, no. 6 (June 1997): 382–87. http://dx.doi.org/10.1177/014556139707600606.
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Vocal process granuloma or contact ulcer is an uncommon disease in which there is chronic irritation and granulation tissue formation at the posterior third of the vocal folds. Thirteen patients (11 men and two women) with vocal process granuloma were enrolled in this study; cases of intubation granuloma were excluded. The most frequent complaints were throat irritation, frequent throat clearing and voice change. Forty-four percent of patients had a recurrence two to four months after surgery. Computed tomography (CT) of the larynx in four patients showed arytenoid sclerosis on the involved side and disclosed moderate enhancement of the vocal fold granuloma after contrast injection in one. Three patients had hyperacidity and four had hyperfunctioning granulomas: two used their voices excessively and the other two had bilateral sulcus vocalis. To our knowledge this is the first report of sulcus vocalis with vocal process granuloma, and of enhanced vocal process granuloma.
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Sincoff, Eric H., James K. Liu, Laura Matsen, Aclan Dogan, Ilman Kim, Sean O. Mcmenomey, and Johnny B. Delashaw. "A novel treatment approach to cholesterol granulomas." Journal of Neurosurgery 107, no. 2 (August 2007): 446–50. http://dx.doi.org/10.3171/jns-07/08/0446.
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✓ The authors report a novel technique for the treatment of cholesterol granulomas. An extradural middle fossa approach was used to access the granuloma, with drainage through silastic tubes into the sphenoid sinus via the anteromedial triangle between V1 and V2. Cholesterol granulomas occur when the normal aeration and drainage of temporal bone air cells is occluded, resulting in vacuum formation and transudation of blood into the air cells. This process results in anaerobic breakdown of the blood with resulting cholesterol crystal formation and an inflammatory reaction. Traditional treatment of this lesion involves extensive drilling of the temporal bone to drain the granuloma cyst and establish a drainage tract into the middle ear. Such drainage procedures can be time consuming and difficult, and potentially involve structural damage to the inner ear and facial nerve. An extradural middle fossa approach provides easy access to the granuloma and anterior petrous bone entry into the granuloma for resection. Granuloma drainage is then achieved using shunt tubing in the sphenoid sinus via a small hole in the anteromedial triangle between V1 and V2. Five patients with symptomatic cholesterol granuloma were treated without complication using this novel extradural middle fossa approach. One patient required reoperation 1-year postoperatively for cyst regrowth and occlusion of the drainage tube. At the 5-year follow-up examination, no patient reported recurrent symptoms. Extradural middle fossa craniotomy and silastic tube drainage into the sphenoid sinus is a viable alternative method for treatment of cholesterol granuloma.
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Mendonça, Rodrigo, Cleiton Schweitzer Peron, Marco Antônio Stefani, and Pasquale Gallo. "Cerebral cholesterol granuloma: case report." Arquivos de Neuro-Psiquiatria 65, no. 2b (June 2007): 540–41. http://dx.doi.org/10.1590/s0004-282x2007000300036.
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Intracranial cholesterol granulomas are rare lesions, and have been registered in petrous apex region. The presence of an intracerebral cholesterol granuloma is an uncommun event. We report the case of a 20-years-old woman who undergone craniotomy for resection of a temporal mass. Pathologic examination show a cholesterol granuloma.
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Metwali, A., D. Elliott, A. M. Blum, J. Li, M. Sandor, and J. V. Weinstock. "T cell vasoactive intestinal peptide receptor subtype expression differs between granulomas and spleen of schistosome-infected mice." Journal of Immunology 157, no. 1 (July 1, 1996): 265–70. http://dx.doi.org/10.4049/jimmunol.157.1.265.
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Abstract Granulomas form in the liver and intestines of mice infected with the parasite Schistosoma mansoni. Vasoactive intestinal peptide (VIP) is a neurokine that can modulate aspects of the immune response by acting through receptors within the granuloma. Cloned are two novel VIP receptor (VIPR) mRNAs (VIPR1 and VIPR2) that also bind a second neurokine called pituitary adenylated cyclase-activating polypeptide (PACAP). The objective of this study was to determine if granulomas express either VIPR1 or VIPR2. Using a radioligand-binding assay, it was established that PACAP is as effective as VIP at displacing radiolabeled VIP from splenocytes and granuloma cells, and that most if not all VIPRs in the spleen and granulomas bind PACAP. PCR amplification of reverse transcribed RNA determined that granulomas express both VIPR1 and VIPR2 mRNAs. Gel electrophoresis and nucleotide sequencing confirmed the authenticity of the PCR products. Also, both receptor subtypes were amplified from several granuloma CD4+ T cell lines; yet reverse transcribed RNA from T cell-depleted, dispersed granuloma cells had only VIPR1 RNA. It is notable that reverse transcriptase-PCR detected only VIPR1 in the thymus and spleen, which are organs rich in T lymphocytes. Thus, the granulomas and spleens from mice with schistosomiasis contain cells that display authentic VIP/PACAP receptors. Moreover, these data suggest that T cells in different compartments vary in VIPR subtype expression. VIPR1 and VIPR2 may have different physiologic roles in inflammation.
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Garza, Armandina, David J. Tweardy, Joel Weinstock, Balaji Viswanathan, and Prema Robinson. "Substance P Signaling Contributes to Granuloma Formation inTaenia crassicepsInfection, a Murine Model of Cysticercosis." Journal of Biomedicine and Biotechnology 2010 (2010): 1–6. http://dx.doi.org/10.1155/2010/597086.
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Cysticercosis is an infection with larval cysts of the cestodeTaenia solium. Through pathways that are incompletely understood, dying parasites initiate a granulomatous reaction that, in the brain, causes seizures. Substance P (SP), a neuropeptide involved in pain-transmission, contributes to inflammation and previously was detected in granulomas associated with deadT. crassicepscysts. To determine if SP contributes to granuloma formation, we measured granuloma-size and levels of IL-1β, TNF-α, and IL-6 within granulomas inT. crassiceps-infected wild type (WT) mice and mice deficient in SP-precursor (SPP) or the SP-receptor (neurokinin 1, NK1). Granuloma volumes of infected SPP- and NK1-knockout mice were reduced by 31 and 36%, respectively, compared to WT mice (P<.05for both) and produced up to 5-fold less IL-1β, TNF-α, and IL-6 protein. Thus, SP signaling contributes to granuloma development and proinflammatory cytokine production inT. crassicepsinfection and suggests a potential role for this mediator in human cystercercosis.
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Miranda, Nadia, and Katrina K. Hoyer. "Coccidioidomycosis Granulomas Informed by Other Diseases: Advancements, Gaps, and Challenges." Journal of Fungi 9, no. 6 (June 9, 2023): 650. http://dx.doi.org/10.3390/jof9060650.
Full textAbstract:
Valley fever is a respiratory disease caused by a soil fungus, Coccidioides, that is inhaled upon soil disruption. One mechanism by which the host immune system attempts to control and eliminate Coccidioides is through granuloma formation. However, very little is known about granulomas during Coccidioides infection. Granulomas were first identified in tuberculosis (TB) lungs as early as 1679, and yet many gaps in our understanding of granuloma formation, maintenance, and regulation remain. Granulomas are best defined in TB, providing clues that may be leveraged to understand Coccidioides infections. Granulomas also form during several other infectious and spontaneous diseases including sarcoidosis, chronic granulomatous disease (CGD), and others. This review explores our current understanding of granulomas, as well as potential mechanisms, and applies this knowledge to unraveling coccidioidomycosis granulomas.
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Singh, Pradeep Kumar, Alekh Kumar, and Gajendra Nayak. "An unusual presentation of postauricular swelling: cholesterol granuloma." International Journal of Research in Medical Sciences 6, no. 10 (September 25, 2018): 3468. http://dx.doi.org/10.18203/2320-6012.ijrms20184064.
Full textAbstract:
Post auricular swellings are not uncommon encounterances in surgical practice. Common differential diagnosis would include dermoid and lymph nodes. Cholesterol granulomas are cystic swellings formed with a multi-nucleated giant cell reaction to red blood cells’ breakdown products, haemosiderin and cholesterol crystals. Any aerated portion of the temporal bone may develop a cholesterol granuloma; the mastoid air cells are the most common location and are the most common cystic lesion of the petrous apex. This is the first, unique and rare case of post auricular presentation of a cholesterol granuloma. 21-year-old female presented with a painless swelling behind the left ear from last four years. The radiological examination revealed a left-sided, soft-tissue mass extending into the posterior fossa. She underwent a surgical exploration and complete resection was achieved. The histopathological and radiological features were consistent with a cholesterol granuloma. Authors have seen first case of a mastoid cholesterol granuloma presented as a postauricular swelling. This case illustrates the need to consider cholesterol granuloma in daily clinical practice. Otologists should be aware of uncharacteristic invasive cholesterol granulomas of the mastoid, which require aggressive surgical obliteration.
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Lukacs, N. W., S. W. Chensue, R. M. Strieter, K. Warmington, and S. L. Kunkel. "Inflammatory granuloma formation is mediated by TNF-alpha-inducible intercellular adhesion molecule-1." Journal of Immunology 152, no. 12 (June 15, 1994): 5883–89. http://dx.doi.org/10.4049/jimmunol.152.12.5883.
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Abstract Recent studies have demonstrated a crucial role for TNF during inflammatory granuloma formation. In addition, TNF has been shown to up-regulate adhesion molecules that participate in cellular recruitment and lymphocyte activation. In the present study, we have examined the mechanism of TNF activation during Schistosoma mansoni egg granuloma formation and its relationship to the expression of ICAM-1. Our initial studies showed that high affinity human soluble TNFR coupled to the Fc portion of an Ig (sTNFR:Fc construct) could effectively diminish granuloma formation and lymphocyte activation in vivo. We have also assessed the increased expression of ICAM-1, its contribution to granuloma development, and its relationship with TNF during lesion formation. Increased steady state ICAM-1 mRNA expression was observed in primary egg granulomas when compared with normal lung and foreign body (Sephadex bead) granulomas, which suggests a role for ICAM-1 in Ag-induced lesion formation. Subsequent studies have demonstrated that sTNFR:Fc treatment down-regulated granuloma formation and ICAM-1 expression, thus suggesting one mechanism of TNF involvement in granuloma formation was through the induction of ICAM-1. Anti-ICAM-1 decreased the soluble egg Ag-specific T cell proliferation in vitro. In addition, passive immunization of mice with anti-ICAM-1 mAb during primary granuloma formation resulted in an attenuation of lesion development as compared with lesion development in a control Ab-treated group. The proliferative response to soluble egg Ag was also significantly reduced in ex vivo experiments that used spleen cells from the anti-ICAM-1 treated mice. These data demonstrate that both TNF and ICAM-1 participate in lymphocyte activation and granuloma formation and suggest that one mechanism of TNF in granuloma development is through TNF-induced ICAM-1 expression.
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Qadir, Khurram, Ahmed Metwali, Arthur M. Blum, Jie Li, David E. Elliott, and Joel V. Weinstock. "TGF-β and IL-10 regulation of IFN-γ produced in Th2-type schistosome granulomas requires IL-12." American Journal of Physiology-Gastrointestinal and Liver Physiology 281, no. 4 (October 1, 2001): G940—G946. http://dx.doi.org/10.1152/ajpgi.2001.281.4.g940.
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Interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) regulate CD4+T cell interferon-γ (IFN-γ) secretion in schistosome granulomas. The role of IL-12 was determined using C57BL/6 and CBA mice. C57BL/6 IL-4 −/− granuloma cells were stimulated to produce IFN-γ when cultured with IL-10 or TGF-β neutralizing monoclonal antibody. In comparison, C57BL/6 wild-type (WT) control granuloma cells produced less IFN-γ. IL-12, IL-18, and soluble egg antigen stimulated IFN-γ release from C57BL/6 IL-4 −/− and WT mice. IFN-γ production in C57 IL-4 −/− and WT granulomas was IL-12 dependent, because IL-12 blockade partly abrogated IFN-γ secretion after stimulation. All granuloma cells released IL-12 (p70 and p40), and IL-12 production remained constant after anti-TGF-β, anti-IL-10, recombinant IL-18, or antigen stimulation. C57 WT and IL-4 −/− mouse granuloma cells expressed IL-12 receptor (IL-12R) β1-subunit mRNA but little β2 mRNA. TGF-β or IL-10 blockade did not influence β1 or β2 mRNA expression. CBA mouse dispersed granuloma cells released no measurable IFN-γ, produced IL-12 p70 and little p40, and expressed IL-12R β2 and little β1 mRNA. In T helper 2 (Th2) granulomas of C57BL/6 WT and IL-4 −/− mice, cells produce IL-12 (for IFN-γ production) and IL-10 and TGF-β modulate IFN-γ secretion via mechanisms independent of IL-12 and IL-12R mRNA regulation. We found substantial differences in control of granuloma IFN-γ production and IL-12 circuitry in C57BL/6 and CBA mice.
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Dhanasekar, G., and N. S. Jones. "Endoscopic trans-sphenoidal removal of cholesterol granuloma of the petrous apex: case report and literature review." Journal of Laryngology & Otology 125, no. 2 (October 26, 2010): 169–72. http://dx.doi.org/10.1017/s0022215110002227.
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AbstractObjective:We report a case of cholesterol granuloma of the petrous apex which was surgically treated via an endoscopic trans-sphenoidal approach.Methods:Case report and review of the literature concerning cholesterol granulomas of the petrous apex and their management.Results:The lesion was approached endoscopically via a bilateral sphenoidotomy with removal of the vomer. A large cholesterol granuloma was evacuated and marsupialised. The patient made an uneventful recovery.Conclusion:Trans-sphenoidal access to the petrous apex represents an alternative route for the drainage and ventilation of cholesterol granulomas. This approach is the technique of choice when the cholesterol granuloma abuts the posterior wall of the sphenoid sinus. The trans-sphenoid approach, unlike other lateral approaches to the petrous apex, spares cochlear and vestibular function and allows post-operative endoscopic follow up.
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Medlicott, Shaun A. C., Leslie Eidus, and Kiril Trpkov. "Isolated Pulse Granuloma in a Mesenteric Lymph Node: Unusual Nodal Manifestation Associated With Crohn Disease Complicated by Ileal Adenocarcinoma." AJSP: Reviews and Reports 23, no. 6 (November 2018): 271–73. http://dx.doi.org/10.1097/pcr.0000000000000273.
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Abstract Pulse granuloma is an unusual inflammatory reaction to legumes. Pulse granulomas of the gastrointestinal tract are typically accompanied by significant mural damage due to ulceration, fistula, or perforation. We describe a solitary pulse granuloma in a mesenteric lymph node of a 74-year-old male patient with Crohn disease, who presented with an ileal adenocarcinoma, but without demonstrable fistula or perforation. To our knowledge, this is only the second reported example of Crohn disease associated with a pulse granuloma in a mesenteric node and also only the second example of a nodal location for any documented pulse granuloma. We postulate that mesenteric lymph node pulse granuloma may represent a unique and unusual type of morphology associated with Crohn disease.
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Srinivas, Teerthanath, and Hariprasad S. "Granulomatous dermatosis: histopathological study in a tertiary care hospital." International Journal of Research in Medical Sciences 5, no. 9 (August 26, 2017): 3869. http://dx.doi.org/10.18203/2320-6012.ijrms20173659.
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Background: Granulomatous dermatosis shares the histological finding of granuloma formation; it is usually formed because of the persistence of a non-degradable product of active hypersensitivity. The identical histological picture may be produced by several causes, which pose a diagnostic challenge to dermatopathologist, Present study aims at classifying cutaneous granulomatous dermatosis based on the morphology and aetiology of granulomas, and to highlight its significance for specific clinical diagnosis.Methods: A retrospective analysis of skin biopsy was done and cases of cutaneous granulomatous lesions diagnosed on histopathological examination were retrieved for a period of 8 years. Clinical data and diagnosis were retrieved from hospital records. Hematoxylin and eosin stained paraffin sections were reviewed. The morphological pattern of granuloma was classified into sarcoidal, necrotizing, necrobiotic and suppurative granulomas and further aetiological evaluation for the granulomatous dermatosis were done using various special stains like Periodic Acid Schiff stain, Fite-Farraco stain, Gomori methenamine silver stain and acid-fast bacilli stain.Results: A total of 228 cases of cutaneous granulomatous lesion were retrieved; out of these 93cases (40.79%) were sarcoidal granuloma type, 83cases (36.40%) were of suppurative granulomas, 29 cases (12.72%) were of necrobiotic granulomas, 20 cases (8.77%) were necrotizing granuloma and 3 cases (1.32%) had granulomatous dermatitis with vasculitis. Infective aetiology was the commonest cause for granulomatous dermatosis (57.89%), mainly by leprosy, tuberculosis and various fungal infection.Conclusions: Granulomatous dermatosis has significant overlap in histopathological picture of various granulomatous reactions. Morphology alone is seldom specific and cannot be used as diagnostic tool. It is better understood based adequate clinical data, morphology of granuloma, special stains and laboratory workup in arriving at a etiology specific diagnosis for definitive clinical management.
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Marcus, Sarah Ann, Melinda Herbath, Zsuzsanna Fabry, and Matyas Sandor. "Dynamic changes in Mycobacterium tuberculosis-induced granulomas: developing new tools." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 117.19. http://dx.doi.org/10.4049/jimmunol.200.supp.117.19.
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Abstract Continuous cell replacement has been demonstrated in a transplantation model of BCG infected liver, however, the Mtb lung granuloma has yet to be studied as lung tissue is not amenable to granuloma transplantation. To demonstrate the plasticity of Mtb lung granulomas, we treated mice 6 weeks post infection with chemokine inhibitors for 7 days. Treated lungs showed a strong, significant reduction in granuloma size, which suggests continuous cell replacement and indicates that Mtb granulomas are actively maintained during infection. To examine cell fate in more detail, we utilized STOCK Tg(CAG-KikGR)33Hadj/J mice to photo-tag lung granulomas in situ. Following exposure to 405 nm light KikGR Red (583/593 nm) photoconverted lung regions or cells could be differentiated from unexposed Green (507/517 nm) systemic cells. These mice were aerosol infected with 200 CFU Mtb H37Rv. Portions of infected lungs were photoconverted 4 wpi, harvested up to 7 days post-exposure, and examined, along with mediastinal lymph nodes, by confocal microscopy. Areas of photoconversion were successfully identified in infected lungs. F4/80+ macrophages and CD4+ T-cells were stained and screened for red versus green fluorescence. Unconverted cells of both types were found, demonstrating the utility of this technique for detecting influx into the granuloma. Efflux of cells from the granuloma was also confirmed by the detection of photoconverted cells within the unconverted MLNs. While further optimization is necessary to use this model for quantitative analysis, these results implicate continuous cell recruitment into granulomatous lesions. Elucidating cell traffic to granulomas with this technique can lead to new therapies for many granulomatous diseases.
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Nugroho, Y. Slamet, Reviono Reviono, Suradi Suradi, and Diding Heri Prasetyo. "Effect of Andrographolide on The Expression of TNF-α and Pulmonary Tuberculosis in Rats Granulomas are Infected With Mycobacterium tuberculosis." Jurnal Respirologi Indonesia 38, no. 2 (April 26, 2018): 75–82. http://dx.doi.org/10.36497/jri.v38i2.161.
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Background. Andrographolide as an anti-inflammatory inhibit activation of NF-κβ, the production of TNF-α, IL-12, pressing the release inducibele nitic oxide synthase (iNOS), inhibiting the release of COX-2 in human fibroblast cells and also prevents the production of oxygen radicals. TNF- α stimulates the migration of immune cells to get to the site of infection, contribute to the formation of granulomas, and can control the disease progresificity.
Methods. The study aims to analyze the effect of andrographolide on the expression of TNF-α and tuberculosis granuloma in mice infected with CFA. Laboratory tests in the laboratory of histology and pathology anatomy medical faculty of UNS. Samples are 30 individuals’ mice, consist of 10 rats as control, 10 rats injected with CFA, and 10 rats injected with CFA+ andrographolide. Histopathology and immunohistochemistry of lung tissue granuloma examinated in the laboratory of pathology anatomy medical faculty of UNS.
Results. The study design was purely experimental or (true experiment, with randomized post test only control group design). Andrographolide lowering the average expression of TNF-α compared to the CFA group, based on the description of the variable expression of TNF-α. The results of the analysis of three different variations or the average using Kruskal Wallis test showed that there are differences in the average number 3 granuloma with P=0.003. It means different average number of granulomas in the control group, CFA and CFA+ Andrographolide completely different convincingly. Compared with the average number of granulomas in the control group, the group CFA has a tendency average number of granuloma higher (increased), then the average number of granuloma in group CFA + Andrographolide has an average lower than the group CFA or mean average granuloma amount can be reduced by giving Andrographolide paniculata extract.
Conclusion. Andrographolide 14.8% paniculata extract shown to decrease the expression of TNF-α induction of pulmonary tuberculosis in mice the CFA. Andrographolide 14.8% paniculata extract shown to reduce the number of lung granuloma in mice induced tuberculosis CFA. There is a positive correlation between the expression of strong TNF-α by the number of granulomas in the lungs in mice induced tuberculosis CFA. (J Respir Indo 2018; 38(2): 75-82)
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Linggawan, Stephani. "Midline Granuloma." Hang Tuah Medical Journal 15, no. 1 (November 21, 2017): 75–88. http://dx.doi.org/10.30649/htmj.v15i1.24.
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Midline granulomaor nasal type extranodal T/NK-cell non-Hodgkin’s lymphoma often cause various problem. This tumor is a disorder of the center of the face with the characteristic of progressive destruction and ulceration, including the nose, paranasal sinuse, palate, eyes, and facial soft tissues. Etiology and pathophysiologyis unclear between inflammatory and tumor reactions. Midline granulomais included innasal granuloma disease based on biopsy examination, where as The Revised European American Lymphoma (REAL) / Wordl Health Organization (WHO) classifiesmidline granulomainextranodal T/NK-cellnon-Hodgkin’s lymphomabased on immunohistologic examination. Epstein-Barr Virus (EBV) infections 90-100% are involved in the tumor formation process. Difficult diagnosis and wide-ranging diagnosis, requiring complete anamnesis and examination, especially biopsy, imunohistology, and cytogenetics in obtaining necrosis features with vascular destruction and ulceration, inflammation with pleomorphic cell infiltrate, CD56+, CD3+, cytotoxict and EBV+ proteins. Management with radiotherapy, chemotherapy, bone marrow transplant, and immunotherapy. Complications can occur locally or systemically with spread to peripheral blood circulation, soft tissue, lung, liver, skin, gastrointestinal tract, testes, central nervous and bone marrow. Poor prognosis is less than 50%of patient who respond fully after chemotherapy and radio therapy. Pronosis can only be assessed by the International Prognostic Index (IPI).
Midline diagnosis of granulomais difficult,management is often delayed, while its progressive nature leads to various complications, thus further aggravating the prognosis.
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Guarner, Jeannette. "Detection of Microorganisms in Granulomas That Have Been Formalin-Fixed: Review of the Literature Regarding Use of Molecular Methods." Scientifica 2012 (2012): 1–16. http://dx.doi.org/10.6064/2012/494571.
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Granuloma is an organized aggregate of immune cells that under the microscope appear as epithelioid macrophages. A granuloma can only be diagnosed when a pathologist observes this type of inflammation under the microscope. If a foreign body or a parasite is not observed inside the granuloma, stains for acid-fast bacilli and fungi are ordered since mycobacteria and fungi are frequently the cause of this type of inflammation. It is calculated that 12 to 36% of granulomas do not have a specific etiology and many have wondered if with new molecular methods we could reduce this number. This paper will summarize the frequently known causes of granulomas and will present the recent literature regarding the use of molecular techniques on tissue specimens and how these have helped in defining causative agents. We will also briefly describe new research regarding formation and function of granulomas and how this impacts our ability to find an etiologic agent.
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Ufimtseva, Elena. "Mycobacterium-Host Cell Relationships in Granulomatous Lesions in a Mouse Model of Latent Tuberculous Infection." BioMed Research International 2015 (2015): 1–16. http://dx.doi.org/10.1155/2015/948131.
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Tuberculosis (TB) is a dangerous infectious disease characterized by a tight interplay between mycobacteria and host cells in granulomatous lesions (granulomas) during the latent, asymptomatic stage of infection.Mycobacterium-host cell relationships were analyzed in granulomas obtained from various organs of BALB/c mice with chronic TB infection caused byin vivoexposure to the Bacillus Calmette-Guérin (BCG) vaccine. Acid-fast BCG-mycobacteria were found to be morphologically and functionally heterogeneous (in size, shape, and replication rates in colonies) in granuloma macrophages, dendritic cells, and multinucleate Langhans giant cells. Cord formation by BCG-mycobacteria in granuloma cells has been observed. Granuloma macrophages retained their ability to ingest damaged lymphocytes and thrombocytes in the phagosomes; however, their ability to destroy BCG-mycobacteria contained in these cells was compromised. No colocalization of BCG-mycobacteria and the LysoTracker dye was observed in the mouse cells. Various relationships between granuloma cells and BCG-mycobacteria were observed in different mice belonging to the same line. Several mice totally eliminated mycobacterial infection. Granulomas in the other mice had mycobacteria actively replicating in cells of different types and forming cords, which is an indicator of mycobacterial virulence and, probably, a marker of the activation of tuberculous infection in animals.
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Rosenbaum, Hanna, Yehudith Ben-Arie, Zaher S. Azzam, and Norberto Krivoy. "Amiodarone-Associated Granuloma in Bone Marrow." Annals of Pharmacotherapy 32, no. 1 (January 1998): 60–62. http://dx.doi.org/10.1345/aph.17061.
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BACKGROUND: Amiodarone hydrochloride is classified as a Vaughan Williams class III antiarrhythmic agent, although class I, II, and IV effects may contribute to its favorable antiarrhythmic profile. It is associated with a wide variety of adverse effects, such as hypothyroidism, hyperthyroidism, interstitial pulmonary disease, hepatitis, coagulation disorders, skin photosensitivity, corneal microdeposits, alopecia, peripheral neuropathy, and cardiovascular arrhythmias. SUBJECTS: Bone marrow aspirations and biopsies were performed on two patients treated with amiodarone, on the first during a follow-up for myelofibrosis and on the second for a suspected lymphoproliferative disorder. Several bone marrow granulomas were found in both patients. The bone marrow specimens for tuberculosis and fungal stains were negative. CONCLUSIONS The temporal relationship between the amiodarone therapy and the development of two cases of asymptomatic bone marrow granuloma suggest the possibility that this antiarrhythmic agent is involved in the etiology of these granulomas. TRASFONDO Hidrocloruro de amiodarone es un agente antiarrítmico clase III en la clasificación Vaughan Williams, aunque posee también propiedades de las clases I, II, y IV. Este medicamento se ha relacionado con una gran variedad de efectos secundarios. Entre estos se encuentran hipotiroidismo, hipertiroidismo, enfermedad intersticial pulmonar, hepatitis, desórdenes de coagulación, fotosensitividad en la piel, microdepósitos en la córnea, alopecia, neuropatía periférica, y arritmias. En este artículo se informan dos casos asintomáticos de granulomas, en la médula ósea asociados al uso de amiodarone. SUJETOS Dos pacientes en tratamiento con amiodarone se sometieron a aspiración de la médula osea y biopsia. En ambos se encontró varios granulomas en la médula. Las muestras de médula ósea fueron negativas para tuberculosis y hongos. El primer caso fue una mujer que había sido diagnosticada en 1979 con un desorden mieloproliferativo pero que había estado asintomática por 10 años. En 1987 comenzó a recibir amiodarone y 18 meses después, en una biopsia de seguimiento, presentó granulomas de tipo epiteloide con necrosis nocaseosa. La paciente sólo utilizaba amiodarone y aspirina en ese momento. El segundo paciente fue otra mujer que comenzó a utilizar amiodarone 18 meses antes de ser sometida a una biopsia de la médula ósea para evaluar la posibilidad de un desorden inmunoproliferativo o linfoproliferativo. La biopsia demostró una médula hipercelular con megacariocitos atípicos y varios granulomas con células epiletoides pero sin necrosis, células gigantes ni fibrosis. CONCLUSIONES La relación temporal entre el inicio del tratamiento con amiodarone y el desarrollo de los granulomas sugiere la posibilidad de que este medicamento contribuya en la etiología de éstos. Se asume que el uso de este fármaco promueve la acumulación de fosfolípidos en los linfoblastos de la médula ósea lo cual resulta en el desarrollo de granulomas. Sin embargo, los mecanismos etiológicos por los cuales ocurre ésto no se conocen con exactitud. Aunque los granulomas aparentan estar asociados a amiodarone, no se puede concluir esto en forma definitiva ya que en el primer caso se continuó con el uso del medicamento y en el segundo caso no se repitió la biopsia al descontinuar el fármaco. El significado clínico, la prognosis y consecuencias de granulomas asintomáticas en la médula ósea en personas sin enfermedad subayacente no se conoce. La presencia de granulomas en la médula ósea es un hallazgo poco frecuente, por lo cual cuando ocurre se debe identificar la causa. OBJECTIF Rapporter deux cas de granulomes asymptomatiques de la moelle osseuse associés à l'utilisation de l'amiodarone. RÉSUMÉ DU CAS Deux patients traités avec de l'amiodarone 200 mg/jour pour 18 mois ont eu une aspiration de la moelle osseuse et une biopsie. Des granulomes de la moelle osseuse ont été identifiés chez ces deux patients. Les échantillons de la moelle osseuse étaient négatifs pour une tuberculose et des infections fongiques. CONCLUSIONS L'amiodarone est un agent antiarythmique de la classe III qui est associee à de nombreux effets indésirables. Les auteurs ont décrit la présence de granulomes asymptomatiques de la moelle osseuse chez deux patients sous traitement avec amiodarone. La relation temporale entre l'apparition des granulomes et la prise d'amiodarone suggère que ce médicament serait impliqué dans l'étiologie de ces granulomes.