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Berlin Brandenburg

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  • 1
    Language: English
    In: Therapeutic Advances in Respiratory Disease, October 2011, Vol.5(5), pp.305-324
    Description: Pulmonary mycoses are among the most feared infections encountered in immunocompromised patients. The problem is amplified by the increasing numbers of chronically immunocompromised patients that have substantially increased both the prevalence and clinical severity of infections caused by fungi. Moreover, fungal infections in this patient population pose challenges in diagnosis and management. Fortunately, recent advances in diagnostics and antifungal therapy, and their direct application to specific diseases, provide important new approaches to this complex and often seriously ill patient population. In this article we review the commonly occurring pulmonary fungal infections in the immunocompromised population with a particular focus on their management.
    Keywords: Antifungal Treatment ; Aspergillosis ; Cryptococcosis ; Fungal Lung Disease ; Histoplasmosis ; Immunocompromised Hosts ; Medicine
    ISSN: 1753-4658
    E-ISSN: 1753-4666
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  • 2
    Language: English
    In: CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne, 04 September 2012, Vol.184(12), pp.1387-90
    Description: Cryptococcus species are environmental fungi, acquired through inhalation, that can cause lifethreatening infections of the pulmonary and central nervous systems. Of the 37 known species, Cryptococcus neoformans and C. gattii are the most commonly identified pathogens, causing a spectrum of disease that...
    Keywords: Cryptococcus Gattii ; Cryptococcosis -- Complications ; Lung Diseases, Fungal -- Microbiology ; Pneumonia -- Microbiology
    ISSN: 08203946
    E-ISSN: 1488-2329
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  • 3
    Language: English
    In: Chest, January 2013, Vol.143(1), pp.238-241
    Description: Pulmonary aspergilloma is a chronic fungal infection that has a high mortality when hemoptysis occurs. Surgery is the treatment of choice, but patients often have severe physiologic impairment putting them at risk for significant surgical morbidity and mortality. We present the case of a 63-year-old woman with a large aspergilloma, unfit for surgery due to medical reasons. The aspergilloma was enlarging, with progression of the patient's symptoms of anorexia, cough, chest discomfort, and hemoptysis. Bronchoscopy revealed an airway leading into a cavity with a large fungal ball. Biopsy confirmed . Using flexible and rigid bronchoscopy, the aspergilloma was mechanically removed. Eighteen months later the patient reported no hemoptysis, reduced pain and cough, significant weight gain, and improved appetite, with no recurrence of the aspergilloma on repeat imaging. To our knowledge, this is the first reported case of bronchoscopic removal of a large cavitary aspergilloma. This important new treatment modality provides a viable alternative therapy for this potentially life-threatening problem.
    Keywords: Medicine
    ISSN: 0012-3692
    E-ISSN: 1931-3543
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  • 4
    Language: English
    In: The Journal of biological chemistry, 25 March 2016, Vol.291(13), pp.6912-22
    Description: The activity of Rac in leukocytes is essential for immunity. However, its role in NK cell-mediated anti-microbial signaling remains unclear. In this study, we investigated the role of Rac in NK cell mediated anti-cryptococcal killing. We found thatCryptococcus neoformansindependently activates both Rac and SFK pathways in NK cells, and unlike in tumor killing,Cryptococcusinitiated a novel Rac → PI3K → Erk cytotoxicity cascade. Remarkably, Rac was not required for conjugate formation, despite its essential role in NK cytotoxicity againstC. neoformans Taken together, our data show that, unlike observations with tumor cells, NK cells use a novel Rac cytotoxicity pathway in conjunction with SFK, to killC. neoformans.
    Keywords: Cellular Signaling ; Cryptococcus ; Rac (Rac Gtpase) ; Src ; Adhesion ; Fungi ; Natural Killer Cells (Nk Cells) ; Phosphatidylinositide 3-Kinase (PI 3-Kinase) ; Cytotoxicity, Immunologic ; Class Ia Phosphatidylinositol 3-Kinase -- Immunology ; Cryptococcus Neoformans -- Physiology ; Killer Cells, Natural -- Immunology ; Rac Gtp-Binding Proteins -- Immunology ; Rac1 Gtp-Binding Protein -- Immunology ; Src-Family Kinases -- Immunology
    E-ISSN: 1083-351X
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  • 5
    Language: English
    In: Journal of immunology (Baltimore, Md. : 1950), 15 October 2018, Vol.201(8), pp.2369-2376
    Description: is a fungal pathogen that causes fatal meningitis and pneumonia. During host defense to , NK cells directly recognize and kill using cytolytic degranulation analogous to killing of tumor cells. This fungal killing requires independent activation of Src family kinase (SFK) and Rac1-mediated pathways. Recognition of requires the natural cytotoxicity receptor, NKp30; however, it is not known whether NKp30 activates both signal transduction pathways or whether a second receptor is involved in activation of one of the pathways. We used primary human NK cells and a human NK cell line and found that NKp30 activates SFK → PI3K but not Rac1 cytotoxic signaling, which led to a search for the receptor leading to Rac1 activation. We found that NK cells require integrin-linked kinase (ILK) to activate Rac1 for effective fungal killing. This observation led to our identification of β1 integrin as an essential anticryptococcal receptor. These findings demonstrate that multiple receptors, including β1 integrins and NKp30 and their proximal signaling pathways, are required for recognition of , which activates a central cytolytic antimicrobial pathway leading to fungal killing.
    Keywords: Cryptococcosis -- Immunology ; Cryptococcus Neoformans -- Physiology ; Integrin Beta1 -- Metabolism ; Killer Cells, Natural -- Immunology ; Rac1 Gtp-Binding Protein -- Metabolism
    ISSN: 00221767
    E-ISSN: 1550-6606
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  • 6
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 23 September 2014, Vol.111(38), pp.13936-41
    Description: CXCR6-GFP(+) cells, which encompass 70% invariant natural killer T cells (iNKT cells), have been found primarily patrolling inside blood vessels in the liver. Although the iNKT cells fail to interact with live pathogens, they do respond to bacterial glycolipids presented by CD1d on liver macrophage that have caught the microbe. In contrast, in this study using dual laser multichannel spinning-disk intravital microscopy of joints, the CXCR6-GFP, which also made up 60-70% iNKT cells, were not found in the vasculature but rather closely apposed to and surrounding the outside of blood vessels, and to a lesser extent throughout the extravascular space. These iNKT cells also differed in behavior, responding rapidly and directly to joint-homing pathogens like Borrelia burgdorferi, which causes Lyme disease. These iNKT cells interacted with B. burgdorferi at the vessel wall and disrupted dissemination attempts by these microbes into joints. Successful penetrance of B. burgdorferi out of the vasculature and into the joint tissue was met by a lethal attack by extravascular iNKT cells through a granzyme-dependent pathway, an observation also made in vitro for iNKT cells from joint but not liver or spleen. These results suggest a novel, critical extravascular iNKT cell immune surveillance in joints that functions as a cytotoxic barrier and explains a large increase in pathogen burden of B. burgdorferi in the joint of iNKT cell-deficient mice, and perhaps the greater susceptibility of humans to this pathogen because of fewer iNKT cells in human joints.
    Keywords: Lyme Arthritis ; Granzyme B ; Joint Inkt Cells ; Immunity, Cellular ; Borrelia Burgdorferi -- Immunology ; Joint Diseases -- Immunology ; Joints -- Immunology ; Lyme Disease -- Immunology ; Natural Killer T-Cells -- Immunology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 7
    Language: English
    In: Cancer Research, 04/15/2012, Vol.72(8 Supplement), pp.1558-1558
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 8
    Language: English
    In: Journal of Clinical Investigation, May, 2010, Vol.120(5), p.1683(11)
    Description: Infectious meningitis and encephalitis is caused by invasion of circulating pathogens into the brain. It is unknown how the circulating pathogens dynamically interact with brain endothelium under shear stress, leading to invasion into the brain. Here, using intravital microscopy, we have shown that Cryptococcus neoformans, a yeast pathogen that causes meningoencephalitis, stops suddenly in mouse brain capillaries of a similar or smaller diameter than the organism, in the same manner and with the same kinetics as polystyrene microspheres, without rolling and tethering to the endothelial surface. Trapping of the yeast pathogen in the mouse brain was not affected by viability or known virulence factors. After stopping in the brain, C. neoformans was seen to cross the capillary wall in real time. In contrast to trapping, viability, but not replication, was essential for the organism to cross the brain microvasculature. Using a knockout strain of C. neoformans, we demonstrated that transmigration into the mouse brain is urease dependent. To determine whether this could be amenable to therapy, we used the urease inhibitor flurofamide. Flurofamide ameliorated infection of the mouse brain by reducing transmigration into the brain. Together, these results suggest that C. neoformans is mechanically trapped in the brain capillary, which may not be amenable to pharmacotherapy, but actively transmigrates to the brain parenchyma with contributions from urease, suggesting that a therapeutic strategy aimed at inhibiting this enzyme could help prevent meningitis and encephalitis caused by C. neoformans infection.
    Keywords: Cell Migration -- Observations ; Endothelium -- Properties ; Encephalitis -- Development And Progression ; Encephalitis -- Care And Treatment ; Meningitis -- Development And Progression ; Meningitis -- Care And Treatment ; Hydrolases -- Health Aspects ; Cryptococcus -- Health Aspects
    ISSN: 0021-9738
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  • 9
    Lexicon Article
    Lexicon Article
    Language: English
    In: Encyclopedia of Intensive Care Medicine
    ISBN: 978-3-642-00418-6
    Source: Gale Virtual Reference Library (GVRL)
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  • 10
    Language: English
    In: Trends in Molecular Medicine, 2011, Vol.17(8), pp.433-441
    Description: Malignant gliomas (MGs) are deadly brain tumors with a median survival after resection, radiotherapy and chemotherapy of only 12 months. The natural immunosuppressive state of MG patients and the locally restricted growth of MGs render this neoplasm an excellent target for immunotherapy. Consequently, several failed attempts were made to treat MGs with immune cells. Recent preclinical experimental studies, however, demonstrate that natural killer (NK) cells can kill MGs and therefore hold promise in immunotherapy of MGs. This review describes the experimental and clinical evidence that support the potential of NK cells in therapy of MGs as well as the limitations to NK therapy. Finally, we propose strategies that could circumvent mitigating factors and enhance NK cell therapy for MG patients.
    Keywords: Medicine ; Biology
    ISSN: 1471-4914
    E-ISSN: 1471-499X
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