31 research outputs found

    Phenotypic and Functional Characterization of Human Memory T Cell Responses to Burkholderia pseudomallei

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    The Gram-negative bacterium, Burkholderia pseudomallei, is a public health problem in southeast Asia and northern Australia and a Centers for Disease Control and Prevention listed Category B potential bioterrorism agent. It is the causative agent of melioidosis, and clinical manifestations vary from acute sepsis to chronic localized and latent infection, which can reactivate decades later. B. pseudomallei is the major cause of community-acquired pneumonia and septicemia in northeast Thailand. In spite of the medical importance of B. pseudomallei, little is known about the mechanisms of pathogenicity and the immunological pathways of host defense. There is no available vaccine, and the mortality rate in acute cases can exceed 40% with 10–15% of survivors relapsing or being reinfected despite prolonged and complete treatments. In this article, we describe cell-mediated immune responses to B. pseudomallei in humans living in northeast Thailand and demonstrate clear evidence of T cell priming in healthy seropositive individuals and patients who recovered from melioidosis. This is the most detailed study yet performed on the cell types that produce interferon-gamma to B. pseudomallei in humans and the antigens that they recognize and the first to study large sample numbers in the primary endemic focus of melioidosis in the world

    Towards a matrix mechanics framework for dynamic protein network

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    Protein–protein interaction networks are currently visualized by software generated interaction webs based upon static experimental data. Current state is limited to static, mostly non-compartmental network and non time resolved protein interactions. A satisfactory mathematical foundation for particle interactions within a viscous liquid state (situation within the cytoplasm) does not exist nor do current computer programs enable building dynamic interaction networks for time resolved interactions. Building mathematical foundation for intracellular protein interactions can be achieved in two increments (a) trigger and capture the dynamic molecular changes for a select subset of proteins using several model systems and high throughput time resolved proteomics and, (b) use this information to build the mathematical foundation and computational algorithm for a compartmentalized and dynamic protein interaction network. Such a foundation is expected to provide benefit in at least two spheres: (a) understanding physiology enabling explanation of phenomenon such as incomplete penetrance in genetic disorders and (b) enabling several fold increase in biopharmaceutical production using impure starting materials

    Immunospecific Responses to Bacterial Elongation Factor Tu during Burkholderia Infection and Immunization

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    Burkholderia pseudomallei is the etiological agent of melioidosis, a disease endemic in parts of Southeast Asia and Northern Australia. Currently there is no licensed vaccine against infection with this biological threat agent. In this study, we employed an immunoproteomic approach and identified bacterial Elongation factor-Tu (EF-Tu) as a potential vaccine antigen. EF-Tu is membrane-associated, secreted in outer membrane vesicles (OMVs), and immunogenic during Burkholderia infection in the murine model of melioidosis. Active immunization with EF-Tu induced antigen-specific antibody and cell-mediated immune responses in mice. Mucosal immunization with EF-Tu also reduced lung bacterial loads in mice challenged with aerosolized B. thailandensis. Our data support the utility of EF-Tu as a novel vaccine immunogen against bacterial infection

    Melioidosis Vaccines: A Systematic Review and Appraisal of the Potential to Exploit Biodefense Vaccines for Public Health Purposes

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    The designation of Burkholderia pseudomallei as a category B select agent has resulted in considerable research funding to develop a protective vaccine. This bacterium also causes a naturally occurring disease (melioidosis), an important cause of death in many countries including Thailand and Australia. In this study, we explored whether a vaccine could be used to provide protection from melioidosis. An economic evaluation based on its use in Thailand indicated that a vaccine could be a cost-effective intervention if used in high-risk populations such as diabetics and those with chronic kidney or lung disease. A literature search of vaccine studies in animal models identified the current candidates, but noted that models failed to take account of the common routes of infection in natural melioidosis and major risk factors for infection, primarily diabetes. This review highlights important areas for future research if biodefence-driven vaccines are to play a role in reducing the global incidence of melioidosis

    Global innovation generation and financial performance in business-to-business relationships: the case of cross-border alliances in the pharmaceutical industry

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    Detection of testicular cancer in men presenting with infertility Detecção de câncer de testículo em homens com infertilidade

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    PURPOSE: Infertility is one of the less common presenting features associated with testicular tumors. We evaluated the histologic and biochemical findings, and pregnancy outcome in patients presenting with infertility who were found to have testicular tumors. METHODS: Seven patients with infertility were found to have testicular cancer over a 15-year period. All patients had a testicular ultrasound evaluation. The indications for the ultrasound were testicular pain in 2 patients, suspicious palpable mass in 4, and to rule out the presence of germ cell neoplasia in a patient with carcinoma in situ detected on a previous biopsy. Physical exam, histological findings, hormonal levels, tumor markers, and pregnancy outcome results were recorded from the patients medical charts. RESULTS: Two men had elevated serum follicle stimulant hormone and luteinizing hormone levels, 1 of them had an abnormally low serum testosterone level. Tumor markers were normal in all patients. In 4 patients the tumor was on the right side and in 3 on the left. The histological diagnoses were seminoma (n = 5), Leydig cell tumor (n = 1), and carcinoma in situ (n = 1). Of the 7 patients, 5 underwent adjuvant radiation therapy. Two patients had sperm cryopreserved. Follow up on fertility status was available in 6 cases. One patient has established a pregnancy and 5 did not achieve a pregnancy after treatment for their cancer. CONCLUSIONS: Most of the men who have testicular cancer and male infertility have a seminona. Therefore, men who present with infertility should be thoroughly investigated to rule out such serious, concomitant diseases along with their infertility.<br>PROPÓSITO: Infertilidade é um dos padrões incomuns associados com tumores de testículo. Nós avaliamos os achados histológicos, bioquímicos, e gravidez em pacientes com infertilidade nos quais foram detectados tumores de testículo. MÉTODOS: Sete pacientes com infertilidade nos quais câncer de testículo foi detectado em um período acima de 15 anos. Todos os pacientes foram avaliados com ultra-sonografia. As indicações para ultra-sonografia foram dor testicular em dois pacientes, suspeita de massa palpável em quatro, e descartar a presença de neoplasia de células germinativas em um paciente com carcinoma in situ detectado em biópsia prévia. Exame físico, achados histológicos, níveis hormonais, marcadores tumorais, e resultados de gravidez foram avaliados nos prontuários dos pacientes. RESULTADOS: Dois homens tinham níveis séricos elevados de hormônio folículo-estimulante e hormônio luteinizante; um destes tinha níveis anormalmente baixos de testosterona. Marcadores tumorais estavam normais em todos os pacientes. Em quatro pacientes, o tumor estava localizado no testículo direito e em três no esquerdo. Os diagnósticos histológicos foram seminoma (n = 5), tumor de células de Leydig (n = 1) e carcinoma in situ (n = 1). Dos sete pacientes, cinco foram submetidos à radioterapia. Dois pacientes congelaram seus espermatozóides. Acompanhamento no estado de fertilidade estava disponível em seis pacientes. Um paciente estabeleceu gravidez e cinco não conseguiram engravidar após tratamento do câncer. CONCLUSÕES: A maioria dos homens com câncer de testículo e infertilidade possui um seminoma. Homens que se apresentam com infertilidade devem ser cuidadosamente investigados para descartar doenças concomitantes e sérias juntamente com a infertilidade
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