Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 3 uppsatser.

Thesis (Ph.D.). / Written for the Dept. of Neurology and Neurosurgery. Title from title page of PDF (viewed 2008/05/12). Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri--Columbia, 1997. / "May 1997." Typescript. Vita. Includes bibliographical references (leaves 147-162). Also available on the Internet.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [93]-107).

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 149-170).

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 174).

Made available in DSpace on 2013-08-07T19:06:28Z (GMT). No. of bitstreams: 1 000437701-Texto+Completo-0.pdf: 658664 bytes, checksum: 3842d70518efb4bc4633c3998b3a5859 (MD5) Previous issue date: 2012 / Sepsis is a systemic inflammatory disorder, and its progression to septic shock is a serious clinical problem associated with a high mortality rate. Despite significant advances in critical care, treatments do not reverse the systemic inflammatory response and its consequences. Gram-negative sepsis is initiated by exposure to a component of gram-negative bacterial membrane, lipopolysaccharide (LPS), and induces overproduction of host inflammatory cytokines, including tumor necrosis factor (TNF- α), interleukin-1 (IL-1) and interleukin-6 (IL-6) from immunocytes such as monocytes. Recent studies have shown that similar to LPS, the Respiratory syncytial virus - leading cause of severe lower respiratory tract infections in infants and young children – requires the toll-like receptor 4 (TLR4) for signaling. Studies have shown that the respiratory syncytial virus attachment glycoprotein (RSV G) modulates cytokine and chemokine production in monocytes, inhibiting the inflammatory response elicited by LPS stimulation. In this report, we use murine monocytes from different knockout mice to show that RSV G can inhibit the release of cytokines in the immune response against lipoplysaccharide induced sepsis. We demonstrate the modulation of IL-1β, IL-6, IL-10 and TNF-α by RSV G in monocytes LPS stimulated. Importantly, we also considered the effect of RSV G subunits (peptides) and future directions for the clinical use of the glycoprotein on LPS-mediated inflammation. / Sepse é uma desordem inflamatória sistêmica e sua progressão para o choque séptico caracteriza um sério problema clínico, apresentando altas taxas de mortalidade. Apesar dos significativos avanços no tratamento intensivo, os mesmos não são capazes de reverter a resposta inflamatória sistêmica, assim como suas conseqüências. A sepse por bactérias gramnegativas é desencadeada pela exposição a um componente da membrana destas bactérias, conhecido como lipopolissacarídeo (LPS), o que leva a uma super produção de citocinas inflamatórias no hospedeiro, incluindo o fator de necrose tumoral (TNF-α), a interleucina-1 (IL-1) e a interleucina-6 (IL-6), por sua vez provindas de células do sistema imune, como os monócitos. Estudos recentes demonstraram que, de forma similar ao LPS, o vírus sincicial respiratório (RSV) – principal causa de infecção respiratória baixa em crianças e recém natos - utiliza o receptor toll-like 4 (TLR4) para sinalização celular. Estudos demonstraram que a glicoproteína de ligação do vírus sincicial respiratório (RSV G) age como imunomoduladora na produção de citocinas e quimiocinas por monócitos, inibindo a resposta inflamatória estimulada por LPS. Neste artigo, nós utilizamos monócitos monócitos murinos de diferentes camundongos knockout para demonstrar que RSV G pode inibir a produção de citocinas na resposta imune contra lipopolissacarídeos em um modelo de sepse. Demonstra-se também a modulação das citocinas IL-1β, IL-6, IL-10 e TNF-α por RSV G em monócitos estimulados por LPS. O artigo ainda considera de forma destacada o efeito de subunidades (peptídeos) de RSV G, bem como destaca perspectivas para o futuro uso clínico de glicoproteínas na modulação da resposta inflamatória mediada por LPS.

One purpose of this study was to determine whether the ras protein from Dictyostelium discoideum (p23) binds guanine nucleotides like the ras proteins from mammals (p21) and yeast. The other purpose of this investigation was to purify or enrich for p23ras from D. discoideum by immunoaffinity chromatography. A number of different approaches were used to determine guanine nucleotide binding by p23RAS . A simple filter binding assay, binding to Western blots, and photoaffinity labeling all failed to demonstrate specific binding with lysates of D. discoideum cells. In contrast p21RAS from transformed NIH-3T3 cell lysate was successfully photoaffinity labeled in the presence of ³²P-α-guanosine 5¹-triphosphate (GTP) suggesting that the technique had been performed correctly. It was concluded that either p23RAS has a very low affinity for guanine nucleotides such that GTP binding was not detectable in these experiments or that the ras protein from D. discoideum simply does not bind guanine nucleotides. The purification of p23RAS from D. discoideum cells was attempted in order to provide a purified protein preparation for guanine nucleotide binding and for reconstitution studies. An anti-ras monoclonal antibody (Y13-259) was used as the ligand for the immunoaffinity chromatography. This approach was not successful in that the ras protein could not be enriched relative to other proteins because the immunoaffinity columns did not bind p23RAS. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

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