Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [85]-98).

Thesis (Ph. D.)--Ohio State University, 2008. / Non-Latin script record

Thesis--University of Helsinki, 1983. / Also published in: Proceedings of the Finnish Dental Society, v. 79, 1983, Supp. III. Bibliography : p. 47-55.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 104-120).

Introdução: O aumento no consumo mundial de imunoglobulina humana tem desafiado os sistemas de saúde no estabelecimento de padrões de utilização adequados a esta terapia. O conhecimento das políticas públicas pelos profissionais de saúde, aderidos a uma conscientização ao uso racional e estudos baseados em evidências científicas é fundamental para assegurar o acesso adequado e uma maior segurança e efetividade de tratamento. Objetivo: Avaliar a utilização de imunoglobulina humana em hospital universitário de alta complexidade do sul do país e suas indicações relacionando as mesmas aos protocolos clínicos estabelecidos. Métodos: Trata-se de um estudo transversal, retrospectivo, baseado na busca de informações através do prontuário eletrônico dos pacientes do Hospital de Clínicas de Porto Alegre no período de janeiro à dezembro de 2015 Resultados: Foram identificadas 191 prescrições de imunoglobulina humana endovenosa, totalizando 116 pacientes. Desses pacientes, 23% apresentaram síndrome de Guillain Barré, púrpura trombocitopênica idiopática, miastenia gravis, transplante renal, imunodeficiência com aumento de IgM e outras anemias hemolíticas autoimunes. Todas essas situações clínicas tem indicação de uso de acordo com os protocolos estabelecidos pelo Ministério da Saúde. Os demais casos identificados (77%) não constam nas indicações previstas nos protocolos do Ministério da Saúde. Conclusão: Foi possível identificar a utilização de imunoglobulina humana endovenosa em hospital de alta complexidade e quantificar os casos clínicos que fazem uso desse medicamento e que apresentam protocolos nacionais orientando os profissionais de saúde quanto a correta administração desse medicamento. Observou-se que a maioria dos casos identificados no estudo não apresentam regulamentos oficiais que autorizem a sua administração. / Introduction: The increase in the world consumption of human immunoglobulin has challenged the health systems in establishing appropriate standards of use for this therapy. Knowledge of public policies by health professionals adhering to rational use awareness and evidence-based studies is critical to ensure adequate access and greater safety and effectiveness of treatment. Objective: To evaluate the use of human immunoglobulin in a university hospital of high complexity in the South of the country and its indications relating them to the established clinical protocols. Methods: This is a cross-sectional, retrospective study based on the search of information through the electronic medical records of patients from the Hospital de Clínicas of Porto Alegre from January to December 2015 Results: 191 prescriptions of intravenous human immunoglobulin were identified, totaling 116 patients. Of these patients, 23% had Guillain Barré syndrome, idiopathic thrombocytopenic purpura, myasthenia gravis, renal transplantation, immunodeficiency with increased IgM and other autoimmune hemolytic anemias. All of these clinical situations are indicated for use according to protocols established by the Ministry of Health. The other cases identified (77%) are not included in the indications provided for in the protocols of the Ministry of Health. Conclusion: It was possible to identify the use of intravenous human immunoglobulin in hospital of high complexity and to quantify the clinical cases that use this medicine and that present national protocols guiding healthcare professionals about the correct administration of this medicine. It was observed that the majority of the cases identified in the study do not present official regulations that authorize its administration.

Made available in DSpace on 2014-06-11T19:31:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-18Bitstream added on 2014-06-13T21:02:22Z : No. of bitstreams: 1 garcia_fai_dr_jabo.pdf: 798787 bytes, checksum: cc4872fa6b42f7f6ec29fb841ea304bd (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente estudo teve como objetivos comparar a resposta da imunoglobulina G e de suas subclasses nos seguintes grupos de animais; cães hígidos (n=45), animais sintomáticos naturalmente infectados por Leishmania sp. (n=45), animais assintomáticos naturalmente infectados por Leishmania sp. (n=45), cães portadores de leishmaniose visceral submetidos à tratamento (n=27) e animais hígidos submetidos à vacinação contra a doença (n=37). Inicialmente foram avaliadas IgG1 e IgG2 utilizando anticorpos policlonais e posteriormente as quatro subclasses de IgG (IgG1, IgG2, IgG3 e IgG4) com anticorpos monoclonais na tentativa de identificar um perfil de resposta para cada grupo de cães. As determinações sorológicas foram realizadas por meio da técnica de ELISA. A avaliação das subclasses de IgG com anticorpos policlonais não permitiu diferenciar os grupos de cães estudados. Por outro lado, com os anticorpos monoclonais observou-se que o grupo sintomático apresentou estimulação de todas as subclasses de IgG enquanto nos animais assintomáticos apenas a fração IgG1 foi estimulada. Nos cães submetidos a tratamento todas as frações encontravam-se elevadas e nos vacinados ocorreu estimulação de IgG1, IgG3 e IgG4. Desta forma, a avaliação das quatro subclasses permitiu a diferenciação entre animais portadores de leishmaniose visceral com e sem quadro clínico; entre cães vacinados e cães assintomáticos acometidos pela doença; e entre cães com leishmaniose visceral submetidos a tratamento e cães infectados assintomáticos. / The present study aimed to compare immunoglobulin G subclasses in the following groups of animals: healthy dogs (n=45); symptomatic Leishmania sp. naturally infected dogs (n=45); asymptomatic Leishmania sp. naturally infected dogs (n=45); dogs with visceral leishmaniasis submitted to treatment (n=27) and healthy dogs vaccinated for visceral leishmaniasis (n=37). First of all IgG1 and IgG2 were evaluated using polyclonals antibodies, and later the four subclasses of IgG (IgG1, IgG2, IgG3 and IgG4) were evaluated with monoclonals antibodies, in order to identify a profile of reply for each group of dogs. Serological tests were carried out using enzyme-linked immunosorbent assay (ELISA). The evaluation of the subclasses with polyclonals antibodies did not allow to differentiate the groups of studied dogs. On the other hand, with monoclonals antibodies it was possible to verify that symptomatic dogs presented stimulation of all subclasses of IgG, while in asymptomatic animals only IgG1 was stimulated. In dogs submitted to treatment all fractions increased, and in vaccinated ones occurred stimulation of IgG1, IgG3 and IgG4. In such a way, the evaluation of the four subclasses allowed the differentiation between symptomatic and asymptomatic infected dogs; between vaccinated dogs and asymptomatic infected dogs; and between infected dogs submitted to treatment and asymptomatic infected dogs.

The effects of induced mood on secretory immunoglobulin A (SIgA) were tested on 104 students (51 men & 53 women) using a mixed design with between subject factors of gender, induced mood (positive vs. negative), method of induction (writing about oneself vs. viewing a video), and a within subject factor, time (baseline vs. posttest). A split-plot multivariate analysis of covariance, controlling for salivary flow rate, did not support a causal link between induced mood alone and change in SIgA concentration. The effect of induced mood on blood pressure and heart rate was also examined. There were no significant main effects, but gender interacted with mood induction such that females experienced an increase in blood pressure in the positive mood induction condition. There was no significant effect of method of mood induction on SIgA, blood pressure, or heart rate. Stable personality traits, however, moderated the effects of mood induction. Persons who scored higher on depression and neuroticism, and lower on positive affect had significantly higher SIgA concentrations in the negative mood condition. There were no significant effects of personality traits on SIgA levels in the positive mood condition, nor did they interact with induced mood to change blood pressure or heart rate. These data suggest that although SIgA concentration may not be subject to short-term laboratory mood manipulations alone, changes in SIgA concentration may be associated with an interaction of stable personality traits and mood state, especially in the case induced negative mood.

Doctor of Philosophy / Department of Biology / Stephen Chapes / Antibodies are an essential part of the immune system. Each B cell, a type of white blood cell, produces a unique antibody. This antibody molecule is comprised of two identical light chains and two identical heavy chains. Each chain has a variable region, which is responsible for antigen binding, and a constant region, which is responsible for effector function in the host. The variable region in the heavy chain is composed of three gene segments, the variable (V), diversity (D), and joining (J) gene segments. The light chain is composed of only V- and J-gene segments. Each immunoglobulin locus contains multiple versions of each gene segment, ranging from over 130 possible V gene segments in the heavy chain to four possible J-gene segments in both the heavy and kappa light chain. The recombination of gene segments occurs in the germline DNA and results in the formation of the unique antibody. The diversity and binding abilities of the antibodies are important for a proper and robust immunological response. Of importance to binding and specificity is the complementary determining region three (CDR3) which plays a major role in determining specificity and antibody-antigen binding. Due to its uniqueness, is used as a measure of diversity in the repertoire. In this work, I used Illumina MiSeq 2x300nt high-throughput sequencing to assess the mouse splenic transcriptome. The work I present here shows the splenic immunoglobulin gene repertoire from unchallenged, unvaccinated conventionally housed mice, mice flown aboard the International Space Station (ISS), and mice challenged with tetanus toxoid (TT) and/or adjuvant (CpG) and subjected to skeletal unloading by antiorthostatic suspension (AOS). AOS is used to induce some of the physiological changes that parallel those that occur during space flight. The characterization of the repertoire includes analysis of V-, D-, and J-gene segment usage, constant region usage, V- and J-gene segment pairing, and CDR3 length and usage. The work included validation of the methodology needed for tissue preparation and storage aboard the ISS, showing that the data obtained was similar to those used in standard ground-based methodologies (Chapter 2). I further validated our nonamplified sequencing methodology with comparisons to methods that use amplification as part of the process (Chapter 3). My work characterized the antibody repertoire of the conventionally housed C57BL/6J mouse (Chapter 4), an important mouse strain in the field of immunology, and demonstrated the homogeneity of gene segment usage in unchallenged animals. We also demonstrated that short duration (~21 days) space flight does not significantly alter the antibody repertoire (Chapter 5). The work culminates in an AOS study to assess changes to the B-cell immunoglobulin repertoire after vaccination with TT and/or CpG. The results show that changes to V-, D-, and J-gene segment usage occur after antigen challenge with AOS causing decreased class switching and frequency of plasma cells. Tetanus toxoid challenge decreased multiple gene segment usage and CpG administration increased isotype switching to the IgA constant region (Chapter 6).

Introdução: O aumento no consumo mundial de imunoglobulina humana tem desafiado os sistemas de saúde no estabelecimento de padrões de utilização adequados a esta terapia. O conhecimento das políticas públicas pelos profissionais de saúde, aderidos a uma conscientização ao uso racional e estudos baseados em evidências científicas é fundamental para assegurar o acesso adequado e uma maior segurança e efetividade de tratamento. Objetivo: Avaliar a utilização de imunoglobulina humana em hospital universitário de alta complexidade do sul do país e suas indicações relacionando as mesmas aos protocolos clínicos estabelecidos. Métodos: Trata-se de um estudo transversal, retrospectivo, baseado na busca de informações através do prontuário eletrônico dos pacientes do Hospital de Clínicas de Porto Alegre no período de janeiro à dezembro de 2015 Resultados: Foram identificadas 191 prescrições de imunoglobulina humana endovenosa, totalizando 116 pacientes. Desses pacientes, 23% apresentaram síndrome de Guillain Barré, púrpura trombocitopênica idiopática, miastenia gravis, transplante renal, imunodeficiência com aumento de IgM e outras anemias hemolíticas autoimunes. Todas essas situações clínicas tem indicação de uso de acordo com os protocolos estabelecidos pelo Ministério da Saúde. Os demais casos identificados (77%) não constam nas indicações previstas nos protocolos do Ministério da Saúde. Conclusão: Foi possível identificar a utilização de imunoglobulina humana endovenosa em hospital de alta complexidade e quantificar os casos clínicos que fazem uso desse medicamento e que apresentam protocolos nacionais orientando os profissionais de saúde quanto a correta administração desse medicamento. Observou-se que a maioria dos casos identificados no estudo não apresentam regulamentos oficiais que autorizem a sua administração. / Introduction: The increase in the world consumption of human immunoglobulin has challenged the health systems in establishing appropriate standards of use for this therapy. Knowledge of public policies by health professionals adhering to rational use awareness and evidence-based studies is critical to ensure adequate access and greater safety and effectiveness of treatment. Objective: To evaluate the use of human immunoglobulin in a university hospital of high complexity in the South of the country and its indications relating them to the established clinical protocols. Methods: This is a cross-sectional, retrospective study based on the search of information through the electronic medical records of patients from the Hospital de Clínicas of Porto Alegre from January to December 2015 Results: 191 prescriptions of intravenous human immunoglobulin were identified, totaling 116 patients. Of these patients, 23% had Guillain Barré syndrome, idiopathic thrombocytopenic purpura, myasthenia gravis, renal transplantation, immunodeficiency with increased IgM and other autoimmune hemolytic anemias. All of these clinical situations are indicated for use according to protocols established by the Ministry of Health. The other cases identified (77%) are not included in the indications provided for in the protocols of the Ministry of Health. Conclusion: It was possible to identify the use of intravenous human immunoglobulin in hospital of high complexity and to quantify the clinical cases that use this medicine and that present national protocols guiding healthcare professionals about the correct administration of this medicine. It was observed that the majority of the cases identified in the study do not present official regulations that authorize its administration.

Abstract Filamins are large dimeric proteins that cross-link actin into three-dimensional bundles or orthogonal networks. In addition to an actin-binding domain, each filamin monomer contains 24 immunoglobulin-like domains separated by flexible regions between domains 15–16 and 23–24. Dimerisation of filamin occurs through the Ig-like domain 24. Filamins bind to a variety of molecules. They provide a link between the plasma membrane and the cytoskeleton through interactions with transmembrane receptors, and at the same time, serve as a platform for signalling molecules. Filamins are involved in several human diseases affecting the central nervous system, vascular system and muscle. In this study the structure of the the carboxy-terminus of filamin was resolved and details of filamins interaction with a platelet surface protein important in haemostasis were analysed. An x-ray structure of the Ig-like domain 24 of human filamin C was solved at the resolution of 1.43 Å. The asymmetric unit of the crystal contains one monomer; a crystallographic dimer is formed by 2-fold axis symmetry. Point mutation studies confirmed that the dimer seen in the crystal is also present in solution. The structure showed that the dimerisation mode of human filamin is completely different from that in the Dictyostelium discoideum amoeba filamin analogue. Human filamin dimerises through β-strands C and D, and the Dictyostelium protein through β-strands B and G located on the opposite edge of the β-sandwich. Based on the sequence homology between vertebrate filamins it was proposed that the interface seen in human filamin is common for all vertebrate filamins. The structure of human filamin C Ig-like domains 23–24 was solved by combining the techniques of x-ray crystallography and small angle x-ray scattering (SAXS). This structure provides further insight into the organization of the domains in the carboxy-terminal part of filamin molecule. One of the first structural examples of the interaction of filamin with a ligand was provided by this study. The x-ray structure of filamin A domain 17 in complex with the alpha subunit of the GPIb-V-IX receptor was solved at a resolution of 2.3 Å. The interaction between filamin and the GPIbα-V-IX receptor is important for maintaining the integrity and shape of blood platelets, as well as for regulating the receptor adhesive function. This study also revealed that the Ig-like domain 17 represents a major binding site of filamin to GPIbα. The Kd of the interaction, determined by calorimetric studies, was 11 μM. The specificity of the filamin A 17 - GPIbα interaction is mainly determined by hydrophobic contacts.