Addenda inserted inside back fly-leaf. / Bibliography: leaves 185-229. / xxiv, 229, [42] leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Using a rat model of CRF (chronic renal failure), examines the effects of treatment with recombinant human (rh)IGF-I, rhGH and rhIGH-I + GH. Tests the hypothesis that uraemic resistance to both GH and IGF-I is evident in derangements in the GH/IGF-I axis contribution to growth retardation in children with CRF. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 1996?

Addendum pasted onto front end-paper. / Bibliography: leaves 176-216. / x, 216 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aim of this project is to determine why LR3IGF-1 has such divergent effects in two different species. The study investigates the endocrine regulation of IGF-I and IGF binding protein-3 (IGFBP-3) in the pig and determines the effects of IGF-I and LR3IGF-I treatment on porcine IGF-I and IGFBP-3 expression at the gene and protein level. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1997

Thesis (Ph.D.) -- University of Adelaide, Dept. of Biochemistry, 1994.

Tübingen, Univ., Diss., 2003.

Thesis (Ph.D.)--Georgetown University, 2008. / Includes bibliographical references.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Sept. 15, 2009). Includes bibliographical references.

Leishmaniasis is a disease that affects humans since ancient times. In the last 20 years an increased number of cases and expansion of the geographic occurrence of leishmaniasis has taken place. In Brazil, the disease is currently found in all states, especially in the North and Northeast regions, with different epidemiological profiles. In vitro studies have shown that the hormone |Insulin-Like Growth Factor| (IGF-I) enhances Leishmania infection in macrophage in vitro and, exacerbates Leishmania infection in vivo in experimental models, treatment with IGF-1. Individuals with a natural mutation of the receptor of growth hormone-releasing hormone (GHRH) and consequent deficiency of growth hormone (GH) and IGF-I have been described in Itabianinha, Sergipe, called Isolated deficiency of growth hormone (DIGH). This mutation affects the growth weight and height, but the immune response of these individuals has not been evaluated. To better understand the role of IGF-1 in susceptibility to Leishmania infection, the purpose of this work was to study the behavior of leishmania infection in vitro in human macrophages from these individuals with IGF-1 deficiency. Leishmania amazonensis infection was compared in monocytes-derived from peripheral blood from two groups of individuals: 1) Individuals affected with homozygous deficiency of GHRH/GH/IGF-I (dwarf phenotype) (n =8), 2) Homozygous controls without this mutation (normal phenotype) (n =7). The number of infected macrophages and the parasitic load/100 macrophages was compared between these groups. These data confirm the data from experimental model that of IGF-I interferes in Leishmania-macrophage interaction, increasing the parasitic load of this infection. / A leishmaniose é uma doença que acomete o homem desde tempos remotos. Um aumento do número de casos e ampliação de sua ocorrência geográfica tem ocorrido nos últimos 20 anos. No Brasil é encontrada atualmente em todos os estados, em especial nas regiões Norte e Nordeste, sob diferentes perfis epidemiológicos. Estudos in vitro mostraram que o peptídeo Insulin-Like Growth Factor type I (IGF-I), principal mediador das ações do hormônio de crescimento (GH), aumenta a infecção de macrófagos por Leishmania. Em modelos experimentais, o tratamento com IGF-I agrava a infecção por Leishmania. Em Itabaianinha, no nordeste do Brasil, foi descrito uma grande coorte de indivíduos homozigotos para a mutação c.57+1G>A (MUT/MUT) no receptor do hormônio liberador do hormônio de crescimento (GHRH), causando um nanismo acentuado devido à deficiência isolada do hormônio de crescimento (DIGH), com concentrações séricas vitalícias muito baixas de GH e IGF-I. O propósito deste trabalho foi avaliar, in vitro, o papel do IGF-I na susceptibilidade à infecção por Leishmania, de macrófagos humanos dos indivíduos com DIGH. O comportamento da infecção in vitro com Leishmania amazonensis foi comparado em macrófagos derivados do sangue periférico de dois grupos de indivíduos: indivíduos MUT/MUT (n= 8), e indivíduos controles homozigóticos normais, N/N (n=7). O número de macrófagos infectados/100 macrófagos e a carga parasitária destes macrófagos (número de amastigotas /100 macrófagos) foram comparados entre estes grupos. Os macrófagos dos indivíduos com DIGH são mais resistentes à infecção com promastigotas de Leishmania amazonensis que os dos N/N e não parecem responder ao estímulo in vitro com IGF-I. Estes resultados comprovam em células humanas, os achados em camundongos que mostram que o IGF-I agrava a infecção na interação macrófago-Leishmania amazonensis.

Com o objetivo de estudar os efeitos do uso da Somatotropina Recombinante Bovina (rBST) no lipidograma e constituição do leite de bubalinos foram utilizadas 28 búfalas divididas em dois grupos: Grupo 1 constituído de 14 búfalas nas quais foi realizada uma aplicação de 500 mg de rBST e Grupo 2 - constituído de 14 búfalas que não receberam qualquer tratamento hormonal (grupo controle). Durante o experimento, os animais tiveram amostras de plasma e soro sanguíneo, bem como de leite colhidas periodicamente nos seguintes momentos: dia da aplicação da rBST, 1º, 3º, 5º, 7º, 10º e 14º dia após a aplicação da rBST. A fim de minimizar possíveis influências da fase da lactação, todas as búfalas utilizadas no experimento estarvam entre 100 e 200 dias de lactação e com produção de leite variando entre 5 e 10 litros por dia. O lipidograma foi avaliado por meio da determinação dos teores séricos de colesterol, triglicérides, ácidos graxos não esterificados e β-HBO e teores plasmáticos de glicose, enquanto a constituição do leite de búfalas foi avaliada por meio de determinação dos teores lácteos de gordura, proteína, lactose, sólidos totais e do número de células somáticas. Durante a avaliação dos resultados obtidos podemos notar que a aplicação da somatotropina recombinante bovina não influenciou os teores séricos de NEFA, colesterol e triglicérides bem como os plasmáticos de glicose. No entanto os teores séricos de β-HBO foram afetados pelo tratamento instituído, pois verificou-se que, a partir do 1º dia após o início do tratamento hormonal, os teores séricos de -HBO no grupo tratado com rBST eram entre 0,21 e 0,55 mg/dL maiores do que os encontrados no grupo controle. Quando avaliamos a composição do leite temos que os resultados nos permitem afirmar que o tratamento instituído não interfere nas concentrações de gordura, lactose, sólidos totais e no número de células somáticas. Nos primeiros dias após a aplicação da rBST ocorria uma diminuição dos teores lácteos de proteína, sendo verificado que no 3º dia após o início do tratamento hormonal os valores lácteos de proteína encontrados no grupo tratado com rBST (3,59 ± 0,22 g/dL) eram significativamente menores do que os observados no grupo controle (3,89 ± 0,22 g/dL). A partir do 5º dia após o início do tratamento hormonal, os valores de proteína passam a oscilar sem que qualquer diferença estatística entre o grupo tratado e controle possam ser observados. / With the aim to evaluate the influence of recombinant bovine somatotropin (rBST) in the lipid profile and milk composition of lactating Murrah water buffaloes, we collected and analyzed samples of blood serum and plasma and milk of clinically healthy animals. We determined the concentrations of cholesterol, triglycerides, nonesterified fatty acids (NEFA), -hydroxibutyrate (-HBO) and glucose from the blood samples. Milk samples were collected after milking and the following parameters were evaluated: fat, protein, lactose, total solids and somatic cell count. The influence of rBST was studied through 28 animals divided in 2 experimental groups: Experimental Group 14 animals that received a single application of 500mg rBST; Control Group - 14 animals that didn´t receive any hormonal treatment. Blood and milk samples were collected in the following moments: day of rBST application, 1st, 3rd, 5th, 7th, 10th and 14th day after the rBST application. To minimize the influence of lactation, the samples were collected between 100-200 days of lactation and the milk yields per cow range from 5 10 Liters. According to the results of this research, we concluded that one single application of rBST didn´t affect the NEFA, cholesterol, triglycerides and glucose blood levels. The serum β-HBO concentration was influenced by the hormonal treatment. In the experimental group, after 24 hours from the treatment, the β-HBO level ranged 0.21 - 0.55 mg/dL and it was greater than that of control group. The fat, lactose, total solids and somatic cell count were not influenced by the rBST treatment. In the first days after the application of rBST, the milk protein decreased gradually reaching its low level in the 3rd day after the application (3.59 ± 0.22 g/dL) and was significant lower than that of control group (3.89 ± 0.22 g/dL). After the 5th day, the milk protein values oscillated without any statistical difference between both groups.

The experimental data included in this thesis examines two events involved in signal transduction by the Epidermal Growth Factor Receptor. The first event (receptor oligomerization) occurs at the cell membrane and is proposed to be involved in activating the tyrosine protein kinase activity of the EGF receptor. Activation of the tyrosine protein kinase is an initial step in signal transduction by the EGF receptor. The second event examined (activation of an EGF stimulated serine/threonine protein kinase activity) occurs in the cytosol and may potentially be involved in final transmission of the EGF signal to the cell nucleus. The role of oligomerization in regulating the EGF receptor tyrosine protein kinase was examined by testing two hypotheses: 1) that PMA controls EGF receptor function by regulating the oligomeric state of the receptor and 2) that oligomerization is required to activate the EGF receptor tyrosine protein kinase. The oligomeric state of the EGF receptor was examined by chemical cross-linking and sucrose density gradient centrifugation analysis. It was determined that protein kinase C inhibition of the EGF receptor tyrosine protein kinase activity is independent of the oligomeric state of the receptor. It was also determined that the tyrosine protein kinase of the EGF receptor can be activated in the absence of receptor oligomerization. Threonine 669 is the major site of phosphorylation of the EGF receptor after treatment of cells with EGF. Phosphorylation of this site is also associated with the transmodulation of the EGF receptor caused by platelet-derived growth factor and phorbol ester. The kinetics of activation of this T669 kinase activity is rapid. Furthermore, it was demonstrated that EGF could activate the T669 kinase in the absence of detectable tyrosine kinase activity. Together, these data suggest that the T669 kinase has a role in intracellular signal transduction. Therefore, the T669 kinase was purified and characterized in order to help understand how EGF binding to its receptor at the cell membrane ultimately leads to signal transduction to the cell nucleus.

No description available.