Thesis (M.S.) in Marine Biology--University of Maine, 2006. / Includes vita. Includes bibliographical references (leaves 39- 43).

Thesis (Ph. D. in Biophysics)--University of California, Berkeley, June 1958. / Bibliography: leaves 77-80.

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 109-119).

No description available.

Haptoglobin is a genetically polymorphic plasma protein which possesses the property of combining specifically with hemoglobin. Haptoglobin binds hemoglobin stoichiometrically in a stable and essentially irreversible complex. The present studies are concerned with the nature of the hemoglobin combining site on haptoglobin in relation to its function. Large quantities of homogeneous haptoglobin have been prepared from ascites fluid by a newly developed method involving first, ammonium sulfate precipitation, followed by DEAE-cellulose chromatography and finally purification by Sephadex G-200 gel filtration. A Sephadex G-200 assay which separates the free hemoglobin from the Hb-Hp complex and enables direct measurement of the amount of hemoglobin bound to haptoglobin has been developed. In order to determine whether the site of polymerization of haptoglobin polymers is distinct from the hemoglobin binding site, haptoglobin polymers partially resolved on Sephadex G-200, were examined for their ability to bind hemoglobin both by the peroxidase assay and the Sephadex assay. Localization of the hemoglobin binding site on the component haptoglobin chains was achieved by determination of the ability of isolated a¹, a² and β chains to bind hemoglobin by means of the Sephadex assay. The binding of globin, myoglobin and various vertebrate hemoglobins were also examined by the Sephadex assay. The effects of environmental factors on the combination of haptoglobin with hemoglobin has been studied by alteration of ionic strength and of pH and by addition of phenol as a tyrosine analogue. The involvement of amino groups of haptoglobin in binding with hemoglobin has been studied by selective chemical modification of haptoglobin amino groups with three reagents of increasing severity followed by measurement of the ability of the chemically modified proteins to bind hemoglobin. An approximate determination of the area of the binding site in the Hb-Hp complex has been made by comparison of the extent of guanidination of amino groups of the individual components with that of the complex and also by comparison with the extent of modification in dissociated hemoglobin and haptoglobin from the guanidinated complex. The results of these studies show that the hemoglobin combining site is distinct from the site of polymerization and that the β haptoglobin chain carries the hemoglobin binding site. Haptoglobin combines with globin but not with myoglobin and it binds stoichiometrically with all animal hemoglobins examined except those of the frog and fish, which may be the result of a conformational change in the Hb-Hp complex which causes expulsion of the heme group. It is shown that electrostatic forces cannot be the sole interrnolecular forces involved in the binding. Chemical modification studies show that the area of contact between the hemoglobin and the haptoglobin in the complex involves only a small area of the haptoglobin molecule of else the area is particularly deficient in lysyl-side chains. It is also shown that amino groups are not directly involved in the binding site and that acylation of amino groups particularly with succinyl group cause a profound change in the haptoglobin molecule and its ability to bind hemoglobin is very much reduced. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

No description available.

Adult hemoglobin (HbA) is made up of two pairs of globin chains. Some rare mutations of the globin chains can result in high affinity towards hemoglobin molecule thus changing the equilibrium of normal oxygen loading in lungs and the delivery of same to the tissues. Because of change in the affinity to the oxygen these mutations can result in erythrocytosis (polycythemia). Here we discuss a case of Familial Polycythemia likely due to novel hemoglobin variant. 42-year Caucasian male presents to the clinic with high hemoglobin for several years but otherwise denies any symptoms of headache, vision changes, chest pain. He had history of multiple phlebotomies. His past medical history is significant for Polycythemia, PICC line associated clot,Type2 Diabetes, Hypertension, Epidural abscess. Social history is significant for smokeless tobacco but otherwise non-smoker, non-alcoholic, not an IVDA and doesn’t use testosterone. Family history is significant for his sister, her two 14year old daughters and multiple other family members with elevated hemoglobin and undergo phlebotomies, maternal grandfather died of cancer in his 30s. Physical examination is only significant for BMI of 32.46 otherwise no skin discoloration or cyanosis. Laboratory data WBC 9.4 with normal differential, hemoglobin 18.2, hematocrit 55.4, platelet count 180,000, peripheral blood smear was within normal limits, negative for JAK-2, normal erythropoietin, negative for hemochromatosis, Oxygen dissociation p50 of 19 which is low indicating left shifted dissociation curve, hemoglobin electrophoresis HbA: 61.2%, HbA2: 3%, HbF: 0%, Beta variant: 35.8%. In order to further characterize beta variant Bi-directional sequence analysis for Molecular alterations was performed and the following alterations were detected Gene: HBB, DNA change: Codon 39, heterozygous CAG>CCG Protein change: P.G1n39Pro. [glutamine (Q) to proline (P)]. HGVS: c.119A>C, p.Q40P, Classification: Likely deleterious variant. (GenBank accession number NM_000518.4). This is a previously unreported beta chain hemoglobin variant present. This hemoglobin variant is named as Hemoglobin Hyden based on the place where this is found in Hyden, Kentucky. There have been four variants reported at codon 40 of the beta globin gene, which is an external contact site between beta globin and alpha-2 globin. One variant, Hb vassa, is associated with mild hemolytic anemia. The three other variants (Hb Alabama, Hb Tianshui and Hb San Bruno) are not associated with clinical or hematological abnormalities. In our opinion p.Q40P is likely a cause of erythrocytosis. In order to further establish the causality it may be beneficial to test first degree relative to in this family in order to determine whether the p.Q40P alteration tracks with disease and is not present in unaffected individuals. Hemoglobin threshold for phelebotomy to lower the risk of thrombosis and cardiovascular events is yet to be defined.

Call number: LD2668 .T4 1931 S52

Call number: LD2668 .T4 1932 K53 / Master of Science

Made available in DSpace on 2018-08-01T23:27:55Z (GMT). No. of bitstreams: 1 tese_9426_Dissertação de Mestrado - Alline Mikaele Nunes Wildemberg Brauer.pdf: 1479016 bytes, checksum: 211ecab2a55e9c0660946ed6fa06d592 (MD5) Previous issue date: 2017-03-31 / O Brasil é considerado o país, extra África, que apresenta o maior contingente de população negra. Contudo, ainda é possível observar, especialmente nas comunidades quilombolas, um cenário marcado pela marginalização socioeconômica e precárias condições de vida e saúde. O presente trabalho trata-se de um estudo transversal, descritivo e quantitativo, com o objetivo de realizar uma avaliação socioeconômica, demográfica, parasitológica e hematológica dos moradores de comunidades quilombolas situadas na região Norte do Espírito Santo, Brasil. A avaliação socioeconômica e demográfica foi executada por unidade familiar, através da aplicação de um questionário baseado na Pesquisa Nacional por Amostra de Domicílios. Para investigação de parasitos intestinais utilizaram-se os métodos de sedimentação espontânea (HPJ) e Kato Katz. No inquérito hematológico foram realizados o hemograma completo, os testes de triagem e confirmatório de hemoglobinopatias (teste de resistência osmótica, eletroforese alcalina em acetato de celulose e cromatografia líquida de alta eficiência). Os resultados obtidos foram avaliados através de ferramentas da estatística descritiva e inferencial, utilizando-se para tanto testes de qui-quadrado de Pearson e análise de regressão de Poisson, adotando o intervalo de confiança 95% (p<0,05). Observou-se que dos 76 chefes de família entrevistados, 90,79% (n=69) possuem água canalizada na residência e 72,37% (n=55) informaram que a origem da água utilizada por eles é de poço ou de nascente. Além disso, 98,68% (n=75) referiram ter banheiro no domicílio, sendo que destes, 90,67% (n=68) relataram ter como escoadouro a fossa rudimentar e 63,16% (n=48) alegaram que o lixo gerado é enterrado ou queimado. Em relação a saúde geral da população, 78,94% (n=60) informaram ter acesso a serviços de saúde pública e 64,47% (n=49) referiram já ter tido doenças parasitárias, sendo que 63,15% (n=48) alegaram conhecer como são transmitidas. Por outro lado, 92,10% (n=70) informaram que não sabem se são portadores da anemia falciforme ou do traço falcêmico e 94,73% (n=72) desconhecem como são adquiridos. Os exames parasitológicos apresentaram resultados positivos em 48% (n=72) do total de amostras analisadas (150), sendo que 25% (n=18) dessas amostras apresentaram dois ou mais parasitos. O parasito mais frequente foi o Ascaris lumbricoides (19,4%, n=14). Entre os comensais a Entamoeba coli (55,6%, n=40), seguido da Endolimax nana (16,7%, n=12). Considerando a avaliação hematológica, das 192 amostras analisadas, observou-se uma frequência de 13,54% (n=26) de indivíduos portadores de anemia, sendo 80,77% (n=21) de gravidade leve. Houve predomínio da anemia normocrômica (92,31%, n=24) e normocítica (73,07%, n=19). Já em relação às hemoglobinopatias 9,37% (n=18) dos indivíduos apresentaram hemoglobinas variantes confirmadas por cromatografia líquida de alta eficiência, observando-se a presença de heterozigose para Hb AS em 6,77% (n=13) e para Hb AC em 2,60% (n=5). Os resultados sugerem a existência de precárias condições socioeconômicas nas comunidades quilombolas do norte do Espírito Santo e indicam a necessidade de se implementar medidas de saúde pública visando reduzir, prevenir e tratar as parasitoses intestinais. A prevalência considerável de hemoglobinas variantes na região e o desconhecimento sobre esse assunto demonstram a importância de capacitar profissionais de saúde para atender portadores de hemoglobinopatias, principalmente atuando no aconselhamento genético.