Made available in DSpace on 2015-10-06T13:03:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-08-21. Added 1 bitstream(s) on 2015-10-06T13:18:20Z : No. of bitstreams: 1 000848977.pdf: 1255909 bytes, checksum: e72eb452aeeef227b5ad181b4d572e4f (MD5) / Leishmaniasis are protozoan zoonotic diseases transmitted in the Americas by female sandflies of the genus Lutzomyia infected by Leishmania infantum chagasi during blood feeding. Although dogs are well established as the main reservoirs for the disease in urban areas, various reports of cats naturally infected worldwide may indicate an important role of this species in the disease cycle. Since the detection of circulating antibodies in infected cats is difficult, and infected cats in endemic areas are reportedly less likely to develop clinical signs when compared to dogs, this study aimed to evaluate cats living in endemic area by means of parasitological and serological (ELISA and IFAT), real time PCR and Montenegro skin test (MST), in order to use the later test to identify infected cats that did not develop antibody titers or clinical signs of the disease. For this purpose, 96 adult cats, regardless of sex, symptomatic or asymptomatic, from Araçatuba, São Paulo, were evaluated. Considering the results of qPCR and/or parasitological examination, the prevalence of infection in the evaluated population was 55.21% (53/96). Of the infected cats, 58.49% (31/53) were asymptomatic, 62.26% (33/53) females and 41.51% (22/53) aged between 1 and 3 years (p = 0.0002). Most of the infected cats had low antibody titers (37/53, 69.81%) and showed no clinical alterations (24/37, 64.86%). Only two (2.08%) were seroreactive by IFAT with titers of antibodies equal to 1:40. All 96 cats showed negative to MST with leishmanin of L. infantum chagasi (4.107 parasites/mL). Of these, 11 cats were selected and just one was positive to MST with leishmanin of L. (L.) amazonensis (107 parasites/mL). These findings indicate that qPCR demonstrated efficacy and should be used for visceral leishmaniasis diagnosis in cats and the MST, in the conditions in which it was tested, does not constitute a tool for identifying cats infected by L. infantum chagasi

Orientadora: Mary Marcondes / Banca: Raimundo Souza Lopes / Banca: Vera Lúcia Fonseca de Camargo Neves / Resumo: A leishmaniose visceral pode ser incluída como uma das causas de miopatia inflamatória em cães, entretanto, pouco se sabe sobre a patogênese da doença no sistema muscular, sendo incriminada muitas vezes apenas à natureza catabólica da enfermidade. O objetivo deste estudo foi avaliar, por meio de imunoistoquímica, a presença de formas amastigotas de Leishmania sp, linfócitos T (CD3+), macrófagos e IgG nos músculos tríceps braquial, extensor carpo radial, bíceps femoral e gastrocnêmio de 23 cães naturalmente acometidos por leishmaniose visceral. Dentre os 92 músculos avaliados,11 (12%) apresentaram marcação antigênica para formas amastigotas de Leishmania sp, 35 (38,1%) para linfócitos T (CD3+), 29 (31,5%) para macrófagos e 14 (12%) para IgG. Os resultados obtidos permitiram concluir que em cães com leishmaniose visceral apresentam imunomarcação para formas amastigotas de Leishmania sp., linfócitos T CD3+, macrófagos e IgG, sugerindo a participação direta do parasito e de uma resposta imune celular e humoral na fisiopatogenia da lesão muscular. / Abstract: Visceral leishmaniasis may be included as a cause of inflammatory myophathy in dogs, however, little is known about the pathogenesis of the disease in the muscular system, which is frequently associated with the catabolic nature of the illness. The purpose of this study was investigate, through immunohistochemistry, the presence of amastigote forms of Leishmania sp, T lymphocytes (CD3+), macrophages and IgG in the muscle triceps brachial, extensor carpi radialis, biceps femoris and gastrocnemius of 23 dogs with visceral leishmaniasis. Among 92 evaluated muscles, 11 (12%) presented antigenic marking for amastigote forms of Leishmania sp., 35 (38,1%) for T lymphocites (CD3+), 29 (31,5%) for macrophages and 14 (12%) for IgG. The results of the present experiment led to the conclusion that in dogs with visceral leishmaniasis there may be a straight participation of the parasite and of cellular and humoral immune response in the ethiopatogeny of the muscular injury. / Mestre

The aim of the thesis is focused on the verification of the detection of rut using pedometres devices fasten on the cattle's limb counting the amount of steps made. According the amount of steps it's decided if the animal is or is not in the estral phase and whether or not proper to insemination

As pesquisas em nutrição de frangos de corte estão em busca de ajustes que forneçam as aves os nutrientes necessários para um ótimo desempenho do sistema imune para que isto reflita em melhor desempenho produtivo. Neste contexto a utilização de microminerais orgânicos vem ganhando força e se mostrando uma alternativa para aumentar a produção. O presente estudo teve como objetivo avaliar os efeitos de 3 fontes e 2 níveis de selênio sobre o desempenho e a imunidade humoral de frangos de corte. Foram utilizados 1440 pintos de um dia, machos, criados até os 42 dias. O delineamento experimental foi inteiramente casualizado com 6 dietas experimentais (A: 0,15 mg/kg Se inorgânico; B: 0,15 mg/kg Se orgânico; C: 0,15 mg/kg Se inorg.+orgânico; D: 0,45 mg/kg Se inorgânico; E: 0,45 mg/kg Se orgânico; F: 0,45 mg/kg Se inorg.+orgânico) e 6 repetições com 40 aves cada. Foi utilizado um arranjo fatorial 3x2 e os dados obtidos foram analisados pelo PROC GLM do SAS. Quanto ao desempenho considerando o período total de criação houve efeito do nível de Se sobre o ganho de peso (GP) e ganho médio diário (GMD), houve interação entre fonte e nível para a conversão alimentar. Quanto a imunidade, a variação dos níveis e fontes de Se não demonstraram efeito sobre os parâmetros avaliados neste trabalho. Foi possível concluir que o nível de inclusão de Se na dieta interfere no ganho de peso médio, ganho médio diário de peso e no peso médio, sendo que a maior inclusão resultou em maior ganho. A interação entre fonte e nível de Se pode alterar uma das variáveis mais importantes de uma produção que é a conversão alimentar. / The research in nutrition of broiler chickens is in search of adjustments that supply to the birds the necessary nutrients an excellent performance of the immune system so that this reflects in better productive performance. In this context the use of organic minerals comes gaining force and if showing an alternative to increase the production. The present study it had as objective to evaluate the effect of 3 sources and 2 levels of selenium on the performance and the humoral immunity of broiler chickens. 1440 young chickens of one day, males had been used, created until the 42 days. The assignment was completely randomized, with 6 experimental diets (A: 0,15 mg/kg inorganic; B: 0,15 mg/kg organic; C: 0,15 mg/kg inorg.+organic; D: 0,45 mg/kg inorganic; E: 0,45 mg/kg organic; F: 0,45 mg/kg inorg.+organic) and 6 repetitions with 40 birds each. 3x2 was used an factorial arrangement and the gotten data had been analyzed by PROC GLM of SAS. The performance considering the total period (42d) had effect of the level of on the weight gain (GP) and average daily gain (GMD), it had interaction between source and level it feed conversion ratio. About the immunity, the variation of the levels and sources had not demonstrated effect on the parameters evaluated in this work. It was possible to conclude that the level of Se in the diet intervenes with the weight gain, average daily gain and in the final weight. The interaction between source and level of Se can modify the feed conversion ratio.

Rodent-borne hantaviruses (family Bunyaviridae) cause two distinct human infections; hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is a common viral zoonosis, characterized by fever, renal dysfunction and hemostatic imbalance. Four HFRS-associated hantaviruses have been described: Hantaan virus and Seoul virus mainly found in Asia, Dobrava virus, encountered in the Balkan region and Puumala virus (PUU), causing mild HFRS (nephropathia epidemica; NE) in Europe. HPS, recently discovered in the Americas, involves adult respiratory distress syndrome with a high mortality rate and is caused by Sin Nombre virus. Hantaviruses are enveloped and carry a RNA genome which encodes a polymerase, two glycoproteins and a nucleocapsid protein. The latter elicits a strong humoral immune response in infected patients. The clinical diagnosis of hantavirus infections has until recently relied on serological confirmation by immunofluorescense assay (IFA) and enzyme-linked immunosorbent assay (ELISA) using cell culture derived viral antigens. Due to the hazardous nature of hantaviruses and variable virus yield in cell culture we aimed at using recombinant hantavirus proteins for serological purposes. We expressed PUU N in E. coli (PUU rN) and found that high levels of IgM to this protein could be detected at onset of NE. This indicated that it was useful as the sole antigen for serodiagnosis. Our finding was confirmed by comparing IFA and PUU rN ELISA using 618 sera collected at the regional diagnostic laboratory. Full-length PUU rN is difficult to purify due to aggregation to E. coli remnants. We therefore located the important domain for the humoral immune response by utilizing truncated PUU rN proteins to its amino-terminal region (amino acid 7-94). Amino acid 1-117 of N of the five major human hantavirus pathogens were produced in E. coli. Serological assays based on them could detect IgM and IgG serum responses in 380 HFRS and HPS patients from Sweden, Finland, Slovenia, China, Korea and the USA with high sensitivity. In an epidemiological investigation of hantavirus serum responses in European Russia we unexpectedly found antibody responses to the hantaviruses found in east Asia and the Balkan region in 1.5 %, speaking in favour for the presence of such virus in this region. The degree of cross reactivity within the hantavirus genus was adressed by following the serum responses in NE patients. We found an increase of cross reactivity during the maturation of the immune response from onset of disease up to three years by comparing the IgG reactivity towards the hantavirus aminoterminal rN proteins. The first human isolate of the causative agent of NE in Scandinavia was recovered in cell culture from phytohemagglutinin stimulated leukocytes. Serological analysis revealed that this virus belongs to the PUU hantavirus serotype, distinct from the rodent prototype PUU Sotkamo. The human PUU Umeå is unique but genetically similar to rodent isolates from northern Sweden. / digitalisering@umu.se

Oncolytic viruses (OVs) are novel biological agents that selectively infect and kill malignant cells. OVs can also generate anti-cancer immunity. Our lab exploited this phenomenon and developed an in vitro vaccine with infected leukemia cells with oncolytic virus vaccine – and named immunotherapy by leukemia-oncolytic virus (iLOV) – that provided in vivo protection in a murine model for acute lymphoblastic leukemia. This work further characterizes iLOV biology and the interaction of its immune responses. An in vitro immune response assay was optimized to detect and quantify the in vivo anti-leukemia immunity generated by iLOV. Anti-viral immunity is an obstacle for OV therapy. Although iLOV created anti-viral antibodies towards itself, these neutralizing antibodies did not hinder the vaccine’s ability to initiate complement or dendritic cell activation. We envision personalized versions of iLOV for leukemia patients in remission to prevent the possibility of relapse. This work highlights new advantages for infected cell vaccines and supports the progress of iLOV toward clinical testing.

My dissertation examines late medieval literature through the lens of medical history, especially humoral psychology. Although the humors are still of interest to the history of medicine, they are often overlooked in current literary criticism. My project examines how the humors influenced representations of bodies in medieval literary texts (St. Erkenwald, Chaucer's Franklin's Tale, Richard Coer de Lyon, and Marie de France's Yonec). In chapters exploring the connection between the humors and religious devotion, marriage, cannibalism, and shape-shifting, I show that humoral psychology was not just a medical theory known to medieval medical practitioners, but also a deeply influential cosmology for the literary representation of bodies and emotions. I approach this project from two angles, using a methodology that relies on textual analysis and cultural contextualization. My work also aligns itself with scholars who have explored early modern works through the lens of historical phenomenology (Smith, Paster, Floyd-Wilson, Rowe). The project moreover encourages and contributes to the dialogue between the humanities and sciences in general and literature and medicine more specifically, as it makes connections to medical theories post-Descartes (Damasio) and to current scholarship regarding non-Western medical practices (Horden; Hsu) that discuss debates about balancing emotions and locating those emotions within the physical body. My project thus provides an analytical approach for interpreting medieval literature via medical models while also showing what the medieval period can contribute to the ongoing work of assessing the role of emotions in the past and its continued resonance in current medical debates.

abstract: Elucidation of Antigen-Antibody (Ag-Ab) interactions is critical to the understanding of humoral immune responses to pathogenic infection. B cells are crucial components of the immune system that generate highly specific antibodies, such as IgG, towards epitopes on antigens. Serum IgG molecules carry specific molecular recognition information concerning the antigens that initiated their production. If one could read it, this information can be used to predict B cell epitopes on target antigens in order to design effective epitope driven vaccines, therapies and serological assays. Immunosignature technology captures the specific information content of serum IgG from infected and uninfected individuals on high density microarrays containing ~105 nearly random peptide sequences. Although the sequences of the peptides are chosen to evenly cover amino acid sequence space, the pattern of serum IgG binding to the array contains a consistent signature associated with each specific disease (e.g., Valley fever, influenza) among many individuals. Here, the disease specific but agnostic behavior of the technology has been explored by profiling molecular recognition information for five pathogens causing life threatening infectious diseases (e.g. DENV, WNV, HCV, HBV, and T.cruzi). This was done by models developed using a machine learning algorithm to model the sequence dependence of the humoral immune responses as measured by the peptide arrays. It was shown that the disease specific binding information could be accurately related to the peptide sequences used on the array by the machine learning (ML) models. Importantly, it was demonstrated that the ML models could identify or predict known linear epitopes on antigens of the four viruses. Moreover, the models identified potential novel linear epitopes on antigens of the four viruses (each has 4-10 proteins in the proteome) and of T.cruzi (a eukaryotic parasite which has over 12,000 proteins in its proteome). Finally, the predicted epitopes were tested in serum IgG binding assays such as ELISAs. Unfortunately, the assay results were inconsistent due to problems with peptide/surface interactions. In a separate study for the development of antibody recruiting molecules (ARMs) to combat microbial infections, 10 peptides from the high density peptide arrays were tested in IgG binding assays using sera of healthy individuals to find a set of antibody binding termini (ABT, a ligand that binds to a variable region of the IgG). It was concluded that one peptide (peptide 7) may be used as a potential ABT. Overall, these findings demonstrate the applications of the immunosignature technology ranging from developing tools to predict linear epitopes on pathogens of small to large proteomes to the identification of an ABT for ARMs. / Dissertation/Thesis / Doctoral Dissertation Biochemistry 2020

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23100号 / 医博第4727号 / 新制||医||1050(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 河本 宏, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background: Throughout human history infectious agents such as viruses have been one of the biggest threats to public health. One example of infectious agents that can cause severe malignant conditions in humans is the Epstein-Barr virus (EBV). This virus has been researched for decades but still a lot of its potential malignant functions remain to be elucidated. Autoimmunity, and especially multiple sclerosis (MS), has been strongly associated to EBV infection for a long time but the exact mechanisms behind this relationship are still largely unknown. Aim: The main aim of this study was to investigate the evidence connecting an EBV-specific dysregulated immune response to MS. Methods: This paper is written as a systematic review examining the latest science within the studied field. PubMed was searched for articles published between 2010-2020. Results: In total 15 studies were reviewed. Five out of seven studies found an altered antibody response towards EBV in patients with MS, while one demonstrated somewhat mixed results and one could not support such a pattern. Seven out of eight studies found an altered T cell response towards EBV in MS patients, while one could only support such a trend. Conclusions: This review confirms that there is strong evidence for a dysregulated EBV-specific immune response in MS patients. Evidence for a causal relationship between the failure to control a reactivated EBV infection and the progression of disease is suggestive, but this needs to be confirmed by further studies.