Thesis (M.S.)--University of Michigan, Ann Arbor, 1984. / Typescript (photocopy). Includes bibliographical references (leaves 67-77). Also issued in print.

Thesis (M.S.)--University of Michigan, Ann Arbor, 1984. / Typescript (photocopy). eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 67-77).

Thesis (doctoral)--Lunds Universitet, 1994. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Lunds Universitet, 1994. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Charles University in Prague Faculty of Pharmacy in HradecKrlov Department of Biological and Medical Sciences Evaluation of endoglin and P-selectin expression and co-expression in aortas of apoE-deficient mice Diploma thesis MonikaBrlicov Supervisor: Mgr.JanaRathousk Background: We observed the expression and the reciprocal co-expression of endoglin (receptor III for TGF- cytokine) and P-selectin (adhesion molecule and marker of endothelial dysfunction) in ascending aortas of apoE-deficient mice which were fed by standard diet for rodents and Western type diet (high-cholesterol diet) for achieving of different phases of the atherosclerotic process. The changes of total cholesterol levels in mice after administration of both types of diets were also evaluated. Methods: The modified strain C57BL/6J of mice with a deficiency of apolipoprotein E, which is prone to aterogenesis was used for this diploma thesis. Mice were divided into three groups. The first group was fed by standard diet (so-called "chow" diet) for a period of two months and the second two groups were fed by Western type diet for a period of two and four months. The levels of total cholesterol in the blood were biochemically determinated and then we statistically evaluated this levels in all groups. Immunohistochemical...

Thesis advisor: Kenneth I. Kersch / There is a widespread belief among Americans that the nation’s political system suffers from dysfunction. It is, therefore, worth asking whether the Constitution has been complicit in contributing to the perceived political dysfunction. Does the United States, in effect, suffer from constitutional dysfunction? I conclude that political and societal developments subsequent to the Founding have retooled and repurposed American governing institutions, rendering their function antithetical to the original design of the Constitution. The long-term and collective effects of these changes may contribute to contemporary constitutional dysfunction. At the outset, I discuss general purposes and functions of constitutions. By describing constitutional functionality, we can better grasp the nature of when constitutions work and when they fail to function. As such, we will be best equipped to not only design a metric by which to measure constitutional dysfunction, but to apply this rubric to the American regime. “Chapter Two” will detail the framing of the American Constitution and explore the principles undergirding its creation. “Chapter Three” will cover the so-called “unfounding,” the processes and developments which have changed the character of governing institutions. “Chapter Four” will focus on proposed solutions which may be both misguided and potentially problematic. Finally, “Chapter Five” will consider the best approach to addressing American constitutional dysfunction. / Thesis (MA) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Political Science.

O objetivo deste trabalho foi determinar um intervalo de pressão capaz de estimular resposta dolorosa em pacientes com sinais e sintomas compatíveis com Disfunção Temporomandibular (DTM), quando comparado a um grupo controle. Para isso, foram selecionados 77 pacientes com sinais e sintomas de DTM de origem miogênica concomitante ou não com alguma patologia articular. Para o grupo controle, foram selecionados 75 indivíduos livres de qualquer queixa dolorosa compatível com DTM. Os indivíduos dos dois grupos foram palpados por um único examinador nos seguintes pontos: corpo do masséter, temporal anterior, temporal médio e temporal posterior. Os dados obtidos foram analisados estatisticamente num nível de significância de 5%. O grupo sintomático apresentou limiar de dor à pressão (LDP) significativamente menor em comparação ao grupo controle (p < 0,001). O masséter apresentou LDP significativamente menor, seguido pelo temporal anterior, médio e posterior (p < 0,001). O lado direito apresentou LDP significativamente menor que o lado esquerdo (p=0,033). Obteve-se uma correlação negativa significativa entre o LDP obtido e a Escala de Análise Visual (p < 0,001). Não foi encontrada correlação entre o LDP obtido e o tempo de experiência com a dor (p=0,310). Foi verificado que o intervalo de pressão mais confiável para o masséter foi de 1,01 - 1,5 kg/cm2, para o temporal anterior e médio foi de 1,51 - 2 kg/cm2 e para o temporal posterior foi de 2,01 - 3 kg/cm2. Os autores concluíram que a palpação mostrou ser um exame confiável para se detectar sensibilidade muscular em pacientes de DTM / The aim of this study was to determine a digital pressure interval able to elicit painful response in patients with signs and symptoms of Temporomandibular Disorders (TMD) when compared to a comparison group. Seventy-seven individuals with myogenic TMD comprised the symptomatic group, while seventy-five TMD symptom-free individuals were selected as controls. The pressure pain thresholds (PPT) were obtained with the aid of an algometer by pressuring the following muscles: masseter and anterior, medium and posterior temporalis. Values of sensitivity and specificity were determined for different pressure intervals. A lower PPT was found for all muscles in the symptomatic group (p < 0,001). The lowest PPT was found for the masseter muscle, followed by the anterior, medium and posterior temporalis. The left side has shown higher PPT than the right side (p < 0,05). A significant negative correlation was found between the PPT and the Visual Analogue Scale (p < 0,001). However, a significant correlation between the PPT and the time of pain experience was not found (p < 0,05). The authors concluded that, within the limitations of this study, the most appropriate pressure interval was 1,01 - 1,5 kg/cm2 for the masseter, 1,51 - 2 kg/cm2 for the anterior and medium temporalis, and 2,01 - 3 kg/cm2 for the posterior temporalis. Yet, according to the above figures, a standardized palpation can be considered a reliable technique in the examination of TMD patients

This work was undertaken to characterise the interaction of the leukocyterestricted integrin LFA-1 (CD1la/CD18) with its ligands. LFA-1 function is critical for an immune response and, for example, allows leukocyte binding and transmigration across the endothelium, antigen presentation and cytotoxic T lymphocyte-mediated killing. The ligands for LFA-1 are the Intercellular Adhesion Molecules (ICAMs), with ICAM-1, ICAM-2 and ICAM-3 being the best characterised. The binding sites on ICAM-1 and ICAM-3 for LFA-1 were investigated with the use of antibodies and mutated proteins. The following regions were found to have a role in binding LFA-1: the CFG face of ICAM-3 domain 1; domain 2 of ICAM-1; a residue in domain 1 of ICAM-1 that is mutated at high frequency in African populations and is associated with susceptibility to cerebral malaria. Binding of Mg2+ or Mn 2+ to the extracellular region of LFA-1 and intracellular signalling can both stimulate LFA-1 to adhere to ICAM-1, but by different processes. The former mechanism induces a high affinity form of LFA-1, which was shown to be achieved by an inter-domain movement involving the I domain of the LFA-1 a subunit. This is the first physical evidence for a conformational change occurring in an integrin upon activation. The mechanism by which intracellular signalling activates LFA-1 was demonstrated to involve calpaindependent clustering of LFA-1 in the membrane, thus increasing the avidity of LFA-1 for ICAM-1. Leukocyte Adhesion Deficiency-1 and Glanzmann's Thrombasthenia are genetic disorders in which mutations in the integrin genes result in absence of expression or expression of a non-functional integrin. The defects in function of leukocytes from a patient with clinical features of both disorders were studied. The results suggest that the patient has a novel form of integrin dysfunction in which integrins are expressed at normal levels, can be induced to bind their ligands by mechanisms which increase the affinity of interaction, but cannot be stimulated to bind ligand by intracellular signalling pathways.

The severity of cardiac dysfunction predicts mortality in septic patients. In this thesis, I have investigated the pathophysiology and the novel therapeutic strategy to attenuate cardiac dysfunction in experimental sepsis. I have developed a model of cardiac dysfunction caused by lipopolysaccharide (LPS)/peptidoglycan (PepG) co-administration or polymicrobial sepsis in young and old, male and female mice. There is good evidence that females tolerate sepsis better than males. Here, I have demonstrated for the first time that the cardiac dysfunction caused by sepsis was less pronounced in female than in male mice; this protection was associated with cardiac activation of a pro-survival pathway [Akt and endothelial nitric oxide synthase], and the decreased activation of a pro-inflammatory signalling pathway [nuclear factor (NF)-κB]. Patients with chronic kidney disease (CKD) requiring dialysis have a higher risk of sepsis and a 100-fold higher mortality. Activation of NF-κB is associated with sepsis-induced cardiac dysfunction and NF-κB is activated by IκB kinase (IKK). Here, I have shown that 5/6th nephrectomy for 8 weeks caused a small, but significant, cardiomyopathy, cardiac activation of NF-κB and expression of inducible nitric oxide synthase (iNOS). When subjected to LPS or polymicrobial sepsis, CKD mice exhibited exacerbation of cardiac dysfunction and cardiac activation of NF-κB and iNOS expression, which were attenuated by a specific IKK inhibitor (IKK 16). Thus, selective inhibition of IKK may represent a novel therapeutic approach for the sepsis-induced cardiac dysfunction in CKD patients. Activation of transient receptor potential vanilloid receptor type 1 (TRPV1) improves outcome in sepsis/endotoxaemia. The identity of the endogenous activators of TRPV1 and the role of the channel in the cardiac dysfunction caused by sepsis/endotoxaemia is unknown. Here, I have shown that activation of TRPV1 by 12-(S)-HpETE and 20-HETE (potent ligands of TRPV1) leads to the release of calcitonin gene-related peptide (downstream mediator of TRPV1 activation), which protects the heart against the cardiac dysfunction caused by LPS.

Autism Spectrum Disorders (ASD) are characterized by a triad of clinical features which include lack of social interaction and communication, behavioral stereotypes, and a range of cognitive deficits. The presence of motor deficits has often been observed in the children with autism who are described as being clumsy or awkward in their movements. There is, however, considerable ambiguity related to universality, severity and exact nature of these motor difficulties. The objective of this study was to assess the movement characteristics of children with ASD and to place their motor dysfunction in the context of their functional independence in the performance of daily living skills. Seventeen children diagnosed with Autism or PDD-NOS in the age range of 5-11 years were recruited and assessed using two standardized tests of motor function; the Bruininks-Oseretsky Test of Motor Proficiency - Second Edition (BOT-2; Bruininks 2005) and the Movement Assessment Battery for children (M ABC-2; Henderson, Sugden, & Barnett 2007) and a third assessment of functional independence in children WeeFIM (WeeFIM System, 1999). Most of the children showed movement characteristics that ranged from mild to severe impairment, though two children showed no motor difficulties. However, when compared, as a group, to age matched norms, it was noted that the motor skill performance of children with ASD was noticeably poorer. Marked impairments were observed in tasks that required manual dexterity, upper limb coordination, strength and agility. Children with ASD also showed greater functional disability compared to age-matched norms, however, their degree of motor dysfunction by itself did not correlate with their performance of daily living skills. This study provides invaluable insights into movement characteristics of children on the autism spectrum and highlights the need for including motor assessment as a routine investigation for children with autism. / text