Thesis (Ph. D.)--University of Wisconsin--Madison, 1938. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references: leaves [100-102].

University of Macau / Institute of Chinese Medical Sciences

published_or_final_version / Community Medicine / Master / Master of Public Health

HIV-associated sensory neuropathy (HIV-SN) is a common complication associated with human immunodeficiency virus (HIV)-infection. A common symptom of HIV-SN is pain. Variation at specific loci within certain candidate genes has been suggested to alter susceptibility to developing HIV-SN as well as the susceptibility to developing pain and the intensity of the pain experienced. Few studies, however, have been conducted in individuals of black African ancestry. The aim of the current research was to conduct an in-depth study, in a black Southern African population, of genes previously associated with susceptibility to developing HIV-SN (TNFA and surrounding genes and IL12B) and variations in pain susceptibility and intensity (GCH1, KCNS1, IL1B, IL6, CCL2 and CCR2) in other neuropathic pain states. Single nucleotide polymorphisms (SNPs) identified in the literature were supplemented with population appropriate tagSNPs to improve assessment of the genes in an African population. Genotyping of previously collected deoxyribonucleic acid (DNA) samples was carried out using a GoldenGate assay with VeraCode microbeads and data were read on an Illumina BeadXpress Reader. Data were statistically analysed to assess the association of the genetic variants with susceptibility to developing HIV-SN and pain and variability of pain intensity in those patients with painful HIV-SN. Although some SNPs and haplotypes in the genes investigated associated with HIV-SN susceptibility (TNFA region), pain susceptibility (TNFA region, IL12B, KCNS1, IL6 and CCR2) or pain intensity (TNFA region, KCNS1, IL1B and IL6), none of the results were consistent with that which has been found in previous studies in non-African populations. Reasons for this may be that associations are population-specific or model-specific. Limitations of the study included the use of a relatively small sample, the method of sampling (convenience sampling), genotyping failure and tagging inefficiency in some instances, and the fact that there is no Southern African population dataset to use for tagSNP selection. My findings emphasise the importance of conducting genetic association studies in separate ethnic groups.

The purpose of the study was to investigate a possible connection between alpha-l-antitrypsin (A1AT) deficiency and familial epilepsy and mental retardation of possible congenital or genetic origin.The individuals were genotyped by using a two dimensional cross-electrophoretic procedure. The electrophoretic procedure involved isoelectric focusing on an acid-starch gel followed by immunoelectrophoresis. The control and experimental groups were then statistically compared to population norms by using the chi-square test. The 0.05 level of significance was established as the critical probability level for the nonacceptance of a connection.ResultsOf the 49 individuals in the control group, 46 had, a protease inhibitor (Pi) genotype of PiMM 1 , and there was 1 each of the Pi MF, Pi MS, and Pi Mz genotypes. Of the 50individuals in the familial epilepsy experimental group, 43 were genotyped as PiMM, 2 as PiMS, and 5 as PIMF. Of the 16 individuals in the mental retardation experimental group, 14 were genotyped as PiMM, 1 as PiMS, and 1 as PiMF.The probability of reoccurrence for the various groups were: control - 0.3 to 0.5; familial epilepsy - 0.3 to 0.5; and mental retardation - 0.7 to 0.8.Conclusions1. The applicability of starch gel electrophoresis in a clinical setting is questionable because of cost, length of time required, and difficulty in handling.2. The control group demonstrated no statistical variation in the 1AT frequency from general population norms.3. The familial epilepsy experimental group showed no statistical evidence linking it to abnormal A1AT genotypes.4. The mental retardation experimental group demonstrated no statistical evidence linking it to abnormal A.1 AT genotypes.

Thesis (Ph.D.)--Virginia Commonwealth University, 2008. / Prepared for: Dept. of Anatomy and Neurobiology. Bibliography: leaves 164-205. Also available online via the Internet.

Methylmercury (MeHg) is a neurotoxic global pollutant that accumulates at high levels in predatory fish and marine mammals. The dietary intake of these animals is the main source of MeHg exposure in humans. At high levels, MeHg is known to damage the sensory and motor systems in both adults and children. Due to the complexity and inaccessibility of the central nervous system (CNS), early dysfunction is difficult to detect. Biochemical markers in the CNS have been used to identify MeHg neurotoxicity in animal models. Analogues of these biochemical targets are also present in peripheral blood tissue and may reflect early CNS dysfunction in human populations. The proposed peripheral biomarkers include (1) lymphocyte muscarinic acetylcholine (mACh) receptor, (2) serum cholinesterase (ChE) and (3) platelet monoamine oxidase (MAO). This thesis evaluates the effects of mercury (Hg) compounds on these CNS and peripheral biochemical markers in laboratory and epidemiological studies. In vitro studies showed that inorganic Hg (HgCl2) and MeHg inhibited mACh receptor binding in human, rat, and mouse brain tissue. Additionally, studies demonstrated that a low-level gestational exposure to MeHg reduced MAO activity in the developing embryo and in adult female offspring. Combined, these studies provide a framework for the assessment of biochemical targets of Hg compounds in humans. A cross sectional study was conducted to evaluate the association between peripheral biochemical markers and MeHg exposure in fish-eating adults (n=129) from Lac St-Pierre, Quebec. Blood-Hg concentrations were used as a marker of exposure and ranged from 0.2 to 17.0 mug/L. Multiple linear regression analysis demonstrated that both blood-Hg (p=0.011) and heavy smoking (p=0.001) were associated with reduced platelet-MAO activity. However, neither lymphocyte mACh receptor nor serum ChE was related to blood-Hg. These results suggest that exposure to MeHg may result in reduced plat

520 L $$aIn the CNS, myelination of axons is essential for the rapid conduction of impulses down the nerve. In demyelinated or failing axons however, conduction is less efficient and requires more energy. The principal function of mitochondria is to provide energy for the axon but in doing so they generate most of the intra-axonal reactive oxygen species (ROS). Therefore and increased energy requirement will promote an increased production of ROS which could lead to significant damage to essential DNA, proteins and lipids and could eventually damage the axon. This thesis investigates the mitochondrial involvement in axonal pathology in the CNS diseases, multiple sclerosis (MS), autosomal dominant optic atrophy (ADOA) and tosomal dominant optic atrophy with cataract (ADOAC).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 219-228).

Thesis (Master's Diploma(Technology (Medical Technology))-- Cape Technikon, 1997 / Meningitis in children is a common and serious disease. Bacterial and tuberculous meningitis often lead to neurological complications. A sensitive marker to predict brain damage in children with meningitis could be of great importance. Frithz F et aI, 1982 suggested that increased adenylate kinase values could indeed be used as a marker for brain damage. Adenylate kinase (AK) is an enzyme present in brain tissue. Low concentrations are present in normal cerebrospinal fluid (CSF) « 1 uti). Increased concentrations were found in cases of ischemic brain damage (Frithz et aI, 1982), malignant brain tumours (Ronquist G et aI, 1977) and bacterial meningitis. As AK has a low molecular weight (22,00 Daltons), in comparison to other kinases (40,000 Daltons) it is one of the first enzymes that can be detected in the CSF after brain damage and it can thus be used as a reliable marker for brain cell damage. The aim of this study was to quantify the AK values in CSF of children with bacterial and tuberculous meningitis and to evaluate their use to predict the neurological outcome in children with bacterial and tuberculous meningitis. Eighty eight children with tuberculous meningitis (TBM) and thirty three children with bacterial meningitis were included in the study. Sixty children with suspected meningitis but who were later diagnosed with urinary tract infections, gasto-enteritis, bronchitis, febrile convulsions or other non-neurological infections were used as controls. The results showed raised AK values in the CSF of children with bacterial- and TB meningitis. There was a statistically significant difference of AK values between stage III and II TBM AK values in patients at week 1 after diagnosis (p=0,03). There was also a statistically significant correlation between CSF AK values and lactate concentrations (P=0,001) which reflected hypoxic brain metabolism. Although AK values did not always correlate directly with the patients’ clinical outcome, there is proof that increased AK values in CSF can be used to predict neurological outcome.