HIV-associated sensory neuropathy (HIV-SN) is one of the most common neurological problems of HIV. It is frequently painful and reduces quality of life. HIV-SN can be caused both by HIV itself and by exposure to neurotoxic antiretrovirals such as stavudine. The South African Department of Health now recommends use of tenofovir in place of stavudine as first line treatment. However many people remain on stavudine and or live with the side effects. Stavudine is still prescribed in many other resource-poor countries. This thesis presents the first systematic study of clinical and genetic risk factors for the development of symptomatic HIV-SN in Black Southern Africans. I recruited 404 Black HIV-positive Africans from the Virology Clinic of the Charlotte Maxeke Academic Hospital, Johannesburg and assessed HIV-SN using the AIDS Clinical Trials Group (ACTG) Brief Peripheral Neuropathy Screen. HIV-SN was defined as present if the patient had both symptoms and signs of peripheral neuropathy. If present, the distribution and intensity of symptoms were recorded. Of those exposed to stavudine, 57% (226/395) had HIV-SN. Pain was the most common symptom and was experienced by 74% (172/226). Of these, 76% (128/172) reported their pain as moderate to severe. As in previous studies, increasing age and height were independently associated with risk of HIV-SN. However nadir and current CD4 T-cell counts and sex were not associated with SN. Patients donated blood for DNA extraction and single nucleotide polymorphisms (SNPs) were selected from the literature and genotyped using Illumina Golden GateTM technology. 342 individuals were assessed for genetic associations with HIV-SN and a subset of 159 positive for HIV-SN were assessed for associations with painful HIV-SN. I completed four genetic analyses: SNPs and haplotypes from TNF and adjacent genes from the major histocompatability complex on chromosome six were assessed for association with HIV-SN. I found no association with TNF-1031, even though this had associated with risk of HIV-SN in Caucasian, Chinese and Malay cohorts. Novel associations were identified between HIV-SN protection and 5 other SNPs (BAT1 rs3130059, rs2523504; ATP6V1G2 rs2071594; NFKBIL1 rs2071592, rs2071591). Associations were also found with haplotypes: FV15-23 weakly associated with risk and FV30-31 associated with protection against HIV-SN in this cohort. Analysis of 8 SNPs not previously assessed produced two novel associations with LTA SNPs (rs1041981, rs909253), where the minor alleles conferred protection against HIV-SN. Analysis of linkage disequilibrium (LD) suggests that there is linkage disequilibrium within the TNF block, that it differs between ethnicities and that TNF-1031 is unlikely to be a causative SNP for risk of HIV-SN. SNPs from other cytokines and chemokines implicated in the pathogenesis of HIVSN and the associated pain were assessed in Chapter 5. The major allele of the antiinflammatory gene IL4 (rs2243250) associated with risk of HIV-SN. This allele has been associated with higher CD4 T-cell counts, so I have proposed a role for high IL- 4 in early stage HIV-SN. A 3-SNP haplotype of IL10 associated with protection against HIV-SN whilst another IL10 haplotype showed a trend for risk of painful HIVSN. These data and the involvement of TNF haplotype (Chapter 4) suggest an inflammatory etiology for HIV-SN. Polymorphisms of UCP2 (rs659366) and UCP3 (rs1800849) have previously associated with risk of diabetic neuropathy. These SNPs encode uncoupling proteins 2 and 3 which regulate reactive oxygen species and may affect development of neuropathy via the effects of oxidative stress and mitochondrial dysfunction. Alleles of these SNPs did not associate with HIV-SN in this cohort. Patterns of linkage disequilibrium may differ between the two ethnicities or UCP2 and UCP3 may associate with a mechanism particular to diabetic neuropathy. I also assessed a ‘pain protective haplotype’ and SNPs of GCH1 which have been associated with decreased pain intensity in radicular pain following lumbar discectomy. Associations of the 3-SNP ‘pain protective’ haplotype (rs10483639*C, rs3783641*A and rs8007267*T) and a 6-SNP haplotype containing this motif with protection against pain were significant but dependent on age, sex and CD4 T-cell count. Association of another 3-SNP haplotype (rs10483639*G, rs3783641*T and rs8007267*C) with increased risk of pain in HIV-SN was also not independent of age, sex and CD4 T-cell count. The weaker associations here compared to Caucasian cohorts may be a result of differing LD between ethnicities or demonstrate different pain mechanisms between HIV-SN and radicular pain following lumbar discectomy. My results highlight the prevalence of HIV-SN and frequency of pain in this Southern African cohort. The genetic studies identify a likely inflammatory component and identify genes worthy of further investigation both in HIV-SN and the associated pain.

No description available.

Thesis (PH.D.)--University of Illinois, 1919. / Thesis note on verso of t.-p. "Contributions from the Zoological laboratory of the University of Illinois under the direction of Henry B. Ward, no. 171." Bibliography: p. 68-70. Also available in print.

Thesis (Ph. D.)--University of Illinois, 1919. / Thesis note on verso of t.p. "Contributions from the Zoological laboratory of the University of Illinois under the direction of Henry B. Ward, no. 171." Bibliography: p. 68-70.

Thesis (Ph. D.)--Catholic University of America.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

The sensory organs in the transverse grooves of the dorsal labium of the water bug, Cenocorixa bifida, (Hungerford) (Hemiptera) were studied with the electron microscope. It was found that each sense organ is supplied by a single, bipolar neuron, which, together with its sheath cell, forms a sensory unit. The dendrite of the neuron is modified into various structures along its length; it has a root system, two basal bodies, and an axial filament complex. These structures are characteristic of many mechanoreceptors and chemoreceptors in insects. The sheath cell surrounding the dendrite possesses many characteristic fine structures, such as the desmosomes and the microtubules. According to their ultrastructure and their location near the mouth opening, it is most likely that these sensory organs are chemoreceptors. The significance of the presence of the ciliary regions in the dendrites of these organs is suggested to be related to the regeneration of the distal portion of the dendrite which may be torn off during the process of moulting. The axial filament complex may also serve as an internal support in the dendrite. / Science, Faculty of / Zoology, Department of / Graduate

No description available.

No description available.

The role of the fish pineal organ has been studied using the goldfish Carassius auratus and the Pacific salmon Oncorhynchus tshawytscha. To this end, the effects of pinealectomy in goldfish on various behavioural responses, endocrine systems, and the reproductive system were studied. The pineal organs and the retinal tissue from mature and immature salmon were examined by thin-layer chromatography and fluorometry to determine if melatonin, a mammalian hormone, is present in the fishes. Goldfish were injected with melatonin to see if the effect of exogenous melatonin was opposite to that of pinealectomy. Pinealectomized goldfish lost the photo-negative response seen in normal goldfish. Blinding had the same effect on phototaxis as pinealectomy and a combination of the two had the same effect as blinding or pinealectomy alone. It was concluded that the normal phototactic response depended upon both the pineal organ and the eyes. Pinealectomy, blinding, or both was followed by a marked increase in swimming activity. Although this increase was correlated with a decrease in the whole brain serotonin level, a causal relationship was not established between the two. Further, pinealectomy alone produced no significant changes in whole brain serotonin level. Melatonin was localized within the pineal organ of salmon and its concentration in this tissue was analyzed. The pineal melatonin store varied during the reproductive cycle and was found in lower concentrations in the pineal organs of mature salmon. Stored melatonin could not be found in the retinal tissue despite evidence for an active tryptophane metabolism in this tissue. Injection of melatonin into goldfish inhibited the increase in gonad size under long photoperiod; this was accompanied by larger gonadotrophs in the melatonin injected fish. Removal of the pineal organ from goldfish held under short photoperiod caused an increase in gonad size similar to that seen in untreated goldfish exposed to long photoperiod. The effect of pinealectomy on the gonads was limited to that season during which the gonads could be stimulated by increasing day length. At other times of the year, neither photoperiod nor pinealectomy produced any significant effect on the gonad size. From this it was concluded that the pineal gland of the goldfish is related to the reproductive cycle and that its function depends upon photoperiod and the production of melatonin. Pinealectomy had no effect on the interrenal tissue, thyroid tissue, plasma osmotic concentration, or plasma levels of Na⁺, Cl⁻, or Ca⁺⁺, indicating that the effects of this operation are specific for the reproductive system. The data obtained from these studies support the hypothesis that the pineal organ of fishes serves a secretory as well as a sensory function. Further, the functional aspects of the mammalian and fish pineal organs are discussed and it is concluded that the role of the pineal organ is similar in the two groups; that is, the pineal organ of mammals and fish is involved in the timing of reproductive events. / Science, Faculty of / Zoology, Department of / Graduate