Thesis (doctoral)--Karolinska Institutet, Stockholm, 1984. / Extra t.p. with thesis statement inserted. Bibliography: p. 30-40.

by Vernon Rowland and Robert Blumenthal ; Yvonne M. Homsy, writer-editor. / "First published as volume 12, no. 1, March 1974, of the Neurosciences Research Program bulletin." Includes index. / Bibliography: p. 154-187.

Structural changes in the frontal and temporal lobes and in subcortical white matter tracts often occur following closed head injury (CHI). In contrast to this well delineated structural pathology, the post-traumatic cognitively-related functional changes in these and other brain regions have not been adequately described. To characterize the long-term functional neuroanatomy of CHI, the present study compared regional cerebral blood flow (rCBF) patterns in 13 severely-injured, well-recovered, unmedicated patients to those from 13 well-matched healthy controls. rCBF was measured using oxygen-15 water intravenous bolus positron emission tomography (PET) while subjects performed the Wisconsin Card Sorting Test (WCST), an indicator of prefrontal lobe functioning that involves matching stimuli to a changing sorting principle based on external feedback, and a Cued Recall Memory Test (CRMT), which involves remembering semantically-related word pairs. The neuropsychological tasks were used to provoke specific neural systems believed to be important in task performance (the prefrontal cortex in the former, the hippocampus in the latter). Subjects also performed two specially designed sensorimotor control tasks to provide measures of baseline rCBF. Given the controversy regarding the statistical analysis of PET data, a two-pronged method was utilized: 1) Statistical Parametric Mapping, the state-of-the-art technique that examines rCBF throughout the entire brain, and 2) region of interest analysis, an anatomically-based method for examining rCBF in a limited set of brain regions. Between-group rCBF differences were tested in the four tasks separately and also in the two neuropsychological tasks after subtracting baseline rCBF (i.e., rCBF activation). To characterize the relationship between cerebral perfusion and behavior, correlations were performed between performance and rCBF activation (i.e., task-control) for each group separately, and between rCBF activation and an index of current neuropsychological functioning for the CHI patients. Analyses of each task separately revealed that, compared to controls, CHI patients showed lower rCBF in anterior cingulate cortex (ACC) and subcortical areas. Analyses of rCBF activation data revealed: 1) increases in left inferior frontal gyrus (including Broca's area) and left hippocampus of CHI patients relative to control subjects during the WCST, 2) a negative correlation between task performance and the right hippocampus during the WCST in CHI patients, and 3) correlations between the hippocampus and performance during the CRMT in the CHI patients that were in the opposite direction to those found in the control subjects. These neurofunctional changes are compatible with the structural and cognitive sequelae of CHI First, given a hypothesized role of the ACC in attentional processes, reduced rCBF in this region of CHI patients may relate to the persistent and often subtle difficulties in attention after CHI, whereas rCBF diminutions in subcortical regions may relate to diffuse damage to or deafferentation of subcortical regions in this CHI sample. Second, given similar (although slightly, but not significantly, poorer) performance on the WCST by the CHI patients, increased left prefrontal cortical activity may partially reflect behavioral compensation (e.g., subvocalization to aid memory during the task) and also physiological compensation for inefficiencies in other brain areas (e.g., subcortical regions). Finally, in light of the relatively poorer task performance of CHI patients (non-significant tendency in the WCST but highly significant in the CRMT), differences between the groups in the direction of the correlations between performance/cognition and hippocampal activation may suggest disorganization of hippocampal functioning in CHI patients. This exploratory and descriptive investigation identifies brain structures with post-traumatic changes that may be important to cognition. These results may provide evidence of both behavioral and neurophysiological compensation in patients with severe CHI. / Graduate

The Gilman's cyclic AMP binding assay was used to examine the possibility of adopting this method for adenylate cyclase determinations. Cyclic AMP determinations were not invalidated by the reagents used in the adenylate cyclase reaction. Cyclic AMP measured by the binding assay was directly proportional to adenylate cyclase activity. Although variability in recovery of cyclic AMP was obtained, it could be reduced by performing triplicate assays. Thus, the cyclic AMP binding assay, with some reservations, would appear applicable for measuring adenylate cyclase activity. Adenylate cyclase in rat brain was studied by using the cyclic AMP binding method for determination of product formed. Rat brain cortex was fractionated by the method of Whittaker. The highest adenylate cyclase activity was found in the fraction containing the highest acetylcholinesterase activity, and this fraction was shown by electronmicroscopic studies to be rich in synaptosomes. A modified sucrose gradient was used for isolating satisfactory synaptosomal fractions (the layer between 1.0 M and 1.1 M sucrose). Properties of synaptosomal adenylate cyclase were examined. The enzyme was dependent on the concentrations of ATP and Mg²⁺ or Mn²⁺ ion. The enzyme was stimulated by fluoride and inhibited by calcium ion. Synaptosomal adenylate cyclase was not sensitive to catecholamines or adenosine. No hormonal stimulation was obtained in the presence of GTP. In experiments where the effects of endogenous catecholamines were reduced by the addition of α and β adrenergic blocking agents or by prior treatment of the animals with reserpine, hormonal stimulation of adenylate cyclase in particulate preparations could not be demonstrated. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Preliminary observations of the restricted regionalization of the enzyme 2' ,3'-cyclic nucleotide-3’ -phosphohydrolase led to an investigation of the subcellular regionalization of this enzyme in cerebral white matter. Since bovine corpus callosum contained eighteen times as much enzyme activity as grey matter, an association of the enzyme with myelin was suggested. Subsequent fractionation of bovine cerebral white matter by sucrose density gradient according to the procedure of Autilio, Norton, and Terry for the purification of myelin (1), showed that greater than 60% of the total activity was associated with the myelin rich fractions. In order to fractionate cerebral white matter more thoroughly, a modified De Robertis fractionation procedure was utilized allowing for separation of nuclear, mitochondrial, and microsomal pellets by differential centrffugation (2). Phosphohydrolase activity was distributed in all fractions, and electron microscopy demonstrated the presence of myelin in all of these fractions. Subsequent fractionation of these primary fractions on a discontinuous sucrose density gradient, showed essentially all of the phosphohydrolase activity in the lightest fraction at the top of each gradient. This band was comprised primarily of myelin figures as verified by electron microscopy. These studies indicated that the enzyme was associated with myelin. The foregoing result was further supported by a study of the increase in enzyme activity during myelination in rats. Myelination is known to occur early in the life of the rat, being initiated a few days after birth, entering a rapid phase of onset at about 10 days and being essentially complete after 50 days (3). Cholesterol was shown to increase in a corresponding manner indicating that myelination was indeed proceeding. Further evidence that the enzyme is associated with myelin came from an investigation of mutant mice. Quaking mice have been shown to be deficient in myelin, containing, according to Bauman and co-workers (4), only 62% of the normal galactolipid levels. Since galactolipids are presently accepted markers for myelin, and since adult quaking mice had 50% of the control enzyme activity, in agreement with the published galactolipid values, it was thought not unlikely that the two phenomena were related. This result also inferred an association of the enzyme with myelin. In attempt to further uncover the physiological role of the 2’,3'-cyclic nucleotide-3'-phosphqhydrolase, investigations have been directed towards elucidation of the substrate specificity of the enzyme. Uridine and guanosine-2’,3'-cyclic phosphothioates, kindly donated by Dr. Fritz Eckstein of the Max Planck Institut für Experimentelle Medizin, were hydrolyzed at rates of l.4 and l4.3% that of adenosine-2’,3'-cyclic phosphate. Cyclic inositol phosphate, synthesized from inositol-2-phosphate in the presence of dicyclohexylcarbodi-imide and pyridine, and glucose-l,2-cyclic phosphate, synthesized from (formula omitted)-D-glucose-l-phosphate, in a similar manner, were not hydrolyzed td any measureable extent. Preliminary results also show that ribose cyclic phosphates are not hydrolyzed, indicating a requirement for a purine or pyrimidine ring in the substrate molecule. These results are discussed with respect to their possible physiological significance. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

No description available.

Miao Ji. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 159-165). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

by Kwok-Ping Ho. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1980. / Bibliography: leaves 111-118.

This thesis details our early efforts towards the discovery of polymeric and macromolecular platforms for the targeted delivery of sensors and actuators to specific cell types in the living brain tissue. Chapter 1 of this thesis discusses the small molecule tropane tag chosen as a homing ligand and the dopamine transporter (DAT) chosen as a cellular target, as well as the synthesis of new tropane-based molecular tags for evaluation in cultured human DAT (hDAT)-expressing cells and targeting in brain tissue. Chapter 2 discusses the results obtained from evaluation of the new tropane tags in hDAT-expressing and hNET-exressing cells, including early results from the first example of a DAT-specific voltage sensing dye. In Chapter 3, we discuss the principles governing molecular targeting of probes in the living brain tissue. Part I of Chapter 3 gives important background necessary for understanding some of the complexities involved in targeting chemical probes to specific sites in living brain tissue. Part II of Chapter 3 discusses early results obtained from targeting of our tropane tags in living brain tissue. We provide, perhaps, the first example of a binding-site barrier effect in healthy tissue and demonstrate successful delivery of a moderate-sized protein, neutravidin, to dopaminergic axons. Chapter 3 also discusses preliminary results demonstrating the behavior of our small molecule tag and tagged quantum dot construct in the living mouse brain. Studies of our tagged polymers in cultured cells and our work thus far in the brain suggest which polymers may be most effective as delivery platforms for chemical targeting to specific cell types in living brain tissue.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 6 uppsatser.