No description available.

The present investigations were aimed at providing an empirical basis for implicating altered prostaglandin (PG) and thromboxane (TX) biosynthesis in the aberrant heme metabolism and erythrocyte membrane properties which have been found to exist in hereditary muscular dystrophy and ataxia. / Picomolar concentrations of PGE(,1) and PGE(,2) were shown to exert opposing, biphasic effects on osmotic fragility, the hemolytic response to ouabain (without any direct effect on cation-activated adenosine triphosphatases), and echinocyte transformation of normal human erythrocytes. Ex vivo erythrocyte porphyrin analysis pointed to a mild depression of erythropoiesis in dystrophic mice that responded to dietary polyunsaturated fatty acids. The discovery of a paraporphyria in patients with hereditary ataxia was extended to in vitro porphyrin studies using 3-acetylpyridine as an experimental model of ataxia. / Systematic pharmacological studies in a newly designed, serum-free liver cell culture model and in ovo, together with chromatographic-fluorometric PG analysis, established that a certain rate or pattern of PG biosynthesis was required for optimal induction of hepatic (delta)-aminolevulinate synthase and porphyrin-heme biosynthesis. Moreover, the dramatic accumulation of protoporphyrin caused by putative, selective inhibitors of thromboxane synthase, and the exacerbation of experimental porphyria by phospholipase inhibitors provided unique evidence for a physiological, regulatory role of PGs and possibly TXA(,2) in heme biosynthesis at the level of mitochondrial ferrochelatase activity. / Original data obtained about PG effects on heme biosynthesis and erythrocyte properties may prove useful in devising effective therapies and monitoring clinical responses in anemias, porphyrias and hematological aspects of neuromuscular disease.

The capability of axons to grow into a peripheral histoincompatible environment, to locate and to functionally innervate their target structures, was examined through documentation of form and function in nonrejected and rejected upper-extremity composite tissue allografts in adult baboons; Papio h. anubis. Immunosuppression with cyclosporine (radioimmunoassay levels in serum ranging from 1000 to 1200 ng/ml, 12 h after intramuscular injection), supplemented with low doses of methylprednisolone (4.4 mg/day) was sufficient to achieve long-term survival of seven neurovascular free flaps and two hand transplants. / Electrophysiological recordings of more than 600 single axons, combined with light microscopy of the target tissues, revealed that muscle and most classes of skin sensory mechanoreceptors within the allografted tissues became reinnervated. Axons which served allografted tissues that had undergone repeated episodes of rejection showed a significant decrease in conduction velocity, and smaller receptive fields of irregular distribution. Processes of allograft rejection, more than any other factor, led to altered axonal response characteristics.

A decade ago Bizzi and collaborators proposed the "linear summation" hypothesis mainly based on the vestibulo-ocular reflex to explain how subjects move their eyes and head simultaneously to acquire a peripheral visual target. We asked human subjects to make rapid horizontal gaze shifts to unpredictable visible or remembered targets situated at offsets ranging from 30$ sp circ$ to 160$ sp circ$. Different experimental paradigms were used to dissociate crucial variables and different perturbations were imposed to our subjects' head movements to test the interaction between the saccadic eye movement and the head displacement. Several assumptions of the "linear summation" hypothesis were questioned by the analysis of results and we proposed a more elaborated gaze control model to explain how subjects could reach a target accurately with their gaze shifts whatever the conditions, even when the target was beyond the subject's oculomotor range. / In parallel with human experiments we developed a technique to record vestibular units in head-free cats during orienting eye-head movements. Preliminary results on several electrophysiologically identified cells show some particular discharge patterns in the head-free condition. They bring some insights to the behavioral results.

In the feline cerebral cortex flurazepam and ethanol potenitated the inhibitory effects of iontophoretically-applied GABA and electrically-evoked inhibition (believed to be mediated by GABA). This effect is specific, since both flurazepam and ethanol antagonized the inhibitory effects of serotonin, dopamine and glycine. Moreover the degree of potentiation of GABA-mediated electrically-evoked cortical inhibition produced by five benzodiazepines (Ro 21-3981, flurazepam, chlordiazepoxide, medazepam and clozapine): (a) correlated with their relative affinities for the benzodiazepine receptor when all five drugs were applied with equal iontophoretic doses; (b) was not significantly different from one drug to another, when the benzodiazepines were applied in doses inversely proportional to their relative affinities for the benzodiazepine receptor. / Iontophoretically-applied flurazepam consistently potentiated the conductance increase produced by iontophoretically-applied GABA in CA1 and CA3 pyramidal neurons in rat hippocampus. Furthermore, both iontophoretically-applied flurazepam and intravenously injected ethanol consistently prolonged the time course of the GABA-mediated IPSP conductance increase evoked in CA1 and CA3 pyramidal hippocampal neurons by ipsilateral entorhinal or fimbrial stimulation. These effects were independent of membrane potential changes. / It is concluded that GABAergic neurotransmission has a special role in the neurophysiology of anxiety. Since anxiety is involved in the etiology of alcoholism, and since chronic ethanol intake decreases GABA levels and alters the density of GABA receptors, the results of this thesis are consistent with the hypothesis that GABAergic mechanisms may be involved in the etiology of alcoholism.

Atrioventricular (AV) nodal conduction and the pathways of propagation through the AV node have remained enigmatic. Histological and immunohistochemical studies have revealed distinct cellular regions within the AV node with varying distribution of specific ion channels. However, to date, there is little information concerning the pattern of localization of the gap junction proteins that mediate intercellular communication. The current immunohistochemical/confocal studies show a non-uniform distribution of three connexin isoforms (Cx 40, Cx 43 and Cx 45) within these cellular regions of the rat AV node with a marked transition from Cx 43 to Cx 40 at the compact node region. In addition, a high resolution mapping system coupled with extracellular recording electrodes was implemented during this study and has allowed for a macroscopic overview of the rabbit AV node. This approach revealed a marked delay in conduction at the area of the compact node. This information in association with the immunohistochemical studies may help to provide further insight into the mechanisms underlying the AV nodal delay.

No description available.

No description available.

No description available.

Thesis (Ph.D.)--Indiana University, Dept. of Biology, 2007. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5693. Adviser: Ellen D. Ketterson. Title from dissertation home page (viewed May 8, 2008).