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Biomedical subjects

P Tillman

Publications and source records attributed to P Tillman.

10 recordsLinked to original sources

Neuronal injury in hippocampus with human immunodeficiency virus transactivating protein, Tat.

Patients with human immunodeficiency virus infection may develop a dementing illness. Using both in vitro and in vivo models, we investigated the susceptibility of the hippocampal formation to the Tat protein of human immunodeficiency virus. We also determined the pattern of hippocampal injury in patients with human immunodeficiency virus encephalitis. Following exposure of hippocampal slices to Tat, marked susceptibility of CA3 region with relative insensitivity of the CA1/2 region was observed. Injection of Tat into different regions of the rat hippocampus produced similar neuronal loss in both CA3 region and the dentate gyrus. In animals administered Tat, lesions were dose-dependent and immunohistochemical staining showed marked gliosis and loss of microtubule associated protein-2 in the affected areas at 3 days post-injection. Interestingly, synaptophysin staining was relatively preserved. In hippocampal tissue from patients with human immunodeficiency virus encephalitis, loss of microtubule-associated protein-2 staining was reduced in the molecular layer of the dentate gyrus. The results of our experiments demonstrate a unique pattern of hippocampal injury in organotypic culture and rats exposed to Tat. Our observations that patients with human immunodeficiency virus reveal a similar pattern of damage suggests that Tat protein may be pathophysiological relevant in human immunodeficiency virus encephalitis.

Adolescent↗

Sphingolipids are potential heat stress signals in Saccharomyces.

The ability of organisms to quickly respond to stresses requires the activation of many intracellular signal transduction pathways. The sphingolipid intermediate ceramide is thought to be particularly important for activating and coordinating signaling pathways during mammalian stress responses. Here we present the first evidence that ceramide and other sphingolipid intermediates are signaling molecules in the Saccharomyces cerevisiae heat stress response. Our data show a 2-3-fold transient increase in the concentration of C18-dihydrosphingosine and C18-phytosphingosine, more than a 100-fold transient increase in C20-dihydrosphingosine and C20-phytosphingosine, and a more stable 2-fold increase in ceramide containing C18-phytosphingosine and a 5-fold increase in ceramide containing C20-phytosphingosine following heat stress. Treatment of cells with dihydrosphingosine activates transcription of the TPS2 gene encoding a subunit of trehalose synthase and causes trehalose, a known thermoprotectant, to accumulate. Dihydrosphingosine induces expression of a STRE-LacZ reporter gene, showing that the global stress response element, STRE, found in many yeast promoter sequences can be activated by sphingolipid signals. The TPS2 promoter contains four STREs that may mediate dihydrosphingosine responsiveness. Using genetic and other approaches it should be possible to identify sphingolipid signaling pathways in S. cerevisiae and quantify the importance of each during heat stress.

Depsipeptides↗

Effect of lumbar sympathectomy in distal arterial obstruction.

We developed a model that simulates distal arterial occlusive disease to determine the effects of sympathectomy on certain hemodynamic changes. Two groups of seven dogs each received unilateral distal popliteal artery ligation. Intra-arterial BPs, angiography, pulse volume recordings (PVRs), and photoplethysmograms were taken of the distal hind limb throughout the experiment. After ligation, PVR and distal hind limb pressures were lowered to less than half of the preligation values. Four days after unilateral distal popliteal artery ligation, group 2 dogs received lumbar sympathectomy on the same side as the ligation. One week after sympathectomy, the PVR amplitudes and pressures showed a transient significant rise. Two weeks after sympathectomy, the PVR pressures and amplitudes returned to the previous, diminished postligation values.

Animals↗

Droperidol-fentanyl as an aid to blood collection in rabbits.

Administration of a droperidol-fentanyl combination to laboratory rabbits at a dose of 2.5 mg/kg and 0.05 mg/kg body weight, respectively, produced vasodilatation which greatly facilitated blood withdrawal from the central auricular artery. The method eliminated the need for vacuum devices or topical irritants and posed little risk or discomfort to the animal.

Animals↗

Testing and treatment of arterial graft thrombosis.

The in vivo technique of Sauvage et al for determining prosthetic arterial graft thrombogenicity was employed in the sheep carotid model using 4 mm commercial expanded polytetrafluoroethylene (Gore-Tex) grafts. Expanded polytetrafluoroethylene was found to be thrombogenic at 4 hours of low flow in this model. At 24 hours all of these grafts were totally occluded at low flow rates. Intravenous use of ibuprofen (Motrin), a thromboxane inhibitor, in this model markedly reduced occlusion and thrombogenicity at 4 and 24 hours. All grafts were patent at 24 hours when ibuprofen was used.

Animals↗

Platelet function and coagulation parameters in sheep during experimental vascular surgery.

Various clotting parameters (prothrombin time, activated coagulation time, activated partial thromboplastin time, platelet counts, and platelet aggregation) were obtained from unanesthetized sheep and from sheep at various times during 5 hours of vascular surgery. The values obtained were not influenced by anesthesia and surgery and were consistent between sheep. Ovine platelets were less prone to aggregate in the presence of collagen, epinephrine, and ristocetin than those of man. Platelet aggregation induced by adenosine diphosphate was similar to that seen in man. Based on these parameters, the sheep would seem to be a reasonable model for experimental vascular surgery when results are to be applied to man.

Animals↗