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W L Thomas

Publications and source records attributed to W L Thomas.

10 recordsLinked to original sources
PubMed1996

Cocaine-induced sensitization of metabolic activity in extrapyramidal circuits involves prior dopamine D1-like receptor stimulation.

Chronic cocaine treatment leads to the development of behavioral sensitization in experimental animals. The neural circuitry underlying sensitization was studied using the quantitative 2-deoxyglucose technique, with a modification of a rapid procedure that produces locomotor and neurochemical sensitization. Acute cocaine treatment, administered by i.p. injection, increased the regional cerebral metabolic rate for glucose (rCMRglc) in various extrapyramidal regions, compared with saline vehicle treatment, as previously reported. Repeated cocaine treatment further increased rCMRglc in the entopeduncular nucleus and the substantia nigra pars reticulata, producing a sensitized metabolic response only in regions innervated by direct striatonigral neurons. Repeated cocaine treatment also increased rCMRglc in the nucleus accumbens, hippocampus, dentate gyrus and laterodorsal thalamus, as well as sensory and motor cortices, compared with saline vehicle treatment. The pharmacology underlying this sensitized metabolic response to cocaine was investigated by administering either dopamine D1- or D2-like receptor agonists on the first treatment day, followed by cocaine on the final day. Prior treatment with quinpirole (0.2 mg/kg, i.p.), a D2-like receptor agonist, produced metabolic responses that were significantly lower than those produced by repeated cocaine treatment in the entopeduncular nucleus and substantia nigra pars reticulata, similar to those of acute cocaine treatment. In contrast, prior treatment with SKF 38393 (2.0 mg/kg, l.p.), a partial D1-like receptor agonist, increased rCMRglc in the entopeduncular nucleus and substantia nigra pars reticulata, although not as much as did repeated cocaine treatment. These data suggest that the development of metabolic sensitization in striatonigral circuits involves prior D1-like receptor activation.

Animals↗
PubMed1995

CD5-mediated specific delivery of DNA to T lymphocytes: compartmentalization augmented by adenovirus.

Specific DNA delivery has been achieved via interactions between an asialoorosomucoid-polylysine conjugate and the asialoglycoprotein receptor. We have now extended this technology to another cell type. In order to achieve DNA delivery uniquely to T cells, we have employed an antibody-polylysine conjugate which binds and is internalized via CD5. Binding analyses of the T101 monoclonal antibody to Jurkat cells and freshly isolated human peripheral T lymphocytes were performed and Scatchard plots revealed Kd values of 1.4 and 1.2 pM, respectively. To introduce DNA into the T cell, a complex of T101-polylysine and the luciferase plasmid was formed (T101-PL-DNA). 125I-labeled antibody alone or T101-PL-DNA complexes were both shown to internalize. Subcellular fractionation indicated that the complex remained in the endosomal compartment of the cell for up to 90 min. However, with the addition of adenovirus particles, there was a decrease of labeled complex in the endosomal fraction over time suggesting it was no longer 'tethered' to the endosome vesicle. In vitro transfections confirmed this result showing the addition of adenovirus particles during incubation resulted in increased expression of the luciferase protein. Without adenovirus, there was limited expression of the transduced gene. These data revealed that T101 can deliver DNA via an antibody-PL conjugate. The addition of adenovirus allowed the DNA to escape the endosome enabling expression of the reporter gene.

Adenoviridae↗
PubMed1995

Pretreatment with a dopamine D1-receptor antagonist prevents metabolic activation by cocaine.

The pharmacological mechanism underlying metabolic activation of the rat extrapyramidal system by acute cocaine was examined using the quantitative 2-deoxyglucose autoradiographic method. Pretreatment with a selective dopamine D1-like receptor antagonist, SCH 23390, prevented cocaine-induced metabolic activation in the entopeduncular nucleus and substantia nigra pars reticulata in a dose-dependent manner. These results suggest that activity in striatonigral circuits is induced by stimulation of D1-like receptors by dopamine in the presence of acute cocaine.

Animals↗
PubMed1986

Brachial artery stenosis secondary to ergotism and responsive to nifedipine.

Ergotism is an uncommon drug reaction that may lead to severe ischemic vasoconstriction, which is usually unilateral and more commonly involves the lower extremities. Successful therapeutic measures have included invasive vascular surgery and the use of various available intravenous and oral vasodilators. Reported here is the case of a 56-year-old woman with Marfan's syndrome and chronic migraine headaches who presented with upper extremity pulselessness that responded promptly to oral nifedipine (Procardia). This relatively inexpensive agent with potent peripheral arterial vasodilative properties appears to be the agent of choice in severe ergotamine poisoning.

Arterial Occlusive Diseases↗
PubMed1972

Occurrence of uridylate-rich oligonucleotide regions in heterogeneous nuclear RNA of HeLa cells.

Heterogeneous nuclear RNA molecules from HeLa cells contain a specific segment of about 30 nucleotides length that is largely (about 80%) uridylic acid. This oligo(U) segment is located predominantly in the larger (70S-90S) heterogeneous nuclear RNA molecules, and is essentially absent in messenger RNA and 45S ribosomal precursor RNA molecules. The oligo(U) hybridizes rapidly to cellular DNA, suggesting that it is transcribed from the repeated regions of the DNA.

Alkaline Phosphatase↗
PubMedDate not supplied

Targeted delivery of DNA using YEE(GalNAcAH)3, a synthetic glycopeptide ligand for the asialoglycoprotein receptor.

In vivo gene therapy shows promise as a treatment for both genetic and acquired disorders. The hepatic asialoglycoprotein receptor (ASGPr) binds asialoorosomucoid-polylysine-DNA (ASOR-PL-DNA) complexes and allows targeted delivery to hepatocytes. The tris(N-acetylgalactosamine aminohexyl glycoside) amide of tyrosyl(glutamyl) glutamate [YEE(GalNAcAH)3] has been previously reported to have subnanomolar affinity for the ASGPr. We have used an iodinated derivative of YEE(GalNAcAH)3 linked to polylysine and complexed to the luciferase gene (pCMV-Luc) in receptor-binding experiments to establish the feasibility of substituting ASOR with the synthetic glycopeptide for gene therapy. Scatchard analyses revealed similar Kd values for both ASOR and the glycopeptide. Binding and internalization of 125I-Suc-YEE(GalNAcAH)3 were competitively inhibited with either unlabeled ASOR or glycopeptide. The reverse was also true; 125I-ASOR binding was competed with unlabeled YEE(GalNAcAH)3 suggesting specific binding to the ASGPr by both compounds. Examination of in vivo delivery revealed that the 125I-labeled glycopeptide complex mimicked previous results observed with 125I-ASOR-PL-DNA. CPM in the liver accounted for 96% of the radioactivity recovered from the five major organs (liver, spleen, kidney, heart, and lungs). Cryoautoradiography displayed iodinated glycopeptide complex bound preferentially to hepatocytes rather than nonparenchymal cells. In vitro, as well as in vivo, transfections using the glycopeptide-polylysine-pCMV-luciferase gene complex (YG3-PL-Luc) resulted in expression of the gene product. These data demonstrate that the YEE(GalNAcAH)3 synthetic glycopeptide can be used as a ligand in targeted delivery of DNA to the liver-specific ASGPr.

Animals↗