Search Results - (Author, Cooperation:C. A. Shaw)

2011-12-14

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Animals ; Breast Neoplasms/*genetics/metabolism/mortality/pathology ; Cell Cycle ; Cell Line, Tumor ; *Cell Transformation, Neoplastic ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Genes, myc ; Humans ; Mammary Neoplasms, Experimental/genetics/metabolism/mortality/pathology ; Mice ; Mice, Nude ; Mitosis ; Neoplasm Transplantation ; Proto-Oncogene Proteins c-myc/*metabolism ; RNA Interference ; RNA, Small Interfering ; Spindle Apparatus/physiology ; Sumoylation ; *Transcription, Genetic ; Transplantation, Heterologous ; Ubiquitin-Activating Enzymes/antagonists & inhibitors/*genetics/metabolism

2015-08-15

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Alu Elements ; Base Sequence ; *DNA Breaks, Double-Stranded ; DNA Repair/*genetics ; DNA Replication/*genetics ; DNA-Binding Proteins/genetics/*metabolism ; DNA-Directed DNA Polymerase/metabolism ; Endonucleases/genetics/*metabolism ; *Genomic Instability ; Humans ; Molecular Sequence Data ; Neoplasms/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics/*metabolism

2015-09-04

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Animals ; Breast Neoplasms/*drug therapy/*genetics/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; Cell Transformation, Neoplastic/drug effects ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, myc/*genetics ; HeLa Cells ; Humans ; Introns/genetics ; Mice ; Mice, Nude ; Neoplasm Metastasis/drug therapy ; Nuclear Proteins/metabolism ; Phosphoproteins/metabolism ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; RNA Precursors/biosynthesis/genetics ; RNA Splicing/drug effects ; RNA, Messenger/biosynthesis/genetics ; Ribonucleoprotein, U2 Small Nuclear/metabolism ; Ribonucleoproteins/metabolism ; Spliceosomes/*drug effects/*metabolism ; Xenograft Model Antitumor Assays

2013-05-31

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; Ataxin-1 ; Ataxins ; Cell Line, Tumor ; Disease Models, Animal ; Down-Regulation/drug effects ; Drosophila melanogaster/genetics/*metabolism ; Female ; Humans ; MAP Kinase Signaling System/drug effects ; Male ; Mice ; Mitogen-Activated Protein Kinases/*metabolism ; Molecular Sequence Data ; Molecular Targeted Therapy ; Nerve Tissue Proteins/chemistry/genetics/*metabolism/*toxicity ; Nuclear Proteins/chemistry/genetics/*metabolism/*toxicity ; Phosphorylation ; Protein Stability/drug effects ; Ribosomal Protein S6 Kinases, 90-kDa/deficiency/genetics/*metabolism ; Spinocerebellar Ataxias/*metabolism/*pathology ; Transgenes ; ras Proteins/*metabolism

2016-04-23

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Adaptor Proteins, Signal Transducing/genetics/metabolism ; Adult ; Aged ; Aged, 80 and over ; Animals ; Bacterial Infections/etiology/*immunology ; Caspase 1/metabolism ; Caspases/metabolism ; Female ; Humans ; Immunity, Innate/genetics/*immunology ; Influenza A virus/*immunology ; Influenza, Human/complications/*immunology ; Interferon-beta/immunology ; Male ; Membrane Glycoproteins/genetics/metabolism ; Mice ; Monocytes/immunology ; Myxovirus Resistance Proteins/genetics/*physiology ; Neutrophils/immunology ; Orthomyxoviridae Infections/*immunology ; Respiratory Tract Infections/*immunology/microbiology ; Toll-Like Receptor 7/genetics/metabolism ; Viral Load ; Young Adult

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The factors responsible for ALS-parkinsonism dementia complex (ALS-PDC), the unique neurological disorder of Guam, remain unresolved, but identification of causal factors could lead to clues for related neurodegenerative disorders elsewhere. Earlier studies focused on the consumption and toxicity of the seed of Cycas circinalis, a traditional staple of the indigenous diet, but found no convincing evidence for toxin-linked neurodegeneration. We have reassessed the issue in a series of in vitro bioassays designed to isolate non-water soluble compounds from washed cycad flour and have identified three sterol β-d-glucosides as potential neurotoxins. These compounds give depolarizing field potentials in cortical slices, induce alterations in the activity of specific protein kinases, and cause release of glutamate. They are also highly toxic, leading to release of lactate dehydrogenase (LDH). Theaglycone form, however, is non-toxic. NMDA receptor antagonists block the actions of the sterol glucosides, but do not compete for binding to the NMDA receptor. The most probable mechanism leading to cell death may involve glutamate neuro/excitotoxicity. Mice fed cycad seed flour containing the isolated sterol glucosides show behavioral and neuropathological outcomes, including increased TdT-mediated biotin–dUTP nick-end labelling (TUNEL) positivity in various CNS regions. Astrocytes in culture showed increased caspase-3 labeling after exposure to sterol glucosides. The present results support the hypothesis that cycad consumption may be an important factor in the etiology of ALS-PDC and further suggest that some sterol glucosides may be involved in other neurodegenerative disorders.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: Amyotrophic lateral sclerosis (ALS) is a human neurodegenerative disorder of unknown origin that is characterized by progressive degeneration of corticospinal tracts and anterior horn cells in the brainstem and spinal cord. Previous studies have indicated that motoneuron degeneration associated with ALS may be triggered by mechanisms leading to increased intracellular Ca2+. In the present report, Ca2+-activated phospholipid-dependent protein kinase C (PKC) was evaluated in cervical spinal cords from ALS patients and control subjects. In patients who died with ALS, PKC histone H1 phosphotransferase activity was significantly increased by 330% in cytosolic- and 118% in particulate-derived extracts compared with controls. This increase in PKC phosphotransferase activity appeared to be partially due to an increase in the amount of PKC protein present in ALS spinal cord tissue. PKC histone H1 phosphotransferase activities of cytosolic- and particulate-derived extracts from motor and visual cortex of ALS patients and controls were not statistically different, nor were there differences in PKC histone H1 phosphotransferase activity in platelets and leukocytes. The specific nature of PKC alterations in affected regions of the CNS supports a role for PKC in the events leading to motoneuron death in sporadic ALS.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract : The tripeptide glutathione (GSH) has been thoroughly investigated in relation to its role as antioxidant and free radical scavenger. In recent years, novel actions of GSH in the nervous system have also been described, suggesting that GSH may serve additionally both as a neuromodulator and as a neurotransmitter. In the present article, we describe our studies to explore further a potential role of GSH as neuromodulator/neurotransmitter. These studies have used a combination of methods, including radioligand binding, synaptic release and uptake assays, and electrophysiological recording. We report here the characteristics of GSH binding sites, the interrelationship of GSH with the NMDA receptor, and the effects of GSH on neural activity. Our results demonstrate that GSH binds via its γ-glutamyl moiety to ionotropic glutamate receptors. At micromolar concentrations GSH displaces excitatory agonists, acting to halt their physiological actions on target neurons. At millimolar concentrations, GSH, acting through its free cysteinyl thiol group, modulates the redox site of NMDA receptors. As such modulation has been shown to increase NMDA receptor channel currents, this action may play a significant role in normal and abnormal synaptic activity. In addition, GSH in the nanomolar to micromolar range binds to at least two populations of binding sites that appear to be distinct from all known excitatory amino acid receptor subtypes. GSH bound to these sites is not displaceable by glutamatergic agonists or antagonists. These binding sites, which we believe to be distinct receptor populations, appear to recognize the cysteinyl moiety of the GSH molecule. Like NMDA receptors, the GSH binding sites possess a coagonist site(s) for allosteric modulation. Furthermore, they appear to be linked to sodium ionophores, an interpretation supported by field potential recordings in rat cerebral cortex that reveal a dose-dependent depolarization to applied GSH that is blocked by the absence of sodium but not by lowering calcium or by NMDA or (S)-2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonists. The present data support a reevaluation of the role of GSH in the nervous system in which GSH may be involved both directly and indirectly in synaptic transmission. A full accounting of the actions of GSH may lead to more comprehensive understanding of synaptic function in normal and disease states.

Electronic Resource

1432-1041

viqualine ; ethanol ; 5-hydroxytryptamine uptake inhibitors ; drug interaction

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary We have studied the interaction of viqualine, a 5-hydroxytryptamine (5-HT) uptake inhibitor, with ethanol in 16 healthy men aged 20 to 34 years. The subjects were randomly assigned to receive ethanol dosed to maintain blood alcohol concentrations of 17–22 mmol · l−1 (n=8) or orange juice (n=8) on each of two test days one week apart and preceded, in random order, by 3 days of viqualine 75 mg bd or placebo. Ethanol had no effect on steady-state viqualine concentrations or the inhibition of 5-HT uptake. Viqualine did not affect acetaldehyde concentrations or cause an aversive alcohol-sensitizing reaction. The deleterious effects of ethanol on word recall, manual tracking, body sway, and self-ratings of intoxication, sedation, and performance were not modified by the presence of viqualine. Within each beverage group performances and self-ratings on viqualine and placebo days were not different. The first dose of viqualine was associated with transient nausea. Viqualine and ethanol do not interact kinetically or dynamically on the variables examined in this study.

Electronic Resource