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  • Dose-Response Relationship, Drug
  • American Association for the Advancement of Science (AAAS)  (107)
  • 2000-2004  (18)
  • 1980-1984  (89)
  • 1950-1954
  • 1925-1929
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  • American Association for the Advancement of Science (AAAS)  (107)
Years
Year
  • 1
    Publication Date: 2002-04-27
    Description: Genes can affect natural behavioral variation in different ways. Allelic variation causes alternative behavioral phenotypes, whereas changes in gene expression can influence the initiation of behavior at different ages. We show that the age-related transition by honey bees from hive work to foraging is associated with an increase in the expression of the foraging (for) gene, which encodes a guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (PKG). cGMP treatment elevated PKG activity and caused foraging behavior. Previous research showed that allelic differences in PKG expression result in two Drosophila foraging variants. The same gene can thus exert different types of influence on a behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ben-Shahar, Y -- Robichon, A -- Sokolowski, M B -- Robinson, G E -- New York, N.Y. -- Science. 2002 Apr 26;296(5568):741-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Entomology, Neuroscience Program, University of Illinois at Urbana-Champaign, 320 Morrill Hall, 505 South Goodwin Avenue, Urbana, IL 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11976457" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; *Alleles ; Animals ; Appetitive Behavior ; Bees/*genetics/*physiology ; *Behavior, Animal ; Brain/metabolism ; Cyclic GMP/*analogs & derivatives/pharmacology ; Cyclic GMP-Dependent Protein Kinases/*genetics/metabolism ; Dose-Response Relationship, Drug ; Drosophila/genetics/physiology ; Feeding Behavior ; Gene Expression Profiling ; *Genes, Insect ; Hierarchy, Social ; In Situ Hybridization ; Mushroom Bodies/metabolism ; Phenotype ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Social Behavior ; Up-Regulation
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  • 2
    Publication Date: 2002-08-10
    Description: Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor-stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhalla, Upinder S -- Ram, Prahlad T -- Iyengar, Ravi -- CA-79134/CA/NCI NIH HHS/ -- CA-81050/CA/NCI NIH HHS/ -- GM-54508/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):1018-23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Biological Sciences, Bangalore 560065 India. bhalla@ncbs.res.in〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12169734" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Adaptation, Physiological ; Animals ; *Cell Cycle Proteins ; Computer Simulation ; Dose-Response Relationship, Drug ; Dual Specificity Phosphatase 1 ; *Feedback, Physiological ; Immediate-Early Proteins/*metabolism ; *MAP Kinase Signaling System ; Mathematics ; Mice ; Mitogen-Activated Protein Kinase 1/*metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/*metabolism ; Models, Biological ; Phospholipases A/antagonists & inhibitors/metabolism ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Protein Kinase C/metabolism ; Protein Phosphatase 1 ; Protein Tyrosine Phosphatases/*metabolism
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  • 3
    Publication Date: 2002-12-10
    Description: Cysteine proteases of Plasmodium falciparum are required for survival of the malaria parasite, yet their specific cellular functions remain unclear. We used a chemical proteomic screen with a small-molecule probe to characterize the predominant cysteine proteases throughout the parasite life cycle. Only one protease, falcipain 1, was active during the invasive merozoite stage. Falcipain 1-specific inhibitors, identified by screening of chemical libraries, blocked parasite invasion of host erythrocytes, yet had no effect on normal parasite processes such as hemoglobin degradation. These results demonstrate a specific role for falcipain 1 in host cell invasion and establish a potential new target for antimalarial therapeutics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Greenbaum, Doron C -- Baruch, Amos -- Grainger, Munira -- Bozdech, Zbynek -- Medzihradszky, Katlin F -- Engel, Juan -- DeRisi, Joseph -- Holder, Anthony A -- Bogyo, Matthew -- MC_U117532067/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2002 Dec 6;298(5600):2002-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, Veterans Affairs Medical Center, University of California, San Francisco, CA 94143, USA. dgreenb@itsa.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471262" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cysteine Endopeptidases/isolation & purification/*metabolism ; Cysteine Proteinase Inhibitors/chemistry/pharmacology ; Dose-Response Relationship, Drug ; Erythrocytes/*parasitology ; Fluorescent Antibody Technique ; Hemoglobins/metabolism ; Humans ; Leucine/*analogs & derivatives/pharmacology ; Life Cycle Stages ; Organelles/enzymology ; Plasmodium falciparum/drug effects/*enzymology/growth & ; development/*pathogenicity ; Proteomics
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  • 4
    Publication Date: 2000-02-11
    Description: The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA(A) receptors], triggers widespread apoptotic neurodegeneration in the developing rat forebrain. Vulnerability coincides with the period of synaptogenesis, which in humans extends from the sixth month of gestation to several years after birth. During this period, transient ethanol exposure can delete millions of neurons from the developing brain. This can explain the reduced brain mass and neurobehavioral disturbances associated with human fetal alcohol syndrome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ikonomidou, C -- Bittigau, P -- Ishimaru, M J -- Wozniak, D F -- Koch, C -- Genz, K -- Price, M T -- Stefovska, V -- Horster, F -- Tenkova, T -- Dikranian, K -- Olney, J W -- AG 11355/AG/NIA NIH HHS/ -- DA 05072/DA/NIDA NIH HHS/ -- MH 38894/MH/NIMH NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Feb 11;287(5455):1056-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pediatric Neurology, Charite, Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10669420" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Benzodiazepines/pharmacology ; Dose-Response Relationship, Drug ; Ethanol/administration & dosage/blood/*toxicity ; Female ; Fetal Alcohol Spectrum Disorders/*pathology ; GABA Modulators/pharmacology ; Humans ; *Nerve Degeneration ; Neurons/cytology/pathology ; Organ Size/drug effects ; Pregnancy ; Prosencephalon/cytology/*drug effects/embryology/growth & development ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A/*drug effects/metabolism ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*drug effects/metabolism ; Synapses/drug effects/physiology
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  • 5
    Publication Date: 2000-07-06
    Description: With the escalation of obesity-related disease, there is great interest in defining the mechanisms that control appetite and body weight. We have identified a link between anabolic energy metabolism and appetite control. Both systemic and intracerebroventricular treatment of mice with fatty acid synthase (FAS) inhibitors (cerulenin and a synthetic compound C75) led to inhibition of feeding and dramatic weight loss. C75 inhibited expression of the prophagic signal neuropeptide Y in the hypothalamus and acted in a leptin-independent manner that appears to be mediated by malonyl-coenzyme A. Thus, FAS may represent an important link in feeding regulation and may be a potential therapeutic target.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loftus, T M -- Jaworsky, D E -- Frehywot, G L -- Townsend, C A -- Ronnett, G V -- Lane, M D -- Kuhajda, F P -- DC02979/DC/NIDCD NIH HHS/ -- DK09623/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2000 Jun 30;288(5475):2379-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10875926" target="_blank"〉PubMed〈/a〉
    Keywords: Acetyl-CoA Carboxylase/antagonists & inhibitors/metabolism ; Animals ; Appetite/*drug effects ; Appetite Depressants/administration & dosage/chemical synthesis/*pharmacology ; Cerulenin/pharmacology ; Dose-Response Relationship, Drug ; Eating/drug effects ; Enzyme Inhibitors/administration & dosage/chemical synthesis/*pharmacology ; Fasting ; Fatty Acid Synthases/*antagonists & inhibitors/metabolism ; Female ; Hypothalamus/drug effects/metabolism ; Injections, Intraventricular ; Leptin/metabolism ; Liver/drug effects/metabolism ; Male ; Malonyl Coenzyme A/metabolism ; Mice ; Mice, Inbred BALB C ; Neurons/drug effects/metabolism ; Neuropeptide Y/administration & dosage/genetics/metabolism/pharmacology ; RNA, Messenger/genetics/metabolism ; Weight Loss/*drug effects
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  • 6
    Publication Date: 2000-10-06
    Description: Benzodiazepine tranquilizers are used in the treatment of anxiety disorders. To identify the molecular and neuronal target mediating the anxiolytic action of benzodiazepines, we generated and analyzed two mouse lines in which the alpha2 or alpha3 GABAA (gamma-aminobutyric acid type A) receptors, respectively, were rendered insensitive to diazepam by a knock-in point mutation. The anxiolytic action of diazepam was absent in mice with the alpha2(H101R) point mutation but present in mice with the alpha3(H126R) point mutation. These findings indicate that the anxiolytic effect of benzodiazepine drugs is mediated by alpha2 GABAA receptors, which are largely expressed in the limbic system, but not by alpha3 GABAA receptors, which predominate in the reticular activating system.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Low, K -- Crestani, F -- Keist, R -- Benke, D -- Brunig, I -- Benson, J A -- Fritschy, J M -- Rulicke, T -- Bluethmann, H -- Mohler, H -- Rudolph, U -- New York, N.Y. -- Science. 2000 Oct 6;290(5489):131-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Pharmacology and Toxicology, University of Zurich, and Swiss Federal Institute of Technology Zurich (ETH), Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11021797" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Anxiety Agents/metabolism/*pharmacology ; Behavior, Animal/drug effects ; Binding Sites ; Brain/drug effects/metabolism ; Cells, Cultured ; Diazepam/metabolism/*pharmacology ; Dose-Response Relationship, Drug ; Female ; Gene Targeting ; Hippocampus/cytology ; Membrane Potentials/drug effects ; Mice ; Patch-Clamp Techniques ; Phenobarbital/pharmacology ; Point Mutation ; Pyramidal Cells/drug effects/physiology ; Receptors, GABA-A/chemistry/genetics/*metabolism ; Synaptic Transmission ; gamma-Aminobutyric Acid/pharmacology
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  • 7
    Publication Date: 2003-07-19
    Description: Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of glucose in cells that express this enzyme, such as pancreatic beta cells and hepatocytes. We describe a class of antidiabetic agents that act as nonessential, mixed-type GK activators (GKAs) that increase the glucose affinity and maximum velocity (Vmax) of GK. GKAs augment both hepatic glucose metabolism and glucose-induced insulin secretion from isolated rodent pancreatic islets, consistent with the expression and function of GK in both cell types. In several rodent models of type 2 diabetes mellitus, GKAs lowered blood glucose levels, improved the results of glucose tolerance tests, and increased hepatic glucose uptake. These findings may lead to the development of new drug therapies for diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grimsby, Joseph -- Sarabu, Ramakanth -- Corbett, Wendy L -- Haynes, Nancy-Ellen -- Bizzarro, Fred T -- Coffey, John W -- Guertin, Kevin R -- Hilliard, Darryl W -- Kester, Robert F -- Mahaney, Paige E -- Marcus, Linda -- Qi, Lida -- Spence, Cheryl L -- Tengi, John -- Magnuson, Mark A -- Chu, Chang An -- Dvorozniak, Mark T -- Matschinsky, Franz M -- Grippo, Joseph F -- New York, N.Y. -- Science. 2003 Jul 18;301(5631):370-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Metabolic Diseases, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12869762" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Allosteric Regulation ; Animals ; Blood Glucose/metabolism ; *Carrier Proteins ; Diabetes Mellitus, Type 2/*drug therapy/metabolism ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Enzyme Activation ; Enzyme Activators/chemistry/pharmacology ; Glucokinase/*metabolism ; Glucose/*metabolism ; Glucose Tolerance Test ; Homeostasis ; Humans ; Hypoglycemic Agents/chemistry/pharmacology ; Insulin/blood/*secretion ; Islets of Langerhans/*drug effects/secretion ; Keto Acids/metabolism ; Liver/*drug effects/metabolism ; Liver Glycogen/biosynthesis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Proteins/metabolism/pharmacology ; Rats ; Rats, Wistar ; Recombinant Proteins/metabolism ; Stereoisomerism ; Thiazoles/chemistry/*pharmacology
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  • 8
    Publication Date: 2004-01-06
    Description: MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes. These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vassilev, Lyubomir T -- Vu, Binh T -- Graves, Bradford -- Carvajal, Daisy -- Podlaski, Frank -- Filipovic, Zoran -- Kong, Norman -- Kammlott, Ursula -- Lukacs, Christine -- Klein, Christian -- Fotouhi, Nader -- Liu, Emily A -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):844-8. Epub 2004 Jan 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Discovery Oncology, Roche Research Center, Hoffmann-La Roche, Inc., Nutley, NJ 07110, USA. lyubomir.vassilev@roche.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14704432" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/*drug effects ; Binding Sites ; Cell Cycle/drug effects ; Cell Division/*drug effects ; Cell Line ; Cell Line, Tumor ; Cell Survival/drug effects ; Crystallization ; Crystallography, X-Ray ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/metabolism ; Dose-Response Relationship, Drug ; Gene Expression ; Genes, p53 ; Humans ; Hydrophobic and Hydrophilic Interactions ; Imidazoles/chemistry/metabolism/*pharmacology ; Mice ; Mice, Nude ; Models, Molecular ; Molecular Weight ; NIH 3T3 Cells ; Neoplasm Transplantation ; Neoplasms, Experimental/drug therapy/metabolism/*pathology ; *Nuclear Proteins ; Phosphorylation ; Piperazines/chemistry/metabolism/*pharmacology ; Protein Conformation ; Proto-Oncogene Proteins/*antagonists & inhibitors/chemistry/metabolism ; Proto-Oncogene Proteins c-mdm2 ; Stereoisomerism ; Transplantation, Heterologous ; Tumor Suppressor Protein p53/*metabolism
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  • 9
    Publication Date: 2004-02-07
    Description: Prefrontal neurons engaged by working memory tasks express a sequence of phasic and tonic activations linked to a train of sensory, mnemonic, and response-related events. Here, we report that the dopamine D2 receptor selectively modulates the neural activities associated with memory-guided saccades in oculomotor delayed-response tasks yet has little or no effect on the persistent mnemonic-related activity, which is instead modulated by D1 receptors. This associates the D2 receptor with a specific component of working memory circuitry and fractionates the modulatory effects of D1 and D2 receptors on the neural machinery of a cognitive process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Min -- Vijayraghavan, Susheel -- Goldman-Rakic, Patricia S -- P50 MH068789/MH/NIMH NIH HHS/ -- P50 MH44866/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):853-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA. min.wang@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764884" target="_blank"〉PubMed〈/a〉
    Keywords: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology ; Animals ; Benzazepines/pharmacology ; Cues ; Dopamine Agonists/pharmacology ; Dopamine Antagonists/pharmacology ; Dopamine D2 Receptor Antagonists ; Dose-Response Relationship, Drug ; Electrophysiology ; Macaca mulatta ; Male ; Memory/*physiology ; Neurons/*physiology ; Prefrontal Cortex/*physiology ; Psychomotor Performance ; Quinpirole/pharmacology ; Raclopride/pharmacology ; Receptors, Dopamine D1/agonists/antagonists & inhibitors/metabolism ; Receptors, Dopamine D2/agonists/*metabolism ; Reward ; Saccades ; Salicylamides/pharmacology
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  • 10
    Publication Date: 2004-10-16
    Description: Topical agents, such as microbicides, that can protect against human immunodeficiency virus (HIV) transmission are urgently needed. Using a chimeric simian/human immunodeficiency virus (SHIV SF162), which is tropic for the chemokine receptor CCR5, we report that topical application of high doses of PSC-RANTES, an amino terminus-modified analog of the chemokine RANTES, provided potent protection against vaginal challenge in rhesus macaques. These experimental findings have potentially important implications for understanding vaginal transmission of HIV and the design of strategies for its prevention.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lederman, Michael M -- Veazey, Ronald S -- Offord, Robin -- Mosier, Donald E -- Dufour, Jason -- Mefford, Megan -- Piatak, Michael Jr -- Lifson, Jeffrey D -- Salkowitz, Janelle R -- Rodriguez, Benigno -- Blauvelt, Andrew -- Hartley, Oliver -- AI 36219/AI/NIAID NIH HHS/ -- AI 51649/AI/NIAID NIH HHS/ -- N01-CO-124000/CO/NCI NIH HHS/ -- New York, N.Y. -- Science. 2004 Oct 15;306(5695):485-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Case Western Reserve University, University Hospitals, 2061 Cornell Road, Cleveland, OH 44106, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15486300" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Intravaginal ; Animals ; Anti-HIV Agents/administration & dosage/*therapeutic use ; Anti-Infective Agents, Local/administration & dosage/*therapeutic use ; Antibodies, Viral/blood ; *CCR5 Receptor Antagonists ; Chemokine CCL5/administration & dosage/*analogs & derivatives/*therapeutic use ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Female ; HIV Infections/*prevention & control/transmission ; HIV-1/drug effects ; Macaca mulatta ; Receptors, CCR5/metabolism ; Simian Acquired Immunodeficiency Syndrome/*prevention & control/transmission ; Simian Immunodeficiency Virus/drug effects/immunology ; Vagina/*virology
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  • 11
    Publication Date: 2004-11-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gura, Trisha -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1453-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15567820" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Appetite/*drug effects ; Appetite Depressants/administration & dosage/*pharmacology ; Body Weight/drug effects ; Dose-Response Relationship, Drug ; Gastric Emptying/drug effects ; Humans ; Macaca mulatta ; Peptide Fragments ; Peptide YY/administration & dosage/metabolism/*pharmacology ; Rats
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  • 12
    Publication Date: 2004-03-06
    Description: The central amygdala (CeA) plays a role in the relationship among stress, corticotropin-releasing factor (CRF), and alcohol abuse. In whole-cell recordings, both CRF and ethanol enhanced gamma-aminobutyric acid-mediated (GABAergic) neurotransmission in CeA neurons from wild-type and CRF2 receptor knockout mice, but not CRF1 receptor knockout mice. CRF1 (but not CRF2) receptor antagonists blocked both CRF and ethanol effects in wild-type mice. These data indicate that CRF1 receptors mediate ethanol enhancement of GABAergic synaptic transmission in the CeA, and they suggest a cellular mechanism underlying involvement of CRF in ethanol's behavioral and motivational effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nie, Zhiguo -- Schweitzer, Paul -- Roberts, Amanda J -- Madamba, Samuel G -- Moore, Scott D -- Siggins, George Robert -- AA06420/AA/NIAAA NIH HHS/ -- AA10994/AA/NIAAA NIH HHS/ -- DA03665/DA/NIDA NIH HHS/ -- DA13658/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2004 Mar 5;303(5663):1512-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuropharmacology and Alcohol Research Center, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15001778" target="_blank"〉PubMed〈/a〉
    Keywords: Alcohol Drinking ; Amygdala/drug effects/*physiology ; Animals ; Corticotropin-Releasing Hormone/pharmacology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Evoked Potentials/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/drug effects/*physiology ; Patch-Clamp Techniques ; Receptors, Corticotropin-Releasing Hormone/antagonists & ; inhibitors/genetics/*metabolism ; Receptors, GABA-A/metabolism ; Stress, Psychological/physiopathology ; Synaptic Transmission/*drug effects ; gamma-Aminobutyric Acid/*metabolism
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  • 13
    Publication Date: 2004-12-14
    Description: The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 mug/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andries, Koen -- Verhasselt, Peter -- Guillemont, Jerome -- Gohlmann, Hinrich W H -- Neefs, Jean-Marc -- Winkler, Hans -- Van Gestel, Jef -- Timmerman, Philip -- Zhu, Min -- Lee, Ennis -- Williams, Peter -- de Chaffoy, Didier -- Huitric, Emma -- Hoffner, Sven -- Cambau, Emmanuelle -- Truffot-Pernot, Chantal -- Lounis, Nacer -- Jarlier, Vincent -- New York, N.Y. -- Science. 2005 Jan 14;307(5707):223-7. Epub 2004 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium. kandries@prdbe.jnj.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15591164" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antitubercular Agents/chemistry/pharmacokinetics/*pharmacology/therapeutic use ; Bacterial Proton-Translocating ATPases/*antagonists & ; inhibitors/chemistry/metabolism ; Diarylquinolines ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Enzyme Inhibitors/chemistry/pharmacology/therapeutic use ; Humans ; Male ; Mice ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Mycobacterium smegmatis/drug effects/enzymology/growth & development ; Mycobacterium tuberculosis/*drug effects/enzymology/growth & development ; Point Mutation ; Protein Subunits/antagonists & inhibitors/chemistry ; Quinolines/chemistry/pharmacokinetics/*pharmacology/*therapeutic use ; Tuberculosis/*drug therapy/microbiology ; Tuberculosis, Multidrug-Resistant/drug therapy/microbiology
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  • 14
    Publication Date: 2004-11-13
    Description: We present a method for high-throughput cytological profiling by microscopy. Our system provides quantitative multidimensional measures of individual cell states over wide ranges of perturbations. We profile dose-dependent phenotypic effects of drugs in human cell culture with a titration-invariant similarity score (TISS). This method successfully categorized blinded drugs and suggested targets for drugs of uncertain mechanism. Multivariate single-cell analysis is a starting point for identifying relationships among drug effects at a systems level and a step toward phenotypic profiling at the single-cell level. Our methods will be useful for discovering the mechanism and predicting the toxicity of new drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perlman, Zachary E -- Slack, Michael D -- Feng, Yan -- Mitchison, Timothy J -- Wu, Lani F -- Altschuler, Steven J -- P01 CA078048/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2004 Nov 12;306(5699):1194-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15539606" target="_blank"〉PubMed〈/a〉
    Keywords: Automation ; Cell Cycle/drug effects ; Cluster Analysis ; DNA/analysis ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical/*methods ; Fluorescent Dyes ; HeLa Cells ; Humans ; Image Processing, Computer-Assisted ; *Microscopy, Fluorescence ; Pharmacology/*methods ; Phenotype ; Statistics as Topic ; Toxicity Tests/*methods
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  • 15
    Publication Date: 2004-09-09
    Description: BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the amphipathic alpha-helical BH3 segment, an essential death domain. We used a chemical strategy, termed hydrocarbon stapling, to generate BH3 peptides with improved pharmacologic properties. The stapled peptides, called "stabilized alpha-helix of BCL-2 domains" (SAHBs), proved to be helical, protease-resistant, and cell-permeable molecules that bound with increased affinity to multidomain BCL-2 member pockets. A SAHB of the BH3 domain from the BID protein specifically activated the apoptotic pathway to kill leukemia cells. In addition, SAHB effectively inhibited the growth of human leukemia xenografts in vivo. Hydrocarbon stapling of native peptides may provide a useful strategy for experimental and therapeutic modulation of protein-protein interactions in many signaling pathways.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360987/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360987/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walensky, Loren D -- Kung, Andrew L -- Escher, Iris -- Malia, Thomas J -- Barbuto, Scott -- Wright, Renee D -- Wagner, Gerhard -- Verdine, Gregory L -- Korsmeyer, Stanley J -- K08 HL074049/HL/NHLBI NIH HHS/ -- K08HL074049/HL/NHLBI NIH HHS/ -- R37CA50239/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2004 Sep 3;305(5689):1466-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Pediatric Hematology/Oncology and Children's Hospital Boston, Massachusetts, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15353804" target="_blank"〉PubMed〈/a〉
    Keywords: *Alkenes ; Animals ; *Apoptosis ; BH3 Interacting Domain Death Agonist Protein ; Bridged Compounds/chemical synthesis/chemistry/metabolism/*pharmacology ; Carrier Proteins/chemistry ; Cell Division/drug effects ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cytochromes c/metabolism ; Dose-Response Relationship, Drug ; Endosomes/metabolism ; Humans ; Jurkat Cells ; Leukemia, Experimental/*drug therapy/pathology ; Leukemic Infiltration ; Mice ; Mice, SCID ; Mitochondria, Liver/drug effects/metabolism ; *Molecular Mimicry ; Neoplasm Transplantation ; Peptide Fragments/*chemistry ; Peptides/chemical synthesis/chemistry/metabolism/*pharmacology ; Protein Binding ; Protein Engineering ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/*chemistry ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Transplantation, Heterologous
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  • 16
    Publication Date: 2004-12-18
    Description: Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fukuhara, Atsunori -- Matsuda, Morihiro -- Nishizawa, Masako -- Segawa, Katsumori -- Tanaka, Masaki -- Kishimoto, Kae -- Matsuki, Yasushi -- Murakami, Mirei -- Ichisaka, Tomoko -- Murakami, Hiroko -- Watanabe, Eijiro -- Takagi, Toshiyuki -- Akiyoshi, Megumi -- Ohtsubo, Tsuguteru -- Kihara, Shinji -- Yamashita, Shizuya -- Makishima, Makoto -- Funahashi, Tohru -- Yamanaka, Shinya -- Hiramatsu, Ryuji -- Matsuzawa, Yuji -- Shimomura, Iichiro -- New York, N.Y. -- Science. 2005 Jan 21;307(5708):426-30. Epub 2004 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Pathophysiology, Graduate School of Medicine, and Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15604363" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/drug effects/metabolism ; Adipose Tissue/*metabolism ; Animals ; Binding Sites ; Blood Glucose/analysis ; Cell Line ; Cells, Cultured ; Cytokines/blood/genetics/*metabolism/pharmacology ; Diabetes Mellitus, Type 2/metabolism ; Dose-Response Relationship, Drug ; Female ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Gene Targeting ; Humans ; Insulin/blood/*metabolism ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Molecular Mimicry ; Muscle Cells/metabolism ; Nicotinamide Phosphoribosyltransferase ; Phosphorylation ; Receptor, Insulin/metabolism ; Recombinant Proteins/pharmacology ; Signal Transduction ; Subcutaneous Tissue ; Viscera
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  • 17
    Publication Date: 2002-02-16
    Description: During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth of the human malaria parasites Plasmodium falciparum and P. vivax and was 1000-fold less toxic to mammalian cell lines. A radioactive derivative specifically accumulated in infected erythrocytes to levels several hundredfold higher than in the surrounding medium, and very low dose G25 therapy completely cured monkeys infected with P. falciparum and P. cynomolgi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wengelnik, Kai -- Vidal, Valerie -- Ancelin, Marie L -- Cathiard, Anne-Marie -- Morgat, Jean Louis -- Kocken, Clemens H -- Calas, Michele -- Herrera, Socrates -- Thomas, Alan W -- Vial, Henri J -- New York, N.Y. -- Science. 2002 Feb 15;295(5558):1311-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS UMR 5539, CP 107, CNRS UMR 5810, CP 22, Universite Montpellier II, Place E. Bataillon, 34095 Montpellier Cedex 5, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11847346" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/administration & dosage/*pharmacokinetics/*pharmacology/therapeutic ; use ; Aotus trivirgatus ; Cell Line ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Erythrocytes/metabolism/*parasitology ; Humans ; Macaca mulatta ; Malaria/*drug therapy/parasitology ; Malaria, Falciparum/drug therapy/parasitology ; Malaria, Vivax/drug therapy/parasitology ; Membrane Transport Modulators ; Membrane Transport Proteins/antagonists & inhibitors ; Parasitemia/drug therapy ; Phosphatidylcholines/biosynthesis ; Plasmodium/*drug effects ; Plasmodium cynomolgi/drug effects ; Plasmodium falciparum/drug effects ; Plasmodium vivax/drug effects ; Pyrrolidines/administration & dosage/*pharmacokinetics/*pharmacology/therapeutic ; use
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  • 18
    Publication Date: 2003-03-29
    Description: Although it has been known for some time that olfactory receptors (ORs) reside in spermatozoa, the function of these ORs is unknown. Here, we identified, cloned, and functionally expressed a previously undescribed human testicular OR, hOR17-4. With the use of ratiofluorometric imaging, Ca2+ signals were induced by a small subset of applied chemical stimuli, establishing the molecular receptive fields for the recombinantly expressed receptor in human embryonic kidney (HEK) 293 cells and the native receptor in human spermatozoa. Bourgeonal was a powerful agonist for both recombinant and native receptor types, as well as a strong chemoattractant in subsequent behavioral bioassays. In contrast, undecanal was a potent OR antagonist to bourgeonal and related compounds. Taken together, these results indicate that hOR17-4 functions in human sperm chemotaxis and may be a critical component of the fertilization process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spehr, Marc -- Gisselmann, Gunter -- Poplawski, Alexandra -- Riffell, Jeffrey A -- Wetzel, Christian H -- Zimmer, Richard K -- Hatt, Hanns -- New York, N.Y. -- Science. 2003 Mar 28;299(5615):2054-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Physiology, Ruhr University Bochum, 150 University Street, D-44780 Bochum, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12663925" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/metabolism ; Aldehydes/chemistry/metabolism/pharmacology ; Binding Sites ; Calcium/metabolism ; Calcium Signaling ; Cell Line ; Chemotactic Factors/chemistry/metabolism/*pharmacology ; *Chemotaxis ; Cloning, Molecular ; Dose-Response Relationship, Drug ; Fertilization ; Gene Expression Profiling ; Humans ; Ligands ; Male ; Molecular Structure ; Odors ; Receptors, Odorant/chemistry/genetics/*physiology ; Recombinant Fusion Proteins/metabolism ; Seminal Plasma Proteins/genetics/*physiology ; *Sperm Motility/drug effects ; Spermatozoa/drug effects/*physiology ; Testis/*metabolism ; Type C Phospholipases/metabolism
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  • 19
    Publication Date: 1980-04-25
    Description: In BALB/c female mice with melanoma transplants, the incidence of "takes" is decreased and survival is increased by hydroquinone, a melanocytolytic agent. The mechanism of drug action is suggested by via DNA. The significant and high degree of positive response to hydroquinone treatment in vivo is encouraging for the clinical management of melanoma with melanocytolytic agents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chavin, W -- Jelonek, E J Jr -- Reed, A H -- Binder, L R -- New York, N.Y. -- Science. 1980 Apr 25;208(4442):408-10.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7367868" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Female ; Hydroquinones/metabolism/*therapeutic use ; Melanocytes/metabolism ; Melanoma/*drug therapy ; Mice ; Neoplasm Transplantation ; Neoplasms, Experimental/drug therapy
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  • 20
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-11-07
    Description: Lanosterol, a cholesterol precursor that increases considerably in the platelets of rats treated with oral contraceptives, was incubated with either platelet-rich plasma or washed platelet suspension. After 2 minutes there was a remarkable dose-related increase in platelet activity. This platelet hyperactivity was measured by clotting time and platelet aggregation could not be reproduced by cholesterol or ethinylestradiol.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ciavatti, M -- Dumont, E -- Benoit, C -- Renaud, S -- New York, N.Y. -- Science. 1980 Nov 7;210(4470):642-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7433990" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Coagulation/*drug effects ; Blood Platelets/*drug effects ; Contraceptives, Oral/*pharmacology ; Dose-Response Relationship, Drug ; Female ; Lanosterol/*pharmacology ; Platelet Aggregation/*drug effects ; Rats
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  • 21
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-03-14
    Description: Mebendazole was highly effective against the helminth parasite Trichinella spiralis in mice subjected to a 3-day course of treatment during the invasive and encystment phases of experimental trichinellosis. When treatment began either 2 or 4 weeks after the mice were inoculated with parasites, the number of larvae developing in the host musculature was greatly reduced by twice-daily oral administration of 3.125, 6.25, or 12.5 milligrams of mebendazole per kilogram of body weight.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCracken, R O -- Taylor, D D -- New York, N.Y. -- Science. 1980 Mar 14;207(4436):1220-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7355285" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Animals ; Benzimidazoles/*therapeutic use ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Larva ; Male ; Mebendazole/administration & dosage/*therapeutic use ; Mice ; Muscles/parasitology ; Trichinella/drug effects ; Trichinellosis/*drug therapy
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  • 22
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-04-18
    Description: In the hot plate test, substance P given intravenously at doses of 5 x 10-5 and 5 x 10-4 gram per kilogram caused analgesia, while lower doses caused hyperalgesia. The influence of substance P on nociception depended on the individual mouse's sensitivity to pain (control response latency). Analgesia was produced by substance P administered to mice with high sensitivity to thermic stimulation, whereas hyperalgesia occurred in mice whose control latencies were longer than normal. This result is interpreted as an indication that substance P is capable of normalizing responsiveness to pain and could be classified as a regulatory peptide.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oehme, P -- Hilse, H -- Morgenstern, E -- Gores, E -- New York, N.Y. -- Science. 1980 Apr 18;208(4441):305-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6154313" target="_blank"〉PubMed〈/a〉
    Keywords: Acetates ; Animals ; Dose-Response Relationship, Drug ; Hot Temperature ; Hyperalgesia/*chemically induced ; Hyperesthesia/*chemically induced ; Mice ; Nociceptors/drug effects ; Pain/*physiopathology ; Perception/*drug effects ; Receptors, Drug/physiology ; Substance P/*pharmacology
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  • 23
    Publication Date: 1980-03-21
    Description: The interplay of insulin, cortisol, and prolactin induces synthesis of casein and alpha-lactalbumin in cultured mammary explants from mature virgin mice. A striking difference has been found between the optimal concentrations of cortisol required for maximal induction of the two milk proteins in vitro: 3 x 10(-8) molar for alpha-lactalbumin and 3 x 10(-6) molar for casein. Moreover, 10(-7) to 10(-5) molar cortisol caused progressive inhibition of alpha-lactalbumin accumulation. Such differential actions of cortisol may partly account for the asynchronous synthesis of the two proteins during pregnancy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ono, M -- Oka, T -- New York, N.Y. -- Science. 1980 Mar 21;207(4437):1367-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6986657" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caseins/*biosynthesis ; Dose-Response Relationship, Drug ; Drug Interactions ; Female ; Hydrocortisone/*pharmacology ; Insulin/pharmacology ; Lactalbumin/*biosynthesis ; Mammary Glands, Animal/drug effects/*metabolism ; Mice ; Organ Culture Techniques ; Pregnancy ; Prolactin/pharmacology
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  • 24
    Publication Date: 1980-06-13
    Description: The cellular basis of kindling was studied electrophysiologically with slices of guinea pig hippocampus. Normally, epileptiform activity can be induced in the slices only by combined exposure to elevated potassium levels and a chemical convulsant such as penicillin. In hippocampal slices from pentylenetetrazole-kindled animals, however, elevated potassium alone can induce seizures. These data suggest that kindling elicits long-term changes in neuronal excitability that may involve ionic mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oliver, A P -- Hoffer, B J -- Wyatt, R J -- New York, N.Y. -- Science. 1980 Jun 13;208(4449):1264-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7375936" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Epilepsy/chemically induced/*physiopathology ; Guinea Pigs ; Hippocampus/drug effects/*physiology ; In Vitro Techniques ; Male ; Neurons/drug effects/physiology ; Pentylenetetrazole/administration & dosage/pharmacology ; Potassium/*pharmacology
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  • 25
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-03-28
    Description: Forty children were given a diet free of artificial food dyes and other additives for 5 days. Twenty of the children had been classified as hyperactive by scores on the Conners Rating Scale and were reported to have favorable responses to stimulant medication. A diagnosis of hyperactivity had been rejected in the other 20 children. Oral challenges with large doses (100 or 150 milligrams) of a blend of FD & C approved food dyes or placebo were administered on days 4 and 5 of the experiment. The performance of the hyperactive children on paired-associate learning tests on the day they received the dye blend was impaired relative to their performance after they received the placebo, but the performance of the nonhyperactive group was not affected by the challenge with the food dye blend.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Swanson, J M -- Kinsbourne, M -- New York, N.Y. -- Science. 1980 Mar 28;207(4438):1485-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7361102" target="_blank"〉PubMed〈/a〉
    Keywords: Child ; Dose-Response Relationship, Drug ; Female ; Food Coloring Agents/*pharmacology ; Humans ; Hyperkinesis/*physiopathology ; Learning/*drug effects ; Male ; Time Factors
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  • 26
    Publication Date: 1980-10-17
    Description: The genotoxicity of the antihypertensive agents hydralazine and dihydralazine was tested in mammalian cells and bacteria. Both drugs elicited DNA repair in rat hepatocyte primary cultures. In the Ames test, both with and without an S-9 fraction, hydralazine was mutagenic in strains TA100 and TA1537, whereas dihydralazine was weakly mutagenic in strain TA1537. These findings support the observation that hydralazine is carcinogenic in mice. The carcinogenicity of many chemicals results from interaction with DNA. Since these studies demonstrate that hydralazine and dihydralazine damage DNA in mammalian cells, these drugs should be viewed as potential human carcinogens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Williams, G M -- Mazue, G -- McQueen, C A -- Shimada, T -- N 01-CP-55705/CP/NCI NIH HHS/ -- New York, N.Y. -- Science. 1980 Oct 17;210(4467):329-30.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7423193" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Biotransformation ; *Carcinogens ; Cells, Cultured ; DNA Repair/*drug effects ; Dihydralazine/*toxicity ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Hydralazine/*analogs & derivatives/*toxicity ; Liver/metabolism ; *Mutagens ; Rats ; Salmonella typhi/drug effects
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  • 27
    Publication Date: 1980-02-15
    Description: In rats, multiple daily amphetamine injections (2.5 milligrams per kilogram of body weight, injected subcutaneously every 4 hours for 5 days) resulted in a progressive augmentation in response, characterized by a more rapid onset and an increased magnitude of stereotypy. By contrast, offset times of both the stereotypy and the poststereotypy hyperactivity periods were markedly shortened. When the animals were retested with the same dose of amphetamine 8 days after the long-term treatment was discontinued, the time of offset of the stereotypy and hyperactivity phases had recovered to values found with short-term amphetamine treatment, whereas the more rapid onset of stereotypy persisted. Brain monoamine and amphetamine concentrations and tyrosine hydroxylase activity were determined in comparably treated rats at times corresponding to the behavioral observations. The behavioral data indicate that enhanced responsiveness to amphetamine following its repeated administration may contribute to the development of amphetamine psychosis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Segal, D S -- Weinberger, S B -- Cahill, J -- McCunney, S J -- New York, N.Y. -- Science. 1980 Feb 15;207(4433):905-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7188815" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior/*drug effects ; Behavior, Animal/*drug effects ; Brain/metabolism ; Brain Chemistry/drug effects ; Dextroamphetamine/administration & dosage/*pharmacology ; Dopamine/metabolism ; Dose-Response Relationship, Drug ; Humans ; Male ; Motor Activity/drug effects ; Norepinephrine/metabolism ; Rats ; Serotonin/metabolism ; Stereotyped Behavior/*drug effects ; Time Factors
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  • 28
    Publication Date: 1981-02-06
    Description: Administration of the herbicide 2,4,5-trichlorophenoxyacetic acid to incubating chicken eggs alters behavior after hatching. Single doses, with no morphological effects, retard learning (lowest dose, 7 milligrams per kilogram of body weight) and increase general activity (27 milligrams per kilogram) and jumping (13 milligrams per kilogram). Day 15 of incubation is the most susceptible stage of development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sanderson, C A -- Rogers, L J -- New York, N.Y. -- Science. 1981 Feb 6;211(4482):593-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7455699" target="_blank"〉PubMed〈/a〉
    Keywords: 2,4,5-Trichlorophenoxyacetic Acid/*pharmacology/toxicity ; Age Factors ; Animals ; Behavior, Animal/*drug effects ; Chick Embryo/drug effects ; Chickens ; Discrimination Learning/drug effects ; Dose-Response Relationship, Drug ; Motor Activity/drug effects
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  • 29
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-07-17
    Description: Bee venom and phospholipase A2 extracted from bee venom enhanced guanylate cyclase (E.C. 4.6.1.2) activity two- to threefold in rat liver, lung, heart, kidney, ileum, and cerebellum. Dose-response relationships revealed that bee venom at concentrations as low as 1 microgram per milliliter and phospholipase A2 at 1 microunit per milliliter caused a maximal enhancement of guanylate cyclase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vesely, D L -- New York, N.Y. -- Science. 1981 Jul 17;213(4505):359-60.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6113689" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bee Venoms/*pharmacology ; Dose-Response Relationship, Drug ; Enzyme Activation ; Guanylate Cyclase/*metabolism ; Kinetics ; Organ Specificity ; Phospholipases/*pharmacology ; Phospholipases A/*pharmacology ; Phospholipases A2 ; Rats
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  • 30
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-04-03
    Description: A chemical impurity isolated from commercially purchased acridine causes cricket embryos to develop extra compound eyes, branched antennae, extra antennae, and extra heads. Purified acridine does not produce similar duplications of cricket heads or head structures nor do the substituted acridines proflavine, acriflavine, or acridine orange. A dose-response relation exists such that the number and severity of abnormalities increase with increasing concentration of the teratogen.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walton, B T -- New York, N.Y. -- Science. 1981 Apr 3;212(4490):51-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6782672" target="_blank"〉PubMed〈/a〉
    Keywords: Abnormalities, Multiple/chemically induced ; Acridines/*isolation & purification/pharmacology ; Animals ; Dose-Response Relationship, Drug ; Drug Contamination ; Embryo, Nonmammalian/drug effects ; Eye Abnormalities ; Head/abnormalities ; Orthoptera/*drug effects ; *Teratogens
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-07-31
    Description: Rats were trained to walk on a treadmill to avoid foot shock. The animals developed tolerance for ethanol if given subsequent practice while ethanol intoxicated. Rats given equivalent doses of ethanol after practice did not develop tolerance, nor did saline-treated controls. These results challenge the hypothesis that mere repeated doses of ethanol are sufficient to induce tolerance. It seems that tolerance does not develop unless the response used to measure tolerance is performed while the subject is intoxicated.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wenger, J R -- Tiffany, T M -- Bombardier, C -- Nicholls, K -- Woods, S C -- 03504/PHS HHS/ -- AA 04658/AA/NIAAA NIH HHS/ -- New York, N.Y. -- Science. 1981 Jul 31;213(4507):575-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7244656" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avoidance Learning/*drug effects ; Dose-Response Relationship, Drug ; Drug Tolerance ; Ethanol/blood/*pharmacology ; Rats
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-04-30
    Description: Calcium ionophore A23187 promotes ooplasmic segregation and orange crescent formation in eggs of the ascidian Boltenia villosa. When eggs were exposed to a gradient A23187 the orange crescent was induced to form in the region corresponding to the highest concentration of ionophore. This result is consistent with the hypothesis that a local increase in intracellular calcium polarizes cytoplasmic localization in the ascidian embryo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jeffery, W R -- 232-HDO-7098/HD/NICHD NIH HHS/ -- HD-13970/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1982 Apr 30;216(4545):545-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6803360" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anti-Bacterial Agents/*pharmacology ; Calcimycin/*pharmacology ; Calcium/*physiology ; Cell Compartmentation/drug effects ; Cytoplasm/ultrastructure ; Dose-Response Relationship, Drug ; Female ; Ovum/*drug effects/ultrastructure ; Urochordata
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-09-24
    Description: Phencyclidine elicits hyperthermia at low doses and hypothermia at high doses in rats. Naloxone antagonizes both effects. Phencyclidine's effects on thermo-regulation are probably mediated by an interaction with a mu opiate receptor.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glick, S D -- Guido, R A -- DA 02534/DA/NIDA NIH HHS/ -- DA 70082/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1982 Sep 24;217(4566):1272-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6287581" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Body Temperature Regulation/*drug effects ; Dose-Response Relationship, Drug ; Female ; Naloxone/pharmacology ; Phencyclidine/antagonists & inhibitors/*pharmacology ; Rats ; Receptors, Opioid/*drug effects
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  • 34
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-09-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 1983 Sep 23;221(4617):1244-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6684327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Ethanol/*adverse effects ; Female ; Pregnancy ; Pregnancy, Animal/*drug effects
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  • 35
    Publication Date: 1983-04-29
    Description: Selective pharmacological inhibition of thromboxane A2 synthesis did not prevent arachidonate-induced aggregation of human platelets in vitro. Prevention was instead achieved by a combination of thromboxane A2 inhibitors with low concentrations of aspirin. The latter partially reduced the proaggregatory cyclooxygenase products that accumulated when thromboxane A2 synthesis was blocked. The aspirin concentrations did not affect per se either platelet aggregation or prostacyclin synthesis in cultured human endothelial cells. The combination of thromboxane synthetase inhibitors with low doses of aspirin may offer greater antithrombotic potential than either drug alone.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bertele, V -- Falanga, A -- Tomasiak, M -- Dejana, E -- Cerletti, C -- de Gaetano, G -- New York, N.Y. -- Science. 1983 Apr 29;220(4596):517-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6682245" target="_blank"〉PubMed〈/a〉
    Keywords: Aspirin/*pharmacology ; Blood Platelets/*drug effects/enzymology ; Dose-Response Relationship, Drug ; Drug Interactions ; Humans ; Imidazoles/pharmacology ; Methacrylates/pharmacology ; Oxidoreductases/*antagonists & inhibitors ; Platelet Aggregation/drug effects ; Thromboxane-A Synthase/*antagonists & inhibitors
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  • 36
    Publication Date: 1983-07-01
    Description: Mammalian atrial extracts possess natriuretic and diuretic activity. In experiments reported here it was found that atrial, but not ventricular, extract also causes relaxation of isolated vascular and nonvascular smooth muscle preparations. The smooth muscle relaxant activity of atrial extract was heat-stable and concentration-dependent and could be destroyed with protease. Rabbit aortic and chick rectum strips were used for the detection of atrial biological activity. The atrial activity was separated by column chromatography into two peaks having apparent molecular weights of 20,000 to 30,000 and less than 10,000. The atrial substance that copurified with the smooth muscle relaxant activity in both peaks caused natriuresis when injected into conscious rats. It appears that atria possess at least two peptides that elicit smooth muscle relaxation and natriuresis, suggesting an endogenous system of fluid volume regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Currie, M G -- Geller, D M -- Cole, B R -- Boylan, J G -- YuSheng, W -- Holmberg, S W -- Needleman, P -- New York, N.Y. -- Science. 1983 Jul 1;221(4605):71-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6857267" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atrial Function ; Chickens ; Chromatography, Gel ; Dogs ; Dose-Response Relationship, Drug ; Humans ; Molecular Weight ; Muscle, Smooth/drug effects ; Muscle, Smooth, Vascular/*drug effects ; Natriuresis/drug effects ; Rabbits ; Rats ; Swine ; Vasodilation/drug effects
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-04-15
    Description: Behavior of squirrel monkeys, maintained by the termination of stimuli associated with electric shock, was suppressed by response-dependent shock delivery. The effects of pentobarbital on this behavior depended on whether monkeys had previously received morphine. In monkeys without experience with drugs, pentobarbital increased responding. In monkeys with recent experience with morphine, however, pentobarbital resulted in a smaller increase or decrease in responding. The rate-decreasing effects of pentobarbital after a history of morphine administration could be reversed by the administration of d-amphetamine. These findings suggest that the behavioral effects of abused drugs may depend on previous experience with other drugs, even when those drugs are from a different pharmacological class.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Glowa, J R -- Barrett, J E -- DA 02658/DA/NIDA NIH HHS/ -- DA 02873/DA/NIDA NIH HHS/ -- MH 07658/MH/NIMH NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1983 Apr 15;220(4594):333-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6682244" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*drug effects ; Dextroamphetamine/pharmacology ; Dose-Response Relationship, Drug ; Drug Interactions ; Humans ; Macaca mulatta ; Male ; Morphine/pharmacology ; Pentobarbital/*pharmacology ; Saimiri ; Substance-Related Disorders/physiopathology
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  • 38
    Publication Date: 1983-12-23
    Description: Endotoxin-free thymosin fraction 5 elevated corticotropin, beta-endorphin, and cortisol in a dose- and time-dependent fashion when administered intravenously to prepubertal cynomolgus monkeys. Two synthetic component peptides of thymosin fraction 5 had no acute effects on pituitary function, suggesting that some other peptides in thymosin fraction 5 were responsible for its corticotropin-releasing activity. In agreement with these observations, total thymectomy of juvenile macaques was associated with decreases in plasma cortisol, corticotropin, and beta-endorphin. These findings indicate that the prepubertal primate thymus contains corticotropin-releasing activity that may contribute to a physiological immunoregulatory circuit between the developing immunological and pituitary-adrenal systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Healy, D L -- Hodgen, G D -- Schulte, H M -- Chrousos, G P -- Loriaux, D L -- Hall, N R -- Goldstein, A L -- CA 24974/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1983 Dec 23;222(4630):1353-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6318312" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenocorticotropic Hormone/*blood ; Animals ; Dose-Response Relationship, Drug ; Endorphins/blood ; Female ; Hydrocortisone/blood ; Kinetics ; Macaca fascicularis ; Thymectomy ; Thymosin/analogs & derivatives/*pharmacology ; Thymus Gland/*physiology ; beta-Endorphin
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-03-04
    Description: Efforts in estimating carcinogenic risk in humans from long-term exposure to chemical carcinogens have centered on the problem of low-dose extrapolation. For chemicals with metabolites that interact with DNA, it may be more meaningful to relate tumor response to the concentration of the DNA adducts in the target organ rather than to the applied dose. Many data suggest that the relation between tumor response and concentration of DNA adducts in the target organ may be linear. This implies that the nonlinearities of the dose-response curve for tumor induction may be due to the kinetic processes involved in the formation of carcinogen metabolite--DNA adducts. Of particular importance is the possibility that the kinetic processes may show a nonlinear "hockey-stick" like behavior which results from saturation of detoxification or DNA repair processes. The mathematical models typically used for low-dose extrapolation are shown potentially to overestimate risk by several orders of magnitude when nonlinear kinetics are present.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoel, D G -- Kaplan, N L -- Anderson, M W -- New York, N.Y. -- Science. 1983 Mar 4;219(4588):1032-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6823565" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinogens/*administration & dosage ; Cell Transformation, Neoplastic/*drug effects ; DNA, Neoplasm/genetics ; Dose-Response Relationship, Drug ; Humans ; Kinetics ; Models, Biological ; Neoplasms/*chemically induced ; Risk
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  • 40
    Publication Date: 1983-06-03
    Description: A synthetic analog of bovine parathyroid hormone (bPTH), [tyrosine-34] bPTH-(7-34)NH2, was found to inhibit parathyroid hormone action in vivo. When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3',5'-monophosphate. When infused alone at the same dose rate, the analog was devoid of agonist activity. The compound was prepared by following design principles developed for inhibitors of parathyroid hormone, and is believed to be the first antagonist of parathyroid hormone that is effective in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Horiuchi, N -- Holick, M F -- Potts, J T Jr -- Rosenblatt, M -- AM11749/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1983 Jun 3;220(4601):1053-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6302844" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Cyclic AMP/urine ; Dose-Response Relationship, Drug ; Male ; Parathyroid Hormone/*antagonists & inhibitors/*pharmacology ; Peptide Fragments/*pharmacology ; Phosphates/urine ; Rats
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  • 41
    Publication Date: 1983-04-01
    Description: The tissue culture condition that is required for the type of chromosome breakage seen at most fragile sites, namely, the absence of folic acid and thymidine in the medium, greatly enhanced micronucleus formation in proliferating lymphocyte cultures from normal individuals. This suggests that chromosome breakage at fragile sites and the apparently spontaneous damage that gives rise to micronuclei are controlled by the same mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacky, P B -- Beek, B -- Sutherland, G R -- New York, N.Y. -- Science. 1983 Apr 1;220(4592):69-70.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6828880" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Cell Nucleus/drug effects/ultrastructure ; Cells, Cultured ; Child ; *Chromosome Aberrations ; Chromosome Fragile Sites ; *Chromosome Fragility ; Culture Media ; Dose-Response Relationship, Drug ; Female ; Folic Acid/pharmacology ; Humans ; Lymphocytes/ultrastructure ; Male ; Middle Aged ; Thymidine/pharmacology
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  • 42
    Publication Date: 1983-11-25
    Description: Intracisternal injection of ovine corticotropin-releasing factor (CRF) into the pylorus-ligated rat or the rat with gastric fistula resulted in a dose-dependent inhibition of gastric secretion stimulated with pentagastrin or thyrotropin-releasing hormone. When injected into the lateral hypothalamus--but not when injected into the cerebral cortex--CRF suppressed pentagastrin-stimulated acid secretion. The inhibitory effect of CRF was blocked by vagotomy and adrenalectomy but not by hypophysectomy or naloxone treatment. These results indicate that CRF acts within the brain to inhibit gastric acid secretion through vagal and adrenal mechanisms and not through hypophysiotropic effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tache, Y -- Goto, Y -- Gunion, M W -- Vale, W -- River, J -- Brown, M -- AM30110/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1983 Nov 25;222(4626):935-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6415815" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenalectomy ; Animals ; Brain/*drug effects ; Cerebral Cortex/drug effects ; Corticotropin-Releasing Hormone/administration & dosage/*pharmacology ; Dose-Response Relationship, Drug ; Gastric Acid/*secretion ; Hypophysectomy ; Hypothalamus/drug effects ; Male ; Pentagastrin/antagonists & inhibitors ; Rats ; Rats, Inbred Strains ; Thyrotropin-Releasing Hormone/antagonists & inhibitors ; Vagotomy
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1984-08-17
    Description: The Interdisciplinary Panel on Carcinogenicity reviewed and reevaluated criteria for assessing evidence of carcinogenicity of chemical substances. The panel reviewed criteria applicable to data derived from human epidemiological studies and from both in vivo and in vitro laboratory studies. A critical appraisal of all these sources of information led to the conclusion that the characterization of human risk always requires interdisciplinary evaluation of the entire array of data on a case-by-case basis. Animal studies, whenever possible, should be augmented by studies of mechanisms, metabolism, and pharmacodynamics. Such studies may assist in assessing risk to man. Recognizing the utility of such data should point the way for better assessment in the future.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉New York, N.Y. -- Science. 1984 Aug 17;225(4663):682-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6463646" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Assay ; *Carcinogens/metabolism/pharmacology ; Carcinogens, Environmental ; Cell Transformation, Neoplastic ; Dose-Response Relationship, Drug ; Environmental Exposure ; Epidemiologic Methods ; Humans ; In Vitro Techniques ; Mixed Function Oxygenases/metabolism ; Mutagenicity Tests ; Neoplasms/chemically induced ; Risk ; Time Factors ; United States
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  • 44
    Publication Date: 1984-01-13
    Description: The cytotoxic activity of natural killer cells was investigated in rats subjected to one of two inescapable footshock stress paradigms, both of which induce analgesia, but only one via activation of opioid mechanisms. Splenic natural killer cell activity was suppressed by the opioid, but not the nonopioid, form of stress. This suppression was blocked by the opioid antagonist naltrexone. Similar suppression of natural killer activity was induced by high doses of morphine. These results suggest that endogenous opioid peptides mediate the suppressive effect of certain forms of stress on natural killer cell cytotoxicity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shavit, Y -- Lewis, J W -- Terman, G W -- Gale, R P -- Liebeskind, J C -- MH15795/MH/NIMH NIH HHS/ -- NS07628/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1984 Jan 13;223(4632):188-90.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6691146" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cytotoxicity, Immunologic/drug effects ; Dose-Response Relationship, Drug ; Endorphins/*physiology ; Female ; Killer Cells, Natural/*immunology ; Morphine/*pharmacology ; Naltrexone/pharmacology ; Rats ; Rats, Inbred F344 ; Stress, Physiological/*immunology
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  • 45
    Publication Date: 1984-06-15
    Description: In an insect, the tobacco hornworm Manduca sexta, the cerebral neuropeptide prothoracicotropic hormone (PTTH), the primary effector of postembryonic development, exists as two molecular forms. These two PTTH's elicit characteristic in vitro dose responses of activation of prothoracic glands from different developmental stages, an indication that during development the glands change in their sensitivity to the neurohormones. Both PTTH's are active in a specific in situ bioassay. Since they may be released in situ at stage-specific times to evoke distinctly different developmental responses, the PTTH neuroendocrine axis appears to be an effective system for determining the functions of molecular forms of a neurohormone in the regulation of growth and development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bollenbacher, W E -- Katahira, E J -- O'Brien, M -- Gilbert, L I -- Thomas, M K -- Agui, N -- Baumhover, A H -- AM-30118/AM/NIADDK NIH HHS/ -- AM-31642/AM/NIADDK NIH HHS/ -- NS-18791/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1984 Jun 15;224(4654):1243-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6732895" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Assay ; Bombyx ; Chromatography, Gel ; Dose-Response Relationship, Drug ; Insect Hormones/pharmacology/*physiology ; Insects/drug effects/growth & development/physiology ; Isoelectric Focusing ; Larva
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  • 46
    Publication Date: 1984-06-22
    Description: Treatment of exponentially growing Chinese hamster ovary cells with bleomycin causes a dose-dependent decrease in cell survival due to DNA damage. This lethal effect can be potentiated by the addition of a nonlethal dose of the anticalmodulin drug N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide ( W13 ) but not its inactive analog N-(4-aminobutyl)-2-naphthalenesulfonamide ( W12 ). By preventing the repair of damaged DNA, W13 also inhibits recovery from potentially lethal damage induced by bleomycin. These data suggest a role for calmodulin in the DNA repair pathway.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chafouleas, J G -- Bolton, W E -- Means, A R -- RR-05425/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1984 Jun 22;224(4655):1346-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6203171" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bleomycin/*pharmacology ; Calmodulin/*antagonists & inhibitors/*physiology ; Cell Division/drug effects ; Cell Line ; Cell Survival/drug effects ; Cricetinae ; Cricetulus ; DNA Repair/*drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Sulfonamides/pharmacology
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  • 47
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-05-27
    Description: Amiloride inhibited the ouabain-sensitive rate of oxygen consumption (QO2) of a suspension of rabbit intact proximal tubules in the presence of different concentrations of extracellular sodium. Measurements of the ouabain-sensitive QO2 in the presence of nystatin, the tissue sodium and potassium contents of the tubules in suspension, and the sodium- and potassium-dependent adenosinetriphosphatase (Na,K-ATPase) activity of lysed tubule membranes indicated that the effect of amiloride was due to a direct inhibition of the Na,K-ATPase activity of the proximal tubule.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soltoff, S P -- Mandel, L J -- AM26816/AM/NIADDK NIH HHS/ -- GM29256/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1983 May 27;220(4600):957-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6302840" target="_blank"〉PubMed〈/a〉
    Keywords: Amiloride/*pharmacology ; Animals ; Dose-Response Relationship, Drug ; Female ; Ion Channels/drug effects ; Kidney Tubules, Proximal/drug effects/*enzymology ; Nystatin/pharmacology ; Ouabain/pharmacology ; Oxygen Consumption/drug effects ; Pyrazines/*pharmacology ; Rabbits ; Rats ; Sodium/metabolism ; Sodium-Potassium-Exchanging ATPase/*antagonists & inhibitors/metabolism
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  • 48
    Publication Date: 1984-05-11
    Description: Arachidonate and other unsaturated long-chain fatty acids were found to activate protein kinase C from human neutrophils. Kinase activation by arachidonate required calcium and was enhanced by diolein but did not require exogenous phosphatidylserine. Submaximal levels of arachidonate also enhanced the affinity of the kinase for calcium during activation by phosphatidylserine. Thus the release of arachidonate, which is triggered in many cell types by ligand-receptor interactions, could play a second messenger role in the regulation of cellular function by activation of protein kinase C.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McPhail, L C -- Clayton, C C -- Snyderman, R -- 5PO1CA29589/CA/NCI NIH HHS/ -- 5RO-1DEO3738/DE/NIDCR NIH HHS/ -- New York, N.Y. -- Science. 1984 May 11;224(4649):622-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6231726" target="_blank"〉PubMed〈/a〉
    Keywords: Arachidonic Acid ; Arachidonic Acids/pharmacology ; Dose-Response Relationship, Drug ; Enzyme Activation ; Fatty Acids, Unsaturated/pharmacology/*physiology ; Humans ; Kinetics ; Neutrophils/enzymology ; Phosphatidylserines/pharmacology ; Protein Kinase C ; Protein Kinases/*metabolism
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  • 49
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1984-02-03
    Description: The neurotoxin kainic acid caused dose-dependent morphological changes in horizontal cells of the retinas of adult cats and rabbits. High concentrations of kainic acid killed the cells, but when exposed to sublethal doses they contracted their dendritic fields and sent sprouting processes into the inner retina. It appears that kainic acid can induce neuronal growth as well as degeneration and that the potential for morphological plasticity is still present in neurons of the adult mammalian retina.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peichl, L -- Bolz, J -- New York, N.Y. -- Science. 1984 Feb 3;223(4635):503-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6691162" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cats ; Dendrites/ultrastructure ; Dose-Response Relationship, Drug ; Kainic Acid/*pharmacology ; Nerve Degeneration/drug effects ; Neurons/cytology/*drug effects ; Pyrrolidines/*pharmacology ; Rabbits ; Retina/cytology/*drug effects
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  • 50
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-01-18
    Description: In view of similarities between the behavioral, biochemical, and electrophysiological effects of amphetamine and stress, we tested the hypothesis that presentation of a stressor, mild tail pressure, can sensitize an animal to the later effects of amphetamine, and vice versa. Our findings supported this hypothesis and suggest that amphetamine and at least some stressors may be interchangeable in their ability to induce a sensitization. The data raise the possibility that stress might be a common variable contributing to both amphetamine psychosis and some forms of schizophrenia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Antelman, S M -- Eichler, A J -- Black, C A -- Kocan, D -- New York, N.Y. -- Science. 1980 Jan 18;207(4428):329-31.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7188649" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/drug effects/*physiology ; Dextroamphetamine/*pharmacology ; Dopamine/physiology ; Dose-Response Relationship, Drug ; Haloperidol/pharmacology ; Humans ; Male ; Rats ; Schizophrenia/physiopathology ; Stereotyped Behavior/drug effects ; Stress, Physiological/*physiopathology
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  • 51
    Publication Date: 1980-07-25
    Description: Serotonin infused into the lateral ventricle in rats produced a dose-dependent depression of the acoustic startle reflex. When infused onto the spinal cord, serotonin produced a dose-dependent increase in startle. Thus the same neurotransmitter can modulate the same behavior in opposite ways, depending on which part of the central nervous system is involved.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Davis, M -- Strachan, D I -- Kass, E -- New York, N.Y. -- Science. 1980 Jul 25;209(4455):521-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7394520" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Kinetics ; Male ; Rats ; Reflex, Acoustic/*drug effects ; Reflex, Startle/*drug effects ; Serotonin/*pharmacology
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  • 52
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-10-10
    Description: Maternal pain thresholds in rats were determined during various stages of pregnancy and parturition by measuring the intensity of electric shock that elicited reflexive jumping. There was a gradual rise in the pain threshold between 16 and 4 days prior to parturition and a more abrupt rise 1 to 2 days before that event. This increase was abolished by long-term administration of the narcotic antagonist naltrexone. The endorphin system is thus an important component of intrinsic mechanisms that modulate responsiveness to aversive stimuli. The data also demonstrate the activation during pregnancy of an endorphin system that is apparently quiescent in nonpregnant female rats treated the same way.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gintzler, A R -- NIMH GRANT DA01771/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1980 Oct 10;210(4466):193-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7414330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Endorphins/antagonists & inhibitors/*physiology ; Female ; Naltrexone/pharmacology ; Pain/*physiopathology ; Pregnancy ; *Pregnancy, Animal ; Rats ; Time Factors
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-04-25
    Description: Tumor-promoting phorbol esters stimulated mouse bone marrow cells to form myeloid colonies in agar cultures without added colony-stimulating factors. The colony-stimulating ability of various phorbol esters correlated well with their ability to promote skin tumors in vivo. These results suggest that phorbol esters mimic the action of specific colony-stimulating factors that regulate growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stuart, R K -- Hamilton, J A -- New York, N.Y. -- Science. 1980 Apr 25;208(4442):402-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6245446" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division/drug effects ; Cells, Cultured ; *Colony-Forming Units Assay ; Colony-Stimulating Factors/pharmacology ; Dose-Response Relationship, Drug ; Hematopoietic Stem Cells/*drug effects ; Macrophages/physiology ; Mice ; Monocytes/physiology ; Phorbol Esters/pharmacology ; Phorbols/*pharmacology ; Receptors, Cell Surface/drug effects ; Structure-Activity Relationship ; Tetradecanoylphorbol Acetate/*pharmacology
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  • 54
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-03-13
    Description: 3-Deazaadenosine, an inhibitor of methylation, increased the frequency of conversion of 3T3-L1 fibroblasts to fat cells in a dose-dependent manner. Once converted, the 3T3-L1 fat cells retained their adipose morphology and accumulated triglycerides even when 3-deazaadenosine was removed from the culture medium. 3-Deazaadenosine may perturb cellular methylation and thereby lead to an increase in the frequency of differentiation of 3T3-L1 fibroblasts to fat cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chiang, P K -- New York, N.Y. -- Science. 1981 Mar 13;211(4487):1164-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7466386" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/*cytology ; Animals ; Carnitine/pharmacology ; Cell Differentiation/*drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Fibroblasts/cytology ; Methylation ; Mice ; Ribonucleosides/*pharmacology ; Tubercidin/*pharmacology
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  • 55
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-11-13
    Description: Circulating metallothionein was measured by radioimmunoassay over a 13-day period in male Sprague-Dawley rats that received a sequence of three intraperitoneal injections (at 3-day intervals) of either 5 milligrams of zinc or 0.8 milligrams of cadmium per kilogram of body weight. These amounts of zinc and cadmium produced metallothionein concentrations in the range of 2 to 5 nanograms per milliliter of serum (zinc) and 2 to 15 nanograms per milliliter of serum (cadmium). In control rats given saline injections over the same period the metallothionein concentration ranged from 1 to 3 nanograms per milliliter of serum.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garvey, J S -- Chang, C C -- ES 01629/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1981 Nov 13;214(4522):805-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7292012" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cadmium/*pharmacology ; Dose-Response Relationship, Drug ; Male ; Metalloproteins/*blood ; Metallothionein/*blood/immunology ; Radioimmunoassay ; Rats ; Rats, Inbred Strains ; Zinc/*pharmacology
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  • 56
    Publication Date: 1982-10-29
    Description: Somatostatin perfused in canine pancreases at 10 to 20 picograms per milliliter or 10 to 20 percent of the pancreatic vein somatostatin concentration inhibited insulin and glucagon secretion. This suggests that the high local concentration of endogenous somatostatin is not in contact with somatostatin receptors of the islets. The integrity of this separation may determine the sensitivity of islet cells to circulating somatostatin.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawai, K -- Ipp, E -- Orci, L -- Perrelet, A -- Unger, R H -- New York, N.Y. -- Science. 1982 Oct 29;218(4571):477-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6126931" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dogs ; Dose-Response Relationship, Drug ; Glucagon/secretion ; Insulin/secretion ; Intercellular Junctions/physiology ; Islets of Langerhans/*secretion ; Receptors, Cell Surface/physiology ; Receptors, Somatostatin ; Somatostatin/*blood/metabolism
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  • 57
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-02-19
    Description: Specific receptors for gonadotropin-releasing hormone (GnRH) in cultured rat pituitary cells were increased by subnanomolar concentrations of GnRH agonists and decreased by high concentrations of these peptides. The antagonist [D-Phe2, Pro3, D-Phe6]GnRH did not alter GnRH binding capacity and blocked the increase in sites induced by GnRH. These findings provide direct evidence for the homologous regulation of GnRH receptors by physiological concentrations of the hypothalamic peptide, an action that could mediate the cyclical and postcastration increases in GnRH receptors and responsiveness of the pituitary gonadotrophs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loumaye, E -- Catt, K J -- New York, N.Y. -- Science. 1982 Feb 19;215(4535):983-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6296998" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Dose-Response Relationship, Drug ; Feedback ; Female ; Gonadotropin-Releasing Hormone/analogs & derivatives/metabolism/pharmacology ; Pituitary Gland/secretion ; Pituitary Hormone-Releasing Hormones/*metabolism/pharmacology ; Rats ; Receptors, Cell Surface/*pharmacology ; Receptors, LHRH
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  • 58
    Publication Date: 1982-07-30
    Description: Cysteamine rapidly reduces the concentration of prolactin in pituitary tissue in vivo and in vitro. The effect is dose-dependent, reversible, and cannot be accounted for by prolactin release. Cysteamine does not appear to exert its effect through dopamine receptors and does not alter lactotrope morphology, as determined by electron microscopy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millard, W J -- Sagar, S M -- Landis, D M -- Martin, J B -- AM 26252/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1982 Jul 30;217(4558):452-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7089575" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cysteamine/*pharmacology ; Domperidone/pharmacology ; Dose-Response Relationship, Drug ; Kinetics ; Male ; Pituitary Gland, Anterior/*metabolism ; Prolactin/analysis/*metabolism/secretion ; Rats ; Receptors, Dopamine/physiology ; Spiperone/pharmacology
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  • 59
    Publication Date: 1982-04-23
    Description: A model of "overdose" deaths among heroin addicts is proposed which emphasizes recent findings concerning the contribution of drug-associated environmental cues to drug tolerance. Results of animal experiments performed to evaluate this model suggest that conditioned drug-anticipatory responses, in addition to pharmacological factors, affect heroin-induced mortality.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Siegel, S -- Hinson, R E -- Krank, M D -- McCully, J -- New York, N.Y. -- Science. 1982 Apr 23;216(4544):436-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7200260" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Tolerance ; Environment ; Heroin/*pharmacology ; Humans ; Male ; Rats ; Substance-Related Disorders/*physiopathology
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-07-02
    Description: Nine expert drivers operated an instrumented vehicle in tests over a highway at night after being treated with diazepam (5 and 10 milligrams), a placebo, and nothing. They reacted to 10 milligrams of diazepam with increased lateral position variability. Potentially dangerous impairment was inferred from the reactions of some subjects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉O'Hanlon, J F -- Haak, T W -- Blaauw, G J -- Riemersma, J B -- New York, N.Y. -- Science. 1982 Jul 2;217(4554):79-81.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7089544" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Automobile Driving ; Diazepam/*pharmacology ; Dose-Response Relationship, Drug ; Double-Blind Method ; Functional Laterality ; Humans ; Male ; Motor Activity/*drug effects ; Placebos
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  • 61
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-06-03
    Description: Dose-response studies of the inhibition of lipolysis by insulin in isolated human adipocytes were conducted with the use of a sensitive bioluminescent assay of glycerol release. The addition of glucose to the incubation medium was associated with an increase in insulin sensitivity and an increase in the maximum insulin effect. The results suggest that glucose plays an important role in regulating the antilipolytic action of insulin in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arner, P -- Bolinder, J -- Ostman, J -- New York, N.Y. -- Science. 1983 Jun 3;220(4601):1057-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6342138" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/cytology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Drug Synergism ; Glucose/*pharmacology ; Humans ; Insulin/*pharmacology ; Isoproterenol/pharmacology ; Lipolysis/*drug effects
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  • 62
    Publication Date: 1982-04-09
    Description: Maximum expiratory flow rate at 30 percent of vital capacity above residual volume served as an index of airway obstruction in comparing the effects of leukotriene C and histamine administered by aerosol to five normal persons. Leukotriene C was 600 to 9500 times more potent than histamine on a molar basis in producing an equivalent decrement in the residual volume. The leukotriene C response was slow in onset and prolonged, reminiscent of the effects of aerosol allergen challenge in asthmatic allergic subjects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weiss, J W -- Drazen, J M -- Coles, N -- McFadden, E R Jr -- Weller, P F -- Corey, E J -- Lewis, R A -- Austen, K F -- AI-00399/AI/NIAID NIH HHS/ -- AI-07722/AI/NIAID NIH HHS/ -- AI-10356/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1982 Apr 9;216(4542):196-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7063880" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Airway Resistance/*drug effects ; Bronchi/*drug effects ; Dose-Response Relationship, Drug ; Female ; Histamine/pharmacology ; Humans ; Male ; Middle Aged ; Prostaglandins F/pharmacology ; SRS-A/*pharmacology ; Time Factors
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  • 63
    Publication Date: 1983-09-23
    Description: A peptide that accumulated as the major product during the proteolysis of arginine vasopressin by rat brain synaptic membranes was isolated and its structure was shown to be the hexapeptide pGlu-Asn-Cys(Cys)-Pro-Arg-Gly-NH2. When administered intracerebroventricularly in extremely low doses, this vasopressin fragment and its desglycinamide derivative facilitated memory consolidation in a passive avoidance situation. These vasopressin metabolites, which are devoid of pressor activity, constitute highly potent neuropeptides with selective effects on memory and related processes; they are activated via proteolytic processing of vasopressin by brain peptidases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burbach, J P -- Kovacs, G L -- de Wied, D -- van Nispen, J W -- Greven, H M -- New York, N.Y. -- Science. 1983 Sep 23;221(4617):1310-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6351252" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Arginine Vasopressin/*metabolism/physiology ; Avoidance Learning/physiology ; Brain/*metabolism ; Dose-Response Relationship, Drug ; Male ; Memory/*physiology ; Oligopeptides/metabolism ; Peptide Hydrolases/metabolism ; Rats ; Structure-Activity Relationship
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-12-16
    Description: The mouse neuroblastoma-rat glioma hybrid cell line NG108-15 was used to study the acute and chronic interaction of ethanol with intact neural cells. In the short term, ethanol inhibited opiate receptor binding, but after long-term exposure the cells exhibited an apparent adaptive increase in the number of opiate binding sites; this was reversible when ethanol was withdrawn. High concentrations of ethanol (200 mM) increased opiate binding after 18 to 24 hours, whereas lower concentrations (25 to 50 mM) produced similar changes after 2 weeks. This model system has potential for exploring the cellular and molecular mechanisms underlying ethanol intoxication, tolerance, and withdrawal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Charness, M E -- Gordon, A S -- Diamond, I -- New York, N.Y. -- Science. 1983 Dec 16;222(4629):1246-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6316506" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Dose-Response Relationship, Drug ; Enkephalin, Methionine/analogs & derivatives/metabolism ; Ethanol/*pharmacology ; Glioma ; Hybrid Cells ; Mice ; Neuroblastoma ; Neurons/*drug effects/metabolism ; Rats ; Receptors, Opioid/*drug effects/metabolism ; Time Factors
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  • 65
    Publication Date: 1983-10-21
    Description: Fluoride is one of the most potent but least well understood stimulators of bone formation in vivo. Bone formation was shown to arise from direct effects on bone cells. Treatment with sodium fluoride increased proliferation and alkaline phosphatase activity of bone cells in vitro and increased bone formation in embryonic calvaria at concentrations that stimulate bone formation in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Farley, J R -- Wergedal, J E -- Baylink, D J -- AM31061/AM/NIADDK NIH HHS/ -- AM31062/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1983 Oct 21;222(4621):330-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6623079" target="_blank"〉PubMed〈/a〉
    Keywords: Alkaline Phosphatase/*metabolism ; Animals ; Bone Development/*drug effects ; Bone and Bones/*cytology/embryology/enzymology ; Cell Division/drug effects ; Cells, Cultured ; Chick Embryo ; Dose-Response Relationship, Drug ; Fluorides/*pharmacology ; Parathyroid Hormone/pharmacology
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  • 66
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-04-01
    Description: The terrestrial snail Cepaea nemoralis, when placed on a 40 degrees C hot plate, lifts the anterior portion of its foot. The latency of this response is influenced by morphine and by naloxone in a dose-dependent and time-dependent manner. Morphine increases the time taken to respond, whereas naloxone reduces it. Furthermore, naloxone abolishes the effect of morphine. These results indicate that an opiate system may have a role in this behavior, which resembles that reported in vertebrates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kavaliers, M -- Hirst, M -- Teskey, G C -- New York, N.Y. -- Science. 1983 Apr 1;220(4592):99-101.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6298941" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/drug effects/*physiology ; Dose-Response Relationship, Drug ; Hot Temperature ; Morphine/pharmacology ; Naloxone/pharmacology ; Receptors, Opioid/drug effects/*physiology ; Snails/*physiology ; Thermoreceptors/physiology
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  • 67
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-09-09
    Description: Peptidergic-noradrenergic interactions were examined in explants of rat sympathetic superior cervical ganglia and in cultures of dissociated cells. The putative peptide transmitters substance P and somatostatin each increased the activity of the catecholamine-synthesizing enzyme tyrosine hydroxylase after 1 week of exposure in culture. Maximal increases occurred at 10(-7) molar for each peptide, and either increasing or decreasing the concentration reduced the effects. Similar increases in tyrosine hydroxylase were produced by a metabolically stable agonist of substance P, while a substance P antagonist prevented the effects of the agonist. The data suggest that the increased tyrosine hydroxylase activity was mediated by peptide interaction with specific substance P receptors and that peptides may modulate sympathetic catecholaminergic function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kessler, J A -- Adler, J E -- Black, I B -- New York, N.Y. -- Science. 1983 Sep 9;221(4615):1059-61.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6192502" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacitracin/pharmacology ; Captopril/pharmacology ; Cells, Cultured ; Culture Techniques ; Dose-Response Relationship, Drug ; Ganglia, Sympathetic/*enzymology ; Rats ; Somatostatin/*pharmacology ; Substance P/*pharmacology ; Tyrosine 3-Monooxygenase/*metabolism
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  • 68
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-04-29
    Description: Compared to nonpregnant controls, pregnant mice injected with phenobarbital had lower concentrations of the drug in the plasma but equivalent concentrations in the brain. In spite of the similar concentrations in the brain, the behavioral response to phenobarbital was greater for pregnant than nonpregnant mice. These results suggest that the concentration of phenobarbital in the plasma, which is commonly used as a basis for adjusting phenobarbital dosage during pregnancy, is not an appropriate indicator of the dynamics of the drug.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Middaugh, L D -- Zemp, J W -- Boggan, W O -- AA03532/AA/NIAAA NIH HHS/ -- DA00041/DA/NIDA NIH HHS/ -- DA01750/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1983 Apr 29;220(4596):534-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6836299" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Chemistry ; Dose-Response Relationship, Drug ; Female ; Humans ; Mice ; Mice, Inbred C57BL ; Motor Activity/drug effects ; Phenobarbital/analysis/*metabolism/pharmacology ; *Pregnancy/drug effects ; Time Factors
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  • 69
    Publication Date: 1983-07-08
    Description: Centrally administered alpha-melanocyte stimulating hormone is much more potent in reducing fever than the widely used antipyretic acetaminophen. This finding supports the hypothesis that the endogenous neuropeptide has a role in the limitation of fever and suggests that it may be clinically useful as an antipyretic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Murphy, M T -- Richards, D B -- Lipton, J M -- NS 10046/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1983 Jul 8;221(4606):192-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6602381" target="_blank"〉PubMed〈/a〉
    Keywords: Acetaminophen/pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Body Temperature/drug effects ; Dose-Response Relationship, Drug ; Fever/drug therapy ; Humans ; Melanocyte-Stimulating Hormones/*pharmacology ; Rabbits
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  • 70
    Publication Date: 1981-06-12
    Description: Somatomedin-C stimulates somatostatin release to a maximum of 390 percent of basal release during short-term (20-minute) incubation of rat hypothalamus. It has no effect on basal or stimulated growth hormone release from primary cultures of rat adenohypophyseal cells during a 4-hour incubation, but inhibits stimulated release by more that 90 percent after 24 hours. These findings suggest that somatomedin-C participates in the growth hormone negative feedback loop with an immediate effect on hypothalamic somatostatin and a delayed effect on the anterior pituitary.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berelowitz, M -- Szabo, M -- Frohman, L A -- Firestone, S -- Chu, L -- Hintz, R L -- AM 18722/AM/NIADDK NIH HHS/ -- AM 24085/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1981 Jun 12;212(4500):1279-81.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6262917" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bucladesine/pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Feedback ; Growth Hormone/pharmacology/*secretion ; Hypothalamus/drug effects/*physiology ; Insulin-Like Growth Factor I ; Kinetics ; Pituitary Gland, Anterior/drug effects/*secretion ; Rats ; Somatomedins/*pharmacology
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  • 71
    Publication Date: 1981-02-13
    Description: Inosine, 2-deoxyinosine, and 2-deoxyguanosine completely reversed the increase in exploratory activity elicited in mice by diazepam. The inhibition of exploratory behavior by purines occurred at doses that when given alone have no effect on exploratory behavior. 7-Methylinosine, which does not bind to the brain benzodiazepine binding site in vitro, had no effect on the diazepam-induced increase in exploratory behavior. Behavioral effects produced by various combinations of inosine and diazepam indicate that the interaction between purine and benzodiazepine is antagonistic and support the hypothesis that the naturally occurring purines function in anxiety-related behaviors that respond to benzodiazepine treatment.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crawley, J N -- Marangos, P J -- Paul, S M -- Skolnick, P -- Goodwin, F K -- New York, N.Y. -- Science. 1981 Feb 13;211(4483):725-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6256859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/*drug effects ; Behavior, Animal/drug effects ; Diazepam/*antagonists & inhibitors ; Dose-Response Relationship, Drug ; Humans ; Inosine/*pharmacology ; Male ; Mice ; Receptors, Drug/*drug effects ; Receptors, GABA-A
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-07-17
    Description: Systemic administration of the neuroleptic drug alpha-flupenthixol attenuated lever-pressing behavior in rats responding for rewarding brain stimulation. The magnitude of this attenuation was dose-dependent and resembled the effects of reward reduction and termination. However, when the operant response requirements of the same rats were changed to nose poking, identical drug treatments produced relatively little attenuation in performance. These data do not support the belief that neuroleptics produce a general state of anhedonia. Rather, the apparent suppression of reinforced behaviors depends at least in part on the kinetic requirements of the response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ettenberg, A -- Koob, G F -- Bloom, F E -- New York, N.Y. -- Science. 1981 Jul 17;213(4505):357-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7244622" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/physiology ; Conditioning (Psychology)/*drug effects ; Dose-Response Relationship, Drug ; Electroshock ; Flupenthixol/*pharmacology ; Male ; Rats ; *Reward ; Thioxanthenes/*pharmacology
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  • 73
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lappe, M -- Hooper, K -- Blake, E -- Pfund, N -- Gardner, E -- Rosenberg, J -- New York, N.Y. -- Science. 1981 Jan 23;211(4480):332-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7221543" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Assay ; *Carcinogens ; Dose-Response Relationship, Drug ; Humans ; Species Specificity
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  • 74
    Publication Date: 1981-05-22
    Description: This study suggests one mechanism by which alveolar macrophages accumulate in the lung in pulmonary emphysema: elastin fragments generated at the diseased sites are potent chemoattractants for monocytes, the precursors of the macrophages. The most chemotactic elastin fragments have a molecular weight between 10,000 and 50,000 and are active at concentrations as low as 3 nanograms per milliliter. By comparison, elastin fragments with higher molecular weights and desmosines are active at concentrations greater than 0.3 microgram per milliliter. In addition, preincubation of monocytes with the 10,000- to 50,000-dalton elastin impairs the ability of the cells to migrate toward elastin fragments but not toward activated serum. Fragments of tropoelastin are not chemotactic for monocytes. Because elastin, but not tropoelastin, contains lysyl-derived cross-links, these structures may be the active chemotactic site on the elastin fragments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hunninghake, G W -- Davidson, J M -- Rennard, S -- Szapiel, S -- Gadek, J E -- Crystal, R G -- New York, N.Y. -- Science. 1981 May 22;212(4497):925-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7233186" target="_blank"〉PubMed〈/a〉
    Keywords: Cells, Cultured ; Chemotaxis, Leukocyte/*drug effects ; Dose-Response Relationship, Drug ; Elastin/*analogs & derivatives/*pharmacology ; Humans ; Macrophages/physiology ; Monocytes/*physiology ; Peptide Fragments/pharmacology ; Pulmonary Emphysema/*physiopathology ; Structure-Activity Relationship ; Tropoelastin/*pharmacology
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  • 75
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-02-20
    Description: A National Research Council report has recommended practices for safe handling and disposal of hazardous chemicals in laboratories. They are a practical alternative to detailed regulations on individual chemicals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McKusick, B C -- New York, N.Y. -- Science. 1981 Feb 20;211(4484):777-80.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7466359" target="_blank"〉PubMed〈/a〉
    Keywords: Air Pollutants, Occupational/adverse effects ; Dose-Response Relationship, Drug ; Explosions/prevention & control ; Laboratories/*standards ; *Occupational Medicine ; Research ; Ventilation
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  • 76
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-11-20
    Description: The nature and extent of positive evidence associated with animal carcinogens vary widely, yet present regulatory policy does not permit adequate discrimination among the many carcinogenic substances. Most are treated as if they pose equal potential risk to humans, and this is not consistent with the available data. Without knowledge of carcinogenic mechanisms, the evaluation of responses in intact mammalian surrogates best reflects the potential levels of human risk. An example of a scoring system is proposed by which animal carcinogens are ranked according to the most relevant toxicological evidence derived from animal and genotoxicity studies. Different classes of animal carcinogens could thus be recognized and would permit several regulatory options and provide a means to establish priorities for public and scientific concerns.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Squire, R A -- New York, N.Y. -- Science. 1981 Nov 20;214(4523):877-80.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7302565" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Carcinogens/toxicity ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical/*methods ; Humans ; Neoplasms/chemically induced ; Neoplasms, Experimental/*chemically induced ; Risk
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  • 77
    Publication Date: 1981-11-06
    Description: Thyrotropin-releasing hormone was microinjected into the dorsal hippocampus of ground squirrels (Citellus lateralis) when they were at different levels of arousal, as assessed by electrophysiological and behavioral criteria. When administered to the awake animal, thyrotropin-releasing hormone produced dose-dependent decreases in body temperature accompanied by behavioral quieting and reductions in metabolic rate and electromyographic activity. The magnitude of these effects was greater when the peptide was microinjected during a period of behavioral activation. In contrast, administration of the peptide during slow wave sleep produced increased thermogenesis, an increase in electromyographic activity, and an increase in the amount of electroencephalographic desynchronization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stanton, T L -- Bechman, A L -- Winokur, A -- New York, N.Y. -- Science. 1981 Nov 6;214(4521):678-81.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6794147" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arousal/*drug effects ; Body Temperature Regulation/*drug effects ; Dose-Response Relationship, Drug ; Female ; Hippocampus/*drug effects ; Male ; Sciuridae/*physiology ; Thyrotropin-Releasing Hormone/*pharmacology ; Wakefulness/drug effects
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  • 78
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-06-25
    Description: When injected continuously into the lateral ventricles of the rat, somatostatin increased the frequency of the migrating myoelectric complexes of the small intestine in a dose-related manner. A significant increase was obtained at a dose as low as 0.066 picomole per minute. In contrast, cholecystokinin octapeptide decreased the frequency of the migrating myoelectric complex of the small intestine or disrupted this pattern when injected into the lateral ventricle at rates of 0.073 to 0.23 picomole per minute. These findings support the hypothesis that somatostatin and cholecystokinin octapeptide act on central nervous system structures that are involved in the control of intestinal motility.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bueno, L -- Ferre, J P -- New York, N.Y. -- Science. 1982 Jun 25;216(4553):1427-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6124037" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cholecystokinin/administration & dosage/analogs & derivatives/*pharmacology ; Dose-Response Relationship, Drug ; *Gastrointestinal Motility ; Injections, Intraventricular ; Male ; Rats ; Rats, Inbred Strains ; Somatostatin/administration & dosage/*pharmacology
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  • 79
    Publication Date: 1982-02-05
    Description: The population dynamics of single-cell stimulation was analyzed by monitoring autofluorescence by flow cytometry. Stimulation of the respiratory burst in human neutrophils by 12-O-tetradecanoyl phorbol-13-acetate (TPA) caused a decline in highly fluorescent cells (characteristic of resting neutrophils) and a corresponding increase in the number of weakly fluorescent cells (characteristic of activated neutrophils). Increasing concentrations of TPA caused increasing numbers of cells to shift from the highly fluorescent population to the weakly fluorescent population without the appearance of intermediate populations. Thus the neutrophil respiratory burst, a component of neutrophil cytotoxic response, is triggered in an all-or none fashion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hafeman, D G -- McConnell, H M -- Gray, J W -- Dean, P N -- 2R01 AI13587/AI/NIAID NIH HHS/ -- CA14533/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1982 Feb 5;215(4533):673-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6800035" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Aggregation/drug effects ; Dose-Response Relationship, Drug ; Edetic Acid/pharmacology ; Flow Cytometry ; Microscopy, Fluorescence ; NAD/*metabolism ; Neutrophils/drug effects/*physiology ; Oxidation-Reduction ; Oxygen/metabolism ; Phorbols/*pharmacology ; Tetradecanoylphorbol Acetate/*pharmacology
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  • 80
    Publication Date: 1982-08-27
    Description: A low intake of dietary cadmium induces specific dose-dependent functional and biochemical changes in the cardiovascular tissues of rats. Maximum changes occur when the cadmium intake is 10 to 20 micrograms per kilogram of body weight per day. The changes reflect the accumulation of "critical" concentrations of cadmium in the cardiovascular tissues. The biologic activity of cadmium is demonstrated for intakes that approach those of the average American adult exposed to the usual environmental concentrations of the element but not to industrial concentrations. The sensitivity of the cardiovascular system to low doses of cadmium could not be anticipated by extrapolation from data on exposure to high concentrations of cadmium. The data support the hypothesis that ingested or inhaled environmental cadmium may contribute to essential hypertension in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kopp, S J -- Glonek, T -- Perry, H M Jr -- Erlanger, M -- Perry, E F -- ESO2397/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1982 Aug 27;217(4562):837-9.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6213041" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Animals ; Blood Pressure/drug effects ; Cadmium/*adverse effects ; Cardiovascular System/*drug effects ; Dose-Response Relationship, Drug ; Environmental Exposure ; Female ; Heart/drug effects ; Humans ; Kidney/drug effects/metabolism ; Liver/drug effects/metabolism ; Myocardium/metabolism ; Phosphocreatine/metabolism ; Rats
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  • 81
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-08-12
    Description: Daytime administration of 5-hydroxytryptophan to sheep elevated serum melatonin more than sevenfold within 2 hours. This suggests that administration of 5-hydroxytryptophan could be used as the basis of a clinical test of pineal function and that melatonin might mediate some clinical effects of 5-hydroxytryptophan.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Namboodiri, M A -- Sugden, D -- Klein, D C -- Mefford, I N -- New York, N.Y. -- Science. 1983 Aug 12;221(4611):659-61.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6867734" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Humans ; Male ; Melatonin/*blood ; Pineal Gland/physiology ; Rats ; Serotonin/*pharmacology ; Sheep ; Tryptophan/pharmacology
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  • 82
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-03-04
    Description: Calcium ions activate muscle contraction. The mechanism depends on the calcium sensitivity of the proteins that regulate contraction. Evidence is presented for the reverse phenomenon, where contraction modulates calcium sensitivity. Increasing the force level increased calcium sensitivity in intact fibers showing that the relation between force and calcium is not unique. A particular calcium concentration can maintain a higher force level than it can create. The results were confirmed in skinned fiber experiments. Transient reduction of the force led to a transient reduction in calcium binding, suggesting a simple mechanism for the hysteresis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ridgway, E B -- Gordon, A M -- Martyn, D A -- NS 08384/NS/NINDS NIH HHS/ -- NS 10919/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1983 Mar 4;219(4588):1075-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6823567" target="_blank"〉PubMed〈/a〉
    Keywords: Aequorin ; Animals ; Calcium/metabolism/*physiology ; Dose-Response Relationship, Drug ; *Muscle Contraction ; Protein Binding ; Thoracica
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  • 83
    Publication Date: 1983-06-10
    Description: Treatment of spleen cells derived from adult thymectomized mice with thymosin fraction 5 resulted in a rapid and dose-dependent stimulation of the release of immunoreactive prostaglandin E2. The release of prostaglandin E2 was associated with induction of theta antigen and was totally inhibited by indomethacin. In contrast, prostaglandin E2 release from spleen cells from intact donors was inhibited by treatment with fraction 5. The data support the concept that prostaglandin E2 mediates the effects of thymosin fraction 5 on lymphocytes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rinaldi Garaci, C -- Favalli, C -- Del Gobbo, V -- Garaci, E -- Jaffe, B M -- New York, N.Y. -- Science. 1983 Jun 10;220(4602):1163-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6574601" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dinoprostone ; Dose-Response Relationship, Drug ; Indomethacin/pharmacology ; Lymphocytes/drug effects/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Prostaglandins E/*physiology ; Spleen/drug effects/physiology ; Thymectomy ; Thymosin/*pharmacology ; Thymus Hormones/*pharmacology
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1981-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ehrenstein, G -- Huang, L Y -- New York, N.Y. -- Science. 1981 Dec 18;214(4527):1365-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7313696" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; Dose-Response Relationship, Drug ; Drug Synergism ; *Drug-Related Side Effects and Adverse Reactions ; Models, Biological ; Receptors, Drug/*drug effects
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  • 85
    Publication Date: 1981-02-06
    Description: Metkephamid is an analog of methionine enkephalin that retains high affinity for the delta receptor and is a systemically active analgesic. Since it is at least 100 times more potent than morphine as an analgesic when placed directly into the lateral ventricles, and is 30 to 100 times more potent on the delta receptor and yet is roughly equipotent on the mu receptor in vitro, it is concluded that it probably produces analgesia by action on delta receptors as well as, or rather than, on mu receptors. It has less tendency to produce respiratory depression, tolerance, and physical dependence than standard analgesics, and it is presently undergoing clinical trial.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Frederickson, R C -- Smithwick, E L -- Shuman, R -- Bemis, K G -- New York, N.Y. -- Science. 1981 Feb 6;211(4482):603-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6256856" target="_blank"〉PubMed〈/a〉
    Keywords: *Analgesics ; Animals ; Brain/*drug effects ; Dose-Response Relationship, Drug ; Endorphins/*pharmacology ; *Enkephalin, Methionine/*analogs & derivatives ; Enkephalins/*pharmacology ; Humans ; Kinetics ; Male ; Mice ; Rats ; Receptors, Opioid/*drug effects ; Structure-Activity Relationship ; Substance-Related Disorders/etiology
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  • 86
    Publication Date: 1982-12-24
    Description: alpha-Factor, a tridecapeptide mating pheromone of yeast (Saccharomyces cerevisiae), has extensive sequence homology with the hypothalamic decapeptide gonadotropin-releasing hormone (GnRH). Both synthetic and natural preparations of alpha-mating factor were found to bind specifically to rat pituitary GnRH receptors and to stimulate the release of luteinizing hormone from cultured gonadotrophs. The ability of the yeast pheromone to reproduce the biological actions of GnRH in the mammalian pituitary gland indicates that the structural and functional properties of GnRH-related peptides may have been highly conserved during evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Loumaye, E -- Thorner, J -- Catt, K J -- New York, N.Y. -- Science. 1982 Dec 24;218(4579):1323-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6293058" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Luteinizing Hormone/metabolism ; Peptides/*pharmacology ; Pituitary Gland/drug effects/metabolism ; Rats ; Receptors, Cell Surface/*drug effects ; Receptors, LHRH ; Saccharomyces cerevisiae/*analysis
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  • 87
    Publication Date: 1982-08-20
    Description: Concentrations of prolactin and growth hormone in the serum of rats were significantly increased by morphine. Dose response studies demonstrated that maximum prolactin release required lower doses of morphine than those needed for the maximum growth hormone response. Selective blockade of mu 1 (high affinity) opiate receptor with the irreversible antagonist naloxazone reduced morphine-induced peak concentrations of prolactin by 80 percent while increasing peak growth hormone levels by 250 percent. These results suggest different receptor mechanisms for the opiate modulation of the two hormones. The mu 1 (high affinity) receptor sites appear to mediate the morphine-induced release of prolactin but not growth hormone.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Spiegel, K -- Kourides, I A -- Pasternak, G W -- CA 23185/CA/NCI NIH HHS/ -- DA 002615/DA/NIDA NIH HHS/ -- P32 GM07547/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1982 Aug 20;217(4561):745-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6285470" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dose-Response Relationship, Drug ; Growth Hormone/*secretion ; Male ; Morphine/*pharmacology ; Naloxone/analogs & derivatives/pharmacology ; Prolactin/*secretion ; Radioimmunoassay ; Rats ; Rats, Inbred Strains ; Receptors, Opioid/*physiology
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  • 88
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-01-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crump, K S -- New York, N.Y. -- Science. 1983 Jan 21;219(4582):236-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6849134" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinogens/*administration & dosage ; Dose-Response Relationship, Drug ; Humans ; Models, Biological
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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-03-28
    Description: Groups of three to four mice were gavaged with aqueous solutions of 2 milligrams of morpholine, after which they were exposed to nitrogen dioxide in inhalation chambers at concentrations of 0.2 to 50 parts per million for up to 4 hours. At sequential intervals during the exposure, mice were frozen and pulverized in liquid nitrogen, and the mice powder was extracted with ice-cold 35 percent aqueous methanol and dichloromethane; organic-phase concentrates were analyzed for N-nitrosomorpholine with a thermal energy analyzer interfaced to a gas chromatograph. The N-nitrosomorpholine yields, ranging up to about 2.3 micrograms per mouse, were time-dependent relative to the duration of exposure to nitrogen dioxide and dose-dependent relative to the concentrations of nitrogen dioxide; control levels (in mice that were gavaged with morpholine or distilled water and then exposed to air instead of nitrogen dioxide) were less than 5 nanograms per mouse. These preliminary studies demonstrate the in vivo nitrosating potential of nitrogen oxides.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Iqbal, Z M -- Dahl, K -- Epstein, S S -- New York, N.Y. -- Science. 1980 Mar 28;207(4438):1475-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7361099" target="_blank"〉PubMed〈/a〉
    Keywords: Amines/metabolism ; Animals ; Ascorbic Acid/pharmacology ; Biotransformation ; Dose-Response Relationship, Drug ; Mice ; Morpholines/*metabolism ; Nitrogen Dioxide/antagonists & inhibitors/*metabolism ; Nitrosamines/*metabolism ; Time Factors
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  • 90
    Publication Date: 1980-07-11
    Description: A new test, the granuloma pouch assay, was used in detecting specific locus mutations in somatic cells of rats in vivo after the animals were treated orally and parenterally with procarbazine hydrochloride, an agent used in cancer chemotherapy. The results indicate that stable intermediates are formed in the body and distributed as proximate mutagens.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maier, P -- Zbinden, G -- New York, N.Y. -- Science. 1980 Jul 11;209(4453):299-301.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7384804" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Animals ; Dose-Response Relationship, Drug ; Granulation Tissue/physiopathology ; Injections, Intraperitoneal ; Injections, Intravenous ; Mutation/*drug effects ; Procarbazine/administration & dosage/*pharmacology ; Rats
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  • 91
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-07-11
    Description: Beta-Lipotropin stimulated the production of aldosterone in collagenase-dispersed rat adrenal capsular cells. The maximum response obtained with beta-lipotropin was the same as the response obtained with corticotropin and was greater than that obtained with angiotensin II. These data suggest that beta-lipotropin may play a role in aldosterone regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsuoka, H -- Mulrow, P J -- Li, C H -- New York, N.Y. -- Science. 1980 Jul 11;209(4453):307-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6247763" target="_blank"〉PubMed〈/a〉
    Keywords: Adrenal Glands/drug effects/*metabolism ; Adrenocorticotropic Hormone/pharmacology ; Aldosterone/*biosynthesis ; Animals ; Corticosterone/*biosynthesis ; Dose-Response Relationship, Drug ; Female ; Rats ; Sheep ; Swine ; beta-Lipotropin/*pharmacology
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  • 92
    Publication Date: 1980-08-15
    Description: Selenium, administered to mice with Ehrlich ascites tumors, effectively limited tumor growth. The response was dependent on the chemical form and dose of selenium administered. At the doses administered, there were no detectable adverse effects to the host.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Greeder, G A -- Milner, J A -- New York, N.Y. -- Science. 1980 Aug 15;209(4458):825-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7406957" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma, Ehrlich Tumor/*drug therapy/pathology ; Cell Line ; Cell Membrane Permeability ; Cystine/analogs & derivatives ; Dose-Response Relationship, Drug ; Male ; Mice ; Neoplasm Transplantation ; Selenium/*administration & dosage/metabolism/therapeutic use ; Selenomethionine/administration & dosage
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  • 93
    Publication Date: 1980-08-22
    Description: Long-term administration of either superactive analog's of gonadotropin-releasing hormone or of testosterone suppresses gonadotropin secretion in male animals and humans. Testosterone administered in combination with gonadotropin-releasing hormone analog further suppresses serum gonadotropin levels in male rats. This observation indicates synergistic activity and suggests that the gonadotropin-releasing hormone analog and testosterone act at independent sites within the hypothalamic-pituitary axis. The primary actions of superactive analog are probably mediated by changes at a postreceptor site in the pituitary gonadotropin-secreting cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Heber, D -- Swerdloff, R S -- New York, N.Y. -- Science. 1980 Aug 22;209(4459):936-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6773142" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Contraceptive Agents, Male/pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Follicle Stimulating Hormone/*secretion ; Gonadotropin-Releasing Hormone/*analogs & derivatives/pharmacology ; Luteinizing Hormone/*secretion ; Male ; Rats ; Spermatogenesis/*drug effects ; Testosterone/*pharmacology
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  • 94
    Publication Date: 1980-08-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haseltine, W A -- Lo, K M -- D'Andrea, A D -- New York, N.Y. -- Science. 1980 Aug 22;209(4459):929-31.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7403858" target="_blank"〉PubMed〈/a〉
    Keywords: Base Sequence ; Benzopyrenes/*pharmacology ; Carcinogens ; *DNA, Bacterial ; Dose-Response Relationship, Drug ; Epoxy Compounds ; Hydrolysis ; Lac Operon ; Mutagens ; Stereoisomerism ; Structure-Activity Relationship
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  • 95
    Publication Date: 1980-01-11
    Description: Stereoisomers of the barbiturate anesthetic pentobarbital were applied to mouse spinal neurons growing in tissue culture. Intracellular recordings of neuronal membrane properties revealed that the (+) and (-) isomers caused direct changes in membrane potential and conductance on some but not all of the cells tested. The action of the (+) isomer was predominantly excitatory, whereas the (-) isomer produced predominantly inhibitory responses. The (-) isomer was considerably more effective in potentiating inhibitory responses to the transmitter gamma-aminobutyric acid. The results show that pentobarbital has multiple effects on neuronal excitability and demonstrate the presence of stereospecific sites of barbiturate action on central neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, L Y -- Barker, J L -- New York, N.Y. -- Science. 1980 Jan 11;207(4427):195-7.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7350656" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/drug effects ; Animals ; Cells, Cultured ; Dose-Response Relationship, Drug ; Electric Conductivity ; Membrane Potentials/drug effects ; Mice ; Neural Inhibition/drug effects ; Neurons/*drug effects ; Pentobarbital/*pharmacology ; Spinal Cord/embryology ; Stereoisomerism ; Structure-Activity Relationship
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  • 96
    Publication Date: 1980-12-05
    Description: Acute electrophysiological effects of ethanol were studied in two lines of mice that differ markedly in their response to the soporific effects of systemic alcohol administration. Cerebellar Purkinje neurons from the genetic line that had long sleep times were one to two orders of magnitude more sensitive to the depressant effects of locally administered ethanol than those from the line that had short sleep times. The data suggest that there are genetically determined specificities in the acute effects of ethanol on central neurons and that such specificities might be used to determine which regions of the cerebellum participate in differences in behavioral responses to this substance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sorensen, S -- Palmer, M -- Dunwiddie, T -- Hoffer, B -- AA-03527/AA/NIAAA NIH HHS/ -- GM-01983/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1980 Dec 5;210(4474):1143-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7444444" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/*drug effects ; Animals ; Behavior, Animal/physiology ; Dose-Response Relationship, Drug ; Ethanol/*pharmacology ; Heart Conduction System/*drug effects ; Mice ; Mice, Mutant Strains ; Neural Inhibition/drug effects ; Purkinje Fibers/*drug effects
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1980-08-29
    Description: Prostaglandins of the A series strongly inhibit the production of Sendai virus in African green monkey kidney cells and are able to prevent the establishment of persistent infection ("carrier" state). This action is specific for prostaglandin A and is not due to alteration in the host cell metabolism or in the virus infectivity. The possibility that this effect is mediated by interferon is discussed.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santoro, M G -- Benedetto, A -- Carruba, G -- Garaci, E -- Jaffe, B M -- New York, N.Y. -- Science. 1980 Aug 29;209(4460):1032-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6157190" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arachidonic Acids/pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Haplorhini ; Interferons/pharmacology ; Parainfluenza Virus 1, Human/*drug effects ; Prostaglandins/pharmacology ; Prostaglandins A/*pharmacology ; Structure-Activity Relationship ; Thromboxanes/pharmacology ; Virus Replication/*drug effects
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  • 98
    Publication Date: 1980-11-21
    Description: Fusion of phospholipid vesicles with a planar phospholipid bilayer membrane that contains a calcium-binding protein appears to mimic the essential aspects of cytoplasmic-vesicle fusion with plasma membranes (exocytosis) in that (i) there is a low basal rate of fusion in the absence of Ca2+, (ii) this basal rate is enormously increased by micromolar (approximately 10 microM) amounts of Ca2+, and (iii) this rate is not increased by millimolar Mg2+. Essential to this process is an osmotic gradient across the planar membrane, with the side containing the vesicles hyperosmotic to the opposite side. Similar osmotic gradients or their equivalent may be crucial for biological fusion events.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zimmerberg, J -- Cohen, F S -- Finkelstein, A -- 5T 32 GM 7288/GM/NIGMS NIH HHS/ -- MH 06418/MH/NIMH NIH HHS/ -- NS 14246-03/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1980 Nov 21;210(4472):906-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7434004" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/*pharmacology ; Calcium-Binding Proteins/*physiology ; Dose-Response Relationship, Drug ; *Exocytosis ; Lipid Bilayers ; Osmolar Concentration ; Phospholipids/*physiology ; Synaptic Membranes/metabolism
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  • 99
    Publication Date: 1984-04-27
    Description: Exogenous cholecystokinin selectively antagonizes opiate analgesia, which suggests that endogenous cholecystokinin may act physiologically as an opiate antagonist and may play a role in opiate tolerance. The use of the selective cholecystokinin antagonist proglumide provided a test of these hypotheses in rats that were either inexperienced with or tolerant to opiates. Proglumide potentiated analgesia produced by morphine and endogenous opiates and seemed to reverse tolerance. These results suggest that endogenous cholecystokinin systems oppose the action of opiates.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Watkins, L R -- Kinscheck, I B -- Mayer, D J -- DA 00576/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 1984 Apr 27;224(4647):395-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6546809" target="_blank"〉PubMed〈/a〉
    Keywords: *Analgesia ; Animals ; Brain/drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Drug Tolerance/drug effects ; Endorphins/physiology ; Enkephalin, Methionine/analogs & derivatives/pharmacology ; Glutamine/*analogs & derivatives ; Humans ; Injections, Spinal ; Morphine/*pharmacology ; Proglumide/administration & dosage/*pharmacology ; Rats ; Spinal Cord/drug effects
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  • 100
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 1984-10-26
    Description: Intracerebroventricular administration of human pancreatic growth hormone-releasing factor caused a dose-dependent inhibition of growth hormone secretion, elevated plasma glucose concentrations, and produced marked behavioral and motor effects. Immunoneutralization with antiserum to somatostatin did not reverse the suppression of growth hormone. These findings suggest that hypothalamic growth hormone-releasing factor may regulate its own neurosecretion through an "ultrashort-loop" negative feedback mechanism and may have important neurotransmitter and neuromodulatory functions in the brain.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tannenbaum, G S -- New York, N.Y. -- Science. 1984 Oct 26;226(4673):464-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6436973" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/*drug effects ; *Blood Glucose ; Dose-Response Relationship, Drug ; Feedback ; Growth Hormone/*secretion ; Growth Hormone-Releasing Hormone/*pharmacology ; Male ; Rats ; Rats, Inbred Strains
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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