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At least 1,081 records · Page 60Linked to original sources
PubMed1983

Selective opiate tolerance in the guinea-pig ileum is not associated with selective dependence.

Opiate dependence attributable to specific types of opiate receptors was studied in the isolated guinea-pig ileum made tolerant/dependent in vivo to a specific narcotic agonist. Apparently, induction of dependence of mu-receptors was associated with dependence of kappa-receptors and vice versa. These investigations involved the use of the irreversible mu-receptor antagonist beta-funaltrexamine to provide preparations with functional kappa-receptors only. The documented cross-dependence between different opiate receptor types suggests a common system with which these opiate receptors interact.

Animals↗
PubMed1988

Rotation following intranigral injections of a selective D1 or a selective D2 dopamine receptor agonist in rats.

Injections of various nonselective dopamine agonists into the substantia nigra, pars reticulata (SNpr), have been reported to produce contralateral rotation in rats. Since a number of recent dopamine receptor distribution studies have indicated a preponderance of D1 compared to D2 dopamine receptor subtypes within the SNpr, we examined the relative behavioral functions of these two subtypes within the nigra by studying rotation following unilateral, local injections of a D1 (SKF38393) and D2 (quinpirole) agonist, Significant, dose-dependent contralateral rotation was observed following injections of R,S-SKF38393. This effect was found to be stereoselective to the R- enantiomer, suggesting that the effect is receptor mediated. In contrast, quinpirole (LY171555) produced significant, dose-dependent ipsilateral rotation following nigral injection. These results suggest that the rotation seen following intranigral injections of nonselective dopamine agonists is due to the simulation of the D1 dopamine receptor, and that nigral D1 and D2 dopamine receptors may play opposite roles in the control of behavior.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Principles of selective inactivation of viral genome. V. Rational selection of conditions for inactivation of the viral suspension infectivity to a given extent by the action of beta-propiolactone.

The influence of the initial concentration of beta-propiolactone, the composition of the solution, temperature, and pH on the bacteriophage MS2 infectivity inactivation kinetics has been studied. Rate constants have been determined for the infectivity inactivation and for the change in the concentration (the consumption) of the reactant under inactivation conditions. These constants have been shown to permit a sufficiently precise description of the phage MS2 survival curves under the action of beta-propiolactone. These data have been used to put forward a kinetic approach for the rational determination of conditions for inactivation of the viral infectivity to a required extent with agents whose concentration decreases during inactivation as a result of hydrolysis and reactions involving the medium components.

Bacteriophages↗
PubMed1992

The sexually differentiated metabolism of [6,7-3H]17 beta-oestradiol in rats: male-specific 15 alpha- and male-selective 16 alpha-hydroxylation and female-selective catechol formation.

The oxygenated-metabolite profiles of exogenous 17 beta-oestradiol (E2) in adult male and female Wistar rats have been characterized and major sex-dependent biotransformations observed which correlate with the regioselectivities of known sexually differentiated hepatic P450. [6,7-3H]E2 (27 micrograms/kg) was given i.v. The metabolites of E2 were rapidly and extensively excreted in bile (46 and 78% of the dose over 1 and 6 h, respectively). Female rats metabolized E2 by one major pathway: oxidation to oestrone (E1) followed by C-2 hydroxylation and O-methylation; the principal aglycones (0-1 h bile collections) were E1 (14%), 2-hydroxyE1 (2-OHE1) (42%) and 2-methoxyE1 (24%). Male rats metabolized E2 principally by two parallel composite pathways of E1 hydroxylation which yielded a complex mixture of mono- and di-oxygenated compounds: 15 alpha-OHE1 (33%), 2,15 alpha-diOHE1 (7%), and 2-methoxy-15 alpha OHE1 (14%); 16 alpha-OHE1 (13%), 2,16 alpha-diOHE1 (4%) and 2-methoxy-16 alpha-OHE1 (2%). 15 alpha-Hydroxylation was unique to males. The balance of aromatic and alkyl hydroxylation in males was dose-dependent: at 3 mg/kg, 15 alpha-hydroxylation was decreased approx. 50% in favour of 2-hydroxylation whilst 16 alpha-hydroxylation was largely unaffected. The male-specific 15 alpha-hydroxylation and male-predominant 16 alpha-hydroxylation of E1 derived from E2 in vivo may be ascribable to the male-specific isoforms P450IIC13 and P450IIC11, respectively.

Animals↗
PubMed2006

Selecting controls is not selecting "normals": design and analysis issues for studying the etiology of polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a highly prevalent disorder among postmenarcheal premenopausal women, accounting for much of anovulatory infertility, and it is associated with several comorbidities. The natural history of PCOS, as well as hypotheses regarding its etiology, facilitates employment of the case-control study design. However, a review of the literature suggested that inconsistency of research findings in relation to the etiology of PCOS might be, in part, due to the different choice of controls for case-control design and application. DESIGN: Investigators have often employed "healthy" control groups and neglected to consider the tenability of the "rare disease" assumption in the analysis when instituting the case-control strategy. This might result in the introduction of a positive bias or overestimation of odds ratios, producing an effect estimate that is more extreme than that in the underlying population. Using several quantitative, though hypothetical, literature-driven examples, this bias is described and demonstrated. In addition, recommendations are provided with regard to case-sampling strategy when the rare disease assumption is untenable, as it may frequently be in studies of PCOS. CONCLUSION(S): It is hoped that more consistent case-control methodology, in concert with recent consensus on case definition, will more effectively facilitate the elucidation of the causes and consequences of PCOS.

Bias↗
PubMed2004

In vitro selection of a peptide with high selectivity for cardiomyocytes in vivo.

One approach to targeted therapies for cardiovascular disease relies on isolating ligands that enhance the tissue-specific uptake of genes or drugs by heart cells. To obtain heart-targeting ligands, phage display biopanning was used to isolate a 20-mer peptide that binds to isolated primary cardiomyocytes. The isolated phage, PCM.1, displays the peptide WLSEAGPVVTVRALRGTGSW, and binds these cells 180 times better than a control phage from the library. Furthermore, phage displaying this peptide preferentially bind to cardiomyocytes when compared with a panel of other cell types. A BLAST search revealed that this peptide contains a 12 amino acid segment with sequence identity to a peptide in tenascin-X, an extracellular matrix protein. Synthetic peptides containing the complete 20-mer or a 12-mer tenascin peptide partially blocked phage binding to the cardiomyocytes. We developed a quantitative real-time PCR assay to assess uptake of this phage by tissues in vivo. Using this assay, preferential localization of the PCM.1 phage in heart was observed compared to the uptake of this phage by other tissues or other phage by heart. Furthermore, PCM.1 phage was associated with cardiomyocytes isolated from mice treated with a phage in vivo. These results demonstrate the utility of biopanning on isolated cells for identifying specific binding peptides that can target a tissue in vivo.

Amino Acid Sequence↗
PubMed1999

N-domain selectivity of angiotensin I-converting enzyme as assessed by structure-function studies of its highly selective substrate, N-acetyl-seryl-aspartyl-lysyl-proline.

The physiological functions of angiotensin I-converting enzyme (ACE) are not limited to its cardiovascular role. ACE constantly degrades N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), a natural circulating regulator of the hematopoietic stem cell proliferation, and thereby may be involved in hematopoietic stem cell regulation. AcSDKP is hydrolyzed 50-fold faster by the N-domain active site compared to the C-domain active site. The aim of the present study was to investigate which aminoacid residues from AcSDKP are required to ensure N-domain specificity. Several peptides were designed by progressively increasing the length of the peptidic chain from a tripeptide to a pentapeptide. Kinetic studies of the wild-type ACE and of the two ACE mutants containing a single active domain (N- or C-domain) were performed using Bz (benzoyl) Asp-Lys-Pro, benzoyl-glycyl (Bz-Gly)-Asp-Lys-Pro, and Bz-Gly-Ser-Asp-Lys-Pro (with its intermediate product Bz-Gly-Ser-Asp) as substrates. The unexpected importance of an aspartic acid in the P1 position was discovered, as well as the interaction of the P2 and P3 positions in the substrate to increase or decrease N-domain specificity. Substrates longer than five residues may involve interdependence between subsites. Finally, the discovery of highly specific and novel N-domain substrates cannot be predicted from single subsite mapping, but may require other approaches such as combinatorial peptide libraries.

Binding Sites↗
PubMed2000

Ion exchange on resins with temperature-responsive selectivity III. Influence of complex formation stoichiometry on temperature dependence of resin selectivity.

The influence of temperature (293 308 K 1:1 IDA:Ni2+ complex is dominating. The Cu2+-Ni2+ exchange equilibrium from sulfate medium is characterized by the formation of nickel complexes of both stoichiometries within the whole temperature range studied. The dependence of alpha on T in Zn2+-Co2+ exchange system has been shown to be weaker than that in the Cu2+-Ni2+ system. This result is in a good agreement with the predictions made in the first communication of this series. The results of thermostripping experiments carried out for Cu2+-Co2+ exchange have shown that the efficiency of the thermostripping process depends on both the interval of working temperatures (deltaT) and its position on the temperature scale. The efficiency of thermostripping rises with an absolute deltaT value and also increases following the shift of temperature interval to the lower temperature range.

Hydrogen-Ion Concentration↗