Search PubMed⌕ Search

Biomedical subjects

R Hurst

Publications and source records attributed to R Hurst.

At least 55 records · Page 3Linked to original sources
PubMed1987

Phosphorothioated binary complex of eukaryotic initiation factor eIF-2 and GDP inhibits protein synthesis in hemin-supplemented reticulocyte lysates.

The rabbit reticulocyte heme-regulated eIF-2 alpha kinase (HRI) utilizes adenosine-5'-0-(3-thiotriphosphate) (ATP-gamma-S) as a substrate for its autophosphorylation and activation, and for the phosphorylation of eIF-2. The phosphorothioated binary complex [eIF-2(alpha-[35S]P) . GDP], interacted with the reticulocyte reversing factor (RF) in in vitro assays, and inhibited the ability of RF to catalyze GDP exchange from (eIF-2 . [3H]GDP) complexes. The phosphorothioate residue in the binary complex was resistant to phosphatase action under protein synthesis conditions. eIF-2(alpha-[35S]P) . GDP inhibited protein synthesis in hemin-supplemented lysates with biphasic kinetics, but had no effect on protein synthesis in heme-deficient lysates. The data reported here indicate that phosphorylation of eIF-2 . GDP alone, through the ability of eIF-2(alpha-P) . GDP to bind and sequester RF, is sufficient to inhibit protein chain initiation in the reticulocyte lysate.

Adenosine Triphosphate↗
PubMed1986

Using federal standards to determine adequacy of consumer product's precautionary labeling.

The results of the present investigation indicate that a majority of the more hazardous products provided some type of warning, although they may not necessarily contain the specific phrases required by the Act. In contrast, products that were deemed minimally hazardous were more likely to omit important precautionary information. In addition, our study also demonstrated that the primary labeling deficiency was the lack of comprehensive first aid information. For the health care professional, the importance of clear, correct, concise and complete first aid information for each potential route of exposure is well appreciated; however, it appears that the manufacturers are reluctant to provide complete first aid information on their product labels. Many manufacturers or sellers offer arguments against providing comprehensive precautionary and first aid information such as: the consumer never reads the label; if the warning label is "too busy", the warning's effect will be minimized; or a seller may lose a competitive edge if his/her product contains a panel of hazard warnings while his/her competitor's identical product provides no warning which may lead a consumer to believe that the competitor's product is safer. While the above arguments may be viable, they are significantly weakened when one considers the potential health risks or costly litigation that may ensue as a result of an inadequate label. Therefore, it is imperative that product manufacturers and sellers become aware of all of the potential hazards associated with their products, and disseminate all of this information through sufficient warning labels.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosol Propellants↗
PubMed1985

Studies in vitro with ICI 174,864, [D-Pen2, D-Pen5]-enkephalin (DPDPE) and [D-Ala2, NMePhe4, Gly-ol]-enkephalin (DAGO).

The interactions of a proposed, selective delta receptor antagonist (ICI 174,864) and selective agonists at mu and delta receptors, [D-Ala2, NMePhe4, Gly-ol]-enkephalin (DAGO) and [D-Pen2, D-Pen5]-enkephalin (DPDPE), respectively, have been studied using the electrically-stimulated mouse isolated vas deferens (MVD) and the guinea-pig isolated ileum (GPI). Incubation of increasing concentrations of ICI 174,864 (10,30,100 and 300 nM) produced a dose-related and parallel rightward displacement of the DPDPE dose-response curve in the MVD. In contrast, ICI 174,864 (300-3000 nM) failed to affect the DAGO dose-response curve in the same tissue. Analysis of the DPDPE-ICI 174,864 interaction in the MVD using the pA2 method revealed a Schild plot slope of -0.68 suggesting the involvement of more than one population of receptors. ICI 174,864 (300 nM) failed to antagonize DPDPE in the GPI at doses up to 30 microM. These results suggest that (a) ICI 174,864 acts as a selective delta antagonist in the MVD; (b) DPDPE interacts with mu receptors in the MVD but only at very high concentrations, and (c) delta receptors appear not to be of functional importance in the GPI.

Animals↗
PubMed1984

Roles of mu, delta and kappa opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot-plate analgesia in the mouse.

The opioid receptors involved in the mediation of thermal analgesia (55 degrees C hot-plate) and inhibition of gastrointestinal transit at the spinal and supraspinal levels were studied in unanesthetized mice. Five receptor-selective compounds were evaluated for effectiveness in eliciting analgesia and inhibiting transit after both i.c.v. and intrathecal administration; these included the proposed mu agonist, [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAGO), the proposed delta agonists, [D-Pen2, L-Pen5]enkephalin (DPLPE), [D-Pen2, D-Pen5]enkephalin (DPDPE) (conformationally constrained delta selective enkephalin analogs) and [D-Thr2, Thr6, Leu5]enkephalin (DTTLE), and the proposed kappa agonist, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate (U-50,488H), as well as the nonselective mu-acting agonist, morphine. All compounds were found to produce analgesia after i.c.v. administration; the rank order of potency by the i.c.v. route was DAGO greater than DTTLE greater than morphine greater than DPLPE greater than DPDPE greater than U-50,488H. The analgesic effectiveness of most of these agonists given i.c.v. was evident for up to 40 min, with only DTTLE and U-50,488H having briefer time courses. Similarly, all the compounds produced analgesic responses after intrathecal administration, with the rank order of potency by this route being DTTLE greater than morphine greater than DAGO greater than DPLPE greater than DPDPE greater than U-50,488H, and all compounds (except U-50,488H) had durations of action of up to 20 to 40 min. These agonists also inhibited gastrointestinal transit after intrathecal administration, with a rank order of potency of DAGO greater than DTTLE greater than DPLPE greater than morphine greater than DPDPE greater than U-50,488H.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1984

Cerebral delta opioid receptors mediate analgesia but not the intestinal motility effects of intracerebroventricularly administered opioids.

Conformationally constrained cyclic enkephalin analogs which possess a high selectivity for the delta opioid receptor were used to determine the relative contribution of mu and delta receptors to brain-mediated changes in small intestinal propulsion and increases in hot-plate response time. Receptor preferences were determined by comparing the relative potencies of several opioid agonists in suppressing the electrically evoked contractions of the guinea-pig ileum and mouse vas deferens preparations. The ratio of IC50 values obtained in the guinea-pig ileum and the mouse vas deferens was used as an index of delta receptor selectivity. Effects on intestinal transit were determined in rats in which a silastic cannula had been implanted in the proximal duodenum and a polyethylene cannula in the right lateral cerebral ventricle (i.c.v.). Movement of a radioactive marker along the length of the small intestine after instillation into the duodenum was used to evaluate drug-induced changes in intestinal transit. The analgesic effects of i.c.v. administered opioids were determined in a second group of rats in which i.c.v. cannulas alone had been implanted. After i.c.v. administration of the agonist, the rats were placed on a 55 degrees C hot plate and the latency to rear paw-lick was timed. Compounds which showed a preference for the mu receptor [( D-Ala2, N-methyl-Phe4, Gly5 -ol]enkephalin and morphine/normorphine) were the most potent agonists at producing thermal analgesia and inhibition of small intestinal transit, whereas nonselective compounds (beta-endorphin and [D-Ala2, Met5]enkephalinamide) were slightly less potent in these assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1983

Conformationally constrained cyclic enkephalin analogs with pronounced delta opioid receptor agonist selectivity.

The enkephalin analogs, [D-Pen2,L-Cys5]- and [D-Pen2,D-Cys5]-enkephalin are cyclic compounds, conformationally constrained by virtue of their 14-membered, disulfide containing rings and by the rigidizing effect of the beta, beta dimethyl substituents of the penicillamine side chain. The analogs exhibit profound delta receptor specificity as assessed by their relative potencies in the guinea pig ileum (GPI) and mouse vas deferens (MVD) assays, exhibiting, respectively, 666 and 215 times higher potency in the latter assay system. By contrast, the receptor selectivities measured in rat brain binding assays in the absence of sodium were much more modest, the cyclic analogs being, respectively, 15.2 and 6.0 times more effective at displacing [3H] [D-Ala2,D-Leu5]enkephalin than [3H]naloxone. However, for binding assays performed in the presence of a sodium concentration equivalent to that used in the GPI and MVD assays, these binding selectivities increased to 167 and 49, respectively.

Animals↗
PubMed1983

Cyclic penicillamine containing enkephalin analogs display profound delta receptor selectivities.

The cyclic, penicillamine(beta, beta dimethylcysteine)-containing enkephalin analogs, [D-Cys2, L-Pen5]-and [D-Cys2, D-Pen5]enkephalin and the corresponding bis-penicillamine analogs, [D-Pen2, L-Pen5]-and [D-Pen2, D-Pen5]enkephalin were synthesized and evaluated for opioid activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD) bioassays and in rat brain and neuroblastoma-glioma cell membrane binding assays. These analogs all displayed delta receptor selectivity as assessed by IC50(GPI)/IC50(MVD) ratios and by their relative potencies for displacing [3H]naloxone (NAL) vs. [3H] [D-Ala2, D-Leu5]enkephalin (DADLE) from rat brain membrane preparations. For [D-Pen2, L-Pen5]- and [D-Pen2, D-Pen5]enkephalin the observed IC50(GPI)/IC50 (MVD) ratios (1088 and 3164) and IC50NAL/IC50DADLE ratios (371 and 175) represent a vast improvement over previously reported delta receptor selective ligands.

Animals↗
PubMed1983

A comparison of the analgesic and gastrointestinal transit effects of [D-Pen2, L-Cys5]enkephalin after intracerebroventricular and intrathecal administration to mice.

Intrathecal (i.t.) administration of the highly delta selective peptide, [D-Pen2, L-Cys5]enkephalin (DPLCE) (1-10 micrograms), effectively inhibited gastrointestinal transit of an orally-given radiolabelled marker in mice. By contrast, the same doses did not affect marker transit after intracerebroventricular (i.c.v.) administration. I.c.v. or i.t. administration of the peptide effectively increased the latency to hindpaw lick using the 55 degrees C hot-plate as the nociceptive stimulus. Maximum analgesic effects were seen with 0.3 micrograms given i.t. or 10 micrograms given i.c.v. Time-response studies showed activity for as long as 20 min after administration by either route. The differential gastrointestinal effects of DPLCE after i.c.v. and i.t. administration to mice suggest that delta receptors in the brain may mediate analgesic but not gut effects while spinal cord receptors may be less functionally selective.

Analgesia↗
PubMed1983

Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors.

The conformationally restricted, cyclic, disulfide-containing, enkephalin analogs [2-D-penicillamine, 5-L-penicillamine]enkephalin [(D-Pen2,L-Pen5]enkephalin) and [2-D-penicillamine, 5-D-penicillamine]enkephalin [(D-Pen2,D-Pen5]enkephalin) were synthesized by solid-phase methods. Selectivities of these analogs for a single class of opioid receptor were investigated by examining relative potencies in the mouse vas deferens assay, in which the functional receptor is the delta receptor, versus the guinea pig ileum assay, in which the mu receptor is the functional receptor, and by determining their relative abilities to displace the prototypical delta receptor ligand [D-Ala2, D-Leu5]enkephalin and the prototypical mu receptor ligand naloxone from rat brain membrane preparations. Based on these comparisons [D-Pen2,L-Pen5]- and [D-Pen2,D-Pen5]enkephalin exhibited delta receptor selectivities of 1,088 and 3,164, respectively, in the bioassays, and 371 and 175, respectively, in the binding assays. Compared with the previously reported delta receptor selective analogs, [D-Ala2,D-Leu5]enkephalin, [D-Ser2,Leu5,Thr6]enkephalin, and [D-Thr2,Leu5,Thr6]enkephalin, the bis-Pen-containing analogs provide an order of magnitude increase in delta receptor selectivity.

Animals↗
PubMed1982

Group B erythrocytes enzymatically converted to group O survive normally in A, B, and O individuals.

With an alpha-galactosidase, B erythrocytes can be converted to blood group O under conditions that neither impair their viability in vitro nor affect their ability to survive normally after transfusion to individuals of groups O, A, and B. Such an approach has the potential for producing enzymatically converted group O cells for use in transfusion therapy. It should also be possible to convert A cells to group O by using the appropriate alpha-N-acetylgalactosaminidase.

ABO Blood-Group System↗
PubMed1982

Preparative countercurrent chromatography for isolation of charge density-fractionated heparin.

A preparative method is described for continuous flow fractionation of heparin according to charge density in two-phase systems of butanol-hexadecylpyridinium chloride/aquaous NaCl. The separation is carried out on a "Slowly-Rotating Coil" device for countercurrent chromatography with 6 coil units and a sample capacity of 80 mg heparin. A turbidometric method is described which can be used to rapidly quantify the distribution of heparin. Characterization of fractions showed that linear charge density, binding constant for acridine orange, and specific activities in a "global" plasma anticoagulant assay and in a specific activities in a specific biochemical thrombin-inhibition assay varied with the NaCl concentration in the eluting phase. Some partial resolution of the two functional activities was observed. The fractions are much more homogeneous in composition than are the usual heparin preparations and may be useful as standards or in structure-function studies.

Acridine Orange↗
PubMed1979

Rubber sump drainage of enterocutaneous fistulae.

Effective sump drainage of high enterocutaneous fistulae, together with alimentary rest and total parenteral nutrition, is now an integral part of the modern management of patients with this condition. The low tissue reactivity of the plastic and polymer materials currently used in most drainage tubes appears however, to be counterproductive to the establishment of a discrete fistula track and control of the fistula. A case is made for the use of red rubber sump drains for enterocutaneous fistulae. The greater tissue reactivity of rubber is reviewed and confirmed by animal experimentation. A method of rubber sump drainage of enterocutaneous fistulae developed during the management of 83 such fistulae is described.

Animals↗