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R Young

Publications and source records attributed to R Young.

At least 235 records · Page 13Linked to original sources
PubMed1986

Isolation of structural genes for yeast RNA polymerases by immunological screening.

A lambda gt11 yeast genomic library was screened with antibodies directed against yeast RNA polymerases A, B, and C. Thirty-five individual recombinant phages that expressed proteins in Escherichia coli that were antigenically related to RNA polymerases A, B, or C were isolated by using 22 distinct antisera. Thus, all 22 genes for the RNA polymerase subunits were potentially cloned. In three cases (lambda A-43, lambda A-40, and lambda A-34.5), an antigenic protein was expressed in E. coli with the same molecular weight as the corresponding subunit. When lambda A-40 DNA was used to hybrid-select yeast mRNA, the protein translated in vitro was the expected size for the A-40 subunit, further supporting our isolation of the A-40 gene. However, mRNA hybrid selected by lambda A-27 DNA did not code for a protein of the correct size. The lengths of the mRNA that hybridized to phage lambda A-190 or lambda C-160 DNA on RNA blots were in agreement with the predicted sizes of the coding regions of the corresponding genes. As predicted by our previous immunological results, yeast DNA inserts of the lambda A-190 and lambda C-160 clones cross-hybridized to the B-220 subunit gene. The cloned genes for the RNA polymerase subunits will prove to be valuable tools for the study of the function, regulation, and genetics of the yeast RNA polymerases.

Antibodies, Fungal↗
PubMed1986

Mutational analysis of bacteriophage lambda lysis gene S.

A plasmid carrying the bacteriophage lambda lysis genes under lac control was subjected to hydroxylamine mutagenesis, and mutations eliminating the host lethality of the S gene were selected. DNA sequence analysis revealed 48 single-base mutations which resulted in alterations within the coding sequence of the S gene. Thirty-three different missense alleles were generated. Most of the missense changes clustered in the first two-thirds of the molecule from the N terminus. A simple model for the disposition of the S protein within the inner membrane can be derived from inspection of the primary sequence. In the first 60 residues, there are two distinct stretches of predominantly hydrophobic amino acids, each region having a net neutral charge and extending for at least 20 residues. These regions resemble canonical membrane-spanning domains. In the model, the two domains span the bilayer as a pair of net neutral charge helices, and the N-terminal 10 to 12 residues extend into the periplasm. The mutational pattern is largely consistent with the model. Charge changes within the putative imbedded regions render the protein nonfunctional. Loss of glycine residues at crucial reverse-turn domains which would be required to reorient the molecule to reenter the membrane also inactivate the molecule. Finally, a number of neutral and rather subtle mutations such as Ala to Val and Met to Ile are found, mostly within the putative spanning regions. Although no obvious explanation exists for this subtle and heterogeneous class of mutations, it is noted that all of the changes result in a loss of alpha-helical character as predicted by Chou-Fasman theoretical analysis. Alternative explanations for some of these changes are also possible, including a reduction in net translation rate due to substitution of a rare codon for a common one. The model and the pattern of mutations have implications for the probable oligomerization of the S protein at the time of endolysin release at the end of the vegetative growth period.

Alleles↗
PubMed1986

L-649,923, sodium (beta S*, gamma R*)-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)-propylthio)- gamma-hydroxy-beta-methylbenzenebutanoate, a selective, orally active leukotriene receptor antagonist.

L-649,923, Sodium (beta S*, gamma R*)-4-(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylthio)- gamma- hydroxy-beta-methylbenzenebutanoate is a selective and competitive inhibitor of [3H]leukotriene D4 (Ki value of 400 nM) and to a lesser extent [3H]leukotriene C4 (Ki value of 8.6 microM) binding in guinea-pig lung homogenates. Functionally, it selectively antagonized contractions of guinea pig trachea induced by leukotriene C4, D4, E4, and F4 but not those induced by acetylcholine, histamine, serotonin, prostaglandin F2 alpha, or U-44069 (stable endoperoxide analogue). Schild plot analysis indicated a competitive inhibition of contractions of guinea-pig ileum induced by leukotriene D4 (pA2 8.1) and contractions of guinea-pig trachea induced by leukotrienes E4 and F4 (pA2 7.1 and 6.9, respectively). In contrast, contractions of guinea-pig trachea induced by leukotrienes C4 (pA2 7.2; slope 0.6) and D4 (pA2 7.2; slope 0.7) were inhibited in a noncompetitive fashion. In vivo, intravenously administered L-649,923 selectively blocked bronchoconstriction induced in anesthetized guinea pigs by leukotriene C4 and D4 (ED50 values i.v. 0.38 and 0.26 mg/kg, respectively) but not that induced by histamine, arachidonic acid, serotonin, U-44069, or acetylcholine. Following intraduodenal administration, L-649,923, blocked leukotriene D4 induced bronchoconstriction (5 and 10 mg/kg). The present findings indicate that selective antagonists, such as L-649,923, may be useful for defining the role of leukotrienes in diseases such as bronchial asthma.

Airway Resistance↗
PubMed1986

L-648,051, sodium 4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)- propylsulfonyl]-gamma-oxo-benzenebutanoate: a leukotriene D4 receptor antagonist.

L-648,051, sodium 4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy) propylsulfonyl]-gamma-oxo-benzenebutanoate is a selective and competitive inhibitor of [3H]leukotriene D4 (KB value of 4.0 microM) and to a lesser extent [3H]leukotriene C4 (Ki value of 36.7 microM) binding in guinea pig lung homogenates. Functionally, it selectively antagonized contractions of guinea pig trachea induced by leukotrienes C4, D4, E4, and F4 in concentrations that did not antagonize contractions induced by acetylcholine, histamine, serotonin, prostaglandin F2 alpha, or U-44069 (endoperoxide analogue). Schild plot analysis indicated that L-648,051 competitively antagonized contractions of guinea pig ileum induced by leukotriene D4 (pA2 7.7) and contractions of trachea induced by leukotrienes D4, E4, and F4 (pA2 7.3, 7.4, and 7.5, respectively). Contractions of guinea pig trachea induced by leukotriene C4 were inhibited in a noncompetitive fashion (Schild plot slope, 0.45). Developed contractions of trachea induced by the leukotrienes were rapidly reversed by L-648,051 greater than FPL-55712 greater than L-649,923. Intravenous L-648,051 selectively blocked bronchoconstriction induced in anaesthetized guinea pigs by intravenous leukotrienes C4, D4, and E4 but not that induced by arachidonic acid, serotonin, U-44069, or acetylcholine. The compound displayed poor activity following intraduodenal administration. The profile of activity for L-648,051 indicates that it may be a useful topical agent for studying the role of leukotrienes in diseases such as bronchial asthma.

Animals↗
PubMed1986

AIDS in a Hong Kong Chinese.

A young Hong Kong Chinese male patient with fever of unknown origin is presented. The diagnosis of acquired immunodeficiency syndrome was made only 5 months after the onset of his illness. The lack of awareness of the syndrome might account for the delay in the diagnosis. The legal attitude towards homosexuality might have an adverse effect on epidemiological studies of AIDS in Hong Kong.

Acquired Immunodeficiency Syndrome↗
PubMed1986

The rise and fall of intra-ocular pressure: the influence of physiological factors.

A number of physiological factors can influence the intra-ocular pressure of patients with normal, healthy eyes leading to the misinterpretation of tonometric findings. The influence and duration of four commonly encountered factors--drinking water, coffee, alcohol, and exercise--were investigated employing a non-contact tonometer. Drinking 1 litre of water increased the IOP for up to 140 min with a mean maximum increase of 4.4 mmHg. A similar change was induced by coffee, the increase lasting up to 95 min and displaying a mean maximum increase of 4.0 mmHg. The intra-ocular pressure fell with alcohol consumption by a maximum of 3.7 mmHg, regaining pre-test values in all subjects after 65 min. Vigorous exercise produced an immediate fall in mean intra-ocular pressure of 4.3 mmHg, initial pressure being restored in all subjects after 65 min. The impact of such factors upon normal physiology are discussed together with the implications for routine tonometry.

Adolescent↗
PubMed1985

Selective abnormality of the cone B-wave in a patient with retinal degeneration.

A 44-year-old woman with midperipheral pigmentary changes that resemble retinitis pigmentosa (RP) is described; unlike typical patients with RP, her photopic b-wave was markedly attenuated as compared with her photopic a-wave. Otherwise, her electroretinogram (ERG) was typical of patients with early stages of photoreceptor degeneration. Scotopic and photopic a-wave amplitudes were reduced about 50%; her scotopic b/a appeared normal.

Adaptation, Physiological↗
PubMed1985

Structure-activity studies on methoxy-substituted phenylisopropylamines using drug discrimination methodology.

Eighteen rats were trained to discriminate 1.0 mg/kg of (+)-amphetamine sulfate from saline in a two-lever operant procedure. Once responding was stable, these animals were administered various doses of sixteen different methoxy-substituted phenylisopropylamines in tests of stimulus generalization. Of three possible mono-methoxyphenylisopropylamines, all three produced amphetamine-appropriate responding, but none was as potent as racemic amphetamine. The amphetamine-stimulus did not completely generalize to any of the di- or tri-methoxyphenylisopropylamines.

Amphetamine↗
PubMed1985

Fluid-sorption phenomena in sterilized polyethylene acetabular prostheses.

The weight changes due to fluid-sorption were measured in 62 radiation-sterilized acetabular sockets and 10 unsterilized discs. The materials included two types of ultra-high molecular weight (UHMW) polyethylene (RCH 1000; Hi-Fax 1900) and a carbon-fibre-reinforced polyethylene (CFPE). The fluid absorption curve was consistently biphasic. In the first 30 d soak-period (Phase 1), the initial rate of fluid absorption averaged 153 micrograms/d for conventional UHMW polyethylene and 278 micrograms/d for carbon-fibre-reinforced polyethylene. In Phase 2, beyond 30 d and up to 400 d, fluid absorption reduced to linear rates of 27 micrograms/d for UHMW polyethylene and 43 micrograms/d for CFPE. The latter soak-weight-gain values corresponded to only 0.00016%/d and 0.00034%/d respectively. There was little difference in absorption rates between sterilized and unsterilized samples. However soak rates were generally higher in water compared to serum.

Absorption↗
PubMed1985

Deletion and fusion analysis of the phage phi X174 lysis gene E.

The lysis gene, E, of bacteriophage phi X174 has been subjected to deletion and gene fusion analysis. C-terminal deletions of as few as 17 of the 91 codons inactivate the cloned E gene, which in its intact form can cause lysis of the host cell. Fusion of lacZ to deletion joints at the 59th codon or beyond apparently restores lethal and lytic competence to the respective E deletion alleles, whereas a fusion at the 23rd codon remains non-lethal. The lethal E phi lacZ fusions are also lethal to a mutant, designated slyD, which was isolated as a spontaneous E. coli mutant resistant to the expression of the intact E gene. slyD appears to be linked to rpsE. The data are interpreted in terms of a model in which E-mediated lethality requires oligomerization of the E gene product. Calculations based on the beta-galactosidase activity accumulated by the time of lethal action of E phi lacZ suggest that fewer than 1000 molecules of E gene product are required for lysis and probably fewer than 100 are required for loss of host viability.

Alleles↗
PubMed1985

Resistance of citrus fruit to mass transport of water vapor and other gases.

The resistance of oranges (Citrus sinensis L. Osbeck) and grapefruit (Citrus paradisi Macf.) to ethylene, O(2), CO(2), and H(2)O mass transport was investigated anatomically with scanning electron microscope and physiologically by gas exchange measurements at steady state. The resistance of untreated fruit to water vapor is far less than to ethylene, CO(2) and O(2). Waxing partially or completely plugs stomatal pores and forms an intermittent cracked layer over the surface of fruit, restricting transport of ethylene, O(2), and CO(2), but not of water; whereas individual sealing of fruit with high density polyethylene films reduces water transport by 90% without substantially inhibiting gas exchange.Stomata of harvested citrus fruits are essentially closed. However, ethylene, O(2) and CO(2) still diffuse mainly through the residual stomatal opening where the relative transport resistance (approximately 6,000 seconds per centimeter) depends on the relative diffusivity of each gas in air. Water moves preferentially by a different pathway, probably through a liquid aqueous phase in the cuticle where water conductance is 60-fold greater. Other gases are constrained from using this pathway because their diffusivity in liquid water is 10(4)-fold less than in air.

Journal Article↗
PubMed1985

Purification of hybrid beta-galactosidase proteins encoded by phi X174 E phi lacZ and Escherichia coli prlA phi lacZ: a general method for the isolation of lacZ fusion polypeptides produced in low amounts.

A facile immunoaffinity chromatography method is described for the purification of lacZ fusion gene products. The method is general for any molecule antigenically related to beta-galactosidase and involves only a single step. We report its use to purify the products of lacZ fusions with a bacteriophage gene, phi X174E, and an Escherichia coli chromosomal gene, prlA. The hybrid protein products of both of these genes are membrane bound and present in very low molar amounts with respect to total cellular protein. Evidence is presented that substrate-affinity chromatography is not applicable to the isolation of low-level fusion proteins such as these.

Bacteriophage phi X 174↗
PubMed1984

Discriminative stimulus properties of the serotonin agonist 1-(3-trifluoromethylphenyl)piperazine (TFMPP).

Using a standard two-lever drug discrimination procedure, twelve rats were trained to discriminate 1.0 mg/kg of the serotonin (5-HT) agonist TFMPP from saline. Once trained, the animals displayed a dose-related decrease in discriminative performance upon administration of lower doses of TFMPP. Tests of stimulus generalization were performed using the purported 5-HT agonist RU-24, 969 and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). While TFMPP produced stimulus effects similar to those of RU-24,969, these effects seem to be dissimilar to those of DOM. The results of the present study suggest that the discriminative stimulus effects of TFMPP may involve a 5-HT1-related mechanism.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1984

Stereoselective stimulus effects of 3-methylflunitrazepam and pentobarbital.

Rats trained to discriminate 3.0 mg/kg of diazepam from saline in a two-lever operant choice task were challenged with the racemic mixture and optical isomers of 3- methylflunitrazepam or pentobarbital. Generalization of the diazepam stimulus was found to occur to (+/-)- and S(+)-3- methylflunitrazepam , with the S(+)-isomer being twice as active as the racemate. Diazepam stimulus generalization also occurred to (+/-)-, S(-)-, and R(+)-pentobarbital, with the S(-)-isomer being approximately twice as active as (+/-)- or R(+)-pentobarbital. In addition, the administration of the imidazobenzodiazepine Ro 15-1788, a selective benzodiazepine receptor antagonist, prior to benzodiazepine or barbiturate administration competitively antagonized the discriminative stimulus properties of the benzodiazepines but was completely ineffective in attenuating the discriminative stimulus effect of the barbiturates. The results of this study suggest that benzodiazepines exert their stimulus effects by a stereoselective interaction at a benzodiazepine receptor and that stereochemical factors are important in evaluating the stimulus properties of benzodiazepines or barbiturates.

Animals↗