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R Young

Publications and source records attributed to R Young.

At least 289 records · Page 16Linked to original sources
PubMed1982

Behavioral and serotonin receptor properties of 4-substituted derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane.

The serotonin (5-HT) receptor affinities and behavioral (discriminative stimulus) properties of a series of 4-substituted derivatives of 1-(2,5-dimethoxyphenyl)-2-aminopropanes (2,5-DMA) were investigated. The substituents at the 4-position included H, OMe, OEt, Me, Et, F, Br, I, and NO2. Substituent lipophilicities (pi values) of these functionalities appear to have a minimal effect on either 5-HT receptor affinity or behavioral activity. Those derivatives previously found to be most potent in human studies possess significant affinity for 5-HT receptors. Furthermore, when rats trained to discriminate (+/-)-1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline were used, generalization was found to occur upon administration of the 4-substituted 2,5-DMA derivatives. Because a direct relationship exists between the ED50 values obtained from these discrimination studies and human hallucinogenic potencies, the discriminative stimulus paradigm, with DOM as a training drug, appears to be a useful tool for comparing the quantitative and qualitative (DOM-like) effects produced by certain hallucinogenic agents.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1982

Effect of zinc supplementation on plasma high-density lipoprotein cholesterol and zinc.

The recent report by Hooper PL, et al. (JAMA 1980;244:1960-1) that pharmacological doses (160 mg) of zinc lowered high-density lipoprotein (HDL)-cholesterol in men and that zinc might be an atherogenic agent prompted this report of the effect of zinc supplementation on HDL-cholesterol in women. Four levels of zinc supplements (0, 15, 50, or 100 mg/day) were given to 32 women for 8 wk. Fasting plasma HDL-cholesterol and zinc were measured at biweekly intervals. Plasma zinc increased in the supplemented groups, peaked at wk 4, then decreased toward initial values. The decline in plasma zinc regardless of continuing zinc administration may reflect a homeostatic response. No significant differences were seen in HDL-cholesterol over the 8 wk except in the 100 mg group at wk 4 when a transient decrease, -8.4% (57 to 48 mg/dl, p less than 0.04) was observed. Thus we conclude that in women the reduction in HDL-cholesterol in response to the pharmacological doses of zinc used in this study was transient and not dose-related.

Adolescent↗
PubMed1982

Regiospecificity in the metabolism of the homologous cyclic nitrosamines, N'-nitrosonornicotine and N'-nitrosoanabasine.

We compared the metabolism in the F-344 rat of the moderately potent esophageal carcinogen N'-nitrosonornicotine (NNN, 2'-(3-pyridyl)-N-nitrosopyrrolidine) and its weakly active homologue N'-nitrosoanabasine (NAB, 2'-(3-pyridyl)-N-nitrosopiperidine). Urine was the major pathway of excretion for both nitrosamines. The major urinary metabolites of dl-NNN resulted from 2'-hydroxylation (8.1% of the dose), 5'-hydroxylation (37.6%), and pyridine N-oxidation (10.8%). The percentages of the dose of the corresponding metabolites of dl-NAB were: 2'-hydroxylation (not detected), 6'-hydroxylation (9.8%), pyridine-N-oxidation (30.0%). Similar results were obtained when the urinary metabolites of l-NNN and l-NAB were compared. In 48 h cultures of rat esophagus, the major metabolites of [2'-14C]dl-NNN resulted from 2'-hydroxylation (47%) and to a lesser extent from 5'-hydroxylation (15%). In contrast the major metabolite of [2'-14C]dl-NAB resulted from 6'-hydroxylation (35%) with lesser amounts from 2'-hydroxylation (8%). 6'-Hydroxylation of [2'-14C]dl-NAB also exceeded 2'-hydroxylation in cultures of 3, 6, 12 or 24 h duration. Pyridine-N-oxidation was not observed in the esophagus for either nitrosamine. These results demonstrate a high degree of regiospecificity in the metabolism of these structurally related nitrosamines. Among the identified urinary metabolites the ratio of alpha-hydroxylation to N-oxidation was 4.2 for NNN and 0.3 for NAB. Among the 48 h esophageal metabolites the ratio of 2'-hydroxylation to 5'- or 6'-hydroxylation was 3.1 for NNN and 0.2 for NAB. The results also suggest a basis for the weak carcinogenicity of NAB: facile excretion as its pyridine-N-oxide and detoxification in the esophagus by 6'-hydroxylation.

Animals↗
PubMed1982

Transcription in bacteria at different DNA concentrations.

The effect of changing the DNA concentration on RNA synthesis, protein synthesis, and cell growth rate was studied in Escherichia coli B/r. The DNA concentration was varied by changing the replication velocity or by changing replication initiation in a thymine-requiring strain with a mutation in replication control. The results demonstrate that changes in DNA concentration (per mass) have no effect on the cell growth rate and the rates of synthesis (per mass) of stable RNA (rRNA, tRNA), bulk mRNA, or protein or on the concentration of RNA polymerase (total RNA polymerase per mass). Thus, transcription in E. coli is not limited by the concentration of DNA, but rather by the concentration of functional RNA polymerase in the cytoplasm. Changing the DNA concentration does, however, affect fully induced lac gene activity, here used as a model for constitutive gene expression. The magnitude of the effect of DNA concentration on lac gene activity depends on the distribution of replication forks over the chromosome, which is a function of the replication velocity. Analysis of these date reinforces the conclusion that transcription is limited by the concentration of functional RNA polymerase in the cytoplasm.

Bacterial Proteins↗
PubMed1982

Lethal action of bacteriophage lambda S gene.

The functions of the bacteriophage lambda lysis genes S, R, and Rz were investigated. Different combinations of wild-type and inactive alleles of all three lysis genes were cloned into the plasmid pBH20 and were expressed under the control of a lac operator-promoter. The involvement of the Rz gene in lysis was proposed in our previous work and was confirmed by the Mg2+-dependent lysis defect of clones in which part of the Rz gene is deleted. Membrane vesicles prepared from induced S+ cells were shown to have a severely reduced capacity for active transport of glucose; this defect was detectable at least 20 min before lysis. Cell viability was also shown to decrease very soon after induction, long before physiological death and lysis; this decrease in viability is absolutely dependent on S expression and independent of R and Rz. The nonviable fraction of cells at any time after induction was demonstrated to be equal to the fraction committed to eventual lysis. Induction of an Sts clone showed that the S gene product is stable and capable of inducing lysis long after the cessation of synthesis of S gene product. A model for S action is proposed.

Bacteriophage lambda↗
PubMed1982

Lytic action of cloned phi X174 gene E.

The phi X174 lysis gene E was placed under control of the lac promoter by cloning into the multicopy plasmid pBH20. Other phi X174 gene sequences were removed by nuclease digestion. Expression of gene E was shown to be necessary and sufficient to produce lysis phenomena exhibited by infection with intact phage. Lysis, its inhibition by MgSO4 and spermine, its progression through a spheroplasting stage, and its dependence on an early chloramphenicol-sensitive step were reproduced in clones induced for expression of the E gene product. Escherichia coli clones carrying the E gene not under lac control, and clones under lac control but only minimally induced for gene E expression, exhibited morphological aberrations consistent with the view that the mechanism by which gene E mediates cell lysis is related to host cell division processes.

Amino Acid Sequence↗
PubMed1982

Discriminative stimulus properties of MDA analogs.

Rats trained to discriminate (+/-) 2,5-dimethoxy-4-methylphenylisopropylamine (DOM) (1.0 mg/kg) from saline, using a standard two-lever operant task, were challenged with various doses of 3,4-methylenedioxyphenylisopropylamine (MDA) and several related agents. The (+/-)-DOM stimulus generalized to (+/-)-MDA, suggesting that both agents apparently produce similar stimulus cues. Related agents, known to produce effects in man similar to those produced by (+/-)-MDA, also resulted in generalization when administered to the DOM-trained animals, e.g., R(-)-MDA and a methoxylated derivative of (+/-)-MDA, (+/-)-2-OMe-4,5-MDA. DOM stimulus generalization was not observed for S(+)-MDA, the N-monomethyl and alpha-demethyl derivatives of MDA, nor for a metabolite of MDA (i.e., 3-methoxy-4-hydroxyphenylisopropylamine). The results suggest that R(-)- and (+/-)-MDA, as well as (+/-)-2-OMe-4,5-MDA, but not the other derivatives of MDA, are capable of producing behavioral (stimulus) effects common to those produced by the training dose of (+/-)-DOM.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1982

Influence of chronic ethanol consumption on the metabolism and carcinogenicity of tobacco-related nitrosamines.

The effect of chronic ethanol consumption by Syrian golden hamsters (SGH) on the carcinogenicity and target tissue metabolism of N-nitroso-pyrrolidine (NPYR) and N'-nitrosonornicotine (NNN) has been examined. Ethanol-consuming hamsters treated with NPYR developed more nasal cavity and tracheal tumours than controls. Ethanol consumption did not affect the carcino-genicity of NNN. When the metabolism of NPYR and NNN by isolated tracheal rings was examined, it was observed that tracheal rings isolated from ethanol-consuming SGH metabolized NPYR at a higher rate than similar preparations from control animals. In contrast, no differences in the rates of metabolism of NNN were observed.

Alcoholism↗
PubMed1981

Behavioral properties of psychoactive phenylisopropylamines in rats.

Rats were trained to discriminate injections of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT, 3.0 mg/kg) a hallucinogenic agent for which a serotonergic mechanism has been implicated, from saline in a two-lever drug discrimination task. After reliable levels of accuracy (greater than or equal to 85%) were attained, the ability of the 5-OMe DMT cue to generalize to 36 substituted phenylisopropylamines (or their optical isomers) was assessed. The results reveal that, in general, the challenge compounds could be differentiated into three broad categories: Those that produced 5-OMe DMT-appropriate responding (generalization), those that produced partial 5-OMe DMT-appropriate responding (partial generalization) and those that produced negligible 5-OMe DMT-appropriate responding. It is concluded that certain of the substituted phenylisopropylamines, unlike amphetamine itself, can produce effects in rats similar to those produced by the training dose of 5-OMe DMT, and that a serotonergic mechanism might be involved.

Amphetamines↗
PubMed1981

Morphologic and autoradiographic evidence for a laminated pretectal olivary nucleus in the squirrel monkey.

The pretectal olivary nucleus of the squirrel monkey was examined in both normal and autoradiographic material. In the Nissl- and fiber-stained tissue the nucleus appears as a laminated structure. The distribution of retinal terminals within the nucleus was examined by the autoradiographic tracing method. These data reveal denser projection to the contralateral pretectal olivary nucleus. When comparing the distribution of the silver grains bilaterally, the pattern of transported label appears to be partially nonoverlapping.

Animals↗
PubMed1981

Cell lysis by induction of cloned lambda lysis genes.

The lysis gene region of bacteriophage lambda, including genes S, R, and Rz, was cloned into the plasmid pBH20. In the recombinant plasmid, the lysis genes are expressed under the control of the lacOP region. Induction of this "lysis operon" with the lac inducer, IPTG, under conditions where transcription from the lacOP region is not subject to catabolite repression, results in a sharply defined lysis after 35 min. Premature lysis can be accomplished by cyanide, chloramphenicol, or chloroform, exactly as in bacteriophage lambda infected cells. The lysis gene region of an S- mutant was also cloned into pBH20. Induction of the S- lysis operon has no apparent effect on culture growth; however, large quantities of bacteriolytic activity accumulate intracellularly. Neither cyanide nor chloramphenicol causes lysis in the induced S- clones. Thus premature lysis appears to be entirely an S-dependent phenomenon. A model for the control of lysis in bacteriophage lambda infections is presented in which it is the accumulation of the S gene product in competition with a host "anti-S" protein that determines lysis timing.

Bacteriophage lambda↗
PubMed1981

DOM and related 2,5-dimethoxy-4-alkylphenylisopropylamines: behavioral and serotonin receptor properties.

Using an isolated rat fundus preparation, the 4-methyl (DOM), ethyl (DOET), propyl (DOPR) butyl (DOBU), tertiary butyl (DOTB) and amyl (DOAM) derivatives of 2,5-dimethoxy-phenylisopropylamine (2,5-DMA) were found to possess quite similar serotonin receptor affinities (pA2 - 7.02-7.22). The fundus preparation could not be used to determine pD2 values because all of the compounds were found to interact in an agonistic manner both with serotonin and PRT (phenoxybenzamine resistant tryptamine) receptors. Administration of DOET, DOPR, DOBU, DOTB and DOAM to animals (rats) trained to discriminate 5-OMe DMT from saline resulted only in partial generalization. While each of these agents possesses a high 5-HT receptor affinity, and while their behavioral effects might, therefore, involve a serotonergic component, the stimulus properties of these compounds are qualitatively dissimilar to those produced by the training dose of 5-OMe DMT.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1981

pi cation radicals of ferrous and free base isobacteriochlorins: Models for siroheme and sirohydrochlorin.

Theoretical and experimental optical, redox, and paramagnetic results are presented for models of siroheme, the iron isobacteriochlorin prosthetic group of nitrite and sulfite reductases, and of sirohydrochlorin, the metal-free siroheme that is an intermediate in the biosynthetic pathway to vitamin B(12). The facile oxidation of many isobacteriochlorins, which distinguishes them from porphyrins and chlorins, suggests that the siroheme macrocycle itself may undergo oxidation in the multi-electron enzymatic cycles that reduce nitrite to ammonia and sulfite to hydrogen sulfide. Extended Hückel MO calculations (i) help rationalize the redox properties of isobacteriochlorins compared with those of porphyrins and chlorins; (ii) indicate that Fe(II) pyridine carbonyl[(py) (CO)] complexes of isobacteriochlorins, unlike those of porphyrins and chlorins, should undergo oxidation from the macrocycle rather than the metal to yield pi cation radicals; (iii) suggest that, in hexacoordinated Fe(II) isobacteriochlorin complexes, the site of oxidation-i.e., the metal or the macrocycle-will depend on the ligand field induced by the axial ligands; and (iv) predict similar unpaired spin density profiles for metal-free and (py) (CO)Fe(II) isobacteriochlorin radicals. Experimental data for three isomeric free-base and (py) (CO)Fe(II) complexes of dimethyloctaethylisobacteriochlorins support the theoretical calculations and establish the existence of Fe(II) isobacteriochlorin pi cations in vitro.

Journal Article↗