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Biomedical subjects

R Young

Publications and source records attributed to R Young.

At least 217 records · Page 12Linked to original sources
PubMed1987

Behavioral effects of several new anxiolytics and putative anxiolytics.

The behavioral effects of several new anxiolytics and putative anxiolytics were evaluated in two tests sensitive for anxiolytic activity. In the first test, rats were trained to lever-respond for sweetened milk under a multiple variable-interval fixed-ratio (VI-FR) schedule of reinforcement. In the FR component a brief electric shock coincided with the presentation of reward (i.e. conflict procedure). Treatment of these rats with diazepam, tracazolate, CGS-9896, and the pyrimidinylpiperazine derivatives buspirone, gepirone and ipsapirone (TVX Q 7821) significantly increased responding that was suppressed by foot-shock. A common metabolite of the pyrimidinylpiperazines, l-PP, had no affect on punished responding. A second group of rats was trained to discriminate diazepam from saline using a two-lever operant choice procedure. Diazepam-stimulus generalization occurred to CGS-9896, CL 218,872, zopiclone and tracazolate, but not to buspirone, gepirone, ipsapirone or l-PP. It was concluded that while all of the new compounds examined appear to share an anxiolytic effect as demonstrated by their activity in the conflict procedure, the pyrimidinylpiperazine agents do not share discriminative stimulus properties which are common to drugs which act via the benzodiazepine receptor.

Animals↗
PubMed1987

[Incidence, etiology and risk of rupture of aortic aneurysm. An autopsy study].

In an unselected series of 3,375 autopsies performed during five years there were 114 cases of aortic aneurysm (3.4%). Males were affected 9.4 times as often as females. Average age at death of those with aneurysm was 72.8 years, of those with rupture 69 years. Of the aneurysms 73.8% were located in the lumbar aorta, 22.8% in the thoracic aorta and 3.5% involved the entire aorta. Saccular or fusiform aneurysms accounted for 73.4%, dissecting ones for 18.4% and pseudoaneurysms for 1.8%. Arteriosclerosis was the underlying cause of the aneurysm in 95.6% of cases; in 41.2% rupture was the direct cause of death. Aneurysms of the thoracic aorta were ruptured in 65.4%, of the lumbar aorta in 32.1%. The incidence of rupture was highest for dissecting aneurysm of the thoracic aorta and the entire aorta--75% each. Hypertension was found to be a risk factor of rupture.

Aged↗
PubMed1987

Effects of pyrazolopyridines and a triazolopyridazine on the pentobarbital discriminative stimulus.

Rats were trained to discriminate injections of racemic pentobarbital (5.0 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performance was attained, stimulus generalization studies were conducted with another barbiturate (barbital), benzodiazepine derivatives (diazepam and chlordiazepoxide), pyrazolopyridine derivatives (etazolate, cartazolate, and tracazolate), and a triazolopyridazine (CL 218, 872). The pentobarbital stimulus generalized to all of these compounds, except cartazolate. In addition, the administration of the benzodiazepine receptor antagonist flumazepil prior to benzodiazepine or triazolopyridazine administration produced a dose-related antagonism of each generalization. In contrast, the administration of flumazepil before barbiturate or pyrazolopyridine (i.e., etazolate or tracazolate) injection resulted in no attenuation of these generalizations. The results indicate that while certain barbiturates, benzodiazepines, pyrazolopyridines and triazolopyridazines are capable of producing similar stimulus effects, the behavioral actions of these agents can be differentiated on the basis of their susceptibility to antagonism by flumazepil.

Animals↗
PubMed1987

Stimulus properties of benzodiazepines: correlations with binding affinities, therapeutic potency, and structure activity relationships (SAR).

Using a two-lever operant choice task, rats were trained to discriminate diazepam (3.0 mg/kg) from saline under a fixed-ratio 10 (FR10) schedule of reinforcement. Once the discrimination was learned, generalization studies were conducted using various doses of 17 benzodiazepine derivatives. The diazepam stimulus generalized in a dose-related manner to each of these compounds. ED50 values were compared with available data on displacing affinities (Ki values) for tritiated diazepam brain binding in man, and with human therapeutic potency. A significant correlation (r = 0.88, n = 9) was found between benzodiazepine binding affinities and ED50 values derived from the diazepam stimulus generalization assay. A significant correlation (r = 0.92, n = 10) was also found between drug discrimination ED50 values and human therapeutic potencies. Finally, the benzodiazepine structure activity relationships generated from the drug discrimination studies closely paralleled the known structure activity relationships for these agents. The results provide further evidence that benzodiazepines exert their pharmacological effects through an interaction with benzodiazepine receptors.

Animals↗
PubMed1987

Adult cutaneous hemangiomas are composed of nonreplicating endothelial cells.

Thirty-four human "cherry" dermal hemangiomas were studied by electron microscopy, immunohistochemistry, and cell culture to assess the neoplastic nature of these lesions. Electron microscopy of nine hemangiomas revealed a pronounced thickening of the basement membrane (0.6 to 14 micron) in 93% of the total 158 vascular structures examined within the lesions. This increase was caused mainly by multiple layers of basal lamina, which were irregular in outline and frequently associated with pericytes. Basement membrane changes were present both in the periphery of the hemangiomas, as well as in the center of the lesions. Immature vessels could not be identified and mitoses were absent in all endothelial cells. Using an immunohistochemical marker (Ki67) specific for proliferating cells in G2 and S phases, positive staining was not found in the endothelial cells lining the hemangiomatous vessels, whereas basal epidermal keratinocytes in the same preparations and cultured microvascular endothelial cells expressed the antigen. Endothelial cells of nine hemangiomas did not stain with an activation-related antibody (E12) specific for endothelial cells. When endothelial cells from 14 hemangiomas were isolated and cultured under conditions that support the growth of normal human skin microvascular endothelial cells, the cells of hemangiomatous origin failed to grow. We conclude that the adult hemangiomas may not be true neoplasms, but a tissue overgrowth composed of mature vessels resembling dermal venules, lined by endothelial cells with virtually no turnover.

Adult↗
PubMed1987

Identification and characterization of the Pasteurella haemolytica leukotoxin.

The identification and chromatographic characterization of the leukotoxin of Pasteurella haemolytica is described. The toxin, which has an apparent native molecular weight of greater than 400,000 as judged by gel exclusion chromatography, has a 105-kilodalton (105K) polypeptide as its major protein component. The proteolytic degradation of the 105K polypeptide could be correlated with the loss of toxin activity in aging cultures of P. haemolytica. Antisera raised against purified 105K polypeptide neutralized toxin activity. A 3.9-kilobase-pair fragment of the P. haemolytica genome cloned into a plasmid vector resulted in the production of intracellular toxin in Escherichia coli host cells. The restriction map of this clone shows significant overlap with the map of a previously reported leukotoxin clone (R. Y. C. Lo, P. E. Shewen, C. A. Strathdee, and C. N. Greer, Infect. Immun. 50:667-671, 1985). Finally, antisera raised against the 105K species labeled the P. haemolytica cell surface in a nonuniform, punctate manner.

Animals↗
PubMed1987

Eucaryotic RNA polymerase conditional mutant that rapidly ceases mRNA synthesis.

We have isolated a yeast conditional mutant which rapidly ceases synthesis of mRNA when subjected to the nonpermissive temperature. This mutant (rpb1-1) was constructed by replacing the wild-type chromosomal copy of the gene encoding the largest subunit of RNA polymerase II with one mutagenized in vitro. The rapid cessation of mRNA synthesis in vivo and the lack of RNA polymerase II activity in crude extracts indicate that the mutant possesses a functionally defective, rather than an assembly-defective, RNA polymerase II. The shutdown in mRNA synthesis in the rpb1-1 mutant has pleiotropic effects on the synthesis of other RNAs and on the heat shock response. This mutant provides direct evidence that the RPB1 protein has a functional role in mRNA synthesis.

Chromosome Mapping↗
PubMed1987

Early experience in the Queensland Orthotopic Liver Transplantation Programme.

The cases of the first nine patients to receive orthotopic liver transplants in the Queensland Liver Transplant Programme are reported. Problems peculiar to this type of operation are discussed generally and in the light of this experience. The anaesthetic technique employed is described. There were no deaths attributable to anaesthesia.

Adult↗
PubMed1987

Pneumonic pasteurellosis: examination of typable and untypable Pasteurella haemolytica strains for leukotoxin production, plasmid content, and antimicrobial susceptibility.

Plasmid DNA screening experiments were conducted to determine whether a relationship existed between the presence of plasmids and antibiotic resistance in Pasteurella haemolytica or the capability to produce hemolysin or leukotoxin (cytotoxin). Regardless of plasmid content, all P haemolytica isolates produced characteristic hemolysis on blood agar plates. Similarly, standardized suspensions of living bacteria and sterile concentrated (approx 200:1) culture supernatant from strains representing each of the 15 recognized P haemolytica serotypes and 7 field strains of P haemolytica (biotype A, serotype 1) produced leukotoxin, which was detected by their capability to cause inhibition of the luminol-dependent chemiluminescence response of bovine neutrophils. However, neither living bacterial suspensions nor concentrated culture supernatant from 4 untypable P haemolytica strains or a P multocida strain caused an inhibition of the luminol-dependent chemiluminescence response. The production of neither hemolysin nor leukotoxin by P haemolytica seemed to be plasmid mediated. Leukotoxin production is apparently a stable phenotypic characteristic of pathogenic P haemolytica strains, and the gene(s) coding for this activity is probably located on the bacterial host chromosome. Antibiotic susceptibility profiles were determined for the different bacterial strains. Studies of ampicillin and penicillin resistance in 8 P haemolytica (biotype A, serotype 1) strains provided evidence that the plasmid, with size of approximately 5,200 base pairs, may code for their resistance to these compounds.

Animals↗
PubMed1986

Two or more copies of Drosophila heat shock consensus sequence serve to activate transcription in yeast.

A synthetic oligonucleotide bearing the Drosophila heat shock consensus sequence confers heat inducibility on a CYC1-lacZ gene in Saccharomyces cerevisiae. This sequence CTGGAATTTTCTAGA was inserted in place of the upstream activation sites of the CYC1 promoter adjacent to CYC1 TATA boxes. These constructs were transformed into yeast and found to be heat-inducible when two or more inserts were present. The level of inducibility seemed to increase with the number of inserted sequences: however, the orientations of these sequences relative to each other did not have much effect.

Animals↗
PubMed1986

Double-labeled metabolic maps of memory.

The physical changes representing a memory are believed to be localized to specific neurons, widely distributed in multiple parallel pathways in the brain. 2-Fluorodeoxyglucose, labeled with two discriminable radioactive tracers, was used to construct quantitative metabolic maps in split-brain cats during a visual task. One side of the brain served to estimate the metabolic variability of nonspecific influences. The other side was used to map metabolic changes related to the presence of previously learned visual cues, as well as changes related to nonspecific influences, in the same periods of time. When the two sides were compared, between 5 million and 100 million neurons (depending upon the significance level selected) were identified in which activity increased during presentation of the familiar cues. The wide distribution of these neurons throughout the brain is compatible with prior evidence of a distributed memory system. However, the large number of neurons involved is difficult to reconcile with theories in which individual neurons are dedicated to specific memories.

Animals↗
PubMed1986

Potencies of diazepam metabolites in rats trained to discriminate diazepam.

The dose-response relationships of diazepam and several of its metabolites were determined in rats trained to discriminate diazepam (3 mg/kg) from saline in a two-lever operant choice task. Generalization of the diazepam stimulus was found to occur with temazepam and oxazepam, which were nearly equipotent with diazepam, and also with desmethyldiazepam, which was about half as potent as diazepam. The hydroxylated metabolites, 4'-hydroxydiazepam and 4'-hydroxydesmethyldiazepam were inactive in doses up to 12 mg/kg. These results show that some diazepam metabolites are quite potent behaviorally and indicate the possibility that these metabolites may contribute to the pharmacological effect of diazepam in vivo.

Animals↗
PubMed1986

Further studies on the dose-dependent stimulus properties of 5-methoxy-N,N-dimethyltryptamine.

Twenty-two rats were trained to discriminate either 1.5 mg/kg of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a standard two-lever operant procedure. Once responding was stable, various doses of several serotonin (5-HT) antagonists, i.e., cyproheptadine (CYP), methysergide (UML), cinanserin (CIN), and methergoline (MCE), were administered in combination with 5-OMe DMT, to assess the ability of each antagonist to attenuate each 5-OMe DMT-stimulus. The 5-OMe DMT-stimulus at 1.5 mg/kg was completely antagonized by CYP, and was partially attenuated by CIN and MCE. UML had negligible effects on 5-OMe DMT-appropriate responding. In the 3.0 mg/kg 5-OMe DMT-trained rats, UML and MCE partially blocked the 5-OMe DMT-stimulus; CYP and CIN had no significant effect on 5-OMe DMT-appropriate responding. The results suggest that until the in vivo effects and mechanism of action of 5-OMe DMT and certain 5-HT antagonists are better understood, caution is advised when conclusions are drawn from studies employing these agents.

Animals↗
PubMed1986

Plasmid expression vector using the lambda late promoter.

A plasmid expression vector called pQTE1 based on the late promoter, pR', and positive control gene Q of bacteriophage lambda has been constructed. This vector has unique cloning sites for placing exogenous DNA under control of pR'. Induction of expression of genes cloned into the pQTE1 plasmid leads to massive overproduction of the gene products. Also, transcription from the pR' promoter on pQTE1 appears to be insensitive to polarity effects.

Bacteriophage lambda↗
PubMed1986

Gene fusion in vivo using transductional cointegrates.

A method is described which allows the efficient construction of hybrids between homologous genes. The technique is based on the phenomenon of cointegrate transduction in which the homology between cloned sequences present on a bacteriophage lambda vector and a plasmid vector is exploited to allow the packaging of a plasmid-phage recombinant. The size of the cointegrate molecule can be far beyond the normal packaging limit of lambda and still allow the transduction of plasmid-borne drug-resistance markers. This method allows the exchange of the 5' and 3' ends of the participating genes as well as the exchange of sequences residing between the end-points of homology between the two genes. Hybrids of either type were constructed between a sea urchin and a Drosophila actin gene using the transductional cointegrate method in vivo. This approach does not require the use of specialized phage or plasmid vectors and can also be used to screen plasmid libraries with a bacteriophage lambda probe.

Actins↗