Behavioural indices of the interaction of clozapine with D1 and D2 dopamine receptors.
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Biomedical subjects
Publications and source records attributed to A M Murray.
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The haemodynamic response to tracheal intubation was compared in 303 patients in whom anaesthesia was induced with either thiopentone 4 mg/kg, etomidate 0.3 mg/kg or propofol 2.5 mg/kg, with and without fentanyl 2 micrograms/kg. There was after propofol alone a significant decrease in arterial blood pressure, which did not increase above control values after intubation. Significant increases in arterial pressure followed intubation in patients induced with thiopentone or etomidate alone. Increases in heart rate occurred with all agents after laryngoscopy. The use of fentanyl resulted in arterial pressures lower than those after the induction agent alone, and in an attenuation, but not abolition of the responses to laryngoscopy and intubation.
An aesthetic solution is offered to the problem of space maintenance following the re-opening of space for an upper central incisor.
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The sensitivity of methodology for measuring the concentration of fluorine species in saliva and in plaque has been tested. Human subjects mouth-rinsed daily with aqueous solutions of NaF and Na2FPO3. Samples of unstimulated whole saliva and of plaque were collected twice weekly at least 18 hr after treatment application. Oral fluoride concentrations rose from placebo values for approximately two weeks before attaining equilibrium and returned to baseline when daily mouthrinsing was stopped. Mean elevated oral fluoride concentrations increased significantly with increasing applied NaF concentration in the range 0-1000 ppm F (0-0.053 mol/L). There appeared to be a linear relationship between saliva and plaque fluoride. The ability of fluoride treatments to sustain elevated oral fluoride levels between daily applications may be of major importance in caries control.
The methods of immunoselection and electrophoretic analysis of [32P]-labelled nucleic acids have been applied to the problem of defining Crohn's disease (CD) specific antigen associated DNA or RNA, with the intention of identifying a presumptive aetiological microbial agent. Mesenteric lymph node derived cells from CD and control gastrointestinal disease cases were cultured in vitro with [32P] orthophosphate after mitogenic stimulation with phytohaemaglutinin and pokeweed mitogen. Total cell lysates were immunoprecipitated with CD and control serum IgG fractions and immune complexes recovered with pansorbin. Antigen associated [32P]-labelled nucleic acids were phenol/chloroform extracted and analysed by electrophoresis on polyacrylamide and agarose gels. No immunoprecipitated nucleic acid specific to CD tissues could be detected and no differences in antigen recognition between CD and control serum IgG were observed. No evidence was obtained for nucleic acid containing antigens either of the autoimmune type or of possible viral or microbial origin in CD mesenteric lymph nodes.
We have isolated a clone from a human genomic lambda library which cross-hybridises with the cloned hamster adenine phosphoribosyl transferase gene (aprt). After restriction mapping and further hybridisation to the hamster gene, a series of putative human aprt-containing fragments has been isolated and tested for ability to transform adenine phosphoribosyl transferase-deficient (aprt-) strains of Chinese hamster ovary (CHO) cells to APRT proficiency. Transforming activity was detected in a 48-kb lambda clone, the 17.4-kb EcoRI insert, and an 8.6-kb HincII fragment. Smaller fragments have thus far shown no transforming activity. Transformants appear to be stable for the APRT+ phenotype, and human aprt DNA sequences are present in the hamster transformants. The 8.6-kb HincII fragment has been subcloned and the insert mapped. Nonrepetitive regions of this subclone have been identified, and should prove valuable for chromosome walking studies on human chromosome 16, familial studies of a human aprt- trait, the analysis of restriction fragment length polymorphisms (RFLPs) in the area surrounding the aprt gene, and the fine structure mapping of the mutations induced by chemical carcinogens and alkylating agents.
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DNA was isolated from human diploid lung epithelial cells treated in culture with [3H]benzpyrene. The DNA contained one covalently bound benzpyrene group per 38 kb and it was digested with a series of restriction endonucleases giving decreasing fragment sizes, and also with DNAase I to 96% acid solubility. The digests were applied to octyl-Sepharose columns under conditions which promote hydrophobic interaction of the benzpyrene groups on the DNA with the octyl groups in the column matrix. Separation of fragments without and with benzpyrene groups was achieved with successive high salt and ethanediol washes. As DNA fragment size is decreased, more DNA-associated benzpyrene is eluted with ethanediol. Under these conditions, DNA from untreated cells is totally removed in the high salt wash and free benzpyrene metabolites are retained on the column. The separation of DNA fragments with covalently-bound hydrophobic benzpyrene groups, from less modified or unmodified DNA will facilitate examination of the distribution of benzpyrene adducts in defined regions of the human genome.
The cells of the bronchial epithelium of man are targets for benzo(a)pyrene carcinogenesis. When cultures of these cells, and of non-target fibroblasts, are exposed to [3H]-benzo(a)pyrene, we find that the epithelial cells metabolise and bind to DNA far greater amounts of benzpyrene than do fibroblasts. By analysis of nuclei of benzpyrene-treated cells for sensitivity to limited digestion with pancreatic DNase I, we have shown that benzpyrene groups bind initially to the DNA of expressed (DNase I sensitive) regions of chromatin in both cell types. Covalent binding of benzpyrene groups to non-expressed (DNase I resistant) regions follows rapidly in the target epithelial cells. These maintain high levels of carcinogen adducts in their DNA. In fibroblasts, benzpyrene group binding to non-expressed DNA occurs more slowly and active removal of adducts from the DNA is evident.
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Functional interactions between D-1 and D-2 dopamine receptor systems appear important in the regulation of psychomotor behavior, and may alter with aging. Male Sprague-Dawley rats of 5 and 20-24 months were challenged with the selective D-2 agonist LY 163502 alone or following pretreatment with the selective D-1 antagonist SCH 23390. Typical sniffing and locomotor responses to LY 163502 alone were significantly reduced in aged animals. Pretreatment with SCH 23390 blocked these typical responses in both young and aged animals, consistent with their regulation by cooperative D-1:D-2 interactions; however, SCH 23390 released a significant excess of atypical limb/body jerking to LY 163502 in aged animals, a response which appears to have its basis in oppositional D-1:D-2 interactions. These results suggest that the net effect of aging on dopaminergic transmission is to reduce tonic activity through D-1 receptors to a greater extent than that occurring through D-2 receptors. As the present aged animals showed a selective loss of striatal D-2 but not of D-1 receptors in radioligand binding studies, such a reduction of D-1-mediated transmission with aging would seem to involve loss of presynaptic function or of postsynaptic mechanisms beyond the D-1 recognition site.
In this electronic age there is a general move towards keeping digital records, and many trades and professions now use digital images exclusively. In this article, the advantages (and occasional disadvantages) of the use of digital photography, digital radiography and the latest development--digital study models--in orthodontics are discussed.
Two adherent sublines, H69V and H69VZ, have been isolated from the classic SCLC cell line NCI-H69. Significant morphological differences were observed between the parental and the derivative cell lines. While NCI-H69 grew as densely packed free floating cellular aggregates the derivative lines grew as a monolayer of epithelioid cells. The growth rates of both the derivative lines were faster than the parental line with doubling times closer to non-SCLC cell lines in the derivative lines. Both H69V and H69VZ either express very low levels or do not express neuroendocrine cell markers including L-dopa-decarboxylase (DDC), creatine kinase-BB isoenzyme (CK-BB), bombesin-like immunoreactivity (BLI), neuron specific enolase (NSE), and neurosecretory type dense core granules (DGCs), compared to the parental cell line. All the lines stained positive for epithelial markers such as CAM5.2. LDH isoenzyme and chromosome analyses confirmed the human origin of all the cell lines. Therefore, it appears that cell line NCI-H69 contains stem cell subpopulation capable of generating cells of both small and non-small cell like phenotypes.