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Biomedical subjects

R Jefferson

Publications and source records attributed to R Jefferson.

13 recordsLinked to original sources
PubMed2001

Efficient or family-centred? Practitioners' goals in decisions regarding parental presence during invasive procedures.

Little is currently documented about how health care professionals determine when parental presence is appropriate during an invasive procedure. The research profiled in this article was a qualitative study of the decision-making by 10 nurses and five physicians in PICU regarding when and how to include parents as witnesses to invasive procedures. This article includes one aspect of the research findings: practitioners' goals in such decisions. Specifically, the authors will detail how practitioners' perspectives about the primacy of particular goals of the child's care influenced their decisions to encourage or discourage parents from remaining with their children during invasive procedures. It was found that participants' decisions whether or not to permit parents to remain during invasive procedures were primarily determined by what the practitioner held as the priority goal of his/her practice (i.e., efficiency or family-centred care). The authors conclude by identifying some clinical and research directives that arise from the research findings.

Attitude of Health Personnel↗
PubMed2000

Cannabinoid properties of methylfluorophosphonate analogs.

Methylarachidonylfluorophosphonate (MAFP) and related analogs have been shown to inhibit fatty acid amidohydrolase activity (FAAH), the enzyme responsible for hydrolysis of the endogenous cannabinoid ligand anandamide. To fully characterize this class of compounds, methylfluorophosphonate compounds with saturated alkyl chains ranging from C8 to C20 along with C20 unsaturated derivatives were synthesized and evaluated for their ability to interact with the CB1 receptor, inhibit FAAH, and produce in vivo pharmacological effects. These analogs demonstrated widely varying affinities for the CB1 receptor. Of the saturated compounds, C8:0 was incapable of displacing [(3)H]CP 55,940 binding, whereas C12:0 exhibited high affinity (2.5 nM). The C20:0 saturated analog had low affinity (900 nM), but the introduction of unsaturation into the C20 analogs restored receptor affinity. However, none of the analogs were capable of fully displacing [(3)H]CP 55,940 binding. On the other hand, all compounds were able to completely inhibit FAAH enzyme activity, with the C20:0 analog being the least potent. The most potent FAAH inhibitor was the short-chained saturated C12:0, whereas the other analogs were 15- to 30-fold less potent. In vivo, the C8:0 and C12:0 analogs were highly potent and fully efficacious in producing tetrahydrocannabinol (THC)-like effects, whereas the other analogs were either inactive or acted as partial agonists. None was capable of attenuating the agonist effects of THC. Conversely, the C20:0 analog potentiated the effects of anandamide but not those of 2-arachidonoyl-glycerol and THC. The high in vivo potency of the novel short-chain saturated MAFP derivatives (C8:0 and C12:0) underscores the complexity of manipulating the endogenous cannabinoid system.

Analgesics, Opioid↗
PubMed1999

Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists.

Structure-activity relation studies have established that the alkyl side chain in tetrahydrocannabinol (THC) plays a crucial role in the activation of the cannabinoid receptor. Unfortunately, the flexible nature of this side chain has hampered efforts to elucidate the precise nature of the interaction of THC with its receptors. Therefore, a series of analogs with structurally restrained side chains of varying length was synthesized and evaluated for pharmacological potency in mice and for receptor affinity. The introduction of cis double bonds inserted rigid angles, whereas triple bonds developed regions of planarity. Receptor affinity for the acetylenic and saturated side chains were the same, whereas double bond substitution increased affinity 10-fold. Moreover, the relationship between receptor affinity and potency was 10-fold less than that of Delta(8)-THC in the case of some acetylenic derivatives, whereas changing the triple bond to a double bond restored the potency/affinity ratio. Additionally, an acetylene at C2-C3 in the octyl and nonyl side chains favored antinociception by as much as 70-fold. Surprisingly, several high-affinity acetylenic derivatives, especially those with cyano substitutions at the terminus of the side chain, were partial agonists or were inactive. Some of these low-efficacy, high-affinity ligands elicited antagonistic activity. The finding that manipulations of the side chain produces high- affinity ligands with either antagonist, partial agonist, or full agonist effects reveals a critical structural feature for receptor activation.

Animals↗
PubMed1990

Transcriptional regulation of a patatin-1 gene in potato.

Patatin is an abundant glycoprotein in the tubers of potato plants that has a lipid acyl hydrolase activity. Fusions of the promoter of patatin genes that are highly expressed in tubers with the reporter gene encoding beta-glucuronidase (GUS) have shown that patatin transcription has a high degree of tuber specificity. Patatin transcription was also inducible in other organs of transgenic potato by growth on high concentrations of sucrose. Experiments were conducted to define regions of the patatin promoter that confered tuber specific expression and sucrose inducibility. Sequences between -40 and -400 bp and between -400 and -957 bp of the transcriptional start site were able to confer tuber-specific expression on a heterologous truncated promoter. The cell specificity of GUS transcription in the transformants indicated that organ specificity was possibly determined by source-sink relationships of sucrose, or a metabolite of sucrose, in the whole plant.

Base Sequence↗
PubMed1989

Tissue- and cell-specific activity of a phenylalanine ammonia-lyase promoter in transgenic plants.

Phenylalanine ammonia-lyase (PAL) catalyses the first step in the biosynthesis of phenylpropanoids, which form a wide variety of plant secondary products. The transcription of PAL is regulated in response to various factors that induce the accumulation of flavonoids, lignin and compounds thought to be involved in plant defence reactions. The 5' upstream sequence of a PAL gene from Phaseolus vulgaris was fused to the coding region of the reporter gene encoding beta-glucuronidase (GUS), and transformed into potato and tobacco plants. Histochemical analysis of GUS expression showed that the PAL promoter was active in specific cell types that accumulated phenylpropanoid derivatives in response to mechanical wounding, and also during normal development of the xylem and flower. In xylem that had undergone secondary thickening, GUS activity occurred in rays of cells thought to be the xylem parenchyma. It was postulated that PAL activity in these cells could provide intermediates for lignin synthesis in xylem vessels that had terminally differentiated.

Ammonia-Lyases↗