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Biomedical subjects

K Daniel

Publications and source records attributed to K Daniel.

At least 19 recordsLinked to original sources
PubMed2006

Influence of tea drinking on manganese intake, manganese status and leucocyte expression of MnSOD and cytosolic aminopeptidase P.

OBJECTIVE: Since black tea contains high levels of manganese (Mn), we investigated the relationship between dietary Mn intake, circulating Mn levels and leucocyte expression of two Mn-dependent enzymes in tea drinkers and non-tea drinkers. DESIGN: We assessed Mn intakes (food frequency questionnaire), fasting whole blood and plasma Mn levels, and quantitative expression of peripheral blood mononuclear cell Mn-dependent superoxide dismutase (MnSOD) and cytosolic aminopeptidase-P (cAP-P). SETTING AND SUBJECTS: In total, 24 tea drinkers (> or = 1 l black tea/day) and 28 non-tea drinkers were recruited from the staff and students of King's College London by circular email. RESULTS: Dietary Mn intakes (mean (range)) were significantly lower (P < 0.0001) in non tea drinkers (3.2 mg/day (0.5-6.5)) than tea drinkers (5.5 mg/day (2-12) or 10 mg/day (5-20) depending upon the value used for Mn levels of black tea). Whole blood, plasma Mn levels and expression of MnSOD and cAP-P did not differ between the groups. In a continuous analysis, whole blood Mn levels and expression of MnSOD correlated inversely but no other parameters associated with each other. CONCLUSIONS: Tea drinking is a major source of dietary Mn and intakes commonly exceed proposed adequate intake values of 1.8-2.3 mg Mn/day and, on occasion, exceed upper limits of 10-11 mg/day. Dietary Mn intake has little influence on markers of Mn status or expression of Mn-dependent enzymes. Fasting whole blood Mn levels and leucocyte expression of MnSOD could, together, be further investigated as markers of Mn status.

Adult↗
PubMed2000

Fusagene vectors: a novel strategy for the expression of multiple genes from a single cistron.

Transduction of cells with multiple genes, allowing their stable and co-ordinated expression, is difficult with the available methodologies. A method has been developed for expression of multiple gene products, as fusion proteins, from a single cistron. The encoded proteins are post-synthetically cleaved and processed into each of their constituent proteins as individual, biologically active factors. Specifically, linkers encoding cleavage sites for the Golgi expressed endoprotease, furin, have been incorporated between in-frame cDNA sequences encoding different secreted or membrane bound proteins. With this strategy we have developed expression vectors encoding multiple proteins (IL-2 and B7.1, IL-4 and B7.1, IL-4 and IL-2, IL-12 p40 and p35, and IL-12 p40, p35 and IL-2 ). Transduction and analysis of over 100 individual clones, derived from murine and human tumour cell lines, demonstrate the efficient expression and biological activity of each of the encoded proteins. Fusagene vectors enable the co-ordinated expression of multiple gene products from a single, monocistronic, expression cassette.

Animals↗
PubMed1999

Factors that influence nurses' customer orientation.

BACKGROUND: Hospital care mostly involves complex processes that are continuously adjusted to match individual client needs. As most patients cannot evaluate the technology used, they focus on personal interactions with care providers when making judgements about the care received. Nurses are the care team members that primarily provide ongoing care. AIMS: This study aims to further understand factors that influence the way nursing staff relate to their patients. A model is presented of the contextual and self-perceptual factors that influence the level of customer/client orientation of nursing services in an Australian hospital setting along with details of a quantitative study. METHODS: Nurses completed an anonymous questionnaire, which was then mailed directly to the researchers. Analysis of the data included factor analysis, regression and path analysis. FINDINGS: The results show that contextual elements such as management commitment to service quality and self-perceptual factors such as role stress impact on the nurses' client service orientation. However, the variables being studied commonly have both direct and indirect effects with feelings about commitment to the organization having a notable mediating influence. The scales adapted from use in other industries are able to measure the perceptual and outcome variables in a health institutional setting. CONCLUSIONS: The managerial implications are that both a comprehensive programme of organizational culture and individual staff member development is needed if an enhanced customer orientation and the consequent improvement in client satisfaction with nursing care is to occur.

Attitude of Health Personnel↗
PubMed1997

Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum.

Several hydroxylated polychlorinated biphenyls (PCBs) identified in human serum have been synthesized and these include 2,2',3,4',5,5'-hexachloro-4-biphenylol; 2,3,3',4',5-pentachloro-4-biphenylol; 2',3,3',4',5-pentachloro-4-biphenylol; 2,2',3,3',4',5-hexachloro-4-biphenylol; 2,2',3,3',4',5,5'-heptachloro-4-biphenylol; 2,2',3,4',5,5',6-heptachloro-4-biphenylol; and 2,2',3',4,4',5,5'-heptachloro-3-biphenylol. The hydroxy-PCBs exhibited minimal binding to the rat uterine cytosolic estrogen receptor (ER) and did not induce proliferation of estrogen-responsive MCF-7 human breast cancer cells at concentrations ranging from 10(-5) to 10(-8) M. The estrogenic activity of these compounds was further investigated utilizing two estrogen-responsive in vitro bioassays, namely, (i) HeLa cells stably transfected with a Gal4:human ER chimera and a 17-mer-regulated luciferase reporter gene, and (ii) MCF-7 cells transiently transfected with a full-length human ER expression plasmid and a plasmid containing an estrogen-responsive vitellogenin A2 promoter linked to a chloramphenicol acetyl transferase (CAT) reporter gene. None of the hydroxy-PCBs significantly induced luciferase activity in the stably transfected HeLa cells or CAT activity in MCF-7 cells at concentrations as high as 10(-5) M. The antiestrogenic effects of the hydroxy-PCBs were also investigated using the same bioassays in which the cells were cotreated with 17beta-estradiol plus the hydroxy-PCBs. All of the hydroxy-PCB congeners inhibited one or more estrogenic response, and one congener, 2,2',3,4',5,5',6-heptachloro-4-biphenylol, inhibited 17beta-estradiol-induced cell proliferation and CAT activity in MCF-7 cells and luciferase activity in HeLa cells.

Adenocarcinoma↗
PubMed1993

Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors.

Receptor-specific or homologous desensitization of beta 2-adrenergic receptors is thought to be effected via phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK), followed by binding of beta-arrestin. We have generated stably transfected Chinese hamster ovary cell lines overexpressing either of the two regulatory proteins and also expressing low or high levels of beta 2-adrenergic receptors (approximately 80 and approximately 600 fmol/mg of membrane protein). In these cells, we studied the process of desensitization induced by the beta-adrenergic receptor agonist isoproterenol. In cells expressing high levels of beta 2-adrenergic receptors, desensitization to high concentrations of isoproterenol (previously shown to be mediated by both beta ARK and protein kinase A) amounted to approximately 50% in control cells, approximately 80% in beta ARK-overexpressing cells, and approximately 90% in beta-arrestin-overexpressing cells. In cells expressing low levels of beta 2-adrenergic receptors, these values were approximately 50, approximately 60, and approximately 60%, respectively. Desensitization to low concentrations of isoproterenol (previously shown to be essentially protein kinase A-mediated and not receptor-specific, i.e. heterologous) was not affected by overexpression of either beta ARK or beta-arrestin. These data suggest that in cells expressing high levels of beta 2-adrenergic receptors, beta-arrestin and beta ARK become limiting for homologous receptor desensitization. They provide further support for the involvement of these two proteins in the regulation of beta 2-adrenergic receptor function.

Adenylyl Cyclases↗
PubMed1990

Childhood lead poisoning, New York City, 1988.

In 1988, a total of 796 cases of childhood lead poisoning were identified through surveillance by the New York City Bureau of Lead Poisoning Control (BLPC), an estimated 0.3 cases identified per 100 children screened. Sixty-two percent of the case-group children had blood-lead levels between 25 and 34 micrograms/dl. One- and two-year-old children accounted for 61% of cases. Of the children in the case group, 59% were black and 27% were Hispanic. From 1986 through 1989, the annual number of children screened increased by 27%, while the annual number of new cases fell by 30%. Because of incomplete screening, false negative results, and lack of information on children with lower but potentially harmful levels of blood lead (10-24 micrograms/dl), the magnitude of excessive lead absorption in New York City children is underestimated. These surveillance data indicate that lead poisoning among children is a persistent public health problem in New York City.

Black or African American↗
PubMed1989

Observations on a new non-invasive monitor of skin blood flow.

1. A 'tissue perfusion monitor' (TPM) to non-invasively provide an index of skin blood flow (SkBF) has been developed; it employs photoelectric plethysmographic principles to measure changes in the nett flux of red blood cells in superficial microvasculature. 2. The 'tissue perfusion index' (TPI) varies in proportion to SkBF, provided local haemoglobin concentration does not change significantly. TPI of humans and experimental animals has been shown to indicate reliably, well established phenomena such as decreased SkBF in response to mechanical restriction, cold or Valsalva's manoeuvre, or increased SkBF in response to heat, acetylcholine, sodium nitrite or local nerve blockade. 3. SkBF in sheep was varied between 1 and 156 mL/100g per min as measured with radioactive microspheres. Simultaneous measurements were made using the TPM and four laser-Doppler instruments. The TPI yielded a correlation coefficient of 0.938, and when data were expressed as percentage change, the regression line did not differ significantly from the line of identity and the root-mean-square-error was 6.2%. Data for the laser-Doppler indices of SkBF were, respectively, 0.549-0.786, highly significant deviations in slopes, and 13.6-16.7%. 4. Thus, the TPI is a reliable index of changes in SkBF. Compared with some other available instruments, the TPM is more precise; it is also less sensitive to movement artefact, can be completely portable by battery operation, probes can be multiplexed to a single meter and it is likely to be much less expensive than current lasers. 5. Applications include, for example, experimental investigations of SkBF in man and animals, clinical uses such as evaluation of the efficacy of regional nerve blockade or of circulatory restitution after reconstructive surgery, and clinical tests of neurovascular function.

Adult↗
PubMed1988

Chimeric alpha 2-,beta 2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity.

The alpha 2 and beta 2 adrenergic receptors, both of which are activated by epinephrine, but which can be differentiated by selective drugs, have opposite effects (inhibitory and stimulatory) on the adenylyl cyclase system. The two receptors are homologous with each other, rhodopsin, and other receptors coupled to guanine nucleotide regulatory proteins and they contain seven hydrophobic domains, which may represent transmembrane spanning segments. The function of specific structural domains of these receptors was determined after construction and expression of a series of chimeric alpha 2-,beta 2-adrenergic receptor genes. The specificity for coupling to the stimulatory guanine nucleotide regulatory protein lies within a region extending from the amino terminus of the fifth hydrophobic domain to the carboxyl terminus of the sixth. Major determinants of alpha 2- and beta 2-adrenergic receptor agonist and antagonist ligand binding specificity are contained within the seventh membrane spanning domain. Chimeric receptors should prove useful for elucidating the structural basis of receptor function.

Amino Acid Sequence↗
PubMed1987

Functional activity and regulation of human beta 2-adrenergic receptors expressed in Xenopus oocytes.

The recently cloned human beta-adrenergic cDNA and several mutated forms have been expressed in Xenopus laevis oocytes by injection of RNA made from the cDNA under the control of the bacteriophage SP6 promoter. The cDNA and gene of the beta 2-adrenergic receptor possess the unusual feature of having a second upstream ATG (-101 base pairs) and a 19-codon open reading frame 5' to the initiator methionine codon of the receptor (Kobilka, B. K., Dixon, R. A. F., Frielle, T., Dohlman, H. G., Bolanowski, M., Sigal, I. S., Yang-Feng, T. L., Francke, U., Caron, M. G., and Lefkowitz, R. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 46-50). RNA lacking this upstream AUG and open reading frame was translated approximately 10-fold more efficiently both in an in vitro rabbit reticulocyte system and in oocytes. Injected oocytes but not water injected controls expressed typical beta 2-adrenergic receptors as assessed by ligand binding (450 fmol/mg membrane protein) and catecholamine-stimulated adenylate cyclase (approximately 20 fold). Moreover, these receptors displayed typical agonist-induced homologous desensitization when oocytes were incubated with isoproterenol at room temperature for 3-24 h. Among a series of mutations, truncations of the membrane-anchored core of the receptor eliminated receptor binding and cyclase stimulating activity. In contrast, disruption of one of the cAMP-dependent protein kinase phosphorylation sites or removal of the serine/threonine-rich carboxyl terminus had little or no effect on these functions or on the extent of agonist-induced desensitization relative to that observed with native receptor. These studies validate the beta 2-adrenergic nature of the cloned human beta-adrenergic cDNA, document the utility of the Xenopus oocyte system for studying functional and regulatory properties of receptors coupled to adenylate cyclase, and suggest the possibility that elements in the 5' untranslated region of the beta 2-adrenergic receptor RNA may regulate its translation in vivo.

Adenylyl Cyclases↗