Cloning human

The cloned human GAL2 receptor binds porcine [125I]-[Tyr26]galanin and couples readily to Gq/Gn-type G proteins or related pathways in vitro. Under certain conditions, GAL2 also appears to couple with G/G0-and G12-type proteins [1, 2]. Specific examples of... 

When assayed in HEK293 cells transfected with the cloned human, rat and guinea pig TRPVl, (23a) showed similar potencies. Not unexpeetedly, (23a) showed poor metabolic stability and a structure-activity study to optimize potency and drug-like properties was initiated. Modification on the left-handed A -aryl section showed that ... 

Felder CC, Briley EM, Axelrod J, Simpson JT, Mackie K, Devane WA. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc Natl Acad Sci USA 1993 90 7656-7660. 

Raynor K, Kong H, Mestek A et al. Characterization of the cloned human p. receptor. J Pharmacol Exp Ther 1995 272 423-428. 

Pinto, A., Iwasa, K., Newland, C., Newsom-Davis, J. and Lang, B. The action of Lambert-Eaton myasthenic syndrome immunoglobulin G on cloned human voltage-gated calcium channels. Muscle Nerve 25 715-724, 2002. 

Cloned Human Potassium Channels. Assessment of effects on cloned HERG K channels stablely expressed in a cell line by measurement of whole cell K current (lKr) using voltage clamp. Other cloned human ion channels (e.g., KvLQTl/minK-IKs currents) are also possible. 

Stem cells and cell therapy is the use of pluripotent and multipotent cells to generate healthy cells and tissues to replace the faulty ones in disease conditions. The main ethical questions are the source of the cells and the possibility of cloning humans. 

Millan Ml, Maiofiss L, Cussac D, Audinot V, Boutin JA, Newman-Tancredi A. (2002) Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drags at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther 303 791-804. 

TABLE 14-1. Properties of cloned human dopamine receptors... 

Compound DA (striatum) NA (cortex) 5-HT (whole brain) Kj (nM), cloned human DA transporter ... 

The existing DA receptors have been fully characterized as 7-trans-membranal G protein-coupled receptors in their five subtypes and multiple variants (Table 14-1]. The availability of cloned human receptors will permit the discovery of more selective drugs for the purposes already partially achieved in depression by the relatively nonselective agonists and antagonists described earlier. New Dj postsynaptic agonists and autoreceptor-selective Dj antagonists may offer the best prospects. It is entirely likely that further subtypes and variants will be added to the present list (P. Seeman and Van Tol 1994 Sibley and Monsma 1992]. 

Human genome map Identification of disease genes Animal cloning Human gene therapy IND J... 

Salmon, S.E., B.G. Durie, L. Young, R.M. Liu, P.W. Trown, and N. Stebbing, Effects of cloned human leukocyte interferons in the human tumor stem cell assay. I Clin Oncol, 1983.1(3) 217-25. 

Week, P.K., S. Apperson, L. May, and N. Stebbing, Comparison of the antiviral activities of various cloned human interferon-alpha subtypes in mammalian cell cultures. I Gen Virol, 1981.57(Pt 1) 233-7. 

While the success in animal cloning is a major achievement, it also raises ethical concerns about attempts to use parallel technology to clone humans. This strategy has been shown to be a viable one for mice, pigs, goats, and cattle. The donor nucleus can be engineered and faithfully and efficiently produced as animal clones that... 

It is of interest that studies with cloned human cytochromes P450 expressed in insect SF9 cells have shown that only CYP2A6 catalysed 7-hydroxylation, while the formation of orl/20-hydroxyphenylacetaldehyde was supported by CYPlAl, 1A2, 2B6, 2E1 and 3A4 (Zhuo et al, 1999). 

Nakane, M., Schmidt, H. H., Pollock, J. S., Forstermann, U., and Murad, F. (1993). Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEES Lett. 316, 175-180. 

At the molecular level, the compound would be screened for activity on the target, for example, receptor binding affinity to cell membranes containing the homologous animal receptors (or if possible, on the cloned human receptors). Early studies would be done to predict effects that might later cause undesired drug metabolism or toxicologic complications. 

---