Author: engeladmin

Author: Hollstein, M.; Sidransky, D.; Vogelstein, B.; Harris, C.C. Description: Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent…

Author: Hall, A.C.; Turcotte, C.M.; Betts, B.A.; Yeung, W.-Y.; Agyeman, A.S.; Burk, L.A. Description: Effects of common monoterpenoid alcohols and ketones were investigated on recombinant human gamma-aminobutyric acid A (GABAA; alpha1beta2gamma2s) and glycine (alpha1 homomers) receptors expressed in Xenopus oocytes. GABA currents were enhanced by coapplications of 10-300 microM: (+)-menthol>(-)-menthol>(-)-borneol>>(-)-menthone=camphor enantiomers>carvone enantiomers, with menthol acting stereoselectively. By contrast, thujone diastereomers inhibited GABAA receptor currents while glycine currents were only markedly potentiated by menthol. Positive modulation by (+)-menthol was explored given its pronounced effects (e.g., at 100 microM, GABA and glycine…

Author: Hall, A.C.; Stevens, R.J.N.; Betts, B.A.; Yeung, W.-Y.; Kelley, J.C.; Harrison, N.L. Description: The volatile anesthetic isoflurane both prolongs and reduces the amplitude of GABA-mediated inhibitory postsynaptic currents (IPSCs) recorded in neurons. To explore the latter effect, we investigated isoflurane-induced inhibition of steady-state desensitized GABA currents in Xenopus oocytes expressing wild-type alpha(1)beta(2), alpha(1)beta(2)gamma(2s), mutant alpha(1)(S270H)beta(2) (serine to histidine at residue 270) or alpha(1)(S270H)beta(2)gamma(2s) receptors. The alpha(1) serine 270 site in TM2 (second transmembrane domain of the subunit) is postulated as a binding site for some volatile agents and is…

Author: Hall, A.C.; Rowan, K.C.; Stevens, R.J.N.; Kelley, J.C.; Harrison, N.L. Description: gamma-aminobutyric acid type A receptors (GABA(A)-R) mediate synaptic inhibition and meet many pharmacological criteria required of important general anesthetic targets. During synaptic transmission GABA release is sufficient to saturate, maximally activate, and transiently desensitize postsynaptic GABA(A)-Rs. The resulting inhibitory postsynaptic currents (IPSCs) are prolonged by volatile anesthetics like isoflurane. We investigated the effects of isoflurane on maximally activated and desensitized GABA(A)-R currents expressed in Xenopus oocytes. Wild-type alpha(1)beta(2) and alpha(1)beta(2)gamma(2s) receptors were exposed to 600 microM GABA until…

Author: Hall, A.C.; Griffith, T.N.; Tsikolia, M.; Kotey, F.O.; Gill, N.; Humbert, D.J.; Watt, E.E.; Yermolina, Y.A.; Goel, S.; El-Ghendy, B.; Hall, C.D. Description: GABA(A) receptors meet all the pharmacological criteria required to be considered important general anaesthetic targets. In the following study, the modulatory effects of various commercially available and novel cyclohexanols were investigated on recombinant human gamma-aminobutyric acid (GABA(A), alpha(1)beta(2)gamma(2s)) receptors expressed in Xenopus oocytes, and compared to the modulatory effects on GABA currents observed with exposures to the intravenous anaesthetic agent, propofol. Submaximal EC(20) GABA currents were…

Author: Dresser, T.H.; Rivera, E.R.; Hoffmann, F.J.; Finch, R.A. Description: The Frog Embryo Teratogenesis Assay-Xenopus (FETAX) was used to assess the teratogenic potential of four solvents. Embryos of the South African clawed frog, Xenopus laevis, were exposed for 96 h to ethanol, dimethyl sulfoxide (DMSO), formamide or glycerol formal. Exposure groups were maintained using a static renewal system in which the exposure media were changed at 24-h intervals. Survival was monitored at 24-h intervals. Length, as an indicator of growth effects, and developmental malformations were determined at the end of…

Author: Daniolos, A.; Lerner, A.B.; Lerner, M.R. Description: Solar radiation induces numerous biologic effects in skin but the mechanism underlying these responses is poorly understood. To study the etiology of these phenomena, we investigated the effect of light on cultured Xenopus laevis melanophores. Visible light stimulated a marked increase in intracellular cAMP levels within the first minute of irradiation. This light-induced elevation in cAMP was blocked by melatonin and was not seen in fibroblasts irradiated in a similar manner. These data show that the photoresponse of pigment cells from amphibian…