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Biomedical subjects

C George

Publications and source records attributed to C George.

At least 91 records · Page 5Linked to original sources
PubMed1995

Comparison of two cochlear implant speech processors in better versus poorer performers.

The performance and subjective preferences for two different speech-processing strategies, the Speak strategy in the Cochlear Spectra 22 speech processor and the Multipeak (Mpeak) strategy in the Mini Speech Processor (MSP), are compared within two adult patient groups. Ten experienced cochlear implant (CI) users were selected for this study. One group of 5 CI users have significant open-set speech recognition, and the second group consisted of experienced CI users who have little or no open-set speech recognition on standardized tests (< 30% on sentence tests; < 10% on monosyllabic word tests). While only 4 of the 5 users in each group were available to complete this evaluation, suitable comparisons on the Speak and Mpeak strategies on test performance were possible within each patient group. The performance tests were necessarily different to suit each patient group; however, general trends of test scores and subjective evaluations of each speech processor are compared between these two groups. While the performance scores and subjective ratings consistently favored the Speak strategy in the first group of users, with good open-set speech recognition, the results within the second group were more variable. These findings have significant implications for individual patient and processor selection.

Cochlear Implants↗
PubMed1994

Methyl N,N-diallyl-O-tert-butyltyrosyl-alpha-aminoisobutyrl-alpha- aminoisobutyrate, C28H43N3O5.

In this N- and C-protected tripeptide the nine back-bone atoms are essentially planar and fully extended except for N1 and C3' which lie below the plane and are folded in towards it. The tyrosine side chain extends away from the opposite side of the plane. There is one (N-H)i ... (O = C)i intramolecular hydrogen bond and a weak (N-H)i+2 ... (O = C)i intermolecular hydrogen bond [where (i) = 2].

Amino Acid Sequence↗
PubMed1994

Crystal structure of deltakephalin: a delta-selective opioid peptide with a novel beta-bend-like conformation.

The solid-state structure of deltakephalin (Tyr-DThr-Gly-Phe-Leu-Thr) has been determined by single-crystal X-ray diffraction. Deltakephalin (DTLET) is a synthetic opioid peptide which differs from enkephalin in that a D-Thr has been substituted for Gly2 and a sixth residue, L-Thr, has been added. Clear colorless plates obtained using vapor diffusion and macro-seeding crystallization techniques were monoclinic; space group C2 with a = 27.389(5), b = 9.205(2), c = 16.788(2) A, beta = 98.87(2) degrees and V = 4181.4(14) A3. The asymmetric unit contained one molecule of DTLET and six molecules of water, giving a calculated density of 1.28 g cm-3. The crystal structure revealed that DTLET has a pseudo type I' beta-bend which is stabilized by an intramolecular side-chain to backbone hydrogen bond. This is the first reported observation of a pseudo beta-bend conformation in a solid-state structure of an enkephalin analog.

Crystallography, X-Ray↗
PubMed1994

Sex, alcohol and violence: a community collaborative action against striptease shows.

Between September 1988 and February 1989, Anyinginyi Congress, an Aboriginal community-controlled health organisation, facilitated a collaborative community action against striptease shows in public bars in Tennant Creek. This action resulted in changes to the guidelines of the Northern Territory Liquor Act to regulate striptease shows in public bars and began other processes of addressing alcohol related problems in the community. The composition and strategies of both the pro- and anti-striptease lobbies are analysed within the context of changing power relationships between Aboriginal and non-Aboriginal people, as epitomised in the growth and consolidation of Aboriginal community-controlled organisations in Tennant Creek. The role of the media in shaping the course and direction of the debates as well as the response of the Northern Territory government as the final arbiter in the striptease conflict are scrutinised. The use of sex to sell alcohol is a legitimate public health concern and community action for healthier public policy is an important strategy in creating supporting environments for health.

Alcohol Drinking↗
PubMed1993

Synthesis, optical resolution, absolute configuration, and preliminary pharmacology of (+)- and (-)-cis-2,3,3a,4,5,9b-hexahydro-1-methyl-1H- pyrrolo-[3,2-h]isoquinoline, a structural analog of nicotine.

Title compound, 8, has been synthesized from isoquinolinone, 1 (an improved preparation for which is presented) and separated into its antipodes with D- and L-di-p-toluoyltartaric acids. These antipodes and the racemic precursor have been evaluated (and found active) in two in vivo systems for their effects. The most potent of the three, (+)-8, has an ED50 of 7.13 mumol/kg for inhibition of spontaneous activity and 7.45 mumol/kg for antinociception compared to 4.44 and 4.81 mumol/kg, respectively, for (S)-(-)-nicotine. Compounds (-)-8 and 7 are about one-fourth as potent. Isomer (+)-8 has the 3aR,9bS configuration, the latter corresponding to (S)-(-)-nicotine as determined by X-ray crystallography. However, (+)-8 failed to compete for [3H]-nicotine binding, and its pharmacological effects were not blocked by mecamylamine. These bridged nicotine analogs either are binding to an as-yet-unidentified nicotinic receptor or they represent a novel class of non-nicotinic analgesics.

Analgesics↗
PubMed1993

Synthesis and binding properties of MK-801 isothiocyanates; (+)-3-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten- 5,10-imine hydrochloride: a new, potent and selective electrophilic affinity ligand for the NMDA receptor-coupled phencyclidine binding site.

Three new site-directed irreversible (wash-resistant) ligands for the high-affinity phencyclidine (PCP) binding site associated with the N-methyl-D-aspartate (NMDA) receptor were synthesized and their binding characteristics were studied. (+)-3- And (+)-2-isothiocyanato-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycl ohepten-5,10 - imine hydrochloride ((+)-8a,b.HCl) were prepared in four steps from the corresponding nitro derivatives (+)-4a,b, which were obtained by nitration of (+)-3 (MK-801). In the same way the optical antipode (-)-8a.HCl was synthesized from (-)-3. At a concentration of 100 nM, the 3-isothiocyanate derivative (+)-8a irreversibly labeled approximately 50% of the (+)-[3H]-3 binding sites, compared to 20 microM needed for its optical antipode (-)-8a and the 2-isothiocyanate (+)-8b. The apparent Ki values for reversible inhibition of (+)-[3H]-3 binding by (+)- and (-)-8a and (+)-8b were 37,838, and 843 nM, respectively. In contrast, metaphit (1b) and etoxadrol m-isothiocyanate (2b), two previously reported irreversible ligands for the PCP binding site, label about 50% of the (+)-[3H]-3 binding sites at 100 microM and 250 nM, respectively, with apparent Ki values for reversible inhibition of 535 and 94 nM. Compound (+)-8a is also a selective affinity ligand, displaying little or no irreversible in vitro affinity at 100 microM for opioid, benzodiazepine, muscarinic, and dopamine receptors. At a 25 microM concentration, (+)-8a caused an irreversible 52% reduction of binding to sigma 1-receptors. Compound (+)-8a is the most potent known electrophilic affinity label for the PCP binding site. Its potency and selectivity should enable it to be a valuable tool for the elucidation of the structure and function of the NMDA receptor-associated PCP binding site in the mammalian central nervous system.

Animals↗
PubMed1993

Accessible, acceptable, appropriate.

In the final article in the homelessness series, Carolyn Clark and Catherine George describe the development of a healthcare purchasing strategy.

Contract Services↗
PubMed1993

Reconstitution of hair follicle development in vivo: determination of follicle formation, hair growth, and hair quality by dermal cells.

Combinations of cultured and uncultured epidermal and dermal cell preparations from newborn and perinatal mice were grafted onto the backs of athymic nude mouse hosts to elucidate the cellular requirements for skin appendage formation. All epidermal populations studied, including a total epidermal keratinocyte preparation from trypsin-split skin, developing hair follicle buds isolated from epidermis, and preformed hair follicles isolated from dermis, make haired skin when grafted with fresh dermal cells. Only pre-formed hair follicles produce haired skin on grafts without an additional dermal component. Hair follicle buds grafted alone or with cultured dermal cells will reconstitute skin but without appendage formation. Thus, cells or factors present in fresh, but not cultured, dermal cells are essential for supporting hair growth from budding follicles, whereas more developed (pre-formed) follicles appear to contain all the necessary components for hair formation. Dissociation of isolated hair follicles by trypsin/ethylenediaminetetraacetic acid prior to grafting is permissive for hair growth, suggesting that follicle cells can be re-induced or reassociate in vivo. Dermal papilla cells, microdissected from rat vibrissal follicles and cultured for up to 14 passages, stimulate hair growth from follicle buds and influence the quality of hair growth from pre-formed hair follicles. Thus, dermal papilla cells maintain inductive capacity in culture and contribute to the reconstituted skin. This reconstitution model should be useful for identifying cell populations within the hair follicle compartment necessary for hair growth and for examining the effects of specific gene products on hair follicle growth and development in vivo.

3T3 Cells↗
PubMed1992

Synthesis, configuration, and activity of isomeric 2-phenyl-2-(N-piperidinyl)bicyclo[3.1.0]hexanes at phencyclidine and sigma binding sites.

The novel semirigid derivatives (+)-cis-1-[2-phenyl-2-bicyclo[3.1.0]hexyl]piperidine [(+)-8], its enantiomer (-)-8, and (+-)-trans-1-[2-phenyl-2-bicyclo[3.1.0]hexyl]piperidine [(+/-)-9] were synthesized as probes to investigate the mode of interaction of phencyclidine (PCP) with its binding site on the N-methyl-D-aspartate receptor complex. Each target compound was obtained in five steps starting from cyclopent-2-enone. (+)- and (-)-8 were obtained in greater than 98% optical purity through three recrystallizations from ethanol of the (S)-(+)- and (R)-(-)-mandelate salts of intermediate (+-)-cis-2-phenyl-2-bicyclo[3.1.0]hexylamine ([(+/-)-16]. Crystallization of the (R)-(-)-mandelate salt afforded (1R,2R,5S)-(-)-16, whereas the (S)-(+)-mandelate salt afforded (1S,2S,5R)-(+)-16; the absolute configuration was determined by single-crystal X-ray analysis of (-)-16.(R)-(-)-mandelate. Single-crystal X-ray analysis of (+/-)-9-picrate confirmed its trans configuration and provided conformational data. (+)- and (-)-8 and (+/-)-9 were examined for their ability to interact with PCP and sigma binding sites in vitro using [3H]TCP and [3H]pentazocine as radioligands. The binding was compared with that of PCP and contrasted with the rigid symmetrical phencyclidine derivatives cis- and trans-1-[3-phenyl-3-bicyclo[3.1.0]hexyl]piperidines (6 and 7). The results of the study indicated that the conformations of PCP represented by 6-9 are not optimal for potent interaction at either of these sites. Affinities ranged from 582 nM [(+/-)-9] to 29,000 nM [(+)-8] at PCP binding sites and from 1130 nM [(-)-8] to 16,300 nM (7) at sigma sites. In this assay, PCP exhibited affinities of 64.5 nM at PCP and 1090 nM at sigma sites. Qualitative correlation between the sigma and PCP binding data suggests some similarities between these binding sites. An axial phenyl and equatorial piperidine ring with the nitrogen lone pair of electrons antiperiplanar to the phenyl ring has been postulated as the receptor-active conformation of PCP-like ligands at the PCP binding site. Comparison of the binding data of 7-9 with that of the previously described methylcyclohexyl-PCP derivatives allowed its rationalization in terms of this model. It is likely that the lowered affinity in this bicyclo[3.1.0]hexane series is a consequence of nonoptimal geometry (pseudoequatorial phenyl or pseudoboat) for binding as opposed to the presence of steric bulk which proved deleterious in the methylcyclohexyl-PCP derivatives.

Animals↗
PubMed1992

Absolute configuration of (-)-alpha-acetylmethadol hydrochloride.

beta-[2-(Dimethylamino)propyl]-alpha-ethyl-beta-phenylbenzeneethanol+ ++ acetate ester hydrochloride, C23H32NO2+. Cl-.H2O, M(r) = 407.9, monoclinic, P2(1), a = 15.608 (4), b = 8.637 (2), c = 17.273 (5) A, beta = 97.71 (2) degrees, V = 2307.4 (1) A3, Z = 4 (two methadol hydrochlorides and two water molecules per asymmetric unit), Dx = 1.17 Mg m-3, lambda (Cu K alpha) = 1.54184 A, mu = 1.64 mm-1, F(000) = 880, T = 295 K, final R = 0.069, wR = 0.064 for 2559 independent observed reflections. Both asymmetric C atoms in the two independent methadol molecules are 'S'. Of the two N-H moieties one acts as a hydrogen-bond donor to a Cl atom (N-H = 1.21, H...Cl = 1.85, N...Cl = 3.03 A, N-H...Cl = 162.3 degrees) and the other is a donor to a water molecule (N-H = 0.90, H...O = 2.06, N...O = 2.80 A, N-H...O = 138.2 degrees). In addition, both water molecules hydrogen bond to both Cl atoms with O...Cl distances in the range 3.06-3.36 A. A comparison of torsion angles for the two independent methadol molecules indicates that there is very little stereochemical similarity between them.

Chemical Phenomena↗
PubMed1992

Probes for narcotic receptor mediated phenomena. 18. Epimeric 6 alpha- and 6 beta-iodo-3,14-dihydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinans as potential ligands for opioid receptor single photon emission computed tomography: synthesis, evaluation, and radiochemistry of [125I]-6 beta-iodo-3,14-dihydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinan.

The epimeric 6 beta- and 6 alpha-iodo-3,14-dihydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinans (1, ioxy) and (2, epioxy), respectively, were each synthesized in five steps starting with naltrexone. The configuration of the 6-iodo group of 1 was unequivocally determined to be beta-based on single crystal X-ray analysis of its precursor 3-acetoxy-6 beta-iodo-14-hydroxy-17-(cyclopropylmethyl)-4,5 alpha-epoxymorphinan (10). Both 1 and 2 as well as their corresponding 3-O-acetates 10 and 11 were found to readily cross the blood-brain barrier and completely reverse the analgesic effects of a 10 mg/kg intraperitoneal dose of morphine sulfate as determined by the paw withdrawal latency test. Compounds 1 and 2 were found to bind with high affinity to mu, delta, and kappa receptors in vitro. In general, 1 and 2 exhibited higher affinity for mu and kappa receptors than naltrexone while the 6 beta-iodo epimer 1 (ioxy) was more potent than its epimer 2. In a comparison of the 6 beta-halogen substituent on binding affinity across opioid receptor subtypes, it was generally found that I greater than Br greater than F. On the basis of the results of in vitro and in vivo testing, 1 was selected as a target for radioiodination and evaluation as a potential single photon emission computed tomography imaging agent for opioid receptors. Carrier-free [125I]-1 was synthesized in near quantitative yield by the sequence of reaction of excess 3-acetoxy-6 alpha-[[(trifluoromethyl)sulfonyl]oxy]-14-hydroxy-17- (cyclopropylmethyl)-4,5 alpha-epoxymorphinan (8) with anhydrous Na125I in dry acetonitrile for 90 min at 76 degrees C followed by deacetylation of the product with 1:1 aqueous ammonia/acetonitrile at 25 degrees C. The potential of [125I]-1 as an in vivo imaging agent for opioid receptors is evaluated and discussed.

Animals↗