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Biomedical subjects

C E Scott

Publications and source records attributed to C E Scott.

5 recordsLinked to original sources

Interaction of [3H]spiperone with rat striatal dopamine D-2 receptors: kinetic evidence for antagonist-induced formation of ternary complex.

The characteristics of [3H]spiperone interactions with rat striatal dopamine D-2 receptor were investigated. Although the association of [3H]spiperone occurred monoexponentially, the pseudo-first order rate constant of association showed a hyperbolic dependence on ligand concentration. The data were therefore analyzed with the assumption of a two-step binding reaction leading to ligand-induced receptor isomerization. For the first equilibrium, the dissociation constant (KD) was 1.2 nM, while for the second equilibrium, the association and the dissociation rate constants were 71.6 X 10(-3) sec-1 and 0.9 X 10(-3) sec-1, respectively. The dissociation rate constant of the overall binding reaction, as determined by inducing the dissociation of [3H]spiperone from its binding sites by 1 microM (+)-butaclamol, was 0.92 X 10(-3) sec-1. However, the kinetically derived KD (15 pM) of the binding reaction differed significantly from the KD (218 pM) obtained from equilibrium binding experiments. This inconsistency between the two KD values appeared to have arisen from using different receptor concentrations in deriving kinetic and equilibrium data. The KD of the equilibrium binding reaction indeed showed significant variation with the receptor concentrations in an inverse way, implicating the involvement of a third component in the two-step binding reaction to form a high affinity ternary complex rather than a simple ligand induced receptor isomerization. Pretreatment of the membrane with 0.1 mM guanosine 5'-imidodiphosphate [Gpp(NH)p] reduced the affinity of the equilibrium binding reaction to a value (KD = 1.2 nM) which corresponded to the kinetically derived KD of the first step of the binding reaction, indicating the involvement of a guanine nucleotide-binding protein or G protein in inducing the formation of the high affinity ternary complex. The affinity of the binding reaction in Gpp(NH)p-pretreated membranes, however, increased with the duration of incubation, indicating that the ligand receptor complex still can couple with the G protein even in the presence of Gpp(NH)p. Pretreatment of the membrane with pertussis toxin irreversibly decreased the affinity of the binding reaction without significantly affecting the total number of binding sites, implying the involvement of the Gi subclass of G protein in the interaction of [3H]spiperone with D-2 receptors. Inhibition of the [3H]spiperone binding by a dopamine receptor agonist, bromocriptine, also yielded a monophasic dose response curve both in the presence and in the absence of Gpp(NH)p.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms

The power of medicine, the power of ethics.

Foucault's genealogies and archeologies provide occasions in which one may come to know the powers, accidents, and influences that have structured a particular knowledge or discipline. The Birth of the Clinic shows the development of modern medicine in a process by which rational inference and emphasis on the history of a disease are replaced by pathological anatomy. In modern anatomy, the corpse, not reason, became the "space" of modern medical knowledge. In this "space" developed a confederation of dead body, knowledge, trained and noninferential gaze, organic unity, and the increased importance of bodily space instead of physical time. The discussion shows how Foucault's genealogy of modern medicine is influenced by and overcomes the knowledge that it describes. In this context, his genealogy is also shown to be self-overcoming and to raise important questions for medical ethics when ethical thought is conceived within the structures of knowledge that have been exposed by the genealogy.

Attitude to Death

Practice effects in industrial hearing screening.

Two samples of employees were drawn at random from the total population of approximately 12,000 employees in one large company. The base-line audiograms and two subsequent annual retests were studies on a sample of 118 employees to determine whether the mean threshold values improved with subsequent years of testing. In addition, the audiometric earphones were reversed so that the right ear was tested first on an automatic audiometer, followed by the left ear on a different sample of 400 employees in an effort to determine whether there is a significant difference between the first and second ear tested. Results indicate that subsequent retests do not show significant improvements. It is possible, however, the small improvements of 1 or 2 dB reported by other investigators over several years of testing may not be seen when mean values are used on populations of this size. Of more importance, however, was the fact that a consistent and significant difference was seen between the first and second ear tested, with the first ear tested showing the poorer threshold. When earphones were reversed, the left or previously poorer ear, showed better thresholds than the right in the low- and midfrequencies. The right ear continued to show better thresholds in the high frequencies, regardless of which ear was tested first.

Audiometry