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Biomedical subjects

R Gill

Publications and source records attributed to R Gill.

At least 127 records · Page 7Linked to original sources

Selective extraction of small and large molecules from the cerebrospinal fluid by Purkinje neurons.

Cerebellar Purkinje neurons accumulated propidium iodide, granular blue, and horseradish peroxidase conjugated to wheat germ agglutinin but not unconjugated horseradish peroxidase, bisbenzimide, or Evans blue when these compounds were infused into the lateral cerebral ventricles of awake, unrestrained rats. Accumulation of propidium iodide by Purkinje neurons of the vermis was associated with a reproducible behavioral abnormality characterized by truncal tremor, ataxia, and nystagmus. Both the accumulation of propidium iodide in Purkinje cells and the behavioral abnormality were prevented by prior intracerebroventricular administration of ouabain or colchicine, drugs that block neuronal transport processes. The ability of cerebellar Purkinje neurons to extract small and large molecules from the cerebrospinal fluid has important implications for their physiology and pathology.

Animals↗

High-performance liquid chromatography systems for the separation of local anaesthetic drugs with applicability to the analysis of illicit cocaine samples.

Two high-performance liquid chromatography (HPLC) systems are presented which are suitable for the separation of local anaesthetic drugs. An octadecyl-silica column is used with aqueous methanolic eluents (15 and 50% respectively) containing n-hexylamine-orthophosphoric acid buffers and data for 36 compounds are given. The HPLC systems have application for the identification of unknown drugs in this class while the first eluent (15% methanol, pH 2.5) is particularly useful for the examination of illicit cocaine samples because it gives good separation of common adulterants and impurities.

Anesthetics, Local↗

High-performance liquid chromatography retention data for 84 basic drugs of forensic interest on a silica column using an aqueous methanol eluent.

High-performance liquid chromatography retention characteristics have been measured for 84 basic drugs of forensic interest using a silica column with a methanol-aqueous ammonium nitrate eluent. The drugs are from two classes of major interest, namely, the narcotic analgesics (including antagonists, metabolites and analogues) and drugs structurally and pharmacologically related to amphetamine.

Amphetamine↗

Modulation of cell-mediated cytotoxicity function after alteration of fatty acid composition in vitro.

Fatty acids incorporated into cytotoxic T lymphocytes (CTL) during in vitro stimulation can enhance or inhibit the subsequent expression of cell-mediated cytotoxicity, depending on the class of fatty acid. Unsaturated fatty acids enhance cytolysis, whereas saturated fatty acids inhibit it. The effects of fatty acids on cytolysis can be mediated in the absence of cell division, thus eliminating relative clonal amplification or contraction as a basis for the observed effects. Nevertheless, the net result of fatty acid alteration is an increase (unsaturated fatty acids) or decrease (saturated fatty acids) in the frequency, in the treated immune population, of CTL capable of lysing target cells. These observations are best explained by a model in which fatty acid incorporated into cell membrane phospholipids results in a direct recruitment into or out of the pool of CTL within the immune population capable of lysing target cells under the conditions employed to assay cytotoxicity.

Animals↗

Applications of rapid-scanning multichannel detectors in chromatography. Plenary lecture.

A review of progress in the field of multichannel detection in column and thin-layer chromatography is presented, together with some novel applications of a computer-based, linear photodiode array UV--visible spectrophotometer for detection in high-performance liquid chromatography (HPLC). Computer-aided methods for simultaneous monitoring of the elution profile at three wavelengths with automatic peak detection and capture of UV spectra are described. The continuous calculation of absorbance ratios during elution is discussed as an index of peak homogeneity. A novel technique for the enhancement of qualitative identification in HPLC, based on transformation of captured spectra to the second derivative or to the decadic logarithm, is proposed. These developments are exemplified by a model system of diacetylmorphine and its principal metabolites and degradation products, morphine and 6-acetylmorphine. The potential utility of three-dimensional projections of (A, lambda, t) data is discussed in the context of pharmaceutical, bioanalytical and forensic applications.

Chromatography, High Pressure Liquid↗

Understanding Cox's regression model.

COX's (1972) regression model has become increasingly popular under many applied statisticians in recent years. On the other hand its use has been attacked on various grounds, the chief of which is that it is supposedly a technique for "data dredging" (which with such a name can obviously not be a good thing). This controversy is sharpened by a lack of understanding on the part of clinicians of what a statistician can do for them, and conversely an inability on the part of statisticians to explain what they can do for the clinician. A final complicating factor is that the methods of statistical analysis advocated by COX (1972) appropriate to his model have been the subject of some mathematical controversy. In this paper we want to explain what the Cox model is and what its place should be in the context of clinical trials. We shall argue that "data dredging", under the name of exploratory data analysis, is a very respectable activity; one which indeed it may be unrespectable not to do. As illustration of the use of the model we refer to the examples in KALBFLEISCH & PRENTICE (1980), MILLER et al. (1980) and KAY (1979). In a section aimed at the mathematical statistician, we draw attention to some recent advances in the mathematics of this subject which should help lessen the controversy surrounding "partial likelihood". It will be apparent to those who attended the 2nd Heidelberg symposium that this paper was prepared after the conference: a previously prepared paper concentrating on the mathematical problems of this subject will appear elsewhere (GILL (1982)). There, a heuristic introduction is given to the counting process approach to censored survival data which we refer to again in the last section. The present paper depends heavily on discussions with, and published and unpublished work by, Niels Keiding, Geert Schou, Bo Pedersen and Per Kragh Andersen (all of the Statistical Research Unit, Copenhagen).

Adult↗

Analysis of barbiturates in blood by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) assay for the identification and quantification of barbiturates in blood at therapeutic levels had been developed. An ODS-silica column is used with an eluent of 40% methanol at pH 8.5. The barbiturates are detected at 240 nm. The sample preparation procedure involves extraction of unfractionated blood (100 microliter) with hexane-diethyl ether (50 : 50, v/v) ang is very rapid. Talbutal is used as an internal standard. The method has been applied to the determination of five barbiturates (amylobarbitone, butobarbitone, cyclobarbitone, pentobarbitone and quinalbarbitone) in blood after therapeutic doses of the drugs. An application of the HPLC assay to forensic casework is demonstrated.

Barbiturates↗

Analytical aspects of barbiturate abuse: identification of drugs by the effective combination of gas-liquid, high-performance liquid and thin-layer chromatographic techniques.

Chromatographic retention data for a group of barbiturates have been measured on seven chromatographic systems (two gas--liquid chromatographic (GLC), three high-performance liquid chromatographic (HPLC) and two thin-layer chromatographic systems) and the value of these for barbiturate identification has been discussed. The overall correlations observed between pairs of systems are generally low; however, specific groups of barbiturates show very high correlations and this determines the approach to the selection of two or more systems to increase chromatographic discrimination of the barbiturate group. Column chromatographic techniques with lipophilic phases (GLC using SE-30, HPLC using ODS-silica) are most suitable for barbiturate identification. Changes of eluent pH in reversed-phase HPLC proved very effective for the separation of barbiturates with closely related structures.

Barbiturates↗

Membrane structure-function relationships in cell-mediated cytolysis. I. Effect of exogenously incorporated fatty acids on effector cell function in cell-mediated cytolysis.

The fatty acid composition of the membrane phospholipids of CTL memory cells restimulated with Con A can be altered significantly when selected exogenous fatty acids are present during the restimulation culture period. Such alterations also lead to significant changes in the subsequent cytolytic capacity of the regenerated CTL. Unsaturated fatty acids increase cytotoxicity, whereas saturated fatty acids lead to decreased cytotoxic function. The kinetics of the fatty acid effect on CTL function is the same as the kinetics of fatty acid incorporation into membrane phospholipids, suggesting that alteration of cytotoxicity results from altering membrane phospholipid fatty acid composition. The initial studies reported here suggest that this effect is mediated at the level of individual CTL, rather than through an alteration of CTL frequency in effector cell populations. Moreover, it seems unlikely that the fatty acids mediate their effect by altering membrane fluidity.

Amino Acids↗