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Biomedical subjects

D A Wilkinson

Publications and source records attributed to D A Wilkinson.

At least 91 records · Page 5Linked to original sources

Specific heats of lipid dispersions in single phase regions.

Differential scanning calorimetry has been used for the first time to measure the specific heat, Cp, as a function of temperature in the single phase regions above and below the main phase transition temperature, Tm, for dispersions of saturated phosphatidylcholines and phosphatidylethanolamines. Within error limits Cp, when expressed per gram, does not vary in any systematic way with chain length or headgroup. Its temperature dependence in both single phase regions qualitatively resembles that of n-alkanes. Contributions to Cp from intrachain vibrations and interchain van der Waals' interactions have been calculated and account for nearly all the measured Cp at temperatures above Tm. However, these contributions do not yield the observed temperature dependence below Tm. It is conjectured that such a temperature dependence arises from the unhindering of chain vibrations as the lipids undergo thermal expansion, and the result of a preliminary calculation which supports this conjecture is presented.

Calorimetry↗

Examination of alcoholics by computed tomographic (CT) scans: a critical review.

Neuroradiological studies have consistently demonstrated that alcoholics have morphological abnormalities of cortical, ventricular, and cerebellar structures suggesting brain atrophy. This atrophy is weakly correlated with impaired psychological test performance. Because brain atrophy and intellectual impairment can also be found in normal aging it is necessary to compare alcoholics with age-matched control subjects. It is currently unknown if alcohol-associated brain atrophy and intellectual impairment are the result of conditions preceding alcohol consumption or conditions only indirectly related such as head trauma or other associated diseases. Direct alcohol toxicity would be supported by quantitative alcohol-atrophy dose-response relationships and by a partial reversal of atrophy and functional impairment following abstinence from alcohol. Because of methodological difficulties inherent in neuroradiological research, data on the exact pathogenesis of abnormalities in alcoholics have not been produced. The design of such studies can be improved to increase the probability that the causes of brain atrophy will be elucidated.

Adolescent↗

Dilatometry and calorimetry of saturated phosphatidylethanolamine dispersions.

The specific volumes of a series of saturated phosphatidylethanolamine dispersions with 12, 14, and 16 carbon atoms per chain have been measured in the region of the chain melting transition, Tm. The change in specific volume at Tm for the 12 and 14 carbon compounds are 0.0160 and 0.0204 mL/g, respectively. Comparisons are drawn between this class of lipids and phosphatidylcholines. In both cases, Tm extrapolates with increasing chain length to the melting point of polyethylene. Both types of lipids appear to be packed in a similar way below Tm. One major difference is that dilaurylphosphatidylethanolamine undergoes a second transition above Tm.

Calorimetry↗

Homeostatic regulation and Pavlovian conditioning in tolerance to amphetamine-induced anorexia.

A series of experiments on the role of Pavlovian processes in tolerance to amphetamine-induced anorexia in rats was conducted. In Experiment 1A, tolerance to the suppressant effect of d-amphetamine (4.0 mg/kg) on milk consumption was substantially diminished in an environment not previously associated with drug administration. Experiment 1B supported the interpretation that Pavlovian compensatory conditioning rather than a nonassociative mechanism mediated this phenomenon. Experiment 2 examined the hypothesis that "contingent tolerance" results from an inadvertent manipulation of Pavlovian cues. As in previous research, tolerance was contingent in that it did not develop if the rats were not exposed to food under the influence of the drug. Tolerance developed only if access to food occurred under the influence of amphetamine, but as in Experiment 1A, it was substantially diminished in an environment not previously associated with drug administration. Thus, tolerance to amphetamine-induced anorexia was shown to be both contingent on previous experience with food in the drugged state and subject to Pavlovian control. No current explanation for the occurrence of contingent tolerance or for the control of tolerance by Pavlovian processes can at once account for both of these findings. Experiment 3 confirmed the hypothesis that interaction with the food stimulus would be necessary to extinguish tolerance. This finding is also problematic for any current behavioral theory of tolerance. It is proposed that interaction with food is necessary for the homeostatic regulation of disturbances in eating caused by amphetamine. When activated, this regulatory process operates by means of Pavlovian conditional compensatory processes.

Animals↗

Cerebral atrophy and functional deficits in alcoholics without clinically apparent liver disease.

Ninety-seven chronic alcoholics, both impaired and unimpaired, without clinically evident liver disease, showed significantly more cerebral atrophy on computed tomography than age-matched neurologic controls. Age was the variable most highly correlated with cerebral atrophy measurements, and it accounted for most of the correlations between atrophy and functional impairment, except in the Wernicke-amnesic group. Analysis of the slopes of atrophy scores versus age showed a more rapid "rate" of development of cerebral atrophy in alcoholics compared with controls. There were no correlations between liver biopsy scores (51 cases), drinking history (47 cases), or dietary intake (39 cases) and cerebral atrophy measurements.

Adult↗

Prolonged cerebrospinal fluid acidosis in recently abstinent chronic alcoholics.

Significant cerebrospinal fluid (CSF) acidosis was evident in 80 chronic alcoholics (mean pH, 7.25 +/- 0.06) who were compared with 14 neurologic controls (mean pH, 7.31 +/- 0.02). Acidosis persisted for many weeks after the last drink, and there was no associated systemic acidosis. CSF pH correlated significantly with CSF anion gap, suggesting a primary cerebral metabolic abnormality. Even though one-quarter of the alcoholic patients had a CSF pH less than 7.21, mental impairment was less than expected for the degree of CSF acidosis noted.

Acidosis↗

EEG correlates of the alcohol-induced organic brain syndrome in man.

Fourteen chronic alcoholics were studied within 1 to 3 weeks of beginning abstinence for a duration of 6 to 10 weeks. Patients were drug-free during the study. Electroencephalograms were recorded on admission, and twice at 2- to 3-week intervals. Neurologic examinations were performed during the same week as EEGs, and patients received a psychologic examination and CT scan within 3 weeks. Two groups could be identified. One group had high neurologic impairment scores, low alpha production, high 20 to 30 Hz power, impaired gait, and mental performance, while the other had low scores, normal alpha rhythm, and reduced degree of mental dysfunction. The impaired group showed marked improvement in neurologic scores, alpha rhythm, and 20 to 30 Hz power within 4 to 6 weeks, in contrast to no change for the unimpaired group. There was no evidence that age, duration of drinking, time from last drink, or cortical atrophy were involved in predisposing alcoholics to demonstrate the observed changes. It is submitted that spontaneous recovery in brain function of neurologically impaired alcoholics accompanies abstinence from chronic alcohol consumption.

Adult↗

Dilatometric study of binary mixtures of phosphatidylcholines.

Volumes of lipid dispersions as a function of temperature have been measured for two different kinds of binary mixtures of lecithins, (1) DMPC and DSPC and (2) DMPC and DC20PC. Emphasis was placed on DMPC-rich compositions so as to resolve ambiguities regarding solid-phase immiscibility in DMPC-DSPC mixtures. Special attention has been paid to problems of equilibration in the low-temperature phase and to methods of mixing the lipids. We find that there is no solid-solid immiscibility in DMPC-DSPC mixtures, although this system is close to exhibiting such immiscibility, and that DMPC-DC20PC mixtures exhibit pronounced solid immiscibility.

Kinetics↗

Lecithin bilayers. Density measurement and molecular interactions.

Density measurement are reported for bilayer dispersions of a series of saturated lecithins. For chain lengths with, respectively, 14, 15, 16, 17, and 18 carbons per chain, the values for the volume changes at the main transition are 0.027, 0.031, 0.037, 0.040 and 0.045 ml/g. The main transition temperature extrapolates with increasing chain length to the melting temperature of polyethylene. Volume changes at the lower transition are an order of magnitude smaller than the main transition. Single phase thermal expansion coefficients are also reported. The combination of X-ray data and density data indicated that the volume changes are predominantly due to the hydrocarbon chains, thus enabling the volume vCH2 of the methylene groups to be computed as a function of temperature. From this and knowledge of intermolecular interactions in hydrocarbon chains, the change in the interchain van der Waals energy, delta UvdW, at the main transition is computed for the lecithins and also for the alkanes and polyethylene at the melting transition. Using the experimental enthalpies of transition and delta UvdW, the energy equation is consistently balanced for all three systems. This yields estimates of the change in the number of gauche rotamers in the lecithins at the main transition. The consistency of these calculations supports the conclusion that the most important molecular energies for the main transition in lecithin bilayers are the hydrocarbon chain interactions and the rotational isomeric energies, and the conclusion that the main phase transition is analogous to the melting transition in the alkanes from the hexagonal phase to the liquid phase, but with some modifications.

Chemical Phenomena↗

Hydration of phosphatidylocholine. Adsorption isotherm and proton nuclear magnetic resonance studies.

Adsorption-desorption isotherms were obtained for water binding by 1,2-dimyristoylphosphatidylcholine in the temperature range 15 degrees-35 degrees C. The isotherms were analyzed by Brunauer et al.'s (BET) theory and also a polarization theory, the latter being more successful in fitting the data. There was some evidence for a change in the surface field of the lipid bilayer around 25 degrees C. Proton T1 and T2 measurements were used to obtain a log-normal molecular correlation time distribution for water protons in these systems. This distribution was compared with the isotherm data to effect a description of several classes of water molecules.

Magnetic Resonance Spectroscopy↗