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Biomedical subjects

M A Mitchell

Publications and source records attributed to M A Mitchell.

At least 109 records · Page 6Linked to original sources
PubMed1985

Barbiturate tolerance and dependence: effects on synaptosomal sodium transport and membrane fluidity.

DBA mice were fed lab chow containing phenobarbital for seven or eight days. Upon withdrawal of the phenobarbital diet, dependence was evidenced by appearance of hypothermia, handling-induced convulsions and lethal seizures. Functional tolerance was determined by injecting phenobarbital into mice treated with the phenobarbital diet or a pair-fed control diet and measuring the brain concentration of phenobarbital at the time of loss of righting reflex and the time of regaining righting reflex. Both measures demonstrated that chronic consumption of phenobarbital resulted in functional tolerance. When the diet was withdrawn for two days, tolerance was no longer present, indicating a rapid reversal of the adaptive changes. The veratridine-stimulated uptake of 24Na by isolated brain synaptosomes was used as a measure of membrane function. Sodium uptake was inhibited in vitro by pentobarbital and ethanol, and the inhibitory effects of these drugs were attenuated by chronic in vivo phenobarbital treatment. The fluidity of brain synaptic plasma membranes was estimated by the fluorescence polarization of the fluorescent probe molecules 1-(4-trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene. Synaptic membranes from mice treated chronically with phenobarbital did not differ from those of control mice with regard to either the baseline fluorescence polarization of the probes or the decrease in fluorescence polarization produced by in vitro exposure to phenobarbital or ethanol. Taken together, these results indicate that although chronic phenobarbital ingestion resulted in tolerance and dependence (studied in vivo), and adaptation of sodium channels (studied in vitro), there was no evidence that these changes were due to alterations in the membrane physical properties.

Animals↗
PubMed1985

Effects of air velocity on convective and radiant heat transfer from domestic fowls at environmental temperatures of 20 degrees and 30 degrees C.

The effects of air movement upon sensible heat loss from individual birds at ambient temperatures of 20 degrees and 30 degrees C were determined by partitional calorimetry using a newly developed wind tunnel calorimeter. The relationship between area specific convective heat loss (W/m2) and air velocity (in the range 0.3 to 1.05 m/s) was described by y = 56.5 + 16.9 log x at an air temperature of 20 degrees C, but at 30 degrees C convective heat loss increased linearly with air speed (y = 11.8 + 40.1 x). At 20 degrees C sensible heat exchange (W/m2) was related to air velocity by y = 70.6 exp (0.099 x) and by y = 41.4 + 25.9 x at 30 degrees C, the proportional increase with air speed being greater at the higher temperature. The differences in the effects of air movement on convective cooling and sensible heat loss at 20 degrees and 30 degrees C reflect the thermoregulatory responses of the birds, induced by the thermal demands of the environment.

Air Movements↗
PubMed1984

A simple method for measuring albumin-bound non-esterified fatty acid concentration in laying-hen plasma.

Selective precipitation of triglyceride-rich (TGR) lipoproteins with dextran sulphate and magnesium chloride provides a simple and effective means of determining albumin-bound non-esterified fatty acids, (NEFA) in laying-hen plasma. Albumin-bound NEFA concentrations in the plasma of laying hens fed ad libitum are very low. Most of the NEFA are associated with TGR-lipoproteins, and their concentration is directly proportional (r = 0.82) to TGR-lipoprotein concentration. Subcutaneous injection of glucagon into laying hens produces an approximately 50% increase in total plasma NEFA concentration that persists for at least 2 hr. Most of this increase occurs in the TGR-lipoproteins, but albumin-bound NEFA concentrations increase at least 5-fold before rapidly returning to near control values. These results demonstrate the importance of measuring both albumin- and TGR-lipoprotein-bound NEFA in studies of plasma fatty acid metabolism in the laying hen.

Animals↗
PubMed1984

Problems involved in correlating changes of functional diffusive and anatomical surface areas of the upper and lower chicken small intestine during fasting.

The anatomic villous surface area and the functional diffusive area (measured by the absorption of 64 mM thiourea) of the jejunum and ileum was estimated in fed and 3-d-fasted chickens. In the jejunum, fasting caused a 50% reduction of the anatomic villous surface area but only a 32% reduction in the functional diffusive area. The jejunal permeability to thiourea was unaltered. The ileal anatomic villous surface area was unaffected by fasting but the ileal functional diffusive area was decreased significantly by 26%, concomitant with a significant reduction of 34% in the permeability to thiourea. The passive absorption of thiourea cannot be used as a simple index of the functional diffusive surface area for dietary-induced changes in the small intestine of the domestic fowl.

Animals↗
PubMed1984

A simplified micro ELISA procedure for the measurement of platelet-associated IgG (PAIgG).

A simplified micro ELISA procedure to measure platelet-associated IgG is described. The platelet-bound IgG first is extracted into the fluid phase by solubilizing washed platelets in 0.1% triton X-100. The solubilized IgG in the extract and IgG standards are incubated in microtiter wells previously coated with antihuman IgG. The IgG in the standards and extract bind to the solid phase antihuman IgG. The bound IgG then is measured by the addition of peroxidase labeled antihuman IgG and appropriate substrate. With this method platelets from normal controls were found to have 1.7 +/- 0.6 fg IgG/platelet (mean +/- SD). Platelets from patients with ATP had values that were two to seven times the control values. The relative advantage of this technic is discussed.

Autoantibodies↗
PubMed1984

Physical properties and lipid composition of brain membranes from ethanol tolerant-dependent mice.

DBA/2 mice were made tolerant to and dependent on ethanol by administration of an ethanol-containing liquid diet for 7 days. Fluorescent probe molecules were used to estimate the fluidity and ethanol sensitivity of brain synaptic membranes from these mice. The fluorescence polarization of cis- parinarate , trans- parinarate , and 1,6-diphenyl-1,3,5-hexatriene (probes of the membrane core) and 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene (a probe of the membrane surface) was higher in membranes from ethanol tolerant-dependent mice than in membranes from control mice. The decrease in fluorescence polarization produced by in vitro exposure to ethanol was attenuated in membranes from ethanol tolerant-dependent mice when 1,6-diphenyl-1,3,5-hexatriene was used as the probe, but not when 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene was used. These results indicate that chronic ingestion of ethanol decreased the fluidity and the ethanol sensitivity of the synaptic membranes. In contrast to the alterations observed with intact membranes, liposomes of lipids extracted from synaptic membranes of control and ethanol tolerant-dependent mice did not differ in their physical properties. Analysis of membrane lipids demonstrated that chronic ethanol treatment selectively decreased the unsaturated acyl groups of phosphatidylserine without altering the acyl composition of other phospholipids or sphingolipids. The amount of each phospholipid was not changed, but membrane cholesterol was decreased by chronic ethanol ingestion. Use of 2-dimensional thin-layer chromatography allowed the quantitation of 10 different gangliosides. The concentrations of these lipids were unchanged in synaptic membranes from ethanol tolerant-dependent mice. Thus, the changes in membrane physical properties produced by chronic ingestion of ethanol may be due, at least in part, to altered acyl composition of phosphatidylserine. The differences observed between intact membranes and extracted lipids suggest, however, that chronic ethanol treatment also produced changes in the lipid arrangement or lipid-protein interactions of the intact membranes.

Alcoholic Intoxication↗
PubMed1983

Comparison of jejunal and ileal absorptive functions for glucose and valine in vivo--a technique for estimating real Km and Jmax in the domestic fowl.

1. A technique is described that enables the kinetic characterisation of the saturable absorption mechanisms in the chicken jejunum and ileum for glucose and valine in vivo (after correction for non-saturating components and unstirred layers) by estimation of real Km and Jmax. 2. In the ileum both nutrients have lower real Km and higher Jmax values than in the jejunum indicating, at least for hexose and amino acids, that the ileal enterocytes are functionally equipped and anatomically well-sited to fulfil the role of scavengers of the small intestine.

Animals↗
PubMed1982

The effects of alcohol withdrawal and acute doses of alcohol on the acid-base balance in mice and rats.

While respiratory alkalosis has been reported to occur in human alcoholics during the withdrawal period, and may causally contribute to the expression of the withdrawal syndrome, we found no evidence of this in either alcohol physically-dependent mice (DBA/2J) or rats (Sprague-Dawley) as reflected in blood pH, plasma pCO2, or intracellular brain pH relative to pair-fed control (no alcohol) animals. The inhalation of atmospheres high in CO2 (5% and 15%), which would be expected to reverse a respiratory alkalotic state, had no effect on the expression of the withdrawal syndrome in alcohol-dependent mice. These results indicate that a withdrawal syndrome of considerable intensity can develop in mice and rats in the absence of an alkalotic state.

Acid-Base Equilibrium↗
PubMed1981

Amino acid absorption in jejunum and ileum in vivo -- a kinetic comparison of function on surface area and regional bases.

Maximum absorptive capacities (Vmax) for the jejunum and ileum corrected for the presence of an unstirred layer of water have been calculated for glycine, valine and methionine in vivo in fowls per unit surface area and per region. Vmax per cm2 showed that ileal enterocytes had a greater absorbing capacity than jejunal for glycine and valine but not for methionine. Vmax for glycine and valine, calculated for the whole jejunum and ileum, however, were not different but for methionine the jejunal value was 1.9 times greater than the ileal.

Amino Acids↗
PubMed1981

Barbiturate physical dependence in mice: effects on body temperature regulation.

Chronic exposure to phenobarbital at a 21-22 degrees C ambient temperature produced marked hypothermia in C57BL/6J male mice, to which functional tolerance gradually developed over a 6.5 day intoxication period. Soon after phenobarbital withdrawal, marked hypothermia again developed, reaching its maximal extent at a time when tremors, convulsions on handling and Straub tail were at their peak frequency. When these mice were placed in a 34 degrees C ambient environment, which prevents the hypothermia, these withdrawal signs were eliminated or greatly reduced in frequency compared to mice at 22 degrees C, whereas the incidence of tonic-clonic seizures was not significantly affected. Core body temperature was found to correlate significantly with the degree of gross intoxication during the intoxication phase and with the withdrawal signs of tremor and Straub tail after withdrawal of the drug. When mice were given a choice between a 23 and a 35 degrees C environment at times of maximal hypothermia, their choice often served to maintain the hypothermic state rather than to reduce it. These results suggest that some of the signs of withdrawal (tremor and Straub tail) may be (in part) secondary responses to a primary dysfunction, which is thermoregulatory in nature.

Animals↗
PubMed1980

Transit of a meal through the stomach, small intestine, and colon in normal subjects and its role in the pathogenesis of diarrhea.

A method for measuring the transit time of a meal, containing sausages, mashed potato, baked beans, and a pineapple custard dessert, through the gastrointestinal tract was evaluated in 14 healthy volunteers. Gastric emptying was determined by incorporating a radioactive marker in the meal and counting over the surface of the stomach using a crystal scintillation detector. Small intestinal transit time was determined by measuring breath hydrogen excretion and by estimating the radioactivity over the cecum. Finally, whole gut transit time was measured by incorporating radiopaque plastic markers or carmine red in the meal and estimating the appearance of these markers in the stool. Our results showed that measurements of small intestinal transit time were reproducible and in the majority of subjects the increase in hydrogen excretion occurred at the same time as the increase in radioactive counts over the surface of the cecum. The passage of the first marker in the stool coincided with the appearance of carmine red. There were no significant correlations between small intestinal transit time and whole gut transit time or the half time for gastric emptying. Incorporation of 10, 25, and 40 g lactulose into our standard meal in place of sucrose increased the rate of transit through the small intestine but did not significantly alter the rate of gastric emptying or the whole gut transit time. Total stool weight for 48 hr after ingestion of the meal was inversely related to whole gut transit time but not to small intestinal transit time suggesting that the tendency to develop diarrhea in response to a meal containing unabsorbable carbohydrate depends more on the lack of colonic accommodation than on the rate of small intestinal transit. Finally, there was no significant correlation between the measurements of small intestinal transit time after a drink of lactulose and the transit time of a meal in the same subjects.

Adult↗
PubMed1974

Hospital-acquired infection: present and future impact and need for positive action.

Surveillance of infections at the Ottawa General Hospital between September 1, 1971 and August 31, 1972 showed that the overall infection rate was 13.5% of which 5.6% was community-acquired while 7.9% was of nosocomial origin. These figures are comparable to those for equivalent hospitals in the United States and lower than those reported from the Boston City Hospital, but they nevertheless indicate that over half the infected patients in the hospital were infected after admission. Urinary tract infections accounted for 44.8% of all nosocomial infections and clearly dominated the picture. The postoperative wound infection rate was 3.9% and accounted for only 18% of nosocomial infections. It is probable that these findings are representative of general hospitals throughout Canada and indicate conditions which will not long be tolerated. The knowledge and techniques exist for the prevention of all hospital cross-infection and much autogenous infection. Specific measures are suggested for working towards this goal. These are (1) the replacement of archaic hospitals and hospital facilities, (2) the establishment in every hospital of an efficient surveillance program, (3) the institution of good catheterization and catheter care techniques, and (4) the establishment by hospitals of a quality control program whereby a specific explanation is required for every infection occurring within the hospital.

Boston↗