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Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 217 records · Page 12Linked to original sources
PubMed1988

Hepatic stores of retinol and retinyl esters in elderly people.

Post-mortem concentrations of hepatic retinol and retinyl esters were determined in 40 subjects aged over 65 years to assess the effects of disease and malnutrition on vitamin A reserves. Three groups of patients (mean age 79.6 years) were studied: (1) previously healthy, (2) chronically ill, (3) chronically ill and wasted. There was no significant difference in height or age between the groups, but group 3 was lighter than both group 1 (P less than 0.001) and group 2 (P less than 0.05). Free retinol and retinyl esters were measured by high pressure liquid chromatography, and the total hepatic retinol calculated. Analysis of variance showed that the three groups differed significantly (P less than 0.02) with regard to total retinol, retinyl palmitate and total retinyl ester content.

Aged↗
PubMed1988

Effects of tracheostomy breathing on brain and body temperatures in hyperthermic sheep.

1. We measured rectal and hypothalamic temperature in sheep breathing nasally and via a tracheostomy, during hyperthermia resulting from exposure to a hot environment, exercise and fever. 2. In normothermic and hyperthermic sheep hypothalamic temperature was up to 1.0 degree C lower than rectal temperature when the sheep breathed nasally. Tracheostomy breathing abolished the rectal-hypothalamic temperature difference. 3. In sheep breathing via the tracheostomy and exposed to a dry-bulb temperature of 45-50 degrees C for 2 h, hypothalamic temperature exceeded rectal temperature by about 0.4 degrees C, and was significantly higher than that in sheep breathing nasally in the same environment. 4. During exercise on a treadmill and in the post-exercise period, the difference between hypothalamic and rectal temperature was abolished in the sheep while breathing through the tracheostomy, and rectal temperature rose to higher levels compared to those evident in the same activity while breathing nasally. 5. After an I.V. injection of 0.4 micrograms/kg lipopolysaccharide (LPS), the difference between hypothalamic and rectal temperature again was abolished in the sheep when breathing through the tracheostomy, but rectal temperature rose significantly less compared to when breathing nasally. 6. Our results indicate that selective brain cooling depends on upper respiratory tract cooling in normo- and hyperthermic states in sheep.

Animals↗
PubMed1988

Sodium aurothiomalate does not block interleukin 1 production in rabbits.

Gold salts may attenuate inflammatory processes by inhibiting interleukin 1 production. It is shown that sodium aurothiomalate does not act as an antipyretic after intravenous injection of two pyrogens into rabbits. Consequently, it cannot suppress interleukin 1 production, a conclusion confirmed by an in vitro lymphocyte activating factor assay. Chronic sodium aurothiomalate treatment, however, did depress the blood leucocyte count significantly.

Animals↗
PubMed1987

Importance of immunoglobulin isotype in therapy of experimental autoimmune encephalomyelitis with monoclonal anti-CD4 antibody.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. Prior studies have established that monoclonal anti-CD4 antibodies can reverse EAE. To determine whether immunoglobulin isotype plays a role in the therapy of EAE with anti-CD4 antibody, an isotype switch variant family of the mouse IgG1 anti-rat CD4 antibody W3/25 was isolated with the fluorescence-activated cell sorter. The IgG1, IgG2b, and IgG2a W3/25 isotype variants all had identical binding capacities for rat CD4+ T cells. Although all three W3/25 isotypes showed some beneficial effects in the amelioration of EAE, the IgG1 and IgG2a W3/25 antibodies were superior to the IgG2b W3/25 in the treatment of EAE. Multiparameter fluorescence-activated cell sorter analysis of T cell subpopulations from treated rats showed that none of the antibodies of the W3/25 isotype switch variant family substantially depleted CD4+ target cells in vivo. These experiments demonstrate that immunoglobulin isotype is important in the monoclonal antibody therapy of autoimmune disease. They indicate that therapy of EAE may be successful without a major depletion of CD4+ lymphocytes. Immunotherapy may be optimized by selecting an appropriate isotype of a monoclonal antibody.

Animals↗
PubMed1987

Selection of medical students--are all matriculation examinations equivalent?

The marks achieved by students vary significantly with the type of matriculation examination written. In particular, students who write the examination set by the Transvaal Education Department score significantly higher matriculation marks than other students but score the same in the first year at medical school as other students. These students have an undeserved advantage in the selection process.

Educational Measurement↗
PubMed1987

Selection of medical students--are interview evaluations consistent?

We report an attempt to evaluate the consistency of interviews used in the selection of medical students. We found that when two teams of two or three members each interviewed candidates independently, the difference between marks (on a scale of 0-10) was less than 2.5 in 90% of comparisons and less than 1.4 in 75%. When candidate variation was eliminated by use of televised interviews differences between teams were reduced. We conclude that teams of two or three interviews can evaluate candidates with acceptable consistency. On the other hand, evaluations by individuals are less consistent and probably should not be used for categorical evaluations.

College Admission Test↗
PubMed1987

Genetic analysis of strains C57BL/6J and BALB/cJ for Ath-1, a gene determining atherosclerosis susceptibility in mice.

We previously reported that mice have at least one major gene determining atherosclerosis susceptibility, Ath-1. Susceptible alleles of Ath-1 are found in strain C57BL/6J and are associated with relatively low levels of high-density lipoprotein cholesterol (HDL-C) when these mice are fed an atherogenic diet. Resistant alleles of Ath-1 are found in strains C3H/HeJ and BALB/cJ and are associated with relatively high levels of HDL-C. Data reported earlier from the set of seven recombinant inbred (RI) strains, derived from C57BL/6By and BALB/cBy, showed that these parental strains differed at Ath-1. However, due to the limited number of RI strains, it was not possible to determine with certainty whether Ath-1 was the only major gene determining atherosclerosis susceptibility in these two strains or to determine its map position accurately. In this report, examination of F1, F2, and backcross progeny from a cross between C57BL/6J and BALB/cJ demonstrates that Ath-1 is the major gene determining atherosclerotic lesion formation and HDL-C levels in female mice. The data from male animals suggest that environmental factors or modifying genes also influence male HDL-C levels and thus partly obscure the Ath-1 phenotype. HDL-C levels in F1 progeny resemble the BALB/c parent. The data from the cross provide confirmatory evidence that Ath-1 is linked to Alp-2 on chromosome 1 with a map distance of 4.8 +/- 2.3 (SE). Combining these data with a previous cross between strain C57BL/6 and strain C3H/HeJ gives a map distance between Ath-1 and Alp-2 of 4.9 +/- 1.8 based on 7 crossovers found among 144 tested chromosomes.

Alleles↗
PubMed1987

Genetic analysis of murine strains C57BL/6J and C3H/HeJ to confirm the map position of Ath-1, a gene determining atherosclerosis susceptibility.

Previous results suggested that strains C57BL/6J and C3H/HeJ differed in a single gene for atherosclerosis susceptibility, called Ath-1. Based on data from recombinant inbred strains Ath-1 was tentatively assigned to chromosome 1 linked to Alp-2. In this report, a cross between C57BL/6 and C3H/HeJ was carried out in order to test whether the tentative map position was correct. Parental strains and F1 and F2 progeny were examined. Susceptible alleles of Ath-1, found in C57BL/6, are associated with relatively low levels of high-density lipoprotein (HDL)-cholesterol in animals fed an atherogenic diet; resistant alleles of Ath-1 are associated with relatively high levels of HDL-cholesterol. F1 progeny have HDL levels that are intermediate between these of the two parental strains. Among the F2 progeny, Alp-2 and Ath-1 cosegregated, providing confirmatory evidence that Ath-1 is linked to Alp-2 on chromosome 1. Three mice recombinant for Alp-2 and Ath-1 were found among the 60 chromosomes tested, giving an estimated map distance between these two genes of 5.0 +/- 2.8 (SE) cM. The phenotypic characteristics of Ath-1 resemble a genetic trait in humans, hyperalphalipoproteinemia, which is characterized by elevated levels of HDL-cholesterol, reduced risk of heart disease, and increased longevity.

Animals↗
PubMed1987

Correction of excision repair in xeroderma pigmentosum by hamster chromosome fragments involves both classes of pyrimidine dimers.

The ultraviolet light-sensitive phenotype of xeroderma pigmentosum (XP) has been corrected by the incorporation into XP cells of small chromosome fragments from Chinese hamster ovary cells. Like normal human and hamster cells, these XP-hamster hybrids are able to excise both of the photoproducts produced by ultraviolet light: cyclobutane pyrimidine dimers and the minor photoproduct, (6-4) pyrimidine-pyrimidone dimers. This excision capacity contrasts with that of an XP revertant, of the same cell line used in this study, which is able to excise only the (6-4) photoproducts. The excision defect of XP has been fully corrected in the hybrids; therefore, the small hamster chromosome fragments they contain should carry the gene for complementation group A of XP.

Animals↗
PubMed1987

Quantitative assessment of atherosclerotic lesions in mice.

The well-defined genetic systems of the mouse are proving useful in experimental studies of atherosclerosis. Inbred mouse strains differ in atherosclerosis susceptibility, and several variants of apolipoproteins have been identified and mapped. This report explores the location and timing of lesion formation in the mouse in an effort to provide a basis for quantitatively comparing groups of mice. After 14 weeks on an atherogenic diet containing 1.25% cholesterol, 15% fat, and 0.5% cholic acid, C57BL/6J female mice had aortic lesions at each of the intercostal arteries, at the junction of the aorta to the heart, and in scattered areas covering 1.1% +/- 0.5 (SD) of the aortic surface. After 9 months on the atherogenic diet, those lesions near the heart and intercostal arteries were extensive, 8% +/- 3 (SD) of the remainder of the aorta was involved in lesions, and lesions were found in the coronary arteries. Results indicated that one suitable location for scoring lesions was in a 300 micron area of the aorta just beyond the aortic sinus. The mean number of lesions/mouse in the selected area after 14 weeks on the atherogenic diet was 1.1 +/- 0.3 (SD). The results were reproducible over 10 separate experiments. The number of lesions per mouse fit a Poisson distribution indicating that the presence of one lesion did not predispose the mouse to acquiring a second lesion. Lesion formation and cholesterol levels did not vary with the season of the year as demonstrated by 9 separate experiments over more than 12 months. Methods of evaluating the number and size of lesions were compared including sizing with a microscope eyepiece grid and computer-assisted planimetry. The resulting data provide reproducible methods of quantitatively comparing lesion formation in various strains or groups of mice, thereby increasing the usefulness of the mouse as an experimental system for atherosclerosis research.

Animals↗
PubMed1987

Comparison of atherosclerotic lesions and HDL-lipid levels in male, female, and testosterone-treated female mice from strains C57BL/6, BALB/c, and C3H.

In order to determine whether male and female mice differed in HDL-lipid levels or in atherosclerotic response to a high fat diet, we examined 3 inbred strains which differed in susceptibility to atherosclerosis; C57BL/6, BALB/c, and C3H. Mice were fed normal chow or an atherogenic diet containing 1.25% cholesterol, 15% fat, and 0.5% cholic acid. Lesion number and size were determined after 14 weeks on the diet; plasma HDL-lipid levels were determined at 0 and 4 weeks on the diet. For C3H, the most atherosclerosis-resistant strain, HDL-lipid levels were very high and not affected by sex or diet. For BALB/c, HDL-lipid levels were intermediate between the other two strains. Male levels were significantly higher than the females, and the atherogenic diet caused a drop in HDL-lipid levels of 14-27% depending on sex. For C57BL/6, the most atherosclerosis-susceptible strain, HDL-lipid levels were low compared to the other two strains. Males and females on normal chow did not differ in HDL-lipid, but females showed a 50% decrease in HDL when fed the atherogenic diet. For both BALB/c and C57BL/6, testosterone-treated females resembled the males. The HDL-lipid levels in mice on atherogenic diet differed over a 3-fold range among the nine groups. When HDL-lipid levels were compared to the number of atherosclerotic lesions or the total lesion area, a high degree of correlation was observed (r = -0.95 for lesion number and -0.93 for total lesion area). This suggests that HDL-lipid levels are important in determining atherosclerosis susceptibility in mice.

Animals↗
PubMed1987

Pyrogens fail to produce fever in the snakes Psammophis phillipsii and Lamprophis fuliginosus.

1. Preferred body temperature of five diurnal, Psammophis philipsii and three nocturnal, Lamprophis fuliginosus, snakes was measured in a thermal gradient chamber by indwelling colonic thermocouples, before and after injection of a variety of pyrogens. 2. The snakes achieved their preferred body temperature by moving up and down in the gradient chamber; it was about 33 degrees C for P. phillipsii and 25 degrees C for L. fuliginosus. 3. The snakes did not develop fever in response to any of the pyrogens, whether gram-negative or gram-positive in origin, either on the day of injection or on the subsequent day. 4. We believe that fever is rare amongst reptiles.

Animals↗
PubMed1987

Pyrogens fail to produce fever in the leopard tortoise Geochelone pardalis.

1. The body temperature of seven tortoises, Geochelone pardalis, was measured in a thermal gradient chamber, by indwelling thermocouples, after injection of various pyrogens. 2. The tortoises regulated their body temperature by moving in the chamber. 3. The tortoises did not develop fever in response to any of the pyrogens we tested. 4. The results support the contention that fever in reptiles is not ubiquitous.

Animals↗