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Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 253 records · Page 14Linked to original sources
PubMed1986

Effect of 3-methylcholanthrene on atherosclerosis in two congenic strains of mice with different susceptibilities to methylcholanthrene-induced tumors.

Inbred mouse strains AKXL-38 and AKXL-38a are congenic strains that differ at the Ah locus, a gene which affects the inducibility of the cytochrome P-450 enzymes. The Ah-responsive strain, AKXL-38a, is more susceptible to 3-methylcholanthrene-induced tumors than the Ah-nonresponsive strain, AKXL-38. We previously reported that 3-methylcholanthrene (MC) increased the number and the size of atherosclerotic lesions in a dose-dependent fashion. We now demonstrate that the effect of MC is greater in Ah-responsive mice than in Ah-nonresponsive mice indicating that Ah-responsive mice not only are more susceptible to MC-induced cancer but also are more susceptible to MC-enhanced atherosclerosis. Mice that received atherogenic diet for 14 weeks but no MC had 1.3-1.4 lesions/mouse regardless of genetic type. When mice were treated with MC, the number of lesions increased to 2.1 +/- 0.1 (SE) in Ah-nonresponsive mice, 2.6 +/- 0.2 in Ah-responsive mice, and 2.3 +/- 0.2 in the F1 hybrid. The total area involved in lesions was 9.3-12.6 micron2 in untreated animals. When mice were treated with MC, the total lesion area increased to 23.5 +/- 5.2 micron2 in Ah-nonresponsive mice, to 43.9 +/- 6.6 micron2 in Ah-responsive mice, and to 36.2 +/- 4.8 micron2 in F1 hybrids. Thus MC increased the lesion area in both strains of mice, but the increase was significantly greater in Ah-responsive than in Ah-nonresponsive animals. High density lipoprotein levels were not significantly affected by MC treatment or Ah genotype. In order to determine whether the increased susceptibility to MC-induced atherosclerosis segregated with the Ah gene, AKXL-38 and AKXL-38a mice were mated and the F1 progeny were backcrossed to the Ah-nonresponsive parent. Backcross progeny were tested for Ah genotype by zoxazolamine sleeping time. Measurements of lesions showed that increased susceptibility to MC-enhanced atherosclerosis segregated with the Ah locus.

Animals↗
PubMed1985

Characteristics of lipopolysaccharide interaction with human peripheral-blood monocytes.

The interaction between radioiodinated lipopolysaccharide from Escherichia coli 0111:B4 (125I-LPS) and human peripheral-blood monocytes was studied. The association of 125I-LPS with monocytes at 37 degrees C appeared to depend on binding to the cell membrane with subsequent internalization of the molecule, and was not saturable with time (up to 2 h) or 125I-LPS concentration (up to 10 micrograms/ml). There was no apparent difference in the behaviour of unlabelled LPS and 125I-LPS with respect to monocyte association. 125I-LPS association with monocytes was inhibited by LPS and O-polysaccharide from E. coli 0111:B4 and Salmonella typhi 0901, but not by lipid A or polymyxin B. We propose that the mechanism of human monocyte stimulation by LPS involves polysaccharide-dependent binding to the cell membrane followed by internalization of the LPS molecule. We were unable to demonstrate a specific LPS receptor such as that found on murine B-lymphocytes.

Electrophoresis, Polyacrylamide Gel↗
PubMed1985

Dose-dependent reduction of lipopolysaccharide pyrogenicity by polymyxin B.

Lipopolysaccharides (LPS) from Gram-negative bacteria are potent pyrogens in mammals. Polymyxin B (PB), a cationic polypeptide antibiotic, binds lipid A, the active moiety of LPS, with high affinity and abrogates several biological responses to LPS. We studied the effect of PB on pyrogenicity of purified LPS from E. coli 0111:B4 in rabbits. PB reduced the pyrogenic response to LPS in a dose-dependent manner at mass ratios (PB:LPS) from 5:1 to 100:1. Previous reports have suggested that PB is effective only at much higher doses. In our hands, PB itself is pyrogenic, unless previously gamma-irradiated. Our results confirm in vivo the anti-endotoxic action of PB.

Animals↗
PubMed1985

Localization and characterization of macrophages in murine uterus.

Macrophages are known to be present in the murine uterus and are known to be among those cells comprising the uterine decidual response to pregnancy. The extent of macrophage involvement in the decidual response has not been documented, and there are unresolved questions regarding expression of markers normally associated with macrophages on cells within the decidua. Using tissue immunohistology, macrophages were identified in virgin and pregnant murine uteri. A significant increase in macrophage density was noted during all stages of pregnancy. When uteri from virgin and pregnant mice were enzymatically digested, 10% of uterine cells from virgin and 22% from pregnant mice expressed macrophage markers (binding of rabbit antimouse macrophage serum, Fc gamma receptor expression). Double labeling immunofluorescence demonstrated that the two markers were associated with the same cells. Those results were confirmed in "panning" experiments using a monoclonal antimouse macrophage reagent. In cell suspensions from pregnant murine (C3H/HeN) uteri, 50% of cells exhibiting macrophage markers were I-Ak positive, and macrophages accounted for nearly all I-Ak positive cells in uterine cell suspensions. The results of this study demonstrate that the murine decidual response to pregnancy includes an increase in Fc gamma receptor-bearing macrophages and that a relatively high percentage of those macrophages are Ia positive.

Animals↗
PubMed1985

Severe illness caused by the products of bacterial metabolism in a child with a short gut.

An 8-year-old boy with a short gut had six episodes of metabolic acidosis and neurological dysfunction over a 1 month period. The neurological features consisted of a depressed conscious state, confusion, aggressive behaviour, slurred speech and ataxia. The organic acid profile of urine demonstrated increased amounts of lactic, 3-hydroxypropionic, 3-hydroxyisobutyric, 2-hydroxyisocaproic, phenyllactic, 4-hydroxyphenylacetic and 4-hydroxyphenyllactic acids. Of the lactic acid 99% was D-lactic acid. The anaerobic gut flora consisted almost entirely of Lactobacilli in unusually large numbers. A course of vancomycin prevented further episodes. A urinary organic acid profile may be diagnostic when a person with a short gut develops metabolic acidosis or an unusual encephalopathy and bacterial metabolites should be considered in other patients with unusual combinations of organic acids in the urine.

Acidosis↗
PubMed1985

Clonal variations in keratin. Intermediate filament expression by human somatic cell hybrids.

The intermediate filament composition of differentiated vertebrate cells provides a stable phenotype which appears to be specifically regulated in each cell type. In order to analyse the regulation of intermediate filament expression we have constructed human somatic cell hybrids from the fusion of the HeLa-derived cell line HEB7A and a normal human diploid fibroblast, GM2291. These parental cells differ with respect to the presence or absence of keratin intermediate filaments. Isolation of independently arising clones produced two classes of hybrids. One class expresses keratin in a stable manner and the other class lacks keratin altogether. Indirect immunofluorescence of hybrid cells using antikeratin antiserum demonstrates that there are variations in the intensity and organization of cytoskeletal keratin staining. SDS-PAGE comparisons of cell extracts from these hybrids indicates that there are quantitative differences in the relative amounts of individual keratin polypeptides as well. These clonal variations have allowed us to begin assessing the consequences of genetic interactions between cell types that are normally capable of closely regulating different subsets of intermediate filament genes.

Cell Fusion↗
PubMed1985

Variation in susceptibility to atherosclerosis among inbred strains of mice.

Ten inbred strains of mice were fed an atherogenic diet containing 1.25% cholesterol, 0.5% cholic acid and 15% fat. The strains were examined for plasma cholesterol and triglyceride levels and for formation of lipid-containing lesions in the aortic wall. The strains differed considerably in the frequency of lesion formation after 14 weeks on the atherogenic diet with a range of 0-1.8 lesions/mouse. The order of susceptibility to lesion formation from the least susceptible to the most susceptible was BALB/cJ, C3H/J, A/J, SWR/J, NZB/J, less than 129/J, AKR/J, DBA/2J, less than C57L/J less than C57BL/6J. Total plasma cholesterol after 5 weeks on the diet varied from 131 mg/dl to 328 mg/dl among strains; however, there was little correlation between total cholesterol levels and susceptibility to lesion formation (r = 0.29). Plasma triglycerides after 5 weeks on the diet varied less than cholesterol with a range of 137-220 mg/dl. An analysis of the genetic differences among inbred strains of mice might provide useful insights into lipid metabolism and the development of atherosclerosis.

Animals↗
PubMed1985

Habituation under stress: shocked mice show nonassociative learning in a T-maze.

Conflicting predictions of reinforcement and neophobia-arousal theories were evaluated in a simple choice task. Four groups of C57BL/6J mice were administered daily two-trial tests in a uniform T-maze for 10 consecutive days. For three groups, the contingencies of footshock treatments were manipulated to reinforce alternation, perseveration, or both. A control group that was not administered footshock alternated, but all three groups that were stressed perseverated more and more across tests, despite the differences in reinforcement contingencies. These results are inconsistent with the predictions of reinforcement theory but consistent with the view that stressed or aroused animals are neophobic and use nonassociative learning (habituation) to distinguish between novel and familiar alternatives.

Animals↗
PubMed1985

Sensory processing in a thermal afferent pathway.

Extracellular recordings were made from cold-receptive afferent fibers in the trigeminal ganglion of rats anesthetized with halothane. By applying a standardized series of steady or changing temperatures to the receptive fields, we recorded the static and dynamic responses of the afferents. Comparable recordings were made from neurons in the marginal layer of the caudal trigeminal nucleus onto which the cold fibers synapse. The static and dynamic responses of the afferent fibers were reproduced faithfully by the second-order neurons, but at a much higher level of activity. Ganglionectomy silenced the second-order cells. Their continuous high level of activity appears to depend on the tonic input from the afferent fibers and not on any intrinsic circuits in the medulla.

Afferent Pathways↗
PubMed1985

Improved immunohistochemical localization of tissue antigens using modified methacarn fixation.

Detailed comparative studies have been carried out using a wide range of aqueous and nonaqueous based fixatives in order to select the optimal fixation schedule for the immunohistochemical localization of four antigens: type IV collagen, actin, Factor VIII, and epithelial membrane antigen (EMA). Modified methacarn fixation provides an ideal combination of maximum staining and morphological preservation for these antigens. Enhanced immunoreactivity with this fixative was also noted for a broad spectrum of antigens, including myoglobin, glial fiber acidic protein, keratin, myosin, laminin, prostatic acid phosphatase, alpha-fetoprotein, and carcinoembryonic antigen. Although it is not recommended for most cell surface antigens, this fixative may have a definite place in diagnostic surgical pathology.

Acetates↗
PubMed1984

Studies on the glutathione S-transferase of human platelets.

The glutathione S-transferases of human platelets have been compared with those of erythrocytes. Although wide variations in activity were found, in individual subjects, the activity in these cell types was significantly correlated. The enzymes demonstrated similar isoelectric points and electrophoretic mobilities and it appears that the platelet enzyme is also a product of the GST3 locus. There was no correlation between platelet enzyme activity and plasma concentrations of retinol and cholesterol, but in men, the relationship between activity and carotene was significant. It is suggested that GST3 isoenzyme activity depends on vitamin A.

Adolescent↗