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Biomedical subjects

D D Myers

Publications and source records attributed to D D Myers.

At least 19 recordsLinked to original sources
PubMed2003

Decrease in fibrin content of venous thrombi in selectin-deficient mice.

The purpose of this study was to quantify the fibrin content of thrombi produced in a mouse model of venous thrombosis and correlate this to thrombus mass. The role of P-selectin, E-selectin, and IL-10 on thrombus fibrin content was analyzed using knockout (KO) mice. Five groups of mice were evaluated: control (N = 10), P-selectin KO (N = 7), E-selectin KO (N = 5), combined E-/P-selectin KO (N = 12), and IL-10 KO (N = 10). Venous thrombosis was induced by ligation of the infrarenal IVC. Mice were sacrificed on postoperative days (POD) 2 and 6. Thrombus mass was calculated. Sections of IVC were stained with an antibody that cross reacts with mouse fibrin. The distribution of RGB color pixels was generated from digitized micrographs of the thrombus of each animal. The mean pixel value for each group was compiled and analyzed using 2-way ANOVA. Mean pixel value per group was correlated with the mean thrombus mass per group. Color analysis demonstrated significant decreases in the analyzed fibrin content on POD-2 between the control vs E-/P-selectin KO (P < 0.05) and control vs IL-10 KO (P < 0.05) groups. In addition, significantly less fibrin staining was noted on POD-6 between the control vs E-selectin KO (P = 0.03), control vs P-selectin KO (P = 0.01), and control vs E-/P-selectin KO (P < 0.01). There was a strong overall correlation between the mean pixel value for each group and the thrombus mass (R = 0.964; P < 0.01). This study demonstrates a difference in fibrin content of thrombi produced in animals deficient in E-selectin, P-selectin, and IL-10, supporting their importance in thrombus amplification, fibrin formation, and the mass of thrombus formed.

Animals↗
PubMed2001

Subcutaneous hemangiosarcomas in a rhesus macaque (Macaca mulatta).

Hemangiosarcoma is a malignant tumor of vascular endothelial cell origin. The occurrence of hemangiosarcoma in nonhuman primates has been rarely documented. An adult male rhesus monkey was reported having a firm subcutaneous swelling, approximately 4.5 cm in diameter, on the ventral midline of the abdomen. Fine-needle aspiration, microbial culture, biopsy, radiographs, exploratory laparotomy, histopathology, immunohistochemistry, hematology, and serology were performed. A second subcutaneous mass approximately 4.5 x 4.0 x 2.7 cm developed on the ventral midline several weeks later. A fine-needle aspirate of the first mass consisted of numerous erythrocytes with few polymorphonuclear cells and lymphocytes. Histopathology showed foci of spindle-shaped cells surrounding the vascular spaces. Many spindle-shaped cells had prominent nucleoli, and mitotic figures could occasionally be seen. Immunohistochemical staining of the masses for Factor VIII-related antigen, an endothelial cell and tumor marker, yielded positive results. Both masses were consistent with hemangiosarcoma.

Abdominal Neoplasms↗
PubMed2001

The impact of reduced frequency of cage changes on the health of mice housed in ventilated cages.

Our purpose in this investigation was to determine if we could reduce cage changing frequency without adversely affecting the health of mice. We housed mice at three different cage changing frequencies: 7, 14, and 21 days, each at three different cage ventilation rates: 30, 60 and 100 air changes per hour (ACH), for a total of nine experimental conditions. For each condition, we evaluated the health of 12 breeding pairs and 12 breeding trios of C57BL/6J mice for 7 months. Health was assessed by breeding performance, weanling weight and growth, plasma corticosterone levels, immune function, and histological examination of selected organs. Over a period of 4 months, we monitored the cage microenvironment for ammonia and carbon dioxide concentrations, relative humidity, and temperature one day prior to changing the cage. The relative humidity, carbon dioxide concentrations, and temperature of the cages at all conditions were within acceptable levels. Ammonia concentrations remained below 25 ppm (parts per million) in most cages, but, even at higher concentrations, did not adversely affect the health of mice. Frequency of cage changing had only one significant effect; pup mortality with pair matings was greater at the cage changing frequency of 7 days compared with 14 or 21 days. In addition, pup mortality with pair matings was higher at 30 ACH compared with other ventilation rates. In conclusion, under the conditions of this study, cage changes once every 14 days and ventilation rates of 60 ACH provide optimum conditions for animal health and practical husbandry.

Air Pollutants↗
PubMed2001

P-selectin antagonism causes dose-dependent venous thrombosis inhibition.

Inhibition of P-selectin by antibody or selectin antagonist decreases inflammation and thrombosis. This study evaluates the dose-response relationship using a selectin receptor antagonist. Eight male baboons (Papio anubis) underwent inferior vena caval thrombosis using a 6 h balloon occlusion model. Three animals received 500 microg/kg P-selectin antagonist (rPSGL-Ig) and five 1 mg/kg rPSGL-Ig with or without a non-anticoagulant dose of Dalteparin. These animals were compared to our published results in this model with 4 saline controls and 8 animals that received 4 mg/kg rPSGL-Ig. A statistically significant dose-response relationship existed between rPSGL-Ig dose and thrombosis (p < 0.01), and between rPSGL-Ig dose and spontaneous recanalization (p<0.05). Inflammatory assessment revealed decreased gadolinium enhancement in all rPSGL-Ig groups compared to previously reported control, despite no significant differences in inflammatory cell extravasation. No dose of rPSGL-Ig caused anticoagulation. Selectin antagonism results in a dose-dependent decrease in thrombosis and increase in spontaneous recanalization.

Animals↗
PubMed2000

Venous thrombosis prophylaxis by inflammatory inhibition without anticoagulation therapy.

OBJECTIVE: This study was performed to determine the effectiveness of recombinant P-selectin glycoprotein ligand Ig (rPSGL-Ig) pretreatment to decrease thrombosis and inflammation in experimental venous thrombosis. rPSGL-Ig, a unique mucin-like glycoprotein, has a high affinity for P-selectin. METHODS: Twelve juvenile baboons underwent inferior vena cava (IVC) thrombosis with temporary 6-hour IVC balloon occlusion. Before balloon placement, the animals received rPSGL-Ig (4 mg/kg; n = 8) or saline solution for control (n = 4). The animals underwent evaluation with duplex ultrasound scan imaging, magnetic resonance venography (MRV), phlebography, coagulation profile, and tissue analysis at death for cytokines and vein wall leukocyte morphometrics. With the MRV results, thrombus development, thrombus resolution, and inflammation (gadolinium; square millimeters of enhancement) were assessed. RESULTS: Each animal provided two time points for evaluation (days 2 and 6 after balloon occlusion). A significant decrease in IVC thrombosis between balloons was found in the rPSGL-Ig animals (1 of 16) versus the control animals (5 of 8; P <.01). The MRV results showed significantly less enhancement in the rPSGL-Ig animals at days 2 and 6 (P <.05). Spontaneous thrombus resolution (including balloon sites) was significantly greater from day 2 to day 6 in the rPSGL-Ig animals versus the control animals (23% vs 2%; P <.001), without pulmonary embolism. Lower interleukin-8, platelet factor IV, and monocyte chemotactic protein-1 levels were found in rPSGL-Ig vein walls without significant differences in vein wall leukocyte morphometrics. There were significantly lower D-dimer levels in the rPSGL-Ig-treated animals (P <.05), but there were no differences in measurements of coagulation. Adequate circulating rPSGL-Ig levels were documented. CONCLUSION: Pretreatment with rPSGL-Ig results in: (1) a significant inhibition of thrombosis and vein wall inflammation; (2) a decrease in vein wall cytokine expression; and (3) a promotion of thrombus resolution. Inflammatory inhibition by rPSGL-Ig without anticoagulation therapy provides effective venous thrombosis prophylaxis in experimental venous thrombosis.

Animals↗
PubMed1999

Control strategies for aeroallergens in an animal facility.

BACKGROUND: Prevalence of the occupational disease laboratory animal allergy could be reduced if aeroallergen reduction strategies are identified. OBJECTIVE: To reduce worker exposure to Mus m 1, an allergen from laboratory mice, the effect of filter cage tops, increased room ventilation, negatively pressurized ventilated cages, and ventilated cage-changing tables were evaluated. METHODS: Aeroallergen was collected in the ambient air and in the breathing zone and quantified by using a competitive immunoassay. RESULTS: When mice were housed in unventilated cages, ambient allergen was reduced from 5.1 ng/m3 with no cage top to 1.3 ng/m3 with a simple filter-sheet top and 0.8 ng/m3 with a fitted filter-bonnet top (P <. 05). Room ventilation was increased from 6 to 10, 15, and 20 air changes per hour and had little effect on aeroallergen levels and no impact on airborne particulate matter. When mice were housed in ventilated cages, ambient allergen was significantly reduced from 1. 1 ng/m3 at positive cage pressure to 0.3 ng/m3 at negative cage pressure (P <.05). Negative cage pressure combined with handling animals under a ventilated table reduced breathing zone allergen from 28 ng/m3 with neither control strategy in place to 9 ng/m3 (P <. 05). Use of a ventilated table controlled bacterial contamination, measured as colony forming units, found in negatively pressurized cages. CONCLUSION: Three aeroallergen control strategies are use of filter cage tops, operation of negatively pressurized cages, and use of ventilated changing tables.

Air Pollution↗
PubMed1999

Neovascularization during venous thrombosis organization: a preliminary study.

PURPOSE: Thrombus organization after venous thromboembolism leading to recanalization occurs at a variable rate. The angiogenic chemokine interleukin-8 (IL-8) has been found in thrombus months after thrombus initiation. We hypothesize that thrombus organization involves neovascularization and leukocyte influx and that IL-8 administered at thrombus induction will promote thrombus organization. METHODS: A group of rats underwent inferior vena caval occlusive thrombosis. At thrombus induction and every 24 hours, the rats were administered IL-8 (1 microgram) or serum albumin. The rats were killed at either day 4, day 8, or day 12, and, at death, colloidal carbon was perfused via the heart. The inferior vena cava was isolated, measured, weighed, and formalin fixed. The sections were stained with anti-polymorphonuclear leukocyte antibody, the endothelial marker factor VIII-related antigen, and with hematoxylin and eosin. Thrombus neovascularization (colloidal carbon) with morphometric analysis was normalized to the total thrombus area. In addition, the rats underwent perfusion with fluorescein isothiocyanate dextran (molecular weight, 150,000) at death to correlate with colloidal carbon perfusion, and thrombus fluorescence was determined. RESULTS: Thrombus cellularity initially involved neutrophils, followed by monocytes. Significantly more neutrophils, monocytes, and cells that were defined as spindle shaped (fibroblasts and endothelial cells) were noted in the animals treated with IL-8. Neovascularization was significantly increased at day 4 in the animals treated with IL-8 versus the animals treated with serum albumin and was corroborated with a significant increase in thrombus fluorescein isothiocyanate dextran fluorescence at day 4 in the rats treated with IL-8. Colloidal carbon perfusion was noted within vascular channels without extravasation and colocalized with factor VIII-related antigen. CONCLUSION: This study shows that thrombus organization involves neovascularization and that IL-8 augments thrombus organization.

Animals↗
PubMed1981

Barbiturate sleeptime in mice exposed to autoclaved or unautoclaved wood beddings.

Effect of unautoclaved or autoclaved contact bedding materials (mixed hardwood, white spruce, white pine, and red cedar shavings) on pentobarbital sleeptime and liver:body weight ratios was assayed in young DBA/2J and C57BL/6J male mice. Analysis of variance indicated that autoclaving the bedding did not alter either parameter in either strain. Within strains, data were pooled and analyzed for bedding effects. Sleeptimes of DBA/2J male mice on mixed hardwood or white spruce bedding were not significantly different, but were significantly longer than sleeptimes of mice on white pine or red cedar bedding. Sleeptimes of DBA/2J mice on white pine were significantly longer than mice on red cedar. Sleeptimes on C57BL/6J male mice on each bedding were significantly different with the following rank order:mixed hardwood greater than white spruce greater than white pine greater than red cedar. In both strains, liver:body weight ratios of mice on red cedar bedding were significantly increased compared to mice on white pine, white spruce, or mixed hardwood beddings. The results of this study indicated that autoclaving these beddings did not alter pentobarbital sleeptimes or liver/:body weight ratios and that softwood beddings differ in their abilities to alter pentobarbital sleeptimes.

Animals↗
PubMed1980

Fibrous waveforms or crimp in surface and subsurface layers of hyaline cartilage maintained in its wet functional condition.

The structural features of hyaline cartilage maintained in its wet functional condition have been examined using the technique of Nomarski interference microscopy. The collagenous arrays and associated chondrocytes in both the extreme superficial layers and in the deeper subsurface zones were satisfactorily imaged with this technique. Most significantly the collagen fibers were observed to possess a geometric waveform or "crimp" of varying acuteness and the role of this crimp is discussed in relation to the mechanical and biological function of the tissue. It is clear from these wet tissue studies that the fibrous layout in hyaline cartilage is considerably more "disciplined" than has been previously recognized from morphological data obtained using more indirect experimental techniques involving prepared histological sections or scanning and transmission electron microscopy.

Animals↗
PubMed1971

Host-gene control of C-type RNA tumor virus: inheritance of the group-specific antigen of murine leukemia virus.

Genetic studies were aimed at elucidation of the mechanism of inheritance of the group-specific antigen of the murine leukemia virus. Two approaches have been used. First, a classical Mendelian hybridization experiment was performed with mice of the high-leukemia AKR strain and the low-leukemia C57L strain; the first filial (F(1)) generation hybrids, the second filial (F(2)) generation hybrids, and the backcrosses to the two parental strains. Second, a number of partially inbred lines derived from the F(2) generation of the same cross were used. The results of these studies demonstrate a specific genetic regulation of expression of group-specific antigens. Genes permissive to the expression of the antigen are dominant or semidominant to their nonpermissive alleles. It appears that two dominant genes carried by the AKR strain, but not by the C57L strain, are necessary for the presence of a complete virus; one of these controls the expression of group-specific antigen.

Animals↗