Stopping CHF while there's still time (continuing education credit).
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Biomedical subjects
Publications and source records attributed to A M Ryan.
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Ocular melanomas in 40 dogs were reviewed and classified by site of origin and cytologic features. An apparent correlation existed between site, cytologic classification, and prognosis. Limbal melanomas and intraocular melanomas classified as spindle A or spindle B were less aggressive and had a more favorable prognosis than intraocular melanomas classified as a mixed-cell type or epithelioid.
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Fluorescent in situ hybridization (FISH) of the cattle cDNA probe bTP-509 to goat (Capra hircus L.) and sheep (Ovis aries L.) R-banded metaphase chromosomes localized the omega (IFNW) and trophoblast (IFNT) interferon genes to goat chromosome 8q15 and sheep chromosome 2p15. Caprine chromosome 8 and ovine chromosome 2p are equivalent in banding pattern to cattle chromosome 8. Since FISH has previously localized IFNW and IFNT genes to cattle chromosome 8q15 and river buffalo 3q15, the localization of IFNW and IFNT genes in goat and sheep provides evidence in support of the hypothesis that chromosome-banding homology among these four species is indicative of underlying genetic homology.
This study investigated the peer group as a context for the socialization of young adolescents' motivation and achievement in school. Social network analysis was used to identify peer groups of adolescents in middle school whose members regularly interacted with each other (N = 331). Actual reports from these peer group members were used to assess peer group characteristics. Multilevel analyses indicated that peer groups did socialize some academic characteristics, controlling for selection factors. Students' peer group context in the fall predicted changes in their liking and enjoyment of school (intrinsic value) and their achievement over the school year. Students' peer group context was unrelated to changes in their beliefs about the importance of school (utility value) or expectancies for success over the school year.
Recombinant humanized antivascular endothelial growth factor (rhuMAbVEGF) is a monoclonal IgG1 antibody that is being developed as an antiangiogenic agent for use in treating a variety of solid tumors. Preclinical safety studies included an immunohistochemical tissue cross-reactivity study, in vitro hemolytic potential and blood compatibility studies, and multiple dose toxicity studies. Toxicity studies were conducted in cynomolgus monkey because rhuMAbVEGF is pharmacologically active in this species and does not bind rat or mouse vascular endothelial growth factor (VEGF). Following twice weekly administration of rhuMAbVEGF for 4 or 13 wk, young adult cynomolgus monkeys exhibited physeal dysplasia characterized by a dose-related increase in hypertrophied chondrocytes, subchondral bony plate formation, and inhibition of vascular invasion of the growth plate. In addition, decreased ovarian and uterine weights and an absence of corpora lutea were observed in females receiving 10 and 50 mg/kg/dose in the 13-wk study. Both the physeal and ovarian changes were reversible with cessation of treatment. No other treatment-related effects were observed following rhuMAbVEGF administration at doses up to 50 mg/kg. These findings indicate that VEGF is required for longitudinal bone growth and corpora lutea formation and that rhuMAbVEGF can reversibly inhibit physiologic neovascularization at these sites.
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Access of recombinant proteins to the retina following intravitreal administration is poorly understood. A study was conducted in male Rhesus monkeys (15 to 28 mo of age; 2.8-3.3 kg) in order to compare the intraocular tissue distribution, pharmacokinetics, and safety of 125Iodine (I)-labeled full-length humanized rhuMAb HER2 antibody (148 kD) and of 125I-labeled humanized rhuMAb vascular endothelial growth factor Fab antibody (48.3 kD) following bilateral bolus intravitreal injection on day 0 (5 animals/group). The dose administered to each eye was 25 microg (9-10 microCi) in 50 microl. Animals were euthanatized on day 0 (1 hr postdose) and on days 1, 4, 7, and 14. Safety assessment included direct ophthalmoscopy, intraocular pressure measurements, clinical observations, body weight, and hematology and clinical chemistry panels. Blood and vitreous samples were collected daily (blood only) and at necropsy for pharmacokinetics and analysis for antibodies to the test materials; the ocular tissue distribution of the test material was evaluated by microautoradiography. All animals completed the study. Microautoradiography demonstrated that the full-length antibody did not penetrate the inner limiting membrane of the retina at any of the time points examined. In contrast, the Fab antibody fragment diffused through the neural retina to the retinal pigment epithelial layer at the 1-hr time point and persisted in this location for up to 7 days. Systemic exposure to test material was low but variable: the highest plasma concentration of the full-length antibody was 20.3 ng/ml, whereas plasma concentrations for the Fab antibody remained below the limit of quantitation (i.e., <7.8 ng/ml). An immune response to the test material was not evident in either treatment group. The half-life in vitreous was 5.6 days for the full-length antibody and 3.2 days for the Fab antibody. The shorter intravitreal half-life of the Fab antibody is related to its smaller size and its significant diffusion through the retinal layers. The differences in pharmacokinetics and tissue distribution that are noted between the full-length and Fab antibodies in this study identify potential therapeutic approaches that may be exploited in specific disease conditions.