Browsing by Author "Bender, Holly S."
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- The actions of gossypol on the physiologic antioxidant defense systemBender, Holly S. (Virginia Polytechnic Institute and State University, 1987)Gossypol , a yellow polyphenolic pigment found in cottonseeds, is known to promote the production of reactive species of oxygen in vitro, and has toxic actions on spermatogenic epithelium, hepatocytes and cardiac myocytes in vivo. Species vary in tissue sensitivity to the toxic effects of gossypol. The spermatogenic epithelium is the most sensitive tissue to gossypol in rats, followed by the liver. Toxic effects to the rat heart are found only after prolonged administration of gossypol. The antioxidant defense system that protects cells from injury by reactive species of oxygen was examined in the present study to determine a possible pathogenesis for gossypol associated tissue damage. The concentrations of several hepatic antioxidants including catalase, glutathione peroxidase, ascorbate and copper-zinc superoxide dismutase were decreased in gossypol treated rats. Catalase, glutathione peroxidase, ascorbate and glucose-6-phosphate dehydrogenase were decreased in the testis. In contrast, antioxidants including catalase and glutathione reductase were increased in the hearts of gossypol treated rats. The selective inhibition of testis and hepatic antioxidants may account for the greater sensitivity of these organs to reactive oxygen species generated by gossypol. The rat heart may adapt to oxidative insult by inducing the production of antioxidants. Glucose-6-phosphate dehydrogenase activity was decreased in the testis but not liver or heart of gossypol treated rats. This important enzyme is known to produce NADPH reducing equivalents for testosterone biosynthesis and the glutathione antioxidant system. In the present study, micromolar concentrations of gossypol inhibited glucose-6-phosphate dehydrogenase in a competitive manner with respect to glucose-6-phosphate. This may explain the degeneration of spermatogenic epithelium as well as decreases in serum testosterone concentrations in gossypol treated rats. Gossypol is known to cause infertility in women and female rats. The present study found irregularities in the estrous cycles and ultrastructural changes in endometrial macula adherentes of gossypol treated female rats.
- Application and Evaluation of Unified Medical Language System Resources to Facilitate Patient Information Acquisition through Enhanced Vocabulary CoverageMills, Eric M. III (Virginia Tech, 1998-04-13)Two broad themes of this research are, 1) to develop a generalized framework for studying the process of patient information acquisition and 2) to develop and evaluate automated techniques for identifying domain-specific vocabulary terms contained in, or missing from, a standardized controlled medical vocabulary with emphasis on those terms necessary for representing the canine physical examination. A generalized framework for studying the process of patient information acquisition is addressed by the Patient Information Acquisition Model (PIAM). PIAM illustrates the decision-to-perception chain which links a clinician's decision to collect information, either personally or through another, with the perception of the resulting information. PIAM serves as a framework for a systematic approach to identifying causes of missing or inaccurate information. The vocabulary studies in this research were conducted using free-text with two objectives in mind, 1) develop and evaluate automated techniques for identifying canine physical examination terms contained in the Systematized Nomenclature of Medicine and Veterinary Medicine (SNOMED), version 3.3 and 2) develop and evaluate automated techniques for identifying canine physical examination terms not documented in the 1997 release of the Unified Medical Language System (UMLS). Two lexical matching techniques for identifying SNOMED concepts contained in free-text were evaluated, 1) lexical matching using SNOMED version 3.3 terms alone and 2) Metathesaurus-enhanced lexical matching. Metathesaurus-enhanced lexical matching utilized non-SNOMED terms from the source vocabularies of the Metathesaurus of the Unified Medical Language System to identify SNOMED concepts in free-text using links among synonymous terms contained in the Metathesaurus. Explicit synonym disagreement between the Metathesaurus and its source vocabularies was identified during the Metathesaurus-enhanced lexical matching studies. Explicit synonym disagreement occurs, 1) when terms within a single concept group in a source vocabulary are mapped to multiple Metathesaurus concepts, and 2) when terms from multiple concept groups in a source vocabulary are mapped to a single Metathesaurus concept. Five causes of explicit synonym disagreement between a source vocabulary and the Metathesaurus were identified in this research, 1) errors within a source vocabulary, 2) errors within the Metathesaurus, 3) errors in mapping between the Metathesaurus and a source vocabulary, 4) systematic differences in vocabulary management between the Metathesaurus and a source vocabulary, and 5) differences regarding synonymy among domain experts, based on perspective or context. Three approaches to reconciling differences among domain experts are proposed. First, document which terms are involved. Second, provide a mechanism for selecting either vocabulary-based or Metathesaurus-based synonymy. Third, assign a "basis of synonymy" attribute to each set of synonymous terms in order to identify the perspective or context of synonymy explicitly. The second objective, identifying canine physical examination terms not documented in the 1997 release of the UMLS was accomplished using lexical matching, domain-specific free-text, the Metathesaurus and the SPECIALIST Lexicon. Terms contained in the Metathesaurus and SPECIALIST Lexicon were removed from free-text and the remaining character strings were presented to domain experts along with the original sections of text for manual review.
- The Design, Development and Evaluation of a Web-based Tool for Helping Veterinary Students Learn How to Classify Clinical Laboratory DataDanielson, Jared Andrew (Virginia Tech, 1999-07-07)Veterinary students face the difficult task of learning to classify clinical laboratory data. In an effort to make this task easier, a computer and web based tool known as the Problem List Generator (PLG) was designed based on current literature dealing with learning theory and medical education which are reviewed in chapter 1. Chapter 2 describes the design and the development process for the PLG. The PLG allows the students to access any number of cases (determined by the professor) of increasing complexity which provide signalment, history, physical exam, and laboratory data for a number of patients. Using the PLG, students analyze the data, identify data abnormalities and mechanisms, arrange them in a problem list, diagnose the problem, and compare their problem list and diagnosis to an expert problem list and diagnosis. The PLG was evaluated using a four step evaluation process involving an expert review, one-to-one evaluations, small group evaluations, and a two-part field trial, and was evaluated in terms of clarity, feasibility, and impact. The PLG is usable, in terms of clarity and feasibility, though fixes are recommended. There is no evidence to infer, statistically, that the PLG has any effect on learning outcomes. However, trends in the quantitative data and logical inference based on the context of the evaluation suggest that the PLG might help students, particularly those of low and average ability to produce more accurate problem lists.
- Immunotoxicity of Dermal Permethrin and Cis-Urocanic Acid: Effects of Chemical Mixtures in Environmental HealthPrater, Mary R. (Virginia Tech, 2002-03-08)The present study examined adverse effects of sunlight exposure (mimicked by intradermal cis-urocanic acid, cUCA) on local and systemic immune responses, with or without co-exposure to the immunotoxic insecticide permethrin. A single exposure to cUCA caused diminished splenic macrophage phagocytosis that was persistent up to 30 days post-exposure. Five-day exposure to cUCA subtly increased splenocyte proliferation in response to the T cell mitogen Concanavalin A. Four-week exposure to cUCA caused increased splenic lymphocyte cellularity, thymic hypocellularity, and enhanced hydrogen peroxide production by splenic leukocytes. Single exposure to topical permethrin resulted in decreased thymic and splenic weight and cellularity, and inhibited antibody production by splenic B cells. cUCA worsened the negative effect of permethrin on both thymic weight and cellularity, and depressed splenocyte blastogenesis, hydrogen peroxide production, and antibody production. Five-day exposure to either cUCA or permethrin also caused persistent decreased contact hypersensitivity responses, an effect that became more than additive when the chemicals were administered concurrently. Defects in antigen processing and presentation by cutaneous Langerhans cells were evaluated as possible contributing mechanisms to the cutaneous immunosuppression, using mice with deleted genes. Vehicle-exposed IFNg knockout mice displayed approximately a 22.1% depression in the ear swelling response as compared to control C57BL/6N mice, suggesting that this cytokine may be required for mounting a control-level hypersensitivity response. Ear swelling in cUCA-exposed IFNg knockout mice displayed a 21.4% depressed response as compared to cUCA-exposed wild-type C57BL/6N mice, again suggesting that IFNg is an important cytokine in the contact hypersensitivity (CH) response. TNFaR knockout mice exposed to cUCA displayed 33.9% greater ear swelling than cUCA-exposed wild-type C57BL/6N mice, suggesting that increased TNFa may be involved in inhibited CH by cUCA. TNFaR knockout mice exposed to permethrin displayed 33.9% greater ear swelling than permethrin-exposed C57BL/6N mice, suggesting that increased TNFa may also be involved in inhibited CH by permethrin. C57BL/6N mice exposed to cUCA + permethrin displayed severe reduction of the CH response to 8.7% of the control level. IFNg knockout mice exposed to permethrin + cUCA showed essentially identical depression of the CH response as IFNg knockout mice exposed to either permethrin or cUCA alone. These results suggest that IFNg is required for the greater than additive immunotoxic effect that occurred when these two agents were co-administered. TNFaR knockout mice exposed to cUCA + permethrin displayed 8.7 fold greater ear swelling than similarly exposed C57BL/6N mice, again suggesting that increased TNFa is involved in inhibited CH by both cUCA and permethrin.