• A qualitative study of urinary excretion of carbohydrates by mentally retarded children

      Cravey, Eurgene C; Department of Cell and Molecular Biology (1964-08)
    • Quantification of PAS reactive materials in the renal cortices of rat and mouse

      Kehl, Thomas E.; Department of Anatomy (1977-07)
      The purpose of this study was_to quantify any age-related changes in PAS reactivi-ty in the renal cortex of ~ndiseased rat and mouse kidneys, and to apply statistical analysis (Student's t-Test) to the data obtained to determine (1) ·intraspecific PAS reactivity changes with age and (2) interspecific PAS.reactivity relationships within four relative age g.roups. The kidneys were removed, longitudinally divided at the hilus, fixed with a solution of ethanol: formalin: acetic acid (AFA), and embedded inparaffin. Sections 1011 in thickness were mounted and stained utilizing routinePAS·procedures. Significant differences were found between age groups within each species, with both rat and mouse exhibit_ing a. peak of PAS reactivity. in a ~iddle ag_e group, with significantly lower reactivity,in the younger and older age groups. The interspecific relationships wer_e· significantly different when identical areas (8 X 104 ]1 2 ) of cortex were compared. In order to cqmpare interspecific tubular ·PAS rea~tive relationships, the number of tubules per area within each age_ group~of each species was determined. No significant intraspecific,. changes in tubules perJarea .occurred with age in either species, but the mouse had significantly more tubules per area than rat. , This data was applied· to the ·area ·comparison to illustrat_e the more intense PAS reactivity· in rat ·tubular basement membranes and brush borde:r;s when compar~d· with· mouse:. tubular basement membra.nes and. brush borders.
    • Quantitative staphylococcal antibodies against Jensen's antigen A

      Rinker, Geraldine; Department of Medicine (1964-06)
    • Race and Income Association with Health Service Utilization for Veterans with Heart Failure

      Landrum, Laurie G.; Department of Nursing (2012-07)
      Disproportionate heart failure outcomes exist for Blacks in the Veterans Health Administration (VHA) despite equitable access and financial barrier minmization. No study has examined the association of race and income with health service utilization for veterans with heart failure. This observational study investigated race and income associations with readmissions, bed days of care, and emergency room (ER) visits for veterans with heart failure after controlling for predisposing, enabling, and illness severity factors. Medical record data were collected for 149 veterans telemonitored for heart failure during 2008-2011. Heart failure symptoms severity and comorbidities were measured using investigator-adapted scales based on the New York Heart Association IIV scale and the Charlson comorbidity index. Heart failure related outcomes (30 day, 90 day, 1 year, and total readmissions, ER visits, and total bed days of care) were modeled controlling for age, marital status, and heart failure and comorbidity severity. Of patients younger than 60 years of age, 18% were Black compared to 11% of Whites, Χ2 (2, N=149) = 5.15, p= .02. Blacks had a much higher comorbidity prevalence than Whites, p = .000. Ischemic heart disease and chronic kidney disease rates were double and triple national VHA rates, respectively, among Whites and Blacks. Race did not predict readmissions, bed days of care, or ER visits. The odds of a readmission or bed day of care ever decreased by 38% and 43%, respectively, for married men, p = .03. The odds of a readmission or bed day of care ever due to severe heart failure—compared to less severe heart failure—were four to five times higher, respectively, p ≤ .004. Income increased the odds of total bed days of care by 14%, p = .00, holding race constant. Overall, the sample experienced far fewer readmissions, bed days of care, or ER visits, compared to VHA national rates, but sample size may have limited accurate comparisons.
    • Radiation adaptation in the rat

      Corrill, Lydia S.; Department Of Biology (1968-09)
    • Rapamycin, an evolving role in up-regulation of autophagy to improve stroke outcome and increase neuronal survival to stroke type injuries

      Buckley, Kathleen; Department of Cellular Biology and Anatomy (2015-10)
      Rapamycin was shown to reduce infarct size in a non-reperfusion and a slow reperfusion model of murine stroke; it also improved neurological score and survival in the slow-reperfusion model. The rapamycin improvement was 50 percent greater than that observed with chloroquine. In HT22 mouse hippocampal neurons, rapamycin was shown to improve survival to an oxidative/reperfusion injury with H2O2 and a hypoxic/ischemic injury with oxygen and glucose deprivation to a larger degree than chloroquine. Rapamycin treatment increased punctate microtubule light chain associated protein 3, LC3, in the HT22 neurons in an uninjured and oxygen and glucose deprivation injured HT22 neurons compared to untreated neurons. Finally, genetic knockdown of autophagy with shRNA to autophagy protein 5, ATG5, abrogated the rapamycin’s positive effect on survival to injury.
    • Reactivation of latent herpes simplex virus and chemotherapy of herpes infection

      Se Kwon, Byoung; Department of Cell and Molecular Biology (1980-12)
    • Recent advances in the technique of cardio-vascular surgery

      Shapiro, Stephen M.; Department of Medical Illustration (1956-06)
    • Receptor-mediated endocytosis of vitellogenin in the oocyte of the frog, xenopus laevis

      Tucciarone, Linda M; Department of Cell and Molecular Biology (1983-05)
      The yolk protein, vitellogenin, is internalized by the developing oocyte by the process of receptor-mediated endocytosis. This process is initiated in Xenopus laevis by gonadotropic hormones. This study w~s designed to characterize the endocytot-ic pathway of vitellogenin in· the Xenopus oocyte and the influence-of gonadotropins on this pathway. One of the molecular-mechanisms of this pathway involves the enzyme transglutaminase which catalyzes E(-y-glutamyl) lysine crosslinks. These studies have demonstrated the presence of transglutaminase activity in Xenopus ovary. By the use of specific inhibitors of transglutaminase, dansylcadaverine and methylamine, the activity of this enzyme has been correlated with vitellogenin uptake by the oocytes. An increase in the activities of· the ovarian transglutaminase was also observed subsequent to in vitro exposure of ovarian fragments to hCG. The relationship of calmodulin, the calcium regulator protein, to transglutaminase activity in the ovary and uptake of vitellogenin was investigated because of the calcium requirement for both of these processes. In this study, the uptake of vitellogenin was shown to be sensitive to the calmodulin-directed drug, Stelazine. However, Stelazine failed to inhibit the transglutaminase activity of the ovary, suggesting that the functional role for calmodulin in endocytosis of vitellogenin must be at another site. The common endocytotic pathway of nutritional protein such as vitellogenin involves clathrin-coated pits and vesicles. Studies utilizing SDS-PAGE and immunolabelling techniques have shown that the 180,000 M r protein, clathrin, is present in both hCG treated and untreated ovaries.Extracts of Xenopus ovary containing coated vesicles have additional proteins in common with pig brain coated vesicles, including the two clathrin light chains of 33,000 M and 36,000 M • r · r An RIA for measuring gonadotropin induced alterations in the levels of clathrin in the ovary was developed. However, ·the sensitivity of the assay was very low and proved inadequate to measure small differences in cilathrin levels in the ovary •
    • Receptor-mediated endocytosis of vitellogenin in the oocyte of the frog, xenopus laevis

      Tuten, Susan Harris; School of Nursing (1988-07)
      The purpose of this study was two~fold: ( 1) to determine if the patency of the peripheral intermittent intravenous device could be maintained with sodium chloride as effectively as with dilute heparin, and (2) to determine if sodium chloride could be used effectively with fewer local co~plicatitins (i.e., infiltrati~n, phlebitis) than d i 1 u t e hepar in so 1 u t ion • The sample consisted of 77 I hospitalized medical surgical patients having a total of 1~4 peripheral intermittent intr~venous devices. During a 60 day period, the devices (N=43) of the 30 patients in the experimental group were maintained with sodium chloride (0.9%) while the devices (N=71) of the 47 patients in the control group were maintained with dilute heparin ClOOU/lml). Three hypotheses were tested utilizing the chi-square procedure with Yates correction for continuity statistical test. An alpha level of p < .OS was used to determine statistical significance. All three hypotheses. were rejected. No incidence of site loss due to coagulation was reported i~ either group, and no significant difference was demonstrated in the incidence of site loss associated with phlebitis cx2 = .140; p = • 708; df = 1) or infiltration C X 2 = • ·a 12 ; p = • 9 1 0 ; d f = 1 > between pat i en t s in the experimental and control groups. These findings indicate that sodium chloride may be used for peripheral intermittent intravenous device maintenance with similar rates of local complications (i.e., coagulation, infiltration, phlebitis) as seen with dilute heparin. It is r~commended that the study-'be replicated in a larger sample representing more diverse·clinical settings, and that the instrument utilized ·in this study be subjected to more rigorous validity and reliability testing.
    • Recombinant Bone Morphogenetic Protein-2 Induces Up-Regulation of Angiogenesis and Inflammatory Transcripts: Role of Reactive Oxygen Species

      Akeel, Sara K; Department of Oral Biology (2012-12)
      Large bone defects in the oral and maxillofacial region are mostly secondary to tumor resection, gunshot wounds or craniofacial anomalies. Reconstruction of large bone defects remains a clinical challenge despite the ability of bone to regenerate itself after fracture, mainly because bone regeneration requires recruitment of new cells as well as development of new bone tissue in order to restore anatomical and mechanical functions. Several biological and mechanical factors regulate bone formation. Early vascularization plays a critical role in skeletal bone development and bone fracture repair, and without a vascular supply, osteogenesis is impaired (Glowacki 1998; Akeno, Czyzyk-Krzeska et al. 2001; Carano and Filvaroff 2003). Furthermore, in the treatment of bone defects, vascularized bone grafts show less bone remodeling when compared to non-vascularized bone grafts (Cutting and McCarthy 1983; Wang, Yamazaki et al. 1996). This highlights the importance of angiogenesis in bone formation and remodeling. The close proximity of osteoblasts and osteoclasts to endothelial cells during bone formation suggests there is a cross-talk between these cells. Osteogenesis-inducing growth factors, such as bone morphogenetic proteins (BMPs), especially BMP-2 and -7, and vascular endothelial growth factor (VEGF) which is known to have a major role in angiogenesis, have been reported in many studies to play a major role in osteoblast-endothelial cell communication (Mayer, Bertram et al. 2005). The general goal of this study is to understand some of the molecular events that occur at the site of bone healing and the interaction of local growth factors produced by resident cells such as osteoprogenitor and endothelial cells. This will help us in developing techniques that enhance bone formation and provide better integration of bone grafts in the recipient site. Specifically, the aim of this study is to understand the mechanism by which recombinant bone morphogenetic protein-2 (rhBMP-2) induces bone formation and whether or not the effect of rhBMP-2 is through enhancing angiogenesis and inflammation.
    • Recombination and genetic polymorphism at the mouse alpha-globin locus

      Lewis, Jill B; Department of Cell and Molecular Biology (1988-12-08)
      Unusual genetic phenomena are often responsible for dramatic evolutionary changes at many mammalian loci. Among the possible genetic mechanisms involved in these changes are point mutation, gene-conversion, and homologous or nonhomologous recombination. Rarely can such evolutionarily significant events be studied as recent occurrences in mammalian systems. In most case.s it can only be postulated that such events occurred ·in the distant past. In the case analyzed in this research, however, the genetic rearrangement has occurred within the last fifteen years since the origination of a certa~n inbred mouse strain known as AKXL-7. The AKXL-7 recombinant inbred strain is the product of inbred parental strains AKR and C57L. AKR.has the Hba "f" genetic type which specifies only alpha-globin chain 5. C57L has the Hba "a" genetic type that specifies only alpha-globin chain 1. Chains 1 and 5 are identical except for a gly --> ala substitution at position 78. Although one would predict that any recombinant inbred strain resulting from thes,e parents would be homozygous for one of these two alpha-globin types, this is not the case for the AKXL-7 strain. These mice express both alpha-globin chains, with chain 1 present in greater amounts than chain 5. The type of genetic reassortment that has occurred has been ascertained through the use of DNA probes to flanking regions of the two non-allelic or "tandem" alpha-globin 1 genes. Southern blot analysis has revealed that the left and right AKXL-7 alphaglobin gene flanking regions are homologous to regions from different parents. This result indicates that the novel AKXL-7 genotype is the result of a reciprocal recombination event. Further analysis using an intergenic region probe narrowed the region of crossover to approximately 5.2 kb. Using the most distal flanking region probes, chromosome walking was performed to recover probes useful for characterization of three different induced mouse alphathalassemia mutations. Results indicate that in all three cases the deletion spans. at least 45 kb, including both alphaglobin genes and the-embryonic alpha-like x gene.
    • Reduced binding to type I collagen of rat tibiae by transposon-mutated staphylococcus aureus

      Buxton, Thomas Brooks; Department of Immunology and Microbiolgy (1992-03)
    • Regional Variability of Dentin Permeability

      Andringa, Hans-Jan; Department of Oral Biology (1987-08)
    • Regulation and Function of the Major Stress-Induced HSP70 Molecular Chaperone in vivo: Analysis of Mice with Targeted Gene Disruption of the HSP70.1 or HSP70A1

      Huang, Lei; Georgia Cancer Center (6/3/2002)
      (First Paragraph) The cellular response to stress, including exposure to environmental (UV radiation, heat shock, heavy metals), pathological (infection, fever, inflammation, malignancy, ischemia) or physiological (growth factor, hormonal stimulation, tissue development) stimuli is represented at the molecular level by synthesis of groups of protein named heat shock proteins [hsp(s)] (Benjamin 1998; Feder and others 1992; Jolly and Morimoto 2000; Li and Mivechi 1986; Lindquist 1986; Smith 1998). The presence of hsp(s) protect host cells from the damage caused by thermal stress, and after induction of hsp expression, cells are protected well from higher temperatures than they can normally tolerate. This phenomenon is defined as themiotoleranee (Gemer 1975; Li and Mivechi 1986). The protective role of hsp(s) is attributed to several functional properties, including active participation in maintaining proteins in their native correctly folded states, promoting degradation and refolding of misfolded proteins, and minimizing aggregation and incorrect interactions between proteins (Agashe and Hartl 2000; Gething and Sambrook 1992). In addition, hsp(s) can function in cellular protection by modulating the engagement and progression of apoptosis induced by a variety of stress stimuli (Beere and Green 2001). Besides the recognition of the cytoprotective function of hsp(s) under stress conditions, widespread clinical interests exist in their chaperone function during a range of human pathologies, including neurodegenerative conditions, such as amyloidosis, prion disease, and Alzheimer's disease, and cardiovascular diseases, such as myocardial ischemia, cardiac hypertrophy, stroke, and blood vessel injury (Benjamin 1998; Planas and others 1997; Smith 1998).
    • The regulation of aldosterone secretion in the rat

      Lin, Cheng-Hsiung; Department of Endocrinology (1973-06)
    • Regulation of androgen receptor expression by testosterone

      Mora, Gloria R.; School of Graduate Studies (1996-03)
    • Regulation of Cytochrome Oxidase and F1Fo ATP Synthase by Protein Kinase C Isozymes: Implications for Cardiac Preconditioning and Ischemia / Reperfusion Injury

      Nguyen, Tiffany Tuyen M.; Department of Pharmacology and Toxicology (2010-03)
      Despite decades of intense research, heart disease associated with myocardial ischemia/reperfusion (IR) injury remains the most frequent cause of lethality worldwide. It has been known for over 2 decades that the mammalian heart can be protected from IR injury if exposed to a paradoxical response known as cardiac ischemic preconditioning (PC). Of interest, mitochondrial protein kinase C (PKC) isozymes have emerged as central players in both PC and IR mechanisms. Mitochondrial oxidative phosphorylation (OXPHOS) complexes are responsible for greater than 90% of myocardial ATP synthesis, and ATP levels decline substantially during myocardial IR injury. Therefore, we determined if direct protein-protein interactions occurred between individual PKC isozyme and specific subunits of each of these complexes during cardioprotective and cardiac IR responses. First, we have utilized an in situ rat coronary ligation model to establish an PKC-cytochrome oxidase subunit IV (COIV) coimmunoprecipitation (co- IP) in myocardium exposed to PC. This co-IP correlated with a 2.8-fold increase in mitochondrial PKC autophosphorylation (activation) and a 2-fold enhancement of cytochrome-c oxidase activity. In a second line of study, we demonstrated that following prolonged 4- phorbol 12-myristate-13-acetate (PMA) and hypoxia (Hx), PKC interacts with the “d” subunit of F1Fo ATP synthase (dF1Fo) to inhibit F1Fo activity in neonatal cardiac myocytes (NCMs). We next developed cell-permeable, mitochondrial-targeted peptide modulators (derived from the amino acid sequence of dF1Fo) based on the PKCdF1Fo interaction. In vitro binding assays and co-IP experiments using NCMs revealed a facilitator [NH2-YGRKKRRQRRMLATRALSLIGKRAISTSVCRVREYEKQLEKIKNMIDYKDDDK- COOH] and an inhibitor peptide [NH2-YGRKKRRQRRMLATRALSLIGKRAISTSVCAGRKLALKTIDWVSFDYKDDDDK- COOH] of the PKC-dF1Fo interaction. The inhibitor peptide reduced PMA/Hx-induced inhibition of F1Fo activity or PMA-Hx-induced PKC-dF1Fo co-IP in NCMs while the facilitator peptide has opposite effects. Administration of the inhibitor peptide to isolated rat hearts immediately after a 20 min global ischemia exposure, and just prior to a 90 min reperfusion, decreased infarct size and released of cardiac troponin I compared to rat hearts receiving a scrambled-sequence (inactive) peptide prior to IR exposures alone. Collectively our studies have revealed two key mitochondrial OXPHOS regulatory events involving PKC-enhancement and protection of cytochrome oxidase by ischemic PC and PKC suppression of F1Fo ATP synthase during IR injury. Further, our work suggests that the PKC-dF1Fo inhibitor peptide may have potential as a therapeutic compound targeting myocardial ischemia in humans.