• Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)

      Ding, Lingling; Kuhne, Wendy W.; Hinton, David E.; Song, Jian; Dynan, William S.; Institute of Molecular Medicine and Genetics (2010-10-11)
      Background: Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research.
    • Questionnaire Design and Responsiveness in a Data Capture Tool for Student Sharing of Experiences of Statewide Clerkship Sites

      Zheng, Stephanie; Behrman, David; Agrawal, Parth; Basco, Brian; Ball, Charlotte; Rose, Jennifer; Miller, Samel; Wood, Elena (2017-03)
      Positive clerkship experiences and student performance in the clinical years has been correlated to perceived quality of education and specialty choice amongst medical students [1-3]. The Medical College of Georgia uses a distributed campus model with more than 250 clerkship rotation sites across the state and beyond, making student clerkship choices imperative to their development as physicians. We developed a survey to collect both quantitative and qualitative data from students during their clerkship years and a system to distribute that information to students. The data allowed us to evaluate the effectiveness of various question formats through responsiveness, the length of responses, and time spent on the survey. In addition to this, we looked at the number of responses per clerkship in order to see whether or not our survey was getting information about all of the 3rd year rotations. We aspire to take these findings and utilize them to expand t he program and improve the questionnaire in order to yield more responsiveness from students.
    • Rab11 in dysplasia of Barrett's epithelia.

      Goldenring, J R; Ray, G S; Lee, J R; Institute of Molecular Medicine and Genetics (2000-05-16)
      Barrett's esophagus predisposes affected patients to the development of esophageal adenocarcinoma. The development of adenocarcinoma proceeds along a progression through low- and high-grade dysplasia. Surveillance of Barrett's patients requires serial endoscopic investigations and grading mucosal biopsies. Unfortunately, grading of biopsies by conventional hematoxylin and eosin staining is fraught with significant interobserver variations. We have found in both biopsy and resection specimens that immunostaining for the small GTP binding protein Rab11 is increased in low-grade dysplastic cells. This staining is lost in high-grade dysplastic cells. These results suggest that low-grade dysplastic cells undergo an apical trafficking blockade, which is released as cells progress to the less differentiated phenotype of high-grade dysplasia and adenocarcinoma. Examination of the SKGT-4 esophageal adenocarcinoma cell line demonstrated prominent mRNA and protein expression for Rab11. Rab11 immunostaining was present in SKGT-4 cells as a perinuclear nidus of punctate staining along with a more diffuse punctate pattern. Thus, Rab11 expression was present in a esophageal adenocarcinoma cells in culture. Markers of vesicle trafficking may be critical factors for grading of mucosal dysplastic transitions leading to adenocarcinoma.
    • Race/ethnicity differences in access to opioid agonist treatment (OAT)

      Covington, Katherine; Chung, Yunmi; Johnson, J. Aaron; Krawczyk, Noa; Augusta University; Johns Hopkins University (2018)
    • RCAD is a Key Post-Translational Modification for the Proper Sorting of Digestive Enzymes and the Secretory Function of the Exocrine Pancreas

      Miller, Camille; College of Science and Mathematics; Sabbatini, Maria (2015-09-25)
      Introduction: Chronic alcohol consumption is one of the main cause of acute pancreatitis. An excess of alcohol causes an increase in free radicals formation and endoplasmic reticulum (ER) stress in pancreatic acinar cells. There are a number of ER proteins that participate in the correct folding/sorting of proteins. One of these proteins is the Ufm1 (Ubiquitin-fold modifier 1) conjugation system, which is a novel ubiquitin-like modification system and part of the unfolded protein response. Regulator of C53 and DDRGK1 (RCAD) has recently been identified as an important regulator of several signaling pathways, including the Ufm1 conjugation system. Endogenous RCAD forms a complex with two proteins, C53 and DDRGK1, and promotes Ufmylation of DDRGK1. Aim: To identify the role of RCAD for the proper sorting of pancreatic enzymes and the normal exocrine function of the pancreas. Methods: The relative expression of RCAD and DDRGK1 in alcoholic-treated rats compared with non-treated rats was evaluated by qPCR analysis. Adult male SD rats were fed the Lieber-DeCarli liquid diet containing ethanol (36 % of total calories) or an isocaloric substitution with maltose-dextrin ad lib for 8 weeks. To determine the functional relevance of RCAD in the exocrine pancreas, isolated pancreatic acini from WT and RCAD inducible conditional KO (CKO) mice were prepared. CCK-induced amylase secretion was measured. Results: Both RCAD and DDRGK1 transcript levels were up-regulated in alcoholic-treated rats. To generate RCAD CKO mice, we crossed RCADTrap-F/+mice with FLPo deleter mice B6(C3)-Tg(Pgk1-FLPo)10Sykr/J to remove the gene trap cassette. The floxed RCAD mice were crossed with ROSA26-CreERT2 mice (B6.129-Gt(ROSA)26Sorotm1(cre/ERT2) Tyj4/J in which CreERT2 was inserted into ROSA26 locus. The constitutive and CCK-inducible amylase secretion was much higher by isolated pancreatic acini prepared from RCAD CKO mice. Conclusion: RCAD is likely to be involved in a post-translational modification system for the proper sorting of amylase and normal pancreatic secretion. The significance of RCAD will provide an important insight into the pathophysiology of acute pancreatitis. Start Time: 34:06 End Time: 46:37
    • Reasons for Campus Preference amoung Medical Student Matriculants: A Qualitative Study at the Georgia Health Sciences University (GHSU) Medical College of Georgia

      Palladino, Christie; Villarosa, M; Elam, Rachel; Wildermuth, K; Richardson, D; Stepleman, Lara M.; Young, G; Fincher, Ruth-Marie; Education Discovery Institute; Medical College of Georiga; et al. (Georgia Health Sciences University, 2011)
      To describe and understand medical student applicants’ reasons for campus preference in our two-campus system, as provided during the application process.
    • Reduced Serum Vitamin Dâ Binding Protein Levels Are Associated With Type 1 Diabetes

      Blanton, Dustin; Han, Zhao; Bierschenk, Lindsey; Linga-Reddy, M.V. Prasad; Wang, Hongjie; Clare-Salzler, Michael; Haller, Michael; Schatz, Desmond; Myhr, Courtney; She, Jin-Xiong; et al. (2011-10-16)
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    • 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).
    • Regulation of cell death in mitotic neural progenitor cells by asymmetric distribution of prostate apoptosis response 4 (PAR-4) and simultaneous elevation of endogenous ceramide

      Bieberich, Erhard; MacKinnon, Sarah; Silva, Jeane; Noggle, Scott A; Condie, Brian G.; Institute of Molecular Medicine and Genetics; Department of Medicine (2003-08-4)
      Cell death and survival of neural progenitor (NP) cells are determined by signals that are largely unknown. We have analyzed pro-apoptotic signaling in individual NP cells that have been derived from mouse embryonic stem cells. NP formation was concomitant with elevated apoptosis and increased expression of ceramide and prostate apoptosis response 4 (PAR-4). Morpholino oligonucleotide-mediated antisense knockdown of PAR-4 or inhibition of ceramide biosynthesis reduced stem cell apoptosis, whereas PAR-4 overexpression and treatment with ceramide analogs elevated apoptosis. Apoptotic cells also stained for proliferating cell nuclear antigen (a nuclear mitosis marker protein), but not for nestin (a marker for NP cells). In mitotic cells, asymmetric distribution of PAR-4 and nestin resulted in one nestin(â )/PAR-4(+) daughter cell, in which ceramide elevation induced apoptosis. The other cell was nestin(+), but PAR-4(â ), and was not apoptotic. Asymmetric distribution of PAR-4 and simultaneous elevation of endogenous ceramide provides a possible mechanism underlying asymmetric differentiation and apoptosis of neuronal stem cells in the developing brain.
    • Regulation of Embryonic Stem Cell Pluripotency and Differentiation by Notch Signaling

      Noggle, Scott A; Institute of Molecular Medicine and Genetics (2004-05)
      (First Paragraph) Mammalian development prior to implantation is primarily involved with establishing the support tissues needed for interaction with the mother’s uterine tissue and blood stream as the uterine tissue prepares to receive the embryo. Development of the embryo proceeds slowly while initiating differentiation of the first cell lineages, trophectoderm and the primitive endoderm, that are necessary for interactions with the mother’s uterine tissue. In mice, development from fertilization to the initiation of implantation of the blastocyst into the uterine wall takes about four and a half days (Fig. 1) whereas this period in human development requires about 7 days. This is in contrast to the much-accelerated development, for example, of amphibian species that produce embryos that develop in isolation of maternal support after fertilization.
    • Regulation of osteoclast function and bone mass by RAGE

      Zhou, Zheng; Immel, David; Xi, Cai-Xia; Bierhaus, Angelika; Feng, Xu; Mei, Lin; Nawroth, Peter; Stern, David M.; Xiong, Wen-Cheng; Institute of Molecular Medicine and Genetics; et al. (2006-04-17)
      The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily that has multiple ligands and is implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative disorders, and inflammatory responses. However, the role of RAGE in normal physiology is largely undefined. Here, we present evidence for a role of RAGE in osteoclast maturation and function, which has consequences for bone remodeling. Mice lacking RAGE had increased bone mass and bone mineral density and decreased bone resorptive activity in vivo. In vitroâ differentiated RAGE-deficient osteoclasts exhibited disrupted actin ring and sealing zone structures, impaired maturation, and reduced bone resorptive activity. Impaired signaling downstream of αvβ3 integrin was observed in RAGEâ /â bone marrow macrophages and precursors of OCs. These results demonstrate a role for RAGE in osteoclast actin cytoskeletal reorganization, adhesion, and function, and suggest that the osteosclerotic-like phenotype observed in RAGE knockout mice is due to a defect in osteoclast function.
    • Regulation of prostaglandin synthesis and cell adhesion by a tryptophan catabolizing enzyme.

      Marshall, Brendan; Keskin, Derin B.; Mellor, Andrew L.; Institute of Molecular Medicine and Genetics (2002-11-19)
      BACKGROUND: The tryptophan catabolizing enzyme, indoleamine 2,3, dioxygenase (IDO) is one of two mammalian enzymes, which can catabolize the rarest essential amino acid, tryptophan. IDO is inducible by cytokines such as interferon-gamma and plays a role in inflammation and maternal tolerance of fetal allografts, although its exact mode of action is unclear. Therefore, we investigated the circumstances under which IDO is expressed in vitro together with the effects of overexpression of IDO on the growth and morphology of cells. RESULTS: Overexpression of IDO in the murine macrophage cell line RAW 264.7 and the murine fibrosarcoma cell line MC57, resulted in the growth of macroscopic cell foci, with altered cell adhesion properties. The expression of IDO was also detected during adhesion of wild type, nontransfected cells in tissue culture to standard cell growth substrates. Inhibition of this expression, likewise resulted in alterations in cell adhesion. Overexpression of IDO or inhibition of endogenous IDO expression was accompanied by changes in metalloproteinase expression and also in the expression and activity of the cyclooxygenase enzymes. In the case of RAW cells, IDO effects on cell growth could be reversed by adding back prostaglandins. CONCLUSIONS: These results suggest that catabolism of the rarest essential amino acid may regulate processes such as cell adhesion and prostaglandin synthesis.
    • Regulation of soluble guanylyl cyclase by phosphorylation

      Zhou, Zongmin; Sayed, Nazish; Pyriochou, Anastasia; Fulton, David; Beuve, Annie; Papapetropoulos, Andreas; Vascular Biology Center (2009-08-11)
    • Regulation of soluble guanylyl cyclase by phosphorylation

      Zhou, Zongmin; Sayed, Nazish; Pyriochou, Anastasia; Fulton, David; Beuve, Annie; Papapetropoulos, Andreas; Vascular Biology Center (2009-08-11)
    • Regulation of T Cell Immunity by Cells Expressing Indoleamine 2,3-Dioxygenase

      Keskin, Derin B.; Georgia Cancer Center (2002-07)
      Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme, that degrades the essential amino acid tryptophan along the kynurenine pathway. Historically, IDO enzyme function was implicated in antibacterial and antiviral innate immunity, inflammation and antioxidative functions. Recently our lab associated IDO enzyme function with regulation of T cell responses and maintenance of maternal immune tolerance during pregnancy. We hypothesize that cells expressing IDO inhibit T cell responses. We will generate IDO expressing cell lines and IDO transgenic mice to investigate regulation of T cell immune responses by IDO enzyme in this thesis project.
    • Regulation of T cell Immunity by Dendritic Cells Expressing Indoleamine 2,3- Dioxygenase (IDO)

      Manlapat, Anna K; Georgia Cancer Center (2006-04)
      IDO-mediated tryptophan depletion inhibits T cell responses in vitro and in vivo. This work investigates the role of IDO-expressing dendritic cells (DCs) in regulating T cell responses. To determine the role of IDO-expressing DCs in the regulation o f T cell immunity, IDO-transfected DCs and IDO transgenic mice over-expressing IDO specifically in DCs were generated, and effects of IDO over-expression on T cell stimulatory functions of DCs were assessed. Results show that inhibition o f T cell proliferation in vivo requires induction of IDO expression in DCs by CTLA4-Ig rather than constitutive over-expression of IDO. In addition, we have recently shown that IDO induction leading to T cell suppression is mediated by CTLA4-Ig ligation of B7 molecules on a minor subset of DCs that express the surface marker CD 19. Interferon-a (IFNa) was rapidly produced by CD 19+ DCs after CTLA4-Ig treatment in vitro, and signaling via IFN a receptors (IFNAR) was essential for activation of the transcription factor STAT1, while IFNy signaling was not. To further understand the role of IDO expressing DCs, DCs from IDO-deficient mice were treated in vitro and in vivo with CTLA4-Ig. In addition, IDO wildtype mice were also treated in vitro with CTLA4-Ig in the presence of the pharmacological IDO inhibitor 1-methyl-tryptophan (1-MT). IFNa production in response to CTLA4-Ig was detected in IDO-WT but not in IDO-KO DCs or IDO-WT treated with 1-MT. These results show that IDO is both upstream and downstream of IFN a production following B7 ligation. This study provides a better understanding of the role of IDO in antigen-presenting cells and evaluates the tolerogenic activity of APCs.
    • Relations of diet and physical activity to bone mass and height in black and white adolescents

      Gutin, Bernard; Stallmann-Jorgensen, Inger S.; Le, Anh H.; Johnson, Maribeth H.; Dong, Yanbin; Georgia Institute for Prevention of Human Diseases and Accidents (2011-06-16)
      Because the development of healthy bodies during the years of growth has life-long health consequences, it is important to understand the early influences of diet and physical activity (PA). One way to generate hypotheses concerning such influences is to conduct cross-sectional studies of how diet and PA are related to different components of body composition. The subjects were 660 black and white adolescents. Total body bone mineral content (BMC) was measured with dual-energy X-ray absorptiometry; free-living diet and PA were assessed with 4â 7 separate 24-h recalls. The main dietary variables investigated were: total energy intake, macronutrient distribution (%), dairy servings, vitamin D, and calcium. The main PA variables were hours of moderate PA (3â 6 METs) and vigorous PA (>6 METs). BMC was higher in blacks than in whites (P<0.01) and it increased more in boys than in girls (age by sex interaction) as age increased (P<0.01). After adjustment for age, race and sex, higher levels of BMC were associated with higher levels of energy intake, dairy servings, calcium, vitamin D, and vigorous PA (all P 's<0.05). In the multivariable model, significant and independent proportions of the variance in BMC were explained by race, the age by sex interaction, calcium, and vigorous PA (all P 's<0.01). When height was used as the outcome variable, similar diet results were obtained; however, there was a sex by vigorous PA interaction, such that vigorous PA was associated with height only in the girls. These data are consistent with the hypothesis that the bone mass and height of growing youths are positively influenced by higher dietary intake of energy and dairy foods, along with sufficient amounts of vigorous PA. This hypothesis needs to be tested in randomized controlled trials.
    • The Relationship Among Predisposing and Enabling Factors or Barriers in Nurses Provision of Tobacco Control Interventions

      Daniel, Sandra D.; Georgia Prevention Institute (2003-05)
      The control o f tobacco use. the single most preventable cause o f disease in the U.S., is a national health priority. An estimated 70% o f smokers desire to quit; however, only 7% who quit remain abstinent one year later. It is recommended that all clinicians assess and document smoking status as the fifth vital sign. There is a demand for nurses, comprising the largest discipline of health care providers, to systematically incorporate tobacco control clinical practice guidelines in their practice as a means to lower tobacco related disease morbidity and mortality. There is a paucity o f knowledge on (a) the extent to which RNs deliver tobacco control interventions, (b) their educational preparation in tobacco control, and (3) factors that are associated with nurses tobacco control interventions. The purpose o f this study was to determine the relationship among predisposing factors and enabling factors or barriers in recently licensed registered nurses’ delivery of tobacco control interventions. The Educational and Ecological Assessment phase o f Green and Kreuter's PRECEDE-PROCEED Model served as the theoretical framework underpinning this study. A descriptive correlational cross-sectional design was utilized. RNs who received initial licensure in Georgia during 1999.2000. and 2001 were sampled utilizing a probability sampling method, stratified random sampling, to obtain a sample size o f approximately 10% o f the population within each year of licensure. The final sample consisted o f 468 participants. Findings indicated nurses’ performance in tobacco control interventions (ask. advise, assess, assist, arrange) was low, with the average score being only 37%. Thirty-percent o f RNs provided no tobacco control interventions. The majority had received no clinical experiences in smoking cessation techniques (78%) or tobacco prevention (70%). Univariable analyses found attitudes, beliefs in the importance o f tobacco control, tobacco education, extent o f education in tobacco cessation techniques, use o f clinical practice guideline, perceived importance of tobacco policy, prevention interventions, and peer barriers were significantly associated (p<.05) with nurses delivery o f tobacco control interventions. Multiple regression analyses utilizing a general linear model found attitudes, belief in importance o f tobacco control, tobacco education, prevention interventions, peer barriers, and institution barriers (negative correlation) accounted for significant variances (p<.05) in the tobacco control intervention scores.
    • Relationship Between Student Resource Utilization in Patient Care and Faculty Ratings and Performance on Exams

      Thomas, Andria M.; Elam, Rachel; London, J; Education Discovery Institute; Medical College of Georiga; Georgia Health Sciences University (Georgia Health Sciences University, 2011)
      The aim of this project was to examine trends in resource utilization by third-year medical students in patient care and to evaluate the relationship between this and 1) faculty ratings of students’ use of literature and 2) student performance on exams.
    • Robust Action Recognition Using Multi-Scale Spatial-Temporal Concatenations of Local Features as Natural Action Structures

      Zhu, Xiaoyuan; Li, Meng; Li, Xiaojian; Yang, Zhiyong; Tsien, Joe Z.; Brain & Behavior Discovery Institute; Department of Neurology; Department of Ophthalmology (2012-10-4)
      Human and many other animals can detect, recognize, and classify natural actions in a very short time. How this is achieved by the visual system and how to make machines understand natural actions have been the focus of neurobiological studies and computational modeling in the last several decades. A key issue is what spatial-temporal features should be encoded and what the characteristics of their occurrences are in natural actions. Current global encoding schemes depend heavily on segmenting while local encoding schemes lack descriptive power. Here, we propose natural action structures, i.e., multi-size, multi-scale, spatial-temporal concatenations of local features, as the basic features for representing natural actions. In this concept, any action is a spatial-temporal concatenation of a set of natural action structures, which convey a full range of information about natural actions. We took several steps to extract these structures. First, we sampled a large number of sequences of patches at multiple spatial-temporal scales. Second, we performed independent component analysis on the patch sequences and classified the independent components into clusters. Finally, we compiled a large set of natural action structures, with each corresponding to a unique combination of the clusters at the selected spatial-temporal scales. To classify human actions, we used a set of informative natural action structures as inputs to two widely used models. We found that the natural action structures obtained here achieved a significantly better recognition performance than low-level features and that the performance was better than or comparable to the best current models. We also found that the classification performance with natural action structures as features was slightly affected by changes of scale and artificially added noise. We concluded that the natural action structures proposed here can be used as the basic encoding units of actions and may hold the key to natural action understanding.