• IGF-1 Induction by Acylated Steryl β-Glucosides Found in a Pre-Germinated Brown Rice Diet Reduces Oxidative Stress in Streptozotocin-Induced Diabetes

      Usuki, Seigo; Tsai, Ying-Ying; Morikawa, Keiko; Nonaka, Shota; Okuhara, Yasuhide; Kise, Mitsuo; Yu, Robert K.; Institute of Molecular Medicine and Genetics (2011-12-14)
      Background: The pathology of diabetic neuropathy involves oxidative stress on pancreatic b-cells, and is related to decreased levels of Insulin-like growth factor 1 (IGF-1). Acylated steryl b-glucoside (PR-ASG) found in pre-germiated brown rice is a bioactive substance exhibiting properties that enhance activity of homocysteine-thiolactonase (HTase), reducing oxidative stress in diabetic neuropathy. The biological importance of PR-ASG in pancreatic b-cells remains unknown.
    • The IL-10 and IFN-gamma pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells.

      Zhou, Li; Wang, Hongjie; Zhong, Xing; Jin, Yulan; Mi, Qing-Sheng; Sharma, Ashok; McIndoe, Richard A; Garge, Nikhil; Podolsky, Robert H.; She, Jin-Xiong; et al. (2008-09-05)
      BACKGROUND: CD8+ NKT-like cells are naturally occurring but rare T cells that express both T cell and natural killer cell markers. These cells may play key roles in establishing tolerance to self-antigens; however, their mechanism of action and molecular profiles are poorly characterized due to their low frequencies. We developed an efficient in vitro protocol to produce CD8+ T cells that express natural killer cell markers (CD8+ NKT-like cells) and extensively characterized their functional and molecular phenotypes using a variety of techniques. RESULTS: Large numbers of CD8+ NKT-like cells were obtained through culture of na??ve CD8+ T cells using anti-CD3/anti-CD28-coated beads and high dose IL-2. These cells possess potent activity in suppressing the proliferation of na??ve responder T cells. Gene expression profiling suggests that the cultured CD8+ NKT-like cells and the na??ve CD8+ T cells differ by more than 2-fold for about 3,000 genes, among which 314 are upregulated by more than 5-fold and 113 are upregulated by more than 10-fold in the CD8+ NKT-like cells. A large proportion of the highly upregulated genes are soluble factors or surface markers that have previously been implicated in immune suppression or are likely to possess immunosuppressive properties. Many of these genes are regulated by two key cytokines, IL-10 and IFN-gamma. The immunosuppressive activities of cells cultured from IL-10-/- and IFN-gamma-/- mice are reduced by about 70% and about 50%, respectively, compared to wild-type mice. CONCLUSION: Immunosuppressive CD8+ NKT-like cells can be efficiently produced and their immunosuppressive activity is related to many surface and soluble molecules regulated by IL-10 and IFN-gamma.
    • The impact of general experience with patients on baseline measures of confidence in an SBIRT training program

      Johnson, J. Aaron; Chung, Yunmi; Brown, Shilpa P.; Augusta University (2016-10)
    • Impact of stress reduction on negative school behavior in adolescents.

      Barnes, Vernon A.; Bauza, Lynnette B; Treiber, Frank A.; Georgia Institute for Prevention of Human Diseases and Accidents; Department of Pediatrics; Department of Psychiatry and Health Behavior (2008-01-16)
      BACKGROUND: The purpose of this study was to determine the effect of stress reduction via the Transcendental Meditation program on school rule infractions in adolescents. METHODS: Forty-five African American adolescents (ages 15-18 years) with high normal systolic blood pressure were randomly assigned to either Transcendental Meditation (n = 25) or health education control (n = 20) groups. The meditation group engaged in 15-min sessions at home and at school each day for 4 months. The control group was presented 15-min sessions of health education at school each day for 4 months. Primary outcome measures were changes in absenteeism, school rule infractions and suspension days during the four-month pretest period prior to randomization compared with the four-month intervention period. RESULTS: Comparing the pretest and intervention periods, the meditation group exhibited a mean decrease of 6.4 absentee periods compared to an increase of 4.8 in the control group (p <.05). The meditation group exhibited a mean decrease of 0.1 infractions over the four months compared to an increase of 0.3 in the control group (p <.03). There was a mean reduction of 0.3 suspension days due to behavior-related problems in the meditation group compared to an increase of 1.2 in the control group (p <.04). CONCLUSION: These findings demonstrate that the Transcendental Meditation program conducted in the school setting has a beneficial impact upon absenteeism, rule infractions, and suspension rates in African American adolescents.
    • Impact of Transcendental Meditation on Left Ventricular Mass in African American Adolescents

      Barnes, Vernon A.; Kapuku, Gaston K.; Treiber, Frank A.; Georgia Institute for Prevention of Human Diseases and Accidents; Department of Pediatrics (2012-05-22)
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    • Impaired membrane resealing and autoimmune myositis in synaptotagmin VIIâ deficient mice

      Chakrabarti, Sabyasachi; Kobayashi, Koichi S.; Flavell, Richard A.; Marks, Carolyn B.; Miyake, Katsuya; Liston, David R.; Fowler, Kimberly T.; Gorelick, Fred S.; Andrews, Norma W.; Institute of Molecular Medicine and Genetics (2003-08-18)
      Members of the synaptotagmin family have been proposed to function as Ca2+ sensors in membrane fusion. Syt VII is a ubiquitously expressed synaptotagmin previously implicated in plasma membrane repair and Trypanosoma cruzi invasion, events which are mediated by the Ca2+-regulated exocytosis of lysosomes. Here, we show that embryonic fibroblasts from Syt VII-deficient mice are less susceptible to trypanosome invasion, and defective in lysosomal exocytosis and resealing after wounding. Examination of mutant mouse tissues revealed extensive fibrosis in the skin and skeletal muscle. Inflammatory myopathy, with muscle fiber invasion by leukocytes and endomysial collagen deposition, was associated with elevated creatine kinase release and progressive muscle weakness. Interestingly, similar to what is observed in human polymyositis/dermatomyositis, the mice developed a strong antinuclear antibody response, characteristic of autoimmune disorders. Thus, defective plasma membrane repair in tissues under mechanical stress may favor the development of inflammatory autoimmune disease.
    • Implementing alcohol screening and brief intervention in primary healthcare: identifying barriers, proposing solutions

      Johnson, J. Aaron; Seale, J. Paul; Georgia Regents University; Mercer University School of Medicine (2014-10-17)
    • Impossibly Complicated Tales of Dispossession and Betrayal: Thomas Pynchon's Vineland and the Neoliberal Shift in America

      Williams, Daniel; Hayes, Adrienne; Atkins, Hunter; Hoffman, Todd; Pamplin College of Arts, Humanities, and Social Sciences (2015-08-10)
      The 1970s were characterized by the ascendancy of a particular breed of right wing conservatism that advanced neoliberal reforms and precipitated the 1980 election of Ronald Reagan. As an economic theory, neoliberalism proposes that the government de-regulate markets and ease financial burdens on corporations thus enabling wealth to be evenly distributed across the social spectrum by natural market processes. In practice, the process of manufacturing consent for these policies mobilized religious and nationalist rhetoric, caused an abiding cultural shift, and resulted in numerous economic crises and inequitable concentrations of wealth. Our project conducts an analysis of Thomas Pynchon's novel Vineland in order to derive insights into this transformation of America. Published in 1990, the scope of Pynchon’s novel encompasses both the hippy movement that peaks in the late 60s and the rise of neoliberalism up through the middle of the Reagan administration in 1984— the year in which the novel takes place. Pynchon’s work is exemplary of what is called postmodern literature—the defining literary genre of the period which in many ways is unique precisely because of its political engagement with post-industrial capitalism—and, as such, encapsulates perhaps better than any writer the effects of neoliberalism. Our project has produced an essay (and a poster) that is comprised of three sections: An economic, cultural, and historical explanation of neoliberalism— An investigation of Pynchon’s critique of the media as it works to assimilate citizens into the cultural hegemony— And Pynchon’s critique of the ideologies and policy decisions surrounding the then contemporary environmental movement.
    • An Improved Test for Detecting Multiplicative Homeostatic Synaptic Scaling

      Kim, Jimok; Tsien, Richard W.; Alger, Bradley E.; Institute of Molecular Medicine and Genetics; Graduate Program in Neuroscience; Department of Neurology (2012-05-17)
      Homeostatic scaling of synaptic strengths is essential for maintenance of network "gain", but also poses a risk of losing the distinctions among relative synaptic weights, which are possibly cellular correlates of memory storage. Multiplicative scaling of all synapses has been proposed as a mechanism that would preserve the relative weights among them, because they would all be proportionately adjusted. It is crucial for this hypothesis that all synapses be affected identically, but whether or not this actually occurs is difficult to determine directly. Mathematical tests for multiplicative synaptic scaling are presently carried out on distributions of miniature synaptic current amplitudes, but the accuracy of the test procedure has not been fully validated. We now show that the existence of an amplitude threshold for empirical detection of miniature synaptic currents limits the use of the most common method for detecting multiplicative changes. Our new method circumvents the problem by discarding the potentially distorting subthreshold values after computational scaling. This new method should be useful in assessing the underlying neurophysiological nature of a homeostatic synaptic scaling transformation, and therefore in evaluating its functional significance.
    • Inactivation of the WASF3 gene in prostate cancer cells leads to suppression of tumorigenicity and metastases

      Teng, Yong; Ren, MingQiang; Cheney, Richard; Sharma, Shruti; Cowell, John K.; GHSU Cancer Center; Department of Pathology (2010-09-28)
      Background:: The WASF3 protein is involved in cell movement and invasion, and to investigate its role in prostate cancer progression we studied the phenotypic effects of knockdown in primary tumors and cell lines.
    • Incidence and survival trends of colorectal cancer from 2002 to 2011

      Ansa, Benjamin E.; Alema-Mensah, Ernest; Claridy, Mechelle D.; Sheats, Joyce Q.; Smith, Selina A.; School of Medicine; Georgia Regents University; Morehouse College (2015-03)
    • Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes.

      Ergul, Adviye; Elgebaly, Mostafa M; Middlemore, Mary-Louise; Li, Weiguo; Elewa, Hazem; Switzer, Jeffrey A; Hall, Christiana; Kozak, Anna; Fagan, Susan C.; Vascular Biology Center; et al. (2007-11-29)
      BACKGROUND: Interruption of flow through of cerebral blood vessels results in acute ischemic stroke. Subsequent breakdown of the blood brain barrier increases cerebral injury by the development of vasogenic edema and secondary hemorrhage known as hemorrhagic transformation (HT). Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury. METHODS: Diabetic Goto-Kakizaki (GK) or control rats underwent 3 hours of middle cerebral artery occlusion and 21 h reperfusion followed by evaluation of infarct size, hemorrhage and neurological outcome. RESULTS: Infarct size was significantly smaller in GK rats (10 +/- 2 vs 30 +/- 4%, p < 0.001). There was significantly more frequent hematoma formation in the ischemic hemisphere in GK rats as opposed to controls. Cerebrovascular tortuosity index was increased in the GK model (1.13 +/- 0.01 vs 1.34 +/- 0.06, P < 0.001) indicative of changes in vessel architecture. CONCLUSION: These findings provide evidence that there is cerebrovascular remodeling in diabetes. While diabetes-induced remodeling appears to prevent infarct expansion, these changes in blood vessels increase the risk for HT possibly exacerbating neurovascular damage due to cerebral ischemia/reperfusion in diabetes.
    • Inflammation and diabetic retinal microvascular complications

      Zhang, Wenbo; Liu, Hua; Al-Shabrawey, Mohamed; Caldwell, Robert William; Caldwell, Ruth B.; Vascular Biology Center; Vision Discovery Institute; Department of Pharmacology and Toxicology; Department of Oral Biology; Department of Cellular Biology and Anatomy; et al. (2011-04)
      Diabetic retinopathy (DR) is one of the most common complications of diabetes and is a leading cause of blindness in people of the working age in Western countries. A major pathology of DR is microvascular complications such as non-perfused vessels, microaneurysms, dot/blot hemorrhages, cotton-wool spots, venous beading, vascular loops, vascular leakage and neovascularization. Multiple mechanisms are involved in these alternations. This review will focus on the role of inflammation in diabetic retinal microvascular complications and discuss the potential therapies by targeting inflammation.
    • Influence of common variants in FTO and near INSIG2 and MC4R on growth curves for adiposity in Africanâ and Europeanâ American youth

      Liu, Gaifen; Zhu, Haidong; Dong, Yanbin; Podolsky, Robert H.; Treiber, Frank A.; Snieder, Harold; Center for Biotechnology and Genomic Medicine (2011-06-5)
      Electronic supplementary material: The online version of this article (doi:10.1007/s10654-011-9583-4) contains supplementary material, which is available to authorized users.
    • Influence of DNA Ends on Structure and Function of the DNA-dependent Protein Kinase

      Jovanovic, Marko; Institute of Molecular Medicine and Genetics (2006-12)
      Non-homologous end joining is a major DNA double-strand break repair pathway in mammalian cells. The DNA-dependent protein kinase (DNA-PK), consisting of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ku heterodimer, is hypothesized to be a key regulator of the pathway. Available data suggest DNA-PKcs may exert this regulatory function by controlling access to the DNA termini and by phosphorylation of itself and other proteins. I further characterized DNA-PK-DNA interaction by studying binding of DNA-PKcs and Ku to oligonucleotides with chemically defined end structures under conditions that preclude synapsis between opposing DNA ends. Binding of DNA-PKcs to DNA varied with the end structure in a manner that suggests that partial melting of DNA ends is necessary for the formation of a stable, enzymatically active complex. Unexpectedly, these studies also revealed that ATP, as well as its nonhydrolyzable analog AMP-PNP, have an allosteric effect on the interaction of DNA-PKcs with DNA.
    • The Influence of Georgia’s Quality Rated System on School Readiness in Preschool Children

      Phillips, Dena; Webb, Nancy C.; Georgia Regents University (2015-07)
    • The Influence of Spatial Ability on Anatomy Examination Questions in an Integrated Medical Curriculum

      Xiong, Jennifer; Department of Cellular Biology and Anatomy (2016-03)
      Background: Students with high spatial visualization ability (Vz) have been found to outperform students with low Vz in anatomy. However, how Vz influences anatomy performance has not been established. Thus, this study aimed to assess the influence of Vz on medical student performance on different levels of anatomy questions categorized by Bloom’s taxonomy levels and discrimination index (DI) and to observe the relationship between Vz and anatomy performance. We hypothesized that there would be a positive correlation between Vz and performance on more difficult exam questions categorized by DI and Bloom’s taxonomy. We also hypothesized that there would be a positive correlation between Vz and anatomy written exam, anatomy lab exam, and overall anatomy performance. Methods: First year medical students in a systems-based integrated medical curriculum (n=61), completed the Mental Rotations Test (MRT) prior to the start of anatomy to e stablish Vz. All anatomy exam questions were categorized into four Bloom’s taxonomy domains of increasing difficulty level (identification, comprehension, application, and analysis). These questions were also categorized into three tiers via DI. Results: No significant relationship (p>0.05) was found between Vz and questions categorized by DI or Bloom’s taxonomy. Data also indicated that although entrance Vz plays an insignificant role in medical student anatomy lab exam, anatomy written exam, and overall performance in the anatomy course, there is a correlation between entrance Vz and anatomy performance in the very first systems-based module (r2=0.017, p≤0.05). Discussion: These findings suggest that entrance Vz may influence anatomy performance at the beginning of the curriculum; however, students with lower Vz find ways to cope and increase anatomy performance throughout the curriculum. Due to the significant relationship between Vz and the first system s-based module, further analysis was completed to assess the relationship between Vz and anatomy question difficulty. This analysis indicated that there was no significant interaction between Vz and questions categorized by DI or Bloom’s taxonomy within that first systems-based module (p>0.05), suggesting that Vz’s effect on performance in anatomy may not have a relationship with question difficulty categorized by Bloom’s taxonomy or DI. Further research is necessary to explore how Vz influences anatomy performance and how students’ ability to train Vz and change study strategies influences the effect of Vz on anatomy performance throughout the medical curriculum.
    • Inhibition ofâ T Cell Proliferation by Macrophage Tryptophan Catabolism

      Munn, David H.; Shafizadeh, Ebrahim; Attwood, John T.; Bondarev, Igor; Pashine, Achal; Mellor, Andrew L.; Institute of Molecular Medicine and Genetics; Department of Pediatrics (1999-05-3)
      We have recently shown that expression of the enzyme indoleamine 2,3-dioxygenase (IDO) during murine pregnancy is required to prevent rejection of the allogeneic fetus by maternal T cells. In addition to their role in pregnancy, IDO-expressing cells are widely distributed in primary and secondary lymphoid organs. Here we show that monocytes that have differentiated under the influence of macrophage colony-stimulating factor acquire the ability to suppress T cell proliferation in vitro via rapid and selective degradation of tryptophan by IDO. IDO was induced in macrophages by a synergistic combination of the T cellâ derived signals IFN-g and CD40-ligand. Inhibition of IDO with the 1-methyl analogue of tryptophan prevented macrophage-mediated suppression. Purified T cells activated under tryptophan-deficient conditions were able to synthesize protein, enter the cell cycle, and progress normally through the initial stages of G1, including upregulation of IL-2 receptor and synthesis of IL-2. However, in the absence of tryptophan, cell cycle progression halted at a mid-G1 arrest point. Restoration of tryptophan to arrested cells was not sufficient to allow further cell cycle progression nor was costimulation via CD28. T cells could exit the arrested state only if a second round of T cell receptor signaling was provided in the presence of tryptophan. These data reveal a novel mechanism by which antigen-presenting cells can regulate T cell activation via tryptophan catabolism. We speculate that expression of IDO by certain antigen presenting cells in vivo allows them to suppress unwanted T cell responses.