• Hb J- Meerut [alpha 120 (H3) Ala ->Glu (alpha1)] in a Turkish male.

      Elam, Dedrey; Kutlar, Abdullah; Kutlar, Ferdane; Dinçol, Gunçag; Güvenç, Serkan; Titus H.J. Huisman Hemoglobinopathy Laboratory, Comprehensive Sickle Cell Center, Medical College of Georgia (2006-03-31)
      Hb J Meerut is an infrequently found alpha-globin variant. It has previously been reported in various populations around the world. One particular case reported in 1994 included a Turkish family. In this report, details of a second case of Hb J Meerut in a Turkish male who is unrelated to the first family are described. In the present case a slight increase in the oxygen affinity of Hb J Meerut, relative to that of the normal control, has been observed as detected by low p50 values in arterial whole blood. Additionally, a slight increase in red blood cell count, as compared against a normal individual, was observed.
    • Health related quality of life among African American female breast cancer survivors and survivors of other cancers

      Smith, Selina A.; Ansa, Benjamin E.; Claridy, Mechelle D.; Damus, Francesca; Alema-Mensah, Ernest; School of Medicine; Georgia Regents University; Morehouse College (2014-10-17)
    • Hepatic gene expression profiling reveals key pathways involved in leptin-mediated weight loss in ob/ob mice.

      Sharma, Ashok; Bartell, Shoshana M; Baile, Clifton A; Chen, Bo; Podolsky, Robert H.; McIndoe, Richard A; She, Jin-Xiong; Center for Biotechnology and Genomic Medicine; Department of Medicine; Department of Pathology (2010-09-02)
      BACKGROUND: Leptin, a cytokine-like protein, plays an important role in the regulation of body weight through inhibition of food intake and stimulation of energy expenditure. Leptin circulates in blood and acts on the brain, which sends downstream signals to regulate body weight. Leptin therapy has been successful in treating leptin deficient obese patients. However, high levels of leptin have been observed in more common forms of obesity indicating a state of leptin resistance which limits the application of leptin in the treatment of obesity. If the central effect of leptin could be by-passed and genes which respond to leptin treatment could be regulated directly, new therapeutic targets for the treatment of obesity may be possible. The purpose of this study was to identify genes and subsequent pathways correlated with leptin-mediated weight loss. METHODOLOGY/PRINCIPAL FINDINGS: WE UTILIZED MICROARRAY TECHNOLOGY TO COMPARE HEPATIC GENE EXPRESSION CHANGES AFTER TWO TYPES OF LEPTIN ADMINISTRATION: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We identified 214 genes that correlate with leptin mediated weight loss. Several biological processes such as mitochondrial metabolic pathways, lipid metabolic and catabolic processes, lipid biosynthetic processes, carboxylic acid metabolic processes, iron ion binding and glutathione S-transferases were downregulated after leptin administration. In contrast, genes involved in the immune system inflammatory response and lysosomal activity were found to be upregulated. Among the cellular compartments mitochondrion (32 genes), endoplasmic reticulum (22 genes) and vacuole (8 genes) were significantly over represented. CONCLUSIONS/SIGNIFICANCE: In this study we have identified key molecular pathways and downstream genes which respond to leptin treatment and are involved in leptin-mediated weight loss. Many of these genes have previously been shown to be associated with obesity; however, we have also identified a number of other novel target genes. Further investigation will be required to assess the possible use of these genes and their associated protein products as therapeutic targets for the treatment of obesity.
    • Heritability of insulin sensitivity and lipid profile depend on BMI: evidence for gene-obesity interaction.

      Wang, X; Ding, Xiuhua; Su, S; Spector, T D; Mangino, M; Iliadou, Anastasia; Snieder, H; Georgia Institute for Prevention of Human Diseases and Accidents (2010-01-21)
      AIMS/HYPOTHESIS: Evidence from candidate gene studies suggests that obesity may modify genetic susceptibility to type 2 diabetes and dyslipidaemia. On an aggregate level, gene-obesity interactions are expected to result in different heritability estimates at different obesity levels. However, this hypothesis has never been tested. METHOD: The present study included 2,180 British female twins. BMI was used as an index of general obesity. Outcome measures were insulin sensitivity (indexed by quantitative insulin-sensitivity check index [QUICKI]) and fasting plasma lipid profile. Structural equation modelling was used to test whether BMI interacted with latent genetic and environmental effects to impact on the outcome measures. RESULTS: Genetic influences on triacylglycerol increased with BMI (p < 0.001) whereas the unique environmental influence on QUICKI decreased with BMI (p < 0.001), resulting in a higher heritability estimate for both measures at higher BMI levels. This was further illustrated by stratified analysis in twin pairs concordant for normal weight and twin pairs concordant for overweight. Heritability was 19 percentage points higher for triacylglycerol (p < 0.001) and 31 percentage points higher for QUICKI (p < 0.01) among twins concordant for overweight than among twins concordant for normal weight. BMI had no moderator effect on the latent genetic and environmental factors for total cholesterol and HDL-cholesterol. CONCLUSIONS/INTERPRETATION: Our results suggest that the expression of genes influencing triacylglycerol and insulin sensitivity can vary as a function of obesity status. The substantial increases in the genetic contribution to the total variance in insulin sensitivity and triacylglycerols at higher BMIs may prove extremely valuable in the search for candidate genes.
    • A Hierarchical Probabilistic Model for Rapid Object Categorization in Natural Scenes

      He, Xiaofu; Yang, Zhiyong; Tsien, Joe Z.; Brain & Behavior Discovery Institute; Department of Ophthalmology; Department of Neurology (2011-05-25)
      Humans can categorize objects in complex natural scenes within 100â 150 ms. This amazing ability of rapid categorization has motivated many computational models. Most of these models require extensive training to obtain a decision boundary in a very high dimensional (e.g., â ¼6,000 in a leading model) feature space and often categorize objects in natural scenes by categorizing the context that co-occurs with objects when objects do not occupy large portions of the scenes. It is thus unclear how humans achieve rapid scene categorization.
    • Histology of the Normal Mouse Trachea

      Latremouille, Rachel; Weinberger, Paul M.; College of Science and Mathematics (2015-02-06)
      The first tissue engineered tracheal transplantation was performed in 2008 and has since been proposed as a treatment for patients who suffer from severe tracheal stenosis. While the procedure has been performed experimentally on several patients in Europe, the outcomes are poorly documented and complications including patient deaths have resulted in a call for more pre-clinical investigations. Due to multiple factors, our laboratory chose to adapt a mouse model for bronchiolitis obliterans, to model tissue-engineered tracheal transplantation. Early on, it was realized that there was little literature on normal murine tracheobronchial anatomy. To resolve this problem, we set out to create a histological atlas of the murine trachea. Histologic images of normal murine tracheae (hematoxylin and eosin, and Masson's trichrome) were obtained using brightfield multispectral imaging at 5x, 1 Ox, and 1 OOx. Images were reviewed and annotated by specialists in airway surgery,veterinary medicine, and anatomic pathology. It is our hope that establishing this atlas will provide important normative data for researchers already using this model , and will cultivate increased interest in the murine model for future tracheal transplantation research. Begin Time: 09:12 End Time: 25:40
    • The Historical Background of Christianity in Medicine

      Nasworthy, Wommack Mandy; Department of Pediatrics (2016-03)
      Trained in an era when spirituality and religion did not have a role in caring for the ill, many physicians today do not address the spiritual components of healing when addressing their patients. It has been shown that many patients desire to discuss religious and spiritual issues with their doctor, and taking the time to talk about religion or the spirit promotes confidence in the physician by the patient. Many patients want to understand their disease in the framework of their religion, and empirical medicine alone simply is not equipped to handle the kinds of questions that this brings up. The dichotomy that exists today between religion and medicine was not always present. People who sought healing wanted a cure for both the body and the soul, and healers of the past were religiously affiliated. In a country where 72% of the population identifies itself as Christian, it is beneficial for physicians who intend to practice in the U.S. to learn about the roots of medicine and Christianity. To better understand the history of medicine and Christianity is to build a foundation for understanding the perspective of many patients in America today. [Introduction]
    • How Perceived Autonomy Affects Teachers Work

      Scalia, Alicia; Avent-Holt, Dustin; Katherine Reese Pamplin College of Arts, Humanities, and Social Sciences; Avent-Holt, Dustin (2015-02-20)
      Education today is made of standardized tests and controlled curriculum, and this is not always beneficial for the students or teachers. Before the standardization teachers had autonomy inside their classroom to make choices on how and what to teach. The impact of how standardization on students has been researched, but it has not been as thoroughly researched for teachers. The lack of autonomy greatly affects teachers work and consequently it affects how children are taught and learn. In order to discover how teachers perceive their autonomy and the affects it has on their work I have interviewed several teachers who work in different subjects and different grades. I have also done historical data analysis to track the change in policies over time and see how it compares to the teachers experiences. It has been found that teacher's perceived lack of autonomy has negatively impacted their ability to teach students who learn differently and has also changed their view of teaching as work. Researching how teachers are affected by the changes in the education system is important because it impacts the quality of teachers attracted to the profession, the ability of teachers to teach, and therefore the children. Begin Time: 28:25 End Time: 52:35
    • How the Quantity of Patient Interactions During Third-Year Cherkships Affects Medical Student Performance

      Elam, Rachel; Thomas, Andria M.; London, J; Education Discovery Institute; Medical College of Georgia; Georgia Health Sciences University (Georgia Health Sciences University, 2011)
      To conduct an exploratory analysis of the relationship between quantity of patient interactions during core third-year clerkships and performance on both national objective tests and faculty evaluations of junior medical students at GHSU’s Medical College of Georgia between academic year 2007 and 2011.
    • HSP90 Inhibitors in Sepsis and Sepsis-induced Acute Lung Injury

      Chatterjee, Anuran; Vascular Biology Center (2007-06)
      Severe sepsis is the leading cause of death for patients in intensive care units. Patients with severe sepsis develop multiple organ failure, including acute lung injury, resulting from a dysregulated inflammatory response. Inhibitors of the ubiquitous chaperone, heat shock protein 90 (hsp90), block the activity of certain pro-inflammatory mediators, in vitro. We hypothesized that hsp90 inhibitors may ameliorate the inflammation and acute lung injury associated with severe sepsis. Male C57Bl/6 mice received either one of two hsp90 inhibitors, radicicol or 17-allylaminodemethoxygeldanamycin (17-AAG), at 24, 12, 6 and 0 hr before receiving a lethal dose of endotoxin (6.75 x 104 EU / g body weight). Outcomes included survival and parameters of systemic inflammation (plasma cytokine, chemokine and nitrite/nitrate levels), pulmonary inflammation (lung NF-κB and myeloperoxidase activities, inducible nitric oxide or iNOS expression, iNOS-hsp90 complex formation, leukocyte infiltration), and lung injury (pulmonary capillary leak, expression of endothelial specific cell-adhesion or adherens junction proteins, lung function). Mice pre-treated with vehicle and receiving endotoxin exhibited 100% 24-hr lethality, dramatic increase in all parameters of systemic and pulmonary inflammation, reduced lung function and increased capillary leak associated with reduced expression of functional adherens junction proteins. In comparison, mice receiving either radicicol or 17-AAG prior to endotoxin, exhibited prolonged survival, reduced or abolished increases in systemic and pulmonary inflammatory parameters, normal lung function and attenuated capillary leak with restored expression of adherens junction proteins. Additionally, in an in vitro model of endotoxin and activated neutrophil-induced endothelial barrier dysfunction, we show that pre-incubation of neutrophils or endothelial cells or both with hsp90 inhibitors impart a profound barrier protective effect, which is mediated, at-least in part, through reduced activation of pp60Src kinase (an hsp90 client protein) and phosphorylation of the focal adhesion protein paxillin, a pp60Src kinase substrate. Hsp90 inhibitors are drugs already in use clinically as adjunct cancer treatment. Therefore, these findings point to a potential clinical use of these drugs in sepsis and sepsis induced ALI.
    • Identification and Characterization of Two New Players in DNA Double-Strand Break Repair - PSF and p54(nrb)

      Udayakumar, Durga; Department of Molecular Medicine (2005-12)
      The stability and integrity of a genome depends on how accurately the genetic information is passed on to each daughter of a dividing cell. This accuracy is compromised when the genome is exposed to various stressful conditions, including ionizing radiation (IR), radiomimetic agents such as bleomycin, neocarzinostatin, and etoposide, free radicals generated from metabolic processes, and also errors during replication. The effect is DNA damage resulting in potentially lethal double-strand breaks (DSBs). The causes are as follows: DSBs are also created as intermediates during specialized recombination processes, such as V(D)J recombination, immunoglobulin class switching and somatic hypermutation.
    • Identification of RAB11-Family Interacting Proteins (RAB11-F1Ps): Integral Components in Plasma Membrane Recycling

      Hales, Chadwick M; Institute of Molecular Medicine and Genetics (2003-05)
      Given the involvement of Rabl la in each of these cellular processes and given the potential impact of Rabl la on human health and disease, we sought to further establish a role for Rabl la in plasma membrane recycling. Since other Rab proteins have numerous characterized interacting proteins and because the repetoire for Rabl la is currently limited to three identified interacting proteins, we hypothesized that other Rabl la binding partners exist as putative downstream effectors for the small GTPase. We therefore proposed the following three aims: Aim 1: Identify R ab lla interacting proteins. Aim 2: Determine the effect of interacting proteins on membrane recycling. Aim 3: Establish an organizational model of a putative Rabl la complex. The progression of studies herein provides insight into the dynamic and complex process of plasma membrane recycling. Yeast two hybrid screening of a parietal cell cDNA library utilizing dominant active Rabl laS20V as the bait identified Rabl 1-Family Interacting Protein 1 (Rabll-FIPl), a novel R ab lla interacting protein. EST database searches with the R abll-FIPl sequence identified three homologous proteins with high carboxyl-terminal identity. Chapter 1 introduces the new family of Rabl la interacting proteins and provides the initial characterization. Interestingly, these studies indicated an interaction between Rabll-Family Interacting Protein 2 (Rabll-FIP2) and myosin Vb tail. Chapter 2 further describes the Rabl l-FIP2/myosin Vb tail binding and provides functional data placing Rabll-FIP2 as an integral component of the plasma membrane recycling system. Finally, recent studies have indicated a recycling system dependence on different kinase activities. Through kinase inhibitor studies and immunofluorescence imaging, evidence presented in Chapter 3 suggests that R ab lla along with multiple Rabll-FIP proteins function as a complex beginning at the process of endocytosis with movement dependent on multiple phosphorylation events. The ultimate goal throughout these studies is to provide a clearer picture of Rabl la function in plasma membrane recycling so that one day a positive impact on human health can be achieved.
    • 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.