Medicine and Health Sciences Commons^™

The Humoral Theory Of Transplantation: Epitope Analysis And The Pathogenicity Of Hla Antibodies., Edward J Filippone, John Farber

Department of Medicine Faculty Papers

Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole HLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA antigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential immunogenicity of given HLA …

Stimulation Of Transforming Growth Factor-Β1-Induced Endothelial-To-Mesenchymal Transition And Tissue Fibrosis By Endothelin-1 (Et-1): A Novel Profibrotic Effect Of Et-1., Peter J. Wermuth, Zhaodong Li, Fabian A. Mendoza, Sergio A. Jimenez

Department of Medicine Faculty Papers

TGF-β-induced endothelial-to-mesenchymal transition (EndoMT) is a newly recognized source of profibrotic activated myofibroblasts and has been suggested to play a role in the pathogenesis of various fibrotic processes. Endothelin-1 (ET-1) has been implicated in the development of tissue fibrosis but its participation in TGF-β-induced EndoMT has not been studied. Here we evaluated the role of ET-1 on TGF-β1-induced EndoMT in immunopurified CD31+/CD102+ murine lung microvascular endothelial cells. The expression levels of α-smooth muscle actin (α-SMA), of relevant profibrotic genes, and of various transcription factors involved in the EndoMT process were assessed employing quantitative RT-PCR, immunofluorescence histology and Western blot analysis. …

Postoperative Intussusception In 10-Year-Old Presenting As Decreased Intestinal Motility, Arielle Spellun, Loren Berman, Stephen Murphy

Department of Medicine Faculty Papers

No abstract provided.

Parental And Staff Perspectives Of Nicu Research Procedures., Christina Freibott, Ursula Guillen, Amy Mackley, Robert Locke

Department of Medicine Faculty Papers

BACKGROUND: There are limited data on parental perception of infant participation in minimal risk and minor increase above minimal risk research focusing on the NICU population. The study objective was to assess parental and NICU staff perceptions concerning minimal risk and minor increase above minimal risk in the NICU setting.

METHODS: Parents of infants and NICU staff were presented with a combination of 4 infant scenarios and 5 hypothetical research procedures. These assessed participants' willingness to allow their infant to participate in research and their attitude towards obligation to assist future children. Linear and hierarchal linear models analyzed the association …

Utilization Of Hiv-1 Envelope V3 To Identify X4- And R5-Specific Tat And Ltr Sequence Signatures., Gregory C Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R Nonnemacher, Jeffrey M Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Gregory Schwartz, Uri Hershberg, Fred C Krebs, Brian Wigdahl

Department of Medicine Faculty Papers

BACKGROUND: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures …

Childhood Psychosocial Determinants Of Cardiovascular Health, Samuel S. Gidding, Erica D. Sood

Department of Medicine Faculty Papers

Understanding risk and protective factors that impact cardiovascular health is of utmost importance. There is ample evidence that cardiovascular health begins in childhood, tracks over time, and is subject to adverse social influences. This paper reviews key studies examining the relations of psychosocial factors in childhood to cardiovascular health in adulthood. The existing literature provides evidence for both individual and cumulative effects of childhood psychosocial factors on adult cardiovascular health across the population, although the specific mechanisms underlying these relationships are not yet fully understood. This paper also includes a discussion of evidence-based strategies for prevention and treatment of childhood …

Hospitalized Patients At High Risk For Obstructive Sleep Apnea Have More Rapid Response System Events And Intervention Is Associated With Reduced Events., Sunil Sharma, Md, Anindita Chowdhury, Lili Tang, Leslee Willes, Brian Glynn, Stuart F Quan

Department of Medicine Faculty Papers

BACKGROUND: Rapid response system (RRS) is a safety tool designed for early detection and intervention of a deteriorating patient on the general floor in the hospital. Obstructive sleep apnea (OSA) has been associated with significant cardiovascular complications. We hypothesized that patients with high-risk of OSA have higher rate of RRS events and intervention with positive airway pressure therapy in these patients can mitigate the RRS events.

METHODS: As part of a clinical pathway, during a 15 month period, patients with BMI ≥ 30 kg/m2 in select medical services were screened with a validated sleep questionnaire. Patients were characterized as high …

Cell-Free Circulating Mitochondrial Dna Content And Risk Of Hepatocellular Carcinoma In Patients With Chronic Hbv Infection., Ling Li, Hie-Won Hann, Shaogui Wan, Richard Hann, Chun Wang, Yinzhi Lai, Xishan Ye, Alison Evans, Ronald E. Myers, Phd, Dsw, Zhong Ye, Bingshan Li, Jinliang Xing, Hushan Yang

Department of Medicine Faculty Papers

Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 …

Evaluation Of Polymorphic Locus Sequence Typing For Candida Glabrata Epidemiology., Santosh Katiyar, Eric Shiffrin, Md, Celeste Shelton, Kelley Healey, John-Paul Vermitsky, Tom Edlind

Department of Medicine Faculty Papers

The opportunistic yeastCandida glabratais increasingly refractory to antifungal treatment or prophylaxis and relatedly is increasingly implicated in health care-associated infections. To elucidate the epidemiology of these infections, strain typing is required. Sequence-based typing provides multiple advantages over length-based methods, such as pulsed-field gel electrophoresis (PFGE); however, conventional multilocus sequence typing (targeting 6 conserved loci) and whole-genome sequencing are impractical for routine use. A commercial sequence-based typing service forC. glabratathat targets polymorphic tandem repeat-containing loci has recently been developed. These CgMT-J and CgMT-M services were evaluated with 56 epidemiologically unrelated isolates, 4 to 7 fluconazole-susceptible or fluconazole-resistant isolates from each of …

A 22-Year-Old Man With Pleural Tuberculosis Associated Hydropneumothorax: Case Report And Literature Review., Lauren A Sharan, Thea Price, Md, Boyd Hehn, David Manoff, Md, Scott W. Cowan, Md

Department of Medicine Faculty Papers

A 22-year-old Asian male presented with fever, non-productive cough, right-sided pleuritic chest pain and was found to have a large right hydropneumothorax. A chest tube was placed. Pleural fluid analysis revealed a lymphocytic predominant exudate and he was subsequently started on four-drug daily anti-tuberculosis therapy (isoniazid, ethambutol, rifampin, pyrazinamide). Pleural biopsy revealed acid-fast bacilli. Given his persistent pleural effusion, he was given four doses of intrapleural tissue plasminogen activator (tPA) and dornase alpha (DNase) via his chest tube over a period of 6 days resulting in clinical and radiologic improvement. Pleural biopsy and pleural fluid culture specimens later revealed Mycobacterium …

Conversion To Eslicarbazepine Acetate Monotherapy: A Pooled Analysis Of 2 Phase Iii Studies., Michael R Sperling, Jacqueline French, Mercedes P Jacobson, Ladislav Pazdera, Mallory Gough, Hailong Cheng, Todd Grinnell, David Blum

Department of Medicine Faculty Papers

OBJECTIVE: To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy.

METHODS: This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical …

Heart Rhythm Monitoring Strategies For Cryptogenic Stroke: 2015 Diagnostics And Monitoring Stroke Focus Group Report., Gregory W. Albers, Richard A. Bernstein, Johannes Brachmann, John Camm, J. Donald Easton, Peter Fromm, Shinya Goto, Christopher B. Granger, Stefan H. Hohnloser, Elaine Hylek, Amir K. Jaffer, Derk W. Krieger, Rod Passman, Jesse M. Pines, Shelby D. Reed, Peter M. Rothwell, Peter R. Kowey

Department of Medicine Faculty Papers

No abstract provided.

Lambda Red-Mediated Recombineering In The Attaching And Effacing Pathogen Escherichia Albertii., Marisa Egan, Jasmine Ramirez, Christian Xander, Chirag Upreti, Shantanu Bhatt

Department of Medicine Faculty Papers

BACKGROUND: The ability to introduce site-specific mutations in bacterial pathogens is essential towards understanding their molecular mechanisms of pathogenicity. This has been greatly facilitated by the genetic engineering technique of recombineering. In recombineering, linear double- or single-stranded DNA molecules with two terminal homology arms are electroporated into hyperrecombinogenic bacteria that express a phage-encoded recombinase. The recombinase catalyzes the replacement of the endogenous allele with the exogenous allele to generate selectable or screenable recombinants. In particular, lambda red recombinase has been instrumental in engineering mutations to characterize the virulence arsenal of the attaching and effacing (A/E) pathogens enteropathogenic Escherichia coli (EPEC), …

Cannibalism, Kuru, And Mad Cows: Prion Disease As A "Choose-Your-Own-Experiment" Case Study To Simulate Scientific Inquiry In Large Lectures., Antonio Serrano, Jeffrey Liebner, Justin K Hines

Department of Medicine Faculty Papers

Despite significant efforts to reform undergraduate science education, students often perform worse on assessments of perceptions of science after introductory courses, demonstrating a need for new educational interventions to reverse this trend. To address this need, we created An Inexplicable Disease, an engaging, active-learning case study that is unusual because it aims to simulate scientific inquiry by allowing students to iteratively investigate the Kuru epidemic of 1957 in a choose-your-own-experiment format in large lectures. The case emphasizes the importance of specialization and communication in science and is broadly applicable to courses of any size and sub-discipline of the life sciences.

Cloning And Transcriptional Activity Of The Mouse Omi/Htra2 Gene Promoter., Dan Liu, Xin Liu, Ye Wu, Wen Wang, Xin-Liang Ma, Huirong Liu

Department of Medicine Faculty Papers

HtrA serine peptidase 2 (HtrA2), also named Omi, is a pro-apoptotic protein that exhibits dramatic changes in expression levels in a variety of disorders, including ischemia/reperfusion injury, cancer, and neurodegeneration. In our study, Omi/HtrA2 protein levels were high in the heart, brain, kidney and liver, with elevated heart/brain expression in aging mice. A similar expression pattern was observed at the mRNA level, which suggests that the regulation of Omi/HtrA2 is predominately transcriptional. Promoter binding by transcription factors is the main influencing factor of transcription, and to identify specific promoter elements that contribute to the differential expression of mouse Omi/HtrA2, we …

Reduction Of Ctrp9, A Novel Anti-Platelet Adipokine, Contributes To Abnormal Platelet Activity In Diabetic Animals., Wenqing Wang, Wayne Bond Lau, Yajing Wang, Xin-Liang Ma, Rong Li

Department of Medicine Faculty Papers

Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic …

Preparation And Biological Activity Of The Monoclonal Antibody Against The Second Extracellular Loop Of The Angiotensin Ii Type 1 Receptor, Mingming Wei, Chengrui Zhao, Suli Zhang, Li Wang, Huirong Liu, Xin-Liang Ma

Department of Medicine Faculty Papers

No abstract provided.