Medicine and Health Sciences Commons^™

Septohippocampal Gabaergic Neurons Mediate The Altered Behaviors Induced By N-Methyl-D-Aspartate Receptor Antagonists., Jingyi Ma, Siew Kian Tai, L Stan Leung

Physiology and Pharmacology Publications

We hypothesize that selective lesion of the septohippocampal GABAergic neurons suppresses the altered behaviors induced by an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine or MK-801. In addition, we hypothesize that septohippocampal GABAergic neurons generate an atropine-resistant theta rhythm that coexists with an atropine-sensitive theta rhythm in the hippocampus. Infusion of orexin-saporin (ore-SAP) into the medial septal area decreased parvalbumin-immunoreactive (GABAergic) neurons by ~80%, without significantly affecting choline-acetyltransferase-immunoreactive (cholinergic) neurons. The theta rhythm during walking, or the immobility-associated theta induced by pilocarpine, was not different between ore-SAP and sham-lesion rats. Walking theta was, however, more disrupted by atropine sulfate in ore-SAP than …

Fak Is A Critical Regulator Of Neuroblastoma Liver Metastasis, Sora Lee, Jingbo Qiao, Pritha Paul, Kathleen L. O'Connor, B. Mark Evers, Dai H. Chung

Surgery Faculty Publications

Neuroblastomas express increased levels of gastrin-releasing peptide receptor (GRP-R). However, the exact molecular mechanisms involved in GRP-R-mediated cell signaling in neuroblastoma growth and metastasis are unknown. Here, we report that focal adhesion kinase (FAK), as a critical downstream target of GRP-R, is an important regulator of neuroblastoma tumorigenicity. We found that FAK expression correlates with GRP-R expression in human neuroblastoma sections and cell lines. GRP-R overexpression in SK-N-SH cells increased FAK, integrin α3 and β1 expressions and cell migration. These cells demonstrated flatter cell morphology with broad lamellae, in which intense FAK expression was localized to the leading edges of …

Evaluation Of Very High- And Very Low-Dose Intravitreal Aflibercept In Patients With Neovascular Age-Related Macular Degeneration., Quan Dong Nguyen, Peter A. Campochiaro, Syed Mahmood Shah, David J. Browning, Henry L. Hudson, Peter L. Sonkin, Seenu M. Hariprasad, Peter K. Kaiser, Jason Slakter, Julia A. Haller, Diana V. Do, William Mieler, Karen Chu, Avner Ingerman, Robert Vitti, Alyson J. Berliner, Jesse Cedarbaum, Clear-It 1 Investigators

Journal Articles: Ophthalmology

PURPOSE: To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD).

METHODS: In this double-masked, phase 1 study, 28 patients with lesions ≤12 disc areas, ≥50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) ≤20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, …

Influence Of Body Mass Index And Antibiotic Dose On The Risk Of Surgical Site Infections In Pediatric Clean Orthopedic Surgery., Jeffrey J Cies, Shannon Chan, Jobayer Hossain, B Randall Brenn, M Cecilia Di Pentima

Department of Anesthesiology Faculty Papers

OBJECTIVE: To evaluate body mass index (BMI) and antimicrobial dose as risk factors for surgical site infections in pediatric patients.

PATIENTS AND METHODS: Children between 2 and 19 years of age undergoing clean orthopedic procedures and receiving at least one dose of perioperative antibiotics (cefazolin, vancomycin, or clindamycin) were studied. The retrospective case-controlled study was conducted at the Alfred I. duPont Hospital for Children, a 180-bed tertiary-care academic pediatric hospital in Wilmington, DE. Data were collected from January 1, 2002, to December 31, 2005.

RESULTS: Underweight children had a higher risk for SSIs than overweight and normal-weight children. American Society …

Effect Of Voxel Size On The Accuracy Of 3d Reconstructions With Cone Beam Ct., Delphine Maret, Norbert Telmon, Ove A. Peters, B. Lepage, J. Treil, J. M. Inglèse, A. Peyre, Jean-Luc Kahn, Michel Sixou

All Dugoni School of Dentistry Faculty Articles

OBJECTIVES: The various types of cone beam CT (CBCT) differ in several technical characteristics, notably their spatial resolution, which is defined by the acquisition voxel size. However, data are still lacking on the effects of voxel size on the metric accuracy of three-dimensional (3D) reconstructions. This study was designed to assess the effect of isotropic voxel size on the 3D reconstruction accuracy and reproducibility of CBCT data.

METHODS: The study sample comprised 70 teeth (from the Institut d'Anatomie Normale, Strasbourg, France). The teeth were scanned with a KODAK 9500 3D® CBCT (Carestream Health, Inc., Marne-la-Vallée, France), which has two voxel …

Treatment Of Steroid-Induced Elevated Intraocular Pressure With Anecortave Acetate: A Randomized Clinical Trial., Ingeborg Stalmans, David G. Callanan, Monte S. Dirks, Marlene R. Moster, Alan L. Robin, Joachim Van Calster, Sally A. Scheib, Jaime E. Dickerson, Theresa A. Landry, Michael V. W. Bergamini

Wills Eye Hospital Papers

PURPOSE: The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy.

METHODS: This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of …

Risk Factors For Wound Complications After Ankle Fracture Surgery., Adam G Miller, Andrew Margules, Steven M Raikin

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: The overall rate of complications after ankle fracture fixation varies between 5% and 40% depending on the population investigated, and wound complications have been reported to occur in 1.4% to 18.8% of patients. Large studies have focused on complications in terms of readmission, but few studies have examined risk factors for wound-related issues in the outpatient setting in a large number of patients. A review was performed to identify risk factors for wound complications tracked in the hospital and outpatient setting.

METHODS: Four hundred and seventy-eight patients underwent open reduction and internal fixation of an ankle fracture between 2003 …

Practice Effects In A Longitudinal, Multi-Center Alzheimer's Disease Prevention Clinical Trial, Erin L. Abner, Brandon C. Dennis, Melissa J. Mathews, Marta S. Mendiondo, Allison Caban-Holt, Richard J. Kryscio, Frederick A. Schmitt, John J. Crowley

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Practice effects are a known threat to reliability and validity in clinical trials. Few studies have investigated the potential influence of practice on repeated screening measures in longitudinal clinical trials with a focus on dementia prevention. The current study investigates whether practice effects exist on a screening measure commonly used in aging research, the Memory Impairment Screen (MIS).

METHODS: The PREADViSE trial is a clinical intervention study evaluating the efficacy of vitamin E and selenium for Alzheimer's disease prevention. Participants are screened annually for incident dementia with the MIS. Participants with baseline and three consecutive follow-ups who made less …

Multivitamin Supplementation In Hiv Infected Adults Initiating Antiretroviral Therapy In Uganda: The Protocol For A Randomized Double Blinded Placebo Controlled Efficacy Trial., David Guwatudde, Amara E. Ezeamama, Danstan Bagenda, Rachel Kyeyune, Fred Wabwire-Mangen, Henry Wamani, Ferdinand Mugusi, Donna Spiegelman, Molin Wang, Yukari C. Manabe, Wafaie W. Fawzi

Journal Articles: Epidemiology

BACKGROUND: Use of multivitamin supplements during the pre-HAART era has been found to reduce viral load, enhance immune response, and generally improve clinical outcomes among HIV-infected adults. However, immune reconstitution is incomplete and significant mortality and opportunistic infections occur in spite of HAART. There is insufficient research information on whether multivitamin supplementation may be beneficial as adjunct therapy for HIV-infected individuals taking HAART. We propose to evaluate the efficacy of a single recommended daily allowance (RDA) of micronutrients (including vitamins B-complex, C, and E) in slowing disease progression among HIV-infected adults receiving HAART in Uganda.

METHODS/DESIGN: We are using a …

Building A Statistical Model For Predicting Cancer Genes, Ivan P. Gorlov, Christopher J. Logothetis, Shenying Fang, Olga Y. Gorlova, Christopher Amos

Dartmouth Scholarship

More than 400 cancer genes have been identified in the human genome. The list is not yet complete. Statistical models predicting cancer genes may help with identification of novel cancer gene candidates. We used known prostate cancer (PCa) genes (identified through KnowledgeNet) as a training set to build a binary logistic regression model identifying PCa genes. Internal and external validation of the model was conducted using a validation set (also from KnowledgeNet), permutations, and external data on genes with recurrent prostate tumor mutations. We evaluated a set of 33 gene characteristics as predictors. Sixteen of the original 33 predictors were …

Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by …

Male Gender Promotes An Increased Inflammatory Response To Lipopolysaccharide In Umbilical Vein Blood., Shunaha Kim-Fine, Timothy Regnault, James S Lee, Sarah A Gimbel, Jill A Greenspoon, Jonathan Fairbairn, Kelly Summers, Barbra De Vrijer

Paediatrics Publications

OBJECTIVES: To establish gender-specific differences in maternal and fetal immune response in healthy human fetuses at term.

METHODS: Forty-five women with elective caesarean sections for uncomplicated singleton pregnancies were recruited for two studies. Using a multiplex biomarker immunoassay system, unstimulated maternal and fetal plasma concentrations of interleukin (IL)-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)-α were measured from one study population. Lipopolysaccharide (LPS)-stimulated cytokine response was measured in a second study.

RESULTS: There were no significant gender differences in either maternal or fetal unstimulated plasma cytokine concentrations, but concentrations of the proinflammatory cytokines IL-1β and …

Trop-2 Inhibits Prostate Cancer Cell Adhesion To Fibronectin Through The Β1 Integrin-Rack1 Axis., Marco Trerotola, Jing Li, Saverio Alberti, Lucia R. Languino

Department of Cancer Biology Faculty Papers

Trop-2 is a transmembrane glycoprotein upregulated in several human carcinomas, including prostate cancer (PrCa). Trop-2 has been suggested to regulate cell-cell adhesion, given its high homology with the other member of the Trop family, Trop-1/EpCAM, and its ability to bind the tight junction proteins claudin-1 and claudin-7. However, a role for Trop-2 in cell adhesion to the extracellular matrix has never been postulated. Here, we show for the first time that Trop-2 expression in PrCa cells correlates with their aggressiveness. Using either shRNA-mediated silencing of Trop-2 in cells that endogenously express it, or ectopic expression of Trop-2 in cells that …

Bandemia With Normal White Blood Cell Counts Associated With Infection., Marci Drees, Narrani Kanapathippillai, Marc T Zubrow

Department of Medicine Faculty Papers

OBJECTIVE: Measuring immature white blood cell forms ("bands") has been considered clinically unnecessary. We performed this study to determine whether elevated band counts, with normal total white blood cells on admission, were associated with infection or in-hospital death.

METHODS: We performed a retrospective cohort study including all patients admitted to the Christiana Care Health System 2-hospital, 1100-bed community-based academic health system in 2009 with normal white blood cells (3800-10,800 per mm(3)) on admission who had manual differentials performed. We defined our band groups as normal (≤10% bands and other immature cells), moderate (11%-19%), or high (≥20%). Via chart review, we …

Longitudinal Documentation Of Serum Cartilage Oligomeric Matrix Protein And Patient-Reported Outcomes In Collegiate Soccer Athletes Over The Course Of An Athletic Season, Johanna M. Hoch, Carl G. Mattacola, Heather M. Bush, Jennifer M. Medina Mckeon, Timothy E. Hewett, Christian Lattermann

Physical Therapy Faculty Publications

BACKGROUND: Serum cartilage oligomeric matrix protein (sCOMP) is a biomarker for cartilage degradation. Patient-reported outcomes (PRO) are used to document postinjury recovery and may be used to prospectively identify changes in the course of a season. It is unknown what effect intense, continuous physical activity has on sCOMP levels and PRO values in athletes over the duration of a soccer season.

HYPOTHESIS/PURPOSE: The purpose of this study was to longitudinally document sCOMP levels and to determine whether changes in PROs occur in collegiate soccer athletes during a season. The hypotheses tested were that sCOMP levels and PRO scores would remain …

A Kidney For Christmas, Stephen Scholand

The Medicine Forum

When Asmar Lawrence first walked into the small examining room in the Jefferson Hospital Ambulatory Practice (JHAP) Clinic, we both had no idea what the future would hold. It was July, 1998 and I was fresh from medical school. Each week, I looked forward to the JHAP experience to develop my clinical skills and follow patients longitudinally. No longer was my learning prescribed from a textbook, this was the 'real world' of medicine where anything could happen and I was supposed to be in control of it. The long white coat probably helped perpetuate some of that illusion. Fortunately our …

Regulatory T-Cells And Associated Pathways In Metastatic Renal Cell Carcinoma (Mrcc) Patients Undergoing Dc-Vaccination And Cytokine-Therapy, Adrian Schwarzer, Benita Wolf, Jan L. Fisher, Thomas Schwaab, Sven Olek, Udo Baron, Craig R. Tomlinson, John D. Seigne, Nancy A. Crosby, Jiang Gui, Thomas H. Hampton, Camilo E. Fadul, John A. Heaney, Marc S. Ernstoff

Dartmouth Scholarship

Purpose: To evaluate CD4+CD25+FOXP3+ T regulatory cells (TREG) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating TREG combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis.

Design: Eighteen patients with mRCC and twelve volunteers (controls) were available for analysis. TREG phenotype was examined using flow cytometry (FCM). TREG were also quantified by analyzing the epigenetic status of the FOXP3 locus using methylation specific PCR. As a third approach, RNA of the PBL was hybridized to Affymetrix GeneChip …

Rod Microglia: Elongation, Alignment, And Coupling To Form Trains Across The Somatosensory Cortex After Experimental Diffuse Brain Injury, Jenna M. Ziebell, Samuel E. Taylor, Tuoxin Cao, Jordan L. Harrison, Jonathan Lifshitz

Neuroscience Faculty Publications

BACKGROUND: Since their discovery, the morphology of microglia has been interpreted to mirror their function, with ramified microglia constantly surveying the micro-environment and rapidly activating when changes occur. In 1899, Franz Nissl discovered what we now recognize as a distinct microglial activation state, microglial rod cells (Stäbchenzellen), which he observed adjacent to neurons. These rod-shaped microglia are typically found in human autopsy cases of paralysis of the insane, a disease of the pre-penicillin era, and best known today from HIV-1-infected brains. Microglial rod cells have been implicated in cortical 'synaptic stripping' but their exact role has remained unclear. This is …

A Case Of A Male With Fever And Fatigue, Steve Ting

The Medicine Forum

This is a case of a 78 year old Caucasian gentleman who presented to the hospital in the early summer with complaints of high fevers and progressive fatigue. The patient lives near Philadelphia and enjoys doing yard work. He reported finding a tick attached to the skin near his groin approximately 3 weeks prior to admission. The tick was removed; however the patient was unsure of the duration of the tick attachment. He also denied developing any significant rash in that area. He had no recent sick contacts and no recent history of travel. He began developing fever spikes up …

Severe Stress Switches Crf Action In The Nucleus Accumbens From Appetitive To Aversive., Julia C Lemos, Matthew J Wanat, Jeffrey S Smith, Beverly A S Reyes, Nick G Hollon, Elisabeth J Van Bockstaele, Charles Chavkin, Paul E M Phillips

Farber Institute for Neuroscience Faculty Papers

Stressors motivate an array of adaptive responses ranging from 'fight or flight' to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. …

Gene Expression Analysis Of A Murine Model With Pulmonary Vascular Remodeling Compared To End-Stage Ipah Lungs, Kayoko Shimodaira, Yoichiro Okubo, Eri Ochiai, Haruo Nakayama, Harutaka Katano, Megumi Wakayama, Minoru Shinozaki, Takao Ishiwatari, Daisuke Sasai, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Katsuhiko Kamei, Kazutoshi Shibuya

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our …

The Long-Term Impact Of Physical And Emotional Trauma: The Station Nightclub Fire, Jeffrey C. Schneider, Nhi-Ha T. Trinh, Elizabeth Selleck, Felipe Fregni, Sara S. Salles, Colleen M. Ryan, Joel Stein

Physical Medicine and Rehabilitation Faculty Publications

BACKGROUND: Survivors of physical and emotional trauma experience enduring occupational, psychological and quality of life impairments. Examining survivors from a large fire provides a unique opportunity to distinguish the impact of physical and emotional trauma on long-term outcomes. The objective is to detail the multi-dimensional long-term effects of a large fire on its survivor population and assess differences in outcomes between survivors with and without physical injury.

METHODS AND FINDINGS: This is a survey-based cross-sectional study of survivors of The Station fire on February 20, 2003. The relationships between functional outcomes and physical injury were evaluated with multivariate regression models …

Treatment Of Cardiomyopathy With Pap Therapy In A Patient With Severe Obstructive Sleep Apnea., Ritu G. Grewal, Md

Department of Sleep Medicine Faculty Papers

Obstructive sleep apnea is common in patients with heart failure. This case illustrates that treatment with PAP therapy can improve cardiac function in patients with both conditions. CPAP-emergent central apnea, as seen in this patient, has multiple etiologies. It is commonly seen in patients with severe sleep apnea, usually resolves over time, and does not need treatment with adaptive servoventilation.

A Phase Ii Study Of Pulse Dose Imatinib Mesylate And Weekly Paclitaxel In Patients Aged 70 And Over With Advanced Non-Small Cell Lung Cancer, Julie E. Bauman, Keith D. Eaton, Sarah G. Wallace, Laurie L. Carr, Sang-Joon Lee, Dennie V. Jones, Hugo Arias-Pulido, Lisa A. Cerilli, Renato G. Martins

Internal Medicine Faculty Publications

BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR).

METHODS: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index …

Clostridium Septicum Growth From A Total Knee Arthroplasty Associated With Intestinal Malignancy: A Case Report, Demetri M. Economedes, Jerome Santoro, Carl A. Deirmengian

PCOM Scholarly Works

BACKGROUND: Previous reports of infection with Clostridium septicum have identified an unexpected association with concurrent malignancy. The reported rate of associated malignancy has been found to be as high as 81 percent. The purpose of this case report was to present a case of a total knee arthroplasty infected with C. septicum and the subsequent finding of an occult colonic malignancy.

CASE PRESENTATION: A 74 year-old man underwent uneventful bilateral total knee arthroplasties. Two weeks post-operatively, he presented with acute swelling, redness and pain of the left knee. Aspiration of the knee was sent for cell count and …

Expanding The Basic Science Debate: The Role Of Physics Knowledge In Interpreting Clinical Findings., Mark Goldszmidt, John Paul Minda, Sarah L Devantier, Aimee L Skye, Nicole N Woods

Brain and Mind Institute Researchers' Publications

Current research suggests a role for biomedical knowledge in learning and retaining concepts related to medical diagnosis. However, learning may be influenced by other, non-biomedical knowledge. We explored this idea using an experimental design and examined the effects of causal knowledge on the learning, retention, and interpretation of medical information. Participants studied a handout about several respiratory disorders and how to interpret respiratory exam findings. The control group received the information in standard "textbook" format and the experimental group was presented with the same information as well as a causal explanation about how sound travels through lungs in both the …

Compliance With Surgical Care Improvement Project Blood Glucose--A Marker For Euglycemia, But Does It Put Our Patients At Risk?, Isaac R Whitman, Maura Murphy, Marta M Gilson, Amy Campfield, Michel Haddad, Elizabeth Moxey, Glenn J R Whitman

Department of Surgery Faculty Papers

To improve outcomes in open heart surgery (OHS) patients, the Surgical Care Improvement Project (SCIP) requires 6 am postoperative day (POD) 1 and 2 blood glucose (BG) to be ≤200mg/dL. This study examined risk factors for SCIP noncompliance when using an insulin infusion protocol (IIP) and evaluated this SCIP metric as a surrogate for glycemic control. The authors divided 99 consecutive OHS patients, all subjected to 1 uniform IIP, into 2 groups: Group 1-SCIP compliant (n=79) and Group 2-SCIP noncompliant (n=20). They determined mean BG for the first 48 postoperative hours, percent of total time with hyperglycemia (% time BG …

Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian

Physiology Faculty Publications

The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …

Predictive Value Of Alpha-Fetoprotein In The Long-Term Risk Of Developing Hepatocellular Carcinoma In Patients With Hepatitis B Virus Infection--Results From A Clinic-Based Longitudinal Cohort., Hie-Won Hann, Xiaoying Fu, Ronald E. Myers, Richard Hann, Shaogui Wan, Su Hee Kim, Natalie Au, Jinliang Xing, Hushan Yang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Although serum level of alpha-fetoprotein (AFP) has long been used to complement imaging tests in the screening and diagnosis of hepatocellular carcinoma (HCC), whether it can be used as a predictive marker of long-term risk for developing HCC in patients with hepatitis B virus (HBV) has not been extensively evaluated and thus remains controversial.

METHODS: We retrospectively conducted a clinic-based longitudinal cohort study including 617 Korean American patients with HBV who had been followed for up to 22 years (median follow-up time, 6.2 years) to evaluate the association between baseline serum AFP level and the long-term risk of HCC. …

The Alternative Crosstalk Between Rage And Nitrative Thioredoxin Inactivation During Diabetic Myocardial Ischemia-Reperfusion Injury., Yi Liu, Yan Qu, Rutao Wang, Yanzhuo Ma, Chenhai Xia, Chao Gao, Jingyi Liu, Kun Lian, Aibing Xu, Xiaoyan Lu, Lu Sun, Lu Yang, Wayne B. Lau, Erhe Gao, Walter Koch, Haichang Wang, Ling Tao

Department of Emergency Medicine Faculty Papers

The receptor for advanced glycation end products (RAGE) and thioredoxin (Trx) play opposing roles in diabetic myocardial ischemia-reperfusion (MI/R) injury. We recently demonstrated nitrative modification of Trx leads to its inactivation and loss of cardioprotection. The present study is to determine the relationship between augmented RAGE expression and diminished Trx activity pertaining to exacerbated MI/R injury in the diabetic heart. The diabetic state was induced in mice by multiple intraperitoneal low-dose streptozotocin injections. RAGE small-interfering RNA (siRNA) or soluble RAGE (sRAGE, a RAGE decoy) was via intramyocardial and intraperitoneal injection before MI/R, respectively. Mice were subjected to 30 min of …