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Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

Doxorubicin Loaded Polymeric Nanoparticulate Delivery System To Overcome Drug Resistance In Osteosarcoma, Michiro Susa, Arun K. Iyer, Keinosuke Ryu, Francis J. Hornicek, Henry Mankin, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Background: Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients dramatically after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since reached plateau at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug resistant (MDR) tumor cells, we explored the possibility of loading doxorubicin onto biocompatible, lipid-modified dextran-based polymeric nanoparticles and evaluated the …

Solution Structure Of The Inhibitory Phosphorylation Domain Of Myosin Phosphatase Targeting Subunit 1., Shunsuke Mori, Ryou Iwaoka, Masumi Eto, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Cell motility, such as smooth muscle contraction and cell migration, is controlled by the reversible phosphorylation of the regulatory light chain of myosin II and other cytoskeletal proteins. Mounting evidence suggests that in smooth muscle cells and other types of cells in vertebrates, myosin phosphatase (MP) plays an important role in controlling the phosphorylation of myosin II as well as other cytoskeletal proteins, including ezrin, moesin, and radixin.1 MP is a holoenzyme consisting of a catalytic subunit of a type-1 Ser/Thr phosphatase (PP1C) delta isoform, a myosin phosphatase targeting subunit 1 (MYPT1), and an accessory subunit M21. In this ternary …

Reactive Oxygen And Nitrogen Species Induce Protein And Dna Modifications Driving Arthrofibrosis Following Total Knee Arthroplasty., Theresa A Freeman, Javad Parvizi, Craig J Della Valle, Marla J Steinbeck

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Arthrofibrosis, occurring in 3%-4% of patients following total knee arthroplasty (TKA), is a challenging condition for which there is no defined cause. The hypothesis for this study was that disregulated production of reactive oxygen species (ROS) and nitrogen species (RNS) mediates matrix protein and DNA modifications, which result in excessive fibroblastic proliferation.

RESULTS: We found increased numbers of macrophages and lymphocytes, along with elevated amounts of myeloperoxidase (MPO) in arthrofibrotic tissues when compared to control tissues. MPO expression, an enzyme that generates ROS/RNS, is usually limited to neutrophils and some macrophages, but was found by immunohistochemistry to be expressed …

Quantitative And Qualitative Findings And Implications Of An Intercultural Sensitivity Assessment Among Employees At A Large Health System, Jarret R. Patton Md, Jay Baglia Phd, Lynn M. Deitrick Rn, Phd, Anthony Nerino Ma, Eric J. Gertner Md, Mph, Judith Sabino Mph, Mary Kay Grim Bs, Debbie Salas-Lopez Md, Mph

Department of Pediatrics

Tuesday, November 10, 2009: 2:45 PM Jarret R. Patton, MD , Department of Pediatrics, Lehigh Valley Health Network, Allentown, PA Jay Baglia, PhD , Department of Family Medicine, Lehigh Valley Health Network, Allentown, PA Lynn M. Deitrick, RN, PhD , Department of Community Health, Health Studies and Education, Lehigh Valley Health Network, Allentown, PA Anthony Nerino, MA , Department of Community Health, Health Studies and Education, Lehigh Valley Health Network, Allentown, PA Eric J. Gertner, MD, MPH , Department of Medicine, Lehigh Valley Health Network, Allentown, PA Judith N. Sabino, MPH , Cultural Awareness, Lehigh Valley Health Network, Allentown, PA …

Medical Education Digest, Vol. 11 No. 6 (November/December 2009), Nova Southeastern University

Medical Education Digest

No abstract provided.

Sox11 Expression Is Highly Specific For Mantle Cell Lymphoma And Identifies The Cyclin D1-Negative Subtype., Ana Mozos, Cristina Royo, Elena Hartmann, Daphne De Jong, Cristina Baró, Alexandra Valera, Kai Fu, Dennis D. Weisenburger, Jan Delabie, Shih-Sung Chuang, Elaine S. Jaffe, Carmen Ruiz-Marcellan, Sandeep Dave, Lisa Rimsza, Rita Braziel, Randy D. Gascoyne, Francisco Solé, Armando López-Guillermo, Dolors Colomer, Louis M. Staudt, Andreas Rosenwald, German Ott, Pedro Jares, Elias Campo

Journal Articles: Pathology and Microbiology

BACKGROUND: Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors.

DESIGN AND METHODS: The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin …

Four Centuries Of Military Surgery In Canada, Vivian Mcalister

Data and Test Instruments

No abstract provided.

Sonography Of The Neonatal Brain, Traci B. Fox

Department of Radiologic Sciences Faculty Papers

Neurosonography is a critical part of the care of the sick newborn. Sonography is superior to other modalities in imaging of the brain because it can be performed at the bedside, is easily reproducible, and does not require ionizing radiation or sedation. This article refreshes the sonographer in the normal anatomy and appear- ance of the neonatal brain using sonography, as well as some of the more common pathologic conditions that may be encountered.

Combination Of Vandetanib, Radiotherapy, And Irinotecan In The Lovo Human Colorectal Cancer Xenograft Model., Phyllis Wachsberger, Randy Burd, Anderson Ryan, Constantine Daskalakis, Adam P. Dicker

Department of Radiation Oncology Faculty Papers

PURPOSE: The tumor growth kinetics of the human LoVo colorectal xenograft model was assessed in response to vandetanib, an orally available receptor tyrosine kinase inhibitor, radiotherapy (RT), or irinotecan (CPT-11), as single therapies and in combination. METHODS AND MATERIALS: LoVo cells were injected subcutaneously into the right hind limb (5 x 10(6) cells in 100 microL phosphate-buffered saline) of athymic NCR NUM mice and tumors were grown to a volume of 200-300 mm(3) before treatment. Vandetanib was administered at 50 mg/kg daily orally for 14 days starting on Day 1. RT was given as three fractions (3 x 3 Gy) …

Hiv/Aids And Pregnancy-Related Deaths In Blantyre, Malawi, V. M. Lema, C. Kanyighe, J. Changole, E. V. Malunga

Obstetrics and Gynaecology, East Africa

Background: HIV/AIDS epidemic is one of the major factors affecting women’s health and impeding national efforts to improve it especially in sub-Saharan Africa. Current evidence indicates that HIV/ AIDS is increasingly becoming a major cause or contributing factor to pregnancy-related deaths, almost overtaking the “traditional” causes and factors.

Objectives: To survey the contribution of HIV infection and AIDS to pregnancy-related deaths in Blantyre, Malawi.

Design: A retrospective, descriptive, facility-based survey.

Setting: The Queen Elizabeth Central Teaching Hospital, Blantyre, Malawi.

Subjects: All women recorded to have had pregnancy-related deaths between January 1, 1999 and December 31, 2000.

Results: There were …

Dysfunctional Attitudes Scale Perfectionism: A Predictor And Partial Mediator Of Acute Treatment Outcome Among Clinically Depressed Adolescents., Rachel H. Jacobs, Susan G. Silva, Mark A. Reinecke, John F. Curry, Golda S. Ginsburg, Christopher J. Kratochvil, John S. March

Journal Articles: Psychiatry

The effect of perfectionism on acute treatment outcomes was explored in a randomized controlled trial of 439 clinically depressed adolescents (12-17 years of age) enrolled in the Treatment for Adolescents with Depression Study (TADS) who received cognitive behavior therapy (CBT), fluoxetine, a combination of CBT and FLX, or pill placebo. Measures included the Children's Depression Rating Scale-Revised, the Suicidal Ideation Questionnaire-Grades 7-9, and the perfectionism subscale from the Dysfunctional Attitudes Scale (DAS). Predictor results indicate that adolescents with higher versus lower DAS perfectionism scores at baseline, regardless of treatment, continued to demonstrate elevated depression scores across the acute treatment period. …

An Exploratory Analysis Of The Impact Of Family Functioning On Treatment For Depression In Adolescents., Norah C. Feeny, Susan G. Silva, Mark A. Reinecke, Steven Mcnulty, Robert L. Findling, Paul Rohde, John F. Curry, Golda S. Ginsburg, Christopher J. Kratochvil, Sanjeev M. Pathak, Diane E. May, Betsy D. Kennard, Anne D. Simons, Karen C. Wells, Michele Robins, David Rosenberg, John S. March

Journal Articles: Psychiatry

This article explores aspects of family environment and parent-child conflict that may predict or moderate response to acute treatments among depressed adolescents (N = 439) randomly assigned to fluoxetine, cognitive behavioral therapy, their combination, or placebo. Outcomes were Week 12 scores on measures of depression and global impairment. Of 20 candidate variables, one predictor emerged: Across treatments, adolescents with mothers who reported less parent-child conflict were more likely to benefit than their counterparts. When family functioning moderated outcome, adolescents who endorsed more negative environments were more likely to benefit from fluoxetine. Similarly, when moderating effects were seen on cognitive behavioral …

Embolic Complication Of Tako-Tsubo Cardiomyopathy., Vincent M. Figueredo, S Gupta

Department of Medical Genetics Faculty Papers

No abstract provided.

Two Cases Of Primary Laryngeal Amyloidosis, Taimur Saleem, Sanna Fatima, Shehzad Ghaffar, Kanwal Aftab, Sohail Awan

Section of Otolaryngology, Head & Neck Surgery

The larynx is a rare site of involvement of amyloidosis. We report two cases of laryngeal amyloidosis. Both patients were middle aged females with history of persistent hoarseness. Fibreoptic laryngoscopy used for diagnosis in both and debulking of the tumour was performed. Histopathological examination confirmed the diagnosis of amyloidosis. Appropriate follow up is an important part of the long-term management of the disease.

Oncolog Volume 54, Number 11/12, November/December 2009, Dawn Chalaire, Joe Munch

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Treating Neurofibromatosis
• Personalized Therapy for Lung Cancer
• House Call: Genetic Screening for Cancer Risks Gives Patients Options

Parent- Versus Child-Reported Functional Health Status After The Fontan Procedure., Linda M. Lambert, L Luann Minich, Jane W. Newburger, Minmin Lu, Victoria L. Pemberton, Ellen A. Mcgrath, Andrew M. Atz, Mingfen Xu, Elizabeth Radojewski, Darlene Servedio, Brian W. Mccrindle, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: We sought to compare perceptions of functional health status between children who had undergone a Fontan procedure and their parents.

METHODS: Fontan procedure survivors 10 to 18 years of age were included in the study if the child completed the Child Health Questionnaire (CHQ) and the parent completed the parent form to assess the child's functional health status. Comparisons were made between raw domain scores for the parent- and child-completed CHQs.

RESULTS: Between March 2003 and April 2004, 1078 Fontan survivors were screened. Of the 546 eligible and consented patients, 354 were 10-18 years of age and 328 parent/child …

Chromosomal Anomalies Influence Parental Treatment Decisions In Relation To Prenatally Diagnosed Congenital Heart Disease., Sinai C. Zyblewski, Elizabeth G. Hill, Girish S. Shirali, Andrew Atz, Geoffrey Forbus, Javier Gonzalez, Anthony Hlavacek

Manuscripts, Articles, Book Chapters and Other Papers

This study aimed to identify the variables that influence parental treatment decisions after a prenatal diagnosis of congenital heart disease (CHD). The authors reviewed all cases of prenatally diagnosed structural CHD from August 1998 to December 2006 at their center. The following variables were studied as potential predictors of parental intent to treat: maternal age, race, insurance status, obstetric history, fetal gender, univentricular versus biventricular cardiac physiology, and fetal chromosomal abnormality. Uni- and multivariable logistic regression analyses were performed. In the review, 252 consecutive cases of prenatally diagnosed CHD were identified. Of these, 204 women pursued full medical treatment, whereas …

Imrt Commissioning: Multiple Institution Planning And Dosimetry Comparisons, A Report From Aapm Task Group 119., Gary A Ezzell, Jay W Burmeister, Nesrin Dogan, Thomas J Losasso, James G Mechalakos, Dimitris Mihailidis, Andrea Molineu, Jatinder R Palta, Chester R Ramsey, Bill J Salter, Jie Shi, Ping Xia, Ning J Yue, Ying Xiao, Phd

Department of Radiation Oncology Faculty Papers

AAPM Task Group 119 has produced quantitative confidence limits as baseline expectation values for IMRT commissioning. A set of test cases was developed to assess the overall accuracy of planning and delivery of IMRT treatments. Each test uses contours of targets and avoidance structures drawn within rectangular phantoms. These tests were planned, delivered, measured, and analyzed by nine facilities using a variety of IMRT planning and delivery systems. Each facility had passed the Radiological Physics Center credentialing tests for IMRT. The agreement between the planned and measured doses was determined using ion chamber dosimetry in high and low dose regions, …

Life Threatening Spinal Shock And Complete Neurological Recovery Following Minor Spinal Cord Trauma In A Patient With Pre-Existing Cervical Canal Stenosis: Case Report, Vitalis Mung’Ayi, Mahmood Qureshi, John Bugo

Anaesthesiology, East Africa

Mild to moderate trauma to the spinal cord that is complicated by existing cervical canal stenosis or spondylosis can be a life threatening event. It is against this background that we present a 41 year old male with cervical spinal stenosis who developed marked quadriparesis and respiratory embarrassment following collision with a colleague. He was admitted to the intensive care unit, electively sedated, paralysed and ventilated for a period of 48 hours. During the initial 24 hours of admission, he received methylprednisolone as per the National Acute Spinal Cord Injury Studies (NASCIS) protocol. Forty five hours later he had regained …

Model For End-Stage Liver Disease (Meld) Score As A Useful Prognostic Marker In Cirrhotic Patients With Infection, Rustam Khan, Shahab Abid, Wasim Jafri, Safia Awan, Saeed Hamid, Hasnain Shah, Shahid Pervez

Section of Gastroenterology

OBJECTIVE: To determine the association of Model for End stage liver disease (MELD) score to the outcome of cirrhotic patients with bacterial infection and to compare it with Child-Turcott-Pugh (CTP) score.

STUDY DESIGN: Descriptive study.

PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January 2005 to December 2007.

METHODOLOGY: Patients with diagnosis of liver cirrhosis and bacterial infection were included. Demographic features, laboratory data and type of infection were recorded. Multiple logistic regression assays were applied to determine the factors associated with poor outcome in cirrhotics with infection. Receiver-Operating Characteristics (ROC) were used to determine the …

Distribution Of Helicobacter Pylori Virulence Markers In Patients With Gastroduodenal Diseases In Pakistan., Javed Yakoob, Shahab Abid, Z Abbas, Wasim Jafri, Zubair Ahmad, Rashida Ahmed, Muhammad Islam

Section of Gastroenterology

BACKGROUND:

Helicobacter pylori (H. pylori) infection is known to be associated with a spectrum of gastroduodenal diseases. We studied the association of H. pylori virulence markers cytotoxin-associated gene (cagA) and vacuolating associated cytotoxin gene (vacA) alleles in patients with non ulcer dyspepsia (NUD), gastric ulcer (GU), gastric carcinoma (GC) and duodenal ulcer (DU).

METHODS:

H. pylori infection established by both rapid urease test and histology were studied. The cagA and vacA allelic status was determined by polymerase chain reaction (PCR). Sequencing of vacA i1 and i2 PCR product was carried out.

RESULTS:

Two hundred and twenty-four patients were included, 141 …

Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman

Dartmouth Scholarship

Natural killer (NK) cells derived from the human female reproductive tract (FRT) are phenotypically and functionally distinct from those obtained from peripheral blood. Because the FRT is a primary site of human immunodeficiency virus type 1 (HIV-1) infection in women, we determined whether soluble factors secreted by uterine-derived NK (uNK) cells inhibit HIV-1 infection. Clonal populations of uNK cells were activated with interleukin-12 (IL-12) and IL-15, and conditioned media (CM) from these cultures evaluated for their ability to inhibit infection of cells by HIV-1_IIIB, HIV-1_NL4.3, and HIV-1_HC4 (X4-tropic) or HIV-1_BaL (R5-tropic) viruses. We found …

Traumatic Thoracic Asia A Examinations And Potential For Clinical Trials, James S. Harrop, Md, Mitchell G. Maltenfort, Phd, Fred H. Geisler, Md, Phd, William Coleman, Phd, Linda A.T. Jones, Pt, Ms, Edward Wirth, Md, Alexander Vaccaro, Md, Phd

Department of Neurosurgery Faculty Papers

Study Design: Retrospective review of prospective database

Objectives: To define the variability of neurologic examination and recovery after non-penetrating complete thoracic spinal cord injuries (ASIA A).

Background Data: Neurologic examinations after SCI can be difficult and inconsistent. Unlike cervical SCI patients, alterations in thoracic (below T1) complete SCI (ASIA A – based on the ASIA Impairment Scale [AIS]) patients’ exams are based only on sensory testing, thus changes in the neurological level (NL) are determined only by sensory changes.

Methods: A retrospective review of the placebo control patients in a multicenter prospective database utilized for the pharmacologic trial of Sygen. …

Comparison Of Estrogen Receptors, Progesterone Receptors And Her-2/Neu Expression Between Primary And Metastatic Breast Carcinoma, Muhammad Azam, Asim Qureshi, Samina Mansoor

Department of Pathology and Laboratory Medicine

OBJECTIVE: To determine whether receptor status and HER-2/neu status remains same in primary and metastatic breast carcinoma to corresponding lymph nodes of individual patients.

METHODS: Estrogen receptors, progesterone receptors and HER-2/neu immunohistochemical stains were performed on primary and metastatic breast carcinoma to axillary lymph nodes in 100 patients. Data was collected on a Performa and age, tumour size, type, grade and expression of ER, PR and HER-2/neu on primary and metastatic tumours were recorded.

RESULTS: Hormone receptor status was compared between primary and metastatic tumours. Estrogen receptor positivity was observed in 28% primary tumours which were reduced to 25% in …

The False Promise Of Adolescent Brain Science In Juvenile Justice, Terry A. Maroney

Vanderbilt Law School Faculty Publications

Recent scientific findings about the developing teen brain have both captured public attention and begun to percolate through legal theory and practice. Indeed, many believe that developmental neuroscience contributed to the U.S. Supreme Court’s elimination of the juvenile death penalty in Roper v. Simmons. Post-Roper, scholars assert that the developmentally normal attributes of the teen brain counsel differential treatment of young offenders, and advocates increasingly make such arguments before the courts. The success of any theory, though, depends in large part on implementation, and challenges that emerge through implementation illuminate problematic aspects of the theory. This Article tests the legal …

Adenoid Cystic Carcinoma Of The External Auditory Canal, Mohammad Hussham Arshad, Umair Khalid, Shehzad Ghaffar

Section of Otolaryngology, Head & Neck Surgery

This is a rare case of a young male with biopsy proven adenoid cystic carcinoma of the external auditory canal who underwent excision of the lesion with superficial parotidectomy sparing the facial nerve. Histopathology showed perineural invasion, which is a diagnostic hallmark of adenoid cystic carcinoma. Clinical examination, chest X-ray and CT scan showed no signs of recurrence or metastasis 2 years postoperatively.

Results Of Bone Marrow Examinations In Patients With Chronic Immune Thrombocytopenic Purpura Treated With Eltrombopag, Mansoor Saleh, James Bussel, Oliver Meyer, Henrik Frederiksen, Diane Johnni, Manuel Aivado, Andres Brainsky

Haematology and Oncology, East Africa

Background: Bone marrow (BM) reticulin fibers can be increased in conditions such as neoplasms and autoimmune diseases (Frisch Haematol [Budap] 1982; Aharon Lupus 1997) and can lead to a clinical situation similar to osteomyelofibrosis. In healthy individuals, grade 1 and 2 reticulin have been reported in 27–70% and 4–20% of BM biopsies, respectively (Hultdin Med Onc 2007; Beckman Arch Path Int Med 1990; Bauermeister Am J Clin Path 1971). The presence of grade 1/2 reticulin was reported in the BM of up to 67% of patients with immune thrombocytopenic purpura (ITP) (Mufti J Supp Onc 2007). Theoretically, prolonged stimulation of …

Adherence To Host Extracellular Matrix And Serum Components By Enterococcus Faecium Isolates Of Diverse Origin, Meng Zhao, Jouko Sillanpää, Sreedhar R Nallapareddy, Barbara E Murray

Faculty, Staff and Student Publications

Enterococcus faecium has emerged as an important cause of nosocomial infections over the last two decades. We recently demonstrated collagen type I (CI) as a common adherence target for some E. faecium isolates and a significant correlation was found to exist between acm-mediated CI adherence and clinical origin. Here, we evaluated 60 diverse E. faecium isolates for their adherence to up to 15 immobilized host extracellular matrix and serum components. Adherence phenotypes were most commonly observed to fibronectin (Fn) (20% of the 60 isolates), fibrinogen (17%) and laminin (Ln) (13%), while only one or two of the isolates adhered to …

Cross Currents In Protein Misfolding Disorders: Interactions And Therapy, Rodrigo Morales, Kristi M Green, Claudio Soto

Faculty, Staff and Student Publications

Protein Misfolding Disorders (PMDs) are a group of diseases characterized by the accumulation of abnormally folded proteins. Despite the wide range of proteins and tissues involved, PMDs share similar molecular and pathogenic mechanisms. Several epidemiological, clinical and experimental reports have described the co-existence of PMDs, suggesting a possible cross-talk between them. A better knowledge of the molecular basis of PMDs could have important implications for understanding the mechanism by which these diseases appear and progress and ultimately to develop novel strategies for treatment. Due to their similar molecular mechanisms, common therapeutic strategies could be applied for the diseases in this …