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Interrelation Of Inflammation And App In Sibm: Il-1 Beta Induces Accumulation Of Beta-Amyloid In Skeletal Muscle., Jens Schmidt, Konstanze Barthel, Arne Wrede, Mohammad Salajegheh, Mathias Bähr, Marinos C Dalakas

Department of Neurology Faculty Papers

Distinct interrelationships between inflammation and beta-amyloid-associated degeneration, the two major hallmarks of the skeletal muscle pathology in sporadic inclusion body myositis (sIBM), have remained elusive. Expression of markers relevant for these pathomechanisms were analysed in biopsies of sIBM, polymyositis (PM), dermatomyositis (DM), dystrophic and non-myopathic muscle as controls, and cultured human myotubes. By quantitative PCR, a higher upregulation was noted for the mRNA-expression of CXCL-9, CCL-3, CCL-4, IFN-gamma, TNF-alpha and IL-1 beta in sIBM muscle compared to PM, DM and controls. All inflammatory myopathies displayed overexpression of degeneration-associated markers, yet only in sIBM, expression of the mRNA of amyloid precursor …

Download The Pdf Of The Entire Issue: Jefferson Surgical Solutions Vol. 3, Issue 1, Spring 2008

Jefferson Surgical Solutions

No abstract provided.

On The Job

Jefferson Surgical Solutions

No abstract provided.

Transplants And Pregnancy: A Surprisingly Good Fit

Jefferson Surgical Solutions

No abstract provided.

Predictive Factors For Early Aspiration In Liver Abscess, Rustam Khan, Saeed Hamid, Shahab Abid, Wasim Jafri, Zaigham Abbas, Mohammed Islam, Hasnain Shah, Shaalan Beg

Department of Medicine

Aim: To determine the predictive factors for early aspiration in liver abscess.

Methods: A retrospective analysis of all Patients with liver abscess from 1995 to 2004 was performed. Abscess was diagnosed as amebic in 661 (68%) Patients, pyogenic in 200 (21%), indeterminate in 73 (8%) and mixed in 32 (3%). Multiple logistic regression analysis was performed to determine predictive factors for aspiration of liver abscess.

Results: A total of 966 Patients, 738 (76%) male, mean age 43 17 years, were evaluated: 540 Patients responded to medical therapy while adjunctive percutaneous aspiration was performed in 426 Patients. Predictive factors for aspiration …

Com Outlook Spring 2008, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Retinopathy Of Prematurity: Frequency And Risk Factors In A Tertiary Care Hospital In Karachi, Pakistan, Ather M. Taqui, Reema Syed, Tanveer Anjum Chaudhry, Khabir Ahmad, Muhammad S. Salat

Section of Ophthalmology

Introduction: To determine the frequency of Retinopathy of Prematurity (ROP) in the premature infants born in a tertiary care hospital and to determine the risk factors associated with it.
Methods: This was a retrospective analysis of premature infants with birth weight < or = 1500 grams or gestational ago < or = 32 weeks, admitted to the Neonatal Intensive Care Unit of a tertiary care hospital in a three year period. The infants underwent eye examinations between their 4th and 7th week of life. Univariate and multiple logistic regression analysis were performed to determine the association between risk factors and ROP development.
Results: Sixty eight infants were included in the analysis. Out of these, 22 (32.4%) developed ROP (inclusive of all stages) and 14 (20.6%) developed threshold disease. Multiple logistic regression analysis revealed that low gestational age, sepsis and respiratory distress syndrome were independent predictors for the development of ROP.
Conclusion: The frequency of ROP in our hospital was on the …

Cannabinoids: A Novel Treatment Strategy For Retinal Neurodegenerative Disorders, Sandeep Samudre

Theses and Dissertations in Biomedical Sciences

Synthetic and naturally occurring cannabinoids are known to decrease intraocular pressure (IOP). Glaucomatous damage to the retina and optic nerve progresses even after therapy to maintain normal intraocular pressure (IOP). Topical application of cannabinoids decreases IOP while not affecting blood pressure or heart rate. Based upon their effects on other tissues, we hypothesize that these analogs reduce IOP and may also confer direct neuroprotective effects on the retina, possibly via CB1 and/or CB2 receptors. The purpose of this study is to determine if the newly synthesized CB agonists, lipid soluble O-1812 (CB 1), and water soluble O-2545 (CB 1

The …

The Application Of Innovative High-Throughput Techniques To Serum Biomarker Discovery, Izabela Debkiewicz Karbassi

Theses and Dissertations in Biomedical Sciences

Time-of-flight mass spectrometry continues to evolve as a promising technique for serum protein expression profiling and biomarker discovery. As seen in our initial SELDI-TOF MS and MALDI-TOF MS profiling study of serum for the assessment of breast cancer risk, many profiling strategies typically employ single chemical affinity beads or surfaces to decrease sample complexity of dynamic fluids like serum. However, most proteins, captured on a particular surface or bead, are not resolved in the lower mass range where mass spectrometers are most effective. To this end we have designed an expression profiling workflow that utilizes immobilized trypsin paramagnetic beads in …

Digest Of The Philadelphia College Of Osteopathic Medicine (Spring 2008), Philadelphia College Of Osteopathic Medicine

Digest

The Spring 2008 issue of the Digest of the Philadelphia College of Osteopathic Medicine includes the following articles:

• Opening Remarks
• PCOM Updates and Kudos
• Development News
• The Arts in Medicine: A Powerful Force of Healing
• Visual Arts: Another Kind of Voice
• Dance: Staying Alive
• Creative Writing: Breaking Down Barriers
• Photography: A Different View
• Year One: Observations from Four Residents
• The Heart of the Matter: Long QT Syndrome Research
• Class Notes
• In Memoriam
• My Turn Essay
• PCOM Events

17beta-Estradiol Increases Basal But Not Bradykinin-Stimulated Release Of Active T-Pa In Young Postmenopausal Women, Mias Pretorius, Gary Van Guilder, Raul J Guzman, James M Luther, Nancy J Brown

Health and Nutritional Sciences Faculty Publications

Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17beta-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2+/-2.3 years) who were randomized to receive 17beta-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before …

Day Care Surgery At A New University Teaching Hospital: A Review Out Of The Aga Khan University Hospital, Nairobi, Edwin Mogere

Master of Medicine in General Surgery

Introduction: Day Care Surgery (DCS) is the surgical care of patients on a planned non-residential basis. The objective of the study was to assess the performance of DCS in the context of a developing country within the private sector. Data from a new DCS unit was compared to internationally accepted indicators of the quality of care. Methodology: A hospital based retrospective chart review of all patients operated on within 10 surgical subspecialties was performed. The review period was the June 2006 to July 2007(12 months). Analysis (SPSS version 11.5): Outcome measures included in-patient to DCS ratio in the various specialties; …

Disruption Of C-Jun Reduces Cellular Migration And Invasion Through Inhibition Of C-Src And Hyperactivation Of Rock Ii Kinase., Xuanmao Jiao, Sanjay Katiyar, Manran Liu, Susette C Mueller, Michael P. Lisanti, Anping Li, Timothy G Pestell, Kongming Wu, Xiaoming Ju, Zhiping Li, Erwin F Wagner, Tatsuo Takeya, Chenguang Wang, Richard G Pestell

Kimmel Cancer Center Faculty Papers

The spread of metastatic tumors to different organs is associated with poor prognosis. The metastatic process requires migration and cellular invasion. The protooncogene c-jun encodes the founding member of the activator protein-1 family and is required for cellular proliferation and DNA synthesis in response to oncogenic signals and plays an essential role in chemical carcinogenesis. The role of c-Jun in cellular invasion remains to be defined. Genetic deletion of c-Jun in transgenic mice is embryonic lethal; therefore, transgenic mice encoding a c-Jun gene flanked by LoxP sites (c-jun(f/f)) were used. c-jun gene deletion reduced c-Src expression, hyperactivated ROCK II signaling, …

Metastatic Disease To The Pancreas And Spleen, Shayna L. Showalter, Eric Hager, Charles J. Yeo

Department of Surgery Faculty Papers

Isolated metastases to the pancreas and spleen are a rare occurrence. When they are diagnosed, pancreatic metastases are most often from renal cell carcinoma, lung cancer, and breast cancer. The most common source of splenic metastases is gynecological in origin; the overwhelming majority is ovarian. If extensive staging studies reveal these metastases to be isolated, then curative resection may be warranted. This review will demonstrate that long-term survival may be achieved in patients with isolated metastases and a prolonged disease-free interval.

Factors Influencing In-Hospital Length Of Stay And Mortality In Cancer Patients Suffering From Febrile Neutropenia, Amar Lal, Yasmin Bhurgri, Nida Rizvi, Mohni Virwani, Rasheed Uddin Memon, Wajeeha Saeed, Muhammad Rizwan Sardar, Pawan Kumar, Asim Jamal Shaikh, Salman Adil, Nehal Masood, Mohammad Khurshid

Section of Haematology/Oncology

Introduction: Febrile neutropenia (FN) is a major complication of chemotherapy, costly in terms of morbidity, mortality and associated financial expenditure. The present study was conducted with the goal of highlighting FN as a serious problem in Pakistan, with the longer term objective of improved cancer survival, reduction in length of stay (LOS) in hospital, morbidity, mortality and costs in our existing developing country scenario. Methods: A cross-sectional descriptive study was conducted on Patients, > or =18 years, admitted with FN as a consequence of chemotherapy at a referral hospital in Karachi from 1st September 2006 to 30th April 2007. Results: A …

Excess Adenosine In Murine Penile Erectile Tissues Contributes To Priapism Via A2b Adenosine Receptor Signaling, Tiejuan Mi, Shahrzad Abbasi, Hong Zhang, Karen Uray, Janci L Chunn, Ling Wei Xia, Jose G Molina, Norman W Weisbrodt, Rodney E Kellems, Michael R Blackburn, Yang Xia

Faculty, Staff and Student Publications

Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was …

Basis For Treatment Of Tuberculosis Among Hiv-Infected Patients In Tanzania: The Role Of Chest X-Ray And Sputum Culture, Muhammad Bakari, Robert D. Arbeit, Lillian Mtei, Johnson Lyimo, Richard Waddell, Mecky Matee, Bernard F. Cole, Susan Tvaroha

Dartmouth Scholarship

Active tuberculosis (TB) is common among HIV-infected persons living in tuberculosis endemic countries, and screening for tuberculosis (TB) is recommended routinely. We sought to determine the role of chest x-ray and sputum culture in the decision to treat for presumptive TB using active case finding in a large cohort of HIV-infected patients. Ambulatory HIV-positive subjects with CD4 counts ≥ 200/mm3 entering a Phase III TB vaccine study in Tanzania were screened for TB with a physical examination, standard interview, CD4 count, chest x-ray (CXR), blood culture for TB, and three sputum samples for acid fast bacillus (AFB) smear and culture.

Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr^-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …

Knowledge And Practice Of Radiation Safety Among Invasive Cardiologists, Nasir Rahman, Sajid H. Dhakam, Azam Shafqut, Sadia Qadir, Fateh Ali Tipoo

Section of Cardiology

OBJECTIVE: To assess the availability, practices and knowledge of radiation safety measures among invasive cardiologists in a tertiary care hospital.

METHOD: A cross sectional survey of invasive cardiologists working in academic institutions was conducted using a questionnaire.

RESULTS: A total of 28 cardiologists completed the questionnaire with a mean working experience of 10.5 + 7.6 years. All were of the opinion that radiation safety is extremely important and 93% always used lead aprons. Less than half of them used other radiation protective measures including thyroid collar, lead eyeglasses and lead shields. Only 7% regularly utilized a radiation dose badge to …

Schizophrenia: A Concept, Haider A Naqvi

Department of Psychiatry

Much of the current research-work into biological basis of mental disorders is predicted on implicit concept of disease that is less critical and sophisticated as it should be. It is remarkable, how the fundamental conceptual frame work of schizophrenia, as proposed by Professor Emil Kraepelin has stayed the same, since its inception almost 100-years ago. This review explores these issues besides highlighting alternative disease classification that suits behavioural neuroscience research.

Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …

Gastric Corpus Polyps Associated With Proton Pump Inhibitors Therapy, Javed Yakoob, Zaigham Abbas, Wasim Jafri, Zubair Ahmad

Section of Gastroenterology

The prevalence of Gastroesophageal Reflux Disease (GERD) is rapidly rising in Asia. We describe here a case of 51 years old man who had surgery for esophageal leiomyoma and received long-term therapy with Proton Pump Inhibitors (PPIs) for persisting reflux symptoms. On Esophago-Gastroduodenoscopy (EGD) several sessile polyps were seen in the gastric corpus. Earlier EGD done 15 years back had not demonstrated those polyps. Sections revealed polypoid fragments of glandular epithelium with dilated glands and negative histology for H. pylori. Polymerase chain reaction for 16S ribosomal RNA gene (16S rRNA PCR) of H. pylori was also negative. This is the …

Unique Structures In A Tumor Herpesvirus Revealed By Cryo-Electron Tomography And Microscopy, Wei Dai, Qingmei Jia, Eric Bortz, Sanket Shah, Jun Liu, Ivo Atanasov, Xudong Li, Kenneth A Taylor, Ren Sun, Z Hong Zhou

Faculty, Staff and Student Publications

Gammaherpesviruses, including the human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, are causative agents of lymphomas and other malignancies. The structural characterization of these viruses has been limited due to difficulties in obtaining adequate amount of virion particles. Here we report the first three-dimensional structural characterization of a whole gammaherpesvirus virion by an emerging integrated approach of cryo-electron tomography combined with single-particle cryo-electron microscopy, using murine gammaherpesvirus-68 (MHV-68) as a model system. We found that the MHV-68 virion consists of distinctive envelope and tegument compartments, and a highly conserved nucleocapsid. Two layers of tegument are identified: an inner tegument layer …

Cryo-Electron Tomography Of Kaposi's Sarcoma-Associated Herpesvirus Capsids Reveals Dynamic Scaffolding Structures Essential To Capsid Assembly And Maturation, Binbin Deng, Christine M O'Connor, Dean H Kedes, Z Hong Zhou

Faculty, Staff and Student Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is a recently discovered DNA tumor virus that belongs to the gamma-herpesvirus subfamily. Though numerous studies on KSHV and other herpesviruses, in general, have revealed much about their multilayered organization and capsid structure, the herpesvirus capsid assembly and maturation pathway remains poorly understood. Structural variability or irregularity of the capsid internal scaffolding core and the lack of adequate tools to study such structures have presented major hurdles to earlier investigations employing more traditional cryo-electron microscopy (cryoEM) single particle reconstruction. In this study, we used cryo-electron tomography (cryoET) to obtain 3D reconstructions of individual KSHV capsids, allowing …

Activation Of Heat Shock And Antioxidant Responses By The Natural Product Celastrol: Transcriptional Signatures Of A Thiol-Targeted Molecule, Amy Trott, James D West, Lada Klaić, Sandy D Westerheide, Richard B Silverman, Richard I Morimoto, Kevin A Morano

Faculty, Staff and Student Publications

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional …

Incorporating Ethnicity Into Genetic Risk Assessment For Alzheimer Disease: The Reveal Study Experience, Peter J. Whitehouse, Melissa Barber Butson

Faculty Scholarship

PURPOSE: To describe how investigators in a multisite randomized clinical trial addressed scientific and ethical issues involved in creating risk models based on genetic testing for African American participants. METHODS: The following informed our decision whether to stratify risk assessment by ethnicity: evaluation of epidemiological data, appraisal of benefits and risks of incorporating ethnicity into calculations, and feasibility of creating ethnicity-specific risk curves. Once the decision was made, risk curves were created based on data from a large, diverse study of first-degree relatives of patients with Alzheimer disease. RESULTS: Review of epidemiological data suggested notable differences in risk between African …

Retinoic Acid Decreases Atf-2 Phosphorylation And Sensitizes Melanoma Cells To Taxol-Mediated Growth Inhibition, Ying Huang, Jennifer Minigh, Sarah Miles, Richard N. Niles

Biochemistry and Microbiology

Cutaneous melanoma is often resistant to chemo- and radiotherapy. This resistance has recently been demonstrated to be due, at least in part, to high activating transcription factor 2 (ATF-2) activity in these tumors. In concordance with these reports, we found that B16 mouse melanoma cells had higher levels of ATF-2 than immortalized, but non-malignant mouse melanocytes. In addition, the melanoma cells had a much higher amount of phosphorylated (active) ATF-2 than the immortalized melanocytes. In the course of determining how retinoic acid (RA) stimulates activating protein-1 (AP-1) activity in B16 melanoma, we discovered that this retinoid decreased the phosphorylation of …

N-Acetyl-B-D-Glucosaminidase And Inflammatory Response After Cardiopulmonary Bypass, Perwaiz Iqbal, Hasanat M Sharif, Naseema Mehboobali, Farzana A Yousuf, Abrar H Khan, Frank W Sellke

Department of Biological & Biomedical Sciences

OBJECTIVE: To determine the changes in activity of plasma N-acetyl-beta-D-glucosaminidase, a marker for inflammation as well as renal, pulmonary and cardiac damage and proinflammatory cytokines in patients undergoing coronary artery bypass grafting and find out the relationship between their plasma levels with clinical outcome of patients.

STUDY DESIGN: Cross-sectional study.

PLACE AND DURATION OF STUDY: The Aga Khan University, Karachi, from January to June 2003.

PATIENTS AND METHODS: N-acetyl-beta-D-glucosaminidase (NAG) activity and concentrations of tumor necrosis factor-alpha of (TNFalpha), interleukin 6 (IL-6), interleukin 8 (IL8) and granulocyte-macrophage colony stimulating factor (GM-CSF) were monitored in plasma samples of 12 angina patients …

Precipitating Factors Of Hepatic Encephalopathy In Patients With Chronic Liver Disease At Civil Hospital Karachi, Dileep K Rohra, Jaipal, Ameer A Khowaja, Khalid Mahmood, Kanya Lal Ahuja

Department of Biological & Biomedical Sciences

No abstract provided.

Precipitating Factors And The Outcome Of Hepatic Encephalopathy In Liver Cirrhosis., Dileep K. Rohra, Jaipal, Ameer A. Khowaja, Khalid Mahmood, Kanya Lal Ahuja

Department of Medicine

No abstract provided.