Medical Specialties Commons^™

Β-Thujaplicin: A Soil Antifungal, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Background: β-thujaplicin (β-Th), also known as hinokitiol, naturally occurs in cedar mulch, is found in personal care products and has in vitro antitumor activities. It is antibacterial and antifungal, but has not been tested on soil. Scedosporium apiospermum (Sce) is an emerging “extremophile” fungal pathogen found in built outdoor environments.

Purpose: Pilot β-Th as “natural” soil antimicrobial or for isolation of extremophiles, and to explore β-Th resistance as selective advantage to Sce in mulched landscape.

Methods: A variety of outdoor and indoor environments were used for 2 sets of 24 paired soil samples. Soil/H20 slurry (0.1 ml) was spread on …

A Cytosolic Multiprotein Complex Containing P85Α Is Required For Β-Catenin Activation In Colitis And Colitis-Associated Cancer, Tatiana Goretsky, Emily M. Bradford, Hyunji Ryu, Maryam Tahir, Mary Pat Moyer, Tianyan Gao, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-Cat^Ser-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85^ΔIEC) mice develop more severe dextran sodium …

Spectrum Of Histopathological Findings In Postmenopausal Bleeding, Muhammad Usman Tariq, Romana Idress, Ahmed Raheem, Naila Kayani

Department of Pathology and Laboratory Medicine

Objective:To determine the frequencies of histopathological findings in endometrial and endocervical biopsy samples with clinical history of Postmenopausal Bleeding (PMB). Study Design:Descriptive cross-sectional study. Place and Duration of Study:Section of Histopathology, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from February 2012 to January 2013. Methodology:Atotal of 157 consecutive endometrial and endocervical biopsy specimens with history of postmenopausal bleeding were included. After microscopic examination, frequencies of histological findings in different age groups were generated. Chi-square and independent sample t-tests were applied to see whether the difference was significant which was set at p < 0.05. Results:One hundred and twenty-one (77.1%) specimens showed benign pathologies while 36 (22.9%) were malignant. Endometrial polyp was seen in 67 (42.7%) cases followed by endometrial carcinomas in 25 (15.9%), endometrial hyperplasia in 21 (13.4%), cervical carcinoma in 12 (7.6%) and cervical polyps in 9 (5.7%) cases. Ahighly significant increase in the percentage of malignant and pre-malignant lesions was seen with increasing age group (p < 0.001). Mean age of patients with type-2 endometrial carcinoma was higher than type-1 endometrial carcinoma but statistical significance was not observed (70.2 ±6.5 vs. 61.8 ±9.1 years respectively, p=0.069). Conclusion:Although benign pathologies were more common in postmenopausal bleeding but the collective proportion of endometrial and cervical malignancies and pre-malignant conditions was quite high. Therefore, PMB should be urgently evaluated for cause and early commencement of treatment

Loss Of Glycosaminoglycan Receptor Binding After Mosquito Cell Passage Reduces Chikungunya Virus Infectivity, Amber M. Paul, Dhiraj Acharya, John F. Anderson, Faqing Huang, Fengwei Bai

Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell derived CHIKV (CHIKVmos) has slower replication than mammalian cell derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic …

Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman

Publications and Research

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic …

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …

Breast Cancer Rehabilitation: Clinical Examination And Outcomes Assessment, Nicole L. Stout, Shana Harrington, Lucinda Pfalzer, Mary Insana Fisher

Physical Therapy Faculty Publications

Breast cancer is the most commonly diagnosed cancer in women in the United States. The treatment for breast cancer occurs along a protracted time period and includes many different disease treatment modalities. These treatments carry with them a large number of adverse effects that negatively impact function in both the short term and long term. It is necessary for rehabilitation providers to interface with patients being treated for breast cancer throughout the continuum of care so that interval assessments can be conducted to identify emerging impairments and alleviate disability. To achieve this, the rehabilitation provider must have an understanding of …

Home Exercise Adherence In An Underserved Ecuadorian Community, Joseph M. Day, Jean Irion, Meridith Anile, Jared Henson, Ben Roussel, Christina Shepherd, Huybrechts Bindele

Physical Therapy Faculty Publications

Purpose: Physical therapy service learning projects and volunteer experiences in foreign countries are becoming more commonplace. Patients in underserved regions are not likely to receive therapy services regularly; therefore, adherence to a home exercise program (HEP) is critical. The primary purpose of this study was to observe home exercise adherence rates between the 1st and 2nd visits in an underserved population. The secondary purpose of this study was to determine specific factors that affect HEP adherence in this population.

Methods: Consecutive patients seen in Santo Domingo, Ecuador were considered for participation in this observational study. All patients were recruited from …

Establishing Quality Control Values For Hematology Parameters: An Insight, Muhammad Shariq Shaikh

Department of Pathology and Laboratory Medicine

No abstract provided.

Hereditary Sensory Autonomic Neuropathy Ii, A Rare Disease In A Large Pakistani Family, Fazal M. Arain, Prem Chand

Department of Paediatrics and Child Health

Hereditary Sensory Autonomic Neuropathy II (HSAN II) is a rare genetic disorder, characterized by severe loss of pain, temperature and touch sensation. Injuries in these patients can progress to necrosis and shedding of digits and limbs. Here we report two cases of HSAN II belonging to a Pakistani family. Individual 1, a forty five year old man, had complete loss of pain sensation since birth. Self-mutilation and complication of injuries resulted in the shedding of all the digits and right foot and surgical amputation of left leg. Individual 2, a five year old girl,had delay in healing of wounds and …

Clinical Significance Of The Integrin Α6Β4 In Human Malignancies, Rachel L Stewart, Kathleen L O'Connor

Pathology and Laboratory Medicine Faculty Publications

Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK, and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome …

Muscle Weakness During Aging: A Deficiency State Involving Declining Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

This essay begins by proposing that muscle weakness of old age from sarcopenia is due in large part to reduced capillary density in the muscles, as documented in 9 reports of aged persons and animals. Capillary density (CD) is determined by local levels of various angiogenic factors, which also decline in muscles with aging, as reported in 7 studies of old persons and animals. There are also numerous reports of reduced CD in the aged brain and other studies showing reduced CD in the kidney and heart of aged animals. Thus a waning angiogenesis throughout the body may be …

Lymphangioma Circumscriptum: Clinicopathological Spectrum Of 29 Cases, Saira Fatima, Nasir Uddin, Romana Idrees, Khurram Minhas, Zubair Ahmad, Rashida Ahmad, Naila Kayani, Muhammad Arif

Department of Pathology and Laboratory Medicine

Objective:
To describe the clinicopathological spectrum of Lymphangioma Circumscriptum (LC).
Study Design:
Observational case series.
Place and Duration of Study:
Department of Pathology and Microbiology, AKUH, Karachi, from 2002 to 2012.
Methodology:
All reported cases of LC were retrieved from medical record. Clinical and pathological features were noted. Frequency percentages were determined.
Results:
There were 29 cases of LC predominantly males (62%). The mean age was 27.17 ±15.5 years. The commonest sites was anal/perianal region (24%) followed by extremities (17%) and tongue, (14%). Vulval LC was seen in 3 patients. Two cases were described on scrotum. The lesions were most …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Meta-Analysis Of Dna Methylation And Expression In Liver Cancer Patients, Daniele Todorov, Barbara Stefanska, Katarzyna Lubecka-Pietruszewska

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hepatocellular carcinoma (HCC), the most common liver cancer, is the second leading cause of cancer-related death worldwide. HCC is often diagnosed at late stages, for which there are no effective chemotherapies. Biomarkers unique to HCC patients could be used to detect HCC early and improve treatment. In the present project, we have performed a meta-analysis to compare the gene-specific DNA methylation and gene expression patterns of HCC patients as reported by four independent studies. Our goal was to discover the strongest changes that distinguish HCC from normal tissue. The relationship between methylation and expression in HCC was examined and genes …

Acute Myocardial Infarction And Myocardial Ischemia-Reperfusion Injury: A Comparison, Satwat Hashmi, Suhail Al-Salam

Department of Biological & Biomedical Sciences

Myocardial infarction (MI) denotes the death of cardiac myocytes due to extended ischemia. Myocardial reperfusion is the restoration of coronary blood flow after a period of coronary occlusion. Reperfusion has the potential to salvage ischemic myocardium but paradoxically can cause injury, a phenomenon called as 'reperfusion injury' (IR). Standard histologic, immunohistochemical and Elisa techniques were used to study the histopathologic, oxidative, apoptotic and inflammatory changes in MI and IR. The IL-6 levels in the LV of the MI group were significantly raised as compared to the IR group (P=0.0008). Plasma IL-6 was also significantly increased in the MI group as …

Autologous Hematopoietic Stem Cell Transplantation-10 Years Of Data From A Developing Country, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh

Department of Pathology and Laboratory Medicine

Intensive chemotherapy followed by autologous stem cell transplantation is the treatment of choice for patients with hematological malignancies. The objective of the present study was to evaluate the outcomes of patients with mainly lymphoma and multiple myeloma after autologous stem cell transplant. The pretransplant workup consisted of the complete blood count, an evaluation of the liver, kidney, lung, and infectious profile, chest radiographs, and a dental review. For lymphoma, all patients who achieved at least a 25% reduction in the disease after salvage therapy were included in the study. Mobilization was done with cyclophosphamide, followed by granulocyte colony-stimulating factor, 300 …

Symptomatic Surgically Treated Non-Neoplastic Cysts Of The Central Nervous System: A Clinicopathological Study From Pakistan, Nasir Ud Din, Huma Arshad, Zubair Ahmad, Sheema H Hasan, Mohammad Ehsan Bar

Department of Pathology and Laboratory Medicine

Objective: To report clinicopathologic features of symptomatic surgically removed non-neoplastic cysts of the central nervous system (CNS). Study Design: Case series. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from 2003 to 2012. Methodology: All non-neoplastic CNS cysts reported during the study period were retrieved and reviewed. Age, gender, location, histologic type and clinical features were noted. Results: A total of 124 cysts were diagnosed in the study period. These included 44 epidermoid cysts (mean age 30.5 ± 13.8 years), 35 colloid cysts (mean age 31 ± 13.2 years), 32 arachnoid cysts (mean age 24.8 ± 20.2 …

Nitric Oxide-Releasing Aspirin Suppresses Nf-Κb Signaling In Estrogen Receptor Negative Breast Cancer Cells In Vitro And In Vivo, Niharika Nath, Mitali Chattopadhyay, Deborah B. Rodes, Anna Nazarenko, Ravinder Kodela, Khosrow Kashfi

Publications and Research

Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model …

Bacterially-Based Immune Challenges And Trauma Elicit Terminal Investment In Male Aedes Aegypti, Molly K. Schumacher

Theses and Dissertations

Investment in life history traits such as immune function and reproduction is constrained by finite available resources. A cost-of-immunity trade-off may occur in response to infection when resources are diverted away from reproductive effort and into an immune response. Alternatively, an infected individual may enhance reproductive effort to maximize terminal reproductive success in response to the survival threat inherent to infection (terminal investment). We measured male Aedes aegypti reproductive behavior following inoculations with: living bacteria; killed bacteria as an immune elicitor; and a sham control. Mating competitiveness relative to naïve males was also determined through a binary mate choice experiment …

Development Of A Biosensor-Based Rapid Urine Test For Detection Of Urogenital Schistosomiasis., Kathleen E Mach, Ruchika Mohan, Shailja Patel, Pak Kin Wong, Michael Hsieh, Joseph C Liao

Urology Faculty Publications

No abstract provided.

Targeting Il13ralpha2 Activates Stat6-Tp63 Pathway To Suppress Breast Cancer Lung Metastasis, Panagiotis Papageorgis, Sait Ozturk, Arthur W. Lambert, Christiana M. Neophytou, Alexandros Tzatsos, Chen K. Wong, Sam Thiagalingam, Andreas I. Constantinou

Anatomy and Regenerative Biology Faculty Publications

Introduction

Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action.

Methods

An unbiased approach using gene expression profiling of a BLBC progression model and in silicoleveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was …

The Mouse That Trolled: The Long And Tortuous History Of A Gene Mutation Patent That Became An Expensive Impediment To Alzheimer's Research, Tania M. Bubela, Saurabh Vishnubhakat, Robert Cook-Deegan

Office of the Provost

This case study presents the tale of the academic discovery of a rare mutation for early-onset Alzheimer's disease that was patented by a sole inventor and licensed to a non-practicing entity (NPE), the Alzheimer's Institute of America (AIA). Our aims are (1) to relate this story about patents, research tools, and impediments to medical progress, and (2) to inform ongoing debates about how patents affect research, disposition of university inventions, and the distribution of benefits from publicly funded research. We present an account of the hunt for Alzheimer's genes, their patenting, assignment, and enforcement based on literature, litigation records and …

Predictors Of Orthopaedic Surgery In Ncaa Athletes, Dean Wang, Caitlin M. Rugg, Erik Mayer, Pamela Sulzicki, Jeremy Vail, Sharon L. Hame

Athletic Training Faculty Publications

Objectives: Orthopaedic injury and surgery is relatively common in National Collegiate Athletic Association (NCAA) athletes and can have devastating career consequences. However, there is a paucity of data regarding predictors of orthopaedic surgery in collegiate athletes. The purpose of this study was to analyze player-related predictors of orthopaedic surgery, including that of the shoulder, hip, and knee, in NCAA athletes. Methods: All NCAA Division I collegiate athletes at a single institution who began participation from the 2003-2004 through 2008-2009 seasons were retrospectively identified. Player-related factors, including gender, sport, and any pre-college upper or lower extremity orthopaedic surgery, were elicited through …

Effect Of Sirna Pre-Exposure On Subsequent Response To Sirna Therapy, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Nicole Chan, Hasan Uludag

Pharmacy Faculty Articles and Research

PURPOSE. An alternative cancer therapy based on RNA interference (RNAi) has shown considerable promise but the possibility of resistance development is not known. This study explored the possibility of therapeutic resistance against siRNA nanoparticles in human cancer cells. METHODS. Two approaches to siRNA treatment were undertaken using lipid-modified polyethylenimines, a single high concentration (shock) and repeated increasing concentrations (gradual). The targets were Mcl-1, RPS6KA5 and KSP in MDA-MB-435 cells. RESULTS. There was no evidence of resistance development in shock-treated cells, while the decrease in mRNA levels of targeted proteins was not as robust in naïve cells in gradual treatment. However, …

Aspergillus Fumigatus Spinal Abscess In An Immunocompetent Child, Mohammad Faizan Zahid, Joveria Farooqi

Department of Pathology and Laboratory Medicine

No abstract provided.

Iron Chelation In Patients With Transfusion Dependent Thalassemia: An Insight On Response To Deferasirox, Muhammad Shariq Shaikh, Salman Naseem Adil

Department of Pathology and Laboratory Medicine

No abstract provided.

Klf4-Sqstm1/P62-Associated Prosurvival Autophagy Contributes To Carfilzomib Resistance In Multiple Myeloma Models., Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 …

The Cognition-Enhancing Effects Of Psychostimulants Involve Direct Action In The Prefrontal Cortex, Robert C. Spencer, David M. Devilbiss, Craig Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Psychostimulants are highly effective in the treatment of attention-deficit/hyperactivity disorder. The clinical efficacy of these drugs is strongly linked to their ability to improve cognition dependent on the prefrontal cortex (PFC) and extended frontostriatal circuit. The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. …

Galectin-1: A Biomarker Of Surgical Stress In Murine Model Of Cardiac Surgery, Satwat Hashmi, Suhail Al-Salam

Department of Biological & Biomedical Sciences

Galectin-1 (GAL-1) belongs to the family of β-galactoside-binding lectins. It regulates cell-cell and cell-matrix interactions, the immune response, apoptosis, cell cycle, RNA splicing and neoplastic transformation. We investigate the effect of heart manipulation secondary to cardiac surgery on the level of GAL-1 in murine heart and plasma. Male C57B6/J mice were used for adopted model of cardiac surgery. Heart samples were processed for immunohistochemical and immunofluorescent labeling, Enzyme linked immunosorbent assay and quantitative RT-PCR to identify GAL-1 levels in the heart and plasma during the first 24 hours following cardiac surgery. There is significant increase of GAL-1 in the LV …