Pathology Commons^™

Most Cancers Are Caused By Bad Luck Mutations: Scientific Explanation?, Shahid Pervez

Department of Pathology and Laboratory Medicine

No abstract provided.

The Role Of P62/Imp2 In Hepatocellular Carcinoma Progression, Mengtao Xing

Open Access Theses & Dissertations

The family of insulin- like growth factor 2 mRNA binding proteins (IMPs) contains three members: IMP1, p62/IMP2 and IMP3. All these proteins are oncofetal proteins, expressed during embryogenesis and lost in most tissues in adults. However, p62/IMP2 were found overexpressed in various cancers but its function in carcinogenesis remains to be investigated. Our previous studies found that p62/IMP2 was not only overexpressed in hepatocellular carcinoma (HCC) tissues, but also overexpressed in HCC cell lines. To explore the biological roles of p62/IMP2 in HCC progression, p62/IMP2 was knockout in two p62/IMP2 positive HCC cell lines (SNU449, HepG2). Due to the low …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Value Of Dedicated Research Time For Imgs In Obtaining Surgical Residency Training Positions: A 10-Year Review Of Applicants From A Medical College In Pakistan, Mohammad Raheel Jajja, Marvi Tariq, Salila Shoaib Hashmi, Thomas F. Dodson, Rashida Ahmed

Department of Pathology and Laboratory Medicine

Objective: International Medical Graduates (IMGs) secured greater than 10% of all general surgery (GS) residency positions in the US during the past decade. The Match process remains competitive, with a significant number of IMGs performing dedicated research before residency application. The impact of such research remains largely unknown. We aimed to provide an objective analysis of the impact of dedicated research time on obtaining a categorical GS residency position.
Design: Data for National Resident Matching Program Match results from 2008-2017 was compiled from annual Match lists of the Aga Khan University, Medical College (Karachi, Pakistan). Medical graduates provided this information …

Blended Learning Mediated Fostering Of Students’ Engagement In An Undergraduate Medical Education Module, Lena Jafri, Hafsa Majid, Salman Siddiqi, Najmul Islam, Faraz Khurshid

Department of Pathology and Laboratory Medicine

Introduction: The study investigated students’ perception of introducing blended learning strategies to engage and motivate them towards lecture halls and Problem Based Learning (PBL) sessions for improving the quality of the overall students’ learning experience.
Methods: A prospective study was conducted at the Aga Khan University Medical College involving a total of one hundred four (104) year II medical students for the Endocrine and Reproduction module in the academic year 2018. This module ran for six weeks. Modifications in teaching methods were made for this module introduced after approval from Endocrine & Reproduction module, year II and curriculum committees. Written …

Assessing Nutritional Status Of Critically Ill Patients Using Serum Prealbumin Levels, Khushbakht Arbab, Hafsa Majid, Lena Jafri, Aysha Habib, Ahmed Raheem, Bushra Jamil, Bushra Akram, Madiha Hashmi

Department of Pathology and Laboratory Medicine

Background: Malnutrition in hospitalized patients, contributes to poor outcomes. Biomarker serum prealbumin, can prevent the complications by commencement of nutritional support to improve clinical outcomes. This study was designed to assess the association between low serum prealbumin level (<18 mg/dl), with length of stay and all cause intensive care unit mortality.
Methods: This cross-sectional study was conducted from July 2016 to July 2017 at Aga Khan University Hospital Karachi Pakistan. All consecutive patients, aged between 18 to 70 years, admitted in medical or surgical intensive care unit were included. Demographic, clinical history and blood samples for analysing serum prealbumin were obtained on first day of admission. Patients were categorized into two groups …

Seroepidemiology Of Parechovirus A3 Neutralizing Antibodies, Australia, The Netherlands, And United States, Eveliina Karelehto, Lieke Brouwer, Kimberley Benschop, Jen Kok, Kerri Basile, Brendan Mcmullan, William Rawlinson, Julian Druce, Suellen Nicholson, Rangaraj Selvarangan, Christopher J. Harrison, Kamani Lankachandra, Hetty Van Eijk, Gerrit Koen, Menno De Jong, Dasja Pajkrt, Katja C. Wolthers

Manuscripts, Articles, Book Chapters and Other Papers

© 2018, Centers for Disease Control and Prevention (CDC). All rights reserved. Recent parechovirus A3 (PeV-A3) outbreaks in Australia suggest lower population immunity compared with regions that have endemic PeV-A3 circulation. A serosurvey among populations in the Netherlands, the United States, and Australia before and after the 2013 Australia outbreak showed high PeV-A3 neutralizing antibody prevalence across all regions and time periods, indicating widespread circulation.

Dichotomous Scoring Of Tdp-43 Proteinopathy From Specific Brain Regions In 27 Academic Research Centers: Associations With Alzheimer's Disease And Cerebrovascular Disease Pathologies, Yuriko Katsumata, David W. Fardo, Walter A. Kukull, Peter T. Nelson

Biostatistics Faculty Publications

TAR-DNA binding protein 43 (TDP-43) proteinopathy is a common brain pathology in elderly persons, but much remains to be learned about this high-morbidity condition. Published stage-based systems for operationalizing disease severity rely on the involvement (presence/absence) of pathology in specific anatomic regions. To examine the comorbidities associated with TDP-43 pathology in aged individuals, we studied data from the National Alzheimer’s Coordinating Center (NACC) Neuropathology Data Set. Data were analyzed from 929 included subjects with available TDP-43 pathology information, sourced from 27 different American Alzheimer’s Disease Centers (ADCs). Cases with relatively unusual diseases including autopsy-proven frontotemporal lobar degeneration (FTLD-TDP or FTLD-tau) …

Bilateral Sternocleidomastoid Variant With Six Distinct Insertions Along The Superior Nuchal Line., Graham Dupont, Joe Iwanaga, Juan J Altafulla, Stefan Lachkar, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

Anatomical variations of the sternocleidomastoid muscle (SCM) have been observed to occupy multiple origins and insertion points and have supernumerary heads, sometimes varying in thickness. During routine dissection, a SCM was observed to have six distinct insertions that interface with the course of the superior nuchal line, ending at the midline, bilaterally. This variation was also seen to receive innervation from the accessory nerve as well as the great auricular nerve. To our knowledge, this variant of supernumerary insertions and nerve innervations has not yet been reported. These variants may pose as problematic during surgical approaches to the upper neck …

Labrad : Vol 44, Issue 3 - December 2018, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• CD20 Negative B-Cell Lymphomas
• Quantification of Monoclonal Protein
• A Quick Guide to Immunofixation Electrophoresis
• Autologous Bone Marrow Transplantation at AKU
• Judicious Use of Immunohistochemistry & Ancillary Techniques in Precise Categorization of Lymphoproliferative Disorders

Loss-Of-Function Mutations In Atp6ap1 And Atp6ap2 In Granular Cell Tumors., Fresia Pareja, Alissa H. Brandes, Thais Basili, Pier Selenica, Felipe C. Geyer, Dan Fan, Arnaud Da Cruz Paula, Rahul Kumar, David N. Brown, Rodrigo Gularte-Mérida, Barbara Alemar, Rui Bi, Raymond S. Lim, Ino De Bruijn, Sho Fujisawa, Rui Gardner, Elvin Feng, Anqi Li, Edaise M. Da Silva, John R. Lozada, Pedro Blecua, Leona Cohen-Gould, Achim A. Jungbluth, Emad A. Rakha, Ian O. Ellis, Maria I.A. Edelweiss, Juan P. Palazzo, Larry Norton, Travis Hollmann, Marcia Edelweiss, Brian P. Rubin, Britta Weigelt, Jorge S. Reis-Filho

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Granular cell tumors (GCTs) are rare tumors that can arise in multiple anatomical locations, and are characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs are currently unknown. Here, we apply whole-exome sequencing and targeted sequencing analysis to reveal mutually exclusive, clonal, inactivating somatic mutations in the endosomal pH regulators ATP6AP1 or ATP6AP2 in 72% of GCTs. Silencing of these genes in vitro results in impaired vesicle acidification, redistribution of endosomal compartments, and accumulation of intracytoplasmic granules, recapitulating the cardinal phenotypic characteristics of GCTs and providing a novel genotypic-phenotypic correlation. In addition, depletion of ATP6AP1 or ATP6AP2 results in …

Task Sharing And Shifting To Provide Pathology Diagnostic Services: The Kenya Fine-Needle Aspiration Biopsy Cytology And Bone Marrow Aspiration And Trephine Biopsy Training Program, Shahin Sayed, Andrew Field, Jamilla Rajab, Anderson Mutuiri, Jessie Githanga, Mary Mungania, Nancy Okinda, Zahir Moloo, Abubakar Abdillah, Brian Ayara, Erick Chesori, Julia Muthua, Leah Obosy, Thaddeus Massawa, Okoth Obiero, Elizabeth Kagotho, Peter K. Shikuku, Andrew K. Gachii, Eunidah Migide, Donstefano Muninzwa, Sanford M. Dawsey, Lucy Muchiri

Pathology, East Africa

Purpose: Fine-needle aspiration biopsy (FNAB) cytology is a simple, inexpensive, and accurate diagnostic test for benign, infectious, and malignant lesions of the breast, thyroid, lymph nodes, and other organs. Similarly, bone marrow aspiration and trephine (BMAT) biopsy procedures are relatively simple and inexpensive techniques that are important for diagnosing and monitoring many hematologic diseases including leukemias and lymphomas. However, the scarcity of pathologists in Kenya limits patient access to these simple diagnostic tests. We describe a task sharing and shifting program that sought to improve the provision of FNABs and BMAT biopsies in tertiary public hospitals in Kenya.

Methods: Between …

Seven Decades Of Vitamin D Research In Pakistan : Too Little, Too Much Or Just Right!, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

No abstract provided.

Tuberculous Granuloma On Bone Marrow Trephine, Farheen Karim, Hira Qadir

Department of Pathology and Laboratory Medicine

Bone marrow examination is a useful tool for diagnosis of many diseases. The utility of bone marrow examination in workup of pyrexia of unknown origin cannot be undermined. Bone trephine of patients presenting with pyrexia of unknown origin must be carefully looked upon for granulomas for evaluation of tuberculosis. In this case, bone marrow trephine aided in timely diagnosis of tuberculosis in a patient.

Wound Closure After Posterior Multi-Level Lumbar Spine Surgery: An Anatomical Cadaver Study And Technical Note., Emre Yilmaz, Tamir Tawfik, Thomas M O'Lynnger, Joe Iwanaga, Ronen Blecher, Amir Abdul-Jabbar, R Shane Tubbs, Cameron K Schmidt, Rod J Oskouian, Jens R Chapman

Articles, Abstracts, and Reports

Meticulous attention to wound closure in posterior lumbar spine surgery is an important principle in reducing surgical site infections. We detail standardized wound closure used for posterior lumbar spine surgery at a tertiary care referral center and illustrate this as a step-by-step cadaveric dissection. The lumbar spine of a cadaveric specimen (male, 73 years at death) was used for dissection. Standardizing wound closure in posterior lumbar spine surgery may help limit wound complications and infection. Some key points of our technique, as demonstrated on a cadaveric specimen, include separating fascial compartments, avoiding suture abscesses, and creating a tension-free wound.

A Retrospective Study Of Laboratory-Based Enteric Fever Surveillance, Pakistan, 2012-2014, Farah Naz Qamar, Mohammad Tahir Yousafzai, Shazia Sultana, Attaullah Baig, Sadia Shakoor, Farzeen Hirani, Abdul Wassay, Sehrish Khushboo, Junaid Mehmood, Alexander Freeman

Department of Paediatrics and Child Health

Introduction: The Surveillance for Enteric Fever in Asia Project (SEAP) is a multisite surveillance study designed to capture morbidity and mortality burden of enteric fever (typhoid and paratyphoid) in Bangladesh, Nepal, and Pakistan. We aim to describe enteric fever disease burden, severity of illness, and antimicrobial resistance trends in Pakistan.
Methods: In this retrospective, cross-sectional study, laboratory records of hospitalized patients who received a blood culture in any of 3 Aga Khan University hospitals in Karachi and Hyderabad, Pakistan, from 2012 to 2014 were reviewed. A case was defined as having a positive blood culture for Salmonella Typhi (S. Typhi) …

Mutant Ubqln2p497h In Motor Neurons Leads To Als-Like Phenotypes And Defective Autophagy In Rats, Tianhong Chen, Bo Huang, Xinglong Shi, Limo Gao, Cao Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mutations in ubiquilin2 (UBQLN2) have been linked to abnormal protein aggregation in amyotrophic lateral sclerosis (ALS). The mechanisms underlying UBQLN2-related neurodegenerative diseases remain unclear. Using a tetracycline-regulated gene expression system, the ALS-linked UBQLN2P497H mutant was selectively expressed in either the spinal motor neurons or astrocytes in rats. We found that selectively expressing mutant UBQLN2P497H in the spinal motor neurons caused several core features of ALS, including the progressive degeneration of motor neurons, the denervation atrophy of skeletal muscles, and the abnormal protein accumulation. Furthermore, mutant UBQLN2P497H accumulation was associated with an age-dependent decrease in several core autophagy-related proteins. ALS-like phenotypes …

Serous Cystadenoma Of Pancreas : A Clinicopathologic Experience Of 23 Cases From A Major Tertiary Care Center, Muhammad Usman Tariq, Zubair Ahmad, Jamshid Abdul Ghafar, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Background: Serous cystadenomas of pancreas are rare benign epithelial neoplasms, which predominantly occur in the pancreatic body and tail of elderly females. Majority of these tumors have microcystic appearance. Macrocystic and solid variants have also been described. A number of more aggressive cystic pancreatic lesions are included in the differential diagnosis. Distinction from such lesions is important for optimal management.
Objective: Our aim was to study the clinical and histological features of serous cystadenomas which would be helpful in making their correct diagnosis and understanding their behavior.
Methods: We reviewed 23 cases of serous cystadenomas diagnosed in our institution between …

Hypoxia-Mediated Mitochondria Apoptosis Inhibition Induces Temozolomide Treatment Resistance Through Mir-26a/Bad/Bax Axis., Xin Ge, Min-Hong Pan, Lin Wang, Wei Li, Chengfei Jiang, Jun He, Khaled Abouzid, Ling-Zhi Liu, Zhumei Shi, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Glioblastoma multiforme (GBM) is one of the most hypoxic tumors of the central nervous system. Although temozolomide (TMZ) is an effective clinical agent in the GBM therapy, the hypoxic microenvironment remains a major barrier in glioma chemotherapy resistance, and the underlying mechanisms are poorly understood. Here, we find hypoxia can induce the protective response to mitochondrion via HIF-1α-mediated miR-26a upregulation which is associated with TMZ resistance in vitro and in vivo. Further, we demonstrated that HIF-1α/miR-26a axis strengthened the acquisition of TMZ resistance through prevention of Bax and Bad in mitochondria dysfunction in GBM. In addition, miR-26a expression levels negatively …

Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (CNS) disease states. Rapidly distinguishing CNS infections from other brain and spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF cytokine levels in various CNS disorders (infections, autoimmune/demyelinating diseases, lymphomas, and gliomas) to determine the potential utility of cytokine patterns in differentiating CNS infections from other CNS diseases. Both …