Pathology Commons^™

Mechanotransduction Signaling In Podocytes From Fluid Flow Shear Stress., Tarak Srivastava, Hongying Dai, Daniel P. Heruth, Uri S. Alon, Robert E. Garola, Jianping Zhou, R Scott Duncan, Ashraf El-Meanawy, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Recently, we and others have found that hyperfiltration-associated increase in biomechanical forces, namely, tensile stress and fluid flow shear stress (FFSS), can directly and distinctly alter podocyte structure and function. The ultrafiltrate flow over the major processes and cell body generates FFSS to podocytes. Our previous work suggests that the cyclooxygenase-2 (COX-2)-PGE2-PGE2 receptor 2 (EP2) axis plays an important role in mechanoperception of FFSS in podocytes. To address mechanotransduction of the perceived stimulus through EP2, cultured podocytes were exposed to FFSS (2 dyn/cm2) for 2 h. Total RNA from cells at the end of FFSS treatment, 2-h post-FFSS, and 24-h …

Molecular Characterization Of Multidrug-Resistant Klebsiella Pneumoniaeand Escherichia Coliharbouring Extended Spectrum Beta-Lactamases Andcarbapenemases Genes At A Tertiary Hospital, Kenya, Daniel Maina, Gunturu Revathi, Andrew C. Whitelaw

Pathology, East Africa

Background: Multidrug-resistant (MDR) Gram negative rods are increasingly being reported in sub-Saharan Africa. Molecular investigations play an important role, alongside other measures, in controlling nosocomial infections attributed to these organisms.

This study aimed to determine the common extended spectrum beta-lactamases (ESBL) and carbapenemases genes, and clonal relationship in MDR Klebsiella pneumoniae and Escherichia coli.

Methods: Fifty-four MDR isolates collected at the Aga Khan University hospital, Nairobi in the month of August 2012 formed the study. These were picked after an increase in the number of resistant strains during the said period was experienced.

Results: blaCTXM was present in 41 (74%) …

Immune Checkpoint Inhibitors In Neuroendocrine Tumors: A Single Institution Experience With Review Of Literature, Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors.

Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series.

Design: Case series and review of literature.

Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab).

Main Outcome(s) and Measures(s): Life expectancy, quality of life, disease progression.

Results: Maximum durable response of 16 months in one of the patients so far. All patients showed improvement in quality of life before disease progression. Two out of four are still on therapy. …

Histomorphology Of Trauma In Charred And Decomposed Remains, Mariya Bezugly

Student Theses

Decomposition and burning of human remains are frequently encountered in forensic cases, and pose a challenge at determining an accurate cause of death. At autopsy, macroscopic techniques fail to reach beyond superficial layers of degraded tissue to identify wound morphology that characterizes blunt-force gunshot, and sharp-force trauma. The postmortem damage imparted on tissue with pre-existing injuries, obstructs the external features of trauma. Exploring beyond charred and decayed superficial tissue, histo-morphological patterns of injury are still identifiable as shown in this thesis. With detailed observation to the pattern of tissue disruption- an understanding of the type of trauma imposed can be …

Comparison Of Equations For Estimating Glomerular Filtration Rate In Screening For Chronic Kidney Disease In Asymptomatic Black Africans: A Cross Sectional Study, Geoffrey Omuse, Daniel Maina, Jane Mwangi, Caroline Wambua, Alice Kiyua, Elizabeth Kagotho, Angela Amayo, Peter Ojwang, Rajiv Erasmus

Pathology, East Africa

Background: Several equations have been developed to estimate glomerular filtration rate (eGFR). The common equations used were derived from populations predominantly comprised of Caucasians with chronic kidney disease (CKD). Some of the equations provide a correction factor for African-Americans due to their relatively increased muscle mass and this has been extrapolated to black Africans. Studies carried out in Africa in patients with CKD suggest that using this correction factor for the black African race may not be appropriate. However, these studies were not carried out in healthy individuals and as such the extrapolation of the findings to an asymptomatic black …

A Gut Pathobiont Synergizes With The Microbiota To Instigate Inflammatory Disease Marked By Immunoreactivity Against Other Symbionts But Not Itself, João Carlos Gomes-Neto, Hatem Kittana, Sara Mantz, Rafael R. Segura Munoz, Robert J. Schmaltz, Laure B. Bindels, Jennifer L. Clarke, Jesse M. Hostetter, Andrew K. Benson, Jens Walter, Amanda Ramer-Tait

Department of Food Science and Technology: Faculty Publications

Inflammatory bowel diseases (IBD) are likely driven by aberrant immune responses directed against the resident microbiota. Although IBD is commonly associated with a dysbiotic microbiota enriched in putative pathobionts, the etiological agents of IBD remain unknown. Using a pathobiont-induced intestinal inflammation model and a defined bacterial community, we provide new insights into the immune-microbiota interactions during disease. In this model system, the pathobiont Helicobacter bilis instigates disease following sub-pathological dextran sulfate sodium treatment. We show that H. bilis causes mild inflammation in mono-associated mice, but severe disease in the presence of a microbiota, demonstrating synergy between the pathobiont and microbiota …

Labrad : Vol 43, Issue 3 - December 2017, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Levey Jennings Chart and Guide to use Westgard Rules
• Quality Assurance in Frozen Section Studies
• Performance Improvement Monitors in Histology
• Quality Assurance in Immunohistochemistry: The Way We Do It
• Quality Assurance in Laboratory Biosafety
• Quality Control of Culture Media Used in Clinical Microbiology
• Quality Assurance (QA) in Qualitative Tests in the Clinical Laboratory
• Radiology Pathology Correlation
• Quality Requirements for Reporting Sickle Haemoglobin
• Meeting Report of International Federation of Clinical Chemistry (IFCC) Conferences- 2017

Cerebrovascular Pathology In Down Syndrome And Alzheimer Disease, Elizabeth Head, Michael J. Phelan, Eric Doran, Ronald C. Kim, Wayne W. Poon, Frederick A. Schmitt, Ira T. Lott

Sanders-Brown Center on Aging Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, …

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

High Burden Of Subclinical Lead Toxicity After Phase Out Of Lead From Petroleum In Pakistan, Hafsa Majid, Aysha Habib Khan, Nadeem Ullah Khan, Imran Siddiqui, Farooq Ghani, Lena Jafri

Department of Pathology and Laboratory Medicine

Objective: To evaluate the frequency of subclinical lead toxicity.
Study design: Cross-sectional study.
Place and duration of study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011 to December 2014.
Methodology: Analysis of laboratory data for blood lead levels (BLL) was performed. Lead was tested by atomic absorption spectrometer. For all subjects, only initial test results were included while the results of repeated testing were excluded. Exemption was sought from institutional ethical review committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively were taken as subclinical lead toxicity.
Result: Amongst …

High Burden Of Subclinical Lead Toxicity After Phase Out Of Lead From Petroleum In Pakistan, Hafsa Majid, Aysha Habib Khan, Nadeem Ullah Khan, Imran Siddiqui, Farooq Ghani, Lena Jafri

Department of Pathology and Laboratory Medicine

Objective: To evaluate the frequency of subclinical lead toxicity.
Study design: Cross-sectional study.
Place and duration of study: Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011 to December 2014.
Methodology: Analysis of laboratory data for blood lead levels (BLL) was performed. Lead was tested by atomic absorption spectrometer. For all subjects, only initial test results were included while the results of repeated testing were excluded. Exemption was sought from institutional ethical review committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively were taken as subclinical lead toxicity.
Results: Amongst …

Cxc Chemokines Exhibit Bactericidal Activity Against Multidrug-Resistant Gram-Negative Pathogens, Erum Khan, Matthew A. Crawford, Debra J. Fisher, Lisa M. Leung, Sara Lomonaco, Christine Lascols, Antonio Cannatelli,, Gian Maria Rossolini, Yohei Doi, David R. Goodlett

Department of Pathology and Laboratory Medicine

The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A. Colistin-resistant K. pneumoniae isolates affected by genetic mutation of the PmrA/PmrB two-component system, a chromosomally encoded regulator of lipopolysaccharide modification, and containing …

Single Nucleotide Polymorphisms In Efflux Pumps Genes In Extensively Drug Resistant Mycobacterium Tuberculosis Isolates From Pakistan, Akbar Kanji, Rumina Hasan, Asho Ali, Ambreen Zaver, Ying Zhang, Kehkashan Imtiaz, Wanliang Shi, Taane G. Clark, Ruth Mcnerney, Jody Phelan

Department of Pathology and Laboratory Medicine

It is challenging to understand mechanisms of drug resistance in Mycobacterium tuberculosis (MTB) due to the large variability in resistance associated genes. Efflux pump genes contribute to drug resistance and thus add to this complexity. Efflux pump gene protein superfamilies have been characterized by genome analysis of drug resistant strains and through invitro transcriptional studies. However, there is limited information regarding efflux pump genes in extensively drug resistant (XDR) tuberculosis (TB) isolates. Whole genome sequencing (WGS) based analysis of 37 extensively drug resistant (XDR) and five drug sensitive (DS) MTB clinical isolates was performed. Single nucleotide polymorphisms (SNPs) in efflux …

Idiopathic Nodular Glomerulosclerosis In A Chronic Marijuana User; A Case Report And Review Of The Literature, Mehri Mollaee, Tibor Fülöp, Sohil Abdul Salim, Seyed Mehrdad Hamrahian

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Nodular glomerulosclerosis is a characteristic histological finding of diabetic nephropathy (DN) with thickened glomerular basement membrane (GBM) and hyalinized arterioles. Idiopathic nodular glomerulosclerosis (ING), a rare distinct clinicopathologic entity, is the term used to denote classic DN confirmed by light microscopy, immuno-fluorescence, and electron microscopy in the absence of diabetes mellitus (DM). ING has been linked to heavy tobacco smoking, chronic hypertension, obesity and insulin resistance. Its association with marijuana use is unknown. Case Presentation: We report a case of biopsy-proved ING in the absence of pre-existing history of DM and heavy smoking. This report addresses the possible accentuation …

How Should Clinicians Weigh The Benefits And Harms Of Discussing Politicized Topics That Influence Their Individual Patients' Health?, Diana Alame, Robert D. Truog

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Health implications of politically charged phenomena are particularly difficult for physicians to discuss with their patients and communities. Addressing climate change and its associated health effects involves trade-offs between health and economic prosperity, necessitating that physicians weigh the potential benefits and risks of discussing climate change health effects. We argue that the potential benefits of physician communication and advocacy ultimately outweigh the potential risks. Therefore, physicians should be supported in their efforts to educate their patients and communities about climate change health effects. Furthermore, democratic deliberation could prove helpful in addressing disagreements among physicians within a practice about such politicized …

Hematopoietic Stem Cell Transplantation In Pakistan – Country Report, Parvez Ahmed, Tahir Sultan Shamsi, Salman Adil, Tariq Mahmood Satti, Qamar Un Nisa Chaudhry, Tahir Sultan Shamsi, Syed Kamran Mahmood, Saqib Ansari, Natasha Bahadur Ali, Tariq Ghafoor

Department of Pathology and Laboratory Medicine

No abstract provided.

Non-Hodgkin And Hodgkin Lymphomas Select For Overexpression Of Bclw., Clare M. Adams, Ramkrishna Mitra, Jerald Z. Gong, Md, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Purpose: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an antiapoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other antiapoptotic BCL2 family members in six different B-cell lymphomas. Experimental Design: We performed a large-scale gene expression analysis of datasets comprising approximately 2,300 lymphoma patient samples, including non-Hodgkin and Hodgkin lymphomas as well as …

Intrahepatic Biliary Cystadenoma Mimicking Hydatid Cyst Of Liver: A Clinicopathologic Study Of Six Cases, Zubair Ahmad, Nasir Uddin, Wasim Memon, Jamshid Abdul Ghafar, Arsalan Ahmed

Department of Pathology and Laboratory Medicine

Background: Intrahepatic biliary cystadenomas are rare hepatic neoplasms, which are usually cystic. These tumors are often misdiagnosed as simple liver cysts and hydatid cysts clinically and radiologically owing to nonspecific clinical and radiologic features. These tumors require complete resection, as recurrence and malignant transformation can occur following incomplete excision. It is essential that these tumors be diagnosed accurately so that they can be adequately excised.
Methods: Clinical and radiological features of six cases of biliary cystadenoma are described.
Results: All of these cases were resected with the clinical and/or radiological impression of simple liver cysts and/ or hydatid cysts. Out …

Precision Newborn Screening For Lysosomal Disorders, Melissa M. Minter Baerg, Stephanie D. Stoway, Jeremy Hart, Lea Mott, Dawn S. Peck, Stephanie L. Nett, Jason S. Eckerman, Jean M. Lacey, Coleman T. Turgeon, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Silvia Tortorelli, Dietrich Matern, Lars Mørkrid, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: The implementation of newborn screening for lysosomal disorders has uncovered overall poor specificity, psychosocial harm experienced by caregivers, and costly follow-up testing of false-positive cases. We report an informatics solution proven to minimize these issues.

Methods: The Kentucky Department for Public Health outsourced testing for mucopolysaccharidosis type I (MPS I) and Pompe disease, conditions recently added to the recommended uniform screening panel, plus Krabbe disease, which was added by legislative mandate. A total of 55,161 specimens were collected from infants born over 1 year starting from February 2016. Testing by tandem mass spectrometry was integrated with multivariate pattern recognition …

Moonlighting Newborn Screening Markers: The Incidental Discovery Of A Second-Tier Test For Pompe Disease, Silvia Tortorelli, Jason S. Eckerman, Joseph J. Orsini, Colleen Stevens, Jeremy Hart, Patricia L. Hall, John J. Alexander, Dimitar Gavrilov, Devin Oglesbee, Kimiyo Raymond, Dietrich Matern, Piero Rinaldo

Pathology and Laboratory Medicine Faculty Publications

Purpose: To describe a novel biochemical marker in dried blood spots suitable to improve the specificity of newborn screening for Pompe disease.

Methods: The new marker is a ratio calculated between the creatine/creatinine (Cre/Crn) ratio as the numerator and the activity of acid α-glucosidase (GAA) as the denominator. Using Collaborative Laboratory Integrated Reports (CLIR), the new marker was incorporated in a dual scatter plot that can achieve almost complete segregation between Pompe disease and false-positive cases.

Results: The (Cre/Crn)/GAA ratio was measured in residual dried blood spots of five Pompe cases and was found to be elevated (range 4.41–13.26; 99%ile …