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2018

Pathology

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Full-Text Articles in Medicine and Health Sciences

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 Dec 2018

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) …


The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic Dec 2018

The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic

Electronic Thesis and Dissertation Repository

TBX3 is a transcriptional regulator involved in embryonic development and in tumorigenesis of several cancer types. There are two isoforms of TBX3 (TBX3iso1 and TBX3iso2) with different DNA binding domains. The large-scale functional roles of TBX3iso1 and TBX3iso2 were characterized in a breast cancer context. Both TBX3 isoforms induced invasiveness and an epithelial-to-mesenchymal (EMT) phenotype. Coupling data from genome-wide ChIP-array and RNA-Seq studies provided a novel list of genes regulated by each isoform. Both TBX3 isoforms regulate expression of several EMT-related genes, including SLUG and TWIST1. Importantly, TBX3 is a direct regulator of SLUG, and SLUG expression is required for …


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 Dec 2018

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 …


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

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

LABRAD

  • 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


Seven Decades Of Vitamin D Research In Pakistan : Too Little, Too Much Or Just Right!, Aysha Habib Khan Dec 2018

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.


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 Dec 2018

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 …


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 Dec 2018

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 …


Tuberculous Granuloma On Bone Marrow Trephine, Farheen Karim, Hira Qadir Nov 2018

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 Nov 2018

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.


White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit Nov 2018

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …


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 Nov 2018

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 Nov 2018

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 Nov 2018

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 Nov 2018

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 Oct 2018

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 …


Bacterial Contamination Of Platelets For Transfusion: Strategies For Prevention., Jerrold H. Levy, Matthew D. Neal, Jay H. Herman Oct 2018

Bacterial Contamination Of Platelets For Transfusion: Strategies For Prevention., Jerrold H. Levy, Matthew D. Neal, Jay H. Herman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Platelet transfusions carry greater risks of infection, sepsis, and death than any other blood product, owing primarily to bacterial contamination. Many patients may be at particular risk, including critically ill patients in the intensive care unit. This narrative review provides an overview of the problem and an update on strategies for the prevention, detection, and reduction/inactivation of bacterial contaminants in platelets. Bacterial contamination and septic transfusion reactions are major sources of morbidity and mortality. Between 1:1000 and 1:2500 platelet units are bacterially contaminated. The skin bacterial microflora is a primary source of contamination, and enteric contaminants are rare but may …


Metabolic Reprogramming Of Murine Cardiomyocytes During Autophagy Requires The Extracellular Nutrient Sensor Decorin., Maria A. Gubbiotti, Erin L. Seifert, Ulrich Rodeck, Jan B. Hoek, Renato V. Iozzo Oct 2018

Metabolic Reprogramming Of Murine Cardiomyocytes During Autophagy Requires The Extracellular Nutrient Sensor Decorin., Maria A. Gubbiotti, Erin L. Seifert, Ulrich Rodeck, Jan B. Hoek, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The extracellular matrix is a master regulator of tissue homeostasis in health and disease. Here we examined how the small, leucine-rich, extracellular matrix proteoglycan decorin regulates cardiomyocyte metabolism during fasting in vivo. First, we validated in Dcn-/- mice that decorin plays an essential role in autophagy induced by fasting. High-Throughput metabolomics analyses of cardiac tissue in Dcn-/- mice subjected to fasting revealed striking differences in the hexosamine biosynthetic pathway resulting in aberrant cardiac O-β-N-Acetylglycosylation as compared with WT mice. Functionally, Dcn-/- mice maintained cardiac function at a level comparable with nonfasted animals whereas fasted WT mice showed …


Multiple Tumor Suppressors Regulate A Hif-Dependent Negative Feedback Loop Via Isgf3 In Human Clear Cell Renal Cancer., Lili Liao, Zongzhi Z. Liu, Lauren Langbein, Weijia Cai, Eun-Ah Cho, Jie Na, Xiaohua Niu, Wei Jiang, Zhijiu Zhong, Wesley L. Cai, Geetha Jagannathan, Essel Dulaimi, Joseph R. Testa, Robert G. Uzzo, Yuxin Wang, George R. Stark, Jianxin Sun, Stephen C. Peiper, Yaomin Xu, Qin Yan, Haifeng Yang Oct 2018

Multiple Tumor Suppressors Regulate A Hif-Dependent Negative Feedback Loop Via Isgf3 In Human Clear Cell Renal Cancer., Lili Liao, Zongzhi Z. Liu, Lauren Langbein, Weijia Cai, Eun-Ah Cho, Jie Na, Xiaohua Niu, Wei Jiang, Zhijiu Zhong, Wesley L. Cai, Geetha Jagannathan, Essel Dulaimi, Joseph R. Testa, Robert G. Uzzo, Yuxin Wang, George R. Stark, Jianxin Sun, Stephen C. Peiper, Yaomin Xu, Qin Yan, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft …


Myocardial Ischemia Reperfusion Injury: Apoptotic, Inflammatory And Oxidative Stress Role Of Galectin-3, Suhail Al-Salam, Satwat Hashmi Oct 2018

Myocardial Ischemia Reperfusion Injury: Apoptotic, Inflammatory And Oxidative Stress Role Of Galectin-3, Suhail Al-Salam, Satwat Hashmi

Department of Biological & Biomedical Sciences

Background/aims: Myocardial reperfusion has the potential to salvage the ischemic myocardium after a period of coronary occlusion. Reperfusion, however, can cause a wide spectrum of deleterious effects. Galectin-3 (GAL-3), a beta galactoside binding lectin, is closely associated with myocardial infarction (MI), myocardial fibrosis and heart failure. In our study, we investigated its role in ischemia-reperfusion injuries (IR) as this phenomenon is extremely relevant to the early intervention after acute MI.
Methods: C57B6/J wild type (WT) mice and GAL-3 knockout (KO) mice were used for murine model of IR injury in the heart where a period of 30 minutes ischemia was …


Effect Of Positive Patient Identification On Wrong Blood In Tube Errors: A Single Center Experience, Faisal Huq Ronny, Md, Phd, Mary Harach, Bs, Mt(Ascp), Cqa(Asq), Ssgb, Jay H. Herman, Md, Fcap Oct 2018

Effect Of Positive Patient Identification On Wrong Blood In Tube Errors: A Single Center Experience, Faisal Huq Ronny, Md, Phd, Mary Harach, Bs, Mt(Ascp), Cqa(Asq), Ssgb, Jay H. Herman, Md, Fcap

Department of Pathology, Anatomy, and Cell Biology Posters

No abstract provided.


Expression Analysis Of Cyclooxygenase-2 In Patients Suffering From Esophageal Squamous Cell Carcinoma, Shahida Tasneem, Muhammad Tahir Sarwa, Muhammad Rizwan Bashi, Hamid Hussain, Jawad Ahmed, Shahid Pervez Oct 2018

Expression Analysis Of Cyclooxygenase-2 In Patients Suffering From Esophageal Squamous Cell Carcinoma, Shahida Tasneem, Muhammad Tahir Sarwa, Muhammad Rizwan Bashi, Hamid Hussain, Jawad Ahmed, Shahid Pervez

Department of Pathology and Laboratory Medicine

Esophageal squamous cell carcinoma (ESCC) is one of the aggressive malignancies and mechanisms underlying its pathogenesis remain unclear. Cyclooxygenase-2 (COX-2) enzyme system plays a crucial role in many gastrointestinal malignancies and is an important regulator of cell growth, proliferation, apoptosis, differentiation and transformation. More precise outcome of COX-2 in ESCC is less investigated. In this study we investigated the risk factors of ESCC and expression of COX-2 in Carcinoma in situ (CIS) and ESCC compared to normal esophageal mucosa. ESCC relationship to clinico-pathological parameters using immunohistochemistry was also part of this investigation. Current study was conducted in the Institute of …


Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, Md Oct 2018

Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Metformin, an oral anti-hyperglycemic drug which inhibits mitochondrial complex I and oxidative phosphorylation has been reported to correlate with improved outcomes in head and neck squamous cell carcinoma (HNSCC) and other cancers. This effect is postulated to occur through disruption of tumor-driven metabolic and immune dysregulation in the tumor microenvironment (TME). We report new findings on the impact of metformin on the tumor and immune elements of the TME from a clinical trial of metformin in HNSCC. Methods: Human papilloma virus-(HPV-) tobacco+ mucosal HNSCC samples (n = 12) were compared to HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples (n …


Vitamin D Status In Healthy Black African Adults At A Tertiary Hospital In Nairobi, Kenya: A Cross Sectional Study, Elizabeth Kagotho, Geoffrey Omuse, Nancy Okinda, Peter Ojwang Oct 2018

Vitamin D Status In Healthy Black African Adults At A Tertiary Hospital In Nairobi, Kenya: A Cross Sectional Study, Elizabeth Kagotho, Geoffrey Omuse, Nancy Okinda, Peter Ojwang

Pathology, East Africa

Background: Vitamin D has been known since the twentieth Century for its benefits in bone health. Recent observational studies have demonstrated its benefits in infectious diseases such as tuberculosis and non-communicable diseases such as diabetes mellitus, cardiovascular diseases and cancer. This has led to a dramatic increase in testing among adults. The cut-offs for vitamin D deficiency have been debated for decades and the current cut off is derived from a Caucasian population. Studies done among black African adults in Africa are few with vitamin D deficiency ranging from 5 to 91%. A few cut- offs have correlated vitamin D …


Paradigm Shift In Anti-Coagulating Patients With Non-Valvular Atrial Fibrillation, Bushra Moiz Oct 2018

Paradigm Shift In Anti-Coagulating Patients With Non-Valvular Atrial Fibrillation, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.


Mitochondrial Fusion And Bid-Mediated Mitochondrial Apoptosis Are Perturbed By Alcohol With Distinct Dependence On Its Metabolism, Shamim Naghdi, William S. Slovinsky, Muniswamy Madesh, Emanual Rubin, György Hajnóczky Oct 2018

Mitochondrial Fusion And Bid-Mediated Mitochondrial Apoptosis Are Perturbed By Alcohol With Distinct Dependence On Its Metabolism, Shamim Naghdi, William S. Slovinsky, Muniswamy Madesh, Emanual Rubin, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Environmental stressors like ethanol (EtOH) commonly target mitochondria to influence the cell’s fate. Recent literature supports that chronic EtOH exposure suppresses mitochondrial dynamics, central to quality control, and sensitizes mitochondrial permeability transition pore opening to promote cell death. EtOH-induced tissue injury is primarily attributed to its toxic metabolic products but alcoholism also impairs tissues that poorly metabolize EtOH. We embarked on studies to determine the respective roles of EtOH and its metabolites in mitochondrial fusion and tBid-induced mitochondrial apoptosis. We used HepG2 cells that do not metabolize EtOH and its engineered clone that expresses EtOH-metabolizing Cytochrome P450 E2 and alcohol …


Microtubule-Associated Protein 1 Light Chain 3b, (Lc3b) Is Necessary To Maintain Lipid-Mediated Homeostasis In The Retinal Pigment Epithelium., Anuradha Dhingra, Brent A Bell, Neal S. Peachey, Lauren L. Daniele, Juan Reyes-Reveles, Rachel C. Sharp, Bokkyoo Jun, Nicolas G. Bazan, Janet R. Sparrow, Hye Jin Kim, Nancy J. Philp, Kathleen Boesze-Battaglia Oct 2018

Microtubule-Associated Protein 1 Light Chain 3b, (Lc3b) Is Necessary To Maintain Lipid-Mediated Homeostasis In The Retinal Pigment Epithelium., Anuradha Dhingra, Brent A Bell, Neal S. Peachey, Lauren L. Daniele, Juan Reyes-Reveles, Rachel C. Sharp, Bokkyoo Jun, Nicolas G. Bazan, Janet R. Sparrow, Hye Jin Kim, Nancy J. Philp, Kathleen Boesze-Battaglia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Like other neurons, retinal cells utilize autophagic pathways to maintain cell homeostasis. The mammalian retina relies on heterophagy and selective autophagy to efficiently degrade and metabolize ingested lipids with disruption in autophagy associated degradation contributing to age related retinal disorders. The retinal pigment epithelium (RPE) supports photoreceptor cell renewal by daily phagocytosis of shed photoreceptor outer segments (OS). The daily ingestion of these lipid-rich OS imposes a constant degradative burden on these terminally differentiated cells. These cells rely on Microtubule-Associated Protein 1 Light Chain 3 (LC3) family of proteins for phagocytic clearance of the ingested OS. The LC3 family comprises …


Prospective Evaluation Of Serum Procalcitonin In Critically Ill Patients With Suspected Sepsis- Experience From A Tertiary Care Hospital In Pakistan, Sibtain Ahmed, Imran Siddiqui, Lena Jafri, Madiha Hashmi, Aysha Habib, Farooq Ghani Oct 2018

Prospective Evaluation Of Serum Procalcitonin In Critically Ill Patients With Suspected Sepsis- Experience From A Tertiary Care Hospital In Pakistan, Sibtain Ahmed, Imran Siddiqui, Lena Jafri, Madiha Hashmi, Aysha Habib, Farooq Ghani

Department of Pathology and Laboratory Medicine

Background: Sepsis is the leading cause of mortality in critically ill patients. Procalcitonin (PCT) is a promising marker for identification of bacterial sepsis. The aim of this study was to determine the diagnostic accuracy of serum PCT concentration in patients with suspected sepsis admitted to mixed medical-surgical Intensive care unit (ICU).
Material and methods: A cross-sectional study conducted at section of Chemical Pathology, Department of Pathology and Laboratory Medicine and ICU. Patients with suspected sepsis were included, serum PCT cut off ≥0.5 ng/ml was taken for diagnosing sepsis. Diagnostic accuracy was measured in terms of sensitivity, specificity, positive predictive value …


Cellular Network Modeling And Single Cell Gene Expression Analysis Reveals Novel Hepatic Stellate Cell Phenotypes Controlling Liver Regeneration Dynamics, Daniel Cook, Sirisha Achanta, Jan B. Hoek, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli Oct 2018

Cellular Network Modeling And Single Cell Gene Expression Analysis Reveals Novel Hepatic Stellate Cell Phenotypes Controlling Liver Regeneration Dynamics, Daniel Cook, Sirisha Achanta, Jan B. Hoek, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Recent results from single cell gene and protein regulation studies are starting to uncover the previously underappreciated fact that individual cells within a population exhibit high variability in the expression of mRNA and proteins (i.e., molecular variability). By combining cellular network modeling, and high-throughput gene expression measurements in single cells, we seek to reconcile the high molecular variability in single cells with the relatively low variability in tissue-scale gene and protein expression and the highly coordinated functional responses of tissues to physiological challenges. In this study, we focus on relating the dynamic changes in distributions of hepatic stellate cell …


Oxcarbazepine Overdose In A Polysubstance Related Suicide, Melissa Beals, Robert J. Krumsick, C. Clinton Frazee Iii, Lindsey J. Haldiman, Uttam Garg Oct 2018

Oxcarbazepine Overdose In A Polysubstance Related Suicide, Melissa Beals, Robert J. Krumsick, C. Clinton Frazee Iii, Lindsey J. Haldiman, Uttam Garg

Posters

Introduction
Oxcarbazepine is a derivative of carbamazepine that is used primarily in the treatment of epilepsy, and experimentally as a mood-stabilizer in adjunctive therapy for the treatment of bipolar disorder. Oxcarbazepine is converted through oxidation to its pharmacologically active metabolite 10-OH-Carbazepine, which is thought to be responsible for most of the anticonvulsant action of the drug. Adverse effects of oxcarbazepine are generally dose-dependent and may include fatigue, somnolence, dizziness, diplopia, nystagmus, and ataxia. Additive sedative effects have been noted when oxcarbazepine is used in combination with other CNS depressionproducing medications. Furthermore, oxcarbazepine and 10-OH-Carbazepine are powerful CYP2C19 inhibitors, potentially increasing …


A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte Oct 2018

A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte

Manuscripts, Articles, Book Chapters and Other Papers

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response …