Pathology Commons^™

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

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 …

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

Department of Pathology and Laboratory Medicine

No abstract provided.

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 …

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

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

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

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

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 …

Epidemiology Of Moderate Alcohol Consumption And Breast Cancer: Association Or Causation?, Samir Zakhari, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Epidemiological studies have been used to show associations between modifiable lifestyle habits and the incidence of breast cancer. Among such factors, a history of alcohol use has been reported in multiple studies and meta-analyses over the past decades. However, associative epidemiological studies that were interpreted as evidence that even moderate alcohol consumption increases breast cancer incidence have been controversial. In this review, we consider the literature on the relationship between moderate or heavy alcohol use, both in possible biological mechanisms and in variations in susceptibility due to genetic or epigenetic factors. We argue that there is a need to incorporate …

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 …

Comprehensive Review Of Spinal Neurenteric Cysts With A Focus On Histopathological Findings., Woong Kee Baek, Stefan Lachkar, Joe Iwanaga, Rod J Oskouian, Marios Loukas, W Jerry Oakes, R Shane Tubbs

Articles, Abstracts, and Reports

Among the occult spinal dysraphisms, neurenteric cysts (NECs) are rare and are thought to arise due to a failure of the separation of the primitive endoderm and ectoderm. Patients experience various neurological symptoms depending on the location of the lesion. As the epithelial morphology of NECs share similarities with other intracranial and intraspinal cystic growths, the definitive diagnosis of NEC can be made after a histochemical analysis with endodermal markers. Complete resection is associated with the lowest disease recurrence rate.

Neuroprotective Role Of Phytochemicals., Bharath Kumar Velmurugan, Baskaran Rathinasamy, Bharathi Priya Lohanathan, Varadharajan Thiyagarajan, Ching-Feng Weng

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to treat neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). In this present review we explored the potential efficacy of phytochemicals such as epigallocatechin-3-galate, berberin, curcumin, resveratrol, quercetin and limonoids against the most common NDs, including Alzheimer's disease (AD) and Parkinson's disease (PD). The beneficial potentials of these phytochemicals have been demonstrated by evidence-based but more …

Prostaglandin D2/J2 Signaling Pathway In A Rat Model Of Neuroinflammation Displaying Progressive Parkinsonian-Like Pathology: Potential Novel Therapeutic Targets, Chuhyon Corwin, Anastasia Nikolopoulou, Allen L. Pan, Mariela Nunez-Santos, Shankar Vallabhajosula, Peter A. Serrano, John Babich, Maria E. Figueiredo-Pereira

Publications and Research

Background: Prostaglandins are products of the cyclooxygenase pathway, which is implicated in Parkinson’s disease (PD). Limited knowledge is available on mechanisms by which prostaglandins contribute to PD neurodegeneration. To address this gap, we focused on the prostaglandin PGD2/J2 signaling pathway, because PGD2 is the most abundant prostaglandin in the brain, and the one that increases the most under pathological conditions. Moreover, PGJ2 is spontaneously derived from PGD2.

Methods: In this study, we determined in rats the impact of unilateral nigral PGJ2-microinfusions on COX-2, lipocalin-type PGD2 synthase (L-PGDS), PGD2/J2 receptor 2 (DP2), and 15 hydroxyprostaglandin dehydrogenase (15-PGDH). Nigral dopaminergic (DA) and …

Fatal Invasive Gastrointestinal Fungal Infection In Three Non-Immunocompromised Patients, Zubair Ahmad, Sidra Arshad, Romana Idress, Nasir Uddin, Jamshid Abdul-Ghafar

Department of Pathology and Laboratory Medicine

The importance and frequency of invasive fungal infections in different organs, including the gastrointestinal tract, has increased due to excessive use of aggressive immunosuppressive and immunomodulatory drugs in malignant diseases and organ transplantations as well as increased infections with the human immunodeficiency virus (HIV). Fungal infections in the small intestine or colon are usually part of a disseminated disease process and reach these organs through the bloodstream. Two of the patients were infants 10 and 15 days of age, while one was 23 years old. Patients presented with abdominal pain, intestinal obstruction, and rectal bleeding. Hirchsprung disease was suspected in …

Invasive Mediastinal Aspergillosis Presenting As Superior Vena Cava Syndrome In An Immunocompetent Patient, Yasmin Rahim, Aisha Memon, Javaid Khan

Section of Pulmonary & Critical Care

Invasive aspergillosis (IA) is a disease of the immunocompromised with a predilection for the lungs, although dissemination to all organs is possible. Its diagnosis remains a challenge due to the absence of specific clinical manifestations and laboratory findings. In most cases, diagnosis is eventually made via invasive methods. It carries with it a high mortality due to late diagnosis and delayed treatment. Here, we report a fascinating case of a young, otherwise healthy, immunocompetent patient that presented to us with superior vena cava syndrome and a mediastinal mass. It was anticipated that a malignancy would be found on further workup …

Integrating Standardized Whole Genome Sequence Analysis With A Global Mycobacterium Tuberculosis Antibiotic Resistance Knowledgebase, Rumina Hasan, Matthew Ezewudo, Amanda Borens, Álvaro Chiner-Oms, Paolo Miotto, Leonid Chindelevitch, Angela M. Starks, Debra Hanna, Richard Liwsk, Matteo Zignol

Department of Pathology and Laboratory Medicine

Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) ( https://github.com/CPTR-ReSeqTB/UVP ) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited …

Variations Of The Transverse Sinus: Review With An Unusual Case Report., Chrissie Massrey, Juan J Altafulla, Joe Iwanaga, Zachary Litvack, Basem Ishak, Rod J Oskouian, Marios Loukas, R Shane Tubbs

Articles, Abstracts, and Reports

The dural venous sinuses are venous channels in the cranium that drain blood and cerebrospinal fluid circulating from the brain into the vascular system via the internal jugular veins. The transverse sinus is a dural venous sinus present in the posterior aspect of the cranium. We report an unusual variant of this sinus with the presence of a fenestration at its proximal segment. We will review and discuss the background and the potential clinical relevance of this anatomical variation.

Large Pseudoencapsulated Subcutaneous Angiomyxoma: Surgical Management., Christine M Shaver, Steven E Kolker, Richard G Bennett

Articles, Abstracts, and Reports

No abstract provided.

Labrad : Vol 44, Issue 2 - September 2018, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Inappropriate Requesting Of Glycated Haemoglobin (HBA1c) By Clinicians
• Fecal Calprotectin (S100a8/S100a9)
• Fecal Pancreatic Elastase: A Test for Pancreatic Insufficiency
• Radiology Pathology Correlation
• Myelodysplastic Syndromes (MDS)
• WHO Classification of Head and Neck Tumours: An Update
• Plasma Metanephrines in Diagnosis of Pheochromocytoma
• Megaloblastic Anemia
• Aplastic AnemiaTransfusion Associated Circulatory Overload (Taco): A Severe But Preventable Transfusion Reaction