Pathology Commons^™

GabaB Receptor Attenuation Of GabaA Currents In Neurons Of The Mammalian Central Nervous System, Wen Shen, Changlong Nan, Peter T. Nelson, Harris Ripps, Malcolm M. Slaughter

Pathology and Laboratory Medicine Faculty Publications

Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABA_B receptor can suppress the ionotropic GABA_A receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains in Xenopus oocytes by microtransplantation …

Microscopic Examination Of Findings Encountered During Cadaver Dissection: Malignant, Benign Or Anatomic Variation?, Maria Cicioni, Vandi Ly, Guiyun Zhang, Bruce Fenderson

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pathologic findings encountered during cadaver dissection provide an opportunity for integrating the preclinical basic sciences and encouraging critical thinking. The objective of this study was to determine whether it is possible to make a pathologic diagnosis of an unknown mass from an embalmed cadaver. Diagnoses would have to be based solely on gross and microscopic appearance of tissue, without clinical histories of the cadaveric donors. The tissue samples we removed from each mass were surprisingly well preserved and showed minimal autolysis. Indeed, some of the histological detail was as clear as may be found in any textbook. We were able …

Relationship Of The Median And Radial Nerves At The Elbow: Application To Avoiding Injury During Venipuncture Or Other Invasive Procedures Of The Cubital Fossa., Vlad Voin, Joe Iwanaga, Juan P Sardi, Christian Fisahn, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

INTRODUCTION: The median and radial nerves are two important neural structures found in the cubital fossa. The trajectory and landmarks used to identify their location are important when procedures are done in this area.

METHODS AND MATERIALS: Ten fresh-frozen cadavers were dissected (20 upper limbs) and measurements were taken from the medial epicondyle to the median and radial nerves as well as to the lateral epicondyle of each limb.

RESULTS: The distance between the medial epicondyle and the median nerve was found to be three centimeters with a range of 2.1 to four centimeters and the distance from the medial …

Camp Signaling Enhances Hiv-1 Long Terminal Repeat (Ltr)-Directed Transcription And Viral Replication In Bone Marrow Progenitor Cells., Anupam Banerjee, Luna Li, Vanessa Pirrone, Fred C. Krebs, Brian Wigdahl, Michael R. Nonnemacher

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

CD34⁺ hematopoietic progenitor cells have been shown to be susceptible to HIV-1 infection, possibly due to a low-level expression of CXCR4, a coreceptor for HIV-1 entry. Given these observations, we have explored the impact of forskolin on cell surface expression of CXCR4 in a cell line model (TF-1). The elevation of intracellular cyclic adenosine monophosphate (cAMP) by forskolin through adenylyl cyclase (AC) resulted in transcriptional upregulation of CXCR4 with a concomitant increase in replication of the CXCR4-utilizing HIV-1 strain IIIB. Transient expression analyses also demonstrated an increase in CXCR4-, CCR5-, and CXCR4-/CCR5-utilizing HIV-1 (LAI, YU2, and 89.6, respectively) promoter …

Osborne's Ligament: A Review Of Its History, Anatomy, And Surgical Importance., Andre Granger, Juan P Sardi, Joe Iwanaga, Thomas J Wilson, Lynda Yang, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

When discussing the pathophysiology of ulnar neuropathy, Geoffrey Vaughan Osborne described a fibrous band that can be responsible for the symptoms seen in this disorder. In this paper, we take a glimpse at the life of Osborne and review the anatomy and surgical significance of Osborne's ligament. This band of tissue connects the two heads of the flexor carpi ulnaris and thus forms the roof of the cubital tunnel. To our knowledge, no prior publication has reviewed the history of this ligament, and very few authors have studied its anatomy in any detail. Therefore, the aim of the present paper …

Diagnosis Of Lchad/Tfp Deficiency In An At Risk Newborn Using Umbilical Cord Blood Acylcarnitine Analysis, Donna Raval, Kristina Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura Kofman, Brendan Lanpher, Natalie Hauser, Debra Regier

Pathology Faculty Publications

Trifunctional protein deficiency/Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD/TFP) deficiency is a disorder of fatty acid oxidation and ketogenesis. Severe neonatal lactic acidosis, cardiomyopathy, and hepatic dysfunction are caused by the accumulation of toxic long-chain acylcarnitines. The feasibility of umbilical cord blood use in screening for acylcarnitine analysis and free carnitine has been hypothesized but not reported in LCHAD/TFP neonates.

We present a 4 week old female who was at risk of inheriting LCHAD/TFP deficiency and was diagnosed at the time of delivery using umbilical cord blood. Umbilical cord blood was collected at delivery and sent for acylcarnitine analysis. Treatment was started …

Labrad : Vol 43, Issue 1 - March 2017, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Chikungunya
• Rapid Molecular Diagnosis of Chlamydia Trachomatis (CT) and Neisseria Gonorrhoeae (NG) Urethritis
• Overview of Rubella Testing
• Most Common Bone and Soft Tissue Infections Seen in our Practice
• Diagnosis of Helicobacter Pylori Infection in Developing Countries- Pros & Cons
• Screening for Neonatal Infections with TORCH Profile
• Blood and Bone Marrow Changes in Viral Infections
• Malaria
• World Rare Disease Day
• Radiology Pathology Correlation

Down-Regulation Of Fructose-1, 6-Bisphosphatase-1 (Fbp1) In High Grade Urothelial Carcinoma (Uc); As A New Diagnostic Marker To Differentiate Nested Variants Of Urothelial Carcinoma From Benign Entities, Taliya Farooq, Anas Mashlah, Faisal Saeed, Humayun Islam, Jonathan I. Epstein, Minghao Zhong

NYMC Faculty Posters

No abstract provided.

Rmdo-2, Olig-2 And Synaptophysin Expression Is A Frequent Event In Malignant Melanoma: Diagnostic Pitfalls In Glial Tumor, Taliya Farooq, Esther C. Yoon, Anas Mashlah, Sina Zomorrodian, George M. Kleinman

NYMC Faculty Posters

No abstract provided.

Giant Arachnoid Granulation Associated With Anomalous Draining Vein: A Case Report., Randle Umeh, Rod J Oskouian, Marios Loukas, R Shane Tubbs

Articles, Abstracts, and Reports

Giant arachnoid granulations (AG) can mimic intracranial lesions. Knowledge of these structures can help avoid misdiagnosis when interpreting imaging. Here, we report a child who presented with a mass within the superior sagittal sinus and an anomalous draining vein. Herein, the diagnosis of a giant AG was made. Clinicians who view or interpret imaging of the head should be aware of these anatomical variants and though when very large, apparently, do not necessarily result in pathology. Based on our case report, giant AG might also demonstrate anomalous draining veins.

Evaluation Of The Parasight Platform For Malaria Diagnosis, Yochay Eshel, Arnon Houri-Yafin, Hagai Benkuzari, Natalie Lezmy, Mamta Soni, Malini Charles, Jayanthi Swaminathan, Hilda Solomon, Pavithra Sampathkumar, Zul Premji, Caroline Mbithi, Zaitun Nneka, Simon Onsongo, Daniel Maina, Sarah Levy-Schreier, Caitlin Lee Cohen, Dan Gluck, Joseph Joel Pollak, Seth J. Salpeter

Pathology, East Africa

The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. Here we present the results from two clinical studies on the commercially available version of this technology, the Sight Diagnostics Parasight platform, which provides malaria diagnosis, species identification, and parasite quantification. We conducted a multisite trial in Chennai, India (Apollo Hospital [n = 205]), and Nairobi, Kenya …

Homocysteine As A Biomarker For Thrombosis: What Is The Learning Curve?, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.

Coinfection With Lichtheimia Corymbifera And Aspergillus Flavus In An Immune-Competent Patient Mimicking As Pulmonary-Renal Syndrome, Ali Bin Sarwar Zubairi, Farah Idress, Kauser Jabeen, Saima Kamal, Afia Zafar

Department of Medicine

Lichtheimia corymbifera and Aspergillus flavus pulmonary coinfection has been rarely reported in immune-competent patients. We report case of a young male who presented with clinical features of pulmonary-renal syndrome and was later diagnosed to have bilateral polymicrobial fungal lung infection.

Tailored Metabolic Workup For Urolithiasis – The Debate Continues, Hammad Ather, Imran Siddiqui, Tahmeena Siddiqui, M Nasir Sulaiman

Department of Surgery Docs

Abstract

Urolithiasis is one of the commonest afflictions of the urinary tract. Stones are of various chemical compositions, some share some common etiology; but most are specific to the structure and composition of stone. In view of highly recurrent nature of this condition, it is logical to have strategies for prevention. However, due to multiple factors most patients receive no or fragmented information on prevention. The current controversy is to the extent of metabolic workup in adult first time stone former. This requires longitudinal studies to show benefit in prevention strategies. Patients at high risk can have recurrence in weeks …

Novel Long-Chain Compounds With Both Immunomodulatory And Mena Inhibitory Activities Against Staphylococcus Aureus And Its Biofilm., Seoung-Ryoung Choi, Joel Frandsen, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Menaquinone (MK) biosynthesis pathway is a potential target for evaluating antimicrobials in gram-positive bacteria. Here, 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) was targeted to reduce methicillin-resistant Staphylococcus aureus (MRSA) growth. MenA inhibiting, long chain-based compounds were designed, synthesized and evaluated against MRSA and menaquinone utilizing bacteria in aerobic conditions. The results showed that these bacteria were susceptible to most of the compounds. Menaquinone (MK-4) supplementation rescued MRSA growth, suggesting these compounds inhibit MK biosynthesis. 3a and 7c exhibited promising inhibitory activities with MICs ranging 1-8 μg/mL against MRSA strains. The compounds did not facilitate small colony variant formation. These compounds also inhibited the …

Death Related To Fistulas Involving The Gastrointestinal And Cardiovascular Systems, Allan Joseph Medwick Edd, Joseph Prahlow

Research Day

BACKGROUND/INTRODUCTION: Gastrointestinal tract fistulas are relatively uncommon and can be congenital or acquired. Fistulas may communicate with a variety of anatomic locations, including body cavities, the skin, and other organ systems. Acquired fistulas which communicate with the cardiovascular system are of particular concern, as they may be associated with significant morbidity and mortality. This study reports on three cases of acquired, post-surgical fistula formation involving the gastrointestinal and cardiovascular systems. CASE REPORTS: Case 1 - A 57-year-old man experienced sudden cardiac death shortly after having a permanent pacemaker placed for atrial fibrillation. Approximately two years earlier, he underwent surgical resection …

State Of Harmonization Of 24 Serum Albumin Measurement Procedures And Implications For Medical Decisions, Lorin M. Bachmann, Min Yu, James C. Boyd, David E. Bruns, W. Greg Miller

Pathology Publications

BACKGROUND: Measurements of serum and plasma albumin are widely used in medicine, including as indicators of quality of patient care in renal dialysis centers.

METHODS: Pools were prepared from residual patient serum (n = 50) and heparin plasma (n = 48) from patients without renal disease, and serum from patients with kidney failure before hemodialysis (n = 53). Albumin was measured in all samples and in ERM-DA470k/IFCC reference material (RM) by 3 immunochemical, 9 bromcresol green (BCG), and 12 bromcresol purple (BCP) methods.

RESULTS: Two of 3 immunochemical procedures, 5 of 9 BCG, and 10 of 12 BCP methods recovered …

Quality Of Life In Chronic Pancreatitis Is Determined By Constant Pain, Disability/Unemployment, Current Smoking, And Associated Co-Morbidities, Jorge D. Machicado, Stephen T. Amann, Michelle A. Anderson, Judah Abberbock, Stuart Sherman, Darwin L. Conwell, Gregory A. Cote, Vikesh K. Singh, Michele D. Lewis, Samer Alkaade, Bimaljit S. Sandhu, Nalini M. Guda, Thiruvengadam Muniraj, Gong Tang, John Baillie, Randall E. Brand, Timothy B. Gardner, Andres Gelrud, Christopher E. Forsmark, Peter A. Banks, Adam Slivka, C. Mel Wilcox, David C. Whitcomb, Dhiraj Yadav

Pathology Publications

OBJECTIVES: Chronic pancreatitis (CP) has a profound independent effect on quality of life (QOL). Our aim was to identify factors that impact the QOL in CP patients.

METHODS: We used data on 1,024 CP patients enrolled in the three NAPS2 studies. Information on demographics, risk factors, co-morbidities, disease phenotype, and treatments was obtained from responses to structured questionnaires. Physical and mental component summary (PCS and MCS, respectively) scores generated using responses to the Short Form-12 (SF-12) survey were used to assess QOL at enrollment. Multivariable linear regression models determined independent predictors of QOL.

RESULTS: Mean PCS and MCS scores were …

Development And Validation Of Clinical Whole-Exome And Whole-Genome Sequencing For Detection Of Germline Variants In Inherited Disease, Madhuri Hegde, Avni Santani, Rong Mao, Andrea Ferreira-Gonzalez, Karen E. Weck, Karl V. Voelkerding

Pathology Publications

Context.-With the decrease in the cost of sequencing, the clinical testing paradigm has shifted from single gene to gene panel and now whole-exome and whole-genome sequencing. Clinical laboratories are rapidly implementing next-generation sequencing-based whole-exome and whole-genome sequencing. Because a large number of targets are covered by whole-exome and whole-genome sequencing, it is critical that a laboratory perform appropriate validation studies, develop a quality assurance and quality control program, and participate in proficiency testing.

Objective.-To provide recommendations for wholeexome and whole-genome sequencing assay design, validation, and implementation for the detection of germline variants associated in inherited disorders.

Data Sources.-An example of …

Development And Validation Of Targeted Next-Generation Sequencing Panels For Detection Of Germline Variants In Inherited Diseases., Avni Santani, Jill Murrell, Birgit Funke, Zhenming Yu, Madhuri Hegde, Rong Mao, Andrea Ferreira-Gonzalez, Karl V. Voelkerding, Karen E. Weck

Pathology Publications

Context.-The number of targeted next-generation sequencing (NGS) panels for genetic diseases offered by clinical laboratories is rapidly increasing. Before an NGS-based test is implemented in a clinical laboratory, appropriate validation studies are needed to determine the performance characteristics of the test.

Objective.-To provide examples of assay design and validation of targeted NGS gene panels for the detection of germline variants associated with inherited disorders.

Data Sources.-The approaches used by 2 clinical laboratories for the development and validation of targeted NGS gene panels are described. Important design and validation considerations are examined.

Conclusions.-Clinical laboratories must validate performance specifications of each test …

Hiv Induces Expression Of Complement Component C3 In Astrocytes By Nf-Κb-Dependent Activation Of Interleukin-6 Synthesis, Jadwiga Nitkiewicz, Alejandra Borjabad, Susan Morgello, Jacinta Murray, Wei Chao, Luni Emdad, Paul B. Fisher, Mary Jane Potash, David J. Volsky

Pathology Publications

Background

Abnormal activation of the complement system contributes to some central nervous system diseases but the role of complement in HIV-associated neurocognitive disorder (HAND) is unclear.

Methods

We used real-time PCR and immunohistochemistry to detect complement expression in postmortem brain tissue from HAND patients and controls. To further investigate the basis for viral induction of gene expression in the brain, we studied the effect of HIV on C3 expression by astrocytes, innate immune effector cells, and targets of HIV. Human fetal astrocytes (HFA) were infected with HIV in culture and cellular pathways and factors involved in signaling to C3 expression …

Evaluation Of The Angiotensin Ii Receptor Blocker Azilsartan Medoxomil In African-American Patients With Hypertension, Wallace Johnson, William B. White, Domenic Sica, George L. Bakris, Michael A. Weber, Alison Handley, Alfonso Perez, Charlie Cao, Stuart Kupfer, Elijah B. Saunders

Pathology Publications

The efficacy and safety of azilsartan medoxomil (AZL-M) were evaluated in African-American patients with hypertension in a 6-week, double-blind, randomized, placebo-controlled trial, for which the primary end point was change from baseline in 24-hour mean systolic blood pressure (BP). There were 413 patients, with a mean age of 52years, 57% women, and baseline 24-hour BP of 146/91mmHg. Treatment differences in 24-hour systolic BP between AZL-M 40mg and placebo (-5.0mmHg; 95% confidence interval, -8.0 to -2.0) and AZL-M 80mg and placebo (-7.8mmHg; 95% confidence interval, -10.7 to -4.9) were significant (P.001 vs placebo for both comparisons). Changes in the clinic BPs …

Donor Ifnl4 Genotype Is Associated With Early Post-Transplant Fibrosis In Recipients With Hepatitis C, Taylor Aiken, Ari Garber, Dawn Thomas, Nicole Hamon, Rocio Lopez, Rajesh Konjeti, Arthur Mccullough, Nizar Zein, John Fung, Medhat Askar, Binu V. John

Pathology Publications

Background and Aims

Early post-transplant hepatic fibrosis is associated with poor outcomes and may be influenced by donor/recipient genetic factors. The rs368234815 IFNL4 polymorphism is related to the previously described IL28B polymorphism, which predicts etiology-independent hepatic fibrosis. The aim of this study was to identify the impact of donor and/or recipient IFNL4 genotype on early fibrosis among patients transplanted for hepatitis C (HCV).

Methods

Clinical data were collected for 302 consecutive patients transplanted for HCV. 116 patients who had available liver biopsies and donor/recipient DNA were included. 28% of these patients with stage 2 fibrosis or greater were compared to …

Simultaneous Papillary Carcinoma In Thyroglossal Duct Cyst And Thyroid, Gustavo Cancela E Penna, Henrique Gomes Mendes, Adele O. Kraft, Cynthia Koeppel Berenstein, Bernardo Fonseca, Wagner José Martorina, Andreise Laurian N. R. De Souza, Gustavo Meyer De Moraes, Kamilla Maria Araújo Brandão Rajão, Bárbara Érika Caldeira Araújo Sousa

Pathology Publications

Thyroglossal duct cyst (TDC) is a cystic expansion of a remnant of the thyroglossal duct tract. Carcinomas in the TDC are extremely rare and are usually an incidental finding after the Sistrunk procedure. In this report, an unusual case of a 36-year-old woman with concurrent papillary thyroid carcinoma arising in the TDC and on the thyroid gland is presented, followed by a discussion of the controversies surrounding the possible origins of a papillary carcinoma in the TDC, as well as the current management options.

The Effect Of Hiv Infection And Hcv Viremia On Inflammatory Mediators And Hepatic Injury-The Women's Interagency Hiv Study., Sheila M Keating, Jennifer L Dodge, Philip J Norris, John Heitman, Stephen J Gange, Audrey L French, Marshall J Glesby, Brian R Edlin, Patricia S Latham, Maria C Villacres, Ruth M Greenblatt, Marion G Peters

Pathology Faculty Publications

Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = …

Glypican-3 And Cd81 Promote Development Of Hepatocellular Carcinoma And Hepatoblastoma Through Negative Selection., Yuhua Xue, Wendy Mars, William Bowen, Aatur D. Singhi, Sarangarajan Ranganathan, George K. Michalopoulos

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Gallium Nanoparticles Facilitate Phagosome Maturation And Inhibit Growth Of Virulent Mycobacterium Tuberculosis In Macrophages., Seoung-Ryoung Choi, Bradley E. Britigan, David M. Moran, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

New treatments and novel drugs are required to counter the growing problem of drug-resistant strains of Mycobacterium tuberculosis (M.tb). Our approach against drug resistant M.tb, as well as other intracellular pathogens, is by targeted drug delivery using nanoformulations of drugs already in use, as well as drugs in development. Among the latter are gallium (III) (Ga)-based compounds. In the current work, six different types of Ga and rifampin nanoparticles were prepared in such a way as to enhance targeting of M.tb infected-macrophages. They were then tested for their ability to inhibit growth of a fully pathogenic strain (H37Rv) or a …

Neuroprotection Through Flavonoid: Enhancement Of The Glyoxalase Pathway., Joel Frandsen, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases - including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder - are often induced or exacerbated by accumulation of methylglyoxal. Antioxidant compounds possess several distinct mechanisms that enhance the glyoxalase pathway and function as neuroprotectants. Flavonoids are well-researched secondary plant metabolites that appear to be effective in reducing levels of oxidative stress and inflammation in neural …

A Previously Unreported Arterial Variant Of The Suboccipital Region Based On Cadaveric Dissection., Christian Fisahn, Brittni Burgess, Joe Iwanaga, Fernando Alonso, Jens R Chapman, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

No abstract provided.

A Rare Case Of Epstein–Barr Virus-Related Plasmacytoma Involving Maxillary Sinus Mucosa, Julie D. Gibbs, Marino E. Leon, Kenia Liu, Johnny Nguyen, Ling Zhang

Pathology and Cell Biology Faculty Publications

No abstract provided.