Medicine and Health Sciences Commons^™

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.

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.

Quality Control Material For The Detection Of Somatic Mutations In Fixed Clinical Specimens By Next-Generation Sequencing, Catherine I. Dumur, Jorge A. Almenara, Celeste N. Powers, Andrea Ferreira-Gonzalez

Pathology Publications

Background: Targeted next generation sequencing (NGS) technology to assess the mutational status of multiple genes on formalin-fixed, paraffin embedded (FFPE) tumors is rapidly being adopted in clinical settings, where quality control (QC) practices are required. Establishing reliable FFPE QC materials for NGS can be challenging and/or expensive. Here, we established a reliable and cost-effective FFPE QC material for routine utilization in the Ion AmpliSeq™ Cancer Hotspot Panel v2 (CHP2) assay.

Methods: The performance characteristics of the CHP2 assay were determined by sequencing various cell line mixtures and 55 different FFPE tumors on the Ion Torrent PGM platform. A FFPE QC …

Quality Control Material For The Detection Of Somatic Mutations In Fixed Clinical Specimens By Next-Generation Sequencing, Catherine I. Dumur, Jorge A. Almenara, Celeste N. Powers, Andrea Ferreira-Gonzalez

Pathology Publications

Background

Targeted next generation sequencing (NGS) technology to assess the mutational status of multiple genes on formalin-fixed, paraffin embedded (FFPE) tumors is rapidly being adopted in clinical settings, where quality control (QC) practices are required. Establishing reliable FFPE QC materials for NGS can be challenging and/or expensive. Here, we established a reliable and cost-effective FFPE QC material for routine utilization in the Ion AmpliSeq™ Cancer Hotspot Panel v2 (CHP2) assay.

Methods

The performance characteristics of the CHP2 assay were determined by sequencing various cell line mixtures and 55 different FFPE tumors on the Ion Torrent PGM platform. A FFPE QC …

Headaches And Hemiparesis In An Immunocompetent Inmate, Andrea Gilbert Jelinek, Christine Fuller, Ahmet Baykal, Kimberly Stogner-Underwood, Hope Richard, Knarik Arkun

Pathology Publications

This is a case of a 22 year-old African American male inmate with no significant past medical history who regularly cleaned moldy bathrooms and showers during his incarceration. The patient presented with progressive development of left-sided weakness, dizziness, headaches, and vomiting over a two month period. In summary, we report this case to boost awareness of the potential for CNS phaeohyphomycosis infection to present as a clinical and radioimaging mimic of high grade glioma. Our patient, a previously healthy adult, is one of less than a dozen cases of cerebral phaeohyphomycosis due to Bipolaris documented in the literature, and is …

Igfbp-3 Inhibits Cytokine-Induced Insulin Resistance And Early Manifestations Of Atherosclerosis, Lathika Mohanraj, Ho-Seong Kim, Wei Li, Qing Cai, Ki E. Kim, Hye-Jung Shin, Yong-Jae Lee, Woo J. Lee, Jung H. Kim, Youngman Oh

Pathology Publications

Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced …

Adenovirus-36 Is Associated With Obesity In Children And Adults In Sweden As Determined By Rapid Elisa, Malin Almgren, Richard Atkinson, Jia He, Agenta Hilding, Emilia Hagman, Alicia Wolk, Anders Thorell, Claude Marcus, Erik Naslund, Claes-Goren Ostenson, Martin Schalling, Catherina Lavebratt

Pathology Publications

Background

Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals.

Principal Findings

Using …

Nuclear Expression Of Klf6 Tumor Suppressor Factor Is Highly Associated With Overexpression Of Erbb2 Oncoprotein In Ductal Breast Carcinomas, Ricardo C. Gehrau, Diego S. D'Astolfo, Catherine I. Dumur, Jose L. Bocco, Nicolas P. Koritschoner

Pathology Publications

Background

Krüppel-like factor 6 (KLF6) is an evolutionarily conserved and ubiquitously expressed protein that belongs to the mammalian Sp1/KLF family of transcriptional regulators. Though KLF6 is a transcription factor and harbors a nuclear localization signal it is not systematically located in the nucleus but it was detected in the cytoplasm of several tissues and cell lines. Hence, it is still not fully settled whether the tumor suppressor function of KLF6 is directly associated with its ability to regulate target genes.

Methodology/Principal Findings

In this study we analyzed KLF6 expression and sub-cellular distribution by immunohistochemistry in several normal and tumor tissues …

Treatment Of Chlordecone (Kepone) Toxicity With Cholestyramine — Results Of A Controlled Clinical Trial, William J. Cohn , M.D., James J. Boylan , M.D., Robert V. Blanke , Ph.D., Marc W. Fariss , B.S., John R. Howell , M.S., Philip S. Guzelian , M.D.

Pathology Publications

Abstract

Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165±27 days — mean ± S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the intestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal …