Pathology Commons^™

Labrad : Vol 40, Issue 1 - April 2014, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Provocative Testing for Growth Hormone Disorders
• Serum Procalcitonin for Early Sepsis Diagnosis
• Monoclonal Gammopathy of Undetermined Significance (MGUS)
• Understanding Six Sigma Methodology
• Blood Collection for Culture
• Molecular Analysis of Alpha Thalassaemia by Multiple Ligation Probe Assay
• Prognostification of Acute Myeloid Leukemia with FLT 3 Mutation
• Interferon Gamma Release Assay (IGRA) for Detection of Mycobacterium Tuberculosis Infection in the Host
• Meeting Report: The 37th Annual Conference of the Pakistan Association of Pathologists

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

Carp-1 Functional Mimetics Are A Novel Class Of Small Molecule Inhibitors Of Malignant Pleural Mesothelioma Cells, Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi

Oncology Faculty Publications

Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of …

Adiponectin Inhibits Tumor Necrosis Factor-Α-Induced Vascular Inflammatory Response Via Caveolin-Mediated Ceramidase Recruitment And Activation., Yajing Wang, Xiaoliang Wang, Wayne Bond Lau, Yuexing Yuan, David Booth, Jing-Jing Li, Rosario Scalia, Kyle Preston, Erhe Gao, Walter Koch, Xin-Liang Ma

Department of Medicine Faculty Papers

RATIONALE: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered.

OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling.

METHODS AND RESULTS: Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P87% of adiponectin-induced nCDase …

Natural History Of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer In Men With Favorable Prognostic Indicators, Andrew Renshaw

All Publications

No abstract provided.

Hiding In Plain Sight: Interplay Between Staphylococcal Biofilms And Host Immunity., Tyler D. Scherr, Cortney E. Heim, John M. Morrison, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus and Staphylococcus epidermidis are notable for their propensity to form biofilms on implanted medical devices. Staphylococcal biofilm infections are typified by their recalcitrance to antibiotics and ability to circumvent host immune-mediated clearance, resulting in the establishment of chronic infections that are often recurrent in nature. Indeed, the immunomodulatory lifestyle of biofilms seemingly shapes the host immune response to ensure biofilm engraftment and persistence in an immune competent host. Here, we provide a brief review of the mechanisms whereby S. aureus and S. epidermidis biofilms manipulate host-pathogen interactions and discuss the concept of microenvironment maintenance in infectious outcomes, as …

Expression Of Mir-15/107 Family Micrornas In Human Tissues And Cultured Rat Brain Cells, Wang-Xia Wang, Robert J. Danaher, Craig S. Miller, Joseph R. Berger, Vega G. Nubia, Bernard R. Wilfred, Janna H. Neltner, Christopher M. Norris, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs), sharing a 5' AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression …

Targeting Fibroblast Activation Protein In Tumor Stroma With Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth And Augment Host Immunity Without Severe Toxicity., Liang-Chuan S. Wang, Albert Lo, John Scholler, Jing Sun, Rajrupa S. Majumdar, Veena Kapoor, Michael Antzis, Cody E. Cotner, Laura A. Johnson, Amy C. Durham, Charalambos C. Solomides, Md, Carl H. June, Ellen Puré, Steven M. Albelda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the …

Response Of An Aggressive Periosteal Aneurysmal Bone Cyst (Abc) Of The Radius To Denosumab Therapy., Chantal Pauli, Bruno Fuchs, Christian Pfirrmann, Julia A. Bridge, Silvia Hofer, Beata Bode

Journal Articles: Pathology and Microbiology

Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the …

Steady Increment Of Immature Platelet Fraction Is Suppressed By Irradiation In Single-Donor Platelet Components During Storage, Hong Hong, Wenbin Xiao, Robert W. Maitta

Faculty Scholarship

Circulating immature platelet fraction (IPF) reflects real-time thrombopoiesis and correlates with platelet recovery from thrombocytopenic presentations. To understand the dynamics of IPF in platelet transfusions, we quantified the %-IPF in single-donor platelet components (SDP) during prolonged storage. %-IPF significantly increased from baseline by day 5 post-donation. Absolute IPF counts (A-IPC) had similar significant increments. However, gamma-irradiation suppressed the increments of %-IPF and A-IPC by >50%. Ultrastructural analysis of SDP units at day 10 showed well preserved morphology of immature platelets. Our findings suggest that IPF might actively expand ex-vivo and may have a longer shelf life than their mature counterparts. …

Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski

Department of Surgery

TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo. In this study, we explored how mGluR1 contributes to TNBC …

Gold(Iii)-Dithiocarbamato Peptidomimetics In The Forefront Of The Targeted Anticancer Therapy: Preclinical Studies Against Human Breast Neoplasia, Chiara Nardon, Sara M. Schmitt, Huanjie Yang, Jian Zuo, Delores Fregona, Q. Ping Dou

Oncology Faculty Publications

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. …

Can Newly Developed, Rapid Immunochromatographic Antigen Detection Tests Be Reliably Used For The Laboratory Diagnosis Of Influenza Virus Infections?, J. J. Dunn, C. C. Ginocchio

Journal Articles

Five years ago, the Point-Counterpoint series was launched. The initial article asked about the role of rapid immunochromatographic antigen testing in diagnosis of influenza A virus 2009 H1N1 infection (1). Since that article, major changes have been made not only in immunochromatographic antigen detection (IAD) test for the influenza viruses but there also has been rapid development of commercially available nucleic acid amplification tests (NAATs) for influenza virus detection as well. Further, a novel variant of influenza A, H7N9, has emerged in Asia and H5N1 is also re-emergent. In this initial article, the editor of this series, Peter Gilligan, identified …

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease), C. Q. Fan, J. M. Crawford

Journal Articles

Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial …

Is Aggressive Digital Papillary Adenocarcinoma Really Aggressive Digital Papillary Adenocarcinoma?, S. Chen, M. Asgari

Journal Articles

No abstract provided.

Papillary Adenocarcinoma In Situ Of The Skin: Report Of Four Cases, S. Chen, M. Asgari

Journal Articles

Although rare isolated cases of adenocarcinoma in situ of skin have been reported in the literature, adenocarcinoma in situ of skin as a concept and as a diagnostic category has not been established in the field of dermatopathology. In this work, four cases of papillary adenocarcinoma in situ of the skin are presented. In addition, the notion that lesions previously reported in the medical literature under the term of "papillary eccrine adenoma" are actually adenocarcinoma in situ is discussed.

Brain Region-Specific Alterations In The Gene Expression Of Cytokines, Immune Cell Markers And Cholinergic System Components During Peripheral Endotoxin-Induced Inflammation, H. A. Silverman, M. Dancho, A. Regnier-Golanov, M. Nasim, M. Ochani, P. S. Olofsson, M. Ahmed, E. J. Miller, S. S. Chavan, E. Golanov, C. Metz, K. J. Tracey, V. A. Pavlov

Journal Articles

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune - brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels) remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum, and thalamus in mice following an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels …

Septic Arthritis Of A Native Knee Joint Due To Corynebacterium Striatum, L. F. Westblade, F. Shams, S. Duong, O. Tariq, A. Bulbin, W. Zhen, S. Sakaria, B. A. Ford, C. A. D. Burnham, C. C. Ginocchio, +1 Additional Author

Journal Articles

We report a case of septic arthritis of a native knee joint due to Corynebacterium striatum, a rare and unusual cause of septic arthritis of native joints. The isolate was identified by a combination of phenotypic, mass spectrometric, and nucleic acid-based assays and exhibited high-level resistance to most antimicrobials.

Expression Of Blimp-1 In Dendritic Cells Modulates The Innate Inflammatory Response In Dextran Sodium Sulfate-Induced Colitis, S. J. Kim, J. Goldstein, K. Dorso, M. Merad, L. Mayer, J. M. Crawford, P. K. Gregersen, B. Diamond

Journal Articles

A single nucleotide polymorphism of PRDM1, the gene encoding Blimp-1, is strongly associated with inflammatory bowel disease. Here, we demonstrate that Blimp-1 in CD103(+) dendritic cells (DCs) critically contributes to the regulation of macrophage homeostasis in the colon. Dextran sodium sulfate (DSS)-exposed Blimp-1(cko) mice with a deletion of Blimp-1 in CD103(+) DCs and CD11c(hi) macrophages exhibited severe inflammatory symptoms, pronounced weight loss, high mortality, robust infiltration of neutrophils in epithelial regions of the colon, an increased expression of proinflammatory cytokines and a significant decrease in CD103(+) DCs in the colon compared with DSS exposed wild-type (WT) mice. Purified colonic macrophages …

Schwannoma Of The Cervical Esophagus, M. Ferrante, A. Khan, C. Fan, F. Z. Jelloul

Journal Articles

Esophageal schwannoma is a rare tumor first described in 1967 by Chaterlin and Fissore. These tumors are most commonly found incidentally or from diagnostic work up of dysphagia or dyspnea. This entity cannot be diagnosed on clinical or radiographic basis alone. Histology demonstrates palisading spindle cells, few if any mitotic figures, and a peripheral cuff of lymphoid cells. Immunohistochemically, tumor cells stain positive for S100, a characteristic marker of Schwann cells. Once diagnosed, surgical enucleation is the typical treatment method employed.

Aggressive Renal Angiomyolipoma Of The Lipomatous Variant With Inferior Vena Cava Thrombus: A Case Report And Review Of The Literature, C. Fox, S. S. Salami, D. M. Moreira, G. S. Landis, D. Chan, O. Yaskiv, M. A. Vira

Journal Articles

Two variants of renal angiomyolipoma (AML)—classic and epithelioid—have been described. Although the epithelioid variant has been reported to demonstrate an aggressive clinical behavior, classic AML is usually benign. Herein, we report a case of a 42-year-old asymptomatic woman with a lipomatous variant of renal AML associated with an inferior vena cava thrombus managed with radical nephrectomy and caval thrombectomy.

Mantle Cell Lymphoma With In Situ Or Mantle Zone Growth Pattern: A Study Of Five Cases And Review Of Literature, P. Hsu, T. Yang, S. Sheikh-Fayyaz, J. Brody, J. Bandovic, S. Roy, J. Laser, J. E. Kolitz, C. Devoe, X. Zhang

Journal Articles

We present two rare cases of in situ mantle cell lymphoma ("in situ MCL") and three cases of MCL with mantle zone growth pattern (MCL-MZGP). The patients include four males and one female, with a median age of 66 years (range, 52 to 86 years). Two present with isolated lymphadenopathy and three with multiple lymphadenopathy. At presentation, the complete blood count (CBC) and serum lactate dehydrogenase (LDH) are normal in all cases. Histologic examination reveals an in situ pattern in two cases and a mantle zone growth pattern in three cases. The staging bone marrow biopsies show minimal involvement by …

Risk Factors For Gi Adverse Events In A Phase Iii Randomized Trial Of Bevacizumab In First-Line Therapy Of Advanced Ovarian Cancer: A Gynecologic Oncology Group Study, R. A. Burger, M. F. Brady, M. A. Bookman, B. J. Monk, J. L. Walker, H. D. Homesley, J. Fowler, S. C. Rubin, N. Katsumata, S. X. Liang, +4 Additional Authors

Journal Articles

Purpose To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Patients and Methods Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade 2 perforation, fistula, necrosis, or hemorrhage. Results Of 1,873 patients enrolled, 1,759 (94%) …

Academic Pathology: A New Journal, J. M. Crawford

Journal Articles

No abstract provided.

The Business Of Genomic Testing: A Survey Of Early Adopters, J. M. Crawford, L. Bry, J. Pfeifer, S. K. Caughron, S. Black-Schaffer, J. A. Kant, J. H. Kaufman

Journal Articles

Purpose: The practice of "genomic" (or "personalized") medicine requires the availability of appropriate diagnostic testing. Our study objective was to identify the reasons for health systems to bring next-generation Sequencing into their clinical laboratories and to understand the process by which such decisions were made. Such information may be of value to other health systems seeking to provide next-generation sequencing-testing to their patient populations. Methods: A standardized open-ended interview was conducted With the laboratory medical directors and/or department of pathology chairs of 13 different academic institutions in 10 different states. Results: Genomic testing for cancer dominated the institutional decision making, …

Tblr1 As An Androgen Receptor (Ar) Coactivator Selectively Activates Ar Target Genes To Inhibit Prostate Cancer Growth, G. Daniels, Y. Li, L. L. Gellert, A. Zhou, J. Melamed, X. Wu, X. Zhang, D. Zhang, D. Meruelo, S. K. Logan, R. Basch, P. Lee

Journal Articles

Androgen receptor (AR), a steroid hormone receptor, is critical for prostate cancer growth. However, activation of AR by androgens can also lead to growth suppression and differentiation. Transcriptional cofactors play an important role in this switch between proliferative and anti-proliferative AR target gene programs. Transducin beta-like-related protein 1 (TBLR1), a core component of the nuclear receptor corepressor complex, shows both corepressor and coactivator activities on nuclear receptors, but little is known about its effects on AR and prostate cancer. We characterized TBLR1 as a coactivator of AR in prostate cancer cells and determined that the activation is dependent on both …

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 …

The Role Of Pdgf C And Its Splice Variant In Breast Cancer, Alyssa Bottrell

Wayne State University Dissertations

The PDGF family consists of four members; while PDGF A and B are secreted as active dimers, PDGF C and D are secreted as latent dimers that undergo serine protease-mediated extracellular proteolytic activation. Gene expression analysis of breast cancer cell lines showed that PDGF C expression is associated with Basal B subtype breast cancer cells which have cancer stem cell-like characteristics. Furthermore, PDGF C expression is associated with triple-negative (estrogen receptor-, progesterone receptor- and HER2/neu-negative) breast cancer cells, a challenging type of breast cancer to treat. During the course of our study, we discovered a splice variant of PDGF C …

Concurrent Non-Ketotic Hyperglycinemia And Propionic Acidemia In An Eight Year Old Boy, Paul Kruszka, Brian Kirmse, Dina Zand, Kristina Cusmano-Ozog, Elaine Spector, John Hove, Kimberly A. Chapman

Pathology Faculty Publications

This is the first reported case of a patient with both non-ketotic hyperglycinemia and propionic acidemia. At 2 years of age, the patient was diagnosed with non-ketotic hyperglycinemia by elevated glycine levels and mutations in the GLDC gene (paternal allele: c.1576_1577insC delT and c.1580delGinsCAA; p.S527Tfs*13, and maternal allele: c.1819G>A; p.G607S). At 8 years of age after having been placed on ketogenic diet, he became lethargic and had severe metabolic acidosis with ketonuria. Urine organic acid analysis and plasma acylcarnitine profile were consistent with propionic acidemia. He was found to have an apparently homozygous mutation in the PCCB gene: c.49C …

Refusal To Autopsy: A Societal Practice In Pakistan Context, Laila Akber Cassum

School of Nursing & Midwifery

Autopsies or post-mortem examinations have become a common practice in Western medicine for verifying the cause of death, and to obtain additional scientific information on certain diseases. In monotheistic religions autopsies present several ethical questions even though the advantages attributed to post-mortems in the West are well acknowledged by people living in this modern world. In Islamic Republic of Pakistan where Islam is the prevailing religion followed by the Muslims, Pakistani society have diverse perception, assumptions and hypothesis on the concept of autopsy. This presumption is due to presence of diverse objections raised in religious and sociocultural context. In our …