Pathology Commons^™

Classical And Alternative Nuclear Factor-Kappab In Epithelium: Impacts In Allergic Airway Disease And Avenues For Redox Regulation, Jane Elizabeth Tully

Graduate College Dissertations and Theses

Nuclear Factor kappaB (NF-êB) is a transcription factor whose activation is increased in settings of allergic asthma. At least two parallel NF-êB pathways exist: the classical pathway, which plays a role in inflammation and cell survival, and the alternative pathway, which regulates lymphoid cell development and organogenesis. The classical NF-êB pathway regulates inflammatory responses derived from lung epithelial cells; however, the role of the alternative pathway in lung epithelial cells remains unclear. We demonstrate that both classical and alternative NF-êB are activated in lung epithelial cells in response to multiple pro-inflammatory agonists, and siRNA-mediated knockdown of alternative NF-êB proteins largely …

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 …

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 …

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 …

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, …

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 …

P90/Cip2a Regulates Lung Cancer Cell Proliferation And Cell Apoptosis Via The Akt Signaling Pathway, Ningjing Lei

Open Access Theses & Dissertations

Cancerous inhibitor of PP2A (CIP2A) is an intracellular endogenous protein phosphatase 2A (PP2A) inhibitor with oncogenic activities. Initially identified as a tumor-associated antigen (TAA) in gastric and liver cancer patients, CIP2A was overexpressed in a variety of cancer types. And the overexpression of CIP2A in cancer cell is associated with increased cell proliferation and decreased cell apoptosis. However, the mechanism of CIP2A in cancer progression is still poorly understood. Here, we reported the evidence that CIP2A can regulate AKT phosphorylation at S473 under growth factor stimulation and our results also showed that CIP2A might regulate cell proliferation and cell apoptosis …

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 …

Network Analysis Of Circular Permutations In Multidomain Proteins Reveals Functional Linkages For Uncharacterized Proteins., Donald Adjeroh, Yue Jiang, Bing-Hua Jiang, Jie Lin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Various studies have implicated different multidomain proteins in cancer. However, there has been little or no detailed study on the role of circular multidomain proteins in the general problem of cancer or on specific cancer types. This work represents an initial attempt at investigating the potential for predicting linkages between known cancer-associated proteins with uncharacterized or hypothetical multidomain proteins, based primarily on circular permutation (CP) relationships. First, we propose an efficient algorithm for rapid identification of both exact and approximate CPs in multidomain proteins. Using the circular relations identified, we construct networks between multidomain proteins, based on which we perform …

Androgen Receptor Expression And Associated Clinico-Pathologic Features In Primary Breast Cancer From Kenya, Joshua Kibera Chege

Theses & Dissertations

Introduction: Breast cancer is a heterogeneous group of diseases classified into various subtypes according to clinical, histological and molecular features as well as by the expression of prognostic and predictive biomarkers. New biomarkers are being studied which may be therapeutic targets in various breast cancer subtypes particularly triple-negative breast cancer. Recent studies show that androgen receptor (AR) expression can be used as a prognostic marker and there is evidence that anti-androgen therapy may be beneficial in oestrogen receptor negative breast cancer. Retrospective studies show that patients with breast cancers co-expressing androgen receptor and oestrogen receptor have a favourable prognosis and …

Applying Consensus Criteria To The Evaluation Of Patients With Suspected Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, E. Mulwa-Babu, Riyat Malkit, D. Parech

Pathology, East Africa

We describe a series of 5 patients in whom the application of consensus criteria for the diagnosis of chronic lymphocytic leukemia (CLL) led to a revised diagnosis. These patients had been recruited in a wider study describing the occurrence of CLL in Kenya. This case series highlights some of the pitfalls of making a diagnosis of CLL without incorporating all criteria.

Low Prevalence Of Methicillin Resistant As Determined By An Automated Identification System In Two Private Hospitals In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Beatrice Kabera, Gunturu Revathi

Pathology, East Africa

Background: Staphylococcus aureus (S.aureus) is a major cause of both healthcare and community acquired infections. In developing countries, manual phenotypic tests are the mainstay for the identification of staphylococci with the tube and slide coagulase tests being relied upon as confirmatory tests for S. aureus. The subjectivity associated with interpretation of these tests may result in misidentification of coagulase negative staphylococci as S.aureus. Given that antibiotic resistance is more prevalent in CONS, this may result in over estimation of methicillin resistant S.aureus (MRSA) prevalence.

Methods: A review of susceptibility data from all non-duplicate S.aureus isolates generated between March 2011 and …

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 …

Harnessing Microbiome And Probiotic Research In Sub-Saharan Africa: Recommendations From An African Workshop, Gregor Reid, Nicholas Nduti, Wilbert Sybesma, Remco Kort, Tobias R. Kollmann, Rodney Adam, Hamadi Boga, Eric M. Brown, Alexandra Einerhand, Hani El-Nezami, Gregory B. Gloor, Irene I. Kavere, Johanna Lindahl, Amee Manges, Wondu Mamo, Rocio Martin, Amy Mcmillan, Jael Obiero, Pamela A. Ochieng’, Arnold Onyango, Stephen Rulisa, Eeva Salminen, Seppo Salminen, Antony Sije, Jonathan R. Swann, William Van Treuren, Daniel Waweru, Steve J. Kemp

Pathology, East Africa

To augment capacity-building for microbiome and probiotic research in Africa, a workshop was held in Nairobi, Kenya, at which researchers discussed human, animal, insect, and agricultural microbiome and probiotics/prebiotics topics. Five recommendations were made to promote future basic and translational research that benefits Africans.

Epidemiology Of Malaria In A Village In The Rufiji River Delta, Tanzania: Declining Transmission Over 25 Years Revealed By Different Parasitological Metrics, Anna Färnert, Victor Yman, Manijeh Vafa Homann, Grace Wandell, Leah Mhoja, Marita Johansson, Salome Jesaja, Johanna Sandlund, Kazuyuki Tanabe, Ulf Hammar, Matteo Bottai, Zul Premji, Anders Björkman, Ingegerd Rooth

Pathology, East Africa

Background: Assessments of the epidemiology of malaria over time are needed to understand changes in transmission and guide control and elimination strategies.

Methods: A longitudinal population study was established in 1985 in Nyamisati village in the Rufiji River Delta, Tanzania. A physician and research team lived in the village 1984–2000. Parasite prevalence by microscopy and two PCR methods, spleen rates and haemoglobin levels were measured in repeated cross-sectional surveys between 1985 and 2010. Passive surveillance of malaria cases was maintained until end 1999. Bed nets were distributed after the surveys 1993, 1999 and 2010.

Results: In 1985, overall parasite prevalence …

Aetiology Of Acute Febrile Episodes In Children Attending Korogwe District Hospital In North-Eastern Tanzania, C. Mahende, B. Ngasala, J. Lusingu, A. Butichi, P. Lushino, M. Lemnge, Zul Premji

Pathology, East Africa

Introduction: Although the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH).

Methods: A hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania. Patients aged 2 to 59 months presenting at the outpatient department with an acute medical condition and fever (measured axillary temperature ≥37.5°C) were enrolled. Blood samples were examined for malaria parasites, human immunodeficiency virus (HIV) and bacterial infections. A urine culture was …

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 …