Pathology Commons^™

On An Ensemble Algorithm For Clustering Cancer Patient Data, Ran Qi, Dengyuan Wu, Li Sheng, Donald E. Henson, Arnold M. Schwartz, Eric Xu, Kai Xing, Dechang Chen

Pathology Faculty Publications

Background

The TNM staging system is based on three anatomic prognostic factors: Tumor, Lymph Node and Metastasis. However, cancer is no longer considered an anatomic disease. Therefore, the TNM should be expanded to accommodate new prognostic factors in order to increase the accuracy of estimating cancer patient outcome. The ensemble algorithm for clustering cancer data (EACCD) by Chen et al. reflects an effort to expand the TNM without changing its basic definitions. Though results on using EACCD have been reported, there has been no study on the analysis of the algorithm. In this report, we examine various aspects of …

Linking Environmental Toxicant Exposure To Diabetes Susceptibility, Jannifer Beth Tyrrell

Wayne State University Dissertations

An important and unresolved question in the environmental health field is whether exposure to common environmental toxicants, such as dioxin and heavy metals like Pb, increase the risk of developing diabetes, especially in combination with other common metabolic stressors such as obesity.

Previous studies suggested that dioxin exposure increased peripheral insulin resistance but did not appear to cause fasting hyperglycemia or elevated hepatic glucose output. In concordance with those findings we observed that dioxin treatment caused a strong suppression of the expression of the key hepatic gluconeogenic genes PEPCK and G6Pase. However, this suppression was not solely mediated by the …

B Cell Acute Lymphoblastic Leukemia Associated With T(8;22)(P11.2q11.2): Role Of Additional Cytogenic Anomalies, Kate M. Serdy, Shireen R. Khoury, Louis Depalma

Pathology Faculty Publications

B lymphoblastic leukemia (B-ALL) may be associated with recurrent cytogenetic and molecular abnormalities. We describe the fourth-known case of B-ALL associated with the t(8;22)(p11.2q11.2) – a translocation seen more frequently in T lymphoblastic leukemia and acute myelogenous leukemia. This patient’s leukemia involves a combination of additional cytogenetic anomalies not yet described in the literature, including del(11)(q13q23), add(9)(p22), and monosomy 7. Given the role in B cell differentiation of genes in the affected regions, including MEN1 (11q13), ATM (11q22), ETS1(11q23), MLL (11q23), AF9 (9p22), and IKZ-F1 (7p12), this case may provide further insight into B cell leukemogenesis associated with the t(8;22). …

Whole Blood Platelet Aggregation And Release Reaction Testing In Uremic Patients, Jay Zeck, Jason Schallheim, Susie Q. Lew, Louis Depalma

Pathology Faculty Publications

Background: Platelet function analysis utilizing platelet-rich plasma and optical density based aggregometry fails to identify patients at risk for uremia associated complications.

Methods: We employed whole blood platelet aggregation analysis based on impedance as well as determination of ATP release from platelet granules detected by a chemiluminescence method. Ten chronic kidney disease (CKD) stage 4 or 5 predialysis patients underwent platelet evaluation. Our study aims to evaluate this platform in this patient population to determine if abnormalities could be detected. Results. Analysis revealed normal aggregation and ATP release to collagen, ADP, and high-dose ristocetin. ATP release had a low response …

Microenvironment Generated During Egfr Targeted Killing Of Pancreatic Tumor Cells By Atc Inhibits Myeloid-Derived Suppressor Cells Through Cox2 And Pge2 Dependent Pathway, Archana Thakur, Dana Schalk, Elyse Tomaszewski, Sri Kondadasula, Hiroshi Yano, Fazlul H. Sarkar, Lawrence G. Lum

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th₁ enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th₁ microenvironment.

Methods

We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] …

Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.

Methods

Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled …

Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

HMLEs (HMLE-SNAIL and Kras-HMLE, Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We had earlier developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using systems biology and pathway network analysis, we show that GN-25 could cause reversal of EMT leading to mesenchymal-to-epithelial transition (MET) in a well-recognized HMLE-SNAIL and Kras-HMLE-SNAIL models.

Results

GN-25 induced MET was found to be consistent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. Pathway network analysis of mRNA expression …

Bronchial Carcinoid Presenting As Multiple Lung Abscesses, Zeeshan Waheed, Muhammad Irfan, Saulat Fatimi, Ruqaiya Shahid

Section of Pulmonary & Critical Care

Bronchial carcinoid tumours is a rare group of pulmonary malignant neoplasm that is derived from neuroendocrine system. Bronchial carcinoid usually present with hilar masses, atelactasis, bronchiectasis, or post-obstructive pneumonia. This case describes a very unusual presentation of bronchial carcinoid tumour with multiple lung abscesses involving the whole lung. This report is of an adult lady who presented with multiple lung abscesses involving her whole of the right lung. She was found to have an endo-bronchial lesion in her right main bronchus which eventually turned out to be carcinoid tumour. She responded to resection and antibiotic therapy.

Expression Of Mismatch Repair Proteins In Colorectal Cancer At Aga Khan University Hospital, Nairobi, Charles M. Wahome

Master of Medicine in Anatomic Pathology

Introduction: Microsatellite instability is one of three molecular pathways described in the pathogenesis of colorectal carcinoma. The presence of microsatellite instability in patients with colorectal cancer has implications for prognosis and family counselling. Deficiency in mismatch repair genes leads to microsatellite instability and this can be reliably demonstrated in formalin fixed paraffin embedded tissue by methods, which include immunohistochemistry for the detection of mismatch repair proteins. Local data show a disproportionately large number of younger patients with colorectal cancer compared to that documented in Caucasians. Colorectal cancer in younger ages is often attributed to deficient mismatch repair. The objective of …

Effectiveness Of Sequential V. Standard Triple Therapy For Treatment Of Helicobacter Pylori Infection In Children In Nairobi, Kenya, Ahmed Laving, Rose Kamenwa, Shahin Sayed, Andrew Nyerere Kimang'a, Gunturu Revathi

Paediatrics and Child Health, East Africa

Background: Once the diagnosis of Helicobacter pylori is confirmed, treatment requires at least two antibiotics and an acid inhibitor for a minimum of seven days. Unfortunately, treatment failures are being frequently reported. Treatment regimens that include sequential administration of antibiotics with acid inhibitors have been developed to try and increase the rate of eradication.

Objective: To determine the effectiveness of a novel 10-day sequential therapy compared with the standard 10-day triple therapy for treatment of H. pylori infection in children.

Methods: A double-blinded, randomised, controlled trial was conducted. Children under the age of 16 years with recurrent abdominal pain associated …

Usefulness Of Plasmodium Falciparum-Specific Rapid Diagnostic Tests For Assessment Of Parasite Clearance And Detection Of Recurrent Infections After Artemisinin-Based Combination Therapy, B. Aydin-Schmidt, M. Mubi, U. Morris, M. Petzold, B.E. Ngasala, Zul Premji, A. Bjorkman, A. Martensson

Pathology, East Africa

Background: Rapid diagnostic test (RDT) is an important tool for parasite-based malaria diagnosis. High specificity of RDTs to distinguish an active Plasmodium falciparum infection from residual antigens from a previous infection is crucial in endemic areas where residents are repeatedly exposed to malaria. The efficiency of two RDTs based on histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens were studied and compared with two microscopy techniques (Giemsa and acridine orange-stained blood smears) and real-time polymerase chain reaction (PCR) for assessment of initial clearance and detection of recurrent P. falciparum infections after artemisinin-based combination therapy (ACT) in a moderately high …

An Exploratory Study Of User-Centered Indexing Of Published Biomedical Images, Sujin Kim

Pathology and Laboratory Medicine Faculty Publications

User-centered image indexing—often reported in research on collaborative tagging, social classification, folksonomy, or personal tagging—has received a considerable amount of attention [1-7]. The general themes in more recent studies on this topic include user-centered tagging behavior by types of images, pros and cons of user-created tags as compared to controlled index terms; assessment of the value added by user-generated tags, and comparison of automatic indexing versus human indexing in the context of web digital image collections such as Flickr. For instance, Golbeck's finding restates the importance of indexer experience, order, and type of images [8]. Rorissa has found a significant …

Peripheral T-Cell Lymphoma With Aberrant Expression Of Cd19, Cd20, And Cd79a: Case Report And Literature Review, Rahul G. Matnani, Rachel L. Stewart, Joseph Pulliam, Chester D. Jennings, Melissa Kesler

Pathology and Laboratory Medicine Faculty Publications

A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a), which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV) or Human Herpes Virus 8 (HHV-8). At the time …

Foot Dimensions As A Tool For Gender Determination In Kenyan Adults, Maureen W. Waithaka

Master of Medicine in Anatomic Pathology

Introduction: Anthropometry has gained popularity over the years as a reliable method to determine gender. In forensic investigation, there are cases where gender cannot be readily determined using anatomy such as in mass casualty disasters with dismemberment and commingling of limbs. Kenyan descriptive data of foot dimensions is lacking as are formulae for estimating gender. Proven differences in foot dimensions across races prevent application of formula obtained using different populations necessitating generation of local data and formulae. Objectives: To describe the foot lengths, breaths and navicular heights of a representative adult Kenyan population, both male and female, and derive from …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

Early Onset Type 2 Diabetes And Associated Risk Factors, Grace Nyambura Kiraka

Master of Medicine in Clinical Pathology

Background: The incidence of type 2 diabetes in patients below the age of 40 (early onset diabetes) is markedly on the rise and has been linked increased prevalence of risk factors such as the metabolic syndrome and family history of diabetes. Objective: To determine the proportion of patients with type 2 diabetes at Aga Khan University Hospital Nairobi (AKUHN) who have early onset type 2 diabetes and the association of age of onset with risk factors (family history of diabetes, obesity, waist circumference, hypertension, low HDL cholesterol and hypertriglyceridaemia) in this group of patients. Methods: This was a cross sectional …

Primary Antiretroviral Drug Resistance Profiles Among Hiv-1 Therapy Naïve Patients In Two Referral Hospitals In Kenya, Simon Onsongo Nyangena

Master of Medicine in Clinical Pathology

Objective: To characterize antiretroviral drug resistance mutations among drug naïve patients in two referral hospitals in Kenya Background: Acquired immunodeficiency syndrome (AIDS) caused by Human immunodeficiency virus (HIV) was first described in 1982. Since then the virus has spread globally to infect millions of people. HIV was first described in Kenya in the period between 1984/1985. Currently, Kenya has an estimated HIV-1 prevalence of 6.2% with a country population of about 40 million people. With the introduction of antiretroviral drugs, the survival of most HIV patients has been prolonged markedly. However this is greatly threatened by increasing rates of antiretroviral …

Genetic Diversity Of Plasmodium Vivax Clinical Isolates From Southern Pakistan Using Pvcsp And Pvmsp1 Genetic Markers, Afsheen Raza, Najia K. Ghanchi, Ali M. Thaver, Sana Jafri, Mohammad A. Beg

Department of Pathology and Laboratory Medicine

Background:
Plasmodium vivax is the prevalent malarial species accounting for 70% of malaria burden in Pakistan; however, there is no baseline data on the circulating genotypes. Studies have shown that polymorphic loci of gene encoding antigens pvcsp and pvmsp1 can be used reliably for conducting molecular epidemiological studies. Therefore, this study aimed to bridge the existing knowledge gap on population structure on P. vivax from Pakistan using these two polymorphic genes.
Methods:
During the period January 2008 to May 2009, a total of 250 blood samples were collected from patients tested slide positive for P. vivax, at the Aga Khan …

Event Related Potential Changes In A Two-Stimulus Auditory Oddball Task In Concussed College Athletes: A Linguistic Component, Paola G. Sanchez

Open Access Theses & Dissertations

"Return to Play" decisions are done based on cognitive-communicative testing and clinical assessments; concussed athletes may benefit from electrophysiological testing for a more accurate representation of their recovery. The purpose of this study is to investigate the electrophysiological performance post-concussion analyzing the attentional differences using the traditional "oddball" paradigm with a CV linguistic component. Participants for this study were 6 male college athletes with a history of concussion and 10 participants with no history of concussion (controls). Athletes were evaluated using event-related potentials (ERPs) that were recorded during a consonant-vowel (CV) auditory oddball task. Both the P300a and P300b components …

Cost Effective Improvement In The Protocol For Detection Of Haemoglobin Variants –A Step Forward In Quality Assurance, Natasha Ali, Mohammad Khurshid

Department of Pathology and Laboratory Medicine

Background: We report the results of a cost effective improvement in the protocol for detection of haemoglobin variants which incorporates the findings of peripheral blood film along with the results of HPLC.
Findings: A total of n = 10,844 samples were received from January 2011 till August 2011. Diagnosis of haemoglobinopathy was made in n = 1123 samples while other abnormalities included iron deficiency anaemia, megaloblastic anaemia, malarial parasite, autoimmune haemolytic anaemia and G6PD deficiency (n = 2473).
Conclusion: We diagnosed 23% of abnormalities other than haemoglobinopathy by reviewing peripheral smear of samples received for detection of …