Pathology Commons^™

Donepezil And Galanin Interactions In An Animal Model Of Alzheimer’S Disease, Jonathan J. Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by a progressive loss of cognitive function. One of the neurobiological hallmarks of AD is a progressive loss of cholinergic neurons and a decrease in the amount of acetylcholine in the brain. Pharmacological therapies have targeted the cholinergic system, specifically first-line, palliative treatment using acetylcholinesterase (AChE) inhibitors, such as donepezil. Donepezil has been shown to increase cholinergic tone and ameliorate some of the cognitive deficits in AD patients. Galanin, a neuropeptide that inhibits the evoked release of several neurotransmitters including acetylcholine as well as modulates seveal intracellular cascades, is overexpressed in AD …

Dysregulation Of The Mitogen Granulin In Human Cancer Through The Mir-15/107 Microrna Gene Group, Wang-Xia Wang, Natasha Kyprianou, Xiaowei Wang, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Granulin (GRN) is a potent mitogen and growth factor implicated in many human cancers, but its regulation is poorly understood. Recent findings indicate that GRN is regulated strongly by the microRNA miR-107, which functionally overlaps with miR-15, miR-16, and miR-195 due to a common 5′ sequence critical for target specificity. In this study, we queried whether miR-107 and paralogs regulated GRN in human cancers. In cultured cells, anti-argonaute RNA coimmunoprecipitation with downstream microarray analyses indicates that GRN mRNA is directly targeted by numerous miR-15/107 miRNAs. We further tested this association in human tumors. MiR-15 and miR-16 are known to be …

Is Manual Reticulocyte Count A Reliable Option For Under Resourced Countries, Afsheen Farzand Ali, Bushra Moiz, Sadia Omer

Department of Pathology and Laboratory Medicine

OBJECTIVES: To establish the credibility of manual reticulocyte counts without compromising the quality of care, and to evaluate the degree of acceptability of manual reticulocyte counts in terms of accuracy and cost effectiveness in comparison with two automated haematology analyzers.

METHODS: Visual reticulocyte enumeration was evaluated for comparability, within-batch precision and costing with respect to Coulter STKS and Gen S haematology analyzers.

RESULTS: The results of reticulocyte estimation for 80 samples as obtained by 3 modes were correlated using Pearson's correlation coefficient (r) which were computed as 0.884, 0.875, and 0.793 for manual-Gen.S, Gen.SSTKS and manual-STKS respectively thus showing positive …

Neonatal Mortality And Prevalence Of Practices For Newborn Care In A Squatter Settlement Of Karachi, Pakistan: A Cross-Sectional Study., Afsheen Ayaz, Sarah Saleem

Department of Pathology and Laboratory Medicine

Background: During the past two decades there has been a sustained decline in child and infant mortality, however neonatal mortality has remained relatively unchanged. Almost all neonatal deaths (99%) occur in developing countries, where the majority are delivered at homes. Evidence suggests that these deaths could be prevented by simple, inexpensive practices and interventions during the pregnancy, delivery and postnatal period. In Pakistan over the last decade extensive efforts have been made by the international donors and government to implement these practices. However, limited attempts have been made to explore if these efforts have made a difference at the grass …

Chronic Gastritis And Helicobacter Pylori: A Histopathological Study Of Gastric Mucosal Biopsies, Mohammad Yawar Yakoob, Akbar Shah Hussainy

Department of Pathology and Laboratory Medicine

The aim of this study was to observe the histological features of chronic gastritis and associated effects due to Helicobacter pylori infection in 176 randomly selected antral biopsy specimens of chronic gastritis cases. The specimens were reviewed for the presence or absence of H.pylori. The activity (neutrophilic infiltration) of gastritis and the presence or absence of mucosa-associated lymphoid tissue (MALT) were also noted. Chi-square test (Pearson value) was used to analyze categorical variables. H.pylori was detected in 110 (62.5%) cases of chronic gastritis. There was a significant association between H.pylori infection and activity of chronic gastritis (p=0.002). Lymphoid aggregates were …

Benign Metastasizing Leiomyoma, Saira Fatima, Zubair Ahmad, Mohammad Azam

Department of Pathology and Laboratory Medicine

Benign metastasizing leiomyoma (BML) is a rare condition, affecting predominantly reproductive-age females with uterine leiomyomata and is most often associated with multiple benign-appearing smooth muscle tumors in lungs. We report herein a case of a 38-year-old woman who presented with multiple uterine fibroids for which hysterectomy was carried out on her. Postoperatively, she developed left-sided pleural effusion. Computed chest tomography (CT) scan revealed multiple nodules in both lungs and pleurae. Histopathology of one of the pleura-based nodules revealed a neoplasm composed of interlacing fascicles of spindle cells with uniform nuclei. The tumor cells were positive for alpha-smooth muscle actin and …

Clonal Dissemination Of Vana Positive Enterococcus Species In Tertiary Care Hospitals In Karachi, Pakistan, Naima Fasih, Afia Zafar, Erum Khan, Kausar Jabeen, Rumina Hasan

Department of Pathology and Laboratory Medicine

OBJECTIVE: To perform molecular typing of vancomycin resistant Enterococcus spp. (VRE) strains endemic in various hospitals of Karachi, to characterize the mechanism of glycopeptide resistance and assess the genetic relatedness, for understanding its transmission locally.

METHOD: This was a cross sectional study conducted in the clinical and research laboratory of Aga Khan University Hospital (AKUH), Karachi, Pakistan from October 2007 to September 2008. Non-duplicate 86 (65 AKUH and 21 non-AKUH) VRE strains were included. Molecular typing of nosocomial isolates of VRE was carried out by using Pulsed field gel electrophoresis (PFGE) and identification of vanA and vanB genes were performed …

Sarcoidosis Cannot Be Reliably Distinguished From Other Causes Of Hepatic Granulomas In A Liver Biopsy Alone, Phililp A. Grieshaber, Md, Whitney Jackson, Md, John L. Farber, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Context:

Hepatic granulomas occur in a variety of circumstances. Sarcoidosis is a common cause with the liver following lymph nodes and the lung in frequency of involvement. The present study aimed to determine where granulomatous hepatisis caused by sarcoidosis can be distinguished in a liver biopsy from other etiologies.

The Added Value Of Molecular Testing In Small Pancreatic Cysts, Adam D. Toll, Md, Marluce Bibbo, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background:

Cystic lesions of the pancreas (CLP) represent a relatively common pathologic entity affecting at least 1% of medical patients and represent a spectrum of lesions from inflammatory pseudocyststo malignant neoplasms. A significant percentage of these cysts are found incidentally during imaging work-up for unrelated conditions and require appropriate diagnostic testing to characterize the nature of the CLP. A multi-disciplinary approach to characterize CLP is currently used involving cytology, imaging, and cyst fluid analysis. The most recent international guidelines recommend resection of pancreatic mucinouscysts >3 cm, or smaller cysts with positive cytology, mural nodules, or symptoms.

Recent work utilized DNA …

Interesting Case Presentation: Placental Site Trophoblastic Tumor, Nicole Qualtieri, Ms, Pa (Ascp), Andrea Gadue, Mhs, Pa (Ascp)

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Case Study:

A 26 year-old female (G3P1) had a D&E in March, 2010 for a blighted ovum. The diagnosis on the uterine contents at an outside institution was placental site trophoblastic tumor. No follow up care was obtained. Four months later (July, 2010), the patient presented to her OB-GYN stating that she had missed a period and had a positive home pregnancy test. An ultrasound examination failed to identify a fetus, and the patient was referred to TJUH.

At Jefferson an MRI showed a poorly defined uterine mass that extended into the myometrium. The slides from the original D&E were …

Proteoglycans In Health And Disease: Novel Regulatory Signaling Mechanisms Evoked By The Small Leucine-Rich Proteoglycans., Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The small leucine-rich proteoglycans (SLRPs) are involved in many aspects of mammalian biology, both in health and disease. They are now being recognized as key signaling molecules with an expanding repertoire of molecular interactions affecting not only growth factors, but also various receptors involved in controlling cell growth, morphogenesis and immunity. The complexity of SLRP signaling and the multitude of affected signaling pathways can be reconciled with a hierarchical affinity-based interaction of various SLRPs in a cell- and tissue-specific context. Here, we review this interacting network, describe new relationships of the SLRPs with tyrosine kinase and Toll-like receptors and critically …

The Mir-15/107 Group Of Microrna Genes: Evolutionary Biology, Cellular Functions, And Roles In Human Diseases, John R. Finnerty, Wang-Xia Wang, Sébastien S. Hébert, Bernard R. Wilfred, Guogen Mao, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

The miR-15/107 group of microRNA (miRNA) gene is increasingly appreciated to serve key functions in humans. These miRNAs regulate gene expression involved in cell division, metabolism, stress response, and angiogenesis in vertebrate species. The miR-15/107 group has also been implicated in human cancers, cardiovascular disease and neurodegenerative disease, including Alzheimer's disease. Here we provide an overview of the following: (1) the evolution of miR-15/107 group member genes; (2) the expression levels of miRNAs in mammalian tissues; (3) evidence for overlapping gene-regulatory functions by different miRNAs; (4) the normal biochemical pathways regulated by miR-15/107 group miRNAs; and (5) the roles played …

Alteration Of Micrornas Regulated By C-Myc In Burkitt Lymphoma, Anna Onnis1, Giulia De Falco, Giuseppina Antonicelli, Monica Onorati, Cristiana Bellan, Omar Sherman, Shahin Sayed, Lorenzo Leoncini

Pathology, East Africa

Background: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, with a characteristic clinical presentation, morphology and immunophenotype. Over the past years, the typical translocation t(8;14) and its variants have been considered the molecular hallmark of this tumor. However, BL cases with no detectable MYC rearrangement have been identified. Intriguingly, these cases express MYC at levels comparable with cases carrying the translocation. In normal cells c-Myc expression is tightly regulated through a complex feedback loop mechanism. In cancer, MYC is often dysregulated, commonly due to genomic abnormalities. It has recently emerged that this phenomenon may rely on an alteration of post-transcriptional …

Demographic And Clinical Features Of Dengue Fever In Pakistan From 2003-2007: A Retrospective Cross-Sectional Study., Erum Khan, Mehreen Kisat, Nabil Khan, Amna Nasir, Salma Ayub, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: Demographic features of dengue fever have changed tremendously in Pakistan over the past two decades. Small scale studies from all over the country have reported different aspects of individual outbreaks during this time. However, there is scarcity of data looking at the overall trend of dengue virus infection in the country. In this study, we examined annual trends, seasonality, and clinical features of dengue fever in the Pakistani population.
Methods: Demographic information and dengue IgM status of all patients tested for dengue IgM antibody at Aga Khan University Hospital from January 2003 to December 2007 were analyzed to look …

One Year Survival With Poorly Differentiated Metastatic Pancreatic Carcinoma Following Chemoembolization With Gemcitabine And Cisplatin., Daniel B Brown, Carin F Gonsalves, Charles J Yeo, Agnes K Witkiewicz, Brian I Carr

Department of Radiology Faculty Papers

While hepatic arterial chemoembolization is efficacious for a number of malignancies, there is scant data regarding treatment of pancreatic adenocarcinoma. We report a complete radiographic response at one year from diagnosis of metastatic pancreatic carcinoma. Gemcitabine/cisplatin based chemoembolization may be of potential benefit for patients with liver-dominant metastases from pancreatic carcinoma. Given the typical survival of 6 months or less in this patient group with standard therapies, further research is warranted.

Pattern Of Drugs Of Abuse Identified In Chemical Samples, Farhan Javed Dar, Aysha Habib Khan, Imran Siddiqui, Farooq Ghani

Department of Pathology and Laboratory Medicine

OBJECTIVE: To determine the pattern of drugs of abuse in urine and blood samples processed at referral laboratory in Pakistan so that information on the type of drugs used can be identified and used for ready reference for future strategy. Study Design: Observational study.

PLACE AND DURATION OF STUDY: Clinical Laboratory of The Aga Khan University Hospital, Karachi, from July 2006 to March 2008. Methodology: Retrospective review of records were done for the common drugs that are used for screening at the Clinical Laboratory include alcohol, amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates. Alcohol was tested in blood and others …

Inducible Clindamycin Resistance Due To Expression Of Erm Genes In Staphylococcus Aureus: Report From A Tertiary Care Hospital Karachi, Pakistan, Naima Fasih, Seema Irfan, Afia Zafar, Erum Khan, Rumina Hasan

Department of Pathology and Laboratory Medicine

OBJECTIVE: To assess the frequency of phenotypic expression of inducible resistance of clindamycin due to expression of erm genes, in clinical isolates of Staphylococcus aureus (S. aureus), by double disk diffusion test (D-test).

METHOD: This was a cross sectional study conducted in the clinical laboratory of Aga Khan University Hospital, Karachi. A total of 2432, non duplicate clinical isolates of S. aureus, consisting of 1562 methicillin sensitive S. aureus (MSSA) and 870 methicillin resistant S. aureus (MRSA), were selected from February 2007 to January 2008. One hundred and thirty eight isolates of S. aureus were selected based on discordant resistance …

Quebec Platelet Disorder, Anwar Hussain Abbasi, Quratulain Shaikh, Syed Ather Hussain

Department of Pathology and Laboratory Medicine

A case of Quebec platelet disorder is hereby reported. A 33 years old woman presented with history of epistaxis and gum bleeding since childhood and menorrhagia and bleeding per vaginum after puberty, also had history of excessive blood loss after birth of child. Her coagulation profile was normal but platelet function testing by platelet aggregation assay showed abnormal aggregation of platelet with epinephrine. This type of response is seen in "Quebec platelet disorder" which is a rare autosomal dominant disorder of platelet function characterized by increased bleeding after any injury or trauma.

Trends In Undergraduate Teaching Of Parasitology In Medical Schools Of Pakistan, Vikram Mehraj, Taimur Saleem, Saima Lalani, Nadia Sani, Imran Khan, Fatima Afridi, Hina Irfan, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

OBJECTIVE: Parasitic diseases are a major public health problem in the tropical and sub tropical countries including the subcontinent region. We aimed to assess methods of Parasitology education in medical schools of Karachi Pakistan.

METHODS: Ten medical schools in Karachi, Pakistan were sent a structured questionnaire collecting information on different aspects of Parasitology education. The collected data was analyzed using SPSS version 14.0.

RESULTS: The response rate of this study was 90%. Majority of the schools in Karachi, Pakistan (78%) taught Parasitology concurrently with Microbiology, Pathology, Pharmacology and Forensic medicine in third and fourth year of undergraduate training. More than …

Immunophenotypic Profile Of Acute Leukemias At Agakhan University Hospital, Nairobi, Beatrice M. Kabera

Master of Medicine in Clinical Pathology

Background: Reliable distinction between AML and ALL is important for the selection of appropriate therapy. The final diagnosis of acute leukemia should be based on clinico-pathological, morphological, cytochemical and molecular cytogenetics data, together with immunophenotypic information. Flow cytometry has become the preferred method for the lineage assignment and maturational analysis of malignant cells in acute leukemias. Immunophenotyping has also allowed the detection of aberrant antigen co expression and the analysis of heterogeneity and clonality of malignant cells in acute leukemias. It is insufficient to merely make a diagnosis of acute leukemia, or even AML or ALL. Further classification is essential …

Detection Of Extended Spectrum Beta Lactamases Genotypes And Their Association With Cephalosporin Susceptibility In Community Acquired Enterobacteriaceae Infections, Daniel W. Maina

Master of Medicine in Clinical Pathology

Background: Infections caused by Extended Spectrum Beta-Lactamases (ESBLs) producing enterobacteriaceae have become a global problem. Initially confined to the hospital set-up, they are increasingly being reported in the community. These infections are often resistant to a wide variety of B- lactams including extended spectrum cephalosporins, with clinical and epidemiological implications for healthcare systems and necessitate surveillance measures based on local data. Local information on the genotypes of ESBLs and their association with cephalosporin resistance in community acquired ESBL-producing Enterobacteriaceae isolates is scanty, hence the need for this study. Aim: To detect ESBLs genotypes and correlate these with susceptibility to cephalosporins …

Nipple Adenoma Of Breast: A Masquerader Of Malignancy, Kanwal Aftab, Romana Idress

Department of Pathology and Laboratory Medicine

Nipple adenoma is a benign condition simulating malignancy such as breast carcinoma and/or Paget’s disease clinically. In this study 19 cases diagnosed as nipple adenoma over a period of 14 years are described. The diagnosis was confirmed by histology alone. All patients were females with age ranging from 23 to 63 years. Most of the cases presented clinically with in duration and ulceration accompanied by pain and itching. The diagnosis was clinically suspected in only 3 cases. This highlights the importance of histological diagnosis in all suspicious breast lesions. In one case, the clinical and histological diagnosis was incorrect leading …

Patterns Of Fatal Gunshot Injuries In Nairobi: A Prospective Forensic Study, Ancent K. Nzioka

Master of Medicine in Anatomic Pathology

Introduction: Gunshot injuries are one of the leading causes of fatal and non fatal injury in many countries (1) .All over the world, injury studies show an increasing preference for the gun as the weapon of choice for homicides and suicides (2).Firearms are more lethal compared to other portable and concealable weapons (2). Gunshot injuries impact severely on the criminal justice as well as health care systems (3, 4). There is no available published statistics on fatal gunshot injuries inKenya. Some basic statistics are important in understanding the magnitude and severity of the socio-economic burden caused by gunshot injuries. Objective: …

Expression Patterns Of Β–Catenin, Cox-2 And P27 In Colorectal Carcinomas At Aga Khan University Hospital, Nairobi, Patricia Okiro

Master of Medicine in Anatomic Pathology

Introduction: Colorectal cancer is the third most common cancer worldwide, as indicated by WHO. Local published and unpublished data indicate that patients in the developing world with colorectal cancer tend to present at an early age, and possibly at a more advanced stage than described in the developed world. The reason for this difference is unclear, and as yet undefined. The Wnt/APC pathway, Microsatellite instability pathway and the Epigenetic pathway are three pathogenetically distinct pathways that have been implicated in the development of colorectal cancer. Exploration of these patterns may allow us to elucidate possible reasons for these differences. Objectives: …

High-Throughput Experimental Studies To Identify Mirna Targets Directly, With Special Focus On The Mammalian Brain, Peter T. Nelson, Marianthi Kiriakidou, Zissimos Mourelatos, Grace S. Tan, Mary H. Jennings, Kevin Xie, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) "targets" with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of "binding rules" for miRNAs has been described. These have focused on the 5' "seed" region of miRNAs binding …

Labrad : Vol 35, Issue 2 - June 2010, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• The Atypical Lymphocytes
• High Performance Liquid Chromatography (HPLC): An Effective Tool for the Diagnosis of Various Hemoglobinopathies
• Platelet Transfusions: What We Need to Know
• Measuring Homocysteine Levels
• Parathyroid Hormone: A Marker of Vitamin D Deficiency and Insufficiency
• Surrogate Measures of Insulin Sensitivity
• Foetal Autopsy
• Laboratory Diagnosis of Vaginitis due to Trichomonas Vaginalis
• AKU Clinical Laboratory Continuing Medical Education Seminars

Epistatic Relationships Between Sara And Agr In Staphylococcus Aureus Biofilm Formation., Karen E. Beenken, Lara N. Mrak, Linda M. Griffin, Agnieszka K. Zielinska, Lindsey N. Shaw, Kelly C. Rice, Alexander R. Horswill, Kenneth W. Bayles, Mark S. Smeltzer

Journal Articles: Pathology and Microbiology

BACKGROUND: The accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) play opposing roles in Staphylococcus aureus biofilm formation. There is mounting evidence to suggest that these opposing roles are therapeutically relevant in that mutation of agr results in increased biofilm formation and decreased antibiotic susceptibility while mutation of sarA has the opposite effect. To the extent that induction of agr or inhibition of sarA could potentially be used to limit biofilm formation, this makes it important to understand the epistatic relationships between these two loci.

METHODOLOGY/PRINCIPAL FINDINGS: We generated isogenic sarA and agr mutants in clinical isolates of S. …

Individual Micrornas (Mirnas) Display Distinct Mrna Targeting "Rules", Wang-Xia Wang, Bernard R. Wilfred, Kevin Xie, Mary H. Jennings, Yanling Hu, Arnold J. Stromberg, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

MicroRNAs (miRNAs) guide Argonaute (AGO)-containing microribonucleoprotein (miRNP) complexes to target mRNAs.It has been assumed that miRNAs behave similarly to each other with regard to mRNA target recognition. The usual assumptions, which are based on prior studies, are that miRNAs target preferentially sequences in the 3'UTR of mRNAs,guided by the 5' "seed" portion of the miRNAs. Here we isolated AGO- and miRNA-containing miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with anti-AGO antibody. Cells were transfected with miR-107, miR-124,miR-128, miR-320, or a negative control miRNA. Co-IPed RNAs were subjected to downstream high-density Affymetrix Human Gene 1.0 ST microarray analyses using …

Osteopontin And Cadherin 11 Are Novel Mediators And Drug Targets For Chronic Lung Diseases, Daniel J. Schneider

Dissertations and Theses (Open Access)

Chronic lung diseases (CLDs) are a considerable source of morbidity and mortality and are thought to arise from dysregulation of normal wound healing processes. An aggressive, feature of many CLDs is pulmonary fibrosis (PF) and is characterized by excess deposition of extracellular matrix (ECM) proteins from myofibroblasts in airways. However, factors regulating myofibroblast biology are incompletely understood. Proteins in the cadherin family contribute epithelial to mesenchymal transition (EMT), a suggested source of myofibroblasts. Cadherin 11 (CDH11) contributes to developmental and pathologic processes that parallel those seen in PF and EMT. Utilizing Cdh11 knockout (Cdh11 -/-) mice, the goal of this …

Loss Of Stromal Caveolin-1 Independently Predicts Poor Disease-Free Survival And Time To Recurrence In Patients With Prostate Cancer, M. Wagner, A. Dasgupta, F. Sotgia, R. B. West, M. P. Lisanti, A. K. Witkiewicz

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Results:

Of the 167 patients originally included in the study, 43 were either lost to follow up or had insufficient clinical data for comparison. Of the remaining 124 cases, 32 showed loss of stromal Cav-1. Statistical analysis revealed no significant association between stromal Cav-1 loss and the usual markers of disease severity including Gleason grade, stage and presence of metastases. Kaplan-Meier curves showed a significant association between stromal Cav-1 loss and poor disease-free survival and time to recurrence (p<0.05), but no significant association with cancer-specific survival.