Pathology Commons^™

Whole Genome Sequencing Based Characterization Of Extensively Drug-Resistant Mycobacterium Tuberculosis Isolates From Pakistan, Asho Ali, Zahra Hasan, Ruth Mcnerney, Kim Mallard, Grant Hill Cawthorne, Francesc Coll, Mridul Nair, Arnab Pain, Taane G. Clark, Rumina Hasan

Department of Pathology and Laboratory Medicine

Improved molecular diagnostic methods for detection drug resistance in Mycobacterium tuberculosis (MTB) strains are required. Resistance to first- and second- line anti-tuberculous drugs has been associated with single nucleotide polymorphisms (SNPs) in particular genes. However, these SNPs can vary between MTB lineages therefore local data is required to describe different strain populations. We used whole genome sequencing (WGS) to characterize 37 extensively drug-resistant (XDR) MTB isolates from Pakistan and investigated 40 genes associated with drug resistance. Rifampicin resistance was attributable to SNPs in the rpoB hot-spot region. Isoniazid resistance was most commonly associated with the katG codon 315 (92%) mutation …

Clinical Isolates Of Salmonella Enterica Serovar Agona Producing Ndm-1 Metallo-Beta-Lactamase: First Report From Pakistan, Seema Irfan, Erum Khan, Kauser Jabeen, Pushpa Bhawan, Katie L. Hopkins, Martin Day, Amna Nasir, Daniele Meunier, Neil Woodford

Department of Pathology and Laboratory Medicine

We report two cases of infantile diarrhea due to multidrug-resistant, NDM-1 metallo-beta-lactamase-producing Salmonella enterica serovar Agona from Pakistan. This study alerts toward possible risk of NDM-1 transmission to enteric fever pathogens and encourages microbiologists to consider active screening of carbapenem resistance in nontyphoidal Salmonella isolates.

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …

Serine Palmitoyltransferase And Giardial Encystation, Monica Delgado

Open Access Theses & Dissertations

Giardia lamblia is a flagellated protozoan parasite responsible for chronic diarrheal disease in humans and animals. Giardia has minimal lipid synThesis machinery and the majority of its lipids are obtained from the small intestine of humans where the trophozoites colonize. Recent results from our laboratory indicate that sphingolipids (SLs) are also important for Giardia and they regulate encystation and cyst production. Only five SL genes are present in this parasite and they are differentially regulated during encystation. In my studies, I found that giardial serine palmitoyltransferase (gSPT) activity is upregulated in encysting cells, suggesting it might play an important role …

Gastrointestinal Stromal Tumors: A Clinicopathologic And Risk Stratification Study Of 255 Cases From Pakistan And Review Of Literature, Nasir Ud Din, Zubair Ahmad, Huma Arshad, Romana Idrees, Naila Kayani

Department of Pathology and Laboratory Medicine

Purpose:
To describe the clinicopathological features of gastrointestinal stromal tumors (GIST) diagnosed in our section and to perform risk stratification of our cases by assigning them to specific risk categories and groups for disease progression based on proposals by Fletcher et al and Miettinen and Lasota.
Material and Results:
We retrieved 255 cases of GIST diagnosed between 2003 and 2014. Over 59% were male. The age range was 16 to 83 years with a mean of 51 years. Over 70% occurred between 40 and 70 years of age. Average diameter of tumors was 10 cms. The stomach was the most …

Hiv Prevalence In Blood Donors And Recipients In Pakistan: A Meta-Analysis And Analysis Of Blood-Bank Data, Bushra Moiz, Barkat Ali, Muhammad Hasnain Chatha, Ahmed Raheem, Hasan Abbas Zaheer

Department of Pathology and Laboratory Medicine

Background:
The first instances of HIV-antibody detection in donated blood in Pakistan were reported in 1988. Since then, documentation of HIV in blood donors and of rates of transmission via transfusion has been limited. Previously assumed to have a low prevalence, HIV is an increasing health concern in Pakistan. Since there is no national, centralized blood-banking system, there are no reliable data on which to base estimated risks of transfusion-associated HIV infection. This study was therefore conducted to estimate the prevalence of HIV in blood donors and recipients in Pakistan between 1988 and 2012.
Methods:
Meta-analyses were undertaken of reported …

Mammary-Type Myofibroblastoma Of The Right Thigh: A Case Report And Review Of The Literature, Jamshid Abdul-Ghafar, Nasir Ud Din, Zubair Ahmad, Steven D. Billings

Department of Pathology and Laboratory Medicine

Introduction:
Mammary-type myofibroblastoma of the soft tissue is a very rare, benign, mesenchymal neoplasm with myofibroblastic differentiation. To date, 20 cases of extra-mammary myofibroblastoma have been described in literature. To the best of our knowledge, this is the largest extra-mammary myofibroblastoma described in the literature, and the first case reported in this location.
Case Presentation:
A 50-year-old Pakistani man presented with a long history of a painless, huge lump on his right thigh. His clinical examination showed normal-looking skin and there was no inguinal lymphadenopathy. The mass was excised with a clinical impression of soft tissue sarcoma. Gross examination showed …

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Leishmania Donovani Bodies In Bone Marrow, Natasha Ali, Shabneez Hussain

Department of Pathology and Laboratory Medicine

We report a case of a 5-year-old female, resident of Afghanistan, who presented with fever and massive splenomegaly. Bone marrow revealed Leishmania donovani bodies (LD bodies) in macrophages characterized by a kinetoplast and characteristic double dot appearance. She was diagnosed as visceral leishmaniasis which is transmitted by sandflies (Phlebotomus).

Chromosomal Abnormalities In Primary Myelodysplastic Syndrome, Anila Rashid, Mohammad Khurshid, Usman Shaikh, Salman Adil

Department of Pathology and Laboratory Medicine

Objective: To determine the frequency of cytogenetic abnormalities in patients diagnosed as primary myelodysplastic syndrome (MDS) using conventional karyotyping. Study Design: Case series. Place and Duration of Study: The Clinical Laboratory, The Aga Khan University Hospital, Karachi, between January 2006 - June 2012. Methodology: Patients of all ages and either gender who fulfilled WHO criteria for MDS were included. Cytogenetic analysis was conducted at the time of diagnosis. Patients who had secondary MDS were excluded from analysis. Chromosome identification and karyotype description was done according to the International System for Chromosome Nomenclature (ISCN, 1995) and described as frequency percentage. Results: …

Shifting Of Vitamin D Deficiency To Hypervitaminosis And Toxicity, Aysha Habib, Hafsa Majid, Romaina Iqbal

Department of Pathology and Laboratory Medicine

No abstract provided.

Tyrosine Kinase Inhibitors In Cancer Therapeutics: Great Expectations From Small Molecules, Zeeshan A Ansar, Tariq Moatter

Department of Pathology and Laboratory Medicine

No abstract provided.

Mycobacterium Tuberculosis Central Asian Strain (Cas) Lineage Strains In Pakistan Reveal Lower Diversity Of Miru Loci Than Other Strains, Asho Ali, Zahra Hasan, Sana Jafri, Raunaq Inayat, Rumina Hasan

Department of Pathology and Laboratory Medicine

Mycobacterium tuberculosis (MTB) Central Asian Strain (CAS) lineage strains are predominant in South Asia. Mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing is an effective way of determining genetic diversity of strains. A maximum of 24 loci-based MIRU-VNTR typing can be used, however, it is important to investigate the relevance of specific MIRU loci for regional strains for more cost-effective MIRU typing. MIRU-VNTR typing was performed on MTB strains from Pakistan. Strains were comprised of CAS (n=113) and non-CAS lineages (n=87) - both multi-drug resistant (MDR) and drug susceptible. Hunter Gaston Discriminatory Index (HGDI) for each MIRU loci …

Drug Resistant Tuberculosis: Challenges Of Urbanization, Rumina Hasan

Department of Pathology and Laboratory Medicine

No abstract provided.

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 …

Ovarian Sex Cord Stromal Tumours In Children And Young Girls - A More Than Two Decade Clinicopathological Experience In A Developing Country, Pakistan, Saroona Haroon, Romana Idrees, Aleena Zia, Aisha Memon, Saira Fatima, Naila Kayani

Department of Pathology and Laboratory Medicine

Background: Ovarian sex-cord stromal tumours (SCST) are rare, and relatively infrequent in children. These have to be distinguished from more common germ cell tumors in children and also from benign epithelial neoplasms.
Objectives: The purpose of our study was to report the clinical and pathological findings in young patients with these tumours in our population.
Material and Methods: The present observational cross-sectional study included all subjects SCST, in Aga Khan University Hospital Histopathology Laboratory, Karachi, Pakistan, from January 1992 till July 2013.
Results: Of the total of 513 SCSTs presented during the study period, 39 fulfilled inclusion criteria and were …

Pleomorphic Lobular Carcinoma Of The Male Breast With Axillary Lymph Node Involvement: A Case Report And Review Of Literature, Muhammad Nauman Zahir, Khurram Minhas, Munira Shabbir-Moosajee

Department of Pathology and Laboratory Medicine

Background: Carcinoma of the male breast is responsible for less than 1% of all malignancies in men but the incidence is rising. Invasive ductal carcinoma is the most common histological subtype while invasive lobular carcinoma is responsible for only 1.5% of the total cases of which pleomorpic lobular carcinoma is an extremely rare variant. We report the case of a gentleman with node positive, pleomorphic lobular carcinoma of the breast.
Case Presentation: An elderly gentleman with a past history of type 2 diabetes and long term ethanol use presented to us with a self-discovered palpable lump in the left breast. …

Development Of A Conditional Mesd (Mesoderm Development) Allele For Functional Analysis Of The Low-Density Lipoprotein Receptor-Related Family In Defined Tissues, Andrew V. Taibi, Janet K. Lighthouse, Richard C. Grady, Kenneth R. Shroyer, Bernadette Holdener

Department of Biomedical Engineering Faculty Publications

The Low-density lipoprotein receptor-Related Protein (LRP) family members are essential for diverse processes ranging from the regulation of gastrulation to the modulation of lipid homeostasis. Receptors in this family bind and internalize a diverse array of ligands in the extracellular matrix (ECM). As a consequence, LRPs regulate a wide variety of cellular functions including, but not limited to lipid metabolism, membrane composition, cell motility, and cell signaling. Not surprisingly, mutations in single human LRPs are associated with defects in cholesterol metabolism and development of atherosclerosis, abnormalities in bone density, or aberrant eye vasculature, and may be a contributing factor in …

Population Genetics And Drug Resistance Markers: An Essential For Malaria Surveillance In Pakistan, Afsheen Raza, Mohammad Asim Beg

Department of Pathology and Laboratory Medicine

Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, …

Illuminating The Dark Side--Vitamin D Status In Different Localities Of Karachi, Romaina Iqbal, Lena Jafri, Ali Haroon, Aysha Habib Khan

Department of Medicine

This study was conducted to determine the association between place of residence (grouped into neighbourhoods), and 25-hydroxy D (25[OH]D) levels of individuals of Karachi. Addresses of 4788 individuals tested for 25[OH]D at the clinical laboratory of the Aga Khan University (AKU), Karachi, from January 2007 to June 2008 were reviewed. The neighbourhoods were categorized into ten, based on locality attributes. A high overall prevalence (74%) of vitamin D deficiency (VDD) was observed. There was a significant difference (p-value < 0.01) between mean log 25[OH]D levels amongst neighbourhoods grouped according to distinct housing structure attributes and localities. A high frequency of VDD in all the studied localities of an urban city warrant dietary vitamin D supplementation and food fortification.

Qcm Aptasensor For Rapid And Specific Detection Of Avian Influenza Virus, Luke Brockman

Graduate Theses and Dissertations

There has been a need for rapid detection of avian influenza virus (AIV) H5N1 due to it being a potential pandemic threat. Most of the current methods, including culture isolation and PCR, are very sensitive and specific but require specialized laboratories and trained personnel in order to complete the tests and are time-consuming. The goal of this study was to design a biosensor that would be able to rapidly detect AIV H5N1 using aptamers as biosensing material and a quartz crystal microbalance (QCM) for transducing method. Specific DNA aptamers against AIV H5N1 were immobilized, through biotin and streptavidin conjugation, onto …

Malignant Vascular Tumours Associatedwith The Breast: A Study Of 7 Cases, Azizun-Nisa, Zeeshanuddin, Naila Kayani

Department of Pathology and Laboratory Medicine

Angiosarcomas account for less than 0.05% of the malignant neoplasms of the breast. We present here 7 cases of malignant vascular neoplasms of the breast, including 2 cases of postmastectomy Stewart-Treves syndrome. In this case series, most of the patients were young. Tumour was bilateral at presentation in one case. The size of the tumours ranged from 1.6 cm to 11 cm. Although breast angiosarcomas are rare neoplasms, with the increasing use of radiation therapy for breast cancer patients, post-radiation skin lesions should not be ignored.

Neuropathogenic Escherichia Coli K1 Does Not Exhibit Proteolytic Activities To Exert Its Pathogenicity, Junaid Iqbal, Mehak Rajan, Ruqaiyyah Siddiqu, Naveed Ahmed Khan

Department of Biological & Biomedical Sciences

Background: Proteases are well-known virulence factors that promote survival, pathogenesis and immune evasion of many pathogens. Several lines of evidence suggest that the blood-brain barrier permeability is a prerequisite in microbial invasion of the central nervous system. Because proteases are frequently associated with vascular permeability by targeting junctional proteins, here it is hypothesized that neuropathogenic Escherichia coli K1 exhibit proteolytic activities to exert its pathogenicity.
Methods: Zymographic assays were performed using collagen and gelatin as substrates. The lysates of whole E. coli K1 strain E44, or E. coli K-12 strain HB101 were tested for proteolytic activities. The conditioned media were …

Frequency Of Precancerous Lesions In Endoscopic Gastric Biopsies In Chronic Gastritis, Saroona Haroon, Naveen Faridi, Faisal Rashid Lodhi, Shafaq Mujtaba

Department of Pathology and Laboratory Medicine

Objective:
To determine the frequency of precancerous lesions in endoscopic gastric biopsies of patients with chronic gastritis.STUDY Design: A case series.
Place and duration of study:
Department of Histopathology, Liaquat National Hospital, Karachi, from July 2008 to January 2009.METHODOLOGY: Over 6 months, 375 endoscopic gastric biopsies of patients with age group of 15-65 years having endoscopic chronic gastritis were included. From final biopsy report, basic information like patient demographics and presence of precancerous lesions i.e. activity (chronic active gastritis), atrophy (atrophic gastritis), intestinal metaplasia and dysplasia were recorded on proforma. Results were described as proportions and frequency.
Results:
The frequency …

Hydraphiles: A Rigorously Studied Class Of Synthetic Channel Compounds With In Vivo Activity, Saeedeh Negin, Bryan Smith, Alexandra Unger, W. Leevy, George Gokel

Chemistry & Biochemistry Faculty Works

No abstract provided.

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 …

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. …

Clinicopathological Spectrum Of Ovarian Sex Cord-Stromal Tumors; 20years' Retrospective Study In A Developing Country, Saroona Haroon, Aleena Zia, Romana Idrees, Aisha Memon, Saira Fatima, Naila Kayani

Department of Pathology and Laboratory Medicine

Background:
Ovarian sex cord stromal tumors are rare neoplasms as compared to epithelial tumors. No large study has been done in Pakistan to find out the frequencies of various sex cord stromal tumors and their clinicopathological behavior in our region. The purpose of our study was to determine the various histological patterns and clinical features of ovarian sex cord stromal tumors along with follow-up in our set-up.
Methods:
It is a retrospective observational study. The study was conducted in section of Histopathology, Aga Khan University Hospital, Karachi, Pakistan. All reported cases of sex cord stromal tumors of ovary during 1992 …

Frequency And Outcome Of Graft Versus Host Disease After Stem Cell Transplantation: A Six-Year Experience From A Tertiary Care Center In Pakistan, Natasha Ali, Salman Naseem Adil, Mohammad Usman Shaikh, Nehal Masood

Department of Pathology and Laboratory Medicine

Objective: The objective of this study was to evaluate the frequency and outcome of graft versus host disease after stem cell transplantation for various haematological disorders in Pakistan.
Materials and Methods: Pretransplant workup of the patient and donor was performed. Mobilization was done with G-CSF 300 mu g twice daily for five day. Standard GvHD prophylaxis was done with methotrexate 15mg/m(2) on day +1 followed by 10mg/m(2) on days +3 and +6 and cyclosporine. Grading was done according to the Glucksberg classification.
Results: A total of 153 transplants were done from April 2004 to December 2011. Out of these were …

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 …