Pathology Commons^™

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …

Medical Interns', Residents' And Attending Physicians' Attitudes Towards Integrative Medicine And Recommended Treatments For Patients With Psoriasis, Jennifer L. Pacyon

PCOM Psychology Dissertations

Background: Psoriasis is a multifactorial disease that effect approximately 7.5 million Americans. There are a variety of traditional treatments for psoriasis (e.g. topical medications, biologics) that for many, are effective in combating the disease. However, traditional treatments often have aversive side effects and may not be appropriate for every patient (e.g. pregnant women). Additionally, the efficacy of these medications are variable leaving some looking for adjunctive treatment options. There is increasing evidence to support the use of adjunctive treatments for psoriatic patients (e.g. psychotherapy, mindfulness). However, research is variable in regards to medical professionals’ attitudes towards integrative medicine (IM) as …

Tmsb4y Is A Candidate Tumor Suppressor On The Y Chromosome And Is Deleted In Male Breast Cancer., Hong Yuen Wong, Grace M Wang, Sarah Croessmann, Daniel J Zabransky, Anita Aggarwal, Min-Ling Liu, + 10 More

Pathology Faculty Publications

Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further understand …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Novel Advances In Alzheimer's Disease, Jacob P. Naumann

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Alzheimer’s disease, the most common form of dementia in adults, is a progressive degenerative neurological disease that affects memory, cognition, and behavior. Dr. Alois Alzheimer discovered and diagnosed the irreversible disease in 1906 after documenting the famous case of Auguste Deter.¹ Since the discovery of the disease, numerous advances have made it possible to not only better understand the causal factors, but also to improve the medical diagnosis and preventative measures that healthcare providers can implement. For the first time since 1984, the National Institute on Aging (NIAA) and the Alzheimer’s Association (AA) proposed and published new diagnostic guideline …

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 …

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.

Eculizumab In The Successful Treatment Of Postpartum Hemolytic Uremic Syndrome - A Case Report, Craig A. Mackaness Do, Frederick S. Fleszler Md

Department of Medicine

No abstract provided.

Lymphoma Masquerading As Pneumonia With Acute Renal Failure: A Rare Clinical And Radiological Presentation Of Diffuse Large B Cell Gastric Lymphoma (Dlbcl), Ranjit R. Nair Md, Cheryl A. Bloomfield Md, Sharif A. Ali Md, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.

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

All Publications

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 …

Sessile Serrated Adenomas In The Proximal Colon Are Likely To Be Flat, Large And Occur In Smokers, Tarun Rustagi, Priya Rangasamy, Matthew Myers, Melinda Sanders, Haleh Vaziri, George Y. Wu, John W. Birk, Petr Protiva, Joseph C. Anderson

Dartmouth Scholarship

Aim: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs).

Methods: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period.

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.

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. …

Interactions Of Nitric Oxide And Superoxide Pathways In Hyperglycemic Endothelial Cells, Steven Clay Rogers

Graduate Theses and Dissertations

Cardiovascular complications arising from diabetic hyperglycemia represents one of the leading causes of death and greatest public health challenges of modern societies. Despite state-of-the-art glucose control, diabetic patients remain at a markedly increased risk of cardiovascular disease. The loss of endothelial function (the development of diabetic endothelial dysfunction) has been implicated in the development of numerous diabetic cardiovascular diseases. The endothelial cell produces many vasoactive substances, hormones and cytoprotective biological factors. Endothelial cells are also involved in and affected by the initiation of inflammatory responses through the release and interaction of cytokines and other immune system molecules. Therefore, regulation of …

Taz As A Regulator Of Mesenchymal Transformation And Clinical Aggressiveness In Gliomas, Katrina Salazar

Dissertations and Theses (Open Access)

Glioblastoma multiforme (GBM) is an aggressive, high grade brain tumor. Microarray studies have shown a subset of GBMs with a mesenchymal gene signature. This subset is associated with poor clinical outcome and resistance to treatment. To establish the molecular drivers of this mesenchymal transition, we correlated transcription factor expression to the mesenchymal signature and identified transcriptional co-activator with PDZ-binding motif (TAZ) to be highly associated with the mesenchymal shift. High TAZ expression correlated with worse clinical outcome and higher grade. These data led to the hypothesis that TAZ is critical to the mesenchymal transition and aggressive clinical behavior seen in …

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 …

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 …

Response Of Imitanib Meysylate In Patients With Gastrointestinal Stromal Cell Tumour, Abdullah Ladha, Mohammad Usman Shaikh

Department of Pathology and Laboratory Medicine

In this study, the response of Imitanib Mesylate in patients with Gastro-intestinal stromal cell tumour (GIST) was assessed. GIST results from a mutation in one of the receptor protein tyrosine kinases. Imitanib Mesylate, a tyrosine kinase inhibitor, has emerged as a promising new treatment for GISTs. Total 16 cases were reviewed. Diagnosis was based on biopsy and immunohistochemistry. Response assessment was done using CT scans, at a median duration of 4 months. The median age of the patients was 52 years, Majority were male (n=14). Most common presenting complaint was abdominal pain (n=7). Commonest primary site was stomach (n=7), Liver …

Frequency Of Primary Solid Malignant Neoplasms In Both Sexes, As Seen In Our Practice, Zubair Ahmad, Najamul Sahar Azad, Nausheen Yaqoob, Akhtar Husain, Aamir Ahsan, Ambreen Nasir Khan, Rashida Ahmed, Naila Kayani, Shahid Pervez, Sheema H. Hassan

Department of Pathology and Laboratory Medicine

Background: To determine the frequency of various histologic types of primary solid malignant neoplasms in males and females, in our practice, in a large series of surgical biopdies.

Method: A retrospective study of 20,000 consecutive surgical biopsies in the section of Histopathology, Aga Khan University Hospital (AKU), Karachi, in 2004.

Results: Squamous cell carcinoma of oral cavity was the commonest malignant neoplasm in males followed by diffuse Large B cell, Non-Hodgkin's lymphoma and Prostatic adenocarcinoma. In females, infiltrating Ductal carcinoma of the breast was overwhelmingly the commonest malignant neoplasm followed by Squamous cell carcinoma of the oral cavity and esophagus. …

P27kip1 And P130 Cooperate To Regulate Hematopoietic Cell Proliferation In Vivo, Inês Soeiro, Azim Mohamedali, Hanna M. Romanska, Nicholas C. Lea, Emma S. Child, Janet Glassford, Stephen J. Orr, Claudia Roberts, Kikkeri N. Naresh, El-Nasir Lalani, David J. Mann, Roger J. Watson, N. Shaun B. Thomas, Eric W. -F. Lam

Department of Pathology and Laboratory Medicine

To investigate the potential functional cooperation between p27^Kip1 and p130 in vivo, we generated mice deficient for both p27^Kip1 and p130. In p27^Kip1−/−;p130^−/− mice, the cellularity of the spleens but not the thymi is significantly increased compared with that of their p27^Kip1−/− counterparts, affecting the lymphoid, erythroid, and myeloid compartments. In vivo cell proliferation is significantly augmented in the B and T cells, monocytes, macrophages, and erythroid progenitors in the spleens of p27^Kip1−/−; p130^−/− animals. Immunoprecipitation and immunodepletion studies indicate that p130 can compensate for the absence …

Follicular Dendritic Cell Sarcoma Of Lymph Node - A Rare Entity, Safoorah Khalid, Nausheen Yaqoob, Shahid Pervez

Department of Pathology and Laboratory Medicine

Follicular dendritic cells (FDC) are non-lymphoid, non-phagocytic accessory cells in the immune system that are essential for antigen presentation and germinal center reaction regulation1. These cells are CD21+, CD35+, CD1a- and S100 protein + and they show desmosomes ultrastructurally.

The most commonly involved sites by FDC tumors are lymph nodes but may arise at a variety of extranodal sites including oral cavity, tonsil, gastrointestinal tract and liver. Most studies represent single case reports or case series.

Our patient presented with tumor in the lymph nodes. Histology revealed tumor cells with abundant eosinophilic cytoplasm, hyperchromatic and pleomorphic nuclei, and prominent nucleoli. …

Role Of Rapid Urease Test And Histopathology In The Diagnosis Of Helicobacter Pylori Infection In A Developing Country, Javed Yakoob, Wasim Jafri, Shahab Abid, Zaigham Abbas, Saeed Hamid, Muhammad Islam, Kashif Anis, Hasnain Ali Shah, Hizbullah Shaikh

Section of Gastroenterology

Background

The aim of this study was to determine the effect of commonly self-prescribed proton pump inhibitors (PPI) on the results of rapid urease test and histology for the diagnosis of H. pylori infection.

Methods

One hundred-nine consecutive patients with dyspeptic symptoms attending the endoscopy suite were enrolled in this study. Antrum biopsy specimens were collected at endoscopy for the rapid urease test (Pronto Dry, Medical Instrument Corp, France) and histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and like-hood ratio of a positive and negative of Pronto Dry test were compared against histology. The gold standard …

Near-Infrared Characterization Of Breast Tumors In Vivo Using Spectrally-Constrained Reconstruction, Subhadra Srinivasan, Brian W. Pogue, Ben Brooksby, Shudong Jiang, Hamid Dehghani, Christine Kogel, Wendy A. Wells, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six …

Trefoil Factor 2 (Tff2) Deficiency In Murine Digestive Tract Influences The Immune System, M. Baus- Loncar, J. Schmid, El-Nasir Lalani, I. Rosewell, R. A. Goodlad, H. G.W. Stamp, N. Blin, T. Kayademir

Department of Pathology and Laboratory Medicine

Background & Aims:

The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency.

Methods:

TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry.

Results:

On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. …

Expression Of Hepatocyte Growth Factor And Its Receptor C-Met, Correlates With Severity Of Pathological Injury In Experimental Alcoholic Liver Disease., El-Nasir Lalani, Richard Poulsom, Gordon Stamp, Franz Fogt, Peter Thomas, Amin A. Nanji

Department of Pathology and Laboratory Medicine

Expression of hepatocyte growth factor (HGF) and its receptor, c-met is up-regulated in various forms of liver injury. This study evaluated the relationship between HGF and c-met expression and pathological changes in experimental alcoholic liver disease. Rats (5 per group) were fed ethanol and a diet containing saturated fat corn oil or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in controls. In a second set of experiments, Kupffer cells, endothelial cells and hepatocytes were isolated from rats in each group. Pathological evaluation and analysis of HGF and c-met expression were performed in liver and the different cell types. …

Plasma Total Homocysteine And The Effect Of B-Group Vitmains. Current Knowledge And Future Directions In Assessment For Cardiovascular Diseases Among U.S. Cardiovascular Specialists, Salam F. Sunna

All-Inclusive List of Electronic Theses and Dissertations

Cardiovascular disease remains the major cause of morbidity and mortality in the United States claiming the lives of over 40% of the nearly 2.4 million Americans who die each year. Recent studies have shown that elevated homocysteine in the blood is related to a higher risk of coronary heart disease, peripheral vascular disease and stroke independent of other classical cardiovascular disease risk factors. The aim of this study is to determine the general awareness and acceptance of U.S. cardiovascular specialists of the homocysteine theory, the criteria used for ordering a homocysteine test, the frequency physicians refer patients to dietitians for …

Transitional Cell Carcinomas Of The Urinary Bladder. A Histopathological Study, Z. Ahmed, S. Muzaffer, M. Khan, N. Kayani, Shahid Pervez, A. S. Husseini, S H. Hasan

Department of Pathology and Laboratory Medicine

Objective:

To determine the histological grading and muscle invasion in Transitional Cell Carcinomas of the Urinary Bladder; and to evaluate whether any correlation exists between tumour grade and muscle invasion.

Method:

A Retrospective study of all consecutive cases of Transitional Cell Carcinomas of the Urinary Bladder diagnosed at Aga Khan University Hospital between 1st Jan 1997 and 31st Dec 2000.

Results:

This study included 495 cases of Transitional Cell Carcinoma of the Urinary Bladder. M: F ratio was 4:1. Ages of patients ranged from 30 years to 87 years. Mean age in males was 59.1 years and in females 58.8 …

Morphological Pattern Of Salivary Gland Tumours, M. S. Gill, S. Muzaffar, I. N. Soomro, Naila Kayani, A. S. Hussainy, Shahid Pervez, S. H. Hasan

Department of Pathology and Laboratory Medicine

Objective: To delineate the spectrum of salivary gland tumors in our setup.

Setting: The Aga Khan University Medical Centre, Karachi.

Method: Tumors were analysed considering histological type, age and sex of the patients and anatomic location. The diagnosis of individual tumours was based on the 1991 World Health Organisation Classification.

Results: During the span of eight years (1991-1998), 379 cases of salivary gland tumours were diagnosed. Of these, 205 (65.7%) were male and 174 (34.3%) were female. The median age at the time of diagnosis was 35 years. The median age for patients with malignant lesions (44 years) was 12 …

Retinoblastoma Tells The Story Of Our Health Care System, Irshad Soomro, Muhammad Nadeem Khan, Suhail Muzaffar, Naila Kayani, Shahid Pervez, Akbar Shah Hussainy, Rashida Ahmed, Sheema H. Hasan

Department of Pathology and Laboratory Medicine

Objective:

To review cases of retinoblastoma.

Setting:

Department of Pathology Aga Khan University Hospital Karachi.

Method:

Twenty three specimens from cases of retinoblastoma received over a period of eight years were routinely processes and stained with haematoxylin and Eosin stain Other stains were used for tuberculosis and melanin. Immunochemistry was resorted to in undifferentiated tumors.

Results:

Over 60% cases of retinoblastoma were diagnosed after 5 years and nine cases showed involvement of opti-nerve.

Conclusion:

Late diagnosis of retinoblastoma effects the stage of the tumors and the prognisis.