Medical Specialties Commons^™

Database-Guided Discovery Of Potent Peptides To Combat Hiv-1 Or Superbugs., Guangshun Wang

Journal Articles: Pathology and Microbiology

Antimicrobial peptides (AMPs), small host defense proteins, are indispensable for the protection of multicellular organisms such as plants and animals from infection. The number of AMPs discovered per year increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been registered into the antimicrobial peptide database (APD). The majority of these AMPs (>86%) possess 11-50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31-70%. This article summarizes peptide discovery on the basis of the APD. The major methods are the linguistic model, database screening, de novo …

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 …

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.

The Line Between Addiction And Medication: Alcohol, Anesthesia, And Analgesia, Priya Joshi, B.S., Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

Alcohol is a particularly dangerous addiction because its consumption is legal even in excess, despite its harmful effects. Because alcohol has a multitude of targets in the central nervous system that are modified during chronic exposure, medications with overlapping targets such as anesthetics and analgesics must be modified when given to alcoholics. Unfortunately, as relatively little is known about the mechanism of addiction, it is difficult to predict how medications will be affected by central adaptation to chronic alcohol exposure. This review summarizes the consequences of alcohol exposure with particular attention to the GABA_Areceptor, and discusses the reasons …

Transfusion Related Acute Lung Injury, Nadia Abidi, Jay Herman, Md, Julie Karp, Md

Department of Pathology Honors Program Student Research Symposium

A 74 year old woman presented with hematemesis. Her medical history was significant for pulmonary embolism treated with warfarin anticoagulation, fibromyalgia treated with NSAIDs/steroids, and a prior bleeding event from a gastric ulcer. On admission she was stable with a hemoglobin of 8.7 g/dL and a therapeutic INR of 3.19. A type and screen determined a blood type of AB positive. In anticipation of endoscopy, the patient received one unit of red blood cells and four units of type AB plasma. Following transfusion, her INR was 1.83. The patient received an additional four units of type AB plasma to further …

Morphologic And Endoscopic Evaluation Of Collagenous Gastritis, Annie Ashok, Ashlie L. Burkart, Md, Cm

Department of Pathology Honors Program Student Research Symposium

Collagenous gastritis (CG) is a rare gastrointestinal condition of unknown etiology and pathogenesis characterized by the presence of a gastric subepithelial collagen band of variable thickness. While little is known about the disease, children and young adults often present with anemia, abdominal pain, and nodular gastric mucosa on endoscopy. In contrast, adults often present with chronic watery diarrhea and normal gastric mucosa on endoscopy. Disease associations (usually in adult cases) include celiac disease, collagenous colitis, collagenous sprue, and lymphocytic colitis. This study aims to further characterize the clinical, endoscopic and morphologic spectrum of CG.

Lumbar Chordoma: A Primary Bone Tumor, Andrew N. Fleischman, Bs, Brian O'Hara, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

• Primary malignant bone tumor of embryonic notochord remnants
• 1-4% of primary bone tumors, <0.1 per 100,000
• Location: Sacral (50%), Skull base (35%), Vertebral column (15%)
• Classic, chondroid (5-15%), and dedifferentiated (5%) variants
• Most commonly in late middle age (50s to 60s)
• Low-grade, slow growing tumor
• But locally aggressive, high rate of local recurrence (20% in 1^st year)
• Local recurrence is most important predictor of mortality
• Metastasis only occurs very late in disease
• Median survival of about 6 years, less than 12 months with mets
• 5 year survival of 70%, 10 year survival of 40%
• Primary therapy- aggressive surgical resection (if possible) …

An Unexpected Immunohistochemical Profile In An Ovarian Lesion, Kate Fritton, Joanna Chan, Md

Department of Pathology Honors Program Student Research Symposium

A 27 year old female presented with pelvic pain and a palpable pelvic mass. Upon histological examination, the cystic mass contained a multi-cellular lining with nuclear grooves. Negative inhibin staining ruled out a follicular cyst and granulosa cell tumor while pan-cytokeratin positivity suggested an epithelial lesion. The lesion stained positive for thrombomodulin, ultimately suggesting a diagnosis of a Brenner cell tumor, although CD56 positivity in the tumor questions the known immunohistochemical profile of Brenner cell tumors. This unusual result opens the door to future research into the role CD56 in the diagnosis of ovarian neoplasms.

Myeloid Sarcoma: Extramedullary Relapse After Allogeneic Bone Marrow Transplant For Chronic Myelogenous Leukemia, Maria Gubbiotti, Alina Dulau Florea, Md, Renu Bajaj, Phd

Department of Pathology Honors Program Student Research Symposium

Myeloid sarcoma (MS) is an extramedullary tumor of myeloid precursor cells, which can precede or occur concomitantly with acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms. Although MS can involve any organ, it is more common in the central nervous system (CNS) and gonads, sites known as “pharmacologic sanctuaries” where leukemic cells can survive despite systemic chemotherapy. Less often, this tumor can be the manner of relapse after allogeneic bone marrow transplantation.

The diagnosis is based on morphology and immunophenotype by either flow cytometry or immunohistochemistry of paraffin-embedded tissue, and confirmed by FISH or molecular studies. Myeloid sarcomas usually express …

A Case Of Hemoglobinopathy-Thalassemia Syndrome, Michele C. Khurana, B.S., Gene Gulati, Ph.D

Department of Pathology Honors Program Student Research Symposium

Patient Presentation

• 43 year-old African American female presents with left lower extremity pain
• Physical exam: unremarkable
• Past medical history:

Anemic since childhood

Avascular necrosis of left hip

DVT

Chronic illnesses: asthma, depression

Surgical history: appendectomy, tubal ligation, splenectomy, cholecystectomy, L hip replacement

• Family history: mother has lupus

Thoracic Dissecting Aneurysm And The Importance Of Genetics, Dan Kramer, Ba, Anthony Prestipino, M.D.

Department of Pathology Honors Program Student Research Symposium

Patient Presentation

• 28 year old white male with a past medical history significant for untreated hypertension
• Presents with 3 day history of chest discomfort, lower extremity weakness, bowel and bladder dysfunction, near-syncopal episodes
• Absent pulse in right femoral artery, weak pulse in left femoral artery
• Echosonography showed acute Type A dissecting aortic aneurysm
• Treatment

Immediately taken to surgery for repair of aorta with a graft and replacement of the aortic valve

• Outcome

Unstable after surgery

Biventricular heart failure

Persistent bleeding into mediastinum due to DIC

Required massive transfusion of RBCs, FFP, Cryoprecipitate, and Platelets

Became anuric and acidotic

Became fluid …

Adenoid Cystic Carcinoma In Unusual Locations – Differential Diagnosis Difficulties, Heather A. Mcmahon, B.S., Madalina Tuluc, Md

Department of Pathology Honors Program Student Research Symposium

Adenoid Cystic Carcinoma (ACC) is an uncommon malignant salivary gland tumor, representing 1% of all malignant tumors of the oral and maxillofacial region and 22% of all salivary gland malignancies. Although in the majority of cases ACC manifests in the major salivary glands, in rare instances it can be found in locations such as the esophagus, larynx, trachea, lacrimal gland, breast, prostate, lungs, or auditory canal. These unusual locations of ACC often pose a diagnostic challenge to the clinician and are associated with poorer outcomes for patients as compared to those ACC of a more typical presentation. In this study …

Correlations Between Gene Amplification And Protein Expression Of Topoisomerase 2a (Top2a) In Squamous Cell Carcinoma Of The Lung, Anita Modi, Msii, Charalambos C. Solomides, Md

Department of Pathology Honors Program Student Research Symposium

Background: While DNA topoisomerase 2A (TOP2A) plays an essential role in maintaining the structural integrity of the double helix during replication and recombination, excessive expression of this enzyme may promote malignant cell transformations. In fact, increased levels of TOP2A have been observed in various cancer cell lines including squamous cell carcinoma of the lung. This study sought to identify correlations between genotypic and phenotypic evidence of TOP2A obtained via in situ hybridization (ISH) and immunohistochemistry (IHC) techniques.

Methods Tissue microarrays created from 29 samples of Stage I Squamous Cell Carcinoma of the lung were stained with VENTANA BenchMark ULTRA platform …

Temporal Lobe Ganglioglioma In An Epilepsy Patient With Worsening Seizures: Case Study And Future Directions, Adam M. Olszewski, Mark Curtis, Md Phd.

Department of Pathology Honors Program Student Research Symposium

Gangliogliomas are rare brain tumors that have both neuronal and glial components. They hold a better prognosis than other infiltrative glial tumors, but differentiating between them can be challenging. While molecular markers are being studied, it is currently a histologic diagnosis.

In this case, the patient presented with epilepsy and worsening seizures secondary to a medial temporal lobe mass. Radiology report was inconclusive. Surgical resection was achieved and based on histologic examination the lesion was diagnosed as ganglioglioma, WHO grade I.

In this patient, pathological diagnosis of ganglioglioma offers a favorable prognosis and low risk of recurrence. In the future, …

Diagnostic Yield Of Endobronchial Ultrasound-Guided Fine Needle Aspiration (Ebus-Fna) In Lung Cancer Staging, Subtyping And Diagnosis Of Unexplained Mediastinal Lymphadenopathy, Rino Sato, Rossitza Draganova-Tacheva, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

• Lung cancer (LC) is the most commonly diagnosed cancer worldwide and the most frequent cause of cancer death in both men and women in the US (more deaths than the next three most common cancers combined)¹
• Clinical staging of LC is an integral part of patient care because it directs therapy and has prognostic value

Patients are routinely investigated with a conventional workup (medical history, PE, lab tests, bronchoscopy), CT and integrated whole-body PET-CT, followed by mediastinal tissue staging for enlarged or PET-positive intrathoracic nodes²

• Mediastinal tissue staging has been classically performed by mediastinoscopy, but they can …

Melanocytoma Of The Cerebellopontine Angle, Pranay Soni, M.D, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Ms. M.G. is a 46-year-old woman with a history of hypertension and prior bilateral laser eye surgery. In 2009, she presented with vertigo, tinnitus, and decreased hearing in the left ear. An MRI scan revealed an enhancing mass in the posterior fossa that was thought to be an acoustic neuroma. In May of 2009, she underwent gamma-knife radiotherapy for the 2.7 cm mass.

In September of 2012, M.G. noted progressive change in her voice quality as well as a swallowing disturbance and left facial spasms. A subsequent MRI showed significant enlargement of the tumor to a maximal size of 3.7 …

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (Dipnech) To Carcinoid: Exploring The Link, Jacob D. Mcfadden Msii, Jeffrey P. Baliff Md

Department of Pathology Honors Program Student Research Symposium

Neuroendocrine cells (NECs) play important roles in normal lung development, autonomic regulation of lung function, and response to hypoxia or injury. They are located between the respiratory epithelium and the basement membrane of bronchi and bronchioles (below), often as single cells or small clusters.

NEC proliferation is a common pathologic occurrence, well established as a reactive response to chronic lung injury. Much less commonly, NEC proliferation is observed in the absence of apparent inciting factors. This neoplastic phenomenon is termed “diffuse idiopathic pulmonary neuroendocrine cell hyperplasia” (DIPNECH).

DIPNECH is recognized as a precursor lesion for carcinoid tumors. While the progression …

Ocular Manifestations Of Rosai-Dorfman Disease, Phoebe L. Mellen, B.S., Ralph C. Eagle Jr., M.D.

Department of Pathology Honors Program Student Research Symposium

History of Rosai-Dorfman Disease

In 1969, Dr. Juan Rosai and Dr. Ronald F. Dorfman reported four cases of an entity that previously had puzzled pathologists and clinicians. The four cases had failed to fit under any diagnosis, but shared a few common characteristics. Each patient presented with painless, massive lymphadenopathy, most commonly of the cervical lymph nodes¹. Other locations included the inguinal, intra-parotid, and axillary lymph nodes. The patients all presented with fever and leukocytosis¹. The differential diagnosis included malignant lymphoma, malignant histiocytosis, reticuloendotheliosis, and chronic inflammation. However, the histopathological characteristics of the cases did not …

To Re-Excise Or Not To Re-Excise: Positive Margins After Excision Of Non-Melanoma Skin Cancers, Ramon Garza, Iii Md, Courtney Edwards Md, Bharat Ranganath Md, Nathan F. Miller Bs, Joshua M. Adkinson Md, Kirsten S. Bellucci Md, Robert X. Murphy Jr, Md, Ms

Department of Surgery

No abstract provided.

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 …

Antimicrobial Resistance Patterns In Extended-Spectrum Β-Lactamase Producing Escherichia Coli And Klebsiella Pneumoniae Isolates In A Private Tertiary Hospital, Kenya, Daniel Maina, Paul Makau, Andrew Nyerere, Gunturu Revathi

Pathology, East Africa

Background: Extended-Spectrum β-Lactamase (ESBL) producing Enterobacteriaceae have become widespread in hospitals and are increasing in community settings where they cause a variety of infections. In addition to hydrolyzing most beta-lactam agents, bacteria harboring these enzymes display resistance to other unrelated antimicrobial agents and thus often pose a therapeutic dilemma. Though these resistance patterns have been studied elsewhere within Africa, such data from hospitals in Kenya are scanty. We therefore undertook to determine these patterns at the Aga Khan University hospital by studying multidrug resistant Escherichia coli and Klebsiella pneumoniae isolates from patients' samples.

Findings: A total of 159 isolates (109 …

Lps And Pan-Induced Podocyte Injury In An In Vitro Model Of Minimal Change Disease: Changes In Tlr Profile., Tarak Srivastava, Mukut Sharma, Kok-Hooi Yew, Ram Sharma, R Scott Duncan, Moin A. Saleem, Ellen T. Mccarthy, Alexander Kats, Patricia A. Cudmore, Uri S. Alon, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement …

A Genetic Resource For Rapid And Comprehensive Phenotype Screening Of Nonessential Staphylococcus Aureus Genes., Paul D. Fey, Jennifer L. Endres, Vijaya Kumar Yajjala, Todd J. Widhelm, Robert J. Boissy, Jeffrey L. Bose, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

UNLABELLED: To enhance the research capabilities of investigators interested in Staphylococcus aureus, the Nebraska Center for Staphylococcal Research (CSR) has generated a sequence-defined transposon mutant library consisting of 1,952 strains, each containing a single mutation within a nonessential gene of the epidemic community-associated methicillin-resistant S. aureus (CA-MRSA) isolate USA300. To demonstrate the utility of this library for large-scale screening of phenotypic alterations, we spotted the library on indicator plates to assess hemolytic potential, protease production, pigmentation, and mannitol utilization. As expected, we identified many genes known to function in these processes, thus validating the utility of this approach. Importantly, we …

Prevalence Of Genital Chlamydia Infection In Urban Women Of Reproductive Age, Nairobi, Kenya, Ruchika Kohli, Walter P. Konya, Timona Obura, William Stones, Gunturu Revathi

Pathology, East Africa

Background: Chlamydia trachomatis is one of the major causes of sexually transmitted infections throughout the world. Most infections are asymptomatic and remain undetected. Burden of disease in the Kenyan population is not well characterised. This study was done to define the prevalence of genital Chlamydia infection in a representative female population.

Findings: A cross-sectional study design was employed. All women attending out-patient clinics (antenatal, gynaecology, family planning) and accident and emergency departments at two study sites over a five month period were invited to consent to completion of a questionnaire and vaginal swab collection. A rapid point-of-care immunoassay based test …

Role Of Deregulated Micrornas In Breast Cancer Progression Using Ffpe Tissue, Liang Chen, Youhuai Li, Yebo Fu, Jin Peng, Meng-Hsuan Mo, Michael Stamatakos, Christine B. Teal, Rachel F. Brem, Alexander Stojadinovic, Michael Grinkemeyer, Timothy A. Mccaffrey, Yan-Gao Man, Sidney W. Fu

Pathology Faculty Publications

MicroRNAs (miRNAs) contribute to cancer initiation and progression by silencing the expression of their target genes, causing either mRNA molecule degradation or translational inhibition. Intraductal epithelial proliferations of the breast are histologically and clinically classified into normal, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). To better understand the progression of ductal breast cancer development, we attempt to identify deregulated miRNAs in this process using Formalin-Fixed, Paraffin-Embedded (FFPE) tissues from breast cancer patients. Following tissue microdissection, we obtained 8 normal, 4 ADH, 6 DCIS and 7 IDC samples, which were subject to RNA isolation …

Protein Tyrosine Phosphatase-1b Regulates The Tyrosine Phosphorylation Of The Adapter Grb2-Associated Binder 1 (Gab1) In The Retina, Ammaji Rajala, Ashok K. Dilly, Raju Vs Rajala

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Gab1 (Grb2-associated binder 1) is a key coordinator that belongs to the insulin receptor substrate-1 like family of adaptor molecules and is tyrosine phosphorylated in response to various growth factors, cytokines, and numerous other molecules. Tyrosine phosphorylated Gab1 is able to recruit a number of signaling effectors including PI3K, SHP2 and PLC-γ. In this study, we characterized the localization and regulation of tyrosine phosphorylation of Gab1 in the retina.

Results

Our immuno localization studies suggest that Gab1 is expressed in rod photoreceptor inner segments. We found that hydrogen peroxide activates the tyrosine phosphorylation of Gab1 ex vivo and …

Pten Loss Mediated Akt Activation Promotes Prostate Tumor Growth And Metastasis Via Cxcl12/Cxcr4 Signaling, M Conley-Lacomb, Allen Saliganan, Pridvi Kandagatla, Yong Q. Chen, Michael L. Cher, Sreenivasa R. Chinni

Wayne State University Associated BioMed Central Scholarship

Abstract

Introduction

The chemokine CXCL12, also known as SDF-1, and its receptor, CXCR4, are overexpressed in prostate cancers and in animal models of prostate-specific PTEN deletion, but their regulation is poorly understood. Loss of the tumor suppressor PTEN (phosphatase and tensin homolog) is frequently observed in cancer, resulting in the deregulation of cell survival, growth, and proliferation. We hypothesize that loss of PTEN and subsequent activation of Akt, frequent occurrences in prostate cancer, regulate the CXCL12/CXCR4 signaling axis in tumor growth and bone metastasis.

Methods

Murine prostate epithelial cells from PTEN^+/+, PTEN ^+/− , and PTEN^−/− (prostate …

Igfbp-3 Inhibits Cytokine-Induced Insulin Resistance And Early Manifestations Of Atherosclerosis, Lathika Mohanraj, Ho-Seong Kim, Wei Li, Qing Cai, Ki E. Kim, Hye-Jung Shin, Yong-Jae Lee, Woo J. Lee, Jung H. Kim, Youngman Oh

Pathology Publications

Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced …

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.