Digital Commons Network^™

Mechanisms That Modify Immune Response In Neonatal Alloimmune Thrombocytopenia, Robert Cooper, Jay H. Herman

Department of Pathology Honors Program Student Research Symposium

What is NAIT?

Neonatal alloimmune thrombocytopenia (NAIT) is a form of fetal and neonatal thrombocytopenia caused by maternal-fetal platelet antigen incompatibility that results in placental transfer of maternal IgG alloantibodies against the platelet antigen. Currently, there are 28 human platelet antigen systems (HPA) that are polymorphisms of various membrane glycoprotein (GP) integrins. The first HPA and most immunogenic was discovered in the 1960’s and is now termed HPA-1, a diallelic system with HPA-1a and HPA-1b on the GPβ3 subunit of the fibrinogen receptor (Murphy). Approximate HPA-1 phenotype frequencies are: homozygous 1a,1a (~70%); heterozygous 1a,1b (~28%); homozygous 1b,1b (~2%).

Typically an …

The 24th Annual Research Conference Abstract Booklet, Nikki Lynn Rogers

University of Gondar Research Conferences

Staff members, postgraduate and senior undergraduate students of the University, invited guests and speakers participated in the conference. The annual conference of the University is meant to share experiences in research activities among juniors and seniors, staff and students, and invited guests. It is also meant to motivate students and young faculty to engage in research and also to initiate and strengthen interdisciplinary collaborations. The findings of the studies and the resulting recommendations are expected to be used in solving the diverse societal problems we have been facing.

Research activities at the University of Gondar are primarily aimed at solving …

A Review Of The Institute Of Medicine’S Analysis Of Using Chimpanzees In Biomedical Research, Robert C. Jones, Ray Greek

Biomedicine and Animal Models in Research Collection

We argue that the recommendations made by the Institute of Medicine’s 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity, are methodologically and ethically confused. We argue that a proper understanding of evolution and complexity theory in terms of the science and ethics of using chimpanzees in biomedical research would have had led the committee to recommend not merely limiting but eliminating the use of chimpanzees in biomedical research. Specifically, we argue that a proper understanding of the difference between the gross level of examination of species and examinations on finer levels can shed light on important methodological …

20 Year-Old Male With Destructive Lesion Of Orbital Roof, Paris A. Barkan, Bs, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Patient History

Mr. G.R. is a 20-year-old man with no significant past medical history. He presented in July of 2013 with two months of worsening pain over the right orbit. Periorbital edema was also present. Initial treatment with eye drops, antibiotics (erythromycin followed by cephalexin), and steroids (prednisone) failed to control his symptoms.

In October of 2013, CT and MRI scans revealed a permeative destructive lesion centered in the right orbital roof with extension into the superior orbit and the floor of the anterior cranial fossa. There was no abnormal enhancement in the visualized brain parenchyma.

The radiologic appearance of …

The Intersection Between Hpv And Hiv Infections: Is There An Increased Susceptibility To Hiv Acquisition In Hpv-Infected Women?, Montida Fleming, Ba, Fred Gorstein, Md

Department of Pathology Honors Program Student Research Symposium

It has been well documented that HIV infection is associated with HPV infection and the progression to cervical carcinoma. Since the spread of HIV/AIDS epidemic, HPV-related cervical carcinoma had such a high prevalence in HIV-infected individuals that it became established as an AIDS-defining illness. Cervical cancer is the most common AIDS-related malignancy, and the sixth most common presenting AIDS-defining illness in women.¹ Additionally, HIV infection leads to a 5-fold increase in multiple new HPV infections within 6 weeks of seroconversion.² Not only does HIV impact acquisition of HPV at molecular and cellular levels, HIV and HPV viruses interact …

Lead Toxicity: What Is It And How Is It Happening?, Kimberly A. Parada, Ba, Jay S. Schneider, Phd

Department of Pathology Honors Program Student Research Symposium

EPIDEMIOLOGY

Lead poisoning accounts for 0.6% of the global burden of disease.

In Pennsylvania in 2010, 148,751 children under 72 months of age were tested for blood lead levels. Of those children, 19,176 had blood lead levels greater than 5 μg/dl.

• A lower socioeconomic status increases the chances for lead exposure.
• Lead toxicity is an under-appreciated problem that is entirely preventable.

Peripheral T-Cell Lymphoma Arising From Age-Related Ebv-Associated Lymphoproliferative Disorder (Ar-Ebvlpd), Alaina Chodoff, Msii, Guldeep Uppal, Md, Jerald Z. Gong, Md

Department of Pathology Honors Program Student Research Symposium

In the setting of underlying immune suppression, Epstein Barr Virus (EBV) is a well-recognized oncogenic agent that induces the malignant proliferation of B-cells. EBV-lymphoproliferative disorders (LPDs) have recently been linked to immunosenescence. We present a unique case of Age-Related EBV-Lymphoproliferative Disorder (AR-EBVLPD) in a 70 year old female that deviates from the characteristic progression of this disease. Over the course of 18 months, the patient’s clinical condition worsened without a definitive diagnosis to explain the severe, atypical widespread chronic inflammation spanning her gastrointestinal tract, from esophagus to small bowel. The diagnosis of AR-EBVLPD, polymorphic extranodal subtype, was delayed until the …

Hiv Associated Neurocognitive Disorders In An Antiretroviral Therapy Era, Molly Halloran, David S. Strayer, Md, Phd

Department of Pathology Honors Program Student Research Symposium

HIV emerged as a major threat to world health over 30 years ago, and while its effects on the immune system are widely known, HIV also has broad and devastating effects on the nervous system. Despite our potent antiretroviral therapies (ART), these HIV-associated neurocognitive disorders (HAND) continue to afflict HIV infected individuals. With over 33 million people infected worldwide and evidence that neurological damage can accrue in virologically well controlled individuals, HAND is a pressing challenge. Nevertheless, many questions remain unanswered about this spectrum of disorders.

Molecular Profiling Of Patients With Non Small Cell Lung Cancer At Jefferson University Hospital, Erin Bange, Renu Bajaj, Ms, Phd, Cg (Ascp), Cm, Facmg

Department of Pathology Honors Program Student Research Symposium

Companion diagnostics is the use of specific tests whose results are linked to a particular drug. It allows clinicians the ability to better target the mechanism of pathology in the patient and follow it up with a therapy specifically designed to treat the disease process at hand. This approach to medicine has particularly been championed in the field of oncology with the development of such drugs as Zelboraf for the treatment of metastatic melanoma with the BRAFV600 mutation or Xalkori for late stage lung cancer expressing an abnormal ALK protein. In the case of non-small cell lung cancer (NSCLC) Jefferson …

Plasmapheresis And Hiv-Associated Thrombotic Microangiopathy: An Institutional Review, Megan Fisher, Ms2, Nancy Edger Hall, Rn, Mba, Jennifer Webb, Md, Julie Karp, Md

Department of Pathology Honors Program Student Research Symposium

Thrombotic thrombocytopenic purpura (TTP) is a systemic disorder that classically results from a deficiency in the von Willebrand factor-cleaving enzyme, ADAMTS13. The human immunodeficiency virus (HIV) is a secondary cause of TTP. It has been recognized that some patients with HIV-associated TTP do not have a deficiency in ADAMTS13 activity. The role of plasmapheresis (PLEX) in these patients is unclear. This study reviewed 8 cases of HIV-associated TTP at Thomas Jefferson University Hospital. All patients responded to treatment; however, we were unable to make any conclusions regarding the use of PLEX in patients with normal ADAMTS13 activity. HAART initiation is …

Her-2 Heterogeneity In Breast Cancer: A Case Study, Kinnari Patel, Theodore Parsons

Department of Pathology Honors Program Student Research Symposium

CASE

The patient is a 75 year-old female with a history of stage 1 invasive ductal carcinoma of the left breast measuring 1.2 cm. Core biopsy of the mass demonstrated Nottingham grade 3 invasive ductal carcinoma; ER negative, PR negative, HER-2 negative (1+). The patient underwent mastectomy in April 2013. Mastectomy confirmed Nottingham grade 3 invasive ductal carcinoma pT1c/pN0/pMX with peritumoral lymphovascular invasion and invasive tumor less than 1 mm from the superoanterior margin. Due to comorbidities the patient was not considered a candidate for adjuvant chemotherapy.

In January 2014 the patient presented with a mastectomy site recurrence. Needle core …

Personalized Immune Therapy For Cancer A Potential Game-Changing Treatment, Emily Evron, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

T-CELL RECEPTOR, NORMALLY

T-cell receptors reside on the surface of T-cells, and recognize a specific antigen presented by an MHC molecule

Next, the T-cells become either CD4 or CD8 cells

Co-stimulation is a key step in activating the T-cell; B7 proteins on the surface of antigen-presenting cells interact with CD28/CTLA-4 receptors on the T-cell.

Haploidentical Hematopoietic Stem Cell Transplantation: Rationale, Development, And Jefferson’S Method, Susan Mcilvaine, Dolores Grosso, Rn, Crnp, Dnp, Beth Colombe

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

There are many indications for hematopoietic stem cell transplantation. In addition to hematologic malignancies, transplants are performed in certain non-hematologic malignancies, for marrow disorders such as Sickle Cell Anemia, and for various inherited disorders such as SCID. Traditionally, transplants have been performed between donors and recipients that are a complete HLA match (typically matched siblings). That is, patients have identical HLA alleles on both copies of chromosome 6. HLA alleles code for major histocompatibility complex molecules, which are the proteins that cause transplant rejection when a mismatch between donor and recipient is present. Thus, matched transplants have been historically …

Small Cell Carcinoma Of The Bladder: A Rare Entity, Andrew H. Matthews, Ruth Birbe, Md

Department of Pathology Honors Program Student Research Symposium

BACKGROUND

Primary small cell carcinoma of the urinary bladder is a rare tumor, accounting for less than 1% of the annual 70,000 cases of urinary bladder cancer.¹ Accordingly, little data is available beyond case series to guide diagnosis or treatment. Overall prognosis remains poor with five year survival often markedly below 50%. Current staging and treatment remains largely based on extrapolation from small cell carcinoma of the lung. We review two recent cases of bladder small cell carcinoma with a focus on comparing and contrasting with lung small carcinoma.

Giant Cell Tumor Of Soft Tissue: A Case Study, Rachel Schneider, Brian J. O'Hara

Department of Pathology Honors Program Student Research Symposium

BACKGROUND

Giant cell tumors of soft tissue are relatively uncommon tumors. They are considered to be the soft tissue counterpart to giant cell tumors of bone. Both tumors consist of multi-nucleated giant cells evenly distributed throughout a background of epithelioid mononuclear cells, and are usually benign, but can be locally invasive. Giant cell tumors of soft tissue typically occur in patients over age 40, and show no gender or racial predilection. They present as firm, well demarcated masses, which are not connected to the underlying muscle, tendon, or bone. Giant cell tumors of soft tissue are generally small, and tend …

Small Cell Carcinoma Of The Breast, Victor Carlson, Paolo Cotzia, Md, Juan P. Palazzo, Md

Department of Pathology Honors Program Student Research Symposium

INTRODUCTION

Small cell carcinoma of the breast (SCCB) is a rare, highly aggressive neoplasm first reported in 1983. With striking histologic similarity to small cell carcinoma of the lung, it is comprised of small cells with relatively large, hyperchromatic nuclei and scanty cytoplasm. While capable of hormone secretion, this is a rare occurrence in this variant of small cell carcinoma. Patients typically present with a suspicious breast mass confirmed on imaging, with variable lymph node invasion.

Fibrosing Cholestatic Hepatitis C Post-Liver Transplantation: A Case Study, Layla Hatem, Wei Jiang, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Introduction:

Liver Transplantation:

• Hepatitis C infection is the most common indication for liver transplantation in the US
• HCV infection of the liver allograft occurs within hours from circulating virions.

-Serum RNA levels are observed in the first several weeks.

-Acute hepatitis occurs in 2-6 months

-Chronic hepatitis occurs in 3-9 months

***Persistence of HCV infection is the rule after transplantation due to immune suppression

Chronic recurrent HCV infection post transplantation

• There are four distinct patterns of recurrent chronic HCV in the liver allograft.

-Usual chronic HCV (>70%)

-Fibrosing Cholestatic Hepatitis C (5-10%)

-Plasma cell-rich HCV

-HCV overlapping with rejection …

Abcc9 Gene Polymorphism Is Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Steven Estus, Erin L. Abner, Ishita Parikh, Manasi Malik, Janna H. Neltner, Eseosa Ighodaro, Wang-Xia Wang, Bernard R. Wilfred, Li-San Wang, Walter A. Kukull, Kannabiran Nandakumar, Mark L. Farman, Wayne W. Poon, Maria M. Corrada, Claudia H. Kawas, David H. Cribbs, David A. Bennett, Julie A. Schneider, Eric B. Larson, Paul K. Crane, Otto Valladares, Frederick A. Schmitt, Richard J. Kryscio, Gregory A. Jicha, Charles D. Smith, Stephen W. Scheff, Joshua A. Sonnen, Jonathan L. Haines, Margaret A. Pericak-Vance, Richard Mayeux, Lindsay A. Farrer, Linda J. Van Eldik, Craig Horbinski, Robert C. Green, Marla Gearing, Leonard W. Poon, Patricia L. Kramer, Randall L. Woltjer, Thomas J. Montine, Amanda B. Partch, Alexander J. Rajic, Katierose Richmire, Sarah E. Monsell, Gerard D. Schellenberg, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer's Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer's Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer's Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically …

Development And Application Of Novel Conformation-Specific Monoclonal Antibodies For Parkinson’S Disease Pathology., Nour Khaled Majbour

Accounting Dissertations

An abundance of genetic, biochemical and histopathological evidence suggests that the formartion of α-synuclein (α-syn) protein deposits is an important, and likely seminal, step in the development of several important neurodegenerative diseases, the so-called synucleinopathies, including Parkinson’s Disease (PD), intensive research, to date, the only accepted diagnosis for PD is based on clinical criteria. α-syn conversion from soluble monomers into oligomers or fibrils represents a crucial step in synucleinopathies pathogenesis; however, the exact mechanism underlying the cellular aggregation has not been fully elucidated. A growing body of evidence suggests that α-syn soluble oligomers, rather than mature fibrils, are the neurotoxic …

Extracellular Traps Are Associated With Human And Mouse Neutrophil And Macrophage Mediated Killing Of Larval Strongyloides Stercoralis., Sandra Bonne-Annee, Laura A. Kerepesi, Jessica A. Hess, Jordan Wesolowski, Fabienne Paumet, James B. Lok, Thomas J. Nolan, David Abraham

Department of Microbiology and Immunology Faculty Papers

Neutrophils are multifaceted cells that are often the immune system's first line of defense. Human and murine cells release extracellular DNA traps (ETs) in response to several pathogens and diseases. Neutrophil extracellular trap (NET) formation is crucial to trapping and killing extracellular pathogens. Aside from neutrophils, macrophages and eosinophils also release ETs. We hypothesized that ETs serve as a mechanism of ensnaring the large and highly motile helminth parasite Strongyloides stercoralis thereby providing a static target for the immune response. We demonstrated that S. stercoralis larvae trigger the release of ETs by human neutrophils and macrophages. Analysis of NETs revealed …

Inhibition Of Food Intake By Pacap In The Hypothalamic Ventromedial Nuclei Is Mediated By Nmda Receptors, Jon M. Resch, Brian Maunze, Kailynn A. Phillips, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Central injections of pituitary adenylate cyclase-activating polypeptide (PACAP) into the ventromedial nuclei (VMN) of the hypothalamus produce hypophagia that is dependent upon the PAC1 receptor; however, the signaling downstream of this receptor in the VMN is unknown. Though PACAP signaling has many targets, this neuropeptide has been shown to influence glutamate signaling in several brain regions through mechanisms involving NMDA receptor potentiation via activation of the Src family of protein tyrosine kinases. With this in mind, we examined the Src-NMDA receptor signaling pathway as a target for PACAP signaling in the VMN that may mediate its effects on feeding behavior. …

Association Between Symptomatic Vulvovaginal Candidiasis And Hiv Rna Levels In Plasma And Genital Secretions Among Women On Haart, Teke Apalata, William H. Carr, Benjamin Longo-Mbenza, Willem A. Sturm, P. Moodley

Publications and Research

Background. Genital tract (GT) inflammation plays a major role in HIV transmission. We aimed to determine the association between symptomatic vulvovaginal candidiasis (VVC) and HIV RNA levels in plasma and GTs of HIV-infected women on highly active antiretroviral therapy (HAART).

Method. Women with VVC on HAART were recruited from a primary healthcare clinic in KwaZulu-Natal Province, South Africa, between June 2011 and December 2011. VVC was diagnosed clinically, supported by Gram staining and culture of genital secretions. HIV RNA load was determined by reverse transcription polymerase chain reaction. CD4+ counts were obtained from patients’ medical records.

Results. Plasma HIV RNA …

Correlational Studies Of Organophosphate Levels And Endocrine Disruption, Immunomodulation, And Altered Glucose Homeostasis In A Human Population Study, Carrie Mckean

Dissertations

Organophosphate (OP) pesticides have become the most widely used insecticides since the removal of organochlorine pesticides (“Ch4 Organophosphate Insecticides.pdf,” n.d.) and are generally the most toxic of all pesticides to vertebrates (Soltaninejad & Abdollahi, 2009). As a result, ongoing research has been aimed at further understanding potential health effects from exposure.

The aim of this dissertation research project is to investigate and characterize correlations of OP body burden with human health effects. This research involves an investigation into three pertinent areas concerning OP exposure: thyroid disruption, altered hematology biomarkers, and alterations of glucose homeostasis. Data under investigation come exclusively from …

Humor's Effect On Short-Term Memory In Older Adults: An Innovative Wellness Paradigm, Gurinder Singh Bains

Loma Linda University Electronic Theses, Dissertations & Projects

Context: With ageing, the detrimental effects of stress can impair the ability to learn and sustain memory. Humor and the associated mirthful laughter can reduce stress by decreasing the hormone cortisol. Chronic release of cortisol can damage hippocampal neurons leading to impairment of learning and memory. Objectives: To examine the effect of watching a humor video on short term memory in older adults. Design: A randomized, controlled trial. Setting: Loma Linda University, Loma Linda, CA. Participants: 30 subjects: 20 normal healthy, older adults, 11 males and 9 females; 10 Type 2 Diabetic older adults, 6 males and 4 females. Intervention: …

Cytokine Control Of Glioma Adhesion And Migration, Negin Baghdadchi

Electronic Theses, Projects, and Dissertations

Glioblastoma multiforme (GBM) is the most lethal primary central nervous system tumor, with median survival after diagnosis of less than 12 months because dissemination into the brain parenchyma limits the long-term effectiveness of surgical resection, and because GBM cells are resistant to radiation and chemotherapy. This sad dismal prognosis for patients with GBM emphasizes the need for greater understand of the fundamental biology of the disease.

Invasion is one of the major causes of treatment failure and death from glioma, because disseminated tumor cells provide the seeds for tumor recurrence. Inflammation is increasingly recognized as an important component of invasion. …

Amino Acid-Dependent Stability Of The Acyl Linkage In Aminoacyl-Trna., Jacob R Peacock, Ryan R Walvoord, Angela Y Chang, Marisa C Kozlowski, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Aminoacyl-tRNAs are the biologically active substrates for peptide bond formation in protein synthesis. The stability of the acyl linkage in each aminoacyl-tRNA, formed through an ester bond that connects the amino acid carboxyl group with the tRNA terminal 3'-OH group, is thus important. While the ester linkage is the same for all aminoacyl-tRNAs, the stability of each is not well characterized, thus limiting insight into the fundamental process of peptide bond formation. Here, we show, by analysis of the half-lives of 12 of the 22 natural aminoacyl-tRNAs used in peptide bond formation, that the stability of the acyl linkage is …

Pd2/Paf1 Depletion In Pancreatic Acinar Cells Promotes Acinar-To-Ductal Metaplasia., Parama Dey, Satyanarayana Rachagani, Arokia P. Vaz, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic differentiation 2 (PD2), a PAF (RNA Polymerase II Associated Factor) complex subunit, is overexpressed in pancreatic cancer cells and has demonstrated potential oncogenic property. Here, we report that PD2/Paf1 expression was restricted to acinar cells in the normal murine pancreas, but its expression increased in the ductal cells of KrasG12D/Pdx1Cre (KC) mouse model of pancreatic cancer with increasing age, showing highest expression in neoplastic ductal cells of 50 weeks old mice. PD2/Paf1 was specifically expressed in amylase and CK19 double positive metaplastic ducts, representing intermediate structures during pancreatic acinar-to-ductal metaplasia (ADM). Similar PD2/Paf1 expression was observed in murine pancreas …

Structural Similarity Between Β3-Peptides Synthesized From Β3-Homo-Amino Acids Or L-Aspartic Acid Monomers, Sahar Ahmed, Tara Sprules, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Formation of stable secondary structures by oligomers that mimic natural peptides is a key asset for enhanced biological response. Here we show that oligomeric β³‐hexapeptides synthesized from l‐aspartic acid monomers (β³‐peptides 1, 5a, and 6) or homologated β³‐amino acids (β³‐peptide 2), fold into similar stable 14‐helical secondary structures in solution, except that the former form right‐handed 14‐helix and the later form left‐handed 14‐helix. β³‐Peptides from l‐Asp monomers contain an additional amide bond in the side chains that provides opportunities for more hydrogen bonding. However, based on the …

Octopamine Neuromodulation Regulates Gr32a-Linked Aggression And Courtship Pathways In Drosophila Males, Jonathan C. Andrews, Maria Paz Fernàndez, Qin Yu, Gregory Patrick Leary, Adelaine K. W. Leung, Michael P. Kavanaugh, Edward A. Kravitz, Sarah J. Certel

Biological Sciences Faculty Publications

Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a …

Extraction Of Intrinsic Fluorescence From Single Fiber Fluorescence Measurements On A Turbid Medium: Experimental Validation, U. A. Gamm, C. L. Hoy, F. Van Leeuwen - Van Zaane, H. J. C. M. Sterenborg, S. C. Kanick, D J. Robinson, A. Amelink

Dartmouth Scholarship

Abstract

The detailed mechanisms associated with the influence of scattering and absorption properties on the fluorescence intensity sampled by a single optical fiber have recently been elucidated based on Monte Carlo simulated data. Here we develop an experimental single fiber fluorescence (SFF) spectroscopy setup and validate the Monte Carlo data and semi-empirical model equation that describes the SFF signal as a function of scattering. We present a calibration procedure that corrects the SFF signal for all system-related, wavelength dependent transmission efficiencies to yield an absolute value of intrinsic fluorescence. The validity of the Monte Carlo data and semi-empirical model is …