Medical Cell Biology Commons^™

Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe

Neuroscience, Cell Biology & Physiology Faculty Publications

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K⁺ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges …

Quantitative Assessment Of Blood Coagulation By Cold Atmospheric Plasma, Caitlin Heslin, Daniela Boehm, Vladimir Milosavljevic, Michelle Laycock, Patrick J. Cullen, Paula Bourke

Articles

Cold atmospheric plasma (CAP) is produced by ionizing a chosen gas, thereby creating charged and reactive species. The reactive species generated are capable of inducing a range of biomedically relevant interactions including blood coagulation. However, the underlying biochemical processes of plasma-assisted blood coagulation are largely unknown, and data quantifying blood clot formation or the impact of system parameters on the intensity of the blood clot are scarce. In this study, blood coagulation was quantified by measuring hemoglobin absorbance. System parameters of the kINPen plasma jet were investigated and compared, including treatment time, distance from the plasma source and gas flow …

Seeing Is Believing: Optical Computed Tomography (Oct) And Histologic Analysis To Define Pathophysiology Of “Very”, Very Late Stent Thrombosis Occurring More Than 7 Years After Drug Eluting Stent Implantation, Antony G. Kaliyadan, Md, Alec Vishnevsky, Md, Henry Siu, Md, David Fishman, Md, John Farber, Md, Nicholas Ruggiero Ii, Md, Michael P. Savage, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Case Presentation

• 58-year-old male with prior non-ST elevation MI with PCI performed using a sirolimus eluting stent placed in a large OM1 branch 86 months prior presented with five hours chest pain similar to prior MI >7 years earlier.
• Additional history of hypertension, hyperlipidemia, non-compliance with antiplatelet therapy and active tobacco abuse at time of presentation.
• Patient reported self-discontinuation of medications (aspirin (time unknown), statin, beta blocker) and resumed smoking.
• Clopidogrel was discontinued by his primary physician 97 days prior to presentation
• Initial electrocardiogram revealed a lateral ST elevation MI and the patient was taken to the cardiac catheterization lab …

Fabrication And Characterization Of Cell Membrane, Ali Naserallah, Valentinas Gruzdys, Xue-Long Sun

Undergraduate Research Posters 2014

Cell membrane plays critical cellular functions in both physiological and pathological pathways and thus is important target for both basic and applied biomedical research. The domain structure features of cell membrane strongly affect the functions of membrane embedded biomolecules such as proteins and carbohydrates. However, understanding the structural aspects of membrane effects on the embedded biomolecule’s function have not been able easily to do due to limited approaches available. We have engaged in fabrication of cell membrane mimetic systems for functional analysis of membrane proteins and cell surface carbohydrates [1,2]. Thrombomodulin (TM), an endothelial integral membrane protein, plays central roles …

The Use Of Elastin-Like Polypeptides As A Drug Carrier Material: A Compatibility Study, Michael G. Price, John P. Gavin, Eric Helm, James T. Cole, Nolan Holland

Undergraduate Research Posters 2014

Stimuli responsive self-assembling nanoparticles of elastin-like polypeptides are promising platforms for targeted drug delivery and release. These particles spontaneously assemble from elastin-like polypeptide building blocks in solution. The nanoparticles stably self-assemble under specific temperature, salt, and pH conditions and can dissociate upon changing of these conditions. With appropriate design, the surface of the particles can be decorated with labels that cause them to accumulate in specific diseased tissues. In addition, the size of the particles is appropriate to minimize undesirable rapid clearance from the body. In this study, we are testing the ability of the elastin-like polypeptide core to store …

Loss Of Miro1-Directed Mitochondrial Movement Results In A Novel Murine Model For Neuron Disease., Tammy T Nguyen, Sang S Oh, David Weaver, Agnieszka Lewandowska, Dane Maxfield, Max-Hinderk Schuler, Nathan K Smith, Jane Macfarlane, Gerald Saunders, Cheryl A Palmer, Valentina Debattisti, Takumi Koshiba, Stefan Pulst, Eva L Feldman, György Hajnóczky, Janet M Shaw

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring …

Functional And Genetic Analysis Of Choroid Plexus Development In Zebrafish, Hannah Elizabeth Henson

Theses and Dissertations (ETD)

The choroid plexus (CP) is an epithelial based structure localized within the brain ventricles and functions as the blood-cerebrospinal fluid barrier (BCSFB). Under normal conditions, the CP is responsible for generating the cerebrospinal fluid (CSF) and regulating its components. Abnormal CP function has been associated with neurodegenerative diseases, tumor formation in CP epithelia (CPe), and hydrocephalus. Despite the significant role of the CP in these disorders, little research has been done to characterize its functional properties and genetically dissect the pathways involved in normal CP development and disease. For this study, we have utilized zebrafish, (Danio rerio), as a model …

Targeting The Redox System To Overcome Mechanisms Of Drug Resistance In Chronic Lymphocytic Leukemia, Marcia A. Ogasawara

Dissertations and Theses (Open Access)

Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia diagnosed in Western countries and is characterized by clonal expansion of B cells. The clinical course of CLL is diverse and nearly 50% of patients present with chromosomal abnormalities. Deletion of the short arm on chromosome 17 (del17p) occurs in 5-7% of cases and presents with the shortest median survival time and often respond poorly to therapy. The tumor suppressor gene, TP53 is located on this region and it is well established that the p53 protein regulates multiple functions including: mitochondria biogenesis, response to DNA damage and redox balance. …

Lineage-Specific Interface Proteins Match Up The Cell Cycle And Differentiation In Embryo Stem Cells, Angela Re, Christopher T. Workman, Levi Waldron, Alessandro Quattrone, Søren Brunak

Publications and Research

The shortage of molecular information on cell cycle changes along embryonic stem cell (ESC) differentiation prompts an in silico approach, which may provide a novel way to identify candidate genes or mechanisms acting in coordinating the two programs. We analyzed germ layer specific gene expression changes during the cell cycle and ESC differentiation by combining four human cell cycle transcriptome profiles with thirteen in vitro human ESC differentiation studies. To detect cross-talk mechanisms we then integrated the transcriptome data that displayed differential regulation with protein interaction data. A new class of non-transcriptionally regulated genes was identified, encoding proteins which interact …

Methylseleninic Acid Sensitizes Notch3-Activated Ovca429 Ovarian Cancer Cells To Carboplatin., Tiffany J. Tzeng, Lei Cao, Yangxin Fu, Huawei Zeng, Wen-Hsing Cheng

CALS Publications

Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3) is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA) induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein …

Stag2 Promotes Error Correction In Mitosis By Regulating Kinetochore–Microtubule Attachments, Marianna Kleyman, Lilian Kabeche, Duane A. Compton

Dartmouth Scholarship

Mutations in the STAG2 gene are present in ∼20% of tumors from different tissues of origin. STAG2 encodes a subunit of the cohesin complex, and tumors with loss-of-function mutations are usually aneuploid and display elevated frequencies of lagging chromosomes during anaphase. Lagging chromosomes are a hallmark of chromosomal instability (CIN) arising from persistent errors in kinetochore-microtubule (kMT) attachment. To determine whether the loss of STAG2 increases the rate of formation of kMT attachment errors or decreases the rate of their correction, we examined mitosis in STAG2-deficient cells. STAG2 depletion does not impair bipolar spindle formation or delay mitotic progression. Instead, …

Succinate Dehydrogenase Deficiency In Sporadic Pituitary Adenomas: A Potential Mechanism For Tumorigenesis, Edward Andrews, Md, Stacey K. Mardekian, Md, Markku Miettinen, Mark T. Curtis, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

In order to determine whether succinate dehydrogenase (SDH) deficiency plays a role in spor-adic, non-familial pituitary adenomas, we analyzed 80 pituitary adenomas for SDH deficiency from patients without familial tumor syndromes or without known SDH deficiency-associated neoplasms. SDH deficiency was determined by immunohistochemical (IHC) stains for SDHB since the loss of any of the four SDH subunits results in the loss of SDHB expression. Three pituitary adenomas showed complete loss of SDHB staining, and of these two also showed loss of SDHA staining. We further characterized these adenomas by looking at Ki67, IGF1R, and 5-hmC levels via IHC. SDHx …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Comparison Of Two Quantitative Image Analysis Systems For Breast Cancer Immunohistochemistry, Reid H. Phillips, Bs, Sue Direnzo, Bs, Charalambos C. Solomides, Md

Department of Pathology Honors Program Student Research Symposium

Automated image analysis systems for breast cancer immunohistochemistry promise efficiency and reliability in the quantification of therapy targets such as the estrogen receptor (ER) or human epidermal growth factor receptor (Her2). Thomas Jefferson University Hospital owns two such systems, the Aperio ScanScope AT (Leica Biosystems) and Ventana iScan Coreo (Roche). A comparison study was performed to determine if choice of system affects target quantification and subsequent clinical tumor classification. Tumor expressions of ER, progesterone receptor (PR), proliferation marker Ki67, and Her2 were quantified with both systems for tissue samples from twenty breast cancer patients. Positive tumor classification was based on …

Evaluating The Utility Of Thyroglobulin Wash Testing In The Management Of Well-Differentiated Thyroid Carcinoma, Katelyn M. Seither, Rossitza Draganova-Tacheva, Md

Department of Pathology Honors Program Student Research Symposium

Introduction

• Thyroid cancer is the most common endocrine neoplasm worldwide, representing 1.7% of new cancer diagnoses and 0.5% of cancer deaths each year (Baldini et al.)
• The majority of thyroid cancers are primary (originating within the gland itself), are well-differentiated, and are derived from follicular epithelial cells
• Papillary thyroid cancer is the most common subtype

70-80% of all thyroid cancers

Peak incidence in women of child-bearing age

Generally indolent behavior, excellent prognosis with total thyroidectomy

30-90% of patients exhibit recurrent or persistent metastasis to the cervical lymph nodes (Torres et al.) and 20% of cases present with occult cancer that …

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 …

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.