Medical Cell Biology Commons^™

Novel Insights Into The Role Of The Smoothened Cysteine Rich Domain In Hedgehog Signalling, Rajashree Rana

Theses and Dissertations (ETD)

The Hedgehog (Hh) signal transduction pathway functions as one of the key developmental pathways and deranged Hh signalling is associated with numerous cancer and tumor conditions. The Smoothened (Smo) G protein coupled receptor (GPCR) functions as the signal transducer of the Hh pathway and is the most attractive drug target of the pathway. The structure of the Smo receptor includes seven membrane spanning domains, extracellular and intracellular loops connecting the membranous domains and the extracellular cysteine rich domain (CRD). The extracellular CRD of the Smo receptor is homologous to the Frizzled (FzD) CRD. The FzD CRD interacts with the physiological …

Suppression Of Invasion And Metastasis Of Triple-Negative Breast Cancer Lines By Pharmacological Or Genetic Inhibition Of Slug Activity., Giovanna Ferrari-Amorotti, Claudia Chiodoni, Fei Shen, Sara Cattelani, Angela Rachele Soliera, Gloria Manzotti, Giulia Grisendi, Massimo Dominici, Francesco Rivasi, Mario Paolo Colombo, Alessandro Fatatis, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Most triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic …

Nprl2/Tusc4 Functions As A Tumor Suppressor By Regulating Brca1’S Stability Via The E3 Ubiquitination Pathway, Yang Peng

Dissertations & Theses (Open Access)

Expression of the tumor suppressor protein BRCA1 is frequently lost in breast cancer patients, and the loss of its expression is associated with disruption of various critical functions in cells and cancer development. In the present study, we demonstrate through microarray analysis that cells with tumor suppressor candidate 4 (NPRL2/TUSC4) knockdown show critical changes to cell cycle, cell death pathways and a global impact on cancer development. More importantly, we observed a clear cluster pattern of NPRL2/TUSC4-knockdown gene profiles with established homologous recombination (HR) repair defect signature. Additionally, NPRL2/TUSC4 protein physically interacts with the E3 ligase HERC2 and prevents ubiquitin …

Mrp4-Dependent Regulation Of Fibroblast Migration, Chandrima Sinha

Theses and Dissertations (ETD)

Roles of cyclic nucleotides and cyclic nucleotide-dependent signaling molecules in regulating several signaling pathways including cell migration have long been known. However, the new and revolutionary concept is that it is not just the absence or presence of cyclic nucleotides, but a highly coordinated balance between these molecules regulates cell migration. Multi-drug resistance protein 4 (MRP4), is a member of the large family of ATP binding cassette (ABC) transporter proteins, that localizes to the plasma membrane and functions as a nucleotide efflux transporter and thus plays a pivotal role in the regulation of intracellular cyclic nucleotide dynamics. In our study …

Pancreatic Beta Cell Plasticity And Involvement Of Insulin-Expressing Progenitor Cells, Christine A. Beamish

Electronic Thesis and Dissertation Repository

Islet transplants have been successfully used as treatment for diabetes, but are limited by shortages of cadaveric insulin-producing β-cells. An alternate source may be the dedifferentiation, expansion, and subsequent redifferentiation of pancreatic islets or β-cells using in vitro techniques prior to transplant. Based on protocols which described the dedifferentiation of human islets to ductal-like cells, we hypothesized that neonatal mouse islets could be similarly dedifferentiated in vitro. Dedifferentiation techniques produced significant duct-like cells, but redifferentiation to insulin-expressing cells was limited. RIPCre;Z/AP+/+ mice were consequently utilized to lineage trace β-cell fate during culture by a human placental alkaline phosphatase (HPAP) reporter. …

Influence Of Polycaprolactone And Basic Fibroblast Growth Factor On Gingival Fibroblasts, Sarah Michelsons

Electronic Thesis and Dissertation Repository

Guided tissue regeneration (GTR) to regenerate periodontal tissue involves placement of a cell-occlusive barrier membrane functionally excluding the gingiva and associated oral epithelium from the periodontal defect. Gingival connective tissue (CT) contains a rich vascular plexus and is a source of progenitor cells which could contribute to periodontal regeneration. We propose the use of a novel biodegradable and bioactive electrospun fibrous polycaprolactone (PCL) scaffold loaded with microspheres releasing basic fibroblast growth factor (bFGF) to promote gingival CT growth while maintaining a barrier to the oral epithelium. Scaffolds supported human gingival fibroblast proliferation and mesenchymal cell infiltration in a bFGF dose …

Hormone-Induced Calcium Oscillations Depend On Cross-Coupling With Inositol 1,4,5-Trisphosphate Oscillations., Lawrence D Gaspers, Paula J Bartlett, Antonio Politi, Paul Burnett, Walson Metzger, Jane Johnston, Suresh K Joseph, Thomas Höfer, Andrew P Thomas

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Receptor-mediated oscillations in cytosolic Ca(2+) concentration ([Ca(2+)]i) could originate either directly from an autonomous Ca(2+) feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca(2+) feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca(2+) oscillations or could just be a secondary response to the [Ca(2+)]i spikes. To investigate this problem, we constructed a recombinant IP3 buffer using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range. This IP3 buffer slows hormone-induced [IP3] dynamics without changing steady-state …

Autoantibodies To The Ny-Eso-1 Tumor Antigen In Metastatic Melanoma: Sialylation Of The Fc Region Of Immunoglobulin G Induces Differential Expression Signatures Of Inflammatory Molecules During Dendritic Cell Differentiation And Maturation, Martin Oaks, Nathaniel Rein, John O. Richards, James Shaffer

Journal of Patient-Centered Research and Reviews

Purpose: We tested the hypothesis that different glycoforms of antibodies from patients with metastatic melanoma have different functional effects on human dendritic cell differentiation and maturation.

Methods: Antibodies to the cancer antigen NY-ESO-1 were affinity-purified from patients with melanoma and further fractionated into different glycoforms by lectin chromatography. Sialic acid-rich and sialic acid-poor fractions of these immunoglobulin G antibodies (IgG) were added to dendritic cell cultures during both differentiation and maturation, and the resulting cellular messenger RNA (mRNA) and culture supernatants were tested by microarray and enzyme-linked immunoassay for molecules related to inflammatory pathways.

Results: We identified unique mRNA and …

Inpp4b Suppresses Prostate Cancer Cell Invasion, Myles C. Hodgson, Elena I. Deryugina, Egla Suarez, Sandra M. Lopez, Dong Lin, Hui Xue, Ivan P. Gorlov

Dartmouth Scholarship

INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer.

We demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine …

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 …

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 …

Quantitative Assessment Of Blood Coagulation By Cold Atmospheric Plasma, Caitlin Heslin, Daniela Boehm, Vladimir Milosavljevic, Michelle Laycock, Patrick 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 …

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 & 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 …

Genomic Predictors Of Drug Response To The Alpha-Specific Phosphoinositol 3-Kinase (Pi3ka-Alpha) Inhibitor Byl719 In Head And Neck Cancers, Giananthony T. Rizzo

Electronic Thesis and Dissertation Repository

PIK3CA is the only frequently mutated, druggable oncogene in head and neck squamous cell cancer (HNSCC), with PIK3CA point mutations and gene amplification rates of 17.5% and 40% respectively, with higher rates in HPV-positive disease. The objective of this research was to determine the effects of BYL719, an α-specific PI3K inhibitor in HNSCC cell lines.

All cell lines with PIK3CA hotspot point mutations or gene amplifications will be sensitive to BYL719.

Twenty-eight HNSCC cell lines were subjected to increasing concentrations of BYL719 and cell viability was measured over time. Cell lines were screened for activating PIK3CA hotspot mutations and amplifications …

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

College of Agriculture & Life Sciences Publications and Scholarship

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 …

Mri Relaxation Rates: A Quantitative Approach To Track Tumour Cells Expressing Maga, Anindita Sengupta

Electronic Thesis and Dissertation Repository

Using magnetic resonance imaging, relaxation rate measurements were

performed in cancer cells overexpressing a magnetotactic bacterial gene, MagA.

Measurements of magnetic resonance relaxation rates in this expression

system is important for optimizing cell detection and specificity, for developing

quantification methods, and for refinement of gene-based iron contrast using

magnetosome associated genes. We measured the total transverse

relaxation rate (R2^*), its irreversible and reversible components (R2 and R2^′,

respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells.

Clonal lines overexpressing MagA were cultured in the presence and absence of

iron supplementation, and mounted in a …

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 …

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 …

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 …

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 …