Medical Cell Biology Commons^™

Mitochondrial Ca(2+) Uptake By The Voltage-Dependent Anion Channel 2 Regulates Cardiac Rhythmicity., Hirohito Shimizu, Johann Schredelseker, Jie Huang, Kui Lu, Shamim Naghdi, Fei Lu, Sarah Franklin, Hannah Dg Fiji, Kevin Wang, Huanqi Zhu, Cheng Tian, Billy Lin, Haruko Nakano, Amy Ehrlich, Junichi Nakai, Adam Z Stieg, James K Gimzewski, Atsushi Nakano, Joshua I. Goldhaber, Thomas M. Vondriska, György Hajnóczky, Ohyun Kwon, Jau-Nian Chen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca(2+) handling, we performed a chemical suppressor screen on zebrafish tremblor embryos, which suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the transfer of Ca(2+) from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+) sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and irregular contractions. We further show that overexpression …

In Vivo Cigarette Smoke Exposure Decreases Ccl20, Slpi, And Bd-1 Secretion By Human Primary Nasal Epithelial Cells, James Jukosky, Benoit J. Gosselin, Leah Foley, Tenzin Dechen, Steven Fiering, Mardi A. Crane-Godreau

Dartmouth Scholarship

Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of …

The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem

Pharmacy Faculty Articles and Research

Polycystic kidney disease (PKD) is the most common life-threatening genetic disease worldwide – affecting about 12.5 million people. Patients with the condition have multiple fluid-filled cysts in their kidneys that lead to a massive enlargement of the organ and gradual worsening of its function, as well as complete failure in many cases. The lack of available treatment means patients may eventually require regular dialysis or a kidney transplant.

The Predictive Value Of The Proliferation Marker Ki-67 In Patients With Fulminant Hepatic Failure, Ashesh P. Shah, Md, Upasana Joneja, Md, David Walls, Md, John Farber, Md

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

INTRODUCTION

In the United States, acute liver failure (ALF) affects an estimated 2,000 people per year and accounts for 6% of all liver transplants. Without transplantation, however, less than 50% of patients survive with medical management alone. Early identification of patients with survivable AFL is important to guiding their management and early referral to transplantation.

Studies have shown that the current prognostic scoring systems used for FHF, including the King’s College Criteria (KCC) and the Model for End- Stage Liver Disease (MELD), have poor sensitivity and negative predictive value for predicting outcome, highlighting a need for more accurate predictive models. …

Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer, Rounak Paramjeet Nande

Theses, Dissertations and Capstones

A major challenge for effective gene therapy is systemic delivery of viruses carrying therapeutic genes into affected tissue. The immunogenic nature of human adenoviruses (Ads) limits their use for intratumoral (IT) injection in gene therapy. Ads transfection is further hampered by the fluctuating presence of Coxsackie and Adenovirus Receptor (CAR) and integrins on the cells’ surface. To circumvent these limitations we developed a novel approach wherein Ads are encapsulated inside the shell of lyophilized, lipid-encapsulated, perfluorocarbon microbubbles (MBs)/ultrasound (US) contrast agents, which act as delivery vehicles for a sitespecific gene transfer system.

We performed infection studies with Ad.GFP (Green Fluorescent …

Stromal Monocarboxylate Transporter Mct4 Is A Poor Prognostic Factor In Squamous Cell Carcinoma, Mehri Mollaee, Md, P. Cotzia, Patrick Tassone, Md, Adam J. Luginbuhl, Md, Ubaldo E. Martinez-Outshoorn, Md, Tingting Zhan, Joseph M. Curry, Md, Madalina Tuluc, Md

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

ABSTRACT

Introduction:

Monocarboxylate transporter 4 (MCT4) is the main exporter of lactate out of cells. It is also a critical component in the glycolytic metabolism of cancer cells. In this study, stromal MCT4 in oral SCC was correlated with risk of recurrence (ROR), extent of primary tumor (pT) and nodal metastasis (pN), perineural invasion (PNI), lymphovascular invasion (LVI), HPV status, extracapsular extension (ECE) and positive margin.

Methods:

Clinical data were collected for 86 consecutive patients with oral HNSCC. Tissue microarrays (TMA) were constructed from paraffin blocks of resection specimens and stained for MCT4. Immunohistochemistry (IHC) staining was assessed and quantified …

Workflow Modifications And Addition Of Maldi-Tof Technology Significantly Improved Turn-Around-Time To Identification Of Common Urine Pathogens, Dimath Alyemni, Md, Christine M. Lam, Amity L. Roberts, Phd, D(Abmm)

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

Background:

In order to improve the identification of common aerobic urine cultures as well as antimicrobial susceptibility testing (AST) setup at an Academic Medical Center, work-flow modifications and MALDI-TOF technology were incorporated. Previously, the majority of species identification was achieved with conventional identification/antimicrobial susceptibility combo panels. All urine cultures, regardless of laboratory receipt time, were previously read once per day on 1st shift.

Methods:

The initial workflow modification involved addition of a 2nd shift urine culture reading. Urine specimens received from 8:00 AM to 4:00 PM were read on 1st shift, while urine specimens received from 4:00 PM to 8:00 …

Is Myeloproliferative Neoplasm With Splanchnic Vein Thrombosis A Distinct Clinical Entity?, Upasana Joneja, Md, Jerald Z. Gong, Md, Guldeep Uppal, Md

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

Clinical History:

A 29 year-old previously healthy female presented with sub-acute symptoms of weight loss, right upper quadrant pain and nausea.

CBC results: WBC-11.7, Hb- 12.5, Platelet- 286, MCV- 90, MCV- 26.8, RDW- 18%.

Imaging: Ultrasound and MRI of the abdomen were suggestive of Budd-Chiari syndrome that was supported by a liver biopsy showing features of hepatic outflow obstruction(Figure 1). There was no clinical or radiological evidence of splenomegaly. The hypercoagulable work-up was negative. An underlying Myeloproliferative Neoplasm (MPN) was suspected.

Validation Of Simple Sequence Length Polymorphism Regions Of Commonly Used Mouse Strains For Marker Assisted Speed Congenics Screening., Channabasavaiah B. Gurumurthy, Poonam S. Joshi, Scott G. Kurz, Masato Ohtsuka, Rolen M. Quadros, Donald W. Harms, K.C. Kent Lloyd

Journal Articles: Genetics, Cell Biology & Anatomy

Marker assisted speed congenics technique is commonly used to facilitate backcrossing of mouse strains in nearly half the time it normally takes otherwise. Traditionally, the technique is performed by analyzing PCR amplified regions of simple sequence length polymorphism (SSLP) markers between the recipient and donor strains: offspring with the highest number of markers showing the recipient genome across all chromosomes is chosen for the next generation. Although there are well-defined panels of SSLP makers established between certain pairs of mice strains, they are incomplete for most strains. The availability of well-established marker sets for speed congenic screens would enable the …

Assessment Of Artificial Mirna Architectures For Higher Knockdown Efficiencies Without The Undesired Effects In Mice., Hiromi Miura, Hidetoshi Inoko, Masafumi Tanaka, Hirofumi Nakaoka, Minoru Kimura, Channabasavaiah B. Gurumurthy, Masahiro Sato, Masato Ohtsuka

Journal Articles: Genetics, Cell Biology & Anatomy

RNAi-based strategies have been used for hypomorphic analyses. However, there are technical challenges to achieve robust, reproducible knockdown effect. Here we examined the artificial microRNA (amiRNA) architectures that could provide higher knockdown efficiencies. Using transient and stable transfection assays in cells, we found that simple amiRNA-expression cassettes, that did not contain a marker gene (-MG), displayed higher amiRNA expression and more efficient knockdown than those that contained a marker gene (+MG). Further, we tested this phenomenon in vivo, by analyzing amiRNA-expressing mice that were produced by the pronuclear injection-based targeted transgenesis (PITT) method. While we observed significant silencing of the …

De Novo Assembly Of The Chimpanzee Transcriptome From Nextgen Mrna Sequences, Mnirnal D. Maudhoo, Jacob D. Madison, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the species most closely related to humans. For this reason, it is especially important to have complete and accurate chimpanzee nucleotide and protein sequences to understand how humans evolved their unique capabilities. We provide transcriptome data from four untransformed cell types derived from the reference Pan troglodytes, "Clint", to better annotate the chimpanzee genome and provide empirical validation for proposed gene models of this important species.

FINDINGS: RNA was extracted from primary cells cultured from four tissues: skin, adipose stroma, vascular smooth muscle and skeletal muscle. These four RNA samples …

Diagnostic Value Of Endoscopic Ultrasound-Guided Fine Needle Aspiration Of Intra-Abdominal Lymph Nodes In Patients With Concurrent Biopsy Of Intra-Abdominal Tumors, Allison F. Goldberg, Md, Charalambos C. Solomides, Md, Marluce Bibbo, Md, Rossitza Draganova-Tacheva, Md

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

BACKGROUND

• Diagnostic endoscopic biopsy of intra-abdominal lesions may be performed prior to surgical resections.

• Endoscopic ultrasound-guided fine needle aspiration of intra-abdominal lymph nodes may also be performed to:

• Yield more information

• Allow for more accurate staging

• We evaluate the additional staging information concurrent fine needle aspiration of intra-abdominal lymph nodes provided

DESIGN

• We included all patients at our institution from January 1, 2000 to March 30, 2015 who, during the same endoscopic procedure, had:

• Endoscopic ultrasound guided fine needle aspiration of an intra-abdominal lymph node AND

• Endoscopic ultrasound guided fine needle aspiration …

Improved Accuracy Of Surgical Pathology Accessioning, Coding, And Billing Practices After Self-Evaluation, Allison F. Goldberg, Md

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

INTRODUCTION

Accurate accessioning, coding, and billing of specimens are vital, but often disregarded, aspects of a surgical pathologist’s job. This study had two aims related to those aspects. First, to evaluate the quality of our systems based practices in order to identify areas for improvement. Second, to assess if changes made based on our self-evaluation improved accuracy.

Tumor Metabolism In The Microenvironment Of Nodal Metastasis In Head And Neck Squamous Cell Carcinoma, Mehri Mollaee, Md, Patrick T. Tassone, Md, David Cognetti, Md, Adam J. Luginbuhl, Md, Joanie Johnson, Ubaldo E. Martinez-Outshoorn, Md, Tingting Zhan, Joseph M. Curry, Md, Madalina Tuluc, Md

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

ABSTRACT

Introduction: Monocarboxylate transporter 4 (MCT4) is a cell membrane transporter of lactate. MCT4 is a tumor-specific marker of oxidative stress, glycolysis and hypoxia in tumor stromal cells. We investigated HPV positive and negative tumors with regional metastases to cervical lymph nodes (LN) to study how the metastatic tumor cells interact with their microenvironment. By selecting cancers with extracapsular extension (ECE), we intended to evaluate the interaction between metastases and the surrounding extranodal tissue.

Methods:

Clinical data were collected from 24 advanced stage oropharyngeal squamous cell carcinoma (OPSCC) patients with neck LN metastasis. All patients presented with at least N1 …

Assessment Of Utility Of Daily Patient Results Averages As Adjunct Quality Control In A Weekday-Only Satellite Chemistry Laboratory, Dimath Alyemni, Md, Laura J. Mccloskey, Md, Barbara Goldsmith, Phd, Facb, Aryana Treweek, Robert T. Stapp, Do, Douglas F. Stickle, Phd

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

ABSTRACT

Background:

Our department operates a weekday-only (8AM-5PM) satellite laboratory in an infusion center with a menu of 18 chemistry tests on a Roche c501 analyzer. We examined whether daily patient results averages (PRA) in this setting might be useful as a patient-based quality control (PBQC) adjunct to standard daily liquid quality control (LQC) measurements. First, we evaluated the reproducibility (coefficient of variation, CV) of daily PRAs for each analyte, and compared these to CVs of LQC. Second, for select analytes found to have relatively low PRA CVs, we evaluated the extent to which use of daily PRA measurements could …

Is Hemoglobin Variant Analysis Helpful In The Diagnostic Work-Up Of Patients Revealing Microcytic Erythrocytosis On Complete Blood Count?, Upasana Joneja, Md, Alina Dulau-Florea, Gene Gulati, Ph.D, Jerald Z. Gong, Md

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

Introduction:

Microcytic erythrocytosis is an abnormal CBC (complete blood count) finding that is under-recognized, poorly understood, and consequently under-utilized in patient care. It is characterized by decreased MCV and increased RBC count. Its etiology is likely multifactorial and includes thalassemias and hemoglobinopathies. The focus of our study was to determine the relative prevalence of hemoglobin-associated disorders in patients revealing microcytic erythrocytosis on CBC and to demonstrate whether or not hemoglobin variant analysis should be included in the diagnostic work-up of such cases.

Analysis Of Patient Results Distributions To Reevaluate A Reference Range Change For Calcium, After A Change In Assay Reagents On The Roche Cobas C500 Analyzer, Upasana Joneja, Md, Laura J. Mccloskey, Md, Douglas F. Stickle, Md

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

Introduction:

A change in reagents for calcium (Ca) on the Roche Cobas c500 used in our laboratory analyzer took place in 2013. The previous reference range (8.5-10.5 mg/dL) was replaced with that from the manufacturer's study (8.6-10.0 mg/dL), based on correlation of results between the new and old assays. As a matter of quality assurance, we undertook a post-assay-change reevaluation of the reference range change, using a method based on that of Bhattacharya [1]. In short, the method relies on the assumption that the reference range is a normal distribution, which assumption enables this distribution to be isolated mathematically from …

Quantification Of Csf Chemokines And Cytokines Allows For Rapid Laboratory Detection Of Cns Infections And Further Discrimination Between Viral And Non-Viral Pathogens, Danielle Fortuna, Md, Am Cardenas, Eh Graf, Amity L. Roberts, Phd, D(Abmm), Larry A. Harshyne, Phd, D. Craig Hooper, Phd, Mark T. Curtis, Md, Phd

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

Background:

Prompt diagnosis of central nervous system (CNS) disease is critical to guide intervention and appropriate therapy. Development of novel laboratory approaches to rapidly classify acute-onset CNS disease is in great demand. Serious microbial pathogens, especially viruses, are quickly expanding beyond their historic geographic range and may not even be considered in the clinician’s differential diagnosis. Unlike bacterial cultures, current viral testing targets a limited number of viruses. Additionally, despite diversity in etiology, signs and symptoms of both infectious and non-infectious CNS disorders can be remarkably similar, which can confuse the clinical picture and delay treatment. Bacterial, viral, fungal and …

Human Parechovirus And Enterovirus Initiate Divergent Innate Immune Responses In The Cns: Pathogenic And Diagnostic Implications, Danielle Fortuna, Md, Ana Maria Cardenas, Phd, Erin H. Graf, Phd, Larry A. Harshyne, Kevin Quann, Bs, D. Craig Hooper, Phd, Mark T. Curtis, Md, Phd

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

The picornaviruses human parechovirus (HPeV) and enterovirus (EV) cause a wide range of diseases, including CNS infections, which can be severe and potentially fatal. EV causes most cases of pediatric meningoencephalitis worldwide, and HPeV type 3 (HPeV3) is the most common cause of viral meningitis in young infants. Each year in the United States, there are over 75,000 cases of aseptic meningitis. Despite reassuring short-term outcomes, negative neurodevelopmental sequalae are increasingly associated with HPeV and EV.

The pathogenesis and severity of HPeV and EV infections are undoubtedly linked to the innate and adaptive immune responses elicited by these viruses. Until …

A Distinct Pattern Of Beclin-1 Staining Helps Distinguish Sessile Serrated Adenomas, Danielle Fortuna, Md, Juan P. Palazzo, Md

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

Autophagy, a lysosomal degradation system, has both cell survival and cell death-promoting capabilities, and its versatility is exploited in many pathologic entities. In neoplastic processes, autophagy has been demonstrated to contribute to both tumor suppression and tumorigenesis in a relatively tumor-specific fashion. Beclin-1 is a protein involved in the formation of the autophagosome, the core unit of autophagy, and serves as one of the general markers for this process. Previous studies have shown Beclin-1 overexpression in both pre-neoplastic and invasive colon carcinoma but weak to absent expression in normal colonic mucosa.

Serrated polyps (SPs) of the colon represent morphologically and …