Medical Pathology Commons^™

Silencing Of The Pink1 Gene Expression By Conditional Rnai Does Not Induce Dopaminergic Neuron Death In Mice., Hongxia Zhou, Björn H Falkenburger, Jörg B Schulz, Kim Tieu, Zuoshang Xu, Xu Gang Xia

Kim Tieu

Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson's disease. The expression of the shRNA …

Temporal Changes In Innate Immune Signals In A Rat Model Of Alcohol Withdrawal In Emotional And Cardiorespiratory Homeostatic Nuclei., Kate Freeman, Anthony Brureau, Rajanikanth Vadigepalli, Mary M Staehle, Melanie M Brureau, Gregory E Gonye, Jan B Hoek, D Craig Hooper, James S Schwaber

Mary Staehle

BACKGROUND: Chronic alcohol use changes the brain's inflammatory state. However, there is little work examining the progression of the cytokine response during alcohol withdrawal, a period of profound autonomic and emotional upset. This study examines the inflammatory response in the central nucleus of the amygdala (CeA) and dorsal vagal complex (DVC), brain regions neuroanatomically associated with affective and cardiorespiratory regulation in an in vivo rat model of withdrawal following a single chronic exposure.

METHODS: For qRT-PCR studies, we measured the expression of TNF-α, NOS-2, Ccl2 (MCP-1), MHC II invariant chain CD74, and the TNF receptor Tnfrsf1a in CeA and DVC …

Follicular Dendritic Cell Sarcoma: A Rare Entity With Variable Pathologic Features And Prognosis, Sharif A. Ali Md, Miriam L. Enriquez Md, Shereen M. Gheith Md

Shereen M.F. Gheith, M.D., PhD.

No abstract provided.

Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen Md, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress Md, Maria Tria Tirona Md

Mohamed Alsharedi

Background: Whether a delay in the initiation of chemotherapy for advanced non-small cell lung cancer (NSCLC) can affect overall survival is not well studied. We aim to evaluate the effect of the time interval between diagnosis and initiation of chemotherapy on overall survival in patients with stage IV NSCLC. Methods: A retrospective review of newly diagnosed stage IV NSCLC patients who received chemotherapy between 1995 and 2012 was conducted. Demographics, histology and site(s) of metastases of patients were reviewed. Time interval between the date of diagnosis and the date of starting chemotherapy was calculated in days. Patients were divided in …

Left Ventricular Noncompaction Syndrome: A Rare Congenital Cardiomyopathy, Ashwini V. Mallad, Mbbs, Waseem Ahmed, Md, Madhulika Urella, Md, Dr. Mehiar El-Hamdani, Md, Facc, Fscai

Mehiar El Hamdani, MD

Isolated left ventricular noncompaction cardiomyopathy (LVNC) is a rare congenital condition occurring due to arrest of myocardial compaction in the first trimester, resulting in a thin layer of compacted epicardium and thick hypertrabeculated myocardium containing deep recesses. This article presents a 44-year-old female with progressive dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and pleuritic chest pain. Examination revealed elevated jugular venous distention, lower extremity edema, and bibasilar crackles on lung auscultation, while the electrocardiogram (EKG) exhibited left bundle branch block. Two-dimensional echocardiography (2D-Echo) showed a dilated left ventricle (LV) with ejection fraction (EF) of 25% and severe diffuse hypokinesia. Cardiac magnetic resonance …

Gradenigo Syndrome: A Rare Complication Of Otitis Media, Paul Brent Ferguson, Md

Paul Ferguson

Gradenigo syndrome is a very rare complication of otitis media that if left unrecognized and subsequently untreated will result in severe neurologic sequelae. Gradenigo Syndrome clinically represented by the triad of otitis media, ipsilateral, abducens nerve palsy and dysasthesia within the V1 and V2 divisions of the trigeminal nerve branches. We describe a 4 year-old patient who presented with headache, facial pain, diplopia and a recent history of upper respiratory tract symptomatology. Examination revealed an abducens palsy with subsequent magnetic resonance imaging demonstrating inflammation in the left petrous apex and along the tracts of the 6th, 7th, and 8th cranial …

Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani

El Nasir Lalani

Background: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined.

Methods: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded …

Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen Md, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress Md, Maria Tria Tirona Md

Maria Tirona

Background: Whether a delay in the initiation of chemotherapy for advanced non-small cell lung cancer (NSCLC) can affect overall survival is not well studied. We aim to evaluate the effect of the time interval between diagnosis and initiation of chemotherapy on overall survival in patients with stage IV NSCLC. Methods: A retrospective review of newly diagnosed stage IV NSCLC patients who received chemotherapy between 1995 and 2012 was conducted. Demographics, histology and site(s) of metastases of patients were reviewed. Time interval between the date of diagnosis and the date of starting chemotherapy was calculated in days. Patients were divided in …

Fair Weight Loss After Gastric Rebanding For Slippage, Ahmed Dalmar, Maharaj Singh, Sara K. Roloff, Thomas Y. Chua

Maharaj Singh

Background: Laparoscopic adjustable gastric banding (LAGB) is one of the most common bariatric surgery procedures performed in the United States. LAGB results in safe and satisfactory weight loss, but it is often complicated with slippage, a complication requiring rebanding (reoperation). There is a paucity of studies and no uniform consensus regarding weight loss after rebanding.

Purpose: This study assessed the effect of rebanding for slippage after LAGB on weight loss up to five years.

Methods: This is a historical cohort study of 865 patients who underwent LAGB from 2001 to 2011. Rebanding was performed in 103 (11.9%) patients. Primary outcome …

Fair Weight Loss After Gastric Rebanding For Slippage, Ahmed Dalmar, Maharaj Singh, Sara K. Roloff, Thomas Y. Chua

Ahmed Dalmar, MD

Background: Laparoscopic adjustable gastric banding (LAGB) is one of the most common bariatric surgery procedures performed in the United States. LAGB results in safe and satisfactory weight loss, but it is often complicated with slippage, a complication requiring rebanding (reoperation). There is a paucity of studies and no uniform consensus regarding weight loss after rebanding.

Purpose: This study assessed the effect of rebanding for slippage after LAGB on weight loss up to five years.

Methods: This is a historical cohort study of 865 patients who underwent LAGB from 2001 to 2011. Rebanding was performed in 103 (11.9%) patients. Primary outcome …

Hysteresis As A Measure Of Ankle Dysfunction, Alissa Cohen, James Mertz, Peggy Stewart, Michael Warner, Michael Kuchera

Michael Kuchera

There is no abstract for this article.

Metastatic Brain Tumors: Current Therapeutic Options And Historical Perspective, Mark Rivkin, Richard Kanoff

Mark Rivkin

Metastatic brain tumors affect more than 150,000 patients annually in the United States. The therapeutic paradigms for these tumors have evolved over the years and currently encompass numerous modalities implemented by treating physicians across several medical disciplines. The armamentarium of brain tumor treatment involves neurosurgical intervention, whole-brain and focused radiation modalities, chemotherapy, and immunotherapy. Patient selection, however, remains critical to achieve maximal therapeutic benefit and depends on functional status, number and location of lesions, and tissue histologic findings. Best outcomes can be expected with a multidisciplinary approach to patient care where state-of-the-art treatment options are readily available.

Emergence Of Bimodal Cell Population Responses From The Interplay Between Analog Single-Cell Signaling And Protein Expression Noise., Marc R Birtwistle, Jens Rauch, Anatoly Kiyatkin, Edita Aksamitiene, Maciej Dobrzyński, Jan Hoek, Walter Kolch, Babatunde A Ogunnaike, Boris N Kholodenko

Anatoly Kiyatkin

BACKGROUND: Cell-to-cell variability in protein expression can be large, and its propagation through signaling networks affects biological outcomes. Here, we apply deterministic and probabilistic models and biochemical measurements to study how network topologies and cell-to-cell protein abundance variations interact to shape signaling responses. RESULTS: We observe bimodal distributions of extracellular signal-regulated kinase (ERK) responses to epidermal growth factor (EGF) stimulation, which are generally thought to indicate bistable or ultrasensitive signaling behavior in single cells. Surprisingly, we find that a simple MAPK/ERK-cascade model with negative feedback that displays graded, analog ERK responses at a single cell level can explain the experimentally …

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

David D Dunigan Ph. D.

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis, …

Human Monoclonal Antibodies Directed Against Toxins A And B Prevent Clostridium Difficile-Induced Mortality In Hamsters, Gregory Babcock, Teresa Broering, Hector Hernandez, Robert Mandell, Katherine Donahue, Naomi Boatright, Anne Stack, Israel Lowy, Robert Graziano, Deborah Molrine, Donna Ambrosino, William Thomas

William D Thomas Jr

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease in hamsters. Transgenic mice carrying human immunoglobulin genes were used to isolate HuMAbs that neutralize the cytotoxic effects of either toxin …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Richard M. Niles

Background Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas. Results HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …