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Autosomal Recessive Polycystic Kidney Disease: The Prototype Of The Hepato-Renal Fibrocystic Diseases, Lisa Guay-Woodford Jan 2014

Autosomal Recessive Polycystic Kidney Disease: The Prototype Of The Hepato-Renal Fibrocystic Diseases, Lisa Guay-Woodford

Pediatrics Faculty Publications

Autosomal recessive polycystic kidney disease (ARPKD) is a severe, typically early onset form of renal cystic disease. The care of ARPKD patients has traditionally been the purview of pediatric nephrologists for management of systemic hypertension and progressive renal insufficiency. However, the disease has multisystem manifestations and a comprehensive care strategy frequently requires a multidisciplinary team. In severely affected infants, the diagnosis often is first suspected by obstetricians when enlarged, echogenic kidneys and oligohydramnios are detected on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. …


Analyzing Networks Of Phenotypes In Complex Diseases: Methodology And Applications In Copd, Jen-Hwa Chu, Craig P. Hersh, Peter J. Castaldi, Michael H. Cho, Benjamin A. Raby, Nan Laird, Russell Bowler, Stephen I. Rennard, Joseph Loscalzo, John Quackenbush, Edwin K. Silverman Jan 2014

Analyzing Networks Of Phenotypes In Complex Diseases: Methodology And Applications In Copd, Jen-Hwa Chu, Craig P. Hersh, Peter J. Castaldi, Michael H. Cho, Benjamin A. Raby, Nan Laird, Russell Bowler, Stephen I. Rennard, Joseph Loscalzo, John Quackenbush, Edwin K. Silverman

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: The investigation of complex disease heterogeneity has been challenging. Here, we introduce a network-based approach, using partial correlations, that analyzes the relationships among multiple disease-related phenotypes.

RESULTS: We applied this method to two large, well-characterized studies of chronic obstructive pulmonary disease (COPD). We also examined the associations between these COPD phenotypic networks and other factors, including case-control status, disease severity, and genetic variants. Using these phenotypic networks, we have detected novel relationships between phenotypes that would not have been observed using traditional epidemiological approaches.

CONCLUSION: Phenotypic network analysis of complex diseases could provide novel insights into disease susceptibility, disease …


Clinical And Computed Tomographic Predictors Of Chronic Bronchitis In Copd: A Cross Sectional Analysis Of The Copdgene Study, Victor Kim, Adam Davey, Alejandro P. Comellas, Meilan K. Han, George Washko, Carlos H. Martinez, David Lynch, Jin Hwa Lee, Edwin K. Silverman, James D. Crapo, Barry J. Make, Gerard J. Criner, The Copdgene® Investigators Jan 2014

Clinical And Computed Tomographic Predictors Of Chronic Bronchitis In Copd: A Cross Sectional Analysis Of The Copdgene Study, Victor Kim, Adam Davey, Alejandro P. Comellas, Meilan K. Han, George Washko, Carlos H. Martinez, David Lynch, Jin Hwa Lee, Edwin K. Silverman, James D. Crapo, Barry J. Make, Gerard J. Criner, The Copdgene® Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways …


Effectiveness Of Treatments For Low Back Pain, Angela K. Salveson Jan 2014

Effectiveness Of Treatments For Low Back Pain, Angela K. Salveson

Physician Assistant Scholarly Project Posters

Low back pain with or without radiculopathy symptoms is increasingly becoming a common complaint for patients. The purpose of this study is to evaluate the most effective treatment for patients experiencing low back pain with or without radiculopathy symptoms with the goal of pain reduction/elimination and positive long term results. The review of literature explores studies that discuss treatment options of surgical intervention or conventional treatment such as physical therapy. This information supplies health care providers with the tools to educate patients on treatment options and possible outcomes in hopes to offer the best treatment for the individual. Results show …


Dnah5 Is Associated With Total Lung Capacity In Chronic Obstructive Pulmonary Disease, Jin Hwa Lee, Merry-Lynn N Mcdonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, David A. Lynch, James D. Crapo, David A. Lomas, Harvey O. Coxson, Per S. Bakke, Edwin K. Silverman, Craig P. Hersh, The Copdgene And Eclipse Investigators Jan 2014

Dnah5 Is Associated With Total Lung Capacity In Chronic Obstructive Pulmonary Disease, Jin Hwa Lee, Merry-Lynn N Mcdonald, Michael H. Cho, Emily S. Wan, Peter J. Castaldi, Gary M. Hunninghake, Nathaniel Marchetti, David A. Lynch, James D. Crapo, David A. Lomas, Harvey O. Coxson, Per S. Bakke, Edwin K. Silverman, Craig P. Hersh, The Copdgene And Eclipse Investigators

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction. The aim of our study was to identify genetic variants associated with TLC in COPD.

METHODS: We performed genome-wide association studies (GWASs) in white subjects from three cohorts: the COPDGene Study; the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); and GenKOLS (Bergen, Norway). All subjects were current or ex-smokers …


Comparing The Long Term Use Of H2 Antagonists (H2ras) And Proton Pump Inhibitors (Ppis) And The Incidence Of Colitis, Reiner Kremer Jan 2014

Comparing The Long Term Use Of H2 Antagonists (H2ras) And Proton Pump Inhibitors (Ppis) And The Incidence Of Colitis, Reiner Kremer

Physician Assistant Scholarly Project Posters

• Commonly used medications for GERD may affect the colonic mucosa

• H2 antagonists (H2RAs) ranitidine, cimetidine famotidine reduce acid secretion by 60 to 70%.

• Proton pump inhibitors (PPIs) omeprazole, pantoprazole, lansoprazole, esomeprazole and rabeprazole reduce acid secretion by inhibiting the H+ (proton) secreting pump, reducing hydrochloric acid by 80 to 95%.

• Diarrhea is one of the most commonly reported adverse events.

• H2RAs and PPIs have the physiological and functional potential to interfere with gastrointestinal physiology by altering intestinal pH.

• Microcytic colitis causing chronic diarrhea and colonic inflammation is a significant complication risk after the > 4-8 …


Development Of Status Epilepticus, Sustained Calcium Elevations And Neuronal Injury In A Rat Survival Model Of Lethal Paraoxon Intoxication, Laxmikant Sudhir Deshpande, Dawn S. Carter, Kristin Phillips, Robert E. Blair, Robert J. Delorenzo Jan 2014

Development Of Status Epilepticus, Sustained Calcium Elevations And Neuronal Injury In A Rat Survival Model Of Lethal Paraoxon Intoxication, Laxmikant Sudhir Deshpande, Dawn S. Carter, Kristin Phillips, Robert E. Blair, Robert J. Delorenzo

Neurology Publications

Paraoxon (POX) is an active metabolite of organophosphate (OP) pesticide parathion that has been weaponized and used against civilian populations. Exposure to POX produces high mortality. OP poisoning is often associated with chronic neurological disorders. In this study, we optimize a rat survival model of lethal POX exposures in order to mimic both acute and long-term effects of POX intoxication. Male Sprague–Dawley rats injected with POX (4 mg/kg, ice-cold PBS, s.c.) produced a rapid cholinergic crisis that evolved into status epilepticus (SE) and death within 6–8 min. The EEG profile for POX induced SE was characterized and showed clinical and …


Clinical Features And Genetic Analysis Of 20 Chinese Patients With X-Linked Hyper-Igm Syndrome, Lin-Lin Wang, Wei Zhou, Wei Zhao, Zhi-Qing Tian, Wei-Fan Wang, Xiao-Fang Wang, Tong-Xin Chen Jan 2014

Clinical Features And Genetic Analysis Of 20 Chinese Patients With X-Linked Hyper-Igm Syndrome, Lin-Lin Wang, Wei Zhou, Wei Zhao, Zhi-Qing Tian, Wei-Fan Wang, Xiao-Fang Wang, Tong-Xin Chen

Pediatrics Publications

X-linked hyper-IgM syndrome (XHIGM) is one type of primary immunodeficiency diseases, resulting from defects in the CD40 ligand/CD40 signaling pathways. We retrospectively analyzed the clinical and molecular features of 20 Chinese patients diagnosed and followed up in hospitals affiliated to Shanghai Jiao Tong University School of Medicine from 1999 to 2013. The median onset age of these patients was 8.5 months (range: 20 days–21 months). Half of them had positive family histories, with a shorter diagnosis lag. The most common symptoms were recurrent sinopulmonary infections (18 patients, 90%), neutropenia (14 patients, 70%), oral ulcer (13 patients, 65%), and protracted diarrhea …


Metabolic Effects Of Acute Thiamine Depletion Are Reversed By Rapamycin In Breast And Leukemia Cells, Shuqian Liu, Sumitra Miriyala, Mignon A. Keaton, Craig T. Jordan, Christina Wiedl, Daret K. St. Clair, Jeffrey A. Moscow Jan 2014

Metabolic Effects Of Acute Thiamine Depletion Are Reversed By Rapamycin In Breast And Leukemia Cells, Shuqian Liu, Sumitra Miriyala, Mignon A. Keaton, Craig T. Jordan, Christina Wiedl, Daret K. St. Clair, Jeffrey A. Moscow

Pediatrics Publications

Thiamine-dependent enzymes (TDEs) control metabolic pathways that are frequently altered in cancer and therefore present cancer-relevant targets. We have previously shown that the recombinant enzyme thiaminase cleaves and depletes intracellular thiamine, has growth inhibitory activity against leukemia and breast cancer cell lines, and that its growth inhibitory effects were reversed in leukemia cell lines by rapamycin. Now, we first show further evidence of thiaminase therapeutic potential by demonstrating its activity against breast and leukemia xenografts, and against a primary leukemia xenograft. We therefore further explored the metabolic effects of thiaminase in combination with rapamycin in leukemia and breast cell lines. …


Near-Infrared Imaging Of Adoptive Immune Cell Therapy In Breast Cancer Model Using Cell Membrane Labeling, Fatma M. Youniss, Gobalakrishnan Sundaresan, Laura J. Graham, Li Wang, Collin R. Berry, Gajanan K. Dewkar, Purnima Jose, Harry D. Bear, Jamal Zweit Jan 2014

Near-Infrared Imaging Of Adoptive Immune Cell Therapy In Breast Cancer Model Using Cell Membrane Labeling, Fatma M. Youniss, Gobalakrishnan Sundaresan, Laura J. Graham, Li Wang, Collin R. Berry, Gajanan K. Dewkar, Purnima Jose, Harry D. Bear, Jamal Zweit

Radiology Publications

The overall objective of this study is to non-invasively image and assess tumor targeting and retention of directly labeled T-lymphocytes following their adoptive transfer in mice. T-lymphocytes obtained from draining lymph nodes of 4T1 (murine breast cancer cell) sensitized BALB/C mice were activated in-vitro with Bryostatin/Ionomycin for 18 hours, and were grown in the presence of Interleukin-2 for 6 days. T-lymphocytes were then directly labeled with 1,1-dioctadecyltetramethyl indotricarbocyanine Iodide (DiR), a lipophilic near infrared fluorescent dye that labels the cell membrane. Assays for viability, proliferation, and function of labeled T-lymphocytes showed that they were unaffected by DiR labeling. The DiR …


Complement Expression In The Retina Is Not Influenced By Short-Term Pressure Elevation, Konstantin Astafurov, Cecilia Q. Dong, Lampros Panagis, Gautam Kamtham, Lizhen Ren, Anna Rozenboym, Tarique D. Perera, Jeremy D. Coplan, John Danias Jan 2014

Complement Expression In The Retina Is Not Influenced By Short-Term Pressure Elevation, Konstantin Astafurov, Cecilia Q. Dong, Lampros Panagis, Gautam Kamtham, Lizhen Ren, Anna Rozenboym, Tarique D. Perera, Jeremy D. Coplan, John Danias

Publications and Research

Purpose: To determine whether short-term pressure elevation affects complement gene expression in the retina in vitro and in vivo.

Methods: Muller cell (TR-MUL5) cultures and organotypic retinal cultures from adult mice and monkeys were sub- jected to either 24-h or 72-h of pressure at 0, 15, 30, and 45 mmHg above ambient. C57BL/6 mice were subjected to microbead-induced intraocular pressure (IOP) elevation for 7 days. RNA and protein were extracted and used for analysis of expression levels of complement component genes and complement component 1, q subcomponent (C1q) and comple- ment factor H (CFH) immunoblotting. …


Broad And Direct Interaction Between Tlr And Siglec Families Of Pattern Recognition Receptors And Its Regulation By Neu1., Guo-Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha Van De Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu Jan 2014

Broad And Direct Interaction Between Tlr And Siglec Families Of Pattern Recognition Receptors And Its Regulation By Neu1., Guo-Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha Van De Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced …


Graduate Medical Education 2013-2014 Annual Report, Children's Mercy Hospital Jan 2014

Graduate Medical Education 2013-2014 Annual Report, Children's Mercy Hospital

GME Annual Reports

Annual report of the Children's Mercy Hospital Graduate Medical Education department, including pediatric residency, internal medicine/pediatrics residency, fellowship programs, medical students, continuing medical education, and library services.


Influence Of Diet And Obesity On Copd Development And Outcomes, Corrine K. Hanson, Erica P. Rutten, Emiel F.M. Wouters, Stephen I. Rennard Jan 2014

Influence Of Diet And Obesity On Copd Development And Outcomes, Corrine K. Hanson, Erica P. Rutten, Emiel F.M. Wouters, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern. Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest. Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases. Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and …


Metabolomic Analysis Of Liver Tissue From The Vx2 Rabbit Model Of Secondary Liver Tumors, Rafael A. Ibarra, J. E. Dazard, Y. Sandlers, F. Rehman, R. Abbas, R. Kombu, G. F. Zhang, H. Brunengraber, Juan R. Sanabria Jan 2014

Metabolomic Analysis Of Liver Tissue From The Vx2 Rabbit Model Of Secondary Liver Tumors, Rafael A. Ibarra, J. E. Dazard, Y. Sandlers, F. Rehman, R. Abbas, R. Kombu, G. F. Zhang, H. Brunengraber, Juan R. Sanabria

Surgery

Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development.

Methods. We used the rabbitVX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT−) as well as liver tissue from controls (LG+/LG−). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using …


Choline Kinase Beta Is Required For Normal Endochondral Bone Formation, Zhuo Li, Gengshu Wu, Roger B. Sher, Zohreh Khavandgar, Martin Hermansson, Gregory A. Cox, Michael R. Doschak, Monzur Murshed, Frank Beier, Dennis E. Vance Jan 2014

Choline Kinase Beta Is Required For Normal Endochondral Bone Formation, Zhuo Li, Gengshu Wu, Roger B. Sher, Zohreh Khavandgar, Martin Hermansson, Gregory A. Cox, Michael R. Doschak, Monzur Murshed, Frank Beier, Dennis E. Vance

Paediatrics Publications

Background Choline kinase has three isoforms encoded by the genes Chka and Chkb. Inactivation of Chka in mice results in embryonic lethality, whereas Chkb-/- mice display neonatal forelimb bone deformations. Methods To understand the mechanisms underlying the bone deformations, we compared the biology and biochemistry of bone formation from embryonic to young adult wild-type (WT) and Chkb-/- mice. Results The deformations are specific to the radius and ulna during the late embryonic stage. The radius and ulna of Chkb-/- mice display expanded hypertrophic zones, unorganized proliferative columns in their growth plates, and delayed formation of primary ossification centers. The differentiation …


High Prevalence Of Early Childhood Infection By Kshv In A Minority Population In China, Yifei Cao, Veenu Minhas, Xiaohua Tan, Jin Huang, Baodong Wang, Meiyi Zhu, Yuan Gao, Tingting Zhao, Lei Yang, Charles Wood Jan 2014

High Prevalence Of Early Childhood Infection By Kshv In A Minority Population In China, Yifei Cao, Veenu Minhas, Xiaohua Tan, Jin Huang, Baodong Wang, Meiyi Zhu, Yuan Gao, Tingting Zhao, Lei Yang, Charles Wood

Nebraska Center for Virology: Faculty Publications

In China, KSHV seroprevalence varies considerably among different regions and ethnicities. But in Xinjiang province, located in the northwestern China, there is a very high seroprevalence of KSHV in adults of Kazak and Ughur ethnicities. However, KSHV prevalence in children and the risk factors associated with the acquisition of infection are currently not known. The aim of this study was to investigate the prevalence of KSHV infection, identify associated socio-economic or behavioral risk factors and the humoral immune response among children in this population. This is a cross-sectional study (N=178) to screen children and their caregivers from Xinjiang for total …


The Role Of Pdgf C And Its Splice Variant In Breast Cancer, Alyssa Bottrell Jan 2014

The Role Of Pdgf C And Its Splice Variant In Breast Cancer, Alyssa Bottrell

Wayne State University Dissertations

The PDGF family consists of four members; while PDGF A and B are secreted as active dimers, PDGF C and D are secreted as latent dimers that undergo serine protease-mediated extracellular proteolytic activation. Gene expression analysis of breast cancer cell lines showed that PDGF C expression is associated with Basal B subtype breast cancer cells which have cancer stem cell-like characteristics. Furthermore, PDGF C expression is associated with triple-negative (estrogen receptor-, progesterone receptor- and HER2/neu-negative) breast cancer cells, a challenging type of breast cancer to treat. During the course of our study, we discovered a splice variant of PDGF C …


Dendrimer Based Nanotherapeutics For Ocular Drug Delivery, Siva Pramodh Kambhampati Jan 2014

Dendrimer Based Nanotherapeutics For Ocular Drug Delivery, Siva Pramodh Kambhampati

Wayne State University Dissertations

PAMAM dendrimers are a class of well-defined, hyperbranched polymeric nanocarriers that are being investigated for ocular drug and gene delivery. Their favorable properties such as small size, multivalency and water solubility can provide significant opportunities for many biologically unstable drugs and allows potentially favorable ocular biodistribution. This work exploits hydroxyl terminated dendrimers (G4-OH) as drug/gene delivery vehicles that can target retinal microglia and pigment epithelium via systemic delivery with improved efficacy at much lower concentrations without any side effects.

Two different drugs Triamcinolone acetonide (TA) and N-Acetyl Cysteine (NAC) conjugated to G4-OH dendrimers showed tailorable sustained release in physiological relevant …


Neighborhood-Level Influences On Delays In Diagnostic Follow-Up From Mammography Screening In African-American Women: A Systematic Review, Barbara A. Fowler Jan 2014

Neighborhood-Level Influences On Delays In Diagnostic Follow-Up From Mammography Screening In African-American Women: A Systematic Review, Barbara A. Fowler

Nursing Faculty Publications

Although there has been a steady decrease in breast cancer deaths among all women (pooled data) age 40 to 65 years during the past two decades in the United States, breast cancer deaths remain substantially higher among African-American women than White women (32.4% vs. 23.9%), resulting in an overall lower five-year survival rate (78.4% vs. 91.2%). These differences are primarily due to delays in diagnostic follow-up from mammography screening (MS) (ACS, 2012]. Following the secondary research data methods by analyzing the popular medical databases and articles published in the peer-reviewed medical journals in US during 2004-2014 the author would like …


Characterization Of Cytomegalovirus Lung Infection In Non-Hiv Infected Children, Sonia M. Restrepo-Gualteros, Lina E. Jaramillo-Barberi, Monica Gonzalez-Santos, Carlos E. Rodriguez-Martinez, Geovanny F. Perez, Maria J. Gutierrez, Gustavo Nino Jan 2014

Characterization Of Cytomegalovirus Lung Infection In Non-Hiv Infected Children, Sonia M. Restrepo-Gualteros, Lina E. Jaramillo-Barberi, Monica Gonzalez-Santos, Carlos E. Rodriguez-Martinez, Geovanny F. Perez, Maria J. Gutierrez, Gustavo Nino

Pediatrics Faculty Publications

Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in …


Lysosomal Abnormalities In Hereditary Spastic Paraplegia Types Spg15 And Spg11, Benoit Renvoise, Jaerak Chang, Rajat Singh, Sayuri Yonekawa, Edmond J. Fitzgibbon, Ami Mankodi, Adeline Vanderver, Alice B. Schindler, Camilo Toro, William A. Gahl, Don J. Mahuran, Craig Blackstone, Tyler Pierson Jan 2014

Lysosomal Abnormalities In Hereditary Spastic Paraplegia Types Spg15 And Spg11, Benoit Renvoise, Jaerak Chang, Rajat Singh, Sayuri Yonekawa, Edmond J. Fitzgibbon, Ami Mankodi, Adeline Vanderver, Alice B. Schindler, Camilo Toro, William A. Gahl, Don J. Mahuran, Craig Blackstone, Tyler Pierson

Neurology Faculty Publications

Objective

Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism.

Methods

We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes.

Results

Fibroblasts …


Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors Jan 2014

Differential Expression Of The Nuclear-Encoded Mitochondrial Transcriptome In Pediatric Septic Shock., Scott L Weiss, Natalie Z Cvijanovich, Geoffrey L Allen, Neal J Thomas, Robert J. Freishtat, Nick Anas, +11 Additional Authors

Pediatrics Faculty Publications

INTRODUCTION: Increasing evidence supports a role for mitochondrial dysfunction in organ injury and immune dysregulation in sepsis. Although differential expression of mitochondrial genes in blood cells has been reported for several diseases in which bioenergetic failure is a postulated mechanism, there are no data about the blood cell mitochondrial transcriptome in pediatric sepsis.

METHODS: We conducted a focused analysis using a multicenter genome-wide expression database of 180 children ≤ 10 years of age with septic shock and 53 healthy controls. Using total RNA isolated from whole blood within 24 hours of PICU admission for septic shock, we evaluated 296 nuclear-encoded …


Benzyl Isothiocyanate As An Adjuvant Chemotherapy Option For Head And Neck Squamous Cell Carcinoma, Mary Allison Wolf Jan 2014

Benzyl Isothiocyanate As An Adjuvant Chemotherapy Option For Head And Neck Squamous Cell Carcinoma, Mary Allison Wolf

Theses, Dissertations and Capstones

Isothiocyanates (ITCs) are natural phytochemicals produced by cruciferous vegetables. Recent evidence supports that, in addition to cancer prevention, ITCs can use various mechanisms to target malignant cells. Current therapies for cancer often provoke detrimental side effects, however clinical evidence supports that ITCs have little to no side effects in patients. Consequently, ITCs may be a promising treatment option for cancer patients, especially patients suffering from head and neck squamous cell carcinoma (HNSCC).

Despite recent improvements in cancer treatment, overall survival of advanced HNSCC has not improved in the past three decades. Metastasis and chemoresistance represent two detrimental events that greatly …


Synthesizing Data And Models For The Spread Of Mers-Cov, 2013: Key Role Of Index Cases And Hospital Transmission, Gerardo Chowell, Seth Blumberg, Lone Simonsen, Mark A. Miller, Cecile Viboud Jan 2014

Synthesizing Data And Models For The Spread Of Mers-Cov, 2013: Key Role Of Index Cases And Hospital Transmission, Gerardo Chowell, Seth Blumberg, Lone Simonsen, Mark A. Miller, Cecile Viboud

Global Health Faculty Publications

The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 209 deaths and 699 laboratory-confirmed cases in the Arabian Peninsula as of June 11, 2014. Preparedness efforts are hampered by considerable uncertainty about the nature and intensity of human-to-human transmission, with previous reproduction number estimates ranging from 0.4 to 1.5. Here we synthesize epidemiological data and transmission models for the MERS-CoV outbreak during April–October 2013 to resolve uncertainties in epidemic risk, while considering the impact of observation bias. We match the progression of MERS-CoV cases in 2013 to a dynamic transmission model that incorporates community and hospital compartments, and …


Pituitary Stalk Interruption Syndrome Presenting As Short Stature: A Case Report, Nanik Ram, Syed Ahsan Ali, Syed Zubair Hussain Jan 2014

Pituitary Stalk Interruption Syndrome Presenting As Short Stature: A Case Report, Nanik Ram, Syed Ahsan Ali, Syed Zubair Hussain

Section of Diabetes, Endocrinology and Metabolism

Introduction: Pituitary stalk interruption syndrome is a rare congenital abnormality of the pituitary that is responsible for anterior pituitary deficiency. It is characterized by a classic triad of interrupted pituitary stalk, absent or ectopic posterior pituitary, and anterior pituitary hypoplasia or aplasia. Clinical presentation varies according to age. In adults it presents as short stature and anterior pituitary deficiency. Without early diagnosis and treatment, mortality and morbidity in these patients is high. Early diagnosis and treatment of this rare disease can prevent permanent short statue of the patient. We report the first case of pituitary stalk interruption syndrome from …


Role Of Complementary And Alternative Medicine In Controlling Dyslipidemia, Waris Qidwai, Firdous Jahan, Kashmira Nanji Jan 2014

Role Of Complementary And Alternative Medicine In Controlling Dyslipidemia, Waris Qidwai, Firdous Jahan, Kashmira Nanji

Department of Family Medicine

No abstract provided.


Examining A Link Between Paraquat, Alpha-Synuclein Fibrillation And Neurodegeneration: A Review, Nikhil Ailaney Jan 2014

Examining A Link Between Paraquat, Alpha-Synuclein Fibrillation And Neurodegeneration: A Review, Nikhil Ailaney

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Parkinson’s disease is a chronic and progressive motor system disorder that is caused by the degeneration of dopaminergic neurons in the central nervous system. At the molecular level, Parkinson’s disease works by decreasing the concentrations of the neurotransmitter dopamine, a chemical messenger involved in motor messaging, within the central nervous system. Low levels of dopamine in the central nervous system causes motor system dysfunction because the insufficient levels of dopamine lead to an inability for neurons to successfully transmit motor messages. At the organismal level, Parkinson’s disease causes tremors, Bradykinesia, and rigidity. These symptoms ultimately lead to a diminished quality …


Neurostimulation For Refractory Primary Chronic Headache Disorders: A Review, Bindu Yoga, Modar Khalil, Hassan Zafar, Fayyaz Ahmed Jan 2014

Neurostimulation For Refractory Primary Chronic Headache Disorders: A Review, Bindu Yoga, Modar Khalil, Hassan Zafar, Fayyaz Ahmed

Pakistan Journal of Neurological Sciences (PJNS)

Headache is the commonest symptom seen in both primary and secondary care. Vast majority are primary i.e. for which no underlying cause has been detected. Tension Headaches, Migraine and Cluster Headaches are the most common primary headache disorders in the population. Although most of the primary headache disorders can be satisfactorily treated with both acute and preventive medications, those that are refractory to conventional treatment pose a great challenge to the headache physician. Moreover some patients are not able to use traditional treatment due to intolerance and co-morbidities. Neurostimulation is a treatment modality that has been used in other neurological …


Gossypiboma Diagnosed Fifteen Years After A Cesarean Section: A Case Report, Abdul Rehman, Noor Ul-Ain Baloch, Muhammad Awais Jan 2014

Gossypiboma Diagnosed Fifteen Years After A Cesarean Section: A Case Report, Abdul Rehman, Noor Ul-Ain Baloch, Muhammad Awais

Department of Biological & Biomedical Sciences

Gossypiboma, a retained surgical sponge, is a rare complication following any surgical procedure and is primarily a result of human error. Such patients often have vague clinical presentations and the diagnosis often comes as a surprise. We present the case of a 40-year-old woman who had a long-standing history of lower abdominal discomfort. She was diagnosed with a gossypiboma fifteen years after a cesarean section. All general physicians, surgeons and radiologists must be aware of this rare but clinically significant entity.