Medical Genetics Commons^™

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Richard M. Niles

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Gene Transfer In The Lung Using Recombinant Adeno-Associated Virus, Alisha Gruntman, Christian Mueller, Terence Flotte, Guangping Gao

Christian Mueller

Adeno-associated virus (AAV) is a small replication-deficient DNA virus belonging to the Parvovirinae family. It has a single-stranded ∼4.7-kb genome. Recombinant AAV (rAAV) is created by replacing the viral rep and cap genes with the transgene of interest along with promoter and polyadenylation sequences. The short viral inverted terminal repeats must remain intact for replication and packaging in production, as well as vector genome processing and persistence in the transduction process. The AAV capsid (serotype) determines the tissue tropism of the rAAV vector. In this unit we will discuss serotype selection for lung targeting along with the factors effecting efficient …

Raav9 Airway Delivery Results In Effective Knockdown Of Mutant Alpha 1-Antitrypsin In The Liver While Upregulating Wildtype Alpha 1-Antitrypsin In The Lung, Alisha Gruntman, Christian Mueller, Qiushi Tang, Lina Song, James M. Wilson, Terence R. Flotte, Maria P. Limberis

Christian Mueller

Alpha 1-Antitrypsin (AAT) deficiency is a human genetic disease resulting in the production of mutant AAT, a hepatocyte produced serine protease inhibitor that functions to prevent alveolar epithelial damage by inhibiting neutrophil elastase. Patients with AAT deficiency have increased lung disease, due to decreased proteolytic protection, as well as sporadic severe liver disease secondary to accumulation of mutant AAT, especially a common mutant form termed PiZ, within hepatocytes. We previously showed, in a PiZ mutant mouse model, simultaneous knock-down of mutant PiZ-AAT and augmentation of wild-type AAT production through intravenous delivery of a recombinant adeno-associated viral (rAAV) vector encoding both …

Stent Placement Compared With Balloon Angioplasty For Obstructed Coronary Bypass Grafts. Saphenous Vein De Novo Trial Investigators., M P Savage, J S Douglas, D L Fischman, C J Pepine, S B King, J A Werner, S R Bailey, P A Overlie, S H Fenton, J A Brinker, M B Leon, S Goldberg

Michael P Savage M.D.

BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts.

METHODS: A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later.

RESULTS: As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate …

Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis Using A Breast Cancer Mouse Model, Aiman Alhazmi

Theses and Dissertations

Understanding the impact of epigenetic mechanisms on tumorigenesis is essential, as epigenetic alterations are associated with tumor initiation and progression. Because epigenetic changes are reversible, they are potential targets for cancer therapy. Nucleosome Remodeling Factor (NURF) is a chromatin-remodeling complex that regulates gene expression by changing nucleosome positioning along the DNA sequence. Previous studies have shown a role for NURF in embryonic development as well as regulating genes involved in tumor progression. In this work we investigated the impact of eliminating NURF function in tumorigenesis in vivo. BALB/c mice challenged with syngeneic 67NR breast cancer cell lines, injected into the …

The Role Of Tetraspanin-8 In Astrocyte Elevated Gene-1 Mediated Progression Of Hepatocellular Carcinoma, Maaged Akiel

Theses and Dissertations

Hepatocellular carcinoma (HCC) is a devastating form of liver cancer that accounts for 80% of liver cancers. HCC has a poor prognosis with five-year survival of less than 12% in the United States. We in previous studies have identified Astrocyte Elevated Gene-1 (AEG-1) as an aberrantly overexpressed gene in many cancers including HCC, regulating tumor progression. Microarray studies identified the small transmembrane protein, tetraspanin8 (TSPAN8) as a downstream of AEG-1. TSPAN8 belongs to the family of TETRASPANINS with the characteristic of crossing the membrane four times, and regulating a wide range of cellular phenomena. TSPAN8 is implicated in metastasis and …

A Strain Of Piscine Myocarditis Virus (Pmcv) Infecting Argentina Silus (Ascanius), Torstein Tengs Dr.

Dr. Torstein Tengs

No abstract.

Overexpression Of A Novel Cell Cycle Regulator Ecdysoneless In Breast Cancer: A Marker Of Poor Prognosis In Her2/Neu-Overexpressing Breast Cancer Patients., Xiangshan Zhao, Sameer Mirza, Alaa Alshareeda, Ying Zhang, Channabasavaiah B. Gurumurthy, Aditya Bele, Jun Hyun Kim, Shakur Mohibi, Monica Goswami, Subodh M. Lele, William West, Fang Qiu, Ian O. Ellis, Emad A. Rakha, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression …

Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib

Theses and Dissertations

Increasingly the role of epigenetic machinery as a bridge between underlying DNA sequence and cellular phenotype is being discovered. The establishment of a myriad of unique cellular types sharing identical gene sequences in a multicellular organism gives a broad sense for the inherent role of epigenetic influence on cell differentiation. Importantly, the epigenetic mechanisms involved in establishing cell identity unsurprisingly contribute to diseased states, including cancer. Recent research continues to elucidate contributory roles of epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA regulation, in human cancers. Additionally, chromatin remodelers, such as the Nucleosome Remodeling Factor (NURF), have been …

Elucidating Genetic And Environmental Influences On Alcohol-Related Phenotypes, Jacquelyn Meyers

Theses and Dissertations

Decades of work has led researchers to believe that risk for complex behavioral phenotypes, such as alcohol use disorders, is likely influenced by multiple genes of small effect acting in conjunction with each other and the environment. Currently, the field of psychiatric genetics is developing methodologies for the identification of genetic risk variants that predispose individuals to the development of complex behavioral disorders. Several challenges related to the complex and polygenic nature of these phenotypes, must be considered. This dissertation study attempts to address these important challenges in the context of alcohol use disorders and related phenotypes. A rich twin …

Role Of The Pituitary-Adrenal Axis In G-Csf Therapy After Neonatal Hypoxia-Ischemia, Melissa Stephanie Charles

Loma Linda University Electronic Theses, Dissertations & Projects

Several reports indicate that the activity of the hypothalamic-pituitary-adrenal axis (HPA) as measured by the increased level of adrenocorticotropic hormone (ACTH), and corticosterone is increased after a brain insult. These hormones are the effectors secreted respectively by the pituitary and adrenal glands. It has been shown that the down-regulation of corticosterone levels can improve detrimental outcomes associated with ischemic brain injuries. Neonatal hypoxia-ischemia (HI) is a devastating perinatal event with a grim prognosis and limited therapeutic strategies. In recent studies, granulocyte-colony stimulating factor (G-CSF) has shown promise in neonatal HI investigations by improving neuromotor function and reducing apoptosis in the …

Otx But Not Mitf Transcription Factors Are Required For Zebrafish Rpe Development, Brandon Lane

Theses and Dissertations

Mitf and Otx transcription factors have been identified as essential to the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific role in the RPE developmental pathway have not been clearly defined. The role of the two Mitf transcription factors (Mitfa and Mitfb) and two Otx transcription factors (Otx1a and Otx2) in zebrafish RPE development was explored in these experiments. The loss of Mitf activity in mitfa, mitfb, or double mitf null mutant fish lines had no effect on RPE pigmentation or development. The loss of Otx2 activity through morpholino knockdown produced a …

Cdo Patterns The Musculature Of The Esophagus And Is Required For Esophageal Motility In Mice, Anthony I. Romera, Jagmohan Singhb, Satish Rattan, Robert S. Krauss

Department of Medicine Faculty Papers

Introduction:

Cdo is a multifunctional cell surface co-receptor that promotes Hedgehog signaling during rostroventral midline development and cadherin-mediated signaling during skeletal myogenesis. We report here novel roles for Cdo in patterning of the murine esophageal musculature and esophageal motility disorders such as achalasia.

Quantification Of Piscine Reovirus (Prv) At Different Stages Of Atlantic Salmon Salmo Salar Production, Torstein Tengs Dr.

Dr. Torstein Tengs

The newly described piscine reovirus (PRV) appears to be associated with the development of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon Salmo salar L. PRV seems to be ubiquitous among fish in Norwegian salmon farms, but high viral loads and tissue distribution support a causal relationship between virus and disease. In order to improve understanding of the distribution of PRV in the salmon production line, we quantified PRV by using real-time PCR on heart samples collected at different points in the life cycle from pre-smolts to fish ready for slaughter. PRV positive pre-smolts were found in about …

Temporal And Functional Profile Of The Transcriptional Regulatory Network In The Early Regenerative Response To Partial Hepatectomy In The Rat., Egle Juskeviciute, Rajanikanth Vadigepalli, Jan B Hoek

Rajanikanth Vadigepalli

BACKGROUND: The goal of these studies was to characterize the transcriptional network regulating changes in gene expression in the remnant liver of the rat after 70% partial hepatectomy (PHx) during the early phase response including the transition of hepatocytes from the quiescent (G0) state and the onset of the G1 phase of the cell cycle. RESULTS: The transcriptome of remnant livers was monitored at 1, 2, 4, and 6 hours after PHx using cDNA microarrays. Differentially regulated genes were grouped into six clusters according their temporal expression profiles. Promoter regions of genes in these clusters were examined for shared transcription …

Ab Deposition In Idiopathic And Dup15q11.2-Q13 Autism Spectrum Disorders, J Wegiel, Janusz Frackowiak, Bozena Mazur-Kolecka, N Carolyn Schanen, Edwin H. Cook Jr, Marian Sigman, Ted Brown, Izabela Kuchna, Jarek Wegiel, Krzysztof Nowicki, Humi Imaki, Shuang Yong Ma, Abha Chauhan, Ved Chauhan, David L. Miller, Pankaj D. Mehta, Michael Flory, Ira L. Cohen, Eric London, Barry Reisberg, Mony J. De Leon, Thomas Wisnieski

N C Schanen

Background: It has been shown that amyloid ß (Ab), a product of proteolytic cleavage of the amyloid b precursor protein (APP), accumulates in neuronal cytoplasm in non-affected individuals in a cell type–specific amount.

Methodology/Principal Findings: In the present study, we found that the percentage of amyloid-positive neurons increases in subjects diagnosed with idiopathic autism and subjects diagnosed with duplication 15q11.2-q13 (dup15) and autism spectrum disorder (ASD). In spite of interindividual differences within each examined group, levels of intraneuronal Ab load were significantly greater in the dup(15) autism group than in either the control or the idiopathic autism group in 11 …

Predictors Of Contralateral Breast Cancer In Brca Negative Women, Ann E. Simmons

Dissertations & Theses (Open Access)

Breast cancer is the most common cancer diagnosis and second leading cause of death in women. Risk factors associated with breast cancer include: increased age, alcohol consumption, cigarette smoking, white race, physical inactivity, benign breast conditions, reproductive and hormonal factors, dietary factors, and family history. Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. Women carrying a mutation in these genes are at an increased risk to develop a second breast cancer. Contralateral breast cancer is the most common second primary cancer in patients treated for a first breast cancer. Other risk …

Evaluation Of Knowledge Regarding Diagnostic Strategies For Genetic Diseases In Select Residents, Samantha Penney

Dissertations & Theses (Open Access)

Genetics education for physicians has been a popular publication topic in the United States and in Europe for over 20 years. Decreasing numbers of medical genetics professionals and an increasing volume of genetic information has created a dire need for increased genetics training in medical school and in clinical practice. This study aimed to assess how well pediatrics-focused primary care physicians apply their general genetics knowledge to clinical genetic testing using scenario-based questions. We chose to specifically focus on knowledge of the diagnostic applicability of Chromosomal Microarray (CMA) technology in pediatrics because of its recent recommendation by the International Standard …

The Use Of Infliximab In Older Inflammatory Bowel Disease Patients, Stephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch

Department of Medicine Faculty Papers

Limited data suggest anti-tumor necrosis factor (TNF) antibodies have equal efficacy but higher morbidity and mortality in older compared to younger inflammatory bowel disease (IBD) patients(1).

Novel Napi-Iic Mutations Causing Hhrh And Idiopathic Hypercalciuria In Several Unrelated Families: Long-Term Follow-Up In One Kindred., Y Yu, S R. Sanderson, M Reyes, A Sharma, N Dunbar, Tarak Srivastava, H Jüppner, C Bergwitz

Manuscripts, Articles, Book Chapters and Other Papers

Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, rickets/osteomalacia, and frequently kidney stones or nephrocalcinosis. Similar albeit less severe biochemical changes are also observed in heterozygous carriers, which are furthermore indistinguishable from those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3 mutations (exons and introns) in two previously not reported HHRH kindreds, which resulted in the identification of three novel mutations. The affected members of kindred A were compound heterozygous …