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You searched for +publisher:"Case Western Reserve University" +contributor:("Hodges, Craig"). One record found.

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Case Western Reserve University

1. Vitko, Megan Sue. Intestinal Dysfunction in Cystic Fibrosis.

Degree: PhD, Genetics, 2016, Case Western Reserve University

Intestinal Dysfunction in Cystic FibrosisAbstract By MEGAN VITKOCystic Fibrosis (CF) is an autosomal recessive genetic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR protein is an anion channel and loss of CFTR function impedes transepithelial chloride permeation leading to dehydration and the accumulation of thick, sticky mucus in vital organs. Many symptoms occur as a result of non-functional CFTR; however mucus accumulation is a hallmark of CF. CF is a systemic disease that most commonly affects the lungs, pancreas, and gastrointestinal system. Severe lung disease is the major cause of morbidity and mortality associated with CF. There have been many advances in CF diagnosis and treatment since CF was initially described and the continued development of treatments and therapies has increased the predicted survival of patients born today to over 40 years old. However, patients still develop symptoms of CF that decrease their quality of life. GI symptoms of CF are a major concern for patients today as they may be lethal if untreated, affect patients of any age, and may greatly decrease the quality of life for patients. Intestinal complications of CF may include Meconium Ileus (~10-25%), Distal Intestinal Obstruction Syndrome (~10-20%), Small Intestine Bacterial Overgrowth (~30-50%), and failure to thrive (~ 25-30%). Many factors, such as pancreatic insufficiency, modifier genes, and the environment, may contribute to the incidence of intestinal symptoms, thus the origin of CF intestinal manifestations is complex and not well understood.Even though CF has been extensively studied, the exact mechanism behind the development of intestinal symptoms remains to be elucidated. It was previously hypothesized that absence of CFTR in the intestinal epithelium was the main cause of intestinal obstruction, however work in our lab showed that absence of CFTR is necessary, but not sufficient to be the sole cause of intestinal obstruction. I analyzed the role of CFTR in the smooth muscle via the use of conditional mouse models that had Cftr inactivated only in the smooth muscle. I determined that Cftr in the smooth muscle contributes to the development of intestinal obstruction. However, absence of Cftr in the intestinal epithelium and smooth muscle together contribute to the development of CF-like intestinal obstruction rates. I have shown that absence of Cftr in the intestinal epithelium leads to dehydration and mucus accumulation and absence of Cftr in the smooth muscle leads to decreased muscle contraction. The decreased muscle contraction may be due to an impairment in calcium reuptake in the sarcoplasmic reticulum. My work provided novel insight into the origin of CF intestinal manifestations. It is known that CF symptoms, including intestinal obstruction are influenced by modifier genes. Genome wide association studies (GWAS) have identified variants in potential modifier genes, however these studies do not provide information about how these variants… Advisors/Committee Members: Hodges, Craig (Advisor), Rebecca , Darrah (Committee Chair).

Subjects/Keywords: Genetics; CFTR; Intestinal Obstruction; Cystic Fibrosis; mouse models

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Vitko, M. S. (2016). Intestinal Dysfunction in Cystic Fibrosis. (Doctoral Dissertation). Case Western Reserve University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1459248266

Chicago Manual of Style (16th Edition):

Vitko, Megan Sue. “Intestinal Dysfunction in Cystic Fibrosis.” 2016. Doctoral Dissertation, Case Western Reserve University. Accessed August 22, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1459248266.

MLA Handbook (7th Edition):

Vitko, Megan Sue. “Intestinal Dysfunction in Cystic Fibrosis.” 2016. Web. 22 Aug 2019.

Vancouver:

Vitko MS. Intestinal Dysfunction in Cystic Fibrosis. [Internet] [Doctoral dissertation]. Case Western Reserve University; 2016. [cited 2019 Aug 22]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1459248266.

Council of Science Editors:

Vitko MS. Intestinal Dysfunction in Cystic Fibrosis. [Doctoral Dissertation]. Case Western Reserve University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1459248266

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