Ostomyland's Wicked Wiki: Articles which explain aspects of Crohn's Disease, why it develops in the first place etc.

Most recent edit on 2007-11-25 06:49:25 by JasonD [Restored to Original Version by Kathy]

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Edited on 2007-11-22 01:32:41 by ErrolLaolo

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Edited on 2006-10-31 03:37:25 by KathyFromEngland

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~*Crohn's Disease Gene Identified

*Researchers On Multicenter Team Linking Gene Mutation To Crohn's Disease

Researchers On Multicenter Team Linking Gene Mutation To Crohn's Disease
31 Oct 2006
The North American IBD Genetics Consortium has linked a gene mutation to the development of Crohn's disease, a chronic, relapsing inflammatory disorder of the gastrointestinal tract that affects 100 to 150 of every 100,000 people of European ancestry. The consortium is composed of IBD genetics research groups from seven centers in North America, including Cedars-Sinai Medical Center, and this effort was led by teams at Yale University and the University of Pittsburgh.
"Crohn's disease and other inflammatory bowel diseases often elude diagnosis for many years while patients suffer and physicians search for clues. The identification of defective genes helps physicians provide early identification of people who are at risk for Crohn's disease and enables pharmaceutical companies to develop targeted drug therapies," said Jerome I. Rotter, M.D., one of several researchers at Cedars-Sinai Medical Center participating in the study. He is director of Research and co-director of the Medical Genetics Institute, and director of the Division of Medical Genetics at Cedars-Sinai.
"The discovery of genetic mutations also may lead to improved research methods and the development of gene therapies targeting Crohn's disease, ulcerative colitis and other inflammatory disorders," Rotter said.
The multicenter research team confirmed the involvement of one gene, called Nod2 or CARD15, and discovered that a defect of the interleukin-23 receptor gene (IL-23R) also led to the development of Crohn's disease.
"Inflammatory bowel disease is an umbrella term that includes a variety of disorders. The more specific we can be in diagnosing a particular disease, the more specific we can be in prescribing an appropriate therapy," said Stephan R. Targan, M.D., director of both the Inflammatory Bowel Disease Center and the Division of Gastroenterology at Cedars-Sinai.
Interleukin-23 is a molecule that enables cells to signal to each other and is also a very precise regulator of parts of the immune system, according to Kent D. Taylor, Ph.D., second author on the study and a research scientist in Cedars-Sinai's Medical Genetics Institute, along with Huiying Yang, Ph.D. The IL-23R gene provides the genetic code for the cell receptor, which is located on the outside surface of a cell. IL-23 binds to the IL-23 receptor to provide instructions for the cell. It is this point in the signaling pathway that has now been implicated in the development of Crohn's disease.
http://www.medilexicon.com/medicalnews.php?newsid=55424∞

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~*Crohn's Disease Gene Identified

Edited on 2006-10-27 03:38:15 by KathyFromEngland

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~*Crohn's Disease: One Gene Copy Too Few Leads To Weakened Defense

*Crohn's Disease Gene Identified

Crohn's Disease Gene Identified
27 Oct 2006
Alterations in the receptor for a known inflammatory response pathway are strongly associated with Crohn's disease and ulcerative colitis, according to a report by a consortium of American and Canadian researchers in the October 26 online Science Express.
Crohn's disease and ulcerative colitis, collectively called inflammatory bowel disease (IBD), are chronic disorders that cause abdominal pain, diarrhea and gastrointestinal bleeding and affect over one million Americans. Because IBD tends to run in families and is more frequent in certain ethnic populations, especially Ashkenazi Jews, scientists have long suspected a significant genetic component.
According to senior author Judy H. Cho, M.D., associate professor in the Departments of Medicine and Genetics at Yale School of Medicine, the team found that mutations in a receptor gene associated with the interleukin-23 (IL-23) pathway, are linked to Crohn's disease. The IL-23 pathway is known to target organ-specific inflammatory responses.
"This finding is particularly intriguing because we appear to have identified a gene variant that protects against development of IBD," said Cho, who also directs the Inflammatory Bowel Disease Center at Yale. "It causes us to think about the genetics of health as well as about the genetics of the disease. One mutation appears to offer significant protection from IBD, and will be a crucial target for drugs that might better manage Crohn's disease and ulcerative colitis."
Previous genetic studies found a link between Crohn's disease and mutations in a gene known as CARD 15, but those mutations alone did not account for all of the genetic components of the disease.
To identify additional genes associated with IBD, the international research team scanned the genome, testing more than 300,000 single nucleotide polymorphisms, or SNPs, in people with Crohn's disease. They compared results with the SNPs in a similar number of people without IBD. In addition to two differences in the CARD 15 gene, they found a third variant SNP, which was in a different gene on a different chromosome-the interleukin-23 receptor.
"We know that the IL-23 receptor plays an important role in activating inflammation, including in organs of the digestive tract, therefore it could be an extremely important target for improving the management of Crohn's disease and ulcerative colitis," said Cho. "However, the IL-23 pathway may serve a useful purpose in protecting us from other diseases, so when seeking to block or manipulate its activity with drugs or other means, we need to take this balancing act into consideration."
Cho and co-authors represent the IBD Genetics Consortium, which is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). Cho said large study sizes made possible by the consortium offer more definitive conclusions.
"This important discovery not only offers new hope for better therapies for patients with Crohn's disease, it also highlights the promise of the human genome project and subsequent investments by the NIH in large scale, collaborative research projects to unravel the causes of, and hopefully better treatments for complex, enigmatic diseases," said Stephen P. James, M.D., director of the Division of Digestive Diseases and Nutrition at the National Institutes of Health's NIDDK.
http://www.medilexicon.com/medicalnews.php?newsid=55198∞

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~*Crohn's Disease: One Gene Copy Too Few Leads To Weakened Defense

Edited on 2006-07-27 13:15:05 by KathyFromEngland

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~*Crohn's Disease: One Gene Copy Too Few Leads To Weakened Defense

Crohn's Disease: One Gene Copy Too Few Leads To Weakened Defense
18 Jul 2006
Patients with Crohn's disease of the colon have one copy less than healthy persons of the beta-defensin 2 gene, a gene coding for an important defense molecule of the body. An international research team comprising scientists of the Robert Bosch Hospital in Stuttgart and the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg have discovered a possible cause of the chronic inflammations.
Crohn's disease (CD) is a chronic inflammatory disease of the intestinal tract affecting most commonly the lower part of the small bowel, called the ileum, and the colon. The cause of the disease is unknown; genetic and environmental factors have been suggested to play a role.
Defensins are part of the arsenal of defense weapons used by the human immune system. The peptides consist of only about 30 protein building blocks and act like our body's own antibiotics that protect the mucous membranes from bacterial invasion. Patients with Crohn's disease of the colon (colonic CD) have a lower level of beta-defensins in the mucous membranes. In a collaborative research project headed by Dr. Klaus Fellermann and Professor Eduard F. Stange, Robert Bosch Hospital, Stuttgart, researchers from the German Cancer Research Center and the Universities of Vienna and Davis, California, have now discovered that the number of defensin gene copies has a crucial influence on the development of the disease.
Defensin genes are arranged in nests, called clusters, on chromosome 8. The number of clusters varies considerably across the population; this is technically called a polymorphism. The research team has now shown that patients with colonic CD have on average only three copies of the gene encoding beta-defensin 2, whereas healthy control persons as well as patients with small bowel CD or ulcerative colitis, another inflammatory bowel disease, have an average of four copies of this gene per cell. The researchers showed that a lower number of gene copies is indeed associated with reduced production of the endogenous antibiotic, which explains the known low defensin level. They presume that this causes the defense of the intestinal mucous membrane to become porous so that bacteria can attach to and invade the mucous membrane, which leads to the typical inflammatory hot spots of Crohn's disease.
The disease, which is named after American physician Dr. Burrill Bernhard Crohn, is characterized by recurring episodes of active disease. It affects approximately 150,000 people in Germany; five new cases per 100,000 inhabitants are diagnosed each year. There has been a substantial rise in incidence rates in recent years. Patients suffering from Crohn's disease also have an elevated risk of developing bowel cancer.
http://www.medilexicon.com/medicalnews.php?newsid=47508∞

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Edited on 2006-07-27 02:56:32 by KathyFromEngland

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Articles which explain aspects of Crohn's Disease, why it develops in the first place etc.

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New Insight Into Cause Of Crohn's Disease

27 Feb 2006

UK scientists have found evidence that suggests Crohn's Disease is caused by a weak immune response. The researchers, who report their findings in an Article in this week's issue of The Lancet, also suggest that sildenafil (Viagra) might help in the treatment of the disease.

Crohn's disease is a chronic inflammatory disorder that causes ulcerations in the small and large intestines. Many scientists consider Crohn's to be an autoimmune disease--an illness that occurs when the body tissues are attacked by its own immune system. However, Anthony Segal (University College London, UK) and colleagues have found that, counter intuitively, the inflammation in Crohn's arises due to a weak immune response.

The investigators looked at the quantities of neutrophils (white blood cells) that patients with Crohn's disease produce in response to trauma at sites in the bowel (intestinal biopsy) and on the skin surface (skin abrasion). They found that in response to trauma, Crohn's disease patients produced much lower quantities of neutrophils and inflammatory mediators when compared with healthy individuals. Cultured blood cells were also abnormal in the patients. To test the inflammatory response to bacteria, the team also measured local inflammatory and blood flow changes in participants after injecting a harmless form of Escherichia Coli under their skin. In the healthy controls, blood flow in the area of inflammation increased approximately ten-fold by 24 hours. Crohn's disease patients, however, had much lower blood flow than controls. The researchers found that the abnormally low blood flow in Crohn's patients could be corrected by treatment with Viagra, indicating a possible role for the drug in the treatment of the disease.

The authors believe that in Crohn's disease, reduced or delayed recruitment of neutrophils to sites at which bacteria penetrate the intestinal wall might lead to the persistence of bacteria and other organic debris in the tissue. The body may respond to this build up of bacteria by secreting inflammatory molecules, which accumulate and lead to the development of chronic inflammation typical of Crohn's.

Professor Segal states: "Our investigations identified defective innate immunity in Crohn's disease. In Crohn's disease, a constitutionally weak immune response predisposes to accumulation of intestinal contents that breach the mucosal barrier of the bowel wall, resulting in granuloma formation and chronic inflammation."

http://www.medilexicon.com/medicalnews.php?newsid=38349∞

Immune Signals Of Variations Of A Single Gene Linked To More Severe Crohn's Disease

24 May 2006

Building on previous evidence supporting the theory that the pathophysiology of Crohn's Disease is altered by genetic variation, recent studies have found that the combination of immune signals given by three variants of a single candidate gene affects the severity of the disease, particularly among Ashkenazi Jews. The findings, presented at the annual meeting of the American Gastroenterological Association, were reported by researchers from Cedars-Sinai Medical Center, the University of Washington and Mount Sinai School of Medicine.

Crohn's Disease is an inflammatory bowel disease that causes inflammation or ulceration of the gastrointestinal tract and can sometimes run in families. While the cause is unknown, many professionals believe that the body's immune system may overreact to normal intestinal bacteria or that disease-causing bacteria and viruses may play a role in triggering the condition.

The recent study, funded by the National Institutes of Health, shows the effect of one particular gene − a Crohn's Disease candidate gene named TLR 5 − on both Jews and non-Jews with the disease.

It is estimated that American Jews are three times more likely to develop Crohn's Disease than the population as a whole. Approximately 80 percent of the six million Jews in the United States are Ashkenazi Jews, an ethnic group whose ancestors are from eastern and central Europe, As Jerome I. Rotter, M.D., first author of the study, director of research and co-director of the Medical Genetics Institute at Cedars-Sinai Medical Center explained, the innate immune system senses micro-organisms and pathogens using a family of proteins known as the Toll-Like Receptors (TLRs). This recognition activates both the innate and adaptive immune system, with each TLR recognizing a specific pattern of microbial components.

The aim of the study was to investigate three TLR5 gene variants and their relationship to Crohn's Disease, the response to two types of bacterial antigens (OmpC porin and CBir1 flagellin) and their relationship to ethnicity. There were 889 Crohn's Disease patients in the study and 236 controls (persons without Crohn's Disease).

"An important part of the study was its approach. By subdividing the subjects by ethnicity and antibody response we were able to show that the candidate gene TLR5 has an effect in both Jews and non-Jews, but its effects are particularly noteworthy in the Jewish population," Rotter said.

While the treatment of Crohn's Disease is improving, it is still associated with a high morbidity and a large number of hospitalizations and surgeries, Rotter said. "This study demonstrates that it will be important to include ethnicity, clinical phenotypes and quantitative physiologic traits in future investigations that may eventually lead to new and better therapies for Crohn's Disease's different sub-forms."

Researchers from Cedars-Sinai's Inflammatory Bowel Disease Center and Medical Genetics Institute authored 23 other studies that will be presented at the association's annual meeting.

The first of eight hospitals in California whose nurses have been honored with the prestigious Magnet designation, Cedars-Sinai Medical Center is one of the largest nonprofit academic medical centers in the Western United States. For 18 consecutive years, it has been named Los Angeles' most preferred hospital for all health needs in an independent survey of area residents. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities, and since 2004 has been fully accredited by the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP). Additional information is available at www.cedars-sinai.edu∞.

http://www.medilexicon.com/medicalnews.php?newsid=43950∞

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Articles which explain aspects of Crohn's Disease, why it develops in the first place etc.