(Press-News.org) DALLAS – May 24, 2011 – A gynecologist and a molecular biologist at UT Southwestern Medical Center have collaborated to show for the first time that pelvic organ prolapse – a condition in which the uterus, bladder or vagina protrude from the body – is caused by a combination of a loss of elasticity and a breakdown of proteins in the vaginal wall.
Pelvic organ prolapse affects many women older than 50 years of age. Besides creating pelvic pressure, prolapse can lead to other pelvic-floor disorders such as urinary and fecal incontinence, and can affect sexual function.
"We found that the protein fibulin-5, which until now simply has been known to be important in generating elastic fibers, actually blocks the enzymes that degrade proteins that support the vaginal wall structure," said Dr. R. Ann Word, professor of obstetrics and gynecology and a co-senior author of the study in May edition of the Journal of Clinical Investigation. "The elastic fibers do play a role, but it's also the enzymes that degrade the matrix that break down both collagen and elastin over time."
More than 225,000 inpatient surgical procedures for pelvic organ prolapse are performed each year in the U.S. at an estimated cost of more than $1 billion. But surgery alone is not always effective in the long run; nearly 30 percent of women report continued problems over a five-year follow-up period because the underlying problem of matrix support has not been corrected. There are no current therapies to prevent the progression of prolapse.
Age and vaginal delivery are the two most common risk factors for prolapse; injury to the vaginal wall may occur during childbirth but prolapse often doesn't occur until decades later. Obesity and menopause are also contributing factors.
"We still don't understand why patient A has a terrible delivery, with a large baby, but she never gets prolapse. And then we see patients who are 28 with no children, and they're already starting to have problems. So we know genetic and environmental factors contribute to this," Dr. Word said.
Using mice, researchers tested how fibulin-5, a protein that is essential for elastic fiber assembly, regulated the activity of matrix metalloprotease-9 (MMP-9), a group of enzymes that break down the matrix of collagen and elastic fibers, leading to a loss of the structural support of the vaginal wall.
Researchers used a fibulin-5 deficient rodent model and a new domain-specific mutant of fibulin-5 to demonstrate that fibulin-5-mediated elastogenesis (development of elastic fibers) is essential to support the pelvic organs. They also showed that prolapse of the vaginal wall requires an increase in MMP-9, but that fibulin-5 inhibits activation of this protease in a tissue-specific manner.
"Matrix assembly of the vaginal wall is a very complicated process," said Dr. Hiromi Yanagisawa, assistant professor of molecular biology and the study's other co-senior author. "We need to decode what is necessary in this process, but degrading enzymes are the main therapeutic focus."
Dr. Word said, "The bottom line is the whole matrix is maintained by a balance between synthesis and degradation. Our goal is to optimize pelvic organ support and target these proteases that degrade the matrix."
###
Other UT Southwestern researchers involved in the study were Dr. Madhusudhan Budatha, postdoctoral researcher of molecular biology and lead author; Dr. Quin Zheng, former postdoctoral researcher of molecular biology; Dr. Shayzreen Roshanravan and Dr. Cecilia Weislander, former postdoctoral researchers of obstetrics and gynecology; and Shelby Chapman, senior research associate of molecular biology. Scientists from UT Health Center in Tyler and McGill University in Montreal also participated.
The study was supported by grants from the National Institutes of Health, the American Heart Association and the Welch Foundation.
Visit http://www.utsouthwestern.org/obgyn to learn more about clinical services for obstetrics and gynecology at UT Southwestern.
This news release is available on our World Wide Web home page at
www.utsouthwestern.edu/home/news/index.html
To automatically receive news releases from UT Southwestern via email,
subscribe at www.utsouthwestern.edu/receivenews
END
PULLMAN, Wash.—Don't get him wrong: Fred Gittes is, in his words, "extremely squeamish."
But then a scientist with forensics training told him that crime scene investigators could use a better way to analyze blood spatters. The physicist in Gittes rose to the challenge.
"It seems as though what was being done was very crude from a physics point of view and that intrigued me," he says.
Along with Chris Varney, a doctoral candidate in physics, Gittes has worked out a system that can often determine exactly where blood spatters originate, a critical piece of evidence in ...
The magnitude 9 earthquake and resulting tsunami that struck Japan on March 11 were like a one-two punch – first violently shaking, then swamping the islands – causing tens of thousands of deaths and hundreds of billions of dollars in damage. Now Stanford researchers have discovered the catastrophe was caused by a sequence of unusual geologic events never before seen so clearly.
"It was not appreciated before this earthquake that this size of earthquake was possible on this plate boundary," said Stanford geophysicist Greg Beroza. "It was thought that typical earthquakes ...
Scientists from the National Physical Laboratory (NPL), in collaboration with Linköping University, Sweden, have shown that regions of graphene of different thickness can be easily identified in ambient conditions using Electrostatic Force Microscopy (EFM).
The exciting properties of graphene are usually only applicable to the material that consists of one or two layers of the graphene sheets. Whilst synthesis of any number of layers is possible, the thicker layers have properties closer to the more common bulk graphite.
For device applications one- and two-layer graphene ...
In a large study of men in Japan, the presence of fatty liver disease by ultrasonography showed an inverse ( reduced risk) association with the frequency of moderate alcohol consumption; however, there was some suggestion of an increase in fatty liver disease with higher volume of alcohol consumed per day. Moderate drinkers had lower levels of obesity than did non-drinkers, and both obesity and metabolic abnormalities were positively associated with fatty liver disease.
These findings support the results of a number of other recent studies showing that moderate drinking ...
We still need to halt the increase of global carbon emissions before 2020 and in the long term reduce emissions by at least 50% up to 2050. Ultimately, we will have to reduce carbon emissions to close to zero or even remove carbon completely from the atmosphere.
However, climate change is not the only energy challenge:
We need energy services to drive global economic development
We need to provide equal access to modern energy worldwide
We need to provide electricity to the 25% of the world's population still without electricity
We need to provide modern energy ...
Boston, MA – Electronic medical records (EMRs) have been in use for more than 30 years, but have only increased in utilization in recent years, due in part to research supporting the benefits of EMRs and federal legislation. As EMRs have become a standard in medical care, there is a need for additional research of how the system and usage can be refined. A group of researchers from Brigham and Women's Hospital have done just that, and discovered that one way false information can make its way into EMRs is due to users' reliance on copying and pasting material within the ...
A novel way to immobilise radioactive forms of iodine using a microwave, has been discovered by an expert at the University of Sheffield.
Iodine radioisotopes are produced by fission of uranium fuel in a nuclear reactor. Radioactive iodine is of concern because it is highly mobile in the environment and selective uptake by the thyroid gland can pose a significant cancer risk following long term exposure. Furthermore, iodine-129, which is a type of radioactive iodine, has an extremely long half life of 15.7 million years, so is one of the most significant long term hazards ...
CAMBRIDGE, Mass. -- Next time you go on vacation, you may want to think twice before shooting hundreds of photos of that scenic mountain or lake.
A new study from MIT neuroscientists shows that the most memorable photos are those that contain people, followed by static indoor scenes and human-scale objects. Landscapes? They may be beautiful, but they are, in most cases, utterly forgettable.
"Pleasantness and memorability are not the same," says MIT graduate student Phillip Isola, one of the lead authors of the paper, which will be presented at the IEEE Conference on ...
The recent data breaches faced by Sony, Epsilon and TJX once again highlight the risks that lapses in governance pose to enterprise data security. To protect valuable company and customer data, enterprises need to implement IT security governance as a mechanism for managing authorization and access via pre-defined rules and policies. Industry-standard technologies, such as the eXtensible Access Control Markup Language (XAMCL), are helping to facilitate this governance by enabling more efficient and nuanced security policy enforcement.
IT architects and developers can ...
COLUMBUS, Ohio – A new study aimed at refining the way scientists measure ice loss in Greenland is providing a "high-definition picture" of climate-caused changes on the island.
And the picture isn't pretty.
In the last decade, two of the largest three glaciers draining that frozen landscape have lost enough ice that, if melted, could have filled Lake Erie.
The three glaciers – Helheim, Kangerdlugssuaq and Jakobshavn Isbrae – are responsible for as much as one-fifth of the ice flowing out from Greenland into the ocean.
"Jakobshavn alone drains somewhere between ...
