Health Sciences Report Summer 2006

Research Headlines
Discoveries from the U of U Reported in Leading National Journals

Embryos Exposed in 3-D

This three-dimensional computer image of a mouse embryo was created using data collected during a CT (computerized tomography) scan of the embryo.

Scientists will be able to see the effects of genetic defects and test the safety of medicines in new, detailed three-dimensional images of mouse embryos.

Combining miniature CT scans with high-tech computer methods, Utah and Texas researchers produced "microCT-based virtual histology," reported in the April 28th issue of PLoS Genetics, an online journal of the Public Library of Science.

"Our method provides a fast, high-quality, and inexpensive way to visually explore the 3-D internal structure of mouse embryos," said co-author Chris Johnson, Ph.D., distinguished professor of computer science and director of the U of U Scientific Computing and Imaging Institute (SCII).

Scientists often use mouse embryos to learn what genes do and to test the safety of new drugs and household chemicals. By "knocking out" a gene, they can see what goes wrong in the embryo and learn the gene's normal function, or learn how a mutant gene can cause cancer. Since mouse embryos are sensitive to toxicity from chemicals, new medicines and chemicals are tested on them to see if any defects develop, indicating their safety for humans.

Charles Keller, M.D., a former postdoctoral fellow in the laboratory of U geneticist Mario R. Capecchi, Ph.D., led the study. Keller is assistant professor at the Children's Cancer Research Institute at the University of Texas Health Sciences Center in San Antonio. U co-authors are medical student Mark S. Hansen and several members of SCII. Capecchi is distinguished professor of human genetics and biology, and co-chair of the U Department of Human Genetics. Full Story

Knee Pain Relief? Not a Simple Answer

In this X-ray of the knees of a patient with osteoarthritis,the arrow indicates where joint spaces have narrowed; the circle shows where osteophytes(bony spurs) have developed.

Although popular dietary supplements glucosamine and chondroitin sulfate proved no better than a placebo in relieving osteoarthritis knee pain in most participants in a major national trial, a smaller subgroup of patients with moderate to severe osteoarthritis knee pain experienced significant pain relief.

"For the study population as a whole, supplements were found to be ineffective," said Daniel O. Clegg, M.D., principal investigator of the national study published Feb. 22 in the New England Journal of Medicine. He is U professor of internal medicine and chief of rheumatology at the George E. Wahlen Department of Veterans Affairs Medical Center in Salt Lake City.

"An exploratory analysis suggested, however, that the combination of glucosamine and chondroitin sulfate might be effective in patients who suffer from moderate to severe osteoarthritis knee pain," he added.

More than 20 million Americans have osteoarthritis. Oral doses of glucosamine and chondroitin sulfate, derived from animal products, have become popular with arthritis sufferers in the past 20 years.

The five-year, $12.5 million Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) was designed to assess the efficacy and safety of the supplements, taken separately or in combination. Nearly 1,600 arthritis patients were assigned randomly to take a placebo, celecoxib (a widely prescribed arthritis pain drug), glucosamine, chondroitin sulfate, or a combination of the supplements for 24 weeks.

Conducted at 16 U.S. academic centers, the study was funded by the National Center for Complementary and Alternative Medicine, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health.    Full Story

First HPV Vaccine

Gardasil, a new vaccine designed to prevent human papillomavirus (HPV) that can cause genital warts and cervical cancer, will be recommended for females ages nine through 26, following approval by the U.S. Food and Drug Administration.

Clinical trials of the drug were held at sites worldwide, including the U of U and Huntsman Cancer Institute, where John Kriesel, M.D., research assistant professor of infectious diseases, was principal investigator. The trial was ended early due to the remarkable efficacy of the vaccine.

HPV is a common sexually transmitted infection that can cause cervical cancer. In the study of 11,000 women, the vaccine prevented virtually all cervical pre-cancers and genital warts associated with four types of HPV included in the vaccine.

Molecular Clue

U researchers discovered and characterized an important connection between two nuclear pore proteins and COPI, a complex of proteins that coats membranes to facilitate vesicle formation.

The study, published in the Feb. 18 issue of Molecular Biology of the Cell, provides a key molecular clue to the question of how the nucleus is disassembled at mitosis. Results also contribute to the longer-term goals of understanding coordination between events of the cell cycle and, ultimately, of developing novel chemotherapeutic strategies.

Amy Prunuske, Ph.D., a recent doctoral candidate, was lead author, along with Jin Lui, Ph.D., in the lab of Katharine Ullman, Ph.D., associate professor of oncological sciences and an investigator at the University's Huntsman Cancer Institute. Full Story

Repeat C-sections

Before choosing elective cesarean deliveries, women planning large families should consider the risks of repeat c-sections, according to findings published May 31 in Obstetrics & Gynecology.

Robert M. Silver, M.D., U professor of obstetrics and gynecology, was lead author on the study, based on an analysis of 30,132 women who had cesarean deliveries at 19 academic medical centers nationwide from 1999-2002. Researchers found that the risks of complications, including urinary and bowel injury, need for postoperative ventilation, intensive care admission, hysterectomy, blood transfusions, and maternal death, increased significantly with the increasing number of c-sections.

Other members of the Maternal-Fetal Medicine Unit at the U of U participating in the study were: Michael Varner, M.D., professor; T. Flint Porter, M.D., assistant professor; Bryan Oshiro, M.D., assistant professor; Michael Belfort, M.D., professor; Kristine Anderson, R.N., B.S.N., nurse coordinator for clinical research, and Anna Guzman, R.N., senior research nurse. Full Story (See pg. 29.)

Disfiguring Syndromes

Researchers traced contractures of muscles in the face, hands, and feet that limit movement and cause deformities to mutations in a gene that makes up part of the contractile machinery of muscle.

The findings were reported in the April 16 online issue of Nature Genetics. Reha M. Toydemir, M.D., and Ph.D. candidate at the U Eccles Institute of Human Genetics, is first author, and Michael J. Bamshad, M.D., University of Washington, corresponding author.

The two disfiguring genetic disorders that cause muscle contractures, Freeman-Sheldon and Sheldon-Hall syndromes, are rare, although congenital contractures such as clubfoot affect thousands of babies every year and often require several surgeries to correct. Full Story

Origin of Cells

In a surprising discovery that has implications for treating muscular dystrophy, researchers found that two groups of adult cells that regulate muscle repair arise from somites: transient blocks of tissue in the embryo.

"It turns out that an adult muscle cell's capacity to repair damaged muscle is directly related to where it comes from, and this has implications for the potential use of SP [satellite and side population] cells in repairing muscle in muscular dystrophy patients," said Gabrielle Kardon, Ph.D., assistant professor at the U Eccles Institute of Human Genetics and senior author of the study published Jan. 24 in the Proceedings of the National Academy of Sciences.

Co-authors include Mark S. Hansen, a lab technician and U medical student.

The Bitter Truth

The ability to taste, or not to taste, a bitter synthetic compound is shared by humans and chimpanzees, but it may be an evolutionary coincidence.

In the April 13 cover story of the journal Nature, Stephen Wooding, Ph.D., U research assistant professor of human genetics, and Michael Bamshad, M.D., University of Washington, reported that the ability to taste PTC (phenylthiocarbamide) and other bitter compounds probably evolved as a way to protect animals from eating poisonous plants. However, evidence suggests that humans and chimps harbor different kinds of mutations, so they may have faced different pressures from natural selection.

Being a PTC taster or non-taster has far-reaching implications for human behavior. PTC tasters are less likely to smoke cigarettes as well as eat cruciferous vegetables, such as broccoli, that are important sources of nutrition.

Risky Vehicles

In the first report of its kind, U researchers found that children hit by a vehicle backing out of a driveway are 2.4 times more likely to be struck by a minivan and 53 percent more likely to be hit by a truck than by a car.

The study, conducted by the U of U Intermountain Injury Control Center, also found that children hit by high-profile vehicles (trucks, SUVs, or minivans) are more likely to require hospitalization, surgery, and treatment in an intensive care unit than children backed over by cars.

Findings were published in the June issue of Pediatric Emergency Care. N. Clay Mann, Ph.D., director of research at the U center, was lead author.

Likely Autism Connection

U researchers confirmed that a region of a single chromosome probably harbors a gene that causes autism.

The study, published online Jan. 13 in Human Heredity, supports Finnish studies of families that linked autism to the same region on chromosome 3.

Hilary Coon, Ph.D., research associate professor of psychiatry, is principal author. Others are: Nori Matsunami and Jeff Stevens, research associates in human genetics; Judith S. Miller, Ph.D., assistant professor of psychiatry, and Carmen Pingree, Neurodevelopmental Genetics Project, Department of Psychiatry; Nicola J. Camp, Ph.D., assistant professor of medical informatics; Alun Thomas, Ph.D., professor of medical informatics; Janet E. Lainhart, M.D., associate professor of psychiatry; Mark Leppert, Ph.D., professor and co-chair of the Department of Human Genetics; and William M. McMahon, M.D., professor of psychiatry. Full Story

Healthy Eye Diet

For the first time, U researchers demonstrated that diet can have a beneficial effect on an inherited macular disorder.

Published in the February issue of the Archives of Ophthalmology, the study focused on a large extended Utah family with an early-onset form of macular degeneration. Researchers studied the fat content of patients' red blood cells and adipose tissue, and found that individuals who consumed the highest amounts of DHA and EPA, fats found primarily in seafood, had the mildest form of the disorder.

Authors included: Paul S. Bernstein, M.D., Ph.D., associate professor of ophthalmology and visual sciences, and director of Retinal Disease and Surgery; Amy Hubbard, former graduate student, and Wayne Askew, Ph.D., professor and chief, Division of Foods and Nutrition, College of Health; Nanda Singh, Ph.D., postdoctoral research associate, and Mark Leppert, Ph.D., professor and co-chair, Department of Human Genetics, School of Medicine. Full Story

Obesity-Psoriasis Link Defined

Being overweight does not trigger the onset of psoriasis, although the incidence of obesity among psoriasis patients at U of U dermatology clinics is twice that of the general population.

In the December 2005 issue of the Archives of Dermatology, researchers reported that, contrary to what they had expected, people with psoriasis were more likely to have developed a weight problem after acquiring the autoimmune skin disease. They also were found to be four times more likely to smoke than obese people in general.

U authors are Gerald G. Krueger, M.D., professor of dermatology, and Mark D. Herron, M.D., former dermatology fellow.  Full Story

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