August 3, 2007 - The Focus News

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Health Pets Could be Source of Multi-Resistant Bacteria Infections in Humans The next time you have difficulty fighting a bacterial infection, your next trip to the doctor might be to the family veterinarian. A new University of Missouri-Columbia study is investigating whether the family pet could be a reservoir for infections of multi-resistant bacteria in humans. Antibiotic resistant bacteria are a growing problem in the medical profession as doctors are prescribing second and third choice medicines when common antibiotics don’t work. In many cases, these other medicines might be less effective or cause more side effects. One particular type of bacterium, Methicillin-resistant Staphylococcus aureus (MRSA), which can be fatal in humans, is the focus of a new research project led by MU veterinarians Stephanie Kottler, Leah Cohn and John Middleton. “We used to think of these antibiotic-resistant infections as a healthcare issue that appeared in post-operative or long-term patients,” said Kottler, a resident at the MU Veterinary Medical Teaching Hospital. “However, we have been seeing more of these infec- On Monday, Supreme Court Chief Justice John Roberts suffered a “grand mal” or generalized seizure. University of Missouri-Columbia neurologist Pradeep Sahota said that seizures such as this represent abnormal electrical activity in the brain. It is like an electrical storm, Sahota said. “Depending on whether a seizure starts in a focal area, which is considered a partial seizure, or involves the whole brain (generalized seizures may involve both hemispheres), there can be many different symptoms that indicate a seizure including violent shaking, staring, and semi-automatic movements such as chewing, swallowing, blinking and repetitive hand movements,” said Sa- We Care. WARRENTON MANOR, LLC #65 Hwy. AA, Warrenton, MO 63383 Contact Tammy Reeves for more information (636) 456-8700 tions that have been acquired throughout the general population, or ‘community acquired’ infections. It’s important to know what environmental factors might be encouraging or prolonging these infections.” MRSA bacteria can live in the noses or on the skin of humans and animals where it might not produce any symptoms. The bacteria become dangerous when they enter the tissue through a cut or puncture, producing a serious infection. In some cases, the bacteria can cause life-threatening problems, such as bloodstream infections or pneumonia. While the infections are most often found in patients after hospitalization, there is an increasing occurrence of community-acquired infections among prison populations, sports teams, military personnel and the general public. Kottler believes that pets might be an important factor behind the increase in community-acquired infections. MRSA rates have increased dramatically since the 1970s. In 1974, MRSA infections accounted for two percent of the total number of staphylococcal infections; in 1995 it was 22 percent, and in 2004, it was 63 percent, according to the Centers for Disease Control. “This study will help us evaluate the various risk factors associated with this problem,” said Middleton, an associate professor of food animal internal medicine. “Are pets a risk factor? This study will help us track where the disease started and determine what questions the physician should be asking if a patient is diagnosed with MRSA.” Currently, the Mizzou researchers, aided by J. Scott Weese, an assistant professor at the University of Guelph Ontario Veterinary College in Canada, are taking samples from 750 to 800 pairs of owners and pets. To date, they have collected about 500 samples and are sorting them into three groups: human healthcare workers and pets, veterinary healthcare workers and pets, and non-healthcare professionals and pets. The study is being funded by the American College of Veterinary Internal Medicine Foundation and the MU Department of Veterinary Medicine and Surgery. MU Neurologist Says Seizures Can Indicate Brain Abnormalities hota, chair of the Department of Neurology in the MU School of Medicine. “Once a seizure has occurred, it is important to try and determine the cause. In the case of Chief Justice Roberts, it is unlikely that an abnormality such as a tumor or stroke caused the seizure because he had a previous episode many years ago and based on available information, the evaluation conducted thus far has not revealed any abnormality.” For those people near a person who has a seizure, Sahota suggests taking the following actions -Be calm - observing a person having a seizure, especially a generalized seizure with shaking, can be a scary experience. -If possible, help the person lie down in a soft place - away from hard or sharp objects because the person having a seizure might fall and injure themselves. -Loosen any tight clothing and turn the patient on his or her side to prevent choking on one’s own saliva, vomit or blood. Tongue biting also might occur during a seizure. -If the person’s mouth is closed due to forceful contraction of jaw muscles, do not try to forcibly open it. -Find a pillow (something soft) to help support the neck. -Do NOT try to stop the shaking. This is almost impossible and could result in an injury to the patient or the person trying to help. Most seizures last two to three minutes. Stay calm and help orient the person after the seizure stops. It may take several minutes before the patient is fully oriented. The key is to make sure that injury due to ongoing violent movements is prevented during the seizure, the person has nothing blocking his airway as the seizure occurs and stops and calm reassurance is given at the end to help the person to reorient after the seizure, Sahota said. If there is an ongoing breathing difficulty or the pa- THE FOCUS NEWS Friday, August 3, 2007 Page tient has choked on something, it must be addressed immediately. “Keep them on their side and let the seizure run its course - usually two to three minutes, rarely more than five minutes,” Sahota said. “It could take the person several minutes to re- Research on the DNA of 15 mouse strains commonly used in biomedical studies is expected to help scientists determine the genes related to susceptibility to environmental disease. The body of data is now publicly available in a catalog of genetic variants, which displays the data as a mouse haplotype map, a tool that separates chromosomes in to many small segments, helping researchers find genes and genetic variations in mice that may affect health and disease. The haplotype map appearing online in the July 29th issue of Nature is the first published full descriptive analysis of the “Mouse Genome Resequencing and SNP Discovery Project” conducted by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health. “These data allow researchers to compare the genetic makeup of one mouse strain to another, and perform the necessary genetic analyses to determine why some individuals might be more susceptible to disease than another. This puts us one step closer to understanding individual susceptibility to environmental toxins in humans. We also hope that pharmaceutical companies developing new treatments for environmental diseases will find these data and this paper as a valuable resource,” said David A. Schwartz. M.D., NIEHS Director. The paper describes in detail the laborious and technology-driven approaches that were used to identify 8.27 million high quality SNPs distributed among the genomes of 15 mouse strains. Single Nucleotide Polymorphisms, or SNPs (known as snips), are single genetic changes, or variations, that can occur in a DNA sequence. Much of the project was conducted through a contract between the National Toxicology Program at NIEHS and Perlegen Sciences, Inc. of Mountain View Calif. “The database of mouse genetic variation should facilitate a wide range of important biological studies, and helps demonstrate the utility of this array technology approach,” said David R. Cox, M.D., Ph.D., chief scientific officer at Perlegen Sciences, Inc. orient after the seizure is over. After the first seizure, the person should get a complete neurological exam to try and discover the cause of the seizure. A seizure is just a symptom and can occur in many different situations.” Mouse Genome Will Help Identify Causes of Environmental Disease The Perlegen scientists used C57BL/6J the first mouse strain to undergo DNA sequencing as their standard reference to conduct the re-sequencing on the four wild-derived and eleven classical mouse strains. The technology used, the oligonucleotide array, was also used to discover common DNA variation in the human genome. The arrays looked at about 1.49 billion bases (58 percent) of the 2.57 billion base pair of their standard reference strain. The data were then used to develop the haplotype map which contains 40,898 segments. “The data will be a valuable resource to many, including the National Toxicology Program,” Schwartz says. The National Toxicology Program (NTP) is an interagency program, headquartered at NIEHS, with the mission to coordinate, conduct and communicate toxicological research across the U.S. government. “The NTP is looking forward to exploring the responses of these strains of mice to various environmental agents,” said John Bucher, Ph.D., the new associate director of the NTP. Frank M. Johnson, Ph. D., an NTP research geneticist and one of the authors of the Nature paper, adds that systematically characterizing even more mouse strains for susceptibility to toxins will not only help with genetic analysis, but better position researchers to do intervention studies. The data are publicly available on the National Center for Biotechnology Information Web site at http://www.ncbi.nlm.nih. gov/SNP/ and at a Web site developed by Perlegen at http:// mouse.perlegen.com which allows researchers to download SNPs, genotypes, and LR-PCR primer pairs, which are currently mapped to NCBI Build 36. In addition to the NTP and Perlegen Sciences scientists, other key collaborators on the project include researchers from the Department of Computer Science and Department of Human Genetics, University of California, Los Angeles; the Department of Computer Science and Engineering, University of California, San Diego; The Jackson Laboratory, Bar Harbor, Maine; Broad Institute of Harvard and MIT; and the Center for Human Genetic Research, Massachusetts General Hospital.
Health Genetic Finding Sheds Light on Diseases Causing Blood Vessel Breakdown By Michael Purdy Twenty-one years after they first described a fatal genetic disorder in Missouri and Arkansas families, scientists at Washington University School of Medicine in St. Louis have linked the condition to mutations in a gene known as TREX1. The study appears online in Nature Genetics. The identification will accelerate efforts to understand and treat retinal vasculopathy with cerebral leukodystrophy (RVCL), a rare condition that usually goes unrecognized or is misdiagnosed. In Asian and Caucasian patients with the disease, a complex and ultimately fatal barrage of primarily central nervous system symptoms begins around age 45 that includes vision loss, mini-strokes and dementia. The symptoms can also mimic a brain tumor or multiple sclerosis. After onset, RVCL is fatal in 10 years or less. Because small blood vessels in the back of the eye and the brain disappear in patients with RVCL, the new link could have important relevance to a much broader range of health problems affecting the elderly, including common diseases like diabetes that also alter microvessels. “Why TREX1 mutations would suddenly cause these blood vessels to start disap- pearing at midlife is a mystery,” says senior author John Atkinson, M.D., the Samuel Grant Professor of Medicine and professor of molecular microbiology. “But now that we have this link, what it teaches us about the health and maintenance of these blood vessels also may help a great deal in understanding and preventing their loss in aging and in diabetes.” Also on the list of disorders linked to blood vessel loss is vascular dementia, a condition that causes memory loss, disorientation, and emotional problems in the elderly. In the United States, vascular dementia is the second-leading cause of these kinds of symptoms after Alzheimer’s disease; in some Asian nations, it is the leading cause of dementia. Gil Grand, M.D., professor of clinical ophthalmology and visual sciences at Washington University, and Atkinson led the research team that in 1986 first reported RVCL as a novel human disease. Since then, researchers have identified other families with RVCL in Europe, Australia and Taiwan. In 2002, Atkinson’s group and colleagues at other institutions tied the condition to a portion of the third chromosome. Unfortunately, the region is rich with more than 150 complex genes, and initial attempts to locate the specific gene that Bring in your paid eye exam receipt & receive up to $ 45 OFF OR Receive 45% OFF a complete pair of glasses or a 6 month supply of disposable contacts Eye Exams available here through independent doctor of optometry * Not valid with any other offers. **Offers cannot be combined. (636) 528-4444 #19 Ellis Avenue Troy, MO 63379 www.info@heres2eyes.com causes RVCL were unsuccessful. With a grant from the Genome Sequencing Center (GSC) at Washington University, scientists recently began a new attempt. The lead researcher, Anna Richards, M.D., Ph.D., at that time a member of the Atkinson lab and now clinical lecturer in nephrology, Royal Infirmary, Edinburgh, elected to begin the search with a simple gene whose structure made it easiest to sequence. In a stroke of good fortune, that gene, TREX1, turned out to be the gene they were looking for. In the 10 families scientists studied, they found that family members with RVCL consistently had one of five different TREX1 mutations. A small but rapidly expanding body of scientific literature already exists on TREX1, which is an important mammalian gene. It is active in almost all cells, where it proofreads DNA for errors and helps correct those mistakes. Cells sometimes introduce such errors into DNA when they copy it prior to cell division, and environmental factors like radiation and reactive chemicals can also create errors. According to Atkinson, though, there’s little in the limited TREX1 literature to suggest why mutations in the gene should cause small blood vessels to start dying off in middleaged RVCL patients. This implies that TREX1 may have a fundamental role in maintaining the health of small blood vessels that has previously gone unrecognized. “We’re going to be working very hard to understand everything we can about TREX1 to try to give us some hints about what’s happening to people with RVCL and how we can help,” Atkinson says. “What we learn may provide insights into why these same vessels sometimes start to die off in the elderly, leading to a variety of complications. The disease was discovered here in St. Louis, its genetic basis was identified by the GSC, and now our goal is to find a treatment.” Atkinson’s lab has already identified a lead. They were able to show that two of the mutations they identified in RVCL patients create a tailless form of the TREX1 protein that can’t properly anchor itself to the part of the cell where it normally does its job. Scientists are currently studying whether this dislocation could have any links to the damage that occurs in RVCL. THE FOCUS NEWS Friday, August 3, 2007 Page 7 Gene Therapy Using Adeno- Associated Virus Linked to Liver Cancer in Mice By Caroline Arbanas Researchers at Washington University School of Medicine in St. Louis have found further evidence linking a method used to deliver gene therapy in humans with the development of liver tumors in mice. The new research, published in the July 27 journal Science, suggests that ferrying a corrective gene into mice using a disabled virus - an adeno-associated virus (AAV) - inadvertently inserts mutations into the mouse DNA that initiate tumor growth. The same delivery method is also used in some gene therapy clinical trials in humans, but as of yet no studies have found an association between the AAV vector and cancer in patients. Still, the Washington University scientists, led by Mark Sands, Ph.D., associate professor of medicine and genetics, say the data in the team’s latest study raise important safety concerns about the use of AAV vectors in patients receiving experimental gene therapy. “While the findings do not eliminate AAV as a potential therapeutic tool, more research is needed to determine the possible longterm toxicity of the AAV vector in humans,” Sands cautions. The current study is a follow-up to Sands’ earlier work, published in 2001 in the journal Gene Therapy, which first suggested an association between AAV and liver cancer in mice. However, that study involved only five mice that had been found to develop liver tumors after the animals lived 18 months, about a year longer than is typical for this type of research. Based on Sands’ research in mice, two human AAV gene therapy trials were briefly halted. The AAV vector has been evaluated in gene therapy clinical trials for cystic fibrosis, hemophilia, Parkinson’s disease, Duchenne’s muscular dystrophy and other diseases. Sands undertook the new research attempting to con- firm his previous findings and to determine how the AAV vector might encourage tumor development. He studies a disease in mice that mimics mucopolysaccharidosis type VII (MPS VII), also know as Sly syndrome in humans. This extremely rare lysosomal storage disease affects only about 1 in 250,000 babies, who are born with two disabled copies of the beta-glucuronidase gene. They are unable to manufacture an enzyme that cells need to properly degrade a certain type of complex carbohydrate. Babies born with the disease often appear healthy at birth, but within a short time they develop skeletal abnormalities and mental retardation. Most do not survive past early adulthood. Sands has been investigating gene therapy in mice as a stepping stone to a potential treatment for the disease in patients. His research, funded by the National Institutes of Health, uses AAV to insert a corrective human gene for beta-glucuronidase into newborn MPS VII mice. Sands has shown he can essentially cure the disease in mice if they are treated immediately after birth, before symptoms of the disease develop. Waiting even one week means that researchers miss the window of opportunity to effectively intervene against the disease. The current report in Science details the association between the AAV vector and liver tumors in more than 150 newborn mice that were divided into various treatment groups. The researchers found that 33 percent (6/18) of the MPS VII mice that received the AAV-directed gene therapy developed liver cancer. To eliminate the possibility that the liver cancer was tied to the lysosomal storage disease itself and not the AAV vector, Sands and his team gave bone marrow transplants to another group of MPS VII mice. The procedure extends CONTINUED ON PAGE 15 A Clear Alternative To Braces! Invisalign is a method of straightening teeth using a series of clear, almost invisible, removable Aligners. It’s a “clear alternative to wires and brackets.” Have you ever wondered what you would look like with straight teeth? With ClinCheck, a virtual 3-D software, we are able to show you how your teeth would look when the invisalign treatment is complete. Call today for a free consultation. (636) 456-2454 Dr. Jerry Paz www.pazdental.com
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August 3, 2007 - The Focus News

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