OREGON STATE UNIVERSITY

college of veterinary medicine

Research could lead to new cancer assay, aid both dogs and humans

CORVALLIS, Ore. – Veterinary researchers at Oregon State University have identified a unique group of proteins that indicate the presence of transitional cell carcinoma – the most common cause of bladder cancer – and may lead to a new assay which could better diagnose this disease in both dogs and humans.

Bladder cancer is particularly common in some dog breeds, such as collies, sheepdogs and terriers, but is rarely diagnosed in animals before it has spread significantly. Some assays exist to detect it in humans, but they often have a high-number of false-positive identifications.

An improved assay to detect this serious disease much earlier in both animals and humans should be possible, scientists said, and may even become affordable enough that it could be used as an over-the-counter product to test urine, much like a human pregnancy test. Some of the work may also contribute to new therapies, they said.

“Research of this type should first help us develop a reliable assay for this cancer in dogs, and improve the chance the disease can be caught early enough that treatments are effective,” said Shay Bracha, an assistant professor in the OSU College of Veterinary Medicine.

“However, this type of cancer is essentially the same in dogs and humans,” Bracha said. “Dogs are an excellent model for human cancer research, and an assay that works with dogs should be directly relevant to creation of a similar assay for humans. We hope to make it inexpensive and convenient, something that people could use routinely to protect either the health of their pets or themselves.”

The findings were published recently in Analytical Chemistry, a professional journal.

In this research, scientists used mass spectrometry and the evolving science of proteomics to identify 96 proteins that appear related to transitional cell carcinoma. This is a fairly common cancer in dogs, often as a result of exposure to pesticides, herbicides, and poor quality foods; and in humans is closely related to smoking.

Advanced-stage disease in both dogs and humans has a poor prognosis, as chemotherapy and radiation treatments are often ineffective. Average survival time is less than one year. Some assays exist to help identify the disease in humans but can produce false positive results, often as a result of urinary tract infections. And the biopsies used to make a definitive diagnosis require general anesthesia and also run the risk of actually spreading the disease.

The group of proteins identified in this research already have a 90 percent accuracy, and researchers say they hope to improve upon that with continued research.

However, researchers say that some of these proteins are more than just biomarkers of the disease – they are part of the disease process. Identifying proteins that are integral to the spread of the cancer may allow new targets for intervention and cancer therapies, they said.

Collaborators on this research included the OSU Department of Chemistry. A mathematical model that was integral to the study was created by Jan Medlock, an OSU assistant professor of veterinary medicine, and veterinary researchers Michael McNamara and Ian Hilgart helped initiate the project. The work was supported in part by the National Institutes of Health.

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Shay Bracha, 541-737-4844

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Border collie

Border collie

OSU assisting in alpaca rescue operation

CORVALLIS, Ore. - The last of about 175 imperiled alpacas that are being removed from a farm near Falls City, Ore., will arrive today or early this week at Oregon State University as part of a continuing rescue operation to help care for and save the lives of these animals.

Transport began late last week but only 54 got through, and operations had to be suspended due to the heavy winter storm, a traffic accident and difficult travel conditions. A team of doctors and veterinary students at OSU will now work with the incoming animals to assess their health, do necessary procedures, improve their nutritional status and aid their recovery.

Owners of the ranch that had housed the alpacas are facing legal charges in Polk County. Meanwhile, the College of Veterinary Medicine has volunteered its facilities to help continue the rescue operation that was begun by the Polk County Sheriff’s Department and Cross Creek Alpaca Rescue volunteers.

Ultimately, all of the animals will be made available for adoption, officials said.

“The OSU College of Veterinary Medicine is one of the few agencies in Oregon that has the ability and expertise to manage an operation of this size,” said Helen Diggs, a professor of veterinary medicine and director of the OSU Laboratory Animal Resources Center. “The Research Office at OSU has also made it clear that we will do what we can to help with this difficult situation.”

Although travel is still difficult, officials hope that most of the remaining alpacas will arrive today or early this week at the Research Animal Isolation Laboratory, one of the campus facilities large enough to handle so many animals at once. Some with special needs are also being treated in the large animal hospital in Magruder Hall on the OSU campus.

“Many of these animals are very thin and we’ve been told that a substantial number have already died,” said Chris Cebra, a professor of large animal internal medicine in the College of Veterinary Medicine, and an expert in the treatment of camelids such as llamas and alpacas.

“From what we’ve seen, we’ll be dealing with malnutrition, heavy parasite loads, some pregnant animals, newborns, and various health conditions,” Cebra said. “We’ll continue to feed the animals, assess and treat medical conditions, check vaccination status, and generally improve their quality of life and suitability for a new home.”

Given the unusually large influx of animals at one time, a number of supervised veterinary students will also work in the rescue operation, allowing them a substantial amount of hands-on training while helping veterinary doctors more quickly and effectively give the entire herd the treatment it needs.

Once the alpacas recover their health, adoption will be possible from the Polk County Sheriff’s Office, which is working with Cross Creek Alpaca Rescue to identify suitable placements. Initial inquiries for adopting one or more of the animals may be directed to Cross Creek Alpaca Rescue, at http://www.crosscreekalpacarescue.org/.

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Helen Diggs, 541-737-6213

 

Chris Cebra, 541-737-4456

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Alpaca

Alpaca needs care


Alpacas being fed

Alpacas being fed

Amber fossil reveals ancient reproduction in flowering plants

CORVALLIS, Ore. – A 100-million-year old piece of amber has been discovered which reveals the oldest evidence of sexual reproduction in a flowering plant – a cluster of 18 tiny flowers from the Cretaceous Period – with one of them in the process of making some new seeds for the next generation.

The perfectly-preserved scene, in a plant now extinct, is part of a portrait created in the mid-Cretaceous when flowering plants were changing the face of the Earth forever, adding beauty, biodiversity and food. It appears identical to the reproduction process that “angiosperms,” or flowering plants still use today.

Researchers from Oregon State University and Germany published their findings on the fossils in the Journal of the Botanical Institute of Texas.

The flowers themselves are in remarkable condition, as are many such plants and insects preserved for all time in amber. The flowing tree sap covered the specimens and then began the long process of turning into a fossilized, semi-precious gem. The flower cluster is one of the most complete ever found in amber and appeared at a time when many of the flowering plants were still quite small.

Even more remarkable is the microscopic image of pollen tubes growing out of two grains of pollen and penetrating the flower’s stigma, the receptive part of the female reproductive system. This sets the stage for fertilization of the egg and would begin the process of seed formation – had the reproductive act been completed.

“In Cretaceous flowers we’ve never before seen a fossil that shows the pollen tube actually entering the stigma,” said George Poinar, Jr., a professor emeritus in the Department of Integrative Biology at the OSU College of Science. “This is the beauty of amber fossils. They are preserved so rapidly after entering the resin that structures such as pollen grains and tubes can be detected with a microscope.”

The pollen of these flowers appeared to be sticky, Poinar said, suggesting it was carried by a pollinating insect, and adding further insights into the biodiversity and biology of life in this distant era. At that time much of the plant life was composed of conifers, ferns, mosses, and cycads.  During the Cretaceous, new lineages of mammals and birds were beginning to appear, along with the flowering plants. But dinosaurs still dominated the Earth.

“The evolution of flowering plants caused an enormous change in the biodiversity of life on Earth, especially in the tropics and subtropics,” Poinar said.

“New associations between these small flowering plants and various types of insects and other animal life resulted in the successful distribution and evolution of these plants through most of the world today,” he said. “It’s interesting that the mechanisms for reproduction that are still with us today had already been established some 100 million years ago.”

The fossils were discovered from amber mines in the Hukawng Valley of Myanmar, previously known as Burma. The newly-described genus and species of flower was named Micropetasos burmensis.

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George Poinar, 541-752-0917

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Ancient flowers

Ancient flower


Pollen tubes

Pollen tubes

Innovative approach could ultimately end deadly disease of sleeping sickness

CORVALLIS, Ore. – A tag team of two bacteria, one of them genetically modified, has a good chance to reduce or even eliminate the deadly disease African trypanosomiasis, or sleeping sickness, researchers at Oregon State University conclude in a recent mathematical modeling study.

African trypanosomiasis, caused by a parasite carried by the tsetse fly, infects 30,000 people in sub-Saharan Africa each year and is almost always fatal without treatment. In a 2008 epidemic, 48,000 people died.

In this research, scientists evaluated the potential for success of a new approach to combat the disease – creating a genetically modified version of the Sodalis bacteria commonly found in the gut of the flies that carry the disease, and using different bacteria called Wolbachia to drive the GMO version of Sodalis into fly populations.

When that’s done, the GMO version of Sodalis would kill the disease-causing trypanosome parasite. According to the analysis published in PLOS Neglected Tropical Diseases, researchers say this should work – and could offer a model system for other tropical, insect-carried diseases of even greater importance, including dengue fever and malaria.

“There are a few ‘ifs’ necessary for this to succeed, but none of them look like an obstacle that could not be overcome,” said Jan Medlock, an assistant professor in the OSU Department of Biomedical Sciences, and lead author on the new report.

“If everything goes right, and we are optimistic that it will, this could be enormously important,” Medlock said. “There’s a potential here to completely solve this disease that has killed many thousands of people, and open new approaches to dealing with even more serious diseases such as malaria.”

Some of the “ifs” include: the transgenic Sodalis has to be reasonably effective at blocking the parasite, at or above a level of about 85 percent; the Wolbachia bacteria, which has some effect on the health of flies affected with it, must not kill too many of them; and the target species of fly has to be a majority of the tsetse flies in the areas being treated.

The research shows that dealing with all of those obstacles should be possible. If so, this might spell the end of a tropical disease that has plagued humans for hundreds, possibly thousands of years. African trypanosomiasis causes serious mental and physical deterioration – including the altered sleep patterns that give the disease its name – and is fatal without treatment. It’s still difficult to treat, and neurologic damage is permanent.

Past efforts to control the disease, including insect traps, insecticide spraying, and use of sterile insects have been of some value, but only in limited areas and the effects were not permanent.

The strength of the new approach, researchers say, is that once the process begins it should spread and be self-sustaining - it should not be necessary to repeatedly take action in the huge geographic areas of Africa. Due to some genetic manipulation, the flies carrying the Wolbachia bacteria should naturally increase their populations and have an inherent survival advantage over conventional tsetse flies.

As the flies carrying transgenic bacteria continue to dominate and their populations spread, trypanosomiasis should fairly rapidly disappear. Whether the mechanism of control could wane in effectiveness over time is an issue that requires further study, scientists said.

Work has begun on the GMO version of Sodalis that has the capability to resist trypanosomes . It’s not yet finalized, Medlock said, but it should be possible, and when complete, the bacteria will be very specific to tsetse flies.

Medlock, an expert in modeling the transmission of various diseases – including human influenza – says the analysis is clear that this approach has significant promise of success. Because of the relatively low infectiousness of the parasite and the ability of Wolbachia to drive the resistance genes, no part of the system has to be 100 percent perfect in order to ultimately achieve near eradication of this disease, he said.

Accomplishing a similar goal with diseases such as malaria may be more difficult, he said, because that disease historically has shown a remarkable ability to mutate and overcome many of the approaches used to attack it. However, at least some near-term gains may be possible, he said.

Collaborators on this study included scientists from the OSU College of Veterinary Medicine and the Yale School of Public Health. It was supported by the National Institutes of Health and the Miriam Weston Trust.

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Jan Medlock, 541-737-6874

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Tsetse fly

Tsetse fly

Gut microbes closely linked to range of health issues

CORVALLIS, Ore. –A new understanding of the essential role of gut microbes in the immune system may hold the key to dealing with some of the more significant health problems facing people in the world today, Oregon State University researchers say in a new analysis.

Problems ranging from autoimmune disease to clinical depression and simple obesity may in fact be linked to immune dysfunction that begins with a “failure to communicate” in the human gut, the scientists say. Health care of the future may include personalized diagnosis of an individual’s “microbiome” to determine what prebiotics or probiotics are needed to provide balance.

Appropriate sanitation such as clean water and sewers are good. But some erroneous lessons in health care may need to be unlearned – leaving behind the fear of dirt, the love of antimicrobial cleansers, and the outdated notion that an antibiotic is always a good idea. We live in a world of “germs” and many of them are good for us.

“Asked about their immune system, most people might think of white blood cells, lymph glands or vaccines,” said Dr. Natalia Shulzhenko, author of a new report in Clinical Reviews in Allergy and Immunology, and assistant professor and physician in the OSU Department of Biomedical Sciences. “They would be surprised that’s not where most of the action is. Our intestines contain more immune cells than the entire rest of our body.

“The human gut plays a huge role in immune function,” Shulzhenko said. “This is little appreciated by people who think its only role is digestion. The combined number of genes in the microbiota genome is 150 times larger than the person in which they reside. They do help us digest food, but they do a lot more than that.”

An emerging theory of disease, Shulzhenko said, is a disruption in the “crosstalk” between the microbes in the human gut and other cells involved in the immune system and metabolic processes.

“In a healthy person, these microbes in the gut stimulate the immune system as needed, and it in turn talks back,” Shulzhenko said. “There’s an increasing disruption of these microbes from modern lifestyle, diet, overuse of antibiotics and other issues. With that disruption, the conversation is breaking down.”

An explosion of research in the field of genomic sequencing is for the first time allowing researchers to understand some of this conversation and appreciate its significance, Shulzhenko said. The results are surprising, with links that lead to a range of diseases, including celiac disease and inflammatory bowel disease. Obesity may be related. And some studies have found relevance to depression, late-onset autism, allergies, asthma and cancer.

In the new review, researchers analyzed how microbe dysfunction can sometimes result in malabsorption and diarrhea, which affects tens of millions of children worldwide and is often not cured merely by better nutrition. In contrast, a high-fat diet may cause the gut microbes to quickly adapt to and prefer these foods, leading to increased lipid absorption and weight gain.

The chronic inflammation linked to most of the diseases that kill people in the developed world today – heart disease, cancer, diabetes – may begin with dysfunctional gut microbiota.

Understanding these processes is a first step to addressing them, Shulzhenko said. Once researchers have a better idea of what constitutes healthy microbiota in the gut, they may be able to personalize therapies to restore that balance. It should also be possible to identify and use new types of probiotics to mitigate the impact of antibiotics, when such drugs are necessary and must be used.

Such approaches are “an exciting target for therapeutic interventions” to treat health problems in the future, the researchers concluded.

The study, supported by OSU, included researchers from both the College of Veterinary Medicine and the College of Pharmacy.

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Dr. Natalia Shulzhenko, 541-737-1051

Smithsonian mobile exhibit on May 19 explores the human-animal bond

 

CORVALLIS, Ore. - The special relationship between humans and animals is explored in a new mobile exhibit from the Smithsonian Institution, which will be open in the Reser Stadium parking lot at Oregon State University on Monday, May 19.

“Animal Connections: Our Journey Together,” a custom-built exhibition housed on an 18-wheel truck that expands into 1,000 square feet of space, is traveling throughout the United States. It’s free, and will be open to the public in Corvallis from 9:30 a.m. to 4:30 p.m.

“Animal Connections” marks the 150th anniversary of the American Veterinary Medical Association, and the exhibit is made possible through the support of founding sponsor Zoetis, Inc., and the AVMA.

A video of the exhibit is available online, at animalconnections.com

The exhibition focuses on animals in the home, on the farm, at the zoo, in the wild and at the veterinary clinic. Visitors are offered a variety of ways to learn through informative displays, dynamic videos and interactive experiences. The exhibit also highlights the roles veterinarians play in the health of animals.

“At the AVMF, we are committed to advancing the well-being and medical care of animals,” said Michael Cathey, AVMF executive director. “This exhibition will not only help inspire the next generation of veterinarians, but improve current animal care through a better understanding of the role animals and veterinarians play in our lives.”

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OSU Pet Day planned for May 3

CORVALLIS, Ore. - Oregon State University will hold its 27th annual Pet Day on Saturday, May 3, when the College of Veterinary Medicine opens its doors for tours, booths, displays and a number of family-oriented events.

Pets are welcome at this always-popular event, on a leash.

Pet Day is designed as a way for the College of Veterinary Medicine to give back to the community, and help Oregon residents understand its operations and legacy of public service. It usually attracts 3,000-4,000 visitors, many who bring their pets. The child-friendly event, which will be held rain or shine, is created, organized, and staffed by students.

Vendors and volunteers from organizations will staff booths at the event and provide information on animal health and wellness, nutrition, adoption and therapy.  Many also provide free samples and other resources, spanning the four-legged gamut from pet food to shelter medicine.

Among the returning activities will be dog agility demonstrations, live reptiles, a petting zoo, tours of the Veterinary Teaching Hospital, a pet costume contest, a dog frisbee show, a cat photo contest, and more. Food booths are also available.

Participants and their pets may join the Fun Run/Walk event at 9 a.m.; online preregistration for that event is requested by April 18. 

Pet Day runs from 10 a.m. to 4 p.m. at Magruder Hall, located on 30th Street in Corvallis just south of Washington Way, and adjacent to the athletic department’s Truax Indoor Center. Admittance and most activities are free, but there is a small charge for a few of the events.

More detailed information on the various events and registration for the fun run/walk is available online at http://vetmed.oregonstate.edu/pet-day

Pet Day is sponsored by the College of Veterinary Medicine, and supported by Banfield Pet Hospital, Hill’s Pet Nutrition, Zoetis, Nestle Purina Pet Care Co., the Oregon Animal Health Foundation and the Student Chapter of the American Veterinary Medical Association.

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Veterinary hospital resuming normal operation after equine influenza outbreak

CORVALLIS, Ore. – The Veterinary Teaching Hospital at Oregon State University has resumed normal operations following an outbreak of equine influenza, which for the past two weeks kept it from accepting horses for anything but emergency services.

There were six confirmed cases of equine influenza, a highly contagious respiratory disease in horses that usually isn’t fatal, but is a particular concern to foals and pregnant horses, since it can cause abortion. The original source of the infection appears to be a horse admitted to the hospital. Four horses are still shedding the virus but are now contained in an isolation facility, and all are expected to make a full recovery.

All horses in the Large Animal Hospital are testing negative for the virus, and stalls have been disinfected, then left empty for at least 48 hours, an adequate time to kill any remaining flu virus in a dry environment.

“We’d like to thank all of our clients for their patience and cooperation while we worked through this issue,” said Ron Mandsager, interim associate director of the Lois Bates Acheson Veterinary Teaching Hospital. “The most important thing is to protect the health of all our animals. Unfortunately, equine influenza is endemic in the U.S. and sometimes these situations occur.”

Equine influenza is not transferable to humans or other animal species, but can spread rapidly among horses and other equines. It is the most common contagious respiratory pathogen for horses and most animals fully recover. However, young, elderly or pregnant animals are more at-risk for viral diseases such as equine influenza.

“The incident should be a reminder to all horse owners,” said Keith Poulsen, associate professor of large animal internal medicine. “It’s important to vaccinate their animals, practice good biosecurity, and monitor horses closely when they are in contact with other horses during and after events like fairs, competitions and trail rides.”

The first clinical sign of this disease in horses is typically a fever, followed by cough, nasal discharge and lethargy. Horses with a fever of greater than 102.5 degrees should be seen by a veterinarian.

Anyone who has concerns about the health of their animals should contact their veterinarian or the Lois Bates Acheson Veterinary Teaching Hospital at OSU, at 541-737-2858 or http://vetmed.oregonstate.edu/

Hospital officials say they plan to investigate the impact the outbreak has had on hospital operations and the local equine community.

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Keith Poulsen, 541-737-6939

Cognitive decline with age is normal, routine – but not inevitable

CORVALLIS, Ore. – If you forget where you put your car keys and you can’t seem to remember things as well as you used to, the problem may well be with the GluN2B subunits in your NMDA receptors.

And don’t be surprised if by tomorrow you can’t remember the name of those darned subunits.

They help you remember things, but you’ve been losing them almost since the day you were born, and it’s only going to get worse. An old adult may have only half as many of them as a younger person.

Research on these biochemical processes in the Linus Pauling Institute at Oregon State University is making it clear that cognitive decline with age is a natural part of life, and scientists are tracking the problem down to highly specific components of the brain. Separate from some more serious problems like dementia and Alzheimer’s disease, virtually everyone loses memory-making and cognitive abilities as they age. The process is well under way by the age of 40 and picks up speed after that.

But of considerable interest: It may not have to be that way.

“These are biological processes, and once we fully understand what is going on, we may be able to slow or prevent it,” said Kathy Magnusson, a neuroscientist in the OSU Department of Biomedical Sciences, College of Veterinary Medicine, and professor in the Linus Pauling Institute. “There may be ways to influence it with diet, health habits, continued mental activity or even drugs.”

The processes are complex. In a study just published in the Journal of Neuroscience, researchers found that one protein that stabilizes receptors in a young animal – a good thing conducive to learning and memory – can have just the opposite effect if there’s too much of it in an older animal.

But complexity aside, progress is being made. In recent research, supported by the National Institutes of Health, OSU scientists used a genetic therapy in laboratory mice, in which a virus helped carry complementary DNA into appropriate cells and restored some GluN2B subunits. Tests showed that it helped mice improve their memory and cognitive ability.

The NMDA receptor has been known of for decades, Magnusson said. It plays a role in memory and learning but isn’t active all the time – it takes a fairly strong stimulus of some type to turn it on and allow you to remember something. The routine of getting dressed in the morning is ignored and quickly lost to the fog of time, but the day you had an auto accident earns a permanent etching in your memory.

Within the NMDA receptor are various subunits, and Magnusson said that research keeps pointing back to the GluN2B subunit as one of the most important. Infants and children have lots of them, and as a result are like a sponge in soaking up memories and learning new things. But they gradually dwindle in number with age, and it also appears the ones that are left work less efficiently.

“You can still learn new things and make new memories when you are older, but it’s not as easy,” Magnusson said. “Fewer messages get through, fewer connections get made, and your brain has to work harder.”

Until more specific help is available, she said, some of the best advice for maintaining cognitive function is to keep using your brain. Break old habits, do things different ways. Get physical exercise, maintain a good diet and ensure social interaction. Such activities help keep these “subunits” active and functioning.

Gene therapy such as that already used in mice would probably be a last choice for humans, rather than a first option, Magnusson said. Dietary or drug options would be explored first.

“The one thing that does seem fairly clear is that cognitive decline is not inevitable,” she said. “It’s biological, we’re finding out why it happens, and it appears there are ways we might be able to slow or stop it, perhaps repair the NMDA receptors. If we can determine how to do that without harm, we will.”

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Kathy Magnusson, 541-737-6923

OSU names Susan Tornquist interim dean of veterinary medicine

CORVALLIS, Ore. – Susan Tornquist, associate dean in the College of Veterinary Medicine at Oregon State University, has been named interim dean of the college.

She succeeds Cyril Clarke, who will become dean of the Virginia-Maryland Regional College of Veterinary Medicine effective Oct. 1.

Tornquist has been on the faculty at Oregon State since 1996, most recently as associate dean of student and academic affairs in OSU’s College of Veterinary Medicine, where she also is a professor of clinical pathology. Her research interests have focused on immune responses to infectious and metabolic diseases in animals, particularly llama and alpacas.

As associate dean Tornquist has helped the college grow its enrollment, coordinate student internships, build partnerships with the Oregon Humane Society and other organizations, and make student experiential learning a hallmark of the program.

Tornquist received her veterinary medical degree from Colorado State University and her doctorate in veterinary pathology from Washington State University.

Sabah Randhawa, OSU provost and executive vice president, said Tornquist will transition into the role of interim dean over the next several weeks. He has begun a national search to fill Clarke’s position.

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Sabah Randhawa, 541-737-2111