Ticks untold

Prime suspects in mystery fevers may hold new tick-borne diseases
Suddenly your horse is sick and you don’t know why. She breathes normally but her temperature is rising, her eyes grow yellow with jaundice, she seems depressed, and barely eats. The fever is clear but the cause is not; even the most experienced experts can offer no concrete answers. Eventually the fever fades, but is that the end of whatever caused it or is the source still lurking somewhere inside?

Horse owners across the states are facing this distressing scenario. At the Cornell University Animal Health Diagnostic Center (AHDC), Dr. Linda Mittel fields a growing number of calls about these mysterious fevers of unknown origins (FUOs). Many come from the Northeast, Mid-Atlantic, and Great Lakes areas: the nation’s topmost hotbeds of human tick-borne disease. This pattern led Mittel to suspect that the culprits of the fever caper could be ticks and the difficult-to-diagnose diseases they carry.

“Tick-borne diseases are some of the fastest growing emerging diseases in the United States right now,” said Mittel. “As ticks continue expanding their numbers and geographic range these diseases may affect new areas. We get calls about fevers at broodmare operations, showbarns, and farms where race horses rest or layup, even in areas where they didn’t know they had ticks. But horses moving between states can move ticks with them, and the effects of this movement are starting to show.”

Mittel and colleagues at the AHDC are embarking on a project to find just what diseases ticks in hotbed zones are carrying and whether they are behind the wash of mystery fevers in horses. The study will use samples from horses suffering FUOs to look for bacterial infections known to be transmitted by ticks (Anaplasma, Babesia, Borrelia, Ehrlichia, and Rickettsia) as well as other bacteria known to cause non-respiratory infection in horses (Leptospira, Bartonella, and Neorickettsia.)

These agents are considered emerging infectious diseases in humans, and this will be the first study determining their presence in horses with FUOs. The study will also sample ticks found on or near horses in designated areas to find which pathogens they carry and to potentially discover previously undocumented tick-borne pathogens.

Many tick-borne diseases are sensitive to specific drugs; others are not sensitive to antibiotics at all. Knowing which diseases are at the root of FUOs will help veterinarians treat them effectively. It will also help owners understand how the causes of fevers might impact affected horses’ futures in racing, performance, or showmanship.

“I’m quite excited to start solving the mysteries of these fevers and to possibly uncover new previously unrecognized diseases – in horses and people,” said Mittel. “If these agents are in the horses, humans may also have them without realizing– people who work with these horses might be particularly at risk. Knowing what we’re dealing with here will hopefully solve the mystery of FUOs and help equine and human medicine recognize and address the growing onslaught of tick-borne disease.”

This research is funded by the Harry M. Zweig Memorial Fund for Equine Research.

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Mike meets Minnie

Cornell University’s Hospital for Animals welcomes its newest resident: Minnie the miniature horse. Minnie’s stint at the hospital as a patient turned into a career as a companion when her owner generously donated her after learning the Hospital was seeking company for Mike, the College’s blood-donor draft-horse.

“Mike lived by himself, and horses are herd animals that do better in groups,” said Dr. Sally Ness, internal medicine resident.

Good timing is a great matchmaker, and despite the size difference the unlikely pair clicked. Minnie has also become a star attraction at the College’s Annual Open House, where she made her first public debut in April 2012 by popular request.

“Twenty kids lined up along the paddock fence asking to ‘pet the pony,’” said Ness. “Students spiffed her up with ribbons, and she was a huge hit. Mike loves his new pal and was actually a little concerned when we borrowed her for the festivities. They are fully moved in together and share his stall and paddock. She is definitely the boss:we were worried about Mike stealing her grain, but in fact she will finish and go over and push him away from his breakfast! But he seems to appreciate the company and doesn’t seem to mind.”

Dr. Cynthia Leifer honored with 2012 Pfizer Animal Health Award

LeiferDr. Cynthia Leifer, assistant professor of immunology at Cornell University’s College of Veterinary Medicine, has been selected to receive the Pfizer Animal Health Award for Veterinary Research Excellence. The award fosters innovative research by recognizing outstanding research and productivity from a faculty member early in his or her career. Nominees are selected for innovative research relevant to animal health that is likely to make national impact.

Leifer’s research sheds light on the currently cloudy causes of autoimmune disease by uncovering inner workings of the innate immune system. Afflicting one in five Americans, autoimmune diseases include a wide array of disorders from rheumatoid arthritis to the skin disease Lupus to irritable bowel syndrome.

“The immune system fights to protect us against invading microorganisms,” said Leifer. “But it must also recognize what to attack and keep its aggressive responses under control to prevent damaging our own bodies.”

When recognition and regulation fail, the immune system can attack the body and lead to autoimmune disorders. Leifer explores how immune cell receptors affect the way these cells recognize and respond to whatever they encounter, whether it’s a microbial invader or a piece of the self.

“Most innate immune receptors identify microbes by detecting unique structures found only on microbes,” said Leifer. “But some work by detecting structures present in both microbes and the self, such as DNA.”

Focusing her research on one such receptor, Toll-like receptor 9 (TLR9), Leifer recently discovered how TLR9 makes the kind of recognition mistakes that lead to autoimmune attacks, opening the door to new possible autoimmune disease therapies.

“Identifying immune-cell regulation systems may reveal therapeutic targets for managing TLR9 function, leading to new treatments for autoimmune diseases,” said Leifer.

Leifer will present her research at a special seminar to be held in September 2012. At a ceremony that follows she will receive an award of $1,000 and an engraved plaque.

“This is a great honor for Dr. Leifer at this stage of her career,” said Dr. Avery August, chair of the department of microbiology and immunology. “Her cutting-edge work on how the immune system senses pathogens is being recognized, and she will join a distinguished list of Cornell faculty who have received this award. We congratulate her on this great accomplishment.”

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College of Veterinary Medicine News
http://www.vet.cornell.edu/news/LeiferPfizer.cfm

 

Flag flown over Afghanistan in honor of Animal Hospital goes on display

 flagA new display featuring a special American flag now adorns Cornell University Hospital for Animals’ waiting room. To express thanks for CUHA’s life-saving services, Jessica and Mark Chamberlin gifted the folded flag to CUHA after Mark returned from military duty in Afghanistan, where he had flown it from a Chinook helicopter in honor of CUHA’s doctors, students, and staff.

While serving as a pilot in Afghanistan from October 2010 to October 2011, U.S. Army Chief Warrant Officer 3 Mark Chamberlin received bad news from his wife back home. Lucy, their husky, had been diagnosed with both acute and chronic liver failure. The prognosis looked bleak but Jessica took Lucy to Cornell to see what could be done.

“A biopsy revealed Lucy had hepatitis, extreme liver inflammation,” said Dr. Andrea Johnston, a third-year resident in Hepatology who led the case. “Much of the damage is irreversible and her liver will never function normally, but we were able to get the inflammation under control and develop a nutritional regime specially adapted to her condition. Jessica and Mark worked diligently with the new diet, home-cooking all the food—it’s clear how committed they are to helping Lucy.”

Lucy’s history of hardship began in an abusive dog yard in Alaska. When she got her foot caught in a chain, her former owners cut it off with a chainsaw and left her without medical care. Animal control officers investigating the dog yard found the injured husky and brought her to the animal hospital where Jessica worked as a licensed veterinary technician.

“It took a week to get the infection under control and we had to amputate her leg,” said Jessica. “I spent so much time with her that I got attached and brought her home. She’s been like a child to us ever since.”

The Chamberlin’s parent-like dedication continued through Lucy’s latest ordeal. On the couple’s 10th anniversary, instead of going on the vacation they had originally planned, Jessica and Mark spent their time in Ithaca supporting Lucy during her biopsy and liver care. After Lucy’s initial recovery, they spent time cooking Lucy’s special diet and nursing her back to health.

Their work paid off, and when Mark returned to Afghanistan to lead the flight mission “Operation Enduring Freedom XI,” he flew a flag from the CH-47F “Chinook” helicopter in CUHA’s honor.

“When we first brought Lucy to Cornell we thought she only had a couple weeks,” said Jessica. “Cornell was able to save our girl, and we wanted to do something special to honor the people at the hospital. We are so grateful that Cornell was an option and that all of the doctors and staff were so kind and helpful in getting Lucy back on her feet. We are honored that Cornell has chosen to display the flag in the lobby.”

The flag is proudly displayed in a wooden plaque along with a certificate signed by Mark Chamberlin and the four other officers who flew during the mission under his command. It can be viewed in CUHA’s waiting room to the right of the reception desk window.

flag

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http://www.vet.cornell.edu/news/Flag.cfm

First discovery of cells expelling mitochondria uncovers newfound survival tactic

An ancient union between cell and organelle has shown the first sign of fracture, challenging common conceptions of a primordial partnership all multicellular organisms rely on to live. Cornell researchers have recorded the first direct evidence of cells expelling intact mitochondria, the cellular machinery responsible for energy production.

AAAmitochondria B

An illustrated mitochondrion

Malfunctioning mitochondria produce free-radicals that damage cells, contributing to aging, mitochondrial myopathies, and disorders ranging from schizophrenia, bipolar disorder, and dementia to Parkinson’s disease and multiple sclerosis. The newfound breakup behaviour, described in Mitochondrion 2011 Nov.11(6), may be an early cell-survival strategy to escape the toxic effects of damaged mitochondria.

“It is very surprising to see living cells actively jettisoning vital parts of themselves,” said Dr. Theodore Clark, immunologist at the College of Veterinary Medicine. “This is the first time full mitochondria have been found outside cells and it may account for 15 years’ worth of unexplained data showing mitochondrial DNA and protein in extracellular spaces. We think these cells’ behaviour reveals a newfound survival tactic deeply rooted in evolution.”

Today’s mitochondria evolved from freewheeling bacteria that settled down in other cells two billion years ago. In exchange for food and shelter, the bacteria helped cells break nutrients into energy. These helpful tenants became modern mitochondria: the power-plants inside all cells of nearly every animal, plant, fungus, and protozoan.

Yet domestic disputes over cellular housekeeping may spur divorce, according to findings from Clark’s lab showing mitochondria moving out.

Graduate student Yelena Bisharyan discovered this while studying an unrelated phenomenon: escape stunts of the fish parasite Ichthyophthirius multifiliis. Clark’s lab had observed these parasitic protozoa avoiding destruction by shaking off attacking antibodies and exiting their hosts and wanted to see how they escaped.

“Attacking antibodies bind to the parasite’s cell surface,” said Clark. “We suspected that when antibodies attach, the parasite can shed them by breaking off its surface proteins – sort of like a lizard shedding its tail.”

tetrehymena 2

Tetrahymena, a protozoan, sheds proteins and mitochondria in response to attacking antibodies

Applying antibodies to parasites in culture, Bisharyan observed the reactions of Ichtyophthirius and Tetrahymena, another ciliated protozoan used as a model system to study fundamental biological principles across species.

Using negative staining and electron microscopy techniques, Bisharyan recorded parasites sacrificing their surface proteins to rid themselves of attached antibodies. Yet her images also captured something completely unexpected: intact and fragmented mitochondria coming out of the parasite’s cells.

This surprising finding won Bisharyan an invitation to present at one of the 2011 Gordon Research Conferences, a prestigious international forum showcasing major discoveries across scientific fields.

“Mitochondria experts were very excited to see this,” said Clark. “Over the past 15 years several papers have reported mitochondrial DNA and proteins floating outside mammalian cells. No one knew how or why they got there. What we’ve found in protozoa may help explain similar processes in mammals.”

Mitochondria (m) are pushed to the surface and jettisoned from the cell

mitochondria shed

Mitochondria (red) discovered outside cells

Certain cellular stressors can trigger mitochondrial expulsion, according to Bisharyan’s study. In protozoa, for example, not only antibodies but also heat shock can induce this effect. These stressors elevate calcium levels within the cell, possibly damaging mitochondria and causing them to produce toxic free-radicals.

“Our hypothesis is that mitochondria become poisoned and these protozoa have found a way to rid themselves of the damaged powerplants before they can cause further harm,” said Clark. “We think their behaviour reveals an early adaption to cellular stress that other species may share.”

Mammals and fish parasites may bear little family resemblance these days, but a common ancestor may have equipped both with emergency mitochondria-removal systems. Understanding this process could illuminate new approaches to reducing mitochondria-induced damage in humans and other animals.

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Cornell University College of Veterinary Medicine news

http://vet.cornell.edu/news/Mitochondria.cfm

Poisoned and burned puppy recovers with skin flap surgery and honey

aMelanie Miller and her Jack Russell terrier, Branson, were traveling the day after Thanksgiving when Miller noticed something was wrong. Usually jovial, the seven-month-old puppy seemed to fade, his eyes began twitching, and he started tremoring in the car. Miller rushed him to a nearby emergency veterinary hospital, where doctors delivered intravenous medicine just in time to get the seizures under control.

Spoiled fish turned out to be the culprit. Fish can spoil quickly, and Branson had eaten leftover fish that had apparently grown mold laden with neurotoxins. For hours the situation looked uncertain. As soon as they stopped the medicine the tremors would start again, but with care and patience the tremors finally passed.

Yet that was just the beginning of Branson’s troubles.

“I noticed a large discolored patch on his belly that hadn’t been there before,” said Miller. “I wasn’t sure what it could be–maybe a reaction to the medicine? It looked really painful and he didn’t seem happy. When we got home to New York I brought him straight to Cornell.”

Dr. Rebecca Kessler, third-year medicine resident, first saw the case. The oddly rectangular-shaped wound was worsening, turning black and leathery and starting to ooze. Kessler gave Branson pain medicine and antibiotics and took a skin biopsy. The results showed that Branson’s skin had been burned.

fDr. Marc Hirshenson, third-year resident in small animal surgery, removed the dead skin before it could become infected. Using an innovative technique to discourage infection, Hirshenson also applied a special topical treatment called Manuka honey to help heal the wound. Well known for its antimicrobrial properties, honey has been used by many cultures throughout history as a way to treat wounds and ward off infection. Manuka honey is produced by bees that feed on nectar from the manuka tree in New Zealand, and licensed wound-care products around the world use it as a special ingredient.

“There has been some evidence in humans that manuka honey is especially good for healing wounds,” said Hirshenson.

Over the next four days the wound improved, developing “granulation tissue” to help itself heal, a sign of a healthy body recovering. But the burn covered such a large area that it looked unlikely that it would fully close without surgery.

To help close the wound and avoid complications, Hirshenson performed a difficult skin flap surgery alongside Associate Professor of surgery Dr. James Flanders.

“Dogs have extra skin around their flanks, and their skin is relatively elastic,” he said. “We were able to stretch this extra skin to cover the area around the abdomen where Branson’s skin had burned and stitch it together around the middle.”

With careful manipulation of the excess skin they were able to close the wound, and after some rest and recuperation Branson was on his way to a full recovery.

“Our job is to help the body heal itself,” said Hirshenson. “Branson had an amazing attitude the whole time that really shined through. He put up with us for a long time, happy to let us handle him even when he was in pain, and was always enthusiastic about walking and eating. His demeanor contributed a lot to his recovery.”

Branson returned home in early December, where Miller reports he is back to his old self.

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http://www.vet.cornell.edu/news/Branson.cfm

Researchers discover what cancer cells need to travel

Feb. 21, 2012

Cancer cells must prepare for travel before invading new tissues, but new Cornell research has found a possible way to stop these cells from ever hitting the road.

Researchers have identified two key proteins that are needed to get cells moving and have uncovered a new pathway that treatments could block to immobilize mutant cells and keep cancer from spreading, says Richard Cerione, Goldwin Smith Professor of Pharmacology and Chemical Biology at Cornell’s College of Veterinary Medicine.

The study, co-authored by graduate student Lindsey Boroughs, Jared L. Johnson, Ph.D. ‘11, and Marc Antonyak, senior research associate, is published in the Journal of Biological Chemistry (286:37094-37107)

Most adult cells stay stationary, but the ability for some to move helps embryos develop, wounds heal and immune responses mobilize. When migrating cells go astray they can cause developmental disorders, ranging from cardiovascular disease to mental retardation. Metastasis (the spread of cancer from one part of the body to another) also relies on cell migration. How exactly cancer cells migrate
and invade tissues continues to be a mystery. However, Cerione’s lab uncovered a potentially important clue when it noticed that cancer cells gearing up to move would collect a protein called tissue transglutaminase (tTG) into clusters near the cell membrane.

meta“TTG is turning up in many aspects of human cancer research and seems to be contributing to the process that turns cells cancerous,” said Cerione. “Lindsey and Marc discovered that cells must gather tTG into a specific place in their membrane before they can move. But tTG is usually inactive, and we’ve been trying to understand how a cell gets this protein to the exact right place so that it can be activated to stimulate cell migration.”

Observing breast-cancer cells in culture, Cerione’s lab found a missing link in our understanding of cell migration: Cancerous cells become hyperactive invasion vehicles by using tTG together with other proteins like wheels, poking them through the surface to form a “leading edge” that pulls the cell forward. But to get the wheels to the leading edge, it turns out they need another protein to roll them there – a “chaperone” protein called heat-shock-protein-70 (Hsp70).

“We’ve known for years that Hsp70 acts as a chaperone to other proteins, ensuring that they assume the right structure and behave properly when a cell is under stress,” said Cerione. “Heat shock proteins have also been implicated in cancer, although scientists have been trying to understand their exact role in cancer. Our research has uncovered a previously unknown role for these chaperones – helping tTG get to the leading edge. TTG must be in this location for cancer to spread.”

migrating cervical cancer cell

A migrating cervical cancer cell stained for tissue transglutaminase (green). Cells must gather this protein at their leading edge in order to move.

When cells become stressed, Hsp70 influences the behavior of their “client” proteins, ensuring they keep the right shape. Cells need chaperones like Hsp70 to ensure that various proteins work correctly and don’t warp, but these same chaperones can help cancer cells spread by helping move tTG to the membrane surface. Using inhibitors that block the function of chaperones, Cerione and his team paralyzed Hsp70s and stopped breast cancer cells in culture from gathering tTG into a leading edge, effectively immobilizing them.

Exactly how Hsp70 gets tTG going remains unknown, but Cerione believes other proteins are involved.

“If we can better understand how Hsp70 influences tTG, we can figure out ways to modulate that interaction to immobilize cancer cells and keep them from becoming invasive,” said Cerione. “We suspect Hsp70 is using a third kind of protein to move tTG, and that’s what we’re trying to figure out now. Finding the next link in this chain of events could have important consequences for preventing cancer migration and metastasis.”

Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.

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Original Press Release:

Cornell University College of Veterinary Medicine news

http://www.vet.cornell.edu/news/Migration.cfm

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Feb12/CancerMovers.html

Ithaca Journal

http://www.theithacajournal.com/article/20120222/LIFE/202220336/Cornell-scientists-find-cancer-cells-need-travel?odyssey=mod|newswell|text|Life|s

PhysOrg

http://www.physorg.com/news/2012-02-cancer-cells.html

ECNMag

http://www.ecnmag.com/News/Feeds/2012/02/blogs-the-cutting-edge-researchers-discover-what-cancer-cells-need-to-tra/

Zeit News

http://www.zeitnews.org/biotechnology/researchers-discover-what-cancer-cells-need-to-travel.html

My Science

http://www.myscience.cc/news/2012/what_cancer_cells_need_to_travel-2012-cornell

Reddit

http://www.reddit.com/r/science/comments/q0swt/cancer_cells_must_prepare_for_travel_before/

Laboratory Equipment

http://www.laboratoryequipment.com/news-Proteins-Key-to-Stopping-Cancer-from-Spreading-022312.aspx