Health News
UF researchers reveal secret lives of genes
during spinal injury
By John Pastor
The body attempts to heal a damaged spinal cord in much the same way it repairs skin after simple cuts and scrapes, an insight that may lead to new treatments for the thousands of people paralyzed each year because of spinal cord injuries, say scientists at the University of Florida Health Science Center.
Writing in the current Journal of Neuroscience, scientists deliver the first-ever glimpse of how thousands of genes swing into action during the weeks and months after a spinal cord injury, suggesting there may be many more chances to treat the injury than commonly thought.
Using a microarray, a powerful tool that screens the activity of more than 8,000 genes simultaneously, researchers checked at six time points after spinal injury in rats and found that 3,638 genes turned on or off in response. The first genes to enter the fray are remarkably similar to those that drive clot formation and the mobilization of immune cells that fix skin wounds.
"Dermal wound healing has been studied for decades," said Margaret "Jo" Velardo, an assistant professor of neuroscience and member of UF's McKnight Brain Institute and the UF Genetics Institute. "Now, with the insights furnished by our study, perhaps spinal injury researchers may take advantage of techniques developed by our wound-healing colleagues and apply them. Our experiments showed that the gene families for tissue, vascular and immune system repair mechanisms appear to follow the same pattern as seen in healing skin."
A quarter of a million Americans currently live with spinal cord injuries, which usually begin with a sudden, traumatic blow to the spine that fractures or dislocates vertebrae, according to the National Institute of Neurological Disorders and Stroke. The number of new injuries each year is relatively small, but the injuries usually occur in young people, striking them down in the prime of life and leaving them to survive for many years afterward with a devastating, debilitating injury. The cost of managing the care of spinal cord injury patients approaches $9 billion a year.
Researchers Henry Baker and Corinna Burger of the molecular genetics and microbiology department and the UF Genetics Institute assembled more than 280,000 bits of information that revealed how armies of genes activated or shut down to deal with the spinal injury, not just within a few days of the injury but for as long as three months afterward.
"The patterns told us that something orderly and amazing was happening," Velardo said. "That motivated us to perform an in-depth analysis so that we could infer the actual biological events occurring at various time intervals after injury."
On the first day, researchers found protective genes turned on to preserve what functional tissue remained at the injury site. By the third day, the character of the genes changed dramatically, with growth and repair genes turning on simultaneously with a huge number of cell division genes.
"It is as if the body creates thousands of cellular machines to move in and manufacture what is needed to repair the damage," Velardo said. "At day 10, we could see the genes increase in expression to repair the ground substance and reform the damaged blood vessels of the spinal cord. From 30 to 90 days, at the gene expression level, we can actually observe the maturation of these new blood vessels and the manufacture of a new type of ground substance that occurs as a wound ages and restructures itself."
The orchestrated, day-to-day process suggests multiple therapeutic opportunities, depending on which genes are being expressed.
"The gene expression changes are related to repair mechanisms," said professor Ed Hall, director of the Spinal Cord and Brain Injury Research Center at the University of Kentucky College of Medicine. "In order to improve repair mechanisms, we need to know which processes to promote or antagonize in the spinal cord. We need more study to go after those pharmacological therapies, but this is a seminal work in the field of spinal cord research."
The UF research also suggests that someone's genetic background may dictate response to spinal cord injury. Scientists compared two strains of rats, one with a normal immune system and one that was deficient in a type of immune cell called a T cell, which is believed to be important in regulating wound-healing processes. The animals had different recovery patterns after injury, with differences in 80 shared wound-healing genes between the two strains of rats.
"It is likely that small differences in important genes can alter the progression and outcome of the injury," Velardo said. "Likewise, if we fine-tune our results using further experiments, we may pinpoint some genes that turn on in a successful wound-healing process in the skin that somehow are detrimental and may actually inhibit the repair and regeneration of the spinal cord."
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UF researcher unearths reports of serial murder by children |
By Melanie Fridl Ross
They leave multiple clues at the scene of the crime. They are impulsive and less adept at hiding their weapons. And they confide in friends who just can't keep a secret. In short, they are terrible at covering their tracks.
Yet until now, the disturbing details of a half-dozen children's serial killing sprees have remained well hidden, concealed in 150 years worth of medical literature, true-crime tales, newspaper clippings and history books, says a University of Florida forensic psychiatrist.
The stories surfaced only recently, shedding light on a previously unknown psychopathic phenomenon, reports Dr. Wade C. Myers, writing in the journal Behavioral Sciences and the Law. Myers initially began studying cases of sexual murder by children and adolescents after he was asked on occasion to evaluate them for the legal system.
"I wanted to see what I could learn from the scientific literature about kids who do these sorts of crimes," Myers said. "When I went to the textbooks to learn more, I found there was almost nothing written about them. That was the impetus for my studies of children who commit sexual homicides. With time, I began to wonder whether there actually ntly committed serial murder, so I hunted through innumerable articles, crime books and other sources in a quest to better understand this form of juvenile murder."
From actor Anthony Hopkins' chilling portrayal of Hannibal Lecter to accounts of the multiple murders of Ted Bundy, Aileen Wuornos or John Wayne Gacy, serial killers both abhor and fascinate. And while cases of children perpetrating such heinous crimes are exceedingly rare, Myers said their stories nonetheless speak to a wider societal issue: the effect of an unstable or abusive family life on juvenile delinquency in general.
Also the disturbing details of a half-dozen children's serial killing sprees have remained well hidden, concealed in 150 years worth of medical literature, true-crime tales, newspaper clippings and history books, says a University of Florida forensic psychiatrist."One of the biggest factors in helping to decrease delinquency or violent acts by children is to arrange for children to have the most stable, caring, loving upbringing possible, with positive role models," said Myers, an associate professor of forensic psychiatry at UF's Health Science Center.
In contrast, the children described in Myers' paper, five boys and a girl, were commonly subjected to cruel discipline, neglect, and physical and emotional abuse. Three were from the United States, two from Europe and one from Central America. All murdered before they turned 18, killing at least two victims - usually other children - most often by cutting, stabbing or strangling them.
The first case involved a boy who was born in Boston in 1859 and killed two young boys when he was 11. The most recent case involved a boy from El Salvador convicted of seven murders in the 1980s and suspected in 10 other killings.
"These children's upbringing was the opposite of 'Leave it to Beaver,'" Myers said. "For instance, one had a prostitute for a mother who abandoned her as a child. Another had a brutally abusive father who butchered farm animals in front of his son from the time he was a toddler. Parental antisocial role models create powerful effects on a child's development and identity formation.
"It's safe to say that none of these children would have committed serial murder had they come from stable backgrounds, and none of them did come from stable backgrounds," he said.
In most cases, the children took a sadistic pleasure in torturing their victims before killing them, and the crimes all had sexual elements, Myers said. Before she was caught, a girl from England taunted the parents of a 4-year-old neighbor boy whom she strangled on the eve of her 11th birthday, asking them if they missed their son. She even attended his funeral, laughing as his coffin passed by. According to the journal article, a psychiatrist who evaluated her "said he had never encountered such a psychopathic child - one as 'intelligent, as manipulative or as dangerous.'"
All six children who committed serial murders waited days or months before murdering again, differentiating their cases from mass or spree murder cases such as the Columbine shootings, which don't have a "cooling off" period between the acts, Myers said.
The research also omitted cases such as that of convicted Beltway sniper John Lee Malvo, who as a minor killed multiple victims but did so while under the direct influence of an adult co-conspirator. In addition, Myers did not include a number of famous serial killers who killed for the first time during adolescence but didn't strike again until adulthood, as they did not meet the definition of committing serial murders while still minors.
None of the children gave any prior indication they were likely to murder, Myers said. And unlike many of their adult counterparts, the children tended to be ill-prepared and impulsive in their modus operandi, leaving a bigger trail of evidence. Moreover, they favored victims who lived nearby, thereby placing themselves in a much smaller pool of suspects and increasing the likelihood they would be caught.
"In some ways, you could see how the abusive background of these children ended up becoming a factor," said Myers, who is now writing a book on the subject. "They had little capacity to feel guilt and displayed psychopathic personality features, such as being emotionally cold, callous and manipulative. What is harder to explain with these children is what actually creates in them a fascination with sadistic acts, that is, pleasure in the harming or killing of others. That's harder to answer. We still don't know where these feelings, urges and fantasies come from."
Forensic psychologist Reid Meloy, a noted expert who served as a consultant on the Oklahoma City bombing and Madonna stalking cases, said Myers' work represents the first time anyone has looked at serial homicide committed by adolescents as a clustering of cases and then tried to delineate the shared characteristics of that group.
"I think it contributes to the understanding of violence in youth," said Meloy, also an associate clinical professor of psychiatry at the University of California, San Diego and president of the nonprofit research group Forensis Inc. "The difficulty, of course, is that these cases are so rare and so unusual it may not shed light on the more common violence we see adolescents committing. In a fortunate way it remains a very rare phenomenon, much rarer than even adult serial homicides. Dr. Myers is the foremost researcher in this area and the work he's done has been pioneering. Nobody has taken the time prior to this to look at these very aberrant and very lethal adolescents."
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UF researchers show mice live longer when they slim down after gene therapy
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By Tom Nordlie
GAINESVILLE, Fla. - Doctors have said it for years: Maintaining a healthy weight can help you live longer.
Now, a University of Florida gene therapy study provides further proof that doctors are right, say researchers who measured the lifespans of mice that were twice as heavy as their normal counterparts.
The mice lacked a crucial weight-control gene, and when the gene was restored to some of the mice they not only slimmed down, two-thirds of them also outlived every mouse in an untreated group, said Satya Kalra, Ph.D., a UF professor of neuroscience. The results of the National Institutes of Health-funded study, presented today at the Society for Neuroscience annual meeting in San Diego, suggest it's never too late to benefit from proper diet and exercise.
"Our study very clearly demonstrates for the first time that if you can reduce obesity or the fat load, you have a greater chance of living longer," said Kalra, who also is a member of UF's McKnight Brain Institute. "Clinical reports are abundant that obesity produces metabolic diseases that shorten the lifespan of obese people."
Obesity is defined using a formula called body mass index, which compares weight with height. People with a body mass index of 30 or more are considered obese, and have increased risks for ailments such as high blood pressure, type 2 diabetes, heart disease, stroke and some forms of cancer, according to the U.S. Centers for Disease Control and Prevention.
Funding for the study was provided by a five-year, $1.9 million grant from the National Institutes of Health.
UF researchers put the missing gene where it was needed most: into cells in a part of the brain called the hypothalamus, which controls many basic body functions, Kalra said. The gene controls production of a protein called leptin, which signals the hypothalamus to reduce appetite and increase metabolism.
Leptin is produced in the fat tissue of all mammals, including people, he said. It is normally released when a mammal eats, traveling to the hypothalamus through the bloodstream. Without adequate leptin, mammals overeat and gain weight, Kalra said.
Some people may carry excess weight because their bodies don't produce enough leptin, a theory that could be demonstrated by future research, he said.
"If it is demonstrated, then there's a good chance that leptin gene therapy may also be beneficial clinically," Kalra said. He emphasized that clinical trials for human patients would be years away and that for now, the best way for people to stay slim is through proper diet and exercise.
The study involved several breakthroughs for researchers, Kalra said.
Most important, the treatment involved a single application of gene therapy, yet produced beneficial results that lasted for the remainder of the animals' lives, which was more than a year, he said. Because many human diseases are caused by missing or faulty genes, the study offers hope that similar treatments may eventually provide long-lasting results in people.
"It's also never been shown that by replacing one gene you can prolong life," said Kalra, who conducted the study with his wife and longtime research partner Pushpa Kalra, Ph.D., a UF professor of physiology and functional genomics, and UF postdoctoral fellows Naohiko Ueno, Ph.D., and Stephane Boghossian, Ph.D.
In the study, 24 male mice 8 weeks to 10 weeks old were separated into two groups of 12. All the mice lacked the gene that controls leptin production, so they weighed between 40 grams and 50 grams, about double the weight of a typical mouse.
Mice in the treated group were injected with a harmless virus modified to carry a gene that controls production of leptin. The untreated group received the same virus, but it carried a gene that produces a protein that glows bright green but has no therapeutic effect.
After the injections, body weight and food intake were monitored weekly for each mouse. The mice treated with leptin ate an average of 15 percent less than the other mice and eventually returned to normal weight. The untreated mice continued to gain weight and began to show increased mortality after 315 days.
In addition, after 595 days, two-thirds of the mice treated with leptin remained alive, but all the untreated mice had died.
The UF study is important because it demonstrates that weight-loss research can be accomplished using animals that voluntarily reduce their food intake instead of being forced to diet by food restriction, said leptin researcher M. Susan Smith, director of the Oregon National Primate Research Center in Portland, Ore.
"Feeling hungry is stressful," Smith said. "So whenever you have stress on top of other factors it makes it much more difficult to understand what is really going on."
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