In the first-ever study of the effects of the absence of microRNAs in the mammalian eye, an international team of researchers directed by the University of Florida and the Italian National Research Council describes a gradual structural decline in retinas that lack microRNAs — a sharp contrast to the immediate devastation that occurs in limbs, lungs and other tissues that develop without microRNAs.

The discovery, reported in today’s (May 7) issue of the Journal of Neuroscience, may lead to new understanding of some blinding diseases and further penetrates the cryptic nature of microRNAs — important gene regulators that a decade ago were considered to be little more than scraps floating around the cell’s working genetic machinery.

“MicroRNAs are behaving differently in the nervous system than they are in other bodily tissues,” said Brian Harfe, an assistant professor of molecular genetics and microbiology at the University of Florida College of Medicine. “Judging by our previous studies in limb development, I was expecting to see lots of immediate cell death in the retina. I was not expecting a normal-looking retina in terms of its form. It would be something like finding a perfectly formed arm at birth that just did not work.”

Production of microRNAs is dependent on Dicer, an enzyme widely used by living things to kick-start the process of silencing unwanted genetic messages. By breeding mice that lack one or both of the forms — or alleles — of the gene that produces Dicer in the retina, scientists were able to observe retinal development when Dicer levels were half of normal or completely eliminated.

Electrical activity in retinas devoid of Dicer was abnormally low at the time of eye opening and became progressively worse at 1-, 3- and 5-month stages. Structurally, the retinas initially appeared normal, but the cells progressively became disorganized, followed by widespread degeneration.

Retinas in animals equipped with a single form of the Dicer gene never underwent the inexorable structural decline that occurs in total absence of Dicer, but they also never functioned normally, according to electroretinograms.

“We have removed Dicer from about 30 different tissues,” said Harfe, a member of the UF Genetics Institute. “In all of those cases with half the amount of Dicer, you still had a normal animal. In the retina, there were functional abnormalities. This is the first indication that the dose of Dicer is important for normal retinal health.”

Inherited forms of retinal degeneration affect about 100,000 people in the United States, according to the National Eye Institute. The problems typically occur with the destruction of photoreceptor cells called rods and cones in the back of the eye. More than 140 genes have been linked to these diseases, which only account for a fraction of the cases.

“We have many types of retinal degeneration and not enough mutations to explain them,” said Enrica Strettoi, a senior researcher at the Institute of Neurosciences of the Italian National Research Council in Pisa, Italy. “Finding that ablation of Dicer causes retinal degeneration might be helpful in discovering candidate disease genes. What we’ve done is target virtually all microRNAs in the retina by ablating Dicer, the core enzyme regulating their synthesis. The next step is to try to address each one separately, and find the role of specific microRNAs. Removal of Dicer from other areas of the central nervous system has also produced functional and structural abnormalities, confirming the fundamental role of this enzyme in neurons.”

More than 400 microRNAs have been identified in both mice and humans, and each one has the potential to regulate hundreds of target genes. They have also been linked to human diseases such as diabetes, hepatitis C, leukemia, lymphoma, Kaposi’s sarcoma and breast cancer.

“This interesting study, together with recent findings reported from three other labs in the United States, provide strong evidence that the microRNA pathway is involved in the health and sickness of many parts of the mammalian nervous system,” said Fen-Biao Gao, an investigator at the Gladstone Institute of Neurological Disease at the University of California-San Francisco, who did not participate in the research. “Additional in-depth studies in the future will likely help develop new therapeutic approaches for many neurodegenerative diseases.”

Additional scientists who participated in the research include Devid Damiani of the Institute of Neurosciences in Pisa; John Alexander, Jason O’Rourke and William Hauswirth of the University of Florida; Michael McManus of the University of California-San Francisco; and Ashutosh Jadhav and Constance Cepko of Harvard Medical School.

The findings, which appear in today’s (May 1) edition of the American Heart Association journal Hypertension, could lead to a new class of antihypertensive drugs designed to address two major problems associated with cardiovascular disease: high blood pressure and the tissue damage associated with it, known as fibrosis.

“When people have heart attacks (or suffer from hypertension) the blood vessels get more rigid,” said study author David Ostrov, an assistant professor in the UF College of Medicine’s department of pathology, immunology and laboratory medicine. “We discovered a compound that reverses the fibrosis that makes the blood vessels more rigid.”

The American Heart Association estimates that 72 million people in the United States have high blood pressure, a major risk factor for stroke, heart attack and death.

Angiotensin-converting enzyme plays a key role in the development of high blood pressure. It produces angiotensin II, a potent hormone that triggers the condition and contributes to the development of cardiovascular disease by constricting blood vessels, causing blood pressure to rise. That’s why millions of Americans with hypertension and cardiovascular disease take ACE inhibitors. But these drugs have limited capacity to repair heart function and to reverse tissue damage.

In contrast, the enzyme ACE2 not only lowers levels of angiotensin II but also converts it to a hormone that helps protect the cardiovascular system.

“Only recently has it come to be appreciated that ACE and ACE2 play a very important role in balancing the activity of the other one to maintain normal blood pressure,” Ostrov said. “They work in harmony.”

Hypothesizing that activating ACE2 could be beneficial, UF scientists set out to discover a compound that enhances the enzyme’s activity.

Researchers used one of the world’s most powerful supercomputers to process 140,000 prospective drug compounds in a matter of weeks. The computer predicted which molecules would be most likely to enhance the activity of ACE2, rotating them in thousands of different orientations to see how they would bind to certain pockets on the enzyme’s surface.

“This project had a very small likelihood of succeeding because it’s much easier to inhibit activity rather than to enhance it. By analogy, it’s easier to break something than to build it,” Ostrov said. “If you consider the structure of an enzyme’s active site it’s easy to see that if you plug up the active site it’s not going to work. But how can one make the enzyme actually work better? This seemed to be a very significant challenge we were probably not likely to overcome. We tried anyway.”

And it worked.

“That in itself is a significant accomplishment because no one has ever specifically identified a compound that enhances the activity of an enzyme using a rational structure-based approach,” he said. “In other words, no one has ever done this before on purpose. People have discovered molecules that enhance the activity of enzymes by trial and error, but no group has ever done it in a specifically pointed way like this.”

Ostrov said the enzyme exists in two forms: like a Pac-Man with a mouth that has chomped closed, and like a Pac-Man with a mouth that remains wide open. The molecule that worked best fit in a structural pocket in the enzyme’s open conformation.

“So in other words, stabilizing the open conformation may be the reason why we enhance the activity of the enzyme,” he said

After hitting on the “lead” compound, UF researchers then tested it in hypertensive rats that had developed fibrosis of the heart and kidney. The animals received the drug for two weeks. Tissue samples from treated animals revealed a significant decrease in fibrosis of the heart, kidney and blood vessels, said Ostrov, who described the findings as “striking and reproducible.”

The study was funded by grants from the National Institutes of Health and the American Heart Association and was a collaborative effort of the UF colleges of Medicine, Pharmacy and Liberal Arts and Sciences. Researchers also included Mohan Raizada, a distinguished professor of physiology and functional genomics, Michael J. Katovich, a professor of pharmacodynamics, and Ronald K. Castellano, an assistant professor of chemistry, among others.

Early results also show the compound inhibits inflammation, which has significant implications for a number of human diseases, including autoimmune diseases such as type 1 diabetes and rheumatoid arthritis as well as other diseases involving fibrosis, such as Alzheimer’s, Ostrov said.

Additional research will continue to explore the compound’s effectiveness in animals and humans.

Scientists studying fruit fly cells discovered that slight changes in the protein scaffolds that support the genes “reaper” and “hid” — aptly named for their roles in triggering cell death — cause the cells to become naturally resistant to X-rays during early development.

“It turns out that a piece of DNA that is required for mediating this process of cell death is blocked,” said Lei Zhou, an associate professor of molecular genetics and microbiology in the UF College of Medicine. “When it is blocked, the cells just don’t die, even when subjected to heavy doses of radiation. This may be what is happening in some resistant cancer cells. The pro-apoptotic genes cannot be induced to cause cell death.”

The study may be the first to link apoptosis, the gene-driven process that leads to the necessary destruction of old, damaged, or infected cells, with epigenetics — the study of how gene function changes even when the genes themselves don’t change.

Scientists believe that defects in cell death regulation may be responsible for tumor formation and the spread of cancer because the cells escape the safeguards that normally clean up malignant cells.

In their experiments, UF researchers found the location of the DNA sequences known to trigger reaper, hid and other genes related to cell death in fruit flies. Similar genes exist in humans.

By monitoring gene activity levels and changes in chromatin — the protein spools that the genes wrap around — researchers were able to detect factors that made the cells resistant to radiation.

Scientists first noticed drastic changes in sensitivity to radiation in developing fruit fly cells in the mid-1970s. Similarly, a sensitive-to-resistant transformation takes place in people during the development of brain cells, which are extremely sensitive to radiation in their formative stages but more durable once they grow into adult neurons.

However, the underlying cellular and molecular causes of the transformations were undetected. The latest findings suggest that like the fruit fly cells, tumor cells may have a degree of epigenetic protection from radiotherapy or chemotherapy.

“We are talking about a piece of DNA that is very sensitive when open, but modification of its supporting structure has caused it to condense,” said Zhou, who is affiliated with the UF Shands Cancer Center and the UF Genetics Institute. “If we reverse this and open the DNA supporting structure, we can conceivably make the cells sensitive to radiation once more. Controlling the blocking-unblocking mechanism to make the cells sensitive could potentially lead to better cancer therapy.”

Conceivably, certain drugs that open “enhancer” regions of cell-death genes in tumor cells could improve the effectiveness of cancer treatments.

“The scientists took a different approach to look at the regions of the genome important for DNA-damage induced cell death,” said Kristin White, an associate professor of dermatology at Harvard Medical School and Massachusetts General Hospital, who did not participate in the research. “One of the most interesting aspects of this work is the finding that changes in chromatin structure regulate the expression of genes that are important in this death, and that this regulation can extend over long distances in the genome.

“The research shows there is still a lot to learn about DNA damage-induced cell death,” she said. “We need to understand all aspects of this if we want to improve cancer therapy. This work suggests that we need to look harder at chromatin-modifying enzymes as new targets to alter the response of cancer cells to radiation.”

The research was supported by a National Institutes of Health grant.

“Within African-American and Latino families, children follow a cultural tradition that places a high value on respecting, obeying and learning from elders, and in our study they did indeed show more respect for parental authority,” said Julia Graber, a UF psychology professor.

However, when African-American and Latina girls do act up, their mothers consider the arguments more intense than those reported by white mothers who clash with their daughters, said Graber, whose study is published in the February issue of the Journal of Family Psychology.

Hispanic and black mothers, who value strong family connections, a deep sense of family loyalty and the importance of extended family and social support networks, seemed to be much more upset if daughters fell short of cultural, good girl expectations, Graber said. “It may be just the kind of issue that pushes their buttons more, thinking of their daughter as no longer being the good, respectful daughter,” she said.

For all girls, discipline was the only factor that influenced how much conflict they perceived in the relationship. The stricter and harsher mothers were, the less conflict their daughters reported, Graber said. However, as girls get older, stricter discipline may lead to greater conflict if girls try to disagree, she said.

The study differs from other research on mother-daughter conflict in that instead of looking at adolescence, it examines girls in middle to late childhood, at an average age of 8½, Graber said. The teenage years are naturally turbulent times for families, but understanding what happens immediately preceding them sets the stage for a smoother or rockier transition, she said.

Teen conflict is a risk for other behavior-related problems, Graber said. “It does seem that when there are higher levels of conflict, those daughters are more likely to have adjustment problems in terms of feeling more depression, sadness, anxiety and those problems,” she said.

The intensity of the conflicts aside, the study found that mothers’ and daughters’ reports of the frequency of conflict were similar, Graber said. The study, which Graber did with Sara Villanueva Dixon, a St. Edward’s University psychology professor, and Jeanne Brooks-Gunn, a Columbia University child development professor, involved 45 African-American, 23 Latina and 65 white girls recruited through fliers while in the third grade and their mothers. The girls and their families were from racially integrated, working and middle-class communities in a large metropolitan area.

The girls’ respect for authority was observed during a series of videotaped interactions with their mothers. Daughters were scored on their listening behaviors, which included attending to their mothers when their mothers were speaking, acknowledging their mothers’ comments and not interrupting their mothers. They also were evaluated for defiant behaviors, such as disobeying their mothers’ requests, being unwilling to cooperate with their mothers and ignoring their mothers during the interaction.

Not only do children need to be more aware of the expectations their parents have for them, but mothers may also want to reassess their feelings about particular issues, she said.

“The challenge for African-American and Latina mothers is they are in an environment where their children are potentially getting messages at school, on television and elsewhere about what normal childhood behavior is like that may conflict with their own expectations for these behaviors,” Graber said.

“In the higher conflict families where mothers and daughters are arguing much more often there seems to be less productive resolution going on and less learning of those skills,” she said. “Everybody feels mad afterwards rather than feeling the potential of moving forward.”

“This is a fascinating study that enhances our understanding of ethnic and racial differences in parent-child relationships,” said Judi Smetana, a University of Rochester psychologist. “One of its strengths is that it examines in a very careful and detailed way how different cultural values are expressed in mother-daughter interactions and how those values influence the quality of family relationships.”

In a study of 210 college students, UF researchers discovered a link between what psychologists call relational victimization in adolescence and depression and anxiety in early adulthood, according to findings published online this month in the journal Psychology in the Schools. Rather than threatening a child with physical violence, these bullies target a child’s social status and relationships by shunning them, excluding them from social activities or spreading rumors, said Allison Dempsey, a doctoral student in the UF College of Education and the study’s lead author.

“Even though people are outside of high school, the memories of these experiences continue to be associated with depression and social anxiety,” said Dempsey, who graduated from Columbine High School in Colorado one year before the 1999 school shooting there and now studies school prevention programs. “It was interesting to see these relationships still continue to exist even though they are in early adulthood now and in a completely different setting.

“I’m hoping this study will help shed light on the fact that this is a real problem and continues to be a real problem after students leave school.”

To uncover the relationships between social bullying and loneliness, depression and anxiety, researchers surveyed college undergraduates between the ages of 18 and 25 and asked them to recall their experiences from high school. They were also looking to see if having friends mitigated some of the effects of bullying and if there was any relationship between gender and the severity of psychological symptoms, said Eric Storch, an assistant professor of psychiatry in the UF College of Medicine and a co-author of the study.

“About 20 years ago people thought of bullying as very physical,” Storch said. “As a result people thought guys did the bullying, and that it wasn’t really a big experience for girls. The problem is that isn’t actually true. There are different types of aggression.

“Boys do tend to be more physical, but both sexes engage in relational victimization. We wanted to see if gender affected strength of the relationship between depressive symptoms and victimization.”

But researchers found no gender difference in the link between this type of bullying and depression. They also discovered that having friends or other positive social relationships didn’t lessen rates of depression and anxiety in adulthood, a finding that surprised them, Dempsey said.

For some children, having friends and positive support can help make them more resilient to the slings and arrows from bullies, Storch said. But other children take the words and abuse more to heart and begin to believe what’s being said about them.

“Those types of negative thoughts are actually believed to be at the core of things like depression and anxiety,” Storch said. “Behaviorally what starts happening is you avoid interactions and situations that could be quite positive for you.”

Currently, there are few prevention or intervention programs that focus specifically on relational victimization, in part because it’s tougher to pinpoint and stop, Dempsey said.

“If a child tries to punch someone or kick someone, there’s evidence of that happening,” Dempsey said. “There’s a definite aggressor and a definite victim. When it comes to spreading rumors and gossiping, that’s a lot more difficult to prove who’s doing it. And it’s harder to provide consequences.”

Dempsey said she hopes this study and others will help other researchers and psychologists design programs that can help stop this form of bullying in schools.

“I think many people have the belief that victimization is a normal rite of passage in childhood,” Storch said. “While it certainly does happen to most kids, it’s not acceptable. And while I think it would be difficult to completely curtail it, by reducing it you’re going to help someone a tremendous amount to not have to go to school and be plagued by this environment of being tortured day in and day out.

“This isn’t a normative experience and we need to do something about it and recognize that not doing something could affect children who are really rising stars.”

Wendy Troop-Gordon, an assistant professor of psychology at North Dakota State University, said understanding how past relational bullying affects people in adulthood is an important step forward for research in this field.

“Turning 18 is not a magical age when you leave all of these experiences behind,” said Troop-Gordon, who is not affiliated with the study. “People do seem to carry these experiences with them.”

The students have designed a headset that shows promise of reducing the extremely loud, repetitive, industrial-like noises that accompany magnetic resonance image examinations. The noises, which range from beeping to whirring to grinding and can often be as loud as a jet engine, stem from the workings of the powerful magnets at the heart of the machines’ ability to produce sharply defined internal images of the body or body parts.

The headset would not only make the experience less off-putting, it might also reduce the number of needed exams, freeing up the machine for access by more patients, said Stephen Forguson, a senior majoring in electrical engineering.

“The sound often makes patients move or wriggle a bit,” he said. “Unfortunately, that can blur the image, which means the operators have to redo the exam.”

Forguson and Chad Dailey, Paul Norris and Christopher Ruesga, all also engineering seniors, designed the headset as part of the College of Engineering’s Integrated Product and Process Design Program. The program pairs student teams with corporate or government sponsors for yearlong design projects of products or processes intended to be useful to the sponsor. The sponsor of the headset project was Invivo Corporation, a Gainesville manufacturer of magnetic coils, monitors and other MRI accessories.

With battery-operated headphones that cancel internal airplane noise or other loud noises already commercially available, muffling the noise a patient hears when inserted into the cylinder-like MRI machines might seem a small challenge.

But the problem is that no electronics are permitted within the MRI chamber because the electronics can distort or disrupt the images scanned by the machines’ magnets. So the difficulty for the UF students was figuring out how to reduce noise without the use of any wires, switches or other electronics with the patient in the chamber.

“Passive” systems that use foam or other sound-deadening materials are insufficient to combat the noise. So the team attempted to solve the problem using existing “air phones,” or headphones attached to small tubes, connected via the tubes to specially crafted electronics and software located outside the MRI machine.

The air phones, which are similar to the headphones once distributed on commercial airplanes, pipe the sound via two tubes to tiny microphones connected to an amplifier and a signal processor several feet away.

That processor taps an algorithm, or set of computer instructions, to produce a sound signal that is the opposite of the signal just received. That opposite signal then gets piped back through a third tube to each of the patient’s ears.

Because the MRI sounds are repetitive and the piped-in sounds are timed to occur on top of the repetitions, the result is that the patient hears the same sound as he or she would have without any intervention — but at a lower volume.

Trials of the system using a loud beeping sound similar to some MRI noises showed it could reduce the noise by as much as 15 decibels. Ambient noise is about 60 decibels, with jet engines and other extremely loud noises reaching 120 decibels. The students were only able to reduce actual MRI sounds by a smaller level, but they said further tweaks of the system and algorithm are likely to improve that result.

The team’s results are “significant and make a difference,” said Gijs Bosman, a professor of electrical and computer engineering and the team’s faculty adviser. “Based on experiments and further testing of the prototype, the team has come up with several recommendations for further improvements.”

Sam Coons, a project manager with Invivo who worked with the UF team, said reducing the MRI noises is also challenging in part because as clinicians develop new scans, new noises emerge. But he said that improving the algorithm at the heart of the headset project should make it more effective against the variety of noises.

The noise-muffling technology is “a big piece” of Invivo’s entertainment system, he said. “We hopefully at some point will incorporate this into all of our systems because noise is such a problem,” he said. “If we can achieve our goals, we will ship this to everyone.”

“For HIV, it’s been shown that if you don’t take a very high percentage of your medication, you may as well not take medication at all,” said Dr. Richard Melker, a professor of anesthesiology at the UF College of Medicine and chief technology officer for Xhale.

Patients who take some but not all of their medication increase the likelihood the virus will mutate into a deadlier, drug-resistant form. Experts have tried literally hundreds, if not thousands, of ways to monitor drug adherence, ranging from daily log books to blister packs that record the time each pill is dispensed. Despite the money, time and effort devoted to these methods, Melker said only one works well: directly observed therapy, or DOT.

“If you have a disease that is deemed to be a public health risk, authorities can put you into a program where you have to come to the clinic every day and be observed putting the pill into your mouth and swallowing it,” Melker said.

But that process is inconvenient for patients, as well as for clinic personnel who have to track them down when they fail to show up. A breath-monitoring device developed by UF scientists and Xhale could change that, allowing patients to participate in a type of virtual DOT from home.

“The machine sits in your home and when it’s time for you to take your medication, it makes a beeping noise. If you don’t hit a button after about five minutes, it’s going to beep louder and louder until you come,” Melker said. “If you don’t come after a certain amount of time, the machine can call the clinical trial coordinator and indicate that subject or patient didn’t take the medication as prescribed.”

The device, which is slightly smaller than a shoebox, records the results of each breath test, allowing patients to bring a memory card or USB key to the clinic once a month and receive a printout of their results. Eventually, the researchers hope to reduce the size of their detection device to fit inside a cell phone. But for now, they’re satisfied that the technology works.

“The doctor can see how often you took it and exactly what time. If it made the patient really sick or dizzy and they didn’t take it, they can find out why,” Melker said. “It’s not just a question of did I or didn’t I take it, but when you took it or why you didn’t take it.”

The researchers developed the adherence monitor by incorporating minute amounts of an alcohol into a gel capsule. The additive, called 2-butanol, is one of many GRAS — Generally Recognized as Safe — compounds approved by the Food and Drug Administration for use in foods.

“We wanted (patients) to swallow a chemical and have it transform into something else that’s easy to monitor,” said Matthew Booth, an assistant professor of anesthesiology at the UF College of Medicine and an investigator in the study. “When it hits the stomach lining and liver, an enzyme converts the alcohol to a gas that can be measured in the breath.”

To determine how well the byproduct could be detected, six healthy volunteers swallowed empty pills in which the capsules contained trace amounts of 2-butanol. After five to 10 minutes, the scientists could measure the volatile byproduct in the volunteers’ breath using a small detector. The scientists say their device could also be used to monitor medication adherence in patients with other communicable diseases, such as tuberculosis.

“It is encouraging that the biological and chemical elements of the adherence system work as predicted. We were able to conclusively show who swallowed the capsules containing the 2-butanol. With further optimization, we are optimistic the device will perform very well,” said Dr. Donn Dennis, the Joachim S. Gravenstein professor of anesthesiology at the UF College of Medicine and an investigator in the study.

The researchers say the device may prove equally helpful for monitoring adherence in clinical trials.

“If you enroll HIV/AIDS patients in a clinical trial and they don’t take the medication, then you may not get adequate proof that the drug is effective,” Melker said. “It might be effective, but some of the patients aren’t taking it.”

Phase 2 trials are often conducted in the community, rather than at research institutions, making it difficult for researchers to monitor adherence. As a result, many trials enroll a larger group of subjects than needed, in hopes they’ll obtain enough data to determine the safety and efficacy of the medication.

“If we had a good way of doing DOT that’s realistic, instead of having someone come to your house or you going to clinic every day of your life, then we would know whether these people stopped taking their medication and why. Right now, nobody knows any of that.” Melker said. “The implications of being able to understand what normal human behavior is in a clinical trial and, of course, in the real world, are huge.”

The barrier deflects damage from radiation or chemotherapy, making some cancer cells difficult to destroy, but researchers from UF and the University of North Carolina at Chapel Hill may have discovered why. Their study revealed that mutations in the tumor-suppressing p53 protein lead to overabundance of a second protein called focal adhesion kinase, or FAK, which makes the cells less vulnerable to attack.

“These findings are significant to future cancer research and the development of new therapies,” said Vita Golubovskaya, an assistant professor in the UF department of surgery, who presented the findings. “The high correlation between these two markers is critical for predicting patient prognosis.”

The next step will involve developing cancer therapies that target this interaction, Golubovskaya added.

Both p53 and FAK are found in low levels in normal, healthy cells. The p53 protein ensures that cells strike a wholesome balance between growth and death. In its normal state, p53 suppresses the FAK protein and weakens the molecular force field around cancer cells. But mutations in the p53 protein can interfere with this regulatory function.

Mutations in the p53 gene are commonly found in patients with cancer, and those with more aggressive forms of the disease boast particularly high levels of p53 and FAK. Most cancer therapies are largely ineffective against the resulting FAK force field, which has been identified in melanoma and most solid tumors of the breast, lung, brain, thyroid and colon.

Scientists are still unsure what causes mutations in p53 and why FAK binds to the damaged protein. But the study revealed that the interaction interferes with the signaling process that normally induces cell death, allowing cancer cells to grow unchecked.

The population-based study centered on 600 patients with breast cancer. UNC researchers, led by Kathleen Conway-Dorsey, an assistant professor of cancer epidemiology, analyzed p53 mutations in tumor tissue samples from the patients. UF researchers then identified the FAK protein in the breast cancer samples and performed a statistical analysis, finding that the p53 mutation is associated with overabundance of FAK.

“Basically, tumors of breast cancer patients with p53 had a higher probability of high expression of FAK,” said Golubovskaya. “We have shown before that FAK overexpression will highly correlate with more aggressive breast cancers.”

The findings provide important information from human tumor samples about how the tumor suppressor p53 acts to negatively regulate FAK expression, said David D. Schlaepfer, a professor of reproductive medicine at the Moores Cancer Center at the University of California, San Diego.

“The results connecting p53 mutations and increased FAK expression further our understanding of the factors that modulate FAK expression during tumor progression,” he said.

Results from the current study could help predict patient prognoses, researchers say. Many patients with mutant p53 and an overabundance of FAK don’t fare well, but new therapies could change that by targeting the protein interaction. The next step will involve identifying the types of p53 mutations that contribute to an overabundance in FAK.

Surgery remains the treatment of choice for patients with cancer, Golubovskaya said. Scientists and surgeons often focus their efforts on determining why cancer developed. Overabundance of the FAK protein can be detected during very early stages of breast cancer, even in pre-malignant tissues. UF cancer researchers are currently developing FAK inhibitors that will pave the way for future therapies.

“We now need to answer questions about why the interaction happens and what regulates it,” Golubovskaya said. “If FAK is overexpressed, how can we stop it early to slow cancer growth and metastasis? Answering these questions together with surgeons and scientists can help to fight this deadly disease.”

The research was supported by Golubovskaya’s grant from Komen for the Cure and a National Institutes of Health grant held by surgical oncologist Dr. William Cance, chairman of the UF College of Medicine’s department of surgery.

Cance and colleagues were the first to pull FAK out of human tumors to show that cancers make the molecule in large quantities. In 1996, the team was the first to show that if a tumor is prevented from producing the enzyme it dies. In 2004, the team found the regulatory region of this protein and in 2005, found the interaction of FAK and p53 proteins. The significance of this finding was reviewed by Golubovskaya and Cance in the journal International Review of Cytology last year.

“These findings put together another piece of the complex cancer puzzle and open the way for highly specific molecular cancer therapy that can target the p53-FAK interaction,” said Cance, who also is an associate director at the UF Shands Cancer Center.

“Searching for the presence of this gene may be one way to better identify patients who are at an increased risk for the phenomenon,” said Dr. David S. Sheps, a professor and associate chairman of cardiovascular medicine at UF’s College of Medicine and the Malcom Randall Veterans Affairs Medical Center.

Those with the gene variation are three times more likely to experience dangerous decreases in blood flow to the heart — a condition doctors call ischemia — than heart disease patients without it. Ischemia increases the chance these patients will suffer a heart attack, heart rhythm abnormalities or sudden death, UF researchers report in the April 14 issue of Archives of Internal Medicine.

“There’s no question that in certain populations it is associated with worse prognosis than in patients who do not have mental stress-induced ischemia in terms of overall adverse events and also mortality,” Sheps said. “And it has become apparent that it is far more prevalent than we initially thought. Most of the studies that have been published to date have involved populations of patients who had coronary disease and positive exercise stress tests. But recently we and other investigators have shown that a much broader category of patients also are prone to mental stress ischemia.”

Past studies have shown that as many as two-thirds of patients with coronary artery disease who experience exercise-related reductions in blood flow to the heart respond similarly to mental stress. These bouts often produce no symptoms of chest pain and are rarely detectable on a standard electrocardiogram. Yet previous UF research has shown that these patients have a threefold greater risk of dying — as large a risk factor as cigarette smoking or high cholesterol. Other studies have linked stress experienced after mass disasters or natural catastrophes with a rise in heart attacks and sudden death.

Psychological stress can leave the heart more prone to developing arrhythmias or electrical instability and the blood more prone to clotting. Stress appears to raise heart rate and rapidly hike blood pressure, increasing the heart’s need for oxygen-rich blood, Sheps said. Yet less oxygen is supplied, in part because coronary arteries constrict, impeding blood flow. Doctors are concerned that this reaction to stress in the laboratory is simply a snapshot of how patients respond to the stress of life on a daily basis.

An estimated 10 percent of all patients with coronary disease experience detectable mental stress-induced reductions in blood flow to the heart. In some subsets of patients the phenomenon may be even more prevalent, involving up to 40 percent of these patients.

UF researchers studied 148 patients with coronary artery disease who were on average about 65 years old. Participants were asked to perform a public speaking test designed to induce stress. Images were taken of blood flow to the heart at rest and during the speech task. Blood samples also were collected and analyzed for five common gene variations.

About a fourth of the patients experienced mental stress-induced reduced blood flow to the heart, and about two-thirds of them harbored a particular variation of the adrenergic beta-1 receptor genotype that was associated with a three-fold increased risk of this phenomenon, said Dr. Mustafa Hassan, the study’s lead author and a research fellow in UF’s division of cardiovascular medicine. This receptor typically helps the body respond to stress by regulating blood pressure and heart rate, but a common variability in its gene may make certain patients more vulnerable to the effects of psychological stress.

The study was funded by the National Heart, Lung and Blood Institute and also was supported by the Malcom Randall Veterans Affairs Medical Center and the UF colleges of Pharmacy and Dentistry.

Why does mental stress restrict blood flow in some patients even when exercise fails to have the same effect? The effects of mental stress could predominantly affect the heart’s smaller vessels, causing them to spasm and temporarily limiting blood flow, Sheps speculated. In contrast, exercise tends to affect the heart’s blood supply through different mechanisms.

“We should focus our research on two areas,” he said. “One is better identification of patients who are prone to have this problem and two is looking for effective treatments once we know they have it. We need to know whether we can reverse this phenomenon. We are embarking on other treatment studies fairly soon.”

UF researchers are hunting for other genetic subtypes that could identify other patients at increased risk, he added.

“One of the advantages of detecting these sorts of things is that we may be able to in the future be more specific about what kind of treatment might work better in certain patients depending on their genetic makeup,” Sheps said. “That is one of the important things happening in many fields of medicine. There are many diseases that already have been shown to respond differently to different types of treatment based on genetic differences.”

GAINESVILLE, Fla. — Vividly colorful giant clams officially called tridacnids decorate many an upscale aquarium. But now experts say they boast an exterior beauty that masks an ugly truth: their potential for carrying foreign diseases.

In findings that may impact the reef clam industry as well as international trade, a University of Florida veterinary pathologist recently discovered Perkinsus olseni, an internationally reportable foreign pathogen, in aquacultured clams imported from Vietnam.

While not believed to be a threat to human health or other reef aquarium species, the pathogen’s presence concerns scientists as well as aquaculture industry representatives and points out the largely unregulated environment in which the importation of aquacultured reef clams from Asia occurs.

“I had 30 clams in my lab as part of a student research project,” said Barbara Sheppard, a clinical associate professor of pathology at the UF College of Veterinary Medicine. “Then they started looking sickly, and within four months, all of them were dead.”

As a pathologist, Sheppard was intrigued. She began investigating the cause of death by freezing tissues, putting them into formalin and conducting histopathology and DNA tests in her laboratory. Her findings, which will appear in an upcoming issue of Diseases of Aquatic Organisms, showed the presence of Perkinsus olseni along with a new species of Perkinsus that has yet to be characterized.

“This is an important finding,” said Ralph Elston, president of AquaTechnics, a Carlsborg, Wash.-based company that provides veterinary, laboratory and environmental assessment services to the shellfish industry. “It indicates the potential risk of the spread of animal disease when health monitoring is not in place to control such risks.”

Elston added that further research is needed to evaluate the distribution of previously unknown species of Perkinsus in Florida.

Giant clams are the largest bivalves in the world. Their range stretches across the Indo-Pacific region from the eastern coast of Africa in the west to the South Pacific in the east, according to the United Nations Environment Program’s World Conservation Monitoring Center. These clams represent an increasingly large proportion of the live invertebrates imported to become aquarium specimens. As a result of overexploitation, all species of giant clams are included in the Convention on International Trade in Endangered Species of Wild Fauna and Flora, an international agreement between governments that aims to ensure that international trade in specimens of wild animals and plants does not threaten their survival.

Based on CITES data from 1993-2001, Vietnam has dominated the export of live giant clams since 1998. The United States and Europe are the main importers, and captive bred, or aquacultured, clams represent only about a third of the nearly 1 million tridacnids traded worldwide.

Sheppard is now collaborating with the Virginia Institute of Marine Sciences, the Maryland Department of Agriculture and Anita Wright, a Perkinsus researcher and associate professor at UF, to further characterize the new exotic species of Perkinsus that Sheppard discovered in her clam colony.

“This is not a zoonotic disease, transmissible to people,” Sheppard said. “No one is going to get sick from this, as far as we know. The problem here is economic and international trade. We know that Perkinsus is a pathogen of aquatic shellfish, and the reason it is so important is that it makes animals very vulnerable to dying when the weather gets hot or when they get stressed in some other way.”

She added that a major pathogen known as Perkinsus marinus is already associated with the depletion of major oyster stocks on the Atlantic coast.

“It’s indigenous; you can’t avoid it, and we know that particular pathogen is already economically devastating to our shellfish industries,” Sheppard said. “They don’t want this Pacific version of Perkinsus (olseni) to be transported here.”

Although the infected clams were found in Florida, tridacnids are imported and distributed to hobbyists throughout the United States. Sheppard’s findings suggest that almost certainly clams infected with Perkinsus olseni and the new Perkinsus species have made their way into consumer aquariums throughout the United States, she said.

“This is a great example of why you should never release an aquarium animal anywhere, under any circumstances,” said Ruth Francis-Floyd, director of UF’s Aquatic Animal Health Program. Aquarium owners seeking an aquatic veterinarian may reference the AquaVets Web site at www.aquavetmed.info/.

The ornamental aquarium trade operates globally with very few restrictions to transport product as quickly as possible, said Craig Watson, director of UF’s Tropical Aquaculture Laboratory in Ruskin.

“There are probably 3,000 species involved, and no one species has the value to justify the cost of a quarantine facility big enough to handle everything,” Watson said.

Members of the clam aquaculture industry as well as the oyster industry are aware of the recent Perkinsus olseni findings and are trying to respond, he added.

Watson said he is working with Florida aquaculture representatives who “really want to do the right thing” and added that his laboratory has proposed a voluntary protocol involving testing and quarantine procedures.

“The cost of doing this, however, is significant,” he said. “The ultimate goal would be to start a Perkinsus-free aquaculture industry in the United States where baby clams that have never been exposed to the disease are produced.”

In his book, “The Sugar Fix: The High-Fructose Fallout That Is Making You Fat And Sick,” Dr. Richard Johnson reviews the increasing evidence that fructose may play a role in the obesity epidemic and proposes a low-fructose diet he believes could help people lose weight and potentially prevent diabetes and cardiovascular disease.

“We recognize that obesity has multiple causes, including eating too much and exercising too little, but we think a missing piece of the obesity puzzle is fructose intake,” said Johnson, the J. Robert Cade professor of medicine and chief of the division of nephrology, hypertension and transplantation in the UF College of Medicine. “It’s not fructose itself that is the problem, but eating too much of it.”

Americans consume nearly three times as much fructose as a century ago, Johnson said. Although the major source of fructose is soft drinks, it’s found in a variety of foods such as fruit, juice, sweetened cereals and pastries.

“We think fructose makes you obese not simply by the calories it provides but because it also tricks hormonal systems that control appetite,” Johnson said. “You don’t get a sense of being full so you keep eating. It (fructose) may also be important in the development of diabetes, kidney disease and heart disease.

“An additional problem is that the more fructose you eat, the more sensitive you become to it,” Johnson said. “If you want to have success losing weight, you have to cut out fructose for two weeks. At that point you are no longer as sensitive and you can resume a low-fructose diet with ease.”

Johnson’s book, which was published by Rodale, contains a diet he developed with nutritionist and dietitian Elizabeth Gollub, as well as tables listing the fructose contents of common foods. Fructose content is not found on most labels.

Unlike other low-carbohydrate diets, which require dieters to reduce all carbs, Johnson’s plan targets fructose. Starchy foods like potatoes and rice aren’t a no-no as in low-carb diets. And after the first two weeks, dieters can resume eating fruit and having treats such as cake in moderation.

“Most people are used to eating about 50 percent of their diet as carbohydrates,” Johnson said “When you cut it way back and have a very high-protein, high-fat diet, it’s very hard to sustain. It’s also not necessarily healthy. What’s great about our diet is we can maintain a normal carbohydrate-protein-fat balance, and when you do that, the diet is much easier to sustain.”

Johnson became interested in fructose while studying hypertension. He and his colleagues discovered that uric acid increased blood pressure in animals and that ingesting fructose seemed to spur production of uric acid. Reducing uric acid in these animals helped control blood pressure and other problems such as pre-diabetes.

“The effect of fructose to cause pre-diabetes and raise blood pressure may be more important than its effects to increase weight,” Johnson said. “Our studies suggest that, even if one can control one’s weight, that excessive intake of fructose may increase the risk for high blood pressure and diabetes. Going on a low-fructose diet will have benefits above and beyond losing weight.”

The research in Johnson’s book came from studies in his own lab as well as from other scientists studying fructose in cells, animals and humans at other institutions, he said.

He also reviews the history of fructose consumption, comparing it with the rise of obesity. The two histories mirror each other, he writes.

Although fructose consumption was already on the rise when high-fructose corn syrup was invented, the introduction of this sweetener in the late 1960s accelerated the increase. High-fructose corn syrup contains about as much fructose as table sugar but is cheaper to produce, leading companies to produce bigger portions of sweets and soft drinks for the same price, Johnson said.

Today, Americans eat 30 percent more fructose than they did in the 1970s and three times as much as in 1900, when the obesity rate was 5 percent, Johnson said. About 33 percent of adults are now overweight or obese, according to the Centers for Disease Control and Prevention.

“After reading this book I found myself looking more carefully at labels, looking specifically for high-fructose corn syrup,” said Dr. Andrew Whelton, an adjunct professor of medicine and the former director of clinical nephrology at Johns Hopkins University. “I was amazed to see it so often.

“Although this book was put together for a lay audience, I thought it would be useful for health-care providers, particularly for anyone who deals with issues of obesity and diabetes.”

Reported this month in the online edition of the Journal of Proteome Research, the advance could one day lead to earlier detection and improved treatment of some types of cancer as well as other diseases.

“With many diseases, the problem has been that we really don’t know what to look for,” said Weihong Tan, a professor of chemistry and the lead author of the paper. “What we’ve done is create a technique to identify the biomarkers despite that limitation.”

Doctors often diagnose cancer and other diseases based on the appearance of a tumor or a patient’s symptoms. While such traditional methods can be effective, they sometimes identify a disease only after it is established. For example, clinicians may get tipped off to the presence of lung cancer — which kills more people than any other type of cancer — based on visible images of a tumor that appear on radiological exams of a patient’s lungs.

Because earlier detection typically improves outcomes, doctors would like to spot disease at the molecular level, before it grows or spreads and manifests itself in more obvious and harmful ways. Given that diseased cells’ molecular structures differ from those of healthy ones, that approach should be possible, and researchers have had some success finding such “biomarkers” using antibodies, Tan said. But despite years of research, biomarkers for most diseases remain elusive or unreliable, he said.

His group turned to “aptamers,” single-strand chains of DNA or RNA that recognize and bind to target protein molecules, as a new tool. His paper reports the first-ever successful use of the aptamers to discover a molecular biomarker — in this case, one for leukemia.

Tan said his group used cell-SELEX, a process his group developed and patented.

Researchers create trillions of different varieties of aptamers in a solution. They then immerse cells known to carry the sought-after disease in the solution. After an incubation period, they rinse the cells.

The vast majority of the aptamers wash away, but those with stronger molecular affinity for the diseased cells remain. The researchers repeat the process several times, eventually shrinking the pool of aptamers to as few as 10 to 25 very strongly attached aptamers — those most closely associated with the diseased cells. Analysis then reveals these aptamers’ molecular structure, as well as the molecular structure of the cells’ biomarkers they bind to.

“As long as the molecules in question are expressed in a substantially different way on diseased and normal cells, they can be identified,” Tan said.

Rebecca Sutphen, associate professor and director of the Genetic Counseling & Testing Service at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, said improved diagnosis may not be the only application of the research.

“The opportunity to identify cancer cell-specific biomarkers and potentially detect small numbers of cancer cells has many potential clinical applications, including disease detection, better imaging of tumors and even potential application for stem cells,” she said.

Other biomarkers have been found for leukemia, but none is particularly reliable, Tan said. Tan and his colleagues reported using aptamers to recognize cancer cells in a 2006 paper in the Proceedings of the National Academy of Sciences. Tan said the latest paper advances that work by revealing the target biomarkers the selected aptamers recognize, Tan said. These targets will form a molecular foundation in understanding diseases, he said.

“In 2006, we did not know what the aptamer recognized on the cancer cell surface,” he said. “In this current work, we report discovering these biomarkers, which then form the molecular foundation for us to understand the cancer and to prepare different molecular tools for molecular medicine.”

Tan said the research is particularly promising because aptamers are relatively easy and inexpensive to manufacture compared with antibodies. “This offers the potential for wider application,” he said, adding that aptamers could one day be used not only to detect disease, but also to ferry therapeutic agents to diseased cells.

The research was funded in part with two grants from the National Institutes of Health. It was also funded with two grants from Florida’s Bankhead-Coley Cancer Research Program and one grant from the State of Florida Center of Excellence in Bio/nano sensors.

The paper’s co-authors are Dihua Shangguan, Zehui Cao, Ling Meng, Prabodhika Mallikaratchy, Kwame Sefah, Hui Wang and Ying Li.

AAA and the University of Florida National Older Driver Research and Training Center are making these and other recommendations for addressing the physical, visual and cognitive changes that affect senior drivers as part of the Smart Features for Mature Drivers program. AAA and UF announced the smart features today (March 21) at the New York International Auto Show.

Reduced range of motion, arthritic joints, diminished fine motor skills and trouble with night vision and recovery from glare are all common age-related physical changes that can affect driving ability. A recent AAA survey found that 43 percent of drivers over 55 suffered from at least one of nine driving-related difficulties commonly caused by aging.

“There are ways to counteract the difficulties brought on by age-related changes so that seniors can maintain their safe driving abilities,” said Dennis McCarthy, co-director of the National Older Driver Research and Training Center and a research assistant professor in the UF College of Public Health and Health Professions’ department of occupational therapy. “One of these is through proper use of particular vehicle features.”

In 2003 about one in seven licensed drivers was 65 or older. By 2029, that proportion is expected to rise to one in four drivers, according to the AARP Public Policy Institute.

“The goal of Smart Features for Mature Drivers is to ensure that mature drivers are comfortable in their vehicles and to keep them driving safely as long as possible,” said Desiree Lanford, a UF driving rehabilitation specialist.

Smart Features for Mature Drivers recommends particular vehicle features based on the driver’s needs. For example, thick steering wheels, keyless entry and ignition, power mirrors and larger dashboard controls can make driving easier for seniors with arthritic hands or diminished fine motor skills. The doors on four-door models require less strength to open and close than two-door vehicles. Those with limited range of motion in the back, neck, shoulder or arm should consider large, wide-angle mirrors, tilt steering wheels and comfortable, six-way adjustable seats with lumbar support when choosing a vehicle. Seniors with vision issues may benefit from extendable sun visors and larger dashboard controls with contrasting text.

“The best vehicle features are those that fit the individual person and his or her limitations or needs,” Lanford said.

AAA and UF experts also suggest all mature drivers consider proven crashworthiness, antilock brakes, head restraints to reduce the risk of neck injuries, dynamic stability control to help prevent loss of control in a turn, and side and dual-stage or dual-threshold air bags that inflate based on the severity of the crash, lowering the risk of injury if airbags deploy with too much force.

“Safe driving is a function of person, environment and vehicle factors,” said Sherrilene Classen, a UF older driver injury prevention researcher and project team member. “The Smart Features for Mature Drivers project recognizes normal age-related changes and provides beneficial vehicle features to accommodate such changes — a critical step in injury prevention.”

To learn more about the Smart Features for Mature Drivers program, visit the Web site www.AAA.com/seniors.

“By providing public services such as Smart Features for Mature Drivers, AAA aims to keep our growing senior population safe behind the wheel,” said AAA President and Chief Executive Officer Robert L. Darbelnet. “We encourage older drivers and their families to use this as a guide in the selection of their next vehicle or evaluating their current one.”

A three-year, three-pronged prevention program did little to keep Chicago middle schoolers from drinking or using drugs, despite its prior success in rural Minnesota, where the program reduced alcohol use 20 to 30 percent, UF and University of Minnesota researchers recently reported in the online edition of the journal Addiction.

“The intervention found to be effective in rural areas was not effective here, which really surprised us,” said Kelli A. Komro, a UF associate professor of epidemiology in the UF College of Medicine and the study’s lead author. “This is an important finding to realize this program was not enough. The bottom line is this: Low-income children in urban areas need more, long-term intensive efforts.”

Adolescents who drink by age 15 — about half of teens — are more likely to struggle in school, abuse alcohol later in life, smoke cigarettes and use other drugs than those who don’t. Even worse, exposure to alcohol at a young age may damage the developing brain, according to a 2007 U.S. Surgeon General report.

“Almost any problem kids might have, alcohol increases that risk,” Komro said.

By targeting middle-school-age children, the UF and University of Minnesota team hoped to reduce these risks. The researchers studied 5,812 sixth-, seventh- and eighth-graders from mostly low-income communities in Chicago, randomly dividing the neighborhoods into two groups: those who would participate in the prevention program and those who would not.

The program, a tweaked version of what Komro and her colleagues developed for their Minnesota study, included three preventive approaches to relay the message that drinking is not acceptable in school, at home and in the community.

In participating schools, an alcohol prevention curriculum was used in the classroom. Students led these sessions because the prevention messages are more accepted when they come from peers rather than teachers, Komro said. The family component included homework assignments that parents and children could complete together, organized events for families, and educational postcards with helpful hints that were sent to parents. For the community aspect of the program, researchers hired organizers to work with community volunteers to change the risks and problems with teen drinking in their neighborhoods.

But at the end of the study, year-end surveys showed no difference in alcohol use among the teens who took part in the project and those who did not. At least 70 percent of the schools in the neighborhoods that did not use the program had some form of drug and alcohol prevention program in the schools. It’s unlikely these programs skewed the results of the study though, Komro said. UF’s prevention program was larger and more comprehensive than the other school-based programs and researchers would have detected a difference among the students had it worked.

One particular problem surfaced during the community component of the project. The organizers struggled to rally some community members around the cause, often having to explain why they should be concerned about adolescent alcohol use. That gave researchers some insight into why the program did not work there.

“People in these areas are concerned with housing, they’re concerned with gangs and other drug use,” Komro said. “There was a whole upfront effort where we had to educate people about how alcohol was related to those other issues, and that it was an important issue to think about with their young people.

“We know from other studies in low-income, urban neighborhoods, there is a higher concentration of alcohol outlets, compared to suburban or rural areas. There were a lot of alcohol ads around these schools and a greater density of pro-alcohol messages these children are exposed to. You mix that with the poverty level and it’s just a high-risk environment.”

Despite the overall results, there were positive findings that researchers hope to build on, Komro said. Of all the components, the family interventions had the most significant effects. And one aspect of the community project worked well: Half of the community teams went to stores that sold alcohol and asked merchants not to sell to underage kids. In those communities, the ability of young people to buy alcohol went down 64 percent.

“While the findings may not be what the investigators were hoping for, they reported them fully and openly, and this is good for the field,” said Brian Flay, a professor of public health and director of the Prevention Research Center at Oregon State University. “Science can advance properly only when both positive and negative findings are reported.”

Just the right amount of concern could solidify ties between parents and their adult children, but too much fretting may become a burden to the relationship, said Elizabeth Hay, a UF psychology professor, who led the research.

“If someone knows you worry about them, they may see it as an expression of love and caring, but at the same time they can feel irritated and annoyed by it,” said Hay, whose study is published in the December issue of the journal Personal Relationships.

To date, most of the studies on worry don’t consider worries experienced within the context of specific relationships and instead focus on pathological worries or anxiety disorders, she said.

Worrying appears to reflect people’s investment in the relationship, Hay said. Parents and their adult children felt more positively about their relationships when the other party worried about them and conveyed their concerns, she said.

At a certain point, however, expressing one’s unease to the other person exacted a cost, Hay said. The more parents and adult children worry about one another and discuss those worries, the more negatively the other party viewed the relationship, she said.

“In a sense it’s socially and emotionally supportive to worry and share your concerns, but you need to do it in a way that doesn’t make the other person feel that you perceive them to be incapable of managing their own affairs,” she said. “Perhaps they feel like you are undermining their autonomy, and maintaining autonomy is important in parent-adult child ties.”

In the study, 70 percent of the adult children said their parents’ health was their biggest worry, while parents expressed a wide range of worries relating to their adult children, according to an analysis she did for a second paper that has not been published yet.

“The interesting thing is that many of the children in our study were in their 20s and their parents were not of advanced age or experiencing any health problems,” Hay said.

The study’s participants were 213 adult children — 110 daughters and 103 sons — between the ages of 22 and 49 and each of their mothers and fathers, whose ages ranged from 40 to 84. They were interviewed by telephone in the Philadelphia area from fall 2002 through fall 2003.

“Very few adults or their parents said they didn’t worry about each other,” Hay said. “Almost everyone could identify a major worry that they could clearly explain, and they reported thinking about it somewhat to a lot of the time.”

Parents worry about their children largely as a continuation of patterns that developed early in the relationship, Hay believes. “When children are young and parents are responsible for so much of their life, they probably worry about a variety of things, which is not likely to just suddenly stop once their children become adults,” she said.

Indeed, while the focus of adult children’s worries overwhelmingly centers on their parents’ health, parents had many diverse worries, the study found. They talked about their children’s health, but they also mentioned finances, relationship issues and problems in balancing work and family, Hay said.

A small proportion of adults brought up more global concerns, such as today’s world being a dangerous place, Hay said. The majority of parents discussed anxieties that were specific to their own situation, though, such as their child having an unsafe job, she said.

The study found that daughters fretted slightly more about their mothers than fathers, while sons worried equally about both parents, Hay said. There were no differences in how much mothers and fathers worried about their daughters and sons, she said.

Worrying was also slightly greater in black families than in white ones, the results showed. Participants in the study included 141 white and 66 black families, with each family consisting of an adult child and two parents.

The study confirms that worrying is still very much a part of family relationships once children have grown and moved out, she said.

“I think the take-home message would be that to a certain degree it is normal to worry about your adult child or to worry about your parents, even if it is before they get very old and have health problems,” she said.

Hay did the research with Karen Fingerman, professor of developmental and family studies at Purdue University, and Eva Lefkowitz, professor of human development and family studies at The Pennsylvania State University.