Research Notes

Updated 8:00 PM September 2, 2005

Research Notes

Researchers synthesize tooth enamel structure in the lab

Researchers at the University have created crystals that can be organized into a structure that mimics enamel of human teeth, a step toward creating fillings to replace material that has been destroyed.

Research investigator Haifeng Chen's laboratory creation is reported in an article in the current issue of the Journal of Colloid and Interface Science.

Chen uses a simple idea to explain why he's excited about simulating the hard, white exterior of teeth. "If you have a cavity and you have two choices of a material to fill a tooth in your mouth—one that's similar to what's in your own teeth, and one that's not—which would you choose?" he asks.

Materials now used to fill cavities all have some drawbacks. For example, porcelain is very hard, which helps it last but also causes wear on teeth that come into contact with one that's been filled. Real enamel contains fluoride and acts as a reservoir of the naturally occurring compound that can help fight tooth decay. Synthesized enamel would mimic that ability.

Brian Clarkson, chair of cariology, restorative sciences and endodontics and the Clifford T. Nelson Professor of Dentistry, is senior author on the paper. He and Chen, a research investigator at the School of Dentistry, worked on the project with Kai Sun and John Mansfield at the U-M Electron Microbeam Analysis Laboratory, where Chen also has an appointment.

Clarkson believes it's possible the researchers could have an enamel-like composite within a year, and produce crowns suitable for repairing decayed teeth within about four years.

The collaboration is funded by the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health.
—Colleen Newvine, News Service

Why don't some patients take their medicines?

Patients who trust their doctors are more likely to stick to their prescription medicines, even if they face high out-of-pocket costs, a new study finds. But patients who have lower levels of trust in their physicians, or who have depression-like symptoms, are much more likely to skip doses or refills when costs become a problem.

The research from a team at U-M and the VA Ann Arbor Healthcare Center was published in the Aug. 8/22 issue of the Archives of Internal Medicine.

In all, nearly 30 percent of people who reported low levels of trust in their doctors and had monthly drug costs of more than $100 said they skipped medicines due to the expense, compared with 11 percent of those who had a more trusting relationship with their doctors and the same level of cost. Among people with incomes under $10,000, cost affected adherence to drugs only among those with low physician trust.

Patients who reported experiencing symptoms of depression on a standardized scale were twice as likely to skip medicines due to cost as patients without depression. And patients who reported problems taking medications for other reasons were much more likely to report that they had cut back on medicine use due to cost.

The findings suggest that a trusting patient-physician relationship can significantly influence whether a person sticks to prescriptions when that patient faces pressures from medication costs, says lead author John Piette, a member of the VA Ann Arbor Center for Practice Management and Outcomes Research and associate professor in the general medicine division of the U-M Medical School.

Piette notes that many patients who cut back on medication use due to cost do not tell their doctors.

In addition to Piette, the paper's authors are senior author Dr. Eve Kerr, VA research scientist and U-M associate professor of internal medicine; Dr. Michele Heisler, VA research scientist and U-M assistant professor of internal medicine; and Sarah Krein, U-M internal medicine research investigator.
—Kara Gavin, UMHS Public Relations

Mutual funds: introducing B and C class shares: the downside

Mutual fund investors who snapped up new classes of shares in the past decade may have jumped prematurely before considering the impact on fund performance, a study by the business school shows.In switching to a multiple-class structure by adding B and C shares to existing A shares, load funds offer mutual fund investors more choices but not necessarily better returns, according to Lu Zheng, assistant professor of finance at the Stephen M. Ross School of Business.

The newer share classes, introduced in the 1990s, offer investors a choice of paying back-end loads—sales charges or commissions paid when an investment is sold—and/or annual fees instead of the hefty front-end loads required for purchases of traditional A shares. Introducing the new classes attracts significantly more new money in the first couple of years, controlling for performance and other fund attributes, Zheng says. The downside, however, is that about two years after introducing the new classes, funds experience a significant drop in performance, which is expected to erode substantially the cash-flow growth induced by new classes.

In their study, Zheng and colleagues Vikram Nanda and Z. Jay Wang examined how the transition to a multiple-class structure affects fund cash flows, investor clientele, performance and expenses.

The study shows that switching from a single A class to a multiple-class fund increases the overall fund cash inflow initially by an estimated 12 percent, controlling for performance and other factors. Given the average fund size in 2002, this amounts to nearly $16 million in new money—but the new growth slows down after the second year.

The results indicate, however, that switching to the multiple-class structure hurts overall fund performance. Starting from the second year after the transition, multiple-class funds underperform their no-load counterparts by 1.2 percent to 1.7 percent annually on a risk-adjusted basis. The fund's diminished performance can reduce the inflow of new investment dollars by 2 percent to 3 percent annually.
—Bernie DeGroat, News Service

Chemical prevents heart failure in mice with MD

A common chemical used in the manufacturing and pharmaceutical industries can repair damage to cardiac muscle cell membranes and prevent heart failure in mice with the genetic mutation that causes Duchenne muscular dystrophy, according to scientists at the Medical School.

The chemical sealant that protected hearts in dystrophic mice from damage is called poloxamer 188. Joseph M. Metzger, a professor of molecular and integrative physiology and of internal medicine in the Medical School who directed the research, says poloxamer 188 can insert itself into small holes in cell membranes.

The study is the first to show what happens to heart muscle cells called myocytes in the absence of dystrophin, and the first to demonstrate a new, promising approach to repair the damage. Many people with Duchenne muscular dystrophy die in their 20s from heart failure caused by cardiomyopathy, a gradual weakening of the heart muscle.

The study was published July 17 in Nature as an advance online publication. It was funded by a grant from the National Institute on Aging.

The key to the discovery was technology developed by Soichiro Yasuda, a postdoctoral fellow and co-first author of the study. He created a device to allow the simultaneous measurement of force and intracellular calcium concentration in individual myocytes as they are stretched.

To test for the presence of tears in myocyte membranes, researchers used a special fluorescent dye, which cannot penetrate an intact cell membrane. After a 20 percent stretch, control myocytes remained stable and showed no fluorescence, while myocytes from mdx mice became unstable, started shaking and showed a steady increase in fluorescence, providing direct evidence of membrane damage.

DeWayne Townsend, a postdoctoral fellow in molecular and integrative physiology in the Medical School, was co-first author of the study. Additional U-M research collaborators included Daniel E. Michele, assistant professor of molecular and integrative physiology and of internal medicine; Elizabeth G. Favre, research associate; and Dr. Sharlene M. Day, clinical lecturer in internal medicine.
—Sally Pobojewski, Medical School Communications

Threat of long sentences has minimal effect on young criminals

Young offenders aren't necessarily deterred from crime after they turn 18, even when they know they could be slapped with a much longer prison sentence if they commit further violations, a study co-authored by a U-M researcher shows.

Offense rates should decline at 18 due to stiffer sanctions once one becomes an adult, but essentially are the same as offense rates just before 18, says Justin McCrary, a professor at the Gerald R. Ford School of Public Policy and Department of Economics. Though it might seem that some individuals should be deterred by the prospect of the stiffer sanctions and fail to commit crimes, lowering the offense rate, the authors' research does not support this contention.

McCrary co-wrote "Crime, Punishment, and Myopia," with David S. Lee, an economics professor at the University of California, Berkeley. The paper appears on the National Bureau of Economic Research Web site.

A natural policy implication of the findings, McCrary says, would be to spend less money on prison expansion and more money on police officers. Alternatively, funds could be targeted toward non-criminal justice programs that attempt to discourage youth from becoming career criminals.

The study examines felony arrests from 1995-2002 in Florida, where the criminal age of majority is 18. The sample involved more than 64,000 individuals who were arrested at least once by their 17th birthday. McCrary emphasizes the importance of the paper's methodology—a comparison of offense rates a handful of weeks before and after the 18th birthday—for answering how responsive individuals are to prison length.
—Jared Wadley, News Service

Study finds women connect sex with submission

A U-M study suggests that women, not men, automatically associate sex with submission, and that connection reduces the quality of their sexual experience.

Researchers Amy Kiefer, a graduate student instructor (GSI) in psychology, Diana Sanchez, a GSI in psychology and women's studies, and Oscar Ybarra, associate professor of psychology conducted four studies to reach the conclusions in the paper, "Sexual Submissiveness in Woman: Costs for Sexual Autonomy and Arousal," scheduled to appear in Personality and Social Psychology Bulletin next year.

Key findings show that women implicitly associate sex with submission and that this leads to a submissive sexual role, which in turn leads to lower arousal and difficulty becoming aroused. This association appears to lower their arousal by reducing sexual autonomy.

Researchers tested subjects by showing target words associated with submission on a computer screen, preceded by subliminal primes—words with a specific connotation, in this case sex primes and neutral primes. For example, sex and oven. Women's responses on average were faster when submissive words were preceded by a sex prime than by a neutral prime. This faster response indicates the two concepts are related in women's minds, says Kiefer, a recent doctoral graduate in the psychology department. Further, on average the quicker the response, the more likely the women were to report engaging in submissive sexual behavior.

The priming results indicate that women may have unconsciously picked up the message that they should be sexually submissive, raising the possibility that women have internalized societal pressure, Sanchez says.

Adopting a submissive role may cause women to have difficulty not only getting aroused, but also impair their communication with partners, undermine their ability to insist on birth control, and increase their susceptibility to sexual coercion.
—Laura Bailey, News Service

Chinese compound shows promise in head and neck cancer

A compound derived from cottonseed could help improve the effectiveness of chemotherapy at treating head and neck cancer, researchers at the Comprehensive Cancer Center have found.

The findings, which appeared in the July issue of the journal Molecular Cancer Therapeutics, could lead to a treatment that provides an effective option to surgically removing the cancer, helping patients preserve vital organs involved in speech and swallowing.

"Patients really benefit long-term by avoiding surgery because the side effects of surgery for head and neck cancer can be particularly difficult for patients. It affects how you talk, how you swallow and how you breathe," says study author Dr. Carol Bradford, professor of otolaryngology at the Medical School and co-director of the Head and Neck Oncology Program at the Comprehensive Cancer Center (CCC).

The compound, (-)-gossypol, works to regulate a protein called Bcl-xL that's overexpressed in cancer cells and makes them survive when they shouldn't. Shaomeng Wang, co-director of the Molecular Therapeutics Program at the CCC, discovered (-)-gossypol, a compound derived from a component of Chinese medicine. Gossypol once was used in China as a male contraceptive. More recently, it's been tested as a cancer treatment.

In the study, researchers developed head and neck cancer cell cultures resistant to the chemotherapy drug cisplatin. The researchers treated these cisplatin-resistant cell lines with (-)-gossypol and found that (-)-gossypol induced the drug resistant tumor cells to undergo programmed cell death.

Thomas Carey, co-director of the Head and Neck Oncology Program at the CCC and a professor in the School of Dentistry and Medical School, authored the study. Collaborators included lead study author Joshua Bauer, a graduate student in pharmacology, and research assistants Bhavna Kumar, Jason Castro, Julia Shin-Jung Lee and Jianyong Chen.
—Nicole Fawcett, Comprehensive Cancer Center

Lives, money could be saved by ending co-pays for ACE inhibitors

U-M Health System (UMHS) researchers have found that giving free ACE inhibitors diabetes medicine to the 8 million Americans over 65 with the disease ultimately would save the Medicare system and society money by preventing heart attacks, strokes and kidney failure.

Lead author Dr. Allison Rosen says patients' out-of-pocket costs such as co-pays are a blunt instrument designed to keep patients from over-using medications, but they create barriers to the use of essential and non-essential medications alike.

A benefit-based co-pay was proposed in 2001 by Dr. Mark Fendrick, a co-author on the new paper and professor of internal medicine at the Medical School. Rosen, an assistant professor of internal medicine in the Medical School and associate professor of health management and policy at the School of Public Health, who performed the research, in part, while at Harvard University, explores drug costs and benefits though computer models. She worked on the paper with Dr. Sandeep Vijan of U-M, also an assistant professor of internal medicine, and the VA Ann Arbor Healthcare Center.

The findings appeared in the July 19 Annals of Internal Medicine.

Researchers assumed that if Medicare made ACE inhibitors available free to any enrollee with diabetes, the use of the drugs would increase from 40 to 60 percent of patients. Based on research into the effect of co-pays on patient behavior, they projected that the new Medicare drug plan, which will cover about one-third of the cost of the drug, will increase usage from 40 percent to about 47 percent.

If Medicare paid for the cost of the drug for all adults over age 65 who have diabetes, added to the existing cost of their entire healthcare until death, the total savings would be $1,606 over a lifetime for each Medicare recipient, Allison says.
—Kara Gavin, UMHS Public Relations

When caregiving is over, some have lasting grief

Low-income caregivers of elderly relatives are more likely than others to continue experiencing high levels of depression after their loved ones die, according to a U-M study.

The vulnerability of low-income caregivers may be related to the fact that poverty itself is a chronic stressor that takes a toll on mental health, in addition to diminishing caregivers' capacity to cope with the loss of their loved ones, says Lydia Li, an assistant professor in the School of Social Work.

Caregivers of recipients with more problematic behaviors have high levels of depression during caregiving, which continues into bereavement. "Such findings suggest that caregiving to elders with more problematic behaviors might have long-term negative effects on caregivers' mental health," Li wrote in the current issue of the Journal of Gerontology: Psychological Sciences.

Li says bereavement support services to caregivers should target vulnerable groups, such as those with low incomes and those of recipients with high levels of problematic behaviors.

On average, family caregivers experience increasing depressive symptoms as their care recipients are closer to death and decreasing symptoms after the death, the study showed. Some caregivers, including those with low incomes and those who have cared for relatives with more problematic behaviors, however, remain distressed even after the stress of caregiving is over.

For some caregivers, the death of their care recipients provided a relief and an opportunity to re-engage in other roles and activities, Li says. Particularly, caregivers who felt overwhelmed during caregiving indicated a great relief after it ended. Wife caregivers, compared to daughter caregivers, also showed steeper reduction in depressive symptoms after exiting the caregiver role. The former, nonetheless, had much higher levels of depression before their husbands' deaths.
—Jared Wadley, News Service

Possible Achilles' heel of the herpes virus found

Herpes simplex virus (HSV) can get inside almost any kind of human cell, reproduce in vast numbers and linger for years in the body. Its complications can kill, and it may increase susceptibility to many nerve and brain disorders.

Scientists haven't fully understood how HSV manages to do this, which until now, has stood in the way of developing more targeted, effective treatments.

In a presentation July 24 at the International Congress of Virology and in two papers in the Journal of Virology, U-M researchers from the Medical School reported the discovery of a receptor that appears to function as one lock HSV opens to allow it to enter human cells. They also have found the gene that controls production of the receptor, deciphered some aspects of its structure, and developed a pig-cell system that could be used to test new anti-herpes drugs.

"This may be one central part of the Achilles' heel in interactions of herpes virus with a cell to start infection. We can use the receptor molecule to try to understand the process and perhaps combat infection at this vulnerable site," says Dr. A. Oveta Fuller, leader of the U-M team, senior author on the papers and an associate professor in the Microbiology and Immunology Department.

Fuller says the search for the mechanisms by which HSV enters cells has been hindered by the fact that the virus is very good at entering so many kinds of cells.

For the studies, Fuller credits the persistence of research team members in working with the genomic library and culture of human and pig cells, especially doctoral graduate Aleida Perez and postdoctoral fellows Qingxue Li and Pilar Perez-Romero. Perez-Romero is first author of one of the papers and a co-author on the other.

The research team included Gregory DeLassus and Santiago Lopez, graduate students recruited by the Program in Biomedical Sciences and the National Institutes of Health-supported Genetics Training Program. Funding for the studies was provided by the NIH, the Herpesvirus Foundation and pilot grants from U-M.
—Kara Gavin, UMHS Public Relations

A rare bird? Genetic analysis says not so

Efforts aimed at saving one of the world's rarest birds of prey from extinction may be too late, a genetic analysis by researchers at U-M and The Peregrine Fund suggests.

The last remaining Cape Verde Kites, considered by some to be the rarest raptors in the world, are not Cape Verde Kites at all, but more common Black Kites, the research shows. The real Cape Verde Kites apparently disappeared some time ago and never were a uniquely different species.

The finding, recently published online in the Proceedings of the Royal Society B, adds a new twist to the ongoing debate about how species are defined and how those definitions are used to guide conservation efforts, says David Mindell, a professor of ecology and evolutionary biology and director of the U-M Museum of Zoology.

It important to recognize distinctive species as the focus for scarce conservation funds, but as this example shows, there are cases in which species that were recognized over 100 years ago actually aren't valid species, Mindell says. In such cases, funds might be redirected to species in dire need. The birds known as Cape Verde Kites live only on the Cape Verde Islands, in the Atlantic Ocean about 300 miles west of the African country of Senegal. Conservationists have been concerned that habitat loss, widespread use of rodent-killing chemicals and other factors were driving the birds to the brink of extinction and threatening other types of wildlife on the islands.

Working with U-M postdoctoral fellow Jeff Johnson and Richard Watson of The Peregrine Fund, Mindell performed a genetic analysis on material from contemporary Black Kites, Red Kites and historical Cape Verde Kite museum specimens collected between 1897-1924, as well as the five kites captured on the Cape Verde Islands in 2002.

Mindell found that the few kites on the island now are not Cape Verde Kites but Black Kites which are widely distributed throughout the Old World and are not in danger.
—Nancy Ross-Flanigan, News Service

Patients learn more from videos but need contact with doctors

In an age when people often learn health information from surfing the Web and watching television shows set in hospitals, researchers have found that showing patients an educational video teaches them about their diseases even better than when doctors tell them about the conditions.

The study by researchers at the U-M Health System (UMHS) also found that anxiety and stress are reduced much more among patients after they have visited with their doctors than after viewing the information on the educational video.

"The study confirmed the informational value of videotape-based educational materials. In fact, patients learned many more facts from the videotape—which was created with information from physicians—than they learned from their doctors during a clinic visit," says Dr. Jeffrey Orringer, lead author of the study, which appears in the Journal of the American Academy of Dermatology. Part of the reason the videotape was such a good educational tool, he says, is that the message was consistent. Patients could watch the tape over and over again, and the unchanging information was reinforced each time for the viewer.

While the video is invariable, a doctor can tailor information to the specific concerns and fears a patient is encountering, says Orringer, clinical assistant professor of dermatology at the Medical School and clinical director of the Cosmetic Dermatology and Laser Center at UMHS.

In addition to Orringer, the authors on the paper were Dr. Timothy M. Johnson, professor dermatology, director of the Cutaneous Surgery and Oncology Unit and the Melanoma Clinic at the Comprehensive Cancer Center, associate professor of surgery, and professor of otolaryngology; Dr. A. Mark Fendrick, professor of internal medicine and associate professor of health management and policy at the School of Public Health; Dr. Christopher Bichakjian, Dr. Jennifer Schwartz, Dr. Timothy Wang, and Dr. Darius Karimipour, clinical assistant professors in the Department of Dermatology; and Peter Trask, formerly a professor at U-M, now at Brown University.
—Katie Gazella, Medical School Communications

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