Medical Research Blog

The body’s ability to heal even small skin wounds normally slows down as we age. But a new study in older adults finds that regular exercise may speed up the wound-healing process by as much as 25 percent.

“This is the first time we’ve been able to document this kind of enhancement associated with exercise,” said Charles Emery, a professor of psychology and the lead author of the Ohio State University study.

The faster that a wound heals, the less chance it will become infected.

The results appear in a recent issue of the Journal of Gerontology: Medical Sciences.

The study included 28 healthy older adults ranging in age from 55 to 77 (average age was 61). The participants hadn’t exercised regularly for at least six months prior to the study. For the research, about half (13) of them exercised three times a week for three months. The other 15 participants served as controls and were asked not to change their physical activity habits during the study period.

Each subject received a small puncture wound on the back of the upper arm. Adults in the exercise group started working out about a month before the wound procedure; this gave their bodies enough time to adapt to a regular exercise program.

The wounds were about 1/8-inch across and deep. The researchers photographed the wounds three times a week until the wounds were no longer visible (about six to seven weeks).

The exercise sessions began with 10 minutes of warm-up floor exercises and stretching followed by 30 minutes of pedaling on a stationary bike. After that, participants either jogged or walked briskly on a treadmill for 15 minutes, followed by about 15 minutes of strength training. All sessions ended with five minutes of cool-down exercises.

Each participant completed assessments of exercise endurance and stress at the beginning and end of the study. The exercise endurance test, completed on a treadmill, measured each subject’s aerobic fitness level by measuring how much oxygen he or she consumed while working out.

The researchers also collected saliva samples from each participant in order to measure levels of cortisol, a primary stress hormone. High cortisol levels indicate that the body is under stress; prior studies have suggested that exercise is associated with lower levels cortisol.

Lastly, each subject completed a questionnaire called the Perceived Stress Scale. This scale let the researchers determine how stressful the respondents perceived their lives to be.

At the end of the study, the researchers found that skin wounds healed an average of 10 days faster in the people who exercised (29 days in the exercise group vs. 39 days in the non-exercise group.)

Not surprisingly, exercise endurance increased in the group that worked out, but remained the same in the non-exercise group.

The researchers were somewhat surprised to find a sharp increase in cortisol levels in the exercise group. The hormone is typically boosted by stress, and other studies have suggested that exercise may lower levels of stress.

“The stress of exercise may enhance the regulation of cortisol,” Emery said. “This increase in cortisol levels may represent a biological pathway by which exercise helps wounds heal.”

There were no changes in perceived stress in either group but none of the adults in this study reported any significant distress in their lives at the beginning of the study.

The current study supports the results of a related study on wound healing conducted at Ohio State a few years ago. That work compared wound-healing rates between older adults caring for a loved one with Alzheimer’s disease to rates of older adults who weren’t caregivers.

The healing rates of those who weren’t caregivers was similar to the healing rates of the non-exercisers in the current studying – wounds in both groups healed in about 40 days. Wounds among older caregivers took about 20 percent longer to completely heal.

“The findings from both studies indicate that the effect of exercise we found in the current study truly represents an enhanced rate of wound healing in older adults,” Emery said.

The next step is to determine if older adults who report a fair amount of stress in their lives – such as dealing with the death of a spouse or financial troubles – get the same kind of benefit from exercise.

Chemists in Chile and Spain have identified a new approach for the possible treatment of Alzheimer’s disease that they say has the potential to destroy beta-amyloid fibrils and plaque — hypothesized to contribute to the mental decline of Alzheimer’s patients. The researchers say the new technique, which they call a type of “molecular surgery,” could halt or slow the disease’s progress without harming healthy brain cells. The research is scheduled for publication in the Jan. 11 issue of the American Chemical Society’s Nano Letters.

Using test tube studies, the scientists attached gold nanoparticles to a group of beta amyloid fibrils, incubated the resulting mixture for several days and then exposed it to weak microwave fields for several hours. The energy levels of the fields were six times smaller than that of conventional cell phones and unlikely to harm healthy cells, the researchers say. The fibrils subsequently dissolved and remained dissolved for at least one week after being irradiated, indicating that the treatment was not only effective at breaking up the fibrils but also resulted in a lower tendency of the proteins to re-aggregate, according to the researchers.

The same approach also holds promise for treating other neurodegenerative diseases that involve protein aggregation, including Parkinson’s and Huntington’s, says study leader Marcelo J. Kogan, of the University of Chile in Santiago. He says that the approach is similar to that of another experimental technique that uses metallic nanoparticles to label and destroy cancer cells. Animal studies are planned, Kogan says.

There’s currently no cure for Alzheimer’s disease and no one is sure of its exact causes. The disease affects an estimated 4.5 million people in the United States, according to the National Institute on Aging. That figure is expected to rise dramatically as the population ages, experts predict.

New research suggests that years of repeated exposure to loud noise increases the risk of developing a non-cancerous tumor that could cause hearing loss.

“It doesn’t matter if the noise comes from years of on-the-job exposure or from a source that isn’t job-related,” said Colin Edwards, a doctoral student in the School of Public Health at Ohio State University.

In the current study, people who were repeatedly exposed to loud noise over the span of several years were on average one-and-a-half times as likely to develop this type of tumor compared to people who weren’t exposed to such noise on a regular basis.

The tumor, called acoustic neuroma, grows slowly and symptoms typically become noticeable around age 50 or older. Of the 146 people with acoustic neuroma in this study, nearly two out of three were 50 or older.

An acoustic neuroma tumor slowly presses the cranial nerve that is responsible for sensing sound and helping with balance. Symptoms include hearing loss and a constant ringing in the ears, or tinnitus.

The study is currently in the online advance access edition of the American Journal of Epidemiology.

Edwards and his colleagues gathered four years of data from the Swedish portion of the INTERPHONE Study, an international study of cell phone use and tumors that affect the brain and head.

The researchers used the Swedish portion of the study because health officials there keep meticulous data on rates of acoustic neuroma development in the country’s population, said Judith Schwartzbaum, a study co-author and an associate professor of epidemiology in the School of Public Health at Ohio State .

In addition to the 146 study participants with acoustic neuroma, another 564 people without the tumor who served as controls were also interviewed by a nurse. The participants in this group were randomly selected from the continuously updated Swedish population registry. Study participants ranged in age from 20 to 69.

All participants were asked if they were regularly exposed to occupational and non-occupational loud noise and, if so, for how many years. “Loud noise” was defined as at least 80 decibels – the sound of city traffic.

If the subjects said that they had been regularly exposed to loud noise, they were then asked to describe the activities during which they were exposed to that noise.

Categories for loud noise exposure included: exposure to machines, power tools and/or construction noise; exposure to motors, including airplanes; exposure to loud music, including employment in the music industry; and exposure to screaming children, sports events and/or restaurants or bars.

The researchers also collected data on the use of hearing protection.

The two types of loud noise posing the highest risk of acoustic neuroma development were exposure to machines, power tools and/or construction (1.8 times more likely to develop the tumor) and exposure to music, including employment in the music industry (2.25 times more likely to develop the tumor.)

Exposure to motors, including airplanes increased acoustic neuroma risk by 1.3 times, while regular exposure to screaming children, sports events and/or bars and restaurants increased the risk by 1.4 times.

The number of years that a person was exposed to any category of loud noise also contributed to the development of acoustic neuroma. Just five years of regular exposure to loud noise increased the chance that a person would develop acoustic neuroma by one-and-a-half times.

“It’s not surprising that the longer that people are exposed to loud noise, the greater their chances become for developing the tumor,” Edwards said.

The study results also suggest the importance of wearing ear protection when exposed to loud noises. People who reported that they protected their ears from loud noise had about the same risk of developing acoustic neuroma as people who were not exposed to loud noise. People who protected their hearing were also half as likely to develop acoustic neuroma as people who didn’t wear ear protection.

The tumor is fairly rare, accounting for only about 6 to 10 percent of tumors that develop inside the skull. Depending on the population, anywhere from one to 20 people per 100,000 develop acoustic neuroma each year. The people with the tumor in this study had the most common type – unilateral acoustic neuroma. About 95 percent of all cases of acoustic neuroma affect only one ear. The other kind, bilateral acoustic neuroma, is inherited and affects both ears.

If the tumor is caught early enough through a thorough examination and hearing tests, a physician may be able to surgically remove it. But as the tumor grows larger, it may become attached to the nerves that control facial movement, balance and hearing, making it far more difficult to remove the entire tumor.

The Journal of Dental Research has just published the results of a study showing that treatment of gum disease may reduce the risk of cardiovascular disease.

Researchers from Australia (Sydney Dental Hospital and Royal North Shore Hospital) and Norway (University of Oslo) collaborated in the PERICAR clinical trial, providing strong evidence linking periodontal (gum) disease to an increased risk of developing blood clots, which could lead to the onset of heart attack and stroke.

In recent years, many studies throughout the world have linked periodontal disease to increased cardiovascular risk, although the reasons for this link have not been fully explained, nor has it been proven that the link is a direct causal one. One explanation is that inflammation and infection have also been related to increased atherosclerosis and cardiovascular risk. Periodontal disease is the most common chronic infection in humans, and symptoms include bleeding, swollen or receding gums, and bad breath. In severe cases, the teeth become loose and may eventually fall out.

Individual participants who were involved in the trial had blood tests before and after treatment of gum disease that was so severe that all their teeth had to be extracted. The blood tests were for blood-clot risk factors and signs of inflammation.

The average level of factors fell when the gum infection was eradicated, suggesting that the risk of heart attacks and clots in the future had reduced. This also indicates that inflammation in the mouth has a measurable effect in the bloodstream, and therefore the rest of the body.

Although these results are exciting they do not yet provide proof of a direct link and more research is needed. With grants from the National Health and Medical Research Council of Australia and the Ramaciotti Foundation, the researchers are currently studying the relationship between gum and heart disease in people with less severe periodontal disease who do not need to have all their teeth extracted.

Dental disease impacts on people’s general health and well-being. Periodontal disease is common, preventable, and treatable. This study suggests that improving periodontal health could significantly reduce the risk of cardiovascular disease.

A study featured in this month’s edition of Gynecologic Oncology examines the challenges associated with the administration of intra-abdominal chemotherapy, also known as intraperitoneal (IP) chemotherapy. This is a companion study to a paper released today in the New England Journal of Medicine showing longer survival for women who received IP chemotherapy compared with those who received the standard intravenous (IV) regimen.

The New England Journal of Medicine study, “Intravenous Cisplatin and Paclitaxel Versus an Intensive Regimen of Intravenous Paclitaxel, Intraperitoneal Cisplatin and Intraperitoneal Paclitaxel in Stage III Ovarian Cancer: A Gynecologic Oncology Group (GOG) Study,” found that women who received part of their chemotherapy via an IP route had a median survival 16 months longer than women who received IV chemotherapy alone (65.6 months versus 49.7 months). Women could only be enrolled in this study if they had undergone thorough surgery resulting in optimal resection of their cancers such that the largest residual tumor nodules were less than 1 cm in diameter prior to initiation of chemotherapy. Segmental bowel resections were required to remove large tumor nodules in 32% of the women treated with IP chemotherapy. This finding highlights the importance of referral of women with known or suspected ovarian cancer to physicians with special expertise and training in the surgical management of ovarian cancer.

The IP therapy was shown to improve survival even though only 42% of patients in the IP therapy arm of the study completed all the prescribed IP treatments. This highlights the importance of continuing efforts to optimize techniques for IP chemotherapy administration.

The companion study published in Gynecologic Oncology, “Intraperitoneal Catheter Outcomes: A Phase III Trial of Intravenous Versus Intraperitoneal Chemotherapy in Optimal Stage III Ovarian and Primary Peritoneal Cancer: A Gynecologic Oncology Group Study,” by Joan L. Walker, MD and colleagues identifies issues and challenges associated with the administration of IP chemotherapy in conjunction with IV chemotherapy. These include proper surgical insertion and maintenance of IP catheters, as well as management of adverse events such as catheter obstruction, infection and bowel complications.

“IP chemotherapy’s success is dependent upon appropriate surgical resection, patient selection, and training of the physicians and nurses,” said Dr. Walker, Chief, Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Oklahoma. “We hope intraperitoneal chemotherapy will be embraced by the oncology community treating ovarian cancer, and will be translated into an improvement in overall survival and quality of life for these women.”

“The Society of Gynecologic Oncologists (SGO) and its members are encouraged by the latest findings on IP chemotherapy,” said Beth Karlan, MD, SGO President and Director of the Women’s Cancer Research Institute and the Division of Gynecologic Oncology at the Cedars-Sinai Medical Center. “IP chemotherapy should be considered by oncologists in women who have had optimal surgical resection for ovarian cancer.”

Ovarian cancer is the leading cause of death from a gynecologic malignancy in the United States. In 2005, the American Cancer Society estimates that there will be approximately 22,000 new cases of ovarian cancer identified in this country and more than 16,000 women will die from the disease.

Carbonated soft drink consumption was previously suggested to be linked to the 350 percent increase of adenocarcinoma of the esophagus since the mid-1970s, but researchers at Yale School of Medicine report that the link is unfounded and that there may, in fact, be a decreased risk of this cancer for diet soda drinkers.

The researchers warn that diet soft drink consumers might differ from other groups because they may engage in other unmeasured healthy behaviors. The study is published in the January 4 issue of Journal of the National Cancer Institute (JNCI).

It was hypothesized by others that carbonated soft drinks might have contributed to the development of adenocarcinoma of the esophagus. The theory was based on factors including similar time trends; acidic carbonated soft drinks causing gastric distension that might affect the lower esophagus; and association of carbonated soft drinks with heartburn at night, a known risk factor for esophageal adenocarcinoma.

“The theory that soft drinks could be causing this cancer was picked up by the media and widely disseminated,” said lead author of the Yale study Susan Mayne, professor in the Department of Epidemiology and Public Health at Yale School of Medicine and associate director of the Yale Cancer Center. “However, there was no direct evidence to bear on this hypothesis, until we initiated our analysis.”

Potential causes of esophageal adenocarcinoma were identified by Mayne and her colleagues in a previously completed population-based, multi-center study of 1,095 cancer patients and 687 control subjects. As part of that study, they conducted a full dietary interview and had access to available data on consumption of both regular and diet soft drinks.

“Our team analyzed that data as the first direct test of the hypothesis that soft drinks might have contributed to the increase in this cancer,” said Mayne. “We found that contrary to the hypothesis put forth by other researchers, carbonated soft drink consumption was inversely associated with esophageal adenocarcinoma risk, mainly attributable to diet soda, and that high intake did not increase risk of any esophageal or gastric cancer subtype in men or women.”

In the January issue of The Journal of Sexual Medicine, researchers have published a new investigation measuring sex hormone binding globulin (SHBG) before and after discontinuation of the oral contraceptive pill. The research concluded that women who used the oral contraceptive pill may be exposed to long-term problems from low values of “unbound” testosterone potentially leading to continuing sexual, metabolic, and mental health consequences.

Sex hormone binding globulin (SHBG) is the protein that binds testosterone, rendering it unavailable for a woman’s physiologic needs. The study showed that in women with sexual dysfunction, elevated SHBG in “Oral Contraceptive Discontinued-Users” did not decrease to values consistent with those of “Never-Users of Oral Contraceptive”. Thus, as a consequence of the chronic elevation in sex hormone binding globulin levels, pill users may be at risk for long-standing health problems, including sexual dysfunction.

Oral contraceptives have been the preferred method of birth control because of their ease of use and high rate of effectiveness. However, in some women oral contraceptives have ironically been associated with women’s sexual health problems and testosterone hormonal problems. Now there are data that oral contraceptive pills may have lasting adverse effects on the hormone testosterone.

The research, in an article entitled: “Impact of Oral Contraceptives on Sex Hormone Binding Globulin and Androgen Levels: A Retrospective Study in Women with Sexual Dysfunction” published in The Journal of Sexual Medicine, involved 124 premenopausal women with sexual health complaints for more than 6 months. Three groups of women were defined: i) 62 “Oral Contraceptive Continued-Users” had been on oral contraceptives for more than 6 months and continued taking them, ii) 39 “Oral Contraceptive Discontinued-Users” had been on oral contraceptives for more than 6 months and discontinued them, and iii) 23 “Never-Users of Oral Contraceptives” had never taken oral contraceptives. SHBG values were compared at baseline (groups i, ii and iii), while on the oral contraceptive (groups i and ii), and well beyond the 7 day half-life of sex hormone binding globulin at 49-120 (mean 80) days and more than 120 (mean 196) days after discontinuation of oral contraceptives (group ii).

The researchers concluded that SHBG values in the “Oral Contraceptive Continued-Users” were 4 times higher than those in the “Never-Users of Oral Contraceptives”. Despite a decrease in SHBG values after discontinuation of oral contraceptive pill use, SHBG levels in “Oral Contraceptive Discontinued-Users” remained elevated when compared to “Never-Users of Oral Contraceptives”. This led to the question of whether prolonged exposure to the synthetic estrogens of oral contraceptives induces gene imprinting and increased gene expression of SHBG in the liver in some women who have used the oral contraceptives.

Dr. Claudia Panzer, an endocrinologist in Denver, CO and lead author of the study, noted that “it is important for physicians prescribing oral contraceptives to point out to their patients potential sexual side effects, such as decreased desire, arousal, decreased lubrication and increased sexual pain. Also if women present with these complaints, it is crucial to recognize the link between sexual dysfunction and the oral contraceptive and not to attribute these complaints solely to psychological causes.”

“An interesting observation was that the use of oral contraceptives led to changes in the synthesis of SHBG which were not completely reversible in our time frame of observation. This can lead to lower levels of ‘unbound’ testosterone, which is thought to play a major role in female sexual health. It would be important to conduct long-term studies to see if these increased SHBG changes are permanent,” added Dr. Panzer.

Dr. Andre Guay, study co-author and Director of the Center for Sexual Function/Endocrinology in Peabody, MA affirmed that this study is a revelation and that the results have been remarkable. “For years we have known that a subset of women using oral contraceptive agents suffer from decreased sex drive,” states Dr. Guay. “We know that the birth control pill suppresses both ovulation and also the male hormones that the ovaries make in larger amounts during the middle third of the menstrual cycle. SHBG binds the testosterone, therefore, these pills decrease a woman’s male hormone availability by two separate mechanisms. No wonder so many women have had symptoms.”

“This work is the culmination of 7 years of observational research in which we noted in our practice many women with sexual dysfunction who had used the oral contraceptive but whose sexual and hormonal problems persisted despite stopping the birth control pill,” said Dr. Irwin Goldstein, a urologist and senior author of the research. “There are approximately 100 million women worldwide who currently use oral contraceptives, so it is obvious that more extensive research investigations are needed. The oral contraceptive has been around for over 40 years, but no one had previously looked at the long-term effects of SHBG in these women. The larger problem is that there have been limited research efforts in women’s sexual health problems in contrast to investigatory efforts in other areas of women’s health or even in male sexual dysfunction.”

To better appreciate the scope of the problem, oral contraceptives were introduced in the USA in 1960 and are currently used for reversible pharmacologic birth control by over 10 million women in the US, including 80% of all American women born since 1945 and, more specifically, 27% of women ages 15-44 and 53% of women age 20-24 years. By providing a potent synthetic estrogen (ethinyl estradiol) and a potent synthetic progesterone (for example – norethindrone), highly effective contraception is achieved by diminishing the levels of FSH and LH, thereby reducing metabolic activity of the ovary including the suppression of ovulation.

Several studies over the last 30 years reported negative effects of oral contraceptives on sexual function, including diminished sexual interest and arousal, suppression of female initiated sexual activity, decreased frequency of sexual intercourse and sexual enjoyment. Androgens such as testosterone are important modulators of sexual function. Oral contraceptives decrease circulating levels of androgens by direct inhibition of androgen production in the ovaries and by a marked increase in the hepatic synthesis of sex-hormone binding globulin, the major binding protein for gonadal steroids in the circulation. The combination of these two mechanisms leads to low circulating levels of “unbound” or “free” testosterone.

Doctors in Canada are studying the effectiveness of permanent radiation seed implants following lumpectomy as an alternative to whole or partial breast irradiation for early-stage breast cancer patients, according to a study published in the January 1, 2006, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology. This type of radiation would cut treatment time for certain patients from several weeks to one day.

For early stage breast cancer, women often undergo a lumpectomy to remove the tumor followed by radiation therapy to kill any cancer cells that may remain. Most women undergo external beam radiation, which is given every day, Monday through Friday, for six to eight weeks. Doctors have been experimenting with ways to shorten this treatment. One technique used by a growing number of radiation oncologists involves the use of temporary radiation implants. These radiation sources are delivered through a catheter into the breast, usually twice a day for one week.

In this study, the first of its kind in the world, doctors wanted to see if it was possible to use permanent implants, like what many men receive to treat prostate cancer, to combat the cancer with only one treatment. These implants, about the size of a grain of rice, would not be removed daily like with the temporary implants. Rather, the radioactive seeds would deliver radiation to the breast area for a number of weeks until they were no longer radioactive. The advantage over the temporary implants is that the patient only has to undergo one surgical procedure to receive the radiation, versus 10 treatments over one week for temporary implants.

The current treatment standard of lumpectomy followed by external beam radiation therapy is proven to keep the cancer from returning, but 38 percent of women develop significant toxicity, which can compromise their quality of life. According to early returns from the study, which began in May 2004, 44 patients have been treated successfully with the permanent implants. So far, none have evidence of their cancer returning and acute skin irritation is six times less frequent when compared to external beam radiation.

“The main motivation was to see if we could reduce the burden of treatment for women suffering from early-stage breast cancer,” said Jean-Philippe Pignol, M.D., Ph.D., lead author of the study and radiation oncologist at Sunnybrook and Women’s College Health Sciences Centre in Toronto, Ontario, Canada. “The seed implants reduce the treatment to a one-time event compared to the current standard of daily treatments over many weeks. The seeds also reduce the amount of radiation the normal breast tissue receives, which lessens the chance of the patient developing problems that affect their post-cancer quality of life. The great thing is that the patient can go home right after the procedure and live a normal life while receiving her radiation.”

The DNA in our cells is constantly being bombarded by environmental, chemical and cellular insults. Fortunately, our cells contain many enzymes devoted strictly to detecting and repairing any damage caused by these insults. In fact, failure of these enzymes to make needed repairs to genes can lead to the accumulation of mutations and, eventually, cell death or possibly cancer. However, it appears that the activity of some DNA repair enzymes is more critical than others, particularly in developing embryos. University of Pittsburgh researchers report in the Jan. 1 edition of Cancer Research that a poorly understood enzyme, known as DNA polymerase zeta, or pol zeta, has the uncanny ability to give cells with even heavily damaged DNA a new lease on life. Furthermore, when the enzyme is absent in cells that already have growth control problems, the consequences to chromosomes are catastrophic and may lead to cancer.

“Pol zeta appears to be the only one of a group of specialized DNA polymerases that is critical for development in animals,” explained John P. Wittschieben, Ph.D., research instructor in the department of pharmacology, University of Pittsburgh School of Medicine, and first author of the study. “Moreover, its loss in animal cells plays a significant role in the development of chromosomal instability, which is a hallmark of cancer. Therefore, we believe its function may be to suppress the development of tumors.”

Although DNA polymerases–enzymes responsible for copying, editing and repairing genes and surrounding DNA–generally have the ability to make completely accurate copies of strands of DNA, in certain situations damaged areas, called lesions, can bring this replication machinery to a complete halt. In the last few years, scientists have learned of the existence of a variety of so-called lesion-replicating polymerases that can overcome these replication “stop signs” and keep cells dividing that would otherwise be killed off by their own suicide mechanisms.

First discovered in budding yeast cells, and later in plants and animals, pol zeta has the remarkable ability, in the test tube, to efficiently extend DNA with lesions that stop most other DNA polymerases in their tracks. Other research has shown that inactivation of this lesion-replicating enzyme in yeast leads to a dramatic decrease in the frequency of mutations induced by a wide range of DNA damaging agents.

In this study, Dr. Wittschieben–working in the laboratory of Richard D. Wood, Ph.D., professor of pharmacology, the Richard M. Cyert Chair in Molecular Oncology and director of the molecular and cellular oncology program at the University of Pittsburgh Cancer Institute–sought to determine pol zeta’s key role in mice cells. To do this, Drs. Wittschieben and Wood disabled, or “knocked out,” the gene for pol zeta’s Rev3L subunit, the part with the lesion-replicating capabilities. However, knocking out the Rev3L gene proved lethal to the mice embryos. The investigators nevertheless isolated fibroblasts from these embryos to see if they could be kept alive in culture. After repeated attempts, the mouse embryonic fibroblasts, or MEFs, failed to divide and died within a few weeks or months.

Suspecting that the MEFs were dying because they were self-destructing, or undergoing apoptosis, the investigators then knocked out the gene for a protein known as p53, which is a cell-suicide-signaling molecule. After matings between the p53 knockout mice and Rev3L knockout mice, the investigators isolated and cultured MEFs from all the offspring of the matings to see if any would grow. Unfortunately, the cells all failed to divide. However, three months later, some cells began to grow and at a surprisingly robust rate.

“Once the cells in which Rev3L and p53 had been knocked out began to divide, they did so very rapidly,” said Dr. Wittschieben. “Because the only Rev3L-deficient cells that began dividing also were p53 deficient, we believe that knocking out their apoptotic mechanism was key to this viability. However, they didn’t begin dividing right away, so something else must have happened. We are still not sure what that something else is.”

When the investigators looked for evidence that these cells were different from normal cells, they didn’t have to look far. Examination of the cells’ chromosomes showed not only a dramatic ten-fold increase in the incidence of swapping and fusing of genes and other genetic material between chromosomes, but also an increase in the number of chromosomes compared to normal cells.

The high frequency of DNA rearrangements in Rev3L/p53-deficient cells suggests that pol zeta in normal cells is responsible for preventing double-stranded breaks from occurring in chromosomes. When pol zeta is absent, it leads to a massive amount of double stranded breaks, some of which are repaired correctly and others that are repaired incorrectly by being fused to other genes or chromosomes.

According to Dr. Wood, these findings have significant implications for human cancer research, in that such a high degree of chromosomal instability is a characteristic of cancer cells. Furthermore, the human Rev3L gene is located in a segment of chromosome 6 where multiple tumor suppressor genes are believed to reside and a slew of human cancers, including a number of leukemias and lymphomas, are associated with chromosomal instabilities in this particular region of chromosome 6.

“Although it requires further investigation, we believe that mutations in this part of chromosome 6 could occur during the development of some cancers and this may have prognostic and therapeutic implications. We are now investigating this hypothesis by selectively deleting the Rev3L gene in adult mouse cells to study how the loss of DNA polymerase zeta influences the development and progression of spontaneous cancers,” explained Dr. Wood.

Oral sex may be a risk factor for nongonococcal urethritis (NGU), one of the most common sexually transmitted diseases affecting both men and women, according to a new study in the February 1 issue of the Journal of Infectious Diseases.

The study is the first major case-control study to simultaneously address all currently hypothesized causes of NGU. The findings help to identify areas for future research on the causes of NGU, and suggest that treatment decisions should be based on clinical features of the disease–not just microscopic assessment. The study also is the first to demonstrate that the causes of NGU in men who have sex with other men are similar to those found in heterosexual men.

NGU is caused by a number of different organisms (most notably, Chlamydia trachomatis) and may lead to pelvic inflammatory disease, infertility, and chronic pelvic pain. Though the cause of NGU is sometimes known, and antibiotics (azithromycin or tetracycline) are generally effective, about half of all cases have no identifiable cause – a fact that makes treatment frustrating and uncertain for physicians and patients. Results of previous studies show that Chlamydia trachomatis causes between 30 percent to 50 percent of cases of NGU and Mycoplasma genitalium, 10 percent to 30 percent.

Chlamydial infection was common in both heterosexual and homosexual men with NGU (22 percent and 15 percent, respectively) and was far more common than in control groups. C. trachomatis and M. genitalium were associated with unprotected vaginal sex. M. genitalium (9 percent), adenoviruses (4 percent), and herpes simplex type 1 (2 percent) were more common in NGU patients than in controls, after adjusting for age and risk, which suggests that these organisms may be causes of NGU.

Adenoviruses and herpes simplex type 1 were associated with oral sex and sex between male partners, suggesting that oral-genital contact may be an important mechanism of NGU pathogen transmission. Additionally, NGU was associated with history of oral sex with new partners. Together, these findings suggest that fellatio plays a significant role as a cause of the syndrome.

The study provides important insight for both heterosexual and homosexual men, as it indicates that NGU may be caused by otherwise harmless organisms shared by monogamous partners. According to Handsfield, this finding may influence clinical management of partners and counseling of couples. In addition, oral sex was associated with NGU in which no pathogen was detected, indicating that there are causes of NGU that have yet to be identified. The study also found that type 1 herpes simplex virus (HSV-1), the usual cause of oral herpes (cold sores), accounted for more NGU cases than did HSV-2; that herpetic NGU was most commonly associated with fellatio; and that up to a third of NGU cases associated with known pathogens were not associated with increased numbers of white blood cells in urethral secretions.