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July 8, 2010

Research Notes

Mutations, prenatal smoke linked

Newborns of non-smoking moms exposed to secondhand smoke during pregnancy have genetic mutations that may affect long-term health, according to a Graduate School of Public Health study published online in The Open Pediatric Medicine Journal.

The abnormalities, which were indistinguishable from those found in newborns of mothers who were active smokers, may affect survival, birth weight and lifelong susceptibility to diseases such as cancer.

The study confirms previous research in which environmental and occupational health faculty member Stephen G. Grant discovered evidence of abnormalities in the HPRT gene located on the X chromosome in cord blood from newborns of non-smokers exposed to environmental tobacco smoke.

In the current study, Grant confirmed smoke-induced mutation in another gene called glycophorin A, or GPA, that is representative of oncogenes — genes that transform normal cells into cancer cells and cause solid tumors. The GPA mutation was the same level and type in newborns of mothers who were active smokers and of non-smoking mothers exposed to tobacco smoke.

The mutations also were found in newborns of women who had stopped smoking during their pregnancies, but who did not  avoid secondhand smoke.

Grant said, “We were able to pick up a completely distinct yet equally important type of genetic mutation that is likely to persist throughout a child’s lifetime. Pregnant women should not only stop smoking, but be aware of their exposure to tobacco smoke from other family members, work and social situations.”

Diabetes research presented

Researchers from the Graduate School of Public Health (GSPH) presented findings from several studies at a meeting of the American Diabetes Association.

No heart benefit to omega-3s for diabetic women

Consuming higher amounts of omega-3 fatty acids does not appear to lower heart disease risk for women with type 1 diabetes, a long-term study found.

Omega-3 fatty acids, primarily found in fish, promote heart health by preventing the buildup of cholesterol in the arteries. Little is known about the effect of consuming omega-3 in people with type 1 diabetes, who are at much greater risk for heart disease.

The study included 601 men and women enrolled in the Pittsburgh Epidemiology of Diabetes Complications Study, a long-term prospective examination of childhood-onset type 1 diabetes.

During the course of the study, 166 participants (27.6 percent) were diagnosed with cardiovascular disease. Generally, omega-3 intake among participants was low. The incidence of heart disease was lowest in men who consumed the highest quantities of omega-3 — more than 0.2 grams per day. Women who consumed similar amounts of omega-3 did not have lower rates of heart disease.

Epidemiology faculty member Tina Costacou, lead author of the study, said: “Although omega-3 is typically associated with decreased risk for cardiovascular disease, this may not be the case for women who have type 1 diabetes. Importantly, our study suggests we shouldn’t assume men and women with type 1 diabetes are the same.”

Trevor Orchard, a faculty member in epidemiology, was a study co-author.

Death risk increased in diabetics with kidney damage

People with type 1 diabetes who have early and asymptomatic kidney damage, as indicated by small amounts of protein in the urine, are six times more likely to die compared to the general population, according to a study that also found that when kidneys remained normal over time, people with type 1 diabetes had no greater risk of death than their healthy counterparts.

The findings were based on data from 658 men and women. Researchers tested participants for levels of albumin, a protein that indicates early kidney damage when elevated in the urine and results in a condition called microalbuminuria.

After 20 years of follow-up, 152 participants (23 percent) with microalbuminuria had died — a rate 6.2 times higher than age- and sex-matched people in the general population. When researchers excluded from the analysis participants who developed kidney damage after initial protein testing, they found that mortality rates for those with normal kidneys were no different than in the general population.

GSPH doctoral student Aaron M. Secrest was the lead author of the study. Co-authors included Rachel G. Miller and Trevor Orchard of epidemiology.

High HDLs, diabetic women’s heart disease linked

Elevated blood levels of high-density lipoprotein (HDL) or “good” cholesterol, typically thought to protect against heart disease, may do the opposite in women with type 1 diabetes, according a study that included 658 men and women.

HDL cholesterol helps prevent arteries from becoming clogged. High levels of HDL cholesterol (more than 60 milligrams per deciliter) generally protect against heart disease, while low levels (less than 40 mg/dL for men and 50 mg/dL for women) increase risk.

For men, as levels of HDL increased, the incidence of heart disease decreased. The same was true for women, except in those with very high levels of HDL (over 80 mg/dL) whose incidence of heart disease increased substantially.

Researchers were unable to draw a meaningful comparison to male participants since only a few had HDL over 80 mg/dL.

Study co-authors included Rhobert Evans and Trevor Orchard of epidemiology.

Mortality improving but high for women, blacks

Advances in treatment and care have reduced overall death rates from type 1 diabetes, with women and African Americans having higher risks of mortality, according to a study based on the Allegheny County Type 1 Diabetes Registry.

The registry includes nearly 1,100 people diagnosed between 1965 and 1979.

As of January 2008, 26 percent of registry participants had died — a rate seven times higher than age- and sex-matched people in the general population. Participants who were diagnosed most recently (1975- 1979) were 5.5 times more likely to have died.

Researchers found that women with type 1 diabetes were 13 times more likely to have died than women in the general population; men’s death rate was five times higher than their healthy counterparts.

When the researchers explored differences in survival by race, they found that after 30 years of diabetes, only 52 percent of African Americans were alive compared to 82 percent of Caucasians.

“The more recent a person was diagnosed with type 1 diabetes, the less likely they were to die, suggesting the positive impact of advances made during the last few decades,” said GSPH doctoral student Aaron M. Secrest, lead author of the study. “Even so, significant disparities in mortality remain and reveal a need for continuing improvements in diabetes treatment and care.”

Trevor Orchard co-authored the study.

Cardiac prognoses re-evaluated

Traditional methods for assessing patients after cardiac arrest may be underestimating their chances for survival and good outcomes, according to a study by School of Medicine researchers available online in the journal Resuscitation.

Lead author was Jon C. Rittenberger, an emergency medicine faculty member.

Currently, physicians assess pupil response, corneal reflexes and motor response to determine a patient’s prognosis after resuscitation to restart the heart. For this study, researchers retrospectively reviewed the neurologic examination findings for 272 cardiac arrest patients upon arrival at the hospital, 24 hours later and 72 hours later. Most of the subjects were men; the mean age was 61. Most were treated with therapeutic hypothermia, which cools the body of a comatose patient to prevent brain injury and other organ damage.

Researchers found that 33 percent of the patients in the study survived, and 20 percent experienced a good outcome, defined as discharge to home or to an acute rehabilitation facility. The association between good outcomes and exam findings did not differ between those treated with or without therapeutic hypothermia. Surprisingly, even those with poor motor examination scores on neurologic exams after 24 and 72 hours showed higher survival rates than clinicians traditionally would have predicted.

The researchers looked specifically at the Glasgow Coma Score (GCS) motor response. Existing guidelines suggest that a GCS motor response of 3 or less is highly predictive of mortality.

Rittenberger and his team found that survival was 17 percent at 24 hours and 20 percent at 72 hours for those with a GCS of 3 or less. When the investigators used a more conservative GCS motor response of 2 or less, the survival rate was 14 percent at 24 hours and 18 percent at 72 hours.

Consistent with existing guidelines, the researchers found that a lack of pupil or corneal response at 72 hours appeared to exclude survival or good outcome.

“The good news is that advances in care for cardiac arrest patients appear to be improving survival rates and positive outcomes,” said Rittenberger. “In light of these changes, we need to re-evaluate and expand our tools for providing a prognosis to patients and their families.”

Pitt astronomer to lead telescope study

Physics and astronomy faculty member Michael Wood-Vasey will lead a multi-year effort to search the sky for explosive and violent deep-space events that could help astronomers better understand cosmic activity.

Wood-Vasey’s group will search images captured by the newly operational PS1 telescope for intense, short-lived “transient events” in space.

The PS1, managed by the University of Hawaii-based Pan-STARRS (Panoramic Survey Telescope and Rapid Response System) consortium, is located atop Hawaii’s Haleakala volcano. It includes a 1.4 billion-pixel camera that will snap about 500 pictures nightly, each of a swath of sky six times wider than the moon. The PS1 is the first of four digital telescopes planned under the Pan-STARRS project.

The team of 11 scientists will identify supernovae, gamma ray bursts and tidal disruption events — when black holes rip young stars apart.

As they observe, the team will provide real-time updates to any of the 300 Pan-STARRS scientists worldwide on the lookout for these bursts of cosmic activity, which can reveal information about the universe’s basic structure.

Wood-Vasey will focus on the various ways a star can meet its end, including tidal disruption events and Type Ia supernovae, the explosive byproducts of dying white dwarf stars. Type Ia supernovae emit a consistent amount of light, so any variation in their visible brightness can help gauge the rate of the universe’s expansion and provide clues to the nature of the as-yet-undetected dark energy thought to make up most of the universe’s mass.

Video Wood-Vasey captured with the PS1 in February showing a Type Ia supernova explosion 420 million light years from Earth is available at

More information and telescope images are available on the Pan-STARRS web site at

Racial difference found in sepsis

Black people are at greater risk than whites for severe sepsis because they are both more susceptible to getting infections and more likely to develop organ injuries, according to a study by School of Medicine researchers published in the Journal of the American Medical Association.

The study also suggests that both community- and hospital-based interventions could help alleviate such racial disparities, said lead author Florian B. Mayr, a research fellow in the Department of Critical Care Medicine.

Annually, more than 750,000 Americans develop severe sepsis, defined as systemic infection plus organ injury, and one out of four people who develop it will die during their hospital stay.

The researchers examined discharge data from hospitals in six states, representing a quarter of the American population, as well as infection-related emergency department visits data from the 2003-2007 National Hospital Ambulatory Care Survey.

After controlling for age and sex, they found that blacks had a 67 percent higher rate of severe sepsis and 80 percent higher mortality. That greater likelihood was explained by an infection rate of 47 blacks and 34 whites per 1,000 people; the odds of a black person developing acute organ dysfunction were 29 percent higher than for whites.

“Given that research has shown that black people are less likely to be hospitalized as a result of an emergency room visit, these results could well be an underestimate,” Mayr noted.

Interventions to narrow the gap could include vaccinating younger black people to prevent some lung infections. Researchers calculated the potential impact of modifying vaccination guidelines to prevent pneumonia caused by strep pneumonia or pneumococcus, which can progress to a systemic infection and subsequent organ injury. Currently, pneumococcal vaccination is recommended for people 65 and older, younger adults with certain chronic illnesses and small children.

Sachin Yende, a faculty member in critical care medicine and the study’s corresponding author, said: “If we also vaccinated black adults younger than 65, we might be able to avoid a significant number of cases of severe sepsis in this population.

“Our analysis showed that 25 percent of pneumococcal infections occurred among 18- to 65-year-olds who had no other illnesses, so they would not have been considered for vaccination.”

Narrowing quality gaps across hospitals in the care of patients who are hospitalized for an infection also could reduce racial disparities in severe sepsis, which may be due in part to socioeconomic factors.

In addition to hospital-based approaches, better management of chronic disease is needed, Yende said.

The researchers are working on identifying biologic differences that might also contribute to differences in susceptibility to infection and risk for organ dysfunction.

Other authors of the paper included Octavia M. Peck-Palmer of pathology, Amber E. Barnato of medicine, Lisa A. Weissfeld of biostatistics and Derek C. Angus of critical care medicine.

Immune system protein studied

A protein found in the nucleus of cells plays a key role in the regulation of the immune system and could provide a target for the development of new treatments for a number of conditions and diseases, according to Pitt research published in the journal Science Translational Medicine.

Researchers led by Yatin Vyas discovered that Wiskott-Aldrich syndrome protein (WASp), which was known to be present in the cell cytoplasm, also is present in the cell nucleus.

The team’s most significant finding is that this nuclear WASp regulates the activation of T-helper type 1 (Th1) cells, a subset of lymphocytes crucial to the immune system.

“Without enough WASp present in the nucleus, Th1 immunity is impaired, and this type of immunity is required to combat most infections and many cancers,” said Vyas, a pediatrics faculty member and hematologist/oncologist at Children’s Hospital. “This finding significantly expands our understanding of the importance of WASp in the biology of the cell and its potential as a therapeutic target.”

According to Vyas, if Th1 is deficient in the nucleus, another group of immune cells known as T-helper type 2 (Th2) dominates the immune system. Overexpression of Th2 is known to lead to autoimmune conditions such as asthma and colitis.

“WASp appears to function as a nuclear protein that participates in the T cell’s program and is designed to balance the two arms of the immune responses, Th1 and Th2,” Vyas said.

“Our discovery could have far-reaching implications to the development of diseases caused by the dysregulation of Th1 and Th2 responses. Now that we have identified that WASp is present in the nucleus, we are interested in exploring the details of how this protein might function in the overall integrity of chromosomes in the immune cells.”

New RVF vaccines developed

Two new approaches could form the basis for the first-ever human vaccine for Rift Valley Fever (RVF), say researchers at the Center for Vaccine Research (CVR). In their work reported in PLoS Neglected Tropical Diseases, experimental vaccines produced strong immune responses in mice and may be safer than the only available RVF vaccine, which is limited to animal use.

Although RVF mainly affects farm animals, the virus has spread to humans causing serious illness and death in Africa and the Middle East. The U.S. government has classified it as a select agent because of its potential use in bio-warfare, prompting vaccine development research.

“RVF is a veterinary and public health threat that continues to spread,” said CVR faculty member and study lead author Ted M. Ross. “Vaccine development has been challenging because of adverse side effects from live virus vaccines and uncertainty about whether the virus could revert to a more dangerous form during vaccine manufacturing.”

Unlike other potential vaccines for RVF, which are derived from live viruses, the vaccines tested by Pitt and University of North Carolina researchers were developed using two approaches — DNA-based and alphavirus replicon-based — that use only a modified portion of an inactivated virus. Mice immunized with either strategy were protected from disease and death when directly exposed to the RVF virus. When the strategies were combined, researchers noted both increased concentrations of antibodies that neutralize infectious agents and heightened cell-based immune responses. “These vaccine strategies may be advantageous to controlling RVF because they provide a safer alternative and appear to work as well as live virus vaccines,” said Ross.

Nitin Bhardwaj, a graduate student researcher in infectious diseases and microbiology, was among the study co-authors.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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