Our brains can talk. In fact, our brain cells chatter with each other all the time. Now, researchers at Washington University School of Medicine report that areas of the brain where there is the most cell communication also appear to produce more amyloid beta, the main ingredient of the plaque lesions related to Alzheimer’s disease.
The research team used genetically altered mice to test how brain activity affects plaque formation. They found that reducing cell chatter in some brain regions seems to reduce the size and number of plaques. The brain regions studied become more active when the brain is not demanding cognitive tasks and are the same regions known to be among the first to develop plaques in most Alzheimer’s patients.
“Engaging the brain in tasks like reading, socializing or studying may be helpful because they reduce activity in susceptible regions and increase activity in regions that seem to be less vulnerable to Alzheimer’s plaque deposition,” says Dr. David Holtzman, head of the department of neurology. “I suspect that sleep deprivation and increased stress, which may affect Alzheimer’s risk, may also increase activity levels in these vulnerable regions.”
About one in 10 babies less than 3 months old have a ‘strawberry mark.’ These benign tumors, clinically known as hemangiomas, are formed by tiny clumps of blood vessels, usually on the face or scalp. They may appear as a flat pink area or a large, raised, red plaque.
Hemangiomas tend to grow quickly in the first months of life, but by 12 months of age, they begin to fade slowly, and 90 percent are gone by age 9. Most heal on their own, although complications can occur.
“More than one-third of affected infants have a hemangioma that grows very fast, is located in a cosmetically sensitive area, interferes with the child’s vision or breathing, or is at risk of ulcerating,” says Dr. Elaine Siegfried, chief of pediatric dermatology at Saint Louis University and SSM Cardinal Glennon Children’s Medical Center. “Treatment may be necessary to prevent or minimize serious complications for these infants.”
Common treatment involves the use of high-dose corticosteroids, a type of medication not tolerated by some patients. A research team led by Siegfried is testing the safety and efficacy of propranolol, a drug most often used to treat hypertension, in shrinking childhood hemangiomas. “More information is needed about the safety and effectiveness of the drug, but if this study is successful, it will pave the way for approval of a less invasive treatment with few side effects,” Siegfried says.
Lymph vessels are part of the body’s system for transporting cells and fluid from across tissues and organs throughout the body. Usually, this is a good thing. However, the lymph system can unwittingly carry cancer cells along its path, spreading disease.
Saint Louis University researchers have found a way to create a biological roadblock for cancer cells that try to travel via the lymph system. The discovery involves molecules known as CRSBP-1 ligands, which bind to receptors on lymph vessels and stimulate a response that allows entry into the vessel. Cancer cells may travel with CRSBP-1 to access the lymph system. The findings also relate to the reduction of localized swelling because CRSBP-1 also opens junctions in the lymph systems where fluid can drain.
By understanding the CRSBP-1 mechanism, researchers hope to find new ways to control lymph vessel access, potentially blocking cancer metastasis, treating fluid build-up and enhancing vaccine effectiveness.
“Once you figure out how breast and other cancers spread, you can begin to work on blocking the process. This is very exciting,” says Dr. Jung Huang, a study co-author and professor of biochemistry and molecular biology.
Without intestinal microbes, our bodies could not break down food to extract the nutrients we need. Usually, our microbial collection is balanced, but scientists suspect that changes in the microbial mix can play a role in obesity, malnutrition, Crohn’s disease and other illnesses.
Washington University scientists are growing personalized collections of human intestinal microbes in the lab, which may lead to more information about the use of probiotics and the potential of transplanting healthy microbes to restore the body’s natural balance. Previous study of lab-grown microbes has been unable to determine whether the colonies mirror actual microbial collections within the body.
The research team used DNA sequencing to follow a gene that can be used to inventory various species present in a microbial community. In all, they discovered that most of the different groups of intestinal bacteria found in an individual also were present in corresponding bacterial collections that were grown, or cultured, in the laboratory.
They then transplanted both cultured and uncultured microbial communities into mice and found that the microbes functioned in virtually the same way, whether they were grown in the lab or not.
The researchers also found that they could use portions of the cultured microbe communities to create personalized collections. These manipulated communities will be used for further research on how specific microbes or groups of microbes influence overall health.
Ten percent of pregnant women experience preeclampsia, a potentially life-threatening condition that causes dangerously high blood pressure, protein in the urine, headaches and swelling. The only treatment is to induce delivery, which can be fatal to the baby if it occurs too early in the pregnancy.
Washington University researchers, as part of an international research team, identified genetic errors in women who have autoimmune diseases that increase the risk of preeclampsia. The findings may lead to new treatments and genetic screening to identify women at higher risk.
“Preeclampsia seems to involve multiple hits,” says Dr. John Atkinson, a senior study author. “First you may have a genetic predisposition for small blood vessels, which can worsen problems with inflammation. Then maybe you have lupus or another autoimmune condition. Then along comes pregnancy, which is a major source of stress on the organs.”
Researchers studied 250 pregnant women who have lupus and/or a related autoimmune disease. Thirty of the women developed preeclampsia during the study, and 10 had developed preeclampsia in previous pregnancies. Researchers examined three genes related to immune response to injury and infection in these 40 women. Seven of the women had at least one gene mutation, and 59 pregnant women who had preeclampsia but no underlying autoimmune disorder also had a mutation on at least one of the three identified genes.
The researchers now plan to study additional pregnant women and other genes known to play a role in regulating immune response to further understand the genetic links to preeclampsia.
Researchers at Washington University’s Genome Institute are gaining ground in understanding the role of genes in cancer. By sequencing a mouse cancer genome, the scientists are able to “rapidly evaluate whether mutations in human tumors are likely to be important,” says oncologist Dr. Timothy Ley. “If we find mutations that occur in mouse models and we see those same mutations, however rare, in human cancers, they are highly likely to be relevant.”
Scientists already sequenced the genomes of about 250 cancer patients, comparing DNA taken from tumors to that of healthy tissue. This comparison shows several mutations that appear to be present in the cancer cells. Yet the sequencing and comparison process is time-consuming and tedious. Using a mouse model streamlines the process of identifying specific mutations that are linked to cancer.
Ley and his colleagues are focusing on genome sequencing related to leukemia. “There’s been ongoing debate about whether mouse models of cancer are relevant to cancer that develops in people,” he explains. “By sequencing this genome, I think the answer is clear: This mouse model is remarkably similar to the human disease. This gives us a new way to use whole-genome sequencing to rapidly identify the most relevant mutations in human cancers.”
Tuberculosis is the world’s second deadliest infectious disease. In 2007, the disease caused 1.8 million deaths. Therefore, finding a safe and effective vaccine is a priority for researchers at the Saint Louis University Center for Vaccine Development.
An investigational vaccine, AERAS-422, currently is being tested. “Not only is the start of the clinical trial of AERAS-422 another important benchmark in the search for more effective TB vaccines, it also is an opportunity to learn more about cellular immunity, which is less understood but crucially important in developing TB vaccines,” says Dr. Daniel Hoft, a researcher at the center and director of infectious diseases, allergy and immunology at the university.
AERAS-422 is a live recombinant vaccine designed to interrupt TB at all stages of infection and protect against all forms of the disease, and SLU is the only phase I test site. Hoft and his colleagues also are studying relevant biomarkers, which are functional and biological immune responses that correlate with vaccine efficacy. The team will conduct both clinical studies of new TB vaccines and basic immune research in his laboratory with the goal of identifying vaccine responses capable of inhibiting growth of the TB germ.
The brain is capable of mounting a protective response to injury from stroke. This capacity is known as ‘tolerance,’ and it can be induced to help protect the brain for several days. However, Washington University researchers have discovered a way to induce tolerance for two months or more, a finding that may have implications for treating a variety of neurodegenerative conditions, such as multiple sclerosis and Alzheimer’s disease.
To induce tolerance, brain tissue must be stressed but not harmed, a process called preconditioning. By repeatably preconditioning the brain—in this case, exposing it to low oxygen levels—every other day for two weeks prior to a stroke, tolerance lasted for two months in experimental mice. Exercise is another type of preconditioning, which temporarily makes cells in the brain, heart and other tissues more resistant to damage.
“If we can learn how these positive effects are created by nature, we might be able to pre-treat patients who are at high risk of stroke, and thus significantly reduce brain injury if a stroke occurs. We might also be able to use tolerance to slow the advance of chronic neurodegenerative diseases,” says Dr. Jeffrey Gidday, associate professor of cell biology and physiology, of neurological surgery and of ophthalmology and visual science.
Gidday and others hope to see sustained tolerance induced in patients already identified as being at increased risk for stroke and other neurological conditions, providing these individuals significant protection should the injurious event occur.
A Saint Louis University neurosurgeon, known as an innovative leader in the field, has developed a technique that could improve outcomes for patients undergoing surgery to treat brain aneurysms.
The new technique, pioneered by Dr. Saleem Abdulrauf, is called ‘high-flow brain bypass’ and is similar to heart bypass procedures. When neurosurgeons replace a blood vessel that has an aneurysm—a weak area in the vessel wall—they typically use a healthy blood vessel from the scalp. However, Abdulrauf’s technique uses an artery from the arm, which allows for more blood flow to the brain. “With this new technique, we can treat patients in a way that minimizes recovery time and offers the best chance at keeping their brains healthy,” Abdulrauf says. The technique was featured on the cover of the March issue of the journal Neurosurgery.
“Saleem’s contribution to the field of neurosurgery will leave a lasting legacy,” said Dr. Philip Alderson, dean of Saint Louis University School of Medicine. “By convention, a new surgical procedure is named after the person who developed the technique. Accordingly, high blood flow brain bypass surgery might well be known as the Abdulrauf bypass.” LN