Genetic Patterns Predict Severe Osteoarthritis

Scientists from University of North Carolina at Chapel Hill School of Medicine and Interleukin Genetics Inc. reported findings from a large clinical study to evaluate the role played by genetic factors in the worsening of osteoarthritis. The study, which was part of the Johnston County Osteoarthritis Project, showed patients with X-ray evidence of knee osteoarthritis who inherited a specific pattern of genetic variations in the interleukin-1 receptor antagonist gene were almost twice as likely to progress to severe disease as other patients. Results from the study, which followed 1,154 patients for up to 11 years, will be presented at the World Congress on Osteoarthritis in Brussels, Belgium.

Genetic Switch Key to Cell Division

Although scientists have spent more than 40 years describing the series of events that occur when a mammalian cell divides, they don't know how the process begins. There are two theories, which now may be reconciled by a third theory being proposed by Duke University bioengineers. These findings could provide insights into the initiation of disease, such as cancer, which is marked by uncontrolled cell proliferation. One of the two prevailing theories says that the beginning of division for any cell is just a random event. The second model assumes that there are intrinsic differences between cells that enable some to enter the process earlier than others. The Duke bioengineers found that a specific gene circuit known as Rb-E2F has the unique ability to tell some cells to start dividing while at the same time telling other cells to lay low. The results of these experiments were published in the Public Library of Science Biology.

Immune Cells Attack Neurons Directly in MS

Researchers in Germany have gained new insight into how the immune system causes damage associated with multiple sclerosis (MS). They were able to show a direct interaction between immune cells and neurons, which plays a significant role in neuronal injury. The study, by a team at the University Medical Center Johannes Gutenberg University, in Mainz, has been published in Immunity. Use of in vivo imaging during disease has led to the characterization of neuronal dysfunction as early and potentially reversible, and suggested that immune-mediated disturbances of the neurons themselves contribute to MS, in addition to interruptions in nerve cell transmission as a result of changes to the myelin sheath.

Improving Bone Marrow Transplants

Identification of a molecular communication path that influences the mobilization of hematopoietic stem cells could lead to targeted therapies for improving bone marrow transplant success rates. Researchers at Cincinnati Children's Hospital Medical Center reported in Nature Medicine that pharmacological inhibition of a signaling pathway triggered by epidermal growth factor receptor increased the mobilization of hematopoietic stem cells in mice. The finding provided a scientific basis for enhancing the effectiveness of autologous bone marrow transplants.

Emerging Infectious Diseases Challenging

Newly recognized disease-causing viruses, bacteria and other infections are continually emerging around the world, posing difficult challenges for diagnosis and treatment and for public health responses. A special symposium section of the American Journal of the Medical Sciences provided a research update on important new infectious pathogens. For instance, of approximately 1,400 infectious pathogens recognized in 2005, about 180 met criteria for emerging or re-emerging pathogens. Many different factors contribute to their emergence, such as changes in land use, societal changes, population health and hospital and medical procedures. The emergence of a hypervirulent strain of Clostridium difficile is a particularly difficult problem. Once found only in patients previously treated with antibiotics, C. difficile is now appearing in other groups as well. And infections with fungal pathogens such as Candida and Aspergillus – once seen mainly in patients with suppressed immune function – have now spread to other groups of patients.

Protein Helps Cells Rapidly Repair

Researchers at Huntsman Cancer Institute (HCI) at the University of Utah have discovered that a protein, zyxin, is necessary for the maintenance and repair of the cell's cytoskeleton, or internal framework, which serves as the muscle and bone of the cell. The research has implications for cancer, as well as other diseases, since alterations in the cytoskeleton are often associated with disease. The research, published in Developmental Cell, pointed out that mechanical stress that is derived from application of physical force is experienced by many organs – such as the lung, which stretches with each breath, the heart, which is physically challenged with each beat, and the uterus, which undergoes intense contractions during labor and childbirth. The Huntsman team was interested in how living cells respond to such stress. They showed that mechanical stress can damage the cytoskeleton but that cells have special machinery that rapidly recognizes the damage and repairs it. They observed a mechanism whereby actin stress fibers maintain homeostasis, or balance. The repair mechanism was directly triggered by force and served to relieve mechanical stress on actin stress fibers, which in turn provided a system for rapid response to force changes in the extracellular environment.

Pathway Regulates Immune Balance

St. Jude Children's Research Hospital scientists have identified a new pathway that helps control the immune balance through reciprocal regulation of specialized T lymphocytes, which play very different inflammatory roles. Scientists also determined that two drugs working in different ways to dampen the inflammatory response in patients with multiple sclerosis or following organ transplantation target the new mechanism. Further research into the pathway might lead to new medications to block other autoimmune disorders or to discover new anti-rejection drugs, researchers said. The work is published in the current online issue of Nature Immunology.

New Approach to Pain Therapy

A study out of Italy has shown how a novel compound boosts levels of a natural painkiller at the site of an injury. Published in Nature Neuroscience, the report showed how the potential drug URB937 acts in peripheral tissue and may have the potential to relieve pain without the side effects associated with many current painkillers that act centrally on the nervous system. The preclinical study by the Drug Discovery and Development (D3) unit of the Italian Institute of Technology and the University of California, Irvine showed that URB937, a potent, second-generation inhibitor of the enzyme fatty acid amide hydrolase (FAAH), controlled pain and inflammation locally at the site by boosting levels of anandamide in peripheral tissues, part of the analgesic and anti-inflammatory endocannabinoid system. The compound is the first FAAH inhibitor produced with restricted access to the central nervous system, whereas current FAAH inhibitors readily cross the blood-brain barrier.

Bacterial Genomes Evolve Fast

Researchers from the Center for Genomic Sciences at Allegheny General Hospital (AGH) in Pittsburgh have made a landmark discovery about the evolutionary nature of bacteria in the setting of chronic infectious disease. Reporting in PLos Pathogens, the AGH team documented for the first time that bacteria engage in a process called horizontal gene transfer to evolve rapidly during the course of a single infection. The result is a group of highly related bacterial strains that are changing genetically so fast that it is likely nearly impossible for the host's immune system to effectively track and eradicate it.

Schizophrenia Risk Gene ID'd

An international team of scientists has identified a risk gene for schizophrenia, including a potentially causative mutation, using genomewide association data-mining techniques and independent replications. The results of the research, led by researchers at Virginia Commonwealth University's School of Medicine and the Virginia Institute for Psychiatric and Behavioral Genetics, were reported in Molecular Psychiatry. In recent years, scientists have used genomewide association studies to identify possible candidate genes responsible for diseases that include Type II diabetes, lung cancer, Parkinson's disease, rheumatoid arthritis and systemic lupus erythematosus. However, the same approach was not as successful for the study of schizophrenia. One reason may be that many genes are involved in schizophrenia and the effect of each individual gene is relatively small. For that reason, according to the team, results obtained from individual samples tend to fluctuate. To get consistent results, researchers need to consider the results from many independent samples. The team used that approach in the study by first screening two genomewide association datasets with statistic, genomic, informatic and genetic data and then ranking the top candidate. The selected candidates were verified by more than 20 independent samples. The work is one of the largest genetic studies of schizophrenia and included more than 33,000 participants that identify cardiomyopathy associated 5, or CMYA5, as a risk gene for schizophrenia. Its function is unknown at this time.

Cell Division May Prevent Liver Injury

Researchers at Oregon Health & Science University have discovered that a form of cell division typically associated with cancer called multipolar mitosis can yield diverse, viable cells capable of protecting the liver from injury and poisonous substances, such as pesticides, carcinogens or drugs. Their findings were published online in the journal Nature.