Immune Research: Immune cells make appendix 'silent hero' of digestive health ♦ A molecular switch to stop inflammation ♦ Alerting the immune system's watchmen to improve vaccines

Immune cells make appendix 'silent hero' of digestive health Innate lymphoid cells (ILCs) are crucial for protecting against bacterial infection in people with compromised immune systems, report investigators.A network of immune cells helps the appendix to play a pivotal role in maintaining health of the digestive system, supporting the theory that the appendix isn't redundant

Neutrophils starve fungal invaders The most frequent immune cells in the human blood, so-called neutrophils, efficiently kill invading microorganisms and slowly starve microbes to death by removing crucial trace elements.

A molecular switch to stop inflammation Our immune system is vital to us and can sometimes overreact causing chronic illnesses, such as for instance rheumatism and allergy. Now, researchers have identified a molecular switch – MYSM1 – that can suppress such an overreaction and avoid inflammation

Alerting the immune system's watchmen to improve inflammation As the days get colder and shorter, we carve jack-o-lanterns and drink pumpkin spice lattes. But one fall tradition can actually keep you healthy: getting your flu shot. Like all vaccines, the flu shot trains the immune system to fend off infection, but some need help to produce the full effect. Researchers now report a new way to help improve vaccines using molecules that more effectively direct the immune system

Cancer Research: Mutations driving leukemia identified ♦Why cancer anemia treatment leads to tumor growth ♦ New test to predict relapse of testicular cancers

Scientists produce clearest-ever images of enzyme that plays key roles in aging, cancer The telomerase enzyme is known to play a significant role in aging and most cancers. Scientists have discovered several major new insights about this enzyme and they are now able to see the complex enzyme's subunits in much sharper resolution than ever before.

New test to predict relapse of testicular cancers Scientists have developed a new test to identify patients who are at risk of suffering a relapse from testicular cancer. Assessing just three features of a common kind of testicular cancer -- called non-seminomatous germ cell tumor -- can identify those at most at risk of relapse even where there is no evidence of tumor spread. The researchers believe the test could be used in the clinic to make decisions about which patients should be given chemotherapy.

Why cancer anemia treatment leads to tumor growth Scientists have shown why a drug widely used to treat chemotherapy-induced anemia in ovarian and breast cancer patients also may shorten survival times in some patients by inadvertently stimulating tumor growth.

Special class of T cells shown to both attack cancer cells and enlist other immune cells New insights about a subset of T cells has been shared by researchers, that suggest that they appear to both inhibit cancer growth and enhance the tumor-killing powers of other immune cells.

Mutations driving leukemia identified An international team of scientists has identified novel genes associated with chronic lymphocytic leukemia through the analysis of high-throughput sequencing data.

Cancer Research:Titanium, gold based compound fights kidney cancer ♦ More precise cancer therapies ♦ Promising drugs turn immune system on cancer

'Remote control' of immune cells opens door to safer, more precise cancer therapies

A molecular "on switch" that allows tight control over the actions of T cells, immune system cells that have shown great potential as therapies for cancer, has been developed by a group of researchers.

Antidepressants plus blood thinners cause brain cancer cells to eat themselves in mice

Antidepressants work against brain cancer by excessively increasing tumor autophagy (a process that causes the cancer cells to eat themselves), new research shows. The scientists next combined the antidepressants with blood thinners -- also known to increase autophagy -- as a treatment for mice with the first stages of human glioblastoma. Mouse lifespan doubled with the drug combination therapy, while either drug alone had no effect.

Promising drugs turn immune system on cancer

A class of experimental drug treatments already in clinical trials could also help the body’s immune system to fight cancer, according to a study

Titanium, gold based compound fights kidney cancer cells

The findings of a new study may provide a new way of treating kidney cancer, opening the potential for more potent and less toxic therapies that would give cancer patients a better quality of life.

Immune System Research: How a single molecule turns one immune cell into another ♦ Susceptibility to allergies can be reduced ♦ Immune cells in the skin remember

Immune cells in the skin remember, defend against parasite For the first time, researchers have found resident T cells in a tissue in response to a parasite infection. The finding could help inform efforts to develop an effective vaccine for leishmaniasis, as well as other diseases such as tuberculosis and leprosy.

How a single molecule turns one immune cell into another All it takes is one molecule to reprogram an antibody-producing B cell into a scavenging macrophage. This transformation is possible, new evidence shows, because the molecule (C/EBPa, a transcription factor) 'short-circuits' the cells so that they re-express genes reserved for embryonic development.

Cirrhosis, antibodies increase risk of poor outcome for autoimmune hepatitis patients New research reports that cirrhosis at first diagnosis and antibodies for the soluble liver antigen/liver pancreas antigen (SLA/LP) are major risk factors for poor short- and long-term outcome in patients with autoimmune hepatitis. Scientists also found that patients diagnosed in childhood were at higher risk of relapse, need of a liver transplant, and reduced life expectancy

Susceptibility to allergies can be reduced Susceptibility to allergies reduced by increased production of regulatory T cells, researchers report, adding that these new findings could lead to preventive treatments being developed for high risk patients in the future.

Immune System Research: Restoring natural immunity against cancers ♦ Scientists map surface of immune cells ♦ Returning killer T cells back to barracks could improve vaccines

Dendritic cells of elite controllers able to recognize, mount defense against HIV Investigators have added another piece to the puzzle of how a small group of individuals known as elite controllers are able to control HIV infection without drug treatment. The research team reports finding that dendritic cells of elite controllers are better able to detect the presence of HIV, which enables them to stimulate the generation of T cells specifically targeting the virus.

Scientists map surface of immune cells The immune system must constantly adapt to its environment in order to protect a body effectively. The so-called T cells are an important example in this regard. One of their functions is to form the immune system's "memory". Researchers recently examined the surface of precursors of these T cells and identified previously unknown proteins there. According to the scientists, the results could lead to new approaches for therapies for asthma and allergies.

Returning killer T cells back to barracks could improve vaccines Just as militaries need to have trained, experienced soldiers ready for future wars, making sure that the immune system has enough battle-ready T cells on hand is important for fast-acting, more effective vaccines, according to researchers

Restoring natural immunity against cancers Scientists have successfully increased the infiltration of immune cells into tumors, thus inducing the immune system to block tumor growth. In a new article, the scientists show that, in combination with existing immunotherapies, this process efficiently destroys cancer cells.

Adenosine in Ambrosia pollen increases allergic response Ragweed (Ambrosia artemisiifolia) -- an otherwise unremarkable plant -- produces pollen that can trigger strong allergic reactions such as asthma even in very small quantities. Scientists have now published a study showing that the substance previously identified as the major allergen only induces such a vigorous allergic response in combination with the adenosine also present in the pollen.

Drugs that activate brain stem cells may reverse multiple sclerosis

Two drugs already on the market — an antifungal and a steroid — may potentially take on new roles as treatments for multiple sclerosis. According to a study published in Nature today, researchers discovered that these drugs may activate stem cells in the brain to stimulate myelin producing cells and repair white matter, which is damaged in multiple sclerosis.

An artist’s representation of the study. Scientists found that certain drugs were able to promote remyelination in mouse models of multiple sclerosis. Image courtesy of Case Western Reserve University; Illustrator: Megan Kern

Specialized cells called oligodendrocytes lay down multiple layers of a fatty white substance known as myelin around axons, the long “wires” that connect brain cells. Myelin acts as an insulator and enables fast communication between brain cells. In multiple sclerosis there is breakdown of myelin and this deterioration leads to muscle weakness, numbness and problems with vision, coordination and balance.

“To replace damaged cells, the scientific field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road. We asked if we could find a faster and less invasive approach by using drugs to activate native nervous system stem cells and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself,” said Paul J. Tesar, Ph.D., associate professor at Case Western Reserve School of Medicine in Cleveland, and senior author of the study.

It is unknown how myelin-producing cells are damaged, but research suggests they may be targeted by malfunctioning immune cells and that multiple sclerosis may start as an autoimmune disorder. Current therapies for multiple sclerosis include anti-inflammatory drugs, which help prevent the episodic relapses common in multiple sclerosis, but are less effective at preventing long-term disability. Scientists believe that therapies that promote myelin repair might improve neurologic disability in people with multiple sclerosis.    

Adult brains contain oligodendrocyte progenitor cells (OPCs), which are stem cells that generate myelin-producing cells. OPCs are found to multiply in the brains of multiple sclerosis patients as if to respond to myelin damage, but for unknown reasons they are not effective in restoring white matter. In the current study, Dr. Tesar wanted to see if drugs already approved for other uses were able to stimulate OPCs to increase myelination.   

OPCs have been difficult to isolate and study, but Dr. Tesar and his colleagues, in collaboration with Robert Miller, Ph.D., professor at George Washington University School of Medicine and Health Sciences in Washington, D.C., developed a novel method to investigate these cells in a petri dish. Using this technique, they were able to quickly test the effects of hundreds of drugs on the stem cells.

The compounds screened in this study were obtained from a drug library maintained by NIH’s National Center for Advancing Translational Sciences (NCATS). All are approved for use in humans. NCATS and Dr. Tesar have an ongoing collaboration and plan to expand the library of drugs screened against OPCs in the near future to identify other promising compounds.

Dr. Tesar’s team found that two compounds in particular, miconazole (an antifungal) and clobetasol (a steroid), stimulated mouse and human OPCs into generating myelin-producing cells.

Next, they examined whether the drugs, when injected into a mouse model of multiple sclerosis, could improve re-myelination. They found that both drugs were effective in activating OPCs to enhance myelination and reverse paralysis. As a result, almost all of the animals regained the use of their hind limbs. They also found that the drugs acted through two very different molecular mechanisms.

“The ability to activate white matter cells in the brain, as shown in this study, opens up an exciting new avenue of therapy development for myelin disorders such as multiple sclerosis,” said Ursula Utz, Ph.D., program director at the NINDS.

Dr. Tesar and his colleagues caution that more research is needed before miconazole and clobetasol can be tested in multiple sclerosis clinical trials. They are currently approved for use as creams or powders on the surfaces of the body but their safety administered in other forms, such as injections, in humans is unknown.

“Off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms. We are working tirelessly to ready a safe and effective drug for clinical use,” Dr. Tesar

2/21/15 Health News: Safety and efficacy of statins exaggerated-- Rivers source antibiotic resistance--Higher risk of second stroke identified-- higher risk of second stroke identified

Safety, life-saving efficacy of statins have been exaggerated, says scientist  Statins, the cholesterol-lowering drugs prescribed to prevent heart attacks, are not as effective nor as safe as we have been led to believe, researchers say. Statins produce a dramatic reduction in cholesterol levels, but have failed to substantially improve cardiovascular outcomes, they add, stating that 'statistical deception' has been used to inflate claims Continue Reading

Thames study: Rivers can be a major source antibiotic resistance  Rivers and streams could be a major source of antibiotic resistance in the environment. A new study found that greater numbers of resistant bacteria exist close to some waste water treatment works, and that these plants are likely to be responsible for at least half of the increase observed. Continue Reading

Patients at higher risk of second stroke identified  Risk of recurrent stroke is higher in patients who have low blood flow to the back of the brain, a six-year, multi-center trial has found, and the condition can be visualized using specialized software that analyzes blood flow using standard MRI. Continue Reading

Immune cells commit suicide to prevent allergy  Scientists have demonstrated that the production of type E immunoglobulins (IgE) by B lymphocytes induces a loss in their mobility and the initiation of cell death mechanisms. These antibodies, present in small quantities, are the most powerful "weapons" in the immune system and can trigger extremely violent immune reactions or immediate allergies (asthma, urticaria, allergic shock) as soon as their levels rise, even slightly. Continue Reading

Anti-inflammatory mechanism of dieting and fasting revealed  Researchers have found that a compound produced by the body when dieting or fasting can block a part of the immune system involved in several inflammatory disorders such as type 2 diabetes, atherosclerosis, and Alzheimer's disease Continue Reading

Binge Drinking Linked to Gut Leakage and Immune Response

A single alcohol binge can cause bacteria to leak from the gut and increase levels of bacterial toxins in the blood, according to a study funded by the National Institutes of Health. Increased levels of these bacterial toxins, called endotoxins, were shown to affect the immune system, with the body producing more immune cells involved in fever, inflammation, and tissue destruction.

Binge drinking is defined by NIAAA as a pattern of drinking alcohol that brings blood alcohol concentration (BAC) to 0.08g/dL or above. For a typical adult, this pattern corresponds to consuming five or more drinks for men, or four or more drinks for women, in about two hours. Some individuals will reach a 0.08g/dL BAC sooner depending on body weight. Binge drinking is known to pose health and safety risks, including car crashes and injuries. Over the long term, binge drinking can damage the liver and other organs.

“While the negative health effects of chronic drinking are well-documented, this is a key study to show that a single alcohol binge can cause damaging effects such as bacterial leakage from the gut into the bloodstream,” said Dr. George Koob, director of the National Institute on Alcohol Abuse and Alcoholism, part of NIH.

In the study, 11 men and 14 women were given enough alcohol to raise their blood alcohol levels to at least .08 g/dL within an hour. Blood samples were taken every 30 minutes for four hours after the binge and again 24 hours later.

The researchers found that the alcohol binge resulted in a rapid increase in endotoxin levels in the blood and evidence of bacterial DNA, showing that bacteria had permeated the gut. Endotoxins are toxins contained in the cell wall of certain bacteria that are released when the cell is destroyed. Compared to men, women had higher blood alcohol levels and circulating endotoxin levels.

“We found that a single alcohol binge can elicit an immune response, potentially impacting the health of an otherwise healthy individual,” said Dr. Szabo. “Our observations suggest that an alcohol binge is more dangerous than previously thought.”

Earlier studies have tied chronic alcohol use to increased gut permeability, wherein potentially harmful products can travel through the intestinal wall and be carried to other parts of the body. Greater gut permeability and increased endotoxin levels have been linked to many of the health issues related to chronic drinking, including alcoholic liver disease.