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Archive - Sep 2014

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September 8th

New, Antibody-Based, Non-Steroidal Treatment for Certain Severe Asthmatics

A team of researchers at McMaster University and St. Joseph's Healthcare Hamilton, both in Canada, have successfully evaluated a new, antibody-based drug for certain patients with severe asthma. The drug – named mepolizumab (image)– can replace traditional, steroid-based treatments for a specific subset of patients, resulting in improved outcomes and reduced side effects. The study and manuscript, published online on September 8, 2014 in the New England Journal of Medicine was led in Canada by Dr. Parameswaran Nair, Staff Respirologist, Firestone Institute for Respiratory Health at St. Joseph's Healthcare Hamilton and Professor of Respirology at the Michael G. DeGroote School of Medicine at McMaster University. Dr. Nair and his colleagues recruited the largest number of participants for this global study. "This new drug is the only therapy that has been proven to be effective in well-established clinical trials to help reduce doses of steroid-based treatments such as prednisone for those with severe asthma," said Dr. Nair, adding that the paper reconfirms the team's observation published in the New England Journal of Medicine in 2009. Patients with severe asthma often require high doses of steroid-based treatments that can significantly impair their quality of life. These high doses can cause debilitating side effects including mood swings, diabetes, bone loss, skin bruising, cataracts, and hypertension. Previous research at the Hamilton institutions has identified specific types of patient with severe asthma who have an overabundance of a particular type of white blood cell (eosinophils) present in their sputum. These patients often suffer from the most severe asthma symptoms and can only be treated through steroid-based medications such as prednisone.

Bacterium Routinely Breaks and Reassembles Its DNA

Life can be so intricate and novel that even a single cell can pack a few surprises, according to a study led by Princeton University researchers. The pond-dwelling, single-celled organism Oxytricha trifallax (image) has the remarkable ability to break its own DNA into nearly a quarter-million pieces and rapidly reassemble those pieces when it's time to mate, the researchers reported online on August 28, 2014 in Cell. The organism internally stores its genome as thousands of scrambled, encrypted gene pieces. Upon mating with another of its kind, the organism rummages through these jumbled genes and DNA segments to piece together more than 225,000 tiny strands of DNA. This all happens in about 60 hours. The organism's ability to take apart and quickly reassemble its own genes is unusually elaborate for any form of life, explained senior author Dr. Laura Landweber, a Princeton professor of ecology and evolutionary biology. That such intricacy exists in a seemingly simple organism accentuates the "true diversity of life on our planet," she said. "It's one of nature's early attempts to become more complex despite staying small in the sense of being unicellular," Dr. Landweber said. "There are other examples of genomic jigsaw puzzles, but this one is a leader in terms of complexity. People might think that pond-dwelling organisms would be simple, but this shows how complex life can be, that it can reassemble all the building blocks of chromosomes." From a practical standpoint, Oxytricha is a model organism that could provide a template for understanding how chromosomes in more complex animals such as humans break apart and reassemble, as can happen during the onset of cancer, Dr. Landweber said.

2014 Lasker Awards Announced, Often Prelude to Nobel Prize

On September 8, 2014, The Albert and Mary Lasker Foundation announced the winners of the 2014 Lasker Awards: Kazutoshi Mori and Peter Walter for basic medical research; Alim Louis Benabid and Mahlon R. DeLong for clinical research; and Mary-Claire King for special achievement. "For nearly 70 years, the Lasker Awards have honored extraordinary individuals who have made fundamental biological discoveries, developed therapies to dramatically improve patient care, and provided mentorship and leadership to pave the way for the next generation of scientists," said Claire Pomeroy, President of the Lasker Foundation. "This year's laureates join that tradition and illustrate to the public why science is so worthy of our support." Walter (University of California, San Francisco) and Mori (Kyoto University, Japan) will receive the 2014 Albert Lasker Basic Medical Research Award for discoveries that elucidate a key quality-control system in the cell, the unfolded protein response. DeLong (Emory University School of Medicine, Atlanta) and Benabid (Joseph Fourier University, Grenoble, France) will receive the 2014 Lasker~DeBakey Clinical Medical Research Award for developing a surgical technique that reduces tremors and restores motor function in patients who have advanced Parkinson's disease. Mary-Claire King (University of Washington, Seattle) will receive the 2014 Lasker~Koshland Special Achievement Award for her contributions to medical science and human rights. Joseph L. Goldstein, Chair of the Lasker Medical Research Awards Jury, observed that the award-winning research was spurred by scientists who anticipated key questions. "This year's Lasker winners have the uncanny ability to spot the next big thing in their field," he said.

Sleeping on Animal Fur in Infancy May Reduce Risk of Asthma

Sleeping on animal fur in the first three months of life might reduce the risk of asthma in later childhood, a new study has found. The new research, presented at the European Respiratory Society (ERS) International Congress in Munich on September 8, 2014 (abstract 1944), suggests that exposure to the microbial environment in animal skin and fur could have a protective effect against asthma and allergies. Previous studies have suggested that exposure to a wider range of environments from a young age could be protective against asthma and allergies. These findings have not been confirmed conclusively in urban settings. In this new study, researchers investigated children from a city environment who had been exposed to animal skin by sleeping on the material shortly after birth. Data from a German birth cohort called Lisaplus were used. The cohort included over 3,000 healthy newborns who were mainly recruited in 1998. The researchers collected information on exposure to animal skin during the first three months of life, along with information on the health of children until the age of 10 years. Information on 2,441 children was used in the study, with 55% of those included sleeping on animal skin in the first three months of life. The results showed that sleeping on animal skin was associated with a reduced risk of a number of factors connected to asthma. The chance of having asthma at the age of 6 years was 79% lower in children who had slept on animal skin after birth compared with those who were not exposed to animal skin. The risk decreased to 41% by the age of 10. Dr. Christina Tischer, from the Helmholtz Zentrum München Research Centre, said: "Previous studies have suggested that microbes found in rural settings can protect from asthma.

September 7th

Method to Create New Muscles Developed, Holds Promise for Treatment of Muscle-Wasting Diseases

Researchers at the Sanford-Burnham Medical Research Institute (Sanford-Burnham) in La Jolla, California have developed a novel technique to promote tissue repair in damaged muscles. The technique also creates a sustainable pool of muscle stem cells (image) needed to support multiple rounds of muscle repair. The study, published onine on September 7, 2014 in Nature Medicine, provides promise for a new therapeutic approach to treating the millions of people suffering from muscle diseases, including those with muscular dystrophies and muscle wasting associated with cancer and aging. There are two important processes that need to happen to maintain skeletal-muscle health. First, when muscle is damaged by injury or degenerative disease such as muscular dystrophy, muscle stem cells—or satellite cells—need to differentiate into mature muscle cells to repair injured muscles. Second, the pool of satellite cells needs to be replenished so there is a supply to repair muscle in case of future injuries. In the case of muscular dystrophy, the chronic cycles of muscle regeneration and degeneration that involve satellite-cell activation exhaust the muscle stem-cell pool to the point of no return. "Our study found that by introducing an inhibitor of the STAT3 protein in repeated cycles, we could alternately replenish the pool of satellite cells and promote their differentiation into muscle fibers," said Alessandra Sacco, Ph.D., Assistant Professor in the Development, Aging, and Regeneration Program at Sanford-Burnham. "Our results are important because the process works in mice and in human muscle cells.

Graphene-Based, Room-Temperature Detector Captures Unprecedented Range of Light, Including Terahertz Waves

New research at the University of Maryland could lead to a generation of light detectors that can see below the surface of bodies, walls, and other objects. Using the special properties of graphene (image), a two-dimensional form of carbon that is only one atom thick, a prototype detector is able to see an extraordinarily broad band of wavelengths. Included in this range is a band of light wavelengths that have exciting potential applications but are notoriously difficult to detect: terahertz waves, which are invisible to the human eye. A research paper about the new detector was published online on September 07, 2014 in Nature Nanotechnology. Lead author Xinghan Cai, a University of Maryland physics graduate student, said a detector like the researchers’ prototype “could find applications in emerging terahertz fields such as mobile communications, medical imaging, chemical sensing, night vision, and security.” The light we see illuminating everyday objects is actually only a very narrow band of wavelengths and frequencies. Terahertz light waves’ long wavelengths and low frequencies fall between microwaves and infrared waves. The light in these terahertz wavelengths can pass through materials that we normally think of as opaque, such as skin, plastics, clothing, and cardboard. It can also be used to identify chemical signatures that are emitted only in the terahertz range. Few technological applications for terahertz detection are currently realized, however, in part because it is difficult to detect light waves in this range. In order to maintain sensitivity, most detectors need to be kept extremely cold, around 4 degrees Kelvin, or -452 degrees Fahrenheit. Existing detectors that work at room temperature are bulky, slow, and prohibitively expensive.

UV Light-Induced Mutation in KNSTRN Gene Drives Many Skin Cancers, Stanford Study Shows

A genetic mutation caused by ultraviolet light is likely the driving force behind millions of human skin cancers, according to researchers at the Stanford University School of Medicine. The mutation occurs in a gene called KNSTRN, which is involved in helping cells divide their DNA equally during cell division. Genes that cause cancer when mutated are known as oncogenes. Although KNSTRN hasn't been previously implicated as a cause of human cancers, the research suggests it may be one of the most commonly mutated oncogenes in the world. "This previously unknown oncogene is activated by sunlight and drives the development of cutaneous squamous cell carcinomas," said Paul Khavari, M.D., Ph.D., the Carl J. Herzog Professor in Dermatology in the School of Medicine and Chair of the Department of Dermatology. "Our research shows that skin cancers arise differently from other cancers, and that a single mutation can cause genomic catastrophe." Cutaneous squamous cell carcinoma is the second most common cancer in humans. More than 1 million new cases are diagnosed globally each year. The researchers found that a particular region of KNSTRN is mutated in about 20 percent of cutaneous squamous cell carcinomas and in about 5 percent of melanomas. A paper describing the research was published online on September 7, 2014 in Nature Genetics. Dr. Khavari, who is also a member of the Stanford Cancer Institute and Chief of the dermatology service at the Veterans Affairs Palo Alto Health Care System, is the senior author of the paper. Postdoctoral scholar Carolyn Lee, M.D., Ph.D., is the lead author. Drs. Lee and Khavari made the discovery while investigating the genetic causes of cutaneous squamous cell carcinoma. They compared the DNA sequences of genes from the tumor cells with those of normal skin and looked for mutations that occurred only in the tumors.

Study ID’s Molecule That Induces Cancer-Killing Protein

A new study by University of Kentucky (UK) researchers has identified a novel molecule named Arylquin 1 as a potent inducer of Par-4 secretion from normal cells. Par-4 is a protein that acts as a tumor suppressor, killing cancer cells while leaving normal cells unharmed. Normal cells secrete small amounts of Par-4 on their own, but this amount is not enough to kill cancer cells. Notably, if Par-4 secretion is suppressed, this leads to tumor growth. To be published online on September 7, 2014 in Nature Chemical Biology, the UK study utilized lab cultures and animal models to show that low levels of Arylquin 1 induced Par-4 secretion without causing harm to the producer cells. Additionally, the researchers found that Par-4 is bound to a protein called vimentin, which contributes to tumor metastasis. Arylquin 1 binds to vimentin, displacing the Par-4 for secretion -- which means it may also be useful for inhibitiing the spread of cancer. These findings have strong implications for the development of future cancer treatments, as researchers are now focusing on developing Arylquin 1 into a drug to inhibit both primary and metastatic tumors. "We found that Par-4 is inactivated by pro-metastasis proteins such as vimentin," said Dr. Vivek Rangnekar, UK professor and Alfred Cohen Chair in Oncology Research in the Department of Radiation Medicine. "This implies that by using small molecule drugs that target metastasis proteins, we may be able to both inhibit the spread of cancer while also releasing the tumor suppressor -- Par-4 -- to then induce the death of the cancerous cells." Dr. Rangnekar, who also serves as Associate Director for the UK Markey Cancer Center, initially discovered the Par-4 gene in 1994. Working closely with UK medicinal chemist Dr.

Inexpensive Lab Tests Identify Resistant Infections Rapidly

Researchers from the Oregon State Public Health Lab have modified the protocol for a relatively new test for a dangerous form of antibiotic resistance, increasing its specificity to 100 percent. The research, confirming the reliability of a test that can provide results in hours and is simple and inexpensive enough to be conducted in practically any clinical laboratory was presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, an infectious disease meeting of the American Society for Microbiology, held in Washington, D.C. September 5-9, 2014. The test, called Carba NP, originally developed by Drs. Patrice Nordmann and Laurent Poirel at the University of Fribourg, Switzerland, and Dr. Laurent Dortet of the University Hospital of the South-Paris Medical School, France, allows for rapid identification of carbapenem-resistant Enterobacteriaceae (CRE), often referred to in the media as "super bugs" for their ability to resist most major antibiotics. Carbapenems (see image) are an important class of powerful antibiotics for treating severe infections caused by multidrug-resistant Gram-negative bacteria. Carbapenemases are enzymes produced by some bacteria which inactivate these antibiotics. "Over the past decade carbapenemase-producing CRE (CP-CRE) have rapidly spread around the globe and are currently considered an urgent public health threat by the Centers for Disease Control and Prevention (CDC)," says Dr. Karim Morey of the Oregon State Public Health Lab, an author on the study.

61 Percent Drop in Female Genital Warts Attributed to Free HPV Vaccination Program in Australia

General practitioners in Australia are managing 61 per cent fewer cases of genital warts among young women since the introduction of the national human papillomavirus (HPV) vaccination program, a new study from the University of Sydney reveals. The study, which reviewed more than a million patient encounters between 2000 and 2012, showed a significant year-on-year reduction in the management rate of genital warts in women aged 15-27 years since the vaccination program started. The findings were published online on September 2, 2014 in the open-access journal PLOS ONE. "The results show that the program has been a widespread success," said lead author of the study Christopher Harrison of the University of Sydney. The HPV vaccination program was introduced in 2007, and the rate of genital wart presentation fell dramatically from 4.33 per 1,000 encounters pre-program (2002-2006) to 1.67 per 1,000 encounters in the post-program period (2008-2012). Australia was one of the first countries to provide the HPV vaccine free to young women through a national immunization program. The vaccine protects against two major viral causes of genital warts (HPV 6 and HPV 11) and two major viral causes of cervical cancer (HPV 16 and HPV 18). "This is the first study to report the impact of HPV vaccinations on genital warts management in general practice, which is where the majority of cases are treated," said Mr. Harrison. "We looked at women potentially covered by the vaccination program (15-27 years), and the data showed a 61 per cent decrease in the management rate of genital warts in the four years after the program started, compared with the four years before the program. "This is an excellent result as not only do genital warts cause distress in affected patients, but treatment is at a substantial cost to the health system.