<a href="/news/mutations-not-inherited-parents-cause-more-half-cases-schizophrenia">Mutations Not Inherited from Parents Cause More than Half the Cases of Schizophrenia</a>

<a href="/news/mutations-not-inherited-parents-cause-more-half-cases-schizophrenia">Mutations Not Inherited from Parents Cause More than Half the Cases of Schizophrenia</a> <ul class="bullet"> <li>Many cases of schizophrenia occur in families with no history of the disease.</li> <li>Rare protein-altering genetic mutations contribute to these cases.</li> <li>Researchers expect to find perhaps hundreds more of such mutations—a necessary step toward understanding how the disease develops. </li> </ul> Columbia University Medical Center researchers have shown that new, or “de novo,” protein-altering mutations—genetic errors that are present in patients but not in their parents—play a role in more than 50 percent of “sporadic” —i.e., not hereditary—cases of schizophrenia. The findings will be published online on August 7, 2011, in <a target="_blank" href="http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.902.html">Nature Genetics</a>. A group led by Maria Karayiorgou, MD, and Joseph A. Gogos, MD, PhD, examined the genomes of patients with schizophrenia and their families, as well as healthy control groups. All were from the genetically isolated, European-descent Afrikaner population of South Africa. These findings build on earlier studies by Karayiorgou, professor of psychiatry at Columbia University Medical Center. More than 15 years ago, Karayiorgou and her colleagues described a rare de novo mutation that accounts for 1–2 percent of sporadic cases of schizophrenia. With advances in technology, three years ago the Columbia team was able to search the entire genome for similar lesions that insert or remove small chunks of DNA. The mutations found accounted for about 10 percent of sporadic cases.   Encouraged by their progress, they wondered whether other, previously undetectable, de novo mutations accounted for an even greater percentage of sporadic cases. Using state-of-the-art “deep sequencing,” they examined the nucleotide bases of almost all the genes in the human genome. This time they found 40 mutations, all from different genes and most of them protein-altering. The results point the way to finding more, perhaps even hundreds, of mutations that contribute to the genetics of schizophrenia—a necessary step toward understanding how the disease develops. “Identification of these damaging de novo mutations has fundamentally transformed our understanding of the genetic basis of schizophrenia,” says Bin Xu, PhD, assistant professor of clinical neurobiology at Columbia University Medical Center and first author of the study. “The fact that the mutations are all from different genes,” says Karayiorgou, “is particularly fascinating. It suggests that many more mutations than we suspected may contribute to schizophrenia. This is probably because of the complexity of the neural circuits that are affected by the disease; many genes are needed for their development and function.” Karayiorgou and her team will now search for recurring mutations, which may provide definitive evidence that any specific mutation contributes to schizophrenia. The potentially large number of mutations makes a gene-therapy approach to treating schizophrenia unlikely. Researchers suspect, however, that all of the mutations affect the same neural circuitry mechanisms. “Using innovative neuroscience methods,” says co-author Dr. Joseph Gogos, MD, PhD, and associate professor of physiology and neuroscience at Columbia University Medical Center, “we hope to identify those neural circuit dysfunctions, so we can target them for drug development.” The study’s results also help to explain two puzzles: the persistence of schizophrenia, despite the fact that those with the disease do not tend to pass down their mutations through children; and the high global incidence of the disease, despite large environmental variations. The study’s authors are Bin Xu (CUMC), J. Louw Roos (University of Pretoria), Phillip Dexheimer (HudsonAlpha Institute), Braden Boone (HudsonAlpha Institute), Brooks Plummer (HudsonAlpha Institute), Shawn Levy (HudsonAlpha Institute), Joseph A. Gogos (CUMC), and Maria Karayiorgou (CUMC). The study was supported by NIMH, the Lieber Center for Schizophrenia Research at Columbia University, and NARSAD. The authors declare no financial conflict of interest.  ####   Columbia University Medical Center provides international leadership in basic, pre-clinical, and clinical research; in medical and health sciences education; and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States. For more information, please visit <a target="_blank" href="http://www.cumc.columbia.edu/news/press_releases/www.cumc.columbia.edu">www.cumc.columbia.edu</a>. <a title="http://columbiapsychiatry.org/" href="http://columbiapsychiatry.org/">Columbia Psychiatry</a> is ranked among the best departments and psychiatric research facilities in the Nation and has contributed greatly to the understanding of and current treatment for psychiatric disorders. Located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Medical Center campus in the Washington Heights community of Upper Manhattan, the department enjoys a rich and productive collaborative relationship with physicians in various disciplines at Columbia University's College of Physicians and Surgeons. Columbia Psychiatry is home to distinguished clinicians and researchers noted for their clinical and research advances in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders, and childhood psychiatric disorders. August 7, 2011 <ul class="bullet"> <li>Many cases of schizophrenia occur in families with no history of the disease.</li> <li>Rare protein-altering genetic mutations contribute to these cases.</li> <li>Researchers expect to find perhaps hundreds more of such mutations—a necessary step toward understanding how the disease develops.</li> </ul> <a href="/news/human-skin-cells-converted-directly-functional-neurons">Human Skin Cells Converted Directly into Functional Neurons</a> Technique moves researchers closer to replacement cell therapy for Alzheimer’s and other neurodegenerative diseases; the cells may prove useful for testing new therapeutic leads. (NEW YORK, NY) – Columbia University Medical Center researchers have for the first time directly converted human skin cells into functional forebrain neurons, without the need for stem cells of any kind. The findings offer a new and potentially more direct way to produce replacement cell therapies for Alzheimer’s and other neurodegenerative diseases.  Such cells may prove especially useful for testing new therapeutic leads.  The study was published in the August 4 online issue of the journal Cell. In another first, the researchers used this method — called direct reprogramming — to generate neurons from skin cells of patients with familial (early-onset) Alzheimer’s disease. The induced neurons were found to differ significantly from those made from healthy individuals, providing new insights into the development of the disease, reports study leader Asa Abeliovich, MD, PhD, associate professor of pathology & cell biology and neurology in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center (CUMC). In the 1980s and 90s, scientists realized that embryonic stem cells, because of their pluripotency (ability to develop into any kind of cell) and capacity for self-renewal, might be useful in regenerating or replacing tissue after injury or disease. However, the use of cells from human embryos raised ethical issues, triggering a search for alternatives. A breakthrough came in 2007, when researchers determined how to genetically reprogram human skin cells to become induced pluripotent stem (iPS) cells, which are similar to naturally pluripotent cells. Although this advance allowed researchers to avoid using embryonic stem cells, iPS technology remains complex, inefficient, and time-consuming. Moreover, the pluripotent stem cells by their nature are capable of forming tumors, leading to potential safety concerns.  In 2010, Stanford University researchers reported turning mouse skin cells directly into neurons using transcription regulators (proteins that switch genes on or off), bypassing the need to create iPS cells. Building on that work, Dr. Abeliovich and his team used a different combination of transcription regulators, plus several neuronal support factors, to convert human skin cells into forebrain neurons. The induced neurons appear to be the same as ordinary neurons, judging from electrophysiological testing and gene expression profiling. The researchers also showed that the neurons are able to send and receive signals in laboratory culture and when transplanted into the central nervous system of mice. These findings indicate that the induced neurons are capable of neuronal activity. “Direct reprogramming is fundamentally different from making neurons with iPS technologies,” says Dr. Abeliovich. “Using direct reprogramming, you could, in theory, take someone’s skin cells and in a couple of weeks have fully functional neurons ready for replacement cell therapy.” “Although the project is still at early stages and certainly not ready for clinical applications, therapies based on direct reprogramming seem more realistic than those based on iPS technology. “What is particularly exciting,” says Dr. Abeliovich, “is that direct reprogramming is broadly applicable to the study and treatment of a host of neurological diseases.” In the second part of the study, Dr. Abeliovich compared neurons made from skin cells of healthy individuals with neurons made from patients with early-onset Alzheimer’s disease. The latter cells exhibited altered processing and localization of amyloid precursor protein (APP) and increased concentration of amyloid beta, a component of APP (Alzheimer’s is thought to develop when abnormal amounts of amyloid beta accumulate in the brain, eventually killing neurons.) APP was found to collect in the cells’ endosomes, cellular compartments that sort molecules for degradation or recycling. These findings suggest that this form of Alzheimer’s is caused, at least in part, by abnormal endosomal function, the researchers report. Dr. Abeliovich’s paper is entitled, “Directed Conversion Of Alzheimer’s Disease Patient Skin Fibroblasts Into Functional Neurons.” His coauthors are Liang Qiang, Ryousuke Fujita, Toru Yamashita, Herve Rhinn, David Rhee, Claudia Doege, Lily Chau, and William B. Vanti at CUMC and Sergio Angulo and Herman Moreno at the State University of New York Downstate Medical Center, Brooklyn, N.Y. The New York State Stem Cell Science (NYSTEM), among others, provided funding for the study. The authors declare no financial or other conflicts of interest. -####- The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain at Columbia University Medical Center is a multidisciplinary group that has forged links between researchers and clinicians to uncover the causes of Alzheimer’s, Parkinson’s and other age-related brain diseases and discover ways to prevent and cure these diseases. It has partnered with the Gertrude H. Sergievsky Center at Columbia University Medical Center which was established by an endowment in 1977 to focus on diseases of the nervous system. The Center integrates traditional epidemiology with genetic analysis and clinical investigation to explore all phases of diseases of the nervous system. For more information about these centers visit: <a href="http://www.cumc.columbia.edu/dept/taub/">http://www.cumc.columbia.edu/dept/taub/</a> <a href="http://www.cumc.columbia.edu/dept/sergievsky/">http://www.cumc.columbia.edu/dept/sergievsky/</a>   Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States.   August 4, 2011 Technique moves researchers closer to replacement cell therapy for Alzheimer’s and other neurodegenerative diseases; the cells may prove useful for testing new therapeutic leads. <a href="/news/new-special-advisors-community-health-affairs">New Special Advisors for Community Health Affairs</a>   Rafael Lantigua, MD, and Dennis Mitchell, DDS, MPH, have been appointed Dean's Special Advisors for Community Health Affairs effective August 1, 2011. In these new roles, Drs. Lantigua and Mitchell will counsel all four medical center deans on community health issues and facilitate new collaborative initiatives with community and academic stakeholders. They also will work closely with the Office of Government & Community Affairs and provide a faculty voice in efforts to engage community health organizations and to optimize academic and community partnerships. Their understanding of the community will help align CUMC and other resources with the goal to improve healthcare services in northern Manhattan. <table width="270" border="0" align="right" class="imagetabler"> <tbody> <tr> <td> <img width="120" vspace="5" hspace="0" height="180" border="0" alt="Dr. Lantigua" src="http://ps.columbia.edu/sites/ps/files/Rafael_Lantigua_09.jpg" /> Rafael Lantigua, MD </td> </tr> </tbody> </table> Dr. Lantigua, professor of clinical medicine and associate director of the Division of General Medicine, and Dr. Mitchell, assistant professor of clinical dentistry and senior associate dean of diversity affairs, bring decades of community health experience in Washington Heights, Inwood and Harlem to their new positions. Since joining P&S in 1980, Dr. Lantigua has had a special interest in improving the health of aging minorities. He was the driving force behind CALME, the Columbia Center for the Active Life of Minority Elders, which supported research to reduce health disparities affecting minority elders and established an important bridge between Columbia researchers and the neighboring community. Dr. Lantigua also helped start the <a target="_blank" href="http://www.cumc.columbia.edu/dept/chum/overviewa.htm">Columbia Center for the Health of Urban Minorities</a> to shift community based-research from studies for the community to studies with the community. He is co-director of the <a target="_blank" href="http://www.cumc.columbia.edu/features/CCPH-brings-fresh-produce-washington-heights">Columbia Community Partnership for Health</a>, part of the Irving Institute for Clinical and Translational Research, and a co-founder of <a target="_blank" href="http://www.alianzaonline.org/main/">Alianza Dominicana</a>. Dr. Lantigua earned his medical degree at the Autonomous University of Santo Domingo in the Dominican Republic. <table width="270" border="0" align="right" class="imagetabler"> <tbody> <tr> <td> <img width="177" vspace="5" hspace="0" height="165" border="0" alt="Dr. Mitchell" src="http://ps.columbia.edu/sites/ps/files/DennisMitchellphoto7-1-04.jpg" /> Dennis Mitchell, DDS, MPH </td> </tr> </tbody> </table> Dr. Mitchell, a member of the College of Dental Medicine faculty since 1991, has a longstanding involvement in research investigating oral health disparities affecting minority and economically disadvantaged populations, particularly in northern Manhattan. Dr. Mitchell helped establish CDM's <a target="_blank" href="http://communitydentcare.columbia.edu/">Community DentCare Network</a> to provide dental services in the community to underserved residents of northern Manhattan who need affordable dental care. The annual number of visits to the community network continues to grow since its inception in 1996, reaching 55,000 visits in the 2009-2010 academic year. Dr. Mitchell is also actively involved in initiatives aimed at increasing the number of minority oral health providers. Dr. Mitchell earned his doctor of dental surgery degree from Howard University and his master's degree in public health from Columbia. August 4, 2011 <a href="/news/study-explains-why-muscles-weaken-age-and-points-possible-therapy">Study Explains Why Muscles Weaken with Age and Points to Possible Therapy</a> (NEW YORK, NY) – Researchers at Columbia University Medical Center have discovered the biological mechanism behind age-related loss of muscle strength and identified a drug that may help reverse this process. Their findings were published in the August 2 online edition of Cell Metabolism. As we grow older, our skeletal muscles tend to wither and weaken, a phenomenon known as sarcopenia. Sarcopenia, which begins to appear at around age 40 and accelerates after 75, is a major cause of disability in the elderly. Exercise can help counter the effects of age-related muscle loss. Otherwise, there are no established treatments. According to the new study, conducted in mice, sarcopenia occurs when calcium leaks from a group of proteins in muscle cells called the ryanodine receptor channel complex. These leaks then trigger a chain of events that ultimately limits the ability of muscle fibers to contract, reports study leader Andrew R. Marks, M.D., chairman and professor of physiology and cellular biophysics, the Clyde and Helen Wu Professor of Medicine, and director of the Wu Center for Molecular Cardiology at Columbia University Medical Center (CUMC). Ryanodine receptors, which are calcium channels found in most body tissues, have been the focus of Dr. Marks’ research since 1989. After cloning the ryanodine receptor gene, he later discovered, in studies of mice, that leaky ryanodine receptors are involved in the development of heart failure and arrhythmias. In 2009, he showed that leaks in these channels also contribute to Duchenne muscular dystrophy, a genetic disorder characterized by rapidly progressing muscle weakness and early death. Since muscular dystrophy and sarcopenia have some commonalities, Dr. Marks suspected that ryanodine receptor leakage may also be involved in age-related muscle loss, which the present study shows is the case. “This is a completely new concept — that the damage that occurs in aging is very similar to what happens in muscular dystrophy,” says Dr. Marks, “thus as we age we essentially develop an acquired form of muscular dystrophy.” Both the aging process and the genetic defect responsible for muscular dystrophy cause an increase in the production of oxygen free radicals, highly reactive and harmful molecules. “Our data suggest that this sets up a vicious cycle, in which the free radicals cause ryanodine receptors to leak calcium into the cell. The calcium poisons mitochondria — organelles that power the cell — leading to the release of even more free radicals. This, in turn, causes more calcium leakage. With less calcium available for contraction, the muscles get weaker,” says first author Daniel C. Andersson, M.D., Ph.D., a postdoctoral fellow in physiology and cellular biophysics at CUMC. The study also points to a possible therapy for sarcopenia: an experimental drug called S107, developed by Dr. Marks and his colleagues. The drug acts by stabilizing calstabin1, a protein that binds to ryanodine receptors and prevents calcium leakage. In the study, 24-month-old mice (roughly the equivalent of 70-year-old humans) were given S107 for four weeks. The mice showed significant improvements in both muscle force and exercise capacity, compared with untreated controls. “The mice ran farther and faster during voluntary exercise,” says Dr. Andersson. “When we tested their muscles, they were about 50 percent stronger.” The drug had no effect on younger mice with normal ryanodine receptors. A similar drug is now in phase II clinical trials for the treatment of heart failure. “Most investigators in the field of aging have been saying that the way to improve muscle strength is to build muscle mass, using such therapies as testosterone, growth hormone, and insulin-like growth factor-1,” says Dr. Marks. “But an increase in muscle mass is not necessarily accompanied by an increase in muscle function. Our results suggest that you can improve muscle function by fixing leaky calcium channels. And in fact, treating aged mice with S107 enhanced muscle strength without increasing muscle size, at least during the four-week treatment period.” Dr. Marks’ paper is titled, “Ryanodine Receptor Oxidation Causes Intracellular Calcium Leak and Muscle Weakness in Aging.” In addition to Dr. Andersson, his coauthors include Mathew J. Betzenhauser, Steven Reiken, Albano C. Meli, Alisa Umanskaya, Wenjun Xie, Takayuki Shiomi, and Ran Zalk at CUMC, and Alain Lacampagne at Universités Montpellier, Montpellier, France. A.R. Marks is a consultant for ARMGO Pharma, Inc., a privately held biopharmaceutical company which has been awarded an exclusive, worldwide license from Columbia University for its ryanodine receptor technology. The company's proprietary drugs, known as "rycals," are a new class of oral agents that act on ryanodine receptors to repair the calcium leak associated with chronic diseases. ARMGO Pharma, Inc. is seeking to discover and develop novel small-molecule therapeutics to treat debilitating cardiac, muscular, and neurological disorders. The company's lead drug candidate is currently undergoing Phase II clinical trials for heart failure. Other programs have not yet entered the clinical phase of development, please visit <a target="_blank" href="http://www.armgo.com">www.armgo.com</a> for further information. This research was supported by grants from the National Heart, Lung, and Blood Institute and the Swedish Research Council. ### Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States. -####- August 2, 2011 Researchers at Columbia University Medical Center have discovered the biological mechanism behind age-related loss of muscle strength and identified a drug that may help reverse this process. Their findings were published in the August 2 online edition of Cell Metabolism. <a href="/news/hail-court-decision-stem-cell-research">Researchers at Columbia University Medical Center Hail Court’s Decision on Stem Cell Research</a> (NEW YORK, NY) – Commenting on today’s ruling in favor of the Obama administration’s continued funding of embryonic stem cell research, Lee Goldman, MD, Dean of the Faculties of Health Sciences and Medicine at Columbia University Medical Center, and Executive Vice President, Columbia University, said:  “We are grateful that the court has correctly rejected this attempt to inject politics into science. Stem cell research offers some of the most promising possibilities to treat and eventually cure major diseases such as diabetes and Parkinson’s disease and to gain important insights into everything from human development to the biological processes that lead to cancer and other diseases. I am pleased that researchers here at Columbia University Medical Center and around the world can proceed with this important scientific work.”  Christopher Henderson, PhD, professor of pathology, neurology and neuroscience, co-director of the Center for Motor Neuron Biology and Disease at Columbia, and senior scientific advisor to the Project A.L.S./ Jenifer Estess Laboratory for Stem Cell Research, said:  “The federal court’s decision is great news for Columbia stem cell researchers and for the community at large. Even though multiple alternative sources of human stem cells are being evaluated, real progress can be made only by allowing objective comparisons between these and the “gold-standard” embryonic stem cells.  Given the immense potential of stem cell research for human health, we hope that funding by the National Institutes of Health in this area will expand to allow support of top-level research using all available models.”  -####-  Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States. -####-   July 27, 2011 <a href="/news/mother-infant-communication">VIDEO: Beatrice Beebe Discusses Mother-Infant Communication on ABC World News Now.</a> VIDEO: <a href="http://www.youtube.com/watch?v=G1g6ecQiw5I" target="_blank">Click here to watch the video</a>.<a target="_blank" href="http://www.youtube.com/watch?v=G1g6ecQiw5I"> </a> July 26, 2011 <a href="/news/understanding-radiation-induced-secondary-cancers">Understanding Radiation-Induced Secondary Cancers</a> <ul class="bullet"> <li>Ionizing radiation damages neighboring cells.</li> <li>In a small percentage of cases, radiation treatment can cause secondary tumors.</li> <li>Researchers are working on ways to prevent such tumors.</li> </ul>  Until about 10 years ago, scientists assumed that ionizing radiation damaged DNA only when it directly hit a cell’s nucleus. But they now understand that neighboring cells can be damaged by so-called “bystander effects.” The single-particle microbeam at Columbia’s Center for Radiological Research (CRR), which can target a single cell or subcellular compartment with either a single or multiple alpha particles, has played a large role in enabling researchers to understand these radiation-induced bystander effects, so they can find ways to reduce them. In 1996, a graduate student of radiation oncology professor Tom Hei was looking for a project for his PhD dissertation. “I suggested he hit the cytoplasm of cells―instead of the nucleus—with alpha particles and look at changes in mitochondrial functions,” said Hei. “When he did so, he found mutations in the nuclei of those cells. I thought something was wrong with the experiment and asked him to repeat it. He did repeat it—seven times—but always with the same result.” This was the first demonstration of an extra-nuclear (outside of the nucleus)response to irradiation. The next step was to administer lethal doses of radiation to select individual cells in a culture. Since dead cells don’t reproduce, any mutations that appeared in the irradiated population must arise from the progeny of non-irradiated bystander cells. This was the first demonstration of extra-cellular (outside of the cell)response to irradiation, says Hei, who is also vice chair of radiation oncology, associate director of CRR, and professor of environmental health sciences. In 2008, Italian researchers published a study on out-of-field—outside of the radiated field―response to irradiation. They shielded the heads of a radiosensitive strain of mice with lead cylinders. When their lower abdomens were irradiated with X rays, the mice developed brain tumors. At the same time, Hei and his group irradiated the lower extremities of mice and found mutations and inflammatory response in out-of-field lung tissue. Bystander effects can damage not only cells that weren’t targeted, but also their progeny. And sometimes mutations don’t appear in the progeny until many generations down the line.  Now that the phenomenon of bystander effects has been established, the challenge is to understand the cell-to-cell communication by which it takes place. Hei and his group are honing in on the enzyme COX-2, which plays a key role in inflammation, as the critical signaling link in the complex cascade of cellular signals. In one experiment, treatment of cells with the COX-2 inhibitor NS, 398 significantly reduced the bystander effect. Ionizing radiation can both cure and induce cancer, and bystander effects could contribute to those cases where cancer is induced. Although clinical radiation oncologists are concerned about the possibility of radiation-induced secondary cancers in patients undergoing radiotherapy, particularly younger patients, improved technology has minimized the dose to adjacent normal tissue. Eventually, Hei and other researchers hope to be able to assess precisely an individual patient’s risk and to prevent such cancers from developing. For the patient who is worried about radiation treatment, Dr. K. S, Clifford Chao, professor and chair of radiation oncology, says that the risk of developing such a cancer is low—less than 0.5 percent, which is lower than the risk of secondary cancer induced by chemotherapy. And the potential risk has to be weighed against the benefit of successfully treating the primary cancer.         <iframe height="349" src="http://www.youtube.com/embed/eW-ekLWCkLw" frameborder="0" width="560" allowfullscreen=""></iframe>   July 22, 2011 <ul> <li>Ionizing radiation damages neighboring cells.</li> <li>In a small percentage of cases, radiation treatment can cause secondary tumors.</li> <li>Researchers are working on ways to prevent such tumors.</li> </ul> <a href="/news/add-unwanted-pregnancy-travails-women-war-torn-lands">Add Unwanted Pregnancy to Travails of Women in War-Torn Lands</a> <img align="right" src="http://www.mailman.columbia.edu/sites/default/files/mainfeature/woman_article.jpg?1311173504" class="imagetabler" alt="" />Violent conflict disrupts all aspects of society, including the delivery of the most basic reproductive health services: prenatal and maternal care, family planning, prevention of HIV and other sexually transmitted infections, abortions and emergency caesarian care. A new study by researchers at Columbia University’s Mailman School of Public Health and collaborators demonstrates and quantifies the alarming gap between the desire of women in war-torn areas to limit their childbearing and the availability of resources and knowledge to enable them to do so. The situation leads to unintended pregnancy among women already contending with the stresses of violence and, in many cases, displacement. The researchers surveyed married women from six areas in Sudan, northern Uganda and Democratic Republic of Congo, about their views on family planning. Full study findings are published in BioMed Central’s open access journal <a href="http://www.conflictandhealth.com/content/pdf/1752-1505-5-11.pdf" target="_blank">Conflict and Health</a>. Participants were young, with mean ages between 27.3 and 28.9 years; they had little education; and, depending on location, their average number of children ranged from 3.2 to 4.2. Study results showed that 30% to 40% of the women did not want to have another child in the next two years and an additional 12% to 35% of the women did not want any additional children. Despite these numbers, the proportion of women who were using modern contraception was under 4% at four of the sites and 12% and 16% in two sites, where there had been some prior family planning services. These rates are low, even for sub-Saharan Africa, and illustrate the gap between what women want and what services are available to them. An assessment by researchers and program staff of 38 local healthcare facilities mandated  to provide family planning services revealed that, at most, only one-third of those had the necessary staff, equipment and supplies. In some areas, no facilities were equipped to provide these services. "It is clear that many women are unable to obtain family planning services during a time when few would choose to become pregnant, and women who have complications due to unsafe abortions have no access to treatment," observed <a href="http://www.mailman.columbia.edu/our-faculty/profile?uni=tjm22">Therese McGinn, DrPH</a>, lead author of the paper and associate professor of Population and Family Health at Columbia’s Mailman School. "It is vitally important that family planning services are made available for conflict-affected men and women as part of strengthening local health services and aid packages," said Dr. McGinn, who directs <a href="http://www.raiseinitiative.org/home/" target="_blank">RAISE Initiative, New York</a>, which works with a variety of partners  to provide reproductive health services to populations in six conflict-affected regions. While providing such services is challenging, the study found good evidence that programs to provide family planning services in culturally sensitive ways do make a difference. Of the six regions studied, use of contraceptives and awareness of modern contraceptive methods was highest in northern Uganda and West Darfur, where RAISE partner organizations Marie Stopes Uganda and Save the Children had established programs offering family planning services. Inadequate funding remains an obstacle. The authors cited a 2009 study showing that less than $1.30 per capita was spent between 2003 and 2006 on reproductive health in 18 conflict-affected countries, of which less than 2% was for family planning.  While the investigators note that political violence often occurs in areas of the world where access to health care is poor even before the conflict began, violence and destruction disrupt health services even further.  Access to facilities that can provide safe delivery, emergency caesarean sections, treat complications of pregnancy and childbirth and offer family planning services becomes limited for those who flee and those who remain behind. Women and girls who are raped or subjected to other violence are vulnerable to unwanted pregnancy and sexually transmitted infections but they can get treatment when staff are skilled and facilities prepared to assist them. Dr. McGinn and her co-authors point out that progress has been made in the field of reproductive health in crisis settings in terms of policy and practice.  But reproductive health services are not yet regularly available, so many women and men are denied this basic health care.  “We can do better,” said Dr. McGinn, “and that is the challenge facing us as we move the field ahead.” About Columbia University's Mailman School of Public Health Founded in 1922 as one of the first three public health academies in the nation, Columbia University’s Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Mailman School is the third largest recipient of NIH grants among schools of public health. Its over 300 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change & health, and public health preparedness. It is a leader in public health education with over 1,000 graduate students from more than 40 nations pursuing a variety of master’s and doctoral degree programs. The Mailman School is also home to numerous world-renowned research centers including the International Center for AIDS Care and Treatment Programs (ICAP), the National Center for Disaster Preparedness, and the Center for Infection and Immunity. Originally posted on the website of Columbia University’s Mailman School of Public Health. July 20, 2011 Study finds that in embattled regions like Darfur and Congo, most women want to limit childbearing, but only 2% to 16% have access and means to use contraceptives <a href="/news/could-birth-control-pill-men-be-horizon">Could a Birth Control Pill for Men be on the Horizon?</a> Retinoic Acid Receptor Antagonist Interferes with Sperm Production   (NEW YORK, NY, June 4, 2011) – Researchers at Columbia University Medical Center are honing in on the development of what may be the first non-steroidal, oral contraceptive for men. Tests of low doses of a compound that interferes with retinoic acid receptors (RARs), whose ligands are metabolites of dietary vitamin A, showed that it caused sterility in male mice.  Earlier results of the experiments using this RAR antagonist were published in the June 1st issue of Endocrinology, and an abstract extending the studies to longer drug delivery periods is scheduled for the Late Breaking Oral Session of ENDO 2011: The 93rd Annual Meeting & Expo in Boston, Massachusetts.  (The abstract, titled Meeting Men’s Contraceptive Needs—Long-Term Oral-Administered Retinoic Acid Receptor Antagonist Inhibits Spermatogenesis in Mice with a Reversible and Rapid Recovery, will be presented at the session by first author Sanny S. W. Chung, Ph.D., on Saturday, June 4, 11:15 a.m., Room 157ABC, Boston Convention & Exhibition Center).  The researchers found that low doses of the drug stopped sperm production with no apparent side effects. And crucial for a contraceptive, normal fertility was restored soon after drug administration was terminated.  Earlier research had led the investigators to the discovery that manipulating the retinoid receptor pathway could interfere with the process of spermatogenesis, which is necessary for sperm production.  Scientists have known for almost 100 years that depriving an animal of dietary vitamin A causes male sterility. While investigating targeted loss of function of the gene encoding one of the RARs, RARalpha, which results in male infertility, senior author Debra J. Wolgemuth, Ph.D., ran across a paper by Bristol-Myers Squibb on a compound that was being tested for the treatment of skin and inflammatory diseases. The compound seemed to cause changes in the testis similar to the mutation that she and Dr. Chung were studying in Dr. Wolgemuth’s lab.  (Dr. Wolgemuth is professor of genetics and development and of obstetrics and gynecology; and Dr. Chung is an associate research scientist, both at Columbia University Medical Center).  Bristol-Myers dropped its interest when it found that the compound also was – in the company’s words – “a testicular toxin.”   The paper did not elaborate on how the drug caused infertility, so Dr. Wolgemuth and her team tested the drug in mice to find out; they noted that the changes it caused were similar to what one sees with vitamin A-deficiency and loss of function of RARalpha.  “We were intrigued,” said Dr. Wolgemuth. “One company’s toxin may be another person’s contraceptive.”  To investigate whether the compound prevented conception at even lower levels than those cited in the company’s study,  Dr. Wolgemuth and her team placed the treated male mice with females and found that reversible male sterility occurred with doses as low as 1.0mg/kg of body weight for a 4-week dosing period.  One advantage of using a non-steroidal approach, the researchers say, is avoiding the side effects commonly associated with steroidal hormone-based methods.  Male steroid-based options have been plagued with adverse effects, including ethnic variability in efficacy, as well as an increased risk of cardiovascular disease and benign prostatic hyperplasia.  Another side effect of hormonal options for men has been diminished libido. That drawback will also likely be avoided if a method involving manipulation of the retinoid receptor pathway proves successful.   “We have seen no side effects, so far, and our mice have been mating quite happily,” said Dr. Wolgemuth.  The researchers say the drug will not affect vision. Although dietary vitamin A is responsible for the production of light-sensitive receptors in the eye, it does not use the RARs in this process.  “An additional benefit of our compound is that it can be taken orally as a pill, avoiding the injection process.  It also appears to have a very rapid effect on sperm production and an even more rapid recovery when fertility is desired,” said Dr. Chung.  But to make the pill a reality, researchers need to show that the compound is safe, effective – and reversible – when used for years.  Drs. Wolgemuth and Chung are now planning longer-term studies to determine how long fertility can be disrupted and still recover after administration of the drug stops. “We hope that in the not so distant future, we may finally have more choices for people,” said Dr. Chung.  Authors of the Endocrinology study are Sanny S. W. Chung, Xiangyuan Wang, Shelby S. Roberts, Stephen M. Griffey, Peter R. Reczek, and Debra J. Wolgemuth.  This study was supported in part by grants initially from CONRAD and subsequently from the NIH, NICHD.  The authors declare no financial or other conflicts of interest.   Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States. -####-     July 4, 2011 Researchers at Columbia University Medical Center are honing in on the development of what may be the first non-steroidal, oral contraceptive for men. Tests of low doses of a compound that interferes with retinoic acid receptors (RARs), whose ligands are metabolites of dietary vitamin A, showed that it caused sterility in male mice. <a href="/news/delayed-access-tertiary-care-associated-higher-death-rate-type-pulmonary-fibrosis">Delayed Access to Tertiary Care Associated with Higher Death Rate from Type of Pulmonary Fibrosis</a>   <ul class="bullet"> <li>Patients with a form of pulmonary fibrosis often do not get referred to a tertiary care center quickly.</li> <li>Delayed access is associated with a higher death rate.</li> <li>Better methods of early detection would shorten time from first symptoms to referral.</li> </ul> Idiopathic pulmonary fibrosis (IPF)―scarring and thickening of the lungs from unknown causes―is the predominant condition leading to lung transplantation nationwide. Columbia University Medical Center researchers confirmed that delayed access to a tertiary care center for IPF is associated with a higher risk of death. The findings were published online in the <a target="_blank" href="http://ajrccm.atsjournals.org/cgi/reprint/201104-0668OCv1">American Journal of Respiratory and Critical Care Medicine</a>on June 30, 2011. A group led by Columbia researcher David J. Lederer followed 129 IPF patients at an academic medical center. They looked at the length of time from the onset of shortness of breath to the first visit to the center. A longer delay was associated with increased risk of death, independent of age, gender, socioeconomic status, lung capacity, disease severity, type of health insurance, or education. The researchers also found no association between the length of delay and the likelihood of the patient’s receiving a lung transplant. IPF leads to respiratory failure and death, usually within three years. It is a relatively rare disease, which afflicts 100,000–120,000 Americans, almost all over the age of 50. Characterized by shortness of breath upon exertion, it is often misdiagnosed, especially in people with other ailments. A delay in making a correct diagnosis can lead to ineffective, or even harmful, treatments. For example, doctors sometimes still treat IPF with steroids, because the disease was originally thought to have an inflammatory component. Now scientists know that steroids are counterproductive. A delay in diagnosis can also delay evaluation for a lung transplant. Although research is underway on potential drug therapies, currently lung transplantation is the only effective treatment. “The initial symptoms of IPF are subtle, and accurate diagnosis may not be feasible for community-based pulmonologists,” explains Lederer, Herbert Irving Assistant Professor of Clinical Medicine and co-director of the New York-Presbyterian Hospital Interstitial Lung Disease Program and Lung Transplant Program. For that reason, earlier access would be aided by improved methods of early detection. But until then, the recognition, or even suspicion, of IPF should prompt referral to a tertiary care center. The study’s authors are Daniela J Lamas (CUMC), Steven M. Kawut (University of Pennsylvania), Emilia Bagiella (CUMC), Nisha Philip (CUMC), Selim M. Arcasoy (CUMC), and David J. Lederer (CUMC). The study was supported by the NIH, the Robert Wood Johnson Foundation, and Herbert and Florence Irving. DL serves as an advisor to Gilead Sciences, Inc. The other authors declare no financial or other conflict of interest. #### Columbia University Medical Center provides international leadership in basic, pre-clinical, and clinical research; in medical and health sciences education; and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest in the United States. For more information, please visit <a target="_blank" href="http://www.cumc.columbia.edu/news/press_releases/www.cumc.columbia.edu">www.cumc.columbia.edu</a>. July 1, 2011 <ul class="bullett"> <li>Patients with a form of pulmonary fibrosis often do not get referred to a tertiary care center quickly.</li> <li>Delayed access is associated with a higher death rate.</li> <li>Better methods of early detection would shorten time from first symptoms to referral.</li> </ul>