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Revealing Leukemia-Initiating Cells
Two new studies reveal a way to increase the body"s appetite for gobbling up the cancer stem cells responsible for acute myeloid leukemia (AML), a form of cancer with a particularly poor survival rate. The key is targeting a protein on the surface of those cells that sends a "don"t eat me" signal to the macrophage immune cells that serve as a first line of defense, according to the reports in the July 24th issue of the journal Cell, a Cell Press publication.

ChIP-Seq, Drosophila Targeted Mutagenesis Featured In Cold Spring Harbor Protocols
High-throughput whole-genome analysis is becoming a standard laboratory approach for investigating cellular processes. Next-generation sequencing is replacing microarrays as the technique of choice for genome-scale analysis, because it offers advantages in both sensitivity and scale. The June issue of Cold Spring Harbor Protocols features "Native Chromatin Preparation and Illumina/Solexa Library Construction" from Keji Zhao and colleagues at the National Heart, Lung and Blood Institute. The article describes sample preparation for sequencing of chromatin-immunoprecipitated DNA (ChIP-Seq) to analyze histone modification patterns using native chromatin and the Solexa/Illumina Genome Analyzer. Step-by-step instructions are given for purification of human CD4+ T cells from lymphocytes and chromatin fragmentation using micrococcal nuclease (MNase) digestion, followed by chromatin immunoprecipitation (ChIP) and construction of a library for sequencing. The article is freely available on the website for Cold Spring Harbor Protocols (http://cshprotocols.cshlp.org/cgi/content/full/2009/6/pdb.prot5237).
News of the day
Washington Post Examines Focus On Abortions Later In Pregnancy After Tiller Murder
The Washington Post on Friday examined the renewed attention on abortion procedures performed later in pregnancy following Kansas provider George Tiller"s shooting death on Sunday. Tiller was one of the few physicians in the U.S. who performed late abortions. The Post reports that these abortions make up a small portion of the 1.2 million abortions performed each year -- more than 88% of abortions are performed in the first trimester and less than 1% are performed after 21 weeks" gestation. Data published in 2001 from 15 states and New York City show that as many as 2,400 abortions after 24 weeks" gestation were performed in the U.S. that year, according to Stanley Henshaw, a senior fellow at the Guttmacher Institute. He added that most of those abortions likely were performed in the 25th or 26th week.Henshaw said that little is known about the circumstances surrounding third trimester abortion procedures and that "information just isn"t available." The government does not collect detailed data regarding the number of such procedures, who is performing them and under what circumstances. In addition, abortion providers who perform the procedure later in pregnancy supply very little published information, the Post reports. According to the Post, most abortion providers will not perform the procedure after 22 or 24 weeks" gestation because of legal and other concerns, social stigma, or inadequate training and lack of experience. A 2001 survey of 1,819 abortion providers indicated that 18 clinics and 12 hospitals performed abortions at 26 weeks" gestation. However, the Post reports that the number of providers offering abortions later in pregnancy likely has declined in correlation with the decreasing number of overall providers. Henshaw said the number of providers offering the procedure later in pregnancy also likely has declined.Abortion-rights supporters say that third-trimester abortions are performed only when medically necessary, such as when a fatal abnormality is detected in the fetus or a life-threatening complication in the woman is discovered. Other circumstances include cases when the woman suffers serious emotional issues or is undergoing cancer treatment, the Post reports. Vicki Saporta, president of the National Abortion Federation, said that women who experience such pregnancies have "no good choice" and "nee[d] to terminate their pregnancies to protect their own health." Tiller "provided both the emotional and physical care for women in that situation," she said (Stein, Washington Post, 6/5).Los Angeles Times Profiles Abortion Provider Hern The Los Angeles Times on Friday profiled Warren Hern, a Colorado-based abortion provider who performs the procedure later in pregnancy and was a close friend of Tiller"s. Hern has provided abortions since 1973 when the Supreme Court legalized the procedure with Roe v. Wade. He said he "felt doing abortions was the most important thing I could do with my life." Hern opened the Boulder Abortion Clinic in 1975, and in the 1980s authored and self-published a textbook, Abortion Practice. He said that he eventually began to focus on abortion procedures later in pregnancy, which currently make up the majority of his practice. Such abortions usually are performed because of medical complications in the woman or abnormalities in the fetus. Patients at Hern"s clinic receive counseling to explain the procedure and to ensure the woman wants it, although he said many women have already made their decision with their own physician. Hern said that although Tiller"s death has been an emotional situation, his clinic is "pretty busy taking care of people who said they couldn"t find anyone else" to perform abortions later in pregnancy (Correll, Los Angeles Times, 6/5).Bond Set for Tiller Shooting Suspect Sedgwick County, Kan., District Judge Warren Wilbert on Thursday set a $5 million bond for Scott Roeder, the man charged with shooting and killing Tiller, the AP/Yahoo! News reports. A preliminary hearing for Roeder is scheduled for June 16. If convicted, Roeder face
Endocrinology

Lives May Be Saved By Osteoporosis Drug's Strengthening Of The Immune System

An osteoporosis drug proven to save lives after hip fractures may do so by strengthening the body"s immune system, according to geriatrics researchers at Duke University Medical Center. In 2007, Duke researchers reported a 28 percent reduction in death among patients who received zoledronic acid (Reclast) within 90 days of surgery for a hip fracture. Zoledronic acid is a yearly intravenous injection of bisphosphonate that inhibits the progression of bone loss. The researchers also reported that the 2,111 people who participated in the study were 35 percent less likely to suffer another fracture. "The findings marked the first time an osteoporosis medication was shown to have an effect on mortality, but they didn"t tell us why the mortality rate was lower," says Cathleen Colon-Emeric, MD, an associate professor of medicine at Duke. "People assumed it was due to a reduction in secondary fractures. We wanted to know if that was the reason or were other conditions being affected by the medication." In the current study, now online in the Journal of Bone and Mineral Research, Colon-Emeric and her colleagues report that the reduction in additional broken bones accounts for only eight percent of the mortality benefit. "Even after adjusting for secondary fractures and other risk factors, we found the risk of mortality was still 23 percent lower in the zoledronic acid-treated participants. That suggests the drug must work in other ways." The link between osteoporosis and an increased risk of death has been observed for some time. Up to 25 percent of the 345,000 Americans hospitalized annually with hip fractures die within a year of their fracture. Typically, most patients die from cardiovascular problems like heart attacks, arrhythmias and strokes, infections such as pneumonia, and cancer. "People who received the drug experienced common complications at the same rate as those who didn"t," says Colon-Emeric. But the people in the zoledronic acid group were better able to survive these events. "In particular, people with certain cardiac problems such as arrhythmias and pneumonias were much less likely to die from those conditions." Patients who lived in a nursing home before their broken hip, or who had high levels of cognitive impairment did not receive a mortality benefit from the drug. It still remains unclear what role zoledronic acid plays. "We know it affects the immune system and inflammation, and both of those are important in fighting infection and cardiovascular disease," Colon-Emeric says. "It may be that the drug is changing the body"s ability to fight off and recover from those illnesses." That idea will require confirmation in new studies. Other investigators participating in this study include: Kenneth W. Lyles, MD and Carl F. Pieper, DrPH, Duke University Medical Center; Steven Boonen, MD, PhD, Katholieke Universiteit Leuven, Belgium; Pierre Delmas, MD, PhD, Claude Bernard University, Lyon, France; Jay Magaziner, PhD, University of Maryland; Peter Mesenbrink, PhD, of Novartis Pharmceuticals, NJ; and Erik F. Eriksen, MD, DMsc, Novartis Pharma AG, Switzerland. This study was funded in part by Novartis Pharmaceuticals. Drs. Colon-Emeric, Lyles, Magaziner, Pieper and Boonen are consultants for Novartis. Debbe Geiger Duke University Medical Center


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