Perinatology: Introducing Baby to the Right Bacteria Nutrition: Macrophage Protein May Block Atherosclerosis Medicine: Breathing New Life into Asthma Therapy Genetics: Gene Found for Rare Bone Disorder Leadership: Lipsitz Named the Head of Division on Aging Minority Health: Symposium Seeks to Advance Multicultural Medicine Recognition: HMS and HSPH Professors Win GM Cancer Award New Books: Summer Bookshelf Medical Education: Shore to Lead Promotion and Review Board Dopamine Shown to Inhibit Growth Factor, Block Angiogenesis Embryo Research: To Ease Suffering or Do Nothing? Novel Structural Protein Discovered in Heart and Muscle On Road to Healthy Aging, Each Person Shares Controls Society of General Internal Medicine Presents HMS Professor with Glaser Award Mount Auburn Cited Among Nation's Top Hospitals for Intensive Care Braunwald to Receive Award at World Congress for Heart Research HMS Faculty Teaching Awards Honors and Advances Meeting Aims to Stir Up Solutions for Postdocs The Sacred Trust Beyond Patient and Doctor Call for Writers Front Page

RESEARCH BRIEFS Dopamine Shown to Inhibit Growth Factor, Block Angiogenesis Dopamine may impede new blood vessel growth by blocking a key angiogenic signaling molecule released by most malignant tumors. Specifically, dopamine appears to selectively inhibit blood vessel leakiness and new vessel growth that is caused by vascular permeability factor/vascular endothelial growth factor, or VPF/VEGF. The factor helps induce angiogenesis in many cancers, rheumatoid arthritis, wound healing, and chronic inflammation. The ears of nude mice treated with the neurotransmitter dopamine (right) developed fewer new blood vessels compared to untreated mice (left) after the ears of both were injected with an adenoviral vector engineered to express mouse VPF/VEGF. Dopamine blocks VPF/VEGF signaling of endothelial cells that line blood vessels. The signals normally induce enzymes that dissolve the sheathlike basement membrane surrounding blood vessels and stimulate endothelial cells to divide and form new blood vessels. Courtesy of Debabrata Mukhopadhyay This may be the first time a neurotransmitter has been identified as an antiangiogenic agent. In addition to its better known activities in the brain, dopamine also is synthesized at some sympathetic nerve endings and in other organs, such as adrenal glands, kidneys, and even the gastrointestinal tract. The study, reported in the May Nature Medicine by researchers at Beth Israel Deaconess Medical Center, was conducted in mice and in cultured human vascular endothelial cells. Yet dopamine's cancer fighting abilities are not news. More than 20 years ago at the Dana–Farber Cancer Institute, oncologist Michael Wick, now CEO of Telik, a California biotechnology company, documented the direct inhibitory effects of high doses of dopamine on melanoma cells. More recently, cancer-fighting mechanisms of dopamine were confirmed and extended by oncologist Sujit Basu working with Partha Sarathi Dasgupta at India's National Cancer Institute in Kolkata. Basu, now an HMS research fellow in pathology, observed that in many but not all tumors, low doses of dopamine blocked cell proliferation by inhibiting DNA synthesis and various enzymes, and that it boosted immunity by stimulating T cells and natural killer cells. At BID, HMS assistant professor of pathology Debabrata Mukhopadhyay invited Basu to investigate dopamine's potential as an antiangiogenic agent. The researchers used assays and a mouse ear model developed by BID pathology chief Harold Dvorak. Dopamine appears to act through the D2 dopamine receptors on endothelial cells, which in turn appear to cause VEGF receptor 2 to be taken up by the cell, presumably by endocytosis, leaving fewer receptors for the early VEGF signaling step. The researchers are working to define further details of the mechanism. —Carol Cruzan Morton Embryo Research: To Ease Suffering or Do Nothing? Is it right to use human embryos and embryonic stem cells in scientific research? In the June 1 Science, Louis Guenin, HMS lecturer on ethics in science, says that under some conditions, it is not only justifiable but admirable. The embryos that are morally permissible to use, he says, are those that were created through in vitro fertilization, remained in storage after the mother had borne all the children she wanted, and were donated to research under specified restrictions. Guenin calls these "epidosembryos," after the Greek epidosis, for a beneficence to the common good. At the crux of his reasoning is the claim that when a woman decides against intrauterine transfer of an embryo, the embryo never becomes enabled. So no possible person corresponds to an epidosembryo. He also argues that embryos less than 14 days old have no personal identity since twinning and genetic recombination can occur up to that point. "Nothing can be gained for an epidosembryo by arranging that it perish as waste rather than perish in aid of others," he says. But through research, scientists can fulfill a collective duty to aid others. According to Guenin, failing to use these surplus embryos would probably not result in the birth of even one more child. "It is virtuous to eliminate suffering in actual lives when we may do so at no cost in potential lives," he writes. A principal thesis of his paper is that two presumed opponents of epidosembryo research, Kant's morality and Catholicism, should be understood as proponents. Rigorous study shows that epidosembryo research is not contradictory to the arguments and fundamental principles of these traditions, Guenin asserts. In fact, he writes, under the Golden Rule, such research is supported. And according to these widespread moral views, Guenin says, "If a government thwarts epidosembryo research, it does a disservice to the cause of morality." —Heather Ettinger Novel Structural Protein Discovered in Heart and Muscle The structural integrity of heart and skeletal muscle cells depends on a complex network of proteins. These include dystrophin, whose gene is mutated in Duchenne muscular dystrophy, and several intermediate filament proteins. Researchers at Children's Hospital report in the May 22 Proceedings of the National Academy of Sciences that they have identified a new component of this structural network, desmuslin (DMN). The researchers discovered DMN, a novel intermediate filament protein, by studying a component of the dystrophin-associated protein complex, dystrobrevin. Although known to bind to dystrophin, dystrobrevin's function has remained "quite a mystery," said senior author Louis Kunkel, HMS professor of pediatrics at Children's. To get a better idea of its function, Kunkel and his colleagues performed a yeast two-hybrid screen. "We went searching, like a fishing expedition, with dystrobrevin," said Kunkel. And they pulled out DMN. The researchers cloned the DMN gene and found that it encodes a novel member of the intermediate filament family of proteins. They also determined that DMN is expressed primarily in heart and skeletal muscle and localizes to the same part of muscle fibers as another intermediate filament protein, desmin. The colocalization of DMN and desmin led the researchers to find that they bind to one another. This binding provides a link between the extracellular matrix, which is connected indirectly to DMN, and myofibrils, which are bound indirectly by desmin. Connections between the extracellular matrix and myofibrils are critical to muscle cell integrity. DMN's interaction with desmin, therefore, suggests that DMN plays an important role in maintaining muscle cell integrity. —Heather Ettinger On Road to Healthy Aging, Each Person Shares Controls An active and happy old age may lie not so much in our stars and genes as in ourselves, says George Vaillant, HMS professor of psychiatry at Brigham and Women's Hospital. This proposition captures the main message of the Study of Adult Development at Harvard, the longest continuous study of mental and physical health in the world. The findings are reported by Vaillant and Kenneth Mukamal, HMS instructor in medicine at Beth Israel Deaconess Medical Center, in the June 1 American Journal of Psychiatry. The researchers found that successful aging, which encompasses both subjective and objective measures of mental and physical health, depends chiefly on factors that are under some personal control. "At age 50, the six most important protective factors leading to good mental and physical health 20 to 30 years later—besides education—were not smoking, no alcohol abuse, warm marriage, adaptive coping mechanisms, normal weight, and at least some exercise," said Vaillant. The predictive power of these factors was equally great for both of the groups comprising the study's participants. One group was composed of Harvard sophomores and the other of inner city schoolboys. Each group's participants were selected in 1940 and were tracked for 60 years or until death. The inner city men experienced a level of poor health at age 65 that the Harvard men experienced at 75. Strikingly, this disparity in health between the groups may be due to education. "For despite great differences in parental social class, prestige of college, tested intelligence, current income, and job status, the health decline of the 25 inner city men who obtained a college education was no more rapid than that of the Harvard sample," said Vaillant. The findings will be featured in an upcoming book titled Aging Well. —Heather Ettinger