This is the twice-per-month electronic newsletter for basic, preclinical and translational research news related to the Johns Hopkins School of Medicine. Please forward freely. Direct comments or questions to Joanna Downer, PhD, in the Office of Corporate Communications (410-614-5105, jdowner1@jhmi.edu).
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IN THIS ISSUE:
RESEARCH HIGHLIGHTS:
+ HLA Gene Contributes to "Disappearing" Cervical Precancers
+ Inflammation-Regulating Gene Contributes to Asthma Susceptibility in Mice
+ Cancer Gene Controls Nerve Cell Death in Huntington's Disease
+ Experts Discuss Use of Human Stem Cells in Ape and Monkey Brains
NEWS BRIEFS:
Tickets Available for Hopkins Day at Six Flags July 30
Correction: Link for G-protein-coupled receptor work
IN THE NEWS:
Jeff Bulte in the Washington Times
Akira Sawa in Chemical & Engineering News
Ruth Faden in the New York Times
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Do you have an interesting research finding about one month from publication or presentation? Send manuscripts to Joanna Downer at jdowner1@jhmi.edu or fax to 410-614-8951. Information about awards and honors received by laboratory personnel and others is welcomed also.
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RESEARCH HIGHLIGHTS:
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7/1/05
HLA Gene Contributes to "Disappearing" Cervical Precancers
New research sheds light on why cervical precancers disappear in some women and not in others. Scientists at the Johns Hopkins Kimmel Cancer Center report in the July 1 issue of Clinical Cancer Research that many lesions' persistence stems from the human papilloma virus (HPV) strain present and characteristics of the woman's individual immune system.
Gynecologic oncologist Cornelia Trimble, MD, closely monitored 100 women with high-grade, precancerous cervical lesions prior to surgery. Some of the lesions - about 28 percent -- regressed by themselves before surgery. Lesions containing the viral strain HPV16 alone are the most troublesome and difficult to resolve. In the subset of 44 patients with HPV16 only, their type of immune system made no impact on whether or not their lesion resolved.
But in 30 women with non-HPV16 lesions, those who carry an immune system gene called HLA*A201 were three times less likely to clear up their lesions than those without the gene (14.3 percent vs. 42.3 percent). According to Trimble, 40 percent of people carry the HLA*A201 gene, which codes for certain white blood cell proteins.
Trimble is studying a larger group of patients to confirm her results and rule out other potentially confounding factors such as age, smoking status, and contraceptive method that may influence how these lesions clear.
http://www.hopkinsmedicine.org/Press_releases/2005/07_01_05.html
Clinical Cancer Research 1 July 2005;11(13):4717-4723.
http://clincancerres.aacrjournals.org/cgi/content/abstract/11/13/4717
(The full text or pdf versions of this article can be accessed online through a computer terminal in the Welch Medical Library or by personal subscription to the journal. For more information on this policy, visit:
http://www.welch.jhu.edu/eresources/notice_aacr.html )
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7/4/05
Inflammation-Regulating Gene Contributes to Asthma Susceptibility in Mice
In mice, disruption of a single gene, Nrf2, plays a critical role in determining the susceptibility to asthma, Johns Hopkins researchers report.
A research team led by Shyam Biswal, PhD, at the Johns Hopkins Bloomberg School of Public Health found the absence of Nrf2 exacerbated allergen-mediated asthma in mouse models. The study's findings, published in the July 4, 2005, edition of the Journal of Experimental Medicine, may hold therapeutic potential for the treatment of human asthma.
A complex disease characterized by airway inflammation and hyperreactivity, asthma is triggered in part by cells' release of reactive oxygen species (ROS) in the airway, which causes the airway lining to swell, restricting airflow. Levels of these damaging oxygen species are normally offset by antioxidants in non-asthmatics.
Suspecting that a defect in antioxidant response might exacerbate asthma severity, Biswal's team began looking into genetic factors that might contribute to a deficiency. Now they report that mice missing Nrf2 have increased migration of inflammatory cells into the airways and an enhanced asthmatic response. The finding builds on the researchers' earlier report that Nrf2 acts as a master regulator of the majority of antioxidant pathways and enzymes that detoxify environmental pollutants.
http://www.jhsph.edu/publichealthnews/press_releases/2005/biswal_asthma.html
J Exp Med 4 July 2005;202(1):47-59.
http://www.jem.org/cgi/content/full/jem;202/1/47
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7/6/05
Cancer Gene Controls Nerve Cell Death in Huntington's Disease
Johns Hopkins scientists have discovered that a gene well known for its role in promoting cancer also helps cause nerve cell death in Huntington's disease, a fatal disease in which specific brain cells gradually die. The discovery is described in the July 7 issue of Neuron.
An important advance in the basic understanding of Huntington's disease, the scientists' discovery may lead to new approaches to combating the disease, for which there is no cure. The researchers caution that any clinical application of the cancer protein's involvement in Huntington's disease is likely a decade away or longer. Whether the gene, p53, is involved in other neurological diseases is unknown.
By examining cells from mice and people with the genetic mutation behind Huntington's disease, the researchers discovered that the faulty huntingtin protein binds to and overstimulates the p53 protein. The overactive p53 causes cells to churn out too much of a variety of other proteins, some of which help cause the cell's death by interfering with the cell's energy-producing factory, the mitochondria. Just like a factory would have to shutdown if its power plant failed, cells shut down when their mitochondria stop working.
"Our discovery is the first to explain how the genetic problem behind Huntington's disease leads to the failure of mitochondria and the cells' eventual death," says Akira Sawa, MD, PhD, an assistant professor at Johns Hopkins in the Department of Neuroscience and in the Department of Psychiatry's neurobiology program. "With more work, we should be able to find new ways to try to prevent the affected brain cells from dying."
http://www.hopkinsmedicine.org/Press_releases/2005/07_07a_05.html
Neuron 7 July 2005;47(1):29-41.
http://dx.doi.org/10.1016/j.neuron.2005.06.005
See a Preview article on p53 in the same issue:
http://dx.doi.org/10.1016/j.neuron.2005.06.023
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7/14/05
Experts Discuss Use of Human Stem Cells in Ape and Monkey Brains
An expert panel of stem cell scientists, primatologists, philosophers and lawyers has concluded that experiments implanting, or grafting, human stem cells into non-human primate brains could unintentionally shift the moral ground between humans and other primates.
Writing in the July 15 issue of Science, the panel reports its recommendations for minimizing the chances that experiments with human stem cells could change the cognitive and emotional capabilities -- and hence the "moral status" -- of the animals.
"Debate is complicated by uncertainty and uncharted territory in all of our fields of expertise. It quickly became clear how little is known," says Ruth Faden, PhD, MPH, director of the Phoebe R. Berman Bioethics Institute at The Johns Hopkins University. Faden, John Gearhart, PhD, of Johns Hopkins' Institute for Cell Engineering, and Guy McKhann, MD, of Hopkins' Zanvyl Krieger Mind/Brain Institute, were co-organizers of the panel.
Although unable to rule out the possibility of morally significant changes resulting from implantation of human stem cells into the non-human primate brain, the panel concluded that cognitive and emotional changes are least likely to occur when such work is conducted on healthy adult members of species distantly related to humans, such as macaques, rather than early in the brain development of our closest biological relatives, the chimpanzees and other great apes.
The panel also recommends that specific ethical oversight be applied to studies that propose grafting human stem cells or cells derived from human stem cells into the brains of other primates.
http://www.hopkinsmedicine.org/Press_releases/2005/07_14_05.html
Science 15 July 2005;309(5733):385-386.
http://www.sciencemag.org/cgi/content/full/309/5733/385
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NEWS BRIEFS:
Hopkins Day at Six Flags Is July 30 -- Tickets are still available for the Johns Hopkins Day at Six Flags America to be held July 30. Prices are $18.30 for an admission ticket, $7 for a parking voucher, and $7.35 for a meal voucher. To purchase tickets, School of Medicine employees may contact Betty Kern in the School of Medicine Human Resources Office at 98 North Broadway, Suite 300, between the hours of 9 a.m. and 4 p.m., Monday through Friday. For additional information, please contact 410-955-2586.
http://www.insidehopkinsmedicine.org/news/news_detail.cfm?id=3321
Correction: Link for G-protein-coupled receptor work -- The link to the full story for "Study: Nose Doesn't Smell Like the Eyes See" was incorrect in the last emailed issue of the JHM Science e-Newsletter. The correct link is:
http://www.hopkinsmedicine.org/Press_releases/2005/07_12_05.html
IN THE NEWS:
Jeff Bulte on nanotechnology and imaging in the Washington Times. "Nano-World: Nano for stem-cell research," by Charles Q. Choi, United Press International, June 14, 2005.
http://www.washtimes.com/upi-breaking/20050610-125435-4252r.htm
http://www.jhu.edu/clips/2005_06/14/nano.html
(Must be at a Hopkins computer to access this page.)
Akira Sawa on p53 and Huntington's disease in Chemical & Engineering News. "Dangerous Liaisons," by Sophie Rovner, Chemical & Engineering News, July 18, 2005.
http://pubs.acs.org/cen/news/83/i29/8329notw4.html
http://www.jhu.edu/clips/2005_07/18/danger.html
(Must be at a Hopkins computer to access this page.)
Ruth Faden on primates and stem cells in the New York Times. "Ethicists Offer Advice for Testing Human Brain Cells in Primates," by Nicholas Wade, the New York Times, July 15, 2005.
http://www.nytimes.com/2005/07/15/science/15stem.html?
http://www.jhu.edu/clips/2005_07/15/ethic.html
(Must be at a Hopkins computer to access this page.)
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John Sales contributed to the Research Highlights for this issue.
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--JHMI--
