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 (4-5105, jdowner1@jhmi.edu).
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IN THIS ISSUE:
+ Hepatitis C "Self-Recovery" Tied To Genotype of Immune Cell Inhibitors
+ Blood Proteins May Identify Ovarian Cancer
+ Last of Known Genes Identified In Complex Obesity Syndrome
+ Modern Heart Devices Appear To Be Safe for MRI
NEWS BRIEFS:
Microarray Seminar Sept. 8
Annual Scott Lecture Sept. 9
Rodent Health Surveillance Seminar Sept. 15
Basic Science Town Meeting Sept. 20
HONORS AND AWARDS:
Haenggeli Awarded ALS Association Fellowship
BME Graduate Students Advance in UK Competition
Nine Hopkins Researchers Receive NARSAD Awards
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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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8/6/04
Hepatitis C "Self-Recovery" Tied To Genotype of Immune Cell Inhibitors
Writing in the Aug. 6 issue of Science, researchers from Johns Hopkins and elsewhere report that genes normally involved in suppressing the body's natural killer immune cells might factor into spontaneous recovery from hepatitis C in people infected by a small amount of virus.
Roughly 20 percent of people infected with hepatitis C generally recover without treatment. To find genetic characteristics more common in people who self-recover than in those who do not, the researchers analyzed key genes of more than 1,000 people infected with hepatitis C.
The genes associated with self-recovery were a specific combination of genes for a receptor family called KIR -- some of which normally activate natural killer cells and some of which inhibit them -- and their ligands, the various human leukocyte antigens (HLA), the researchers report. Different HLA proteins bind to different versions of the KIR receptor with different affinities, which affect the strength of the activating or inhibiting signal.
The researchers discovered that people whose KIR and HLA combination doesn't inhibit natural killer cells as well as other combinations were more likely to self-recover from infection if they'd been exposed to a presumably small amount of hepatitis C virus. Specifically, those who had inherited gene versions called KIR2DL3 and HLA-C1 from both parents were the most protected.
"This study highlights the importance of natural killer cells in self-recovery from a hepatitis C virus infection," says Chloe Thio, MD, assistant professor of medicine at Johns Hopkins. "It remains to be explained how these genes and viral dose at the time of infection interact in determining self-recovery from hepatitis C."
Of the 543 participants who were infected via injection drug use or needle stick, as opposed to blood transfusion, 187 self-recovered. Of this group of 187, 20 percent had only genes for KIR2DL3 and HLA-C1. Just 10 percent of the presumed "low dose" study participants who did not self-recover were homozygous for these gene versions.
http://www.hopkinsmedicine.org/Press_releases/2004/08_05_04.html
Science 6 Aug 2004;304(5685):872-874
http://www.sciencemag.org/cgi/content/full/305/5685/872
See a Perspectives on this topic in the same issue:
http://www.sciencemag.org/cgi/content/full/305/5685/786
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8/15/04
Blood Proteins May Identify Ovarian Cancer
Johns Hopkins Kimmel Cancer Center researchers have designed a blood test to detect ovarian cancer using three proteins found in common in the blood of women with the disease. Their preliminary studies with the new test suggest a molecular signature exclusive to this cancer, known for its ability to remain undetected and spread quickly.
Writing in the Aug. 15 issue of Cancer Research, the researchers show that high levels of a truncated form of transthyretin, and low levels of both a fragment of ITIH4 and apolipoprotein A1 can distinguish most ovarian cancers from benign disease and normal tissue in the patient samples they studied. These three proteins were teased out by rigorous evaluation of protein patterns in blood samples from ovarian cancer patients at several U.S. and international hospitals, says Daniel Chan, PhD, professor and director of the Biomarker Discovery Center at Johns Hopkins.
"Typically, only half of early-stage ovarian cancer patients have elevated blood levels of a standard marker called CA125," adds Zhen Zhang, PhD, associate professor and associate director of the Hopkins center. "But combining CA125 with our new markers may improve early detection capabilities."
This research was funded by the National Cancer Institute and Ciphergen Biosystems, which has licensed the test. The test will not be commercially available until completion of further validation studies in larger groups of patients.
http://www.hopkinsmedicine.org/Press_releases/2004/08_15_04.html
Cancer Research 15 Aug 2004;64(16):5882-5890
http://cancerres.aacrjournals.org/
[This journal is accessible online from Welch Library terminals only or via individual subscriptions. For more information on this limitation, visit http://www.welch.jhu.edu/eresources/notice_aacr.html]
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8/15/04
Last of Known Genes Identified In Complex Obesity Syndrome
By using comparative genomics and adding some good old-fashioned genetic analysis, an international team of scientists has uncovered the identity of the last of eight genes known to contribute to Bardet-Biedl syndrome, a rare disorder characterized by a combination of problems including obesity, learning difficulties, diabetes and asthma.
Family studies had managed to link BBS3 to a region of chromosome 3, but getting to the gene had proven challenging. Now, by taking advantage of the role faulty cilia likely play in BBS and of a genomic comparison that identified cilia-related genes, the researchers uncovered the BBS3 gene's real identity.
BBS3 is actually a gene formerly known as ARL6, the international team reports in the Aug. 15 advance online section of Nature Genetics. Importantly, ARL6 is the first BBS culprit to belong to a family of genes and proteins with a known function, opening the door to figuring out what's really happening in people with the condition.
"We can use BBS3/ARL6 and its known function -- binding the molecule GTP -- as a great place to start to unravel the details of the other BBS proteins," says Nicholas Katsanis, PhD, assistant professor in Johns Hopkins' McKusick-Nathans Institute of Genetic Medicine.
The identification of the BBS3 gene ends the search for primary BBS-causing genes in families studied for years by a team of scientists from the United States, Canada and the United Kingdom. However, the scientists are still hunting for other, less obvious genetic influences in these families.
http://www.hopkinsmedicine.org/Press_releases/2004/08_16_04.html
Nat Gen (advance online publication 15 Aug 2004)
http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/vaop/ncurrent/full/ng1414.html
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From the Clinic, almost
8/2/04
Modern Heart Devices Appear To Be Safe for MRI
In animal and laboratory studies, scientists at Johns Hopkins have shown that modern implanted cardiac devices -- such as pacemakers and defibrillators -- can be safe for use in magnetic resonance imaging (MRI) machines, diagnostic and imaging tools long ruled off-limits for more than 2 million Americans with these implanted devices.
"It [was] feared that the electromagnetic fields of the MRI may heat up metal components, or pull on and dislodge the device," says Henry Halperin, MD, professor of medicine, radiology and biomedical engineering at Hopkins. "[But we've shown that] you can do a high-energy scan for a long period of time without doing any long-term damage to select devices."
The Hopkins team tested a range of devices from the hundreds of brands and models in use. Each type of device was tested under a variety of conditions using a 1.5T MRI scanner by General Electric, the most widely available scanner in North America.
Results, published in the Aug. 3 issue of Circulation, showed that most modern devices are safe and perform well in both standard MRI scans and scans performed using electromagnetic fields at maximum strength.
http://www.hopkinsmedicine.org/Press_releases/2004/07_28_04.html
Circulation 3 Aug 2004;110(5):475-482
http://circ.ahajournals.org/cgi/content/full/110/5/475
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Microarray Seminar Sept. 8 -- Rafael Irizarry, PhD, associate professor of biostatistics at the Bloomberg School of Public Health, will present the first of this academic year's "Top 10 Things to Know in Microarray Data Analysis" lecture series. His one-hour lecture, "Graphing Microarray Data and the Use of Log Transformation," will begin at 2:30 pm, Wed., Sept. 8, in room E9519 in BSPH. The event is sponsored by the JHMI Microarray Core Facility, The Hopkins Expressionists (BSPH), and the Department of Biostatistics (BSPH). For more information, contact seminar@microarray.jhmi.edu .
http://www.microarray.jhmi.edu/seminar
Annual Scott Lecture Sept. 9 -- Charles Sawyers, MD, director of the Genitourinary Oncology Program Area at the University of California Los Angeles, will deliver the 4th annual William Wallace Scott lecture starting at 8 am, Thursday, Sept. 9, in the Weinberg Auditorium. His talk is entitled "Molecular Studies of Prostate Cancer Progression."
Rodent Health Surveillance Seminar Sept. 15 -- William Shek, DVM, PhD, of Charles River Laboratories will present "Rodent Health Seminar: Health Surveillance," starting at 1 pm, Wednesday, Sept. 15, in Tilghman Auditorium. This hour-long seminar is presented by the Johns Hopkins University Office of Research Animal Resources and the Animal Care and Use Committee. For more information, contact Kinta Diven at kdiven1@jhmi.edu or 443-287-3743. For topics in the ACUC's regular training and education seminar series, visit:
http://www.jhu.edu/animalcare/training4.html
Basic Science Town Meeting Sept. 20 -- The next Basic Science Town Meeting with Edward Miller, MD, dean of the medical faculty, and Chi Dang, MD, PhD, vice dean for research, will be held 3 pm to 4 pm, Monday, Sept. 20, in PCTB 517.
Haenggeli Awarded ALS Association Fellowship -- Christine Haenggeli, MD, a neurology research fellow working with Jeffrey Rothstein, MD, PhD, has been awarded the Milton Safenowitz Post-Doctoral Fellowship for ALS Research by the ALS Association (ALSA). The fellowship is made possible by a $1 million grant from Marilyn Safenowitz and the Milton and Marilyn Safenowitz Family Foundation through ALSA's Greater New York Chapter. Milton Safenowitz died of amyotrophic lateral sclerosis, or ALS, in 1998.
BME Graduate Students Advance in UK Competition -- A team of four biomedical engineering graduate students has successfully completed the first round of competition in the Biotechnology Young Entrepreneurs Scheme, a British government-sponsored academic business plan competition. Team captain David Noren and team members Blanka Sharma, Raymond Cheong (an MD/PhD candidate) and Saurabh Paliwal, under the moniker Innovative Clinical Unlimited, outlined a plan for the use of an automated device to image the retina, which would allow primary care physicians to diagnose potentially blinding diseases before patients lose their sight. The Hopkins team and three other North American teams will now travel to either Oxford, England, or Edinburgh, Scotland, for round two. This is the first year that teams from the U.S. and Canada have been eligible for the eight-year-old competition.
http://www.biotechnologyyes.co.uk/overview.html
Nine Hopkins Researchers Receive NARSAD Awards -- Nine Johns Hopkins researchers have recently received awards the National Alliance for Research on Schizophrenia and Depression to study causes and treatments for mental illness. Christopher Ross, MD, PhD, professor of psychiatry, has received a Distinguished Investigator Award to develop models for schizophrenia and other psychiatric disorders focusing on the DISC-1 gene. Young Investigator Awards went t Susan E. Holmes, PhD; Francis M. Mondimore, MD; Jennifer L. Payne, MD; Akira Sawa, MD, PhD; Shanthini Sockanathan, PhD; Virginia L. Willour, PhD; Sarah H. Ying, MD; and Peter P. Zandi, PhD, MPH, MHS.
http://www.narsad.org/research/
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--JHMI--
