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:
RESEARCH HIGHLIGHTS:
+ New Compounds Show Promise in Fighting Malaria and Cancer
+ Ciliary Defects in Rare Obesity Syndrome Compromise Sense of Smell
+ Nitroxyl-Releasing Drugs Promise To Revive Failing Hearts
NEWS BRIEFS:
Rodent Health Surveillance Seminar Sept. 15
Basic Science Town Meeting Sept. 20
Lab Animal Feed To Change
Animal Care and Use Seminars
HONORS AND AWARDS:
Cheng Receives Prestigious PECASE Award
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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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8/22/04
Nitroxyl-Releasing Drugs Promise To Revive Failing Hearts
For 25 years, nitroglycerin and other drugs that release nitric oxide (NO) into the bloodstream have been the usual approach to treating heart failure, which is marked by the heart's declining ability to pump blood effectively. Although these agents help the heart relax, they also negatively affect its capacity for pumping.
Hoping to improve that balance, Johns Hopkins researchers have developed a new class of NO-based compounds, called diazeniumdiolates, that are sources of nitroxyl (HNO). In early studies, these compounds seem to play a role in protecting the cardiovascular system from further damage during heart failure and in restoring function to organs affected by it.
"Our goal is not only to develop new classes of nitroxyl precursors, but also to figure out the mechanisms by which they seem to affect heart function," says John P. Toscano, PhD, professor of chemistry in the Krieger School of Arts and Sciences.
In studies with normal dogs and those with heart failure, Toscano's research partner, Nazareno Paolocci, MD, PhD, assistant professor of cardiology, found that a compound called Angeli's salt, which generates HNO, doubled the dogs' hearts' ability to pump and enhanced their ability to relax between contractions.
Paolocci and his team also have tested, on dogs, two of the new class of derivatives -- one a pure HNO donor, which behaves similarly to Angeli's salt, and one a pure NO donor, which behaves analogously to standard NO donors. The scientists announced their results in late August at the American Chemical Society's annual summer meeting.
http://www.jhu.edu/news_info/news/home04/aug04/cardio.html
Abstract, American Chemical Society annual meeting
http://oasys2.confex.com/acs/228nm/techprogram/P757525.HTM
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8/23/04
Ciliary Defects in Rare Obesity Syndrome Compromise Sense of Smell
By studying people and mice, Johns Hopkins researchers have discovered that the genetic defects that cause the rare condition Bardet-Biedl syndrome (BBS) also compromise the sense of smell.
The findings, described in the September issue of Nature Genetics, offer the first direct evidence that BBS-causing mutations cause ciliary defects that actually lead to problems seen in the condition, says Nicholas Katsanis, PhD, an assistant professor in the McKusick-Nathans Institute of Genetic Medicine.
The advance builds on last year's proposal by Katsanis and others that faulty cilia may be behind the symptoms seen in BBS, which include obesity, learning difficulties, eye problems and asthma. The olfactory system, which is responsible for the sense of smell, is perhaps the most cilia-rich system in the body, relying on a bed of the tentacle-like structures to detect odiferous molecules as they pass through the nose.
After simple smell tests revealed that fully half of BBS patients have difficulty detecting odors, the Johns Hopkins researchers turned to mice missing either of two BBS-causing genes (BBS1 or BBS4) to prove that faulty cilia, rather than any other problems, were to blame.
Randall Reed's research assistant Heather Kulaga and Katsanis's research assistant Carmen Leitch found that overall organization of the olfactory system seemed normal in these mice. However, instead of the normal patch of lengthy cilia, they had only short, stumpy cilia wannabes that couldn't detect odor-causing molecules, says Reed, a professor of molecular biology and genetics in Hopkins' Institute for Basic Biomedical Sciences and a Howard Hughes Medical institute investigator.
http://www.hopkinsmedicine.org/Press_releases/2004/08_23_04.html
Nat Genetics Sept 2004;36(9):994-998
http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v36/n9/full/ng1418.html
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8/24/04
New Compounds Show Promise in Fighting Malaria and Cancer
Using an ancient Chinese folk remedy as a model, Johns Hopkins researchers have designed several new compounds that, in early testing, promise to be both safer and more effective in fighting malaria and some forms of cancer than the current "gold standard" drug treatments.
Scientists announced their successful results in late August at the American Chemical Society's annual summer meeting, held this year in Philadelphia. Some of the results also appeared in the January 2004 issue of the Journal of Medicinal Chemistry.
"Preliminary data show that our laboratory-synthesized compounds have a therapeutic index -- the measure of a drug's safety and efficacy -- that is better, in some cases many times better, in rodents than the drugs currently considered the gold standard for chemotherapy of both malaria and prostate cancer," said Gary Posner, PhD, Scowe Professor of Chemistry in the Krieger School of Arts and Sciences at Johns Hopkins.
To tackle the challenge presented by drug resistant malaria, Posner's research team, which also includes Theresa Shapiro, MD, PhD, professor of clinical pharmacology at the Johns Hopkins School of Medicine, designed a series of compounds called trioxanes. These compounds are aimed at mimicking the mechanism of action of artemisinin, the active agent in the Artemisia annua plant, which has been used in China as an herbal remedy for malaria and other fevers for thousands of years.
http://www.jhu.edu/news_info/news/home04/aug04/posner.html
J Med Chem 31 Jan 2004;47(5);1299-1301
http://pubs.acs.org/cgi-bin/article.cgi/jmcmar/2004/47/i05/html/jm0303711.html
Abstract, American Chemical Society annual meeting:
http://oasys2.confex.com/acs/228nm/techprogram/P743798.HTM
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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.
Lab Animal Feed To Change -- Research Animal Resources has recently reviewed characteristics and costs of the feed currently given to research animals and compared them to those of other commercial options. Based on both quality and cost measures, RAR has decided to switch from Purina feed to Harlan Teklad. RAR expects a smooth transition in implementing this change in feed institution?wide by the end of September. Researchers conducting experiments that might be affected by a switch in diet should contact RAR to have their current feed continued. For more information, contact Lindsay Barnes, Director of Laboratory Animal Management, RAR, at lbarne15@jhmi.edu or 410?955?3273. Or read the official "Memo to Faculty" by going to https://quickplace.jhmi.edu/animalresources and clicking on "Changes in Animal Feed" memo.
Animal Care and Use Seminars -- Tim Allen from the National Agriculture Library, Animal Welfare Information Center, USDA, will present "Meeting the Information Requirements of the Animal Welfare Act" Thursday, Sept. 23, at noon in Ross 403. during this lecture he will discuss how to identify alternatives to painful procedures and what resources are available. On Thursday, Oct. 28 at noon in Ross 403, the Animal Care and Use Committee will present "Semiannual inspections: What Do They Mean for You?" Also, on Oct. 14 starting at 9 am, a "Rodent Surgery Class" will be held; this class is limited to 10 people and registration is required (email acuc@jhmi.edu or call 443?287?3744 or 443?287?3738).
http://www.jhu.edu/animalcare/training4.html
Cheng Receives Prestigious PECASE Award -- Linzhao Cheng, PhD, an assistant professor of obstetrics and gynecology in the Institute for Cell Engineering's Stem Cell Biology Program, has received a Presidential Early Career Award for Scientists and Engineers. He was one of 12 winners nominated by the National Institutes of Health and one of 57 winners overall. The awards were officially presented during a ceremony at the Eisenhower Executive Office Building in Washington, DC, Sept. 9. According to the citation from the NIH, Cheng was nominated and chosen "for outstanding accomplishments in the field of stem cell research including pioneering research that is advancing our knowledge of human embryonic stem cell self?renewal and differentiation of blood cells."
http://www.whitehouse.gov/news/releases/2004/09/20040909?9.html
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--JHMI--
