Biotech Business Week
JOHNS HOPKINS UNIVERSITY, U.S.;
Scientists from Johns Hopkins University,
U.S., publish new research findings
SECTION: EXPANDED REPORTING; Pg. 2138
Scientists from Johns Hopkins University,
U.S., publish new research findings.
This trend article about Johns Hopkins
University, U.S., is an immediate alert from NewsRx to identify developing
directions of research.
Study 1: Researchers detail in "Toti
"potent" repressors," new data in teratoma. According to recent
research from the United States, "A fascinating property of germ cells is
their ability to maintain totipotency throughout development. At fertilization,
this totipotency is unleashed and the egg generates all the cell types needed
to make a brand new organism."
"Occasionally, germ cells differentiate
precociously in the embryo or in the gonads and form teratomas, tumors
containing many differentiated somatic cell types. Until recently, the genetic
basis for teratoma formation was not known," wrote C.M. Gallo and
colleagues, Johns Hopkins University, Howard Hughes Medical Institute.
The researchers concluded: "The
unexpected discovery of a teratoma in a C. elegans double mutant points to translational
control as a key mechanism to maintain totipotency in developing germ
Gallo and colleagues published their study in
BioEssays (Toti "potent" repressors. BioEssays,
For additional information, contact C.M.
Gallo, Howard Hughes Medical Institute, Dept. of Molecular Biology and Genetics,
Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
Study 2: A long-term follow-up study shows
that the heart failure characteristics of patients rather than arrhythmia
characteristics better predicted implantable cardioverter-defibrillator shock
probability and survival.
Researchers working in the United States
report, "Implantable cardioverter-defibrillators (ICDs) are increasingly
used for primary and secondary prevention of sudden cardiac death.
Defibrillators were introduced into clinical practice in 1980. Since that time,
factors affecting long-term survival and the natural history of defibrillator
patients have not been described. The purpose of this study was to identify
clinical predictors of long-term survival in patients receiving ICDs."
"The prognostic value of several
clinical variables on the likelihood of survival or appropriate ICD therapy in
1,382 consecutive patients receiving ICDs from 1980 to 2003 were
evaluated," explained Johns Hopkins University investigators H. Tandri and
colleagues. "Data were collected at the time of device implantation, and
follow-up was completed through March 2005."
"In 70±51 months of follow-up (range
0-282 months), 792 patients died and 421 patients received appropriate ICD
therapy at least once," they reported. "Age, left ventricular
ejection fraction, New York Heart Association (NYHA) functional class, Charlson
comorbidity index, and anti-arrhythmic drug use correlated with mortality.
Beta-blocker and angiotensin-converting enzyme inhibitor use was associated
with improved survival. Only NYHA functional class correlated with ICD
"Patients free of shocks for the first 5
years after ICD implantation had continued risk of arrhythmia recurrence,"
the co-investigators noted. "The heart failure characteristics of patients
predicted ICD shock probability and survival better than the arrhythmia
characteristics or the underlying heart disease. Anti-arrhythmic drug use was
associated with increased mortality. Beta-blocker and angiotensin-converting
enzyme inhibitor use was associated with improved survival."
"A measurable arrhythmic risk even after
prolonged shock-free intervals indicates the need for continued ICD therapy in
all patients with appropriate ICD indications," concluded the authors.
Tandri and colleagues published their study
in Heart Rhythm (Clinical course and long-term follow-up of patients
receiving implantable cardioverter-defibrillators. Heart Rhythm,
For more information, contact J.K. Donahue,
Case Western Reserve University, 2500 Metrohealth Dr., Hamann 322, Cleveland,
OH 44109, USA.
Study 3: At least three severe, potentially
fatal genetic diseases leave patients with aortas so flimsy that they can
rupture in pregnancy and labor or even lesser activities, often without
warning. Beta blockers, curbing exercise, proactive blood vessel surgery and
other approaches can be helpful, but their usefulness varies according to which
disease and when they're offered.
Now a large follow-up study of more than 50
families by a multi-institutional team led by Johns Hopkins scientists should
bring better guidelines for treating the disorders. The work, published in The
New England Journal of Medicine, closely compares patients having one of
two types of the lesser known Loeys-Dietz syndrome or Ehlers-Danlos syndrome with better-understood
Marfan syndrome. It stresses the importance of comprehensive clinical
evaluations when diagnosing the diseases.
People with Loeys-Dietz syndrome have wideset
eyes, a cleft palate or split uvula (the tissue that hangs down in the back of
the throat), and a convoluted arrangement of the body's blood vessels, in addition
to aggressive swelling of the aorta. In these patients, the aorta breaks at a
much smaller size than it does in people with Marfan syndrome or most other
causes of aortic aneurysm.
Marfan and Ehlers-Danlos
syndromes both are similar heritable conditions with overlapping
symptoms that affect the connective tissue, the tissue that holds the body
together. Marfan syndrome can affect many body systems, including the skeleton,
eyes, heart and blood vessels, nervous system, skin and lungs. The vascular variant
of Ehlers-Danlos also affects skin, muscles and ligaments and causes
hypermobility of joints and fragile blood vessels that tear easily.
"This study shows that both clinical and
molecular analyses can distinguish patients with Loeys-Dietz syndrome from
those with either Marfan syndrome or vascular Ehlers-Danlos
syndrome," said Harry Dietz, MD, director of the William S.
Smilow Center for Marfan Syndrome Research at Johns Hopkins, professor in the
McKusick-Nathans Institute of Genetic Medicine, and a Howard Hughes Medical
Institute investigator, "Distinguishing these conditions is essential in
many ways. For example, when compared to Marfan syndrome, Loeys-Dietz patients
are at high risk of rupturing their blood vessels at smaller dimensions, at a
younger age, and in a wider distribution throughout the body. They are also at
a much greater risk of tear or rupture of blood vessels or the uterus during
pregnancy. When compared to people with vascular Ehlers-Danlos
syndrome, patients with Loeys-Dietz syndrome do much better with
cardiovascular surgery, highlighting the importance of aggressive surgical
intervention for this disorder."
"Because Loeys-Dietz shares so many
symptoms with other conditions like Marfan or vascular Ehlers-Danlos, it's
critical that diagnostic distinctions are made accurately."
The researchers gathered detailed information
on patients' physical characteristics, their symptoms, course of disease and
timing and effect of treatments. They also used gene analysis of the DNA
sequences that encode for two proteins, the transforming growth factor-beta
protein receptors type 1 (TGF-betaR1) and type 2 (TGF-betaR2). All cases of
Loeys-Dietz studied so far have mutations in either TGF-betaR1 or TGF-betaR2.
The two TGF-beta receptors act together to
bind TGF-beta, a family of signaling molecules that controls cell growth,
movement, activity and death by controlling whether certain genes are turned on
or off. TGF-beta receptors normally are found on the cell's surface, facing the
outside of the cell, where TGF-beta can be found floating around.
The receptors contain specialized domains -
dubbed kinase domains - that, when bound by TGF-beta, add a chemical phosphate
group to molecules that set in motion a domino-like effect within the cell to
activate other chemical reactions that eventually lead to changes in cellular
growth or movement or activity.
Nearly all Loeys-Dietz patients studied thus
far have mutations in or near the kinase domains in their TGF-beta receptors.
The mutations are passed on through families; however, syndrome-causing
mutations also have been found in patients whose parents were not affected.
A diagnostic test is available at Johns
Hopkins' DNA Diagnostic Laboratory.
This article was prepared by Biotech Business
Week editors from staff and other reports.
Copyright 2007, Biotech Business Week via NewsRx.com.
LOAD-DATE: April 6, 2007
Copyright 2007 Biotech Business Week via
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