Unmasking Elusive Enzyme Reveals Known Villain
Cancer Risk May Be Higher for Young Smokers
Use of Hormone Replacement Therapy
Not Determined by Clinical Factors
Sowing Better Seeds
Angiogenesis Inhibitors May Slow Clogging of Arteries
Nipping Anorexia in the Bud
Vitamins May Protect Against Heart Disease
Choosier than Believed
Conference on Academic Values Set
Town Meeting on Gay and Lesbian Issues To Be Held at HMS
Appointments to Full and Endowed Professorships
In Memoriam: Robert A. Dorwart
To Speak at Soma Weiss Day Program
Honors and Advances
Students Teach Community Youngsters About Good Oral Health
Why Not Harvard Medical?
Sowing Better Seeds
A team of scientists at Massachusetts General Hospital has made
a discovery that could someday be used to improve crop quality.
To nourish young seedlings, flowering plants deposit
storage compoundsproteins, lipids, and starchin their seeds,
but they do so in different proportions. Cereal plants deposit relatively
more carbohydrates while legume seeds contain relatively more proteins
and lipids. In the April 9 Science, Yun Lin, research
fellow in genetics; Howard Goodman, professor of genetics;
and their colleagues report that they have identified a gene in
the Arabidopsis plant that, when altered, can cause a normally
oil- and protein-rich seed to switch to storing predominantly carbohydrates.
bodies (OB) and a few large protein bodies (PB) are visible
in the normal seed (left). Mutants (right) contain few
oil bodies and no protein bodies and instead are filled
with starch granules (st).
The gene, SSE1, appears to be involved
in the formation of the actual storage binsthe organellesthat
contain protein and oil inside the cells. Seeds with mutant versions
of the gene lack protein bodies and have few oil organelles. Intriguingly,
unlike normal Arabidopsis seeds, they are rich in carbohydrates.
The existence of high levels of starch in the mutants suggests protein
and oil bodies are somehow inhibiting the formation of starch in
the normal Arabidopsis seeds. "Knowing the mechansim
for how this occurs could allow us to manipulate these seed storage
deposits," says Lin.
Clogging Of Arteries
Drugs known to shrink tumors may also slow down atherosclerosis,
the thickening of the arteries that commonly leads to heart disease,
according to a new study by Children's Hospital researchers.
In the study, mice with already thickened coronary
arteries were treated with one of two substances known to inhibit
new blood vessel growth, or angiogenesis. At the end of sixteen
weeks, mice given endostatin averaged 85 percent less new thickening
compared to untreated animals of the same strain. Mice treated with
another angiogenesis inhibitor, TNP-470, averaged 70 percent less
new growth compared to controls. The study by Karen Moulton,
instructor in cardiology; Judah Folkman, the Julia Dyckman
Andrus professor of pediatric surgery; and their colleagues appears
in the April 6 issue of Circulation.
The study suggests a new understanding of
how atherosclerosisthe number one killer of adults in this
countrydevelops. The disorder occurs when plaquesdeposits
of cells, cholesterol, lipids, and debrisform in the walls
of arteries. As plaques expand, artery channels narrow. This, in
turn, causes the blood supply to the heart to dwindle. Plaques can
also rupture, throwing off clots that may block arteries and trigger
Researchers have known that capillaries can grow
through the artery wall and invade plaques. In fact, some have speculated
that these tiny blood vessels may, by causing bleeding inside plaques,
be the reason plaques rupture and cause heart attacks. The new study
suggests that the tiny vessels are vital to the establishment and
growth of the plaques as well as their disruption.
Nipping Anorexia in the Bud
Eating disordersanorexia nervosa, bulimia nervosa,
binge-eating disorder, and their variantsaffect an estimated
5 million Americans every year. Up to 50 percent of cases may go
unrecognized in the doctor's office and other clinical settings.
Patients, who are usually (though by no means only) young women,
are often reluctant to disclose symptoms to doctors and family members,
and may even conceal them out of a lack of awareness of their effect
on health, ignorance of available treatment, or shame at the prospect
of having to talk about them. The result is that though effective
treatments are available, substantial delays often occur between
the onset of symptoms and treatment.
Given the widespread prevalence and also the
risks of the diseaseyoung women with anorexia have 12 times
the mortality rate of unaffected womenphysicians need to know
how to spot, assess, and treat eating disorders. In the April 8
New England Journal of Medicine, Anne Becker, assistant
professor of medical anthropology in the Department of Social Medicine;
David Herzog, professor of psychiatry at Massachusetts General
Hospital; and their colleagues outline key symptoms and discuss
how to assess and treat a variety of eating disorders.
"The goals of treatment for all eating disorders
include stabilization of medical and nutritional status, identification
and resolution of psychosocial precipitants of the disorder, and
reestablishment of healthful patterns of eating," the authors
Vitamins May Protect Against
Giving a child a vitamin a day could later keep the heart
doctor away, according to researchers at HMS, HSPH, and other institutions.
The researchers found that children who take a multivitamin had
lower levels of homocysteinea substance associated with heart
disease in adults.
Although it is not clear whether high levels of
homocysteine actually cause cardiovascular disease, "the potential
for prevention provides a strong rationale for understanding the
determinants of homocysteine in children," write the researchers,
who include Meir J. Stampfer, associate professor of medicine
at HMS; Donna Spiegelman, associate professor of epidemiology
and biostatistics at HSPH; and Eric Rimm, associate professor
of epidemiology and nutrition at HSPH. Their study appears in the
April 7 Journal of the American Medical Association.
Research on adults had shown that low levels of
vitamins B6 and B12 and folic acidin addition to age, smoking,
and being malewere associated with high levels of homocysteine.
A study of 756 Norwegian children had identified folic acid and
family history of cardiovascular disease as important correlates
of homocysteine levels in children, but no data had been reported
on large multiethnic samples of healthy children living in the U.S.
Data on the 3,524 children, aged 13 to 14, were
collected through classroom-administered questionnaires and screening
for levels of homocysteine, vitamins B6 and B12, and folic acid.
The data were tabulated for all children by sex and ethnic subgroups.
Homocysteine was, on average, higher in boys compared with girls
and blacks compared with whites and Hispanics.
The good news is that homocysteine levels respond
rapidly to nutrient supplementation. Taking folic acid can reduce
levels as much as 40 percent.
Microbial Enzymes Choosier than Believed
Given the stiff competition between microbesmillions jockey
for position in the human gut, armpit, and mouthit makes sense
that they would have evolved chemical weapons to wipe out their
competitors. In fact, most of the antibiotics that people use were
invented by microbes. That goes for the most well-known antibiotic
of all, penicillin.
Penicillin and other antibiotics such as vancomycin
are made by a class of enzymes that join amino acids together. Researchers
have suspected that the enzymes, nonribosomal peptide synthetases,
are relatively promiscuous molecules, capable of joining together
many different kinds of amino acids.
Using a novel technique, Peter Belshaw
and Torsten Stachelhaus, both research fellows in biological
chemistry and molecular pharmacology; and Christopher Walsh,
the Hamilton Kuhn professor of biological chemistry and molecular
pharmacology, evaluated the promiscuity of a specific amino acidjoining
region on the enzyme, a condensation domain. While the domain accepted
a broad variety of amino acids at one end of the amino acid chain
(the N terminal), it appeared to be much more selective at the other
(the C terminal). Their discovery appears in the April 16 Science.
The researchers plan to test their method on
other enzyme domains to see if specificity is a general property.
"If in fact they are specific, it may be tougher to engineer
new antibiotic compounds. But we need to know this," Belshaw
says. "Ultimately, our aim is to engineer microorganisms to
produce new compounds of our own design."
In a separate piece appearing in the same issue
of Science, Walsh describes how scientists at other institutions
have successfully attacked the problem of bacterial resistance to
the powerful antibiotic vancomycin. "By modifying the sugar
groups attached to vancomycin's peptide backbone, these investigators
synthesized analogs that were not only more efficient than the parent
compound at dispatching vancomycin-resistant bacteria but were also
better at killing vancomycin-sensitive organisms," he writes.
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