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Selected Research Advances of NIH
NIH has trained a host of scientists in its intramural programs
and supported the training of hundreds of thousands of scientists
at universities and medical schools around the country through research
grants. These scientists have gone on to become leaders in biomedical
research at universities and companies around the country, fueling
a great many advances in the understanding and treatment of human
diseases. What follows is only a sampling of the scientific advances
supported by NIH thus far this year. |
Year 2004
Disease Prevention, Diagnosis, and Treatment
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Gene Mutation Linked to Drug Effectiveness
in Lung Cancer Mutation of a gene involved in non-small
cell lung cancer determines whether the drug gefitinib (Iressa™)
will cause the tumors to shrink. Gefitinib is one of a new generation
of cancer chemotherapy drugs designed to target specific molecular
defects that cause cancer. Previously, gefitinib had been shown to
cause tumor regression in certain patients but not others, and researchers
hadn’t been able to predict which ones would respond. The mutation,
discovered by a team that included NIH researchers, is in a gene that
codes for the epidermal growth factor (EGF) receptor – the enzyme
through which EGF sparks cell growth. Inhibition of this type of enzyme
has recently been a focus for cancer researchers, but gefitinib had
not been as effective as some had expected based on earlier clinical
trials conducted in Japan. With this new discovery, doctors will be
able to select those lung cancer patients who could benefit from gefitinib. |
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Effectiveness of Safer Smallpox Vaccine Demonstrated
Against Monkeypox A mild, experimental smallpox vaccine
known as modified vaccinia Ankara (MVA) is nearly as effective as
the standard smallpox vaccine in protecting monkeys against monkeypox,
a study by NIH researchers found. Monkeypox is used to test the effectiveness
of a smallpox vaccine because of its similarity to the smallpox virus.
These findings are important in the search for a replacement vaccine
for people with health conditions that would prevent them from using
the current smallpox vaccine. |
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Estrogen and Heart Disease NIH instructed
participants in the estrogen-alone study of the Women’s Health
Initiative (WHI), a large multi-center trial, to stop taking their
study pills and to begin the follow-up phase of the study. After careful
consideration of the data, NIH concluded that with an average of nearly
7 years of follow-up completed, estrogen alone does not appear to
affect (either increase or decrease) heart disease, a key question
of the study. At the same time, estrogen alone appears to increase
the risk of stroke and decrease the risk of hip fracture. It has not
increased the risk of breast cancer during the time period of the
study. The increased risk of stroke in the estrogen-alone study is
similar to what was found in the WHI study of estrogen plus progestin
when that trial was stopped in July 2002. The NIH believes that an
increased risk of stroke is not acceptable in healthy women in a research
study. |
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Rotavirus Vaccine Created by NIH Scientists
Licensed for Commercialization An effective oral rotavirus
vaccine created by NIH scientists in the 1980s and developed further
through a cooperative research and development agreement with an industry
partner has now been licensed by the NIH Office of Technology Transfer
to BIOVIRx, Inc. This vaccine can help prevent the hundreds of thousands
of deaths annually from rotavirus diarrhea in children living in developing
countries. |
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Substances Found in Blood May Predict Development
of Preeclampsia Abnormal levels of two molecules found
in the blood appear to predict the development of preeclampsia, a
life-threatening complication of pregnancy, according to a study by
a team that included NIH researchers. Pregnant women with preeclampsia
can develop dangerously high blood pressure and begin excreting protein
in the urine. In some cases, the condition may progress to eclampsia,
a series of potentially fatal seizures. Being able to predict the
development of preeclampsia may enable doctors to treat the condition
before it becomes a serious problem. |
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"Care Managers" Help Depressed Elderly
Reduce Suicidal Thoughts An intervention that includes
staffing doctors’ offices with depression care managers helps
depressed elderly patients reduce suicidal thoughts, a study funded
by NIH found. Older Americans comprise 13 percent of the population
but account for 18 percent of all suicides. The major risk factor
for suicide in late life is major depression. Since most older Americans
who kill themselves have seen their doctor within the previous month,
treating depression in primary care can be an effective way to save
lives. |
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Methamphetamine Withdrawal and Brain Changes
NIH researchers were part of a team that used PET (positron emission
tomography) scans to find that people who have recently stopped abusing
the powerfully addictive drug methamphetamine may have brain abnormalities
similar to those seen in people with mood disorders. The findings
suggest that health workers might improve success rates for methamphetamine
users receiving addiction treatment by also providing therapy for
depression and anxiety. |
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Emotion-Regulating Protein Lacking in Panic
Disorder Three brain areas of panic disorder patients are
lacking in a key component of a chemical messenger system that regulates
emotion, researchers at NIH discovered. The scientists used PET (positron
emission tomography) scans to visualize a type of serotonin receptor
called the serotonin 5-HT1A receptor, and compared the brains of people
who suffered from panic disorder to those who did not. A new radioactive
tracer developed by NIH Clinical Center PET scan scientists binds
to the receptors, revealing their locations and a numerical count
by brain region. In the panic disorder patients, the receptor is reduced
by nearly a third in three structures straddling the center of the
brain. This finding is the first in living humans to show that 5-HT1A,
which is pivotal to the action of widely prescribed anti-anxiety medications,
may be abnormal in panic disorder patients. |
Genomics and Genetics
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Scientists Compare Rat Genome With Human, Mouse
An international research team supported by NIH completed a
high-quality draft sequence of the genome of the laboratory rat, and
used that data to explore how the rat's genetic blueprint stacks up
against those of mice and humans. The rat sequence draft represents
the third mammalian genome to be sequenced to high quality and described
in a major scientific publication. Comparing the human genome with
those of other organisms is helping researchers to better understand
the complex genomic components involved in human health and disease. |
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Gene Variants May Increase Susceptibility to
Type 2 Diabetes International research teams that included
several NIH researchers found variants in a gene called hepatocyte
nuclear factor 4 alpha (HNF4A) that may predispose people to type
2 diabetes, the most common form of the disease. For years, scientists
have known that single-gene mutations contribute to rare forms of
diabetes that account for about 2 to 3 percent of all diabetes cases,
but type 2 diabetes, which accounts for 90 to 95 percent of all diabetes
cases in the U.S., is caused by more than a problem with one gene.
Type 2 diabetes usually begins after age 40 in overweight, inactive
people and is more common in those with a family history of diabetes.
In the United States, type 2 diabetes disproportionately affects African
Americans, Hispanic/Latino Americans, and American Indians. Finding
a gene that may increase susceptibility to type 2 diabetes is a major
breakthrough, but translating this discovery into a treatment that
benefits people with diabetes or those at risk is still years away.
Scientists need to learn much more about this gene. |
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Genome Sequence Reveals Leaner, Meaner Intestinal Parasite
Researchers supported by NIH completed the genome sequence of Cryptosporidium
parvum, an insidious, one-celled, waterborne parasite that lodges
in the intestines of infected people and animals, and for which there
is currently no effective treatment. Cryptosporidium is an
extremely hardy parasite found in water supplies throughout the world,
including the United States. For people with weakened immune systems
such as those with HIV/AIDS, the parasite can lead to serious or life-threatening
illness. Cryptosporidium has been difficult to study up until
now because it has been virtually impossible to grow in the laboratory.
With a better understanding of this parasite’s biology, researchers
will be better positioned to find treatments that zero in on unique
biological processes essential for the organism's survival. |
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Chicken Genome Assembled The first
draft of the chicken genome sequence has been deposited into free
public databases for use by biomedical and agricultural researchers
around the globe. Researchers supported by NIH successfully assembled
the genome of the Red Jungle Fowl, Gallus gallus, which is
the ancestor of domestic chickens. Comprised of about 1 billion DNA
base pairs, the chicken genome is the first avian genome to be sequenced.
Recent outbreaks of avian flu have highlighted the importance of learning
more about the chicken genome and how genetic variation may play a
role in the susceptibility of different strains to the disease. |
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Gene Involved in Juvenile Rheumatoid Arthritis
A genetic variation within the interleukin-6 (IL-6) gene
increases susceptibility to systemic juvenile rheumatoid arthritis
(JRA), according to researchers funded by NIH and the Arthritis Research
Campaign. Juvenile rheumatoid arthritis, which has three main forms,
affects each child differently. Some experience swollen, painful or
stiff joints. Other common symptoms include skin rashes, weak muscles,
fevers and swollen glands. Systemic juvenile rheumatoid arthritis,
the most severe type, can also affect internal organs such as the
heart, liver, spleen and lymph nodes. Twenty percent of children with
JRA have the systemic form. Scientists suspect that JRA is caused
by a combination of environmental and genetic factors. |
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Genes That Determine How Pollution Affects
Allergies Researchers funded by NIH identified a set of
genes that influences how pollution affects allergies. People with
certain versions of the genes were more likely to have an allergic
reaction to ragweed when it was mixed with diesel exhaust particles.
These genes code for antioxidant proteins in the lungs that the scientists
believe detoxify chemicals found in diesel exhaust particles. This
discovery may help scientists identify people whose asthma and hay
fever are more affected by pollution. It might also help accelerate
the development of drugs to treat and prevent these disorders. |
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Honey Bee Genome Assembled The first draft version
of the honey bee genome sequence has been deposited into free public
databases. The sequence of the honey bee, Apis mellifera, was
funded largely by NIH, along with the U.S. Department of Agriculture.
The honey bee is valued by farmers for its ability to produce honey
and pollinate crops. Biologists also are interested in the honey bee's
social instincts and behavioral traits. |
New Research Directions
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Brain Signal Predicts Working Memory Prowess
A person’s capacity for visual working memory can be
predicted by his or her brainwaves, researchers funded by NIH discovered.
Some people are better than others at remembering what they have just
seen — holding mental pictures in mind from moment to moment.
The researchers found that a key brain electrical signal leveled off
when the number of objects held in a person’s mind exceeded
their capacity to accurately remember them, while it continued to
soar in those with higher capacity. |
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New Technique Helps Scientists Solve 3-D Protein
Structures A new technique for engineering protein crystals
is helping scientists figure out the three-dimensional structures
of some important biological molecules, including a key plague protein
whose structure has previously eluded researchers. The “crystal
engineering” technique, developed with support from NIH, promises
to help pharmaceutical companies develop more effective drugs to treat
various diseases by tailor-making molecules to "fit" a protein's
shape. |
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New Eggs Continue to Develop in Adult Mice
Contrary to long-held scientific views that the number of oocytes
(eggs) in the ovaries of most mammals is fixed at birth, scientists
supported by NIH reported that new oocyte-containing follicles continue
to develop in the ovaries of adult mice. The research suggests that
these new oocytes come from stem cells located in the ovary. Scientists
have long believed that no new oocytes were made after the ovary of
any mammal, including a woman, was formed, but this study provides
evidence challenging this belief. |
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HIV-Blocking Protein in Monkeys
Scientists funded by NIH identified a protein that blocks HIV replication
in monkey cells. Humans have a similar protein, although it is not
as effective at stopping HIV. The protein, called TRIM5-alpha, blocks
a key early stage of HIV infection: the removal, or uncoating, of
the protective shell surrounding HIV’s genetic material. This
coat, called the capsid, must be removed before HIV can insert its
genetic material into the host cell’s DNA and begin to make
copies of itself. The identification of a specific protein that powerfully
inhibits viral uncoating provides a scientific springboard for future
HIV/AIDS therapies. |
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Monkey Talk, Human Speech Share Left-Brain
Processing NIH researchers were part of a team that used
PET (positron emission tomography) to pinpoint circuits in the monkey
brain that could be precursors of those in humans for speech and language.
As in humans, an area specialized for processing species-specific
vocalizations is on the left side of the brain. An area near the left
temple responded significantly more than the same area on the right
to monkey calls, but not to other animal calls, human voices or various
other sounds. |
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Transgenic Animals Produced Using Cultured Sperm NIH
researchers, in collaboration with Japanese colleagues, successfully
created transgenic zebrafish ones to which novel genes have
been added using sperm cells grown under laboratory, or in
vitro, conditions. This is the first time that sperm cells have
been cultured entirely in vitro and used to produce a transgenic
animal. This achievement has implications for a wide range of research
from developmental biology to gene therapy. The new technique has
the potential to speed the production of many different types of transgenic
animals that can shed new light on human development and disease. |
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Prepared by Harrison Wein, Ph.D.
Email: weinh@od.nih.gov
May 4, 2004 |
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