Historical Resources
Selected Research Advances
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 in the past years.
2005
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1970s | 1960s
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1887-1950
2005
Disease
Prevention, Diagnosis, and Treatment
Study
Shows Diuretics Work Better than Newer Medicines
for High Blood Pressure The Antihypertensive
and Lipid-Lowering Treatment to Prevent Heart
Attack Trial (ALLHAT), a long-term, multi-center
trial of antihypertensive therapies funded by
NIH, found that diuretics work better than newer
therapies in treating high blood pressure and
reducing the risk of heart disease in both black
and non-black patients. The large study, with
33,357 participants, concluded that diuretics
should be the first therapy for most patients
with high blood pressure.
Tight
Glucose Control Cuts Heart Disease by Half in
People with Type 1 Diabetes People
with type 1 diabetes can lower their risk of heart
disease and stroke by about 50% by tightly controlling
their blood glucose levels, according to a study
supported by NIH. The findings were based on a
follow-up study of patients who took part more
than a decade ago in the Diabetes Control and
Complications Trial, a major clinical study funded
by NIH along with Genentech, Inc. Continuing studies
will reveal whether the same applies to those
with type 2 diabetes, the more prevalent form
of the disease.
Computer
Models Guide Avian Flu Outbreak Planning
Computer models developed by the NIH-funded
Models of Infectious Disease Agent Study (MIDAS)
research network found that a carefully chosen
combination of public health measures, if implemented
early, could stop the spread of an avian flu outbreak
at its source. The researchers found that antiviral
treatment is a critical component of a multi-pronged
approach.
Cognitive
Therapy Reduces Repeat Suicide Attempts by 50
Percent People who had recently attempted
suicide were 50% less likely to try to kill themselves
again within 18 months when they were treated
with cognitive therapy, according to researchers
supported by NIH and the Center for Disease Control
and Prevention.
First
Phase II Trial of HIV/AIDS Vaccine
An HIV/AIDS vaccine developed by scientists at
NIH's Dale and Betty Bumpers Vaccine Research
Center moved into its second phase of clinical
testing in October. This vaccine contains synthetic
genes representing HIV subtypes found in Europe,
North America, Africa and Asia that account about
85% of HIV infections worldwide.
Study
Finds Vitamin E Does not Protect Women from Heart
Attack, Stroke or Cancer The Women's
Health Study, a long-term clinical trial funded
by NIH, found that vitamin E supplements don't
protect healthy women against heart attacks and
stroke. They also had no effect on the most common
cancers in women or on total cancers.
Older Children Can Benefit From Treatment
For Childhood's Most Common Eye Disorder
Surprising results from a nationwide clinical
trial supported by NIH showed that many children
age seven through 17 with amblyopia (lazy eye)
may benefit from treatments that are more commonly
used on younger children. Treatment improved the
vision of many of the 507 older children with
amblyopia studied at 49 eye centers. Previously,
many eye care professionals thought that treating
amblyopia in older children would be of little
benefit.
NIH
Researchers Confirm Effectiveness of Immunotherapy
Approach to Melanoma A team of NIH
researchers found that patients with advanced
melanoma who hadn't responded to standard therapies
had a significant reduction in the size of their
cancers as a result of receiving a new immunotherapy.
This immunotherapy consisted of a combination
of chemotherapy and reintroduction of the patients'
own white blood cells. The white blood cells were
removed from the patients, "re-educated"
to attack the tumor, and then reintroduced into
the patient. The promise of this therapy is that
a patient's own immune system can be used to effectively
treat existing tumors.
Possible
Treatment Changes for Asthma Some people
with mild persistent asthma may be able to control
their asthma by taking corticosteroids only when
needed, according to a new study supported by
NIH. Official guidelines for this type of asthma
recommend daily long-term control medication to
prevent symptoms, along with quick-relief medication
as needed to treat acute symptoms. In this study,
those who took corticosteroids based on their
symptoms had about the same number of asthma flare-ups
as those taking daily, long-term control medications.
The finding needs to be confirmed in a larger
study, but it raises the possibility that some
patients may be able to safely avoid the expense
and inconvenience of daily medication.
Substance
in Urine Predicts Development of Preeclampsia
A substance found in the urine of pregnant women
can be measured to predict the later development
of preeclampsia, according to research supported
by NIH. A pregnant woman with preeclampsia develops
dangerously high blood pressure and begins excreting
protein in her urine. In some cases, the condition
may progress to eclampsia, a series of potentially
fatal seizures. Researchers found that women were
highly likely to develop preeclampsia if they
had low levels of a substance known as placental
growth factor in their urine. They plan to try
to refine the finding into an accurate clinical
test.
Study
Links Obesity and Dementia In a 27-year
study of over 10,000 people supported by NIH,
researchers found that middle-aged people who
were obese (those with a body mass index of 30
or above) had a 74% increased risk of dementia
later in life compared to people of normal weight
(body mass index 18.6-24.9), while overweight
people (body mass index 25.-29.9) had a 35% greater
risk. It's not clear why heavier people developed
dementia more often, but eating a low-fat diet
and exercising regularly may help reduce the risk
of developing the memory loss, concentration problems
and other symptoms of dementia later in life.
Rapid
New Test Developed for Inherited Immune Deficiency
NIH researchers developed a new laboratory method
that rapidly identifies babies born with inherited
forms of Severe Combined Immunodeficiency (SCID),
an illness in which the infant fails to develop
a normal immune system. SCID babies can be infected
by a wide range of viruses, bacteria and fungi
that are normally controlled by a healthy baby's
immune system. If undetected and untreated, SCID
typically leads to death before the baby's first
birthday. The new genetic test, which still must
be validated before widespread use, could someday
be added to the panel of tests that already screen
newborns for a variety of disorders.
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Genomics
and Genetics
Dog
Genome Sequence Published An international
team supported by NIH published the genome sequence
of the dog. Because of selective breeding over
the past few centuries, modern dog breeds are
a model of genetic diversity, from 6-pound Chihuahuas
to 120-pound Great Danes, from high-energy Jack
Russell Terriers to mild-mannered basset hounds,
and from the herding instincts of Shetland sheepdogs
to pointers pointing. However, selective breeding
has also caused many dog breeds to be predisposed
to genetic disorders including heart disease,
cancer and blindness. In combination with the
human genome, the dog genome sequence will help
researchers identify genetic contributors to several
diseases.
Genome
Comparison Finds Chimps, Humans Very Similar at
the DNA Level The Chimpanzee Sequencing
and Analysis Consortium, which is supported in
part by NIH, described its landmark analysis comparing
the genome of the chimp ( Pan troglodytes ) with
that of humans ( Homo sapiens ). The chimp sequence
draft represents the first non-human primate genome.
Our closest living relatives share 96% of our
DNA sequence.
Three
Deadly Parasite Genomes Sequenced An
international group of researchers working in
more than 20 laboratories around the globe and
funded in part by NIH sequenced the genomes of
three parasites that cause deadly insect-borne
diseases: African sleeping sickness, leishmaniasis
and Chagas disease. Knowing the full genetic make-up
of the three parasites might lead to better ways
to treat or prevent the diseases they cause.
Map
of Human Genetic Variation Completed
The International HapMap Consortium, a public-private
effort to chart patterns of genetic variation
in the world's population, published the human
haplotype map, or HapMap. With more than 1 million
markers of genetic variation, the HapMap is a
comprehensive catalog of human genetic variation
showing neighborhoods of correlated genetic
variation, or haplotypes, across the entire human
genome. Researchers will be able to identify genetic
contributions to common diseases far more efficiently
using HapMap data than with traditional approaches.
Multi-Species
Genome Comparison Sheds New Light on Evolution
and Cancer Researchers reconstructed
the genomes of long-extinct mammals and determined
the rates of mammalian chromosome evolution by
aligning the human, mouse, rat, cow, pig, dog,
cat and horse genomes. The study, funded in part
by NIH, found that evolution rates dramatically
accelerated around 65 million years ago, a period
that marked the end of the age of reptiles and
the arrival of the age of mammals. The researchers
also found that, contrary to what scientists had
long thought, mammalian chromosomes seem to have
breakpoint "hotspots." These tend to
have a high gene density and also seem to be associated
with cancer-associated chromosome abnormalities.
As more genomes become available, these relationships
will become clearer.
Gene
Found to Increase Risk of the Most Common Cause
of Blindness Three independent research
teams supported by NIH found a gene, called complement
factor H (CFH), that affects a person's risk of
developing age-related macular degeneration (AMD),
the leading cause of blindness in people over
age 60. One team, which included NIH's own researchers,
found that people with this variant of the CFH
gene are more than seven times more likely to
develop the disease. The discovery suggests new
avenues for researchers to pursue in developing
ways to diagnose and treat AMD.
Gene
Found to Increase Risk of the Most Common Cause
of Blindness Three independent research
teams supported by NIH found a gene, called complement
factor H (CFH), that affects a person's risk of
developing age-related macular degeneration (AMD),
the leading cause of blindness in people over
age 60. One team, which included NIH's own researchers,
found that people with this variant of the CFH
gene are more than seven times more likely to
develop the disease. The discovery suggests new
avenues for researchers to pursue in developing
ways to diagnose and treat AMD.
Scientists
Detect Probable Genetic Cause of Some Parkinson's
Disease Cases Two new studies strongly
suggest that a mutation in a recently discovered
gene is the most common genetic cause of Parkinson's
disease identified to date. The finding could
lead to the development of a genetic test to detect
the mutation in individuals at risk. Parkinson's
disease, which affects at least 500,000 Americans,
is a progressive neurological disorder that is
caused by the degeneration of nerve cells in the
portion of the brain that controls movement. Scientists
have long suspected genetics play a role in the
onset of the disease. In these studies, the investigators,
which included investigators at NIH, found that
a mutation in the gene LRRK2 appears to occur
in at least one of every 60 people who have the
disease.
Scientists
Analyze Human Chromosomes 2 and 4 A
detailed analysis of chromosomes 2 and 4 by researchers
supported by NIH detected the largest "gene
desert," a region without of any protein-coding
genes, known in the human genome and uncovered
more evidence that human chromosome 2 arose from
the fusion of two ancestral ape chromosomes. Chromosome
4 has long been of interest to the medical community
because it holds the gene for Huntington's disease,
polycystic kidney disease, a form of muscular
dystrophy and a variety of other inherited disorders.
Chromosome 2 is noteworthy for being the second
largest human chromosome, trailing only chromosome
1 in size, and home to the gene with the longest
known protein-coding sequence for a muscle protein
called titin.
Research
Sheds New Light on Role of Sex Chromosomes in
Health and Disease Two studies provided
a detailed analysis of the X chromosome's DNA
sequence and a survey of its gene activity. This
first comprehensive analysis of the sequence of
the human X chromosome, supported by NIH as well
as by the Department of Energy, provides new insights
into the evolution of sex chromosomes and the
biological differences between males and females.
Even though it contains only 4% of all human genes,
the X chromosome accounts for almost 10% of inherited
diseases caused by a single gene, including red-green
color blindness, hemophilia, some forms of mental
retardation and Duchenne muscular dystrophy. More
than 300 diseases have already been linked to
it.
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New
Research Directions
Protein
Structure Initiative Advances to Rapid Production
Phase The Protein Structure Initiative
(PSI) completed its first 5-year phase and moved
into its second. The PSI, which is funded largely
by NIH, aims to figure out the three-dimensional
shapes of proteins, with the long-term goal of
being able to predict most protein structures
from their DNA sequences. More than 1,100 protein
structures were solved in the PSI's first phase,
which was dedicated to figuring out how to process
proteins and determine their three-dimensional
structures more efficiently. Phase 2 is the production
phase, in which thousands more protein structures
will be solved and put into the Protein Data Bank
(http://www.rcsb.org/pdb/
), a public repository with powerful tools
for processing protein structure information.
Scientists
Discover How Ebola Virus Infects Cells
Researchers supported in part by NIH identified
two cellular enzymes that the Ebola virus must
have to reproduce. Ebola virus reproduction in
laboratory-grown cells was severely hampered by
chemicals that inhibited these enzymes. These
chemicals will now be further studied as possible
treatments for Ebola virus infections in humans.
Combination
Therapy Leads to Partial Recovery from Spinal
Cord Injury in Rats A new method using
both stem cells and gene therapy promoted the
growth of myelin, the "insulation" around
nerve fibers, in the damaged spinal cords of rats.
It improved the animals' motor function and electrical
conduction from the brain to the leg muscles.
The finding, which was funded in part by NIH,
may lead to new ways of treating spinal cord injury
in humans.
Gene
Knockout Creates Fearless Mouse Knocking
out a gene in the brain's fear hub created mice
unperturbed by situations that would normally
trigger fear responses, researchers funded in
part by NIH discovered. The gene codes for a protein
called stathmin, which appears to be critical
for the amygdala, where the brain's fear circuitry
is centered, to rearrange connections and form
fear memories. This finding may eventually lead
to improved treatments for anxiety disorders.
Brain
Chemical Plays Key Role in Both Food and Drug-Seeking
Behavior Orexin, a brain chemical involved
in feeding behavior, arousal and sleep, also plays
a role in reward function and drug-seeking behavior,
according to NIH-funded research in rats. Activation
of orexin-secreting brain cells in the hypothalamus,
a brain region that controls many vital functions
such as eating, body temperature and fat metabolism,
is strongly correlated with food- and drug-seeking
behaviors. This finding helps to better identify
the neural pathways involved in drug abuse, craving
and relapse, and may ultimately help scientists
find more effective therapies.
Researchers
Pinpoint Chemical that Links Taste Buds to the
Nervous System Researchers funded by
NIH pinpointed the chemical responsible for transmitting
signals from the taste buds small sensory bumps
on the tongue, throat and roof of the mouthto
the taste nerves leading to the brain. Adenosine
5'-triphosphate (ATP), a high-energy molecule
crucial for helping cells in the body to function,
turns out also to be the key neurotransmitter
linking taste buds to the nervous system. This
finding provides scientists with a more complete
picture of the complicated process, helping advance
the study of taste and taste disorders.
Exercise
Slows Development of Alzheimer's-Like Brain Changes
in Mice Physical activity appears to
inhibit Alzheimer's-like brain changes in mice,
according to a new study supported by NIH. Long-term
physical activity enhanced the learning ability
of mice and decreased the level of plaque-forming
beta-amyloid protein fragments a hallmark characteristic
of Alzheimer's disease in their brains. Further
research will help reveal if the same holds true
in people.
Possible
Mechanism for Link between Sleep Disturbances
and Metabolic Syndrome A new mouse
study supported by NIH suggests that a brain system
that controls the sleep/wake cycle might also
play a role in regulating appetite and metabolism.
Mice with a mutation in a gene called "Clock,"
which helps drive circadian rhythm, ate significantly
more and gained more weight. This finding could
help explain why disrupted sleep patterns particularly
when combined with a high-fat diet are sometimes
associated with excessive weight gain and the
onset of metabolic syndrome, a cluster of conditions
shown to increase a person's risk of heart disease
and stroke. At least 40 million Americans have
chronic sleep problems, and an additional 20 million
experience occasional sleeping problems. As many
as 47 million Americans have metabolic syndrome.
Microbicides
Protect Monkeys Against HIV-Like Virus
Experiments in female monkeys showed for the
first time that vaginal gels known as microbicides
can protect against an HIV-like virus. The research,
funded largely by NIH, suggests that microbicides
could potentially provide a safe, effective and
practical way to prevent HIV transmission to women.
Artificial
Light at Night Stimulates Breast Cancer Growth
in Laboratory Mice Results from a study
in laboratory mice showed that nighttime exposure
to artificial light stimulated the growth of human
breast tumors by suppressing levels of the hormone
melatonin. The study, which was supported by NIH,
also showed that extended periods of nighttime
darkness greatly slowed the growth of these tumors.
These results might explain why female night shift
workers have a higher rate of breast cancer. They
also offer a potential explanation for the epidemic
rise in breast cancer incidence in industrialized
countries like the U.S.
Substance
Protects Resilient Staph Bacteria NIH
researchers identified a promising new target
in their fight against a dangerous bacterium that
sickens people in hospitals, especially people
who receive medical implants such as catheters,
artificial joints and heart valves. A substance
found on the surface of Staphylococcus epidermidis
was, for the first time, shown to protect the
harmful pathogen from natural human defense mechanisms
that would otherwise kill the bacteria. S. epidermidis
is one of several hard-to-treat infectious agents
that can be transmitted to patients in hospitals
via contaminated medical implants.
Novel
Therapy Tested in Mice Could Chase Away Cat Allergies
A molecule designed to block cat allergies successfully
prevented allergic reactions in laboratory mice
as well as in human cells in a test tube, NIH-funded
researchers reported. The injectable treatment
puts a brake on the release of a key chemical
from cells involved in cat allergy reactions.
That chemical, histamine, brings on allergy symptoms
such as sneezing, wheezing, itching, watery eyes,
and sometimes asthma. When a cat-allergic person
touches or inhales a protein found in cat saliva
or dander (small flakes from its skin or hair),
key immune system cells respond by spewing out
histamine. Allergy experts estimate that 14 percent
of children 6 to 19 years old are allergic to
cats. In the future, the investigators say, these
promising results could lead to a new therapy
not only for human cat allergies, but also possibly
for severe food allergies such as those to peanuts.
Gene
Therapy Restores Hair Cells and Improves Hearing
in Deaf Guinea Pigs Researchers supported
by NIH successfully used gene therapy to grow
new hair cells and restore some hearing in deaf
guinea pigs. The scientists used a harmless virus
to insert a gene called Atoh1, a key regulator
of hair cell development, into cells in the inner
ears of deaf adult guinea pigs. Eight weeks after
treatment, new hair cells had grown in the ears
treated with Atoh1, and their hearing had improved.
This is the first time that researchers have restored
auditory hair cells in live adult mammals. The
researchers caution that it will be several years
before Atoh1 gene therapy will be ready to test
in humans. Nevertheless, this study is an important
advance in hearing research. Scientists are now
one step further in the search for new ways to
treat hearing loss, a condition affecting about
28 million Americans.
Prepared
by Harrison
Wein, Ph.D.
January, 2006
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2004
Disease
Prevention, Diagnosis and Treatment
New Treatment Improves Outlook for Breast
Cancer Survivors — An international
clinical trial supported in part by NIH concluded
that women should consider taking letrozole after
five years of tamoxifen treatment to continue
to reduce the risk of breast cancer recurrence.
This very important advance in breast cancer treatment
will improve the outlook for many thousands of
women.
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.
Molecular Test Can Predict Risk of Breast
Cancer Recurrence — A new test
can predict the risk of breast cancer recurrence
and may help identify women who will benefit most
from chemotherapy, according to research supported
by NIH. The researchers used tissue samples and
medical records from women enrolled in clinical
trials of the cancer drug tamoxifen, which blocks
the effect of estrogen on breast cancer cells.
These women had a kind of breast cancer called
estrogen receptor-positive, lymph node-negative
(which means it needs estrogen to grow but has
not spread to the lymph nodes). Using samples
from 447 patients and a collection of 250 genes,
the researchers created a formula that can measure
the risk that a given cancer will recur. Their
results suggest that almost half of the 43,000
US women that are diagnosed with estrogen-dependent,
lymph-node negative breast cancer every year may
not need to go through the discomfort and side
effects of chemotherapy.
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.
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.
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.
Mutant Gene Linked to Treatment-Resistant
Depression — A mutant gene that
starves the brain of serotonin, a mood-regulating
chemical messenger, has been discovered and found
to be ten times more prevalent in depressed patients,
researchers funded by NIH have found. The gene
codes for the brain enzyme tryptophan hydroxylase-2,
which makes serotonin. The mutant version results
in 80 percent less of the neurotransmitter. It
was carried by nine of 87 depressed patients,
three of 219 healthy controls and none of 60 bipolar
disorder patients. Patients with the mutation
failed to respond well to the most commonly prescribed
class of antidepressant medications, which work
via serotonin, suggesting that the mutation may
underlie a treatment-resistant version of the
illness.
Combination Treatment Most Effective in
Adolescents with Depression — A
clinical trial of 439 adolescents with major depression
found a combination of medication and psychotherapy
to be the most effective treatment. Funded by
the NIH, the study compared cognitive-behavioral
therapy (CBT) with fluoxetine, currently the only
antidepressant approved by the Food and Drug Administration
for use in children and adolescents. Seventy-one
percent of participants responded to the combination
of fluoxetine and CBT.
Researchers Report Early Success Using
Saliva to Detect Oral Cancer —
Scientists funded by NIH took a major step forward
in using saliva to detect oral cancer. The scientists
found that they could measure for elevated levels
of four distinct cancer-associated molecules in
saliva and distinguish with 91 percent accuracy
between healthy people and those diagnosed with
oral squamous cell carcinoma. This so-called "proof-of-principle"
study marks the first report in the scientific
literature that distinct patterns of "messenger
RNA" not only are measurable in saliva but
can indicate a developing tumor. Messenger RNA
(mRNA) is the molecular intermediate between gene
and protein, using the information in a gene to
guide how a protein is made. With further refinement
of this test, the researchers hope to attain the
necessary 99 to 100 percent accuracy of commercial
diagnostic tests. Oral squamous cell carcinoma
is the sixth most common cancer in the US. Currently,
no biochemical or genetic diagnostic tests are
commercially available for oral cancer.
Crohn's Disease Treatment Shows Promise
in Clinical Trial — In a small,
initial clinical trial led by NIH researchers,
doctors found that up to 75 percent of people
with Crohn's disease responded to an experimental
new treatment and up to 50 percent had long-term
remission of symptoms. Crohn's, which affects
an estimated 500,000 Americans, is an autoimmune
disease that attacks the bowels, causing abdominal
pain, cramping, diarrhea and rectal bleeding.
In severe cases, damaged bowel sections have to
be surgically removed. The new treatment is an
antibody designed to disable interleukin-12 (IL-12),
an immune system protein involved in inflammation.
People with Crohn's produce excess IL-12.
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.
"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.
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.
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.
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Genomics and Genetics
Sequencing Consortium Reports Finished
Human Genome Sequence — The International
Human Genome Sequencing Consortium, led in the
United States by NIH's National Human Genome Research
Institute (NHGRI) and the Department of Energy
(DOE), published its scientific description of
the finished human genome sequence, reducing the
estimated number of human protein-coding genes
from 35,000 to only 20,000-25,000, a surprisingly
low number for our species.
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.
Researchers Compare Chicken and Human
Genomes — An international research
consortium supported by NIH has found that chickens
and humans share more than half of their genes,
but that their DNA sequences diverge in ways that
may explain some of the important differences
between birds and mammals. The International Chicken
Genome Sequencing Consortium analyzed the sequence
of the Red Jungle Fowl (Gallus gallus), which
is the progenitor of domestic chickens. The chicken
is the first bird, as well as the first agricultural
animal, to have its genome sequenced and analyzed.
Recent outbreaks of avian flu have highlighted
the importance of learning more about the chicken
genome.
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.
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.
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.
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.
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.
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New Research Directions
Sperm Provides Target for New Contraceptive
Approach — A team of researchers
funded by NIH found an enzyme in sperm that is
necessary for sperm movement. Mice bred to lack
this enzyme produce sperm that cannot swim toward
egg cells to fertilize them. The enzyme, known
as GAPDS, is essentially the same as an enzyme
produced in human sperm. It is found in the sperm's
flagellum, the snake-like tail which whips back
and forth to propel the sperm forward. Researchers
believe that designing a drug to disable this
enzyme might provide the basis for an effective
new form of male contraception. An understanding
of the enzyme and related chemical reactions might
also lead to insights into treatment for some
forms of male infertility.
Researchers Identify Brain Protein that
Halts Progression of Alzheimer's —
Researchers funded by NIH have identified a protein
in the brain that halts the progression of Alzheimer's
disease in human brain tissue. The protein, known
as transthyretin, protects brain cells from gradual
deterioration by blocking another toxic protein
that contributes to the disease. Scientists are
hopeful that this research will inspire a new
approach to the treatment of Alzheimer's, one
focused on preventing the loss of the brain cells
instead of treating the resulting symptoms. More
studies are needed to understand how transthyretin
might be used in treating Alzheimer's patients.
Scientists Take 'Snapshot' of Molecular
Tether for Anthrax and Staph Bacteria
— Scientists funded by NIH have snapped
a picture of the molecular tether that anthrax-
and staph-causing bacteria use to hook onto human
red blood cells. The tether, an enzyme called
sortase B, allows the bacteria to rob the cells
of iron, which they need to survive. Anthrax infection
can be life-threatening, while staph is responsible
for a range of health problems, including skin
infections and food poisoning. The scientists
hope to use their knowledge of this enzyme's structure
to rationally design new antibiotics that would
nip dangerous bacteria in the bud, before they
have a chance to cause infections.
Researchers Find Protein That Makes Long-Term
Memory Possible — From language
to literature, from music to mathematics, a single
protein, known as mBDNF, appears central to the
formation of the long-term memories needed to
learn these and all other disciplines. This discovery
brings the possibility of studying this protein
system in people with learning and memory disorders
and perhaps designing new medications to help
compensate for these problems.
Brain Signal Predicts Working Memory Prowess
— A person’s capacity for visual working
memory can be predicted by his or her brain waves,
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.
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.
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.
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.
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.
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.
Prepared by Harrison Wein, Ph.D.
Email: weinh@od.nih.gov
May 12, 2005
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2003
 |
Human Genome Project Completed — The International Human Genome Sequencing Consortium, led in the United States by NIH, completed the Human Genome Project more than 2 years ahead of schedule and for a cost substantially less than the original estimates. The international effort to sequence the 3 billion DNA letters is considered by many to be one of the most ambitious scientific undertakings of all time. The first draft of the human sequence was completed in June 2000. Since then, researchers have worked to convert the "draft" sequence into a "finished" sequence, which covers about 99 percent of the human genome's gene-containing regions, and has been sequenced to an accuracy of 99.99 percent. All of the sequence data have been deposited into public databases and made freely available to scientists around the world, with no restrictions on their use or redistribution.
Anthrax Genome Completed — The complete genetic blueprint of Bacillus anthracis — the microbe that gained notoriety during the 2001 anthrax mail attacks — has been completed by NIH-funded researchers. This bacterium, which can cause potentially fatal inhalational anthrax, differs very little from a common soil bacterium related to it. Scientists hope that the genetic differences between these two may reveal valuable clues to its vulnerabilities.
New "Prehypertension" Category — NIH published new clinical practice guidelines for the prevention, detection, and treatment of high blood pressure — a major risk factor for heart disease and the chief risk factor for stroke and heart failure. The guidelines define a new blood pressure category called "prehypertension" that includes about 22 percent of American adults, or about 45 million people. Americans' lifetime risk of developing hypertension is greater than previously thought, according to the new guidelines. Medications and lifestyle changes are both crucial parts of treatment.
SARS Cause Identified — NIH-supported investigators studied 50 Hong Kong patients with severe acute respiratory syndrome (SARS) and identified the virus that was causing the disease. It was revealed to be a new strain of coronavirus, a type of virus formerly associated in humans only with the common cold. Over 8,000 people worldwide became sick with SARS during the outbreak of 2003, according to the World Health Organization; of these, 774 died. The virus's isolation set the stage for the rapid sequencing of its genome as well as investigations into diagnostic tests and therapeutics to combat it.
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Heart Stem Cells Identified — A new study funded by NIH shows that the adult heart may contain stem cells that have the potential to regenerate tissue when the heart is damaged, such as during a heart attack. The heart had long been considered an organ that wasn't able to renew itself. Scientists now hope to harness these cells to develop new therapies to repair damaged hearts.
Ebola Vaccine Progress — A single shot of a fast-acting, experimental Ebola vaccine successfully protected monkeys from the deadly virus after only one month. Scientists at NIH's Dale and Betty Bumpers Vaccine Research Center (VRC) and the United States Army Medical Research Institute of Infectious Diseases at Fort Detrick, MD designed the vaccine. If this vaccine proves similarly effective in humans, it may one day allow scientists to quickly contain Ebola outbreaks with the same strategy successfully used in the past against smallpox. In November, VRC scientists opened the first human trial of a vaccine designed to prevent Ebola infection, administering the vaccine to a volunteer at the NIH Clinical Center in Bethesda.
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Structure of HIV-Neutralizing Antibody Solved — A team of scientists whose leaders are funded by NIH solved the three-dimensional structure of an antibody that is able to neutralize HIV, the virus that causes AIDS. The antibody, called 2G12, was isolated about a decade ago from one of the rare HIV-positive people whose body is able to successfully combat the virus. The structure of the 2G12 antibody provides scientists with a template in their attempts to design innovative vaccines to trigger the body's production of HIV-neutralizing antibodies.
New Treatment For Breast Cancer Survivors — An international clinical trial found that post-menopausal survivors of early-stage breast cancer who took the drug letrozole after completing an initial 5 years of tamoxifen therapy had a significantly reduced risk of cancer recurrence compared to women taking a placebo. The women taking letrozole had a reduction in the number of recurrences of cancer in their previously affected breast, a reduction in the number of new cancers in their opposite breast, and a reduction in the spread of the cancer outside their breast. Deaths from breast cancer were also reduced. While tamoxifen is widely used to prevent breast cancer recurrence in post-menopausal women, it stops being effective after about 5 years because, researchers believe, tumors become resistant to it. NIH participated in and partly supported this Canadian-led study. Novartis, which manufactures letrozole (also known as Femara®), provided the drug for the trial.
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Gene Linked to Depression — Researchers supported by NIH found a gene, the serotonin transporter gene (5-HTT), that influences whether people become depressed when faced with major life stresses such as relationship problems, financial difficulties and illness. The gene by itself does not cause depression, but it does affect how likely people are to get depressed when faced with major life stresses. Those who carried one version of the gene had more symptoms of depression, more diagnoses of depression, and more thoughts of or attempts at suicide after stressful life events than those who didn't carry it. Significantly, among those who hadn't experienced major life stresses during the study, the gene played no detectable role in their risk of depression or suicide.
Gene Affects College Drinking Habits — Researchers identified a gene, the serotonin transporter gene (5-HTT), that may predispose young people to harmful drinking habits. A team of scientists interviewed college students about their alcohol consumption and then analyzed their genetic profiles, or genotypes. They found that students who shared a particular variant of 5-HTT consumed more alcohol per occasion, more often drank expressly to become inebriated, and were more likely to engage in binge drinking than students without the variant.
Gene Signaling Puberty — NIH-funded researchers, using tools from the NIH-sponsored Human Genome Project, identified a gene that appears to be a crucial signal for the beginning of puberty in human beings as well as in mice. Without a functioning copy of the gene, both humans and mice appear to be unable to enter puberty normally.
Stem Cells from Baby Teeth — A team led by NIH researchers discovered that "baby" teeth, the temporary teeth that children begin losing around their sixth birthday, contain a rich supply of stem cells in their dental pulp. The cells, named SHED, remain alive inside the tooth for a short time after it falls out of a child's mouth. This easily accessible source of stem cells could be readily harvested for research. Scientists hope they can learn to manipulate them to repair damaged teeth, induce the regeneration of bone, and treat neural injury or disease.
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Women's Heart Attack Signs Differ From Men's — A new study — one of the first to look at symptoms before and during heart attacks in women — found that fewer than 30% of women reported chest pain and discomfort prior to a heart attack, and 43% didn't experience chest pain during one. Most doctors consider chest pain the most important heart attack symptom for both men and women, but the women's most frequently reported early warning symptoms were unusual fatigue (70.7%), sleep disturbance (47.8%), and shortness of breath (42.1%). This finding may help women and their doctors more accurately identify the early warning symptoms of a heart attack so that they can better forestall or prevent the attacks.
Moderate Physical Activity Promotes Weight Loss — Women trying to lose weight can benefit as much from moderate physical activity as from an intense workout, according to a new study supported by NIH. With a diet reduced in calories and fat, physical activity of moderate intensity is enough to help overweight people lose weight. The key is not how intense your workouts are, the study suggests, but how much total energy you burn in the end.
Insight into Parkinson's Disease — NIH researchers were part of a team that discovered that too much of a normal form of the α-synuclein gene may cause Parkinson's disease. Mutations in the α-synuclein gene were previously linked to the disease in some families. These researchers were investigating a rare form of early-onset Parkinson's disease in one family for many years, and were puzzled because a genetic analysis of some family members failed to reveal an α-synuclein mutation. The scientists thought perhaps an entirely different genetic mutation might account for this family's Parkinson's disease. But they found that, instead of the usual two copies of the α-synuclein gene, the people in this family had four copies. This multiplication of the α-synuclein gene resulted in them having too much synuclein. Buildup of the protein is believed to cause their Parkinson's disease symptoms. Parkinson's disease is the second most common neurodegenerative disease in the U.S., after Alzheimer's disease, currently affecting at least 500,000 Americans.
Potential Screening Tool for Alzheimer's Disease — NIH scientists found that levels of two key proteins could be used to distinguish clinically diagnosed Alzheimer's patients from controls. The proteins, beta-amyloid and tau, are located in the cerebrospinal fluid, which bathes the brain. Scientists hope that "markers" such as these could eventually be used as predictive and diagnostic tools to help identify people at risk for developing Alzheimer's disease who may not yet show any symptoms. Longer term studies are now under way to further test these markers.
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Very Low Lead Levels Linked with IQ Deficits— A study funded by NIH suggested that lead may be harmful to young children even at very low blood concentrations. The five-year study found that children who have blood lead concentration lower than 10 micrograms per deciliter suffer intellectual impairment from the exposure. Previous research has focused primarily on lead's effects in the 10 to 30 micrograms per deciliter range. Ten micrograms per deciliter is the threshold currently used by the Centers for Disease Control and Prevention to define an elevated lead level.
Diagnosis and Treatment of Liver Cancer — A pattern of gene activity unique to hepatocellular carcinoma (HCC), a type of liver cancer, was identified by NIH researchers in collaboration with surgeons in Shanghai, China. The pattern, akin to a molecular signature, can be used to classify metastatic HCC patients and identify genes related to patient survival. Researchers identified one particular gene called osteopontin as a potential therapeutic target. HCC is one of the most common and aggressive malignant tumors worldwide. These findings pave the way for development of a diagnostic test that may help predict whether a cancer will spread, and might help physicians decide on the best treatment for a patient.
Protein Tied to Preeclampsia — Researchers supported by NIH linked excess levels of a protein called sFlt1 to the condition preeclampsia, a leading cause of fetal complications including low birth weight, premature birth, and stillbirth. Preeclampsia affects up to 5 percent of pregnancies. It is characterized by increased blood pressure and protein in the mother's urine. Preeclampsia can cause seizures and lead to eclampsia, the second leading cause of maternal death in the U.S. This discovery is an important step in the effort to design better treatments for the condition.
How the Embryo Attaches to the Uterus — Researchers supported by NIH have discovered how an embryo attaches to the wall of the uterus in what may be one of the earliest steps needed to establish a successful pregnancy. After an egg is fertilized, a specialized protein called L-selectin on the embryo surface binds to carbohydrates on the uterine wall. Scientists think that this interaction slows the embryo down to a complete stop so it can then attach to the wall of the uterus. The finding may lead to insights into infertility and early pregnancy loss.
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Filtering Water with Cloth Reduces Cholera — An international research team funded by NIH found that filters made from old cotton saris cut the number of cholera cases in rural Bangladesh villages almost in half. Other inexpensive cloth should work just as well in other parts of the world where cholera is endemic. Cholera is a waterborne disease that causes severe diarrhea and vomiting, killing thousands of people around the world every year. This simple preventive measure has the potential to make a significant impact on a global health problem.
Single Protein Key to Both Bacterial and Viral Infections — A single protein acts as a key switch point in frontline immune system reactions to both bacterial and viral infections, according to a team of scientists supported by NIH. This may explain why certain symptoms, such as fever, occur regardless of the cause of infection.
Understanding Anthrax — A study of anthrax in mice by NIH scientists showed that the toxins released by the bacteria don't kill as scientists had previously believed. Anthrax was thought to kill like many other bacteria, through the body's release of chemicals called cytokines. But this study found no link between cytokines and anthrax's toxic effects. Researchers still don't know exactly how the anthrax toxins lead to death, but this result suggests that current efforts to design cytokine-suppressing drugs to treat anthrax may be misguided. This information is crucial for the design of future therapies.
New Insights Into Antidepressants — Blocking the formation of neurons in the hippocampus area of the brain blocks the behavioral effects of antidepressants in mice, according to researchers funded by NIH. Their finding lends new credence to the idea that antidepressants lift mood, at least in part, by causing new neurons to grow in the brain. This idea also may explain why antidepressants typically take a few weeks to work.
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New Drug to Suppress the Immune System — A new immunosuppressant drug, CP-690,550, developed by Pfizer Global Research and Development with help from NIH researchers, has been successfully tested in mice and monkeys, and may eventually prove to be a major help for those needing organ transplants or with autoimmune diseases. Immunosuppressant drugs are designed to inhibit the body's immune system so that the body doesn't reject transplanted organs, and to treat autoimmune diseases such as lupus, rheumatoid arthritis, eczema and psoriasis — conditions in which the body's own immune system attacks healthy, normal tissue as if it were an invading microbe. The new drug suppresses the immune system with fewer side effects than other drugs. Further animal studies are now being done to determine if it could be tested safely in humans.
Progress Shown in Death Rates From Four Leading Cancers — Death rates from the four most common cancers — lung, breast, prostate, and colorectal — continued to decline in the late 1990s according to new data from the "Annual Report to the Nation on the Status of Cancer, 1975-2000." For all cancers combined, the death rate began to stabilize in the late 1990s, showing neither an increase nor a decrease, while the incidence rate (newly diagnosed cases) began to stabilize in the middle of the decade.
Cigarette Smoke Affects More Than the Lungs — Research supported by NIH shows that cigarette smoke not only directly and often fatally damages the lungs; it also decreases levels of a critical enzyme called monoamine oxidase B (MAO B) in the kidneys, heart, lungs, and spleen. The researchers compared PET scans showing MAO B activity in both smokers and nonsmokers. They observed that MAO B activity in the peripheral organs was reduced by one-third to almost one-half in the smokers. While the medical consequences of this finding aren't yet clear, it highlights the fact that many organs throughout the body are affected by the chemical compounds in tobacco smoke.
Subversive Strep Bug Strategy Revealed — NIH researchers have discovered how Streptococcus pyogenes (S. pyogenes), the bacterium responsible for strep throat and "flesh-eating" infections, gains a foothold in the body by subverting a key immune system cell. Using microarray technology, which allows researchers to determine which genes are active within cells, the researchers created a "snapshot" of how all the genes in neutrophils — a type of white blood cell and central player in the body's innate immune system — react following exposure to a variety of bacteria. S. pyogenes stimulated almost 400 neutrophil genes that were not activated by the other kinds of bacteria, and also caused the neutrophils to self-destruct in an uncontrolled fashion. Knowing how this common bug bacterium evades our immune defenses opens exciting new avenues for research into ways to hamper it.
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Promising West Nile Virus Vaccine Protects Monkeys — NIH scientists have created a promising vaccine against West Nile virus by replacing parts of a distantly related virus with proteins from the West Nile virus. This hybrid vaccine protects monkeys from West Nile infection. West Nile virus is spread to people by mosquitoes. It usually produces mild, flu-like symptoms but can cause a deadly encephalitis, or inflammation of the brain. The disease is most severe among the elderly, and has sickened over 8,500 and claimed around 200 lives in the United States in 2003.
Estrogen and Progestin Therapy Increases Risk of Dementia — Healthy postmenopausal women taking combination hormone therapy had twice the rate of dementia as those taking a placebo. The findings are part of the Women's Health Initiative, a large multi-center research study funded by NIH. The women had stopped taking the therapy in July 2002 when participants were found to have an increased risk of breast cancer, heart disease, stroke, and blood clots. These findings further support the conclusion that the risks of taking estrogen plus progestin outweigh the benefits.
Gene for premature aging disorder identified — A team led by NIH scientists found that mutations in a gene called lamin A (LMNA) are responsible for Hutchinson-Gilford progeria syndrome (HGPS), a disorder that causes a dramatic form of premature aging, with death coming on average at age 13. LMNA is a key protein component of the membrane surrounding the cell's nucleus. This discovery may shed light on the general phenomenon of human aging as well as HGPS.
Key to Hepatitis C Virus Persistence Found — NIH-funded scientists discovered how hepatitis C virus (HCV) thwarts the immune system's efforts to eliminate it. Persistent HCV infection is a major cause of liver disease worldwide and is the leading reason for liver transplants in this country. Using cells grown in the laboratory, researchers found that a type of enzyme manufactured by HCV called a protease inhibits an immune system molecule called interferon regulatory factor-3 (IRF-3), which is a key player in fighting viruses. Researchers showed that interfering with the protease restored IRF-3 function. They hope this finding could eventually lead to more effective treatments for liver disease caused by HCV.
Warfarin Prevents Recurrence of Blood Clots — Long-term, low-dose warfarin treatment prevents the recurrence of the blood-clotting disorders deep vein thrombosis (DVT) and pulmonary embolism. A large NIH-funded trial showed so much benefit to the patients taking warfarin that the study was stopped early. These findings show that recurrent blood clots can be avoided using an inexpensive and safe therapy.
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Tamoxifen Reduces Breast Cancer Risk — More than two million women who have a high risk of developing breast cancer would be likely to benefit from taking the breast cancer prevention drug tamoxifen, according to an analysis by NIH researchers. Tamoxifen was approved five years ago as the first drug to prevent breast cancer. It can halve the incidence of breast cancer in women who are most likely to develop the disease. The decision to take tamoxifen will depend on factors such as a woman's age, breast cancer risk factors, and family history.
Protein
From Algae Inhibits Ebola —
A bacterial protein known to reduce the
ability of the human immunodeficiency virus
(HIV) to infect cells was also found to
inhibit the Ebola virus. The protein, cyanovirin-N,
is found in blue-green algae. An NIH-led
team found that the protein inhibits Ebola
infection by interfering with the virus's
ability to enter cells, and can extend the
survival of Ebola-infected mice. This study
provides important insights that may help
in the development of medicines to combat
Ebola infection, which causes severe hemorrhagic
fever and has a high mortality rate.
prepared
by:
Carol Torgan, Ph.D. and Harrison Wein, Ph.D.
Email: weinh@od.nih.gov
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2002
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