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September 10, 2008, 10:05 PM CT

Killing bacteria isn't enough to restore immune function

Killing bacteria isn't enough to restore immune function
A bacterial molecule that initially signals to animals that they have been invaded must be wiped out by a special enzyme before an infected animal can regain full health, scientists at UT Southwestern Medical Center have found.

Using a genetically engineered mouse model, the team observed that simply eradicating the infection-causing bug isn't enough to restore an animal's immune function. Lipopolysaccharide, or LPS, the dominant bacterial "signal" molecule that heralds the invasion, must also be inactivated. The findings are to appear online Sept. 11 in Cell Host & Microbe.

"We think this is the first evidence that killing the causative agent of a bacterial infection isn't enough for an animal to recover fully," said Dr. Robert Munford, professor of internal medicine and microbiology, and senior author of the study. "You've got to get rid of this molecule that the host is responding to or else its immune system remains suppressed."

By sensing and responding to LPS, animals mobilize their defenses to attack and kill the bacteria. This immune response also causes inflammation in the host. For a few days after the infection begins, however, an animal's ability to sense the bacteria is turned down, presumably to prevent further inflammation. In the current study, the scientists observed that mice didn't recover from this "tolerant" period unless the LPS was inactivated by acyloxyacyl hydrolase, an enzyme discovered in 1983 by Dr. Munford and Dr. Catherine Hall, now an assistant professor of internal medicine at UT Southwestern.........

Posted by: Scott      Read more         Source


September 10, 2008, 8:43 PM CT

Gap junction protein vital to successful pregnancy

Gap junction protein vital to successful pregnancy
Deleting the Cx43 gene in the uterus immediately after pregnancy in mice dramatically reduced blood vessel growth and in most cases prevented successful pregnancy. The image on the left shows normal blood vessel growth in the mouse uterus following pregnancy. On the right, a uterus lacking Cx43.

Credit: Photo by Mary J. Laws

Scientists studying a critical stage of pregnancy implantation of the embryo in the uterus have found a protein that is vital to the growth of new blood vessels that sustain the embryo. Without this protein, which is produced in higher quantities in the presence of estrogen, the embryo is unlikely to survive.

This is the first study to detail the mechanism by which the steroid hormone estrogen spurs cell differentiation and blood-vessel growth in the uterus during pregnancy, the scientists report.

The findings, from scientists at the University of Illinois, Emory University, Baylor College of Medicine and New York University, appear in the journal Development

Connexin 43 (Cx43) belongs to a family of proteins that form junctions between cells that regulate the flow of ions and small signaling molecules from cell to cell. At the time of embryo implantation, this gap junction protein is essential to the rapid growth of new blood vessels needed to support the development of the embryo and allow it to implant in the uterine wall, the scientists discovered.

The scientists chose to study Cx43 after analyzing genes that are activated in the presence of estrogen in uterine cells. They observed that Cx43 was prominent among the genes whose expression was increased in cells after exposure to estrogen.........

Posted by: Emily      Read more         Source


September 10, 2008, 7:28 PM CT

Individuals vary their immune response

Individuals vary their immune response
Is it always good to respond maximally when pathogens or disease strike, or should individuals vary their immune response to balance immediate and future costs? This is the question evolutionary physiologists Oliver Love, Katrina Salvante, James Dale, and Tony Williams asked when they examined how a simple immune response varied at different life stages across the life-span of individual zebra finches (Taeniopygia guttata), as per a research findings reported in the recent issue of the American Naturalist

When transitioning from nest-bound juveniles to adults, female immune responses matured slowly whereas males showed dramatic variation potentially due to the costs of molting into their colorful sexually dimorphic plumage. Adult males showed little variation in immune response despite changes in resource quality. Likewise, when females laid eggs under high-quality resource conditions, immune responses were also consistent with those during non-breeding and similar to male responses. However, when laying on reduced resources females reduced their immune response and their reproductive output consistent with a facultative (resource-driven) effect of reproductive effort on immunity. Moreover, even under high-resource conditions during the chick-rearing stage mothers showed reduced immune responses in comparison to fathers suggesting a residual energetic cost of egg-laying. Perhaps most importantly, immune responses of juveniles of both sexes did not predict their subsequent adult responses. Immune responses of adult females were only predictable when the quality of the environment remained constant; as soon as conditions deteriorated, individual females mandatory flexibility in both the immune and reproductive systems. However, the degree of flexibility came at a cost as only individuals with high immune responses as non-breeders had the capacity to reduce responses when times became tough. These results underlie the fact that immunity is a highly plastic trait that can be modulated in a sex- and context-dependent manner. Given the need for individual flexibility in the immune system, this suggests that an immune response at one stage may provide limited information about immune response at future stages.........

Posted by: Janet      Read more         Source


September 3, 2008, 6:38 PM CT

NTP finalizes report on Bisphenol A

NTP finalizes report on Bisphenol A
Current human exposure to bisphenol A (BPA), a chemical used in a number of polycarbonate plastics and epoxy resins, is of "some concern" for effects on development of the prostate gland and brain and for behavioral effects in fetuses, infants and children, as per a final report released recently by the National Toxicology Program (NTP).

The report provides the NTP's current opinion on BPA's potential to cause harm to human reproduction or development. The conclusions are based primarily on a broad body of research involving numerous laboratory animal studies. The report is part of a lengthy review of the scientific literature on BPA and takes into consideration public and peer review comments received on an earlier draft report. The final report is available at http://cerhr.niehs.nih.gov/chemicals/bisphenol/bisphenol.pdf.

"There remains considerable uncertainty whether the changes seen in the animal studies are directly applicable to humans, and whether they would result in clear adverse health effects," said NTP Associate Director John Bucher, Ph.D. "But we have concluded that the possibility that BPA may affect human development cannot be dismissed."

About the impact that these findings may have on consumers, CERHR Director Michael Shelby, Ph.D., said, "Unfortunately, it is very difficult to offer advice on how the public should respond to this information. More research is clearly needed to understand exactly how these findings relate to human health and development, but at this point we can't dismiss the possibility that the effects we're seeing in animals may occur in humans. If parents are concerned, they can make the personal choice to reduce exposures of their infants and children to BPA".........

Posted by: Janet      Read more         Source


September 2, 2008, 8:08 PM CT

Age-related memory loss tied to slip in filtering information quickly

Age-related memory loss tied to slip in filtering information quickly
Researchers have identified a way in which the brain's ability to process information diminishes with age, and shown that this break down contributes to the decreased ability to form memories that is linked to normal aging.

The finding, published in the current online early edition of Proceedings of the National Academy of Sciences, fuels the researchers' efforts, they say, to explore strategies for enhancing brain function in the healthy aging population, through mental training exercises and pharmaceutical therapys.

This research, which was conducted by University of California, San Francisco and University of California, Berkeley scientists, builds on the team's seminal 2005 discovery ("Nature Neuroscience," October 2005) that the brain's capacity to ignore irrelevant information diminishes with age.

The capacity to ignore irrelevant information -- such as most of the faces in a crowded room when one is looking for a long-lost friend and to enhance pertinent information -- such as the face of a new acquaintance met during the search for the old friend is key to memory formation. This process is known as top-down modulation.

In the 2005 study, the team recorded brain activity in younger and elderly adults given a visual memory test in which they were shown sequences of images (sets of two faces and two scenes), told to remember a specific category, and then asked to identify an image from that category nine seconds later. The scientists, using functional magnetic resonance imaging (fMRI), determined that the neurons of the older participants (ages 60 to 72) responded excessively to the images they should have ignored, in comparison to the younger adults (ages 19 to 33). This attention to the distracting information directly correlated with how well the participants did on the memory test.........

Posted by: Daniel      Read more         Source


August 31, 2008, 9:03 PM CT

Radiation Risks Among Heart Doctors

Radiation Risks Among Heart Doctors
The IAEA is organizing a study to test the eyes of interventional cardiologists participating in a regional cardiology conference organized by SOLACI in Bogota, Colombia, in September. (Photo: Morguefile)

Patients are not the only ones at risk during cardiac procedures. Doctors performing heart surgery also face health risks, namely to their eyes.

The IAEA is helping to raise awareness of threats, through training in radiation protection correlation to medical uses of X-ray imaging systems.

The issue of radiation protection for medical personnel is especially acute in the case of lengthy angioplasty and other cardiac interventions performed under X-ray fluoroscopic guidance. The procedure can cause extensive radiation exposure to heart specialists that could lead to cataracts, alongside other longer term health risks. Fluoroscopy provides X-ray images of a patient that physicians can view on a display screen or monitor in real time.

The IAEA is helping the medical community to address this problem through a major international initiative aimed at training heart specialists and other medical professionals in radiation protection. This September in Latin America, the IAEA is organizing a study to test the eyes of interventional heart specialists participating in a regional medical conference. The Cardiology Conference is organized by the Latin American Society of Interventional Heart specialists (SOLACI) in Bogota, Colombia.

The study is being led by a team of experts, including Prof. Eliseo Vano, Radiology Department of the Complutense University of Madrid; Prof. Norman Kleiman, Columbia University, New York; local ophthalmologists from Bogota; and Mr. Raul Ramirez of the IAEA Department of Technical Cooperation. The initiative is part of an International Action Plan on the radiological protection of patients spearheaded by the IAEA.........

Posted by: Janet      Read more         Source


August 31, 2008, 8:47 PM CT

Magnesium Sulfate Reduces Risk of Cerebral Palsy

Magnesium Sulfate Reduces Risk of Cerebral Palsy
Results of a 10-year study reported in the August 28 issue of the New England Journal (NEJM) observed that magnesium sulfate administered to women delivering before 32 weeks of gestation reduced the risk of cerebral palsy by 50 percent. The Beneficial Effects of Antenatal Magnesium Sulfate (BEAM) trial was conducted in 18 centers in the U.S., including Northwestern Memorial, and is the first prenatal intervention ever found to reduce the instance of cerebral palsy correlation to premature birth.

Magnesium sulfate is traditionally used in obstetrics to stop premature labor and prevent seizures in women with hypertension. The BEAM trial studied the link between magnesium sulfate and cerebral palsy by identifying 2,240 women who were likely to give birth more than two months premature. Half of the women intravenously received magnesium sulfate while the other half received a placebo. Children born to the women in the study were examined at two-years-old, and results observed that the children in the magnesium group were 50 percent less likely to develop cerebral palsy in comparison to children in the placebo group.

"This is a substantial breakthrough in maternal fetal medicine that could positively impact the health of thousands of babies," said Alan Peaceman, MD, chair of the Division of Maternal Fetal Medicine at Northwestern Memorial Hospital, professor of Obstetrics and Gynecology at the Northwestern University Feinberg School of Medicine, and an investigator in the study. "After 10 years of studying the effects of magnesium sulfate, it has proven to be a successful method of reducing the outcome of cerebral palsy in premature births".........

Posted by: JoAnn      Read more         Source


August 31, 2008, 8:37 PM CT

Door to new cancer, aging treatments

Door to new cancer, aging treatments
Scientists at The Wistar Institute have deciphered the structure of the active region of telomerase, an enzyme that plays a major role in the development of nearly all human cancers. The landmark achievement opens the door to the creation of new, broadly effective cancer drugs, as well as anti-aging therapies.

Scientists have attempted for more than a decade to find drugs that shut down telomerasewidely considered the No. 1 target for the development of new cancer therapysbut have been hampered in large part by a lack of knowledge of the enzyme's structure.

The findings, published online August 31 in Nature, should help scientists in their efforts to design effective telomerase inhibitors, says Emmanuel Skordalakes, Ph.D., assistant professor in Wistar's Gene Expression and Regulation Program, who led the study.

"Telomerase is an ideal target for chemotherapy because it is active in almost all human tumors, but inactive in most normal cells," Skordalakes says. "That means a drug that deactivates telomerase would likely work against all cancers, with few side effects".

The study elucidates the active region of telomerase and provides the first full-length view of the telomerase molecule's critical protein component. It reveals surprising details, at the atomic level, of the enzyme's configuration and how it works to replicate the ends of chromosomesa process critical to both tumor development and the aging process.........

Posted by: Scott      Read more         Source


August 31, 2008, 8:34 PM CT

The association with stress and depression

The association with stress and depression
The brain is the key organ in the response to stress. It reacts in a complex, orchestrated manner that is correlation to the activation and inhibition of neural structures involved in sensory, motor, autonomic, cognitive and emotional processes. It is the brain which finally determines what in the world is threatening and might be stressful for us, and which regulates the stress responses that can be either adaptive or maladaptive. Chronic stress can affect the brain and lead into depression: Environmental stressors (e.g. job and family situation, neighborhood) and particularly stressful life events such as trauma or abuse are amongst the most potent factors to induce depression. Since the development of novel approaches to antidepressant therapy is based upon an improved neurobiological understanding of this condition, new information about the cellular changes that take place in the brain is required.

Depression: a growing public health burden

Depression is a chronic, recurring, multifactorial, and life-threatening disorder, which represents a collection of psychological, neuroendocrine, physiological and behavioural symptoms. Chronicity and frequency of these symptoms constitute the clinical condition. Depressive disorders affect up to 20% of people at some time in their life. In primary care, an estimated 20��% of patients suffer from depression, but often are not diagnosed correctly (Wittchen, 2000).........

Posted by: JoAnn      Read more         Source


August 31, 2008, 8:31 PM CT

New genes for inflammatory bowel disease in children

New genes for inflammatory bowel disease in children
Scientists have discovered two new genes that increase the risk of developing inflammatory bowel disease (IBD) in childhood.

While further study is needed to identify the specific disease-causing mutations in these new genes, the scientists say the genes are especially strong candidates to be added to the list of genes already known to affect IBD. "As we continue to find genes that interact with each other and with environmental influences in this complex, chronic disease, we are building the foundation for personalized therapys tailored to a patient's genetic profile," said co-first author Robert N. Baldassano, M.D., director of the Center for Pediatric Inflammatory Bowel Disease at The Children's Hospital of Philadelphia.

"We will resequence the gene regions we have identified to pinpoint the causative mutations in these genes," added study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at Children's Hospital. "We strongly suspect one gene will provide a compelling target for drug development, given what's known about its biology".

Both authors direct research programs at Children's Hospital and are also faculty members of the University of Pennsylvania School of Medicine. Their study, performed in collaboration with scientists from the Medical College of Wisconsin, The University of Utah, Cincinnati Children's Hospital and two research hospitals in Italy, appears in advance online publication Aug. 31 in Nature Genetics........

Posted by: Scott      Read more         Source



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Did you know?
Scientists at Yale have brought to light a mechanism that regulates the way an internal organelle, the Golgi apparatus, duplicates as cells prepare to divide, according to a report in Science Express.Graham Warren, professor of cell biology, and colleagues at Yale study Trypanosoma brucei, the parasite that causes Sleeping Sickness. Like a number of parasites, it is exceptionally streamlined and has only one of each internal organelle, making it ideal for studying processes of more complex organisms that have a number of copies in each cell.

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