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April 23, 2007, 5:17 PM CT

Protecting Nerve Fibers In MS

Protecting Nerve Fibers In MS
Oregon Health & Science University neuroresearchers are eyeing a protein as a potential therapeutic target for multiple sclerosis because de-activating it protects nerve fibers from damage.

OHSU researchers, working with colleagues at the Portland Veterans Affairs Medical Center and the University of Padova in Italy, have shown that genetically inactivating a protein called cyclophilin D can protect nerve fibers in a mouse model of multiple sclerosis. Cyclophin D is a key regulator of molecular processes in the nerve cell's powerhouse, the mitochondrion, and can participate in nerve fiber death. Inactivating cyclophilin D strengthens the mitochondrion, helping to protect nerve fibers from injury. The findings are published recently in Proceedings of the National Academy of Sciences.

"We're extremely excited," said Michael Forte, Ph.D., senior scientist at the Vollum Institute at OHSU and the study's lead author. "While we can't genetically inactivate cyclophilin D in people, there are drugs out there that can block the protein. Our research predicts that drugs that block cyclophilin D should protect nerve fibers from damage in MS".

Such a drug would be the first treatment specifically for secondary-progressive MS, one of the more debilitating forms of MS involving an initial period of relapsing and remitting, followed by a steady worsening of symptoms. It affects half of the estimated 2 million people with MS.........

Posted by: Scott      Read more         Source


April 23, 2007, 5:14 PM CT

Protein Is Critical To Formation Of Muscles

Protein Is Critical To Formation Of Muscles
Proper formation of the proteins that power heart and skeletal muscle seems to rely on a precise concentration of a "chaperone" protein known as UNC-45, as per a new study.

This basic discovery may have important implications for understanding and eventually treating heart failure and muscle wasting elsewhere in the body resulting from burns, brain trauma, diabetes, cancer and the effects of aging, the senior author of the paper said. The finding resulted from experiments using tiny, genetically engineered worms at the University of Texas Medical Branch at Galveston (UTMB), and is reported in a paper featured on the cover of the April 23, 2007, issue of the Journal of Cell Biology.

Chaperone proteins (known to biologists simply as chaperones) guide other newly formed proteins into the shapes that enable them to perform their specific functions.

In muscle cells, UNC-45 acts as a chaperone for myosin proteins, helping them fold into long, thin stable structures which clump together to form the thicker filaments that give heart and skeletal muscle its striated appearance. Chemical signals cause these myosin filaments to contract -- producing a heartbeat, for example, or an arm movement.

Researchers already knew that a shortage of UNC-45 disrupted myosin formation, leading to muscle paralysis. The reason: when there's not enough UNC-45 to go around, myosin proteins still not in their final, stable form fall victim to a cellular cleanup squad called the ubiquitin/proteasome system (UPS), which breaks unstable (and presumably malfunctioning) proteins down into their amino acid components.........

Posted by: Scott      Read more         Source


April 21, 2007, 8:16 AM CT

Benefits Of Remote Monitoring

Benefits Of Remote Monitoring Image courtesy of medic4all-services.com
Scientists from Canada and Australia have observed that the use of remote monitoring for patients with chronic heart failure has the potential to significantly improve clinical outcomes (mortality, morbidity and quality indicators).

The use of remote monitoring (telephone support or telemonitoring) to electronically transfer a patients' physiological data such as blood pressure, weight and ECG and oxygen details, to their healthcare provider has increased in prevalence over the past years. As per research recently published in The British Medical Journal, remote monitoring for patients with chronic heart failure helped reduce heart failure admissions to hospitals and lowered all cause mortality by nearly twenty per cent.

"What we found is that the use of remote monitoring programs can improve outcomes in patients with heart failure and such an approach could help deal with the increasing number of patients with chronic heart failure that cannot be accommodated in existing specialty clinics due to access issues correlation to geography, lack of resources or infirmity, said Dr. Finlay McAlister, University of Alberta researcher.

Because remote monitoring (either through close telephone follow-up with specially trained nurses or telemonitoring involving the daily transmission of a patients vital signs, weight and symptoms to health care providers) permits closer follow-up of patients with heart failure, this allows for the potential for earlier detection and management of changes in a patients health.........

Posted by: Janet      Read more         Source


April 21, 2007, 6:49 AM CT

Brain networks strengthened by ion channels

Brain networks strengthened by ion channels
Yale School of Medicine and University of Crete School of Medicine scientists report in Cell April 20 the first evidence of a molecular mechanism that dynamically alters the strength of higher brain network connections.

This discovery may help the development of drug therapies for the cognitive deficits of normal aging, and for cognitive changes in schizophrenia, bipolar disorder, or attention deficit hyperactivity disorder (ADHD).

"Our data reveal how the brains arousal systems influence the cognitive networks that subserve working memorywhich plays a key role in abstract thinking, planning, and organizing, as well as suppressing attention to distracting stimuli," said Amy Arnsten, lead author and neurobiology professor at Yale.

The brains prefrontal cortex (PFC) normally is responsible for so-called executive functions. The ability of the PFC to maintain such memory-based functions declines with normal aging, is weakened in people with ADHD, and is severely disrupted in disorders such as schizophrenia and bipolar disorder.

The current study observed that brain cells in PFC contain ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN), that reside on dendritic spines, the tiny protrusions on neurons that are specialized for receiving information. These channels can open when they are exposed to cAMP (cyclic adenosine monophosphate). When open, the information can no longer flow into the cell, and thus the network is effectively disconnected. Arnsten said inhibiting cAMP closes the channels and allows the network to reconnect.........

Posted by: Daniel      Read more         Source


April 19, 2007, 7:42 PM CT

How Viruses Invade The Brain

How Viruses Invade The Brain
A molecule thought crucial to ferrying the deadly rabies virus into the brain, where it eventually kills, apparently isnt. The surprising finding, say scientists at Jefferson Medical College in Philadelphia, may change the way researchers think about how central nervous system-attacking viruses such as herpes viruses invade the brain and cause disease.

As per Matthias Schnell, Ph.D., professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University, viruses such as rabies must be actively transported to the brain and central nervous system. The LC8 protein was thought to tether viruses to the cellular transport machinery in order to get there.

But Dr. Schnell and his co-workers observed that this protein complex is instead a "transcription factor" that plays a role in virus reproduction. "We believe that this finding has implications not only for rabies but a number of viruses that previously were thought to use this complex for transport, such as herpes viruses," he says. They report their results online this week in the journal Proceedings of the National Academy of Sciences.

To understand the role of LC8 in rabies disease in the brain, the team compared a rabies virus strain with the LC8 "binding domain" (where the rabies virus and LC8 protein interact) to a virus lacking it. They showed that in mice that were infected with rabies without the LC8 binding domain, the virus was still able to infect the brain, but did not cause disease. The virus ability to reproduce was greatly diminished.........

Posted by: Daniel      Read more         Source


April 19, 2007, 7:34 PM CT

Novel drug for treating leukemia

Novel drug for treating leukemia
Scientists from the Children's Cancer Hospital at The University of Texas M. D. Anderson Cancer Center have observed that a novel targeted treatment effectively treats acute leukemia in animal models by preventing cancer cells from being purged of damaged proteins.

In the March online issue of the journal Blood, researchers reported that the new proteasome inhibitor, NPI-0052, not only successfully kills leukemia cells, but also shows greater efficacy than its predecessor bortezomib when combined with other agents in animal models.

As per researchers, proteasomes clean out mutated or damaged proteins within cells, which promotes cell growth and allows cancer cells to rapidly reproduce. Proteasome inhibitors block this process, resulting in apoptosis, or cell death, of the cancerous cells.

Bortezomib is the first and only FDA-approved proteasome inhibitor. Eventhough it is effective for treating multiple myeloma and mantle cell lymphoma, it was proven to be ineffective as a single agent against leukemia in clinical trials. NPI-0052 varies from bortezomib in ways that scientists at M. D. Anderson hope will make NPI-0052 effective in a human clinical trial.

"NPI-0052 targets the proteasome through different intermediaries and is more potent than bortezomib in leukemia cells," says senior author Joya Chandra, Ph.D., assistant professor of pediatrics from the Children's Cancer Hospital at M. D. Anderson. "Therefore we can use less of the drug to inhibit the proteasome".........

Posted by: Janet      Read more         Source


April 17, 2007, 11:13 PM CT

Stem cells decrease ischemic injury

Stem cells decrease ischemic injury
This is the impressive result of a study carried out by a group of scientists coordinated by Dr. Maria Grazia De Simoni of the Mario Negri Institute in Milan, Italy in cooperation with the Istituto Neurologico Besta (Milan) and the University of Lausanne. The study appears in the April 18th issue of the international, peer-evaluated, open-access online journal of the Public Library of Science, PLoS ONE.

Stroke is the first cause of permanent invalidity and the third cause of death in industrialized countries.

Despite the recent advancements in the management of ischemic patients (early diagnosis, thrombolysis, stroke units and rehabilitation centers), stroke still represents a major and unresolved medical issue.

"Stroke causes the death of a number of nervous cells that, in theory, could be substituted by stem cells. A few studies have shown that these cells can be effective, eventhough various issues about their use and the mechanisms of their protective action remained unsolved," says Maria Grazia De Simoni.

"Our research has underlined a possible mechanism of action. Once introduced in the area of the brain hit by a stroke, stem cells induce the development of a protective effect in this same area," explains De Simoni. "Therefore, it is not necessary, as proposed in past studies, for stem cells to turn into neurons in order to protect the brain from ischemic injury and restore brain functions. Their presence in brain tissue is sufficient to induce a protective reaction".........

Posted by: Daniel      Read more         Source


April 17, 2007, 10:58 PM CT

Insights Into Multiple Sclerosis

Insights Into Multiple Sclerosis Myelin Sheath and Astroglial Filaments
Scientists have developed a way to use three types of microscopic imaging techniques simultaneously to analyze living tissue and learn more about the molecular mechanisms of multiple sclerosis, information that could help lead to earlier detection and new therapys.

The combined imaging method is enabling the scientists to study how multiple sclerosis causes an overproduction of "astroglial filaments," which form bundles between critical nerve fibers and interfere with proper spinal cord functioning. The technique also promises to yield new information about how the disease degrades the myelin sheath, which insulates nerve fibers and enables them to properly conduct impulses in the spinal cord, brain and in the "peripheral nervous system" throughout the body, said Ji-Xin Cheng, an assistant professor in Purdue University's Weldon School of Biomedical Engineering and Department of Chemistry.

The three imaging techniques - called sum frequency generation, two-photon-excitation fluorescence and coherent anti-Stokes Raman scattering - ordinarily are used alone. Purdue scientists have developed a way to combine all three methods in the same platform, promising to reveal new details about the spinal cord and myelin sheath, Cheng said.

"Combining these three methods allows us to conduct more specific and precise molecular analyses," he said. "Ultimately, this work paves the way toward studying the degradation of the myelin sheath as a result of multiple sclerosis and analyzing living tissue to study the mechanisms of disease".........

Posted by: Daniel      Read more         Source


April 17, 2007, 5:05 AM CT

Gene Crucial For Nerve Cell Insulation

Gene Crucial For Nerve Cell Insulation
Scientists funded by the National Institutes of Health have discovered how a defect in a single master gene disrupts the process by which several genes interact to create myelin, a fatty coating that covers nerve cells and increases the speed and reliability of their electrical signals.

The discovery has implications for understanding disorders of myelin production. These disorders can affect the peripheral nervous systemthe nerves outside the brain and spine. These disorders are known collectively according toipheral neuropathies. Peripheral neuropathies can result in numbness, weakness, pain, and impaired movement. They include one of the most common genetically genetic disorders, Charcot-Marie-Tooth disease, which causes progressive muscle weakening.

The myelin sheath that surrounds a nerve cell is analogous to the insulating material that coats an electrical cord or wire, keeping nerve impulses from dissipating, allowing them to travel farther and faster along the length of the nerve cell.

The scientists discovered how a defect in just one copy of the gene, known as early growth response gene 2 (EGR2) affects the normal copy of the gene as well as the functioning of other genes, resulting in peripheral neuropathy.

"The scientists have deciphered a key sequence essential to the assembly of myelin," said Duane Alexander, M.D., Director of the NICHD, the NIH institute that funded the study. "Their discovery will provide important insight into the origins of disorders affecting myelin production".........

Posted by: Daniel      Read more         Source


April 15, 2007, 8:56 PM CT

New non-invasive diagnostic technologies

New non-invasive diagnostic technologies
Molecular messages and signals circulating in blood or contained in cells lining the airway can identify early stage cancer, as per research reported today at the 2007 Annual Meeting of the American Association for Cancer Research. Researchers looking to apply basic science knowledge to medical practice are in the process of developing tests that diagnose, predict or monitor cancer risks, without invasive tissue sampling. Such tests could benefit all, especially underserved populations, such as the poor, who often wait until symptoms appear before seeing a doctor.

Lung carcinogenesis tracked by DNA methylation mapping from exhaled breath of ambulatory subjects: Abstract 827

A series of quietly exhaled breaths might indicate whether or not a patient is at risk for lung cancer, as per scientists from the New York State Department of Health. Using DNA recovered from exhaled breath, scientists can examine the state of cells that line the lungs, and potentially detect cancer at an early stage, when therapy may be most successful.

"Early detection of lung cancer is vital, yet there is no current non-invasive means of identifying cancer in a clinical setting," said Simon Spivack, M.D., M.P.H, research doctor in the Human Toxicology & Molecular Epidemiology Laboratory at the New York State Department of Healths Wadsworth Center. "We have observed that exhaled breath contains DNA, we believe from the cells lining the lungs, which may then tell us whether that person is at risk for cancer".........

Posted by: Janet      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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