#Early inflammatory response paralyzes T cells In a discovery that is likely to rewrite immunology text books,
immune components that help orchestrate the body's response to pathogens and other invaders. This mechanism may act as a firewall,
However, from a clinical standpoint, this discovery could lead to more effective cancer immunotherapies, better drugs for autoimmune conditions and new ways to expedite recovery from sepsis.
The research online July 28, appears in today's print edition of the journal Immunity.""There's a three-signal process to activate T cells
of which each component is essential for proper activation, "said first author Gail Sckisel, a postdoctoral fellow."
"To be activated, T cells must first recognize an antigen, receive appropriate costimulatory signals, and then encounter inflammatory cytokines to expand the immune response.
Until now, no one realized that sending the third signal early--as is done with some immunotherapies--could actually hamper overall immunity."
that approach could damage a patient's ability to fight off pathogens. While immunotherapies might fight cancer,
they may also open the door to opportunistic infections.""This was shown in mice which, after receiving systemic immunotherapy,
had trouble mounting a primary T-cell response. The finding was confirmed in samples from patients receiving high-dose interleukin 2 therapy to treat metastatic melanoma."
"We need to be very careful because immunotherapy could be generating both short-term gain and long-term loss,"noted lead author William Murphy, professor and acting chair in the UC Davis Department of Dermatology."
"The patients who were receiving immunotherapy were totally shut down, which shows how profoundly we were suppressing the immune system."
"In addition to illuminating how T cells respond to cancer immunotherapy, the study also provides insights into autoimmune disorders.
The researchers believe this CD4 paralysis mechanism could play a role in preventing autoimmunity, a hypothesis they supported by testing immunotherapy in a multiple sclerosis model.
By shutting down CD4 T cells, immune stimulation prevented an autoimmune response. This offers the potential to paralyze the immune system to prevent autoimmunity
"Transplant patients go on immunosuppressants for the rest of their lives, but if we could safely induce paralysis just prior to surgery,
it's possible that patients could develop tolerance, "said Sckisel. CD4 paralysis may also be coopted by pathogens, such as HIV,
which could use this chronic inflammation response to disable the immune system.""This really highlights the importance of CD4 T cells,
"For elderly people who have flu or pneumonia, their immune systems are activated, but maybe they can't fight anything else,
we may be able to better fight infection
#Engineers identify how to keep surfaces dry underwater for months Imagine staying dry underwater for months.
#New aortic heart valve does not require open surgery A new aortic heart valve does not require open heart surgery.
The system is much less invasive than open surgery. The device is called the Corevalve Evolut R System.
The system is much less invasive than open surgery. The newly designed system enables the physician to recapture
and design of the device, is a clinical associate professor in the Department of Thoracic and Cardiovascular Surgery.
Dr. Lewis is an interventional cardiologist and a professor in the Department of Medicine. Dr. Tuchek said the unique design of the Corevalve Evolut R System llows for superior control during deployment of the Corevalve,
Loyola director of Interventional Cardiology. here no question that this is a superior product, Dr. Leya said. he technology is a game changer for patients with aortic stenosis.
Dr. Leya is a professor in the Division of Cardiology of Loyola University Chicago Stritch School of medicine.
which was published in the New england Journal of Medicine. The study found that patients who received the device had significantly lower mortality than heart valve patients who underwent open-heart surgery.
Loyola dedicated implanting team includes two cardiovascular surgeons (Drs. Tuchek and Mamdouh Bakhos, MD) and two interventional cardiologists (Drs.
Leya and Lewis). The team is participating in ongoing Corevalve trials and leads the state in implanting the device.
The improved device now is approved FDA for patients judged to be at high or extremely high risk for conventional open-heart aortic valve surgery (with an estimated 30-day mortality rate of at least 15 percent.
The trial is called SURTAVI (SURGICAL vs. Transcatheter Aortic valve Implantation. SURTAVI is being conducted in 76 sites in eight countries for patients who do not qualify for the transcatheter valves commercially.
Dr. Bakhos is chair of the Department of Thoracic and Cardiovascular Surgery. For more information,
Symptoms include fatigue, dizziness, chest pain/pressure, heart murmurs, shortness of breath during activity, heart palpitations and fainting.
Aortic stenosis can lead to heart failure and death. About 100,000 people in the United states have aortic stenosis a
55 patients with atypical moles agreed to have monitored their skin by researchers at Pisa University Hospital using a laser Doppler system.
which means that melanoma is identified in all cases where it is ruled present, and out in 90.9%of cases where it is not."
"Skin malignant melanoma is a particularly aggressive cancer associated with quick blood vessel growth which means early diagnosis is vital for a good prognosis.
The current diagnostic tools of examination by doctors followed by biopsy inevitably leads to many unnecessary invasive excisions."
"This simple, accurate, in vivo distinction between malignant melanoma and atypical moles may lead to a substantial reduction in the number of biopsies currently undertaken
#Turning breath into words: New device unveiled to give paralysis victims a voice A new device
which transforms paralysis victims'breath into words--believed to be the first invention of its kind--has been developed by academics from Loughborough University.
Billed as a tool to help bring back the art of conversation for sufferers of severe paralysis and loss of speech,
the prototype analyses changes in breathing patterns and converts'breath signals'into words using pattern recognition software and an analogue-to-digital converter.
and Dr Kaddour Bouazza-Marouf, Reader in Mechatronics in Medicine, said the device learns from its user,
The academics have been joined in the project by Dr Atul Gaur, Consultant Anaesthetist at Glenfield Hospital."
or other speech disorders communicate. In an intensive care setting, the technology has the potential to be used to make an early diagnosis of locked-in syndrome (LIS),
by allowing patients, including those on ventilators, to communicate effectively for the first time by breathing--an almost effortless act
Robert is no stranger to AAC devices, having already invented a prototype called the m (eye) DAQ--a low cost digital letter board that allows victims of paralysis to communicate via eye blinks or finger movements s
and decide which ones to implant to have the best chance of success, "said Dr Melanie White e
#New synthetic tumor environments make cancer research more realistic University of Illinois researchers have developed a new technique to create a cell habitat of squishy fluids, called hydrogels,
and grow into a tumor. They were able to observe how differently cells act in the three-dimensional, gel-like environment,
and expensive mouse avatars that are created by injecting human tumor cells into mice.""This is really the first time that it's been demonstrated that you can use a rapid methodology like this to spatially define cancer cells and macrophages,
Can therapeutics be used to disrupt that communication? What sets the team's model apart from mouse avatars
and finds out they've been diagnosed with some sort of solid tumor, "Kilian said.""You take a biopsy of those cells,
you put it into this device, grow them and see how they respond to different treatments
Scientists can use the NAPA to determine changes in cellular metabolite level distributions and metabolic noise upon environmental stress
the research group has determined the metabolic response of individual yeast cells to oxidative stress. Additionally, the NAPA platform has shown the capabilities to analyze a wide variety of biomolecules
#Scientists create designer proteins that control enzyme activity Scientists from the University of Chicago have developed a novel approach to control the activity of enzymes through the use of synthetic, antibody-like proteins known as monobodies.
have widespread implications for a broad range of industrial, scientific and medical applications in which enzymes are used."
who also serves as a Scientific Director for the Chicago Biomedical Consortium.""In this paper, we demonstrated their efficacy on sugars,
such as the preparation of foods, dietary supplements, therapeutics and chemical materials. A major goal in biotechnology is to modify enzyme activity
Koide and his colleagues approached this problem by leveraging their longstanding expertise in designing monobodies--compact proteins that function as synthetic antibodies.
Like antibodies, monobodies recognize and bind to specific target proteins, serving as a marker or affecting function.
Coupled with their small size (around 15 times smaller than an antibody) and simple structure,
we could be taking samples of different components of a cancer patient's mammary gland and building a model of their tissue to use as a personalized drug screening platform.
But in diseases such as breast cancer, the breakdown of this order has been associated with the rapid growth and spread of tumors."
it sets the stage for cancer.""But studying how the cells of complex tissues like the mammary gland self-organize,
and break down in disease has been a challenge to researchers. The living organism is often too complex to identify the specific causes of a particular cellular behavior.
but also to experiment with specifically adding in a single cell with a known cancer mutation to different parts of the organoid to observe its effects.
or more cells expressing low levels of the cancer gene Rasg12v affected the cells around them.
or structural changes in mammary glands can lead to the breakdown of tissue architecture associated with tumors that metastasize,
and the UCSF Program in Breakthrough Biomedical Research h
#Alzheimer disease: Overlooked for 30 years, there is a new kid on the block Alzheimer's disease is associated with the appearance of characteristic neurotoxic protein aggregates in various regions in the brain.
Chemical analysis of these insoluble deposits reveals that they are made up of a family of short protein fragments,
referred to as beta-amyloid peptides, which are derived from a precursor protein called APP by the sequential action of two enzymes.
An international team of researchers led by Christian Haass (Professor of Metabolic Biochemistry at LMU and Speaker for the German Center for Neurodegenerative Diseases in Munich) and Dr. Michael Willem (LMU) has made now a discovery
which extends this picture of the pathogenesis of Alzheimer's disease, and has potentially far-reaching implications for our understanding of the condition:"
"A second mode of APP cleavage exists, which involves a previously unknown cleavage and generates an alternative peptide,
the proteolytic enzyme that initiates the release of the toxic beta-amyloid from APP, can reduce memory loss in patients with Alzheimer's.
transmit neurodegeneration Multiple System Atrophy (MSA), a neurodegenerative disorder with similarities to Parkinson's disease, is caused by a newly discovered type of prion,
akin to the misfolded proteins involved in incurable progressive brain diseases such Creutzfeldt-jakob disease (CJD), according to two new research papers led by scientists at UC San francisco. The findings suggest new approaches to developing treatments for MSA,
which currently has no cure, but also raise a potential concern for clinicians or scientists who come in contact with MSA tissue.
The new findings mark the first discovery of a human disease caused by a new prion in 50 years
since work at the National institutes of health in the 1960s showed that human brain tissue infected with CJD could transmit neurodegeneration to chimpanzees.
It wasn't until 1982 that UCSF's Stanley Prusiner, MD isolated the causative agent for a related disease called scrapie,
found in sheep, and characterized it as a prion, for"infectious protein.""He then determined that the same prion protein caused bovine spongiform encephalopathy (BSE),
and spread disease was dismissed by the scientific community, as a tenet of modern biology held that only viruses
and living microbes such as bacteria could transmit disease. But subsequent work by Prusiner and others led to an understanding of how prions function at a molecular level.
Prusiner, a professor of neurology and director of the Institute for Neurodegenerative Diseases (IND) at UCSF
was awarded the Nobel prize in Physiology or Medicine for this work in 1997. Prion researchers have suggested
since that similar misfolded proteins may contribute to more common forms of neurodegeneration, such as Parkinson's disease and Alzheimer's disease."
"said UCSF's Kurt Giles, DPHIL, associate professor of neurology, IND researcher and senior author on the second of the two new studies."
First described in 1960, MSA is a progressive neurodegenerative disorder that is rare but more common than CJD:
Its early symptoms can be mistaken for those of Parkinson's disease, and include movement and balance problems,
Unlike Parkinson's patients, who often live 10 to 20 years after their diagnosis, MSA patients typically die within five to 10 years
As in Parkinson's disease, neurodegeneration in MSA is accompanied by a buildup of clumps of alpha-synuclein protein within brain cells.
Both MSA and PD can arise sporadically in families with no history of the disease,
such as cellular stress and the aging process also are thought to make misfoldings more likely. The new work has its origins in experiments conducted in Prusiner's lab in 2013,
showing that samples of brain tissue from two human MSA patients were able to transmit the disease to a mouse model for Parkinson's disease,
the Massachusetts Alzheimer's disease Research center in Boston, the Parkinson's UK Brain Bank at Imperial College London,
When exposed to human MSA tissue, the mice developed neurodegeneration. In addition, the team found that the brains of infected mice contained abnormally high levels of insoluble human alpha-synuclein,
and that infected mouse brain tissue could itself spread the disease to other mice. The discovery that alpha-synuclein prions can transmit MSA raises a public health concern about treatments
and research that involve contact with brain tissue from neurodegeneration patients, because standard disinfection techniques that kill microbes do not eliminate the Prp prions that cause CJD.
Whether the same challenges hold for alpha-synuclein prions in MSA remains to be determined. The authors write that clinicians
and researchers should adopt much more stringent safety protocols when dealing with tissue from patients with MSA and other neurodegenerative diseases, many
of which they believe may also be caused by prions. For instance, MSA is diagnosed frequently initially as Parkinson's disease,
which is treated often with deep-brain stimulation. The disease could potentially be transmitted to other patients
if deep-brain stimulation equipment is reused.""You can't kill a protein, "Giles said.""And it can stick tightly to stainless steel,
People are living longer and likely getting more brain surgeries. There could be undiagnosed neurodegenerative diseases that
--if they're caused by prions--mean infection could be a real worry.""Unlike the danger of BSE from contaminated beef, the researchers stress that there is no apparent risk of infection by MSA prions outside of specialized medical or research settings.
In the earlier of the group's two PNAS papers published this month, Woerman led a research team in the development of a rapid new method to test prion transmission using human cell cultures.
The team demonstrated that it only takes 4 days for human MSA tissue to infect cultured cells with alpha-synuclein mutations,
in contrast to the 120 days it takes for the disease to spread to mouse models."
"The challenge of studying neurodegeneration is that it's a disease of aging, "Woerman said."
"You have to let the mouse models develop for such a long time that research on cures is really slow to progress.
They presented their findings Aug 26 at the 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society in Milan, Italy.
The researchers also pointed out that this technique does not pose any serious health risks. Since this technique is intended for applications in ultra low power communication systems
the transmitting power of the magnetic signals sent through the body is expected to be many times lower than that of MRI SCANNERS and wireless implant devices.
#Genetic cause of unknown disease uncovered Using modern high-tech methods, followed by thorough clinical, biochemical and molecular biological investigations,
and characterized the disease which is given the name RCDP5. The researchers believe that studies of the effect of the newly discovered genetic error will provide new insight into other diseases.
Arrayin 2004, professor Petter Strømme examined a child with congenital cataract, growth delay and symptoms from the brain, the peripheral nervous system,
and muscles as well as calcifications in cartilage tissue. The patient had two siblings with similar symptoms
Strømme assumed that the disease was caused by a defective gene inherited from the parents, whom he suspected were both carriers of the unknown disease causing mutation.
After clinical and diagnostic odyssey in the following years, and in depth discussions with colleagues internationally, the cause remained unknown.
leaving them more open to illness. Most sleep research focuses on the effects of sleep deprivation
Behavior and Immunity--is a rare look into the circadian process, a brain-driven clock that controls the rhythms of various biological processes, from digestion to blood pressure, heart rate to waking and sleeping.
or an overactive response in others, suggesting the altered circadian cycle made them potentially less able to fight illness
facilitate the development of therapeutics that prevent the proliferation of harmful viruses. The scientific paper entitled"Mutational interference mapping experiment (MIME) for studying RNA structure
Many of the most threatening diseases are transmitted by so-called RNA VIRUSES, such as HIV, influenza, and hepatitis C. What they have in common is that the genome does not consist of DNA, but RNA.
Using MIME, scientists can determine how the genetic material of a virus is incorporated into nascent virions at the end of its reproductive cycle.
This has great significance for medical practice: If it was possible to stop this process, e g.,
, by introducing therapeutic (e g. COMPLEMENTARY RNA, the virus could be rendered harmless. Currently, many RNA-based therapies are under investigation worldwide.
The MIME method can make a significant contribution to this research by helping to identify the appropriate RNA segments.
which mutations are tolerated by the virus and which not, a factor that is useful for the design of therapeutic RNA,
complete paralysis has regained enough voluntary control to actively work with a robotic device designed to enhance mobility.
In addition to the robotic device, the man was aided by a novel noninvasive spinal stimulation technique that does not require surgery.
That earlier achievement is believed to be the first time people who are paralyzed completely have been able to relearn voluntary leg movements without surgery.
and suffered a spinal cord injury that left him paralyzed from the waist down. At UCLA, Pollock made substantial progress after receiving a few weeks of physical training without spinal stimulation
The research will be published by the IEEE Engineering in Medicine and Biology Society, the world's largest society of biomedical engineers."
"It will be difficult to get people with complete paralysis to walk completely independently, but even if they don't accomplish that,
and quality of life,"said V. Reggie Edgerton, senior author of the research and a UCLA distinguished professor of integrative biology and physiology, neurobiology and neurosurgery.
"We need to expand the clinical toolbox available for people with spinal cord injury and other diseases."
and we are encouraged by these findings to broaden our understanding of possible treatment options for paralysis,
"Given the complexities of a spinal cord injury, there will be no one-size-fits-all cure but rather a combination of different interventions to achieve functional recovery."
and approaches to remind the spine of its potential even years after an injury, "he said.
"This is a great example of a therapeutic approach that combines two very different modalities--neuromodulation
This multi-device approach, much like multi-drug therapy, may ultimately benefit patients with impaired mobility in a wide variety of rehabilitation settings."
"Neurorecovery Technologies, a medical technology company Edgerton founded, designs and develops devices that help restore movement in patients with paralysis. The company provided the device used to stimulate the spinal cord in combination with the Ekso in this research.
he now believes it is possible to significantly improve quality of life for patients with severe spinal cord injuries,
mobile microscope could significantly improve malaria diagnoses and treatment in developing countries that often lack the resources to address the life-threatening disease,
says a Texas A&m University biomedical engineer who has created the tool. The add-on device, which is similar in look
and feel to a protective phone case, makes use of a smart phone's camera features to produce high-resolution images of objects 10 times smaller than the thickness of a human hair,
accurate diagnosis. While polarized light has been preferred the option for malaria detection due to its increased sensitivity,
"MOPID could represent a significant advancement in the detection methods for malaria, a disease that the World health organization estimates was responsible for 584,000 deaths in 2013,
along with an estimated 198 million new cases in that span of time. Given those numbers, a dire need exists for a low-cost, accurate and portable method of detection, particularly in areas of the world with few resources,
While failure to treat malaria can be fatal the administering of unnecessary malaria medications as a result of misdiagnoses can results in new, drug-resistant strains of the disease in addition to increasing costs for malaria medications, Coté notes.
Coté's solution takes advantage of existing mobile phone technology and networks--something to which a whopping 75 percent of the world has access.
This ever-increasing access to mobile networks and the fact that most mobile phones are equipped with advanced camera features make mobile phones the ideal platform for advanced imaging applications such as MOPID,
and specificity to detect malaria with both ios -and Android-based devices and requires less user expertise than traditional microscopy,
That user friendly aspect, coupled with the system's portability and expected low cost of about $10 per unit, makes it an easily adoptable technology in low-resource areas ravaged by malaria,
complexity and lack of expertly trained technicians can often prohibit the use of a polarized microscopy technique or even traditional laboratory microscopy as the standard of diagnosis,
while being worn on the wrist could bridge the communications gap between the deaf and those who don't know sign language,
Researchers discover a gene variant that provides a delaying mechanism for Alzheimer's disease Medical research has yet to discover an Alzheimer's treatment that effectively slows the disease's progression,
The findings appear in the journal Molecular Psychiatry. Lead author Matthew Lalli who earned his Ph d. working in UCSB's Kosik Research Group,
These individuals have a rare gene mutation that leads to full-blown disease around age 49. However, in a few outliers, the disease manifests up to a decade later."
"We wanted to study those who got the disease later to see if they had a protective modifier gene,
"said co-author Kenneth S. Kosik, co-director of UCSB's Neuroscience Research Institute and a professor in the Department of Molecular, Cellular and Developmental biology."
We hypothesized the existence of gene variant actually pushes the disease onset as much as 10 years later."
the UCSB researchers collaborated with UC San francisco to study 150 individuals affected with Alzheimer's or dementia.
whether blood transfusion from young individuals to older ones confers benefits.""The results of this work may provide additional evidence that eotaxin plays a role in the deleterious effects of aging,
then we can modify the level of eotaxin in individuals to treat the disease. But our results must be replicated
#How anesthesia may fight lung infections: Mouse study The Johns Hopkins and University of Buffalo research team built its experiments on previous research showing that children with upper viral respiratory tract infections who were exposed to the anesthetic halothane during minor surgical procedures had significantly less respiratory symptoms
and a shorter duration of symptoms compared with children who did not receive halothane during surgeries.
Arraythe team discovered that giving the animals volatile anesthetics, such as halothane, led to decreased bacterial burden and lung injury following infection.
The researchers report that the anesthetics augmented the antibacterial immune response after influenza viral infection by blocking chemical signaling that involves type I interferon
a group of proteins that help regulate the activity of the immune system. Using a combination of genetic, molecular,
as if the animals were infected never with a prior influenza virus. Array"Our study is giving us more information about how volatile anesthetics work with respect to the immune system,
suggest that volatile anesthetics may someday be helpful for combatting seasonal and pandemic influenza, particularly when there are flu vaccine shortages or limitations."
"A therapy based on these inhaled drugs may help deal with new viral and bacterial strains that are resistant to conventional vaccines
and treatments and could be a game changer in terms of our preparedness for future pandemics and seasonal flu outbreaks because it's focusing on host immunity,
"says Chakravarthy.""We hope our study opens the door to the development of new drugs
and therapies that could change the infectious disease landscape.""The investigators say they are currently testing an oral small molecule immune modulator in phase 2 clinical trials that acts like volatile anesthetics to help reduce secondary infections after someone becomes sick with the flu u
#Mathematical'Gingko trees'reveal mutations in single cells that characterize diseases A new interactive analysis program called Gingko has been released that reduces the uncertainty of single-cell analysis
and provides a simple way to visualize patterns in copy number mutations across populations of cells.
Detailed knowledge of CNVS can point to specific treatment regimens. The problem is that current techniques for acquiring this knowledge are difficult
disease can occur. Such mutations have been linked not only with cancer but a host of other illnesses, including autism and schizophrenia.
Researchers can learn a lot by analyzing CNVS in bulk samples--from a tumor biopsy for example--but they can learn more by investigating CNVS in individual cells."
"You may think that every cell in a tumor would be the same, but that's actually not the case,"says CSHL Associate professor Michael Schatz."
"We're realizing that there can be a lot of changes inside even a single tumor, "says Schatz."
"If you're going to treat cancer, you need to diagnose exactly what subclass of cancer you have."
"Simultaneously employing different drugs to target different cancer subclasses could prevent remission, scientists have proposed. One powerful single-cell analytic technique for exploring CNV is whole genome sequencing.
The challenge is that, before sequencing can be done, the cell's DNA has to be amplified many times over.
This process is rife with errors, with some arbitrary chunks of DNA being amplified more than others. In addition, because many labs use their own software to examine CNVS,
there is little consistency in how researchers analyze their results. To address these two challenges, Schatz and his colleagues created Gingko.
which has documented many well therapeutic benefits.""We like to think our Gingko'trees'will provide benefits as well,
Right now, CNV is not a commonly used diagnostic measurement in the clinic.""We're looking into the best way of collecting samples,
He adds that CSHL has collaborations with many hospitals, notably Memorial Sloan Kettering Cancer Center and the North Shore-LIJ Health System,
to bring single-cell analysis to the clinic. For Schatz, Gingko represents a culmination of CSHL's efforts over the past decade--spearheaded by CSHL Professor Michael Wigler--to pioneer techniques for studying single cells."
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