Miraca Holdings Inc., a Japan-based holding company in the healthcare sector, recently announced that its affiliate Innogenetics N.V. in Ghent (Belgium) had changed its name to Fujirebio Europe N.V. The name change is the next logical step in an integration process that was launched by the acquisition in September 2010 of Innogenetics N.V. by Fujirebio Inc., a subsidiary of Miraca Holdings. Fujirebio is recognized as a key player in oncology for routine and novel IVD markers. Th e name change confirms Fujirebio’s strong commitment to the introduction of the Lumipulse immunoanalyser range in laboratories across Europe. The Lumipulse G1200 was presented to the European market for the first time in Italy in November 2011 and this fully automated chemiluminescent enzyme immunoassay (CLEIA) system is now available to laboratories in Spain and will soon be available in Germany and France.
www.fujirebio-europe.com
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Kashin-Beck disease (KBD) and Keshan disease (KD) are major endemic diseases in China. Postgraduate Xi Wang et al., under the guidance of Professor Xiong Guo from the Institute of Endemic Diseases of the Faculty of Public Health, Medicine College of Xi’an Jiaotong University, Key Laboratory of Environment and Gene Related Diseases in Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases of Health Ministry, set out to tackle these two endemic diseases. After several years of innovative research, they have made significant progress in determining the etiology and pathogenesis of these diseases at a molecular level; in particular, the identification of some common differentially expressed genes.
KBD and KD are distributed from the northeast to the southwest of China, where the selenium content is low in the soil. In China, there are 660000 KBD and 40000 KD patients, and approximately 30 million people are at risk. KBD is an endemic osteoarthropathy, the pathologic changes of KBD included significant alterations in chondrocyte phenotype, necrosis, and apoptosis, and abnormal terminal chondrocyte differentiation. The mainly pathologic changes of KD are multifocal myocardial necrosis and fibrosis that can result in cardiogenic shock and congestive heart failure. KD is an endemic myocardosis that happened in women and pre-schoolers. Since osteoarthritis and myocardium deformities, the most of KBD and KD patients will partially or completely lose their abilities to work even self-care, which seriously reduces their quality of life, and also bring heavy medical burden to society; the etiology and pathogenesis of KBD and KD remain unclear. However, both diseases happened in the same area of China. Moreover, the living conditions of KBD and KD patients are similar, for example, most patients live in remote rural areas and the areas of awful transportation, have a meager income, and a simply diet. There is little research conducted to compare KBD and KD gene expression profiles. Therefore, the two diseases may have a further relationship at the molecular biology level.
In this study, the Agilent Human 1A Oligo microarray was used to compare gene expression profiles of peripheral blood mononuclear cells (PBMCs) between KBD or KD patients and healthy controls, and identified the common genes differentially expressed in both diseases groups. One hundred and thirty-six differentially expressed genes (53 up-regulated and 83 down-regulated) were identified between KBD and normal controls. Moreover, comparing KD and normal controls, 3310 differentially expressed genes (3154 up-regulated and 156 down-regulated) were identified. Comparing all identified differentially expressed genes, 16 genes showed differential expression in both diseases, including nine with synchronous and seven with asynchronous expression. These 16 genes were subdivided into 11 categories, namely metabolism, cytochrome enzymes, transcription-related, G-protein-related, receptor, cytokine factor, ion channel transport protein, signal transduction, hematopoietic related, interleukin, and immune-related.
The distribution of KBD and KD is in the similar geographical regions, although the clinical presentations and target pathological focus are not same. The common differentially expressed genes identified in both KBD and KD could be helpful to identify the potential mechanisms of the different organ lesions, caused by similar environmental risk factors, selenium deficiency. These findings make a great contribution towards clarifying the etiology and pathogenesis of KBD and KD.
EurekAlert
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Type 2 diabetes accounts for 90 % of cases of diabetes around the world, afflicting 2.5 million Canadians and costing over 15 billion dollars a year in Canada. It is a severe health condition which makes body cells incapable of taking up and using sugar. Dr. Alexey Pshezhetsky of the Sainte-Justine University Hospital Research Center, affiliated with the University of Montreal, has discovered that the resistance to insulin seen in type 2 diabetics is caused partly by the lack of a protein that has not previously been associated with diabetes. This breakthrough could potentially help to prevent diabetes.
‘We discovered that Neu1, a protein nicknamed after ‘neuraminidase 1’, turns the absorption of sugar ‘on’ or ‘off’ in body cells, by regulating the amount of sialic acid on the surface of cells’, Dr. Pshezhetsky explains.
‘We are now trying to find a way to restore Neu1 levels and function in diabetes. If we can remove sialic acid residues from the cell surface, this will force the insulin receptor do its job of absorbing blood sugar properly. This could give doctors an opportunity to reduce the use of insulin therapy, and might help to reduce the diabetes epidemic, says Dr. Pshezhetsky.
Although type 2 diabetes is initially treated with diet, exercise and tobacco avoidance, doctors try to restore normal levels of insulin by prescribing it when this fails. The number of cases diagnosed around the world continues to grow incredibly quickly: according to the United States Center Disease Control, cases in that country grew on average by 82% between 1995 and 2010. In Oklahoma, the number increased by 226%. The disease accounts for 90% of diabetes cases around the world, and its prevalence has increased in parallel with the obesity epidemic. Obesity is in fact thought to cause this disease which can in turn lead to heart disease, strokes and even limb amputation due to poor circulation.
University of Montreal
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Researchers have identified a set of genes that allow melanoma cells, a type of cancer cell, to change rapidly between two shapes to escape from the skin and spread around the body. This new research – funded by the Wellcome Trust, Cancer Research UK and the US National Institutes of Health – could pave the way for scientists to develop desperately needed drugs for malignant melanoma, the deadliest form of skin cancer, which kills more than 2200 people every year.
The most dangerous aspect of melanoma is its ability to spread, or become malignant, to other parts of the body in the later stages of disease. This most often includes the liver, lungs and brain.
Dr Chris Bakal, a Wellcome Trust research fellow at the Institute of Cancer Research, London, explains: ‘We already knew that metastatic melanoma cells, or cells that are able to spread through the body, have to be able to adopt different shapes so that they can squeeze their way between healthy cells and move around the body.
‘The cells have to become rounded to travel through the bloodstream or invade soft tissues such as the brain, but they take on an elongated shape to travel through harder tissues like bone. But until now, we knew hardly anything about how the cells assume either of these shapes and how they switch between the two.’
To investigate this, researchers at the Institute of Cancer Research, London, and Weill Cornell Medical College in Houston started out by looking at fruit fly cells. They found that under normal conditions, the fruit fly cells grew in five different shapes. By switching off specific genes, they were able to change the mix of shapes among the fruit fly cells and identify several different genes that control a cell’s shape-shifting ability.
When they looked in human melanoma cells, they found that the human versions of these genes had a similar effect. In particular, they noted that switching off a gene called PTEN increased the proportion of cells that were elongated rather than rounded.
PTEN is a gene that is also involved in stopping healthy cells from becoming cancer cells, a so-called ‘tumour suppressor’ gene. This particular gene is switched off in around 1 in 8 melanoma patients and in almost half of melanoma patients who carry a mutation in another cancer gene called BRAF.
‘We think that metastatic melanoma cells lose their PTEN function so that they can increase their shape-shifting ability, which in turn enables them to move to many different tissues within the body. It’s early days, but taken together our findings offer new opportunities to develop drugs to try and stop the spread of melanoma,’ Dr Bakal added.
Dr Julie Sharp, Senior Science Communications Manager at Cancer Research UK, said: ‘This is still early research, but it gives us a better grasp of the way cancer cells behave in the body. By mimicking these conditions, our researchers are learning more about melanoma and bringing us closer to beating it.
Wellcome Trust
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Life-threatening blood clots can form in anyone who sits on a plane for a long time, is confined to bed while recovering from surgery, or takes certain medications.
There is no fast and easy way to diagnose these clots, which often remain undetected until they break free and cause a stroke or heart attack. However, new technology from MIT may soon change that: A team of engineers has developed a way to detect blood clots using a simple urine test.
The noninvasive diagnostic, relies on nanoparticles that detect the presence of thrombin, a key blood-clotting factor.
Such a system could be used to monitor patients who are at high risk for blood clots, says Sangeeta Bhatia, senior author of the paper and the John and Dorothy Wilson Professor of Biochemistry.
‘Some patients are at more risk for clotting, but existing blood tests are not consistently able to detect the formation of new clots,’ says Bhatia, who is also a senior associate member of the Broad Institute and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).
Blood clotting is produced by a complex cascade of protein interactions, culminating in the formation of fibrin, a fibrous protein that seals wounds. The last step of this process — the conversion of fibrinogen to fibrin — is controlled by an enzyme called thrombin.
Current tests for blood clotting are very indirect, Bhatia says. One, known as the D-dimer test, looks for the presence of fibrin by-products, which indicates that a clot is being broken down, but will not detect its initial formation.
Bhatia and her colleagues developed their new test based on a technology they first reported last year for early detection of colorectal cancer. ‘We realised the same exact technology would work for blood clots,’ she says. ‘So we took the test we had developed before, which is an injectable nanoparticle, and made it a thrombin sensor.’
The system consists of iron oxide nanoparticles, which the Food and Drug Administration has approved for human use, coated with peptides (short proteins) that are specialized to interact with thrombin. After being injected into mice, the nanoparticles travel throughout the body. When the particles encounter thrombin, the thrombin cleaves the peptides at a specific location, releasing fragments that are then excreted in the animals’ urine.
Once the urine is collected, the protein fragments can be identified by treating the sample with antibodies specific to peptide tags included in the fragments. The researchers showed that the amount of these tags found in the urine is directly proportional to the level of blood clotting in the mice’s lungs.
In the previous version of the system, reported last December in Nature Biotechnology, the researchers used mass spectrometry to distinguish the fragments by their mass. However, testing samples with antibodies is much simpler and cheaper, the researchers say.
MIT
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Researchers from King’s College London and the University of Nottingham have identified neuroimaging markers in the brain which could help predict whether people with psychosis respond to antipsychotic medications or not.
In approximately half of young people experiencing their first episode of a psychosis (FEP), the symptoms do not improve considerably with the initial medication prescribed, increasing the risk of subsequent episodes and worse outcome. Identifying individuals at greatest risk of not responding to existing medications could help in the search for improved medications, and may eventually help clinicians personalise treatment plans.
In a study, researchers used structural Magnetic Resonance Imaging (MRI) to scan the brains of 126 individuals – 80 presenting with FEP, and 46 healthy controls. Participants had an MRI scan shortly after their FEP, and another assessment 12 weeks later, to establish whether symptoms had improved following the first treatment with antipsychotic medications.
The researchers examined a particular feature of the brain called ‘cortical gyrification’ – the extent of folding of the cerebral cortex and a marker of how it has developed. They found that the individuals who did not respond to treatment already had a significant reduction in gyrification across multiple brain regions, compared to patients who did respond and to individuals without psychosis. This reduced gyrification was particularly present in brain areas considered important in psychosis, such as the temporal and frontal lobes. Those who responded to treatment were virtually indistinguishable from the healthy controls.
The researchers also investigated whether the differences could be explained by the type of diagnosis of psychosis (eg. with or without affective symptoms, such as depression or elated mood). They found that reduced gyrification predicted non-response to treatment independently of the diagnosis.
Dr Paola Dazzan from the Department of Psychosis Studies at King’s College London’s Institute of Psychiatry, and senior author of the paper, says: ‘Our study provides crucial evidence of a neuroimaging marker that, if validated, could be used early in psychosis to help identify those people less likely to respond to medications. It is possible that the alterations we observed are due to differences in the way the brain has developed early on in people who do not respond to medication compared to those who do.’
She continues:’There have been few advances in developing novel anti-psychotic drugs over the past 50 years and we still face the same problems with a sub-group of people who do not respond to the drugs we currently use. We could envisage using a marker like this one to identify people who are least likely to respond to existing medications and focus our efforts on developing new medication specifically adapted to this group. In the longer term, if we were able to identify poor responders at the outset, we may be able to formulate personalised treatment plans for that individual patient.’
Dr Lena Palaniyappan from the University of Nottingham adds: ‘All of us have complex and varying patterns of folding in our brains. For the first time we are showing that the measurement of these variations could potentially guide us in treating psychosis. It is possible that people with specific patterns of brain structure respond better to treatments other than antipsychotics that are currently in use. Clearly, the time is ripe for us to focus on utilising neuroimaging to guide treatment decisions.’
King’s College London
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Sensory processing disorders (SPD) are more prevalent in children than autism and as common as attention deficit hyperactivity disorder, yet it receives far less attention partly because it’s never been recognised as a distinct disease.
In a groundbreaking new study from UC San Francisco, researchers have found that children affected with SPD have quantifiable differences in brain structure, for the first time showing a biological basis for the disease that sets it apart from other neurodevelopmental disorders.
One of the reasons SPD has been overlooked until now is that it often occurs in children who also have ADHD or autism, and the disorders have not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.
‘Until now, SPD hasn’t had a known biological underpinning,’ said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF. ‘Our findings point the way to establishing a biological basis for the disease that can be easily measured and used as a diagnostic tool,’ Mukherjee said.
Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with social interaction. Furthermore, a sound that one day is an irritant can the next day be sought out. The disease can be baffling for parents and has been a source of much controversy for clinicians, according to the researchers.
‘Most people don’t know how to support these kids because they don’t fall into a traditional clinical group,’ said Elysa Marco, MD, who led the study along with postdoctoral fellow Julia Owen, PhD. Marco is a cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital, ranked among the nation’s best and one of California’s top-ranked centers for neurology and other specialties, according to the 2013-2014 U.S. News & World Report Best Children’s Hospitals survey.
‘Sometimes they are called the ‘out of sync’ kids. Their language is good, but they seem to have trouble with just about everything else, especially emotional regulation and distraction. In the real world, they’re just less able to process information efficiently, and they get left out and bullied,’ said Marco, who treats affected children in her cognitive and behavioural neurology clinic.
‘If we can better understand these kids who are falling through the cracks, we will not only help a whole lot of families, but we will better understand sensory processing in general. This work is laying the foundation for expanding our research and clinical evaluation of children with a wide range of neurodevelopmental challenges – stretching beyond autism and ADHD,’ she said.
University of California – San Francisco
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Diagnostica Stago S.A.S, a privately held company that provides reference tests and instrumentation in hemostasis, announced that the company has entered a joint research agreement with Bristol-Myers Squibb Company (BMY) to develop an assay for measuring the circulating blood concentration of the oral Factor Xa inhibitor ELIQUIS (apixaban). No commercial assay is presently available to specifically measure apixaban plasma concentration. Terms of the agreement were not disclosed.
“Stago is pleased to have the opportunity to develop this test”, said Tristan Herve, Director of Pharmaceutical Development, “These oral Factor Xa inhibitors address an important unmet need for patients requiring anticoagulant therapy”.
Stago has already completed prototype development and will be applying for health authority approvals of the assay worldwide. Diagnostica Stago retains 100 percent global development and commercialization rights for the assay.
www.stago.com
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What are some of the most troubling numbers in mental health? Six to 10 — the number of years it can take to properly diagnose a mental health condition. Dr. Elizabeth Osuch, a Researcher at Lawson Health Research Institute and a Psychiatrist at London Health Sciences Centre and the Department of Psychiatry at Western University, is helping to end misdiagnosis by looking for a ‘biomarker’ in the brain that will help diagnose and treat two commonly misdiagnosed disorders.
Major Depressive Disorder (MDD), otherwise known as Unipolar Disorder, and Bipolar Disorder (BD) are two common disorders. Currently, diagnosis is made by patient observation and verbal history. Mistakes are not uncommon, and patients can find themselves going from doctor to doctor receiving improper diagnoses and prescribed medications to little effect.
Dr. Osuch looked to identify a ‘biomarker’ in the brain which could help optimise the diagnostic process. She examined youth who were diagnosed with either MDD or BD (15 patients in each group) and imaged their brains with an MRI to see if there was a region of the brain which corresponded with the bipolarity index (BI). The BI is a diagnostic tool which encompasses varying degrees of bipolar disorder, identifying symptoms and behavior in order to place a patient on the spectrum.
What she found was the activation of the putamen correlated positively with BD. This is the region of the brain that controls motor skills, and has a strong link to reinforcement and reward. This speaks directly to the symptoms of bipolar disorder. ‘The identification of the putamen in our positive correlation may indicate a potential trait marker for the symptoms of mania in bipolar disorder,’ states Dr. Osuch.
In order to reach this conclusion, the study approached mental health research from a different angle. ‘The unique aspect of this research is that, instead of dividing the patients by psychiatric diagnoses of bipolar disorder and unipolar depression, we correlated their functional brain images with a measure of bipolarity which spans across a spectrum of diagnoses.’ Dr. Osuch explains, ‘This approach can help to uncover a ‘biomarker’ for bipolarity, independent of the current mood symptoms or mood state of the patient.’
Moving forward Dr. Osuch will repeat the study with more patients, seeking to prove that the activation of the putamen is the start of a trend in large numbers of patients.
Lawson Health Research Institute
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Chlamydia trachomatis is a human pathogen that is the leading cause of bacterial sexually transmitted disease worldwide with more than 90 million new cases of genital infections occurring each year. About 70 percent of women infected with Chlamydia remain asymptomatic and these bacteria can establish chronic infections for months, or even years. Even when it causes no symptoms, Chlamydia can damage a woman’s reproductive organs. In addition, standard antibacterial drugs are proving increasingly ineffective in complete eradication, as Chlamydia goes in to persistent mode, leading to asymptomatic chronic infection. Researchers at the Max Planck Institute for Infection Biology in Berlin (MPIIB) now show that Chlamydia infections can cause mutations in the host DNA by overriding the normal mechanisms by which their host prevents unregulated growth of genetically damaged cells that pave the way for the development of cancer.
Owing to their intracellular lifestyle Chlamydia depend on various host cell functions for their survival. Chlamydia manipulates the host cell mechanism to favour its growth, however the consequences of such alterations on the fate of host cells remains enigmatic. Even more worrying is mounting epidemiological evidence which links Chlamydia infections with the development of cervical and ovarian cancer. Cindrilla Chumduri, Rajendra Kumar Gurumurthy and Thomas F. Meyer, researchers at the Max Planck Institute for Infection Biology in Berlin, have now discovered that Chlamydia induces long-lasting effects on the genome and epi-genome of their host cells. Such changes are increasingly implicated in the development of a range of cancers.
The team found increased levels of DNA breaks in Chlamydia-infected cells. In normal cells, depending on the extent of damage, cells either ‘commit suicide’ or activate repair by special protein complexes in a process called the DNA Damage Response, which reseals the broken strands of DNA and makes sure the sequence of the genetic code has not been changed. Crucially, in Chlamydia-infected cells the DNA Damage Response was impaired, leading to an error-prone repair of the DNA breaks- a potential cause of mutations. Strikingly, despite the presence of extensive DNA damage, Chlamydia infected cells continued to proliferate, facilitated by additional pro-survival signals activated in the host cells by Chlamydia. The flip-side of this forced survival of damaged cells is an increased tendency to evade the normal mechanisms that eliminate cells carrying mutations that could lead to cancer. The team believe that this could be the first step on the path to carcinogenesis of the infected cells, due to uncontrolled cell growth in the presence of accumulating DNA damage – the hallmark of cancer.
The identification of infections as the origin of human cancers is important since it would allow early prevention of cancerogenesis by means of vaccination or antibiotic treatment. Such preventive strategies are currently successfully pursued against the cancer-inducing agents Human Papiloma Virus (HPV) and Helicobacter pylori, the etiological agents of cervical and gastric cancer, respectively. However, many infection-based cancer etiologies have not been firmly established and therefore cancer treatment is usually restricted to patients at an advanced stage and with an established cancer diagnosis. The department of Professor Meyer at MPIIB therefore vigorously pursues several lines of research to unequivocally assess the linkage between bacterial infections and cancer, apart from the well-known carcinogenic role of H. pylori. The current paper by Chumduri et al. constitutes one important mosaic piece, corroborating a potential link between female ascending Chlamydia infections and ovarian cancer in particular.
Max Planck Society
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