Bleeding disorders could one day be diagnosed by putting platelets through strength tests, researchers have proposed. Biomedical engineers from Emory University and the Georgia Institute of Technology have devised a microfluidic testing ground where platelets can demonstrate their strength by squeezing two protein dots together. Imagine rows and rows of strength testing machines from a carnival, but very tiny. A platelet is capable of exerting forces that are several times larger, in relation to its size, than a muscle cells.
After a blood clot forms, it contracts, promoting wound closure and restoration of normal blood flow. This process can be deficient in a variety of blood clotting disorders. Previously, it was difficult to measure an individual platelet’s contributions to contraction, because clots’ various components got in the way.
“We discovered that platelets from some patients with bleeding disorders are ‘wimpier’ than platelets from healthy people,” says Wilbur Lam, an assistant professor in the Department of Pediatrics at Emory University School of Medicine and in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “Our device may function as a new physics-based method to test for bleeding disorders, complementary to current methods.”
The first author of the paper is David Myers, an instructor at Emory’s medical school. Lam is also a physician in the Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta.
The scientists infer how strong or wimpy someone’s platelets are by measuring how far the protein dots move, taking a picture of the rows of dots, and then analysing the picture on a computer.
The dots are made of fibrinogen, a sticky protein that is the precursor for fibrin, which forms a mesh of insoluble strands in a blood clot.
In addition to detecting problems with platelet contraction in patients with known inherited disorders such as Wiskott Aldrich syndrome, Myers, Lam and colleagues could also see differences in some patients who had bleeding symptoms, but who performed normally on standard diagnostic tests.
The researchers also used chemical tools to dissect the process of platelet contraction. They showed that inhibitors of Rho/ ROCK enzymes shut down platelet contraction, but inhibitors of a related pathway, MLCK (myosin light chain kinase), did not. Individual platelet contraction could become an assay for development or refinement of blood thinning drugs, Lam says.

Georgia Techhttp://tinyurl.com/j8byzzg

National Human Genome Research Institute (NHGRI) researchers have identified new genes associated with the Erdheim-Chester disease (ECD) and some possible new therapies.  This ultra-rare disease is found in approximately 600 people in the world.
"The discovery of new genes associated with ECD provides hope for improving the diagnoses of a disease that affects so many parts of the body. We also hope it will help us identify new treatments," said Juvianee I. Estrada-Veras, M.D., clinical investigator and staff clinician in NHGRI’s Medical Biochemical Genetics Residency Program. "Our work on ECD builds on the institute’s goals to advance medical knowledge about rare diseases and to potentially provide insights into more common disorders."
ECD is caused by the accumulation of specialized white blood cells called histiocytes in different organs. The resulting inflammation damages organs and tissues throughout the body, causing them to become thickened, dense and scarred. Histiocytes normally function to destroy foreign substances and protect the body from infection. ECD has no standard therapy, although consensus guidelines for clinical management were published in 2014.
Between 2011 and 2015, researchers examined 60 adults with ECD at the NIH Clinical Center. Of 59 samples that were available for molecular testing, half had BRAF V600E gene mutations, which is sometimes seen in colon cancer, lung cancer, thyroid cancer, brain tumours and some blood cancers. Other patients had mutations in genes of the MAPK pathway, which controls cell growth and proliferation. These findings indicate that, despite the presence of inflammation and the absence of metastases (spread of cancer cells from the place where they first formed to another part of the body), ECD should be considered a type of cancer and treated by oncologists, researchers wrote.
Until now, the most common treatment for ECD has been interferon, a drug that interferes with the division of cancer cells and slows tumour growth. Some patients with severe forms of disease can succumb to the illness even with treatment. The mortality rate for ECD has been estimated at 60 percent at 3 years from the time of diagnosis.
Researchers suggested that therapies that stop the growth and proliferation of cells by blocking the MAPK pathway — vemurafenib, dabrafenib and trametinib — may provide new hope for treating and improving the survival of people with ECD. A therapeutic trial of dabrafenib and trametinib is now enrolling new ECD patients with BRAF V600E mutations.

National Human Genome Research Institute
www.genome.gov/27568398/2017-news-feature-genes-associated-with-erdheimchester-disease-also-linked-to-cancer/

A highly sensitive method that can detect even the earlier stages of colorectal cancer has been developed by researchers in Japan. Shimadzu Corporation, the Kobe University Graduate School of Medicine, and the National Cancer Center in Japan have collaborated to develop a new screening method that comprehensively analyses the metabolites in our blood.
Colorectal cancer is one of the most common causes of cancer death, and cases of this cancer are increasing in developed countries. In 2012, a group headed by Associate Professor YOSHIDA Masaru at Kobe University used gas chromatography-mass spectrometry (GC/MS) and clinical metabolomic analysis methods to analyse serum samples from colorectal cancer patients and healthy subjects. The group succeeded in identifying four metabolite markers that can be used to diagnose colorectal cancer and developed a highly reliable diagnostic prediction model using those markers. This model was considered to be more practical in comparison with existing tumour markers, but it lacked sensitivity and specificity when actually used as a screening method.
Following this, a research team combining members from Shimadzu Corporation and Kobe University developed an analytical approach that enabled much more accurate measurement of metabolites in blood plasma. To achieve this, they used high-speed and high-sensitivity GC-MS/MS, which relies on Shimadzu’s Advanced Scanning Speed Protocol (ASSP) and Smart MRM technologies.
By using this approach to analyse a large number of samples (at least 600) with known clinical data stored at the National Cancer Center, they were able to develop a high-performance screening method. After reviewing the results of comprehensive analyses of the metabolites contained in blood plasma from colorectal cancer patients and healthy subjects, they discovered eight multi-biomarkers that can be used to diagnose colorectal cancer.
Based on the data for these eight metabolites, they were able to create a diagnostic prediction model for colorectal cancer that exceeded 96% for both sensitivity and specificity. They also confirmed that the sensitivity of this new model remained at high levels even with early-stage colorectal cancer patients (stage 0 and stage I).

Kobe University
www.kobe-u.ac.jp/research_at_kobe_en/NEWS/news/2017_04_26_01.html

Beckman Coulter Life Sciences has launched an international HIV/AIDS award at the 2016 conference for the African Society for Laboratory Medicine (ASLM) recently held in Cape Town, South Africa (December 3 to 8).
The annual award is part of the company’s global CARES Initiative dedicated to helping people who are living with HIV/AIDS. Beckman Coulter’s CARES award is designed to recognize individuals who have shown ‘care, dedication and commitment’ in their communities as part of the fight against HIV/AIDS. The winner will receive a $5,000 (€4,700) donation in their name to one of the selected causes, with the three individual stories that receive the most nominations publicized around the world on the CARES Initiative website.
Potential winners can be nurses, healthcare workers, national coordinators, lab scientists and even clinicians; or lay people who are active in community outreach work. This could include a social worker providing AIDS counselling.
CARES supports the UNAIDS 90-90-90 target to ensure that by the year 2020, 90% of people living with HIV will know their status, 90% of those with diagnosed HIV infection will receive sustained antiretroviral therapy, and 90% of all people receiving antiretroviral therapy will have viral suppression.
It focuses on providing innovative solutions for the monitoring of HIV and AIDS treatment. CARES was inspired by the work of Professor Debbie Glencross, a South African laboratory pathologist, who found a different and less expensive way to measure a patient’s CD4 count.
While this is intended as an international award, in its first year, the award  will focus on recognizing the dedication of people in Africa, one of the areas in the world most affected by HIV/AIDS. The 2017 award will be launched at the annual meeting of the African Society for Laboratory Medicine (ASLM), a pan-African professional body aiming to improve laboratory services.  

Recognition for unsung heroes
Samuel Boova, Beckman Coulter’s Director Alliance Development, High Burden HIV Markets,  said: “The award is to give a platform to the work and stories of those we see as the unsung heroes of individual communities. These are people who have shown individual dedication, commitment and courage or who have made a difference in the battle against HIV/AIDS.
“However, it is not just the final winner we want to publicaly recognize. We hope the award will encourage communities to learn about and honour the work of every nominee, so that more people will come forward to help and support those living with HIV/AIDS.”
Nominations must first be made via the CARES website. Once a name has been nominated, the local community will be given the opportunity to vote in support. People with the greatest number of votes will be put forward for the final assessment panel.  Rules of entry and full details are available in full from http://www.beckman.com/cares.
Mr Boova gave the following examples of ordinary people who support their local communities in the field of HIV/AIDS. “We are looking for dedicated and committed individuals like these who work in the community helping others to live with, and manage, the disease,” he added.

Potential Nominees
The first example is how a young HIV positive woman in Uganda was inspired and empowered by a community charity, PINA (People In Need Agency), to rebuild her life and become an advocate herself for young people living with HIV. This was the objective of PINA when it was first set up by a local case worker – to work with young people, helping them overcome the stigma of living with HIV and rebuild their self-esteem.
Mr Boova also pointed out that there are many women in rural Africa who walk miles every day to see patients to ensure they are compliant with their medications. Medication alone does not help without the commitment of these women – and they have to walk many miles between patients each day and every day, whatever the conditions.www.beckman.com/cares

“Mutations are part of life. They are mistakes in a gene like typos in a text message,” said Watanabe-Smith, a postdoctoral fellow with the OHSU Knight Cancer Institute. “But which mutations cause cancer? That’s the real question. And this problem is impossible to understand without a strong model system to test those mutations.”

Watanabe-Smith’s research sought to better understand one “typo” in a standard leukaemia assay, or test. While studying cancer biology and completing his doctorate in the lab of Brian Druker, M.D., at the OHSU Knight Cancer Institute, Watanabe-Smith encountered a new problem: an issue with the model system itself.

“When I was sequencing the patient’s DNA to make sure the original, known mutation is there, I was finding additional, unexpected mutations in the gene that I didn’t put there. And I was getting different mutations every time,” said Watanabe-Smith.

He decided to formally study this phenomenon with his lab advisers, who included Druker; Cristina Tognon, Ph.D., scientific director, Druker lab; and Anupriya Agarwal, Ph.D., assistant professor of hematology & medical oncology, OHSU School of Medicine; researcher with the OHSU Knight Cancer Institute, all co-authors on the paper.  

His initial research, identifying and characterizing a growth-activating mutation in a patient with T-cell leukaemia and was first published last April. This research published was focused on better understanding the lab’s model system, to ensure that future researchers trying to identify cancer-causing mutations are using accurate and reproducible methods.

Their research investigates a common cell line assay, used since the 1980’s, to detect which mutations are important in driving leukaemia and other cancers. They found this assay is prone to a previously unreported flaw, where the cells, called Ba/F3 cells, can acquire additional mutations.

“The potential impact is that a non-functional mutation could appear functional, and a researcher could publish results that would not be reproducible,” Watanabe-Smith said. “Then we had the question: ‘Did the cells transform because of a mutation the patient had, or did they transform because these new mutations they managed to pick up somewhere?’”

Ultimately, he says, the research team recommends an additional step in the Ba/F3 assay (sequencing outgrown cell lines) to improve reproducibility of future results. While the results urge further research, the message to scientific community is clear: There seems to be more potential for problems than previously anticipated in this standard assay.

OHSU Knight Cancer Institutenews.ohsu.edu/2017/02/21/gene-mutations-cause-leukemia-but-which-ones