Biomarker in blood may help predict recovery time for sports concussions

Researchers at the National Institutes of Health found that the blood protein tau could be an important new clinical biomarker to better identify athletes who need more recovery time before safely returning to play after a sports-related concussion. The study, supported by the National Institute of Nursing Research (NINR) with additional funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), published online in the Jan. 6, 2017 issue of Neurology(link is external), the medical journal of the American Academy of Neurology.

Despite the millions of sports-related concussions that occur annually in the United States, there is no reliable blood-based test to predict recovery and an athlete’s readiness to return to play. The new study shows that measuring tau levels could potentially be an unbiased tool to help prevent athletes from returning to action too soon and risking further neurological injury.

“Keeping athletes safer from long-term consequences of concussions is important to players, coaches, parents and fans. In the future, this research may help to develop a reliable and fast clinical lab test that can identify athletes at higher risk for chronic post-concussion symptoms,” said NINR Director Patricia A. Grady Ph.D., R.N.

Athletes who return to play before full recovery are at high risk for long-term symptoms like headaches, dizziness, and cognitive deficits with subsequent concussions. About half of college athletes see their post-concussive symptoms resolve within 10 days, but in others, the symptoms become chronic.

Tau is also connected to development of Alzheimer’s and Parkinson’s diseases, and is a marker of neuronal injury following severe traumatic brain injuries.

In the study, led by Dr. Jessica Gill, NIH Lasker Clinical Research Scholar and chief of the NINR Division of Intramural Research’s Brain Injury Unit, researchers evaluated changes in tau following a sports-related concussion in male and female collegiate athletes to determine if higher levels of tau relate to longer recovery durations.

“Incorporating objective biomarkers like tau into return-to-play decisions could ultimately reduce the neurological risks related to multiple concussions in athletes,” said Gill.

To measure tau levels, a group of 632 soccer, football, basketball, hockey, and lacrosse athletes from the University of Rochester first underwent pre-season blood plasma sampling and cognitive testing to establish a baseline. They were then followed during the season for any diagnosis of a concussion, with 43 of them developing concussions during the study. For comparison, a control group of 37 teammate athletes without concussions was also included in the study, as well as a group of 21 healthy non-athletes.

Following a sports-related concussion, blood was sampled from both the concussed and control athletes at six hours, 24 hours, 72 hours, and seven days post-concussion.

Concussed athletes who needed a longer amount of recovery time before returning to play, (more than 10 days post-concussion) had higher tau concentrations overall at six, 24, and 72-hours post-concussion compared to athletes who were able to return to play in 10 days or less. These observed changes in tau levels occurred in both male and female athletes, as well as across the various sports studied.

Together, these findings indicate that changes in tau measured in as short a time as within six hours of a sports-related concussion may provide objective clinical information to better inform athletes, trainers, and team physicians’ decision-making about predicted recovery times and safe return to play.

Further research will test additional protein biomarkers and examine other post-concussion outcomes.

About the National Institute of Nursing Research (NINR): NINR supports basic and clinical research that develops the knowledge to build the scientific foundation for clinical practice, prevent disease and disability, manage and eliminate symptoms caused by illness, and enhance end-of-life and palliative care. For more information about NINR, visit the website at www.ninr.nih.gov.

About the Eunice Kennedy Shrive National Institute of Child Health and Human Development (NICHD): NICHD conducts and supports research in the United States and throughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit NICHD’s website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Diffuse large B-cell lymphoma , blood cancer in older adults and aspartame -sugar

Diffuse large B-cell lymphoma (DLBCL or DLBL) is a cancer of B cells, a type of white blood cell responsible for producing antibodies. It is the most common type of non-Hodgkin lymphoma among adults,[1] with an annual incidence of 7–8 cases per 100,000 people per year.[2][3] This cancer occurs primarily in older individuals, with a median age of diagnosis at approximately 70 years of age,[3] though it can also occur in children and young adults in rare cases.[4] DLBCL is an aggressive tumor which can arise in virtually any part of the body,[5] and the first sign of this illness is typically the observation of a rapidly growing mass, sometimes associated with B symptomsfever, weight loss, and night sweats.[6]

The causes of diffuse large B-cell lymphoma are not well understood. Usually DLBCL arises from normal B cells, but it can also represent a malignant transformation of other types of lymphoma or leukemia. An underlying immunodeficiency is a significant risk factor.[7] Infection with Epstein–Barr virus has also been found to contribute to the development of some subgroups of DLBCL.[8]

Diagnosis of DLBCL is made by removing a portion of the tumor through a biopsy, and then examining this tissue using a microscope. Usually a hematopathologist makes this diagnosis.[9] Several subtypes of DLBCL have been identified, each having a different clinical presentation and prognosis. However, the usual treatment for each of these is chemotherapy, often in combination with an antibody targeted at the tumor cells.[10] Through these treatments, more than half of patients with DLBCL can be cured,[11] and the overall five-year survival rate for older adults is around 58%.


Aspartame – sugar

  • The longest ever human aspartame study, spanning 22 years, found a clear association between aspartame consumption and non-Hodgkin’s Lymphoma and leukemia in men
  • Leukemia was associated with diet soda intake in both sexes
  • The study was done out of Harvard but after caving to pressure from industry, a press release was issued that minimized the impact of the study
  • The long-term nature of this study is crucial as one of the primary tricks companies use to hide the toxicity of their products is short-term tests of a few weeks. The longest study prior to this one was only four and half months, far too short to reveal any toxicity from chronic exposure
  • Another trick, especially with aspartame, is to use animal models and not humans. This is problematic because animals are protected from methanol toxicity, unlike humans
  • Another recent study found that compared with sucrose (regular table sugar), saccharin and aspartame caused greater weight gain in adult rats, and this weight gain was unrelated to caloric intake.

A number of animal studies have clearly documented the association between aspartame and cancer, as the study points out. But what most researchers do not appreciate is that humans are the only animals that do NOT have the protective mechanism to compensate for methanol toxicity. So evaluating methanol toxicity in animals is a flawed model for testing human toxicity.

This is due to alcohol dehydrogenase (ADH). In humans, methanol is allowed to be transported in the body to susceptible tissues where this enzyme, ADH, then converts it to formaldehyde, which damages protein and DNA that lead to the increased risk of cancer and autoimmune disease.

Interestingly, the previous AARP Diet and Health Study, which did not find an association with aspartame and cancer, used fruit juice as the control. Most are unaware that canned or bottled fruit juice is loaded with methanol that dissociates from the pectin over time and can actually cause similar problems as aspartame. This does not occur in freshly consumed fruits and vegetables, only ones that are bottled or canned. Hence no major difference could be discerned between the aspartame and the control group.

http://articles.mercola.com/sites/articles/archive/2012/11/07/aspartame-causes-blood-cancer.aspx

10 blood tests for your physical check up

 

    • Female Comprehensive Hormone Panel
    • Item Catalog Number: LC100011
    This panel contains the following tests:

    • Chemistry Panel (Complete metabolic panel with lipids)
    • CBC
    • DHEA-S
    • Estradiol
    • Total Estrogen
    • Progesterone
    • Pregnenolone
    • Total and Free Testosterone
    • Sex Hormone Binding Globulin (SHBG)
    • TSH
    • Free T3
    • Free T4
    • Cortisol

    Sample Report

    As women enter the menopausal years, their bodies’ production of estrogen, progesterone, and other hormones needed to maintain youthful vitality rapidly declines. Continual assessment of hormone levels is necessary for women seeking to maintain a healthy hormonal balance.

    This comprehensive hormone panel is designed by Life Extension® for women looking to monitor their hormone status.

    An 8 to 12 hour fast is required for this blood test. However, drink plenty of water and take your medications as prescribed.

    Special Note:
    If you are supplementing with any hormones, it is important to take them approximately 2 hours prior to having your blood drawn. Any type of contraceptives that contain hormones will invalidate hormone results.

  • Male Comprehensive Hormone Panel
  • Item Catalog Number: LC100010
This panel contains the following tests:

  • Chemistry Panel (complete metabolic panel with lipids)
  • CBC
  • DHEA-S
  • DHT
  • Estradiol
  • PSA
  • Pregnenolone
  • Total and Free Testosterone
  • Sex Hormone Binding Globulin (SHBG)
  • TSH
  • Free T3
  • Free T4
  • Cortisol

Sample Report

As men enter the andropause years, their bodies’ production of dehydroepiandrosterone (DHEA), free and total testosterone, and other hormones needed to maintain youthful vitality rapidly declines, while PSA and estrogen may rise.

This comprehensive hormone panel is designed by Life Extension® for men looking to monitor their hormone status.

An 8 to 12 hour fast is required for this blood test. However, drink plenty of water and take your medications as prescribed.

Special Note:
If you are supplementing with any hormones, it is important to take them approximately 2 hours prior to having your blood drawn. Ejaculation within 48 hours preceding the blood draw may elevate the PSA in some men.

Email motherhealth@gmail.com for more info and free personalized diet plan.

Newborn genetic screening in one blood test

American College of Medical Genetics recommendations

Core panel

The following conditions and disorders were recommended as a “core panel” by the 2005 report of the American College of Medical Genetics (ACMG).[1] The incidences reported below are from the full report, though the rates may vary in different populations.[2]

Blood cell disorders

Inborn errors of amino acid metabolism

Inborn errors of organic acid metabolism

Inborn errors of fatty acid metabolism

Miscellaneous multisystem diseases

Newborn screening by other methods than blood testing

Secondary targets

The following disorders are additional conditions that may be detected by screening. Many are listed as “secondary targets” by the 2005 ACMG report.[1] Some states are now screening for more than 50 congenital conditions. Many of these are rare and unfamiliar to pediatricians and other primary health care professionals.[1]

Blood cell disorders

Inborn errors of amino acid metabolism

Inborn errors of organic acid metabolism

Inborn errors of fatty acid metabolism

Miscellaneous multisystem diseases

Bioethics

As additional tests are discussed for addition to the panels, issues arise. Many question if the expanded testing still falls under the requirements necessary to justify the additional tests.[50] Many of the new diseases being tested for are rare and have no known treatment, while some of the diseases need not be treated until later in life.[50] This raises more issues, such as: if there is no available treatment for the disease should we test for it at all? And if we do, what do we tell the families of those with children bearing one of the untreatable diseases?[51] Studies show that the more rare the disease is and the more diseases being tested for, the more likely the tests are to produce false-positives.[52] This is an issue because the newborn period is a crucial time for the parents to bond with the child, and it has been noted that ten percent of parents whose children were diagnosed with a false-positive still worried that their child was fragile and/or sickly even though they were not, potentially preventing the parent-child bond forming as it would have otherwise.[51] As a result, some parents may begin to opt out of having their newborns screened. Many parents are also concerned about what happens with their infant’s blood samples after screening. The samples were originally taken to test for preventable diseases, but with the advance in genomic sequencing technologies many samples are being kept for DNA identification and research,[50][51]increasing the possibility that more children will be opted out of newborn screening from parents who see the kept samples as a form of research done on their child.


Connie’s comments: In the past, it takes 5 years or more to do one test at a time for any metabolic or newborn health screens. Now with the latest medical device and biotech technologies, multiple health screens (genetic) can be done in one blood test.

https://clubalthea.com/2016/12/12/genetic-tests-for-1-5yr-olds-to-help-you-prepare-for-any-health-issues-18yrs-later-2/

 

Acute Lymphoblastic Leukemia genes

Molecular Profiling of Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a cancer of the blood that originates in the hematopoietic cells in bone marrow. It is the most common type of cancer in children (NCI 2012). Together, leukemias represent 26% of cancer diagnoses in children under the age of 20; ALL makes up 78% of leukemia cases in children under the age of 15 (SEER 1999). Approximately 2,400 children are diagnosed with ALL in the U.S. each year (SEER 1999). The five-year survival rate for children with ALL is over 80% (SEER 1999). In all age groups, 6,590 ALL diagnoses and 1,430 deaths are expected in the U.S. in 2016 (ACS 2016).

In ALL, normal differentiation of blood stem cells in the bone marrow is disrupted along B- or T-cell lineage development (NCI 2012). ALL is divided into subtypes based on tumor cell immunophenotype and histology: lymphoblasts of B-, T-, or biphenotypic lineage. (NCI 2012). Childhood ALL is generally treated with 2-3 years of chemotherapy, beginning with remission induction therapy, followed by postinduction consolidation/intensification therapy and maintenance therapy (NCI 2012).

Each of the main subtypes of ALL has characteristic molecular features; many of these have prognostic significance (Harrison 2011). For precursor B-cell ALL, the uses of tyrosine kinase inhibitors, CD19 antibodies, and CD20 antibodies as targeted therapeutics have all been explored (Oyekunle et al. 2011). Recently, preclinical models have been used to test efficacy of mTOR and JAK inhibitors in CRLF2-rearranged and JAK2-mutated high-risk precursor B-cell ALL (Maude et al. 2011). JAK2 inhibitors are currently being tested in phase I clinical trials.

 

Contributors: Valerie Brown, M.D., Ph.D., Scott C. Borinstein, M.D., Ph.D., Debra Friedman, M.D.

Suggested Citation: Brown, V., S. Borinstein, D. Friedman. 2016. Molecular Profiling of Acute Lymphoblastic Leukemia. My Cancer Genome https://www.mycancergenome.org/content/disease/acute-lymphoblastic-leukemia/ (Updated January 26).

Last Updated: January 26, 2016

Disclaimer: The information presented at MyCancerGenome.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.

A DNA Ultra-sensitive test for cancers, HIV

Catching a disease in its earliest stages can lead to more effective therapies. Stanford chemists have increased the likelihood of detecting these diseases via a test that is thousands of times more sensitive than current diagnostics.

A common theme in medicine is that detecting a disease early on can lead to more effective treatments. This relies partly on luck that the patient gets screened at the right time, but more important is that the testing techniques are sensitive enough to register the minuscule hints that diseases leave in the blood stream.

Cheng-ting Tsai and Peter Robinson with apparatus to analyze DNA-tagged biomarker

Graduate students Cheng-ting “Jason” Tsai and Peter Robinson prepare a gel electrophoreresis experiment to analyze a DNA-tagged biomarker. (Image credit: L.A. Cicero)

A new technique developed by a team of chemists at Stanford has shown promise to be thousands of times more sensitive than current techniques in lab experiments, and it is now being put to test in real-world clinical trials.

When a disease – whether it’s a cancer or a virus like HIV – begins growing in the body, the immune system responds by producing antibodies. Fishing these antibodies or related biomarkers out of the blood is one way that scientists infer the presence of a disease. This involves designing a molecule that the biomarker will bind to, and which is adorned with an identifying “flag.” Through a series of specialized chemical reactions, known as an immunoassay, researchers can isolate that flag, and the biomarker bound to it, to provide a proxy measurement of the disease.

The new technique, developed in the lab of Carolyn Bertozzi, a professor of chemistry at Stanford, augments this standard procedure with powerful DNA screening technology. In this case, the chemists have replaced the standard flag with a short strand of DNA, which can then be teased out of the sample using DNA isolation technologies that are far more sensitive than those possible for traditional antibody detections.

“This is spiritually related to a basic science tool we were developing to detect protein modifications, but we realized that the core principles were pretty straightforward and that the approach might be better served as a diagnostic tool,” said Peter Robinson, a co-author on the study and graduate student in Bertozzi’s group.

The researchers tested their technique, with its signature DNA flag, against four commercially available, FDA-approved tests for a biomarker for thyroid cancer. It outperformed the sensitivity of all of them, by at least 800 times, and as much as 10,000 times. By detecting the biomarkers of disease at lower concentrations, physicians could theoretically catch diseases far earlier in their progression.

“The thyroid cancer test has historically been a fairly challenging immunoassay, because it produces a lot of false positives and false negatives, so it wasn’t clear if our test would have an advantage,” Robinson said. “We suspected ours would be more sensitive, but we were pleasantly surprised by the magnitude.”

Putting basic research to use in a clinical setting has been a focus of Bertozzi’s since she arrived at Stanford.

“I moved to Stanford with the anticipation that translation of my students’ innovations to clinically impactful products and technologies would be enabled,” said Bertozzi, who is a faculty fellow of Stanford ChEM-H, as well as a professor, by courtesy, of radiology and of chemical and systems biology. “That goal is being delightfully fulfilled.”

Based on the success of the thyroid screening, the group has won a few grants to advance the technique into clinical trials. One trial underway in collaboration with the nearby Alameda County Public Health Laboratory will help evaluate the technique as a screening tool for HIV. Early detection and treatment of the virus can help ensure that its effects on the patient are minimized and reduce the chance that it is transmitted to others. This effort is supported by a pilot grant from Stanford-Spectrum, funded by the National Center for Advancing Translational Sciences at the National Institutes of Health.

“Many of our collaborators are excited that the test can be readily deployed in their lab,” said co-author Cheng-ting “Jason” Tsai, a graduate student in Bertozzi’s group. “In contrast to many new diagnostic techniques, this test is performed on pre-existing machines that most clinical labs are already familiar with.”

The researchers are also pursuing tests for Type 1 diabetes, for which early detection could help patients manage the disease with fewer side effects.


Antibodies are widely used biomarkers for the diagnosis of many diseases. Assays based on solid-phase immobilization of antigens comprise the majority of clinical platforms for antibody detection, but can be undermined by antigen denaturation and epitope masking. These technological hurdles are especially troublesome in detecting antibodies that bind nonlinear or conformational epitopes, such as anti-insulin antibodies in type 1 diabetes patients and anti-thyroglobulin antibodies associated with thyroid cancers. Radioimmunoassay remains the gold standard for these challenging antibody biomarkers, but the limited multiplexability and reliance on hazardous radioactive reagents have prevented their use outside specialized testing facilities. Here we present an ultrasensitive solution-phase method for detecting antibodies, termed antibody detection by agglutination-PCR (ADAP). Antibodies bind to and agglutinate synthetic antigen–DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. ADAP detects zepto- to attomoles of antibodies in 2 μL of sample with a dynamic range spanning 5–6 orders of magnitude. Using ADAP, we detected anti-thyroglobulin autoantibodies from human patient plasma with a 1000-fold increased sensitivity over an FDA-approved radioimmunoassay. Finally, we demonstrate the multiplexability of ADAP by simultaneously detecting multiple antibodies in one experiment. ADAP’s combination of simplicity, sensitivity, broad dynamic range, multiplexability, and use of standard PCR protocols creates new opportunities for the discovery and detection of antibody biomarkers.

http://pubs.acs.org/doi/abs/10.1021/acscentsci.5b00340

 


Detecting the onset of cancer at the cellular level

A chemical profiling technique that has potential for detecting the onset of cancer at the cellular level has been developed by scientists with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California at Berkeley.

Science image spacer image
Carolyn Bertozzi was recently named Director of Berkeley Lab’s Molecular Foundry. She is a chemist with Berkeley Lab’s Materials Sciences and Physical Biosciences Divisions, a UC Berkeley professor, and an investigator with the Howard Hughes Medical Institute.

In a paper published in the Proceedings of the National Academy of Sciences (PNAS) that is now on-line, a team of researchers, led by chemist Carolyn Bertozzi, has reported a technique for rapidly profiling O-linked glycoproteins in living animals. Changes in O-linked protein glycosylation – the attachment of sugars to proteins through an oxygen atom on the protein – are known to correlate with cancers and other diseases, such as inflammations and bacterial infections. Until now, however, scientists have lacked a practical means of monitoring such changes in a physiological setting.

“With our profiling technique, we can take pictures over time of the sugars that coat a cell’s surface or are released by the cell into the bloodstream and monitor any changes that occur,” said Bertozzi. “We can then compare the sugars produced by cells that become cancerous with the sugars from normal cells. Ultimately, the idea would be to use this information to create a simple blood test that would diagnose a patient for cancer.”

Bertozzi is the Director of Berkeley Lab’s Molecular Foundry, a faculty scientist with Berkeley Lab’s Materials Sciences and Physical Biosciences Divisions, the T.Z. and Irmgard Chu Distinguished Professor of Chemistry and professor of Molecular and Cell Biology at UC Berkeley. She is also an investigator with the Howard Hughes Medical Institute (HHMI). Co-authoring the PNAS paper with her were Danielle Dube, Jennifer Prescher and Chi Quang, who were all members of her research group when this work was done.

The key to successful cancer treatment is detection at an early stage of development – the sooner the better. While detecting an over-abundance of an antigen has been used to create an effective blood test for prostate cancer, it is believed that even more effective blood tests for a large number of epithelial cancers, also known as carcinomas, could be realized if a practical means of detecting the sugars attached to blood-borne proteins were available. Most proteins are modified post-translationally (i.e., after a protein’s polypeptide chain has been formed), and one of the most common of these events is glycosylation, which can be either oxygen or nitrogen-linked. Glycoproteins are ubiquitous on the surfaces of most cells and help a cell communicate with its neighbors.

“Studies of cells in culture have suggested that monitoring changes in O-linked glycoproteins would be an effective biomarker for cancer, but for the past three decades if you wanted to know which glycans were present on a cell, you had to isolate the surface proteins one at a time,” said Bertozzi. “Our profiling technique lets you quickly scan all the proteins at once. Once we attach our tags and probes, the proteins either light up due to the presence of sugars or they don’t.”

The profiling technique developed by Bertozzi and her team starts by tagging certain glycoproteins with a metabolic label called N-azidoacetylgalactosamine (GalNAz). An over-secretion of the labeled glycoproteins, which form the lubricant that protects the surfaces of cells, is known to increase the potential of cancer to spread.

Science image
Profiling mucin-type O-linked glycoproteins by metabolic labeling with an azido GalNAc analog (Ac4GalNAz) followed by Staudinger ligation with a phosphine probe (Phos-FLAG). R and R’ are oligosaccharide elaborations from the core GalNAc residue.

GalNAz has an azide group, which can be chemically tagged with probes that can be visualized. The probes react with the azide by virtue of a phosphine group, a process developed in Bertozzi’s laboratory called the Staudinger ligation, named for the German synthetic-organic chemist and Nobel laureate Hermann Staudinger, who first described the reaction between azides and a phosphines almost 100 years ago.

“After injection of mice with GalNAz, azide-labeled glycoproteins were observed in a variety of tissues,
including liver, kidney, and heart, and also in serum and on isolated splenocytes,” Bertozzi and her co-authors state in their PNAS paper. “B cell glycoproteins were robustly labeled with GalNAz but T cell glycoproteins were not, suggesting fundamental differences in glycosylation machinery or metabolism.

“Furthermore, GalNAz-labeled B cells could be selectively targeted with a phosphine probe by Staudinger ligation within the living animal. Metabolic labeling with GalNAz followed by Staudinger ligation provides a means for proteomic analysis of posttranslational modifications and for identifying O-linked glycoprotein fingerprints associated with disease.”

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our Website at www.lbl.gov.


Email motherhealth@gmail.com for a DNA test (blood test) to detect cancer early.