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  1. Article: S100B and S100B autoantibody as biomarkers for early detection of brain metastases in lung cancer.

    Choi, Humberto / Puvenna, Vikram / Brennan, Chanda / Mahmoud, Shamseldeen / Wang, Xiao-Feng / Phillips, Michael / Janigro, Damir / Mazzone, Peter

    Translational lung cancer research

    2016  Volume 5, Issue 4, Page(s) 413–419

    Abstract: Background: S100B is an astrocytic protein that enters the blood stream when there is disruption of the blood-brain barrier (BBB). Over time, antibodies against S100B develop in the sera of patients who experience persistent or repeated BBB disruptions. ...

    Abstract Background: S100B is an astrocytic protein that enters the blood stream when there is disruption of the blood-brain barrier (BBB). Over time, antibodies against S100B develop in the sera of patients who experience persistent or repeated BBB disruptions. We explored the use of serum S100B protein and S100B autoantibodies for the detection of brain metastasis in patients with lung cancer.
    Methods: One hundred and twenty eight untreated patients with lung cancer who had brain imaging performed as part of their routine evaluation, participated. Serum S100B protein levels were measured by direct ELISA and S100B autoantibody levels by reverse ELISA. These levels in patients with brain metastases were compared alone and in combination to those without brain metastases.
    Results: Eighteen (14%) patients had brain metastasis at the time of lung cancer diagnosis. An S100B cutoff of 0.058 ng/mL had a sensitivity of 89% and specificity of 43% for brain metastasis. When an autoantibody threshold of <2.00 absorbance units was used in conjunction with S100B, the sensitivity remained at 89%, and the specificity increased to 58%. The overall accuracy was 51% with S100B alone, improving to 62.5% when combined with autoantibodies.
    Conclusions: Serum S100B and S100B autoantibody levels may help to identify which lung cancer patients have brain metastases.
    Language English
    Publishing date 2016-08-25
    Publishing country China
    Document type Journal Article
    ZDB-ID 2754335-3
    ISSN 2226-4477 ; 2218-6751
    ISSN (online) 2226-4477
    ISSN 2218-6751
    DOI 10.21037/tlcr.2016.07.08
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Significance of ubiquitin carboxy-terminal hydrolase L1 elevations in athletes after sub-concussive head hits.

    Puvenna, Vikram / Brennan, Chanda / Shaw, Gerald / Yang, Cui / Marchi, Nicola / Bazarian, Jeffrey J / Merchant-Borna, Kian / Janigro, Damir

    PloS one

    2014  Volume 9, Issue 5, Page(s) e96296

    Abstract: The impact of sub-concussive head hits (sub-CHIs) has been recently investigated in American football players, a population at risk for varying degrees of post-traumatic sequelae. Results show how sub-CHIs in athletes translate in serum as the appearance ...

    Abstract The impact of sub-concussive head hits (sub-CHIs) has been recently investigated in American football players, a population at risk for varying degrees of post-traumatic sequelae. Results show how sub-CHIs in athletes translate in serum as the appearance of reporters of blood-brain barrier disruption (BBBD), how the number and severity of sub-CHIs correlate with elevations of putative markers of brain injury is unknown. Serum brain injury markers such as UCH-L1 depend on BBBD. We investigated the effects of sub-CHIs in collegiate football players on markers of BBBD, markers of cerebrospinal fluid leakage (serum beta 2-transferrin) and markers of brain damage. Emergency room patients admitted for a clinically-diagnosed mild traumatic brain injury (mTBI) were used as positive controls. Healthy volunteers were used as negative controls. Specifically this study was designed to determine the use of UCH-L1 as an aid in the diagnosis of sub-concussive head injury in athletes. The extent and intensity of head impacts and serum values of S100B, UCH-L1, and beta-2 transferrin were measured pre- and post-game from 15 college football players who did not experience a concussion after a game. S100B was elevated in players experiencing the most sub-CHIs; UCH-L1 levels were also elevated but did not correlate with S100B or sub-CHIs. Beta-2 transferrin levels remained unchanged. No correlation between UCH-L1 levels and mTBI were measured in patients. Low levels of S100B were able to rule out mTBI and high S100B levels correlated with TBI severity. UCH-L1 did not display any interpretable change in football players or in individuals with mild TBI. The significance of UCH-L1 changes in sub-concussions or mTBI needs to be further elucidated.
    MeSH term(s) Athletes/statistics & numerical data ; Blood-Brain Barrier/metabolism ; Blood-Brain Barrier/pathology ; Brain Concussion/blood ; Brain Concussion/enzymology ; Brain Concussion/metabolism ; Brain Injuries/blood ; Brain Injuries/enzymology ; Brain Injuries/metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; S100 Calcium Binding Protein beta Subunit/blood ; Transferrin/metabolism ; Ubiquitin Thiolesterase/blood ; Ubiquitin Thiolesterase/metabolism
    Chemical Substances S100 Calcium Binding Protein beta Subunit ; S100B protein, human ; Transferrin ; UCHL1 protein, human ; Ubiquitin Thiolesterase (EC 3.4.19.12)
    Language English
    Publishing date 2014-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0096296
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy.

    Puvenna, Vikram / Engeler, Madeline / Banjara, Manoj / Brennan, Chanda / Schreiber, Peter / Dadas, Aaron / Bahrami, Ashkon / Solanki, Jesal / Bandyopadhyay, Anasua / Morris, Jacqueline K / Bernick, Charles / Ghosh, Chaitali / Rapp, Edward / Bazarian, Jeffrey J / Janigro, Damir

    Brain research

    2016  Volume 1630, Page(s) 225–240

    Abstract: Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but ... ...

    Abstract Repetitive traumatic brain injury (rTBI) is one of the major risk factors for the abnormal deposition of phosphorylated tau (PT) in the brain and chronic traumatic encephalopathy (CTE). CTE and temporal lobe epilepsy (TLE) affect the limbic system, but no comparative studies on PT distribution in TLE and CTE are available. It is also unclear whether PT pathology results from repeated head hits (rTBI). These gaps prevent a thorough understanding of the pathogenesis and clinical significance of PT, limiting our ability to develop preventative and therapeutic interventions. We quantified PT in TLE and CTE to unveil whether a history of rTBI is a prerequisite for PT accumulation in the brain. Six postmortem CTE (mean 73.3 years) and age matched control samples were compared to 19 surgically resected TLE brain specimens (4 months-58 years; mean 27.6 years). No history of TBI was present in TLE or control; all CTE patients had a history of rTBI. TLE and CTE brain displayed increased levels of PT as revealed by immunohistochemistry. No age-dependent changes were noted, as PT was present as early as 4 months after birth. In TLE and CTE, cortical neurons, perivascular regions around penetrating pial vessels and meninges were immunopositive for PT; white matter tracts also displayed robust expression of extracellular PT organized in bundles parallel to venules. Microscopically, there were extensive tau-immunoreactive neuronal, astrocytic and degenerating neurites throughout the brain. In CTE perivascular tangles were most prominent. Overall, significant differences in staining intensities were found between CTE and control (P<0.01) but not between CTE and TLE (P=0.08). pS199 tau analysis showed that CTE had the most high molecular weight tangle-associated tau, whereas epileptic brain contained low molecular weight tau. Tau deposition may not be specific to rTBI since TLE recapitulated most of the pathological features of CTE.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain/metabolism ; Brain/pathology ; Brain/surgery ; Brain Injury, Chronic/metabolism ; Brain Injury, Chronic/pathology ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Epilepsy/metabolism ; Epilepsy/pathology ; Epilepsy/surgery ; Female ; Humans ; Immunohistochemistry ; Infant ; Male ; Middle Aged ; Phosphorylation ; Young Adult ; tau Proteins/metabolism
    Chemical Substances MAPT protein, human ; tau Proteins
    Language English
    Publishing date 2016-01-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2015.11.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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