| 1. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 3. |
- Czigner, Andrea, et al.
(författare)
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Dynamics and regional distribution of c-fos protein expression in rat brain after a closed head injury
- 2004
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 14:2, s. 247-252
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to define the time- and brain-area-related distribution of c-fos expression in the brain during the first 24 h following a closed head injury in rats. In the control groups (n = 32), only a few c-fos positive nuclei were observed in the brain and the c-fos staining did not change during the next 24 h. In the closed head injury group c-fos-positive cells were rare in the brain regions during the first 30 min. During the next 2 h, the number of c-fos-positive cells increased rapidly in the basal ganglions, the ventricular ependyma cells the corticospinal tract, the area postrema, the cerebral neocortex, and the corpus callosum. The increase was highest in the corpus callosum (317 +/- 44.5 mm(-2)), in the thalamic reticular nucleus (474.8 +/- 49.2 mm(-2)), in the dentate hilus (1090 +/- 187 mm(-2)) and in the cerebral neocortex (992 +/- 93 mm(-2)). Thereafter, the elevated c-fos expression gradually decreased and at 6 h post-closed head injury no significant differences were observed between the controls and the trauma group. We conclude that a closed head injury induces a large, transient increase of c-fos expression in the brain. Since the observed time course and regional differences in c-fos expression are in good agreement with the cognitive and memory deficits observed after human TBI it can be utilized in further investigations, especially to test the effects of various forms of pharmacological or cellular therapy.
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| 4. |
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| 5. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 6. |
- Bazarian, Jeffrey J., et al.
(författare)
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Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI) : a multicentre observational study
- 2018
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Ingår i: Lancet Neurology. - : Lancet Publishing Group. - 1474-4422 .- 1474-4465. ; 17:9, s. 782-789
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Tidskriftsartikel (refereegranskat)abstract
- Background: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI.Methods: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT.Findings: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative.Interpretation: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted.Funding: Banyan Biomarkers and US Army Medical Research and Materiel Command.
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| 7. |
- Büki, Andras, 1966-, et al.
(författare)
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Baleseti agysérültek ellátásának irányelvei -2017 : [GUIDELINES FOR THE TREATMENT OF TRAUMATICBRAIN INJURY – 2017]
- 2017
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Ingår i: Ideggyógyászati szemle. - : Literatura Medica Kiado. - 0019-1442 .- 2498-6208. ; 70:7-8, s. 223-245
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury (TBI) is recognized to be the main cause of death and disability in the first four decades representing a major socio-economical problem worldwide. Recent communications revealed a particularly worrying image about the quality of care for TBI in Hungary. For any improvement a systematic approach characterized by utilization of scientific evidence based guidelines forming the basis for close monitoring of the actual care are considered a prerequisite. In Hungary the first evidence based guidelines in the field of TBI have been issued by the National Society for Anesthesiology and Intensive Care more than two decades ago followed by joint guidelines of the Hungarian Neurosurgical Society and the Hungarian College of Neurosurgeons. These publications were primarily based on the work of the European Brain Injury Consortium as well as guidelines issued by the Brain Trauma Foundation. Recent renewal of the latter and a need to refresh the outdated national guidelines was met by a call from regulatory authorities to issue the updated version of the Hungarian TBI-guidelines. The present review is aimed to briefly summarize the most fundamental elements of the national head injury guidelines that would hopefully be officially issued in a far more detailed format soon.
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| 8. |
- Büki, Andras, 1966-, et al.
(författare)
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Clinical and model research of neurotrauma
- 2009
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Ingår i: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1064-3745 .- 1940-6029. ; 566, s. 41-55
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Tidskriftsartikel (refereegranskat)abstract
- Modeling traumatic brain injury represents a major challenge for neuroscientists - to represent extremely complex pathobiological processes kept under close surveillance in the most complex organ of a laboratory animal. To ensure that such models also reflect those alterations evoked by and/or associated with traumatic brain injury (TBI) in man, well-defined, graded, simple injury paradigms should be used with clear endpoints that also enable us to assess the relevance of our findings to human observations. It is of particular importance that our endpoints should harbor clinical significance, and to this end, biological markers ultimately associated with the pathological processes operant in TBI are considered the best candidate. This chapter provides protocols for relevant experimental models of TBI and clinical materials for neuroproteomic analysis.
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| 9. |
- Bukovics, Peter, et al.
(författare)
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Changes of PACAP level in cerebrospinal fluid and plasma of patients with severe traumatic brain injury
- 2014
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 60, s. 18-22
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Tidskriftsartikel (refereegranskat)abstract
- PACAP has well-known neuroprotective potential including traumatic brain injury (TBI). Its level is up-regulated following various insults of the CNS in animal models. A few studies have documented alterations of PACAP levels in human serum. The time course of post-ictal PACAP levels, for example, show correlation with migraine severity. Very little is known about the course of PACAP levels following CNS injury in humans and the presence of PACAP has not yet been detected in cerebrospinal fluid (CSF) of subjects with severe TBI (sTBI). The aim of the present study was to determine whether PACAP occurs in the CSF and plasma (Pl) of patients that suffered sTBI and to establish a time course of PACAP levels in the CSF and Pl. Thirty eight subjects with sTBI were enrolled with a Glasgow Coma Scale ≤8 on admission. Samples were taken daily, until the time of death or for maximum 10 days. Our results demonstrated that PACAP was detectable in the CSF, with higher concentrations in patients with TBI. PACAP concentrations markedly increased in both Pl and CSF in the majority of patients 24-48h after the injury stayed high thereafter. In cases of surviving patients, Pl and CSF levels displayed parallel patterns, which may imply the damage of the blood-brain barrier. However, in patients, who died within the first week, Pl levels were markedly higher than CSF levels, possibly indicating the prognostic value of high Pl PACAP levels.
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| 10. |
- Czeiter, Endre, et al.
(författare)
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Brain Injury Biomarkers May Improve the Predictive Power of the IMPACT Outcome Calculator
- 2012
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 29:9, s. 1770-1778
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Tidskriftsartikel (refereegranskat)abstract
- Outcome prediction following severe traumatic brain injury (sTBI) is a widely investigated field of research. A major breakthrough is represented by the IMPACT prognostic calculator based on admission data of more than 8500 patients. A growing body of scientific evidence has shown that clinically meaningful biomarkers, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and alpha II-spectrin breakdown product (SBDP145), could also contribute to outcome prediction. The present study was initiated to assess whether the addition of biomarkers to the IMPACT prognostic calculator could improve its predictive power. Forty-five sTBI patients (GCS score <= 8) from four different sites were investigated. We utilized the core model of the IMPACT calculator (age, GCS motor score, and reaction of pupils), and measured the level of GFAP, UCH-L1, and SBDP145 in serum and cerebrospinal fluid (CSF). The forecast and actual 6-month outcomes were compared by logistic regression analysis. The results of the core model itself, as well as serum values of GFAP and CSF levels of SBDP145, showed a significant correlation with the 6-month mortality using a univariate analysis. In the core model, the Nagelkerke R-2 value was 0.214. With multivariate analysis we were able to increase this predictive power with one additional biomarker (GFAP in CSF) to R-2 = 0.476, while the application of three biomarker levels (GFAP in CSF, GFAP in serum, and SBDP145 in CSF) increased the Nagelkerke R-2 to 0.700. Our preliminary results underline the importance of biomarkers in outcome prediction, and encourage further investigation to expand the predictive power of contemporary outcome calculators and prognostic models in TBI.
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| 11. |
- Czeiter, Endre, et al.
(författare)
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Calpain inhibition reduces axolemmal leakage in traumatic axonal injury
- 2009
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 14:12, s. 5115-5123
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Tidskriftsartikel (refereegranskat)abstract
- Calcium-induced, calpain-mediated proteolysis (CMSP) has recently been implicated to the pathogenesis of diffuse (traumatic) axonal injury (TAI). Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP) alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA) and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA) was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor) or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.
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| 12. |
- Czeiter, Endre, et al.
(författare)
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Traumatic axonal injury in the spinal cord evoked by traumatic brain injury
- 2008
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 25:3, s. 205-213
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Tidskriftsartikel (refereegranskat)abstract
- Although it is well known that traumatic brain injury (TBI) evokes traumatic axonal injury (TAI) within the brain, TBI-induced axonal damage in the spinal cord (SC) has been less extensively investigated. Detection of such axonal injury in the spinal cord would further the complexity of TBI while also challenging some functional neurobehavioral endpoints frequently used to assess recovery in various models of TBI. To assess TAI in the spinal cord associated with TBI, we analyzed the craniocervical junction (CCJ), cervico-thoracic (CT), and thoraco-lumber (ThL) spinal cord in a rodent model of impact acceleration of TBI of varying severities. Rats were transcardially fixed with aldehydes at 2, 6, and 24 h post-injury (n = 36); each group included on sham-injured rodent. Semi-serial vibratome sections were reacted with antibodies targeting TAI via alteration in cytoskeletal integrity or impaired axonal transport. Consistent with previous observations in this model, the CCJ contained numerous injured axons. Immunoreactive, damaged axonal profiles were also detected as caudal, as the ThL spinal cord displayed morphological characteristics entirely consistent with those described in the brainstem and the CCJ. Quantitative analyses demonstrated that the occurrence and extent of TAI is positively associated with the impact/energy of injury and negatively with the distance from the brainstem. These observations show that TBI can evoke TAI in regions remote from the injury site, including the spinal cord itself. This finding is relevant to shaken baby syndrome as well as during the analysis of data in functional recovery in various models of TBI.
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| 13. |
- Farkas, Orsolya, et al.
(författare)
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Effects of pituitary adenylate cyclase activating polypeptide in a rat model of traumatic brain injury
- 2004
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Ingår i: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 123:1-3, s. 69-75
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide that has numerous different actions. Recent studies have shown that PACAP exerts neuroprotective effects not only in vitro but also in vivo, in animal models of global and focal cerebral ischemia, Parkinson's disease and axonal injuries. Traumatic brain injury has an increasing mortality and morbidity and it evokes diffuse axonal injury which further contributes to its damaging effects. The aim of the present study was to examine the possible neuroprotective effect of PACAP in a rat model of diffuse axonal injury induced by impact acceleration. Axonal damage was assessed by immunohistochemistry using an antiserum against beta-amyloid precursor protein, a marker of altered axoplasmic transport considered as key feature in axonal injury. In these experiments, we have established the dose response curves for PACAP administration in traumatic axonal injury, demonstrating that a single post-injury intracerebroventricular injection of 100 microg PACAP significantly reduced the density of damaged, beta-amyloid precursor protein-immunoreactive axons in the corticospinal tract.
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| 14. |
- Kövesdi, Erzsébet, et al.
(författare)
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A novel PARP inhibitor L-2286 in a rat model of impact acceleration head injury : an immunohistochemical and behavioral study
- 2010
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 11:4, s. 1253-1268
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Tidskriftsartikel (refereegranskat)abstract
- We examined the neuro/axono-protective potential of a novel poly (ADP-ribose) polymerase (PARP) inhibitor L-2286 in a rat impact acceleration brain injury model. Male Wistar rats (n = 70) weighing 300-350 grams were used to determine the most effective intracerebroventricular (i.c.v.) dose of L-2286 administered 30 min after injury, and to test the neuroprotective effect at two time points (immediately, and 30 min after injury). The neuroprotective effect of L-2286 was tested using immunohistochemical (amyloid precursor protein and mid-sized mouse anti-neurofilament clone RMO-14.9 antibody) and behavioral tests (beam-balance, open-field and elevated plus maze). At both time-points, a 100 microg/rat dose of i.c.v. L-2286 significantly (p < 0.05) reduced the density of damaged axons in the corticospinal tract and medial longitudinal fascicle compared to controls. In the behavioral tests, treatment 30 min post-injury improved motor function, while the level of anxiety was reduced in both treatment protocols.
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| 15. |
- Kövesdi, Erzsébet, et al.
(författare)
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Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats
- 2008
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Ingår i: Neurotoxicity research. - : Springer. - 1029-8428 .- 1476-3524. ; 13:2, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- Several in vitro and in vivo experiments have demonstrated the neuroprotective effects of pituitary adenylate cyclase activating polypeptide (PACAP) in focal cerebral ischemia, Parkinson's disease and traumatic brain injury (TBI). The aim of the present study was to analyze the effect of PACAP administration on diffuse axonal injury (DAI), an important contributor to morbidity and mortality associated with TBI, in a central fluid percussion (CFP) model of TBI. Rats were subjected to moderate (2 Atm) CFP injury. Thirty min after injury, 100 mu g PACAP was administered intracerebroventricularly. DAI was assessed by immunohistochemical detection of beta-amyloid precursor protein, indicating impaired axoplasmic transport, and RMO-14 antibody, representing foci of cytoskeletal alterations (neurofilament compaction), both considered classical markers of axonal damage. Analysis of damaged, immunoreactive axonal profiles revealed significant axonal protection in the PACAP-treated versus vehicle-treated animals in the corticospinal tract, as far as traumatically induced disturbance of axoplasmic transport and cytoskeletal alteration were considered. Similarly to our former observations in an impact acceleration model of diffuse TBI, the present study demonstrated that PACAP also inhibits DAI in the CFP injury model. The finding indicates that PACAP and derivates can be considered potential candidates for further experimental studies, or purportedly for clinical trials in the therapy of TBI.
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| 16. |
- Kövesdi, Erzsébet, et al.
(författare)
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Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics
- 2010
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Ingår i: Acta Neurochirurgica. - : Springer. - 0001-6268 .- 0942-0940. ; 152:1, s. 1-17
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Forskningsöversikt (refereegranskat)abstract
- Purpose: This review summarizes protein biomarkers in mild and severe traumatic brain injury in adults and children and presents a strategy for conducting rationally designed clinical studies on biomarkers in head trauma.Methods: We performed an electronic search of the National Library of Medicine's MEDLINE and Biomedical Library of University of Pennsylvania database in March 2008 using a search heading of traumatic head injury and protein biomarkers. The search was focused especially on protein degradation products (spectrin breakdown product, c-tau, amyloid-beta(1-42)) in the last 10 years, but recent data on "classical" markers (S-100B, neuron-specific enolase, etc.) were also examined.Results: We identified 85 articles focusing on clinical use of biomarkers; 58 articles were prospective cohort studies with injury and/or outcome assessment.Conclusions: We conclude that only S-100B in severe traumatic brain injury has consistently demonstrated the ability to predict injury and outcome in adults. The number of studies with protein degradation products is insufficient especially in the pediatric care. Cohort studies with well-defined end points and further neuroproteomic search for biomarkers in mild injury should be triggered. After critically reviewing the study designs, we found that large homogenous patient populations, consistent injury, and outcome measures prospectively determined cutoff values, and a combined use of different predictors should be considered in future studies.
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| 17. |
- Lückl, Jááos, et al.
(författare)
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Protein biomarkerek szerepe a koponyasérüles kísérletes modelljeiben és a klinikumban : [Protein biomarkers in experimental models and in clinical care of traumatic brain injury]
- 2007
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Ingår i: Ideggyogyaszati Szemle. - : Literatura Medica Kiado. - 0019-1442 .- 2498-6208. ; 60:7-8, s. 284-294
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury is the leading cause of mortality in Hungary in the population under 40 years of age. In Western societies, like the United Sates, traumatic brain injury represents an extreme social-economic burden, expected to become the third leading cause of mortality until 2020. Despite its' epidemiological significance, experimental therapeutic modalities developed in the last few decades did not prove efficient in the clinical care of severe traumatic brain injury. The reason for such a lack of success in terms of translating experimental results to clinical treatment at least partially could be explained by the paucity and the low sensitivity and specificity of clinical parameters endowing us to monitor the efficacy of the therapy. The drive for finding clinical parameters and monitoring tools that enable us to monitor treatment efficacy as well as outcome focused recent attention on biomarkers (and) surrogate markers that are based on rational pathological processes associated with/operant in traumatic brain injury. This review summarizes those biomarkers that could purportedly be used to monitor the treatment of the severely head injured while also providing information on salvageability facilitating the conduction of more rationally designed clinical studies.
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| 18. |
- Mondello, Stefania, et al.
(författare)
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CSF and Plasma Amyloid-β Temporal Profiles and Relationships with Neurological Status and Mortality after Severe Traumatic Brain Injury
- 2014
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- The role of amyloid-beta (A beta) neuropathology and its significant changes in biofluids after traumatic brain injury (TBI) is still debated. We used ultrasensitive digital ELISA approach to assess amyloid-beta(1-42) (A beta 42) concentrations and time-course in cerebrospinal fluid (CSF) and in plasma of patients with severe TBI and investigated their relationship to injury characteristics, neurological status and clinical outcome. We found decreased CSF A beta 42 levels in TBI patients acutely after injury with lower levels in patients who died 6 months post-injury than in survivors. Conversely, plasma A beta 42 levels were significantly increased in TBI with lower levels in patients who survived. A trend analysis showed that both CSF and plasma A beta 42 levels strongly correlated with mortality. A positive correlation between changes in CSF A beta 42 concentrations and neurological status as assessed by Glasgow Coma Scale (GCS) was identified. Our results suggest that determination of A beta 42 may be valuable to obtain prognostic information in patients with severe TBI as well as in monitoring the response of the brain to injury.
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| 19. |
- Mondello, Stefania, et al.
(författare)
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Glial Neuronal Ratio : A Novel Index for Differentiating Injury Type in Patients with Severe Traumatic Brain Injury
- 2012
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 29:6, s. 1096-1104
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Tidskriftsartikel (refereegranskat)abstract
- Neurobiochemical marker levels in blood after traumatic brain injury (TBI) may reflect structural changes detected by neuroimaging. This study evaluates whether correlations between neuronal (ubiquitin carboxyterminal hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarkers may be used as an indicator for differing intracranial pathologies after brain trauma. In 59 patients with severe TBI (Glasgow Coma Scale [GCS] score <= 8) serum samples were obtained at the time of hospital admission and analyzed for UCH-L1 and GFAP. Glial neuronal ratio (GNR) was evaluated as the ratio between GFAP and UCH-L1 concentrations. A logistic regression analysis was used to identify variables associated with type of injury. GNR had a median of 0.85 and was positively correlated with age (R = 0.45, p = 0.003). Twenty-nine patients presented with diffuse injury and 30 with focal mass lesions as assessed by CT scan at admission and classified according to the Marshall Classification. GNR was significantly higher in the focal mass lesion group compared with the diffuse injury group (1.77 versus 0.48, respectively; p = 0.003). Receiver operating characteristic curve analysis showed that GNR discriminated between types of injury (area under the curve [AUC] = 0.72; p = 0.003). GNR was more accurate earlier (<= 12 h after injury) than later (AUC = 0.80; p = 0.002). Increased GNR was independently associated with type of injury, but not age, gender, GCS score, or mechanism of injury. GNR was significantly higher in patients who died, but was not an independent predictor of death. The data from the present study indicate that GNR provides valuable information about different injury pathways, which may be of diagnostic significance. In addition, GNR may help to identify different pathophysiological mechanisms following different types of brain trauma, with implications for therapeutic interventions.
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| 20. |
- Pettkó-Szandtner, Aladár, et al.
(författare)
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Activation of an alfalfa cyclin-dependent kinase inhibitor by calmodulin-like domain protein kinase.
- 2006
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Ingår i: Plant Journal. - 0960-7412. ; 46:1, s. 111-23
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Tidskriftsartikel (refereegranskat)abstract
- Kip-related proteins (KRPs) play a central role in the regulation of the cell cycle and differentiation through modulation of cyclin-dependent kinase (CDK) functions. We have identified a CDK inhibitor gene from Medicago truncatula (Mt) by a yeast two-hybrid screen. The KRPMt gene was expressed in all plant organs and cultured cells, and its transcripts accumulated after abscisic acid and NaCl treatment. The KRPMt protein exhibits seven conserved sequence domains and a PEST motif that is also detected in various Arabidopsis KRPs. In the yeast two-hybrid test, the KRPMt protein interacted with CDK (Medsa;CDKA;1) and D-type cyclins. However, in the pull-down assays, B-type CDK complexes were also detectable. Recombinant KRPMt differentially inhibited various alfalfa CDK complexes in phosphorylation assays. The immunoprecipitated Medsa;CDKA;1/A;2 complex was strongly inhibited, whereas the mitotic Medsa;CDKB2;1 complex was the most sensitive to inhibition. Function of Medsa;CDKB1;1 complex was not inhibited by the KRPMt protein. The mitotic Medsa;CYCB2 and Medsa;CYCA2;1 complexes responded weakly to this inhibitor protein. Kinase complexes from G2/M cells showed increased sensitivity towards the inhibitor compared with those isolated from G1/S-phase cells. In vitro phosphorylation of Medicago retinoblastoma-related protein was also reduced in the presence of KRPMt. Phosphorylation of this inhibitor protein by the recombinant calmodulin-like domain protein kinase (MsCPK3) resulted in enhanced inhibition of CDK function. The data presented emphasize the selective sensitivity of various cyclin-dependent kinase complexes to this inhibitor protein, and suggest a role for CDK inhibitors and CPKs in cross-talk between Ca2+ signalling and regulation of cell-cycle progression in plants.
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| 21. |
- Rakonczai, Pal, et al.
(författare)
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Autocopulas: Investigating the Interdependence Structure of Stationary Time Series
- 2012
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Ingår i: Methodology and Computing in Applied Probability. - : Springer Science and Business Media LLC. - 1573-7713 .- 1387-5841. ; 14:1, s. 149-167
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Tidskriftsartikel (refereegranskat)abstract
- Here we present a novel approach to the description of the lagged interdependence structure of stationary time series. The idea is to extend the use of copulas to the lagged (one-dimensional) series, to the analogy of the autocorrelation function. The use of such autocopulas can reveal the specifics of the lagged interdependence in a much finer way. However, the lagged interdependence is resulted from the dynamics, governing the series, therefore the known and popular copula models have little to do with that type of interdependence. True though, it seems rather cumbersome to calculate the exact form of the autocopula even for the simplest nonlinear time series models, so we confine ourselves here to an empirical and simulation based approach. The advantage of using autocopulas lays in the fact that they represent nonlinear dependencies as well, and make it possible e.g. to study the interdependence of high (or low) values of the series separately. The presented methods are capable to check whether autocopulas of an observed process can be distinguished significantly from the autocopulas a of given time series model. The proposed approach is based on the Kendall's transform which reduces the multivariate problem to one dimension. After illustrating the use of our approach in detecting conditional heteroscedasticity in the AR-ARCH vs. AR case, we apply the proposed methods to investigate the lagged interdependence of river flow time series with particular focus on model choice based on the synchronized appearance of high values.
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| 22. |
- Sándor, János, et al.
(författare)
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A subduralis vérzés miatt kezelt betegek halálozását befolyásoló tényezók : [Predictors of lethal outcome in subdural haemorrhage]
- 2003
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Ingår i: Ideggyogyaszati Szemle. - : Literatura Medica Kiado. - 0019-1442 .- 2498-6208. ; 56:11-12, s. 386-395
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Tidskriftsartikel (refereegranskat)abstract
- Background: Subdural haemorrhage (SDH) is of high public health importance because of its frequency, high case fatality ratio (CFR) and the young age of affected population. Despite the fact that the effectivity of guideline based treatment has been improved in the last decade, the Hungarian praxis shows variable compliance for recommendations.Objectives: The study aimed to describe the heterogeneity of the treatment effectivity (by geographically identifying the populations provided with appropriate or non-optimal level care), to determine the relationship between the institutional proxies quality and the results of treatment for SDH by linking the proxies properties to the patients' records.Methods: The institutions' protocols were assessed by a self-completed questionnaire in 1997. The participating hospitals treated 79% of the Hungarian patients with SDH. The Hungarian hospital discharge data in 1997-1999 were the source of patient specific data. The risk factors of lethal outcome were investigated by logistic regression analysis.Results: High proportion of patients had been treated in hospital with low compliance for guidelines. The non-permanent access to neurosurgical service and CT facility, the lack of intracranial pressure monitoring and the respiration support provided out of intensive care units worsened the survival of subjects. It was quantified that the full compliance could have diminished the case fatality ratio by 15-20%. The ratio of extreme county level CFRs exceeded 2.36 and extrapolating the effectivity observed in the county with lowest lethality, the Hungarian CFR would have been reduced by 21% among patients with SDH main diagnosis. (The interpretation of findings is limited by the lack of differentiation between acute and chronic cases and of direct categorisation of severity for subdural haemorrhage in the official hospital discharge records).Discussion: The study results urge the increase of compliance for evidence based guidelines, since despite of some validity issues, it was demonstrated that the deviation from recommended practice is reflected in the disadvantageous outcome.
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| 23. |
- Sranko, David, et al.
(författare)
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Synthesis and properties of novel Ba(II)Fe(III) layered double hydroxides
- 2010
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Ingår i: Applied Clay Science. - : Elsevier BV. - 1872-9053 .- 0169-1317. ; 48:1-2, s. 214-217
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Tidskriftsartikel (refereegranskat)abstract
- Double hydroxides of Ba(II) and Fe(III) were prepared by the co-precipitation method. Co-precipitation was facilitated by applying highly alkaline, carbonate free NaOH solutions with varying base concentrations (2-20 M). The substances, thus obtained, were characterised by thermal methods. XRD spectra of samples treated at various temperatures, Mossbauer and X-ray absorption spectroscopies. It was found that in extremely concentrated base solutions (>= 10 M) layered double hydroxides, most probably with intercalated OH ions, were formed, indeed, while at low base concentration the Fe(III) ions were precipitated as various oxyhydroxides and the Ba(II) ions remained dissolved. (C) 2009 Elsevier B.V. All rights reserved.
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| 24. |
- Tamas, Andrea, et al.
(författare)
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Effect of PACAP in central and peripheral nerve injuries
- 2012
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 13:7, s. 8430-8448
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Forskningsöversikt (refereegranskat)abstract
- Pituitary adenylate cyclase activating polypeptide (PACAP) is a bioactive peptide with diverse effects in the nervous system. In addition to its more classic role as a neuromodulator, PACAP functions as a neurotrophic factor. Several neurotrophic factors have been shown to play an important role in the endogenous response following both cerebral ischemia and traumatic brain injury and to be effective when given exogenously. A number of studies have shown the neuroprotective effect of PACAP in different models of ischemia, neurodegenerative diseases and retinal degeneration. The aim of this review is to summarize the findings on the neuroprotective potential of PACAP in models of different traumatic nerve injuries. Expression of endogenous PACAP and its specific PAC1 receptor is elevated in different parts of the central and peripheral nervous system after traumatic injuries. Some experiments demonstrate the protective effect of exogenous PACAP treatment in different traumatic brain injury models, in facial nerve and optic nerve trauma. The upregulation of endogenous PACAP and its receptors and the protective effect of exogenous PACAP after different central and peripheral nerve injuries show the important function of PACAP in neuronal regeneration indicating that PACAP may also be a promising therapeutic agent in injuries of the nervous system.
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| 25. |
- Tamás, Andrea, et al.
(författare)
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Postinjury administration of pituitary adenylate cyclase activating polypeptide (PACAP) attenuates traumatically induced axonal injury in rats
- 2006
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 23:5, s. 686-695
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary adenylate cyclase activating polypeptide (PACAP) has several different actions in the nervous system. Numerous studies have shown its neuroprotective effects both in vitro and in vivo. Previously, it has been demonstrated that PACAP reduces brain damage in rat models of global and focal cerebral ischemia. Based on the protective effects of PACAP in cerebral ischemia and the presence of common pathogenic mechanisms in cerebral ischemia and traumatic brain injury (TBI), the aim of the present study was to investigate the possible protective effect of PACAP administered 30 min or 1 h postinjury in a rat model of diffuse axonal injury. Adult Wistar male rats were subjected to impact acceleration, and PACAP was administered intracerebroventricularly 30 min (n = 4), and 1 h after the injury (n = 5). Control animals received the same volume of vehicle at both time-points (n = 5). Two hours after the injury, brains were processed for immunohistochemical localization of damaged axonal profiles displaying either beta-amyloid precursor protein (beta-APP) or RMO-14 immunoreactivity, both considered markers of specific features of traumatic axonal injury. Our results show that treatment with PACAP (100 microg) 30 min or 1 h after the induction of TBI resulted in a significant reduction of the density of beta-APP-immunopositive axon profiles in the corticospinal tract (CSpT). There was no significant difference between the density of beta-APP-immunopositive axons in the medial longitudinal fascicle (MLF). PACAP treatment did not result in significantly different number of RMO-14-immunopositive axonal profiles in either brain areas 2 hours post-injury compared to normal animals. While the results of this study highlighted the complexity of the pathogenesis and manifestation of diffuse axonal injury, they also indicate that PACAP should be considered a potential therapeutic agent in TBI.
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| 26. |
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| 27. |
- Wahlgren, Weixiao Yuan, 1970, et al.
(författare)
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The catalytic aspartate is protonated in the Michaelis complex formed between trypsin and an in vitro evolved substrate-like inhibitor: a refined mechanism of serine protease action.
- 2011
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 286:5, s. 3587-96
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of serine proteases prominently illustrates how charged amino acid residues and proton transfer events facilitate enzyme catalysis. Here we present an ultrahigh resolution (0.93 Å) x-ray structure of a complex formed between trypsin and a canonical inhibitor acting through a substrate-like mechanism. The electron density indicates the protonation state of all catalytic residues where the catalytic histidine is, as expected, in its neutral state prior to the acylation step by the catalytic serine. The carboxyl group of the catalytic aspartate displays an asymmetric electron density so that the O(δ2)-C(γ) bond appears to be a double bond, with O(δ2) involved in a hydrogen bond to His-57 and Ser-214. Only when Asp-102 is protonated on O(δ1) atom could a density functional theory simulation reproduce the observed electron density. The presence of a putative hydrogen atom is also confirmed by a residual mF(obs) - DF(calc) density above 2.5 σ next to O(δ1). As a possible functional role for the neutral aspartate in the active site, we propose that in the substrate-bound form, the neutral aspartate residue helps to keep the pK(a) of the histidine sufficiently low, in the active neutral form. When the histidine receives a proton during the catalytic cycle, the aspartate becomes simultaneously negatively charged, providing additional stabilization for the protonated histidine and indirectly to the tetrahedral intermediate. This novel proposal unifies the seemingly conflicting experimental observations, which were previously seen as either supporting the charge relay mechanism or the neutral pK(a) histidine theory.
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| 28. |
- Welch, Robert D, et al.
(författare)
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Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B to Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury.
- 2016
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 33:2, s. 203-214
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Tidskriftsartikel (refereegranskat)abstract
- Head Computed Tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multi-center observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (Glial Fibrillary Acidic Protein [GFAP], Ubiquitin C-Terminal Hydrolase-L1 [UCH-L1] and S100B measured within 6-hours of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury), was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value > 40 pg/ml. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/ml) and S100B had a specificity of only 2% (cutoff value 30 pg/ml). All three biomarkers had similar values for areas under the receiver operator characteristic curve; 0.79 (95% CI; 0.70 to 0.88) for GFAP, 0.80 (0.71 to 0.89) for UCH-L1, and 0.75 (0.65 to 0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p=0.21 and p=0.77 respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values < 40 pg/ml could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
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| 29. |
- Welch, Robert D., et al.
(författare)
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Ability of serum glial fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B to differentiate normal and abnormal head computed tomography findings in patients with suspected mild or moderate traumatic brain injury
- 2016
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 33:2, s. 203-214
-
Tidskriftsartikel (refereegranskat)abstract
- Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
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| 30. |
- Zhang, Bo, et al.
(författare)
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The chromatin-modifying protein HUB2 is involved in the regulation of lignin composition in xylem vessels
- 2020
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Ingår i: Journal of Experimental Botany. - : Oxford University Press. - 0022-0957 .- 1460-2431. ; 71:18, s. 5484-5494
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Tidskriftsartikel (refereegranskat)abstract
- PIRIN2 (PRN2) was earlier reported to suppress syringyl (S)-type lignin accumulation of xylem vessels of Arabidopsis thaliana. In the present study, we report yeast two-hybrid results supporting the interaction of PRN2 with HISTONE MONOUBIQUITINATION2 (HUB2) in Arabidopsis. HUB2 has been previously implicated in several plant developmental processes, but not in lignification. Interaction between PRN2 and HUB2 was verified by β-galactosidase enzymatic and co-immunoprecipitation assays. HUB2 promoted the deposition of S-type lignin in the secondary cell walls of both stem and hypocotyl tissues, as analysed by pyrolysis-GC/MS. Chemical fingerprinting of individual xylem vessel cell walls by Raman and Fourier transform infrared microspectroscopy supported the function of HUB2 in lignin deposition. These results, together with a genetic analysis of the hub2 prn2 double mutant, support the antagonistic function of PRN2 and HUB2 in deposition of S-type lignin. Transcriptome analyses indicated the opposite regulation of the S-type lignin biosynthetic gene FERULATE-5-HYDROXYLASE1 by PRN2 and HUB2 as the underlying mechanism. PRN2 and HUB2 promoter activities co-localized in cells neighbouring the xylem vessel elements, suggesting that the S-type lignin-promoting function of HUB2 is antagonized by PRN2 for the benefit of the guaiacyl (G)-type lignin enrichment of the neighbouring xylem vessel elements.
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