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Molecular markers to predict stroke

Brian C Searle, Rachel M Gittelman, Ohad Manor, Joshua M Akey
Gene expression levels are dynamic molecular phenotypes that respond to biological, environmental, and technical perturbations. Here we use a novel replicate classifier approach for discovering transcriptional signatures and apply it to the Genotype-Tissue Expression (GTEx) data set. We identified many factors contributing to expression heterogeneity, such as collection center and ischemia time and our approach of scoring replicate classifiers allows us to statistically stratify these factors by effect strength...
October 11, 2016: Genetics
A D Kjaergaard, J S Johansen, S E Bojesen, B G Nordestgaard
This review summarizes present evidence for the role of YKL-40 in the diagnosis, prognosis and cause of cardiovascular and alcoholic liver disease. The question of whether YKL-40 is merely a marker or a causal factor in the development of cardiovascular and liver disease is addressed, with emphasis on the Mendelian randomization design. The Mendelian randomization approach uses genetic variants associated with lifelong high plasma YKL-40 levels that are largely unconfounded and not prone to reverse causation...
December 2016: Critical Reviews in Clinical Laboratory Sciences
Sally Caine, Mark J Hackett, Huishu Hou, Saroj Kumar, Jason Maley, Zurab Ivanishvili, Brandon Suen, Aleksander Szmigielski, Zhongxiang Jiang, Nicole J Sylvain, Helen Nichol, Michael E Kelly
Stroke is a major global health problem, with the prevalence and economic burden predicted to increase due to aging populations in western society. Following stroke, numerous biochemical alterations occur and damage can spread to nearby tissue. This zone of "at risk" tissue is termed the peri-infarct zone (PIZ). As the PIZ contains tissue not initially damaged by the stroke, it is considered by many as salvageable tissue. For this reason, much research effort has been undertaken to improve the identification of the PIZ and to elucidate the biochemical mechanisms that drive tissue damage in the PIZ in the hope of identify new therapeutic targets...
July 2016: Neurobiology of Disease
Timothy Hudson Rainer, Ling Yan Leung, Cangel Pui Yee Chan, Yuk Ki Leung, Jill Morales Abrigo, Defeng Wang, Colin A Graham
OBJECTIVES: This study aimed to investigate plasma concentrations of miR-124-3p and miR-16 as prognostic markers in emergency department patients with acute stroke. DESIGN AND METHODS: Plasma concentrations of miR-124-3p and miR-16 of 84 stroke patients (presenting to the emergency department within 24h from onset of symptoms) were determined by RT-qPCR. The primary outcome measure was 3-month mortality and the secondary outcome measure was post-stroke modified Rankin Score (mRS)...
June 2016: Clinical Biochemistry
I Barchetta, D Capoccia, M G Baroni, R Buzzetti, M G Cavallo, S De Cosmo, F Leonetti, S Leotta, S Morano, L Morviducci, S Prudente, G Pugliese, V Trischitta
BACKGROUND AND AIMS: The rate of mortality in diabetic patients, especially of cardiovascular origin, is about twice as much that of nondiabetic individuals. Thus, the pathogenic factors shaping the risk of mortality in such patients must be unraveled in order to target intensive prevention and treatment strategies. The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with type 2 diabetes mellitus (T2DM)...
February 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Shinichi Asano, Paul D Chantler, Taura L Barr
Biomarker profiling is utilized to identify diagnostic and prognostic candidates for stroke. Clinical and preclinical biomarker data suggest altered circulating immune responses may illuminate the mechanisms of stroke recovery. However, the relationship between peripheral blood biomarker profile(s) and brain profiles following stroke remains elusive. Data show that neutrophil lymphocyte ratio (NLR) predicts stroke outcome. Neutrophils release Arginase 1 (ARG1) resulting in T lymphocyte suppression in peripheral blood...
February 2016: Current Opinion in Pharmacology
Magdalena M Przybycien-Szymanska, William W Ashley
BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating problem. Overall, the mortality rate associated with aSAH is 32% to 67%, which makes it the most lethal type of hemorrhagic stroke. Once the aneurysm has been treated, cerebral vasospasm is the leading cause of morbidity and mortality associated with aSAH. Thus, ability to effectively prevent or treat cerebral vasospasm could result in significantly improved survival and quality of life for aSAH patients. Unfortunately, partly because of poor understanding of the mechanisms of vasospasm, current diagnosis and treatment can be inconsistent and/or ineffective...
July 2015: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Yu Han, Chuanyu Gao, Bingyu Qin, Hongdang Xu, Xianrong Song, Bin Li, Bangtian Peng, Taibing Fan, Zhaoyun Cheng
OBJECTIVE: To study the effect of anticoagulant therapy with low molecular weight heparin (LMWH) on coagulation and inflammation markers in sepsis patients. METHODS: A prospective randomized controlled trial ( RCT ) was conducted. Eighty-seven patients suffering from septic shock undergoing mechanical ventilation in Department of Critical Care Medicine of Subei People's Hospital from June 2012 to September 2014 were enrolled. The hemodynamic changes before and after PLR were monitored by pulse indicated continuous cardiac output ( PiCCO ) and PVI monitoring...
February 2015: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Wolf-Dieter Heiss
Ischemic stroke is caused by interruption or significant impairment of blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphologic damage. The changes in regional cerebral blood flow and regional metabolism can be assessed by radionuclide imaging, especially SPECT and PET. SPECT and PET have broadened our understanding of flow and metabolic thresholds critical for maintenance of brain function and morphology: PET was essential in the transfer of the concept of the penumbra to clinical stroke and thereby had a great impact on developing treatment strategies...
November 2014: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Wolf-Dieter Heiss
Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies...
October 2014: Neuroscience Bulletin
Luye Qin, Deqiang Jing, Sarah Parauda, Jason Carmel, Rajiv R Ratan, Francis S Lee, Sunghee Cho
Little is known about the influence of genetic diversity on stroke recovery. One exception is the polymorphism in brain derived neurotrophic factor (BDNF), a critical neurotrophin for brain repair and plasticity. Humans have a high-frequency single nucleotide polymorphism (SNP) in the prodomain of the BDNF gene. Previous studies show that the BDNF Val66Met variant negatively affects motor learning and severity of acute stroke. To investigate the impact of this common BDNF SNP on stroke recovery, we used a mouse model that contains the human BDNF Val66Met variant in both alleles (BDNF(M/M))...
February 12, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Víctor Llombart, Carmen Dominguez, Alejandro Bustamante, Victor Rodriguez-Sureda, Pilar Martín-Gallán, Angel Vilches, Teresa García-Berrocoso, Anna Penalba, Mar Hernández-Guillamon, Marta Rubiera, Marc Ribó, Christoph Eschenfelder, Dolors Giralt, Carlos A Molina, José Alvarez-Sabín, Anna Rosell, Joan Montaner
BACKGROUND AND PURPOSE: Fluorescent molecular peroxidation products (FMPPs) are considered potential markers of molecular oxidative damage and may provoke increased permeability and disruption of the blood-brain barrier. This study aimed to determine the value of FMPPs as a biomarker to predict neurological worsening related to early hemorrhagic transformation. METHODS: Baseline FMPP levels were measured in 186 consecutive acute ischemic stroke patients before tissue plasminogen activator treatment was administered...
February 2014: Stroke; a Journal of Cerebral Circulation
Rie Okamoto, Akihiro Hirashiki, Xian Wu Cheng, Takashi Yamada, Shuzo Shimazu, Norihiro Shinoda, Takahiro Okumura, Kyosuke Takeshita, Yasuko Bando, Takahisa Kondo, Toyoaki Murohara
Cardiac troponins provide diagnostic and prognostic information on ischemic heart disease, but their roles in hypertrophic cardiomyopathy (HCM) are unclear. We sought to investigate the associations between elevated serum cardiac troponins T (cTnT) and I (cTnI) levels and cardiac injury in patients with HCM. We measured serum cTnT and cTnI in a peripheral vein of 73 consecutive HCM patients in stable condition. In addition, to examine the transcardiac release of cTnT and that of cTnI, we measured them in the aortic root and coronary sinus...
2013: International Heart Journal
Bin Peng, Dianwen Zhu, Bradley P Ander, Xiaoshuai Zhang, Fuzhong Xue, Frank R Sharp, Xiaowei Yang
The discovery of genetic or genomic markers plays a central role in the development of personalized medicine. A notable challenge exists when dealing with the high dimensionality of the data sets, as thousands of genes or millions of genetic variants are collected on a relatively small number of subjects. Traditional gene-wise selection methods using univariate analyses face difficulty to incorporate correlational, structural, or functional structures amongst the molecular measures. For microarray gene expression data, we first summarize solutions in dealing with 'large p, small n' problems, and then propose an integrative Bayesian variable selection (iBVS) framework for simultaneously identifying causal or marker genes and regulatory pathways...
2013: PloS One
Elen A Romão, Charles M Lourenço, Wilson Marques Júnior, Arndt Rolfs, Veronica Muñoz, Osvaldo M Vieira Neto, Marcio Dantas, Gyl E B Silva, Roberto S Costa
Fabry disease is an X-linked inborn error of metabolism, which is caused by the deficiency of α-galactosidase A, leading to progressive accumulation of neutral glycosphingolipids and a-galactosyl breakdown products in most body fluids and several tissues, resulting in the clinical manifestations. The onset of Fabry disease symptoms in females is not observed as early as in males. We report a novel presentation of Fabry disease in a female patient with medical history of relapsing strokes and brain magnetic resonance angiography showing signs of microangiopathy and multiple lacunar strokes that were first diagnosed as Moyamoya disease (a chronic progressive cerebrovascular disease)...
April 2013: Clinical Nephrology
Maria Viviana Miramontes-Espino, Marina Maria de Jesus Romero-Prado
C-reactive protein (CRP) is a homopentameric oligoprotein composed of monomeric subunits that are about 21 kD each. The form of detectable native CRP in validated assays was developed in 2007 and from that time has been considered as an excellent biomarker for peripheral artery disease and/or atherosclerosis, as well as a cardiovascular disease marker for risk prediction. The improvements in the detection of CRP levels could predict significantly the population that have increased risk of stroke being the modulation of CRP levels as a therapeutical outcome for prevention of cardiovascular diseases...
December 2013: Recent Patents on DNA & Gene Sequences
Christos Angelidis, Spyridon Deftereos, Georgios Giannopoulos, Nikolaos Anatoliotakis, Georgios Bouras, Georgios Hatzis, Vasiliki Panagopoulou, Vlasios Pyrgakis, Michael W Cleman
Cystatin C (cys-C) is a small protein molecule (120 amino acid peptide chain, approximately 13kDa) produced by virtually all nucleated cells in the human body. It belongs to the family of papain-like cysteine proteases and its main biological role is the extracellular inhibition of cathepsins. It's near constant production rate, the fact that it is freely filtered from the glomerular membrane and then completely reabsorbed without being secreted from the proximal tubular cells, made it an almost perfect candidate for estimating renal function...
2013: Current Topics in Medicinal Chemistry
Na Li, Yan Fang Liu, Li Ma, Hans Worthmann, Yi Long Wang, Yong Jun Wang, Yi Pei Gao, Peter Raab, Reinhard Dengler, Karin Weissenborn, Xing Quan Zhao
BACKGROUND AND PURPOSE: Perihematomal edema contributes to secondary brain injury in intracerebral hemorrhage (ICH). Increase of matrix metalloproteinases (MMPs) and growth factors is considerably involved in blood-brain barrier disruption and neuronal cell death in ICH models. We therefore hypothesized that increased levels of these molecular markers are associated with perihematomal edema and clinical outcome in ICH patients. METHODS: Fifty-nine patients with spontaneous ICH admitted within 24 hours of symptom onset were prospectively investigated...
March 2013: Stroke; a Journal of Cerebral Circulation
Betânia L D Hatzlhofer, Marcos André C Bezerra, Magnun N N Santos, Dulcinéia M Albuquerque, Elizabete M Freitas, Fernando F Costa, Aderson S Araújo, Maria Tereza C Muniz
Vaso-occlusion is a determinant for most signs and symptoms of sickle-cell anemia (SCA). The mechanisms involved in the pathogenesis of vascular complications in SCA remain unclear. It is known that genetic polymorphisms associated with thrombophilia may be potential modifiers of clinical features of SCA. The genetic polymorphisms C677T and A1298C relating to the enzyme methylenetetrahydrofolate reductase (MTHFR), a clotting Factor V Leiden mutation (1691G→A substitution of Factor V Leiden), and the mutant prothrombin 20210A allele were analyzed in this study...
September 2012: Genetic Testing and Molecular Biomarkers
Robert D Bell
The vascular system plays an integral role during Alzheimer's disease (AD). Both systemic circulatory changes and alterations directly within the brain vasculature have been suggested to contribute to both the onset and progression of neurological conditions such as AD. It is now well established that vascular risk factors including hypertension, diabetes, obesity, atherosclerosis, metabolic syndrome, and stroke significantly increase one's risk of later developing AD. Research within the last decade has begun to identify specific vascular molecules associated with such risk factors as well as elucidate the biological role they may play in the pathological processes linked to AD...
2012: Journal of Alzheimer's Disease: JAD
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