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  • 1
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    MMP9 Variation After Thrombolysis Is Associated With Hemorrhagic Transformation of Lesion and Death [Brief Reports] (2013)
    American Heart Association (AHA)
    In: Stroke
    Details
    Publication Date: 2013-09-24
    Description: Background and Purpose— Experimentally, matrix metalloproteinases (MMPs) play a detrimental role related to hemorrhagic transformation and severity of an ischemic brain lesion. Tissue-type plasminogen activator (tPA) enhances such effects. This study aimed to expand clinical evidence in this connection. Methods— We measured MMPs 1, 2, 3, 7, 8, 9, and tissue inhibitors of metalloproteinases 1, 2, 4 circulating level in blood taken before and 24 hours after tPA from 327 patients (mean age, 68.9±12.1 years; median National Institutes of Health Stroke Scale, 11) with acute ischemic stroke. Delta median values ([24 hours post tPA–pre tPA]/pre tPA) of each MMP or tissue inhibitors of metalloproteinase were analyzed across subgroups of patients undergoing symptomatic intracerebral hemorrhage, 3-month death, or 3-month modified Rankin Scale score 3 to 6. Results— Adjusting for major clinical determinants, only matrix metalloproteinase-9 variation proved independently associated with death (odds ratio [95% confidence interval], 1.58 [1.11–2.26]; P =0.045) or symptomatic intracerebral hemorrhage (odds ratio [95% confidence interval], 1.40 [1.02–1.92]; P =0.049). Both matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-4 changes were correlated with baseline, 24 hours, and 7 days National Institutes of Health Stroke Scale (Spearman P from 〈0.001 to 0.040). Conclusions— Our clinical evidence corroborates the detrimental role of matrix metalloproteinase-9 during ischemic stroke treated with thrombolysis, and prompts clinical trials testing agents antagonizing its effects.
    Keywords: Acute Cerebral Infarction, Thrombolysis
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 2
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    Nicotine-Induced Structural Plasticity in Mesencephalic Dopaminergic Neurons Is Mediated by Dopamine D3 Receptors and Akt-mTORC1 Signaling [Articles] (2013)
    The American Society for Pharmacology and Experimental Therapeutics (ASPET)
    Details
    Publication Date: 2013-05-15
    Description: Although long-term exposure to nicotine is highly addictive, one beneficial consequence of chronic tobacco use is a reduced risk for Parkinson’s disease. Of interest, these effects both reflect structural and functional plasticity of brain circuits controlling reward and motor behavior and, specifically, recruitment of nicotinic acetylcholine receptors (nAChR) in mesencephalic dopaminergic neurons. Because the underlying cellular mechanisms are poorly understood, we addressed this issue with use of primary cultures of mouse mesencephalic dopaminergic neurons. Exposure to nicotine (1–10 μ M) for 72 hours in vitro increased dendritic arborization and soma size in primary cultures. These effects were blocked by mecamylamine and dihydro- β -erythroidine, but not methyllycaconitine. The involvement of α 4 β 2 nAChR was supported by the lack of nicotine-induced structural remodeling in neurons from α 4 null mutant mice (KO). Challenge with nicotine triggered phosphorylation of the extracellular signal-regulated kinase (ERK) and the thymoma viral proto-oncogene (Akt), followed by activation of the mammalian target of rapamycin complex 1 (mTORC1)-dependent p70 ribosomal S6 protein kinase. Upstream pathway blockade using the phosphatidylinositol 3-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4 H -1-benzopyran-4-one hydrochloride] resulted in suppression of nicotine-induced phosphorylations and structural plasticity. These effects were dependent on functional DA D3 receptor (D3R), because nicotine was inactive both in cultures from D3R KO mice and after pharmacologic blockade with D3R antagonist trans -N-4-2-(6-cyano-1,2,3, 4-tetrahydroisoquinolin-2-yl)ethylcyclohexyl-4-quinolinecarboxamide (SB-277011-A) (50 nM). Finally, exposure to nicotine in utero (5 mg/kg/day for 5 days) resulted in increased soma area of DAergic neurons of newborn mice, effects not observed in D3 receptor null mutant mice mice. These findings indicate that nicotine-induced structural plasticity at mesencephalic dopaminergic neurons involves α 4 β 2 nAChRs together with dopamine D3R-mediated recruitment of ERK/Akt-mTORC1 signaling.
    Print ISSN: 0026-895X
    Electronic ISSN: 1521-0111
    Topics: Chemistry and Pharmacology , Medicine
    Published by The American Society for Pharmacology and Experimental Therapeutics (ASPET)
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  • 3
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    Glycoproteins in Angiogenesis and Validation in Zebrafish [Glycobiology and Extracellular Matrices] (2015)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2015-02-07
    Description: The formation of new vessels in the tumor, termed angiogenesis, is essential for primary tumor growth and facilitates tumor invasion and metastasis. Hypoxia has been described as one trigger of angiogenesis. Indeed, hypoxia, which is characterized by areas of low oxygen levels, is a hallmark of solid tumors arising from an imbalance between oxygen delivery and consumption. Hypoxic conditions have profound effects on the different components of the tumoral environment. For example, hypoxia is able to activate endothelial cells, leading to angiogenesis but also thereby initiating a cascade of reactions involving neutrophils, smooth muscle cells, and fibroblasts. In addition, hypoxia directly regulates the expression of many genes for which the role and the importance in the tumoral environment remain to be completely elucidated. In this study, we used a method to selectively label sialoglycoproteins to identify new membrane and secreted proteins involved in the adaptative process of endothelial cells by mass spectrometry-based proteomics. We used an in vitro assay under hypoxic condition to observe an increase of protein expression or modifications of glycosylation. Then the function of the identified proteins was assessed in a vasculogenesis assay in vivo by using a morpholino strategy in zebrafish. First, our approach was validated by the identification of sialoglycoproteins such as CD105, neuropilin-1, and CLEC14A, which have already been described as playing key roles in angiogenesis. Second, we identified several new proteins regulated by hypoxia and demonstrated for the first time the pivotal role of GLUT-1, TMEM16F, and SDF4 in angiogenesis.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 4
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    Three classical Cepheid variable stars in the nuclear bulge of the Milky Way (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-08-26
    Description: The nuclear bulge is a region with a radius of about 200 parsecs around the centre of the Milky Way. It contains stars with ages ranging from a few million years to over a billion years, yet its star-formation history and the triggering process for star formation remain to be resolved. Recently, episodic star formation, powered by changes in the gas content, has been suggested. Classical Cepheid variable stars have pulsation periods that decrease with increasing age, so it is possible to probe the star-formation history on the basis of the distribution of their periods. Here we report the presence of three classical Cepheids in the nuclear bulge with pulsation periods of approximately 20 days, within 40 parsecs (projected distance) of the central black hole. No Cepheids with longer or shorter periods were found. We infer that there was a period about 25 million years ago, and possibly lasting until recently, in which star formation increased relative to the period of 30-70 million years ago.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsunaga, Noriyuki -- Kawadu, Takahiro -- Nishiyama, Shogo -- Nagayama, Takahiro -- Kobayashi, Naoto -- Tamura, Motohide -- Bono, Giuseppe -- Feast, Michael W -- Nagata, Tetsuya -- England -- Nature. 2011 Aug 24;477(7363):188-90. doi: 10.1038/nature10359.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Kiso Observatory, Institute of Astronomy, University of Tokyo, 10762-30 Mitake, Kiso-machi, Kiso-gun, Nagano 397-0101, Japan. matsunaga@ioa.s.u-tokyo.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21866100" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    An eclipsing-binary distance to the Large Magellanic Cloud accurate to two per cent (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-03-08
    Description: In the era of precision cosmology, it is essential to determine the Hubble constant to an accuracy of three per cent or better. At present, its uncertainty is dominated by the uncertainty in the distance to the Large Magellanic Cloud (LMC), which, being our second-closest galaxy, serves as the best anchor point for the cosmic distance scale. Observations of eclipsing binaries offer a unique opportunity to measure stellar parameters and distances precisely and accurately. The eclipsing-binary method was previously applied to the LMC, but the accuracy of the distance results was lessened by the need to model the bright, early-type systems used in those studies. Here we report determinations of the distances to eight long-period, late-type eclipsing systems in the LMC, composed of cool, giant stars. For these systems, we can accurately measure both the linear and the angular sizes of their components and avoid the most important problems related to the hot, early-type systems. The LMC distance that we derive from these systems (49.97 +/- 0.19 (statistical) +/- 1.11 (systematic) kiloparsecs) is accurate to 2.2 per cent and provides a firm base for a 3-per-cent determination of the Hubble constant, with prospects for improvement to 2 per cent in the future.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pietrzynski, G -- Graczyk, D -- Gieren, W -- Thompson, I B -- Pilecki, B -- Udalski, A -- Soszynski, I -- Kozlowski, S -- Konorski, P -- Suchomska, K -- Bono, G -- Moroni, P G Prada -- Villanova, S -- Nardetto, N -- Bresolin, F -- Kudritzki, R P -- Storm, J -- Gallenne, A -- Smolec, R -- Minniti, D -- Kubiak, M -- Szymanski, M K -- Poleski, R -- Wyrzykowski, L -- Ulaczyk, K -- Pietrukowicz, P -- Gorski, M -- Karczmarek, P -- England -- Nature. 2013 Mar 7;495(7439):76-9. doi: 10.1038/nature11878.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Universidad de Concepcion, Departamento de Astronomia, Casilla 160-C, Concepcion, Chile. pietrzyn@astrouw.edu.pl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23467166" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 6
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    RR-Lyrae-type pulsations from a 0.26-solar-mass star in a binary system (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-04-07
    Description: RR Lyrae pulsating stars have been extensively used as tracers of old stellar populations for the purpose of determining the ages of galaxies, and as tools to measure distances to nearby galaxies. There was accordingly considerable interest when the RR Lyrae star OGLE-BLG-RRLYR-02792 (referred to here as RRLYR-02792) was found to be a member of an eclipsing binary system, because the mass of the pulsator (hitherto constrained only by models) could be unambiguously determined. Here we report that RRLYR-02792 has a mass of 0.26 solar masses M[symbol see text] and therefore cannot be a classical RR Lyrae star. Using models, we find that its properties are best explained by the evolution of a close binary system that started with M[symbol see text] and 0.8M[symbol see text]stars orbiting each other with an initial period of 2.9 days. Mass exchange over 5.4 billion years produced the observed system, which is now in a very short-lived phase where the physical properties of the pulsator happen to place it in the same instability strip of the Hertzsprung-Russell diagram as that occupied by RR Lyrae stars. We estimate that only 0.2 per cent of RR Lyrae stars may be contaminated by systems similar to this one, which implies that distances measured with RR Lyrae stars should not be significantly affected by these binary interlopers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pietrzynski, G -- Thompson, I B -- Gieren, W -- Graczyk, D -- Stepien, K -- Bono, G -- Moroni, P G Prada -- Pilecki, B -- Udalski, A -- Soszynski, I -- Preston, G W -- Nardetto, N -- McWilliam, A -- Roederer, I U -- Gorski, M -- Konorski, P -- Storm, J -- England -- Nature. 2012 Apr 4;484(7392):75-7. doi: 10.1038/nature10966.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departamento de Astronomia, Universidad de Concepcion, Casilla 160-C, Concepcion, Chile. pietrzyn@astrouw.edu.pl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22481359" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
    Electronic Resource
    Electronic Resource
    Comparative study with EMG, pressure algometry and manual palpation in tension-type headache and migraine (1994)
    USA/Oxford, UK : Blackwell Science Ltd
    Cephalalgia 14 (1994), S. 0 
    Details
    ISSN: 1468-2982
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: According to International Headache Society classification criteria, the presence of pericranial muscle disorder in tension-type headache should be evaluated using one of the following methods: EMG, pressure algometry or manual palpation. The purpose of this study was to compare the results of these three methods in 15 patients with episodic tension-type headache, 29 with chronic tension-type headache and 22 presenting migraine without aura compared to those obtained in healthy individuals. Algometric and EMG recordings at the frontalis muscle during mental arithmetic were more impaired in episodic and chronic tension headache patients than in controls and migraine patients. Chronic tension headache patients were significantly impaired at the trapezius muscle in all three tests compared to controls. Our data indicate that when two or three tests were carried out the diagnostic capacity was significantly improved in comparison to only one test. Moreover, since a different pattern could be seen with pain and without pain, the existence of headache at the time of testing should be taken into consideration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1468-2982.1994.1406451.x
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  • 8
    Electronic Resource
    Electronic Resource
    Pain pressure threshold in cluster headache patients (1996)
    USA/Oxford, UK : Blackwell Science Ltd
    Cephalalgia 16 (1996), S. 0 
    Details
    ISSN: 1468-2982
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Pain perception threshold (PFT) in the head was assessed with a pressure algometer in 58 cluster headache (CH) patients (52M, 6F; 41 episodic and 17 chronic). Fourteen patients in cluster period were retested in remission. Thresholds were assessed at 10 symmetrical points on each side of the head and at the deltoid. Compared with controls (n = 80), CH patients had lower PPT in the head and in the deltoid. PPT was lower on the symptomatic side than on the non-symptomatic side in patients with episodic CH during a cluster period (p〈0.001) and in patients with chronic CH (p〈0.05). This pattern was more evident during a cluster period than during remission (p〈0.05). A reduced PPT did not correlate with illness duration and pain side. The lowest PPT mean values were found at the anterior and intermediate levels of the temporal muscle on the symptomatic side. These results imply a central mechanism underlying the pathogenesis of CH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1468-2982.1996.1601052.x
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  • 9
    Electronic Resource
    Electronic Resource
    Changes in the 24-hour prolactin pattern in cluster headache (1982)
    USA/Oxford, UK : Blackwell Science Ltd
    Cephalalgia 2 (1982), S. 0 
    Details
    ISSN: 1468-2982
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The regulation of prolactin (PRL) secretion periodicity in cluster headache (CH) and in atypical facial pain (AFP) has been studied in nine and seven patients, respectively. The physiological periodicity of the hormone secretion, with its highest levels during night sleep and its lowest during the waking hours, is upset in CH, but not in AFP. A rhythmicity occurs in CH only in the presence of severe pain, which appears to be the synchronizing event. Lithium carbonate treatment does not interfere with the mentioned changes in PRL secretion in CH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1468-2982.1982.0201001.x
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  • 10
    Electronic Resource
    Electronic Resource
    Safety Profile of Flunarizine (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 522 (1988), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1988.tb33418.x
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