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991.
Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion 总被引:6,自引:1,他引:6
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Schäfer A Schulz C Eigenthaler M Fraccarollo D Kobsar A Gawaz M Ertl G Walter U Bauersachs J 《Blood》2004,103(2):407-412
Chemokines released by the endothelium have proaggregatory properties on platelets. Fractalkine, a recently discovered membrane-bound chemokine with a transmembrane domain, is expressed in vascular injury; however, the effects of fractalkine on platelets have not yet been investigated. Blood was taken from healthy Wistar-Kyoto rats and the expression of the fractalkine receptor on platelets was demonstrated. The modulation of surface expression of P-selectin was assessed by flow cytometry. P-selectin expression was significantly enhanced by in vitro stimulation with recombinant rat fractalkine compared with baseline levels. Selectively inhibiting the function of recombinant fractalkine by an antagonizing antibody or the disruption of the G-protein-coupled intracellular signaling cascade of the fractalkine receptor by pertussis toxin (PTX) completely prevented fractalkine-mediated platelet activation. Preincubation with apyrase significantly attenuated the fractalkine-induced degranulation. In a flow chamber model of platelet adhesion, stimulation with fractalkine significantly enhanced platelet adhesion to collagen and fibrinogen. Similar to P-selectin expression, enhanced adhesion could be prevented by the antagonizing antibody or preincubation of platelets with PTX. Fractalkine, which is overexpressed in atherosclerosis and vascular injury, contributes to platelet activation and adhesion and hence is likely to play a pathophysiologically important role for increased thrombogenesis in vascular diseases. 相似文献
992.
Raloxifene concurrently stimulates osteoprotegerin and inhibits interleukin-6 production by human trabecular osteoblasts 总被引:6,自引:0,他引:6
Viereck V Gründker C Blaschke S Niederkleine B Siggelkow H Frosch KH Raddatz D Emons G Hofbauer LC 《The Journal of clinical endocrinology and metabolism》2003,88(9):4206-4213
Raloxifene reduces bone loss and prevents vertebral fractures in postmenopausal women. Its skeletal effects are mediated by estrogen receptors (ER) and their modulation of paracrine osteoblastic factors. Receptor activator of nuclear factor-kappa B ligand is essential for osteoclasts and enhances bone resorption, whereas osteoprotegerin (OPG) neutralizes receptor activator of nuclear factor-kappa B ligand. Here, we assessed the effects of raloxifene on OPG production in human osteoblasts (hOB). Raloxifene enhanced gene expression of ER-alpha and progesterone receptor. Moreover, raloxifene increased OPG mRNA levels and protein secretion by hOB in a dose- and time-dependent fashion by 2- to 4-fold with a maximum effect at 10(-7) M and after 72 h (P < 0.001). Treatment with the ER antagonist ICI 182,780 abrogated the effects of raloxifene on OPG production. Moreover, raloxifene enhanced osteoblastic differentiation markers, type 1 collagen secretion, and alkaline phosphatase activity by 3- and 2-fold, respectively (P < 0.001). In addition, raloxifene inhibited expression of the bone-resorbing cytokine IL-6 by 25-45% (P < 0.001). In conclusion, our data suggest that raloxifene stimulates OPG production and inhibits IL-6 production by hOB. Because OPG production increases with osteoblastic maturation, enhancement of OPG production by raloxifene could be related to its stimulatory effects on osteoblastic differentiation. 相似文献
993.
Haude M Caspari G Baumgart D Ehring T Schulz R Roth T Koch L Erbel R Spiller P Heusch G 《Basic research in cardiology》2000,95(3):261-270
The evaluation of regional myocardial blood flow (RMBF) during cardiac catheterization is of particular diagnostic interest.
The purpose of this investigation was to validate x-ray densitometric parameters for the evaluation of RMBF.
In five anesthetized dogs, arterial flow in the circumflex coronary artery was measured continuously with an electromagnetic
flowmeter, and RMBF was determined by colored microspheres. Five different perfusion levels were created by mechanical obstruction
of the coronary artery or by intravenous infusion of adenosine. At each steady-state perfusion level, digital subtraction
coronary angiograms were obtained for densitometric analysis.
Results documented a close correlation between the related time parameters 1/Mean Transit Time (1/MTT, r2 = 0.969), and 1/Rise Time (1/RT, r2 = 0.965) and RMBF over a wide range between 0.36 ml/(min · g) and 11.16 ml/(min · g). Maximum myocardial contrast density
(Imax) also showed a good, but inverse correlation (r2 = 0.889) with RMBF and, therefore, did not reflect vascular volume. Contrast medium Appearance Time (AT) showed no correlation
to RMBF (r2 = 0.017). Repeat densitometric measurements for different perfusion levels revealed a good reproducibility for MTT (accuracy:
0.001 s; precision: 0.447 s or 6.7%) and RT (accuracy: 0.014 s; precision: 0.202 s or 10.4%), while AT (accuracy: 0.072 s;
precision: 0.420 s or 68.5%) and Imax (accuracy: 0.022 GL; precision: 1.197 GL or 44.5%) showed substantial variation. Myocardial
perfusion reserve (MPR) calculated from RT (r2 = 0.90) or MTT (r2 = 0.94) showed better correlations to RMBF reserve than MPR calculated from AT (r2 = 0.04).
In conclusion, only 1/MTT and 1/RT showed a good reproducibility and a close correlation to RMBF. Therefore, only these parameters
can be recommended for calculations of RMBF and its reserve under clinical conditions.
Received: 2 November 1999, Returned for revision: 5 January 2000, Revision received: 1 February 2000, Accepted: 6 February
2000 相似文献
994.
Perla Oliveira Schulz Fabio Gon?alves Ferreira Maria de Fátima Araújo Nascimento Andrea Vieira Mauricio Alves Ribeiro André Ibrahim David Luiz Arnaldo Szutan 《World journal of gastroenterology : WJG》2015,21(3):913-918
AIM:To investigate the association between nonalcoholic fatty liver disease(NAFLD) and liver cancer,and NAFLD prevalence in different liver tumors.METHODS:This is a retrospective study of the clinical,laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation,with subsequent evaluation of the explant or liver biopsy.The following criteria were used to exclude patients from the study:a history of alcohol abuse,hepatitis B or C infection,no tumor detected in the liver tissue examined by histological analysis,and the presence of chronic autoimmune hepatitis,hemochromatosis,Wilson’s disease,or hepatoblastoma.The occurrence of NAFLD and the association with its known risk factors were studied.The risk factors considered were diabetes mellitus,impaired glucose tolerance,impaired fasting glucose,body mass index,dyslipidemia,and arterial hypertension.Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation.Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade.RESULTS:No difference was found in the association of NAFLD with the general population(34.2% and 30.0% respectively,95%CI:25.8-43.4).Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma(OR = 3.99,95%CI:1.78-8.94,P < 0.001 vs OR = 0.60,95%CI:0.18-2.01,P = 0.406 and OR = 0.70,95%CI:0.18-2.80,P = 0.613,respectively).There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma(OR = 3.50,95%CI:1.06-11.57,P = 0.032).Evaluation of the relationship between the presence of NAFLD,nonalcoholic steatohepatitis,and liver fibrosis,and their risk factors,showed no significant statistical association for any of the tumors studied.CONCLUSION:NAFLD is more common in patients with liver metastases caused by colorectal cancer. 相似文献
995.
996.
Corticosterone and corticotropin‐releasing factor acutely facilitate gamma oscillations in the hippocampus in vitro
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Gürsel Çalışkan Steffen B. Schulz David Gruber Joachim Behr Uwe Heinemann Zoltan Gerevich 《The European journal of neuroscience》2015,41(1):31-44
Stressful experiences do not only cause peripheral changes in stress hormone levels, but also affect central structures such as the hippocampus, implicated in spatial orientation, stress evaluation, and learning and memory. It has been suggested that formation of memory traces is dependent on hippocampal gamma oscillations observed during alert behaviour and rapid eye movement sleep. Furthermore, during quiescent behaviour, sharp wave‐ripple (SW‐R) activity emerges. These events provide a temporal window during which reactivation of memory ensembles occur. We hypothesized that stress‐responsive modulators, such as corticosterone (CORT), corticotropin‐releasing factor (CRF) and the neurosteroid 3α, 21‐dihydroxy‐5α‐pregnan‐20‐one (THDOC) are able to modulate gamma oscillations and SW‐Rs. Using in vitro hippocampal slices, we studied acute and subacute (2 h) impact of these agents on gamma oscillations in area cornu ammonis 3 of the ventral hippocampus induced by acetylcholine (10 μm ) combined with physostigmine (2 μm ). CORT increased the gamma oscillations in a dose‐dependent fashion. This effect was mediated by glucocorticoid receptors. Likewise, CRF augmented gamma oscillations via CRF type 1 receptor. Lastly, THDOC was found to diminish cholinergic gamma oscillations in a dose‐dependent manner. Neither CORT, CRF nor THDOC modulated gamma power when pre‐applied for 1 h, 2 h before the induction of gamma oscillations. Interestingly, stress‐related neuromodulators had rather mild effects on spontaneous SW‐R compared with their effects on gamma oscillations. These data suggest that the alteration of hippocampal gamma oscillation strength in vitro by stress‐related agents is an acute process, permitting fast adaptation to new attention‐requiring situations in vivo. 相似文献
997.
Andreas Brodehl Anna Gaertner‐Rommel Bärbel Klauke Simon Andre Grewe Ilona Schirmer Andreas Peterschröder Lothar Faber Matthias Vorgerd Jan Gummert Dario Anselmetti Uwe Schulz Lech Paluszkiewicz Hendrik Milting 《Human mutation》2017,38(8):947-952
Restrictive cardiomyopathy (RCM) is a rare heart disease characterized by diastolic dysfunction and atrial enlargement. The genetic etiology of RCM is not completely known. We identified by a next‐generation sequencing panel the novel CRYAB missense mutation c.326A>G, p.D109G in a small family with RCM in combination with skeletal myopathy with an early onset of the disease. CRYAB encodes αB‐crystallin, a member of the small heat shock protein family, which is highly expressed in cardiac and skeletal muscle. In addition to in silico prediction analysis, our structural analysis of explanted myocardial tissue of a mutation carrier as well as in vitro cell transfection experiments revealed abnormal protein aggregation of mutant αB‐crystallin and desmin, supporting the deleterious effect of this novel mutation. In conclusion, CRYAB appears to be a novel RCM gene, which might have relevance for the molecular diagnosis and the genetic counseling of further affected families in the future. 相似文献
998.
Measuring symptoms and diagnosing mental disorders in the elderly community: the test–retest reliability of the CIDI65+
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Hans‐Ulrich Wittchen Jens Strehle Anja Gerschler Jana Volkert Maria Christina Dehoust Susanne Sehner Karl Wegscheider Berta Ausìn Alessandra Canuto Mike Crawford Chiara Da Ronch Luigi Grassi Yael Hershkovitz Manuel Munoz Alan Quirk Ora Rotenstein Ana Belén Santos‐Olmo Arieh Shalev Kerstin Weber Holger Schulz Martin Härter Sylke Andreas 《International journal of methods in psychiatric research》2015,24(2):116-129
999.
Memory CD8+ T cells colocalize with IL‐7+ stromal cells in bone marrow and rest in terms of proliferation and transcription
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![点击此处可从《European journal of immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Özen Sercan Alp Sibel Durlanik Daniel Schulz Mairi McGrath Joachim R. Grün Marcus Bardua Koichi Ikuta Evridiki Sgouroudis René Riedel Sandra Zehentmeier Anja E. Hauser Motokazu Tsuneto Fritz Melchers Koji Tokoyoda Hyun‐Dong Chang Andreas Thiel Andreas Radbruch 《European journal of immunology》2015,45(4):975-987