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排序方式: 共有547条查询结果,搜索用时 909 毫秒
101.
Emilia A. Korhonen Aino Murtomki Sawan Kumar Jha Andrey Anisimov Anne Pink Yan Zhang Simon Stritt Inam Liaqat Lukas Stanczuk Laura Alderfer Zhiliang Sun Emmi Kapiainen Abhishek Singh Ibrahim Sultan Anni Lantta Veli-Matti Leppnen Lauri Eklund Yulong He Hellmut G. Augustin Kari Vaahtomeri Pipsa Saharinen Taija Mkinen Kari Alitalo 《The Journal of clinical investigation》2022,132(15)
Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C–induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110α subunit or with small-molecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C–induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling. 相似文献
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104.
Gerhard Stark Ulrike Stark Hellmut Samonigg Katharina Kasparek Andreas Lueger Svila Nagl Herwig Bertuch Ernst Pilger Helmut A. Tritthart 《Cancer chemotherapy and pharmacology》1990,26(6):415-418
This study was performed to evaluate the acute effects of two anthracycline derivatives, doxorubicin and 4'O-tetrahydropyranyl-doxorubicin [(THP)-doxorubicin], on the conduction intervals, heart rate and refractoriness of isolated spontaneously beating guinea-pig hearts using a high-resolution ECG recording technique (SST-ECG). Doxorubicin as well as (THP)-doxorubicin were added to the perfusate in increasing concentrations of 0.1, 1 and 10 microM. Doxorubicin did not significantly alter the heart rate or conduction intervals. Only the rate-dependent QT interval was significantly shortened under the influence of 10 microM doxorubicin. In contrast, 10 microM (THP)-doxorubicin led to a significant reduction in the heart rate (-13% +/- 3%; P less than 0.01, n = 7) and to a prolongation of atrioventricular conduction time (24% +/- 10%; P less than 0.05, n = 7). The rate-dependent repolarization period (QT interval) was only insignificantly shortened in the presence of 10 microM (THP)-doxorubicin. The maximal following frequencies of each part of the conduction system were not changed by 10 microM doxorubicin. In the presence of (THP)-doxorubicin, the maximal following frequency of the ventricular myocardium was increased by as much as 36% +/- 8% (P less than 0.01, n = 7), indicating a shortening of the effective refractory period of the ventricular myocardium (V-ERP). These results show that the activation of (THP)-doxorubicin resembles the effects of Ca-antagonistic compounds on the heart (i.e. decrease in the spontaneous sinus rate and prolongation of the AV-nodal conduction interval). Changes in the QT interval exerted by doxorubicin and the shortening of the ventricular effective refractory period by (THP)-doxorubicin may indicate an alteration of the K(+)-conductance of the membrane. As the acute electrophysiological effects of doxorubicin and (THP)-doxorubicin are modest and occur only at excessive concentrations (10 microM), a direct influence on the generation of arrhythmias in healthy hearts is unlikely. 相似文献
105.
Andrea Lippoldt Beth Andbjer Hellmut Gerst Detlev Ganten Kjell Fuxe 《Brain research》1996,730(1-2):1-16
Basic fibroblast growth factor (bFGF) gene expression as well as its immunoreactivity were studied after partial unilateral hemitransection of the rat brain during a time course of 24 h, 72 h, 7 and 14 days. The mechanical injury resulted in a global increase of bFGF gene expression at the 24-h time interval. This global increase was seen at the ipsilateral site at the level of the lesion as well as rostral to the lesion in the ipsilateral hemisphere. The upregulation in bFGF gene expression was in most of the areas investigated due to an upregulation in glial cells as seen by means of nonradioactive in situ hybridization compared with immunocytochemistry for glial fibrillary acidic protein (GFAP). Basic FGF immunoreactivity (IR) was increased around the lesion in glial cell nuclei 7 days after the injury. This increase was also detected in GFAP positive glial cells surrounding small vessels in the lesioned area. Moreover, in the present paper we demonstrate increased tenascin immunoreactivity in the lesioned area 7 days after injury. The tenascin IR was increased at the edges of the lesion as well as in vessel like structures. The tenascin IR was partially codistributed with GFAP IR in the lesioned area. The lesion was also characterized by an increase in vimentin IR as well as in laminin IR. It is suggested that the observed changes in the expression of bFGF, matrix proteins (laminin, tenascin) and intermediate filaments (vimentin) are involved in (a) tissue repair, (b) protection of neuronal cells from excitotoxic influences and (c) formation of new vessels in the lesioned area. 相似文献
106.
107.
Atrial inversion was achieved by a modified Mustard operation in 334 patients with various types of transposition of the great arteries (TGA) between January, 1974, and January, 1983, in Hannover, West Germany. The overall mortality was 4.2% (N = 14). Between March, 1978, and January, 1983, 197 of the patients were operated on using a new design of a Gore-Tex prosthetic baffle. In February, 1982, a new step was integrated into our modification of the Mustard operation. It consisted of creating a pericardial flap that serves to enlarge the pulmonary venous atrium. This article describes the modified Mustard operations with Gore-Tex baffle used in 52 children with TGA between October, 1981, and January, 1983. Special attention is focused on operative techniques and on postoperative dysrhythmias and hemodynamics. 相似文献
108.
Hellmut Becher 《Anatomy and embryology》1921,61(1-2):114-136
Ohne Zusammenfassung 相似文献
109.
H Jakob D Maass W Schmiedt H Schild H Oelert 《The Journal of cardiovascular surgery》1989,30(1):112-117
Six patients with extensive iliofemoral and/or caval thrombosis were treated by thrombectomy and subsequent implantation of an expandable endoluminal spiral prosthesis in case of congenital caval stenoses (1) or extravascular compression or traction (5). Five of these patients had undergone previous surgery and thrombosis had developed despite low dose heparin given postoperatively. Three patients had had an unsuccessful thrombectomy prior to spiral implantation. No complications related to the endoluminal prosthesis occurred. There was one retroperitoneal hematoma from guide wire perforation of the inferior vena cava (IVC) necessitating laparotomy and reversal of the previously constructed femoral av-fistula with subsequent iliofemoral rethrombosis. All other endoluminally reconstructed veins remained open at early and late (up to 12 months) review confirmed by phlebography. We conclude that with increasing clinical experience endoluminal relining of obstructed major veins will probably become a valuable method of venous reconstruction with minimal surgical trauma. 相似文献
110.