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71.
72.
Samantha A. Chalmers Rajalakshmy Ayilam Ramachandran Sayra J. Garcia Evan Der Leal Herlitz Jeanette Ampudia Dalena Chu Nicole Jordan Ting Zhang Ioannis Parodis Iva Gunnarsson Huihua Ding Nan Shen Michelle Petri Chi Chiu Mok Ramesh Saxena Krishna R. Polu Stephen Connelly Cherie T. Ng Chandra Mohan Chaim Putterman 《The Journal of clinical investigation》2022,132(1)
T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of CD6+ and ALCAM+ cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target. 相似文献
73.
Albert C. Ludolph MD Johannes Dorst MD Jens Dreyhaupt PhD Jochen H. Weishaupt MD Jan Kassubek MD Ulrike Weiland MD Thomas Meyer MD Susanne Petri MD Andreas Hermann MD PhD Alexander Emmer MD Julian Grosskreutz MD Torsten Grehl MD Daniel Zeller MD Matthias Boentert MD Bertold Schrank MD Johannes Prudlo MD Andrea S. Winkler MD Stanislav Gorbulev PhD Francesco Roselli MD PhD Joachim Schuster PhD Luc Dupuis PhD for the LIPCAL-ALS Study Group 《Annals of neurology》2020,87(2):206-216
74.
Diekmann Kristin Kuzma-Kozakiewicz Magdalena Piotrkiewicz Maria Gromicho Marta Grosskreutz Julian Andersen Peter M. de Carvalho Mamede Uysal Hilmi Osmanovic Alma Schreiber-Katz Olivia Petri Susanne Körner Sonja 《Journal of neurology》2020,267(7):2130-2141
Journal of Neurology - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with loss of muscle function. The pathogenesis is still unclear and the heterogeneity of ALS... 相似文献
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76.
Ohne Zusammenfassung 相似文献
77.
Tobias Gassenmaier Nils Petri Thomas Allmendinger Thomas Flohr David Maintz Wolfram Voelker Thorsten A. Bley 《European radiology》2014,24(11):2953-2961
Objectives
To evaluate in-stent lumen visibility of 27 modern and commonly used coronary stents (16 individual stent types, two stents at six different sizes each) utilising a third-generation dual-source CT system.Methods
Stents were implanted in a plastic tube filled with contrast. Examinations were performed parallel to the system's z-axis for all stents (i.e. 0°) and in an orientation of 90° for stents with a diameter of 3.0 mm. Two stents were evaluated in different diameters (2.25 to 4.0 mm). Examinations were acquired with a collimation of 96?×?0.6 mm, tube voltage of 120 kVp with 340 mAs tube current. Evaluation was performed using a medium-soft (Bv40), a medium-sharp (Bv49) and a sharp (Bv59) convolution kernel optimised for vascular imaging.Results
Mean visible stent lumen of stents with 3.0 mm diameter ranged from 53.3 % (IQR 48.9???56.7 %) to 73.9 % (66.7???76.7 %), depending on the kernel used at 0°, and was highest at an orientation of 90° with 80.0 % (75.6???82.8 %) using the Bv59 kernel, strength 4. Visible stent lumen declined with decreasing stent size.Conclusions
Use of third-generation dual-source CT enables stent lumen visibility of up to 80 % in metal stents and 100 % in bioresorbable stents.Key Points
? Blooming artefacts impair in–stent lumen visibility of coronary stents in CT angiography. ? CT enables stent lumen visibility of up to 80 % in metal stents. ? Stent lumen visibility varies with stent orientation and size. ? CT angiography may be a valid alternative for detecting in-stent restenosis. 相似文献78.
Metsärinne KP Vehmaan-Kreula P Kovanen PT Saijonmaa O Baumann M Wang Y Nyman T Fyhrquist FY Eklund KK 《Arteriosclerosis, thrombosis, and vascular biology》2002,22(2):268-273
Subendothelial mast cells have been implicated in the pathogenesis of allergic inflammation, in atherosclerosis, and in the regulation of vascular tone. Because endothelin-1 (ET-1) is an important regulator of vascular tone and has also been implicated in the pathogenesis of atherosclerosis, we studied the role of mast cells in the metabolism of endothelial cell-derived ET-1. In mast cell-endothelial cell cocultures, activation of the mast cells with ensuing degranulation was accompanied by the increased expression of ET-1 mRNA in the endothelial cells, yet the immunoreactive ET-1 protein in the coculture medium disappeared almost completely during the 24-hour coculture. Activation of the mast cells with the ensuing degranulation resulted in proteolytic degradation of ET-1 by the 2 neutral proteases, chymase and carboxypeptidase A, of the exocytosed mast cell granules. With synthetic ET-1 and purified mast cell granule enzymes, efficient degradation of ET-1 by chymase and carboxypeptidase A was verified. These in vitro results imply a novel role for mast cell-derived neutral proteases in ET-1 metabolism and suggest that activated subendothelial mast cells are important local regulators of ET-1 metabolism. 相似文献
79.
Herfarth H Gross V Andus T Caesar I Vogelsang H Adler G Malchow H Petri A Gierend M Schölmerich J;German/Austrian Budesonide Study Group 《International journal of colorectal disease》2004,19(2):147-152
Background and aims The nonsystemic steroid budesonide has been used to treat active ileocecal and ileocolonic Crohn's disease (CD). This study investigated the optimal budesonide dose using a pH-dependent release formulation. The goal of treatment was the remission of CD (CDAI <150) within 6 weeks of treatment.Patients and methods The study was of randomized, double-blind, dose-finding design. Patients with active CD ileocolitis without steroid pretreatment were treated with 3×2 mg (n=39), 3×3 mg (n=33), or 3×6 mg (n=32) oral pH-modified released budesonide daily.Results The remission rates after 6 weeks were 36% with 3×2 mg, 55% with 3×3 mg, and 66% with 3×6 mg. Significantly more patients were in remission while treated with 3× 6mg than with 3×2 mg budesonide/day. Subgroup analyses revealed that patients with high disease activity (CDAI 300) or ileocolonic disease with disease manifestation distal to the transverse colon responded better to the highest budesonide dose.Conclusion Oral pH-modified released budesonide shows a dose-dependent effectiveness in patients with active ileocolonic CD. In the majority of patients 9 mg budesonide per day is sufficient. However, in patients with highly active disease or ileal disease with distal colonic manifestation higher doses of budesonide could increase the therapeutic response 相似文献
80.
Parkhitko A Myachina F Morrison TA Hindi KM Auricchio N Karbowniczek M Wu JJ Finkel T Kwiatkowski DJ Yu JJ Henske EP 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(30):12455-12460
Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome characterized by benign tumors in multiple organs, including the brain and kidney. TSC-associated tumors exhibit hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), a direct inhibitor of autophagy. Autophagy can either promote or inhibit tumorigenesis, depending on the cellular context. The role of autophagy in the pathogenesis and treatment of the multisystem manifestations of TSC is unknown. We found that the combination of mTORC1 and autophagy inhibition was more effective than either treatment alone in inhibiting the survival of tuberin (TSC2)-null cells, growth of TSC2-null xenograft tumors, and development of spontaneous renal tumors in Tsc2(+/-) mice. Down-regulation of Atg5 induced extensive central necrosis in TSC2-null xenograft tumors, and loss of one allele of Beclin1 almost completely blocked macroscopic renal tumor formation in Tsc2(+/-) mice. Surprisingly, given the finding that lowering autophagy blocks TSC tumorigenesis, genetic down-regulation of p62/sequestosome 1 (SQSTM1), the autophagy substrate that accumulates in TSC tumors as a consequence of low autophagy levels, strongly inhibited the growth of TSC2-null xenograft tumors. These data demonstrate that autophagy is a critical component of TSC tumorigenesis, suggest that mTORC1 inhibitors may have autophagy-dependent prosurvival effects in TSC, and reveal two distinct therapeutic targets for TSC: autophagy and the autophagy target p62/SQSTM1. 相似文献