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1.
Marthe C.J. Roex Charissa Wijnands Sabrina A.J. Veld Esther van Egmond Lisette Bogers Jaap J. Zwaginga Tanja Netelenbos Peter A. von dem Borne Hendrik Veelken Constantijn J.M. Halkes J.H. Frederik Falkenburg Inge Jedema 《Cytotherapy》2021,23(1):46-56
Background aimsTo reduce the risk of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloSCT), T-cell depletion (TCD) of grafts can be performed by the addition of alemtuzumab (ALT) “to the bag” (in vitro) before transplantation. In this prospective study, the authors analyzed the effect of in vitro incubation with 20 mg ALT on the composition of grafts prior to graft infusion. Furthermore, the authors assessed whether graft composition at the moment of infusion was predictive for T-cell reconstitution and development of GVHD early after TCD alloSCT.MethodsSixty granulocyte colony-stimulating factor-mobilized stem cell grafts were obtained from ≥9/10 HLA-matched related and unrelated donors. The composition of the grafts was analyzed by flow cytometry before and after in vitro incubation with ALT. T-cell reconstitution and incidence of severe GVHD were monitored until 12 weeks after transplantation.ResultsIn vitro incubation of grafts with 20 mg ALT resulted in an initial median depletion efficiency of T-cell receptor (TCR) α/β T cells of 96.7% (range, 63.5–99.8%), followed by subsequent depletion in vivo. Graft volumes and absolute leukocyte counts of grafts before the addition of ALT were not predictive for the efficiency of TCR α/β T-cell depletion. CD4pos T cells were depleted more efficiently than CD8pos T cells, and naive and regulatory T cells were depleted more efficiently than memory and effector T cells. This differential depletion of T-cell subsets was in line with their reported differential CD52 expression. In vitro depletion efficiencies and absolute numbers of (naive) TCR α/β T cells in the grafts after ALT incubation were not predictive for T-cell reconstitution or development of GVHD post- alloSCT.ConclusionsThe addition of ALT to the bag is an easy, fast and generally applicable strategy to prevent GVHD in patients receiving alloSCT after myeloablative or non-myeloablative conditioning because of the efficient differential depletion of donor-derived lymphocytes and T cells. 相似文献
2.
Soede RD Zeelenberg IS Wijnands YM Kamp M Roos E 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(7):4293-4301
Dissemination of T cell hybridomas in mice, a model for in vivo migration of memory T cells and for T lymphoma metastasis, depends on the chemokine stromal cell-derived factor-1 (SDF-1) and the integrin LFA-1 and correlates well with invasion into fibroblast cultures. In addition to the known role of the pertussis toxin-sensitive heterotrimeric GTPase G(i), we show that also the pertussis toxin-insensitive GTPase G(q/11) is required for dissemination and invasion. Furthermore, we show that the small GTPases, Cdc42 and RhoA, are involved, and that invasion is blocked by inhibitors of actinomyosin contraction. G(q/11), RhoA, and contraction are specifically required for LFA-1 activation, since 1) they are essential for LFA-1-dependent migration toward low SDF-1 concentrations through ICAM-1-coated filters, but not for migration toward high SDF-1 levels, which is LFA-1 independent; 2) G protein (AlF(4)(-))-induced adhesion to ICAM-1 requires RhoA and contraction; 3) constitutively active G(q) induces aggregation, mediated by LFA-1. We previously reported that binding of this activated LFA-1 to ICAM-1 triggers a signal, transduced by the zeta-associated protein 70 tyrosine kinase, that activates additional LFA-1 molecules. This amplification of LFA-1 activation is essential for invasion. We show here that zeta-associated protein 70-induced LFA-1 activation requires neither Cdc42 and RhoA nor contraction and is thus quite different from that induced by SDF-1. We conclude that two modes of LFA-1 activation, with distinct underlying mechanisms, are required for the in vivo migration of T cell hybridomas. 相似文献
3.
Crystal structures of active fully assembled substrate- and product-bound complexes of UDP-N-acetylmuramic acid:L-alanine ligase (MurC) from Haemophilus influenzae
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Mol CD Brooun A Dougan DR Hilgers MT Tari LW Wijnands RA Knuth MW McRee DE Swanson RV 《Journal of bacteriology》2003,185(14):4152-4162
UDP-N-acetylmuramic acid:L-alanine ligase (MurC) catalyzes the addition of the first amino acid to the cytoplasmic precursor of the bacterial cell wall peptidoglycan. The crystal structures of Haemophilus influenzae MurC in complex with its substrate UDP-N-acetylmuramic acid (UNAM) and Mg(2+) and of a fully assembled MurC complex with its product UDP-N-acetylmuramoyl-L-alanine (UMA), the nonhydrolyzable ATP analogue AMPPNP, and Mn(2+) have been determined to 1.85- and 1.7-A resolution, respectively. These structures reveal a conserved, three-domain architecture with the binding sites for UNAM and ATP formed at the domain interfaces: the N-terminal domain binds the UDP portion of UNAM, and the central and C-terminal domains form the ATP-binding site, while the C-terminal domain also positions the alanine. An active enzyme structure is thus assembled at the common domain interfaces when all three substrates are bound. The MurC active site clearly shows that the gamma-phosphate of AMPPNP is positioned between two bound metal ions, one of which also binds the reactive UNAM carboxylate, and that the alanine is oriented by interactions with the positively charged side chains of two MurC arginine residues and the negatively charged alanine carboxyl group. These results indicate that significant diversity exists in binding of the UDP moiety of the substrate by MurC and the subsequent ligases in the bacterial cell wall biosynthesis pathway and that alterations in the domain packing and tertiary structure allow the Mur ligases to bind sequentially larger UNAM peptide substrates. 相似文献
4.
Balagopal P Pandey M Chandramohan K Somanathan T Kumar A 《World journal of surgical oncology》2003,1(1):4
Background
Choriocarcinoma is an aggressive neoplasm arising in the body of the uterus. The disease normally spreads to lung and brain. 相似文献5.
Introduction
Development of cell therapies for repairing the intervertebral disc is limited by the lack of a source of healthy human disc cells. Stem cells, particularly mesenchymal stem cells, are seen as a potential source but differentiation strategies are limited by the lack of specific markers that can distinguish disc cells from articular chondrocytes. 相似文献6.
Kaptein A Oubrie A de Zwart E Hoogenboom N de Wit J van de Kar B van Hoek M Vogel G de Kimpe V Schultz-Fademrecht C Borsboom J van Zeeland M Versteegh J Kazemier B de Roos J Wijnands F Dulos J Jaeger M Leandro-Garcia P Barf T 《Bioorganic & medicinal chemistry letters》2011,21(12):3823-3827
The identification of a potent, selective, and orally available MK2 inhibitor series is described. The initial absence of oral bioavailability was successfully tackled by moving the basic nitrogen of the spiro-4-piperidyl moiety towards the electron-deficient pyrrolepyridinedione core, thereby reducing the pKa and improving Caco-2 permeability. The resulting racemic spiro-3-piperidyl analogues were separated by chiral preparative HPLC, and the activity towards MK2 inhibition was shown to reside mostly in the first eluting stereoisomer. This led to the identification of new MK2 inhibitors, such as (S)-23, with low nanomolar biochemical inhibition (EC50 7.4 nM) and submicromolar cellular target engagement activity (EC50 0.5 μM). 相似文献
7.
Apetroaie C Andersson MA Spröer C Tsitko I Shaheen R Jääskeläinen EL Wijnands LM Heikkilä R Salkinoja-Salonen MS 《Archives of microbiology》2005,184(3):141-151
Producers of cereulide, the emetic toxin of Bacillus cereus, are known to constitute a specific subset within this species. We investigated physiological and genetic properties of 24
strains of B. cereus including two high cereulide producers (600–1,800 ng cereulide mg−1 wet weight biomass), seven average producers (180–600 ng cereulide mg−1 wet weight biomass), four low cereulide producers (20–160 ng cereulide mg−1 wet weight biomass) and 11 non-producers representing isolates from food, food poisoning, human gut and environment. The
13 cereulide producers possessed 16S rRNA gene sequences identical to each other and identical to that of B. anthracis strains Ames, Sterne from GenBank and strain NC 08234–02, but showed diversity in the adk gene (two sequence types), in ribopatterns obtained with EcoRI and PvuII (three types of patterns), in tyrosin decomposition, haemolysis and lecithin hydrolysis (two phenotypes). The cereulide-producing
isolates from the human gut represented two ribopatterns of which one was novel to cereulide-producing B. cereus and two phenotypes. We conclude that the cereulide-producing B. cereus are genetically and biochemically more diverse than hitherto thought. 相似文献
8.
9.
Role of Germinant Receptors in Caco-2 Cell-Initiated Germination of Bacillus cereus ATCC 14579 Endospores
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Luc M. Hornstra Menno van der Voort Lucas M. Wijnands Petra J. Roubos-van den Hil Tjakko Abee 《Applied microbiology》2009,75(4):1201-1203
Spores obtained from Bacillus cereus ATCC 14579 and mutant strains lacking each of seven germinant receptor operons were exposed to differentiated Caco-2 cells and monitored for germination. Spores of the gerI and gerL mutants showed a reduced germination response, pointing to a role for these receptors in Caco-2-induced germination. 相似文献
10.
Periconceptional parental conditions and perimembranous ventricular septal defects in the offspring
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Kim P.J. Wijnands Gerda A. Zeilmaker Willemijn M. Meijer Willem A. Helbing Régine P.M. Steegers‐Theunissen 《Birth defects research. Part A, Clinical and molecular teratology》2014,100(12):944-950
Background: The perimembranous ventricular septal (pVSD) defect is the most common congenital heart disease phenotype. Several parental factors are associated with pVSD risk in the offspring. To contribute to the future prevention of pVSDs, we investigated associations with nongenetic parental conditions. Methods: In a case–control study with standardized data collection at 17 months after birth, 115 parents of a child with pVSD and 484 parents of a healthy child completed questionnaires about periconceptional nongenetic conditions. Univariable and multivariable logistic regression analyses were used to estimate odds ratios (OR) with 95% confidence intervals (95% CI). Results: Complete data were available for 588 families (98%). Maternal risk conditions associated with pVSD offspring were a positive family history of congenital heart disease (OR, 2.61; 95%CI, 0.98–6.91), medication use (OR, 1.80; 95%CI, 1.13–2.85) and advanced age (OR, 1.07; 95%CI, 1.02–1.12). Exposure to phthalates (OR, 1.93; 95%CI, 1.05–3.54) was the only paternal risk condition associated with pVSD offspring. Conclusion: Four periconceptional parental conditions contributed to pVSD risk in the offspring. Couples planning pregnancy should be counseled on these risk conditions which are partially modifiable to contribute to the future prevention of pVSDs. Birth Defects Research (Part A) 100:944–950, 2014. © 2014 Wiley Periodicals, Inc. 相似文献