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1.
Dirk J. Lefeber Johannes Schönberger Eva Morava Karin M. Huyben Olga Grafakou Frank W. Preijers Jef Yildiz Martha Spilioti Dominique Klein Hisashi Ashida Yusuke Maeda Martin Lammens Ron A. Wevers 《American journal of human genetics》2009,85(1):76-86
Alpha-dystroglycanopathies such as Walker Warburg syndrome represent an important subgroup of the muscular dystrophies that have been related to defective O-mannosylation of alpha-dystroglycan. In many patients, the underlying genetic etiology remains unsolved. Isolated muscular dystrophy has not been described in the congenital disorders of glycosylation (CDG) caused by N-linked protein glycosylation defects. Here, we present a genetic N-glycosylation disorder with muscular dystrophy in the group of CDG type I. Extensive biochemical investigations revealed a strongly reduced dolichol-phosphate-mannose (Dol-P-Man) synthase activity. Sequencing of the three DPM subunits and complementation of DPM3-deficient CHO2.38 cells showed a pathogenic p.L85S missense mutation in the strongly conserved coiled-coil domain of DPM3 that tethers catalytic DPM1 to the ER membrane. Cotransfection experiments in CHO cells showed a reduced binding capacity of DPM3(L85S) for DPM1. Investigation of the four Dol-P-Man-dependent glycosylation pathways in the ER revealed strongly reduced O-mannosylation of alpha-dystroglycan in a muscle biopsy, thereby explaining the clinical phenotype of muscular dystrophy. This mild Dol-P-Man biosynthesis defect due to DPM3 mutations is a cause for alpha-dystroglycanopathy, thereby bridging the congenital disorders of glycosylation with the dystroglycanopathies. 相似文献
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Ali C Akyildiz Lambert Speelman Harald van Brummelen Miguel A Gutiérrez Renu Virmani Aad van der Lugt Anton FW van der Steen Jolanda J Wentzel Frank JH Gijsen 《Biomedical engineering online》2011,10(1):25
Background
Rupture of the cap of a vulnerable plaque present in a coronary vessel may cause myocardial infarction and death. Cap rupture occurs when the peak cap stress exceeds the cap strength. The mechanical stress within a cap depends on the plaque morphology and the material characteristics of the plaque components. A parametric study was conducted to assess the effect of intima stiffness and plaque morphology on peak cap stress. 相似文献5.
van Wering ER van Lochem EG Leenders M van der Sluijs-Gelling AJ Wind H Gratama JW Kraan J Preijers FW 《Journal of biological regulators and homeostatic agents》2004,18(3-4):313-326
Multiparameter flowcytometry offers an insight into differentiation pathways, maturation stages and abnormal features of cell (sub)populations thus helping to establish and classify hematological malignancies. The Dutch Foundation for Immunophenotyping of Hematological Malignancies (SIHON) has formulated a guideline for a rapid screening followed by confirmation and classification in a standardized way. For this aim seven carefully composed monoclonal antibody combinations are elucidated for screening the test sample in a first phase. In this phase a relative frequency distribution of the cells will be established and a decision will be made about abnormal cells present, as well as their mature or immature state and the cell lineage they belong to. In a second phase, panels with cell lineage dependent monoclonal antibody combinations may be used to confirm and classify the abnormal cell population indicated in phase 1, as well as to establish the presence or absence of an abberant immunophenotype. 相似文献
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Willemijn Hobo Leonie Strobbe Frans Maas Hanny Fredrix Annelies Greupink-Draaisma Ben Esendam Theo de Witte Frank Preijers Henriëtte Levenga Bas van Rees Reinier Raymakers Nicolaas Schaap Harry Dolstra 《Cancer immunology, immunotherapy : CII》2013,62(8):1381-1392
The introduction of autologous stem cell transplantation (SCT) and novel drugs has improved overall survival in multiple myeloma (MM) patients. However, minimal residual disease (MRD) remains and most patients eventually relapse. Myeloma plasma cells express tumor-associated antigens (TAA), which are interesting targets for immunotherapy. In this phase 1 study, we investigated the safety and immunological effects of TAA-mRNA-loaded dendritic cell (DC) vaccination for treatment for MRD in MM after SCT. Mature monocyte-derived DCs were pulsed with keyhole limpet hemocyanin (KLH) and electroporated with MAGE3, Survivin or B-cell maturation antigen (BCMA) mRNA. Twelve patients were vaccinated three times with intravenous (5–22 × 106 DCs) and intradermal vaccines (4–11 × 106 DCs), at biweekly intervals. Immunological responses were monitored in blood and delayed-type hypersensitivity (DTH) biopsies. All patients developed strong anti-KLH T-cell responses, but not KLH antibodies. In 2 patients, vaccine-specific T cells were detected in DTH biopsies. In one patient, we found MAGE3-specific CD4+ and CD8+ T cells, and CD3+ T cells reactive against BCMA and Survivin. In the other patient, we detected low numbers of MAGE3 and BCMA-reactive CD8+ T cells. Vaccination was well tolerated with limited toxicity. These findings illustrate that TAA-mRNA-electroporated mature DCs are capable of inducing TAA-T-cell responses in MM patients after SCT. 相似文献
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Frank JH Gijsen Francesco Migliavacca Silvia Schievano Laura Socci Lorenza Petrini Attila Thury Jolanda J Wentzel Anton FW van der Steen Patrick WS Serruys Gabriele Dubini 《Biomedical engineering online》2008,7(1):23
Background
The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis. 相似文献8.
Forbes SH; Hogg JT; Buchanan FC; Crawford AM; Allendorf FW 《Molecular biology and evolution》1995,12(6):1106-1113
We compared genotypes at eight (AC)n microsatellite loci in domestic sheep
(Ovis aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The
domestic sheep had greater genetic variation, higher allele-size variances,
and larger allele sizes than the wild sheep. Accumulating evidence from
higher taxonomic comparisons shows that these parameters are biased if
microsatellite loci are selected in one taxon and used in another. Our
results demonstrate similar biases between congeneric species. We compared
standard measures of genetic variation, differentiation, and distance
within and between species (H, D, FST) to newer measures based on
allele-size variance (SW, SB, RST). The size-based distances better
detected species-level divergence, but standard measures better
distinguished allopatric populations. Empirical calibration of these
measures at the subspecies level is needed to establish their useful
ranges.
相似文献
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Spanholtz J Preijers F Tordoir M Trilsbeek C Paardekooper J de Witte T Schaap N Dolstra H 《PloS one》2011,6(6):e20740
Natural killer (NK) cell-based adoptive immunotherapy is a promising treatment approach for many cancers. However, development of protocols that provide large numbers of functional NK cells produced under GMP conditions are required to facilitate clinical studies. In this study, we translated our cytokine-based culture protocol for ex vivo expansion of NK cells from umbilical cord blood (UCB) hematopoietic stem cells into a fully closed, large-scale, cell culture bioprocess. We optimized enrichment of CD34(+) cells from cryopreserved UCB units using the CliniMACS system followed by efficient expansion for 14 days in gas-permeable cell culture bags. Thereafter, expanded CD34(+) UCB cells could be reproducibly amplified and differentiated into CD56(+)CD3(-) NK cell products using bioreactors with a mean expansion of more than 2,000 fold and a purity of >90%. Moreover, expansion in the bioreactor yielded a clinically relevant dose of NK cells (mean: 2×10(9) NK cells), which display high expression of activating NK receptors and cytolytic activity against K562. Finally, we established a versatile closed washing procedure resulting in optimal reduction of medium, serum and cytokines used in the cell culture process without changes in phenotype and cytotoxic activity. These results demonstrate that large numbers of UCB stem cell-derived NK cell products for adoptive immunotherapy can be produced in closed, large-scale bioreactors for the use in clinical trials. 相似文献
10.
Olfactory sensitivity in tsetse flies: a daily rhythm 总被引:3,自引:0,他引:3
The diurnal tsetse Glossina morsitans morsitans bites especially in early
morning and late afternoon; around midday feeding is at a low. In
laboratory apparatus that measures the amount of locomotion under constant
conditions over the photophase, the flies display a similar patterning of
activity levels. The profile of daily rhythms for G. morsitans reported in
the literature includes a number of motor and sensory motor systems that
fluctuate cophasically. Lacking is a study on the patterning of the senses'
response levels. In this paper we present the first instance of a daily
modulation in the sense of smell. We stimulated the antennae with
concentration series of host-derived odours and measured the spiking rate
of cells at different times during the photophase. The
concentration-response curves suggest that the sensitivity of antennal
olfactory cells flows in parallel with the other daily rhythms. This was
also reflected in electroantennograms (EAGs). The electroantennography was
extended to G. fuscipes fuscipes, whose level of spontaneous locomotor
activity--instead of following a U- shaped pattern--rises gradually over
the photophase. Again, the EAGs appeared to parallel the species' locomotor
activity. What we believe happens is that the organism tones down the
sensitivity of its odour receptors during periods of anticipated inactivity
for reasons of economy.
相似文献