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121.
Angela L. Foreman Angela L. Foreman Brigitte Lemercier Angela L. Foreman Brigitte Lemercier Annick Lim 《Autoimmunity》2013,46(1):80-86
We have analyzed the IgM, IgG and IgA BCR repertoire in PBC patients by means of quantitative RT-PCR and CDR3-spectratyping with immunoscope technology. PBMC from 35 PBC patients and 18 normal controls were analyzed. Quantitative B cell repertoire analysis of IgM from healthy donors showed the preferential usage of VH3a, VH3b and VH4 families. Very similar VH family usage was observed in IgM B cells from PBC patients. CDR3 spectratyping of IgM BCR rearrangements showed a Gaussian distribution for dominant VH families in control donors, and similar diversity was found for the VH3b family in PBC patients. In contrast, VH3a and VH4 families showed oligoclonal expansions in some patients. Quantitative B cell repertoire analysis of IgG and IgA did not reveal any difference in VH chain distribution in PBC patients as compared to the control donors. Immunoscope profiles of CDR3 length distribution showed several peak expansions in B cells from control donors, particularly for the VH3a and VH4 families. CDR3 length distribution profiles of IgG and IgA from PBC patients were oligoclonal too, with expansions throughout the various VH chains. However, no common expansions within the CDR3 region were found intraindividually between IgG, IgA and IgM, and between patients. In conclusion, immunoscope technology does provide, for the first time, a sensitive and rapid method for detailed immunoglobulin gene usage analysis in peripheral B cells from PBC patients. This study failed to demonstrate preferential B cell rearrangements in the blood of patients with PBC, but this technology may be more successful if applied to the analysis of compartmental B cells (i.e. liver infiltrating B cells). 相似文献
122.
Dieter Schröder Matthias Ratke Uta Christina Bauer Ingrid Klöting Brigitte Ziegler Siegfried Schmidt 《Autoimmunity》2013,46(2):143-153
Normoglycemic diabetes-prone BB/OK rats aged 33, 45 or 75 days were subjected to prophylactic insulin treatment by means of a single subcutaneous application of a sustained release insulin implant. The single application of a sustained release insulin implant decreased the incidence of diabetes or delayed the onset of the disease in BB/OK rats of all treatment groups. Prophylactic insulin administration caused a transient hypoglycemic period accompanied by an inhibition of glucose stimulated insulin secretion and a decrease of the insulin content of Langerhans' islets as detectable in vitro . Compared to islets of normoglycemic controls pancreatic islets isolated from hypoglycemic BB/OK rats within 7-21 days after the insulin application at 45 days of age displayed a decreased susceptibility of the cells to complement-dependent cytotoxicity of the monoclonal islet cell surface antibody (ICSA) K14D10 but not to the cytotoxic effect of the ICSA M3aG8. The appearance of complement-dependent antibody-mediated cytotoxicity to islet cells and pancreatic exocrine cells in serum regarded as a sign of immune dysregulation in BB/OK rats seems not to be affected by insulin prophylaxis and was detectable during hypoglycemia as well as in the subsequent normoglycemic state. In conclusion, BB/OK rats of different age can be protected from diabetes by a single application of a sustained release insulin implant. Insulin and/or hypoglycemia seem to influence the expression of cell surface antigens, thus render the islets of Langerhans less vulnerable to immune cytolysis, whereas the appearance of humoral immunological abnormalites is not affected. 相似文献
123.
Thomas Perwein Martin Benesch Daniela Kandels Torsten Pietsch Ren Schmidt Franz Quehenberger Brigitte Bison Monika Warmuth-Metz Beate Timmermann Jürgen Krauss Ulrich-Wilhelm Thomale Rolf-Dieter Kortmann Pablo Herniz Driever Astrid Katharina Gnekow 《Neuro-oncology》2021,23(7):1148
BackgroundKnowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce.MethodsWe analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n = 36), SIOP-LGG 2004 (n = 56), and the subsequent LGG-Interim registry (n = 36).ResultsSpinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93% ± 2% and 38% ± 5%, respectively. Disseminated disease (n = 16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n = 24) or subtotal/partial resection (n = 74), biopsy (n = 16), or radiologic diagnosis only (n = 3). Eleven patients were treated first with chemotherapy (n = 9) or irradiation (n = 2). Up to 20.8 years after diagnosis/initial intervention, 73/128 patients experienced one (n = 43) or up to six (n = 30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required nonsurgical treatment (chemotherapy, n = 20; radiotherapy, n = 10; multiple treatment lines, n = 17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n = 57) or repeated (n = 16) resections, and in 35/47 patients after nonsurgical treatment.ConclusionsThe majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets. 相似文献
124.
Mathieu Fusaro Jérémie Rosain Virginie Grandin Nathalie Lambert Sylvain Hanein Cécile Fourrage Nicholas Renaud Marine Gil Samuel Chevalier Wadih Abou Chahla Brigitte Bader-Meunier Vincent Barlogis Stéphane Blanche David Boutboul Martin Castelle Thibault Comont Jean-Sébastien Diana Claire Fieschi Capucine Picard 《The Journal of allergy and clinical immunology》2021,147(2):734-737
125.
126.
Beate Vajen Ute Modlich Andrea Schienke Susanne Wolf Britta Skawran Winfried Hofmann Guntram Büsche Hans Kreipe Christopher Baum Irene Santos‐Barriopedro Alejandro Vaquero Brigitte Schlegelberger Cornelia Rudolph 《Genes, chromosomes & cancer》2013,52(4):423-430
Suv39h1 mediates heterochromatin formation in pericentric and telomeric regions by trimethylation of lysine 9 of histone 3 (H3K9me3). Yet, its role in the induction of chromosomal instability is poorly understood. We established a leukemia model by retrovirally expressing Myc in wild‐type and histone methyltransferase Suv39h1‐deficient hematopoietic cells and characterized the resulting leukemias for chromosomal instability. All mice that received cells overexpressing Myc developed myeloid leukemia with a median survival of 44 days posttransplantation. Myc‐overexpressing wild‐type leukemias demonstrated clones with numerical chromosomal aberrations (5/16). In secondary transplantations of these leukemic cells, structural changes, mostly end‐to‐end fusions of chromosomes, appeared (10/12). In contrast, leukemic cells overexpressing Myc with reduced or no Suv39h1 expression had a normal karyotype in primary, secondary, and tertiary transplantations (16/16). Myc‐transduced Suv39h1‐deficient cells showed less critically short telomeres (P < 0.05) compared with Myc‐transduced wild‐type bone marrow cells. Gene expression analysis showed upregulation of genes involved in the alternative lengthening of telomeres (ALT) mechanism. Thus, we hypothesize that loss of Suv39h1 implies activation of the ALT mechanism, in turn ensuring telomere length and stability. Our data show for the first time that Suv39h1 deficiency may prevent chromosomal instability by more efficient telomere stabilization in hematopoietic bone marrow cells overexpressing Myc. © 2013 Wiley Periodicals, Inc. 相似文献
127.
Aliya Ishmukhametova Jian‐Min Chen Rafaëlle Bernard Bernard de Massy Frédéric Baudat Amandine Boyer Déborah Méchin Delphine Thorel Brigitte Chabrol Marie‐Claire Vincent Mireille Claustres Sylvie Tuffery‐Giraud 《Human mutation》2013,34(8):1080-1084
Pathogenic complex genomic rearrangements are being increasingly characterized at the nucleotide level, providing unprecedented opportunities to evaluate the complexities of mutational mechanisms. Here, we report the molecular characterization of a complex duplication–triplication rearrangement involving exons 45–60 of the DMD gene. Inverted repeats facilitated this complex rearrangement, which shares common genomic organization with the recently described duplication‐inverted triplication–duplication (DUP–TRP/INV‐DUP) events; specifically, a 690‐kb region comprising DMD exons from 45 to 60 was duplicated in tandem, and another 46‐kb segment containing exon 51 was inserted inversely in between them. Taking into consideration (1) the presence of a predicted PRDM9 binding site in the near vicinity of the junction involving two inverted L1 elements and (2) the inherent properties of X–Y chromosome recombination during male meiosis, we proposed an alternative two‐step model for the generation of this X‐linked DMD DUP–TRP/INV‐DUP event. 相似文献
128.
Dr. Andreas Schindler Rainer Thomasius Peter-Michael Sack Brigitte Gemeinhardt Udo Küstner 《Attachment & human development》2013,15(2):111-126
Abstract A new approach to assessing family attachment patterns is presented, using a composite measure of individual attachment representations based on the Bartholomew Attachment Interview. A cluster analysis yielded three different patterns in a sample of N = 37 families with a drug dependent adolescent (age 14 – 25) and both biological parents. A “triangulated” pattern (mothers: preoccupied; fathers: dismissing; adolescents: fearful) was found in 65% of the sample. A total of 19% showed an “insecure” pattern (mothers, fathers, and adolescents: fearful) and 16% a “near-secure” pattern (mothers and adolescents: secure; fathers preoccupied). Preliminary comparisons between these groups indicate differences in comorbid psychiatric disorders, in individual and family functioning, but not in addiction severity. There is a trend towards differences in outcome of family therapy. Implications for treatment and further research are discussed. 相似文献
129.
130.
Klaus A. Siebenrock Karl-Philipp Kienle Simon D. Steppacher Moritz Tannast Tallal C. Mamisch Brigitte von Rechenberg 《Clinical orthopaedics and related research》2015,473(4):1318-1324
BackgroundCam-type femoroacetabular impingement (FAI) resulting from an abnormal nonspherical femoral head shape leads to chondrolabral damage and is considered a cause of early osteoarthritis. A previously developed experimental ovine FAI model induces a cam-type impingement that results in localized chondrolabral damage, replicating the patterns found in the human hip. Biochemical MRI modalities such as T2 and T2* may allow for evaluation of the cartilage biochemistry long before cartilage loss occurs and, for that reason, may be a worthwhile avenue of inquiry.Questions/purposesWe asked: (1) Does the histological grading of degenerated cartilage correlate with T2 or T2* values in this ovine FAI model? (2) How accurately can zones of degenerated cartilage be predicted with T2 or T2* MRI in this model?MethodsA cam-type FAI was induced in eight Swiss alpine sheep by performing a closing wedge intertrochanteric varus osteotomy. After ambulation of 10 to 14 weeks, the sheep were euthanized and a 3-T MRI of the hip was performed. T2 and T2* values were measured at six locations on the acetabulum and compared with the histological damage pattern using the Mankin score. This is an established histological scoring system to quantify cartilage degeneration. Both T2 and T2* values are determined by cartilage water content and its collagen fiber network. Of those, the T2* mapping is a more modern sequence with technical advantages (eg, shorter acquisition time). Correlation of the Mankin score and the T2 and T2* values, respectively, was evaluated using the Spearman’s rank correlation coefficient. We used a hierarchical cluster analysis to calculate the positive and negative predictive values of T2 and T2* to predict advanced cartilage degeneration (Mankin ≥ 3).ResultsWe found a negative correlation between the Mankin score and both the T2 (p < 0.001, r = −0.79) and T2* values (p < 0.001, r = −0.90). For the T2 MRI technique, we found a positive predictive value of 100% (95% confidence interval [CI], 79%–100%) and a negative predictive value of 84% (95% CI, 67%–95%). For the T2* technique, we found a positive predictive value of 100% (95% CI, 79%–100%) and a negative predictive value of 94% (95% CI, 79%–99%).ConclusionsT2 and T2* MRI modalities can reliably detect early cartilage degeneration in the experimental ovine FAI model.