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Jo-Lynn S. Tan Niranjan Sathianathen Marcus Cumberbatch Prokar Dasgupta Alexandre Mottrie Ronney Abaza Koon Ho Rha Thyavihally B. Yuvaraja Dipen J. Parekh Umberto Capitanio Rajesh Ahlawat Sudhir Rawal Nicolò M. Buffi Ananthakrishnan Sivaraman Kris K. Maes Gagan Gautam Francesco Porpiglia Levent Turkeri Mahendra Bhandari Benjamin Challacombe James Roscoe Porter Craig R. Rogers Daniel A. Moon 《BJU international》2021,128(Z3):30-35
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Natacha Martin Anne Bergougnoux Nesrine Baatallah Benoit Chevalier Jessica Varilh David Baux Bruno Costes Pascale Fanen Caroline Raynal Isabelle Sermet-Gaudelus Emmanuelle Girodon Magali Taulan-Cadars Alexandre Hinzpeter 《Journal of cystic fibrosis》2021,20(3):464-472
BackgroundMinigenes and in silico prediction tools are commonly used to assess the impact on splicing of CFTR variants. Exon skipping is often neglected though it could impact the efficacy of targeted therapies. The aim of the study was to identify exon skipping associated with CFTR variants and to evaluate in silico predictions of seven freely available software.MethodsCFTR basal exon skipping was evaluated on endogenous mRNA extracted from non-CF nasal cells and on two CFTR minigene banks. In silico tools and minigene systems were used to evaluate the impact of CFTR exonic variants on exon skipping.ResultsData showed that out of 65 CFTR variants tested, 26 enhanced exon skipping and that in silico prediction efficacy was of 50%-66%. Some in silico tools presented predictions with a bias towards the occurrence of splicing events while others presented a bias towards the absence of splicing events (non-detection including true negatives and false negatives). Classification of exons depending on their basal exon skipping level increased prediction rates up to 80%.ConclusionThis study indicates that taking basal exon skipping into account could orientate the choice of the in silico tools to improve prediction rates. It also highlights the need to validate effects using in vitro assays or mRNA studies in patients. Eventually, it shows that variant-guided therapy should also target exon skipping associated with variants. 相似文献
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Jignesh K. Patel Guillaume Coutance Alexandre Loupy Deanna Dilibero Michele Hamilton Michelle Kittleson Evan Kransdorf Babak Azarbal Osamu Seguchi Xiaohai Zhang David Chang Dael Geft Lawrence Czer Shaida Varnous Jon A. Kobashigawa 《American journal of transplantation》2021,21(7):2479-2488
Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037. 相似文献
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Using two-dimensional Western blot analysis with a pan-ras antibody, we previously defined conditions that allow to resolve the four post-translational p21-H-ras products expressed in normal mature rat tissues. Using the same approach, we conducted experiments that sometimes revealed deviations from the normal basal p21-H-ras pattern in primary human liver tumors. One type of alteration encountered was indicative of modifications in the relative rate of accomplishment of the different steps in the post-translational metabolisation of the protein, resulting in the accumulation of precursors of the fully-processed p21-H-ras product. This was also observed during ontogenesis and might thus be correlated with either cellular growth potential or differentiation. The second type of altered pattern is defined by the detection of abnormal spots and probably corresponds to the presence of mutant p21-ras products. 相似文献
70.
Unrelated living donor kidney transplantation 总被引:1,自引:0,他引:1
J. P. Squifflet Y. Pirson A. Poncelet P. Gianello G. P. J. Alexandre 《Transplant international》1990,3(1):32-35
Since 1966, we have performed 41 renal transplants from unrelated living donors (ULD), 39 of which were emotionally related. All donor-recipient pairs included in the present series were AB0-compatible. Recipients included 37 with primary and 4 with secondary transplants; 2 of the latter were diabetics. We compared these results to those of 41 recipients of cadaver donor kidneys matched for age, sex, immunosuppressive regimen, rank, and year of transplant, focusing our attention of the subgroups of patients under cyclosporin A (CyA) therapy (n=24). We found that ULD transplantation was as successful as cadaver transplantation with good HLA matching: at 3 years, graft survival rates were 81% in ULD versus 86% in the control group under CyA. Moreover, grafts from ULD functioned more rapidly (no post-transplant dialysis and 70% of the patients with serum creatinine below 2 mg/dl within 3 days post-transplant). Graft tolerance was equivalent in both groups (50% of the patients experienced no rejection). We conclude that despite poor HLA matching, ULD transplantation with CyA as the basic immunosuppressive agent offers good results: benefiting from the quality of living donor kidney grafts, it helps to alleviate the persistent shortage of cadaver donors. 相似文献