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21.
Sustained engraftment and tissue enzyme activity after liver cell transplantation for argininosuccinate lyase deficiency 总被引:11,自引:0,他引:11
BACKGROUND & AIMS: Donor cell engraftment with expression of enzyme activity is the goal of liver cell transplantation for inborn errors of liver metabolism with a view to achieving sustained metabolic control. METHODS: Sequential hepatic cell transplantations using male and female cells were performed in a 3.5-year-old girl with argininosuccinate lyase deficiency over a period of 5 months. Beside clinical, psychomotor, and metabolic follow-up, engraftment was analyzed in repeated liver biopsies (2.5, 5, 8, and 12 months after first infusion) by fluorescence in situ hybridization for the Y-chromosome and by measurement of tissue enzyme activity. RESULTS: Metabolic control was achieved together with psychomotor catch-up, changing the clinical phenotype from a severe neonatal one to a moderate late-onset type. The child was no longer hospitalized and was able to attend normal school. Sustained engraftment of male donor liver cells was shown in repeated biopsies, reaching 19% at 8 months and 12.5% at the 12-month follow-up. XXYY tetraploid donor cells were mainly detected during the infusion period (2.5- and 5-month biopsies), whereas in the follow-up 8-month and 1-year biopsies, diploid donor cell subpopulations had become dominant. Moreover, argininosuccinate lyase activity, originally absent, became measurable in 2 different biopsy samples at 8 months, reaching 3% of control activity, indicating in situ metabolic effect and supporting the clinical evolution to a moderate form of the disease. CONCLUSIONS: Liver cell transplantation can achieve donor cell engraftment in humans in a significant proportion, leading to sustained metabolic and clinical control with psychomotor catch-up. 相似文献
22.
Cochand-Priollet B Ziol M;Commission "frottis cervico-utérins" de l'AFAQAP Cartier I Dubois A Michiels-Marzais D Müller J Picot R Tartar MD Vacher-Lavenu MC Vincent S 《Annales de pathologie》2006,26(5):382-388
The 2001 Bethesda System is a uniform system of terminology for reporting results of pap smears. It is acknowledged by most cytopathologists worldwide as a standard for cervical cytology reports. In France, several national surveys have confirmed its current utilization. However, more specific analysis have shown that the Bethesda System may be routinely modified by individual laboratories or even individual cytopathologist working within the same department. The aim of this progress report was to emphasize the importance of fully understanding the Bethesda System and applying it in a rigorous and standardized way. 相似文献
23.
Vacher-Lavenu MC 《Annales de pathologie》2006,26(5):369-374
The cytological test issue mostly from individual opportunistic or for some department from organized screening programme, must benefit of the same quality in all the procedures. Pathologists are very implicated in. The purpose of this document is to summarize cytopathologists' initiatives and to present their specific tools for that. The French association for quality assurance in pathology (AFAQAP) has been validated by HAS in March 2006 for EPP. Commission 1 of AFAQAP organized an annual voluntary test for diagnostic evaluation since 2000 with the adoption of new technologies (CD-rom, virtual digital slides), and in 2005 a test of Pap Smear reporting quality concerning TBS 2001 use. A referring evaluation on this theme is in press. Furthermore pathologists made tools are available to codify lesions they diagnose (ADICAP), to collect and to study data (FCRISAP), to standardize the histological and cytological reports (CRFS), to evaluate the procedures and structural requirements and techniques. Pathologists participate in the elaboration of national guidelines (ANAES 1998 et 2002, DGS 2006) and performance indicators with InVS. The cervix cancer screening programme must take in account and valorises the role of pathologists according to assessment of efficacy and evaluation of the screening. 相似文献
24.
von Doernberg MC von Rechenberg B Bohner M Grünenfelder S van Lenthe GH Müller R Gasser B Mathys R Baroud G Auer J 《Biomaterials》2006,27(30):5186-5198
The goal of the present study was to assess the effect of macropore size on the in vivo behavior of ceramic scaffolds. For that purpose, beta-tricalcium phosphate (beta-TCP) cylinders with four different macropore sizes (150, 260, 510, and 1220 microm) were implanted into drill hole defects in cancellous bone of sheep and their resorption behavior was followed for 6, 12 and 24 weeks. The scaffolds were evaluated for biocompatibility, and new bone formation was observed macroscopically, histologically and histomorphometrically. Histomorphometrical measurements were performed for the whole defect area and for the area subdivided into three concentric rings (outer, medial, and inner ring). All implants were tolerated very well as evidenced by the low amount of inflammatory cells and the absence of macroscopic signs of inflammation. Resorption proceeded fast since less than 5% ceramic remained at 24-week implantation. Hardly any effect of macropore size was observed on the in vivo response. Samples with an intermediate macropore size (510 microm) were resorbed significantly faster than samples with smaller macropore sizes (150 and 260 microm). However, this fast resorption was associated with a lower bone content and a higher soft tissue content. At 12 and 24 weeks, the latter differences had disappeared. Bone was more abundant in the outer ring than in the rest of the blocks at 6 weeks, and in the outer and medial ring compared to the inner ring at 12 weeks. 相似文献
25.
Schuster H Blanc MC Neveux N Bonnefont-Rousselot D Le Tourneau A De Bandt JP Cynober L 《Scandinavian journal of gastroenterology》2006,41(11):1342-1349
OBJECTIVE: Some amino acids (AAs) display potent regulatory activities on cell metabolism, including via anti-oxidative defences. The aim of this study was to evaluate the protective effect of these AAs on warm ischaemia-reperfusion (I/R) injury in the isolated perfused rat liver. MATERIAL AND METHODS: Livers from fasted male Sprague-Dawley rats were isolated and perfused without (control group) or with (AP group) a mixture of regulatory AAs (glutamine, histidine, leucine, methionine, proline, phenylalanine, tryptophan and alanine). After 45 min of perfusion, warm ischaemia was induced for 45 min by clamping the portal vein catheter; thereafter, reperfusion was performed for 30 min. RESULTS: TNF-alpha production was significantly lower in the AP group during reperfusion (Control: 39+/-7 versus AP: 16+/-2 pg min-1 g-1, p<0.05), and lactate dehydrogenase (LDH) release decreased significantly during the last 15 min of reperfusion (Control: 0.13+/-0.03 versus AP: 0.04+/-0.02 IU min-1 g-1, p<0.05), despite similar levels of oxidative stress. The addition of regulatory AAs was not associated with variations in portal flow, bile flow, hepatic glucose or urea metabolism. However, significant changes in intrahepatic glutamine (Control: 1.4+/-0.2 versus AP: 2.6+/-0.5 micromol g-1, p < 0.05) together with higher glutamate release in the AP group (Control: 10.2+/-5.4 versus AP: 42.6+/-10.9 nmol min-1 g-1, p < 0.05) indicated modifications in nitrogen metabolism. CONCLUSIONS: Taken together, the lower TNF-alpha production, suggesting decreased inflammatory response, the decrease in LDH release in the AP group, demonstrating a better preservation of liver viability, and the increase in hepatic glutamine indicate that AAs play an important role in the liver's response to I/R. 相似文献
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29.
Tlili A Erard M Faure MC Baudin X Piolot T Dupré-Crochet S Nüsse O 《Journal of leukocyte biology》2012,91(1):83-95
Production of ROS by the leukocyte NADPH oxidase is essential for the destruction of pathogenic bacteria inside phagosomes. The enzyme is a complex of cytosolic and membranous subunits that need to assemble upon activation. Biochemical data suggest that the complex is renewed continuously during activity. Furthermore, it is generally assumed that complex assembly and activity occur in parallel. However, information about the oxidase assembly in individual phagosomes in live cells is scarce. We studied the dynamic behavior of the crucial cytosolic NADPH oxidase component p67(phox) during phagocytosis by videomicroscopy. p67(phox) is involved in the regulation of electron flow from NADPH to oxygen, leading to superoxide radical formation inside the phagosome. p67(phox)-citrine, expressed in myeloid PLB-985 cells, accumulated at the phagosomal membrane during phagocytosis of yeast particles. Using photobleaching techniques (FRAP, FLIP), we demonstrated that p67(phox)-citrine diffused freely in this phagosomal membrane, but the phagosomal pool of p67(phox)-citrine did not exchange with the cytosolic pool. This result suggests that once assembled in the NADPH oxidase complex, p67(phox) is stable in this complex. Furthermore, the time of the presence of p67(phox)-citrine at the phagosome increased substantially in the presence of complement in the opsonizing serum compared with decomplemented serum. PI(3)P also accumulated around phagosomes for twice as long in the presence of complement. The presence of p67(phox)-citrine was correlated with the duration of phagosomal ROS production in different opsonization conditions. These data support the critical role of p67(phox) for ROS production on the level of individual phagosomes. 相似文献
30.
Nicolas Penel Sylvie Bonvalot Marie-Cécile Le Deley Antoine Italiano Camille Tlemsani Diane Pannier Clémence Leguillette Jean-Emmanuel Kurtz Maud Toulmonde Julien Thery Daniel Orbach Pascale Dubray-Longeras Benjamin Verret François Bertucci Cécile Guillemet Lucie Laroche Armelle Dufresne Jean-Yves Blay Axel Le Cesne 《International journal of cancer. Journal international du cancer》2023,153(2):407-416
The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders. 相似文献