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91.
92.
Furan is toxic and carcinogenic in rodents. Because of the large potential for human exposure, furan is classified as a possible human carcinogen. The detailed mechanism by which furan causes toxicity and cancer is not yet known. Since furan toxicity requires cytochrome P450-catalyzed oxidation of furan, we have characterized the urinary and hepatocyte metabolites of furan to gain insight into the chemical nature of the reactive intermediate. Previous studies in hepatocytes indicated that furan is oxidized to the reactive α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA), which reacts with glutathione (GSH) to form 2-(S-glutathionyl)succinaldehyde (GSH-BDA). This intermediate forms pyrrole cross-links with cellular amines such as lysine and glutamine. In this article, we demonstrate that GSH-BDA also forms cross-links with ornithine, putrescine, and spermidine when furan is incubated with rat hepatocytes. The relative levels of these metabolites are not completely explained by hepatocellular levels of the amines or by their reactivity with GSH-BDA. Mercapturic acid derivatives of the spermidine cross-links were detected in the urine of furan-treated rats, which indicates that this metabolic pathway occurs in vivo. Their detection in furan-treated hepatocytes and in urine from furan-treated rats indicates that polyamines may play an important role in the toxicity of furan. 相似文献
93.
Schabort EJ van der Merwe M Niesler CU 《Journal of muscle research and cell motility》2011,31(5-6):359-367
Following muscle injury, the damaged tissue and influx of inflammatory cells stimulate the secretion of growth factors and cytokines to initiate repair processes. This release of chemotactic signaling factors activates resident precursor cells and stimulates their mobilization and migration to the site of injury where terminal differentiation can occur. The three transforming growth factor-β (TGF-β) isoforms, and insulin-like growth factor-1 (IGF-1) are among the known regulatory factors released following muscle damage. We investigated the effect of recombinant active TGF-β1, -β2, -β3 and IGF-1 on C2C12 skeletal muscle satellite cell and P19 embryonal carcinoma cell terminal differentiation and migration. C2C12 myoblast fusion as well as P19 embryoid body formation and myogenic differentiation was assessed following 72?h TGF-β treatment (5?ng/ml), whereas the effect of the TGF-β isoforms on migration was determined following 7?h incubation. Our results showed that TGF-β decreases C2C12 myoblast fusion in an isoform-independent manner, whereas in the P19 cell lineage, results demonstrate that TGF-β1 specifically and significantly increased P19 embryoid body formation, but not expression of Connexin-43 or Myosin Heavy Chain. IGF-1 significantly increased migration compared to TGF-β isoforms, which, on their own, had no significant effect on the mobilization of either C2C12 or P19 cells. TGF-β isoforms decreased IGF-1-induced migration of both cell lineages. By distinguishing the factors involved in, and the molecular signals required for, myoblast recruitment during repair processes, strategies can be developed towards improved cell-mediated therapies for muscle injury. 相似文献
94.
95.
Niaudet P Charbit M Loirat C Lapeyraque AL Tsimaratos M Cailliez M Foulard M Dehennault M Marquet P Chaouche-Teyara K Lemay D 《Pediatric nephrology (Berlin, Germany)》2009,24(2):395-402
Data on the use of enteric-coated mycophenolic acid (EC-MPS) in pediatric transplantation cases are scarce. We undertook a
12-month, multicenter, open-label pilot study in which 16 de novo renal transplant patients aged 5–16 years received EC-MPS
with cyclosporine A microemulsion (CsA-ME), steroids, and anti-interleukin-2 receptor antibody induction. The mean dose of
EC-MPS was 916 ± 93 mg/m2 per day during weeks 1–2, 810 ± 193 mg/m2 per day during months 3–6, and 827 ± 153 mg/m2 per day during months 6–12. The mean CsA C2 level exceeded target range up to month 6 post-transplant. Efficacy failure (biopsy-proven acute rejection, graft loss, death
or loss to follow-up) occurred in two patients: one patient with primary non-function underwent nephrectomy, and one patient
experienced biopsy-proven acute rejection (Grade 1B, day 344) following EC-MPS dose reduction. There were no deaths. Creatinine
clearance (Schwartz) was 103 ± 30 mL/min per 1.73 m2 at month 6 and 100 ± 16 mL/min per 1.73 m2 at month 12. The majority of adverse events were mild or moderate (101/126, 80.2%). In this pilot study, EC-MPS 450 mg/m2 administered twice daily with CsA, steroids, and interleukin-2 antibody induction resulted in a low rate of rejection with
good renal function in a pediatric population. However, a larger, controlled trial is required to confirm these results. 相似文献
96.
Elizabeth I. Johnson Olivier Grondin Marion Barrault Malika Faytout Sylvia Helbig Mathilde Husky Eric L. Granholm Catherine Loh Louise Nadeau Hans‐Ulrich Wittchen Joel Swendsen 《International journal of methods in psychiatric research》2009,18(1):48-57
Computerized ambulatory monitoring overcomes a number of methodological and conceptual challenges to studying mental disorders, however concerns persist regarding the feasibility of this approach with severe psychiatric samples and the potential of intensive monitoring to influence data quality. This multi‐site investigation evaluates these issues in four independent samples. Patients with schizophrenia (n = 56), substance dependence (n = 85), anxiety disorders (n = 45), and a non‐clinical sample (n = 280) were contacted to participate in investigations using computerized ambulatory monitoring. Micro‐computers were used to administer electronic interviews several times per day for a one‐week period. Ninety‐five percent of contacted individuals agreed to participate in the study, and minimum compliance was achieved by 96% of these participants. Seventy‐eight percent of all programmed assessments were completed overall, and only 1% of micro‐computers were not returned to investigators. There was no evidence that missing data or response time increased over the duration of the study, suggesting that fatigue effects were negligible. The majority of variables investigated did not change in frequency as a function of study duration, however some evidence was found that socially sensitive behaviors changed in a manner consistent with reactivity. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
97.
Kros JM Gorlia T Kouwenhoven MC Zheng PP Collins VP Figarella-Branger D Giangaspero F Giannini C Mokhtari K Mørk SJ Paetau A Reifenberger G van den Bent MJ 《Journal of neuropathology and experimental neurology》2007,66(6):545-551
The diagnosis of anaplastic oligodendroglioma (AOD) or anaplastic oligoastrocytoma (AOA) is subject to interobserver variation. The aim of this study was to estimate consensus in typing and grading of these tumors using tumor material collected in a large prospective randomized phase III study and to correlate the consensus diagnosis with the 1p/19q status of the tumors and the clinical outcome. The available pathology material of the first 150 patients, randomized into the European Organization for Research and Treatment of Cancer Trial 26951, was reviewed by an independent panel of 9 neuropathologists. The presence of deletions of 1p and 19q was assessed by fluorescence in situ hybridization with locus-specific probes. The panel reached consensus on the diagnosis of AOD in 52% of the tumors that had been diagnosed as AOD by the local pathologists, whereas only 8% of the local diagnosis of AOA was confirmed with consensus. The concordance on the panel diagnosis of AOD was high (intraclass correlation = 86%). The survival curves for AOD with 1p/19q loss, AOD without these losses, and AOA without 1p/19q loss ran separately in this order. The absence of necrosis and the presence of endothelial abnormalities were correlated with better outcomes. In multivariate analysis, patients' age, 1p/19q loss, and necrosis were identified as independent prognostic factors. 相似文献
98.
Nijkeuter M Kwakkel-van Erp H Söhne M Tick LW Kruip MJ Ullmann EF Kramer MH Büller HR Prins MH Leebeek FW Huisman MV;Christopher Study Investigators 《Thrombosis and haemostasis》2007,97(6):944-948
It is unknown whether strategies validated for diagnosing pulmonary embolism (PE) are valid in patients with a history of PE. It was the objective of this study to investigate whether a diagnostic algorithm consisting of sequential application of a clinical decision rule (CDR), a quantitative D-dimer test and computed tomography (CT) safely ruled out a clinical suspicion of acute recurrent PE. Data were obtained from a diagnostic outcome study of patients suspected of PE. Acute recurrent PE was ruled out by an unlikely probability of PE (CDR score = 4 points) combined with a normal D-dimer test (= 500 ng/ml) or by a normal CT in all other patients. The primary outcome was the incidence of acute recurrent venous thromboembolism during three months of follow-up in patients with normal tests and not treated with anticoagulants. Of 3,306 patients suspected of acute PE, 259 patients (7.8%) had a history of PE of whom 234 were not treated with anticoagulants. The probability of PE was unlikely in 82 of 234 patients (35%), and 42 had a normal D-dimer test (18%), excluding recurrent PE. None of these patients had a thrombotic event during follow-up (0%, 95%CI: 0-6.9). A CT was indicated in all other patients (192) and ruled out recurrent PE in 127 patients (54%). Only one patient with a negative CT had a fatal recurrent PE during follow-up (0.8%; 95%CI: 0.02-4.3). In conclusion, this prospective study demonstrates the safety of ruling out a clinical suspicion of acute recurrent PE by a simple diagnostic algorithm in patients with a history of PE. 相似文献
99.
Taal W Dubbink HJ Zonnenberg CB Zonnenberg BA Postma TJ Gijtenbeek JM Boogerd W Groenendijk FH Kros JM Kouwenhoven MC van Marion R van Heuvel I van der Holt B Bromberg JE Sillevis Smitt PA Dinjens WN van den Bent MJ;Dutch Society for Neuro-Oncology 《Neuro-oncology》2011,13(2):235-241
Only a few studies examined the effect of temozolomide (TMZ) in recurrent low-grade astrocytoma (LGA) after surgery, none of which included a homogeneous and sufficiently sized group of patients with progression after radiotherapy (RT). We evaluated a cohort of 58 patients treated with TMZ for progression after RT of a previous LGA and investigated the relation between outcome and mutations in the IDH1, IDH2, and TP53 genes, O6-methylguanine-methyltransferase (MGMT) promoter methylation, trisomy of chromosome 7, and loss of chromosomes 1p and 19q. All patients received first-line TMZ 200 mg/m2/day on days 1–5 every 4 weeks for a progressive LGA with a contrast-enhancing lesion on MRI after RT. Six months progression-free survival (PFS) was 67%, and the median overall survival was 14 months. An objective response was obtained in 54%. TP53 mutations and loss of chromosome 19q showed a borderline association with PFS, but none of the other molecular characteristics were correlated with the outcome to TMZ. Both a methylated MGMT promoter gene and IDH1 mutations were found in 86% of the tumor samples. A correlation was found between IDH1 mutations and MGMT promoter methylation (P < .001). Neither MGMT promoter methylation nor IDH1 mutations correlated with PFS, but the interval between the very first symptom of the LGA and the start of the TMZ was significantly longer in the patients with IDH1 mutations (P = .01) and a methylated MGMT promoter (P = .02). We conclude that MGMT promoter methylation and IDH1 mutations seem to predict survival from the time of diagnosis, but not PFS to TMZ. 相似文献