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51.
Montse Iglesias Rosa M. Soler Dale D. Hunter Joan Ribera Josep E. Esquerda Joan X. Comella 《Journal of neurocytology》1995,24(12):903-915
Summary The purpose of the work reported here is to identify molecular components of the synaptic basal lamina of skeletal muscle fibres which allow recognition of original synaptic sites by regenerating motor axons. We focused on s-larninin and components recognized by the lectinDolichos biflorus agglutinin previously shown to be specifically located at the synaptic basal lamina. We used a cryoculture bioassay in which chick ciliary ganglion neurons grow on rat skeletal muscle cryostat sections. In control cultures, neurites extended over the muscle sections in close association with the muscle cell surface. It was observed that most of the neurites that extended towards the endplate zone and reached an area of 40 m around the neuromuscular junction ceased to grow when they contacted the synaptic site. Masking either lectin receptors or some s-laminin molecule epitopes prior to the culture of neurons alters the behaviour of growing neurites. On sections treated either withDolichos biflorus agglutinin or anti s-laminin monoclonal antibodies (D5 and C4) most of the neurites did not stop their growth at the synaptic regions. Moreover, treating muscle sections withDolichos biflorus agglutinin removed the gradient of substratum affinity around the endplate. These results indicate that the s-laminin andDolichos biflorus agglutinin receptors present on muscle cell surfaces may play a functional role in the interaction of growing neurites with original synaptic sites in the process of neuromuscular regeneration. 相似文献
52.
Juan J. Tarin Josep LL. Romero Fernando Bonilla-Musoles 《Journal of assisted reproduction and genetics》1994,11(9):463-469
Purpose
To characterize and predict cycles generating slowcleaving embryos in in vitro fertilization, 86 cycles were retrospectively divided into two groups (slow, n=41, and fast, n=45 according to whether the number of blastomeres per embryo on day 3 was or > than the mean of the distribution, respectively.Results
Cycles generating slowcleaving embryos were treated with luteinizing hormonereleasing hormone agonist before ovarian stimulation for a shorter period (12.1±0.5 versus 15.6±1.1 days; P0.01) and had higher immaturity grade of oocyte-corona-cumulus complexes which resulted in embryos (1.6±0.1 vs 1.3±0.1; P0.05) when compared to cycles producing fastcleaving embryos. Both variables entered in a logistic regression model applied in order to predict the probability of a cycle generating slowcleaving embryos (goodness-of-fit chisquare=180.0, degrees of freedom (df)=80, P=0.4786. This model predicted correctly 86.7% (13 of 15) of cycles generating slowcleaving embryos and 83.3% (10 of 12) of cycles producing fastcleaving embryos when the estimated probability of a cycle producing slowcleaving embryos was 0.7 or 0.3, respectively.Conclusion
Shorter treatment with hormone-releasing hormone agonist before ovarian stimulation and higher immaturity grade of oocyte-corona-cumulus complexes which result in embryos are predictive characteristics of in vitro fertilization cycles generating slow-cleaving embryos. 相似文献
53.
54.
João Luis Callegari Lopes Izabel Cristina Casanova Myrian C. Garcia de Figueireido Francisco Carlos Nather Wagner E. Paiva Avelar 《Archives of environmental contamination and toxicology》1992,23(3):351-354
The mussel Anodontites trapesialis (Lam, 1819) was used as an indicator of organochlorine pollutants in the Pardo River, located in the municipality of Ribeirão Preto (21° 07S and 47° 45W), State of São Paulo, Brazil.Biological monitoring was performed for one year at the site of a sugar cane grove on the left bank of the river. Forty-three animals were placed in two aluminum enclosures on the river bottom at this site and 4 animals of each enclosure were sacrificed for pesticide analysis at 3-month intervals, each collection corresponding to one season of the year.The animals were found to have been exposed to DDT, lindane, heptachlor, aldrin and dieldrin. Endrin was not detected in any of the analyses.Research supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). 相似文献
55.
56.
Carolina Armengol Gemma Tarafa Loreto Boix Manel Solé Rosa Queralt Dolors Costa Oriol Bachs Jordi Bruix Gabriel Capellá 《Clinical cancer research》2004,10(6):2150-2157
PURPOSE: To allow the longitudinal investigation of molecular events associated with the progression of human hepatocellular carcinoma (HCC), we sought to develop a murine model by orthotopic implantation of tumor fragments obtained from patients diagnosed at early stage. EXPERIMENTAL DESIGN: Tumor pieces (2 x 2 mm) were implanted on the liver surface of nu/nu mice. After xenograft growing, subsequent passages were performed to achieve long-term implant viability. Isolation of tumoral hepatocytes was done to establish new cell lines. HCC characteristics, proliferation rate, apoptotic index (terminal deoxynucleotidyl transferase-mediated nick end labeling), and expression of cell-cycle regulators (cyclins E and A, p21(Cip1), p27(Kip1), p16(INK4a), pRb, and p53) were assessed by Western Blot and immunohistochemistry, to correlate them with tumor progression. RESULTS: Five (50%) of the 10 primary HCCs resulted in small slow-growing liver implants. Three of them are viable after 48 months, whereas the remaining two survived for 15 and 13 months. Xenografts throughout passages exhibited a more aggressive phenotype with a poorer degree of differentiation, intense proliferation, moderate apoptosis, cell-cycle deregulation, p53 alterations, microvascular invasion, and dissemination. In one single passage, we observed critical growth delay, which was associated with significant p27(kip1) overexpression. We established the anchor-free growing BCLC-9 cell line from one xenograft. This has gains of chromosomes 7, 5p, 6q, and 9q, is hepatitis B virus-DNA positive, does not secrete alpha-fetoprotein, and has TP53 missense mutations in codons 192 and 242. CONCLUSIONS: The orthotopic implantation of early HCC fragments in nude mice provides a useful model to investigate the mechanisms of human HCC evolution and to establish new cell lines. 相似文献
57.
Josep Maria Peralba Linda DeGraffenried William Friedrichs Letitia Fulcher Viktor Grünwald Geoffrey Weiss Manuel Hidalgo 《Clinical cancer research》2003,9(8):2887-2892
CCI-779 is an ester of rapamycin and inhibitor of mammalian target of rapamycin (mTOR) currently in Phase II clinical development for the treatment of patients with cancer. CCI-779 interacts with mTOR and inhibits its kinase activity, resulting in inhibition of the mTOR-regulated translational controllers p70(s6) kinase and 4E-BP1. Ultimately, CCI-779 decreases the translation of mRNAs involved in the control of the cell cycle, resulting in cell cycle arrest. The objective of this study was to develop a method to determine the pharmacodynamic effects of CCI-779 suitable for use in clinical trials. Exposure of Raji lymphoblastoid cells to increasing concentrations of rapamycin resulted in a linear concentration-dependent inhibition of p70(s6) kinase activity, suggesting that p70(s6) kinase activity could be an appropriate marker for mTOR-interacting agents. In subsequent experiments, treatment of nude mice bearing the CCI-779 susceptible breast cancer cell line MDA-468 with a single dose of 10 mg/kg CCI-779 resulted in a >80% inhibition of p70(s6) kinase activity in peripheral blood mononuclear cells (PBMCs) 72 h after treatment. Importantly, the degree of p70(s6) kinase inhibition was identical in PBMCs and simultaneously collected tumor tissue, suggesting that the PBMCs are an adequate surrogate tissue for p70(s6) kinase activity in vivo. The intrasubject coefficient of variation of p70(s6) kinase activity measured in PBMCs collected from five healthy volunteers on days 1, 4, and 8 was 14%, indicating that p70(s6) kinase activity in PBMCs remains relatively stable over time. Finally, p70(s6) kinase activity was measured in PBMCs from nine patients with renal cell cancer treated with a single dose of 25, 75, or 250 mg of CCI-779 i.v. (three patients each). PBMCs were collected on days 2, 4, and 8 after CCI-779 treatment. In this small data set, eight of the nine patients had evidence of p70(s6) kinase activity inhibition after treatment that was independent of the administered dose. There was a significant linear association between time to disease progression and inhibition of p70(s6) kinase activity 24 h after treatment. In conclusion, these results indicate that the pharmacodynamic effects of CCI-779 can be determined using a p70(s6) kinase assay in PBMCs. This assay is currently being incorporated in Phase I and II studies with CCI-779 to determine its relationship with dose and plasma concentration of the agent and its value as a predictor of treatment efficacy. 相似文献
58.
José Rosselló-Urgell Josep Vaqué-Rafart Eduardo Hermosilla-Pérez Alejandro Allepuz-Palau 《Infection control and hospital epidemiology》2004,25(1):41-46
OBJECTIVE: To analyze a method that identifies potentially preventable nosocomial infections, as a tool to evaluate the performance of infection control programs through quantification of their potential for reducing nosocomial infections. METHODS: The database of the Study of the Prevalence of Nosocomial Infections in Spain (EPINE) was reanalyzed. The method was based on the use of false negatives of the classification table obtained from application of a fixed multiple logistic regression model, as an estimator of the number of potentially preventable nosocomial infections. RESULTS: The calculated number of patients with preventable infections was 7,493, which constituted 21.6% of the infected patients. Among hospital areas, intensive care had the lowest preventability rate (4.6%), whereas gynecology and obstetrics had the highest (40.6%). There was a significant inverse exposure-effect relationship between the proportion of preventable infections and the National Nosocomial Infections Surveillance (NNIS) System risk index. No correlation was observed between the prevalence of patients with nosocomial infection and the percentage of preventable infections. CONCLUSION: This analysis suggests that fewer nosocomial infections may be preventable in Spanish hospitals than previously assumed. 相似文献
59.
Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. 总被引:2,自引:0,他引:2
Carol Moreno Neus Villamor Dolors Colomer Jordi Esteve Rodrigo Martino Josep Nomdedéu Francesc Bosch Armando López-Guillermo Elías Campo Jorge Sierra Emili Montserrat 《Journal of clinical oncology》2005,23(15):3433-3438
PURPOSE: To investigate whether allogeneic stem-cell transplantation (allo-SCT) may overcome the negative impact of unmutated VH genes in the outcome of patients with chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: We analyzed the outcome of patients who underwent SCT according to their VH mutational status. RESULTS: Thirty-four patients (14 allo-SCT and 20 autologous SCT [auto-SCT]) presented unmutated VH genes and 16 patients presented mutated VH genes (nine allo-SCT and seven auto-SCT). Tumoral burden pre-SCT was significantly higher in the allo-SCT patients independent of the VH mutational status. The risk of relapse was significantly higher after auto-SCT (5-year risk, 61%; 95% CI, 44% to 84%) than after allo-SCT (5-year risk 12%, 95% CI, 3% to 44%; P < .05). In the unmutated group, 13 of 20 auto-SCT and two of 14 allo-SCT patients experienced disease progression, with a risk of relapse at 5 years of 66% (95% CI, 48% to 93%) v 17% (95% CI, 5% to 60%), respectively (P = .01). CONCLUSION: These results show that allo-SCT may overcome the unfavorable effect of unmutated VH genes in patients with CLL. 相似文献
60.
FGFR3 and Tp53 mutations in T1G3 transitional bladder carcinomas: independent distribution and lack of association with prognosis. 总被引:3,自引:0,他引:3
Silvia Hernández Elena López-Knowles Josep Lloreta Manolis Kogevinas Roberto Jaramillo Alex Amorós Adonina Tardón Reina García-Closas Consol Serra Alfredo Carrato Núria Malats Francisco X Real 《Clinical cancer research》2005,11(15):5444-5450
FGFR3 and Tp53 mutations have been proposed as defining two alternative pathways in the pathogenesis of transitional bladder cancer. FGFR3 mutations are associated with low-grade tumors and a favorable prognosis. Tp53 alterations are associated with advanced tumors and, possibly, with a poor prognosis. We focus here on the subgroup of T1G3 superficial tumors because they are a major clinical challenge. Patients (n = 119) were identified from a prospective study of 1,356 cases. Mutations in FGFR3 (exons 7, 10, and 15) and Tp53 (exons 4-9) were analyzed using PCR and direct sequencing. All cases were followed for recurrence and death. Survival was analyzed using Kaplan-Meier curves and multivariable Cox regression. FGFR3 mutations were detected in 20 (16.8%) tumors; 100 mutations in Tp53 were found in tumors from 78 (65.5%) cases. Multiple alterations in Tp53 were present in 19 tumors (16%). Inactivating mutations were present in 58% of tumors. The combined mutation distribution (FGFR3/Tp53) was: wt/wt (34.5%), mut/wt (7.6%), wt/mut (48.7%), and mut/mut (9.2%), indicating that the presence of either mutation did not depend on the other (P value = 0.767). FGFR3 and Tp53 mutations were not associated with clinicopathologic characteristics of patients and did not predict, alone or in combination, recurrence or survival. Taking the risk of the wt/wt group as reference, the mutation-associated risks of cancer-specific mortality were: mut/wt 1.42 (0.15-13.75), wt/mut 0.67 (0.19-2.31), mut/mut 1.62 (0.27-9.59). These molecular features support the notion that T1G3 tumors are at the crossroads of the two main molecular pathways proposed for bladder cancer development and progression. 相似文献