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41.
MUC1 expression is correlated with nuclear grade and tumor progression in pT1 renal clear cell carcinoma 总被引:3,自引:0,他引:3
Leroy X Zerimech F Zini L Copin MC Buisine MP Gosselin B Aubert JP Porchet N 《American journal of clinical pathology》2002,118(1):47-51
We studied, by immunohistochemical analysis, the expression of MUC1 and epithelial membrane antigen in 44 stage pT1 renal cell carcinomas (RCCs). Six patients had a metastatic evolution. The percentage of stained cells was determined for each tumor. All tumors and normal adjacent renal parenchyma were stained. In normal kidney, distal convoluted tubules and collecting ducts stained strongly with an apical distribution. In tumors, there was a significant statistical correlation of the MUC1 expression level with the nuclear grade and with tumor progression. High-grade tumors had more stained cells than did low-grade tumors. Metastatic tumors also were more stained than nonmetastatic lesions. By using the Kaplan-Meier method and the log-rank test, we observed that patients with fewer than 10% of stained cells had no metastatic evolution. In contrast, patients with 70% or more stained cells had significantly lower metastasis-free survival rates. We conclude that MUC1 is expressed in RCC and is associated with tumor progression in pT1 RCC. 相似文献
42.
Ludwig DL Witte L Hicklin DJ Prewett M Bassi R Burtrum D Pereira DS Jimenez X Fox F Saxena B Zhou Q Ma Y Kang X Patel D Barry M Kussie P Zhu Z Russell DA Petersen WL Jury TP Gaitan-Gaitan F Moran DL Delannay X Storrs BS Tou J Zupec ME Gustafson KS McIntyre J Tarnowski SJ Bohlen P 《Human antibodies》2004,13(3):81-90
Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed. Both corn antibodies were shown to be functionally indistinguishable from mammalian-derived C225 in demonstrating high-affinity binding to the EGF receptor, blocking of ligand-dependent signaling, and inhibiting cell proliferation. In addition, consistent with cetuximab, both corn antibodies possessed strong anti-tumor activity in vivo. Acute dose primate pharmacokinetic studies, however, revealed a marked increase in clearance for the glycosylated corn antibody, while the aglycosylated antibody possessed in vivo kinetics similar to cetuximab. This experimentation established that corn-derived receptor blocking monoclonal antibodies possess comparable efficacy to mammalian cell culture-derived antibody, and offer a cost effective alternative to large-scale mammalian cell culture production. 相似文献
43.
Multiscale structure of sheet nacre 总被引:20,自引:0,他引:20
Rousseau M Lopez E Stempflé P Brendlé M Franke L Guette A Naslain R Bourrat X 《Biomaterials》2005,26(31):6254-6262
This work was conducted on Pinctada maxima nacre (mother of pearl) in order to understand its multiscale ordering and the role of the organic matrix in its structure. Intermittent-contact atomic force microscopy with phase detection imaging reveals a nanostructure within the tablet. A continuous organic framework divides each tablet into nanograins. Their shape is supposed to be flat with a mean extension of 45nm. TEM performed in the darkfield mode evidences that at least part of the intracrystalline matrix is crystallized and responds like a 'single crystal'. The tablet is a 'hybrid composite'. The organic matrix is continuous. The mineral phase is thus finely divided still behaving as a single crystal. It is proposed that each tablet results from the coherent aggregation of nanograins keeping strictly the same crystallographic orientation thanks to a hetero-epitaxy mechanism. Finally, high-resolution TEM performed on bridges from one tablet to the next, in the overlying row, did not permit to evidence a mineral lattice but crystallized organic bridges. The same organic bridges were evidenced by SEM in the interlaminar sequence. 相似文献
44.
Contreras X Bennasser Y Chazal N Moreau M Leclerc C Tkaczuk J Bahraoui E 《Virology》2005,332(1):316-328
HIV-1 Tat protein, acting at the cell membrane, stimulates the production by human monocytes of TNF-α, a cytokine implicated in both HIV-1 replication and pathogenesis. Here, we analyze, in primary human monocytes, the mechanisms involved in Tat-stimulated calcium mobilization and its relationship with TNF-α production. We show that the Tat protein induces a calcium signal by mobilizing calcium from extracellular stores. This calcium signal is totally blocked when cells are stimulated in the presence of DHP receptor inhibitors such as nimodipine or calcicludine, thus suggesting the implication of this L-type calcium channel. By using RT-PCR amplification, Western blot with antibodies directed against the α1D subunit, binding assays with specific agonists or antagonists, and inhibition with specific antisense oligonucleotides, we show that DHP receptors are expressed and functional in primary human monocytes. Interestingly, we demonstrate that Tat-induced calcium mobilization is tightly linked to TNF-α production, thus indicating that Tat-induced mobilization and TNF-α production are entirely mediated by DHP receptors, as shown by their total inhibition by nimodipine, calcicludine, or anti-α1D antisense oligonucleotides. 相似文献
45.
Diffuse optical tomography with a priori anatomical information 总被引:1,自引:0,他引:1
Diffuse optical tomography (DOT) poses a typical ill-posed inverse problem with a limited number of measurements and inherently low spatial resolution. In this paper, we propose a hierarchical Bayesian approach to improve spatial resolution and quantitative accuracy by using a priori information provided by a secondary high resolution anatomical imaging modality, such as magnetic resonance (MR) or x-ray. In such a dual imaging approach, while the correlation between optical and anatomical images may be high, it is not perfect. For example, a tumour may be present in the optical image, but may not be discernable in the anatomical image. The proposed hierarchical Bayesian approach allows incorporation of partial a priori knowledge about the noise and unknown optical image models, thereby capturing the function-anatomy correlation effectively. We present a computationally efficient iterative algorithm to simultaneously estimate the optical image and the unknown a priori model parameters. Extensive numerical simulations demonstrate that the proposed method avoids undesirable bias towards anatomical prior information and leads to significantly improved spatial resolution and quantitative accuracy. 相似文献
46.
Genetic diversity among clinical isolates of Candida glabrata analyzed by randomly amplified polymorphic DNA and multilocus enzyme electrophoresis analyses 下载免费PDF全文
Boldo XM Villa-Tanaca L Zúñiga G Hernández-Rodríguez C 《Journal of clinical microbiology》2003,41(10):4799-4804
The genetic diversity of 47 clinical and reference strains of Candida glabrata from several geographical origins and diverse clinical disorders, with different antifungal susceptibilities, as well as their genetic relationships were studied through multilocus enzyme electrophoresis (MLEE) and randomly amplified polymorphic DNA (RAPD) techniques. The genetic diversity estimated for 11 MLEE loci measured as average heterozygosity (h) was 0.055. A high level of genetic relatedness among isolates was established by cluster analysis. Forty-nine RAPD markers were analyzed, and the average genetic diversity among isolates, estimated by Shannon's index (Ho), was 0.372. The PhiST values estimated through an analysis of molecular variance to assess genetic differentiation among isolates revealed no genetic differentiation among them. Our results revealed very low genetic diversity among isolates, a lack of differentiation, and no association with their geographic origin and the clinical characteristics. 相似文献
47.
Nicolle DM Pichon X Bouchot A Maillet I Erard F Akira S Ryffel B Quesniaux VF 《Laboratory investigation; a journal of technical methods and pathology》2004,84(10):1305-1321
To assess the role of Toll-like receptor (TLR) signalling in host response to mycobacterial infection, mice deficient in the TLR adaptor molecule myeloid differentiation factor 88 (MyD88) were infected with the vaccine strain Mycobacterium bovis (BCG), and the immune response and bacterial burden were investigated. Macrophages and dendritic cells from MyD88-deficient mice stimulated in vitro with BCG mycobacterial antigens produced very low levels of proinflammatory cytokines, while the expression of costimulatory molecules such as CD40 and CD86 was preserved. Upon systemic infection with BCG (2 x 10(6) CFU i.v.) MyD88-deficient mice developed confluent chronic pneumonia with two log higher CFU than wild-type mice. Interestingly, the infection was controlled in liver and spleen and there was efficient systemic T-cell priming with high IFNgamma production by CD4+ splenic T cells in MyD88-deficient mice. Lung infiltrating cells showed IFNgamma production by pulmonary CD4+ T cells upon specific restimulation, and a reduced capacity to produce nitric oxide and IL-10. In summary, despite the dramatic reduction of the innate immune response, MyD88-deficient mice were able to mount an efficient T-cell response to mycobacterial antigens, which was however insufficient to control infection in the lung, resulting in chronic pneumonia in MyD88-deficient mice. 相似文献
48.
Ribasés M Gratacòs M Fernández-Aranda F Bellodi L Boni C Anderluh M Cavallini MC Cellini E Di Bella D Erzegovesi S Foulon C Gabrovsek M Gorwood P Hebebrand J Hinney A Holliday J Hu X Karwautz A Kipman A Komel R Nacmias B Remschmidt H Ricca V Sorbi S Wagner G Treasure J Collier DA Estivill X 《Human molecular genetics》2004,13(12):1205-1212
Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene (-270C>T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and UK) participating in the 'Factors in Healthy Eating' project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors. 相似文献
49.
BACKGROUND: Rates of remission and relapse were studied over more than 2 years in a sample of Spanish outpatients with DSM-III-R criteria of unipolar major depressive episodes. METHODS: Patients were treated following standardised pharmacological protocols at our centre. In the first visit, the structured clinical interview for DSM-III-R (SCID) was used. The following visits were held monthly. Phases of evolution were recorded using the Hamilton Depression Rating Scale (HDRS), applying the Frank criteria. RESULTS: A significantly greater proportion of relapse was observed in the partial remission group compared to the complete remission one. The rate of relapses for patients in complete remission was 15.18%, while for patients in partial remission was 67.61%. Partial remission was significantly associated with relapses. LIMITATIONS: The short duration of the study and the decreasing sample size during the follow-up. CONCLUSIONS: Partial remission after a depressive episode seems to be strongly associated with relapses. Moreover, this clinical factor could by itself fully predict short-term relapses. CLINICAL RELEVANCE: The study shows the importance of reaching complete remission to decrease the rate of short-term relapses. 相似文献
50.
Martinez X Regner M Kovarik J Zarei S Hauser C Lambert PH Leclerc C Siegrist CA 《Virology》2003,305(2):428-435
The relative immaturity of the neonatal immune system limits CD4(+) Th1 and cytotoxic T lymphocyte (CTL) responses, and represents a significant challenge for the development of vaccines against intracellular pathogens. In this report, we demonstrate the ability of a non-replicative delivery system based on parvovirus-like particles (VLP) to induce CTL responses in the neonatal period. A single immunization of 1-week-old BALB/c mice with recombinant VLP carrying a CD8(+) T cell determinant from lymphocytic choriomeningitis virus (VLP-LCMV) induced antigen-specific CD8(+) cytotoxic T cells that were similar to those elicited by adult immunization, as assessed by cytotoxic activity, interferon (IFN)-gamma secretion, cytotoxic precursor cell frequencies, in vitro avidity for antigen and protective activity against viral challenge. These CTL responses are elicited within 2 weeks of a single immunization, in the absence of adjuvant and independently of the presence and help of CD4(+) T cells, highlighting the potential of VLP as candidate vaccine vectors in early life. 相似文献