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11.
A mouse model of hepatocellular carcinoma: ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice 下载免费PDF全文
Nicholes K Guillet S Tomlinson E Hillan K Wright B Frantz GD Pham TA Dillard-Telm L Tsai SP Stephan JP Stinson J Stewart T French DM 《The American journal of pathology》2002,160(6):2295-2307
Most mouse models of hepatocellular carcinoma have expressed growth factors and oncogenes under the control of a liver-specific promoter. In contrast, we describe here the formation of liver tumors in transgenic mice overexpressing human fibroblast growth factor 19 (FGF19) in skeletal muscle. FGF19 transgenic mice had elevated hepatic alpha-fetoprotein mRNA as early as 2 months of age, and hepatocellular carcinomas were evident by 10 months of age. Increased proliferation of pericentral hepatocytes was demonstrated by 5-bromo-2'-deoxyuridine incorporation in the FGF19 transgenic mice before tumor formation and in nontransgenic mice injected with recombinant FGF19 protein. Areas of small cell dysplasia were initially evident pericentrally, and dysplastic/neoplastic foci throughout the hepatic lobule were glutamine synthetase-positive, suggestive of a pericentral origin. Consistent with chronic activation of the Wingless/Wnt pathway, 44% of the hepatocellular tumors from FGF19 transgenic mice had nuclear staining for beta-catenin. Sequencing of the tumor DNA encoding beta-catenin revealed point mutations that resulted in amino acid substitutions. These findings suggest a previously unknown role for FGF19 in hepatocellular carcinomas. 相似文献
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Stéphanie Chasseigneaux Stéphane Haïk Isabelle Laffont-Proust Olivier De Marco Martine Lenne Jean-Philippe Brandel Jean-Jacques Hauw Jean-Louis Laplanche Katell Peoc’h 《Neuroscience letters》2006
A valine to isoleucine mutation at residue 180 was identified in a French patient with Creutzfeldt-Jakob disease (CJD). The mutation is located in the close vicinity of one of the two N-glycosylation sites of the cellular prion protein (PrPC). Western blot analysis revealed accumulation in the brain of the pathogenic proteinase K-resistant PrP (PrPSc) isoform with the notable absence of the diglycosylated band. The mutant protein expressed in CHO cells was correctly glycosylated, suggesting that the atypical glycosylation pattern of PrPSc was not due to the mutation at position 180. These results suggest that the diglycosylated form of the mutant PrP180I prevents its conversion into the pathogenic mutant form PrPSc180I, supporting a central role of N-linked glycan chains in the PrP conversion process. 相似文献
13.
What and where in human audition: selective deficits following focal hemispheric lesions 总被引:8,自引:0,他引:8
Clarke S Bellmann Thiran A Maeder P Adriani M Vernet O Regli L Cuisenaire O Thiran JP 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2002,147(1):8-15
A sound that we hear in a natural setting allows us to identify the sound source and localize it in space. The two aspects
can be disrupted independently as shown in a study of 15 patients with focal right-hemispheric lesions. Four patients were
normal in sound recognition but severely impaired in sound localization, whereas three other patients had difficulties in
recognizing sounds but localized them well. The lesions involved the inferior parietal and frontal cortices, and the superior
temporal gyrus in patients with selective sound localization deficit; and the temporal pole and anterior part of the fusiform,
inferior and middle temporal gyri in patients with selective recognition deficit. These results suggest separate cortical
processing pathways for auditory recognition and localization.
Electronic Publication 相似文献
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Monosomy 9q and trisomy 16q in a case of congenital solitary infantile myofibromatosis 总被引:1,自引:0,他引:1
Sirvent N Perrin C Lacour JP Maire G Attias R Pedeutour F 《Virchows Archiv : an international journal of pathology》2004,445(5):537-540
Although infantile myofibromatosis (IM) is the most common fibrous proliferation of infancy, many aspects of this benign lesion have not been explored. IM histogenesis is still poorly understood, despite immunohistochemical staining and ultrastructural features that suggest a myofibroblastic origin. IM diagnosis is often made difficult by the predominance of small primitive spindle cells over myofibrobasts and the presence of intravascular growth. Genetic information is scarce, with only one karyotyped case. Here we describe a case of solitary IM discovered at birth in an otherwise healthy girl. The tumor was well circumscribed, arranged in nodules and made up of ovoid cells without atypia, in a myxoid background. Immunohistochemical evaluation indicated a myofibroblastic differentiation. The cytogenetic and fluorescence in situ hybridization analyses revealed an abnormal chromosome 9, derived from an unbalanced whole-arm translocation between chromosomes 9 and 16. On both chromosomes, the breakpoints were located in the pericentric heterochromatic region. This clonal abnormality has not been reported in other tumors and is different from the chromosome 6q deletion reported in the single previous reported IM karyotype. 相似文献
16.
Jean-Philippe Gaillard Rgis Bataille Herv Brailly Caroline Zuber Kiyoshi Yasukawa Michel Attal Naoko Maruo Tetsuya Taga Tadamitsu Kishimoto Bernard Klein 《European journal of immunology》1993,23(4):820-824
Soluble human interleukin-6 receptor (sIL-6R) was measured in the serum of 30 healthy individuals, 32 individuals with monoclonal gammopathy of undetermined significance (MGUS), 20 patients with early multiple myeloma (MM) and 54 patients with overt MM. The serum activity recognized by an immunoradiometric assay was determined to be sIL-6R, because of its binding capacity to IL-6 and its molecular mass of 55 kDa. All sera of healthy individuals contained sIL-6R (mean value: 89 ng/ml, range 17-300 ng/ml). Serum sIL-6R levels were increased by 51% in patients with MGUS (mean value: 135 ng/ml, p<0.005), by 44% in patients with early myeloma (mean value: 128 ng/ml, p<0.001) and by 116 % in patients with overt MM (mean value: 193 ng/ml, p<0.001). In patients with MM, a complete lack of correlation (p>0.7) was found between serum sIL-6R levels and other previously recognized prognostic factors in this disease, particularly serum IL-6 levels and those factors related to tumor cell mass. The independence of serum sIL-6R levels on tumor cell mass was directly demonstrated by studying four patients with MM treated with autologous bone marrow transplantation for periods of between 320 and 760 days. These levels were found to be remarkably stable and constant, independent of whether patients relapsed or achieved complete remission. Finally, physiological concentrations of sIL-6R were found to increase by tenfold the sensitivity of human myeloma cell lines to IL-6. These observations suggest a high control of the sIL-6R level in vivo, and, possibly, an important functional role of this circulating protein in patients with monoclonal gammopathies. 相似文献
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Thierry Conroy Bernard Paillot Eric Fran?ois Roland Bugat Jacques-Henri Jacob Ulrich Stein Salvador Nasca Jean-Philippe Metges Olivier Rixe Pierre Michel Emmanuelle Magherini Aliette Hua Gael Deplanque 《Journal of clinical oncology》2005,23(6):1228-1236
PURPOSE: To evaluate response rate and toxicity of irinotecan and oxaliplatin plus fluorouracil (FU) and leucovorin (Folfirinox) in advanced pancreatic adenocarcinoma (APA). PATIENTS AND METHODS: Chemotherapy-naive patients with histologically proven APA and bidimensionally measurable disease were treated with Folfirinox therapy every 2 weeks, which comprised oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) plus leucovorin 400 mg/m(2) followed by bolus FU 400 mg/m(2) on day 1, then FU 2,400 mg/m(2) as a 46-hour continuous infusion. Quality of life (QOL) was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). RESULTS: Forty-seven patients were entered, and 46 received treatment. Thirty-five patients (76%) had metastatic disease. A total of 356 cycles were delivered, with a median of eight cycles per patient (range, one to 24 cycles). All patients were assessable for safety. No toxic death occurred. Grade 3 to 4 neutropenia occurred in 52% of patients, including two patients with febrile neutropenia. Other relevant toxicities included grade 3 to 4 nausea (20%), vomiting (17%), and diarrhea (17%) and grade 3 neuropathy (15%; Levi's scale). The confirmed response rate was 26% (95% CI, 13% to 39%), including 4% complete responses. Median time to progression was 8.2 months (95% CI, 5.3 to 11.6 months), and median overall survival was 10.2 months (95% CI, 8.1 to 14.4 months). Between baseline and end of treatment, patients had improvement in all functional scales of the EORTC QLQ-C30, except cognitive functioning. Responders had major improvement in global QOL. CONCLUSION: With a good safety profile, a promising response rate, and an improvement in QOL, Folfirinox will be further assessed in a phase III trial. 相似文献
19.
Aline M. Studerus-Germann Jean-Philippe Thiran Alessandro Daducci 《The International journal of neuroscience》2016,126(4):289-298
Mild traumatic brain injury (mTBI) is one of the most frequently diagnosed neurological disorders in emergency departments. Although there are established recommendations for the diagnosis and treatment in the acute stage, there is an on-going debate in which diagnostic methods and risk factors predict unfavourable long-term outcome after mTBI. This literature review addresses the question, which diagnostic approaches may best predict persistent post-traumatic symptoms (pPTS). A literature search for experimental studies from January 2000 to September 2014 evaluating the following diagnostic approaches (1) susceptibility weighted imaging (SWI), (2) diffusion tensor imaging (DTI), (3) magnetic resonance spectroscopy (MRS), (4) functional magnetic resonance imaging (fMRI), as predictive factors of pPTS or unfavourable cognitive outcome in adult populations with mTBI was performed. DTI has been proved to be a valuable tool to identify diffuse axonal injury (DAI) after mTBI. Additionally, some studies showed associations between DAI and unfavourable cognitive outcome. SWI has shown to be a highly sensitive imaging method to identify microbleeds. The presence and quantity of microbleeds in this imaging technique can further provide aetiological evidence for pPTS. MRS provides information about local neurons metabolism and preliminary data show that creatine–phosphocreatine levels measured after mTBI are predictive of cognitive outcome and emotional distress. The results of one study have shown fMRI as a useful tool to differentiate mTBI patients with pPTS from controls and mTBI patients without pPTS in a resting-state condition. From the evaluated diagnostic approaches to predict pPTS after mTBI, DTI, SWI, MRS, and fMRI seem to have adequate sensitivity and specificity as predictive diagnostic tools for pPTS. Large longitudinal clinical trials are warranted to validate the prognostic applicability and practicability in daily clinical practice. 相似文献
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