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31.
Expression of human CD81 in transgenic mice does not confer susceptibility to hepatitis C virus infection 总被引:6,自引:0,他引:6
Masciopinto F Freer G Burgio VL Levy S Galli-Stampino L Bendinelli M Houghton M Abrignani S Uematsu Y 《Virology》2002,304(2):187-196
We previously demonstrated that hepatitis C virus (HCV) binds to human CD81 through the E2 glycoprotein. Therefore, expression of the human CD81 molecule in transgenic mice was expected to provide a new tool to study HCV infection in vivo, as the chimpanzee is the only species currently available as a laboratory animal model that can be infected with HCV. We produced transgenic mice expressing the human CD81 protein in a wide variety of tissues. We confirmed binding of recombinant E2 glycoprotein to the liver tissue as well as to thymocytes and splenic lymphocytes in the transgenic mice. We inoculated chimpanzee plasma infected with HCV into these animals. None of these transgenic animals showed evidence of viral replication. Furthermore, human CD81 transgenic mice that lack expression of endogenous mouse CD81 were also resistant to HCV infection. We conclude that expression of human CD81 alone is insufficient to confer susceptibility to HCV infection in the mouse. The presence of additional possible factors for HCV infection is discussed. 相似文献
32.
Maria Luisa Gaspar Melchor Alvarez-Mon Carmen Gutierrez 《Journal of clinical immunology》1988,8(4):266-274
Recent knowledge of B-lymphocyte physiology has clarified the role of T cell-derived lymphokines in clonal proliferation and differentiation of B-cell responses. Lymphokine production was analyzed in 19 systemic lupus erythematosus (SLE) patients and sex- and age-matched controls in relation to clinical activity and steroid treatment. Whenin vitro production of interleukin-2 (IL-2) and B-cell growth factor (BCGF) was tested, both activities were found to be diminished in the group of patients (P<0.01), while B-cell differentiation factor (BCDF) activity was higher in this group with respect to normal controls (P<0.01). Interestingly enough, thisin vitro BCDF synthesis was positively correlated with clinical activity regardless of low-dose steroid treatment. A correlation was also found between BCDF production and the levels of IgG (r=0.64,P<0.01), anti-DNA antibodies (r=0.52,P<0.05), and the IgG/IgM ratio (r=0.7,P<0.01) in serum. Implications of these abnormal T-lymphocyte functions in SLE with respect toin vivo B-cell function are discussed. 相似文献
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Zankl A Neumann L Ignatius J Nikkels P Schrander-Stumpel C Mortier G Omran H Wright M Hilbert K Bonafé L Spranger J Zabel B Superti-Furga A 《American journal of medical genetics. Part A》2005,(1):61-67
Platyspondylic lethal skeletal dysplasia (PLSD) Torrance type (PLSD-T) is a rare skeletal dysplasia characterized by platyspondyly, brachydactyly, and metaphyseal changes. Generally a perinatally lethal disease, a few long-term survivors have been reported. Recently, mutations in the carboxy-propeptide of type II collagen have been identified in two patients with PLSD-T, indicating that PLSD-T is a type 2 collagen-associated disorder. We studied eight additional cases of PLSD-T and found that all had mutations in the C-propeptide domain of COL2A1. The mutational spectrum includes missense, stop codon and frameshift mutations. All non-sense mutations were located in the last exon, where they would escape non-sense-mediated RNA-decay. We conclude that PLSD-T is caused by mutations in the C-propeptide domain of COL2A1, which lead to biosynthesis of an altered collagen chain (as opposed to a null allele). Similar mutations have recently been found to be the cause of spondyloperipheral dysplasia, a non-lethal dominant disorder whose clinical and radiographical features overlap those of the rare long-term survivors with PLSD-T. Thus, spondyloperipheral dysplasia and PLSD-T constitute a novel subfamily within the type II collagenopathies, associated with specific mutations in the C-propeptide domain and characterized by distinctive radiological features including metaphyseal changes and brachydactyly that set them apart from other type 2 collagenopathies associated with mutations in the triple-helical domain of COL2A1. The specific phenotype of C-propeptide mutations could result from a combination of diminished collagen fibril formation, toxic effects through the accumulation of unfolded collagen chains inside the chondrocytes, and alteration of a putative signaling function of the carboxy-propeptide of type 2 collagen. 相似文献
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Laura Masi Raffaella Recenti Sandra Silvestri Pamela Pinzani Monica Pepi Milena Paglierani Maria Luisa Brandi Alessandro Franchi 《Applied immunohistochemistry & molecular morphology》2007,15(1):70-76
Several studies indicate that cyclooxygenase-2 (COX-2) is overexpressed in human malignancies, where it produces high levels of prostaglandins and contributes to tumor growth. In this study we have analyzed the expression of COX-2 in a series of 48 skeletal osteosarcomas of different subtypes by immunohistochemistry. In addition, we examined the effects of the specific COX-2 inhibitor Celecoxib on the growth of the human osteosarcoma cell line SaOS-2. Immunoreactivity for COX-2 was observed in 39 out of 48 tumors (81.2%), 30 (76.9%) of which showed a moderate or diffuse immunostaining. Considering the group of 42 primary osteosarcomas, COX-2 immunoreactivity was significantly higher in high grade osteosarcomas, where moderate or diffuse expression was detected in 23 out of 32 cases (71.8%), than in low grade osteosarcomas, where moderate or diffuse expression was detected in 2 out of 10 cases (20%) (P = 0.008, Fisher exact test). In addition, low COX-2 expression was always associated with a good response to chemotherapy (5 out of 5 cases), whereas moderate or diffuse COX-2 expression was associated with a good response in 11 out of 20 cases (55%) (P = 0.12, Fisher exact test). In SaOS-2 osteosarcoma cells, which express COX-2, treatment with Celecoxib determined inhibition of cell proliferation and induction of apoptosis. These results indicate that COX-2 is expressed at high levels in high grade osteosarcomas and support the use of COX-2 inhibitors to improve both the tumor response to chemotherapy and the outcome of osteosarcoma patients. 相似文献
38.
Mancuso M Conforti FL Rocchi A Tessitore A Muglia M Tedeschi G Panza D Monsurrò M Sola P Mandrioli J Choub A DelCorona A Manca ML Mazzei R Sprovieri T Filosto M Salviati A Valentino P Bono F Caracciolo M Simone IL La Bella V Majorana G Siciliano G Murri L Quattrone A 《Neuroscience letters》2004,371(2-3):158-162
Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease. 相似文献
39.
Panu R Bo Minelli L Botti M Gazza F Acone F Ragionieri L Palmieri G 《The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology》2003,275(2):1102-1108
The aim of this study was to locate in male pigs the sensory and autonomic ganglia innervating the retractor penis muscle (RPM), which was taken as an experimental model of the genital smooth musculature. The retrograde neuronal tracers horseradish peroxidase (HRP), Fast Blue (FB), and diamidino yellow (DY) were injected into the bulbopenile portion of the left RPM. The tracers highlighted a different affinity for the neuronal structures, although labelled cells supplying the RPM were generally found in bilateral dorsal root ganglia (DRGs, S1-S3), in bilateral paravertebral ganglia (PaGs, L2-S3), and in the left and right caudal mesenteric ganglia (CMGs). The mean number of labelled FB cells was 795 (range, 645-952) in DRGs, 16046.25 (range, 10226-18742) in PaGs, and 635.25 (range, 333-786) in CMGs. The mean diameter of pseudounipolar DRG cells was 60-75 microm, while the multipolar neurons of PaGs and CMGs had dimensions varying between 20-50 microm and 20-30 microm, respectively. 相似文献
40.
Molecular and serological evaluation of surface antigen negative hepatitis B virus infection in blood donors from Venezuela 总被引:2,自引:0,他引:2
Gutiérrez C Devesa M Loureiro CL León G Liprandi F Pujol FH 《Journal of medical virology》2004,73(2):200-207
Surface antigen negative hepatitis B virus (HBV) infection was evaluated in Venezuela, by molecular characterization of blood samples positive for antibodies to core antigen (anti-HBc) and negative for surface antigen (HBsAg) in blood donors (residual infections). HBV DNA was found in 11/258 samples (4.3%), and was significantly associated with high levels of anti-HBc antibodies (>25 UI/ml, P < 0.05), while no correlation was found between the presence of HBV DNA and the levels of anti-HBs. Synonymous and non-synonymous mutations were found in the HBV surface region (but not vaccine escape mutants) and in the precore/core region (precore mutants in 2/7 samples and 33-45 bp deletions near the N-terminal core region in 4/19 samples). While HBV genotype F prevails among HBsAg positive samples from blood donors in Venezuela, residual infection isolates were mainly genotypes A and D. Phylogenetic analysis of viral surface and core region revealed discrepancies in genotype designation in 6/9 samples, suggesting the presence of mixed infection or recombination. In conclusion, HBV residual infection in Venezuela does not seem to be frequently observed in HBV genotype F. This type of infection is frequently associated with variants exhibiting mutations in the surface gene that might be affecting the correct recognition by commercial tests, with precore mutants and with core internal deletions. These variants do not seem to cause severe liver disease, and on the contrary, were found circulating at low viremia. 相似文献