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51.
胰岛素样生长因子Ⅰ与肝纤维化 总被引:1,自引:1,他引:1
胰岛素样生长因子I(IGF-I)是体内普遍存在的多肽,循环系统中IGF-I主要来源于肝脏.在垂体生长激素的调控下,IGF-I对多种细胞如成纤维细胞、成骨细胞、平滑肌细胞等的有丝分裂均有调节作用.目前观点认为肝星状细胞(HSC)活化后可分泌大量胶原纤维,是肝纤维化时细胞外基质的主要来源.实验表明 IGF-I能够促进体外培养HSC增殖、活化并抑制其凋亡.而体内研究发现,肝硬化患者血清IGF-I浓度显著下降,外源性小剂量IGF-I 注射能够改善肝功能,为肝纤维化的治疗提供了新的理念. 相似文献
52.
The color complementation assay (CCA) is a method of allele-specific DNA amplification by which competitive priming and extension of fluorescently labeled oligonucleotide primers determine the color of DNA amplification product. This diagnostic method precludes the need for radioisotopes, electrophoresis, and multiple high-stringency reaction conditions. The multiplicity of mutant globin genes present in Southeast Asians complicates clinical diagnosis and underscores the importance of DNA-based diagnostic methods. We have applied CCA to distinguish beta A and beta E alleles. Competing 15mer primers were a fluorescein-labeled complement to beta A and a rhodamine-labeled complement to beta E, identical except for their central nucleotides. A common unlabeled primer was used to amplify DNA product, the color of which was determined by the perfectly complementary primer. Color photography and spectrofluorometry, as well as a method of black-white photography that we developed to distinguish fluorescein- and rhodamine- labeled DNA, were used to record results. We applied CCA to define the complex genotype of a Thai woman with thalassemia intermedia, 96% HbE, and 4% HbF whose possible genotypes included several permutations of alpha-thalassemia, beta-thalassemia, and beta E genes. zeta-Globin gene mapping of DNA doubly digested with Bg/II and Asp 718 showed the -alpha 3.7/--SEA genotype, and CCA confirmed homozygous beta E/beta E. The CCA is useful for diagnosing the compound hemoglobin genotypes of Southeast Asians and could be applied also to prenatal diagnosis in this population. 相似文献
53.
Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants 总被引:8,自引:6,他引:8
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Volpi I Perruccio K Tosti A Capanni M Ruggeri L Posati S Aversa F Tabilio A Romani L Martelli MF Velardi A 《Blood》2001,97(8):2514-2521
In human leukocyte antigen haplotype-mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4- and IL-10-producing CD4(+) cells not expressing the IL-12 receptor beta(2) chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12-producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4(+) cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4(+) cell counts increased in significantly less time. Finally, elimination of G-CSF-mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell-depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery. 相似文献
54.
Four patients with Philadelphia (Ph') positive chronic myeloid leukemia (CML) were studied before, after, and on relapse following allogeneic bone marrow transplantation (BMT). Southern analysis of DNA from cells collected before and at relapse after BMT was performed in order to investigate the origin of the leukemia at relapse. Using minisatellite probes we showed that the relapse occurred in cells of host origin in all four patients and this was confirmed with a Y chromosome specific probe in two male patients who had a female donor. Furthermore, using two probes for the breakpoint cluster region (bcr) on chromosome 22, we showed that leukemic cells at relapse bore identical rearrangements to those in the disease at time of presentation of each patient. We conclude that relapse in all four patients is due to re-emergence of the original leukemic clone. 相似文献
55.
Antonella de Luca Sanne P. Smeekens Andrea Casagrande Rossana Iannitti Kara L. Conway Mark. S. Gresnigt Jakob Begun Theo S. Plantinga Leo A. B. Joosten Jos W. M. van der Meer Georgios Chamilos Mihai G. Netea Ramnik J. Xavier Charles A. Dinarello Luigina Romani Frank L. van de Veerdonk 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(9):3526-3531
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Francesca Ferri Marianna Busiello Giovanna C. Campione Elisa De Stefani Alessandro Innocenti Gian Luca Romani Marcello Costantini Maurizio Gentilucci 《The European journal of neuroscience》2014,39(5):841-851
Request and emblematic gestures, despite being both communicative gestures, do differ in terms of social valence. Indeed, only the former are used to initiate/maintain/terminate an actual interaction. If such a difference is at stake, a relevant social cue, i.e. eye contact, should have different impacts on the neuronal underpinnings of the two types of gesture. We measured blood oxygen level‐dependent signals, using functional magnetic resonance imaging, while participants watched videos of an actor, either blindfolded or not, performing emblems, request gestures, or meaningless control movements. A left‐lateralized network was more activated by both types of communicative gestures than by meaningless movements, regardless of the accessibility of the actor's eyes. Strikingly, when eye contact was taken into account as a factor, a right‐lateralized network was more strongly activated by emblematic gestures performed by the non‐blindfolded actor than by those performed by the blindfolded actor. Such modulation possibly reflects the integration of information conveyed by the eyes with the representation of emblems. Conversely, a wider right‐lateralized network was more strongly activated by request gestures performed by the blindfolded than by those performed by the non‐blindfolded actor. This probably reflects the effect of the conflict between the observed action and its associated contextual information, in which relevant social cues are missing. 相似文献
58.
Recurrent ∼100 Kb microdeletion in the chromosomal region 14q11.2, involving CHD8 gene,is associated with autism and macrocephaly
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59.
60.
Alessandro Cama Fabio Verginelli Lavinia Vittoria Lotti Francesco Napolitano Annalisa Morgano Andria D’Orazio Michele Vacca Silvia Perconti Felice Pepe Federico Romani Francesca Vitullo Filippo di Lella Rosa Visone Massimo Mannelli Hartmut P. H. Neumann Giancarlo Raiconi Carlo Paties Antonio Moschetta Roberto Tagliaferri Angelo Veronese Mario Sanna Renato Mariani-Costantini 《Acta neuropathologica》2013,126(4):575-594
Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests of neurosecretory and glial cells embedded in vascular stroma, provide a remarkable example of organoid tumor architecture. To identify genes and pathways commonly deregulated in head and neck paraganglioma, we integrated high-density genome-wide copy number variation (CNV) analysis with microRNA and immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a list of 104 genes most significantly targeted by tumor-associated alterations. The “NOTCH signaling pathway” was the most significantly enriched term in the list (P = 0.002 after Bonferroni or Benjamini correction). Expression of the relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine) and endothelial cells was confirmed by immunohistochemistry in 47 head and neck paraganglioma cases. There were no relationships between level and pattern of NOTCH1/JAG2 protein expression and germline mutation status in the SDH genes, implicated in paraganglioma predisposition, or the presence/absence of immunostaining for SDHB, a surrogate marker of SDH mutations. Interestingly, NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH signaling genes, suggesting altered epigenetic modulation of this pathway. To address this issue we performed microarray-based microRNA expression analyses. Notably 5 microRNAs (miR-200a,b,c and miR-34b,c), including those most downregulated in the tumors, correlated to NOTCH signaling and directly targeted NOTCH1 in in vitro experiments using SH-SY5Y neuroblastoma cells. Furthermore, lentiviral transduction of miR-200s and miR-34s in patient-derived primary tympano-jugular paraganglioma cell cultures was associated with NOTCH1 downregulation and increased levels of markers of cell toxicity and cell death. Taken together, our results provide an integrated view of common molecular alterations associated with head and neck paraganglioma and reveal an essential role of NOTCH pathway deregulation in this tumor type. 相似文献