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61.
Leslie L Muldoon Jorge I Alvarez David J Begley Ruben J Boado Gregory J del Zoppo Nancy D Doolittle Britta Engelhardt John M Hallenbeck Russell R Lonser John R Ohlfest Alexandre Prat Maurizio Scarpa Richard J Smeyne Lester R Drewes Edward A Neuwelt 《Journal of cerebral blood flow and metabolism》2013,33(1):13-21
The brain is in many ways an immunologically and pharmacologically privileged site. The blood–brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting. 相似文献
62.
G Giannini L Di Marcotullio E Ristori M Zani M Crescenzi S Scarpa G Piaggio A Vacca F A Peverali F Diana I Screpanti L Frati A Gulino 《Cancer research》1999,59(10):2484-2492
HMGI-C and HMGI(Y) are architectural DNA-binding proteins that participate in the conformational regulation of active chromatin. Their pattern of expression in embryonal and adult tissues, the analysis of the "pygmy" phenotype induced by the inactivation of the HMGI-C gene, and their frequent qualitative or quantitative alteration in experimental and human tumors indicate their pivotal role in the control of cell growth, differentiation, and tumorigenesis in several tissues representative of the epithelial, mesenchymal, and hematopoietic lineages. In contrast, very little information is available on their expression and function in neural cells. Here, we investigated the expression of the HMGI(Y) and HMGI-C genes in neuroblastoma (NB), a tumor arising from an alteration of the normal differentiation of neural crest-derived cells and in embryonal and adult adrenal tissue. Although HMGI(Y) is constitutively expressed in the embryonal and adult adrenal gland and in all of the NB cell lines and ex vivo tumors examined, its regulation appears to be associated to growth inhibition and differentiation because we observed that HMGI(Y) expression is reduced by retinoic acid (RA) in several NB cell lines that are induced to differentiate into postmitotic neurons, whereas it is up-regulated by RA in cells that fail to differentiate. Furthermore, the decrease of HMGI(Y) expression observed in RA-induced growth arrest and differentiation is abrogated in cells that have been made insensitive to this drug by NMYC overexpression. In contrast, HMGI-C expression is down-regulated during the development of the adrenal gland, completely absent in the adult individual, and only detectable in a subset of ex vivo NB tumors and in RA-resistant NB cell lines. We provide evidence of a causal link between HMGI-C expression and resistance to the growth arrest induced by RA in NB cell lines because exogenous HMGI-C expression in HMGI-C-negative and RA-sensitive cells is sufficient to convert them into RA-resistant cells. Therefore, we suggest that HMGI-C and HMGI(Y) may participate in growth- and differentiation-related tumor progression events of neuroectodermal derivatives. 相似文献
63.
64.
B Massidda R Migliari A Padovani R M Scarpa P Pellegrini E Cortesi E Usai A Pellegrini 《Journal of chemotherapy (Florence, Italy)》1991,3(6):387-389
42 patients with advanced renal cell carcinoma were treated with a combination therapy with interferon alpha 2a (mean dosage 16 x 10(6) U i.m. 3 times/week) and vinblastine (0.1 mg/Kg every 21 days). 12 patients (28.5%) had a positive response. Of them 1 presented a complete response (2.38%), 5 a partial response (11.9%) and 6 a stable disease (14.2%). No significant side effects were observed apart from the flu-like syndrome (all patients) and a moderate leukopenia (45.2%). The median duration of responses was 10+ months (range 3-37 months). At 4-year follow-up the median survival time was 16.0 months (range 4-37 months). 相似文献
65.
Although relatively rare, endocrine tumors of the digestive tract and pancreas have been widely investigated and represent a complex tumor entity. The two major categories of well-differentiated and poorly differentiated tumors show important phenotypic and clinical differences. In well-differentiated tumors the multiple endocrine neoplasia syndrome of Type 1 (MEN1) gene is frequently abnormal, though a complex multiple gene involvement is postulated for different tumor types. Poorly differentiated carcinomas show frequent p53 gene hyperexpression/defects, characterizing severe cell abnormality and possibly accounting for the malignancy of such carcinomas. 相似文献
66.
Ferrari S Kitson C Farley R Steel R Marriott C Parkins DA Scarpa M Wainwright B Evans MJ Colledge WH Geddes DM Alton EW 《Gene therapy》2001,8(18):1380-1386
Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier can, in part, be overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine using either a cationic lipid or a cationic polymer as the gene transfer agent. Further, in vivo application of either Nacystelyn or the anticholinergic glycopyrrolate, both clinically used agents, resulted in increased reporter gene expression in the mouse lung, but no significant correction of the bioelectric defect in CF null mice. These results, whilst unlikely to be sufficient in themselves to achieve clinically relevant gene therapy, may be a further useful step in the attainment of this goal. 相似文献
67.
68.
Fabio Scarpa Daria Sanna Tiziana Lai Piero Cossu Marco Curini-Galletti Marco Casu 《Conservation Genetics Resources》2016,8(4):411-413
The order Proseriata (Platyhelminthes) represents one of the most abundant soft-bodied meiofaunal groups. These minute interstitial organisms are characterized by a very simple morphology, which often hides the occurrence of cryptic species. Accordingly, molecular analyses are often needed to provide reliable taxonomic assessment and/or species identification. For these purposes the 18S and 28S rDNA genes have been so far the markers of choice. Here, we present a set of new primers for the sequencing of the whole ribosomal region in Proseriata, which improves the size of the sequenced segment from the current 3100 bp (18S + 28S D1–D6) to about 6300 bp. A broader molecular dataset may be used to achieve deeper insights on the systematics of Proseriata. 相似文献
69.
70.
Although neurodegenerative diseases are most prevalent in the elderly, in rare cases, they can also affect children. Lysosomal
storage diseases (LSDs) are a group of inherited metabolic neurodegenerative disorders due to deficiency of a specific protein
integral to lysosomal function, such as enzymes or lysosomal components, or to errors in enzyme trafficking/targeting and
defective function of nonenzymatic lysosomal proteins, all preventing the complete degradation and recycling of macromolecules.
This primary metabolic event determines a cascade of secondary events, inducing LSD’s pathology. The accumulation of intermediate
degradation affects the function of lysosomes and other cellular organelles. Accumulation begins in infancy and progressively
worsens, often affecting several organs, including the central nervous system (CNS). Affected neurons may die through apoptosis
or necrosis, although neuronal loss usually does not occur before advanced stages of the disease. CNS pathology causes mental
retardation, progressive neurodegeneration, and premature death. Many of these features are also found in adult neurodegenerative
disorders, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. However, the nature of the secondary events and their
exact contribution to mental retardation and dementia remains largely unknown. Recently, lysosomal involvement in the pathogenesis
of these disorders has been described. Improved knowledge of secondary events may have impact on diagnosis, staging, and follow-up
of affected children. Importantly, new insights may provide indications about possible disease reversal upon treatment. A
discussion about the CNS pathophysiology involvement in LSDs is the aim of this review. The lysosomal involvement in adult
neurodegenerative diseases will also be briefly described. 相似文献