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991.
The mechanisms of coronary restenosis: insights from experimental models 总被引:31,自引:0,他引:31
Since its introduction into clinical practice, more than 20 years ago, percutaneous transluminal coronary angioplasty (PTCA) has proven to be an effective, minimally invasive alternative to coronary artery bypass grafting (CABG). During this time there have been great improvements in the design of balloon catheters, operative procedures and adjuvant drug therapy, and this has resulted in low rates of primary failure and short-term complications. However, the potential benefits of angioplasty are diminished by the high rate of recurrent disease. Up to 40% of patients undergoing angioplasty develop clinically significant restenosis within a year of the procedure. Although the deployment of endovascular stents at the time of angioplasty improves the short-term outcome, 'in-stent' stenosis remains an enduring problem. In order to gain an insight into the mechanisms of restenosis, several experimental models of angioplasty have been developed. These have been used together with the tools provided by recent advances in molecular biology and catheter design to investigate restenosis in detail. It is now possible to deliver highly specific molecular antagonists, such as antisense gene sequences, to the site of injury. The knowledge provided by these studies may ultimately lead to novel forms of intervention. The present review is a synopsis of our current understanding of the pathological mechanisms of restenosis. 相似文献
992.
Hviid L Akanmori BD Loizon S Kurtzhals JA Ricke CH Lim A Koram KA Nkrumah FK Mercereau-Puijalon O Behr C 《International immunology》2000,12(6):797-805
TCR gamma delta(+) cells constitute <5% of all circulating T cells in healthy, adult Caucasians, and V(delta)1(+) cells constitute a minority of these cells. In contrast to TCR alpha beta(+) cells, their repertoire is selected extrathymically by environmental antigens. Although increased frequencies of V(delta)1(+) cells are found in several diseases, their function remains obscure. Here we show that the frequency of peripheral blood gamma delta T cells in healthy West Africans is about twice that of Caucasians, mainly due to a 5-fold increase in V(delta)1(+) cells, which is consequently the dominant subset. No age dependency of V(delta)1 frequencies was identified and the V(delta)1(+) cells in the African donors did not show preferential V(gamma) chain usage. Analysis of the CDR3 region size did not reveal any particular skewing of the V(delta)1 repertoire, although oligoclonality was more pronounced in adults compared to children. The proportions of CD8(+), CD38(+) and CD45RA(hi)CD45RO(-) cells within the V(delta)1(+) subset were higher in the African than in the European donors, without obvious differences in expression of activation markers. No significant correlations between levels of V(delta)1(+) cells and environmental antigens or immunological parameters were identified. Taken together, the evidence argues against a CDR3-restricted, antigen-driven expansion of V(delta)1(+) cells in the African study population. Our study shows that high frequencies of TCR gamma delta(+) cells with dominance of the V(delta)1(+) subset can occur at the population level in healthy people, raising questions about the physiological role of V(delta)1(+) T cells in the function and regulation of the immune system. 相似文献
993.
J. Gabrilovac M. Boranić B. Kušić D. Batinić L. Rajić A. Tiefenbach 《Journal of molecular medicine (Berlin, Germany)》1988,66(8):354-360
Summary Natural killer (NK) activity against cells of the K-562 line was significantly depressed in 12 of 18 children (66%) with untreated acute lymphocytic leukemia (ALL). No suppression of allogeneic NK activity was observed with sera of the patients, regardless of the level of NK depression. The ability of peripheral blood lymphocytes (PBLs) to suppress allogeneic NK activity was tested in two ALL patients — one with no detectable NK activity, and one with high NK activity. No NK-suppressive activity was found with PBLs of the areactive patient; PBLs of the reactive patients exhibited some suppressive activity, but only at a particular suppressor-to-effector cell ratio. Leukemic blasts were resistant to killing by autologous NK cells stimulated by IFN, as well as to killing by allogeneic, IFN-stimulated PBLs. Leukemic blasts of an ALL patient inhibited lysis of K-562 cells in an 18-h, but not in a 4-h NK assay. The inhibition could partly be reversed by pretreatment of ALL cells with alpha interferon, suggesting that the blasts might inhibit the lysis of K-562 targets in a competitive manner. Disturbed function and/or regulation of NK cells may influence attempts at NK cell activation by lymphokines.Abbreviations ALL
acute lymphocytic leukemia
- AML
acute myeloid leukemia
- CLL
chronic lymphocytic leukemia
- CML
chronic myeloid leukemia
- IFN
interferon
- IL-2
interleukin-2
- LGL
large granular lymphocyte
- NK cell
natural killer cell
- PBL
peripheral blood lymphocyte
- Poly I:C
polyinosinic-polycytidylic acid 相似文献
994.
Luis Gandía Baldomero Lara Julita S. Imperial Mercedes Villarroya Almudena Albillos Rosario Maroto A. G. García Baldomero M. Olivera 《Pflügers Archiv : European journal of physiology》1997,435(1):55-64
The characteristics of the binding sites for the Conus magus toxins ω-conotoxin MVIIC and ω-conotoxin MVIID, as well as their effects on K+-evoked 45Ca2+ entry and whole-cell Ba2+ currents (I
Ba), and K+-evoked catecholamine secretion have been studied in bovine adrenal chromaffin cells. Binding of [125I] ω-conotoxin GVIA to bovine adrenal medullary membranes was displaced by ω-conotoxins GVIA, MVIIC and MVIID with IC50 values of around 0.1, 4 and 100 nM, respectively. The reverse was true for the binding of [125I] ω-conotoxin MVIIC, which was displaced by ω-conotoxins MVIIC, MVIID and GVIA with IC50 values of around 30, 80 and 1.200 nM, respectively. The sites recognized by ω-conotoxins MVIIC and MVIID in bovine brain
exhibited higher affinities (IC50 values of around 1 nM). Both ω-conotoxin MVIIC and MVIID blocked I
Ba by 70–80%; the higher the [Ba2+]o of the extracellular solution the lower the blockade induced by ω-conotoxin MVIIC. This was not the case for ω-conotoxin
MVIID; high Ba2+ (10 mM) slowed down the development of blockade but the maximum blockade achieved was similar to that obtained in 2 mM Ba2+. A further difference between the two toxins concerns their reversibility; washout of ω-conotoxin MVIIC did not reverse the
blockade of I
Ba while in the case of ω-conotoxin MVIID a partial, quick recovery of current was produced. This component was irreversibly
blocked by ω-conotoxin GVIA, suggesting that it is associated with N-type Ca2+ channels. Blockade of K+-evoked 45Ca2+ entry produced results which paralleled those obtained by measuring I
Ba. Thus, 1 μM of each of ω-conotoxin GVIA and MVIIA inhibited Ca2+ uptake by 25%, while 1 μM of each of ω-conotoxin MVIIC and MVIID caused a 70% blockade. K+-evoked catecholamine secretory responses were not reduced by ω-conotoxin GVIA (1 μM). In contrast, at 1 μM both ω-conotoxin
MVIIC and MVIID reduced the exocytotic response by 70%. These data strengthen the previously established conclusion that Q-type
Ca2+ channels that contribute to the regulation of secretion and are sensitive to ω-conotoxins MVIIC and MVIID are present in
bovine chromaffin cells. These channels, however, seem to possess binding sites for ω-conotoxins MVIIC and MVIID whose characteristics
differ considerably from those described to occur in the brain; they might represent a subset of Q-type Ca2+ channels or an entirely new subtype of voltage-dependent high-threshold Ca2+ channel.
Received: 16 April 1997 / Received after revision: 10 July 1997 / Accepted: 23 July 1997 相似文献
995.
Paneth cell-rich carcinoma of the stomach 总被引:1,自引:0,他引:1
996.
Paolo Leoncini Marcella Cintorino Carla Vindigni Lorenzo Leoncini Doretta Armellini Massimo Bugnoli Omar Skalli Giulio Gabbiani 《Virchows Archiv : an international journal of pathology》1988,412(4):329-337
Summary We have evaluated by means of immunocytochemistry the distribution of various cytoskeletal and contractile proteins (cytokeratins, vimentin, desmin and -smooth muscle actin) in 23 salivary or lacrimal gland primary tumours (15 pleomorphic adenomas and 8 carcinomas in pleomorphic adenoma), one third of which contained areas of normal gland. Normal epithelial luminal cells were stained by cytokeratin antibodies with a general specificity, while myoepithelial cells were selectively stained by a monoclonal antibody (SK2-27) reacting in immunoblots with cytokeratin polypeptides 14, 16 and 17, according to the classification of Moll et al. (1982) and by an antibody directed against -smooth muscle actin (Skalli et al. 1986). In pleomorphic adenomas, both epithelial and myoepithelial cells displayed typical topographic distributions; moreover, myoepithelial cells showed two distinct cytoskeletal phenotypes. These findings could account in part for the heterogeneity of aspects observed in this tumour. In carcinomas, malignant cells were always positive to cytokeratin antibodies with general specificity and myoepithelial cells were absent as judged by anticytokeratin SK2-27 and anti--smooth muscle actin immunostainings. However, interestingly, there was in all cases a strong positivity for -smooth muscle actin in stromal cells, similarly to what has previously been described for mammary carcinoma (Skalli et al. 1986). Our findings may be useful for the interpretation of the histogenesis of salivary and lacrimal tumour and stromal cells. 相似文献
997.
Peripheral nerve grafts lacking viable Schwann cells fail to support central nervous system axonal regeneration 总被引:3,自引:0,他引:3
G. V. Smith J. A. Stevenson 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1988,69(2):299-306
Summary Peripheral nerve grafts were implanted bilaterally into the diencephalon of adult hamsters. One graft segment contained both viable Schwann cells and their basal lamina tubes. The Schwann cell population in the second graft segment was killed by freezing prior to implantation. Seven weeks after graft implantations, the extracranial end of each graft segment was exposed, transected and labelled with a fluorescent tracer substance. One week after the labelling procedure each animal was perfused and the diencephalon and midbrain were examined. Ultrastructural analyses of both types of graft demonstrated the persistence of the Schwann cell-derived basal lamina tubes. Retrogradely labelled neurons were found in all cases in which an intact graft remained in place for two months, but were seen in only one case with a frozen graft. Large numbers of myelinated and unmyelinated axons were seen within the intact grafts, but no axons were found in the previously frozen grafts. These results indicate that lesioned CNS axons are able to regenerate vigorously when provided with an environment which includes viable Schwann cells. But, CNS axons regenerate less well, if at all, when Schwann cells are absent. Further, it appears that Schwann cell-derived basal lamina tubes, when isolated from their parent cells, are insufficient to initiate or sustain CNS axonal regeneration.This material is based upon work supported by the National Science Foundation under grant BNS-8416911 相似文献
998.
J. B. Matthews A. Pitigala-Arachchi I. J. Crane C. Scully S. S. Prime 《Virchows Archiv : an international journal of pathology》1988,413(6):521-528
Summary The development of oral epithelial expression of Ia antigens and its relationship to the presence of IL-2r+ (CD25+) cells was investigated in rats treated with the water soluble carcinogen 4-nitroquinoline-N-oxide (4NQO). Acetone fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (I-A & I-E) and IL-2 receptor. After 4 weeks 4NQO treatment all rats expressed oral epithelial Ia but thereafter (2–9 months) expression was present in only 20–40% of animals. Epithelial expression of Ia by histologically normal, dysplastic and neoplastic epithelium was always associated with the presence of an underlying inflammatory cell infiltrate containing CD25+ cells. Overall there were significantly more CD25+ cells in tissue specimens containing Ia+ epithelium compared with Ia– epithelium. Furthermore, during the first 4 weeks of carcinogen treatment, a significant positive correlation was found between the CD25+ cell density and occurrence of focal epithelial Ia expression. These results, together with analysis of the T cell, NK cell, macrophage and B cell content of the infiltrates induced by 4NQO, suggest that the CD25+ cells represent activated T cells. Thus, our results in this experimental model are consistent with the idea that epithelial expression of Ia is the result of production of IFN- by locally activated T cells. 相似文献
999.
Myoblasts fail to stimulate T cells but induce tolerance 总被引:1,自引:0,他引:1
Warrens Anthony N.; Zhang Jun Yan; Sidhu Sid; Watt Diana J; Lombardi Giovanna; Sewry Caroline A; Lechler Robert I. 《International immunology》1994,6(6):847-853
Recent interest in myoblast transfer and in the use of myoblastsas vehicles in gene therapy has made it important to understandthe potential immunogenicity of allogeneic or neoantlgen-expresslngmyoblasts. Given the problems of producing a pure populationof myoblasts, In this study we used a tumour-derived musclecell line (TE671), with phenotyplc features of myoblasts, whichwe transfected to express HLA-DR1. However, this cell line wasunable to stimulate either established HLA-DR1-specific alloreactlveT cell clones or a primary alloresponse. Nor could it presenthaemagglutlnln peptide HA 306–324 to DR1-restricted, HA306–324-speciflc T cell clones or lines. Indeed, prelncubatlonwith DR1-expressing TE671 and HA 306–324 rendered suchT cells tolerant as Judged by their subsequent inability toproliferate in response to a DR1+ B cell line plus peptide HA306–324. These results imply that myoblasts do not providecostlmulatory signals, and are therefore unlikely to stimulateallospeclfic T cells following myoblasts transplantation orto initiate neoantlgen-speclfic immune responses following Invivo transfection. 相似文献
1000.
Kikuyoshi Yoshida Timo K. Van Den Berg Christine D. Dijkstra 《European journal of immunology》1994,24(2):464-468
In the present study, we have investigated the capacity of follicular dendritic cells (FDC) to trap immune complexes (IC) in the splenic white pulp of severe combined immunodeficient (SCID) mice and the influence of lymphocyte transfer on FDC function. FDC are absent in the splenic white pulp of naive SCID mice as revealed by in vitro IC trapping assay. One week after transfer of syngeneic lymphocytes, functional FDC with complement receptors appeared in the primary follicles coincident with B cell segregation, and IC were trapped on those FDC in a complement-dependent manner. Next, we immunized the reconstituted SCID mouse to see whether another type of FDC could be induced in the secondary follicle. Antigenic stimulation induced FDC with an additional capacity to capture IC via FcR γ II. As seen in immunocompetent mice, this type of FDC was located only in the light zone of the secondary follicle. The newly generated FDC did not carry H-2 antigen of transferred lymphocytes from F1 mice. In SCID mice, in which normally no functional FDC are detectable, the microenvironments of the splenic white pulp have a capacity to develop and differentiate normally after transfer of lymphocytes. Apparently, the generation of functional IC-trapping FDC causes the induction of complement receptor(s) and Fc receptor on meshwork cells, which requires the presence of the lymphocytes. 相似文献