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61.
T-gamma lymphoproliferative disease (T-gamma LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T- cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T-cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR alpha- and beta-chain genes in patients with T-gamma LPD, we cloned and sequenced TCR alpha- and beta-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common V alpha nor a common J alpha segment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the beta chain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common V alpha (V alpha 19.1). In contrast to this common V alpha usage, there was a marked diversity of the J alpha segments and N-region addition that were associated with the V alpha 19.1 segment. This pattern of common V alpha usage associated with different N and J alpha segments suggests an immune-mediated selection process affecting the TCR alpha chain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreactivity conferred by the selected TCR alpha chain and that this autoreactivity might be implicated in this patient's anemia. 相似文献
62.
C Pothoulakis U Galili I Castagliuolo CP Kelly S Nikulasson PK Dudeja TA Brasitus JT LaMont 《Gastroenterology》1996,110(6):1704-1712
BACKGROUND & AIMS: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans. Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. METHODS: Fluid secretion, [3H]-mannitol permeability, and release of rat mast cell protease II and prostaglandin E2 were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer. RESULTS: Toxin A (5 micrograms) and antigalactose (250 micrograms) but not control immunoglobulin (250 micrograms) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release. Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E2, but only toxin A produced acute inflammation of rat colonic mucosa. Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 10(-8) mol/L, respectively. CONCLUSIONS: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc. (Gastroenterology 1996 Jun;110(6):1704-12) 相似文献
63.
Homing receptors on human and rodent lymphocytes--evidence for a conserved carbohydrate-binding specificity 总被引:26,自引:0,他引:26
Lymphocyte recirculation begins with the attachment of circulating cells to the structurally distinctive postcapillary venules of lymphoid organs termed high-endothelial venules (HEVs). In both rodents and humans, the attachment of lymphocytes to the HEVs of peripheral lymph nodes (PNs) on the one hand and gut-associated lymphoid tissues (GALTs) on the other appears to involve discrete adhesive structures on the surfaces of the interacting cells. In rodents, we previously showed that a carbohydrate-binding receptor at the lymphocyte surface participates in the attachment to the HEV of peripheral nodes. The studies reported herein document the involvement of a similar receptor in the selective attachment of human peripheral blood lymphocytes to the HEVs of PNs. We argue that the close functional relationship between the human and rodent receptors indicates that this component of the adhesive interaction has been conserved through evolution. 相似文献
64.
Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria 总被引:2,自引:3,他引:2
Endo M; Ware RE; Vreeke TM; Singh SP; Howard TA; Tomita A; Holguin MH; Parker CJ 《Blood》1996,87(6):2546-2557
The purpose of these studies was to determine the molecular basis of the phenotypic mosaicism that is a defining feature of paroxysmal nocturnal hemoglobinuria (PNH). Analysis of T cell clones from a female patient revealed four distinct phenotypes based on surface expression of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). When PIG-A (the gene that is mutant in PNH) from these clones was analyzed, four discrete somatic mutations were identified. Analysis of X chromosomal inactivation among the abnormal T cell clones was consistent with polyclonality. Together, these studies demonstrate that the phenotypic mosaicism that is characteristic of PNH is a consequence of genotypic mosaicism and that, at least in this case, PNH is a polyclonal rather than a monoclonal disease. That four distinct somatic mutations were present in a single patient suggests that in conditions that predispose to PNH PIG-A may be hypermutable. 相似文献
65.
1G10, a monoclonal IgM antibody that identifies a differentiation antigen on human granulocytes and a subpopulation of monocytes, was found to react specifically with glycosphingolipids bearing the Gal beta 1-4(Fuc alpha 1-3)GlcNAc hapten (X determinant). This carbohydrate determinant was found on both glycolipid and glycoprotein molecules isolated from HL-60 cells (a promyelocytic leukemia cell line). Thus, this highly conserved carbohydrate-defined determinant previously described on mouse embryonic and mouse and human carcinoma cells is also expressed as a tissue-specific differentiation antigen on normal human granulocytes. 相似文献
66.
目的探讨电解剖系统指导在房性心律失常射频导管消融中的作用和优势。方法对25例心房颤动(阵发性15例、持续性10例)在电解剖系统指导下进行重建左心房后行线性消融,7例持续性房性心动过速(右心房性4例、左心房性3例)在电解剖系统指导下重建左/右心房标测激动顺序后行消融。结果25例心房颤动均完成预定的线性消融,其中14例阵发性者在窦性心律下电学隔离成功,10例持续性和1例阵发性者在心房颤动时电学隔离成功。7例持续性房性心动过速均在消融过程中转为窦性心律。电解剖系统指导下平均手术时间心房颤动为220min,房性心动过速为86min;平均X线透视时间心房颤动为48min,房性心动过速为20min。所有患者手术过程中均无并发症。结论在电解剖系统指引下,环肺静脉电隔离治疗心房颤动安全有效;有助于设计房性心动过速消融径线,缩短手术时间,提高成功率。 相似文献
67.
To determine whether cytomegalovirus (CMV) antigenemiaguided ganciclovir treatment may be as effective, may require less treatment, and thus may cause less marrow toxicity than ganciclovir administered at engraftment, 226 marrow transplant recipients were randomized at engraftment to receive placebo (antigenemia-ganciclovir group) or ganciclovir (ganciclovir group) until day 100 in a double-blind study. In patients with antigenemia of 3 or more positive cells in 2 slides and/or viremia, study drug was discontinued and ganciclovir was started for at least 3 weeks or until negative CMV antigenemia and resumed only if antigenemia recurred. More patients in the antigenemia-ganciclovir group developed CMV disease before day 100 after transplantation compared with the ganciclovir group (14% v 2.7%, P = .002). Of the 16 patients with CMV disease before day 100 in the antigenemia-ganciclovir group, 10 (8.8%) had disease before or during the first episode of antigenemia and 6 (5.3%) developed disease after discontinuation of ganciclovir. Untreated low-grade antigenemia progressed to CMV disease in 19% of patients with grade 3-4 compared with 0% of patients with grade 0-2 acute graft-versus-host disease (P = .04). There was no significant difference in CMV disease by day 180 after transplantation and thereafter. CMV-related death, transplant survival, and neutropenia were not significantly different between the groups. In the ganciclovir group, more invasive fungal infections occurred (P = .03) and more ganciclovir was used (P < .0001). Thus, delaying the start of ganciclovir until highgrade antigenemia and discontinuing ganciclovir based on negative antigenemia results in more CMV disease by day 100 than ganciclovir administered at engraftment. However, ganciclovir at engraftment is associated with more early invasive fungal infections and more late CMV disease resulting in similar survival rates. 相似文献
68.
69.
TZE‐FAN CHAO M.D. YENN‐JIANG LIN M.D. HSUAN‐MING TSAO M.D. SHIH‐LIN CHANG M.D. LI‐WEI LO M.D. YU‐FENG HU M.D. TA‐CHUAN TUAN M.D. CHENG‐HUNG LI M.D. HUNG‐YU CHANG M.D. TSU‐JUEY WU M.D. WEN‐CHUNG YU M.D. SHIH‐ANN CHEN M.D. 《Journal of cardiovascular electrophysiology》2013,24(4):375-380
Electromechanical Interval and Strokes After Ablations of AF . Introduction: Atrial fibrillation (AF) is associated with increased risk of embolic stroke. Catheter ablation of AF provides an effective therapy for patients with symptomatic and drug‐refractory AF. The aim of this study was to evaluate whether the atrial electromechanical interval is useful in identifying patients at risk of stroke after successful catheter ablation. Methods and Results: A total of 279 AF patients who received catheter ablation and showed no evidence of recurrences were enrolled. Electromechanical interval (PA–PDI) was determined as the time interval from the initiation of P wave deflection to the peak of mitral inflow A wave on pulse wave Doppler imaging. The PA–PDI interval was measured for each patient after the 3‐month blanking period of catheter ablation. The clinical endpoint was the occurrence of ischemic stroke. During the follow‐up of 46.5 ± 17.2 months, 6 patients suffered from ischemic strokes. Patients with strokes had higher CHA2DS2–VASc scores and longer PA–PDI intervals (138.7 ± 12.4 ms vs 161.2 ± 7.7 ms, P value < 0.001) compared to those without strokes. At a cutoff point of 150 ms identified by ROC curve, the positive and negative predictive values of the PA–PDI interval to predict stroke were 86.7% and 100%, respectively. The PA–PDI interval improved the predictive performance of the CHA2DS2–VASc score, and the area under the ROC curve increased from 0.75 to 0.85. Conclusions: Our results suggest that the PA–PDI interval is a useful tool to identify patients with high risk of stroke after successful catheter ablation of AF. (J Cardiovasc Electrophysiol, Vol. 24, pp. 375‐380, April 2013) 相似文献
70.
PCI-32765和Bortezomib对B细胞肿瘤细胞系细胞增殖、凋亡的影响及其机制的研究 总被引:1,自引:0,他引:1
本研究旨在探讨Btk抑制剂PCI-32765和蛋白酶体抑制剂bortezomib对Raji、Ramos细胞的增殖、凋亡的影响及其作用机制.PCI-32765和bortezomib单药及联合用药处理Raji和Ramos细胞后,分别运用CCK-8法及流式细胞术检测细胞的增殖与凋亡,Western blot法检测Btk、NFκB、c-IAP1、Bcl-xL、caspase-3等蛋白的表达.结果表明:①PCI-32765(0.5、1.0、2.0、3.0、4.0、5.0、6.0μmol/L)和bortezomib(10、20、30、40、50、60、80 nmol/L)处理Raji和Ramos细胞48 h,均可抑制细胞增殖,抑制率呈剂量依赖性,且两药具有协同作用;②PCI-32765(2.0μmol/L)、bortezomib(20 nmol/L)单药及联合用药处理Raji和Ramos细胞不同时间(8、12、24、36、48、72 h),均可抑制细胞存活率,抑制率呈时间依赖性,且两药具有协同作用;③PCI-32765(2μmol/L)和bortezomib(20 nmol/L)单药及联合用药处理Raji和Ramos细胞48 h,可明显促进Raji及Ramos细胞的凋亡.Raji细胞实验结果,空白对照组、PCI-32765和bonezomib单药组、联合用药组的细胞凋亡率分别为10.34±0.53%、24.26±0.91%、43.66±1.08%与74.06±0.72%,各组间有统计学差异(P<0.05);Ramos细胞实验结果,空白对照组、PCI-32765和bortezomib单药组、联合用药组的细胞凋亡率分别为15.16±1.49%、71.36±0.82%、75.32±2.36%与84.30±0.91%,各组间有统计学差异(P<0.05);④PCI-32765和bonezomib单药处理Raji、Ramos细胞后,细胞内Btk、NFκB、Bcl-xl及c-.IAP1的表达水平较对照组降低,Caspase-3的表达水平升高,两药联用后,作用增强.结论:PCI-32765和bonezomib可以协同抑制Raji与Ramos细胞的增殖,促进其凋亡,其机制可能与抑制Btk、NFκB的活性,下调Bcl-xl及c-IAP1等抗凋亡蛋白,同时上调Caspase-3等凋亡蛋白的表达而发挥作用. 相似文献