Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria

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.     

Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study

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.     

A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

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)     

Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2

Human T-cell lymphotropic virus I (HTLV-I)-induced adult T-cell leukemia (ATL) cells constitutively express interleukin-2 (IL-2) receptors identified by the anti-Tac monoclonal antibody (MoAb), whereas normal resting cells do not. This observation provided the scientific basis for a trial of intravenous anti-Tac in the treatment of nine patients with ATL. The patients did not suffer untoward reactions and did not have a reduction in the normal formed elements of the blood, and only one of the nine produced antibodies to the anti-Tac MoAb. Three patients had transient mixed, partial, or complete remissions lasting from 1 to more than 8 months after anti-Tac therapy, as assessed by routine hematologic tests, immunofluorescence analysis of circulating cells, and molecular genetic analysis of HTLV-I provirus integration and of the T-cell receptor gene rearrangement. The precise mechanism of the antitumor effects is unclear; however, the use of a MoAb that prevents the interaction of IL-2 with its receptor on ATL cells provides a rational approach for the treatment of this malignancy.     

骨质疏松症中医体质与辨证分型的相关性研究——附300例临床分析

目的 探讨骨质疏松症中医体质与辨证分型之间的相关性。方法 按照中西医诊断标准,将确诊的骨质疏松症患者进行中医体质分类与中医辨证分型的临床研究,找出其相关性与规律性,并进行总结。 结果 对300例患者进行中医辨证分型发现脾胃气虚证最多,占总病例数的23.00%,其次为肝肾不足证,占22.00%,以后依次为肾阳虚证、肾阴虚证、气血不足证、血瘀证、骨痿证、肝气郁结证、痰湿证、湿热证;在9种体质分类中阴虚质发病率排在第一位,其次为气虚质,以后依次为阳虚质、血瘀质、特禀质、平和质、痰湿质、湿热质与气郁质。结论 提示9种中医体质中阴虚质与气虚质发病率较高, 辨证分型中发病率较高的2个证型是脾胃气虚型与肝肾阴虚型。说明了体质类型与OP发病率有密切的相关性。     

17-β雌二醇对不同月龄大鼠成骨细胞雌激素受体β表达的影响

目的探讨17-β雌二醇对不同月龄大鼠成骨细胞雌激素受体β（ERβ）表达的影响。方法雌性大鼠颅盖骨经多次酶消化、反复贴壁法分离纯化培养得到大量纯净成骨细胞并进行形态学检查和碱性磷酸酶（ALP）染色;免疫组化法（SABC）进行雌激素受体染色;用10-8mol/L17-β雌二醇处理培养的成骨细胞,SDS-PAGE电泳和western blot法检测雌激素受体。结果成骨细胞碱性磷酸酶染色阳性率为90%以上。形态学检查符合成骨细胞的特征。免疫组化染色显示大鼠的成骨细胞存在雌激素受体β,且位于胞核内。Western blot结果表明,与对照组相比,处理组的各月龄大鼠雌激素受体β表达均有上调。结论17-β雌二醇能提高各月龄组大鼠成骨细胞雌激素受体β表达水平,不同月龄间上调水平不同,以4、8月龄组最为显著。     

EFFECTS OF IMPLEMENTATION OF 18 CLINICAL PATHWAYS ON COSTS AND QUALITY OF CARE AMONG PATIENTS UNDERGOING UROLOGICAL SURGERY

PURPOSE: We evaluated the effects on the costs and quality of care of implementation of 18 clinical pathways for urological operations. MATERIALS AND METHODS: From April 1997 to March 1998 patients undergoing 1 of 18 urological operations were treated according to clinical pathways. The outcomes in terms of length of hospital stay and admission charges of these patients were compared with those of patients treated between April 1996 and March 1997 before clinical pathways were implemented. We also selected 7 clinically relevant quality indicators to assess the quality of care before and after clinical pathway implementation. RESULTS: Of the 1,784 patients undergoing urological surgery from April 1997 to March 1998, 1,382 (77.5%) were treated according to 1 of the 18 clinical pathways. Before implementation 1,279 of 1,615 patients (79.2%) underwent these procedures. The length of hospital stay decreased from 5.5 to 4.9 days (p < 0.01) and the average hospital admission charges decreased by 12.9% (p < 0.01) after implementation. Five of the quality indicators, including the rate of surgical complications, were significantly improved after pathway implementation. The hospitalization rate was not affected (1.3 before versus 0.8% after implementation, p = 0.18). Variations from the clinical pathways occurred in 543 cases (39.3%) and affected the length of hospital stay only (11.6%) or the admission charge only (12.9%) more often than both (7.8%, p < 0.01) or neither (7.0%, p < 0.01). The most common variances in these patients were patient related (30.8%). CONCLUSIONS: Implementation of multiple clinical pathways in a urology department can improve urological practice by decreasing the length of hospital stay, admission charges and rate of surgical complications, and by improving the quality of care.     

小牛血去蛋白提取物对胃溃疡患者的疗效评价

目的：探讨小牛血去蛋白提取物(DCBE)对胃溃疡的治疗作用。方法：选择年龄20～70岁之间，经胃镜检查确诊为活动期胃溃疡的住院患60例。治疗组32例采用静脉滴注DCBE(800mg，qd)和法莫替丁(100mg,bid)治疗；对照组28例采用静脉滴注法莫替丁(100mg，bid)单独治疗。用药2、4wk行胃镜检查，观察自觉缓解症状、时间、愈合率和总有效率。结果：治疗组自觉症状缓解时间明显缩短；给药后2、4wk治疗组及对照组胃镜检查溃疡愈合率分别为78.1％，46.4％及84.4％，71.4％。结论：DCBE能显促进胃溃疡的愈合。