Autoantibodies in insulin-dependent diabetes recognize distinct cytoplasmic domains of the protein tyrosine phosphatase-like IA-2 autoantigen

Protein tyrosine phosphatase-like IA-2 is a major autoantigen in insulin-dependent diabetes. It has been identified as both a specificity of cytoplasmic islet cell Abs and one of the precursors of the 40- and 37-kDa tryptic fragment islet autoantigens. To characterize autoantibody binding to IA-2 and determine whether humoral autoimmunity extends to other tyrosine phosphatases, we analyzed serum reactivity in 100 patients with insulin-dependent diabetes against different in vitro translated portions of the IA-2 protein as well as the tyrosine phosphatase domains of HPTPbeta and HPTPdelta. All autoantibody reactivity was confined to the cytoplasmic portion of IA-2 (amino acids 601-979). At least four epitopes were found. These were contained within amino acids 605 to 620 and 605 to 682 of the juxtamembrane region and within amino acids 777 to 937 and 687 to 979 in the IA-2 tyrosine phosphatase-like domain. Footprinting studies confirmed the presence of multiple epitopes. Fifty-six percent of sera with IA-2 Abs bound epitopes within the juxtamembrane region, and 83% bound epitopes in the tyrosine phosphatase-like domain; 39% had Abs to both regions. No reactivity against the IA-2 ectodomain or the tyrosine phosphatase domains of HPTPbeta and HPTPdelta was found. These data suggest that the cytoplasmic region, in particular the tyrosine phosphatase-like domain, is the major target of IA-2 Abs in insulin-dependent diabetes, and that autoantibody reactivity is specific for IA-2 or IA-2-like molecules.     

Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party

To determine the incidence and outcome of hepatic veno-occlusive disease (VOD) after blood or marrow transplantation (BMT), we prospectively evaluated all consecutive patients receiving a BMT during a 6-month period in participating EBMT centers. All of them were evaluated for occurrence of VOD according to previously defined clinical criteria. The clinical course, outcome, value of prophylactic and therapeutic interventions, and the influence of previously described risk factors were analyzed. During the study period, 1,652 BMT were performed in 73 centers. VOD was diagnosed in 87 patients (5.3%; 95% confidence interval [CI], 4.2% to 6.4%). Fifty-six of 631 allogeneic BMT (8.9%) and 31 of 1,010 autologous BMT (3.1%) developed this complication (P <.0001). VOD was classified as mild in 7 (8%), moderate in 56 (64.4%), and severe in 24 (27.6%) cases. Sixteen patients died of VOD (corresponding to 1% of the whole series, 18.4% of VOD patients, and 66.7% of severe VOD). The use of unfractionated heparin did not significantly decrease the incidence of VOD. Independent variables associated with an increased risk of VOD were allogeneic BMT (relative risk [RR], 2.8; P <.001), pre-BMT elevation of serum aspartate aminotransferase (RR, 2.4; P =.001), high-dose cytoreductive therapy (RR, 2.3; P =.003), Karnofsky performance score less than 90% (RR, 2.7; P =.006), and prior abdominal radiation (RR, 2.9; P =.03). In conclusion, this prospective study shows that (1) the incidence of VOD is lower than that reported in smaller studies from single centers, (2) about one fourth of cases of VOD progress to severe disease, (3) main risk factors have a major impact on incidence of VOD, and (4) the use of prophylactic unfractionated heparin does not seem to reduce the incidence of VOD.     

Effect of diets containing different amounts of precursor and derivative fatty acids on serum TXB2

Dietary precursor and derivative polyunsaturated fatty acids influence metabolic parameters, such as eicosanoid synthesis. We have studied the effect of dietary intakes of lipids containing different amounts of precursor and derivative fatty acids (olive oil, olive-blackcurrant-fish oil mixture, blackcurrant-fish oil mixture, MCT (medium chain triglycerides)-soyabean oil mixture) on serum thromboxane B2 (TXB2) in four groups of rats. Plasma fatty acid composition showed differences related to dietary intakes. TXB2 levels were similar in all conditions except in the group receiving the mixture of olive-blackcurrant-fish oils which showed lower values.     

Unalloyed copper inclusions in ancient bronze artefacts

Ancient bronze artifacts, that represent a considerable part of the archeological finds, have been largely studied because of their complex degradation phenomena taking place in the long time span that have not been fully understood. One of the peculiar features of ancient bronzes is the presence of inclusions of copper unalloyed with tin. Unalloyed Copper Inclusions (UCI) have been observed in buried archaeological bronze artefacts by several authors, but each paper reports only on a limited number of cases. In our extensive studies on bronze artefacts, UCI have been observed in many bronze artefacts with very different features and purposes. Both as-cast and wrought artefacts were studied, so that the influence of the manufacturing process and the composition of the artefacts on the formation of UCI might be evaluated. The microstructure and composition of these artefacts were studied and the features of UCI have been related with those of the surrounding phases. The results have been discussed and compared with those obtained by other authors. The presence of UCI in buried archaeological bronze artefacts could indicate some unusual corrosion processes that might need to be accounted for when designing conservation treatments.     

一个急待开发的领域——建筑用铜管接头深加工

本文阐述了在建筑工程中用铜管取代白铁管作冷热水进水管的优越性,以及世界各国建筑业对铜管及其接头的需求不断增长的趋势,进而谈到铜管接头这一深加工制品在我国的发展前景和适宜的工艺方法。     

炼油化工企业蒸汽管网的数值模拟及分析

蒸汽管网系统是炼油及石化企业热、功集成的关键设施。本课题利用流体及电网络相似性原理建立蒸汽网络的数学模型，结合网络技术解决两相流体动力学以及网络系统的传热、散热问题。工程实践证明，该数学模型具有良好的数值稳定性和收敛性，可用来求解大规模的复杂管网系统问题。     

PKRD: a pharmacokinetic program for least-squares and bayesian analysis of repeated-dose pharmacokinetic curves.

A microcomputer program is presented which analyses multiple-dose pharmacokinetic curves using either a least-squares nonlinear analysis or a bayesian fit. The least-squares subroutine is designed to fit retrospective pharmacokinetic curves and can generate the so-called population pharmacokinetic parameters using the Standard Two-Stage method. The bayesian subroutine can instead be used prospectively to individualise the dosage regimen of a patient based on the concentrations measured in the initial phases of the drug treatment. All the pharmacokinetic subroutines of the program use the one-compartment model with either constant-rate intravenous infusion or oral route with zero-order absorption. The program was tested in a series of ten bone marrow transplantation patients treated with cyclosporine. The least-squares estimates of the one-compartment parameters, calculated by the program, were compared with those generated by the SIMKIN program.     

Effects of flour storage and heat generated during milling on starch,dietary fibre and polyphenols in stoneground flours from two durum‐type wheats

In the perspective of cereal‐based functional food development, the research compared stone watermill and stone mill which differed in the heating generated during grinding (30 and 60 °C) and the effects of storage on the preservation of phytochemicals. After 6‐month storage of flour, a decrease in soluble dietary fibre (loss of 1.9–2.5 g 100 g^?1) and bound polyphenols (loss of 6.2–8.5%) was observed, while other wheat grain components remained unvaried. Comparing the milling techniques, stoneground wheat grains (60 °C) showed the highest amylose (34.7–36.9% of total starch) and resistant starch amounts (0.85–1.16% of total starch), which could be of interest for lowering Glycaemic Index. Stoneground KAMUT^® starch had higher tendency to be converted into resistant starch and it also showed the higher degree of starch damage, as compared to the durum wheat variety Claudio. The study provided suggestions for modulating the production chain with the aim of supplying added value to wheat‐based products.     

四川电网黑启动恢复控制研究及试验(二)——频率、并网控制及二次设备配置

在四川某电网黑启动现场试验的基础上,对黑启动期间孤网系统的频率、并网控制及相应二次设备的调整进行了分析.在考虑发电机组一次调频及负荷频率调节效应的基础上,根据系统的运行方程推导出负荷恢复后的频率降落公式;同时,结合实际中二次设备的配置原则及保护动作原理对黑启动期间二次装置的适应性和电网的抗干扰性分别进行讨论,并从使其最有利于系统恢复的方面提出了相应的调整及配置原则.     

Effects of cyclosporin A on erythropoietin production by the human Hep3B hepatoma cell line

There is evidence that the inadequate erythropoietin (Epo) production observed in patients undergoing allogeneic bone marrow transplantation (BMT) might be ascribed to an inhibitory effect caused by the immunosuppressive drug cyclosporin A (CsA). In this in vitro study, we have evaluated the effects of CsA on the release of Epo in the culture medium by the human Hep3B hepatoma cell line. In cultures incubated with both CsA and the nonimmunosuppressive CsA analog MeAla-6, but not with the CsA-unrelated immunosuppressive agent FK-506, the levels of Epo in the medium were significantly reduced in comparison with controls, at concentrations (0.01 to 1.6 mumol/L) not affecting total protein synthetic rate nor the constitutive secretion of alpha-fetoprotein. Hep3B cells were found to contain a CsA-binding molecule, with an M(r) of 18 Kd, as assessed by high performance liquid chromatography (HPLC) and ligand-blotting analysis. CsA did not affect the expression of the Epo gene, as judged by Northern blot analysis, but caused a significant amount of Epo to remain unsecreted within the cells; almost all (97% of total) of the intracellular Epo was associated with the plasma membrane subcellular fraction. We conclude that: (1) CsA is able to inhibit Epo release in vitro by Hep3B cells, further supporting the hypothesis that the drug might have a role in the inappropriately low Epo levels observed in BMT patients; (2) the inhibitory effect appears to be specific and not caused by a general impairment of protein synthesis and/or secretion; and (3) the reduced Epo levels found in the medium of CsA-treated Hep3B cultures are supposed to be the consequence of an inability of the cells to correctly process Epo molecules for the secretory pathway.