Interleukin-2 inhibits graft-versus-host disease-promoting activity of CD4+ cells while preserving CD4- and CD8-mediated graft-versus-leukemia effects

We have recently shown that a short course of high-dose interleukin-2 (IL-2) can markedly inhibit the graft-versus-host disease (GVHD)-promoting activity of donor CD4+ T cells. The difficulty in dissociating GVHD-promoting from graft-versus-leukemia (GVL) effects of alloreactive donor T cells currently prevents clinical bone marrow transplantation (BMT) from fulfilling its full potential. To test the capacity of IL-2 treatment to promote such a dissociation, we have developed a new murine transplantable acute myelogenous leukemia model using a class II major histocompatibility complex-positive BALB/c Moloney murine leukemia virus-induced promonocytic leukemia, 2B-4-2. BALB/c mice receiving 2.5 x 10(5) 2B-4-2 cells intravenously 1 week before irradiation and syngeneic BMT died from leukemia within 2 to 4 weeks after BMT. Administration of syngeneic spleen cells and/or a 2.5-day course of IL-2 treatment alone did not inhibit leukemic mortality. In contrast, administration of non-T-cell-depleted fully allogeneic B10 (H-2b) spleen cells and T-cell-depleted B10 marrow led to a significant delay in leukemic mortality in IL-2-treated mice. In these animals GVHD was inhibited by IL-2 treatment. GVL effects were mediated entirely by donor CD4+ and CD8+ T cells. Remarkably, IL-2 administration did not diminish the magnitude of the GVL effect of either T-cell subset. This was surprising, because CD4-mediated GVHD was inhibited in the same animals in which CD4-mediated GVL effects were not reduced by IL-2 treatment. These results suggest a novel mechanism by which GVHD and GVL effects of a single unprimed alloreactive T-cell subset can be dissociated; different CD4 activities promote GVHD and GVL effects, and the former, but not the latter activities are inhibited by treatment with IL-2.     

Interaction of the second binding region of troponin I with the regulatory domain of skeletal muscle troponin C as determined by NMR spectroscopy

Two dimensional 1H,15N-heteronuclear single quantum correlation NMR was used to monitor the resonance frequency changes of the backbone amide groups belonging to the 15N-labeled regulatory domain of calcium saturated troponin C (N-TnC) upon addition of synthetic skeletal N-acetyl-troponin I 115-131-amide peptide (TnI115-131). Utilizing the change in amide chemical shifts, the dissociation constant for 1:1 binding of TnI115-131 to N-TnC in low salt and 100 mM KCl samples was determined to be 28 +/- 4 and 24 +/- 4 microM, respectively. The off rate of TnI115-131 was determined to be 300 s-1 from observed N-TnC backbone amide 1H,15N-heteronuclear single quantum correlation cross-peak line widths, which is on the order of the calcium off rates (Li, M. X., Gagné, S. M., Tsuda, S., Kay, C. M., Smillie, L. B., and Sykes, B. D. (1995) Biochemistry 34, 8330-8340), and agrees with kinetic expectations for biological regulation of muscle contraction. The TnI115-131 binding site on N-TnC was determined by mapping of chemical shift changes onto the N-TnC NMR structure and was demonstrated to be in the "hydrophobic pocket" (Gagné, S. M., Tsuda, S., Li, M. X., Smillie, L. B., and Sykes, B. D. (1995) Nat. Struct. Biol. 2, 784-789).     

Single nucleotide polymorphisms (SNPs) in key cytokines may modulate food allergy phenotypes

Single nucleotide polymorphisms (SNPs) can play a direct or indirect role in phenotypic expression in food allergy pathogenesis. Our goal was to quantitate the expression of SNPs in relevant cytokines that were expressed in food allergic patients. SNPs in cytokine genes IL-4 and IL-10 are known to be important in IgE generation and regulation. We examined IL-4 (C-590T), IL-4Rα (1652A/G) and IL-10 (C-627A) SNPs using real-time PCR followed by restriction fragment length polymorphism (RFLP) analysis. Our results show that the AA, AG and GG genotypes for IL-4Rα (1652A/G) polymorphisms were statistically different in radioallergosorbent test (RAST) positive versus negative patients, and although no statistically significant differences were observed between genotypes in the IL-4 (C-590T) and IL-10 (C-627A) SNPs, we observed a significant decrease in IL-4 (C-590T) gene expression and increase in IL-4Rα (1652A/G) and IL-10 (C-627A) gene expression between RAST⁺ versus RAST^? patients, respectively. We also observed significant modulation in the protein expression of IL-4 and IL-10 in the serum samples of the RAST⁺ patients as compared to the RAST^? patients indicating that changes in SNP expression resulted in altered phenotypic response in these patients.     

Degradation of organic coatings in a corrosive environment: a study by scanning Kelvin probe and scanning acoustic microscope

Degradation of pigmented epoxy coatings on a steel substrate during exposure to aerated 3% NaCl solution has been investigated using the scanning Kelvin probe (SKP) and scanning acoustic microscopy (SAM). A method for processing SKP potential maps has been used to visualize the distribution of anodic and cathodic current. It was observed that rust deposited at the defects, or later beneath the coating, acted as a cathodic reactant, leading to development of new anodes beneath the coating. Exposure of rusty samples to moist air (rather than salt solution) during SKP mapping is shown to lead to more noble potentials at the defect that influence the electrochemistry of under-film processes.     

NMR study of the differential contributions of residues of transforming growth factor alpha to association with its receptor

A heteronuclear NMR study of human transforming growth factoralpha (TGF     

Value of Monod's Affinity Constant in Activated Sludge

In mixed species, mixed substrate cultures represented by aggregate variables such as biochemical oxygen demand, chemical oxygen demand, or volatile suspended solids, the magnitude of Monod's affinity constant Ks is an indicator of the number of species and substrates present.     

Kinetics of drying apple slices

The process of drying apple tissue under most conditions may be divided into two main periods viz primary and secondary falling-rate periods. For most drying conditions the secondary falling-rate period is longer and has the greater influence on the overall rate. When the drying capacity of the air is very low an initial constant-rate period may occur. The drying rate constant varies with temperature with an Arrhenius-type relationship and the available evidence suggests that temperature-induced changes in the rate may be caused by vapor pressure changes Air velocity and relative humidity have their greatest influence in the early part of the drying process Towards the end of drying, internal resistance to water movement becomes rate-controlling, and external factors have little influence. An explanation of the observed drying characteristics of apple tissue in terms of the diffusion of water vapour through a ‘skin’ of dried cells is suggested.     

趋势和发展——全球印刷业面临的形势

这次会议正好赶上全球经济危机.自今年9月以来,全球主要国家的银行业均受到重挫,证券市场跌到一个从未有过的低位.货币也受到负面的影响.各国政府不得不拯救一些大的金融机构,而其他没有得到救济的机构则面临倒闭的窘境.2008年10月24日,道琼斯工业指数相对2007年10月9日的历史最高点已经下降了40.9%,标准普尔500指数下跌了44%,纳斯达克技术板块指数下降了45.7%.这是市值的极度缩水.