Recognition of the Qa-2k tumor antigen by T cell receptor γ/δ of an immunopotentiator-induced tumoricidal T cell of mice

Tumor-specific expression of Qa-2^k antigen coded by the Q5^k gene on various mouse tumor cells and immunological response of the host mice to the antigen have been demonstrated [Seo et al. (1992) J Exp Med 175: 547; Tanino et al. (1992) Cancer Immunol Immunother 35: 230]. The possibility was examined that Qa-2 antigen is one of the recognition target molecules of immunopotentiator-induced, H-2-nonrestricted tumoricidal lymphocytes of Qa-2^– mice. Lymphocytes stimulated in vivo withP. acnes or culture-induced anomalous killers of B6.K1 mice did not exhibit significant in vitro cytotoxicity against B6.K1 lymphoblasts but lysed their Qa-2,3-congenic counterpart B6 lymphoblasts. To demonstrate the Qa-2 specificity of such cytotoxic cells more precisely, an L cell transformant clone (L^Q7b/Kb), which expressed the 1 and 2 domains of the Qa-2 antigen (Q7^b gene product), was generated by transfecting a cloned plasmid DNA containing a hybrid gene constructed from the 5 half of the Q7^b gene and the 3 half of the H-2K^b gene (pQ7^b/K^b). Using L^Q7b/Kb cells as the target cells and the nylon-wool-nonadherent fraction of lymphocytes fromP. acnes-stimulated (C3H/He × B6.K1)F1 mice (H-2^k, Qa-2^–) as the effector cells of the in vitro cytotoxicity reaction, the presence of cytotoxic cells that recognize the 1/2 region of the Q7^b gene product was demonstrated. The cytotoxic activity was dependent on T cells bearing T cell receptors of the / type (TCR/). The (C3H/He × B6.K1)F1 effector cells, as well as the B6.K1 effector cells also lysed BW5147 lymphoma cells (Qa-2^k+) derived from AKR mice (Qa-2^–, H-2^k). By target-competition experiments it was shown that some of the effector cells lytic to BW5147 were identical to those that lysed L^Q7b/Kb. Therefore some of the tumoricidal cells induced by the immunopotentiator interact with the target tumor cells through recognition of the 1/2 region of the Qa-2^k tumor antigen by TCR/.     

Antiviral Activity of 1-β-D-Arabinofuranosyl-E-5-(2-Bromovinyl)Uracil against Thymidine Kinase Negative Strains of Varicella-Zoster Virus

Mechanism of antiviral activity of 1-β-d -arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) against the YSR strain of varicella-zoster virus (VZV), which is a mutant derived from the wild YS strain and is completely deficient in viral thymidine kinase (TK), was searched in comparison with antiviral activity of other thymidine analogues, guanosine analogue and thymidylate synthase (TS) inhibitor in human embryo lung fibroblast cells. Thymidine analogues, such as BV-araU, 5-iododeoxyuridine (IUDR), 1-β-d -arabinofuranosylthymine (araT), and guanosine analogue, such as 9-(2-hydroxyethoxymethyl)guanine (ACV), showed higher antiviral activity to the YS strain than to the YSR strain. Though, BV-araU also had the antiviral activity of a microgram level against the YSR strain. In contrast to these results, TS inhibitor, 5-fluorodeoxyuridine (FUDR), had higher antiviral activity to the YSR strain than to the YS strain. Highly synergistic antiviral activities of FUDR to the YS strain and the YSR strain were observed in combination with IUDR, araT, or ACV. However, weakly synergistic or additive inhibition to the YSR strain was shown in combination of BV-araU and FUDR, in spite of highly synergistic effect of this combination to the YS strain. The viral and cellular TS activity was partially inhibited by BV-araU monophosphate, but not by BV-araU. These results indicate that BV-araU is converted into BV-araU monophosphate by cellular TK, and the inhibition of TS activity by BV-araU monophosphate in the YSR strain-infected cells results in the suppression of viral replication.     

Release of Prostaglandin E2 by Human Mononuclear Cells Exposed to Heat-Killed Salmonella typhi

Human mononuclear cells pre-labeled with [³H]arachidonic acid were shown to release metabolites following in vitro addition of heat-killed Salmonella typhi (HKST). The amount of label released was significantly higher than that seen with live S. typhi (LST). Addition of increasing amounts of HKST resulted in an increased release of metabolites. Enzyme immunoassay of the culture supernatants revealed that the bulk of the metabolite released was prostaglandin E₂ (PGE₂). Leukotriene B₄ (LTB₄) and leukotriene C₄ (LTC₄) were not detectable in the culture supernatants. The significance and implications of these results are discussed.     

Cloning and Sequencing of Two New Verotoxin 2 Variant Genes of Escherichia coli Isolated from Cases of Human and Bovine Diarrhea

We cloned and sequenced two new Verotoxin 2 (VT2) variant genes: one from an Escherichia coli strain from a case of bovine diarrhea and the other from an E. coli strain from a patient with diarrhea. The nucleotide and amino acid sequences of these two genes were highly homologous with, but distinct from those of the VT2, VT2vha, VT2vhb, SLT-IIv (VT2vp1) and SLT-IIva (VT2vp2) genes. Their nucleotide sequences were much more closely homologous to that of VT2vh than to that of VT2vp. Search for these two new genes in other Verocytotoxin-producing E. coli strains resulted in the isolation of 2 strains carrying one of the new VT2 variant genes, one strain from Tokyo and the other from Canada.     

基于肠道微生态改善的益生菌抗糖尿病作用机制研究进展

2型糖尿病(type 2 diabetes, T2D)会引起糖脂代谢紊乱,严重危害人类健康,为了防治这一流行病,急需寻找安全和无副作用的抗糖尿病的方法,其中,基于微生物方法治疗T2D最常见的策略是补充益生菌,其可通过对不同组织和代谢通路的调节来实现抗糖尿病的功效。益生菌摄入可通过降低慢性低度炎症,减少氧化应激,调节肠道菌群,增加短链脂肪酸含量来达到调控血糖的目的;通过增加胆固醇与胆盐的共沉淀作用,胆固醇在胃肠道内转化为粪甾醇,降低肝脏中3-羟基-3-甲基戊二酸单酰辅酶A还原酶活性,降低胆固醇转运体的表达及对脂肪细胞的调节来达到降脂的目的。本综述系统总结了益生菌抗糖尿病现状和基于肠道微生态的抗糖尿病分子机制,以期为益生菌作为降糖降脂等保健产品的开发利用提供理论依据。     

脉叶罗汉松化学成分的研究

从脉叶罗汉松(Podocarpus neriifolius D.Don)的枝叶中分离到11种化合物,根据光谱数据和物理常数测定,分别鉴定为正三十四烷醇(1)、β-谷甾醇硬脂酸酯(2)、β-谷甾醇(3)、金松双黄酮(sciadopitysin,3)、罗汉松双黄酮 B(podocarpusflavone B,12)、罗波斯塔黄酮-7″-甲醚(robustaflavone-7″-methyl ether,13)罗汉松双黄酮 A(podocarpusflaveone A,14)、罗波斯塔黄酮(robustaflavone,15)、对羟基苯甲酸(p-hydroxyl-benzoic acid,16)、2″-O-鼠李糖扫帚黄甙(2″-O-rhamnosylscoparin,23)和2″-O-鼠李糖牡荆黄甙(2″-O-rhamnosylvitexin,24)。其中,化合物23和24为首次从罗汉松科分得的化合物,化合物8、13和15首次从该植物分离到。     

Induction of high polyploidy in Phaseolus cell cultures by the protein kinase inhibitor,K-252a

Summary Somatic polyploidy of species-specific and tissue-specific degrees occurs in almost all plant species studied so far, but nearly nothing is known about the control mechanisms switching the mitotic cycle to an endoreduplication cycle. In order to search for a possible role of the cdc2 kinase, cell suspension cultures of the Runner bean, Phaseolus coccineus (Leguminosae) were treated with K-252a, an inhibitor of protein kinase activity. The treatment resulted in continuous cell cycles without mitosis, and hence induced polyploidy levels up to 2048C. It is, therefore, suggested that phosphorylation of a protein kinase, probably of the cell cycle-important p34^cdc2 type, is involved in the control of endoreduplication.     

氯化镧对玉米根切段钾离子外渗影响的动力学研究

研究了氯化镧对玉米(Zea mays L.)“京早8号”根切段细胞膜透性及质子分泌的影响,并用动力学方法研究了钾离子外渗过程的变化。氯化镧处理可降低外渗液的电导率及K~ 和糖的外渗量,使质子分泌活动增强。用动力学方法分析玉米根切段K~ 外渗过程的结果表明:(1)应用于K~ 吸收研究的数学模型也能适应于K~ 外渗的研究;(2)在LaCl_3和(或)CaCl_2存在的条件下,最大吸收速度(V_(max))升高,而米氏常数(K_m)没有变化;(3)在LaCl_3和(或)CaCl_2存在的条件下,K~ 外渗量降低是由于最大吸收速度(V_(max))升高所致。     

Lysozyme as a regulator of interleukin-2-activated lymphocyte proliferation

Summary Lysozyme at 1 to 100μg/ml of exposure levels augmented or inhibited proliferative response of human peripheral blood lymphocytes stimulated with interleukin-2 (IL-2). This contradictory effect of lysozyme depended on IL-2 concentration, activating state of lymphocytes, addition time of lysozyme, and serum existence. Lymphocytes increased their IL-2-mediated proliferating ability in response to lysozyme when stimulated with less than suboptimal concentration of IL-2. Lymphocyte activation with anti-CD3 antibody changed the augmented proliferative response into the inhibited response by lysozyme addition whereas elimination of MHC class II molecule-expressing cells augmented the response. Addition of lysozyme within 1 h after IL-2 exposure was most effective in promoting the proliferation whereas additions after 16 to 24 h were ineffective or inhibitory. Addition after longer than 24 h inversely restored the proliferative response. Serum seemed to retard lysozyme action because either sequential serum addition 1 h after exposure of IL-2 and lysozyme to cells or exposure of IL-2 and serum after pretreatment of cells with lysozyme changed the proliferative responsiveness from inhibition into augmentation. Thus lysozyme may regulate lymphocyte proliferation responding to a magnitude of antigenic stimuli and to the progression of cellular events that periodically occur.