Host defense against infections and inflammations: Role of the multifunctional IL-6/IFN-β2 cytokine

Summary IL-6/IFN-2 appears to be one of the important mediators of the response to viral and bacterial infections and to shock. The biological effects now associated with IL-6/IFN-2 include: stimulation of immunoglobulin secretion by mature B lymphocytes (BSF-2 activity), growth stimulation of plasmacytomas and hybridomas (HGF activity), activation of T cells, stimulation of hepatic acute phase protein synthesis (HSF activity), stimulation of hematopoiesis, cell differentiation (DIF activity), inhibition of tumor cell growth (AP activity) and other IFN-like effects. As a typical cytokine, IL-6/IFN-2 is secreted by many cell types and acts in various combinations with other interleukins and interferons.     

热性惊厥儿童血液IL-6、IL-10和MMP-9表达的研究

目的 热性惊厥是儿童痫性发作最常见的形式.炎性细胞因子可能导致热性惊厥的发展.本研究探讨白介素-6(IL-6)、白介素-10(IL-100和金属蛋白酶-9(MMP-9)等炎性细胞因子在小儿热性惊厥中是否被激活以及其表达与原发性癫痫中的不同.方法 回顾性研究自2010年12月到2012年11月入院的相关病人资料.分热性惊厥组(N=43)、高热对照组(N=40)、原发性癫痫组(N=32)及正常儿童组(N=15).在惊厥发生的24h内收集病人血液.酶联免疫吸附试验(ELISA)进行IL-6、IL-10和MMP-9等细胞因子水平测定.结果 IL-6、IL-10和MMP-9在热性惊厥组的表达均高于原发性癫痫组(p＜0.05)和正常组(p＜0.05).IL-6与MMP-9在热性惊厥组的表达高于高热对照组,IL-10的表达在热性惊厥组与高热对照组之间无明显差异(P＞0.05).结论 IL-6、IL-10和MMP-9在热性惊厥儿童表达明显升高;炎性因子可能参与热性惊厥的病理过程,且其参与机制可能不同于其在原发性癫痫病理过程中的作用.     

Graves病患者IL-6、IL-10、IFN-γ水平的变化及临床意义

目的 通过检测GD患者外周血血清中IL-6、IL-10、IFN-γ三种细胞因子水平于治疗前后的变化及关系,探讨其与甲状腺功能变化的相关性及临床意义.方法 取GD患者共32例.缓解期患者组共33例为确诊的GD患者,接受系统抗甲状腺药物治疗,临床症状缓解,甲状腺功能恢复正常者定为缓解组.以上两组患者均无其它自身免疫性疾病和感染性疾病.另取正常健康人40倒.均无甲状腺疾病史及甲状腺疾病家族史定为正常对照组.取所有受试者静脉血测定FT3、FT4、TSH、TMAb、TGAb、IL-6、IL-10、IFN-γ值.结果 IL-6:GD组较缓解组显著增高(P<0.01),缓解组与对照组无明显差异(P>0.05)IL-10:GD组与缓解组较对照组显著增高(P<0.01),GD组与缓解组无明显差异(P>0.05)IFN-γ:GD组与缓解组较对照组显著增高(P<0.01),GD组与缓解组无明显差异.结论 IFN-γ可诱导甲状腺细胞Ⅱ型抗原的表达,进而增强这些细胞的免疫原性.IFN-γ单独或与TNF-α联合作用可促进甲状腺细胞表达胞间粘附分子Ⅱ(ICAM-Ⅱ)及HLA-Ⅱ类抗原.并且TNF-α可增强IFN-γ对TEC的MHC-Ⅱ分子抗原的高效表达,而表达的异常则可使自身免疫反应得以发生及进行性发展.随治疗过程的进展,IFN-γ仍处于较高水平.高于正常对照组,反映了免疫治疗过程的滞后性.     

NLRP3 inflammasome activation in macrophage cell lines by prion protein fibrils as the source of IL-1β and neuronal toxicity

Prion diseases are fatal transmissible neurodegenerative diseases, characterized by aggregation of the pathological form of prion protein, spongiform degeneration, and neuronal loss, and activation of astrocytes and microglia. Microglia can clear prion plaques, but on the other hand cause neuronal death via release of neurotoxic species. Elevated expression of the proinflammatory cytokine IL-1β has been observed in brains affected by several prion diseases, and IL-1R-deficiency significantly prolonged the onset of the neurodegeneration in mice. We show that microglial cells stimulated by prion protein (PrP) fibrils induced neuronal toxicity. Microglia and macrophages release IL-1β upon stimulation by PrP fibrils, which depends on the NLRP3 inflammasome. Activation of NLRP3 inflammasome by PrP fibrils requires depletion of intracellular K⁺, and requires phagocytosis of PrP fibrils and consecutive lysosome destabilization. Among the well-defined molecular forms of PrP, the strongest NLRP3 activation was observed by fibrils, followed by aggregates, while neither native monomeric nor oligomeric PrP were able to activate the NLRP3 inflammasome. Our results together with previous studies on IL-1R-deficient mice suggest the IL-1 signaling pathway as the perspective target for the therapy of prion disease.     

Correlation between serum dopamine-β-hydroxylase activity and dopamine-β-hydroxylase and tyrosine hydroxylase activities in central and peripheral adrenergic neurons and adrenal glands

Summary Serum dopamine--hydroxylase activity in spontaneously hypertensive rats and Wistar-Kyoto rats had a positive correlation with dopamine--hydroxylase and tyrosine hydroxylase activities in mesenteric vessels, vas deferens, and adrenal glands at 14–16 weeks of age, a negative correlation with dopamine--hydroxylase activity in locus coeruleus at 3 weeks and 14–16 weeks of age, and a positive correlation with tyrosine hydroxylase activity only at 3 weeks of age, but not at 14–16 weeks of age.     

Allozyme polymorphism and linkage disequilibrium ofAdh and α-Gpdh loci in wine cellar and field populations ofDrosophila melanogaster

Summary Over three years, theAdh and -Gpdh loci have been studied in two cellar populations ofDrosophila melanogaster and in two field populations which were each near to one of the cellars. Analyses of gene frequencies indicate that the divergence among subpopulations is greater in theAdh locus than in the -Gpdh locus. Selection for or againstAdh ^S allele acting on theIn(2L)t inversion influences of the -Gpdh alleles. This phenomenon may contribute to explain the maintenance of theAdh and -Gpdh polymorphism and of theIn(2L)t inversion.     

Human Genome and Diseases:¶Cellular and molecular aspects of Zellweger syndrome and other peroxisome biogenesis disorders

Peroxisomes are single-membrane-bound organelles present in virtually all eukaryotic cells. They are involved in numerous metabolic processes, both catabolic and anabolic, including β-oxidation of very long chain fatty acids, metabolism of hydrogen peroxide, plasmalogen biosynthesis and bile acid synthesis. In several genetic diseases, there is either isolated deficiency of a specific peroxisomal protein (single-protein deficiencies) or a defect in the formation of the organelle with loss of multiple peroxisomal functions (peroxisome biogenesis disorders). X-linked adrenoleukodystrophy is an example of the former, and the Zellweger spectrum of the latter. Peroxisome biogenesis disorders are inherited in an autosomal recessive manner and result from mutations in any of at least 12 PEX genes that encode peroxins. This article reviews the peroxisomal system, the clinical, biochemical and molecular aspects of peroxisomal disorders, and discusses recent scientific advances in the understanding of peroxisome biogenesis. Received 16 October 2001; received after revision 2 January 2002; accepted 3 January 2002     

Human Genome and Diseases:¶Double-strand breaks and translocations in cancer

The correct repair of double-strand breaks (DSBs) is essential for the genomic integrity of a cell, as inappropriate repair can lead to chromosomal rearrangements such as translocations. In many hematologic cancers and sarcomas, translocations are the etiological factor in tumorigenesis, resulting in either the deregulation of a proto-oncogene or the expression of a fusion protein with transforming properties. Mammalian cells are able to repair DSBs by pathways involving homologous recombination and nonhomologous end-joining. The analysis of translocation breakpoints in a number of cancers and the development of model translocation systems are beginning to shed light on specific DSB repair pathway(s) responsible for the improper repair of broken chromosomes. Received 19 June 2001; received after revision 6 September 2001; accepted 11 September 2001     

Can consumer sentiment and its components forecast Australian GDP and consumption?

This paper examines whether the disaggregation of consumer sentiment data into its sub‐components improves the real‐time capacity to forecast GDP and consumption. A Bayesian error correction approach augmented with the consumer sentiment index and permutations of the consumer sentiment sub‐indices is used to evaluate forecasting power. The forecasts are benchmarked against both composite forecasts and forecasts from standard error correction models. Using Australian data, we find that consumer sentiment data increase the accuracy of GDP and consumption forecasts, with certain components of consumer sentiment consistently providing better forecasts than aggregate consumer sentiment data. Copyright © 2009 John Wiley & Sons, Ltd.     

α- andβ-Guttiferins

Zusammenfassung Die Isolierung, Charakterisierung und antibiotischen Eigenschaften von-Guttiferin (I), C₃₃H₃₈O₈ (Smp. 113–115°), aus den Samenhülsen und vom nahe verwandten-Guttiferin (II), C₂₉H₃₆O₆ oder C_33–34H_38–40O₈ (Smp. 86–91°) (möglicherweise identisch mit-Gambogasäure), aus Gummigutt, dem harzigen Sekret vonGarcinia morella, wurden beschrieben und ihre Verwandtschaft zu Morellin und Moreollin, den beiden bekannten Pigmenten der Samenhülsen, dargelegt. Für I wurde eine Partialstruktur vorgeschlagen. Die Bildung derselben komplexen bromhaltigen Säure vom Smp. 199 bis 200° unter der Einwirkung von Natriumhypobromit auf I und II spricht ferner für deren nahe strukturelle Verwandtschaft.     

Serglycin – Structure and biology

Serglycin is a proteoglycan found in hematopoietic cells and endothelial cells. It has important functions related to formation of several types of storage granules. In connective tissue mast cells the covalently attached glycosaminoglycan is heparin, whereas mucosal mast cells and activated macrophages contain oversulfated chondroitin sulfate (type E). In mast cells, serglycin interact with histamine, chymase, tryptase and carboxypeptidase, in neutrophils with elastase, in cytotoxic T cells with granzyme B, in endothelial cells with tissue-type plasminogen activator and in macrophages with tumor necrosis factor-α. Serglycin is important for the retention of key inflammatory mediators inside storage granules and secretory vesicles. Serglycin can further modulate the activities of partner molecules in different ways after secretion from activated immune cells, through protection, transport, activation and interactions with substrates or target cells. Serglycin is a proteoglycan with important roles in inflammatory reactions. Received 2 October 2007; received after revision 7 November 2007; accepted 12 November 2007     

α-Actinin structure and regulation

Alpha-actinin is a cytoskeletal actin-binding protein and a member of the spectrin superfamily, which comprises spectrin, dystrophin and their homologues and isoforms. It forms an anti-parallel rod-shaped dimer with one actin-binding domain at each end of the rod and bundles actin filaments in multiple cell-type and cytoskeleton frameworks. In non-muscle cells, alpha-actinin is found along the actin filaments and in adhesion sites. In striated, cardiac and smooth muscle cells, it is localized at the Z-disk and analogous dense bodies, where it forms a lattice-like structure and stabilizes the muscle contractile apparatus. Besides binding to actin filaments alpha-actinin associates with a number of cytoskeletal and signaling molecules, cytoplasmic domains of transmembrane receptors and ion channels, rendering it important structural and regulatory roles in cytoskeleton organization and muscle contraction. This review reports on the current knowledge on structure and regulation of alpha-actinin.     

Synthesis and some pharmacological properties of α-methyltryptamine and its 5-methoxy derivative

Résumé L'-méthyltryptamine et le 5-méthoxy dérivé ont été synthétisés en utilisant une variante de la méthode d'Abramovitch etShapiro.Des expériencesin vitro ont montré que ces deux amines ne subissent pas de désamination par la monoaminoxydase du cerveau des rats blancs. La 5-méthoxy--methyltryptamine injectée aux souris blanches en dose de 10 mg/kg semble accroître l'activité de la monoaminoxydase du cerveau.     

Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation

Ablation of tetraspanin protein TSPAN12 from human MDA-MB-231 cells significantly decreased primary tumor xenograft growth, while increasing tumor apoptosis. Furthermore, TSPAN12 removal markedly enhanced tumor-endothelial interactions and increased metastasis to mouse lungs. TSPAN12 removal from human MDA-MB-231 cells also caused diminished association between FZD4 (a key canonical Wnt pathway receptor) and its co-receptor LRP5. The result likely explains substantially enhanced proteosomal degradation of β-catenin, a key effecter of canonical Wnt signaling. Consistent with disrupted canonical Wnt signaling, TSPAN12 ablation altered expression of LRP5, Naked 1 and 2, DVL2, DVL3, Axin 1, and GSKβ3 proteins. TSPAN12 ablation also altered expression of several genes regulated by β-catenin (e.g. CCNA1, CCNE2, WISP1, ID4, SFN, ME1) that may help to explain altered tumor growth and metastasis. In conclusion, these results provide the first evidence for TSPAN12 playing a role in supporting primary tumor growth and suppressing metastasis. TSPAN12 appears to function by stabilizing FZD4–LRP5 association, in support of canonical Wnt-pathway signaling, leading to enhanced β-catenin expression and function.     

川芎嗪对IL-1β诱导的兔原代软骨细胞增殖和凋亡影响

目的 观察川芎嗪对白细胞介素-1β诱导的软骨细胞的增殖及凋亡的影响.方法 兔原代软骨细胞培养及鉴定,用IL-1β10ng/ml和/或不同浓度川芎嗪共培养兔原代软骨细胞48h后,利用流式细胞仪检测各组软骨细胞的周期及凋亡率;利用MTT法检测软骨细胞的生长状态.结果 与对照组比较,IL-1β诱导下软骨细胞的凋亡率显著增加,差异具有显著统计学意义(P＜0.01);加入川芎嗪能明显降低IL-1β诱导的软骨细胞凋亡率,有显著统计学意义(P＜0.01);与对照组比较,IL-1β诱导下软骨细胞被明显阻滞在G1期(P＜0.01);加入川芎嗪能明显降低IL-1β对软骨细胞G1期的阻滞作用,细胞增殖指数明显增加(P＜0.05或P＜0.01).结论 川芎嗪对IL-1β诱导的兔原代软骨细胞抑制凋亡并促进生长.     

C16-methyl derivatives of progesterone and 17α-acetoxyprogesterone: Preparation and biological activities

Zusammenfassung Mehrere Derivate des 16-Methyl-progesteron wurden synthetisiert und biologisch geprüft. Die Einführung einer C16-Methylgruppe ergab keine gesteigerte Progesteronaktivität in den getesteten Verbindungen.