微泵输注氟尿嘧啶结合生长抑素治疗壶腹部周围癌

目的 :生长抑素 (SS)结合氟尿嘧啶 (5 - Fu)治疗晚期壶腹部周围癌的疗效评价。方法 :2 8例晚期壶腹部周围癌患者均采用静脉插管及随身携带微型输注泵 ,SS/ 5 - Fu持续静脉滴注 (civ法 )。结果 :经 2周期治疗后 ,临床症状缓解 (DRSI)为 89.3% (2 5 / 2 8) ;肿瘤完全缓解 (CR)占 3.7% ,部分缓解 (PR) ,占 2 8.6 % ,稳定 (NC)占 4 6 .4 % ,有效率为 32 .1%。结论 :SS/ 5 - Fu化学治疗效果稳定 ,毒副作用轻微 ,是治疗晚期壶腹部周围癌的有效手段之一。     

A comparative study of the proteolytic enzymes of Trypanosoma brucei, T. equiperdum, T. evansi, T. vivax, Leishmania tarentolae and Crithidia fasciculata

Four types of proteolytic activity were detected in the bloodstream form of each of the four Trypanosoma species: (i) HPAase, active on hide powder azure and detected on polyacrylamide gels containing denatured haemoglobin; (ii) AZCase, active on azocasein; (iii) type 1, active on the chromogenic peptide N-benzoyl-L-prolyl-L-phenylalanyl-L-arginine p-nitroanilide in the presence of dithiothreitol, and (iv) type 2, active against several nitroanilide derivatives in the absence of dithiothreitol. Studies of the pH optimum, dithiothreitol requirement and inhibitor sensitivities of the proteolytic activities suggested that: (a) HPAase and type 1 activities could be due to the same enzymes, probably a family of cysteine proteinases; (b) AZCase had some characteristics of a cysteine proteinase, but was not identical to HPAase, and (c) type 2 activity could be due to a serine proteinase. Procyclic T. brucei contained relatively low cysteine proteinase activities (HPAase, AZCase and type 1) but high type 2 activity. Their proteolytic enzymes thus were apparently more similar to those in Crithidia fasciculata and Leishmania tarentolae promastigotes than those in T. brucei bloodstream forms.     

Association of stress proteins with autoantigens: a possible mechanism for triggering autoimmunity?

Patterns of autoantibody production are diagnostic of many autoimmune disorders; the recent observation of additional autospecificities towards stress-induced proteins may also provide insight into the mechanisms by which such responses arise. Grp78 (also known as BiP) is a target of autoaggressive B and T cell responses in our murine model of anti-Ro (SS-A) autoimmunity and also in rheumatoid arthritis. In this report we demonstrate reciprocal intermolecular spreading occurs between Ro52 and Grp78 in immunized mice, reflecting physiological association of these molecules in vivo. Moreover, we provide direct biochemical evidence that Grp78 associates with the clinically relevant autoantigen, Ro52 (SS-A). Due to the discrete compartmentalization of Ro52 (nucleocytoplasmic) and Grp78 (endoplasmic reticulum; ER) we propose that association of these molecules occurs either in apoptotic cells, where they have been demonstrated indirectly to co-localize in discrete apoptotic bodies, or in B cells themselves where both Ro52 and Grp78 are known to bind to immunoglobulin heavy chains. Tagging of molecules by association with Grp78 may facilitate receptor mediated phagocytotsis of the complex; we show evidence that exogenous Grp78 can associate with cell surface receptors on a subpopulation of murine splenocytes. Given the likelihood that Grp78 will associate with viral glycoproteins in the ER it is possible that it may become a bystander target of the spreading antiviral immune response. Thus, we propose a model whereby immunity elicited towards Grp78 leads to the selection of responses towards the Ro polypeptides and the subsequent cascade of responses observed in human disease.     

四种调理脾胃药对大鼠胃肠激素影响的差异性研究

目的:探讨四种经典的调理脾胃方药对大鼠胃肠激素的影响。方法:SD大鼠,分别胃饲补中益气汤、大承气汤、归牌汤、温胆汤、双蒸水,用药15天后,放免法测大鼠小肠、血液中SS、SP、VIP、NPY的含量。结果:补中益气汤可显著升高小肠及血液SS的含量;大承气汤可显著升高小肠SS、降低小肠SP、降低小肠和血液VIP的含量;归脾汤可显著升高血液SS、降低小肠和血液SP、降低小肠VIP的含量。     

壮医药线点灸对脾虚大鼠垂体生长抑素的影响

目的:探讨壮医药线点灸对实验性脾虚大鼠垂体生长抑素(Somatostatin)的影响。方法:用耗气破气加饥饱失常法建立100只大鼠实验性脾虚模型,用放射免疫分析法检测壮医药线点灸治疗前后大鼠垂体及血浆中SS的含量,并设立空线点灸对照、中药四君子汤治疗对照、模型自然恢复对照及正常健康对照。结果:脾虚大鼠脑垂体和血浆中的SS含量明显高于同期正常健康对照(P<0.01)。壮医药线点灸治疗后,脑垂体及血浆中的SS含量明显降低,治疗前后比较差异有显著性,P<0.05;治疗后与同期模型组及空线点灸治疗对照组比较差异也有显著性,P<0.05;与中药治疗组比较差异无显著性,P>0.05。结论:壮医药线点灸对实验性脾虚大鼠垂体SS有调整作用。     

Structural basis of eukaryotic cell targeting by type III secretion system (T3SS) effectors

Type III secretion systems (T3SS) are macromolecular complexes that translocate a wide number of effector proteins into eukaryotic host cells. Once within the cytoplasm, many T3SS effectors mimic the structure and/or function of eukaryotic proteins in order to manipulate signaling cascades, and thus play pivotal roles in colonization, invasion, survival and virulence. Structural biology techniques have played key roles in the unraveling of bacterial strategies employed for mimicry and targeting. This review provides an overall view of our current understanding of structure and function of T3SS effectors, as well as of the different classes of eukaryotic proteins that are targeted and the consequences for the infected cell.     

Markers of pathogenicity islands in strains of Aeromonas species of clinical and environmental origin

The aim of this study was to investigate the presence of markers of pathogenicity islands that may be informative to detect the virulent PAI carriers of clinical and environmental strains of Aeromonas spp. isolated in Mexico. virB2, virB9 and virB11 genes were found in Aeromonas strains isolated from environmental and clinical sources while cagE and tfc16 genes were only in strains of environmental origin. Having performed the wide screening presented in this study, we now have a set of strains to map and confirm the presence of a pathogenicity island in Aeromonas strains isolated in Mexico.     

Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.     

Role of viral RNA and lipid in the adverse events associated with the 2010 Southern Hemisphere trivalent influenza vaccine

In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in post-marketing adverse event reports of febrile seizures (FS) in children under 5 years of age shortly after vaccination with the CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described the contribution to these adverse events of the 2010 SH influenza strains as expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from whole blood cells and induction of NF-κB activation in HEK293 reporter cells. The aim of the present study was to identify the root cause components that elicited the elevated cytokine/chemokine and NF-κB signature. Our studies demonstrated that the pyrogenic signal was associated with a heat-labile, viral-derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral lipid-mediated delivery of short, fragmented viral RNA was the key trigger for the increased cytokine/chemokine secretion and NF-κB activation. It is likely that the FS reported in children <5 years were due to a combination of the new influenza strains included in the 2010 SH TIV and the CSL standard method of manufacture preserving strain-specific viral components of the new influenza strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1 A/California/07/2009). These combined to heighten immune activation of innate immune cells, which in a small proportion of children <5 years of age is associated with the occurrence of FS. The data also demonstrates that CSL TIVs formulated with increased levels of splitting agent (TDOC) for the B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro, identifying a potential path forward for generating a CSL TIV indicated for use in children <5 years.