Absence of antibody-dependent, complement-mediated lysis of feline infectious peritonitis virus-infected cells

Cats infected with virulent feline coronavirus which causes feline infectious peritonitis (FIP) usually succumb to disease despite high antibody concentrations. One of the mechanisms that can help resolving infection is antibody-dependent, complement-mediated lysis (ADCML) of infected cells. ADCML consists of virus-specific antibodies that bind to cell surface expressed viral proteins which result in complement activation and cell lysis. The objective of this study was to determine the sensitivity of FIP-virus (FIPV) infected cells towards ADCML and to examine the role of the accessory proteins 3abc and 7ab in this process. ADCML assays, using FIPV strain 79-1146 and its deletion mutant strain Δ3abc/Δ7ab, were performed on: (i) CrFK cells that show surface-expressed viral antigens, (ii) monocytes without surface-expressed viral proteins due to retention and (iii) monocytes with surface-expressed viral proteins since the antibody-mediated internalization of these proteins was blocked. As expected, no ADCML was detected of the monocytes without surface-expressed viral antigens. Surprisingly, no lysis was observed in the CrFK cells and the monocytes that do show surface-expressed viral proteins, while controls showed that the ADCML assay was functional. These experiments proof that FIPV can employ another immune evasion strategy against ADCML (besides preventing surface expression): the inhibition of complement-mediated lysis. This new evasion strategy is not attributed to the group-specific proteins since lysis of cells infected with FIPV Δ3abc/Δ7ab was not detected.     

Molecular mechanisms and functions of pyroptosis,inflammatory caspases and inflammasomes in infectious diseases

Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase-1, human caspase-4 and caspase-5, or mouse caspase-11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore-forming effector protein gasdermin D by inflammatory caspases. Physical rupture of the cell causes release of the pro-inflammatory cytokines IL-1β and IL-18, alarmins and endogenous danger-associated molecular patterns, signifying the inflammatory potential of pyroptosis. Here, we describe the central role of inflammatory caspases and pyroptosis in mediating immunity to infection and clearance of pathogens.     

Immune surveillance of human cancer: if the cytotoxic T-lymphocytes play the music, does the tumoral system call the tune?

Abstract
Accumulating evidence indicates that the innate and adaptive immune systems participate in the recognition and destruction of cancer cells by a process known as cancer immunosurveillance. Tumor antigen-specific cytotoxic T-lymphocytes (CTL) are the major effectors in the immune response against tumor cells. The identification of tumor-associated antigen (TAA) recognized primarily by CD 8⁺ T-lymphocytes has led to the development of several vaccination strategies that induce or potentiate specific immune responses. However, large established tumors, which are associated with the acquisition of tumor resistance to specific lysis, are usually not fully controlled by the immune system. Recently, it has become clear that the immune system not only protects the host against tumor development but also sculpts the immunogenic phenotype of a developing tumor and can favor the emergence of resistant tumor cell variants. Moreover, it has become obvious that the evasion of immunosurveillance by tumor cells is under the control of the tumor microenvironment complexity and plasticity. In this review, we will focus on some new mechanisms associated with the acquisition of tumor resistance to specific lysis during tumor progression, involving genetic instability, structural changes in cytoskeleton, and hypoxic stress. We will also discuss the interaction between CTLs and tumor endothelial cells, a major component of tumor stroma.     

Towards defining parameters for a successful single embryo transfer in frozen cycles

BACKGROUND: Twin pregnancies in IVF should be avoided by transferring embryos one at a time, even for frozen cycles. In this study, we investigated the effect of blastomere lysis and cleavage in singleton frozen embryo transfer (sFET) cycles. Outcomes were compared with the transfer of two embryos in frozen transfer cycles (dFET). METHODS: A retrospective analysis was performed on 891 FET cycles, involving 404 sFET and 487 dFET cycles. RESULTS: Overall, in sFET cycles, the pregnancy and implantation rates were 8.9 and 8.7%. When blastomere lysis was more than 25% but no greater than 50%, the pregnancy and implantation rates were 3.2%. If blastomere lysis was greater than 50% there were no pregnancies. If blastomere lysis was less than 25%, but with no cleavage, the pregnancy and implantation rates were 4.1%. The results significantly improved (P = 0.007) in the group with less than 25% lysis, when cleavage occurred. The pregnancy and implantation rates for this group were 17.3 and 16.6%. This was not significantly different from unselected two embryo transfers (22 and 12.7%,P = 0.2 and 0.19, respectively). There were 21 twins with dFET (19.6% of pregnancies) and none in sFET. CONCLUSION: Both blastomere lysis and cleavage affect the outcome in sFET. To avoid the risk of twins, sFET should be considered when the embryo shows less than 25% blastomere lysis and at least one blastomere cleaves.     

胸腔镜术后复发性气胸的再次胸腔镜手术治疗

目的 探讨再次胸腔镜手术治疗胸腔镜术后复发性气胸的可行性.方法 2009年1月～2012年11月对77例胸腔镜手术后复发性气胸再次胸腔镜手术治疗,行粘连松解、肺大疱切除、胸膜固定、闭式引流等.结果 77例均在胸腔镜下顺利完成手术,术中见胸腔均有较重粘连,无术中大出血及围术期死亡等严重并发症.手术时间35 ～87 min,(59±12)min;术中出血量30 ～160 ml,(92±33)ml.77例随访1～46个月,(22±13)月,无气胸复发.结论 术后复发性气胸再次胸腔镜手术可行、安全、有效,术中应选择性地松解胸腔粘连.     

Impact of dialysis requirement on outcomes in tumor lysis syndrome

Tumor lysis syndrome (TLS) is a life threatening emergency due to destruction and massive release of intracellular metabolites from cancer cells often resulting in acute kidney injury (AKI), sometimes severe enough to require dialysis (AKI‐D). The impact of dialysis requirement in AKI has not been explored. We utilized data from the Nationwide Inpatient Sample and using International Classification of Diseases, 9th Revision, diagnoses codes for TLS, AKI and dialysis, evaluated the incidence, risk factors and impact of AKI‐D on mortality, adverse discharge and length of stay (LOS). Survey multivariable logistic regression was used to compute adjusted Odds Ratios (aOR and 95% confidence intervals (CI). An estimated 12% (2,919) of all TLS hospitalizations (n = 22 875) develop AK‐D. After adjustment for confounders, AKI‐D was associated with greater odds of mortality (aOR 1.98; (95% CI 1.60–2.45)), adverse discharge (aOR 1.63 (95% CI 1.19–2.24)) and longer LOS (19 vs 14.6 days; P < 0.01) compared with those without AKI‐D. Further studies to evaluate the association of AKI‐D on long‐term outcomes in patients with TLS are needed.     

超声引导下药物注射联合针刀治疗桡骨茎突狭窄性腱鞘炎

目的探讨超声引导下药物注射联合针刀治疗桡骨茎突狭窄性腱鞘炎的临床价值。方法将52例桡骨茎突狭窄性腱鞘炎患者随机分为超声组和对照组,每组各26例。对超声组先行超声检查,观察桡骨茎突处的拇长展肌和拇短伸肌肌腱、腱鞘改变及毗邻关系;选择最佳穿刺点,于实时超声引导下行药物注射联合针刀治疗。对照组根据触诊定位进行药物注射及针刀治疗治疗。采用视觉模拟评分法(VAS)评估患者疼痛程度,并采用Quinnell评分评估腕关节功能,并进行统计学分析。结果超声组与对照组术前VAS评分、Quinnell评分差异均无统计学意义(P均0.05)。对超声组均成功完成超声引导下药物注射联合针刀治疗,对照组亦均按触诊定位完成药物注射及针刀治疗。术后1周,超声组及对照组VAS评分、Quinnell评分均明显低于术前(P均0.05),且超声组VAS评分、Quinnell评分均明显低于对照组。结论超声引导下药物注射联合针刀治疗桡骨茎突狭窄性腱鞘炎疗效确切。     

D-dimer relates positively with increased blood pressure in black South Africans: The SABPA study

Introduction

Hypertension is highly prevalent in black South Africans in which morbidity and mortality from stroke are on the increase. Elevated blood pressure and haemostatic markers can induce changes in blood rheology and endothelial function which could result in a procoagulant state that increases the risk for cerebrovascular disease. Information about the coagulation and fibrinolytic systems of people from African descent are limited. We therefore, investigated the haemostatic profile and its relationships with blood pressure in black South Africans.

Materials and methods

We measured ambulatory blood pressure and haemostatic markers of 201 black and 208 white school teachers. The haemostatic markers included measurements representing coagulation and fibrinolysis (von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1, fibrin D-dimer and clot lysis time).

Results

Black participants displayed significantly higher blood pressure, von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1 and D-dimer levels and longer clot lysis times (p ≤ 0.001). Single, partial and multiple regression analyses showed that systolic (p ≤ 0.011) and diastolic blood pressure (p = 0.010) correlated positively with D-dimer in black participants, while systolic (p ≤ 0.001) and daytime diastolic blood pressure (p = 0.011) correlated negatively with clot lysis time in white participants.

Conclusion

The black population had a more prothrombotic profile, with higher levels of coagulation markers and inhibited fibrinolysis, than the white study participants. The positive association between blood pressure and elevated D-dimer in the blacks may contribute to the high prevalence of hypertension and related increased cardiovascular and cerebrovascular risk in this group.     

脑出血后脑水肿经时变化机制的探讨

目的 研究脑出血(mtracerebral hemorrhage，ICH)后血肿周围脑水肿与血脑屏障(blood-brain barrier，BBB)随时间变化的机制，从而为预防脑水肿提供依据。方法90只大耳白兔随机分为3组。1组：在立体定向仪下将300μl生理盐水注入兔左侧基底节；2组：注入200μl自身动脉血与100μl生理盐水；3组：注入200μl自身动脉血与100μl水蛭素。每组每时相(6h、12h、24h、48h、72h)各6只兔。脑组织含水量采用干湿重法测量，血脑屏障的通透性测定采用伊文思兰法。结果动脉血组及水蛭素干预组血肿周围脑组织含水量均在48h达到高峰．此后逐步降低。动脉血组伊文思兰(EB)于24h到达高峰，水蛭素干预组伊文思兰(EB)于48h达高峰。结论脑出血后脑水肿是多种因素综合作用的结果。早期可能和血块凝缩、流体静力压有关；至中期时凝血酶是主导因素；后期则主要由于红细胞裂解物的损害。