Activation of invariant NK T cells protects against experimental rheumatoid arthritis by an IL-10-dependent pathway

Invariant natural killer T (iNKT) cells are a unique lymphocyte subtype implicated in the regulation of autoimmunity and a good source of protective Th2 cytokines. Agonist alpha-galactosylceramide (alpha-GalCer) of iNKT cells exert a therapeutical effect in type 1 diabetes. We investigated whether iNKT activation with alpha-GalCer was protective in collagen-induced arthritis (CIA) in DBA/1 mice, a standard model of rheumatoid arthritis. Here, we have shown that in vivo iNKT cell function was altered in DBA/1 mice since stimulation with alpha-GalCer led to decreased IL-4 and IFN-gamma levels in sera, as compared with C57BL/6 mice. alpha-GalCer induced a clear-cut diminution of clinical and histological arthritides. An anti-IL-10 receptor antibody abrogated the protective effect of alpha-GalCer, suggesting a key role for IL-10 in the protection against CIA by activated iNKT cells. Confirming these data, disease protection conferred by alpha-GalCer correlated with the ability of LN CD4+ cells to secrete larger amounts of IL-10. These findings suggest that in CIA susceptibility to autoimmunity is associated with dysfunctions of iNKT cells. Our demonstration that iNKT cell activation by alpha-GalCer remains efficient in CIA-prone DBA/1 mice to provide protective IL-10 suggests that this could be used therapeutically to treat autoimmune arthritis.     

Chemical and biological properties of a peptidoglycan isolated from Treponema pallidum kazan.

A peptidoglycan layer of Treponema pallidum kazan was isolated by solubilization of whole cells with 1% warm sodium dodecyl sulfate and subsequent digestion of an insoluble residue with proteases. Electron microscopy revealed that the peptidoglycan was isolated as a single-layered sacculus of less than 5 nm in thickness, freed from axial filaments and an envelope sheath. An isolated peptidoglycan fraction was mainly composed of glucosamine, muramic acid, alanine, glutamic acid, ornithine, and glycine in molar ratios of 0.65:0.68:1.63:1.00:0.75:1.03. Amino (N)- and carboxyl (C)-terminal amino acid analyses suggested the involvement of at least a part of the glycine residue in cross-linking between the amino group of ornithine residue at one strand of the stem peptide subunit and the carboxyl group of alanine of the neighboring strand. The treponemal peptidoglycan lacked the immunoadjuvant activity both to stimulate antibody production and to induce delayed-type hypersensitivity against ovalbumin, as well as the properties necessary to stimulate guinea pig and mouse splenocytes and guinea pigs peritoneal macrophages, unlike the cell walls or peptidoglycans (group A type of Schleifer and Kandler's classification, Bacteriol. Rev. 36:407-477, 1972) isolated from many bacterial species parasitic to the mammal. However, the peptidoglycan activated the human complement system through the alternative pathway, as well as the classical one, and caused a liberation of 5-hydroxytryptamine in rabbit blood platelets in a similar manner to the cell wall peptidoglycans of both group A and B types.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.     

Hyperosmolarity response of ocular standing potential as a clinical test for retinal pigment epithelium activity normative data

The standing potential of the eye is decreased by intravenous administration of hypertonic solutions. This hyperosmolarity-induced response has been recorded in normal subjects by the use of electro-oculography (EOG) in the dark. An intravenous administration of Fructmanit^® (1.4 × 10³ mOsmol) (150 500ml, 2.37 9.70ml/kg, 0.08 0.36 ml/kg/min) was used to evoke the hyperosmolarity response. The amplitude of the response was expressed in percentage, V₀ – V_min/V₀ × 100, where V₀ is the base value of the EOG before administration of the hypertonic solution and V_min is a minimum EOG amplitude after administration. The distribution of the amplitude of the hyperosmolarity response was approximated by the normal distribution in normal subjects. The minimum, the maximum, the mean and the standard deviation of the amplitude of the hyperosmolarity response were respectively 34.2%, 52.3%, 42.6% and 4.6% in normal subjects. The normal range of the hyperosmolarity response would be 33.4 51.8% (M ± 2SD). The hyperosmolarity response, which originates mainly in the retinal pigment epithelium, is a useful new quantitative and specific test of the activity of the retinal pigment epithelium in clinical practice.     

Hyperosmolarity response of ocular standing potential as a clinical test for retinal pigment epithelium activity rhegmatogenous retinal detachment

The hyperosmolarity response of the ocular standing potential was recorded in unilateral rhegmatogenous retinal detachment (8 eyes) and in the fellow healthy eye (8 eyes). The hyperosmolarity response was greatly suppressed (M-4 SD: M and SD indicate respectively the mean and the standard deviation in normal subjects) in all affected eyes (p < 0.005), and slightly abnormal in 2 fellow eyes. The L/D ratio was normal in 2 affected eyes and in all fellow eyes. The hyperosmolarity response in the affected eyes was still greatly suppressed 14 months after successful surgical treatment.     

周围神经端侧缝合与神经移植的实验研究

目的　比较周围神经端侧缝合与神经移植的效果。方法　选用体重 2 0 0～ 30 0gWistar大白鼠 ,左侧后肢腓总神经与胫神经端侧缝合 ,右侧腓总神经采用神经移植修复。结果　 3个月后运动神经传导速度分别为2 9.6 8± 5 .34m/s、 30 .87± 6 .0m/s(P >0 .0 5 ) ,潜伏期 2 .1± 0 .1ms ,2 .0± 0 .1ms(P >0 .0 5 ) ,波幅 12 .5± 0 .6mV、13.9± 0 .5mV(P >0 .0 5 ) ,组织切片中 ,两组均可见大量神经纤维和髓鞘 ,有髓神经纤维计数分别为 75 7.2± 2 2 .31、775± 2 1.87(P >0 .0 5 )。结论　①正常神经发出侧芽能通过端侧缝合口长入远端神经 ,使变性神经再神经化 ;②周围神经端侧缝合能取得与神经移植相近的结果。     

The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation

High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low-risk (0–3), medium-risk (4–5), and high-risk (6–10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT.     

动态增强磁共振成像在评估女性乳房乳头乳晕血供的应用

目的探究动态增强磁共振成像(DCE-MRI)用于评估女性乳房乳头乳晕血供特点的可行性,为乳房整形手术提供乳头乳晕的血供参考。方法从2012年3月至2019年10月华中科技大学同济医学院附属同济医院影像数据库中收集女性乳腺DCE-MRI图像资料,选择未发现肿物的正常乳房的DCE-MRI图像进行研究。在西门子工作站将患者乳腺DCE-MRI图像通过图像减影获取乳房血管图像,分别对轴位、冠状位和矢状位的最大密度投影(MIP)图像进行评估,结合三维MIP图像识别所有供应乳头乳晕的血管。乳头乳晕的血供被划分为内上、内侧、内下、外上、外侧、外下、中央、上方和下方9个象限,对各个象限血管进行统计和分析,并测量血管至乳房皮肤表面投影的最大距离。采用SPSS 19.0软件进行统计分析,通过卡方检验分别比较左侧与右侧乳房的乳头乳晕复合体(NAC)血供象限分布构成比。计算血管到皮肤距离的平均值、标准差及95%置信区间,通过方差分析比较各象限血管至皮肤距离的差异。P<0.05为差异具有统计学意义。结果共收集到245例患者490只女性乳房DCE-MRI图像,其中97例患者97只乳房发现有乳腺肿物,其余393只为正常乳房(97例单侧乳房、148例双侧乳房),将其作为研究对象。患者年龄23~72岁,平均43.7岁。393只乳房(左侧200只、右侧193只)共发现有637条(左侧311条、右侧326条)乳头乳晕供应血管。在637条血管中,内上象限269条(42.2%),外上180条 (28.3%),内侧57条(8.9%),下方37条(5.8%),中央30条(4.7%),内下25条(3.9%),外下25条(3.9%),上方11条(1.7%),外侧3条(0.5%)。卡方检验表明左侧乳房和右侧乳房在NAC血供象限分布构成比差异无统计学意义(χ2 =6.4,P=0.602)。除中央象限血管以外,所有血管到皮肤表面投影最大距离的平均值为0.91 cm, 95%置信区间为0.86~0.96 cm。方差分析表明各象限供血血管到皮肤投影的最大距离,差异有统计学意义(F=11.4,P<0.001)。结论 DCE-MRI可以清晰地显示乳头乳晕的血供来源。乳头乳晕血供主要来源于内上象限和外上象限的血管,血管在皮下约1 cm深度走行。     

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Annals of Surgical Oncology - The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to...     

Das akute Koronarsyndrom in der prähospitalen Phase und in der Notaufnahme

Notfall + Rettungsmedizin - Das akute Koronarsyndrom ist der häufigste Grund für einen Rettungsdiensteinsatz in Deutschland. So resultieren in etwa 20–25 % aller Einsätze...