Inhibition of CXCR3-mediated chemotaxis by the human chemokine receptor-like protein CCX-CKR

Background and Purpose

Induction of cellular migration is the primary effect of chemokine receptor activation. However, several chemokine receptor-like proteins bind chemokines without subsequent induction of intracellular signalling and chemotaxis. It has been suggested that they act as chemokine scavengers, which may control local chemokine levels and contribute to the function of chemokines during inflammation. This has been verified for the chemokine-like receptor proteins D6 and DARC as well as CCX-CKR. Here, we provide evidence for an additional biological function of human (h)CCX-CKR.

Experimental Approach

We used transfection strategies in HEK293 and human T cells.

Key Results

Co-expression of hCCX-CKR completely inhibits hCXCR3-induced chemotaxis. We found that hCCX-CKR forms complexes with hCXCR3, suggesting a relationship between CCX-CKR heteromerization and inhibition of chemotaxis. Moreover, negative binding cooperativity induced by ligands both for hCXCR3 and hCCX-CKR was observed in cells expressing both receptors. This negative cooperativity may also explain the hCCX-CKR-induced inhibition of chemotaxis.

Conclusions and Implications

These findings suggest that hCCX-CKR prevents hCXCR3-induced chemotaxis by heteromerization thus representing a novel mechanism of regulation of immune cell migration.     

太白木根皮的齐墩果酸皂甙

从太白木（ＡｒａｌｉａｔａｉｂａｉｅｎｓｉｓＺ．Ｚ．ＷａｎｇｅｔＨ．Ｃ．Ｚｈｅｎｇ）根皮中首次分离到５个齐墩果酸皂甙，根据理化性质和光谱数据，分别鉴定为木皂甙Ａ（１），３Ｏ［αＬ呋喃阿拉伯糖（１→４）βＤ吡喃葡萄糖醛酸丁酯］齐墩果酸２８ＯβＤ吡喃葡萄糖甙（２），３Ｏ［αＬ呋喃阿拉伯糖（１→４）βＤ吡喃葡萄糖醛酸乙酯］齐墩果酸２８ＯβＤ吡喃葡萄糖甙（３），屏边三七甙Ｒ２（４）和３Ｏ｛βＤ吡喃葡萄糖（１→３）［αＬ呋喃阿拉伯糖（１→４）］βＤ吡喃葡萄糖醛酸乙酯｝齐墩果酸２８ＯβＤ吡喃葡萄糖甙（５）。２，３和５为新化合物，分别命名为太白木皂甙Ｉ（ｔａｉｂａｉｅｎｏｓｉｄｅＩ）、太白木皂甙Ｉ（ｔａｉｂａｉｅｎｏｓｉｄｅＩ）和太白木皂甙ＩＩ（ｔａｉｂａｉｅｎｏｓｉｄｅＩＩ）。     

The effect of overweight and obesity on psoriasis patients in Chinese Han population: a hospital‐based study

Background Accumulating evidence indicates that psoriasis is associated with increased risk of overweight and obesity. However, few studies have investigated this relationship in Chinese Han population. Objective The aim of this study was to explore the relationship between overweight/obesity and psoriasis and to evaluate the overweight/obesity effect on the clinical features of psoriasis in Chinese Han population. Methods A hospital‐based study was conducted, which involved in 4452 patients and 1166 controls of Chinese Han through epidemiological investigation. Controls used in the study were individuals without psoriasis from health examination centre, and other skin disease patients from outpatient department. Results Compared with the control group, a significantly greater prevalence of overweight and obesity was observed in psoriasis patients. The estimated ORs were 1.301 (95% CI, 1.105–1.531) and 1.680 (95% CI, 1.134–2.491) respectively. The disease severity of psoriasis measured by psoriasis area and severity index (PASI) was statistically correlated with body mass index (BMI) (r = 0.184, P < 0.01). Moreover, a high proportion of overweight patients had affected hands or/and feet, buttocks, trunk, legs, arms and arthritis (P < 0.01). Conclusions Our study suggested that psoriatic patients have a higher prevalence of overweight and obesity compared with non‐psoriatic patients in Chinese Han population. Overweight and obesity has different risk effect on severity and manifestations of psoriasis and might be useful for better evaluating psoriasis clinically.     

Evaluation of routinely performed hematological and biochemical parameters for the prognosis of acute ischemic stroke patients

We have investigated serial changes in routine hematological and biochemical analysis in the follow-up samples collected from acute ischemic stroke (AIS) patients (n = 17) at admission (0 h) and 24, 48, 72 and 144 h after admission, respectively, to determine their prognostic significance. Blood samples from age and sex matched healthy control subjects (n = 12) were also collected. We observed significant changes in erythrocyte sedimentation rate (ESR), white blood cell count (WBC), polymorph, lymphocyte, and total protein levels in discharged and expired AIS patients. These changes were more in expired AIS patient throughout the follow-up. Similarly low hemoglobin (Hb) and globulin were observed only in expired AIS patient. Thus ESR, WBC, polymorph, lymphocyte, and total protein may be used as a predictor for severity of AIS. Similarly low Hb and globulin in AIS patient may be used as a predictive biomarker for short-term mortality after AIS.     

粗大运动功能测试量表与Gesell发育量表在脑性瘫痪疗效评估中的应用比较

目的:比较粗大运动功能测试量表及Gesell发育量表在脑性瘫痪康复疗效评估中的应用效果。方法:选择2005-05/12在山东大学齐鲁儿童医院康复中心初次接受康复治疗的脑性瘫痪患儿25例,符合2004年全国小儿脑性瘫痪研讨会制定的诊断标准(金标准),监护人均知情同意。脑性瘫痪患儿均采用综合康复治疗:①Vojet法。②Bobath法。③推拿。④针灸,每次留针1h。每周连续治疗6d,休息1d,持续治疗3个月为1个疗程。所有患儿在接受康复治疗前及治疗1个疗程后均进行粗大运动功能测试量表和Gesell发育量表粗大运动发育龄、发育商评估。①粗大运动功能测试量表:总分100分表明患儿能完全完成该量表的全部内容,0分表明患儿不能完成该量表的最低运动评估项目。总分百分比为5个能区原始分占各自总分百分比之和再除以5。②Gesell发育量表:发育龄=∑(M×n)÷∑n(M代表测查取的月龄,n代表测查通过的项目,∑为若干数据的总和);发育商为测得的发育年龄与实际年龄的百分比。大运动发育商数55～75为轻度障碍,40～54为中度障碍,25～39为重度障碍,<25为极重度障碍。结果:25例患儿全部进入结果分析,无脱落。①治疗前及治疗1个疗程后患儿的量表评分比较:康复治疗进行1个疗程后患儿的粗大运动功能测试量表总分百分比及Gesell粗大运动发育龄显著高于治疗前[(22.64±4.18)%,(11.92±3.42)个月;(16.96±4.50)%,(10.18±3.48)个月(t=28.74,16.44,P<0.01)],而发育商显著低于治疗前(50.05±8.04,51.12±8.20,t=11.85,P<0.01)。②两个量表的敏感性比较:粗大运动功能测试量表总分百分比治疗后提高百分比为(6.46±5.65)%,Gesell发育量表粗大运动发育龄治疗后提高百分比为(1.28±1.29)%,两者之间差异具有显著性意义(P<0.01)。结论:Gesell发育量表在脑性瘫痪康复疗效评估中有一定的局限性,粗大运动功能测试量表可用于脑性瘫痪康复疗效的评估,而且对康复训练也能起到指导意义。     

Prognostic implications of left ventricular dilation in patients with nonischemic heart failure: interactions with restrictive filling pattern and mitral regurgitation

The aim of this study was to evaluate whether small left ventricular (LV) volumes increase the negative prognostic impact of a restrictive filling pattern (RFP) and that of mitral regurgitation (MR) in patients with nonischemic heart failure (HF). The Meta-analysis Research Group in Echocardiography (MeRGE) is a meta-analysis that collated individual patient data from several prospective echocardiography outcome studies. This analysis was restricted to 10 studies and 601 patients with nonischemic HF. The role of MR was tested in a subgroup of 252 patients. A total of 106 deaths occurred during a median follow-up of 32 months. At multivariate analysis, RFP (hazard ratio [HR], 4.16; 95% confidence interval [CI], 1.54-11.23; P=.005) and New York Heart Association class III or IV (HR, 2.15; 95% CI, 1.33-3.47; P=.001) were the independent predictors of poor prognosis, and there was no statistically significant interaction between LV dilation and RFP. Moderate/severe MR was associated with poorer outcome in the group of patients with normal volumes, whereas it was not a significant predictor of mortality in patients with any degree of LV dilation. In patients with nonischemic HF, RFP is the most important indicator of poor prognosis, irrespective of the degree of LV dilation. Normal LV volumes increase the negative prognostic impact of moderate to severe MR.     

FS09.7Standardisation of the "strip" patch test: a multicentre study

Objectives:  The strip patch test (SPT), proposed by Spier and Sixt (Hautarzt 1955;6:152–9), is a modification of the patch test (PT). This technique is used to enhance penetration through the stratum corneum for poorly penetrating substances such as medicaments. So far, a standardised procedure is lacking. This multicentre study aims at standardising the SPT procedure.
Methods:  A total of 83 healthy volunteers participated. In each subject, we determined the number of strips (A) until the surface became glistening and then calculated the median number of strips in the sample (Ā = 26). We ascertained the median number of strips in the sample (ā = 11) that was necessary to achieve a first statistically significant and medically relevant increase of the TEWL revealing a critical stratum corneum strip depth. For the finally calculated number of strips for each subject (a/A = (ā/Ā)⇔a = A × (ā/Ā)), the actual increase in test sensitivity was substantiated employing SLS 0.125% aqueous.
Standardisation results:  Perform stripping at one upper part of the back until the surface becomes glistening: gently press a 25 mm diameter adhesive tape downward vertically for about 2 seconds and then remove it in one quick movement at the angle in direction of adherence; continue stripping with a new tape cut on exactly the same skin area. Multiply number of strips by the correction factor ( cf  = ā/Ā = 11/26 = 0.4). Perform calculated number of strips likewise on the contralateral site and then apply there the test preparation for 24 hours.
Conclusions:  If clinically an allergic contact dermatitis is expected but PT is negative, the SPT might reveal the potential allergen.