Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling

Leukocyte rolling and firm adhesion at the venular endothelium are two discrete events in the cellular inflammatory response mediated via selectin and integrin adhesion molecules, respectively. The dependency of chemoattractant-induced firm leukocyte adhesion on the preceding rolling interaction was investigated in rat mesenteric microvessels through use of intravital microscopy. Leukocyte rolling was dose-dependently inhibited by systemic treatment with the sulphated polysaccharide fucoidin. The firm leukocyte adhesion following stimulation with the chemotactic peptide fMLP was similarly inhibited when fMLP challenge was performed subsequent to inhibition of leukocyte rolling by fucoidin. Thus, based on paired observations in single venules before and after fucoidin treatment, reduced rolling leukocyte flux prior to fMLP challenge was paralleled over a wide range by a proportional decrease in fMLP-induced leukocyte adhesion. The results demonstrate quantitatively a close relationship between the extent of leukocyte rolling and the magnitude of the subsequent firm adhesion response, and, that an initial rolling interaction is a precondition for firm adhesion to occur at physiological blood flow rates in vivo.     

Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis

Anti-tumor necrosis factor (TNF) antibodies inhibit passively transferred experimental allergic encephalomyelitis (EAE) in SJL mice. The possibility that this occurs through interference in TNF's upregulation of endothelial cell adhesion molecules was investigated. Expression of both vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on spinal cord vessels increased during EAE. The upregulation of VCAM-1 was markedly reduced or prevented by anti-TNF treatment. Leukocytic infiltration was 15-fold lower in anti-TNF-treated than diseased animals. Spinal cord endothelial expression of VCAM-1, though not ICAM-1 or fibronectin, positively correlated with the extent of T cell, B cell or monocyte infiltration in each animal.     

Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma

BACKGROUND: Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) are thought to contribute to the airway inflammation and airway hyper-responsiveness (AHR) of allergic asthma. Some differences from allergic asthma have been noted, including airway neutrophilia, and the involvement of ICAM-1 in toluene diisocyanate (TDI) asthma is currently unclear. OBJECTIVE: We utilized mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in airway inflammation and AHR in TDI-induced asthma. METHODS: Male C57BL/6J mice (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed 24 h after challenge by TDI or solvent. The production of antigen-specific IgG and IgE by TDI sensitized and non-sensitized mice was determined. RESULTS: TDI challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein-2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable. CONCLUSION: These results suggest that ICAM-1 plays an essential role in airway inflammation and AHR in TDI-induced asthma.     

水蛭注射液对大白鼠血小板粘附和血小板聚集功能的影响

目的　探讨水蛭注射液对大白鼠血小板粘附性和聚集性的影响。方法　采用大白鼠 2 4只 ,随机分成两组 ,实验组给药 ,对照组以实验组同样的方法和剂量给予生理盐水 ,5d后由颈总动脉取血 ,做血小板粘附性和聚集性试验。结果　水蛭注射液对大鼠血小板粘附性和聚集性具有显著的抑制作用 ,实验组与对照组抑制率有显著的统计学意义 (P <0 0 0 1)。结论　水蛭注射液能够抑制大白鼠血小板的粘附和聚集。     

Effect of a single dose of the selectin inhibitor TBC1269 on early and late asthmatic responses

BACKGROUND : Selectins participate in the initial phase of leucocyte migration from circulation to inflamed tissues and may play a role in inflammatory cellular influx into airways in asthma. In the sheep asthma model, TBC1269, a pan-selectin antagonist, reduced late allergen response by 74%. OBJECTIVE : To determine whether a single dose of TBC1269 inhibits early (EAR) and late (LAR) asthmatic responses, and whether it inhibits sputum leucocyte influx after inhalation allergen challenge in atopic asthmatic subjects treated with bronchodilators only. METHODS : Twenty-one asthmatic subjects (mean+/-SD, age=32.5+/-6.7 years, 8 males, FEV1 percent predicted=84+/-15%) with known late asthmatic response based on a screening inhalation allergen challenge were randomly assigned to receive intravenous treatment with either placebo (n=11) or TBC1269 (n=10, 30 mg/kg) infused over 15 min immediately prior to a second (post-treatment) allergen challenge at least 4 weeks after the screening challenge. After each challenge, EAR and LAR were monitored for 7 h. In addition, sputum was induced 1 day before and 1 day after each allergen challenge. RESULTS : TBC1269 did not attenuate the EAR compared with placebo (largest fall in FEV1 within 1 h of 34.1+/-13.9% vs. 31.8+/-12.2% for TBC1269 and placebo groups respectively, P=0.61) or the LAR (largest fall in FEV1 between 3 and 7 h of 39.3+/-15.3% vs. 32.6+/-13.8%, P=0.24). TBC1269 had only minor effects on allergen-induced sputum eosinophilia. CONCLUSION : We conclude that TBC1269 administered before allergen challenge as a single intravenous dose does not attenuate early or late asthmatic responses to allergen in asthmatic subjects.     

New Insights into the Pathogenesis and the Therapy of Recurrent Focal Glomerulosclerosis

Recurrent focal glomerulosclerosis (FSGS) in renal allografts has remained a frustrating and enigmatic disease. Recent studies on gene mutations encoding podocin and other components of the slit-diaphragm in patients with native kidney nephrotic syndrome have underscored the heterogenecity of the idiopathic form of FSGS. While familial FSGS rarely recurs following transplantation, the sporadic variety of FSGS is associated with a 30% recurrence rate. The patients with the sporadic variety of FSGS who have homozygous or complex heterozygous podocin mutations have a low recurrence rate. In the other patients with sporadic FSGS, a more complex and likely multifactorial etiology accounts for the recurrence of FSGS. The role of CD80 expression on podocytes is intriguing but requires confirmation in kidney biopsies of patients with recurrent FSGS. Recent findings on podocin genomics, the permeability factor and CD80 expression may ultimately lead to a better understanding of recurrent FSGS as well as a more effective approach to its prevention and treatment.     

透明质酸钠预防粘连性肠梗阻术后再粘连临床观察

Objective To investigate the prevention of intestines adhesion about sodium hyaluronic acid in postoperative intestines adhesion.Methods Eighteen cases of adhesive intestine obstruction were done intestinal release or bowel resection.2～4mL sodium hyaluronic acid was put to the wound,anastigmatic and rough surface of peritoneal.Gastrointestinal decompression,anti-infective and infusion were taken after oper-ations.Followed up 8～24 months.Results Obstructive symptoms haven't happened,the effective rate is 100%.Only 2 cases have intermittent abdominal pain without obstruction,the incidence was 11%.Conclu-sion Sodium hylauronic acid is effective to prevent the adhesion of postoperative intestines adhesion,simp-ler use,fewer side-effects and great value to appliance.     

Syndecan-1和E-candherin在声门上型喉鳞状细胞癌中的表达及意义

目的：探讨Syndecan—1和E—candherin两种黏附分子在声门上型喉鳞状细胞癌中的表达情况及与喉癌生物学行为之间的关系。方法：应用SP免疫组织化学法检测了38例声门上型喉鳞状细胞癌和7例喉黏膜慢性炎症组织中的Syndecan-1和E—candherin的表达并根据阳性瘤细胞占肿瘤细胞总数的比率进行半定量分析和统计检验。结果：Syndecan-1和E—candherin的阳性染色部位主要集中于细胞膜，E—candherin也可表达于细胞间质。Syndecan-1和E-candherin在恶性程度高的癌细胞上膜表达明显缺失，并与组织学分化、肿瘤大小密切相关。Syndecan-1和E-candherin在喉鳞状细胞癌细胞上的表达结果有相关性，但无敏感性差异。结论：Syndecan-1和E-candherin的表达可能在声门上型喉鳞状细胞癌的发生发展等生物学行为中起着重要的作用。     

子宫内膜异位症患者血清及腹腔液中血小板衍生生长因子、血管细胞粘附分子水平的变化及其意义

目的通过检测子宫内膜异位症(EMs)患者血清及腹腔液中血小板衍生生长因子(PDGF)、血管细胞粘附分子-(VCAM-1)浓度,探讨PDGF和VCAM-1在EMs发病中的作用。方法选取手术后病理证实为EMs的40例患者为EMs组,其中I~II期17例,III~IV23例;非EMs组20例作为对照组。应用酶联免疫吸附法(ELISA)检测血清及腹腔液中PDGF和VCAM-1水平。结果EMs组血清及腹腔液中PDGF、VCAM-1水平均明显高于对照组(P<0.01)。随EMs期别的增加,其血清和腹腔液中PDGF、VCAM-1含量呈上升趋势;EMsIII~IV期水平显著高于I~II期(P<0.05)。EMs患者PDGF与VCAM-1呈正相关性(P<0.05)。结论EMs患者PDGF、VCAM-1表达水平升高,在EMs的发生发展中具有重要作用。     

Cytochemical Redistribution of 5'-Nucleotidase in the Developing Cat Visual Cortex

The adenosine-producing ectoenzyme 5'-nucleotidase has recently been shown to undergo a marked redistribution during development of the cat visual cortex and to be involved in the remodelling of ocular dominance columns (Schoen et al., J. Comp. Neurol. , 296 , 379 – 392, 1990). Using an enzyme-cytochemical technique, we now investigate the developmental redistribution of 5'-nucleotidase activity in area 17 of kittens at the ultrastructural level. Between postnatal days 35 and 42, when 5'-nucleotidase is concentrated in layer IV, enzyme reaction product occupies the clefts of asymmetrical synapses within the neuropil. During later development (9th and 13th postnatal weeks), when 5'-nucleotidase spreads over all cortical laminae, the enzyme disappears from its synaptic localization and becomes increasingly associated with astrocytic membranes. The transient appearance of 5'-nucleotidase at synapses parallels the time-course and laminar profile of the synaptic remodelling which takes place during the critical period of visual cortex development. This suggests that synapse-bound 5'-nucleotidase activity plays a role in synaptic malleability, whereas its later association with glial profiles is likely to reflect other functions of the enzyme.