Neutrophil Adhesion Molecule Expression and Serum Concentration of Soluble Adhesion Molecules during and after Pediatric Cardiovascular Surgery with or without Cardiopulmonary Bypass

Background: Increased neutrophil activation by cardiopulmonary bypass (CPB) during cardiovascular surgery is thought to be responsible for postoperative complications. In children, the contribution of cardiovascular surgery alone to this response is not well-characterized.

Methods: Children undergoing surgery with CPB (CPB group, n = 35) and without CPB (control, n = 22) were studied (age, 3-17 yr). Blood was drawn 24 h preoperatively before medication, after anesthesia, after connection to CPB, at reperfusion, 4 h to 2 days after surgery, at discharge, and months after surgery. Neutrophil antigen expression and serum concentration of adhesion molecules, interleukin 8, and C5a (fragment of C5 complement) were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively.

Results: With and without CPB, anesthesia and surgery induced decreased LFA-1 (CD11a-CD18), Mac-1 (CD11b-CD18), CD45, and CD54 (intercellular adhesion molecule 1) surface expression and sICAM-1 serum concentrations (all P < 0.001). sL-selectin serum concentration decreased with CPB (P < 0.001) but was not significantly altered in the control. In contrast, CD62L expression increased during CPB (P < 0.001). The time course of all analyzed markers was not significantly different between CPB and control, with the exception of sL-selectin (P = 0.017). One-day preoperative baseline values were reached days to months after surgery. Interleukin 8 and C5a serum concentrations increased after surgery in both the CPB group and the control group.     

Low Expression of Junctional Adhesion Molecule A Is Associated with Metastasis and Poor Survival in Pancreatic Cancer

Background

Characterized by its highly aggressive tumor biology, pancreatic cancer still remains a fatal diagnosis. The junctional adhesion molecule A (JAM-A) is a type I transmembrane glycoprotein, which recently has been shown to affect the prognosis of several human malignancies.

Methods

JAM-A antigen expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumor tissue samples from a series (n?=?186) of consecutive patients with pancreatic adenocarcinoma. Survival was calculated by Kaplan?CMeier curves. Parameters found to be of prognostic significance in univariate analysis were verified in a multivariate Cox regression model.

Results

Low expression of JAM-A was observed in 79 (42?%) of 186 pancreatic cancer specimens and was significantly associated with poor overall survival (P?<?0.01). By univariate analysis, low expression of JAM-A was found to correlate with positive lymph node status (P?=?0.02), the presence of distant metastasis (P?=?0.05), and tumor grade (P?=?0.04), suggesting it may be an important event involved in cancer progression. Furthermore, in the subgroup of patients with surgically resected pancreatic cancer, low expression of JAM-A significantly correlated with decreased progression-free survival (P?<?0.01). Multivariate analysis revealed JAM-A to be an independent predictor of poor outcome.

Discussion

These findings suggest for the first time that low levels of JAM-A expression in pancreatic cancer are associated with poor clinical outcome. JAM-A may represents a target molecule for functional inactivation and serve as a novel biomarker of adverse prognosis in pancreatic cancer.     

大鼠急性胰腺炎时ICAM-1在胰、肺组织的表达特征与作用的观察

目的：探讨急性坏死性胰腺炎（ANP）时细胞间粘附分子-1（ICAM-1）在胰腺及肺组织的表达特征和作用。方法。用3.5%的牛磺胆酸钠逆行胰胆管注射制备ANP模型，采用免疫组化技术等方法动态观察ANP时胰腺、肺组织ICAM-1的表达改变和PMN组织聚集的变化。结果：胰腺及肺组织ICAM-1的表达分别在ANP造模后3H、6h明显增强，并于12h达高峰。结论：ICAM-1介导的PMN大量组织聚集可能是ANP早期胰腺及肺组织损伤的重要参与因素。     

Paclitaxel Impairs Endothelial Cell Adhesion But Not Cytokine-Induced Cellular Adhesion Molecule Expression

Local delivery of antiproliferative agents using drug-eluting stents has become a productive area of research for preventing in-stent restenosis. Recently, the microtubule stabilizing drug paclitaxel has been used to coat stents. While the actions of paclitaxel on smooth muscle are well documented, effects on endothelial cells (ECs) are largely unknown. Nevertheless, restoration of EC function is a critical step in repairing the vascular lesion. We assessed the effects of paclitaxel by examining three events that are critical in controlling the severity of vascular injury: (1) adhesion of ECs to matrix proteins, (2) EC migration, and (3) cytokine-stimulated cellular adhesion molecule (CAM) expression on the surface of ECs. Paclitaxel inhibited both EC adhesion and migration of ECs; however, it had no effect on tumor necrosis-stimulated CAM expression on ECs. The mechanisms of paclitaxel action on matrix adhesion and migration are not clear, but protein kinase C and myosin light chain kinase do not appear to play a role as they are unaffected by treatment of the cells with paclitaxel. On the other hand, the MAP kinase ERK1/2 is modestly inhibited by paclitaxel. While paclitaxel-coated endovascular stents may prevent smooth muscle proliferation, their attenuation of EC migration and adhesion to the lesion coupled with an inability to reduce cytokine-induced CAM expression on ECs may limit their effectiveness.     

活化白细胞黏附分子在IgA肾病中的表达及意义

目的:探讨活化白细胞黏附分子(CD166)在IgA肾病中的表达及与IgA肾病临床病理特征的关系.方法:用免疫组化二步法检测CD166蛋白在79例IgA肾病患者肾组织的表达.结果:CD166在IgA肾病患者肾小管、间质普遍表达,按Lee分级的级别增加逐渐增高.与单纯性血尿患者(A组)相比,混合蛋白尿、血尿患者(B组)肾小管间质CD166表达明显增高.肾小管间质CD166表达与患者病理分级、小管间质病变、单个核细胞浸润程度及血清C反应蛋白(CRP)水平正相关.结论:CD166在IgA肾病中表达异常,在IgA肾病小管、间质病变及疾病进展中起一定作用.     

活化白细胞粘附分子在前列腺上皮内瘤和前列腺癌中的表达及意义

目的 :探讨活化白细胞粘附分子 (ALCAM)在前列腺上皮内瘤 (PIN)和前列腺癌中的表达及与前列腺癌临床病理特征的关系。　方法 :用免疫组化EnVisionTM方法检测ALCAM蛋白在 4 1例前列腺癌和癌旁PIN、良性腺上皮的表达情况。　结果 :ALCAM在前列腺腺上皮普遍表达 ,在大部分PIN和低分化的前列腺癌表达增加 ,在部分高分化前列腺癌出现表达降低。ALCAM蛋白表达与前列腺癌病理分级相关 ,与术前血清前列腺特异性抗原水平、肿瘤分期无相关性。　结论 :ALCAM在PIN和前列腺癌中存在表达紊乱 ,提示ALCAM在前列腺癌发生发展中起一定作用。     

Complement and Neutrophil Function Changes After Liver Resection in Humans

Background  

Complement activation contributes to the regulation of liver regeneration after liver resection (LR) in mice.     

体外循环期间心脏瓣膜置换术患者白细胞粘附分子的表达

目的了解体外循环期间心瓣膜置换手术患者外周血白细胞表面粘附分子表达情况。方法采用流式细胞仪测定了１２例患者体外循环前后多时间点外周血白细胞表面粘附分子的表达。结果体外循环后患者白细胞ＣＤ１１ａ,ＣＤ１８,ＣＤ１１ａ／ＣＤ１８,ＣＤ１１ｂ,ＣＤ１１ｂ／ＣＤ１８表达明显增加（Ｐ＜０．０５）。结论体外循环后心瓣膜置换术患者外周血白细胞激活,其粘附分子表达上调     

Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Acute Rejection of Human Renal Allografts

Background

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed on various cell types and mediates homophilic cell adhesion. CEACAM1 plays an important role in cell morphogenesis and angiogenesis. Furthermore, CEACAM1 regulates adhesive activity of immune-competent cells, suggesting an additional role in inflammatory processes.

Methods

Therefore, in the present study the expression of CEACAM1 was analysed retrospectively in renal biopsies from kidney transplant recipients (stable graft [Ctr; n = 18], acute vascular rejection [AVR; n = 14], acute tubulointerstitial rejection [AIR; n = 9], and combined vascular and interstitial rejection [AVIR; n = 7]). Expression patterns of CEACAM1 were determined using immunohistochemistry and quantitative morphometry.

Results

All biopsy specimens from patients with stable grafts showed low CEACAM1 levels, suggesting a constitutive expression in renal transplants. In patients with acute rejection, CEACAM1 was markedly up-regulated. AVR revealed the highest tubular CEACAM1 levels (4.9 ± 0.5% [AVR] vs 2.2 ± 0.3% [Ctr] of tubular area; P < .05), whereas interstitial rejections showed the highest glomerular expressions (4.5 ± 0.5% [AIR] vs 0.9 ± 0.1% [Ctr] of glomerular area; P < .05).

Conclusions

An up-regulated expression of CEACAM1 in tubular and/or glomerular cells is an indicator of acute inflammatory processes in biopsy specimens from patients with acute renal allograft rejections and, therefore, might be used as a new clinical marker.     

Islet Allograft Rejection in Rats: A Time Course Study Characterizing Adhesion Molecule Expression,MHC Expression,and Infiltrate Immunophenotypes

Wistar Furth (RT1^u) islets transplanted under the renal capsules of streptozotocin-diabetic Lewis (RT1^l) rats reject after 5–6 days of normoglycemia. Hand-picked WF islets (1500–2000) were transplanted under the kidney capsules of diabetic Lew or WF rats. Rats bearing iso- or allografts were killed on posttransplant days 2, 4, and 6. Serial frozen sections of grafts and controls were stained by immunoperoxidase for rat MAC-1, class II MHC, CD2, CD4, CD8, B-cells, VLA-4, LFA-1, L-selectin, ICAM-1, and VCAM-1. Infiltrating cells, parenchymal cells, and endothelial cells in five distinct compartments (i.e., peritoneal reflection, subcapsular perivascular space, islet grafts, graft–kidney interface, and kidney) were evaluated for expression of the various markers at each interval. Significant infiltrates arrived in three distinct waves in both iso- and allografts. First, macrophages blanketed the peritoneal capsular reflection and infiltrated by day 2. Second, the first wave of lymphocytes arrived in the edematous subcapsular soft tissue via capsular vessels by day 2 (allo > iso). Third, the second wave of lymphocytes arrived from the renal parenchyma to form a dense band at the graft–kidney interface and around grafts by days 4 and 6 (allo >>> iso); CD4+ cells vastly outnumbered CD8+ cells, with CD4+ cells being mobilized first and from interstitial vessels throughout the entire kidney. CD8+ cells emigrated only from renal interstitial vessels adjacent to the graft. Large numbers of L-selectin+, VLA-4+, and LFA-1+ cells were seen in the infiltrates with the most intensely staining cells being intravascular. B-cells composed a very small proportion of infiltrating cells in both allo- and isografts. Endothelial staining for ICAM-1 and VCAM-1 was prominent throughout. Both class II MHC and ICAM-1 expression were induced on renal tubular epithelial cells, but neither was found on islet parenchymal cells. In conclusion, this study shows that islet allograft rejection is more complex than previously realized.     

Age-Related Changes in the Expression of Cadherin-11, the Mesenchyme Specific Calcium-Dependent Cell Adhesion Molecule

Cadherin-11 is a calcium-dependent cell adhesion molecule that is expressed in cells of the mesenchymal lineage during embryonic development. In this study we show, for the first time, that cadherin-11 gene is expressed in the bone marrow and bone cells obtained from rabbits of various age groups. Furthermore, a quantitative measurement of gene expression revealed that cadherin-11 was expressed in young rabbits (6 week-old: open epiphysis) at a level of 6.7 × 10⁵± 0.7 × 10⁵ molecules; in mature rabbits (8–10 month-old: closed epiphysis) at 11 × 10⁵± 0.9 × 10⁵ molecules; and in aged rabbits (4–5 year-old) at a level of 1.2 × 10⁵± 0.2 × 10⁵ molecules/μg total RNA. The relative level of cadherin-11 gene expression in mature rabbit marrow was found to be approximately 50% greater than in young rabbits. However, aged animals showed a reduction in cadherin-11 specific gene expression of greater than 900% as compared with mature animals. Age-related changes in bone remodeling/turnover lead to reduced bone density and high fracture risk, and since cadherins play a crucial role in tissue morphogenesis, this marked decrease may represent an index of the aging process in bone. Received: 2 January 1997 / Accepted: 29 September 1997     

Endothelial Function and Novel Adhesion Molecule CD44 in Kidney Allograft Recipients

Background

Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these 2 processes and inflammation is closely related to endothelial dysfunction.

Patients and Methods

This cross-sectional study on serum concentrations of markers of endothelial damage and inflammation in relation to adhesion molecules was performed in 90 kidney allograft recipients and 30 healthy volunteers. We measured markers of endothelial damage—von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), CD146, CD44, and CD40L; markers of inflammation—high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFα), and interleukin-6 (IL-6); and other hemostatic parameters—thrombin-antithrombin complexes (TAT), plasmin-antiplasmin complexes, and thrombin activatable fibrinolysis inhibitor (TAFI) using commercially available kits.

Results

Markers of endothelial dysfunction and inflammation were significantly elevated in kidney allograft recipients compared with control subjects. CD44 was independently related to hsCRP (r = .37; P < .01), ICAM (r = .23; P < .05), eGFR (r = −.37; P < .01), thrombomodulin (r = .43; P < .001), VCAM (r = −.44; P < .001), hemoglobin (r = −.26; P < .01), red blood cell count (r = −.25; P < .05), creatinine (r = .37; P < .01), CD146 (r = .34; P < .01), and CD40L (r = .23; P < .05). Upon multiple regression analysis the predictors of elevated CD44 were hsCRP concentration (beta = .25; P < .05), CD146 (beta = .39; P < .05), creatinine (beta = .55; P < .01), and thrombomodulin (beta = .39; P < .05) with an adjusted R² = .40 (F = 4.12; P < .00028; SE of estimate = 151.19).

Conclusions

As demonstrated in multiple regression analysis, kidney function was strictly linked to the degree of inflammation and endothelial injury. Endothelial cell injury and the presence of an inflammatory state, as reflected by elevated marker concentrations, and endothelial activation/injury may play roles in the pathogenesis of atherosclerosis and cardiovascular complications among kidney allograft recipients.     

黏附分子CD146与肾脏疾病的研究进展

近年来发现黏附分子CD146在肾脏疾病中表达增加,探讨CD146与肾病的关系有助于进一步了解肾脏疾病的发病机制.本文就近年来CD146与肾脏疾病的研究进展作一综述.     

Neutrophil Elastase Inhibitor, ONO-5046, Modulates Acid-induced Lung and Systemic Injury in Rabbits

Background: Acid instillation leads to direct lung and to secondary systemic organ injury, probably via activated macrophages and neutrophils. This study investigated the effects of neutrophil elastase on organ injury after unilateral lung acid instillation by administrating a specific neutrophil elastase inhibitor, ONO-5046, before acid instillation.

Methods: Three groups of anesthetized rabbits (n = 12 in each group) underwent tracheostomies, and instillations were made into their right lower lobe airspaces with either phosphate buffered saline (pH, 7.4; volume, 1.2 ml/kg; n = 12) or HCl (pH, 1.25; volume, 1.2 ml/kg; n = 24). In half of the acid-instilled rabbits, ONO-5046,10 mg/kg, was given intravenously 15 min before the HCl instillation, and then 10 mg [center dot] kg sup -1 [center dot] h sup -1 of the drug was continuously infused throughout the experiment. The other groups of animals received the vehicle intravenously. Anesthesia and mechanical ventilation was continued for 8 h, whereas arterial blood gases were sampled intermittently. Eight hours after saline or acid instillation, the animals were killed, and their lungs, heart, kidneys, liver, and small intestines were harvested. Wet-to-dry weight ratios (W/D) and myeloperoxidase (MPO) assays of these organs were done, and elastase assays on the bronchoalveolar lavage fluids (BALF) obtained from each lung also were performed.

Results: Pretreatment with ONO-5046 attenuated the physiologic changes seen in the vehicle-treated animals. Significant decreases in W/D of the noninstilled lungs and of the small intestine and normalization of the oxygenation of the experimental animals occurred. The ONO-5046 pretreatment did not affect the neutrophil sequestration in the lungs or in the other organs as determined by neutrophil counts in BALF and by the MPO assays.     

The Effect of Alendronate on Cytokine Production, Adhesion Molecule Expression, and Transendothelial Migration of Human Peripheral Blood Mononuclear Cells

Since both osteoclasts and macrophages belong to the mononuclear phagocytic system it is conceivable that bisphosphonates not only affect bone metabolism but also inflammatory responses. The migration of mononuclear cells into perivascular tissue is a central event in inflammatory reactions. We studied the effects of the aminobisphosphonate alendronate on the transendothelial migration of human peripheral blood mononuclear cells in an in vitro model. Alendronate (at a concentration of 100 μM) significantly increased the percentage of peripheral blood mononuclear cells that migrated through endothelial cell monolayers. Similar results were obtained with another aminobisphosphonate, viz, pamidronate. An overnight treatment of the endothelial cell monolayers with alendronate did not alter the rate of peripheral blood mononuclear cells that subsequently migrated. The overnight cultivation of the peripheral blood mononuclear cells in the presence of alendronate resulted in an increased surface expression of CD54 (intercellular adhesion molecule-1, ICAM-1) in both CD14⁺ and CD3⁺ cells; in CD14⁺ cells also the expression of CD49d (α₄ subunit of late activation antigen-4, VLA-4) increased after alendronate treatment. Alendronate treatment of peripheral blood mononuclear cells also resulted in an increased production of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). We conclude that alendronate has a distinct effect on the transendothelial migration of human peripheral blood mononuclear cells in vitro. Alendronate may either directly or indirectly, e.g., by augmenting the production of proinflammatory cytokines, influence the expression of certain adhesion molecules and thereby facilitate transendothelial migration. These effects could be related to the transient leukopenia reported following intravenous administration of relatively high doses of aminobisphosphonates for the treatment of hypercalcemia of malignancy. Received: 11 September 1997 / Accepted: 20 February 1998     

三参冲剂对肺癌患者粘附因子的影响

目的 研究中药三在冲剂抗肺癌转移机理。方法 采用前瞻性对照研究方法，进行三参冲剂与化疗对中晚期非小细胞肺癌患者粘附因子ＣＤ４４、ＣＤ４９、ＣＤ３１表达和对人皮细胞（ＣＥＣ）影响研究。结果 本研究通过中药三参冲剂对肿瘤患者ＣＤ４４、ＣＶＤ４９、ＣＤ３、ＣＥＣ的影响，初步证实粘附因子、循环内皮细胞在晚期肺癌的表达增加，经中药治疗后可以明显掏肺癌患者Ｄ４４、ＣＤ４９、ＣＤ３１粘附因子和ＣＥＣ的表达，与化     

Constitutive Cyclooxygenase-2 Is Involved in Central Nociceptive Processes in Humans

Background: Prostaglandins play a major role in inflammation and pain. They are synthesized by the two cyclooxygenase (COX) isoforms: COX-1, which is expressed constitutively in many cell types, and COX-2, which is induced at the site of inflammation. However, unlike peripheral tissues, COX-2 is expressed constitutively in the central nervous system and may play a role in nociceptive processes. The current study aimed to investigate the role of constitutive COX-2 in the spinal transmission of nociceptive signals in humans.

Methods: The authors used 12 healthy volunteers to compare the effects of the specific COX-2 inhibitor sodium parecoxib (1 mg/kg) or placebo, administered intravenously in a double-blind and crossover fashion, on the electrophysiologic recordings of the nociceptive flexion (RIII) reflex. The RIII reflex is an objective psychophysiologic index of the spinal transmission of nociceptive signals and was recorded from the biceps femoris after electrical stimulation of the sural nerve. Two experiments, 7 days apart, were conducted in each volunteer. On each experimental day, the effects of parecoxib or placebo were tested on (1) the RIII reflex threshold, (2) the stimulus-response curves of the reflex up to the tolerance threshold (frequency of stimulation: 0.1 Hz), and (3) the progressive increase of the reflex and pain sensations (i.e., "windup" phenomenon) induced by a series of 15 stimulations at a frequency of 1 Hz (intensity 20% above RIII threshold).

Results: Parecoxib, but not placebo, significantly reduced the slope of the stimulus-response curve, suggesting a reduction in the gain of the spinal transmission of nociceptive signals. By contrast, the windup phenomenon was not significantly altered after administration of parecoxib or placebo.     

Intestinal Ischemia-Reperfusion Is Attenuated by Treatment With Atenolol in Rabbits

To study whether treatment with the beta-blocker atenolol (AT) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rabbits were treated with AT (1 mg · kg⁻¹, introvenously) or saline solution (SS) prior to I (60 minutes), which was produced by occlusion of the superior mesenteric artery, and/or R (120 minutes). After I or I/R, 2-cm jejunal segments were mounted in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl using a digital recording system. Thin jejunal slices were stained hematoxylin and eosin for analysis by optical microscopy. Compared to the sham group, the jejunal contractions were similar in the I + AT and the I/R + AT groups, but reduced in the I + SS and the I/R + SS groups. The jejunal enteric nerves were damaged in the I + SS and the I/R + SS groups, but not in the I + AT and the I/R + AT. These results suggest that AT may attenuate intestinal dysfunction caused by I and I/R.     

黏附分子CD146及其与肾脏疾病关系的研究进展

细胞间通过一些连接复合体彼此联系,在维持细胞极性、组织完整性、参与细胞各种生理和病理功能等方面发挥着重要的作用.CD146是一种近年发现的细胞黏附分子,研究发现CD146有着广泛的组织分布.更深入的研究认为CD146除有"分子胶"功能以外,其与肾脏疾病、免疫应答、炎症及肿瘤关系密切,本文对该分子的结构、功能以及其与肾脏疾病的关系作一综述.