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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils and monocytes (phagocytes) are important mediators of injury in many inflammatory diseases, including glomerulonephritis and vasculitis. Current treatment modalities (eg, corticosteroids, cytotoxic agents) are relatively nonspecific in their actions, frequently ineffective, and often associated with immunologic or metabolic complications. Recent advances in cellular and molecular immunobiology have suggested novel targets for therapeutic intervention. Phagocyte adhesion to endothelial cells, in particular, is a central event in the recruitment of phagocytes to sites of inflammation. Phagocyte trafficking to the extravascular space requires the coordinated interactions of several families of adhesion molecules, including the selectins, integrins, and immunoglobulin-like molecules. Initial attachment appears to be achieved by the interaction of phagocyte or endothelial cell selectins with carbohydrate-containing counter-receptors. These events facilitate immobilization of phagocytes via the interaction of phagocyte integrins with immunoglobulin-like molecules on endothelial cells and diapedesis to the extravascular tissue. Chemoattractants and cytokines regulate adhesion by altering the avidity or surface expression of preformed molecules and by influencing de novo synthesis of adhesion molecules. The intensity and composition of leukocyte infiltrates at sites of inflammation likely reflect the local balance of pro- and anti-inflammatory chemoattractants and cytokines and the profile of adhesion molecules on invading and resident cells. Adhesion may also promote tissue injury by augmenting phagocyte oxidative bursts and lysosomal enzyme release and by facilitating release of these cytotoxic molecules in close proximity to tissue cells. In addition, adhesion may amplify the levels and types of inflammatory mediators within a local milieu by promoting transcellular eicosanoid biosynthesis during cell-cell interaction. Increased adhesion molecule expression has been reported in glomerulonephritis, vasculitis, tubulointerstitial nephritis, transplant rejection, and hemodialysis "first-use" reactions. In addition, leukocyte adhesion may be an important event in the pathophysiology of ischemia-reperfusion injury. Monoclonal antibodies against adhesion molecules confer dramatic protection in several models of renal inflammation. Further studies in this area may yield potent and specific therapies for common renal diseases.
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PMID:Leukocyte adhesion molecules: potential targets for therapeutic intervention in kidney diseases. 792 75

Extravasation of leukocytes at the sites of ischemia-reperfusion is thought to exacerbate the tissue injury. It has been proposed that leukocyte accumulation is a secondary effect of the ischemic damage, mediated by inflammatory cytokines. We have recently demonstrated that physiologically low levels of oxygen tension alone can have a direct effect on the adhesive characteristics of mesenchymal cells for lymphocytes. We now report that decrease of oxygen tension in the environment induces the adhesion of neutrophils to human endothelial cells in culture. Adhesion of human neutrophils to human umbilical vein, bovine aortic, and mouse microvascular endothelial cell monolayers, which had been incubated at pO2 of 50 torr for 3 hours, increased 2.5-fold, 2-, and 1.5-fold, respectively. The effects of decreased oxygen concentration on adhesion were not mediated by a soluble factor elaborated by the hypoxic cells. Low oxygen tension upregulates a saturable, endothelial cell-associated adhesion mechanism, capable of withstanding centrifugation forces greater than 160g. Hypoxia-induced adhesion was inhibited by LFA-1-specific (CD11a/CD18 integrin) antibodies, but not by antibodies directed against the ICAM-1 ligand for the LFA-1 receptor. These studies demonstrate that decreases in oxygen tension alone increase the adhesive properties of endothelial cells for leukocytes. In addition, they provide evidence for the existence of a new ligand for the LFA-1 molecule on endothelial cells which can be affected by hypoxic environments.
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PMID:Oxygen tension regulates neutrophil adhesion to human endothelial cells via an LFA-1-dependent mechanism. 825 69

Adhesion of leukocytes (L) to microvascular endothelium (E) is a required step in the L-E interaction leading to tissue injury in ischemia-reperfusion. To assess the optimum period for therapy aimed at ameliorating negative effects of this required step, we investigated the time course of L-E adhesion in the hamster cheek pouch using 2 hr of ischemia and 1 hr of reperfusion in our model of I-R injury (Am. J. Physiol-261: 1626, 1991). Leukocytes adhering (stationary for > or = 30 sec) to postcapillary venules (15-30 microns in diameter) were counted after labeling with acridine orange. Prior to the induction of ischemia, there were no significant differences in the number of adherent leukocytes in each area chosen for study (1.9 +/- 0.6 vs 2.0 +/- 0.3; mean number of leukocytes/100-microns vessel length +/- SD). After 10 and 20 min of reperfusion there was no significant difference in leukocyte adhesion in the ischemic area relative to the control (2.7 +/- 0.5 vs 2.8 +/- 0.8, and 5.3 +/- 2.8 vs 2.4 +/- 0.6, respectively). Leukocyte adherence increased significantly after 30 min of reperfusion and remained elevated at 1 hr of reperfusion in the postischemic area relative to the nonischemic control area (7.8 +/- 1.3 vs 3.6 +/- 0.6, and 8.3 +/- 0.8 vs 4.1 +/- 0.6, respectively; P < 0.01). Leukocyte adhesion in the postischemic area after 30 min reperfusion was not significantly different from the adhesion at the end of 1 hr reperfusion. These data suggest that (1) peak leukocyte adhesion occurs after 30 min of normal reperfusion and (2) postischemic therapeutic intervention may be most beneficial when instituted within this early time period.
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PMID:Time course of leukocyte adhesion to endothelium in ischemia-reperfusion. 876 56

A burst of endothelial derived oxidants including hydrogen peroxide (H2O2) and superoxide (.O2-) occurs on reperfusion of ischemic tissues that directly causes injury; however, it is not known if this also triggers further injury due to subsequent leukocyte adhesion and adhesion molecule expression. Therefore, studies were performed in an isolated heart model developed to enable study of the role of isolated cellular and humoral factors in the mechanism of postischemic injury. Isolated rat hearts were subjected to 20 min of 37 degrees C-global ischemia followed by reperfusion with polymorphonuclear leukocytes (PMNs) and plasma in the presence or absence of superoxide dismutase (SOD), 200 U/ml, or catalase, 500 U/ml. Measurements of contractile function, coronary flow, high-energy phosphates, free radical generation, and PMN accumulation were performed. Adhesion molecule expression was measured on the surface of effluent PMNs by fluorescence flow cytometry and within the tissue using immunohistochemistry. SOD or catalase treatment resulted in 2- to 3-fold higher recoveries of contractile function, coronary flow, and high energy phosphates. EPR spin trapping measurements demonstrated that SOD totally quenched the free radical generation observed upon reperfusion while catalase prevented the formation of hydroxyl and alkyl radicals derived from superoxide. SOD or catalase treatment decreased PMN accumulation in the reperfused heart and prevented the marked upregulation of CD18 expression seen after reperfusion. These experiments demonstrate that in addition to their direct antioxidative actions, SOD and catalase each decrease PMN adhesion and CD18 expression resulting in marked suppression of PMN-mediated injury in the postischemic heart. Thus, endothelial derived H2O2 and .O2- further amplify postischemic injury by triggering CD18 expression on the surface of PMNs leading to increased PMN adhesion within the heart.
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PMID:Superoxide and hydrogen peroxide induce CD18-mediated adhesion in the postischemic heart. 878 38

Bovine Leukocyte Adhesion Deficiency (BLAD) is a genetic disease of cattle affecting the hematopoietic system. In the last decade BLAD has become a disease of economic importance in the dairy industry. As such, this overview describes the chronological developments and thinking that led to the elucidation of BLAD as a distinct disease entity from previous models in canine and human populations. All species affected exhibit symptoms of chronic and recurrent infections. Necrotic and/or gangrenous infections of soft tissues are prevalent, as well as secondary infections with bacteria or fungi. Low birthweight and unthriftiness are key symptoms of neonates in all species affected by LAD. Dermatomycoses and impaired pus formation are also common findings. The physiological basis for BLAD is a deficiency in leukocyte (particularly neutrophil) chemotactic and phagocytic properties. The inhibition of diapedesis in the inflammatory response prevents normal immune reactions to invading pathogens. Chronic infections are a consequence of the faulty immune mechanisms. The biochemical etiology of BLAD involves cell surface glycoprotein molecules known as integrins. These are responsible for cell-cell interactions necessary for neutrophils to adhere to vascular endothelium in a normal individual. Experiments using monoclonal antibodies to block LFA-1, Mac-1, and p150,95 (three integrins vital for cell-cell interactions) mimic BLAD symptomatology and have led to the discovery of the reciprocal Intercellular Adhesion Molecule (ICAM). Through pedigree analysis and biochemical detection with restrictive endonucleases BLAD has been isolated genetically to a single gene locus. The economic significance and prophylaxis are briefly discussed. In addition, the beneficial aspects of the study of BLAD are addressed. There are advantages of producing a BLAD-like state in preventing transplant rejection, ischemia-reperfusion injury, and other scenarios arising from the deleterious effects of the inflammatory response.
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PMID:Bovine leukocyte adhesion deficiency: a brief overview of a modern disease and its implications. 882 96

Polymorphonuclear leukocytes (PMN) are directly involved in development of ischemic myocardial injury. Adhesion of PMN to endothelial cells is an initial step that triggers a sequential process leading to acute inflammatory responses. Interaction between P-selectin and its oligosaccharide ligand, sialyl Lewis x (sLex), plays an important role in the early stage of the adhesion. To examine the role of P-selectin in various animal disease models especially in rats, we have cloned rat E- and P-selectin cDNAs and established monoclonal antibodies against these rat selectins. In this report, we describe the generation and characterization of anti-rat P-selectin antibodies (ARPs). These antibodies detect cell surface P-selectin on thrombin-stimulated rat platelets. More importantly, intravenous administration of ARP2-4 reduced infarction developed after 30 min of ischemia followed by 24 h of reperfusion in a rat myocardial injury model. In addition, similar protective effect was also observed by administration of a sLex-oligosaccharide. These results indicate that cell adhesion mediated via P-selectin is involved in the development of ischemia and reperfusion injury in rat heart.
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PMID:Reduction of rat myocardial ischemia and reperfusion injury by sialyl Lewis x oligosaccharide and anti-rat P-selectin antibodies. 884 11

Intestinal injury caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased mucosal permeability, microvascular injury, focal intravascular thrombus formation, fibrin deposition, and neutrophil infiltration. Ulcerations and adhesions are also prominent feature of this injury. Although NSAID-induced inhibition of prostaglandin formation has been suggested to produce ischemic injury and inflammation, no studies have directly assessed intestinal blood flow in experimental NSAID-induced enteropathy. This study tested the hypothesis that indomethacin-induced small bowel injury and inflammation result from intestinal ischemia. With the use of pulsed Doppler flowmetry, superior mesenteric artery blood flow was continuously monitored in conscious rats after doses of indomethacin known to promote acute and then chronic small bowel inflammation (7.5 mg/kg, 2 sc doses spaced 24 h apart). After 72 h, rats were anesthetized and a section of small bowel was removed for histology and intestinal myeloperoxidase activity measurements. Mean arterial blood pressure was not affected until 32 h after indomethacin, when it decreased 20% (P < 0.05) to P < 0.01). Sustained blood flow changes first occurred at 20 h, when an increase of 15% (P < 0.01) was observed, whereas flow resistance decreased. Flow resistance continued to decrease for the remainder of the 72-h period, and there was an accompanying blood flow increase to +40% (P < 0.05 to P < 0.01). Intestinal ulcers developed in 86% of indomethacin-treated rats. Adhesions, dilation, and thickening of the distal jejunum and proximal ileum were observed in most indomethacin-treated rats. Histological grading of intestinal injury yielded scores of 7.1 +/- 1.2 and zero for indomethacin-treated and vehicle-injected rats, respectively (P < 0.01). Myeloperoxidase activity was greater in indomethacin-treated rats (6.7 +/- 1.9 vs. 1.8 +/- 0.3 U/cm, P < 0.05). These results suggest that indomethacin-induced enteropathy is associated with an increase, not a decrease, in superior mesenteric artery blood flow. Therefore, ischemia dose not appear to be a mechanism by which subcutaneous indomethacin administration produces small intestinal injury and inflammation.
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PMID:Superior mesenteric artery blood flow and indomethacin-induced intestinal injury and inflammation. 889 79

Peritonitis was induced in 12 horses by median celiotomy and 1 hour of small intestinal ischemia. Six horses had primary closure of the incision, whereas six horses had a plastic mesh sutured to the ventral abdominal wall leaving the abdomen open for ventral drainage. The mesh was removed after 5 days and the abdominal wall was closed by apposition of the linea alba and subcutaneous tissues and approximation ef the skin edges. Peritoneal fluid was collected and analyzed for nucleated cell count and total protein concentration on days 0 and 5. Serum biochemical profiles, serum electrolyte concentrations, and complete blood counts were performed on days 0, 1, 2, 5, 6, 10, and 14. Body weight, rectal temperature, and physical examination findings were recorded daily for 30 days, then horses were euthanatized and the abdominal cavity was examined for the presence of adhesions. Histological examination was performed to assess the inflammatory response of the healing body wall; inflammation scores were significantly lower in horses that had primary closure of the incision. The mesh was well tolerated by all horses and allowed egress of peritoneal fluid for 5 days. Adhesions were present in four control horses and in two horses that had open peritoneal drainage. All horses that had open drainage developed incisional infections after mesh removal. Abdominal wall herniation did not occur in any of the horses. The mild peritonitis induced in this study was insufficient to establish the efficacy of open peritoneal drainage for an established peritonitis in horses; however, the results of this study indicate that open peritoneal drainage is feasible in horses.
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PMID:Open peritoneal drainage in horses with experimentally induced peritonitis. 901 2

Adhesions, which occur after 67% to 93% of abdominal operations, represent a major clinical problem, resulting in intestinal obstruction, infertility, and pain and incurring considerable economic costs. The magnitude and seriousness of the problem of adhesions have been underappreciated. Moreover, efforts to prevent or reduce adhesions largely have been unsuccessful, hindered by their empirical basis, the lack of good predictive animal models, and the biochemical complexities of adhesiogenesis. The two major strategies for adhesion prevention or reduction are adjusting surgical technique and applying adjuvants. Modifications in technique that all surgeons should implement include minimizing the invasiveness of surgery, minimizing surgical trauma, such as ischemia from peritoneal suturing, and avoiding the introduction of foreign material, e.g., starch glove powder, into the body. Given the adhesiogenic nature of peritoneal repair, however, improvements in surgical technique alone will help decrease but not prevent adhesion formation. Adjuvant therapy is necessary. Adjuvants fall into two main categories, drugs and barriers. Nonsteroidal anti-inflammatory drugs have shown questionable clinical efficacy, possibly because of difficulties in drug delivery. Corticosteroids, alone or with antihistamines, also have had equivocal clinical results and may be immunosuppressive and delay wound healing. Experimentally, fibrinolytics such as tissue plasminogen activator (tPA), administered systemically or intraperitoneally (i.p.), have demonstrated conflicting results and hemorrhagic complications. However, recently, tPA, administered topically in a carboxymethylcellulose (CMC) gel, has been effective in reducing and preventing adhesions in rabbits. Phosphatidylcholine, given i.p. or orally, also has shown promise in animal studies. Barriers, by separating traumatized surfaces for the critical first five to seven days of peritoneal re-epithelialization, are useful adjuvants, and include macromolecular solutions and mechanical devices. Dextran, a macromolecular solution, has been studied widely, but has not demonstrated consistent clinical efficacy and has been largely abandoned as an anti-adhesion barrier. A newly developed hyaluronic acid-phosphate-buffered saline solution applied intraoperatively to protect peritoneal surfaces from indirect surgical trauma effectively and safely reduced adhesions in a large multicenter study of women undergoing gynecological laparotomy. Three recently developed mechanical barriers also have demonstrated clinical progress in adhesion prevention. A bioresorbable membrane consisting of hyaluronic acid and CMC has gained regulatory approval for clinical use in both general and gynecological surgery following demonstration of efficacy and safety in reducing adhesions. A barrier made of expanded polytetrafluoroethylene and another developed from oxidized regenerated cellulose are currently available for gynecological surgery. With continued research, new and improved approaches hopefully will become available to prevent adhesion formation.
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PMID:Adhesions: preventive strategies. 907 50

This article summarizes the discussions of the faculty and chairpersons on four major topics on postsurgical adhesions examined at the symposium, "Adhesions: Pathogenesis and Prevention". These topics are: 1) clinical significance; 2) pathogenesis; 3) research status and directions; and 4) recommendations for reduction or prevention. Abdominal postsurgical adhesions develop following trauma to the mesothelium, which is damaged often by surgical handling and instrument contact, foreign materials such as sutures and glove dusting powder, desiccation, and overheating. Postoperative adhesions occur after most surgical procedures and can result in serious complications, including intestinal obstruction, infertility, and pain. A long-term and unpredictable problem, postoperative adhesions impact the surgical workload and hospital resources, resulting in considerable health care expenditures. Although understanding of the pathogenesis of adhesions has improved recently, the molecular mechanisms involved continue to be delineated. Adhesions result from the normal peritoneal wound healing response and develop in the first five to seven days after injury. Adhesion formation and adhesion-free re-epithelialization are alternative pathways, both of which begin with coagulation which initiates a cascade of events resulting in the buildup of fibrin gel matrix. If not removed, the fibrin gel matrix serves as the progenitor to adhesions by forming a band or bridge when two peritoneal surfaces coated with it are apposed. The band or bridge becomes the basis for the organization of an adhesion. Protective fibrinolytic enzyme systems of the peritoneum, such as the plasmin system, can remove the fibrin gel matrix. However, surgery dramatically diminishes fibrinolytic activity. The pivotal events determining whether the pathway taken is adhesion formation or re-epithelialization are therefore the apposition of two damaged surfaces and the extent of fibrinolysis. Research in postsurgical adhesion formation and prevention abounds in a variety of avenues of investigation, including: 1) identification on a molecular level of the components involved in adhesiogenesis and their interactions; 2) clarification of the role of fibrin and fibrinolysis in adhesion formation; 3) standardization of design in preclinical and clinical studies of adhesion formation and prevention; 4) delineation of the relationship between adhesion formation and adhesive complications; and 5) elucidation of efficient, site-specific methods of prophylactic drug delivery. Currently, it seems logical to focus preventive research on development of barriers, fibrinolytic drugs, and selected agents such as phospholipids. The major strategies for adhesion prevention or reduction are adjusting surgical practice and applying adjuvants. Surgeons should adjust their major practices by: 1) becoming aware of the potential adhesive complications of a procedure; 2) minimizing the invasiveness of surgery; and 3) minimizing surgical trauma, ischemia, exposure to intestinal contents, introduction of foreign material into the body, and the use of talc- or starch-containing gloves. Available adjuvants include a newly developed by hyaluronic acid-phosphate-buffered saline solution applied intraoperatively to protect peritoneal surfaces from indirect surgical trauma and three mechanical barriers. One of these, a bioresorbable membrane consisting of hyaluronic acid and carboxymethylcellulose, has demonstrated efficacy and safety in both general and gynecological surgery. The other two barriers, one made of expanded polytetrafluoroethylene and one developed from oxidized regenerated cellulose, are indicated only for use in gynecological surgery.
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PMID:Adhesions: pathogenesis and prevention-panel discussion and summary. 907 53


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