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Spontaneous Migration (spontaneous + migration)
Selected AbstractsRole for cAMP-protein kinase A signalling in augmented neutrophil adhesion and chemotaxis in sickle cell diseaseEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2007Andreia A. Canalli Abstract The significance of the leukocyte in sickle cell disease (SCD) pathophysiology is becoming increasingly recognised; we sought to examine whether the chemotactic properties of neutrophils of SCD individuals may be altered and, further, to better understand the signalling events that mediate altered SCD neutrophil function. Adhesion to immobilised fibronectin (FN) and chemotaxis of control and SCD neutrophils were assessed using in vitro static adhesion assays and 96-well chemotaxis chamber assays. Adhesion assays confirmed a significantly higher basal adhesion of SCD neutrophils to FN, compared with control neutrophils. Chemotaxis assays established, for the first time, that SCD neutrophils demonstrate greater spontaneous migration and, also, augmented migration in response to IL-8, when compared with control neutrophils. Co-incubation of SCD neutrophils with KT5720 (an inhibitor of PKA) abrogated increased basal SCD neutrophil adhesion, spontaneous chemotaxis and IL-8-stimulated chemotaxis. Stimulation of SCD neutrophils with IL-8 also significantly augmented SCD neutrophil adhesion to FN with a concomitant increase in cAMP levels and this increase in adhesion was abolished by KT5720. Interestingly, the adhesive properties of neutrophils from SCD individuals on hydroxyurea therapy were not significantly altered and results indicate that a reduction in intracellular cAMP may contribute to lower the adhesive properties of these cells. Data indicate that up-regulated cAMP signalling plays a significant role in the altered adhesive and migratory properties in SCD neutrophils. Such alterations may have important implications for the pathophysiology of the disease and the cAMP-PKA pathway may represent a therapeutic target for the abrogation of altered leukocyte function. [source] Simvastatin regulates oligodendroglial process dynamics and survivalGLIA, Issue 2 2007Veronique E. Miron Abstract Simvastatin, a lipophilic statin that crosses the blood-brain barrier, is being evaluated as a potential therapy for multiple sclerosis (MS) due to its anti-inflammatory properties. We assessed the effects of simvastatin on cultures of rat newborn and human fetal oligodendrocyte progenitor cells (OPCs) and human adult mature oligodendrocytes (OLGs) with respect to cellular events pertaining to myelin maintenance and repair. Short-term simvastatin treatment of OPCs (1 day) induced robust process extension, enhanced differentiation to a mature phenotype, and decreased spontaneous migration. These effects were reversed by isoprenoid products and mimicked with an inhibitor of Rho kinase (ROCK), the downstream effector of the isoprenylated protein RhoA GTPase. Prolonged treatment (2 days) caused process retraction that was rescued by cholesterol, and increased cell death (4 days) partially rescued by either cholesterol or isoprenoid co-treatment. In comparison, simvastatin treatment of human mature OLGs required a longer initial time course (2 days) to induce significant process outgrowth, mimicked by inhibiting ROCK. Prolonged treatment of mature OLGs was associated with process retraction (6 days) and increased cell death (8 days). Human-derived OPCs and mature OLGs demonstrated an increased sensitivity to simvastatin relative to the rodent cells, responding to nanomolar versus micromolar concentrations. Our findings indicate the importance of considering the short- and long-term effects of systemic immunomodulatory therapies on neural cells affected by the MS disease process. © 2006 Wiley-Liss, Inc. [source] Ricochet of a Bullet in the Spinal Canal: A Case Report and Review of the Literature on Bullet MigrationJOURNAL OF FORENSIC SCIENCES, Issue 5 2010Audrey Farrugia M.D. Abstract:, Ricochet of a bullet in the spinal canal is well known by neurosurgeons but relatively not a common event in usual medico-legal autopsy practice. This article presents a homicide case of a penetrating gunshot injury of the lumbar spine through the T12-L1 intervertebral foramen with active movement of the projectile within the spinal canal to the L5-S1 level. This case illustrates a bullet intradural and intramedullary active movement because of a ricochet of the body of T12 with active redirection of the path. In the current literature, different types of migration in caudal or cranial direction, intradural, or intramedullary are reported. If spontaneous migration of T10 to S1 seems to be more frequent, some authors reported a C1 to S2 migration. Such migration could be asymptomatic or induce neurological impairment. The medico-legal consequences of these migrations within the spinal canal are described. [source] Gastrointestinal and biliary stentsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2010Hoon Jai Chun Abstract Advances in stent design have led to a substantial increase in the use of stents for a variety of malignant and benign strictures in the gastrointestinal tract and biliary system. Whereas early stents were mostly composed of plastic, the majority of contemporary stents are self-expanding metal stents that are composed of either nitinol or stainless steel. These stents are able to exert an adequate expansile force and, at the same time, are highly flexible and biocompatible. Covered stents have been introduced to minimize tumor ingrowth through the metal mesh but are associated with higher rates for spontaneous migration. This has led to the development of covered stents with uncovered ends and stents with both covered and uncovered layers. Drug-eluting and biodegradable stents are also likely to become available in the near future. Although stents appear to be the preferred form of palliation for some patients with advanced cancer, many patients will benefit from a multidisciplinary approach that usually includes surgeons and oncologists. [source] CXCR4 chemokine receptors (CD184) and ,4,1 integrins mediate spontaneous migration of human CD34+ progenitors and acute myeloid leukaemia cells beneath marrow stromal cells (pseudoemperipolesis)BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Jan A. Burger Summary. Marrow stromal cells play an important role in regulating the development and proliferation of haematopoietic stem cells (HSC) within the marrow microenvironment. However, the molecular mechanisms of stem cell,stromal cell interactions are not fully understood. We observed that mobilized peripheral blood and cord-blood-derived CD34+ progenitor cells, or CD34+ acute myeloid leukaemia (AML) cells spontaneously migrated beneath marrow stromal cells, an in vitro migration phenomenon termed pseudoemperipolesis. In contrast, the CD34+ myeloid leukaemia cell line, Kasumi-1, did not display pseudoemperipolesis. Cord blood CD34+ cells had a higher capacity than granulocyte-colony-stimulating-factor-mobilized CD34+ cells for pseudoemperipolesis (28·7 ± 12%vs 18·1 ± 6·1% of input cells within 24 h, mean ± SD, n = 8), whereas 9·4 ± 12·6% (mean ± SD, n = 10) of input AML cells displayed this phenomenon. Pseudoemperipolesis of CD34+ progenitor and AML cells was significantly inhibited by pertussis toxin and antibodies to the CXCR4 chemokine receptor (CXCR4, CD184), but not control antibodies. Moreover, CD34+ and AML cell migration was significantly inhibited by a CS1 peptide that blocks ,4,1 integrin binding, but not by a control peptide, in which the fibronectin binding motif was scrambled. Pseudoemperipolesis was associated with an increased proliferation of migrated CD34+ progenitor cells but not AML cells within the stromal layer, demonstrated by cell cycle analysis and cell division tracking. We conclude that ,4,1 integrin binding and CXCR4 chemokine receptor activation are prerequisites for the migration of CD34+ haematopoietic progenitors and AML cells beneath marrow stromal cells. These observations suggest a central role of marrow stromal cells for HSC trafficking and homing within the marrow microenvironment. [source] | ||||||||||