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Electron microscope study on the contact of neural crest cells in the early stage of migration in bantam embryos.

The early stage of migration of neural crest cells was observed in the mid-brain level of bantam embryos (5-somite stage to 15-somite stage) by transmission) electron microscopy. It was confirmed that the migration of the neural crest cells starts at the stage of 7-8 somites and ends at the stage of about 14 somites. During this period, not only the contact of migrating crest cells with each other but also the contact between migrating cells and superficial ectodermal cells and/or neural tube cells was observed. Intercellular distance in those contact regions was 3-4 nm. The contact between the migrating crest cell and the basement membrane of the neural tube cell and of the ectodermal cell as well as the contact between the neural crest cell and the fibrillar structure in the environment was also seen. These findings suggest the possibility of transitory interaction for migration between neural crest cells with each other, between neural crest cells and cellular components of the environment where these crest cells migrate, and between neural crest cells and extracellular structures in the environment.

Animals

Interactions between salmonellae and macrophages of guinea pigs. IV. Relationship between migration inhibition and antibacterial action of macrophages.

The in vitro macrophage migration inhibition test was used to detect the development of delayed-type hypersensitivity in guinea pigs infected with Salmonella typhimurium. Four different preparations from supernatants of S. typhimurium cultures were used as the antigens in this test. They included the concentrated bacterial antigens, the high-molecular-weight (>50,000) antigens, the ammonium sulfate-precipitated antigens, and the ribonuclease-treated antigens. All four antigen preparations were shown to inhibit the migration of peritoneal macrophages of salmonella-infected (immune) guinea pigs from capillary tubes, in comparison with cells of normal control animals. By use of the high-molecular-weight antigens and the ammonium sulfate-precipitated antigens, the production of the migration inhibition factor(s) was elicited from cultures of lymphocytes obtained from the peripheral blood of immune guinea pigs. The activity of the migration inhibition factor(s) was demonstrated by its ability to inhibit the migration of peritoneal macrophages of normal guinea pigs from capillary tubes. In contrast, normal peritoneal macrophages exposed to products of antigen-stimulated immune lymphocytes did not exhibit an enhanced phagocytic or bactericidal action against virulent S. typhimurium as compared with those of the normal control. The present study indicated that the bacterial antigens responsible for the elicitation of the production of the migration inhibition factor from lymphocytes of immune guinea pigs are inactivated by proteolytic enzymes, but not by ribonuclease, and have molecular weights of >50,000.

Animals

[Effect of synovial fluid from rheumatoid arthritis patients on leukocyte migration].

By means of the migration inhibition test, the influence of the synovial fluid of rheumatoid arthritis patients on normal blood lymphocytes was investigated. There was the hypothesis that the migration inhibitory factor is already formed in the synovial membrane of rheumatoid arthritis patients. In 35 cases a migration inhibition could be demonstrated, in 3 cases the migration of normal lymphocytes remained uninfluenced, in 6 cases a migration enhancement occurred. The demonstration of the rheumatic factor in the synovial fluids used was partly positive, partly negative. Especially the demonstration of a migration enhancement--this phenomenon could be reproduced repeatedly--cannot yet be interpreted unequivocally and requires further investigations.

Arthritis, Rheumatoid

Leucocyte capillary migration: an adherence dependent phenomenon.

To determine the mode of action of leucocyte inhibitory factor (LIF) on polymorphonuclear leucocyte (PMN) migration out of capillary tubes, this phenomenon has been compared with PMN adhesion to cotton wool columns. Colchicine and vinblastine sulphate had no effect on either of these processes but cytochalasin B caused marked inhibition of PMN migration and increased PMN adhesion. The cytochalasin B effect could be reversed in the presence of drugs known to increase intracellular levels of cyclic AMP. For inhibition of PMN migration by LIF, Mg2+ but not Ca2+ was essential. LIF not only inhibited PMN migration but also increased PMN adhesion to cotton wool columns. LIF inhibitory activity on PMN migration was not affected by colchicine or vinblastine. Leucocyte migration and adhesion depend on similar mechanisms, and are both influenced by LIF which probably acts by affecting micro-filament function.

Calcium

Delayed hypersensitivity to human encephalitogenic protein as assayed by agarose leucocyte migration in multiple sclerosis patients.

Using a leucocyte migration test (Clausen's direct agarose gel migration method) hypersensitivity to human encephalitogenic protein has been examined in 50 multiple sclerosis patients (group 1), 50 healthy persons (group 2) and 25 patients with other neurological diseases (group 3). In group 1, 30 MS patients (60%) show an abnormal migration index, manifested either as inhibition or stimulation of migration; 29 controls in group 2 (58%), 11 O.N.D. patients in group 3 (44%) show an abnormal migration index. These results mean that lymphocyte hypersensitivity to myelin basic protein appears neither to be constant nor specific to multiple sclerosis. Three migration index curve types at different antigen concentration are obtained: monophasic curves within the normal index zones; monophasic curves staying in the inhibition or stimulation zone and biphasic curves with dose-effect relationship. Whatever the antigen used, this dose-effect relationship implies that the test must be carried out at different concentrations. The meaning of spontaneous sensitisation in healthy controls is discussed.

Adolescent

Regulation of macrophage migration by products of the complement system.

Agents formerly shown to induce rapid macrophage spreading were examined for their ability to modify the migration of macrophages in the capillary tube assay. Products of the activation of the contact phase of blood coagulation as well as the purified component Bb, the large cleavage fragment of factor B of the alternative complement pathway produced a dose-dependent inhibition of migration. In addition, inflammatory macrophages elicited with either a lipopolysaccharide endotoxin or thioglycollate medium exhibited rapid spreading and inhibited migration, whereas resident cells did not. A close correlation existed, therefore, between enhanced spreading and inhibited migration under both in vitro induced and in vivo situations. Cleavage products of component C5 of the classical complement pathway enhanced macrophage migration and did not alter spreading. In mixtures of C5 cleavage products and Bb, the predominant peptide determined the outcome of the reaction. Factor B, a normal secretory product of macrophages, may represent a common substrate for several of the proteases that induce spreading, inhibit migration, and lead to the generation of the enzymatically active fragment Bb.

Ascitic Fluid

Human leucocyte response to migration inhibitory activity from lymphocytes. Modification by aprotinin, Tranexamic acid and phenylmethyl sulfonylfluoride.

Human lymphokines can elicit several effects associated with inflammation, e.g. leucocyte migration inhibition and fibrinolysis. These effects can be assessed in vitro by the leucocyte migration agarose technique (LMAT) and the leucocyte migration fibrinolysis technique (LMFT). The present study shows that preincubation of normal leucocytes with aprotinin, tranexamic acid and phenyl-methyl-sulfonylfluoride (PMSF) reduces or abolishes their migration inhibition response to leucocyte migration inhibition factor. The compounds exert this effect at non-toxic concentrations, which do not otherwise interfere with migration or fibrinolysis, and are non-toxic as estimated by PHA stimulation of lymphocytes. The LMFT is more sensitive to the modifying effect than the LMAT. The effect of aprotinin and tranexamic acid is reversible, the effect of PMSF is irreversible.

Aprotinin

Leukocyte migration in agarose, a study on multiple sclerosis.

The effect of low concentrations of bovine encephalitogenic protein on the migration of human peripheral leukocytes in agarose was studied. A concentration of 0.3 mug/ml of the protein stimulated the migration of cells from many donors, including some healthy subjects. An indirect technique suggested that the migration enhancement is due to the production of soluble factor, possibly corresponding to the leukocyte migration enhancement factor described by others. The frequency of subjects whose cells could be stimulated and the recorded degree of stimulation tended to be higher in a group of patients with multiple sclerosis than in a group of healthy subjects. When the effect of some of the main peptide fragments of the protein was studied on cells that were stimulated by the intact protein, one or more of these peptides sometimes induced the opposite effect: a migration inhibition. There is, apparently, a complex balance between enhancing and inhibiting factors acting on leukocyte migration in vitro; and the character of the antigen seems to be one important factor.

Amyotrophic Lateral Sclerosis

Chemotaxis or migration inhibition of rabbit peritoneal polymorphonuclear leukocytes caused by chemoattractants at various concentrations.

Purified lipopolysaccharide (LPS) from Veillonella incubated in normal rabbit serum was tested for chemotactic activity on rabbit polymorphonuclear leukocytes (PMNs) in modified Boyden chambers. In doses above those giving optimal response (over-optimal dose), a decrease of the PMN migration activity was found. This decrease also correlated well with an increase in the migration inhibition of the PMNs as demonstrated with the capillary tube assay. The PMN chemotactic factor isolated from LPS-induced inflammatory exudate (LPS-CF) in rabbits, produced both a decrease in chemotactic response and a migration inhibition of PMNs in over-optimal doses. This inhibitory effect was not due to cytotoxicity, proved by the trypan blue exclusion test. Also, a reduced locomotion of PMNs first preincubated with chemoattractants and then reactivated, was shown when the same PMNs were restimulated to migration using the same chemoattractants. This was interpreted as a deactivation of the cells. A cross-deactivation was demonstrated between LPS-CF and casein. The results from the experiments reported show that the Boyden chamber may be used to disciminate directional chemotaxis and migration inhibition. It may also be concluded from the study that the reduced migration activity of PMNs at over-optimal doses of chemoattractants is not due to cytotoxicity, but most probably is caused by a deactivation of the cells.

Animals

Platelet migration inhibtion as an indicator of immunologically mediated target cell injury in canine ehrlichiosis.

A platelet migration inhibition test was devised to determine the presence of antiplatelet activity in serum collected from experimentally produced and natural cases of canine ehrlichiosis. The maximum platelet migration inhibition effect was observed during the acute phase of the disease and before the appearance of specific humoral antibody, measured by the indirect fluorescent-antibody test. Platelet migration inhibition may be one of the earliest events leading to pancytopenia. In most cases, sera positive for humoral antibodies also were positive for platelet migration inhibition, although no direct correlation was evident between the serological titer and the degree of platelet migration inhibition. Inoculation of dogs with uninfected canine blood did not induce the production of inhibition factor or antibody activity, which precluded a histocompatibility response to the cellular elements in the inoculum. Scanning electron microscopy indicated that the platelet inhibition factor interfered with platelet migration by inhibiting pseudopod formation. Affected platelets became rounded and showed evidence of clumping and leakage.

Animals

Inhibition of macrophage migration by muramyl peptides.

In the capillary tube migration system a synthetic muramyl dipeptide (MDP; N-acetylmuramyl-L-alanyl-D-isoglutamine), a part of bacterial cell wall peptidoglycans, inhibited the migration of peritoneal exudate macrophages from normal guinea pigs or rats. The migration inhibition was also caused by some MDP-containing peptidoglycan fragments from cell walls of Lactobacillus plantarum and Staphylococcus epidermidis. The migration inhibition could not be explained on the basis of macrophage migration inhibitory factor. A stereochemically highly specific structure of MDP required for its adjuvant activity was also required for the macrophage migration inhibition. These findings suggest that MDP and MDP-containing cell wall fragments may activate macrophages and that this activation may be important in the exertion of their adjuvant activity.

Acetylmuramyl-Alanyl-Isoglutamine

Preoperative Proximal Migration of the Radial Head as an Independent Predictor of Suboptimal Outcomes After Osteochondral Autograft Transplantation for Capitellar Osteochondritis Dissecans: A Retrospective Cohort Study.

BACKGROUND: Osteochondral autograft transplantation (OAT) is widely performed for capitellar osteochondritis dissecans (OCD). However, preoperative predictors of suboptimal postoperative outcomes remain unclear. PURPOSE/HYPOTHESIS: The authors aimed to evaluate clinical outcomes after OAT for capitellar OCD and identify preoperative risk factors associated with suboptimal outcomes. They hypothesized that radiographic indicators of disease severity, including preoperative proximal migration of the radial head, lesion size, and lateral wall disruption, would be associated with suboptimal postoperative clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of adolescent athletes who underwent OAT for capitellar OCD with a minimum 2-year follow-up were retrospectively reviewed. Clinical outcomes included elbow range of motion (ROM) and Timmerman-Andrews (T-A) score. A suboptimal outcome was defined as a postoperative T-A score <160. Preoperative radiographs were used to measure proximal migration of the radial head relative to the coronoid process, hypertrophy of the radial head, OCD lesion area, and a 5-grade lateral wall disruption classification; measurement reliability was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of a suboptimal outcome, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for proximal migration. RESULTS: A total of 69 elbows (mean age, 13.6 years; mean follow-up, 48 months) were included. ROM and T-A scores improved significantly after OAT, and all athletes returned to any sports. Of these, 50 elbows (72%) achieved good outcomes, whereas 19 (28%) had suboptimal outcomes. Preoperative proximal migration was significantly greater in the suboptimal outcome group compared with the good outcome group (mean, 2.1 &#xb1; 2.3 vs 0.5 &#xb1; 1.7 mm; P = .002), as were lesion area (mean, 70 &#xb1; 16 vs 58 &#xb1; 20 mm2; P = .02) and lateral wall disruption grade (median, 5 vs 3; P = .01). On multivariate analysis, proximal migration of the radial head was the only independent predictor of a suboptimal outcome (adjusted OR, 1.47 per 1-mm increase; 95% CI, 1.03-2.09; P = .033). ROC analysis showed an area under the curve of 0.72 with an optimal cutoff of 2.2 mm (sensitivity, 56%; specificity, 84%). CONCLUSION: OAT resulted in significant clinical improvement in adolescents with capitellar OCD; however, 28% of patients were classified as having suboptimal outcomes. Preoperative proximal migration of the radial head is an independent predictor of a suboptimal postoperative outcome. A value >2.2 mm may indicate advanced radiocapitellar incongruity, a condition in which OAT may be less effective.

Humans

Migration strategies, connectivity and corridor features of the partial migrant little bustard (Tetrax tetrax) across the Iberian Peninsula.

The study of migration ecology is crucial for understanding the factors and pressures affecting migratory species. Here, we studied the migratory ecology of the little bustard (Tetrax tetrax), a steppe bird that has suffered a sharp decline over recent decades, mainly due to agricultural intensification. Using 105 adult birds tagged across the main Iberian regions where the species is present (Alentejo, Extremadura, Ebro Valley, Northern Plateau, Southern Plateau and Guadalquivir Valley), we analysed the ratio of migratory and resident birds in each population and assessed their connectivity during the three main migratory periods (summer, winter and pre-breeding). Additionally, we describe the features of the migrations recorded in terms of length, duration and day period. Our results corroborate that little bustards can be considered partial migrants across Iberia, although the proportion of residents versus migrants varied between populations: the Alentejo (94.74%) and Northern Plateau (93.75%) had the highest proportion of migrants, followed by Guadalquivir Valley (81.82%), Extremadura (65.38%), Southern Plateau (55.56%) and Ebro Valley (25.93%). Migratory connectivity varied between periods: the pre-breeding and summering migrations showed a trend to move northwards, while birds moved southwards for winter. Regarding the migratory corridors obtained from the 253 migrations identified, we found three main routes: one corridor that connects the Northern Plateau with the western part of the Southern Plateau and Extremadura, another one that connects the Southern Plateau, Extremadura, Alentejo and Guadalquivir Valley, and one corridor that concentrates migrations within the Ebro Valley, and between the Ebro Valley and the Southern Plateau. Finally, analyses showed that little bustards migrate at night through areas dominated by herbaceous cover (avoiding tree-covered land and water bodies) and of low elevation and terrain roughness. Our results highlight the importance of developing an international and inter-regional conservation strategy to protect not only the breeding and wintering quarters, but also this endangered species' migratory corridors, thus supporting the viability of the metapopulation.

Brownian bridge kernel

[Investigations about the influence of immune complexes on in vitro migration of human neutrophilic blood granulocytes (author's transl)].

We studied the influence of cell-free culture supernatants of human blood mononuclear cells exposed to precipitated immune complexes on the migration of polymorphnuclear leukocytes. During the first phase of incubation supernatants from apparently unaffected control cultures were found to stimulate the spontaneous and chemotactic migration (migration enhancing factor, chemotactic factor). In the further course mononuclear cells spontaneously produced a migration inhibitory activity. The presence of immune complexes increased the production of the neutrophil migration inhibitory activity and of the chemotactic factor. Considering our recently published results the experiments confirm the concept that immune complexe act on granulocyte migration in two ways: they induce a release of mediators from neutrophils as well as from mononuclear cells. Our present investigations deal with the question what type of cells-monocytes or lymphocytes-is responsible for this effect.

Antigen-Antibody Complex

A multinational Andean genetic and health program. VIII. Lung function changes with migration between altitudes.

Studies of lung function in high altitude populations have suggested the influence of hypoxic environment on the development of this characteristic independent of confounding variables such as ethnicity and habitual exercise. However, often the effect of altitude on vital capacity is greater in children than adults, suggesting that more than developmental adaptation is operative. Also selective migration could account for the similarity of migrants and permanent residents at a destination altitude. To explore these problems we studied the lung function (FVC, FEV1, PFR) of 377 individuals who had migrated between altitudes in northern Chile. Migrant measurements were adjusted to those of permanent residents of appropriate age, sex and height at the altitudes of origin and destination. The measurements were then related to ethnicity (Spanish-Aymara ancestry), occupation and permanence, the latter combining information on both age at migration to and length of stay at a destination altitude. Upward migration was associated with increased chest depth, FVC and FEV1, but not height or other chest measurements. Downward migration had no significant effect. The flow-dependent test PFR was so sensitive to observer variability and occupation that it was difficult to establish its relationship to permanence. Unlike the body measurements, lung function measurements (especially PFR) tended to deviate from permanent controls at the origin altitude in a direction suggestive of selective migration, nor was permanence itself independent of ethnicity and occupation. Because of these difficulties the question of developmental adaptation in lung function may not be answerable in cross-sectional studies like the present and previous efforts, but rather in longitudinal investigations in which the control is the individual him/herself.

Adaptation, Physiological

Recruitment of effector lymphocytes by initiator lymphocytes. In vivo migration of in vitro sensitized initiator T lymphocytes.

We previously found that mouse T lymphocytes sensitized in vitro against allo- or syngeneic fibroblasts, upon injection into syngeneic recipients, do not themselves differentiate into effector cells, but recruit effector T lymphocytes within the draining lymph nodes. As a result of sensitization, these initiator lymphocytes acquire a trypsin-sensitive membrane property which is necessary for recruitment. We now report studies on the in vivo migratory behavior of initiator lymphocytes following sensitization. We injected 51Cr-labeled initiator lymphocytes into recipient footpads and found significantly increased migration of sensitized cells to the draining popliteal lymph node (PLN) during the first day. By amputation of the foot at various times, we showed that migration during the first 12-24 hours was critical for subsequent recruitment. Trypsin treatment of initiator lymphocytes abolished this accelerated migration. Lymphocytes triggered nonspecifically by Con A migrated to the PLN like antigen-sensitized cells. We also compared the migration of injected lymphocytes from the footpad to the PLN in graft-versus-host and host-versus-graft reactions, and found these reactions to differ both from each other and from recruitment in terms of lymphocyte migration. These findings are discussed in terms of the physiology of the cell-mediated immune response and the notion of peripheral sensitization.

Animals

The in vitro migration of murine fetal liver cells to thymic rudiments.

The migration of murine fetal liver cells to thymus rudiments was studied in vitro using a migration under agar technique. There appeared to be a minor population that migrated specifically to the thymus from the age of 10 to 14 days of gestation. The specificity of migration was demonstrated in 12-day fetal liver cells by a series of competition studies. The ability of these cells to colonize a thymus rudiment was shown by further incubation after invasion of the epithelial thymus rudiments: small colonies of lymphoid cells were present in invaded tissue but absent from uninvaded control tissue. At 13 to 14 days of gestation, there appeared an additional population that migrated specifically to the spleen, as demonstrated, again, with a competition protocol. Studies with avian and human tissue as attractants in the same system showed that migration was specific to the thymus and did cross species barriers. This observation was used to demonstrate a similar attractant activity in cell-free conditioned medium from human thymus epithelial cultures, and to demonstrate the absence of such a cell-attractant factor in the conditioned medium from the thymus of a child with previously documented severe combined immunodeficiency disease.

Animals

Reversibility of Nuclear and 3D Genomic Changes in Non-Cancerous Fibroblasts After Constricted Migration.

Metastatic cancer cells and healthy fibroblasts must traverse constrictive spaces to reach secondary sites. After passing through multiple constrictions, cancer cells often experience stable changes to their nucleus morphology, 3D genome structure, and migratory phenotype. Here, we investigate whether fibroblasts (BJ-5ta), which are non-cancerous and have an inherent ability to migrate to fulfill roles in wound repair, likewise experience nuclear and 3D genomic changes with constricted migration. We find that BJ-5ta cells only slightly increase their migratory capacity after sequential constricted migrations but do experience nuclear deformations and 3D genome alterations at the compartment level after constricted migration. Transient compartment shifts spatially rearranged genes associated with preparation for and response to migration. Unlike the stable changes associated with long term phenotype changes in cancer cells, however, the nucleus deformations recovered back to unmigrated levels following proliferation and cell movement. Some compartment changes persist and might influence responses to future stimuli, but most 3D genome changes revert to the unmigrated state after cell proliferation. Our study shows that non-cancerous migratory cells are not necessarily less susceptible to nucleus and 3D genome alterations caused by constricted migration, but do recover from such alterations more readily than cancer cells. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].

Journal Article