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Garlic extract (allium sativum) reduces migration of neutrophils through endothelial cell monolayers.

Leukocytes play an important role during inflammation. They migrate from intravascular spaces into tissues and attack micro-organisms. In a recent study, the inhibitory effects of the non-steroidal anti-inflammatory drug, ibuprofen, on leukocyte transmigration were demonstrated using an in vitro assay. Little is know about the cellular effects of garlic extracts (allium sativum). The aim of the current study was to investigate the influence of garlic extract on leukocyte migration through endothelial cell monolayers and thereby evaluate a possible role in inflammatory processes. Human umbilical endothelial cells were cultured on microporous membranes to make an endothelial cell monolayer (ECM). Freshly isolated neutrophils were used in a recently described migration assay. The amount of untreated neutrophils migrating through the untreated ECM was used as control and set at 100%. Neutrophils and/or ECM were pre-treated with garlic extract using moderate, as well as higher and lower concentrations. Moderate plasma concentrations garlic extract inhibited neutrophil migration through ECM significantly (64 +/- 5.8% SD; P < 0.05), when both cell types were treated, (a situation that may have clinical relevance). Treating either neutrophils or ECM alone showed significant reductions in migratory rate (neutrophils treated alone: 81 +/- 7.7% SD, p < 0.05; ECM alone: 70 +/- 6.7%, p < 0.05). Thus, garlic extract is identified as a potent inhibitor of leukocyte migration through endothelial cell monolayers. Treatment of both cell types has an additive effect. Endothelial cells seem to be more affected than neutrophils. Further investigations are necessary to understand the potential clinical consequences. During inflammation, neutrophils play an important role. They migrate rapidly from the vascular space into tissues to destroy invading micro-organisms. During migration through endothelial cell monolayers (ECM), neutrophils undergo morphologic changes from rounded, relatively smooth cells to elongated, ruffled cells with pseudopodia. Recently, the influence of the non-steroidal anti-inflammatory drug, ibuprofen, on leukocyte function was investigated using an in vitro double chamber migration assay that includes ECM. Garlic extract (allium sativum) is a widely used "over the counter" herbal preparation. The effect of garlic on lipid metabolism is well documented. Previous studies have examined the influence of the extract on leukocyte function, e.g. respiratory burst. The effect of garlic on thrombocyte aggregation has also been recently described as has an anti-fungal effect. To our knowledge, nothing is known about the effect of garlic leukocyte transmigration. Therefore, we aimed to examine the effects of garlic extract on leukocyte transmigration through ECM in an in-vitro cell co-culture system.

Allium↗

The effects of migration on the establishment of networks: caste disintegration and reformation among the Indians of Fiji.

"This article focuses on how migration auspices affect the formation of migrant networks and ethnic communities. Using ethnographic data and migration histories to focus on caste ¿reformation' in the subcommunities of the Indians of Fiji, the ability to reestablish and maintain subcaste group ¿extensions' in Fiji is shown as directly related to the migration auspices that originally established the community. By determining the characteristics of migrants, the reason for migrating, and the magnitude and duration of migration streams, migration auspices define a migration type. This migration type affects the strength and density of social ties present in migration streams. It also affects the strength and density of network ties that members of a migrant community can establish in a receiving society."

Asia↗

Inhibition of lymphocyte endothelial adhesion and in vivo lymphocyte migration to cutaneous inflammation by TA-3, a new monoclonal antibody to rat LFA-1.

Lymphocyte function-associated Ag-1 (LFA-1) or CD11a/CD18 mediates lymphocyte adhesion to cultured vascular endothelial cells (EC). Thus, LFA-1 likely plays a major role in lymphocyte migration out of the blood, but there is little information on this in vivo. Small peritoneal exudate lymphocytes (sPEL) and lymph node (LN) lymphoblasts adhere to cytokine-activated EC and preferentially migrate to cutaneous inflammatory sites. The role of LFA-1 in the adherence and in vivo migration of these T cells was determined. Because of a lack of anti-rat LFA-1, mAb were prepared to rat T cells. One mAb, TA-3, inhibited homotypic aggregation; T cell proliferation to Ag, alloantigens, and mitogens; stained all leukocytes; and immunoprecipitated 170- and 95-kDa polypeptides from lymphocytes and neutrophils. TA-3 binding to lymphocytes also required Ca2+, but not Mg2+. Thus, TA-3 appears to react with rat LFA-1. TA-3 inhibited spleen T cell adhesion to unstimulated EC by 30% and to IFN-gamma, TNF-alpha, IL-1 alpha, and LPS stimulated EC by 50 to 60% but inhibited sPEL EC adhesion by only 10%. TA-3 also strongly inhibited anti-CD3-stimulated LN T cell adherence. The migration of spleen T cells to delayed-type hypersensitivity and skin sites injected with LPS, poly I:C, IFN-gamma, IFN-alpha/beta, and TNF was inhibited by 72 to 88% by TA-3, and was decreased by 50% to peripheral LN. TA-3 caused less but still 50 to 60% inhibition of sPEL migration to inflamed skin. Lymphoblast migration to skin was inhibited 40 to 80% and to PLN by 30%. Migration of lymphocytes from all sources to mesenteric LN was inhibited by 32 to 60%. In conclusion, LFA-1 mediates much of the adherence of spleen T cells and lymphoblasts to EC in vitro, most of the migration of these cells to dermal inflammation and about 50% of the homing of LN and spleen T cells to peripheral and mesenteric LN. sPEL are less dependent on LFA-1 for adhesion to EC in vitro and for migration to inflamed skin and LN in vivo.

Animals↗

Inhibition of leukocyte migration by the agarose plate technique. Application to antigen from Candida albicans and Fusobacterium nucleatum.

Leukocyte migration inhibition by antigen from Candida albicans and Fusobacterium nucleatum was studied in man by means of the direct leukocyte migration agarose technique (LMAT). Antigens were prepared by prolonged ultrasonication and were added to the leukocyte cultures in the original as well as in the concentrated solutions. Significant inhibition of migration with a 10-fold concentrated solution of candida antigen was demonstrated in subjects showing apositive intracutaneous reaction to candida. With the fusobacterial antigen, inhibition of migration or stimulation of migration were demonstrated in subjects with slight peridontal inflammation. A 5-fold increase in the concentration of fusobacterial antigen resulted in increased stimulation of migration or inhibition of migration. Preincubation of the leukocytes with puromycin abolished both inhibition and stimulation of migration by candidal or fusobacterial antigen. The study confirms that it is important to study dose-related effects when applying the LMAT to test cell-mediated immunity. The study is in support of stimulation of migration being an immunologic reaction.

Antigens, Fungal↗

Migration trends in British rural areas from the 18th to the 20th centuries.

"Longitudinal residential histories are used to examine the extent to which three rural areas in Britain had distinctive migration histories from the 18th to the 20th centuries. Migration flows into and out of the regions are used to examine the extent to which the regions were integrated into the British migration system, and the relative importance of rural to urban migration is assessed.... Analysis reveals a high degree of short-distance mobility within regions and emphasises the dominance of London in longer-distance migration.... It is also suggested that the role of towns in the migration system has previously been overemphasised, with much migration taking place between small settlements and some movement from large cities to smaller towns and villages.... The analysis challenges some accepted notions about migration in the past, and contributes to the debate about the extent to which British regions became part of a national economic and social system from the 18th century."

Demography↗

Immigration impacts on internal migration of the poor: 1990 census evidence for U.S. states.

"This article presents newly-available migration data from the 1990 U.S. census to assess immigration and internal migration components as they affect state poverty populations. New immigrant waves are heavily focused on only a few 'port-of-entry' states. It is suggested that these immigrants have begun to impact upon internal migration into and out of these 'high immigration states', and have also altered the national system of internal migration patterns. This article addresses three questions: How do the magnitudes of poverty population out-migration from high immigration states compare with those of other states? Is this out-migration selective on particular social and demographic groups? Is immigration a significant determinant of internal migration of the poor population? The results of this analysis are consistent with the view that recent, focused immigration is associated with out-migration among a state's poor longer-term residents."

Americas↗

Migration behaviour among the unemployed and the role of unemployment benefits.

"In this paper the migration behaviour of young unemployed people in Sweden is analysed. The migration stream is divided into labour market migration and migration motivated by other reasons. The results show that a larger part of total migration is motivated by reasons other than pure labour market considerations. Explanatory factors have different effects on the two streams. Labour market motivated migration is sensitive to local labour market conditions while migration motivated by other reasons is not. Those who are receiving unemployment benefits are less willing to migrate than those who are not receiving such benefits."

Demography↗

Migration between the United States and Canada: a study of labour market adjustment.

"... The main purpose of this study is to examine population flows between Canada and the United States [from mid-1947 to mid-1972] in order to investigate the degree to which labour market adjustment is aided by such movements. [The author considers] several functional forms of the migration relationship in an attempt to empirically determine how the decision to migrate is formed. [He also compares the] results with those obtained by Courchene...for Canadian interprovincial migration in an effort to compare the effects of international and internal migration on labour market adjustment." It is found that "migration between the United States and Canada over the post-war period is an economic variable. In fact, [a] simple model employing differences in income levels and unemployment rates has been able to explain nearly ninety-five per cent of the variation in the migration rate." The author also notes that "although migration between Canada and the United States does occur in such a way as to aid labour market adjustment, it is not as efficient as internal migration." (summary in FRE, SPA)

Americas↗

Shifts in Grenadian migration: an historical perspective.

Migration from Grenada has been varied and large over the past century, reaching levels which even resulted in negative population growth. This article focuses on changes in Grenadian migration over the past 80 years, with emphasis on the Grenada Revolution, 1979-1983. After the 1979 revolution there were some changes in the attitudes of Grenadians to migration, although many of the expected socioeconomic and demographic features of migration were still present. Migration may be seen as a means of circumventing low wages and limited opportunities, as a culturally specific pattern of behavior, or as a combination of economic, political and cultural factors. After reviewing the pattern of Grenadian migration over the past 80 years, some of the causes of and attitudes to migration are examined, and the meaning of migration for Grenadians is discussed.

Age Factors↗

Income, self-selection, and return and onward interprovincial migration in Canada.

"Estimated returns to migration based on comparison of individual migrants may be biased owing to self-selection in the migration process. Using data derived from the 1986 Canadian census, I will study the effects of expected wage differentials in determining the return or onward migration decision of nonnative adults aged 20 to 64 years. Evidence was found that return migrations were in the 'right' direction, as they are observed to respond to provincial economic variables (that is, average employment growth and income levels) in a rational manner. After accounting for self-selectivity, I found that...return migrants...are negatively selected, and experience lower income levels, following the return migration, than onward migrants would have, had they chosen the return migration option. This drop in expected wages decreases the propensity associated with making a return migration. Despite this drop in income, the large proportion selecting the return migration option suggests the importance of the province of birth in the mental map of nonnative migrants."

Americas↗

Patterns, trends and future of international migration: some causes and consequences.

"This study examines the main trends of various models of international migration for the nineteenth and early twentieth centuries, and places emphasis on the volume and direction of various models of migration at present. Permanent migration, illegal migration in search of work and compulsory migration (refugees) are discussed in some detail with reference to the occasional difficulty of distinguishing between the various types of migration. When discussing the volume and sources of migration, the study indicates some of its motives and implications at origin and at destination and presents some of the future prospects and major factors that contribute to the continuation of the flow of the different types of migration." The geographical scope is worldwide.

Behavior↗

Migration in a socialist transitional economy: heterogeneity, socioeconomic and spatial characteristics of migrants in China and Guangdong province.

The peculiar features of China's socialist transitional economy, including the coexistence of "plan" and "nonplan" mechanisms, the hukou institution, uneven spatial development, and gendered constraints and opportunities, have brought about a high degree of heterogeneity among population movements. Using the 1990 Census data on reasons for migration, and an empirical analysis of both national patterns and migration in Guangdong, the author documents the socioeconomic characteristics and spatial patterns of major types of migration, focusing on migration for employment in industry and business, male migration due to job transfer, and female marriage migration. The author argues that the multitude of migration types, and the contrasts among them, are products of the combination of state-planning and market mechanisms. The findings highlight institutional explanations for migration, and show that the "plan"/"nonplan" dichotomy is more meaningful that the economic-social dichotomy for understanding population movements in China.

Asia↗

Low concentrations of fibrinogen increase cell migration speed on fibronectin/fibrinogen composite cables.

Optimal cell migration rate in a given direction (velocity) is a function of speed and directional persistence. Migration speed has been reported to be a function of adhesion strength such that optimal cell migration occurs where the cell is able to form enough stable attachments for good traction while allowing attachments at the trailing end to be broken during locomotion. This is particularly important in peripheral nerve regeneration where rapid Schwann cell recruitment across the injury site will lead to better functional recovery and reduced end organ atrophy. The aim here was to investigate the effects of changing adhesion properties of Fn materials by adding fibrinogen in order to design an optimal material for repair processes. Cell migration on Fn/Fg-cables increased with increasing content of %Fg to a peak cell migration velocity (Schwann cells) of 49 microm/h, at 50% Fg. Further increases in Fg content hindered cell migration. Vinculin-rich attachment plaques were reduced in a dose-dependent manner as the content of %Fg was increased whilst cells at the optimum Fg proportion for cell migration were moderately well spread. These results support the idea that optimum cell migration rates occur at intermediate attachment conditions, in this case at 50% Fg. These results show that incorporation of Fg into Fn-based materials will enhance the speed of Schwann cell migration and this would be likely to improve peripheral nerve regeneration. Indeed, directionally aligned Fn-based materials can now be engineered to give optimal cell velocity during repair cell recruitment in a range of tissue repair or tissue engineering applications.

Animals↗

Migration of hypoglossal myoblast precursors.

The intrinsic hypoglossal musculature develops from precursor myoblasts which undergo long-range migration from the occipital somites to the tongue. Little detail is known about the precise spatiotemporal pathway taken by these cells or the factors controlling migration. In this study, chick/quail chimeras in which the occipital paraxial mesoderm is quail derived, reveal that the pathway taken by the tongue muscle progenitors is both complex and highly specific. Precursor myoblasts are Pax-3 positive cells which descend from the somite and migrate around the pharyngeal endoderm. They then course rostrally, following the base of the pharynx, remaining in a tight strand. We have examined a number of factors implicated in the control of migration of the hypoglossal precursors. Replacement of the occipital somites with those originating in the flank reveals that intrinsic differences do not exist between these somites with respect to their capacity to respond to migratory cues. The lack of high level HGF/SF expression along the pathway of the migrating hypoglossal precursors suggests that this factor is not involved in the actual process of migration of the hypoglossal precursors to the tongue. The pathway followed by the migrating precursors is identical to that of both the developing hypoglossal nerve and the circumpharyngeal crest--a subpopulation of the cranial neural crest, and importantly these populations utilize this pathway before the myoblast precursors. However, ablation neither of the hypoglossal nerve nor of the neural crest results in a perturbation in the ability of this Pax-3 positive population to migrate. This demonstrates that migration of the precursors is independent of both of these cell populations, and that it is controlled by the peripheral tissues.

Animals↗

Chemotactic migration of mesencephalic neural crest cells in the mouse.

We examined the roles of fibroblast growth factor (FGF)-2 and FGF-8 in the migration of mesencephalic mouse neural crest cells. Our in vitro migration assay has shown that FGF-2 (basic FGF) and FGF-8 have chemotactic activity for these cells. Chemotaxis was inhibited by anti-FGF-2 and anti-FGF-8 neutralizing antibodies. In addition, anti-FGF-2 blocked neural crest cell migration in cranial organ cultures. This observation suggests that FGF-2 functions as a chemoattractant in migration of mesencephalic neural crest cells in vivo. In organ culture, the antagonist of FGF binding to a low-affinity fibroblast growth factor receptor (FGFR) heparan sulfate, inositolhexakisphosphate (InsP6), inhibited migration as well. Mesencephalic neural crest cells had high-affinity FGFRs, in particular FGFR-1 and FGFR-3. Thus, the chemotactic activities of FGF-2 can be mediated by the low-affinity FGFR alone or by a combination of low- and high-affinity FGFRs (FGFR-1, FGFR-3, or both). Moreover, differential localization of FGF-2 was found at the mesencephalic axial level of intact embryos during neural crest cell migration. FGF-2 protein expression was predominant in the target regions, in particular the mandibular mesenchyme, that are colonized by mesencephalic neural crest cells. This characteristic distribution supports the notion that FGF-2 acts as a chemoattractant in the mouse embryo that directs mesencephalic neural crest cell migration. Whereas FGF-8 showed chemotactic activity in vitro, neural crest cell dispersion was observed in explants that had been treated with anti-FGF-8 neutralizing antibodies. This result suggests that FGF-8 may not be a chemoattractant in vivo. However, the distribution of neural crest cells in explants treated with anti-FGF-8 differed from that in control explants or in intact embryos. Extreme FGF-2 distribution was observed in the mandibular arch and FGF-8 is expressed in the epithelium. FGF-8 may play a role in mesencephalic neural crest cell migration, and its role may be concerned with the differential localization of FGF-2. To establish this notion, we performed immunohistochemical examination of FGF-2 distribution in explants treated with FGF-8 and analysis of FGF-2 gene expression levels by reverse transcriptase-polymerase chain reaction by using RNA from explants. The data indicate that FGF-2 is distributed throughout the mesenchyme in FGF-8-treated explants and that expression of FGF-2 is promoted by FGF-8. Therefore, we conclude that the expression of FGF-8 in the mandibular arch epithelium is a prerequisite for the differential localization of FGF-2 and that the FGF-2 distribution pattern is essential for chemotaxis of mesencephalic neural crest cell migration.

Animals↗

Hepatocyte growth factor/scatter factor induces not only scattering but also cohort migration of human colorectal-adenocarcinoma cells.

We presented earlier a 2-dimensional cell-motility assay using a highly metastatic variant (L-10) of human rectal-adenocarcinoma cell line RCM-1 as a motility model of tumor cells of epithelial origin. In this model, L-10 cells moved as coherent cell sheets when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and we called this type of movement "cohort migration". Electron- and immunoelectron-microscope study of the migrating cell sheets demonstrated localized release from cell-cell adhesion only at the lower portion of the cells with loss of E-cadherin immunoreactivity, and this change was associated with increased tyrosine phosphorylation of the E-cadherin-catenin complex, including beta-catenin. In the present study, to obtain evidence to support the relevance of our model to carcinoma-cell movement in vivo, we sought a naturally occurring motogenic factor(s) able to induce this cohort migration. Among the factors examined, hepatocyte growth factor/scatter factor (HGF/SF) clearly induced cohort migration of L-10 cells. Additionally, not only L-10 but several other human colorectal-carcinoma cell lines showed this type of migration in response to HGF/SF, while yet others showed scattering-type motility. In this HGF/SF-induced migration, localized release from cell-cell adhesion was induced only at the lower portion of the cells, allowing them to extend leading lamellae, whereas close cell-cell contacts remained at the upper portion of the cells, as seen in TPA-induced cohort migration. Scattering-type cell lines tended to express more c-Met (receptor for HGF/SF) mRNA than the cell lines that showed cohort-type migration. LoVo, one of the scattering-type cell lines, expressed more c-Met protein and less E-cadherin than L-10, which showed cohort-type migration. HGF/SF treatment of LoVo reduced the amount of alpha-catenin complexed with E-cadherin more markedly than in L-10, but in both cell lines this reduction was not accompanied by increased tyrosine phosphorylation of beta-catenin, suggesting the presence of a mechanism other than phosphorylation for release from cell-cell adhesion during cell motility.

Adenocarcinoma↗

Protein kinase C mediates up-regulation of urokinase and its receptor in the migrating keratinocytes of wounded cultures, but urokinase is not required for movement across a substratum in vitro.

Both in cell culture and in vivo, keratinocytes that are migrating in response to a wound express enhanced levels of both urokinase-type plasminogen activator (uPA) and the uPA cell surface receptor (uPA-R). To explore the mechanism of this up-regulation, keratinocyte cultures were treated proir to wounding with a variety of metabolic and growth factor inhibitors in order to evaluate their effect on uPA and uPA-R expression. Actinomycin D and cycloheximide inhibited the up-regulation of both uPA and uPA-R, as determined by immunohistochemistry, indicating that RNA and protein syntheses are required for their induction in migrating keratinocytes. Neither removal of protein growth factors from the medium nor addition of inhibitory antibodies to a number of growth factors depressed uPA or uPA-R induction; these findings suggest that a variety of exogenous or endogenous growth factors [i.e., basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), amphiregulin, and tumor necrosis factor-alpha (TNF-alpha) do not have a critical role in the induction of uPA or uPA-R. In contrast, when protein kinase C (PKC) was either down-regulated with bryostatin 5 or inhibited with Ro31-8220 or staurosporine, the expression of both uPA and uPA-R was greatly decreased in migrating keratinocytes. Furthermore, pharmacologic activation of PKC enhanced uPA levels in non-wounded cultures. These data suggest that the enhanced expression of uPA and uPA-R in migrating keratinocytes is mediated by selective activation of PKC in these cells, perhaps secondary to alterations in the cytoskeleton induced by wounding. To test the requirement for uPA during keratinocyte migration in vitro, the extent of migration was quantified in the presence and absence of a variety of inhibitors in the wounded culture model. Migration was not altered by actinomycin D, cycloheximide, any of the above growth factor inhibitors, anti-uPA antibodies, a variety of inhibitors of uPA or plasmin enzymatic activity, or exogenous uPA. The independence of keratinocyte migration in vitro from uPA was further suggested by experiments which combined the phagokinetic assay of migration and the zymographic assay for pericellular uPA activity; no relationship was observed between pericellular uPA activity and the motility of individual cells.

Antibodies↗

Dual activities of 22-24 kDA basic fibroblast growth factor: inhibition of migration and stimulation of proliferation.

Basic fibroblast growth factor (FGF2) is synthesized as four isoforms with molecular weights of 24, 22.5, 22, and 18 kDa, with each of the three higher molecular weight forms (hmwFGF2) produced by the initiation of translation at one of three upstream CUG codons. We have shown that bovine arterial endothelial cells export the high molecular weight forms of FGF2 (hmwFGF2) in a 17beta-estradiol-dependent manner (Piotrowicz et al., 1997, J Biol Chem 272:7042-7047). To determine whether the hmwFGF2 forms affected cell behavior after release, we evaluated the effect of recombinant hmwFGF2 on the growth and migration of endothelial cells and mammary carcinoma cells (MCF-7). Treatment with the recombinant protein resulted in the inhibition of endothelial cell migration by 45% and MCF-7 cell migration by 70%. HmwFGF2-dependent inhibition was observed when endothelial cell migration was stimulated by 18 kDa FGF2 or vascular endothelial growth, and MCF cell migration was stimulated with insulin-like growth factor. In each case, inclusion of an antibody against the 55 amino acid amino terminal end of 24 kDa FGF2 abrogated the inhibition of migration, while antibodies to the 18 kDa FGF2 domain had no effect. When endothelial cells were cultured under conditions which promoted export of hmwFGF2, a 40% decrease in motility was observed which was reversed by the antibodies to the 24 kDa FGF2. Thus, both recombinant and endogenously produced hmw-FGF2 are capable of inhibiting migration. In contrast to the ubiquitous effect on migration, hmwFGF2 had no effect on endothelial cell growth but stimulated MCF-7 growth equally as well as the 18 kDa FGF2 (threefold). Antibodies to the 18 kDa domain of 24 kDa FGF2 blocked the growth-promoting activity of hmwFGF2, but those to the amino terminal end were ineffective. These data suggest that hmwFGF2 has dual activities, an inhibitory effect on cell migration and a growth-stimulating effect. The two activities can be localized to different parts of hmwFGF2: inhibitory activity to the amino terminal 55 amino acids (which are absent from the 18 kDa FGF2) and growth-promoting activity to the 18 kDa domain. Therefore, the ratio of hmwFGF2 and 18 kDa FGF2 in the extracellular space may provide a mechanism of control for angiogenesis and mammary tumor development.

Animals↗