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The effect of endothelial cell overexpression of plasminogen activator inhibitor-1 on smooth muscle cell migration.

INTRODUCTION: Plasminogen activator inhibitor-1 (PAI-1), a known inhibitor of plasminogen activators, may regulate smooth muscle cell migration (SMC) through alteration in matrix metalloproteinase (MMP) activity. METHODS: To study the effect of endothelial cell (EC) PAI-1 overexpression on SMC migration, RT-PCR was used to clone the full length PAI-1 gene, which was ligated into the pCMV/myc/ER expression vector. With electroporation, bovine aortic ECs were transfected with either the PAI-1 construct or the empty vector as control. EC PAI-1 overexpression was shown with a specific PAI-1 activity assay and enzyme-linked immunosorbent assay. The effect of EC PAI-1 overexpression on SMC migration was measured with a modified Boyden-chamber assay. SMC MMP expression was measured with zymography. RESULTS: Selected clones (EC9, EC21) had a three-fold to five-fold increase in PAI-1 activity compared with untransfected EC and empty vector EC (ECC). Similarly, enzyme-linked immunosorbent assay results showed a 3.5-fold to 5.5-fold increase in PAI-1 levels in EC9 and EC21 versus ECC. Untransfected EC and ECC had similar effects on SMC migratory patterns. Migration of SMC exposed to PAI-1 overexpressing EC was inhibited by 35% to 57% compared with ECC. This inhibitory effect was reversed with addition of exogenous urokinase-type plasminogen activator (uPA). Zymography showed downregulation of MMP-2 and MMP-9 in SMCs exposed to PAI-1 overexpressing EC. CONCLUSION: PAI-1 overexpression with transfected EC inhibits SMC migration. This effect may be mediated through decreased SMC MMP activity.

Animals↗

Dependence of polymerase chain reaction product inactivation protocols on amplicon length and sequence composition.

Specific diagnostic test results generated by polymerase chain reaction (PCR) depend upon control of amplicon contamination in the clinical laboratory. We compared photochemical (isopsoralen [IP]) and enzymatic (uracil N-glycosylase [UNG]) methods for their ability to prevent carryover of amplicons generated from genomic targets of five viruses. PCR products (amplicons) (herpes simplex virus, 342 bp; cytomegalovirus, 250 bp; Epstein-Barr virus, 240 bp) exposed to UV light in the presence of various concentrations of IP compound 10 (IP-10) resulted in apparent increased molecular sizes of the products, as indicated by migration patterns after gel electrophoresis, and were predictive of inactivation by the agent. For amplicons of < or = 100 bp, IP-10-induced electrophoretic shifts were related to the guanidine-cytidine (G + C) content of the PCR product; no apparent shift and no inactivation were observed for a 92-bp herpes simplex virus amplicon (G + C content, 65%), whereas the 100-bp human papillomavirus product (G + C content, 42%) showed a concentration-dependent shift (25 to 100 micrograms/ml) in electrophoretic migration and was partially inactivated. UNG effectively controlled amplicon carryover for target DNA of > or = 240 bp; however, this treatment did not inactivate the two amplicons of < or = 100 bp, regardless of the G + C content of the product. Larger products were inactivated efficiently by both methods, regardless of their G + C contents. We concluded that both IP and UNG effectively inactivated PCR amplicons but not short amplicons of < or = 100 bp. We recommend that with the adoption of PCR technology in clinical laboratories, primers should be designed to produce amplicons of at least 240 to 350 bp (depending on G + C content) and that at least one effective method of controlling carryover contamination should be incorporated into each PCR protocol.

Base Composition↗

Risk based management of contaminated sediments: consideration of spatial and temporal patterns in exposure modeling.

This paper addresses interactions among foraging behavior, habitat preferences, site characteristics, and spatial distribution of contaminants in developing PCB exposure estimates for winter flounder at a hypothetical open water dredged material disposal site in the coastal waters of New York and New Jersey (NY-NJ). The implications of these interactions for human health risk estimates for local recreational anglers who fish for and eat flounder are described. The models implemented in this study include a spatial submodel to account for spatial and temporal characteristics of fish exposures and a probabilistic adaptation of the Gobas bioaccumulation model that accounts for temporal variation in concentrations of hydrophobic contaminants in sediment and water. We estimated the geographic distribution of a winter flounder subpopulation offshore of NY-NJ based on species biology and its vulnerability to local recreational fishing, the foraging area of individual fish, and their migration patterns. We incorporated these parameters and an estimate of differential attraction to a management site into a spatially explicit model to assess the range of exposures within the population. The output of this modeling effort, flounder PCB tissue concentrations, provided exposure point concentrations for an estimate of human health risk through ingestion of locally caught flounder. The risks obtained for the spatially nonexplicit case are as much as 1 order of magnitude higher than those obtained with explicit consideration of spatial and temporal characteristics of winter flounder foraging and seasonal migration. This practice of "defaulting" to extremely conservative estimates for exposure parameters in the face of uncertainty ill serves the decision-making process for management of contaminated sediments in general and specifically for disposal of dredged materials. Consideration of realistic spatial and temporal scales in food chain models can help support sediment management decisions by providing a quantitative expression of the confidence in risk estimates.

Animals↗

Molecular mechanisms governing thymocyte migration: combined role of chemokines and extracellular matrix.

Cell migration is crucial for thymocyte differentiation, and the cellular interactions involved now begin to be unraveled, with chemokines, extracellular matrix (ECM) proteins, and their corresponding receptors being relevant in such oriented movement of thymocytes. This notion derives from in vitro, ex vivo, and in vivo experimental data, including those obtained in genetically engineered and spontaneous mutant mice. Thymic microenvironmental cells produce both groups of molecules, whereas developing thymocytes express chemokine and ECM receptors. It is important that although chemokines and ECM proteins can drive thymocyte migration per se, a combined role of these molecules likely concurs for the resulting migration patterns of thymocytes in their various differentiation stages. In this respect, among ECM moieties, there are proteins with opposing functions, such as laminin or fibronectin versus galectin-3, which promote, respectively, adhesion and de-adhesion of thymocytes to the thymic microenvironment. How chemokines and ECM are produced and degraded remains to be more clearly defined. Nevertheless, matrix metalloproteinases (MMPs) likely play a role in the intrathymic ECM breakdown. It is interesting that these molecules also degrade chemokines. Thus, the physiological migration of thymocytes should be conceived as a resulting vector of multiple, simultaneous, or sequential stimuli, involving chemokines, adhesive, and de-adhesive ECM proteins. Moreover, these interactions may be physiologically regulated in situ by matrix MMPs and are influenced by hormones. Accordingly, one can predict that pathological changes in any of these loops may result in abnormal thymocyte migration. This actually occurs in the murine infection by the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. In this model, the abnormal release of immature thymocytes to peripheral lymphoid organs is correlated with the higher migratory response to ECM and chemokines. Lastly, the fine dissection of the mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells. The most important function of the thymus is to generate T lymphocytes, which once leaving the organ, are able to colonize specific regions of peripheral lymphoid organs, the T cell zones, where they can mount and regulate cell-mediated, immune responses. This intrathymic T cell differentiation is a complex sequence of biological events, comprising cell proliferation, differential membrane protein expression, gene rearrangements, massive programmed cell death, and cell migration. In this review, we will focus on the mechanisms involved in controlling the migration of thymocytes, from the entrance of cell precursors into the organ to the exit of mature T cells toward peripheral lymphoid organs. Nevertheless, to better comprehend this issue, it appeared worthwhile to briefly comment on some key aspects of thymocyte differentiation and the tissue context in which it takes place, the thymic microenvironment.

Animals↗

Migration trends and regional labour market change in Poland.

The author examines internal migration and its relation to economic conditions in Poland during the period since World War II. The "basic facets of internal migration in Poland, as they prevailed over the last decades, will be summarized in Section 2 and [compared] with the most recent mobility trends. Section 3 will focus on migration flows within and among 49 regions over the 1975-1983 period while taking account of changing industrial employment levels in individual regions. Alternative interpretations of observed migration patterns will be sought in Section 4. Preliminary conclusions and some further questions will be listed in Section 5."

Demography↗

Immunity to colon cancer assessed by antigen-induced inhibition of mixed mononuclear cell migration.

A purified preparation of mixed human peripheral blood lymphocytes and monocytes was used in an inhibition-of-migration assay for cell-mediated immunity to cancer of the colon. This preparation was reproducibly antigen-responsive and migrated with greater reliability than did a more complex cell mixture. Of 27 patients with this disease, cells from 24 showed inhibited migratio in response to colon carcinoma antigen. Uninhibited migration patterns were found in each of the 52 cancer-free controls, including eight patients with nonmalignant disease initially diagnosed as cancer of the colon, and in nine patients with surgically cured adenocarcinoma of the colon.

Adenocarcinoma↗

The new United States Cancer Atlas.

Published in 1975, the Atlas of Cancer Mortality for U.S. Counties: 1950-1969 proved useful in identifying geographic patterns, especially clusters of high-rate areas, that have stimulated further epidemiologic study of specific cancer sites. These data have been updated to include population and mortality statistics through 1980. Our new atlas presents static maps of area-specific mortality rates for each decade from 1950 to 1980 among white males and females for 33 cancer sites, along with dynamic maps illustrating the trends in these rates over time. Although the geographic distribution of mortality rates has become more uniform for most cancer sites, clusters of high-rate areas have persisted for several common tumors. However, some new patterns have appeared, notably the emergence of several high-rate areas for lung cancer among women. Possible explanations for the geographic peculiarities of cancer are considered, based on the results of correlation and analytic studies prompted by the earlier maps. These successive studies indicate the value of monitoring mortality statistics on a small-area scale as a strategy for generating etiologic clues and targeting epidemiologic research, although one must be mindful of geographic fluctuations in diagnostic and reporting practices, survival rates, and migration patterns.

Chronology as Topic↗

The role of population in understanding Honduran land use patterns.

Land use patterns are usually influenced by large variety of factors that act over a broad range of scales. Biophysical, climatic, and socioeconomic factors are important and need to be considered, when distribution of land use is to be understood. The main objective of this study is to test this hypothesis using a statistical analysis at 'supra-local' level. Regression analysis is used to describe land use patterns in Honduras, selected because of its rare combination in Latin America of high population growth and poor biophysical conditions. Furthermore, the aim of the analysis is to specifically highlight two aspects, the effect of spatial and temporal scale and the influence of population density: to determine the influence of spatial and temporal scale, six spatial resolutions at two points in time (1974 and 1993) were included. To determine the role of population density and population growth, this factor was singled out; an analysis of migration patterns was performed; and a measure for technological development was calculated. Multiple regression equations indicate the importance of soil-related, climatic and demographic factors for most of the land uses. Relations appear to be stable in space and time. Rural population density dominates as driver over the whole range of resolutions and for both years, especially for maize where it explains up to 80% of the variation. The strong constant relationship between population and agricultural area could be caused by a lack of technological development. An analysis of yield development confirms that for most annual crops yield increases lag behind area growth. Besides, the strong correlation could be explained by assuming rural population density to be a proxy for a range of other factors, like labour costs, or accessibility that are the direct drivers of land use change. In any case, this study suggests that for a specific--relatively coarse--window of temporal and spatial scale, land use patterns can be described with very simple relationships, with a strong contribution of population density. More local studies are needed to test the hypothesis that rural population density is a proxy for other variables.

Agriculture↗

Analyzing the migration of labeled T cells in vivo: an essential approach with challenging features.

T cells are involved in the pathogenesis of many diseases. To exert a pathological effect, T cells enter the tissues. We show that the determination of their entry site requires isolation of the respective T cell population, injection into genetically un-manipulated animals, and identification of the cells in vivo at various time points after injection. We indicate variables influencing in vivo migration experiments artificially, and outline how resulting problems can be either avoided or taken into account. Reviewing experiments performed according to the outlined criteria reveals two types of migration patterns for T cell subsets in vivo: 1). Naïve and memory T cells enter lymphoid and non-lymphoid organs in comparable numbers, but selectively accumulate in lymphoid tissues over time, 2). Effector T cells, too, enter lymphoid and non-lymphoid organs in comparable numbers. However, most of them die within 24 hours. Depending on the presence of cytokines, chemokines and extracellular matrix compounds they are able to survive, thereby preferentially accumulating in their target tissues. This information might help to understand the role of migration in the pathogenesis of T cell mediated diseases.

Animals↗

Small intestinal motor patterns in critically ill patients after major abdominal surgery.

OBJECTIVES: In patients who have had major surgery or trauma, early enteral feeding is safer and more effective than parenteral or nasogastric feeding but is frequently associated with diarrhea. Limited recordings have shown that the patterning of duodenal interdigestive motor activity is frequently abnormal after surgery or in patients who are critically ill. The aims of this study were to evaluate the effects of major abdominal surgery on small intestinal motility, and to elucidate the motor patterns that occur postoperatively in critically ill patients in response to enteral feeding. METHODS: The effects of elective aortic aneurysm repair on small intestinal motility were studied in 11 patients aged 63-77 yr. A 3.5-mm diameter multilumen extrusion was used to monitor pressures at 12 points, distributed between the antrum and 100 cm distal to the pylorus. An additional lumen allowed enteral feeding into the duodenum. Recordings commenced immediately postoperatively and continued for up to 4 days. Data are given as means and SEMs. RESULTS: Bursts (frequency > 10/min) of small intestinal pressure waves that resembled phase III interdigestive motor activity occurred in all patients immediately after surgery. During mechanical ventilation, the timing of bursts along the segment evaluated was frequently abnormal for true interdigestive phase III activity, with simultaneous onset in multiple channels (46%), multiple or distal origins (8%), or retrograde migration (20%). When patients were not being ventilated, the migration pattern of the bursts was more typical of interdigestive phase III activity. The interval between bursts was unusually short for interdigestive motor activity, although it increased from 30+/-12 min on day 1 to 41+/-18 min on day 3 (p < 0.05). A phase II pattern of pressure waves was virtually absent in all patients on all study days. In six patients who received postoperative enteral nutrition, the bursts of pressure waves were not abolished by feeding, contrary to normal phase III activity. CONCLUSIONS: Small intestinal pressure wave bursts are seen immediately after elective aortic aneurysm repair, but the migration of these bursts is frequently abnormal for phase III interdigestive activity. Duodenal nutrient delivery did not interrupt the occurrence of these bursts. Persistence of pressure wave bursts in this setting may be important in the delivery of enteral nutrition.

Aged↗

Lymphoscintigraphy in oncology: a rediscovered challenge.

The validation of the sentinel node concept in oncology has led to the rediscovery of lymphoscintigraphy. By combining preoperative lymphatic mapping with intraoperative probe detection this nuclear medicine procedure is being increasingly used to identify and detect the sentinel node in melanoma, breast cancer, and in other malignancies such as penile cancer and vulvar cancer. In the past lymphoscintigraphy has been widely applied for various indications in oncology, and in the case of the internal mammary lymph-node chain its current use in breast cancer remains essential to adjust irradiation treatment to the individual findings of each patient. In another diagnostic area, lymphoscintigraphy is also useful to document altered drainage patterns after surgery and/or radiotherapy; its use in breast cancer patients with upper limb oedema after axillary lymph-node dissection or in melanoma patients with lower-extremity oedema after groin dissection can provide information for physiotherapy or reconstructive surgery. Finally, the renewed interest in lymphoscintigraphy in oncology has led not only to the rediscovery of findings from old literature reports, but also to a discussion about methodological aspects such as tracer characteristics, image acquisition or administration routes, as well as to discussion on the study of migration patterns of radiolabelled colloid particles in the context of cancer dissemination. All this makes the need for standardized guidelines for lymphoscintigraphy mandatory.

Breast Neoplasms↗

Lung allograft rejection in the rat. II. Specific immunological properties of lung grafts.

The immunological mechanism of lung allograft rejection was studied in inbred rats, in order to explain the rapid progress of the rejection response against RT1-incompatible lung grafts. Histological appearances of the graft and of the recipient's spleen were studied, migration patterns of graft and recipient lymphocytes were assessed, and titers of circulating alloantibodies were determined. Histologically, we discriminated four phases of the rejection response in lung grafts: sequentially the latent, vascular, alveolar, and destruction phases. Early in the vascular phase, recipient lymphocytes primarily infiltrated the bronchus-associated lymphoid tissue (BALT) of the graft, causing a local immune response. Concurrent with these local rejection phenomena in the graft, a strong systemic immune response developed in the recipient's spleen, presumably induced by the great number of lymphocytes that migrated from the graft's BALT into the recipient's lymphoid tissues. We conclude that BALT facilitates a fast and intensive interaction between lung graft and recipient that is likely to accelerate the induction of the rejection response both locally in the graft and systemically in the recipient's lymphoid organs.

Animals↗

An assessment of the human capital content of international migrants: an application to U.S. immigration.

The authors present a methodology for measuring the magnitude of international migration flows that includes an earnings equation approach as an economic dimension. "Applying our methodology to U.S. immigration, we find considerable variation across source regions in the value of immigrants. Moreover, we find that simply comparing initial earnings without controlling for differences in the characteristics and migration patterns of immigrants from the various source regions can misrepresent the relative earnings potential or value of migrants." (SUMMARY IN FRE AND GER)

Americas↗

Some models for patterns of urbanization, migration and development.

"This paper aims to study the pattern of urbanization and the evolution of [the] relationship between rural-urban migration and the degree of economic development taking Gross National Product...into consideration. Intercensal age-specific rural net out-migration rates are also estimated from [tabulations] of the proportion of rural population of India by age through a recently developed procedure based on generalized stable population by Stupp (1989). A comparative study is also made between [the] survival column of India with a developed nation like Japan."

Age Distribution↗

Circulation and migration in third world settings: a comparison in Ecuador.

This study is concerned with circulation, defined as temporary and repetitive migration that lacks any declared intention of a permanent or long-lasting change in residence. "The first section of the paper reviews pertinent circulation literature. Attention then turns to describing circulation and migration patterns in Ecuador, and identifying relationships between these patterns and regional differentials in economic development, both through cartographic and statistical analyses. A summary and conclusions comprise the last section."

Americas↗

[Italian immigration into Imperial Germany up to World War I].

"A rapid growth, both economic and industrial, of the German Empire during the last decade of the nineteenth century...produced a major switch in Germany's status from that of a country of emigration to a country of immigration.... The essay gives a concise description of the characteristics of Italian migration flows towards Germany, integration processes and chain migration patterns. The impact of immigration on the receiving country is...analyzed, both in terms of economic development and from a social, political and legal point of view." (SUMMARY IN ENG AND FRE)

Acculturation↗

Developing a model of DNA replication to be used for Monte Carlo calculations that predict the sizes and shapes of molecules resulting from DNA double-strand breaks induced by X irradiation during DNA synthesis.

A Monte Carlo computer program was written to introduce double-strand breaks (DSBs) randomly into cellular DNA that is configured according to different models of DNA replication. Then, from a review of the literature using DNA fiber autoradiography and other studies relating to rates of replication of DNA that is organized in approximately 3-Mbp regions or bands, a particular model for DNA replication was developed. Using this model, Monte Carlo calculations were made to predict the types and sizes of molecules that would result from introducing DSBs into DNA when synchronous cells are irradiated in the middle of S phase. Then results of the Monte Carlo calculations were compared with migration profiles obtained by pulsed-field gel electrophoresis (PFGE) for molecular size distributions of linear DNA molecules. For these comparisons, CHO cells irradiated in S phase also were pulse-labeled at the time of irradiation with [3H]dThd for 15 min to compare the migration patterns of 3H-labeled replicating DNA with those of the mass of S-phase DNA, measured by imaging with a CCD camera. For the Monte Carlo calculations, we assumed from the reports in the literature that molecules containing replication bubbles with and without forks would be trapped in the PFGE plug. We also assumed that those molecules that are < or = 8 Mbp, both linear and with replication forks, would be released into the lane. However, approximately 75% of the 3H-labeled DNA that is released from the plug migrated much more slowly than linear molecules, which we attributed to the slow migration of 3H-labeled molecules having replication forks not attached to bubbles. The percentages of both mass of S-phase DNA and 3H-labeled replicating DNA released from the plug, as determined by PFGE, were compared with comparable values determined from Monte Carlo calculations. A DNA replication model that provides good agreement between the PFGE results and Monte Carlo calculations is described. Furthermore, Monte Carlo methodology is presented that can be used for comparing data obtained with PFGE with results of Monte Carlo calculations that are based on different models of DNA replication and different assumptions for the migration of various types of replicating molecules.

Animals↗

Analysis of human ocular mucus: effects of neuraminidase and chitinase enzymes.

PURPOSE: Our goal was to establish the characteristic migration pattern on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of high molecular weight mucins from human ocular mucus and the effects of treatment with exo- and endoglycosidases. METHODS: Chromatography by gel filtration with Sepharose CL-4B was performed on samples collected from normal subjects. Human ocular mucins from the high molecular weight fraction were digested with exoglycosidases (neuraminidase, N-acetyl-beta-D-glucosaminidase, beta-D-glucosidase) and endoglycosidases (chitinase, lysozyme); and the resulting products were analyzed by electrophoresis. Carbohydrate identification was performed using lectin probes. RESULTS: The migration of the ocular mucins on SDS-PAGE stopped after treatment with neuraminidase, which removes the terminal negatively charged sialic acid residues from mucin. Chitinase (beta(1-4)N-acetylglucosaminidase) treatment increased the electrophoretic migration of mucins. Staining with wheat germ agglutinin and Maackia amurensis agglutinin lectins showed that these mucins contain beta(1-4)NAcGlc and SAa(2-3)Gal linkages. CONCLUSIONS: These studies demonstrate that the mobility of human ocular mucins on SDS-PAGE is determined by their intrinsic total negative charge and is not dependent on SDS treatment. It is interesting to note that human ocular mucus contains chitinous material resistant to lacrimal lysozyme, which is accessible to chitinase, an enzyme now found to degrade human ocular mucins. These chitinous linkages could be in part responsible for the mucus resistance.

Adolescent↗