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Perinuclear location and recycling of epidermal growth factor receptor kinase: immunofluorescent visualization using antibodies directed to kinase and extracellular domains.

This paper describes studies on the migratory behavior of epidermal growth factor (EGF) receptor kinase using antibodies that are specific for either the kinase domain or the extracellular domain of the receptor. Antiserum was raised to a 42,000-D subfragment of EGF receptor, which was shown earlier to carry the kinase catalytic site but not the EGF-binding site. Another antiserum was raised to the pure intact 170,000-D EGF receptor. The specificities of these antibodies were established by immunoprecipitation and immunoblotting experiments. The domain specificity was examined by indirect immunofluorescent staining of fixed cells. The anti-42-kD peptide antibody could bind specifically to EGF receptors of both human and murine origin and was found to be directed to the cytoplasmic part of the molecule. It did not bind to EGF receptor-negative cells, which contained other types of tyrosine kinases. The antibodies raised against the intact receptor recognized only EGF receptor-specific epitopes and were directed to the extracellular part of the molecule. The anti-receptor antibodies described above were used to visualize the cyclic locomotory behavior of EGF receptor kinase under various conditions of EGF stimulation and withdrawal. The receptor was examined in fixed and permeabilized cells by indirect immunofluorescent staining. The results demonstrate the following: (a) the receptor kinase domain migrates to the perinuclear region upon challenge with EGF; (b) both extracellular and cytoplasmic domains of the receptor are involved in migration as a unit; (c) withdrawal of EGF results in rapid recycling of the perinuclear receptors to the plasma membrane; (d) this return to the cell surface is inhibited by methylamine, chloroquine, and monensin; and (e) neither the internal migration nor the recycling process is blocked by inhibitors of protein biosynthesis.

Animals↗

Leukocyte-endothelium interaction promotes SDF-1-dependent polarization of CXCR4.

Chemokine-driven migration is accompanied by polarization of the cell body and of the intracellular signaling machinery. The extent to which chemokine receptors polarize during chemotaxis is currently unclear. To analyze the distribution of the chemokine receptor CXCR4 during SDF-1 (CXCL12)-induced chemotaxis, we retrovirally expressed a CXCR4-GFP fusion protein in the CXCR4-deficient human hematopoietic progenitor cell line KG1a. This KG1a CXCR4-GFP cell line showed full restoration of SDF-1 responsiveness in assays detecting activation of ERK1/2 phosphorylation, actin polymerization, adhesion to endothelium under conditions of physiological flow, and (transendothelial) chemotaxis. When adhered to cytokine-activated endothelium in the absence of SDF-1, CXCR4 did not localize to the leading edge of the cell but was uniformly distributed over the plasma membrane. In contrast, when SDF-1 was immobilized on cytokine-activated endothelium, the CXCR4-GFP receptors that were present on the cell surface markedly redistributed to the leading edge of migrating cells. In addition, CXCR4-GFP co-localized with lipid rafts in the leading edge of SDF-1-stimulated cells, at the sites of contact with the endothelial surface. Inhibition of lipid raft formation prevents SDF-1-dependent migration, internalization of CXCR4, and polarization to the leading edge of CXCR4, indicating that CXCR4 surface expression and signaling requires lipid rafts. These data show that SDF-1, immobilized on activated human endothelium, induces polarization of CXCR4 to the leading edge of migrating cells, revealing co-operativity between chemokine and substrate in the control of cell migration.

Actins↗

Use of immigration policy to manage nursing shortages.

PURPOSE: To examine long-term implications of using temporary, nonimmigrant nurse programs to manage fluctuations in the demand for registered nurses. ORGANIZING FRAMEWORK: This discussion is located in the full context of migration--reviewing theories and concepts of labor migration--referring to experience with guest-worker programs worldwide, outlining recent nursing shortages in the United States, describing the Immigration Nursing Relief Act (INRA), and raising questions for nurses in the United States and in the global marketplace. SOURCES: Review of scholarly literature on international migration, existing studies on nurse migration to the United States, and original research, conducted between 1992 and 1994, for the Immigration Nursing Relief Advisory Committee (INRAC) Report. METHODS: Policy analysis of theories, concepts, and perspectives related to nurse migration. FINDINGS: In the United States, highly skilled foreign nurses tend to complement rather than displace local labor. Yet recruiting foreign-educated nurses for entry-level jobs perpetuates patterns of dependency in the sending country and delays creative solutions to staff development in the host country. Nonimmigrant status creates a vulnerable workforce. There may be a disparity between the ideal of nurse migration as collaborative exchange and the reality of institutionalized occupational migration networks. CONCLUSIONS: While foreign nurse recruitment might solve short-term needs, repetitive temporary nurse migration programs create long-term consequences that are not in the best interests of the profession. The absence of consistent policy creates an opportunity for nursing to take an active role in developing the rules and direction of future nurse migration.

Emigration and Immigration↗

Child health outcomes among Central American refugees and immigrants in Belize.

The purpose of this study was to investigate the effect of international migration, including refugee status, upon child health outcomes. Data were drawn from a survey conducted in 1989 in three settlements in Belize, Central America, that have a high proportion of refugees and economic immigrants living side-by-side with the local population. In two of the settlements, the entire population of mothers with children under 6 was interviewed; in the third settlement a two-thirds random sample was interviewed. Health history data were obtained for 255 children of 134 mothers, from whom sociodemographic data were also collected. The majority of children were born to Salvadoran or Guatemalan mothers, but native and naturalized Belizeans in the survey communities were included for comparison purposes. Migration, the exposure variable, was characterized by mother's residency/refugee legal status, nationality, and duration of time in country. Socioeconomic and proximate control variables were included as suggested by the Mosley-Chen framework. Despite normal birthweight averaging 3374 g, a large proportion of children are at the lowest percentiles of the weight-for-age curves (44% below the tenth percentile for the international reference population). A high incidence of diarrheal and respiratory illnesses (30% and 47% of children, respectively, having frequent episodes), and 50% of children with measles vaccination appropriate for age, indicate a population with high potential morbidity. Logistic regression was used to model the effects of migration on weight-for-age and frequency of diarrheal and respiratory tract episodes independent of socioeconomic and proximate factors, as suggested by the Mosley-Chen framework.(ABSTRACT TRUNCATED AT 250 WORDS)

Belize↗

Nursing migration: global treasure hunt or disaster-in-the-making?

International nurse migration--moving from one country to another in the search of employment--is the focus of this article. The majority of member states of the World Health Organization report a shortage, maldistribution and misutilisation of nurses. International recruitment has been seen as a solution. The negative effects of international migration on the 'supplier' countries may be recognised today but are not effectively addressed. Nurse migration is motivated by the search for professional development, better quality of life and personal safety. Pay and learning opportunities continue to be the most frequently reported incentives for nurse migration, especially by nurses from less-developed countries. Career opportunities were considered key incentives for nurses emigrating from high-income countries. Language was reported to be a significant barrier. The positive global economic/social/professional development resulting from international migration needs to be weighed against a substantial 'brain and skills drain' experienced by supplier countries. The vulnerable status of migrant nurses is also of concern in certain cases. The focus on short-term solutions as opposed to resolving the problem of a worldwide shortage of nurses causes great concern. Recent initiatives attempt to curb or channel international recruitment. The delicate balance between recognising the right of individual nurses to migrate and a collective concern for the health of a nation's population must be achieved.

Attitude of Health Personnel↗

Expression of 'segmentation' genes during larval and juvenile development in the polychaetes Capitella sp. I and H. elegans.

Polychaete annelids and arthropods are both segmented protostome invertebrates. To investigate whether the segmented body plan of these two phyla share a common molecular ground pattern, we report the developmental expression of orthologues of the arthropod segment polarity genes engrailed (en), hedgehog (hh), and wingless (wg/Wnt1) in larval and juvenile stages of the polychaete annelid Capitella sp. I and en in a second polychaete, Hydroides elegans. Temporally, neither Wnt1 nor hh are detected in the segmented region of the larval body until after morphological segmentation is apparent. Expression of CapI-Wnt1 is limited to a ring of ectoderm marking the future anus during larval segmentation. CapI-hh is expressed in a ring of the hindgut internal to that of CapI-Wnt1, as well as in a subset of ventral nerve cord neurons, anterior gut tissue, and mesoderm. In both H. elegans and Capitella sp. I, en is expressed in a spatially and temporally dynamic manner in segmentally iterated structures as well as a population of cells that migrate internally from ectoderm to mesoderm, possibly representing a population of ecto-mesodermal precursors. Significantly, the expression patterns we report for wg, en, and hh orthologues in Capitella sp. I and for en in larval development of H. elegans are not comparable to the highly conserved ectodermal segment polarity pattern observed in arthropods at any life history stage, consistent with distinct origins of segmentation between annelids and arthropods.

Amino Acid Sequence↗

Variations in demographic behaviour by levels of living in Pakistan.

This paper utilizes data from the Population, Labour Force, and Migration Survey of 1979 which collected information from about 10,000 households in Pakistan. Poverty was directly related to household size and also to the average number of children under 15, which meant higher dependency ratios for the poor. Poorer ever-married women had higher fertility rates than richer women. However, the association between fertility and levels of living was not monotonically inverse. Schooling rates of 5-9 year olds varied positively with levels of living and, conversely, labor force participation rates for boys aged 10-14 were generally higher in the poorer deciles. The value of children and their utility varies across the deciles. Data from Pakistan show only broad negative associations between infant mortality and standard of living. It could be argued that relatively higher mortality is experienced by those at lower standards of living, which leads at 1st to diminished household size, but eventually to higher fertility and larger household size. Out-migration, particularly to the Middle East, seems to have occurred in reasonably well-off households, or at least has not affected the poorest strata of society. Remittances have further enhanced the standard of living of out-migrants' households. The fertility of migrant households may also be lower than that of nonmigrants and may explain smaller household size. However, internal migration to urban areas tends to increased size as rural migrants live jointly in households away from their families.

Asia↗

[The dream of the Far West: French physicians in the United States].

At the end of 1996, there were 115,484 foreign medical graduates in the US. More than one quarter of the US physician workforce were FMGs, among them 973 came from a French medical school (nearly 0.6% of the French physician workforce). French-trained doctors in the US are mainly located in New York, New Jersey, California and Florida, i.e. in the urban areas. However, their membership to the medical learned societies is less frequent than their American colleagues. In general, their ways of practice evidence a lower level of professional status. Based on training costs, the loss for France, due to migration to the US of these 973 doctors could be estimated between 1.2 billion and 8.5 billion French Francs. One has to remind that, at the same time, France "imports" doctors trained in other countries for fulfilling medical posts in hospitals in remote areas. The process occurs in a context of oversupply of physicians in France. A large-scale study of international migration of physicians and nurses was undertaken under the aegis of the World Health Organization in the early 70's. It seems now of interest to re-examine again the issue.

Adult↗

Risk of HIV/AIDS in China: subpopulations of special importance.

OBJECTIVE: To describe the HIV/AIDS epidemic in mainland China. METHODS: We review the magnitude of the HIV/AIDS epidemic and the social characteristics and geographic distribution of at-risk groups in China based on published literature and unpublished official data. RESULTS: Injection drug use has been the dominant route for HIV infection in China, and will continue to be a major risk factor with increasing numbers of new drug users and needle sharing. Commercial plasma donation with unhygienic re-infusion of red blood cells was common in rural communities in the early 1990s. While this is unlikely to constitute a major factor for future HIV spread, those already infected represent a formidable treatment challenge. Huge seasonal work migration facilitates disease spread across regions. Many homosexual men have unprotected sex with men, women, or both, and may contract or spread HIV. Though commercial sex workers have contributed to a small proportion of the reported epidemic thus far, flourishing commercial sex is of growing concern and may have a bridging role in transmitting HIV from core groups to the general population. CONCLUSION: Increasing numbers of sex workers and drug users, internal migration, high risk behaviours, and low condom use suggest a future upward trend for HIV/AIDS and underscore the urgency of scaling up interventions in China.

Blood Transfusion↗

Migration and AIDS in Mexico: an overview based on recent evidence.

OBJECTIVES: Provide an overview of the relation between migration to the United States and AIDS cases in Mexico. Characterize the sexual behaviors of Mexican migrants. Describe HIV/AIDS prevention and clinical attention actions developed. METHODS: The following were analyzed: AIDS cases databases, various prevalence studies, the migrants survey, and information of the Ministries of the Interior and of Health. A documental analysis was undertaken of works published between 1992 and 2000 on migration and AIDS. RESULTS: In terms of their sexual practices, migrants in the past year had more sexual partners, tended to use a condom in their most recent relation in greater proportion, and had greater use of injected medicines and drugs. Two bi-national programs undertake epidemiological surveillance activities, while several initiatives have used innovative formats to provide prevention information to migrants. Imminent universal coverage leaves the challenge to assure quality of attention for migrants. CONCLUSIONS: Studies to evaluate the impact of international migration on distribution of infected persons will be indispensable to establish priorities in prevention and attention among migrants. More information is needed on bi-national health projects to understand the impact they may have in prevention, while continuity of the prevention initiatives must be guaranteed. Attention to migrants in bi-national contexts requires information exchange agreements on migrants living with the HIV/AIDS.

Acquired Immunodeficiency Syndrome↗