Biomedical subjects

E Roos

Publications and source records attributed to E Roos.

At least 19 recordsLinked to original sources

PubMed2001

[Small changes in health differences in the Nordic countries during the 1980s and 1990s].

The study examined changes over time in health inequality in Denmark, Finland, Norway and Sweden. Data derive from comparable interview surveys carried out in 1986/87 and 1994/95. Limiting long-standing illness and perceived ill health were analysed regarding age, gender; educational attainment, and employment status. Age adjusted prevalence rates were calculated. Changes in differences in health were found in education and employment status groups. There was little or no change in the prevalence of ill health during the time period studied. Despite social and economic changes differences in health remained broadly stable in the examined countries.

Age Factors↗

PubMed2001

Stromal cell-derived factor-1-induced LFA-1 activation during in vivo migration of T cell hybridoma cells requires Gq/11, RhoA, and myosin, as well as Gi and Cdc42.

Dissemination of T cell hybridomas in mice, a model for in vivo migration of memory T cells and for T lymphoma metastasis, depends on the chemokine stromal cell-derived factor-1 (SDF-1) and the integrin LFA-1 and correlates well with invasion into fibroblast cultures. In addition to the known role of the pertussis toxin-sensitive heterotrimeric GTPase G(i), we show that also the pertussis toxin-insensitive GTPase G(q/11) is required for dissemination and invasion. Furthermore, we show that the small GTPases, Cdc42 and RhoA, are involved, and that invasion is blocked by inhibitors of actinomyosin contraction. G(q/11), RhoA, and contraction are specifically required for LFA-1 activation, since 1) they are essential for LFA-1-dependent migration toward low SDF-1 concentrations through ICAM-1-coated filters, but not for migration toward high SDF-1 levels, which is LFA-1 independent; 2) G protein (AlF(4)(-))-induced adhesion to ICAM-1 requires RhoA and contraction; 3) constitutively active G(q) induces aggregation, mediated by LFA-1. We previously reported that binding of this activated LFA-1 to ICAM-1 triggers a signal, transduced by the zeta-associated protein 70 tyrosine kinase, that activates additional LFA-1 molecules. This amplification of LFA-1 activation is essential for invasion. We show here that zeta-associated protein 70-induced LFA-1 activation requires neither Cdc42 and RhoA nor contraction and is thus quite different from that induced by SDF-1. We conclude that two modes of LFA-1 activation, with distinct underlying mechanisms, are required for the in vivo migration of T cell hybridomas.

Animals↗

PubMed2001

The GATA factor Serpent is required for the onset of the humoral immune response in Drosophila embryos.

Innate immunity in Drosophila is characterized by the inducible expression of antimicrobial peptides. We have investigated the development and regulation of immune responsiveness in Drosophila embryos after infection. Immune competence, as monitored by the induction of Cecropin A1-lacZ constructs, was observed first in the embryonic yolk. This observation suggests that the yolk plays an important role in the humoral immune response of the developing embryo by synthesizing antimicrobial peptides. Around midembryogenesis, the response in the yolk was diminished. Simultaneously, Cecropin expression became inducible in a large number of cells in the epidermis, demonstrating that late-stage embryos can synthesize their own antibiotics in the epidermis. This production likely serves to provide the hatching larva with an active antimicrobial barrier and protection against systemic infections. Cecropin expression in the yolk required the presence of a GATA site in the promoter as well as the involvement of the GATA-binding transcription factor Serpent (dGATAb). In contrast, neither the GATA site nor Serpent were necessary for Cecropin expression in the epidermis. Thus, the inducible immune responses in the yolk and in the epidermis can be uncoupled and call for distinct sets of transcription factors. Our data suggest that Serpent is involved in the distinction between a systemic response in the yolk/fat body and a local immune response in epithelial cells. In addition, the present study shows that signal transduction pathways controlling innate and epithelial defense reactions can be dissected genetically in Drosophila embryos.

Animals↗

PubMed2001

The imd gene is required for local Cecropin expression in Drosophila barrier epithelia.

Surfaces of higher eukaryotes are normally covered with microorganisms but are usually not infected by them. Innate immunity and the expression of gene-encoded antimicrobial peptides play important roles in the first line of defence in higher animals. The immune response in Drosophila promotes systemic expression of antimicrobial peptides in response to microbial infection. We now demonstrate that the epidermal cells underlying the cuticle of larvae respond to infected wounds by local expression of the genes for the antimicrobial peptide cecropin A. Thus, the Drosophila epidermis plays an active role in the innate defence against microorganisms. The immune deficiency (imd) gene was found to be a crucial component of the signal-induced epidermal expression in both embryos and larvae. In contrast, melanization, which is part of the wound healing process, is not dependent on the imd gene, indicating that the signalling pathways promoting melanization and antimicrobial peptide gene expression can be uncoupled.

Animals↗

PubMed2001

Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridoma.

The dissemination of T cell hybridomas to multiple nonhematopoietic tissues is blocked by pertussis toxin, suggesting the involvement of a chemokine. To study whether this chemokine is SDF-1, we employed a strategy proposed previously for gene therapy of AIDS, whereby the SDF-1 receptor CXCR4 (also a coreceptor for HIV) is retained in the endoplasmic reticulum (ER) and fails to reach the cell surface. We transfected SDF-1, carrying an ER retention sequence, into a T cell hybridoma. This altered chemokine is retained in the ER, where it binds CXCR4 and prevents the latter protein from reaching the surface. These cells failed to migrate toward SDF-1 or to invade fibroblast monolayers, although they could still migrate toward thymus and activation-regulated chemokine (TARC) and invade TARC-treated monolayers. Furthermore, the ability of the transfected cells to disseminate to multiple organs upon intravenous injection into mice was abolished. This dissemination reflects the in vivo migration patterns of activated and memory T cells into nonhematopoietic tissues, which is thus likely to depend on CXCR4. Attempts to block CXCR4 function as a therapy for AIDS may affect this migration with consequences for T cell function. Our results also suggest a decisive role for CXCR4 in the dissemination of hematopoietic malignancies expressing this receptor.

Animals↗

PubMed2001

Changing health inequalities in the Nordic countries?

The Nordic countries, referring here to Denmark, Finland, Norway, and Sweden, have often been viewed as a group of countries with many features in common, such as geographical location, history, culture, religion, language, and economic and political structures. It has also been habitual to refer to a "Nordic model" of welfare states comprising a large public sector, active labour market policies, high costs for social welfare as well as high taxes, and a general commitment to social equality. Recent research suggests that much of this "Nordicness" appears to remain despite the fact that the Nordic countries have experienced quite different changes during the 1980s and 1990s. How this relates to changes in health inequalities is in the focus of this supplement.

Finland↗

PubMed2000

Gi and Gq/11 proteins are involved in dissemination of myeloid leukemia cells to the liver and spleen, whereas bone marrow colonization involves Gq/11 but not Gi.

The migration of leukocytes into tissues is regulated by chemokines and other chemotactic factors that act on receptors that signal through Gi proteins. It seems likely that the colonization of tissues during dissemination of hematopoietic tumor cells is similarly regulated. In fact, dissemination of a T-cell hybridoma, a model for T lymphoma, was blocked when Gi proteins were inactivated by the S1 catalytic subunit of pertussis toxin that had been transfected into those cells. Pertussis toxin S1 blocked dissemination of MDAY-D2 murine myeloid leukemia cells to the liver and spleen, as in T-cell hybridoma cells, but it did not prevent bone marrow colonization. In contrast, overexpression of a function-defective mutant of the Gq/11 protein blocked dissemination to the bone marrow and also prevented Gq/11 dissemination to the liver and spleen. This indicates that the influx of these myeloid cells into all tissues requires the Gq/11 protein in addition to the Gi protein in the liver and spleen. (Blood. 2000;96:691-698)

Animals↗

PubMed2000

Cytoplasmic domain mutants of beta1 integrin, expressed in beta 1-knockout lymphoma cells, have distinct effects on adhesion, invasion and metastasis.

Structural requirements for beta 1 integrin cytoplasmic domain functions in adhesion, migration and signaling have been studied mainly for fibroblasts in vitro. The relevance for beta 1-dependent in vivo migration of lymphoid cells has not been assessed. To study this, we transfected beta 1 mutants into beta 1-deficient double knockout (DKO) ESb lymphoma cells, and tested the capacity of the cells to metastasize to liver and spleen. This was compared to alpha 4 beta 1-dependent invasion into cell monolayers in vitro and Mn2+-induced adhesion to fibronectin. Deletion of the five C-terminal residues or mutation of both threonines T788 and T789 to alanines blocked invasion and metastasis and greatly reduced adhesion, in line with known in vitro effects. However, mutations of the NPXY motif tyrosines had unexpected consequences. A Y783F mutation had no effect at all, but a Y783,795F double mutation strongly reduced Mn2+-induced adhesion, whereas it had limited effects on invasion and metastasis. Furthermore, cells expressing a beta 1 beta 2 chimeric subunit, which contains phenylalanines in the NPXY/F motifs, adhered poorly but invasion and metastasis was fully restored to the same levels as for cells expressing wild-type beta 1. We conclude that part of the functions of the beta 1 cytoplasmic domain that are required for adhesion are not essential for beta 1-dependent invasion and metastasis.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Encapsulation matrices for neurotrophic factor-secreting myoblast cells.

Encapsulated-cell therapy is an emerging technology that entails implantation of cell-containing devices that secrete therapeutic factors. One potential application of this technology is the delivery of neurotrophic factors to treat neurodegenerative disease. These devices typically use an internal matrix to serve as a cell scaffold. This study compares collagen-coated polyethylene terephthalate (PET) yarn scaffold versus collagen as a matrix for engineered C2C12 myoblasts. C2C12 cells transfected to secrete ciliary neurotrophic factor (CNTF) were immobilized in matrices and encapsulated into hollow fiber membrane devices. Encapsulated cells were monitored in vitro for viability, morphology, and factor secretion. Two independent methods (histology assessment and metabolic assay) were used to estimate viable cell density; a high correlation between the methods was found. After 4 weeks, encapsulated devices with PET scaffold had an almost nine-fold greater number of viable cells compared to collagen. PET matrix devices contained a thick annulus of compact, highly oriented cells. Collagen matrix devices contained sparse viable cells in a thin rim. Secretion assays showed cells in PET matrix released approximately four-fold the amount of CNTF versus cells in collagen (averaging 542 and 129 ng/day per device for PET and collagen matrix, respectively). The choice of encapsulation matrix was found to have a profound effect on cell morphology, level of secreted factor, and viability of encapsulated C2C12 cells.

Animals↗

PubMed1999

LFA-1 to LFA-1 signals involve zeta-associated protein-70 (ZAP-70) tyrosine kinase: relevance for invasion and migration of a T cell hybridoma.

We previously showed that LFA-1-dependent in vitro invasion and in vivo migration of a T cell hybridoma was blocked in cells overexpressing a truncated dominant-negative zeta-associated protein (ZAP)-70. The truncated ZAP-70 also blocked LFA-1-dependent chemotaxis through ICAM-1-coated filters induced by 1 ng/ml stromal cell-derived factor-1, but not LFA-1-independent chemotaxis induced by 100 ng/ml stromal cell-derived factor-1. This suggested that LFA-1 engagement triggers a signal that amplifies a weak chemokine signal and that dominant-negative ZAP-70 blocks this LFA-1 signal. Here we show that cross-linking of part of the LFA-1 molecules with Abs causes activation of free LFA-1 molecules (not occupied by the Ab) on the same cell, which then bind to ICAM-2 on other cells. This causes cell aggregation that was also blocked by dominant-negative ZAP-70. Thus, an LFA-1 signal involving ZAP-70 activates other LFA-1 molecules, suggesting that the chemokine signal can be amplified by multiple cycles of LFA-1 activation. The chemokine and the LFA-1 signal were both blocked by a phospholipase C inhibitor and a calpain inhibitor, suggesting that one of the amplified signals is the phospholipase C-dependent activation of calpain. Finally, we show that both Src-homology 2 domains are required for inhibition of invasion, chemotaxis, and aggregation by the truncated ZAP-70, suggesting that ZAP-70 interacts with a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) sequence. Remarkably, this is not an ITAM in the TCR/CD3 complex because this is not expressed by this T cell hybridoma.

Animals↗

PubMed1999

From regional ethnographies to interdisciplinary approaches-research on meals in Finland.

The paper reviews Finnish research on meals and meal patterns since the turn of the century. The main research traditions and cases representing various methodological approaches-qualitative interview, health behaviour questionnaire and dietary survey-are discussed. In line with studies undertaken in other industrialized countries, the Finnish studies show that meal patterns are related to socio-economic structure, work schedules, lifecourse, living conditions and food availability. Meal patterns vary by individual energy needs, and the nutrient contents of meals can be different from those of snacks. It is difficult to account for all determinants and characteristics of meals in a single study. The three cases shed light on the various aspects of the meal. When planning an empirical study on meals the researcher should ask herself/himself at least four questions: (1) who defines the meal?; (2) are meal patterns assumed to vary by time and between subgroups of the study population?; (3) is information on nutrient content of various eating occasions relevant to the study?; and (4) could information on meals be obtained from existing data sources?

Cultural Characteristics↗

PubMed1999

The effect of breakfast cereal on diet and serum cholesterol: a randomized trial in North Karelia, Finland.

OBJECTIVE: To test the hypothesis that a high carbohydrate breakfast with breakfast cereal leads to a meaningful reduction in dietary energy intake from fat, especially from saturated fat, and thus lower serum cholesterol levels. DESIGN: An open randomized controlled cross-over trial. The subjects were randomized into intervention breakfast cereal or usual breakfast (control) groups. SETTING: Free-living subjects aged 29-71 y in Eastern Finland SUBJECTS: 224 enrolled, 209 completed the study. The subjects were recruited from a survey of a random population sample and from other sources, and their serum cholesterol was not lower than 5.0 mmol/l. Recruited persons did not have any chronic disease or very low saturated fat intake. INTERVENTION: The cereal group consumed 80 g (men) or 60 g (women) cereal at breakfast and the control group continued their usual dietary habits for six weeks. After a wash out of six weeks, a cross-over with another six week trial period took place. Measurements (including serum samples and a 3 d food record) took place before and after the two trial periods. RESULTS: The intervention period led to 2.5 en% (energy percent units) reduction in saturated fatty acids intake. The reduction in total fat intake was 5.5 en%. This was compensated for by increased intake of carbohydrates. The reduction in saturated fatty acids intake led to modest (but in group 1 significant) 0.15 mmol/l (2.5%) reduction in total serum cholesterol level. CONCLUSIONS: The trial showed that regular cereal breakfast can lead to reduced intake of total and saturated fatty acids of the daily diet and consequently to reduction in serum cholesterol level.

Adult↗

PubMed1999

Dif and cactus are colocalized in the larval nervous system of Drosophila melanogaster.

The Rel protein Dif is a transcription factor suggested to control part of the immune response in the fruit fly Drosophila melanogaster. In uninfected animals, Dif is normally located in the cytoplasm, most likely in a complex with an IkappaB molecule such as Cactus. Upon infection, Dif is enriched in the nucleus of immunoresponsive tissues such as fat body and blood cells. Rel proteins in mammals not only participate in the control of the immune response, but are also thought to play important roles in the function of the nervous system. Here, we demonstrate that both Dif and Cactus are expressed in the central nervous system (CNS) of Drosophila. Interestingly, Dif and Cactus colocalize in their distribution, suggesting a functional link between these proteins in the CNS. In the larval CNS, both Dif and Cactus are expressed at relatively low levels in most cells and at high levels in the mushroom bodies and in small subsets of neurosecretory cells. The cytoplasmic localization of Dif and Cactus in the CNS cells is not affected by bacterial challenge. Instead, we observed changes in nuclear versus cytoplasmic localization of Cactus (but not Dif) along the dark-light cycle, with a strong nuclear localization in perineurial glia toward the end of the dark period. In the CNS of the prepupa, the intensity of the immunostaining for both Dif and Cactus is higher than in the larva. Interestingly, in fat body of uninfected prepupae, the Dif localization was mainly nuclear, suggesting a function for Dif during the process of pupariation.

Animals↗

PubMed1998

ZAP-70 tyrosine kinase is required for LFA-1-dependent T cell migration.

The ZAP-70 tyrosine kinase is essential for T cell activation by the T cell receptor. We show that ZAP-70 is also required for migration of T cells that is dependent on the integrin LFA-1. Invasion of TAM2D2 T cell hybridoma cells into fibroblast monolayers, which is LFA-1-dependent, was blocked by overexpression of dominant-negative ZAP-70 and by piceatannol but not by herbimycin A. The Syk inhibitor piceatannol blocks the Syk homologue ZAP-70, which is expressed by TAM2D2 cells, with the same dose dependence as the inhibition of invasion. Dominant-negative ZAP-70 completely inhibited the extensive metastasis formation of TAM2D2 cells to multiple organs upon i.v. injection into mice. Migration of TAM2D2 cells through filters coated with the LFA-1 ligand ICAM-1, induced by 1 ng/ml of the chemokine SDF-1, was blocked by anti-LFA-1 mAb and also abrogated by dominant-negative ZAP-70 and piceatannol. In contrast, migration induced by 100 ng/ml SDF-1 was independent of both LFA-1 and ZAP-70. LFA-1 cross-linking induced tyrosine phosphorylation, which was blocked by dominant-negative ZAP-70 and piceatannol. We conclude that LFA-1 engagement triggers ZAP-70 activity that is essential for LFA-1-dependent migration.

Animals↗

PubMed1998

Targeted disruption of the beta1 integrin gene in a lymphoma cell line greatly reduces metastatic capacity.

Integrins have been implicated in tumor metastasis. To investigate this, we generated beta1 integrin-negative double knockout (DKO) mutants of the highly metastatic ESb murine T-lymphoma cell line. The in vivo growth capacity of the mutants, which had lost alpha4beta1 and alpha6beta1 expression, was not altered, but their metastatic capacity was greatly reduced. Tail vein injection of 10(4) ESb and single-knockout cells led to death of all animals within 9-11 days. In contrast, only one-half of the animals injected with 10(4) DKO cells died, but much later, after 20-60 days. The other one-half remained disease-free for up to 100 days. Whereas ESb and single-knockout cells disseminated predominantly to liver and spleen, metastasis of DKO cells to these organs was rare, even after this prolonged period. Instead, skeletal muscles were invaded extensively. Metastatic capacity was largely restored in a DKO clone, which had been transfected with beta1 cDNA and expressed beta1 at similar levels as ESb cells. We conclude that beta1 integrins are essential for efficient liver and spleen colonization by the ESb lymphoma.

Alleles↗

PubMed1998

Gender, socioeconomic status and family status as determinants of food behaviour.

This study examines social structural and family status factors as determinants of food behaviour. The data were derived from the FINMONICA Risk Factor Survey, collected in Finland in spring 1992. A multidimensional framework of the determinants of food behaviour was used, including social structural position, family status and gender. The associations between the determinants of food behaviour were estimated by multivariate logistic regression models, adjusted for age and regional differences. Food behaviour was measured by an index including six food items which were chosen based on Finnish dietary guidelines. In general, women's food behaviour was more in accordance with the dietary guidelines than that of men. The pattern of association between educational level and food behaviour was similar for both genders, but slightly stronger for men than women. Employment status was associated only with women's food behaviour, but the tendency was the same for men. Marital status was associated with men's as well as women's food behaviour. The food behaviour of married men and women was more in line with the dietary guidelines than the food behaviour of those who had been previously married. Parental status, however, was only associated with women's food behaviour, that is, the food behaviour of women with young children was more closely in line with the dietary guidelines than that of the rest of the women.

Adult↗

PubMed1998

In vivo regulation of tissue-specific and LPS-inducible expression of the Drosophila Cecropin genes.

The inducible production of antibacterial cecropins in Drosophila fat body and haemocytes is controlled at the level of transcriptional induction. We demonstrate using germ-line transformation that a short, highly conserved, DNA region, including the insect kappaB motif, is necessary for tissue-specific expression in larvae and adults. Quantitative measurements of reporter gene activity in extracts from transgenic larvae confirmed the requirement of this proximal region for LPS-inducible expression in vivo. Transient expression in a blood cell line indicates the existence of positively acting elements further upstream of the conserved region. Furthermore, our in vivo data suggests that the distal upstream region contains negatively acting element(s).

Animals↗

PubMed1998

Isokinetic knee extensor strength and functional performance in healthy female soccer players.

The aims of this study were to determine the relationship between isokinetic knee extensor muscle strength at 60 degrees/s and 180 degrees/s and five functional performance tests (one-leg-hop, triple-jump, vertical-jump, one-leg-rising and square-hop), to determine the relationship between the five different functional performance tests and to present normative data and limb symmetry index concerning healthy female soccer players. In total 101 female soccer players (X = 20.3 years) were tested. A limb symmetry index, using weak/strong leg, varied from 83.9 to 96.3 in the tests. Between the functional performance tests there were in general correlations of r = 0.4-0.8 (P < 0.001). A correlation of r = 0.77 (P < 0.001) was obtained between one-leg-hop and triple-jump. No differences were found between the right and the left leg or the dominant and the non-dominant leg. Using linear regression models corrected for body weight, height and age, there were low correlations between the isokinetic strength measurements and the functional tests. It is not recommended using functional performance testing and isokinetic testing interchangeably.

Adult↗