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Biomedical subjects

E Roos

Publications and source records attributed to E Roos.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1997

v-src-induced cell shape changes in rat fibroblasts require new gene transcription and precede loss of focal adhesions.

The mechanism of v-src-induced morphological transformation is still obscure. We compared LA29 rat fibroblasts, which express a temperature-sensitive (ts) v-src mutant, with D1025 rat fibroblasts, transfected with a ts mutant of v-fps. Upon transformation, LA29 cells adopted an elongated shape with reduced focal adhesions and loss of actin stress fibers. In contrast, activation of v-fps in D1025 cells had little effect on morphology. In both cells, paxillin was strongly tyrosine phosphorylated upon activation of the kinases. This indicates that paxillin phosphorylation is not required, or not sufficient, for the v-src-induced disruption of focal adhesions. As previously described by others, v-src activated the ras-MAP kinase (MAPK) pathway, as indicated by tyrosine phosphorylation of the rasGAP-associated proteins p62 and p190 and MAPK phosphorylation. Since MAPK affects transcription, this suggested that novel gene transcription was required. This notion was confirmed using actinomycin D and cycloheximide, which did not impair activation of v-src kinase activity, but completely blocked v-src-induced morphological changes, as demonstrated using image analysis. Furthermore, we observed that v-src-induced changes in cell shape occurred before the reduction in number and size of focal adhesions. We conclude that v-src-induced transformation of rat fibroblasts depends on synthesis of a protein, which induces rapid changes in cell shape that precede the loss of focal adhesions.

Actin Cytoskeleton↗
PubMed1997

alphaV Integrins on HT-29 colon carcinoma cells: adhesion to fibronectin is mediated solely by small amounts of alphaVbeta6, and alphaVbeta5 is codistributed with actin fibers.

HT-29 colon carcinoma cells form liver metastases upon intrasplenic injection, and adhesion to fibronectin under the liver microvascular liver endothelium is likely to be important for metastasis formation. We have therefore studied the integrins involved in fibronectin adhesion. This was not affected by blocking antibodies against the beta1, alpha3, and alpha5 integrin subunits, but it was blocked by an RGD-containing peptide, indicating involvement of RGD-dependent non-beta1 alphaV integrins. Both alphaVbeta5 and alphaVbeta6 were detected on HT-29 cells. Blocking mAb against alphaV, but not against alphaVbeta5, abolished adhesion. From a HT-29 cell lysate, only alphaVbeta6 bound to a fibronectin-Sepharose column. Thus, alphaVbeta6 is the main fibronectin receptor on HT-29 cells, despite the very low levels of alphaVbeta6 and the much higher levels of alphaVbeta5. The HT29 cells did not spread on fibronectin in the absence of serum, not even after a three- to fourfold increase in alphaVbeta6 levels, induced by interleukin 4. The cells did spread on vitronectin. Using immunofluorescence we observed that both on vitronectin and on fibronectin alphaVbeta5 was arranged in a striped pattern, aligned with actin fibers, and not in focal adhesions. On fibronectin, but not on vitronectin, alphaVbeta6 was concentrated in a punctate pattern at the periphery of cell islands.

Actins↗
PubMed1997

Activation of G-proteins with AIF-4 induces LFA-1-mediated adhesion of T-cell hybridoma cells to ICAM-1 by signal pathways that differ from phorbol ester- and manganese-induced adhesion.

T-cell hybridomas metastasize widely, and the extent of dissemination correlates with invasiveness in fibroblast cultures. Previously, we provided evidence that both metastasis and in vitro invasion require activation of LFA-1, induced by G-protein-transduced signals triggered by as yet unidentified factors. We show here that LFA-1-mediated adhesion of TAM2D2 T-cell hybridoma cells to ICAM-1 can in fact be induced by direct activation of G-proteins using AIF-4, to the same extent as by using PMA or Mn2+. We assessed effects of protein kinase C (PKC), tyrosine kinase (TK), PI3-kinase (PI3K), and phospholipase C (PLC) inhibitors. Both AIF-4-induced adhesion and invasion were completely blocked by the TK inhibitor genistein and partially blocked by the PI3K inhibitor wortmannin, but not influenced by PKC inhibitor GF109203X. Downregulation of PKC did not affect invasion or adhesion induced by AIF-4 either. In contrast, GF109203X and PKC downregulation blocked PMA-induced adhesion, but genistein and wortmannin had no effect. Invasion and both AIF-4- and PMA-induced adhesion were completely blocked by the PLC inhibitor U73122. Mn(2+)-induced adhesion, which was not or was only partially blocked by the other inhibitors, was delayed by U73122, and spreading of Mn(2+)-treated cells was completely prevented by U73122. However, PLC activity during adhesion was not detected. We conclude that signals required for invasion and G-protein-induced adhesion are similar and are distinct from PKC-induced adhesion, and that in all cases PLC is likely to be activated, but is probably too local and/or transient to be detected.

Aluminum Compounds↗
PubMed1997

Meal pattern and nutrient intake among adult Finns.

The purpose of this study was to investigate the relationship between meal pattern and diet. Nutrient contents of meals, snacks and other eating occasions were compared and differences in dietary intake analysed between respondents following a conventional meal pattern and others. A random sample of 1861 adults aged 25-64 from four regions of Finland completed a mailed questionnaire and 3-day food record in the spring of 1992. A conventional meal pattern was defined on the basis of national dietary guidelines as including breakfast, warm lunch and warm dinner, and subjects were identified with the help of the questionnaire. Meals and snacks were defined according to the respondents subjective criteria. Forty-four percent of all respondents followed the conventional meal pattern. Meal pattern has no effect on nutrient intake in men and small effects in women. Women following the conventional meal pattern had higher energy and cholesterol intake and lower alcohol and vitamin C intake than other women. Meals contributed to energy, protein and fat intake, and snacks to sugar and alcohol. Meal pattern had only a small effect on diet and conventional meal pattern cannot be considered healthier than other meal patterns.

Adolescent↗
PubMed1997

Increasing prevalence of underreporting does not necessarily distort dietary surveys.

OBJECTIVES: To study the magnitude of and trends in energy underreporting and to compare food consumption, nutrient intake and socioeconomic characteristics of underreporters to those of other Finnish adults. DESIGN: Cardiovascular risk factor surveys in 1982 and 1992 using a 3 d food record. Underreporting was defined as energy intake lower than 1.27* BMR, since energy intake < 1.27* BMR is improbable. SETTING: Four areas in Finland, both rural and urban. SUBJECTS: 1746 men and 1921 women, aged, 25-64 y. RESULTS: Proportion of underreporters has increased from 33% in 1982 to 46% in 1992 among women and from 27% in 1982 to 42% in 1992 among men. In a logistic regression model, BMI over 25 kg/m2, female gender, age over 45 y and high educational level predicted underreporting. Shares of energy intake from fat, carbohydrates, protein and alcohol remained the same whether or not underreporters were excluded. However, underreporters consumed significantly higher proportion of vegetables, fish, meat, potatoes, fruit and berries and less fat than others. In the 1992 data the absolute intake of most micronutrients increased and micronutrient densities decreased when underreporters were excluded. CONCLUSIONS: The proportion of underreporters has grown from 1982 to 1992. Results expressed as a percentage of energy intake are not affected by the exclusion of underreporters. In contrast, micronutrient intakes, both absolute and energy density values, were distorted by underreporting. Underreporting should be taken into account in future studies.

Adult↗
PubMed1997

Alcohol beverage drinking, diet and body mass index in a cross-sectional survey.

OBJECTIVE: The study was carried out to determine the associations of alcohol beverage drinking with macronutrients, antioxidants, and body mass index. SETTING: Dietary subsample of the 1992 Finmonica cardiovascular risk factor survey in Finland; a cross-sectional study. SUBJECTS: 985 women and 863 men were drawn from the population register in the four monitoring areas. All subjects were 25-64 y of age. METHODS: The mailed questionnaire included questions covering socioeconomic factors, physical activity, smoking, and alcohol consumption. The diet was assessed using a three-day food record. RESULTS: The dietary differences between abstainers and alcohol consumers were more significant than between consumers of different alcoholic beverages. Among drinkers, fat intake as a percentage of energy was higher and carbohydrate intake was lower than among abstainers. Those who preferred wine, however, had the highest vitamin C intake; female wine drinkers also had the highest carotenoid intake. With the exception of those who mainly preferred spirits, alcohol energy was not added to the diet but seemed to substitute food items both in men and women. Despite the similar total daily energy intakes, daily energy expenditure, and physical activity index, male drinkers were leaner than abstainers. In women, the proportion of underreporters of energy intake increased with increasing alcohol consumption, and the association between alcohol and body mass index was similar to that in men after the exclusion of underreporters. CONCLUSIONS: Alcohol consumers were leaner than abstainers, and wine drinkers in particular had more antioxidants in their diet.

Adult↗
PubMed1996

Expression of pertussis toxin adenosine diphosphate-ribosyltransferase in a T-cell hybridoma reduces metastatic capacity.

T-cell hybridomas are highly metastatic, and their in vitro invasiveness correlates with metastatic capacity. Invasion is blocked by pertussis toxin (PT), which adenosine diphosphate (ADP)-ribosylates G1-proteins, and we have provided evidence that the PT-sensitive signal stimulates leukocyte function-associated antigen-1 (LFA-1)-mediated adhesion required for invasion. PT pretreatment of TAM2D2 T-cell hybridoma cells reduced metastasis, but only to a limited extent. In the present study, we have transfected the cDNA of the PT ADP-ribosyltransferase S1 subunit into TAM2D2 cells to abrogate G1-protein function permanently. We report here a substantial reduction in the metastatic capacity of two transfectants, S05 and S09, in which 88% and 95% of the G1-proteins was ADP-ribosylated. Two-thirds of the mice injected with S09 cells were tumor-free. Metastasis to the liver was almost completely prevented and less metastases were formed in the spleen and kidneys. Metastasis formation by S05 cells in liver and spleen was much reduced, but in lymph nodes and peritoneal tissues, metastases occurred with a frequency similar to that of controls. We conclude that G1-proteins play an important role in T-cell hybridoma metastasis. We propose that the reduction in metastasis is due to diminished entry of tumor cells from the blood into tissues.

Animals↗
PubMed1996

Inhibition and stimulation of LFA-1 and Mac-1 functions by antibodies against murine CD18. Evidence that the LFA-1 binding sites for ICAM-1, -2, and -3 are distinct.

The murine CD18 monoclonal antibody (mAb) M18/2 was reported to inhibit lymphoma metastasis [Zahalka, M. A. et al. (1993) J. Immunol. 150, 4466]. To identify the pathways potentially blocked, we studied the effects of M18/2 compared with two new mAb against murine CD18, GAME-46, and -245. Whereas the GAME mAb blocked most Mac-1-mediated interactions, M18/2 had no effect, or even stimulated. The same was true for adhesion of LFA-1 to ICAM-1. To test effects on interactions with different ICAMs, we used L cells transfected with human ICAM-1, -2, and -3. As previously described, mouse LFA-1 does not bind to human ICAM-1 but we show here that mouse LFA-1 does bind to human ICAM-2 and -3. Again, the GAME mAb blocked completely, but M18/2 did not. These results indicate that the LFA-1 binding sites for ICAM-1 and ICAM-2 and -3, although in close vicinity, are distinct. Furthermore, effects of M18/2 on metastasis cannot be ascribed to blocking of any known beta2-integrin activity.

Animals↗
PubMed1996

Modern and healthy?: socioeconomic differences in the quality of diet.

OBJECTIVE: The purpose of this study was to describe how nutrient intake and food consumption varied according to education and household income in men and women. The second aim was to find out to what extent the goals of the national dietary guidelines were met in different socioeconomic groups. DESIGN: A random dietary survey using a 3 d estimated food record and a self-administered questionnaire. SETTING: Individuals from four different regions in Finland in spring 1992. SUBJECTS: 870 men and 991 women aged 25-64 y. MAIN OUTCOME MEASURES: Food group and nutrient consumption, two saturated fat indices, educational level and household income. MAIN RESULTS: Men with a higher educational level had a lower energy intake and women with a higher income a lower intake of carbohydrates. The intake of vitamin C and carotenoids increased with increasing socioeconomic status. Otherwise, no socioeconomic differences in energy intake, densities of fat and saturated fat, macronutrient or fibre were found. Higher socioeconomic groups consumed more cheese, vegetables, fruit and berries and candies and less milk, butter and bread. CONCLUSIONS: Higher socioeconomic groups did not follow current national dietary guidelines better than lower socioeconomic groups. Higher socioeconomic groups consumed more of the modern recommended foods, such as vegetables and fruit and berries, but less traditional recommended foods, such as bread and potatoes.

Adult↗
PubMed1995

Spreading and focal contact formation of human melanoma cells in response to the stimulation of both melanoma-associated proteoglycan (NG2) and alpha 4 beta 1 integrin.

In this study, we evaluated the potential role for a specific melanoma-associated chondroitin sulfate proteoglycan core protein, termed NG2, to collaborate with alpha 4 beta 1 integrin in focal contact formation in human melanoma cells. Although melanoma cells adhered to substrata coated with either the alpha 4 beta 1 integrin binding fibronectin synthetic peptide CS1-OVA or anti-NG2 mAbs, no spreading or focal contact formation was observed on either substratum. However, melanoma cells spread and formed focal contacts on "chimeric substrata" coated with CS1-OVA and the anti-NG2 mAb, 9.2.27, indicating that engaging both adhesion receptors changes the adhesion phenotype of melanoma cells by reorganizing the cytoskeleton. The collaboration between the two receptors is specific to fibronectin, since cells adherent on substrata coated with low concentrations of either laminin and 9.2.27 or type IV collagen and 9.2.27 failed to spread, while cells adherent on low concentrations of fibronectin and 9.2.27 exhibited a fully spread morphology. Two selective tyrosine kinase inhibitors, genistein and herbimycin A, totally inhibited cell spreading on the substrata coated with CS1-OVA and 9.2.27, indicating that tyrosine kinase(s) is important for cell spreading and focal contact formation. When cells were cultured on substrata coated with CS1-OVA and 9.2.27, two proteins (M(r) 130,000 and 120,000) were tyrosine phosphorylated in a genistein- and herbimycin A-sensitive fashion. These proteins were not immunologically related to pp125FAK or alpha 4 beta 1 integrin. Importantly, when melanoma cells were cultured on substrata coated with CS1 and then stimulated with 9.2.27-conjugated microsphere beads, formation of focal contacts and stress fibers was also observed, indicating that NG2 can collaborate with alpha 4 beta 1 integrin when each receptor is engaged on distinct and separate substrata. These results demonstrate that NG2 acts as a coreceptor for spreading and focal contact formation in association with alpha 4 beta 1 integrin in melanoma cells and suggest a model in which the NG2 core protein communicates to alpha 4 beta 1 integrin by an inside-out signaling mechanism.

Antibodies, Monoclonal↗
PubMed1995

Adhesion of carcinoma cells to rat hepatocytes and rat fibronectin is inhibited by the OPAR monoclonal antibody, which is directed against a rat liver-specific carbohydrate epitope.

The OPAR mouse monoclonal antibody (mAb) directed against rat hepatocytes was previously shown to inhibit adhesion of TA3/Ha mammary carcinoma cells to hepatocytes. The antigen is abundantly present at the surface of hepatocytes beneath the endothelium of liver capillaries where we have observed invasion of carcinoma cells to occur. The OPAR mAb reacted with three major bands on a Western blot of liver plasma membrane proteins. The same proteins were also seen upon immunoprecipitation from iodinated liver plasma membrane proteins. We have isolated OPAR antigens by lectin wheat germ agglutinin (WGA) and OPAR affinity chromatography. Amino acid sequence analysis revealed that two of the bands were alpha 1-macroglobulin and C4-binding protein, which are serum components produced by hepatocytes. The presence of the epitope on distinct proteins and our previous observation that it can be detected in the Golgi apparatus but not in the endoplasmic reticulum, suggested that OPAR reacts with a liver-specific glycoconjugate. Loss of OPAR reactivity after neuraminidase and N-glycosidase F treatment showed that the epitope contains sialic acid residues on N-linked sugar moieties. OPAR also reacted with rat fibronectin, and inhibited adhesion of TA3/St cells to fibronectin. This explains the inhibition by the OPAR mAb of TA3/St cell adhesion to hepatocytes, which we have shown to be due mainly to interaction with hepatocyte surface-associated fibronectin. However, adhesion of the related TA3/Ha cells to hepatocytes, which is mediated by the alpha 6 beta 4 integrin, and does not involve binding to fibronectin, is also inhibited. This suggests that alpha 6 beta 4 on liver-metastasizing carcinoma cells binds to an OPAR epitope-carrying glycoprotein produced by hepatocytes.

Amino Acid Sequence↗
PubMed1995

Targeted disruption of CD44 in MDAY-D2 lymphosarcoma cells has no effect on subcutaneous growth or metastatic capacity.

CD44 splice variants have been shown to be involved in metastasis of carcinomas. In addition, the standard form of CD44 has been implicated in metastasis, particularly of melanomas and lymphomas. To investigate this, we have generated a CD44-negative mutant of the highly metastatic murine MDAY-D2 lymphosarcoma. The two CD44 alleles of this diploid cell line were sequentially disrupted by homologous recombination, using isogenic CD44 genomic constructs interrupted by a neomycin or hygromycin resistance-conferring gene. The resulting double knockout (DKO) cells had completely lost the capacity to bind to immobilized hyaluronic acid, but did not differ from MDAY-D2 cells in integrin expression or in vitro growth. Subcutaneous (s.c.) growth potential and metastatic capacity of MDAY-D2 and DKO cells were assessed by s.c. and i.v. injection of the lowest cell dose (10(3) or 10(4), respectively) that gave rise to tumor formation by MDAY-D2 cells in approximately 100% of the mice. Quite unexpectedly, we observed no difference at all in either s.c. growth rate or local invasion into surrounding tissues between MDAY-D2 cells and the CD44-negative DKO cells. Also hematogenous metastasis formation upon i.v. injection was similar: both parental and DKO cells metastasized extensively to the spleen, liver, and bone marrow. We conclude that, at least for these MDAY-D2 lymphosarcoma cells, the standard form of CD44 is dispensable for tumor growth and metastasis. Our results show that targeted disruption of genes in tumor cells is a feasible approach to study their role in tumorigenesis and metastasis.

Animals↗
PubMed1995

Adhesion of lymphoma cells to fibronectin: differential use of alpha 4 beta 1 and alpha 5 beta 1 integrins and stimulation by the 9EG7 mAb against the murine beta 1 integrin subunit.

Murine ESb and MDAY-D2 lymphoma cells are highly metastatic, in particular to the liver, and are highly invasive in hepatocyte cultures. This may involve adhesion to hepatocyte surface-associated fibronectin (Kemperman et al., 1994, Cell Adh. and Communic. 2:45). Both ESb and MDAY-D2 cells express the fibronectin receptor alpha 4 beta 1, and MDAY-D2 cells in addition also alpha 5 beta 1. Yet, adhesion of ESb cells to fibronectin was low, and MDAY-D2 cells did not adhere at all, but adhesion of both cells was stimulated by phorbol myristate acetate (PMA) and Mn2+. In ESb cells, this adhesion was mediated by alpha 4 beta 1. In MDAY-D2 cells, however, only alpha 5 beta 1 was involved, despite alpha 4 beta 1 levels similar to ESb cells. The alpha 4 beta 1 integrin was functional since it mediated adhesion of MDAY-D2 cells to VCAM-1. An alpha 5 beta 1-negative variant of MDAY-D2 adhered to fibronectin and this was mediated by alpha 4 beta 1. These results indicate that alpha 4 beta 1 function in these cells is suppressed in the presence of alpha 5 beta 1. Adhesion of ESb cells to hepatocytes was inhibited by anti-alpha 4 antibody, but only by 30%, and fibronectin adhesion was found to have no role in the interaction of MDAY-D2 cells with hepatocytes. This suggests that alpha 4 beta 1 and alpha 5 beta 1 function is not activated during this interaction. The 9EG7 antibody against mouse beta 1 integrin was described to inhibit beta 1 integrins (Lenter et al., 1993, Proc. Natl. Acad. Sci. USA, 90, 9051). In contrast, we observed that 9EG7 stimulated beta 1-integrin function: Adhesion of ESb and MDAY-D2 cells not only to fibronectin, but also to laminin was induced or enhanced.

Animals↗