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K Nygard

Publications and source records attributed to K Nygard.

11 recordsLinked to original sources

Emerging Salmonella Enteritidis anaerogenic phage type 14b: outbreak in Norwegian, Swedish and Finnish travellers returning from Greece.

In July 2001, the Norwegian Institute of Public Health (Folkehelseinstituttet, FHI) reported a cluster of Salmonella Enteritidis of phage type 14b infections in Norwegian travellers returning from Greece. An increase in the same uncommon phage type was also registered in Sweden and Finland at the same time. Cases of S. Enteritidis PT 14b in patients returning from Greece were reported in these three Nordic countries in 2001 (303 cases), 2002 (164 cases) and 2003 (199 cases). Case-control studies performed in 2001 in Norway and Sweden indicated that consumption of chicken was associated with illness. In 2002 and 2003, continuing case reports indicated that this uncommon phage type had probably become established in the Greek food chain. Tour operators were informed and contacts were made with Greek public health authorities. Because place of infection is not systematically included in most Salmonella notification systems, the S. Enteritidis phage type 14b outbreak reported here may represent only part of a larger outbreak among travellers visiting Greece. Infections are often reported only in the tourists' home countries and public health authorities in the tourist destinations may not be aware of the problem. Further collaboration between national institutes of public health in Europe is needed to detect outbreaks occurring among tourists.

Adult↗

Altered expression of IGFs and IGF-binding proteins during intrauterine growth restriction in guinea pigs.

The IGF system is one of the most important endocrine and paracrine growth factor systems that regulate fetal and placental growth. We hypothesized that intrauterine growth restriction (IUGR) in guinea pigs is mediated by the altered expression of IGFs and/or IGF binding protein (BP) mRNAs in tissues and is related to growth of specific tissues. IUGR was induced by unilateral uterine artery ligation on day 30 of gestation, and fetal plasma, amniotic fluid and tissue samples were collected at 55-57 days (term about 68 days) from paired IUGR and control fetuses (n=6). Western ligand blotting and immunoblotting were used to compare IGFBP levels in plasma and amniotic fluid. Total RNA was extracted from placenta and fetal tissues, and the relative abundance of IGF-II and IGFBP-1-6 mRNA was determined by Northern blotting, using species-specific probes where available. IUGR fetuses had decreased (P<0.01, by Student's t-test) placental weight and body weight with an increase in the brain:liver weight ratio. The principal IGFBPs in fetal plasma migrated at 40-35, 30 and 25 kDa and were identified as IGFBP-3, -2 and -4 respectively. IUGR was associated with elevated plasma IGFBP-2 and IGFBP-4 and reduced IGFBP-3 levels. IGFBPs were detected at low levels in amniotic fluid of control fetuses but at higher levels in IUGR fetuses. In IUGR placentae, there was a small increase in IGFBP-4 mRNA (P<0.05). IGFBP-2 mRNA increased (P<0.001) in liver of IUGR fetuses. IGF-II and IGFBP mRNA expression did not change in fetal muscle. The results are consistent with reduced IGF action, directly or through inhibition by IGFBPs, particularly by circulating and tissue IGFBP-2, as a potential causal factor in decreased growth of the placenta and certain fetal tissues.

Amnion↗

Reducing agent and tunicamycin-responsive protein (RTP) mRNA expression in the placentae of normal and pre-eclamptic women.

Recently, the gene encoding a new stress-induced protein termed reducing agent and tunicamycin-responsive protein (RTP) was identified. The function of RTP is unknown, however, the strong upregulation of RTP during cellular differentiation, and exposure to stress conditions including hypoxia suggests a specific role for RTP in these processes. In pre-eclampsia, impaired spiral artery remodelling and reduced perfusion may reduce oxygen tension in the placenta and thereby alter trophoblast differentiation and function. We therefore hypothesized that the expression of RTP mRNA is altered in the placentae of women with pre-eclampsia. The aims of this study were to determine the regional distribution and cellular localization of RTP mRNA expression and compare mRNA abundance in different regions of normotensive control and pre-eclamptic placentae. In normal and pre-eclamptic placentae, RTP mRNA was expressed in the syncytiotrophoblasts and in the intermediate trophoblasts of the basal plate. In early onset pre-eclampsia, RTP mRNA was more abundant in the chorionic villi regions. A further increase was localized to the syncytial knots and to the trophoblasts in the peri-infarct regions. The increased RTP expression may reflect lower oxygen tension and/or other stress stimuli in the placenta in pre-eclampsia.

Adult↗

Adrenomedullin messenger ribonucleic acid expression in the placentae of normal and preeclamptic pregnancies.

In pathological pregnancies, alterations in circulating maternal and fetal adrenomedullin (ADM) concentrations may mediate compensatory vascular responses in the fetal or placental circulation. To address whether ADM is a potential paracrine vasoactive factor within the placenta, the regional distribution and cellular localization of ADM mRNA expression were determined by Northern blot and in situ hybridization of different regions of the placenta and fetal membranes from pregnancies complicated by severe preeclampsia [<28 wk (n = 7) and >28 wk (n = 13)] and from normotensive pregnancies [<28 wk (n = 6) and >28 wk (n = 15)]. Northern blotting revealed that ADM mRNA (1.3 kb) was expressed in chorionic villi and basal plate regions, but was most abundantly expressed in the choriodecidua. By in situ hybridization, ADM mRNA was localized to the syncytiotrophoblasts and the extravillous cytotrophoblasts in the basal plate and choriodecidua regions. ADM mRNA expression was increased in the choriodecidua, syncytial knots, and cytotrophoblasts in peri-infarct regions in preeclampsia. In chorionic villous explant studies maintained at reduced oxygen tension, ADM mRNA abundance was increased at 12, 24, and 48 h. ADM mRNA expressed in syncytiotrophoblasts and cytotrophoblasts in the basal plate decidua and choriodecidua may contribute to the maternal and fetal plasma levels. In preeclampsia, regional increases in ADM mRNA may be induced by hypoxia and mediate local fetal/placental adaptive responses to reduced placental perfusion.

Adrenomedullin↗

Modulation of insulin-like growth factor (IGF) and IGF binding protein biosynthesis by hypoxia in cultured vascular endothelial cells.

Endothelial cells (EC) are hypoxia-tolerant and their capacity to proliferate in low oxygen tension is essential to maintain vascular endothelium integrity. The present study addresses whether hypoxia alters the expression of insulin-like growth factor (IGF) and IGF binding protein (IGFBP) genes in bovine aortic EC (BAEC) and bovine pulmonary artery EC (BPAEC). EC were cultured in normoxic (21%) conditions and exposed to 0% oxygen for 24, 48, or 72 h; some cells were reoxygenated by exposure to 21% oxygen for 24 or 48 h following hypoxia. IGF-I peptide and mRNA levels were very low in both cell types, and decreased further with exposure to hypoxia. Ligand blotting showed that both cell types synthesized 24 kDa (IGFBP-4), 30 kDa (IGFBP-5 and/or IGFBP-6), 43 kDa and 48 kDa IGFBPs (IGFBP-3 glycosylation variants). IGFBP-4 was the predominant IGFBP expressed by both cell types and did not change with exposure to hypoxia. Hypoxia caused a significant increase in IGFBP-3 secretion in BPAEC but not in BAEC. IGFBP-3 stable mRNA levels in BPAEC were increased correspondingly. IGFBP-5 was expressed only in BAEC and decreased with exposure to hypoxia. IGFBP-6 mRNA expression was low and increased in both cell types with exposure to hypoxia. These results demonstrate that EC IGFBP baseline expression as well as its expression in hypoxia vary in different vascular beds and suggest that the IGFBPs may be the dominant paracrine regulators of proliferation of EC as well as maintenance of endothelium integrity during hypoxia.

Animals↗

Cellular distribution of insulin-like growth factor binding protein mRNAs and peptides during rat lung development.

A role for IGF binding proteins (IGFBPs) in lung development is suggested by the identification of IGFBPs in lung tissue and production of IGFBPs by fetal lung cells in culture. To characterize the expression of IGFBPs during lung development in the rat in vivo (16 days gestation through adulthood), the expression of IGFBP mRNAs (IGFBP-1 to IGFBP-6) was examined by Northern analysis and in situ hybridization, and IGFBP peptides (IGFBP-2, IGFBP-3, and IGFBP-5) were localized by immunohistochemistry. IGFBP-1 mRNA was not detectable. IGFBP-2 mRNA (1.8 kb) was expressed in both fetal and postnatal life with peak expression during the fetal pseudoglandular stage. IGFBP-2 mRNA was localized mainly to airway epithelium. IGFBP-3 mRNA (2.4 kb) was maximally expressed postnatally in the saccular stage of lung development; it was identified in airway epithelium and interstitium in the fetal lung, but predominantly in airway epithelium after birth. IGFBP-4 (2.6 kb) and IGFBP-5 (6.0 kb) mRNA levels were maximal after birth, from 3 to 21 days postnatal (saccular and alveolar stage). IGFBP-4 mRNA was localized primarily to the interstitium and blood vessels early in development, but was abundant in airway epithelium in the adult. IGFBP-5 mRNA was most abundant in the airway epithelium. IGFBP-3, IGFBP-4, IGFBP-5, and to a lesser extent IGFBP-6 were localized to the large cartilaginous airways in the adult. IGFBP-2, IGFBP-3, and IGFBP-5 peptides were distributed more widely than their respective mRNAs, with a temporal pattern of immunoreactivity following that of their mRNAs. Maximal staining was noted in airway epithelium for IGFBP-2 in the newborn, for IGFBP-3 in the saccular stage (newborn to 3 days postnatal), and for IGFBP-5 in the alveolar stage (5 to 21 days postnatal). Our studies demonstrate that IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-5 are synthesized and distributed in spatially and temporally different patterns in the developing lung. The widespread distribution of IGFBP immunoreactivity compared with their respective mRNAs suggests that IGFBPs are important paracrine factors in the regulation of IGF action in the developing lung.

Animals↗

IGF-binding protein mRNAs in the human fetus: tissue and cellular distribution of developmental expression.

Insulin-like growth factors (IGF-I and IGF-II) are synthesized by most embryonic and fetal tissues, and regulate cellular growth and differentiation as autocrine/paracrine factors. A family of six IGF-binding proteins (IGFBPs) modulate IGF biological actions as both negative (inhibitory) and positive (potentiating) modulators. To determine the tissue distribution of IGFBP mRNA expression, we performed Northern blot analysis and in situ hybridization of human fetal tissues during gestational ages 10-16 weeks (n = 8). IGFBP-1 mRNA was expressed only in the liver, whereas other IGFBP mRNAs were expressed in variable abundance in every tissue examined. IGFBP-2 mRNA was expressed in moderate abundance in every tissue with the highest level observed in the liver; IGFBP-3 mRNA was expressed most abundantly in the skin, muscle and heart; IGFBP-4 mRNA was expressed in moderate abundance equally in all tissues; IGFBP-5 mRNA was expressed most abundantly in the skin, muscle and stomach, and IGFBP-6 mRNA was expressed in low abundance in all tissues. Notable exceptions were that liver expressed little or no IGFBP-4, -5 and -6 mRNAs, spleen and thymus expressed low levels of IGFBP-5 mRNA, and brain expressed little or no IGFBP-5 and IGFBP-6 mRNA. In situ hybridization of human fetal tissues showed IGFBP mRNAs were expressed in both epithelial and mesenchymal cells depending on the specific IGFBP and the stage of development. IGFBP-3, -4, and -5 mRNAs were localized mainly in the mesenchymal cells, and IGFBP-2 mRNA was localized predominantly in the epithelial cells. IGFBP-6 mRNA was localized in low abundance in both epithelial and mesenchymal cells. These studies indicate that IGFBPs are important paracrine modulators of IGF action on cellular growth and differentiation, by modulating IGF-dependent or IGF-independent actions.

Fetus↗

Induction of transforming growth factor-alpha gene expression in rat decidua is independent of the conceptus.

We have previously shown that decidua is the major site of transforming growth factor-alpha (TGF-alpha) gene expression at the feto-maternal interface during the early stages of pregnancy in the rat. The present study was undertaken to determine whether the presence of TGF-alpha mRNA in the decidua was in direct response to a signal derived from the conceptus. We therefore used the model of pseudopregnancy in rat, inducing decidualization in the absence of a conceptus. TGF-alpha mRNA expression was examined using Northern blot analysis, and TGF-alpha peptide was localized using immunohistochemistry. Pseudopregnancy was produced through standard hormonal priming followed by an artificial stimulus of intrauterine sesame oil or PBS to induce decidualization. Northern blot analysis demonstrated TGF-alpha mRNA expression specifically in the deciduoma beginning on the day of decidual stimulus (Day 4), increasing on Day 6, and continuing through Day 14. In contrast to decidua of normal pregnancy, an additional transcript of 3.0 kb was present in the deciduoma. Immunohistochemistry of tissues from Day 9 of pseudopregnancy revealed specific cytoplasmic immunoreactivity in the majority of stromal type decidual cells of the antimesometrial area, whereas mesometrial decidual cells were not immunoreactive. The results indicate that the induction of decidual TGF-alpha gene expression is not in direct response to a signal derived from the conceptus but is a de novo event associated with the decidual reaction, and that the resulting TGF-alpha peptide is present in the majority of stromal type antimesometrial decidual cells. These findings also suggest that TGF-alpha could be playing a role in proliferation and/or differentiation of the decidua.

Animals↗

Mitogenic activity of epidermal growth factor on newborn rat astroglia: interaction with insulin-like growth factors.

Newborn rat astroglia cells possess epidermal growth factor (EGF) and insulin-like growth factor (IGF) receptors, which suggests that these growth factors regulate their growth and development. To determine the relative roles and interactions between the two growth factors on astroglial growth, primary cultures of astroglial cells from newborn rats (1 day postnatal) were treated with pure peptides, singly or in combination in various concentrations, and the growth response was determined by DNA synthesis ([3H]thymidine incorporation). EGF, IGF-I, and IGF-II, as single peptides, stimulated DNA synthesis, with half-maximal stimulatory concentrations of 0.25 ng/ml for EGF, 2.0 ng/ml for IGF-I, and 25 ng/ml for IGF-II, respectively. These findings indicate that astroglial cells are responsive to these growth factors in physiological concentrations, with the relative sensitivity of EGF greater than IGF greater than IGF-II. When EGF and IGF-I were added in combination, the growth stimulatory effect was greater than the additive effects of each growth factor added alone, indicating that the two growth factors act in synergism with each other. In particular, addition of increasing concentrations of EGF from 0.25-10 ng/ml to a constant concentration of 50 ng/ml IGF-I resulted in significant potentiation of [3H]thymidine incorporation of astroglial cells. To determine if the synergistic effect was due to a local synthesis of IGF-I by astroglia, a specific monoclonal antibody against IGF-I (Sm 1.2) was added to the peptides. Sm 1.2 decreased not only IGF-I-stimulated DNA synthesis, but also EGF-stimulated DNA synthesis, suggesting that the effects of EGF were contributed to in part by the local synthesis of IGF-I by astroglial cells. Analysis of conditioned medium from cells treated with EGF revealed a significant increase (approximately 2-fold) in IGF-I (from 4.5 to 8.8 ng/ml), but not IGF-II. To determine if the EGF effect on IGF synthesis was at the level of IGF-I mRNA transcription, stable IGF-I mRNA levels were determined in the astroglial cells before and after stimulation with EGF, using Northern analysis and quantification by densitometry. Astroglia expressed four IGF-I mRNA transcripts as in the adult and fetal liver, but only one (3.6 kilobases) IGF-II mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The expression of insulin-like growth factor and insulin-like growth factor binding protein mRNAs in mouse placenta.

Insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) are paracrine regulators of tissue growth and development, and are expressed at the sites of biological action. To study the role of the IGFs and IGFBPs in mouse placental development, we determined the temporal and spatial expression patterns of the mRNAs at embryonic days 10.5 to 18.5 by in situ hybridization. IGF-II mRNA was expressed strongly in mesoderm and fetal blood vessels of early placenta and in labyrinthine trophoblast of later placenta. In the junctional zone, IGF-II mRNA was expressed first in spongiotrophoblasts, later strongly in glycogen cells and variably in giant cells. IGFBP-2 mRNA was expressed weakly in spongiotrophoblasts and glycogen cells. IGFBP-2, -5 and -6 mRNAs were detected in the stroma of the metrial gland. Myometrium expressed IGFBP-2 mRNA strongly, IGFBP-6 mRNA moderately and IGFBP-5 mRNA weakly. The endothelium of maternal blood vessels in decidua expressed IGFBP-3 and -5 mRNAs, and some deeper vessels expressed IGFBP-4 mRNA. In the yolk sac, IGF-II mRNA was expressed in endoderm and mesoderm, whereas IGFBP-1, -2 and -4 mRNAs were expressed only in endoderm, and IGFBP-4 mRNA in mesoderm. Strong expression of IGF-II mRNA in glycogen cells suggests a role in the autocrine/paracrine regulation of invasion. Similar to rat and guinea pig, but in contrast to man and primates, IGFBP mRNAs, except IGFBP-4, were not expressed in mouse decidua. However, IGFBP-3, -4 and -5 mRNAs were expressed in endothelium of maternal blood vessels, and IGFBP-2 and -6 mRNAs in myometrium, where IGFBPs may play a critical role in regulating trophoblast invasion. These findings suggest possible biological roles of the peptides at the feto-maternal interface.

Amnion↗