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| 2. |
- Junttila, T T, et al.
(författare)
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Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells
- 2005
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Ingår i: Cancer Research. - 1538-7445. ; 65:4, s. 1384-1393
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Tidskriftsartikel (refereegranskat)abstract
- ErbB1 and ErbB2 receptors are well-characterized targets for anticancer drugs, but the clinical relevance of the related ErbB4 receptor is unknown. Here, we have assessed the clinical significance of the proteolytically cleavable ErbB4 isoforms in breast cancer patients and investigated their functions in vitro. The expression of transcripts encoding the cleavable ErbB4 isoforms associated with estrogen receptor-{alpha} (ER) expression (P < 0.001) and a high histologic grade of differentiation (P ≤ 0.002) in real-time reverse transcription-PCR analysis of 62 breast cancer samples. Despite high ErbB4 mRNA expression levels in a subset of samples, ErbB4 gene amplification was not observed. High ErbB4 protein expression levels, as assessed by immunohistochemistry, associated with a favorable outcome in ER-positive cases from a series of 458 breast cancer patients (P = 0.01), whereas no association between ErbB4 expression and survival was found among women with ER-negative cancer (P = 0.86). However, nuclear ErbB4 immunoreactivity was associated with poor survival as compared with women whose cancer had membranous ErbB4 staining (P = 0.04). In vitro, overexpression of a cleavable ErbB4 isoform in ER-positive breast cancer cells resulted in translocation of a proteolytically released intracellular ErbB4 receptor fragment into the nucleus, as well as, enhanced proliferation, anchorage-independent growth, and estrogen response element–mediated transcriptional activity. These results suggest that the association of ErbB4 expression with clinical outcome is dependent on the subcellular localization of ErbB4 and that a proteinase-cleavable ErbB4 isoform promotes growth of ER-positive breast cancer and enhances ER-mediated gene transcription.
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| 3. |
- Parikka, V, et al.
(författare)
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Estrogen responsiveness of bone formation in vitro and altered bone phenotype in aged estrogen receptor-alpha-deficient male and female mice
- 2005
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 1479-683X .- 0804-4643. ; 152:2, s. 301-314
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Although the beneficial effects of estrogen on bone are well known, the roles of estrogen receptors (ERs) in mediating these effects are not fully understood. Methods: To study the effects of long-term ERalpha deficiency, bone phenotype was studied in aged ERalpha knockout (ERKO) mice. In addition, ERKO osteoclasts and osteoblasts were cultured in vitro. Design and results: Histomorphometric analysis showed that the trabecular bone volume and thickness were significantly increased and the rate of bone formation enhanced in both male and female ERKO mice in comparison to the witd-type animals. In ERKO males, however, the bones were thinner and their maximal bending strengths decreased. Consistent with previous reports, the bones of knockout mice, especially of female mice, were shorter than those of wild-type mice. In addition, the growth plates were totally absent in the tibiae of aged ERKO females, whereas the growth plate cartilages were detectable in wild-type females as well as in all the males. Analysis of cultured bone marrow cells from 10- to 12-week-old mice demonstrated that 17beta-estradiol could stimulate osteoblastic differentiation of bone marrow cells derived from ERKO mice relatively to the same extent as those derived from wild-type mice. This was demonstrated by increases in synthesis of type I collagen, activity of alkaline phosphatase and accumulation of calcium in cultures. Total protein content was, however, reduced in ERKO osteoblast cultures. Conclusions: These results show altered bone phenotype in ERKO mice and demonstrate the stimulatory effect of estrogen on ostcoblasts even in the absence of full-length ERalpha.
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| 4. |
- Arcalis-planas, A., et al.
(författare)
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Limited use of sea ice by the Ross seal (Ommatophoca rossii), in Amundsen Sea, Antarctica, using telemetry and remote sensing data
- 2015
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Ingår i: Polar Biology. - : Springer Science and Business Media LLC. - 0722-4060 .- 1432-2056. ; 38:4, s. 445-461
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Tidskriftsartikel (refereegranskat)abstract
- To understand the use and importance of the Antarctic sea ice to the Ross seal (Ommatophoca rossii), four adult females were tagged with Argos satellite transmitters in the Amundsen Sea, Antarctica. The Ross seal is the least studied of the Antarctic seal species and nothing was previously known about their behaviour in the Amundsen Sea. During almost 1 year, their movements, haul out behaviour and time spent at different temperatures were logged. By comparing their movements with daily ice maps, distances to the ice edge were calculated, and seals dependence on sea ice for resting, breeding and moulting was analysed. The tagged seals spent on average 70.8 % (range 66.8–77.8 %) of their time in the water and hauled out mainly during the moult in December–January, and in late October–mid-November during breeding. During the pelagic period, they were on average 837.5 km (range 587–1,282 km) from the ice edge indicating a fully pelagic life during several months. Their pelagic behaviour suggests that Ross seals, although being an ice obligate species, may adapt comparatively easy to climate change involving ice melting and recession and thereby potentially being less sensitive to the reduction of sea ice than other Antarctic seal species. Although nothing is known about their mating behaviour, they appear to be relatively stationary during moulting and breeding, hence requiring a small ice surface. Although previous studies in other parts of Antarctica have found similar results, still many questions remain about this peculiar species.
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| 5. |
- Bäcklin, B-M, et al.
(författare)
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Undersökning av sälar insamlade 2015
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sedan 1970-talet har gråsäl (Halichoerus grypus), knubbsäl (Phoca vitulina) och vikare (Phoca hispida) insamlats och undersökts på Naturhistoriska riksmuseet (NRM). Majoriteten av de undersökta sälarna är gråsälar. Beroende på jakt under 1900-talet och nedsatt reproduktion under århundradets senare del så minskade sälpopulationerna i Östersjön. Under 1970-och 1980-talet noterades ett antal sjukliga förändringar som kallades Baltic Seal Disease Complex framför allt hos gråsäl och som misstänktes ha samband med höga halter av miljögifter som PCB och DDT. Förekomsten av flera av dessa förändringar liksom halterna av PCB och DDT har minskat sedan dess. Hos gråsäl har därefter förekomst av tarmsår ökat och minskat, späcktjockleken minskat och förekomst av leverparasiter ökat.Under år 2015 insamlades och undersöktes sälar och prover från 137 gråsälar, 44 knubbsälar och 27 vikare. I övrigt inrapporterades 196 döda sälar funna på stränder av allmänheten.Gråsälspopulationen ökar för närvarande med ca 8% per år och 85% av de undersökta honorna mellan 6-24 år var dräktiga. Knubbsälspopulationerna ökar för närvarande med 7-9% per år. Antal undersökta knubbsälar var visserligen betydligt färre än antal undersökta gråsälar men andel dräktiga honor i motsvarande åldersgrupp var endast 57%. Vikarepopulationen i Bottenviken ökar för närvarande med ca 4,5% per år. Hos vikare inkom endast en könsmogen hona från dräktighetsperioden och hon var dräktig.Av de undersökta vikarna var 20 av 27 yngre än 4 år gamla. Två två-åriga vikarhonor hade missbildningar i form av diafragmabråck hos den ena och avsaknad av ett livmoderhorn hos den andra.Sammanfattningsvis ser hälsosituationen för undersökta gråsälar i Östersjön delvis bättre ut än tidigare och populationstillväxten har varit stabil under de senaste 15 åren. Antal undersökta knubbsälar och vikare är för få för att redovisa patologiska trender men undersökta knubbsälar visade tendens till låg dräktighetsfrekvens som bör studeras närmare. De båda västliga bestånden av knubbsälar drabbades av epidemier 1988, 2002 och 2014 och populationstillväxten hos dessa bestånd har minskat efter 2002. Däremot har populationen av knubbsälar på östkusten visat på en stadig populationstillväxt sedan 1970-talet. Vikarepopulationen i Bottniska viken har en fortsatt låg tillväxt
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| 6. |
- Gu, G, et al.
(författare)
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Estrogen protects primary osteocytes against glucocorticoid-induced apoptosis
- 2005
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Ingår i: Apoptosis. - : Springer Science and Business Media LLC. - 1360-8185 .- 1573-675X. ; 10:3, s. 583-595
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoid-induced osteoporosis may be at least in part due to the increased apoptosis of osteocytes. To study the role of osteocyte apoptosis in glucocorticoid-induced osteoporosis, we isolated primary osteocytes from murine calvaria for the analysis of the effects of dexamethasone in in vitro culture. The cells were identified by morphology, cytochemical staining, immunocytochemical staining and mRNA expression of phosphate-regulating gene with homology to endopeptidases on the X chromosome (PHEX) and sclerosteosis/van Buchem disease gene (SOST). We found that dexamethasone induced osteocyte apoptosis in a dose-dependent manner. A glucocorticoid receptor antagonist, mifepristone (RU486), suppressed dexamethasone-Induced osteocyte apoptosis, suggesting that it was mediated by glucocorticoid receptor. Immunocytochemical stainings showed that glucocorticoid receptors are present in primary osteocytes, and they were translocated to nuclei after the exposure to dexamethasone. Addition of estrogen prevented glucocorticoid receptor translocation into nuclei. Corresponding antiapoptotic effects in primary osteocytes were also seen after the pretreatment of primary osteocytes with a picomolar concentration of estrogen. The pure antiestrogen ICI 182,780 inhibited estrogen effect on apoptosis induced by dexamethasone. These data suggest that glucocorticoid receptors play an important role in glucocorticoid-induced osteocyte apoptosis. Most importantly, estrogen has a protective effect against osteocyte apoptosis. To conclude, the mechanism of glucocorticoid-induced osteoporosis may be due to the apoptosis of osteocytes, which can be opposed by estrogen.
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| 7. |
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| 8. |
- Harding, Karin C., 1968, et al.
(författare)
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The 2002 European seal plague: epidemiology and population consequences
- 2002
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Ingår i: Ecology Letters. - 1461-023X. ; 5:6, s. 727-732
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Tidskriftsartikel (refereegranskat)abstract
- We present the first epidemiological data on the 2002 outbreak of phocine distemper virus (PDV) in European harbour seals (Phoca vitulina). The epizootic curve to date supports a mortality rate and probability of infection identical to that of the 1988 outbreak, which killed 58% of the population. Thus immunity is playing no significant role in the dynamics of the current outbreak. Because the timing of the outbreak is important in determining local mortality rates, we predict higher mortality rates on the European continent than in Great Britain or Ireland. A stochastic model is used to quantify how recurrent epizootics affect the long-term growth, fluctuation, and persistence of the population. Recurrent PDV epizootics with the observed frequency and severity would reduce the long-term stochastic growth rate of the harbour seal population by half, and significantly increase the risk of quasi-extinction.
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| 9. |
- Harsunen, Minna, et al.
(författare)
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Identification of monogenic variants in more than ten per cent of children without type 1 diabetes-related autoantibodies at diagnosis in the Finnish Pediatric Diabetes Register
- 2023
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 66:3, s. 438-449
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Monogenic forms of diabetes (MODY, neonatal diabetes mellitus and syndromic forms) are rare, and affected individuals may be misclassified and treated suboptimally. The prevalence of type 1 diabetes is high in Finnish children but systematic screening for monogenic diabetes has not been conducted. We assessed the prevalence and clinical manifestations of monogenic diabetes in children initially registered with type 1 diabetes in the Finnish Pediatric Diabetes Register (FPDR) but who had no type 1 diabetes-related autoantibodies (AABs) or had only low-titre islet cell autoantibodies (ICAs) at diagnosis. Methods: The FPDR, covering approximately 90% of newly diagnosed diabetic individuals aged ≤15 years in Finland starting from 2002, includes data on diabetes-associated HLA genotypes and AAB data (ICA, and autoantibodies against insulin, GAD, islet antigen 2 and zinc transporter 8) at diagnosis. A next generation sequencing gene panel including 42 genes was used to identify monogenic diabetes. We interpreted the variants in HNF1A by using the gene-specific standardised criteria and reported pathogenic and likely pathogenic findings only. For other genes, we also reported variants of unknown significance if an individual’s phenotype suggested monogenic diabetes. Results: Out of 6482 participants, we sequenced DNA for 152 (2.3%) testing negative for all AABs and 49 (0.8%) positive only for low-titre ICAs (ICAlow). A monogenic form of diabetes was revealed in 19 (12.5%) of the AAB-negative patients (14 [9.2%] had pathogenic or likely pathogenic variants) and two (4.1%) of the ICAlow group. None had ketoacidosis at diagnosis or carried HLA genotypes conferring high risk for type 1 diabetes. The affected genes were GCK, HNF1A, HNF4A, HNF1B, INS, KCNJ11, RFX6, LMNA and WFS1. A switch from insulin to oral medication was successful in four of five patients with variants in HNF1A, HNF4A or KCNJ11. Conclusions/interpretation: More than 10% of AAB-negative children with newly diagnosed diabetes had a genetic finding associated with monogenic diabetes. Because the genetic diagnosis can lead to major changes in treatment, we recommend referring all AAB-negative paediatric patients with diabetes for genetic testing. Low-titre ICAs in the absence of other AABs does not always indicate a diagnosis of type 1 diabetes. Graphical abstract: [Figure not available: see fulltext.]
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| 10. |
- Huttunen, Roope J., et al.
(författare)
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Quantitative detection of cell surface protein expression by time-resolved fluorimetry
- 2007
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Ingår i: Luminescence. - : Wiley. - 1522-7243 .- 1522-7235. ; 22:3, s. 163-170
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Tidskriftsartikel (refereegranskat)abstract
- A method is introduced for quantitative detection of cell surface protein expression. The method is based on immunocytochemistry, the use of long decay time europium(III) chelate and platinum(II) porphyrin labels, and detection of photoluminescence emission from adhered cells by time-resolved fluorimetry. After immunocytochemistry, the assay wells are evaporated to dryness and measured in the dry state. This protocol allows repeated and postponed analysis and microscopy imaging. In order to investigate the performance of the method, we chose expression of intercellular adhesion molecule-1 (ICAM-1) of endothelial cell line EAhy926 as a research target. The expression of ICAM-1 on the cells was enhanced by introduction of a cytokine, tumour necrosis factor-alpha (TNF alpha). The method gave signal: background ratios (S:B) of 20 and 9 for europium and platinum labels, respectively, whereas prompt fluorescent FITC label gave a S:13 of 3. Screening window coefficients (=Z'-factor) were >0.5 for all the three labels, thus indicating a score for an excellent screening assay. In conclusion, the method appears to be an appropriate choice for protein expression analysis, both in high-throughput screening applications, and for detailed sample investigation by fluorescent microscopy imaging. Copyright (C) 2007 John Wiley & Sons, Ltd.
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