| 51. |
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| 52. |
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| 53. |
- Hosokawa, K, et al.
(författare)
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Dominant expression and distribution of oestrogen receptor beta over oestrogen receptor alpha in the human corpus luteum
- 2001
-
Ingår i: Molecular human reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 7:2, s. 137-145
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the potential importance of oestrogen as a local regulator of human corpus luteum function, the mRNA expression pattern and cellular localization of oestrogen receptors (ERs), ER-alpha and ER-beta, were studied in corpora lutea grouped according to age, where days 2-5 post-LH rise were designated as the early luteal phase, days 6-10 as mid-luteal and days 11-14 as the late luteal phase respectively. Northern blot analysis using an ER-beta probe in samples from whole ovarian tissue and isolated corpora lutea, revealed a major band at 7.5 kb and several minor bands between 4-10 kb, while no signals for ER-alpha mRNA were obtained. However, using a semi-quantitative reverse transcription-polymerase chain reaction followed by Southern blotting, ER-beta mRNA levels were found to be 63% lower (P: < 0.05, n = 39) in the mid-luteal phase compared with the early luteal phase, while ER-alpha mRNA expression showed no statistical differences between the different age groups. Using in-situ hybridization, ER-beta mRNA expression was localized to the steroidogenic luteal cells as well as perivascular cells and fibroblasts in the corpus luteum. Immunohistochemistry confirmed the localization of ER-beta protein, but no clear staining of luteal cells was found using antibodies against ER-alpha. Collectively, the findings of low to moderate expression of ER-beta mRNA and protein in the steroidogenic cells, and also in vascular endothelial cells of the corpus luteum, as opposed to diminutive amounts of ER-alpha mRNA, suggest that oestrogen activity is primarily transduced via ER-beta in the human corpus luteum.
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| 54. |
- Hsueh, A J, et al.
(författare)
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Gonadotropin-releasing hormone induces ovulation in hypophysectomized rats : studies on ovarian tissue-type plasminogen activator activity, messenger ribonucleic acid content, and cellular localization.
- 1988
-
Ingår i: Endocrinology. - 0013-7227 .- 1945-7170. ; 122:4, s. 1486-95
-
Tidskriftsartikel (refereegranskat)abstract
- GnRH and its agonists are known to induce ovulation in hypophysectomized rats by acting directly at the ovary. Because tissue-type plasminogen activator (tPA) has been implicated in the gonadotropin induction of ovulation, we examined the effect of an ovulatory dose of GnRH on ovarian tPA activity, mRNA content, and cellular localization. Hypophysectomized immature rats were injected sc with 20 IU PMSG and a single dose of a GnRH agonist (GnRHa; des-Gly10,DLeu6(N alpha Me)Leu7,Pro9NHEt-GnRH) 58 h later. At different times after treatment, ovaries were prepared for morphological analysis. Using a fibrin overlay method, tPA activities were measured in ovarian homogenates and cumulus-oocyte complexes, whereas granulosa cells were cultured for 24 h to estimate tPA secretion. Total ovarian RNA was prepared for hybridization analysis of tPA message levels, and tPA localization was studied by immunohistochemistry of ovarian sections. GnRHa induced ovulation in PMSG-primed hypophysectomized rats 14-16 h after injection in a dose-dependent manner, and the GnRHa action was blocked by concomitant treatment with a GnRH antagonist. GnRHa stimulated the induction of tPA, but not urokinase-type PA, activity in ovarian homogenates and granulosa cell-conditioned medium in a time-dependent manner, reaching a maximum before ovulation. tPA activity in cumulus-oocyte complexes was also increased before ovulation, but this increase was sustained. Hybridization analysis of steady state tPA mRNA levels was performed using a rat cRNA probe. Northern blot analysis of total ovarian RNA demonstrated that GnRHa stimulated tPA mRNA levels 12 h after treatment, with a subsequent decrease 24 h after treatment. Immunohistochemistry indicated substantial increases in tPA staining in granulosa cells and oocytes of preovulatory follicles before ovulation. Thus, GnRHa acts through specific receptors to increase ovarian tPA enzyme activity, mRNA content, as well as immunostaining in granulosa cells and oocytes. Like gonadotropins, GnRH may induce ovulation by directly stimulating tPA levels in the ovary.
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| 55. |
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| 56. |
- Hu, Z Y, et al.
(författare)
-
Expression of tissue type and urokinase type plasminogen activators as well as plasminogen activator inhibitor type-1 and type-2 in human and rhesus monkey placenta.
- 1999
-
Ingår i: Journal of Anatomy. - 0021-8782 .- 1469-7580. ; 194 ( Pt 2), s. 183-95
-
Tidskriftsartikel (refereegranskat)abstract
- The distribution of mRNAs and antigens of tissue type (t) and urokinase type (u) plasminogen activators (PA) plus their corresponding inhibitors, type-1 (PAI-1) and type-2 (PAI-2) were studied in human and rhesus monkey placentae by in situ hybridisation and immunocytochemistry. Specific monkey cRNA and antibodies against human tPA, uPA, PAI-1 and PAI-2 were used as probes. The following results were obtained. (1) All the molecules tPA, uPA, PAI-1 and PAI-2 and their mRNAs were identified in the majority of the extravillous cytotrophoblast cells of the decidual layer between Rohr's and Nitabuch's striae and in cytotrophoblast cells of the chorionic plate, basal plate, intercotyledonary septae and cytotrophoblast cells of the chorionic villous tree. (2) Expression of uPA and PAI-2 was noted in villous trophoblast whereas tPA and PAI-1 were mainly concentrated where detachment from maternal tissue occurs. (3) No expression of tPA, uPA, PAI-1 and PAI-2 was observed in the basal plate endometrial stromal cells, chorionic plate connective tissue cells, septal endometrial stromal cells or villous core mesenchyme. (4) The distribution of probes observed following in situ hybridisation is generally consistent with the immunofluorescence pattern of the corresponding antigens and no significant interspecies differences were noted. It is possible that both decidual and extravillous trophoblast cells of placentae of human and rhesus monkey are capable of producing tPA, uPA, PAI-1 and PAI-2 to differing extents. Coordinated expression of these genes in the tissue may play an essential role in the maintenance of normal placentation and parturition. The differences in distribution we observed are consistent with the suggestion that coordinated expression of tPA and its inhibitor PAI-1 may play a key role in fibrinolytic activity in the early stages of placentation and separation of placenta from maternal tissue at term. On the other hand, uPA with its inhibitor PAI-2 appears mainly to play a role in degradation of trophoblast cell-associated extracellular matrix, and thus may be of greatest importance during early stages of placentation.
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| 57. |
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| 58. |
- LaPolt, P S, et al.
(författare)
-
Basic fibroblast growth factor induction of granulosa cell tissue-type plasminogen activator expression and oocyte maturation : potential role as a paracrine ovarian hormone.
- 1990
-
Ingår i: Endocrinology. - 0013-7227 .- 1945-7170. ; 127:5, s. 2357-63
-
Tidskriftsartikel (refereegranskat)abstract
- Gonadotropin-induced ovulation is associated with oocyte maturation and preovulatory increases of tissue plasminogen activator (tPA) expression. Basic fibroblast growth factor (bFGF), an angiogenic factor found in many organs including the ovary, modulates steroidogenesis in granulosa cells and increases PA activity in endothelial cells. Here studies were performed to examine the possible roles of bFGF as an intragonadal regulator of tPA expression and oocyte maturation. In cultured granulosa cells, bFGF caused a time-dependent (onset at 24 h) and dose-dependent (ED50 = 0.6 nM) increase (up to 5-fold) in tPA enzyme activity as measured by the fibrin overlay technique. Northern blot hybridization also revealed that treatment of cells with bFGF (2 nM) increased the level of the 22S tPA messenger RNA. Slot blot analysis indicated that the effects of bFGF were time dependent and dose dependent; tPA message levels increase before tPA activity levels. bFGF (0.6 nM) also significantly increased granulosa cell cAMP production in both the absence and presence of a phosphodiesterase inhibitor. In follicle-enclosed oocytes incubated for 24 h in media with or without increasing concentrations of LH or bFGF, germinal vesicle breakdown was observed in only 1.6% of controls, but 85% of LH (1 microgram/ml)-treated oocytes underwent maturation. Likewise, bFGF induced germinal vesicle breakdown (10-80%) over a dose range of 0.6 to 333 nM. In the same follicles, bFGF, like LH, also stimulated prostaglandin E production. These results, coupled with the identification of bFGF in growing follicles, suggest that bFGF acts as an intraovarian inducer of granulosa cell tPA gene expression and oocyte maturation.
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| 59. |
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| 60. |
- Leanderson, T, et al.
(författare)
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Interferon-specific effects on protein synthesis in P3HR-1 cells.
- 1982
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Ingår i: EMBO Journal. - 0261-4189 .- 1460-2075. ; 1:12, s. 1505-11
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of interferon (IFN) on protein synthesis was studied in the Burkitt's lymphoma cell line P3HR-1 by [35S]methionine labelling of the cells, followed by two-dimensional gel electrophoresis of cell extracts. De novo synthesis of three proteins (mol. wts. 33 000, 62 000, and 98 000, respectively) and alterations in the rate of synthesis for a small number of additional proteins were observed during the first 12 h of treatment, while the rate of overall protein synthesis was unaffected. Treatment of P3HR-1 cells with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or hydrocortisone (HC), which induce similar changes in cell cycle distribution as does IFN, did not induce comparable changes in the rates of protein synthesis. Thus, the effects were specific for IFN and not induced by the change in cell cycle distribution per se, i.e., accumulation in G0. Treatment of cells with 2'-5' pA core did not mimic the effect of IFN at the translational level. A substrain of P3HR-1 cells, selected for resistance to the anti-proliferative effect of IFN, lacked six proteins found in the wild-type. The 62 000 mol. wt. protein was induced in this substrain as well as in native P3HR-1 cells on addition of IFN. The resistant substrain still developed an anti-viral effect in response to IFN. Thus, it seems as if the anti-proliferative and anti-viral effects of IFN, at least in some cells are mediated by different intracellular molecular mechanisms.
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| 61. |
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| 62. |
- Lemoine, J E, et al.
(författare)
-
Factor structure and psychometric properties of the Body Appreciation Scale-2 among adolescents and young adults in Danish, Portuguese, and Swedish
- 2018
-
Ingår i: Body Image. - : Elsevier BV. - 1740-1445 .- 1873-6807. ; 26, s. 1-9
-
Tidskriftsartikel (refereegranskat)abstract
- In recent years, the study of body image shifted from focusing on the negative aspects to a more extensive view of body image. The present study seeks to validate a measure of positive body image, the Body Appreciation Scale-2 (BAS-2; Tylka & Wood-Barcalow, 2015a) in Denmark, Portugal, and Sweden. Participants (N = 1012) were adolescents and young adults aged from 12 to 19. Confirmatory factor analyses confirmed the one-dimensional factor structure of the scale. Multi-group confirmatory factor analyses indicated that the scale was invariant across sex and country. Further results showed that BAS-2 was positively correlated with self-esteem, psychological well-being, and intuitive eating. It was negatively correlated with BMI among boys and girls in Portugal but not in Denmark and Sweden. Additionally, boys had higher body appreciation than girls. Results indicated that the BAS-2 has good psychometric properties in the three languages.
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| 63. |
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| 64. |
- Liu, Y X, et al.
(författare)
-
Gonadotropin regulation of tissue-type and urokinase-type plasminogen activators in rat granulosa and theca-interstitial cells during the periovulatory period.
- 1987
-
Ingår i: Molecular and Cellular Endocrinology. - 0303-7207 .- 1872-8057. ; 54:2-3, s. 221-9
-
Tidskriftsartikel (refereegranskat)abstract
- Plasminogen activators (PAs) are believed to be involved in ovulation. Because both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are secreted by cultured rat granulosa cells, we have examined the activities of these proteins in ovarian homogenates as well as granulosa and theca-interstitial (TI) cells during gonadotropin-induced ovulation. Immature rats were injected with 20 IU pregnant mare serum gonadotropin (PMSG) to initiate follicle development, followed by treatment with 10 IU hCG 48 h later to induce ovulation. Ovarian proteins were separated by SDS-PAGE and PA activity determined by fibrin overlay. The activity of tPA, but not uPA, was stimulated following PMSG treatment in ovarian homogenates. Subsequent hCG injection further increased the tPA activity in a time-dependent manner, reaching a maximum (12 h after hCG treatment) immediately prior to ovulation and declined thereafter. Similar preovulatory increases in tPA activity were detected in isolated granulosa cells. Although both tPA and uPA activities were increased in TI cells after PMSG administration, no further increases were detected after hCG treatment. To estimate enzyme secretion, ovarian cells obtained at various preovulatory periods were incubated for 24 h in vitro. The ability of granulosa cells to secrete tPA, but not uPA, increased following in vivo PMSG and hCG treatment in a time-dependent manner, reaching a maximum immediately prior to ovulation. During the preovulatory period, an abrupt increase in tPA secretion by TI cells was also detected. Using immunohistochemical staining for tPA, it was found that ovarian sections from preovulatory rats at 12 h after hCG injection stained positively in granulosa, theca interna, and interstitial gland cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 65. |
- Liu, Y X, et al.
(författare)
-
Localization and distribution of tissue type and urokinase type plasminogen activators and their inhibitors Type 1 and 2 in human and rhesus monkey fetal membranes
- 1998
-
Ingår i: Placenta. - : Saunders Elsevier. - 0143-4004 .- 1532-3102. ; 19:2-3, s. 171-180
-
Tidskriftsartikel (refereegranskat)abstract
- Fetal membranes consist of 10 distinct layers including components of amnion, chorion and decidua, the latter being of maternal origin. They form mechanically integrated sheets capable of retaining amniotic fluid and play an essential role in protecting fetal growth and development in the pregnant uterus. The extracellular matrix, substrate for plasminogen activators (PAs), is an important supportive framework of the fetal membranes. Fetal membranes from women with preterm premature rupture of membranes may differ in their protease activity compared with normal membranes. To identify the presence of PAs and their inhibitors (PAI) and their possible role in the process of fetal membrane rupture, this study investigated the distribution and localization of both protein and mRNA for tissue (t) and urokinase (u) PA and their inhibitors type 1 (PAI-1) and type 2 (PAI-2) in amniochorion of human and rhesus monkey using conventional and confocal immunofluorescence microscopy. In situ hybridization analysis showed that the distribution and localization of mRNAs for tPA, uPA, PAI-1 and PAI-2 were similar in the fetal membranes of human and rhesus monkey; no obvious species difference was observed. Evidence of tPA mRNA was detected in amniotic epithelium, trophoblast cells and nearly all cells of the decidual layer. Strong expression of uPA mRNA was noted in the decidual cells which increased in intensity as the abscission point was approached. Weak staining in chorion laeve trophoblast was also detected. In situ hybridization experiments showed PAI-1 mRNA to be concentrated mainly in the decidual cells, some of which were interposed into the maternal-facing edge of the chorion laeve. Maximal labelling of the decidua occurred towards the zone of abscission. Weak expression of PAI-1 mRNA was also noted in some cells of the chorion laeve. The distribution of PAI-2 mRNA in amniochorion was also concentrated in the cells of the decidual layer, maximum expression of the mRNA was in the level of abscission. No detectable amount of mRNAs for tPA, uPA, PAI-1 and PAI-2 was found in the fibroblast, reticular and spongy layers. Distribution of the proteins of tPA, uPA and PAI-1 in the fetal membranes of these two species was consistent with the distribution of their mRNA. Anti-PAI-2 immunofluorescence was found to be strongly concentrated in the amniotic epithelium, but PAI-2 mRNA was negative in this layer, suggesting that the epithelium-associated PAI-2 is not of epithelial origin. These findings suggest that a local fibrinolysis in fetal membranes generated by precisely balanced expression of PAs and their inhibitors via paracrine or autocrine mechanisms may play an essential role in fetal membrane development, maturation and in membrane rupture. Following an analysis of the distribution and synthesis of activators and inhibitors it was found that they may play a role in abscission during the third stage of labour.
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| 66. |
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| 67. |
- Magnusson, S, et al.
(författare)
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Heme oxygenase-1, heme oxygenase-2 and biliverdin reductase in peripheral ganglia from rat, expression and plasticity
- 2000
-
Ingår i: Neuroscience. - 1873-7544. ; 95:3, s. 821-829
-
Tidskriftsartikel (refereegranskat)abstract
- The expression of inducible and constitutive heme oxygenase and biliverdin reductase was studied in normal and cultured peripheral ganglia from adult rats, using immunocytochemistry and in situ hybridization. Dramatic changes were induced by one to two days' culturing of dorsal root ganglia, nodose ganglia, otic ganglia, sphenopalatine ganglia and superior cervical ganglia. An up-regulation of inducible heme oxygenase was found in satellite cells of the cultured nodose ganglia, dorsal root ganglia, sphenopalatine ganglia and otic ganglia, whereas only a few satellite cells in the superior cervical ganglia responded with an increase in inducible heme oxygenase immunoreactivity. In the superior cervical ganglia inducible heme oxygenase also appeared in a subpopulation of macrophages. During culturing, expression of inducible heme oxygenase immunoreactivity also increased in axons and in nerve cell bodies. In situ hybridization corroborated the immunocytochemical findings, revealing a strong up-regulation of inducible heme oxygenase messenger RNA in satellite cells, and less pronounced up-regulation in nerve cell bodies. Constitutive heme oxygenase immunoreactivity was found in most neurons in all of the ganglia studied. No significant changes in constitutive heme oxygenase immunoreactivity could be observed in cultured ganglia. Biliverdin reductase immunoreactivity was barely detectable in any of the normal ganglia; however, after culturing it appeared in axons, single nerve cell bodies and nerve cell nuclei. The results show that inducible heme oxygenase is up-regulated in peripheral ganglia after axonal injury, and suggest a role for carbon monoxide in cellular signaling and a requirement for the antioxidant (bilirubin) during the regeneration process.
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| 68. |
- Ngwa, MC, et al.
(författare)
-
The cholera risk assessment in Kano State, Nigeria: A historical review, mapping of hotspots and evaluation of contextual factors
- 2021
-
Ingår i: PLoS neglected tropical diseases. - : Public Library of Science (PLoS). - 1935-2735. ; 15:1, s. e0009046-
-
Tidskriftsartikel (refereegranskat)abstract
- Nigeria is endemic for cholera since 1970, and Kano State report outbreaks annually with high case fatality ratios ranging from 4.98%/2010 to 5.10%/2018 over the last decade. However, interventions focused on cholera prevention and control have been hampered by a lack of understanding of hotspot Local Government Areas (LGAs) that trigger and sustain yearly outbreaks. The goal of this study was to identify and categorize cholera hotspots in Kano State to inform a national plan for disease control and elimination in the State. We obtained LGA level confirmed and suspected cholera data from 2010 to 2019 from the Nigeria Centre for Disease Control (NCDC) and Kano State Ministry of Health. Data on inland waterbodies and population numbers were obtained from online sources and NCDC, respectively. Clusters (hotspots) were identified using SaTScan through a retrospective analysis of the data for the ten-year period using a Poisson discrete space-time scan statistic. We also used a method newly proposed by the Global Task Force on Cholera Control (GTFCC) to identify and rank hotspots based on two epidemiological indicators including mean annual incidence per 100 000 population of reported cases and the persistence of cholera for the study period. In the ten-year period, 16,461 cholera cases were reported with a case fatality ratio of 3.32% and a mean annual incidence rate of 13.4 cases per 100 000 population. Between 2010 and 2019, the most severe cholera exacerbations occurred in 2014 and 2018 with annual incidence rates of 58.01 and 21.52 cases per 100 000 inhabitants, respectively. Compared to 2017, reported cases and deaths increased by 214.56% and 406.67% in 2018. The geographic distribution of outbreaks revealed considerable spatial heterogeneity with the widest in 2014. Space-time clustering analysis identified 18 out of 44 LGAs as high risk for cholera (hotspots) involving both urban and rural LGAs. Cholera clustered around water bodies, and the relative risk of having cholera inside the hotspot LGA were 1.02 to 3.30 times higher than elsewhere in the State. A total of 4,894,144 inhabitants were in these hotspots LGAs. Of these, six LGAs with a total population of 1.665 million had a relative risk greater than 2 compared to the state as a whole. The SaTScan (statistical) and GTFCC methods were in agreement in hotspots identification. This study identified cholera hotspots LGAs in Kano State from 2010–2019. Hotspots appeared in both urban and rural settings. Focusing control strategies on these hotspots will facilitate control and eliminate cholera from the State.
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| 69. |
- Ny, Lars, 1967, et al.
(författare)
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A magnetic resonance imaging study of intestinal dilation in Trypanosoma cruzi-infected mice deficient in nitric oxide synthase.
- 2008
-
Ingår i: The American journal of tropical medicine and hygiene. - 1476-1645. ; 79:5, s. 760-7
-
Tidskriftsartikel (refereegranskat)abstract
- Infection with Trypanosoma cruzi causes megasyndromes of the gastrointestinal (GI) tract. We used magnetic resonance imaging (MRI) to monitor alterations in the GI tract of T. cruzi-infected mice, and to assess the role of nitric oxide (NO) in the development of intestinal dilation. Brazil strain-infected C57BL/6 wild-type (WT) mice exhibited dilatation of the intestines by 30 days post-infection. Average intestine lumen diameter increased by 72%. Levels of intestinal NO synthase (NOS) isoforms, NOS2 and NOS3, were elevated in infected WT mice. Inflammation and ganglionitis were observed in all infected mice. Intestinal dilation was observed in infected WT, NOS1, NOS2, and NOS3 null mice. This study demonstrates that MRI is a useful tool to monitor intestinal dilation in living mice and that these alterations may begin during acute infection. Furthermore, our data strongly suggests that NO may not be the sole contributor to intestinal dysfunction resulting from this infection.
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| 70. |
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| 71. |
- Ny, S, et al.
(författare)
-
Genome and plasmid diversity of Extended-Spectrum β-Lactamase-producing Escherichia coli ST131 - tracking phylogenetic trajectories with Bayesian inference
- 2019
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10291-
-
Tidskriftsartikel (refereegranskat)abstract
- Clonal lineages of ESBL (Extended-Spectrum β-Lactamase)-producing E. coli belonging to sequence type 131 (ST131) have disseminated globally during the last 30 years, leading to an increased prevalence of resistance to fluoroquinolones and extended-spectrum cephalosporins in clinical isolates of E. coli. We aimed to study if Swedish ESBL-producing ST131 isolates originated from single or multiple introductions to the population by assessing the amount of genetic variation, on chromosomal and plasmid level, between Swedish and international E. coli ST131. Bayesian inference of Swedish E. coli ST131 isolates (n = 29), sequenced using PacBio RSII, together with an international ST131 dataset showed that the Swedish isolates were part of the international ST131 A, C1 and C2 clades. Highly conserved plasmids were identified in three clusters although they were separated by several years, which indicates a strong co-evolution between some ST131 lineages and specific plasmids. In conclusion, the tight clonal relationship observed within the ST131 clades, together with highly conserved plasmids, challenges investigation of strain transmission events. A combination of few SNPs on a genome-wide scale and an epidemiological temporospatial link, are needed to track the spread of the ST131 subclones.
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| 72. |
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| 73. |
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| 74. |
- Olofsson Bagge, Roger, 1978, et al.
(författare)
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Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases: A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial)
- 2023
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 41:16, s. 3042-50
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSEAbout half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking.METHODSIn this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety.RESULTSNinety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group.CONCLUSIONIHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.
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| 75. |
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| 76. |
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| 77. |
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| 78. |
- Peng, X R, et al.
(författare)
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Localization of luteinizing hormone receptor messenger ribonucleic acid expression in ovarian cell types during follicle development and ovulation.
- 1991
-
Ingår i: Endocrinology. - 0013-7227 .- 1945-7170. ; 129:6, s. 3200-7
-
Tidskriftsartikel (refereegranskat)abstract
- The action of LH is mediated through specific plasma membrane receptors that are both up- and down-regulated in the ovary during the reproductive cycle. Using immature rats treated with PMSG and hCG as a model system, we have studied the regulation and distribution of LH receptor mRNA in different cell types during follicle development, ovulation, and luteinization by Northern blot and in situ hybridization. In untreated rats, LH receptor mRNA was below the detection level in granulosa cells, cumulus cells, and oocytes, while low levels of LH receptor mRNA were found in the thecal cells. After stimulation with PMSG, expression of LH receptor mRNA was enhanced in the thecal-interstitial cells, while a more dramatic increase in receptor mRNA abundance took place in granulosa cells of large tertiary follicles. In these follicles, the abundance of LH receptor mRNA varied among different subpopulations of granulosa cells, with mural granulosa cells close to the basement membrane exhibiting higher levels than granulosa cells located closer to the antrum, and cumulus cells and the oocyte lacking detectable hybridization signal. The uneven expression of LH receptor mRNA endows different ovarian cells with varying hormonal responsiveness. After an ovulatory dose of hCG, LH receptor mRNA levels were dramatically decreased, particularly in the granulosa cells of preovulatory follicles, to reach the lowest levels just before ovulation. During the transformation of ovulated follicles into corpora lutea, the expression of LH receptor message was again increased. Our results reveal that the previously documented regulation of the LH receptor-binding activity during ovarian development correlates with expression of the LH receptor transcripts, suggesting that the LH receptor gene is regulated in a complex manner during the periovulatory period to achieve cell-specific expression together with gonadotropin induction and suppression of receptor gene activity.
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| 79. |
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| 80. |
- Strandberg, L, et al.
(författare)
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Fluorescence studies on plasminogen activator inhibitor 1 : reactive centre cysteine mutants remain active after fluorophore attachment.
- 1994
-
Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 76:3, s. 253-67
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate structural-functional aspects of plasminogen activator inhibitor 1 (PAI-1) we have taken advantage of the lack of cysteines in the PAI-1 molecule and replaced Ser344 (P3) and Asn329 (P18) with cysteine residues, thereby creating unique attachment sites for extrinsic fluorescent probes. After expression in E. coli and purification to homogeneity, both of the mutant proteins were found to have similar biochemical characteristics as wild type PAI-1 (wtPAI-1). Following labelling with 4-chloro-7-nitrobenzofurazan (NBD) and 2-(4'-iodoacetamido-anilino)naphtalene-6-sulfonic acid (IAANS) the mutant inhibitors showed similar inhibitory activities and heat stability as wtPAI-1. The purified complex between uPA and NBD-labelled P3cys mutant was found to be extremely stable, suggesting that no slow cleavage or reversible reaction occurs in complexes that have been properly formed. The rate of labelling of both mutants was decreased when the mutants were in the latent form indicating that these cysteine residues may be less accessible in the latent configuration. The PAI-1 mutants labelled with both NBD and IAANS could convert from the active to the latent form, but P3cys labelled with the larger IAANS chromophore showed a two fold decrease in the rate of conversion to latency, suggesting that a large chromophore in the P3 position may interfere with the active to latent conversion. The fluorescence spectra of the two NBD labelled mutants were similar, but the intensity was three times higher for the P3cys mutant than for P18cys. No significant spectral changes could be seen when the P3cys mutant was transferred to latency. In contrast, the P18cys mutant showed a major change in the excitation spectra characteristic of migration of the NBD chromophore from a thiol to an amine. Complex formation with uPA had no effect on the fluorescence spectrum of P18cys-NBD while the spectrum of P3cys-NBD revealed changes consistent with a restriction of the mobility of NBD probe in the uPA-PAI-1 complex.
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| 81. |
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| 82. |
- Sundström, S, et al.
(författare)
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Growth-state independent induction of specific proteins in Swiss 3T3 cells by interferon.
- 1983
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Ingår i: Journal of interferon research. - 0197-8357. ; 3:2, s. 223-9
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Tidskriftsartikel (refereegranskat)abstract
- The early effects of interferon (IFN) on the pattern of protein synthesis in Swiss 3T3 mouse fibroblasts were investigated by two-dimensional gel electrophoresis of 35S-methionine labeled cell extracts. IFN induced within 4 h the synthesis of three proteins with molecular weights of 48, 49, and 50 kD. An increase in the rate of synthesis of a 31 kD protein was also found. These changes were observed after IFN treatment of exponentially growing cells, density-inhibited cells, serum-starved cells, and serum-stimulated quiescent cells. The same protein patterns were obtained from cells treated with IFN-alpha or IFN-beta. The IFN response was blocked by the addition of actinomycin D, implying de novo transcription of the corresponding species of messenger RNA.
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| 83. |
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| 84. |
- Tripputi, P, et al.
(författare)
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Tissue-type plasminogen activator gene is on chromosome 8.
- 1986
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Ingår i: Cytogenetics and Cell Genetics. - 0301-0171 .- 1421-9816. ; 42:1-2, s. 24-8
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Tidskriftsartikel (refereegranskat)abstract
- Tissue plasminogen activator is one of the two plasminogen activators, both serine proteases, that catalyze the conversion of inactive plasminogen to plasmin, which then degrades the fibrin network of blood clots. By combining somatic cell genetics, in situ hybridization, and Southern blot hybridization, we localized the human tissue plasminogen activator gene to the pericentromeric region of chromosome 8.
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| 85. |
- Tsafriri, A, et al.
(författare)
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Suppression of ovulation rate by antibodies to tissue-type plasminogen activator and alpha 2-antiplasmin.
- 1989
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Ingår i: Endocrinology. - 0013-7227 .- 1945-7170. ; 124:1, s. 415-21
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Tidskriftsartikel (refereegranskat)abstract
- Indirect evidence has suggested a role for plasminogen activator (PA) in ovulation. Our recent studies demonstrated that 1) tissue-type PA (tPA) is the predominant PA produced by preovulatory rat follicles in response to gonadotropins or GnRH; and 2) several inhibitors of the serine proteases, to which PA and plasmin belong, block ovulation. Here, the role of tPA and plasmin in ovulation was examined directly by the use of specific antibodies to tPA and alpha 2-antiplasmin (alpha 2AP). Immature female rats at 25-26 days of age were treated (sc) with 15 IU PMSG to induce multiple preovulatory follicles. Fifty-four hours later, tPA antibodies and alpha 2AP were injected into one of the ovarian bursae to check their ability to block ovulation, which was initiated with an ovulatory dose (4 IU) of hCG. The data are expressed as percent inhibition of ovulation in the treated vs. the untreated ovaries. A significant decrease in the ovulation rate was obtained by administration of 500 micrograms antibodies to tPA (39.6%) or 1-50 micrograms alpha 2AP (36-44%), whereas minimal inhibition (12%) was found at lower doses of anti-tPA (10 micrograms) or alpha 2AP (0.1 micrograms). Furthermore, nonimmune immunoglobulin G (500 micrograms) and heat-inactivated alpha 2AP were not effective. Anti-tPA and alpha 2AP suppressed ovulation only when injected at the time of hCG administration; later injections (4-h delay) were ineffective, suggesting that PA and plasmin are involved in the early follicular responses to the ovulatory stimulus. Histological observation of the ovaries did not reveal any pathological changes associated with the anti-tPA and alpha 2AP treatment. Suppression of ovulation, as evidenced by decreased number of tubal ova, was frequently accompanied with intraovarian release of the eggs into the follicular thecal compartment. Thus, these results provide direct evidence for an essential role of tPA and plasmin in ovulation.
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| 86. |
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| 87. |
- Winkel, Jörgen, 1946, et al.
(författare)
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Factors facilitating and inhibiting Value Stream Mapping processes at hospital units in three Nordic countries - A Nordic Multicenter study
- 2014
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Ingår i: O. Broberg, N. Fallentin, P. Hasle, P.L. Jensen, A. Kabel, M.E. Larsen, T.Weller (Editors). 11th International Symposium on Human Factors in Organisational Design and Management 46th Annual Nordic Ergonomics Society Conference. - 9788793130135
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 1.Conceptual framework and Purpose In healthcare Value Stream Mapping (VSM) is a common Lean tool used to improve the efficiency of patient flows by identifying and minimizing waste (Keyte & Locher, 2004). It is a participatory tool, i.e. those affected by this type of rationalization are performing the analyses and subsequently suggesting appropriate interventions. Participation has been shown to be crucial to obtain ownership of the suggested interventions and thereby increase impact. VSM has been shown to be a powerful rationalization tool. However, the resulting interventions may imply physical work intensification and impaired psychosocial work environment. Due to this, Lean is often perceived as a “threat” by employees at hospitals (Härenstam et al 2000, personal communications). Physical and psychosocial working conditions should therefore be taken into account in the rationalization process to obtain sustainable solutions, i.e. solutions that allow for competitive performance and acceptable work environment in a long term perspective. On this background we have complemented the VSM tool by an ergonomic module assisting the users to consider also physical and psychosocial implications of the suggested interventions. This ErgoVSM tool is now evaluated in a Nordic Multicenter Study including Denmark, Iceland and Sweden (Winkel et al, 2012). The aim of this paper is to present observations that may indicate facilitating and inhibiting factors for the VSM process. 2.Methods Seven wards have used the ErgoVSM and seven the traditional VSM. Information was obtained by screening key hospital documents and interviewing participants in the VSM processes. 3.Results In Sweden one out of three wards using VSM decided not to fulfil the VSM process. On Iceland the only ward using VSM also decided not to fulfil their VSM process. The hospitals of the investigated wards using VSM in Sweden and Iceland had a strong primary focus on financial balance of the business according to key documents. Decisions on when and which value stream to analyse were made by management with little/no dialog with the employees. Work environment issues were not discussed as part of this. In addition, Iceland had a short experience of Lean, mainly based on support from McKinsey, an American global management consulting firm that focuses on solving issues of concern to senior management (http://en.wikipedia.org/wiki/McKinsey_%26_Company). Thus, they had no attention to the wellbeing to the employees and their work environment when introducing Lean. In general, the Icelandic Lean coaches had problems motivating the employees. However, they perceived a facilitated VSM process at the investigated ErgoVSM ward. Due to this, the main Lean coach decided to include work environment aspects in the VSM processes performed at other wards not part of the present Multicenter Study. Positive effects on those VSM processes were reported back to the researchers. In Denmark all three wards using VSM fulfilled their VSM process. This hospital had a long Lean experience. The main Lean coach reported process problems during their 3 initial years when using a top-down approach. Before the present project was initiated they had turned to a bottom-up initiation of the VSM processes. The Lean coach also expressed that work environment issues might be articulated as part of the VSM process. All seven wards using ErgoVSM in the 3 countries fulfilled the process. 4.Conclusion When using the Lean tool “Value Stream Mapping” it seems to be important not only to focus on efficiency but also on issues that are perceived important for the well-being of the individual employee. 5.Financial support The Nordic Council of Ministers and national grants. 6.References Härenstam A, Bejerot E, Johansson K, Leijon O, Schéele P. “Mager och god” eller ”Lean and mean”? Samband mellan organisationsförändringar och arbetsförhållanden. In: Barllöf K (Ed.) Smärtgränsen? En antologi om hälsokonsekvenser I magra organisationer. Rådet för arbetslivsforskning, pp 2000 Keyte, B., Locher, D., 2004. The Complete Lean Enterprise. Value Stream Mapping for Administrative and Office Processes. Productivity Press, New York. Winkel J, Birgisdóttir B D, Dudas K, Edwards K, Gunnarsdóttir S, Jarebrant C, Johansson Hanse J (2012). A Nordic work environment complement to Value Stream Mapping (VSM) for sustainable patient flows at hospitals – A NOVO Multicenter study. 6th NOVO Symposium: Sustainable Health Care: Continuous Improvement of Processes and Systems. Karolinska Institute, Stockholm Sweden. November 15-16, 2012, pp 58-59. ISBN: 978-91-637-2380-3
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| 88. |
- Winkel, Jörgen, 1946, et al.
(författare)
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Introduction of Lean/Value Stream Mapping at hospital units in three Nordic countries and expected impact on the working environment - A Nordic Multicenter study
- 2013
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Ingår i: International HELIX Conference 2013.
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Konferensbidrag (refereegranskat)abstract
- Conceptual framework and Purpose A recent review has documented mostly negative effects of rationalization on musculoskeletal and mental health and corresponding risk factors. This goes in particular for the healthcare sector (Westgaard & Winkel, 2011). Lean Practices are increasingly used in healthcare and Value Stream Mapping (VSM) seems to be a commonly used tool to identify and minimize waste (Keyte & Locher, 2004). The health impact of Lean varies considerably between investigations. This may to a large extend be due to differences in the operationalization of Lean (Brännmark et al, 2012). VSM is a participatory tool, i.e. those affected by this type of rationalization are performing the analyses and subsequently suggesting the interventions. Participation has been shown to be crucial to obtain ownership of the suggested interventions and thereby increased impact. On this background rationalizations based on VSM may offer a procedure that also includes working environment issues. In addition, workplaces in the Nordic countries seem to offer good opportunities for realizing a true participatory approach considering also working environment issues when rationalizing a value stream (Guðmundsson, 1993; Westgaard & Winkel, 2011). VSM has been shown to be a powerful rationalization tool in the elimination of non-value-adding tasks (non-VAT). Several studies show that non-VAT generally offer less risky physical and mental exposures (e.g. Kazmierczak et al, 2005; Østensvik et al, 2008; Palmerud et al, 2012; Jonker et al, 2013). According to this, non-VAT is usually named “the porosity of the working day” (Marx, 1867; Westgaard & Winkel, 2011; Winkel & Westgaard, 2001). Strong political demands to maximize efficiency in healthcare may thus potentially result in an excessive rationalization causing a too large reduction in porosity and thus too risky work intensification. In practice Lean is often perceived as a “threat” by employees at hospitals (Härenstam et al, 2000; many personal communications). In contrast, most Lean consultants generally describe Lean as an opportunity for improvements also in terms of the working environment (numerous personal communications). On this background an ergonomic complement to VSM, the ErgoVSM, has been developed based on existing scientific evidence and in close co-operation with Swedish industry and the healthcare sector (Jarebrant et al, 2013). The ErgoVSM also considers health issues, i.e. risk factors for musculoskeletal and mental health in addition to reduction of waste (Jarebrant et al, 2004; 2009). In this paper we present some preliminary data based on 1st line managers’ assessments of expected impact of action plans based on VSM and ErgoVSM. The presented data are retrieved from a larger NOVO Multicenter Study (Winkel et al, 2012). Design/Methodology Fourteen hospital wards in Denmark, Iceland and Sweden are investigated. Seven of these are using VSM and the remaining the ErgoVSM to improve the efficiency of their patient flows. Current and future states are assessed and action plans presented. 1st line managers are then interviewed and asked to assess expected impact of each suggested intervention in the action plan in terms of efficiency, treatment quality, physical and psychosocial working environment. So far five of the fourteen 1st line managers have been interviewed. Two of the wards have used the VSM tool and 3 the ErgoVSM tool. Results and Discussion All together 103 amendments for improved performance have been assessed in the five action plans. Eighty-one of these were assessed also to imply improvements in the working environment. Three suggestions were expected to imply a negative impact and four no impact on the working environment. Fifteen suggestions were not rated as they were decided not to be realized. Using VSM or ErgoVSM did not influence the assessment of expected impact of amendments in the action plan. The dominance of expected positive impact on the working environment of the amendments will be discussed in terms of potential bias and real opportunities. The Multicenter Study includes follow-up investigations of realized impact on the working environment as well as potential national differences between the three investigated countries (cf. Birna & Gunnarsdóttir, 2012; Edwards & Winkel, 2012; Jarebrant et al, 2012).
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| 89. |
- Yu, NY, et al.
(författare)
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Acute doses of caffeine shift nervous system cell expression profiles toward promotion of neuronal projection growth
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 11458-
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Tidskriftsartikel (refereegranskat)abstract
- Caffeine is a widely consumed psychoactive substance, but little is known about the effects of caffeine stimulation on global gene expression changes in neurons. Here, we conducted gene expression profiling of human neuroepithelial stem cell-derived neurons, stimulated with normal consumption levels of caffeine (3 μM and 10 μM), over a period of 9 h. We found dosage-dependent activation of immediate early genes after 1 h. Neuronal projection development processes were up-regulated and negative regulation of axon extension processes were down-regulated at 3 h. In addition, genes involved in extracellular matrix organization, response for wound healing, and regulation of immune system processes were down-regulated by caffeine at 3 h. This study identified novel genes within the neuronal projection guidance pathways that respond to acute caffeine stimulation and suggests potential mechanisms for the effects of caffeine on neuronal cells.
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