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  • 1.
    Abujrais, Sandy
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Ahnoff, Martin
    Department of Marine Sciences, University of Gothenburg, Carl Skottbergs gata 22B, SE-41319 Gothenburg, Sweden..
    Rasmusson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Åkerfeldt, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    A sensitive method detecting trace levels of levonorgestrel using LC-HRMS.2019Ingår i: Contraception, ISSN 0010-7824, E-ISSN 1879-0518, Vol. 100, nr 3, s. 247-249Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To develop a high resolution mass spectrometry (HRMS) method to quantify levonorgestrel (LNG) in serum.

    STUDY DESIGN: Levonorgestrel was extracted using solid phase extraction and measured using liquid chromatography (LC) HRMS.

    RESULTS: Low limit of quantification (LLOQ) was 25pg/mL and low limit of detection (LLOD) was 12.5pg/mL. Precision and accuracy bias were<10%. LNG in serum samples from Mirena® users ranged between 37 to 219pg/mL (n=12). In eight out of 22 patients with suspected intrauterine device (IUD) expulsion LNG was detected (26 to 1272pg/mL).

    CONCLUSION: A sensitive, fast and simple LC-HRMS method was developed to detect trace levels of LNG.

  • 2.
    Andersson, Helén
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Helmestam, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Zebrowska, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Brittebo, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Tamoxifen-Induced Adduct Formation and Cell Stress in Human Endometrial Glands2010Ingår i: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 38, nr 1, s. 200-207Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The beneficial effects of tamoxifen in the prevention and treatment of breast cancer are compromised by an increased risk of endometrial polyps, hyperplasia, and cancer. Tamoxifen is metabolized to an array of metabolites with estrogenic effects but also to reactive intermediates that may form protein and DNA adducts. The aim of this study was to investigate cellular [(3)H]tamoxifen adduct formation by light microscopic autoradiography and cell stress by immunohistochemical analysis of glucose-regulating protein 78 (GRP78), nuclear factor kappaB (NF-kappaB), and caspase 3 in human endometrial explants after short-term incubation with tamoxifen. The cellular expression of tamoxifen-metabolizing enzymes in human endometrial biopsy samples was also determined by immunohistochemistry. The results showed selective [(3)H]tamoxifen adduct formation in glandular and surface epithelia after incubation with a nontoxic concentration of [(3)H]tamoxifen (6 nM). There was also a selective expression of the endoplasmic reticulum stress chaperone GRP78 and activated caspase 3 at these sites after incubation with cytotoxic concentrations of tamoxifen (10-100 microM). The cell stress was preferentially observed in samples from women in the proliferative menstrual phase. No treatment-related expression of NF-kappaB was observed. Constitutive expression of the tamoxifen-metabolizing enzymes CYP1B1, CYP2A6, CYP2B6, CYP2C8/9/19, CYP2D6, and SULT2A1 in glandular and surface epithelia was shown, but there was a large interindividual variation. The colocalization of [(3)H]tamoxifen adducts, expression of GRP78, caspase 3, and tamoxifen-metabolizing enzymes in human glandular and surface epithelia suggest a local bioactivation of tamoxifen at these sites and that epithelial cells are early target sites for tamoxifen-induced cell stress.

  • 3.
    Arnadottir, Ragnheidur
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Hudecova, Miriam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Stavreus-Evers, Anneli
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Kunovac-Kallak, Theodora
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Poromaa, Inger Sundstrom
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Steroid hormone receptor expression, proliferative activity and microvessel density in the endometrium of women with polycystic ovary syndrome2012Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, s. 64-64Artikel i tidskrift (Övrigt vetenskapligt)
  • 4.
    Berg, Cecilia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.
    Lundstedt-Enkel, KatrinUppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Miljötoxikologi.Olovsson, MattsUppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.Persson, SaraSveriges lantbruksuniversitet, Institutionen för kliniska vetenskaper.
    Female Reproduction and Endocrine Disrupting Chemicals (FEMREP 2013)2013Proceedings (redaktörskap) (Övrigt vetenskapligt)
  • 5.
    Berggrund, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Enroth, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Lundberg, Martin
    OLINK Prote, Uppsala Sci Pk, SE-75183 Uppsala, Sweden.
    Assarsson, Erika
    OLINK Prote, Uppsala Sci Pk, SE-75183 Uppsala, Sweden.
    Stålberg, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Lindquist, David
    Umeå Univ, Dept Radiat Sci, SE-90187 Umeå, Sweden.
    Hallmans, Göran
    Umeå Univ, Dept Publ Hlth & Clin Med, Nutr Res, SE-90187 Umeå, Sweden.
    Grankvist, Kjell
    Umeå Univ, Dept Med Biosci, Clin Chem, SE-90187 Umeå, Sweden.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Gyllensten, Ulf
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Identification of Candidate Plasma Protein Biomarkers for Cervical Cancer Using the Multiplex Proximity Extension Assay2019Ingår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, nr 4, s. 735-743Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared with controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared with population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.

  • 6. Bostrom, P.
    et al.
    Lovkvist, L.
    Gustafsson, M.
    Alexandersson, O.
    Bruse, C.
    Liffner, C.
    Holmberg, J.
    Edlund, M.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Cost of illness in women with endometriosis2012Ingår i: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 15, nr 7, s. A538-A538Artikel i tidskrift (Övrigt vetenskapligt)
  • 7. Bostrom, Per
    et al.
    Lovkvist, Lena
    Edlund, Mans
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Burden of illness in women with endometriosis2012Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, s. 37-37Artikel i tidskrift (Övrigt vetenskapligt)
  • 8.
    Bourlev, V
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Pavlovitch, S
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Stygar, D
    Volkov, N
    Lindblom, B
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Olovsson, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Different proliferative and apoptotic activity in peripheral versuscentral parts of human uterine leiomyomas.2003Ingår i: Gynecol Obstet Invest, Vol. 55, s. 199-Artikel i tidskrift (Refereegranskat)
  • 9.
    Bourlev, Vladimir
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Ilyasova, Natalia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Adamyan, Leyla
    Research Centre of Obstetrics, Gynecology and Perinatology, Russian Academy of the Medical Sciences, Moscow, Russia.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Signs of reduced angiogenic activity after surgical removal of deeply infiltrating endometriosis2010Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 94, nr 1, s. 52-57Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To study the concentrations of vascular endothelial growth factor A (VEGF-A), soluble vascular endothelial growth factor receptors-1 and -2 (sVEGFR-1 and -2), angiogenin, and angiopoietin-2 (Ang-2) in serum and peritoneal fluid from healthy controls and women with advanced endometriosis. Further, we addressed the question of whether surgical removal of endometriotic lesions was associated with normalization of the serum concentrations of the same markers. DESIGN: Patients with endometriosis before and after surgery were compared with control patients. SETTING: University Hospital. PATIENT(S): Twenty-one healthy controls and 32 women with advanced endometriosis. INTERVENTION(S): In women with endometriosis we performed surgical removal of endometriotic lesions using laparoscopy. MAIN OUTCOME MEASURE(S): Data on serum and peritoneal fluid concentrations of selected markers in healthy controls and women with endometriosis before surgery and in serum 5 to 7 days after surgery. RESULT(S): Women with endometriosis had elevated levels of VEGF-A, sVEGFR-1, and Ang-2 in serum and all studied markers in peritoneal fluid compared with healthy controls. Surgical removal of endometriotic lesions resulted in decreased serum levels of pro-angiogenic VEGF-A and increased levels of sVEGFR-2 that negatively regulates the action of VEGF. CONCLUSION(S): Women with advanced endometriosis have serum and peritoneal fluid concentrations of several factors involved in the regulation of angiogenesis that differ from those in healthy women, and these changes at least partly normalize within a week after surgical removal of the endometriotic lesions.

  • 10.
    Bourlev, Vladimir
    et al.
    Research Centre of Obstetrics, Gynaecology and Perinatology, Russian Academy of the Medical Sciences, Moscow, Russia.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. klinisk kemi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Elevated levels of fibroblast growth factor-2 in serum from women with endometriosis.2006Ingår i: Am J Obstet Gynecol, ISSN 1097-6868, Vol. 194, nr 3, s. 755-9Artikel i tidskrift (Refereegranskat)
  • 11.
    Bourlev, Vladimir
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi. Minist Healthcare Russian Federat, Natl Med Res Ctr Obstet Gynecol & Perinatol, Moscow, Russia.
    Moberg, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Ilyasova, Natalia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi. Minist Healthcare Russian Federat, Natl Med Res Ctr Obstet Gynecol & Perinatol, Moscow, Russia.
    Davey, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Kallak, Theodora Kunovac
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Vasoactive intestinal peptide is upregulated in women with endometriosis and chronic pelvic pain2018Ingår i: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 80, nr 3, artikel-id e12857Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Problem: Chronic pelvic pain (CPP) causes compromised the quality of life in women with endometriosis and is often attributed to local inflammation and ingrowth of nerve fibers. In this pilot study, we aimed to investigate whether the inflammation‐related vasoactive intestinal peptide (VIP) and interleukin (IL)‐6 were increased in affected patients.

    Method of study: Endometrial and endometriotic tissue biopsy specimens, and serum and peritoneal fluid (PF) samples, were obtained from 85 endometriosis patients and 53 controls. VIP and IL‐6 analysis and measurement of microvessel density in tissue were performed using immunohistochemistry, Western blotting, RT‐qPCR, and ELISA.

    Results: Compared with controls, VIP transcript and protein levels were increased in endometrium from endometriosis patients and further elevated in patients with CPP. In addition, microvessel density, a measurement of angiogenic activity, was increased in the endometrium and in endometriosis lesions in the same subset of patients. Serum and PF levels of VIP and IL‐6 were higher in women with endometriosis and CPP compared with endometriosis patients who reported no chronic pain.

    Conclusion: Vasoactive intestinal peptide is upregulated in endometriosis patients reporting chronic pain. Increased microvessel density in tissue and peritoneal fluid concentrations of IL‐6 indicate an elevated inflammation in the pelvic microenvironment of these patients.

  • 12. Bourlev, Vladimir
    et al.
    Pavlovitch, Stanislav
    Stygar, Denis
    Volkov, Nikolai
    Lindblom, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Different proliferative and apoptotic activity in peripheral versus central parts of human uterine leiomyomas2003Ingår i: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002X, Vol. 55, nr 4, s. 199-204Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To determine whether there are differences in proliferative and apoptotic activity and in expression of sex steroid receptors between central and peripheral parts of human uterine leiomyomas in different menstrual cycle phases.

    METHODS:

    Biopsy specimens of the myometrium and peripheral and central parts of uterine leiomyomas were obtained from 15 women in the proliferative phase and 8 women in the secretory phase. Mitotic cells were detected by immunohistochemical staining for Ki67. Apoptotic cells were detected by the TUNEL method. Mitotic and apoptotic indexes were calculated. Tissue levels of oestrogen and progesterone receptors were measured using a commercial monoclonal receptor enzyme immunoassay kit.

    RESULTS:

    During the secretory phase the mitotic index was significantly higher in the peripheral than in the central parts of the leiomyomas. During the proliferative phase the apoptotic index was significantly higher in the peripheral compared with the central parts. These differences were not reflected by differences in receptor expression.

    CONCLUSIONS:

    The results of this study suggest that the growth of a human uterine leiomyoma mainly occurs in the peripheral parts of the tumour, during the secretory phase of the menstrual cycle. The findings emphasise the importance of being consistent when taking samples for research work.

  • 13.
    Bourlev, Vladimir
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Volkov, N.
    Pavlovitch, S.
    Lets, N.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions2006Ingår i: Reproduction, ISSN 1470-1626, E-ISSN 1476-3990, Vol. 132, nr 3, s. 501-509Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studies were performed to elucidate the possible relationship between microvessel density, proliferative activity and angiogenesis in eutopic endometrium from women with and without endometriosis and peritoneal endometriotic lesions. The question whether changes in these parameters in endometriotic lesions were reflected by the level of vascular endothelial growth factor-A (VEGF-A) in serum and peritonea fluid was also studied. Biopsy specimens of both eutopic endometrium and peritoneal endometriotic lesions from women with endometriosis (n=25) as well as eutopic endometrium from women without endometriosis (n=14) were analysed immunohistochemically regarding microvessel density, proliferative activity, and expression of VEGF-A and its receptors vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2) in stroma, glands and blood vessels. The VEGF-A concentration was measured in peritoneal fluid and serum. Secretory phase eutopic endometrium from women with endometriosis had significantly higher microvessel density, expression of VEGF-A in glandular epithelium and VEGFR-2 in endometrial blood vessels than those from women without endometriosis. Endometriotic lesions with high proliferative activity had a higher microvessel density and showed higher vascular expression of VEGFR-2 as well as being accompanied by higher levels of VEGF-A in peritoneal fluid and serum, compared with lesions with low proliferative activity. In conclusion, there seems to be a dysregulation of angiogenic activity in the eutopic endometrium of women with endometriosis and endometriotic lesions with high proliferative activity were accompanied by higher local angiogenic activity and higher levels of VEGF in serum and peritoneal fluid.

  • 14.
    Bredhult, Carolina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Bäcklin, Britt-Marie
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Effects of some endocrine disruptors on the proliferation and viability of human endometrial endothelial cells in vitro2007Ingår i: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 23, nr 4, s. 550-559Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endocrine disrupting chemicals (EDCs) pose a potential threat to human reproductive health. We studied the proliferation and viability of human endometrial endothelial cells (HEECs) in vitro after exposure to 2,2-bis(o,p-chlorophenyl)-1,1,1-trichloroethane (o,p′-DDT), 3,3′,4,4′-tetrachlorobiphenyl (CB 77), 3,3′,4,4′,5-pentachlorobiphenyl (CB 126), di-n-butyl phthalate (DBP), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and 17β-oestradiol, progesterone, 17α-ethynyl oestradiol and levonorgestrel. Cell proliferation was studied using immunocytochemistry for PCNA expression and a 5-bromo-2′-deoxyuridine assay. Cell viability was studied by vital staining with propidium iodide and Hoechst 33258. HEECs in primary culture responded with increased proliferation to oestradiol and with decreased proliferation to levonorgestrel and the EDCs. Some EDCs also affected cell viability and increased the proportion of necrotic cells. However, the decrease in proliferation in response to DBP and TCDD cannot be explained by cell death. In light of these results, it is possible that the EDCs could have effects in vivo as well as in vitro, and influence processes involving for example endometrial angiogenesis.

  • 15. Bremer, Susanne
    et al.
    Brittebo, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Dencker, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Knudsen, Lisbeth Ehlert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Mathisien, Line
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Pazos, Patricia
    Pellizzer, Cristian
    Paulesu, Luana Ricci
    Schaefer, Wolfgang
    Schwarz, Michael
    Staud, Frantisek
    Stavreus-Evers, Anneli
    Dept Clinical Science, Intervention and Technology, Karolinska Institutet, Hospital Huddinge, Stockholm, Sweden.
    Vähänkangas, Kirsi
    In vitro tests for detecting chemicals affecting the embryo implantation process: The report and recommendations of ECVAM workshop 62 - a strategic workshop of the EU ReProTect project2007Ingår i: ATLA (Alternatives to Laboratory Animals), ISSN 0261-1929, Vol. 35, nr 4, s. 421-439Artikel, forskningsöversikt (Refereegranskat)
  • 16.
    Brodin, Thomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Hadziosmanovic, Nermin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Bergh, Torbjorn
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Holte, Jan
    Antimullerian hormone predicts pregnancy and live-birth rates after assisted reproduction and reflect oocyte quality besides oocyte quantity2012Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 91, s. 35-35Artikel i tidskrift (Övrigt vetenskapligt)
  • 17.
    Brodin, Thomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Hadziosmanovic, Nermin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Holte, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Antimüllerian hormone levels are strongly associated with live-birth rates after assisted reproduction2013Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, nr 3, s. 1107-1114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Previous studies have suggested that antimullerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality. Objective: The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos. Design: The study was a prospective cohort study between April 2008 and June 2011. Setting: The study was done at a university-affiliated private infertility center. Patients: The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles. Intervention(s): AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome. Main Outcome Measures: Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured. Results: AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH < 0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH > 2.94 ng/mL (75th percentile), P-trend < .0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores. Conclusions: AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality.

  • 18.
    Brodin, Thomas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. Carl von Linne Clin, S-75183 Uppsala, Sweden..
    Hadziosmanovic, Nermin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden..
    Holte, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi. Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.;Carl von Linne Clin, S-75183 Uppsala, Sweden.;Ctr Reprod Biol Uppsala CRU, Uppsala, Sweden..
    Comparing four ovarian reserve markers: associations with ovarian response and live births after assisted reproduction2015Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 94, nr 10, s. 1056-1063Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction. We compared the ability of four different ovarian reserve tests (ORTs) to predict live births per started in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycle, and poor and excessive response to controlled ovarian hyperstimulation. Material and methods. This was a cohort study in a private infertility center in collaboration with Uppsala University, comprising 1230 IVF-ICSI cycles in 892 consecutive women between April 2008 and June 2011. Anti-Mullerian hormone (AMH) levels, antral follicle counts (AFC), combinations of basal levels of follicle-stimulating hormone and luteinizing hormone, and menstrual cycle lengths were analyzed for correlation and treatment outcome prediction in age-adjusted statistical models. Stepwise multivariable generalized estimating equation analyses were carried out in a sub-group with complete data on all four ORTs (620 cycles in 443 women). Odds ratios and c-statistics were calculated in the largest available set of data for each significant variable. Primary outcomes were live birth rate per started cycle and poor and excessive ovarian response to controlled ovarian hyperstimulation (defined by the ovarian sensitivity index). Results. All ORTs correlated significantly with each other, with the strongest correlation between AFC and AMH (r = 0.71, p < 0.0001). Univariately, AMH and age equivalently predicted live birth (c-statistic 0.61), and together they provided a significantly better model (c-statistic 0.64). For prediction of poor and excessive response the best model included AMH, AFC and age (c-statistic 0.89). Conclusions. AMH improves the ability to estimate live birth rates after assisted reproduction compared with female age alone. AMH, AFC and age together constituted the best model for prediction of ovarian response.

  • 19. Bäcklin, B-M
    et al.
    Eriksson, L
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Histology of uterine leiomyoma and occurrence in relation to reproductive activity in the Baltic gray seal (Halichoerus grypus).2003Ingår i: Veterinary pathology, ISSN 0300-9858, E-ISSN 1544-2217, Vol. 40, nr 2, s. 175-180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A high prevalence of uterine leiomyoma has been reported in Baltic gray seals aged 15 years and above. Studies on Baltic seals during the 1970s revealed high tissue concentrations of the organochlorines bis(chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), lowered reproduction rate, and pathologic changes. In the second half of the 1970s, decreases of PCB and DDT in Baltic biota occurred, and the prevalence of pregnancies in Baltic seals increased. Between 1975 and 1997, 53 Baltic gray seal females of age 15-40 years were found dead and sent to the Swedish Museum of Natural History. Seals were autopsied and 34/53 (64%) had uterine leiomyomas. Samples from 15 were sufficiently well preserved for histologic examination. Uterine leiomyomas were found most commonly in the uterine corpus but also were observed in the uterine horns, cervix, and vagina. Cut surfaces of the leiomyomas appeared as whorled white fibrous tissue. Histologically, spindle cells were arranged in a whorl-like pattern. The nuclei were rod-like and strikingly uniform in shape and size. Mitotic figures were rare. Immunohistochemical staining of the tumors showed a positive reaction to antibodies recognizing smooth muscle actin. Reproductively active gray seals have an ovarian corpus luteum or albicans for most of the year. In 22/34 (65%) gray seals with uterine leiomyomas, ovaries did not contain corpora. In gray seals without macroscopically detected uterine leiomyoma, ovaries from 6/19 (32%) seals had no corpora. It is possible that the development of leiomyoma in the seals is associated with organochlorines and the previous low reproductive activity.

  • 20. Bäcklin, Britt-Marie
    et al.
    Bredhult, Carolina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Proliferative Effects of Estradiol, Progesterone, and Two CB Congeners and Their Metabolites on Gray Seal (Halichoerus grypus) Uterine Myocytes in Vitro2003Ingår i: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 75, nr 1, s. 154-160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gray seal females living in the Baltic Sea have been found to exhibit a high prevalence of uterine leiomyomas. These animals are also known to accumulate lipid-soluble PCBs in their blubber. PCBs have documented endocrine-disrupting effects; to investigate whether the PCBs could be part of the genesis of uterine smooth muscle tumors in this species, gray seal myometrial cell cultures were exposed to two CBs and their metabolites, as well as to estradiol and progesterone, after which the effects were analyzed in terms of proliferative activity by measurements of BrdU absorbance and protein content. Progesterone was found to have an inhibitory effect, whereas one CB acted as a stimulant on the myometrial cell proliferation. One of the CB metabolites also seemed to have an inhibitory effect, although this could not be statistically verified. These results suggest that some CBs have effects on uterine myometrial cell proliferation in gray seals and, thus, may also take part in the growth regulation of uterine leiomyomas.

  • 21.
    Ciray, H N
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Fu, X
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Ahlsen, G
    Shuman, C
    Lindblom, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Ulmsten, U
    Presence and localization of connexins 43 and 26 in cell cultures derived from myometrial tissues from nonpregnant and pregnant women and from leiomyomas2000Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 182, nr 4, s. 926-930Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    Our objective was to study the appearance and distribution of connexins 43 and 26 in various human myometrial cell cultures.

    STUDY DESIGN:

    Scrape loading, Western blotting, and immunohistochemical techniques were applied to cultured cells derived from myometrial tissues obtained from nonpregnant and pregnant women (upper and lower uterine segments) and from leiomyomas (tumor and analogous myometrial tissues).

    RESULTS:

    Scrape loading revealed the presence of metabolic coupling in all tissues. Indirect immunohistochemical studies showed membrane localization of connexin 43 in all myometrial cultures. Western blots and indirect immunohistochemical studies showed the presence and localization of the connexin 26 protein and associated gap junctions in tissues from myomas and from nonpregnant and pregnant women except for those derived from the upper segment of the pregnant uterus.

    CONCLUSION:

    These results show that human myometrial cultures express various gap junction proteins and that there are regional differences in expression of connexins in tissues from pregnant women.

  • 22.
    Comasco, Erika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Iliadis, Stavros I
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Oreland, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Sundström-Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Skalkidou, Alkistis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Adipocytokines levels at delivery, functional variation of TFAP2 beta, and maternal and neonatal anthropometric parameters2013Ingår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, nr 10, s. 2130-2137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE

    Adipocytokines participate in the regulation of glucose metabolism and foetal development. The transcription factor activating protein 2B (TFAP2β) has been associated with adipocytokine regulation, and gene variations with type 2 diabetes and obesity. This study investigated associations between maternal TFAP2B variation, adipocytokines levels and maternal and neonatal anthropometric characteristics.

    DESIGN AND METHODS

    A population-based sample of women was followed from delivery to six months postpartum. Adiponectin, leptin and interleukin-6 levels at delivery, and maternal as well as neonatal anthropometric variables were assessed. The TFAP2β intron 1 variable number tandem repeat (VNTR) was genotyped.

    RESULTS

    Maternal interleukin-6 correlated positively with leptin at delivery, with peripartum weight changes and weight of newborn males, adjusted for potential confounders. Leptin at delivery was associated with TFAP2β intron 1 VNTR genotype, adjusted for confounders, maternal weight and negatively with birth weight among female neonates. A path model suggested a link between TFAP2β genotype, leptin levels and newborn females' weight.

    CONCLUSIONS

    The present results stress a role for the TFAP2 β in adiposity-related conditions and intrauterine growth. The association between neonatal birth weight and maternal adipocytokine levels, together with the observed sex effect, call for further studies on the mechanisms behind neuro-endocrine foetal programming.

  • 23.
    Dommett, Emilie
    et al.
    Univ Cambridge, Cambridge, England..
    Colleoni, Francesca
    Univ Cambridge, Cambridge, England..
    Kingdom, John
    Univ Toronto, Toronto, ON, Canada..
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Murray, Andrew
    Univ Cambridge, Cambridge, England..
    Burton, Graham
    Univ Cambridge, Cambridge, England..
    Yung, Hong Wa
    Univ Cambridge, Cambridge, England..
    Reduced Mitochondrial Respiration In Placentas From Early Onset Pre-Eclampsia: Potential Roles Of The Mitochondrial Unfolded Protein Response2017Ingår i: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 57, s. 274-275Artikel i tidskrift (Övrigt vetenskapligt)
  • 24.
    Edelstam, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi. Danderyd Hosp, Dept Obstet & Gynaecol & Clin Sci, SE-18288 Stockholm, Sweden.
    Makdessi, Lollo
    Vrinnevi Hosp, S-60379 Norrkoping, Sweden.
    Hagmar, Magnus
    Danderyd Hosp, Dept Obstet & Gynaecol & Clin Sci, SE-18288 Stockholm, Sweden.
    Moberg, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Spira, Jack
    InSpira Med AB, Tyresö, Sweden.
    Optimised gynaecological examination with a new pelvic examination chair2019Ingår i: Sexual & Reproductive HealthCare, ISSN 1877-5756, E-ISSN 1877-5764, Vol. 19, s. 84-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: The present aim was to contribute to improving the traditional pelvic examination chair with vertical leg support and to evaluate patients' and examiners' experience of a new gyneacological and urological examination chair with heated upholstery.

    Study design: A new gynaecological and urological examination chair was constructed with laterally adjustable leg support, a foot-plate and the perineum exposed only during the examination procedure. Patients (n = 131) with or without endometriosis were invited to participate in an anonymous questionnaire survey concerning how they experienced a gynaecological examination.

    Main outcome measures: The patients and the gynaecologists who performed the examinations answered questionnaires evaluating the examination procedure in the traditional and in the new gynaecological and urological examination chair, respectively. The questionnaires asked about comfort, heating, integrity and the experience of pelvic examination with vertical or lateral leg support. The examination times were measured with a stopwatch.

    Results: The majority of the answers (n = 131) were significantly (p < 0.05-0.001) in favour of the new concept with lateral leg support and with increased comfort and integrity. The average examination time was significantly shortened and the patients more relaxed in the new gynaecological and urological examination chair.

    Conclusion: The traditional gynaecological chair with vertical leg support has remained basically unchanged for many years. The present study showed that the pelvic examination procedure can be significantly optimized with easy patient-friendly adaptations.

  • 25.
    Enroth, Stefan
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Berggrund, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lycke, Maria
    Broberg, John
    Lundberg, Martin
    Assarsson, Erika
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Stålberg, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Sundfeldt, Karin
    Gyllensten, Ulf B.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer2019Ingår i: Communications biology, ISSN 2399-3642, Vol. 2, artikel-id 221Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ovarian cancer is usually detected at a late stage and the overall 5-year survival is only 30-40%. Additional means for early detection and improved diagnosis are acutely needed. To search for novel biomarkers, we compared circulating plasma levels of 593 proteins in three cohorts of patients with ovarian cancer and benign tumors, using the proximity extension assay (PEA). A combinatorial strategy was developed for identification of different multivariate biomarker signatures. A final model consisting of 11 biomarkers plus age was developed into a multiplex PEA test reporting in absolute concentrations. The final model was evaluated in a fourth independent cohort and has an AUC = 0.94, PPV = 0.92, sensitivity = 0.85 and specificity = 0.93 for detection of ovarian cancer stages I-IV. The novel plasma protein signature could be used to improve the diagnosis of women with adnexal ovarian mass or in screening to identify women that should be referred to specialized examination.

  • 26.
    Enroth, Stefan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Berggrund, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lycke, Maria
    Gothenburg Univ, Inst Clin Sci, Sahlgrenska Acad, Dept Obstet & Gynecol, Gothenburg, Sweden.
    Lundberg, Martin
    OLINK Prote, Uppsala Sci Pk, S-75183 Uppsala, Sweden.
    Assarsson, Erika
    OLINK Prote, Uppsala Sci Pk, S-75183 Uppsala, Sweden.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Stålberg, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktiv hälsa.
    Sundfeldt, Karin
    Gothenburg Univ, Inst Clin Sci, Sahlgrenska Acad, Dept Obstet & Gynecol, Gothenburg, Sweden.
    Gyllensten, Ulf B.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer2018Ingår i: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 15, artikel-id 38Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Over 500,000 women worldwide are diagnosed with ovarian or endometrial cancer each year. We have used a two-step strategy to identify plasma proteins that could be used to improve the diagnosis of women with an indication of gynecologic tumor and in population screening.

    Methods: In the discovery step we screened 441 proteins in plasma using the proximity extension assay (PEA) and five Olink Multiplex assays (CVD II, CVD III, INF I, ONC II, NEU I) in women with ovarian cancer (n=106), endometrial cancer (n=74), benign ovarian tumors (n=150) and healthy population controls (n=399). Based on the discovery analyses a set of 27 proteins were selected and two focused multiplex PEA assays were developed. In a replication step the focused assays were used to study an independent set of cases with ovarian cancer (n=280), endometrial cancer (n=228), women with benign ovarian tumors (n=76) and healthy controls (n=57).

    Results: In the discovery step, 27 proteins that showed an association to cancer status were identified. In the replication analyses, the focused assays distinguished benign tumors from ovarian cancer stage III-IV with a sensitivity of 0.88 and specificity of 0.92 (AUC=0.92). The assays had a significantly higher AUC for distinguishing benign tumors from late stage ovarian cancer than using CA125 and HE4 (p=9.56e-22). Also, population controls could be distinguished from ovarian cancer stage III-IV with a sensitivity of 0.85 and a specificity of 0.92 (AUC=0.89).

    Conclusion: The PEA assays represent useful tools for identification of new biomarkers for gynecologic cancers. The selected protein assays could be used to distinguish benign tumors from ovarian and endometrial cancer in women diagnosed with an unknown suspicious pelvic mass. The panels could also be used in population screening, for identification of women in need of specialized gynecologic transvaginal ultrasound examination.

  • 27. Fu, X
    et al.
    Liu, Y J
    Ciray, N
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Ulmsten, U
    Gylfe, E
    Oxytocin-induced oscillations of cytoplasmic Ca2+ in human myometrial cells.2000Ingår i: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 79, nr 3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: To investigate the mechanisms of oxytocin (OT) induced oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]i) in cultured human myometrial cells.

    METHODS: [Ca2+]i was measured in individual myometrial cells by dual wavelength spectrophotofluorometry using the fluorescent indicator fura-2. Myometrium was obtained at abdominal hysterectomy (n=8) and during cesarean section (n=7).

    RESULTS: OT (10-300 nM) typically induced [Ca2+]i oscillations with frequencies in the 0.6-0.8/min range. There were no obvious differences in the responses of cells taken from non-pregnant and term pregnant women. The frequency and amplitude of the oscillations were not significantly affected by OT concentrations up to 300 nM. The amplitude of the oscillations decreased in the presence of the voltage-dependent Ca2+ channel antagonist verapamil and gradually disappeared in Ca2+-free medium. The oscillations were further blocked by the inorganic Ca2+ antagonist La3+ and by the intracellular Ca2+-ATPase inhibitor 2.5-di-tert-butylhydroquinone (DTBHQ). Caffeine inhibited the OT-induced oscillations in a concentration-dependent manner. DTBHQ and high concentrations of OT made [Ca2+]i remarkably sensitive to changes in the external Ca2+ concentration.

    CONCLUSIONS: The results indicate that OT-induced [Ca2+]i oscillations in human myometrial cells are due to inositol 1,4,5-trisphosphate-mediated release of intracellular Ca2+ combined with capacitative as well as voltage-dependent influx of the ion.

  • 28.
    Fu, X
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Liu, YJ
    Ciray, N
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Olovsson, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Ulmsten, U
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Gylfe, E
    Institutionen för medicinsk cellbiologi.
    Oxytocin-induced oscillations of cytoplasmic Ca2+ in human myometrial cells2000Ingår i: Acta Obstet. Gynecol. Scand., Vol. 79, s. 174-Artikel i tidskrift (Refereegranskat)
  • 29.
    Gambadauro, Pietro
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Persson, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Unusually rapid growth of bilateral endometriomas and acute bilateral hydronephrosis2011Ingår i: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 27, nr 11, s. 948-950Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Ultrasonography can detect ovarian endometriomas, but negative findings cannot exclude other localizations of endometriosis, especially in symptomatic patients. We describe a case of sudden development of large bilateral endometriomas after a series of negative ultrasound scans, causing bilateral hydronephrosis. Our patient is a 32-year-old nulligravida with long-lasting dysmenorrhea, urinary symptoms, and familiarity for endometriosis, who had voluntarily discontinued oral contraceptives. Various pelvic scans had not shown pathological findings. Five months following the last negative scan, she presented with pain and increase of abdominal girth. Ultrasonography and computed tomography showed large ovarian cysts (16 cm right - 10 cm left) and hydronephrosis bilaterally. She underwent conservative surgery followed by GnRH analogs. At a 6-months follow-up, she was symptom-free and ultrasonography showed no recurrence. Endometriosis has still an unknown mechanism of proliferation and its clinical behavior or progression is highly unpredictable. Severe uropathy is commonly related to direct ureteral involvement, but can also depend on an ab-extrinseco compression by large, rapidly growing endometriomas. Women at risk of endometriosis, who are not receiving empirical medical treatment, should be adequately and regularly assessed via pelvic ultrasonography and/or submitted to diagnostic laparoscopy in order to prevent serious consequences such as silent renal loss.

  • 30.
    Gustavsson, Inger M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Aarnio, Riina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Berggrund, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lindberg, Julia Hedlund
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Sanner, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Wikström, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Enroth, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Gyllensten, Ulf B.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.2019Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, nr 1, s. 89-97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if the HPV prevalence is independent of sampling location (vagina versus cervix) and the person performing the sampling. The second aim was to evaluate if the two sampling strategies differed in the detection rate of CIN2+. In total, 19,523 women were randomised into two groups, with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were applied to the indicating FTA elute card and analysed for high-risk HPV using the hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7% of invited women participated in the study, as compared to 34.2% in the AS arm. All samples contained sufficient amount of nuclear DNA for a valid HPV result, with vaginal samples having a higher DNA amount than cervical samples (p < 4.62 × 10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 × 10-2 ), and the distribution of HPV types similar between arms. There was no difference in the prevalence of CIN2+ per 1000 women screened between arms (p = 0.86). The results show that vaginal self-sampling is an equivalent alternative to sampling by medical personnel for HPV typing and identification of CIN2+.

  • 31.
    Gustavsson, Inger M.
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Aarnio, Riina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Berggrund, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lindberg, Julia Hedlund
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Strand, Ann-Sofi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sanner, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Wikström, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Enroth, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Gyllensten, Ulf B.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Randomised study shows that repeated self-sampling and HPV test has more than two-fold higher detection rate of women with CIN2+ histology than Pap smear cytology2018Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 118, nr 6, s. 896-904Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background:

    This randomised study compared the detection rate of cervical intraepithelial neoplasia-positive (CIN2+) based on histology in women performing repeated self-sampling of vaginal fluid (VF) for human papillomavirus (HPV) test with a control group following the ordinary screening by Pap smear cytology.

    Methods:

    36390 women aged 30–49 years scheduled for invitation to organised screening were randomised in two groups, one to perform self-sampling of VF for HPV test (n=17 997, HPV arm) and the other group to perform screening by PAP smear cytology (n=18 393, control arm). HPV positive women in the HPV arm repeated the self-sampling and the HPV test on average 4.4 months later and those with two consecutive positive HPV tests were referred to colposcopy. Outcome was CIN2+ based on histology during 18-month follow-up.

    Results:

    Participation rate was 47% in the HPV arm and 39% in the control arm. The HPV prevalence in the first self-sampling was 6.9%, and 71% of these women were HPV positive in their second test. For the per-protocol approach, cumulative prevalence of histological CIN2+ in the HPV arm was 20.2 per 1000 women screened as compared to 10.8 in the control arm. The cumulative prevalence of CIN2+ diagnosed per 1000 years screened was 160.8 in the HPV arm as compared with 25.4 in the control arm.

    Conclusions:

    Repeated self-sampling of VF and HPV test had more than a two-fold higher discovery rate of CIN2+ per 1000 women screened as compared with PAP smear cytology.

  • 32.
    Gustavsson, Inger M.
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Aarnio, Riina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Myrnäs, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi. Uppsala Univ, Dept Womens & Childrens Hlth, SE-75185 Uppsala, Sweden.
    Lindberg, Julia Hedlund
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Taku, Ongeziwe
    Univ Cape Town, Fac Hlth Sci, Div Med Virol, Anzio Rd, ZA-7925 Cape Town, South Africa.
    Meiring, Tracy
    Univ Cape Town, Fac Hlth Sci, Div Med Virol, Anzio Rd, ZA-7925 Cape Town, South Africa.
    Wikström, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Enroth, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Williamson, Anna-Lise
    Univ Cape Town, Fac Hlth Sci, Div Med Virol, Anzio Rd, ZA-7925 Cape Town, South Africa.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Gyllensten, Ulf B.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Clinical validation of the HPVIR high-risk HPV test on cervical samples according to the international guidelines for human papillomavirus DNA test requirements for cervical cancer screening2019Ingår i: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 16, nr 1, artikel-id 107Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The indicating FTA card is a dry medium used for collection of cervical samples. HPVIR is a multiplex real-time PCR test that detects 12 high-risk human papillomavirus types (hrHPV) and provides single genotype information for HPV16, − 31, − 35, − 39, − 51, − 56, and − 59 and pooled type information for HPV18/45 and HPV33/52/58. The aim of this study was to evaluate whether a strategy with cervical samples collected on the FTA card and subsequently analysed with the HPVIR test complies with the criteria of the international guidelines for a clinically validated method for cervical screening.

    Methods

    We performed a non-inferiority test comparing the clinical sensitivity and specificity of the candidate test (FTA card and HPVIR) with a clinically validated reference test (Cobas® HPV test) based on liquid-based cytology (LBC) samples. Two clinical samples (LBC and FTA) were collected from 896 participants in population-based screening. For evaluation of the specificity we used 799 women without ≥ CIN2, and for clinical sensitivity we used 67 women with histologically confirmed ≥ CIN2. The reproducibility was studied by performing inter- and intra-laboratory tests of 558 additional clinical samples.

    Results

    The clinical sensitivity and specificity for samples collected on the FTA card and analysed using the HPVIR test were non-inferior to samples analysed with the Cobas® HPV test based on LBC samples (non-inferiority test score, p = 1.0 × 10− 2 and p = 1.89 × 10− 9, respectively). Adequate agreement of > 87% was seen in both the intra- and inter-laboratory comparisons.

    Conclusions

    Samples collected on the indicating FTA card and analysed with HPVIR test fulfil the requirements of the international guidelines and can therefore be used in primary cervical cancer screening.

  • 33.
    Gustavsson, Inger
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Sanner, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Lindell, Monica
    Strand, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Wikström, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Wilander, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge2011Ingår i: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 51, nr 4, s. 255-258Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Most procedures for self-sampling of cervical cells are based on liquid-based media for transportation and storage. An alternative is to use a solid support, such as dry filter paper media.

    Objectives

    To evaluate if self-sampling of cervicovaginal fluid using a cytobrush (Viba-brush; Rovers Medical Devices B.V., Oss, The Netherlands) and a solid support such as the Whatman Indicating FTA® Elute cartridge (GE Healthcare, United Kingdom) can be used for reliable typing of human papillomavirus (HPV), as compared to cervical samples obtained by a physician using a cytobrush and the indicating FTA® Elute Micro card and biopsy analysis.

    Study design

    A total of 50 women with a previous high-risk (HR) HPV positive test were invited to perform self-sampling using the Viba-brush and the FTA cartridge and thereafter a physician obtained a cervical sample using the cytobrush and a FTA card, together with a cervical biopsy for histology and HPV typing. Detection of HR-HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 was performed using three multiplex real-time polymerase chain reaction (PCR) assays.

    Result

    All samples contained sufficient amounts of genomic DNA and the self-samples yielded on average 3.5 times more DNA than those obtained by the physician. All women that were positive for HR-HPV in the biopsy sample also typed positive both by self-sampling and physician-obtained sampling. For women with a histological diagnosis of cervical intraepithelial neoplasia grades 2–3 (CIN 2–3) all three HPV samples showed 100% concordance. A higher number of women were HPV positive by self-sampling than by physician-obtained sampling or by biopsy analysis.

    Conclusion

    The Viba-brush and the FTA cartridge are suitable for self-sampling of vaginal cells and subsequent HR-HPV typing.

  • 34.
    Helmestam, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Andersson, Helén
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Stavreus-Evers, Anneli
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Brittebo, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Tamoxifen Modulates Cell Migration and Expression of Angiogenesis-Related Genes in Human Endometrial Endothelial Cells2012Ingår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 180, nr 6, s. 2527-2535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The selective estrogen receptor modulator tamoxifen is used for the prevention and treatment of breast cancer. The adverse effects of tamoxifen include vaginal endometrial bleeding, endometrial hyperplasia, and cancer, conditions associated with angiogenesis. The aim of this study was to examine the effects of tamoxifen on cell migration and angiogenesis-related gene expression in human endometrial endothelial cells (HEECs). The regulatory effects of tamoxifen on endometrial stromal cells and HEECs were also examined. HEECs and stromal cells were isolated and grown In monocultures or co-cultures, and incubated with 0.1 to 100 mu mol/L tamoxifen for 48 hours. Quantitative PCR demonstrated that tamoxifen decreased the mRNA expression of vascular endothelial growth factor-A (VEGF-A) and increased the mRNA expression of VEGF receptor-1 and placental growth factor (PLGF) in HEECs. Tamoxifen's effects on VEGF-A were inhibited when HEECs were co-cultured with stromal cells. In addition, tamoxifen reduced VEGF-induced HEEC migration. The tamoxifen-metabolizing enzymes CYP1A1 and CYP1B1 were detected by immunohistochemistry in and around endometrial blood vessels and by quantitative PCR in HEECs. Our data suggest that tamoxifen changes the regulation of angiogenesis in the endometrium, likely by reducing angiogenic activity. The results also indicate that endometrial stromal cells regulate some of tamoxifen's effects in HEECs, and the presence of tamoxifen-metabolizing enzymes suggests tamoxifen bioactivation in the endometrial vasculature in vivo. These findings may help to elucidate the mechanism of the bleeding disturbances associated with tamoxifen treatment.

  • 35.
    Helmestam, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Davey, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Stavreus-Evers, Anne Li
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Bisphenol A affects human endometrial endothelial cell angiogenic activity in vitro2014Ingår i: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 46, s. 69-76Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The widespread Bisphenol A (BPA) is classified as an endocrine-disrupting chemical (EDC) with estrogenic properties. Human endometrial endothelial cells (HEECs) play a key role in the endometrial angiogenesis that is under the control of estradiol. The hypothesis was that BPA may affect endometrial angiogenesis by disturbing some functional properties of the HEEC. To study this, primary HEECs were exposed to environmentally relevant doses of BPA. The HEECs were co-cultured with primary endometrial stromal cells to create conditions as similar to the in vivo situation as possible. The effects of BPA were evaluated by proliferation and viability assays, tube-formation assays, quantitative PCRs, Western blots and ELISAs. BPA slightly increased HEEC tube formation and VEGF-D protein expression compared with vehicle, without affecting HEEC viability or proliferation. Bisphenol A thus caused changes in HEEC activities in vitro, and may therefore have disturbing effects on endometrial angiogenesis. (C) 2014 Elsevier Inc. All rights reserved.

  • 36.
    Helmestam, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Lindgren, Karin Elvine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Stavreus-Evers, Anneli
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Mifepristone exposure of human endometrial endothelial cells in vitro2014Ingår i: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 21, nr 3, s. 408-414Artikel i tidskrift (Refereegranskat)
  • 37.
    Hermansson, Ruth S.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi. Orebro Univ, Fac Med & Hlth, Dept Oncol, Orebro, Sweden..
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Hoxell, Emelie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Lindström, Annika K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk och reproduktiv hälsoforskning. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Orebro Univ, Fac Med & Hlth, Clin Res Ctr, Orebro, Sweden..
    HPV prevalence and HPV-related dysplasia in elderly women2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 1, artikel-id e0189300Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above.

    Patients and methods: From September 2013 until June 2015, 1051 women aged 60-89 years (mean 68 years) were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC), after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained.

    Results: The prevalence of HPV was 4.1%, (95% CI 3.0-5.5, n = 43) at the first test, and at the second test 2.6% remained positive (95% CI 1.7-3.8, n = 27). The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27) (4 CIN 2-0.4%, 18 CIN 1-1.7%). HPV-related dysplasia was found in 2.1%, (95% CI 1.3-3.2,n = 22) of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected.

    Conclusion: A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity.

  • 38.
    Holte, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Brodin, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Hadziosmanovic, Nermin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Bergh, Torbjörn
    Carl von Linné Clinic, Uppsala Science Park.
    Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries2011Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 96, nr 3, s. 594-599Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC. Design: Prospective observational study. Setting: University-affiliated private infertility center. Patient(s): 2,092 women undergoing 4,308 IVF-ICSI cycles. Intervention(s): AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age. Main Outcome Measure(s): Pregnancy rate, live-birth rate, and stimulation outcome parameters. Result(s): The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC similar to 30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved. Conclusion(s): Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity.

  • 39.
    Hudecova, Miriam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Holte, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Moby, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk endokrinologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin diabetes och metabolism.
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Androgen levels, insulin sensitivity, and early insulin response in women with polycystic ovary syndrome: a long-term follow-up study2011Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 95, nr 3, s. 1146-1148Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Thirty-four women with polycystic ovary syndrome who previously had participated in studies with intravenous glucose tolerance test and hyperinsulinemic, euglycemic clamp between 1987 and 1995 underwent anthropometric, endocrine (T and sex-hormone binding globulin serum concentration), and metabolic (intravenous glucose tolerance test, hyperinsulinemic, euglycemic clamp, and androgens) measurements. Free androgen levels and β-cell function decreased over time in women with polycystic ovary syndrome, but insulin sensitivity remained unaltered.

  • 40.
    Hudecova, Miriam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Holte, Jan
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sundstrom-Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Prevalence of the metabolic syndrome in women with a previous diagnosis of polycystic ovary syndrome: long-term follow-up2011Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 96, nr 5, s. 1271-1274Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine the prevalence of the metabolic syndrome (MetS) according to the scientific statement of the American Heart Association and the US National Cholesterol Education Program/Adult Treatment Panel III in middle-aged Swedish women previously diagnosed with polycystic ovary syndrome (PCOS) in comparison with age-matched healthy controls.

    DESIGN: Long-term follow-up study.

    SETTING: Department of Obstetrics and Gynecology, Uppsala University.

    PATIENT(S): Eighty-four women diagnosed with PCOS between 1987 and 1995; and 87 controls randomly selected from the general population.

    INTERVENTION(S): Anthropometric measurements and blood tests.

    MAIN OUTCOME MEASURE(S): Body mass index, waist circumference, blood pressure, lipids, and glucose.

    RESULT(S): The prevalence of MetS in women with PCOS (mean ± SD age, 43.0 ± 5.8 years) was 23.8% and in controls was 8.0%, and it did not differ according to PCOS phenotype at the index assessment (polycystic ovaries [PCO], oligomenorrhea, and hirsutism: 10 [22.7%]; PCO and oligomenorrhea: 8 [22.2%]) or according to the persistence of PCOS features at follow-up (persisting PCOS: 25.8%; resolved PCOS: 16.7%).

    CONCLUSION(S): The MetS occurred more often in patients with PCOS than in controls and did not depend on phenotypic presentation at the index assessment or the persistence of PCOS at follow-up.

  • 41. Jain, Arjun
    et al.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Burton, Graham J.
    Yung, Hong-wa
    Endothelin-1 Induces Endoplasmic Reticulum Stress by Activating the PLC-IP3 Pathway Implications for Placental Pathophysiology in Preeclampsia2012Ingår i: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 180, nr 6, s. 2309-2320Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent evidence implicates placental endoplasmic reticulum (ER) stress in the pathophysiological characteristics of preeclampsia. Herein, we investigate whether endothelin (ET)-1, which induces Ca2+ release from the ER, can induce placental ER stress. Loss of ER Ca2+ homeostasis impairs post-translational modification of proteins, triggering ER stress-response pathways. IHC confirmed the presence of both ET-1 and its receptors in the syncytiotrophoblast. Protein levels and immunoreactivity of ET-1 and the endothelin B receptor (ETBR) were increased in preeclamptic samples compared with normotensive controls. JEG-3 and BeWo choriocarcinoma cells treated with ET-1 displayed an increase in ER stress markers. ET-1 induced phospho-activation of the ETBR. Treating cells with BQ788, an ETBR antagonist, or small-interfering RNA knockdown of the receptor inhibited induction of ER stress. ET-1 also stimulated p-phospholipase C (PLC)gamma 1 levels. By using inhibitors of PLC activation, U73122, and the inositol 1,4,5-triphosphate (IP3) receptor, xestospongin-C, we demonstrated that ET-1 induces ER stress via the PLC-IP3 pathway. Furthermore, ET-1 levels increased in the syncytiotrophoblast of explants from normal placentas after hypoxia-reoxygenation in vitro. Conditioned medium from hypoxia-reoxygenation explants also contained higher ET-1 levels, which induced ER stress in JEG-3 cells that was abolished by an ET-1 neutralizing antibody. Collectively, the data show that ET-1 induced ER stress in trophoblasts via the ETBR and initiation of signaling through the PLC-IP3 pathway, with the potential for autocrine stimulation.

  • 42.
    Junus, Katja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Centlow, Magnus
    Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Avdelningen för obstetrik och gynekologi.
    Wikström, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Larsson, Irene
    Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Avdelningen för obstetrik och gynekologi.
    Hansson, Stefan R
    Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Avdelningen för obstetrik och gynekologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia: down-regulation of the angiogenesis related genes ACVRL1 and EGFL7 in early-onset disease2012Ingår i: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 18, nr 3, s. 146-155Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The underlying mechanisms behind the obstetric condition pre-eclampsia (PE) are still unclear. Manifestation of PE is heterogeneous and it has therefore been proposed to be a syndrome with different causes rather than one disease with a specific aetiology. Recently, we showed differences in circulating angiogenic factors between two subgroups - early- and late-onset PE. To further elucidate the differences between the two, we investigated placental gene expression profiles. Whole genome microarray technology and bioinformatic analysis were used to evaluate gene expression profiles in placentae from early- (24-32 gestational weeks, n=8) and late-onset (36-41 gestational weeks, n=7) PE. The results were verified by using quantitative real-time PCR. We found significant differences in the expression of 196 genes in early- compared with late-onset PE, 45 of these genes showing a fold change above 2. Bioinformatic analysis revealed alterations in angiogenesis and regulation of cell motility. Two angiogenesis-associated transcripts (Egfl7 and Acvrl1) showed lower expression in early-onset PE vs. late-onset PE (p=0.037 and p=0.003) and vs. gestational age-matched controls (p=0.007 and p=0.011). We conclude that angiogenesis-associated genes are regulated in a different manner in the two subgroups, and that the gene expression profiles of early- and late-onset PE diverge, supporting the hypothesis of early- and late-onset PE being at least partly two separate entities.

  • 43.
    Junus, Katja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Majali-Martinez, Alejandro
    Department of Obstetrics and Gynecology, Medical University of Graz, Austria.
    Kallak, Theodora Kunovac
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Primary Term Trophoblasts Release NT-proBNPManuskript (preprint) (Övrigt vetenskapligt)
  • 44.
    Junus, Katja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Wikström, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Early second-trimester plasma levels of NT-proBNP in women who subsequently develop early-onset preeclampsia2017Ingår i: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 30, nr 18, s. 2163-2165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Plasma levels of NT-proBNP are elevated in women with preeclampsia at the time of diagnosis. The objective of this case-control study was to evaluate N-terminal proBNP (NT-proBNP) in maternal plasma as an early second-trimester biomarker for prediction of early-onset preeclampsia. In early second-trimester samples, women who later developed preeclampsia at gestational age 34 wk + 0 or earlier (n = 16) had similar plasma levels of NT-proBNP (median 51.8, range 26.1-131.9 pg/ml) as women with uncomplicated pregnancy outcomes (n = 43) (53.0, 14.9-184.2 pg/ml). The early second-trimester level of NT-proBNP cannot therefore be used as a predictive biomarker of early-onset preeclampsia.

  • 45.
    Junus, Katja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Wikström, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Placental Expression of proBNP/NT-proBNP and Plasma Levels of NT-proBNP in Early- and Late-Onset Preeclampsia2014Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 27, nr 9, s. 1225-1230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Levels of plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) are elevated in preeclampsia. In this study, the possibility that the placenta produces and releases proBNP/NT-proBNP was explored. Plasma levels of NT-proBNP in early- and late-onset preeclampsia were also measured.

    METHODS: Placental proBNP mRNA in early-onset preeclampsia (n = 7), late-onset preeclampsia (n = 8), and controls of similar gestational age (n = 10) was assessed by quantitative real-time polymerase chain reaction. ProBNP/NT-proBNP protein was studied in placental samples with immunohistochemistry (n = 8) and tissue culture (n = 2). Plasma levels of NT-proBNP were measured in early-onset preeclampsia (n = 18), late-onset preeclampsia (n = 20), and relevant controls (n = 36).

    RESULTS: Transcripts of proBNP mRNA were found in 20 out of 25 samples, there were no differences in expression between the groups. ProBNP/NT-proBNP protein was observed in maternal spiral arteries and in syncytiotrophoblasts in all placental samples. After placental tissue culture, there were measurable amounts of NT-proBNP in the culture media. Women with both early- (365 [14-9815] pg/ml) and late-onset preeclampsia (176 [33-2547] pg/ml) had higher levels of NT-proBNP than their controls (P < 0.001). There was a tendency toward higher levels of NT-proBNP in women with early-onset preeclampsia than in women with late-onset preeclampsia (P = 0.057).

    CONCLUSION: The results indicate possible placental production and release of proBNP/NT-proBNP into the maternal circulation.

  • 46.
    Katja, Junus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Anna-Karin, Wikström
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Anders, Larsson
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    PP015. Plasma levels and placental expression of BNP/NT-proBNP in early and late onset preeclampsia2013Ingår i: Pregnancy Hypertension, ISSN 2210-7789, E-ISSN 2210-7797, Vol. 3, nr 2, s. 73-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION:

    Women with preeclampsia (PE) have elevated plasma levels of NT-proBNP. We hypothesized that the placenta may be a source to these elevated levels.

    OBJECTIVES:

    Our objectives were to study the plasma levels of NT-proBNP and the protein and mRNA expression of placental BNP in women with early and late onset PE and controls.

    METHODS:

    Plasma levels of NT-proBNP were measured in women with early (n=18) and late (n=20) onset PE, in two groups of healthy pregnant women in gestational week 24-32 (n=22) and 36-42 (n=14), and in non-pregnant women (n=20). Placental BNP protein and mRNA was studied with immunohistochemistry and qPCR. Placental release of NT-proBNP was studied with tissue culturing.

    RESULTS:

    Women with early (365 (14-9815) pg/ml) and late (176 (33-2547) pg/ml) onset PE had higher levels of NT-proBNP in plasma than their respective controls (p<0.001). A tendency towards higher plasma levels in early compared to late onset PE was observed (p=0.057). 20 out of 25 placental tissue samples had proBNP mRNA, no differences between the study groups were found. BNP protein was found in maternal spiral arteries and syncytiotrophoblasts. NT-proBNP peptide (6-7pg/ml) was present in medium used for placenta cultures.

    CONCLUSIONS:

    Our results suggest that there may be a placental source of NT-proBNP. If this source is responsible for the elevated plasma levels of NT-proBNP in preeclamptic women and what role, if any, BNP/NT-proBNP play in PE pathophysiology remains to be elucidated.

  • 47.
    Lindahl, Magnus S.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Nyberg, Sigrid
    Thorsen, Kim
    Olsson, Tommy
    Sundström Poromaa, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Increased cortisol responsivity to adrenocorticotropic hormone and low plasma levels of interleukin-1 receptor antagonist in women with functional hypothalamic amenorrhea2007Ingår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 87, nr 1, s. 136-142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls. DESIGN: Cross-sectional study. SETTING: Umeå University Hospital, Umeå, Sweden. PATIENTS: Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer. RESULTS: Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels. CONCLUSION: The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.

  • 48. Lindblom, B
    et al.
    Blanck, A
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    [Growth factors in the uterus are surveyed].1997Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 94, nr 43Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    The central localisation of the uterus in the female body may be seen as reflecting its central function in human reproduction, though in rare cases pregnancy may be established even in the absence of uterus. The sex steroids are largely responsible for the central regulation of uterine function, and recent productive research has shown the significance of peptide growth factors for various physiological functions, including the development and repair of the endometrium during the menstrual cycle, as well as the adaptation and growth of the organ during pregnancy. The possible involvement of angiogenic peptides in endometrial neovascularisation is discussed, as is the significance of proto-oncogenes and growth factors for the development of uterine fibroids. Further development in this field may have a variety of clinical implications, including the possibility of promoting or inhibiting implantation by manipulation of endometrial angiogenesis.

  • 49.
    Lindström, Annika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Örebro Univ, Clin Res Ctr, Fac Med & Hlth, Örebro, Sweden.
    Sanchez Hermansson, Ruth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi. Örebro Univ, Fac Med & Hlth, Dept Oncol, Örebro, Sweden.
    Gustavsson, Inger M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Lindberg, Julia Hedlund
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Reproduktionsbiologi.
    Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 12, artikel-id e0207714Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background About 30% of the cervical cancer cases in Sweden occur in women older than 60. The primary aim was to evaluate the acceptability of repeated self-sampling at home for HPV-testing in elderly women. The prevalence of HPV and HPV related dysplasia as well as the sensitivity of cytology was evaluated. Methods Repeated self-sampling at home for HPV testing was offered 375 women in each of the four age groups 60, 65, 70 and 75 years. Women with two consecutive positive HPV tests were examined with sampling for histology and cytology. Findings A self-sample was provided by 59.5% (893/1500) of the invited women. The overall prevalence of HPV was 4.4% (95% CI 3.2-6.0, n = 39) in the first test, and 2.5% were persistent positive in the second test (95% C 1.6-3.8, n = 22) collected on average 5.5 months later. Dysplasia, was found in 1.8% (16/893) (95% CI 1.1-3.0) and CIN 2+ in 1.0% (9/893) (95% CI 0.5-2.0) of the women. Of the 16 women with dysplasia in histology, 13 (81.2%) had a normal cytology. Interpretation Repeated self-sampling at home combined with HPV testing was well accepted among elderly women. A high prevalence of CIN was diagnosed by histology. Cytology showed extremely low sensitivity and should not be recommended for this age group.

  • 50.
    Lipcsey, Miklos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Larsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Einarsson, Roland
    Abdul Qadhr, Goran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    The brain is a source of S100B increase during endotoxemia in the pig2010Ingår i: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 110, nr 1, s. 174-180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Cerebral dysfunction frequently complicates septic shock. A marker of cerebral dysfunction could be of significant value in managing sedated septic patients. Plasma S100 (S100B) proteins increase in sepsis. S100B is present not only in the brain but also in other tissues. The source of this protein has not been investigated in sepsis. Our aim in this study was to determine whether the brain is an important source of S100B in an experimental sepsis model.

    METHODS:

    Twenty-seven pigs were anesthetized and randomized to either infusion of endotoxin at the rate of 1 µg · kg-1 · h-1 (n = 19) or saline (n = 8). Catheters were inserted into a cervical artery and the superior sagittal sinus. Blood samples were collected from both sites and physiologic data were registered before the start of the endotoxin infusion and hourly during the experiment. After 6 h, the animals were killed and brain tissue samples were taken from the left hemisphere. S100B in plasma was measured by enzyme-linked immunosorbent assay. Brain tissue samples were stained with biotinylated S100B antibodies.

    RESULTS:

    In the endotoxemic animals, the arterial S100B concentration increased to 442 ± 33 and 421 ± 24 ng/L at 1 and 2 h, respectively, vs 306 ± 28 and 261 ± 25 ng/L in controls (P = 0.018 and 0.00053, respectively). Mean superior sagittal sinus S100B concentrations were higher than mean arterial concentrations at all time points in the endotoxemic animals; however, significance was only reached at 2 h (P = 0.033). The focal glial S100B expression was more intense in the endotoxemic pigs than in controls (P = 0.0047).

    CONCLUSIONS:

    Our results support the hypothesis that the brain is an important source of S100B in endotoxemia even though there may be other sources. These findings make S100B a candidate as a marker of cerebral dysfunction in septic shock.

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