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Sökning: WFRF:(Mints Miriam)

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  • Andersson, Emil, et al. (författare)
  • Low pericyte coverage of endometrial microvessels in heavy menstrual bleeding correlates with the microvessel expression of VEGF-A.
  • 2015
  • Ingår i: International Journal of Molecular Medicine. - D.A. Spandidos. - 1791-244X. ; 35:2, s. 433-438
  • Tidskriftsartikel (refereegranskat)abstract
    • A prospective clinical study was carried out to investigate whether endometrial microvessels in patients with idiopathic heavy menstrual bleeding (HMB) of endometrial origin (HMB-E) are fragile due to low pericyte coverage. Idiopathic HMB-E is characterized by large endothelial cell gaps related to the microvascular overexpression of vascular endothelial growth factor (VEGF)-A and VEGF receptors 1-3. A total of 10 women with a normal menstrual cycle and a history of HMB of <5 years, and 17 healthy women with a normal menstrual cycle were recruited from the Karolinska University Hospital. Blood samples were obtained for hormone analysis and coagulation tests. Endometrial biopsies were collected in the proliferative or in the secretory phase. Pericyte coverage was assessed using immunohistochemical staining for smooth muscle actin-α (SMAα) and by image analysis (microvascular density) of endometrial biopsies from 10 patients with HMB-E and 17 healthy ovulating women (control subjects). Previously published data on endothelial cell gap size and the expression of VEGF receptors were used. Although microvascular density did not differ between the patients with HMB-E and the control subjects, the number of SMAα-positive microvessels in the proliferative phase was significantly (P=0.005) lower in the patients with HMB-E than in the control subjects. Moreover, the number of SMAα-positive microvessels in the control subjects was significantly fewer in the secretory (P=0.04) than in the proliferative phase, whereas this number did not differ among the patients with HMB-E regardless of phase. A significant negative correlation was observed between the number of VEGF-A-positive microvessels and microvessels with pericyte coverage (r=0.8; P=0.04). Finally, the endothelial cell layer was significantly thicker in the patients with HMB-E than in the control subjects. Thus, the upregulation of VEGF-A in idiopathic HMB-E is associated with a low pericyte coverage during the proliferative phase of intense angiogenesis, which may confer vessel fragility, possibly leading to excessive blood loss.
  • Andersson, Sonia, et al. (författare)
  • Acceptance of Self-Sampling Among Long-Term Cervical Screening Non-Attenders with HPV-Positive Results : Promising Opportunity for Specific Cancer Education
  • 2019
  • Ingår i: Journal of Cancer Education. - Springer. - 0885-8195 .- 1543-0154.
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>This study aims to investigate acceptance of vaginal self-sampling for high-risk human papilloma virus (HPV) among long-term screening non-attenders at increased cervical cancer risk and to identify leverage points to promote screening adherence among these women. Forty-three long-term screening non-attenders performed home vaginal self-sampling for HPV, had positive HPV results, and subsequently attended gynecologic examination. Sixteen (37.2%) had high-grade cervical intraepithelial neoplasia (CIN2 or 3), and two had invasive cervical cancer. Forty-one of these women completed a questionnaire concerning Specific Knowledge about HPV, CIN, and cervical cancer, potential barriers to screening and views about self-sampling. Results were compared with 479 women treated for CIN2+ who attended gynecologic follow-up and also performed self-sampling. Significant multivariate predictors of long-term non-attender status compared with referents were low Specific Knowledge, high confidence in self-sampling, and potential barriers-refraining from activity to attend gynecologic examination, needing another's help to attend, and long travel time. Non-attenders citing fear/refraining from gynecologic examination as why they preferred self-sampling significantly more often had lowest Specific Knowledge compared with other non-attenders. All non-attenders could envision themselves doing self-sampling again while only 74% of referents endorsed this statement (p = 0.0003). We conclude that HPV self-sampling is an acceptable option for women at increased cervical cancer risk who have been long-term screening non-attenders. Educational outreach to enhance Specific Knowledge about HPV, CIN and cervical cancer is critical. Those non-attenders who explicitly avoid gynecologic examinations need special attention. Trial Registry: Clinicaltrials.gov NCT02750124.</p>
  • Andersson, Sonia, et al. (författare)
  • Results of cytology and high-risk human papillomavirus testing in females with cervical adenocarcinoma in situ
  • 2013
  • Ingår i: Oncology Letters. - 1792-1074 .- 1792-1082. ; 6:1, s. 215-219
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged &lt;40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma in situ (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological results from AIS-adjacent squamous mucosa. Databases were used to identify 32 female patients with AIS treated for various conditions between 2009 and 2012 at the Department of Gynecology, Uppsala University Hospital (Uppsala, Sweden) and previous cytological, HPV and histological results. Of the individuals in the study, 64.3% had a previously recorded cytological result showing squamous cell abnormalities; five had glandular cell abnormalities (18%) and two had AIS (7.1%). Among the patients with available HPV results, 95% were HR-HPV-positive; HPV18/45 predominated (77%), followed by HPV16 (27%). The patients with multiple HPV infections were aged &lt;= 32 years, while patients aged &gt;= 38 years were only infected with HPV18/45. All but three patients had cervical intraepithelial neoplasia (CIN) in the AIS-adjacent squamous mucosa, 79% of which was CIN2 or worse. The present retrospective database study suggests that AIS is detected at screening mainly due to simultaneous squamous precursor lesions and that HPV18/45 infection is an increasing co-factor for AIS in older patients. HPV analyses of glandular precursor lesions aid in the identification of female individuals at risk of progression to invasive disease, and thus have a favorable effect on adenocarcinoma prevention, together with vaccination.</p>
  • Andersson, Sonia, et al. (författare)
  • Uneven distribution of human papillomavirus 16111 cervical carcinoma in situ and squamous cell carcinoma in older females : A retrospective database study
  • 2014
  • Ingår i: Oncology Letters. - 1792-1074 .- 1792-1082. ; 8:4, s. 1528-1532
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.</p>
  • Govorov, Igor, et al. (författare)
  • Blood inflammatory and endothelial markers in women with von Willebrand disease
  • 2019
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Introduction: VWD-affected females often experience menorrhagia. Periodical fluctuations of the sex steroids during the menstrual cycle cause changes both in the coagulation and immune system. The aim of the current study was to assess the changes in selected inflammatory and endothelial markers in women with VWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with corresponding data from healthy controls.</p><p>Materials and methods: The study group included 12 VWD-affected females with regular menstrual cycle, with none of them being prescribed hormone treatment. They were not pregnant or breastfeeding. The control group consisted of 102 healthy females, matched for age and BMI.</p><p>Results: Within the VWD group, endostatin was higher during the follicular phase, compared to the luteal phase, although the difference was not significant (p = 0.062). sICAM-1 and IL-6 were higher in VWD-affected females, compared to the controls, sVCAM-1, cathepsin S and sP-selectin were lower (p&lt;0.003 for all cases). The pattern was constant throughout the menstrual cycle.</p><p>Conclusions: Higher levels of endostatin during early follicular phase could potentially predispose women with VWD to the development of heavy menstrual bleeding, due to antiangiogenic properties and ability to suppress several coagulation factors. Lower p-selectin levels in VWD group, compared to controls, may also contribute to the bleeding tendency. Changes in other proteins, involved in angiogenesis are hypothetically related to the formation of angiodysplasia—common complication of VWF deficiency. The latter statement requires confirmation in larger studies.</p>
  • Govorov, Igor, et al. (författare)
  • Thrombin generation during a regular menstrual cycle in women with von Willebrand disease
  • 2018
  • Ingår i: Scientific Reports. - NATURE PUBLISHING GROUP. - 2045-2322 .- 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Fluctuations of the sex steroids during the menstrual cycle might significantly influence hemostasis. This association, derived from a number of the observations on healthy women, is yet to be described in females affected by bleeding disorders. The aim of the current study was to assess the changes in hemostatic variables in women with vWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with healthy controls. The study group included 12 vWD-affected females with regular menstrual cycle, with none of them being prescribed any hormonal treatment. The control group consisted of 102 healthy females, matched for age and BMI. Within the vWD group FVIII and FX were both significantly higher during follicular phase than in luteal phase (p=0.013 and p=0.033 respectively). AT, FII, FVII and FX were higher in women with vWD, compared with controls during both phases of the menstrual cycle (pamp;lt;0.0005, pamp;lt;0.0005, p=0.001 and pamp;lt;0.0005). In women with vWD, lag time and time to peak were prolonged during both phases of the menstrual cycle(pamp;lt;0.0005), while peak thrombin concentration was reduced (p=0.003 and p=0.002 during follicular and luteal phase respectively) compared to healthy peers. Lower levels of FVIII and FX during luteal phase may predispose women to the development of the menorrhagia - common complication of vWD. Women with vWD need more time to reach the peak thrombin concentration, while the latter still remains less than in healthy women. Higher levels of AT in vWD-affected females, compared to controls, may also contribute to the existing bleeding tendency in this cohort.</p>
  • Ha, Chunfang, et al. (författare)
  • Adrenomedullin and its receptor, calcitonin receptor-like receptor, are aberrantly expressed in women with idiopathic menorrhagia
  • 2009
  • Ingår i: Molecular Medicine Reports. - 1791-2997. ; 2:1, s. 7-11
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The human endometrium undergoes a unique process of benign angiogenesis under the control of ovarian steroids during reproductive life. Aberrant angiogenesis has been implicated in idiopathic menorrhagia, a common gynaecological complaint. One of the key factors involved in endometrial angiogenesis is adrenomedullin (AM), a multifunctional 52-amino acid peptide. AM mediates the activities of endometrial angiogenesis via calcitonin receptor-like receptor (CLR). The objective of the present study was to compare the endometrial expression of AM and CRL in women with and without idiopathic menorrhagia. Endometrial biopsies were obtained from 9 women with menorrhagia (&gt;= 80 ml per menstruation) and 12 women with normal blood loss (&lt;80 ml per menstruation). Protein and mRNA expression levels of AM and CLR were determined using immunohistochemistry and real-time PCR. Compared to the controls, patients with menorrhagia exhibited low immunostaining intensity of AM, while high CLR staining was observed in the epithelium (p&lt;0.05). No difference in mRNA expression was observed between the groups. These data suggest that an imbalance in the AM/CLR system might alter endometrial angiogenesis in menorrhagia.</p>
  • Hildenbrand, Anna, et al. (författare)
  • Aquaporin 1 is expressed in the human endometrium during normal cycle and increases after mifepristone treatment.
  • 2008
  • Ingår i: International Journal of Molecular Medicine. - 1107-3756 .- 1791-244X. ; 22:1, s. 49-53
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Aquaporin-1 (AQP1) is involved in the angiogenesis and structural modifications of microvessels and possibly also in the pathogenesis of idiopathic menhorrhagia, where a reduced AQP1 expression is seen in the endometrium. Mifepristone treatment induces reduced menstrual bleeding and amenorrhea and also has a direct effect on endometrial arterioles. Administered with gestagen-only contraceptive methods, antiprogestins improve the bleeding pattern. The objective of this study was to evaluate the AQP1 expression in endometrial blood vessels during normal cycle and after mifepristone treatment. Localization and expression of AQP1 was determined using immunohistochemistry and reverse transcriptase chain reaction (RT-PCR) in 43 biopsies from human endometrium taken during a normal cycle and after mifepristone treatment. AQP1 expression in human endometrial vessels is not cycle dependent and is stronger in capillaries and arteries than in veins. After mifepristone treatment the staining intensity was increased, but not the number of stained vessels. The presence of AQP1 was also confirmed using RT-PCR. The changes in AQP1 expression could contribute to the reduced bleeding seen following mifepristone treatment and could be an effect of either antagonizing progesterone or cortisol.</p>
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