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Biomedical subjects

Anne Cathrine Staff

Publications and source records attributed to Anne Cathrine Staff.

17 recordsLinked to original sources
PubMed2006

The activated nerve growth factor receptor p-TrkA is selectively expressed in advanced-stage ovarian carcinoma.

The objective of this study was to compare the expression of the nerve growth factor (NGF) receptors TrkA and p75 in ovarian borderline tumors, International Federation of Gynecology and Obstetrics (FIGO) stage I carcinomas and advanced-stage (FIGO stage III-IV) carcinomas, and to assess a possible association between NGF receptor expression and mitogen-activated protein kinase (MAPK) activation in borderline tumors and FIGO stage I carcinomas. Sections from 119 borderline tumors, 57 FIGO stage I invasive ovarian carcinomas, and 56 advanced-stage carcinomas were evaluated for expression of activated phospho-TrkA (p-TrkA) and p75 using immunohistochemistry. MAPK activation was analyzed in stage I carcinomas and borderline tumors using phospho-specific antibodies against the extracellular-regulated kinase (p-ERK), the high osmolarity glycerol response kinase (p-p38), and the c-jun amino-terminal kinase (p-JNK). p-TrkA membrane expression was significantly more frequent in advanced-stage carcinomas compared with both borderline and stage I carcinomas (P < .001). p75 membrane expression was comparable in the 3 groups (P > .05). p-ERK and p-p38 expression was comparable in borderline and stage I carcinomas, whereas p-JNK was more frequently expressed in stage I ovarian carcinomas (P < .001). NGF receptor expression showed no association with MAPK activation in borderline and stage I carcinomas. In conclusion, expression of biologically active p-TrkA receptor at the cell membrane is up-regulated along tumor progression in ovarian carcinoma, whereas p75 expression remains unaltered. These data provide further evidence regarding the clinical role of p-TrkA in ovarian carcinoma. NGF receptors probably signal via MAPK-independent pathways in ovarian carcinoma.

Adolescent↗
PubMed2006

Regulation of ADRP expression by long-chain polyunsaturated fatty acids in BeWo cells, a human placental choriocarcinoma cell line.

Transplacental transfer of maternal fatty acids is critical for fetal growth and development. In the placenta, a preferential uptake of fatty acids toward long-chain polyunsaturated fatty acids (LCPUFAs) has been demonstrated. Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that has been ascribed a role in cellular fatty acid uptake and storage. However, its role in placenta is not known. We demonstrate that ADRP mRNA and protein are regulated by fatty acids in a human placental choriocarcinoma cell line (BeWo) and in primary human trophoblasts. LCPUFAs of the n-3 and n-6 series [arachidonic acid (20:4n-6), docosahexaenoic acid (22:6n-3), and eicosapentaenoic acid (20:5n-3)] were more efficient than shorter fatty acids at stimulating ADRP mRNA expression. The fatty acid-mediated increase in ADRP mRNA expression was not related to the differentiation state of the cells. Synthetic peroxisome proliferator-activated receptor and retinoic X receptor agonists increased ADRP mRNA level but had no effect on ADRP protein level in undifferentiated BeWo cells. Furthermore, we show that incubation of BeWo cells with LCPUFAs, but not synthetic agonists, increased the cellular content of radiolabeled oleic acid, coinciding with the increase in ADRP mRNA and protein level. These studies provide new information on the regulation of ADRP in placental trophoblasts and suggest that LCPUFA-dependent regulation of ADRP could be involved in the metabolism of lipids in the placenta.

Cell Differentiation↗
PubMed2005

Augmented oxidative stress as well as antioxidant capacity in maternal circulation in preeclampsia.

OBJECTIVES: Isoprostanes are stable markers of oxidative stress. We wanted to assess maternal circulating levels of total 8-isoprostane and indices of antioxidant capacity in preeclampsia compared to uneventful pregnancies. STUDY DESIGN: Total 8-isoprostane concentrations, FRAP (ferric reducing ability of plasma), Vitamin E and d-ROM (diacron reactive oxygen metabolites) were measured in maternal venous blood samples from preeclamptic (n=21) and uncomplicated (n=38) pregnancies at cesarean section. RESULTS: Median total 8-isoprostane concentration was elevated in preeclampsia compared to uncomplicated pregnancies (354 and 218 pg/mL, P=0.02). Median FRAP level was also elevated in preeclampsia compared to uncomplicated pregnancies, but to a lesser degree than 8-isoprostane. A positive correlation between 8-isoprostane and previously analyzed placenta-derived sFlt1 (soluble fms-like tyrosine kinase 1) levels in the maternal circulation was found in preeclampsia. CONCLUSION: We found a relative more increase for the oxidative stress marker (8-isoprostane) than for the antioxidant capacity (FRAP) in preeclampsia compared to uneventful pregnancies.

Adult↗
PubMed2005

The AP-2gamma transcription factor is upregulated in advanced-stage ovarian carcinoma.

OBJECTIVE: To analyze the expression of the AP-2gamma transcription factor in ovarian borderline tumors, early-stage ovarian carcinoma and advanced-stage ovarian carcinoma, and to evaluate its prognostic role in advanced-stage tumors. METHODS: Sections from 14 normal ovaries, 75 borderline tumors, 22 FIGO stage I invasive ovarian carcinomas, and 306 advanced-stage (FIGO stages II-IV) ovarian carcinomas (42 primary tumors, 62 solid metastases, 202 effusions) were evaluated for expression of the transcription factor AP-2gamma using immunohistochemistry. Sixty-three effusions and two cell lines (SKOV-3 and OVCAR-3) were additionally studied using immunoblotting. The prognostic role of AP-2gamma in advanced-stage carcinomas was analyzed. RESULTS: AP-2gamma was detected in the nucleus of tumor cells in 28/75 (37%) borderline tumors, 13/22 (59%) FIGO stage I carcinomas, and 255/306 (83%) advanced-stage carcinomas (P < 0.001, Chi-square test). Benign ovaries were uniformly negative. Expression was largely limited to carcinoma cells in effusions. Solid lesions and effusions from advanced-stage carcinomas showed comparable expression. Immunoblotting showed AP-2gamma expression in 59/61 effusions and both cell lines. AP-2gamma expression did not correlate with survival. CONCLUSIONS: AP-2gamma expression is upregulated in advanced-stage ovarian carcinoma compared to early-stage carcinomas, borderline tumors, and the ovarian surface epithelium, and AP-2gamma is specifically localized to cancer cells in effusions, suggesting a role in tumor progression. The lack of predictive value for this transcription factor in advanced-stage disease may be related to its frequent expression.

Adult↗
PubMed2005

Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia.

OBJECTIVE: We hypothesized that umbilical vein serum soluble fms-like tyrosine kinase 1 (sFlt1) concentration was augmented in pre-eclampsia. We also explored a possible association between fetal and maternal concentrations of sFlt1. STUDY DESIGN: At cesarean delivery, maternal serum samples from pre-eclamptic (n=38) and uncomplicated (n=32) pregnancies were obtained, as well as umbilical vein serum and amniotic fluid samples. ELISA for human sFlt1, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were performed. RESULTS: Median sFlt1 concentrations were elevated in pre-eclampsia compared to uncomplicated pregnancy, in umbilical venous serum (246 and 163 pg/mL, P=0.04), in maternal serum (9932 and 3417 pg/mL, P<0.001), as well as in amniotic fluid (51,040 and 33,490 pg/mL, P=0.03). A positive association between the fetal and maternal serum levels of sFlt1 was found in the pre-eclampsia group. Median PlGF concentration in the maternal serum was significantly lower in the pre-eclampsia group compared to the control group (82 pg/mL and 169 pg/mL, P<0.001). CONCLUSIONS: sFlt1 concentration is elevated in the fetal circulation in pre-eclampsia, but at a much lower level than in the maternal circulation. The results of our study do not support a substantial fetal contribution to the elevated circulating maternal sFlt1 protein concentration in pre-eclampsia.

Adult↗
PubMed2005

[Effects of public initiatives aimed at reducing neural tube defects with folic acid supplementation].

BACKGROUND: In order to prevent neural tube defects, a daily supplement of 400 microg (microgram) folic acid has been recommended in Norway since 1998, during the last month before conception and the first two or three months of pregnancy. Compliance with and effects of this recommendation has recently been evaluated in Norway in a report to the Directorate of Health and Social Welfare. MATERIAL AND METHODS: Reports published on periconceptional folic acid intake in Norway and some other countries from 1998 to autumn 2003 have been evaluated. RESULTS: In spite of several information activities, few Norwegian women start folic acid supplementation before verified pregnancy. The supplementation is started too late for the prevention of neural tube defects. A reduction is not observed in Norway. Internationally, information has not proven effective either, whereas compulsory fortification of foods with folic acid has been associated with reduced incidence. Information about periconceptional folic acid intake should be intensified. Compulsory fortification of foods with folic acid will affect the whole population, not only the target group of fertile women. If ongoing large intervention studies show improved clinical prognosis for patients with cardiovascular disease, this will be an additional argument for fortification of foods.

Female↗
PubMed2005

[Does folic acid have effects on other health problems than neural tube defects?].

BACKGROUND: While it is widely accepted that periconceptional supplement of 400 microg (microgram) folic acid reduces the risk of neural tube defects in pregnancy, it remains to be established whether folic acid has other beneficial effects on larger population groups. Evidence concerning effect of increased intake on cardiovascular disease, cancer and other diseases has recently been evaluated in a report to the Directorate of Health and Social Welfare in Norway. MATERIAL AND METHODS: Research reports published mainly from 1998 to 2003 on folic acid intake and disease have been evaluated. RESULTS: Sufficient evidence that increased folic acid intake may prevent cancer or cardiovascular diseases is not yet available, hence at present there is no indication for recommending augmented intake for other groups than fertile women. However, several intervention studies with folic acid supplementation are in progress to establish its effect on cardiovascular mortality and morbidity. INTERPRETATION: If the ongoing intervention studies show a beneficial clinical effect on cardiovascular disease, it would be a further argument for fortification of foods, in addition to reducing the risk of neural tube defects in pregnancy.

Cardiovascular Diseases↗
PubMed2005

Calprotectin, a marker of inflammation, is elevated in the maternal but not in the fetal circulation in preeclampsia.

OBJECTIVE: Preeclampsia is associated with excessive inflammatory response compared with normal pregnancy. Calprotectin is an inflammation marker not previously explored in preeclampsia. STUDY DESIGN: Calprotectin in maternal and fetal plasma and amniotic fluid was investigated at cesarean delivery in normal pregnancies and preeclampsia. C-reactive protein (CRP) and plasminogen activator inhibitor type1 (PAI-1) were also analyzed. RESULTS: Maternal median calprotectin, CRP, and PAI-1 concentrations were elevated in preeclampsia (1081 microg/L, 4.8 mg/L, and 51.0 U/mL) compared with control levels (552 microg/L, 3.8 mg/L, and 36.5 U/mL). In the umbilical vein, there were no differences between preeclampsia and controls regarding calprotectin and CRP levels. Maternal calprotectin concentrations correlate with CRP and PAI-1 values for the total study group, but a statistical significant correlation was not found in the preeclamptic group. CONCLUSION: Calprotectin is elevated in the maternal circulation in preeclamptic pregnancies. We found no evidence of inflammatory response in the fetal circulation in preeclampsia.

Adult↗
PubMed2005

Reduction in hospitalized women with pelvic inflammatory disease in Oslo over the past decade.

BACKGROUND: A tuboovarian abscess (TOA) is a common complication of pelvic inflammatory disease (PID), occurring world-wide in 15-30% of women with PID. The aim of the study was to identify changes during the last 10 years in the number of women hospitalized with PID in Oslo, as well as a change regarding the frequencies of the subdiagnoses salpingitis and tuboovarian abscess. METHODS: We performed a review of computerized diagnosis lists and manual check of the medical records of women hospitalized with PID in Oslo. The years 1990-92 and 2000-02 were included, resulting in information from two time periods 10 years apart. Cases were registered as salpingitis, oophoritis or tuboovarian abscess. Medical and demographic variables from the medical records of women diagnosed during 4 out of the 6 years were described in detail. RESULTS: We identified 523 women with the diagnosis of PID hospitalized during 1990-92 and 2000-02. There was a 35% reduction in hospitalized cases of salpingitis over the period of 10 years, but the number of cases of tuboovarian abscesses among women admitted for PID remained unchanged from 1990-92 to 2000-02. We found low frequencies of Chlamydia trachomatis and Neisseria gonorrhoea infections, although documented bacteriological sampling was insufficient. CONCLUSIONS: Fewer patients were hospitalized in Oslo for PID during the time period of 2000-02 compared with 10 years earlier, but a higher percentage of patients had developed TOA compared with the first time period (43% compared with 26%, p = 0.013), indicating a changing clinical panorama of PID.

Abscess↗
PubMed2005

Calprotectin plasma level is elevated in preeclampsia.

BACKGROUND: Calprotectin is a protein found in myelomonocytic cells and plays a role in various physiological functions such as inflammatory processes and antiproliferation of cells, and in the neutrophil defense against bacterial infections. Preeclampsia is characterized by maternal endothelial dysfunction and by insufficient trophoblast invasion into the maternal endometrium (decidua). In addition, preeclampsia is associated with maternal leukocyte activation and we therefore wanted to investigate whether calprotectin levels in plasma from women with preeclampsia differed from the levels in normotensive pregnant and nonpregnant women. METHOD: Calprotectin measurements were included in a case-control study of 20 preeclamptic women matched with 20 normotensive pregnant women regarding age, pregnancy length, parity and body mass index (BMI). We also measured calprotectin in 12 nonpregnant women. Calprotectin plasma levels were analyzed using an enzyme-linked immunosorbent assay (ELISA). RESULTS: We discovered significantly elevated plasma calprotectin levels in preeclamptic patients compared to matched normotensive pregnancies: 768 (612-1016) microg/L vs. 445 (276-598) microg/L (medians, 25, 75 percentiles, respectively), p = 0.002. CONCLUSIONS: The elevated plasma calprotectin levels demonstrated in the preeclampsia group supports the notion that leukocytes are activated in preeclampsia. The elevated calprotectin level might constitute a part of the innate defense in myelomonocytic cells against microorganisms in pregnancy. We suggest further elucidation of a role for calprotectin in the development of pregnancy disorders such as preeclampsia.

Adult↗
PubMed2004

Leukocyte adhesion molecules and reactive oxygen species in preeclampsia.

OBJECTIVE: The aim of our study was to compare the expression of leukocyte adhesion molecules, intracellular reactive oxygen species, and vasoactive substances in preeclampsia and matched normotensive pregnancies and to explore differences between pregnancy and the nonpregnant state regarding these parameters. METHODS: Flow cytometry was used to analyze the monocyte and granulocyte expression of adhesion molecules from 20 matched pairs of preeclampsia/normotensive pregnancies and 12 nonpregnant subjects. Basal levels of CD11b, CD11c, CD62L, and CD14 were measured. In addition, expression of human lymphocyte antigen-DR, CD4, CD8, and CD4/CD8 ratio were assessed. Basal reactive oxygen species levels, as well as reactivity upon in vitro stimulation with phorbol 12-myristate 13-acetate, were measured in monocytes and granulocytes with the probes dihydroethidium, dichlorofluorescein-diacetate, and dihydrorhodamine-123. Further, the plasma levels of endothelin-1, the nitric oxide metabolites nitrite/nitrate, and total antioxidant status were analyzed. RESULTS: Monocytes expressed significantly higher levels of CD11b and CD14 in preeclamptic patients compared with normotensive pregnant subjects, whereas CD11c was elevated on both monocytes and granulocytes in pregnancy compared with the nonpregnant state. Both monocytes and granulocytes displayed higher basal, as well as phorbol 12-myristate 13-acetate-stimulated, amounts of reactive oxygen species in the preeclampsia group compared with the normotensive group. We also found the endothelin-1 and antioxidant levels significantly elevated in preeclampsia patients compared with normotensive subjects, whereas no differences were seen between the groups regarding nitrite/nitrate levels. CONCLUSION: These results show that the maternal blood leukocytes are activated in preeclampsia and support the view that oxidative stress is a contributing factor in the pathophysiology of preeclampsia.

Adult↗
PubMed2004

The decidual suction method: a new way of collecting decidual tissue for functional and morphological studies.

BACKGROUND: Studies of extravillous trophoblasts and placental bed spiral arteries are essential for a better understanding of pathological pregnancies such as preeclampsia, intrauterine growth restriction and diabetes mellitus. A major challenge is to obtain representative and sufficient tissue for morphological and functional investigations. Currently, tissue material is mostly harvested by placental bed biopsy (PBB). We describe a new suction method to obtain a larger volume of decidual tissue from the placental bed. METHODS: Tissue was harvested in 51 cesarean sections by vacuum suction of the placental bed. Sections from formalin-fixed, paraffin-embedded tissue were routinely stained with hematoxylin and eosin (H&E), immunostained with a panel of antibodies and morphologically examined for the presence of trophoblasts and spiral arteries. The results were compared with those from archive material from PBBs and placental basal plate sections (BPSs). Short-term adverse events were registered for the study patients. Long-term complications were registered from medical charts of 151 women having undergone the decidual suction method (DSM), with a follow-up of 38-60 months. RESULTS: In 86% (n = 44), one random section from the decidual suction material demonstrated at least one spiral artery. In 37% (n = 19), six or more spiral arteries were present. All sections revealed extravillous trophoblasts. No short- or long-term morbidity was recorded. CONCLUSIONS: The decidual suction method represents an important improvement in the work to obtain sufficient decidual tissue for morphological and functional studies of extravillous trophoblast function and spiral artery adaptation. The method is safe, as no short- or long-term complications were registered.

Decidua↗
PubMed2004

Adiponectin is reduced in gestational diabetes mellitus in normal weight women.

BACKGROUND: Adiponectin is an adipose tissue-derived protein counteracting insulin resistance and inflammation. We have compared women with gestational diabetes mellitus (GDM; n = 22) and normal pregnancies (controls; n = 29) to evaluate whether adiponectin represents a link between endocrine function of adipose tissue and the development of diabetes during pregnancy. METHODS: The participants were categorized according to their prepregnancy body mass index (BMI) into two classes: BMI < 25 and BMI = 25. Plasma concentrations of adiponectin, leptin and insulin were measured by radioimmunoassay (RIA). Total cholesterol, high density lipoprotein (HDL) cholesterol and triacylglycerol were determined by routine enzymatic methods. Expression of adiponectin/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was determined by real-time reverse transcription polymerase chain reaction (RT-PCR) in subcutaneous adipose tissues obtained by excision at cesarean delivery. RESULTS: Among individuals with GDM and BMI < 25 kg/m2 (n = 8), plasma adiponectin concentration was lower than in the controls (n = 20), 8.1 +/- 1.2 microg/mL vs. 12.2 +/- 1.1 microg/mL; p = 0.04). The mean plasma leptin concentrations did not differ between the GDM and control groups. Plasma concentrations of insulin and C-peptide were significantly higher among GDM than control individuals independent of BMI. For all the women included in the study, we found that plasma adiponectin only correlated negatively with prepregnancy and third-trimester (sampling day) BMI (p = 0.03 vs. p = 0.01). In abdominal subcutaneous adipose tissue of pregnant women, adiponectin mRNA levels were lower in GDM than in control subjects (0.77 +/- 0.18 vs. 1.39 +/- 0.15; p = 0.05). CONCLUSIONS: These results indicate that low plasma adiponectin concentration is associated with GDM. In addition, we found that adiponectin mRNA levels in adipose tissue biopsies from GDM subjects were reduced.

Adiponectin↗
PubMed2004

Dietary supplementation with L-arginine or placebo in women with pre-eclampsia.

BACKGROUND: To investigate the effect of dietary intake of the NO-donor L-arginine on the diastolic blood pressure in women with pre-eclampsia. METHODS: A randomized double-blind study was designed to compare the effect of L-arginine and placebo in pre-eclamptic women with gestational length ranging from 28+0 to 36+0 weeks. The women received orally 12 g of L-arginine or placebo daily for up to 5 days. The primary end-point was to identify a difference in diastolic blood pressure alteration between the two groups after 2 days of intervention. Secondary end-points included the interval from study start to delivery, the proportion of women delivered after 2, 5 or 10 days from treatment start and mean birth weight. RESULTS: There was no statistically significant alteration in diastolic blood pressure in the L-arginine group compared with the placebo group after 2 days of treatment (p = 0.4). No differences in the proportions of women delivered by day 2, 5 or 10 after study start, in the mean interval from study start to delivery, or in mean birth weight percentile were observed between the two groups. CONCLUSIONS: Oral L-arginine supplementation did not reduce mean diastolic blood pressure after 2 days of treatment compared with placebo in pre-eclamptic patients with gestational length varying from 28 to 36 weeks. Whether L-arginine treatment could be clinically beneficial for the mother or the fetus if started earlier in the disease process than for the women in our study remains to be seen.

Adult↗
PubMed2003

Periconceptional use of folic acid supplements in Oslo.

BACKGROUND: Periconceptional supplementation with folic acid has been shown to decrease the occurrence of neural tube defects (NTD). A daily supplement of 400 micro g folic acid from the month before pregnancy and the first 2 to 3 months of pregnancy is recommended in Norway. We wanted to evaluate the use of folic acid supplements among pregnant women in Oslo, and to explore demographic factors that were associated with periconceptional intake. METHODS: All women attending antenatal ultrasound screening at the two main obstetric departments in Oslo during 3 months in 2001 were invited to answer questions regarding folic acid supplementation before and during their present pregnancy. RESULTS: A total of 1541 women (91, 5%) participated in the study, of which 26% were nonwestern immigrants. Only 17% of all women had started the folic acid supplementation preconceptionally (22% of the nonimmigrant vs. 2% of the immigrant population). Folic acid had been used by 58% at some time during the present pregnancy (73% of the nonimmigrant vs. 19% of the immigrant population). Regression analysis demonstrated that the difference in periconceptional use of folic acid between the two population groups could not be explained by registered demographic factors other than immigrant status. CONCLUSIONS: Most pregnant women in Oslo do not use folic acid as recommended and a dramatically low usage is seen among the immigrant population, indicating that more widespread information is necessary. Furthermore, fortification of cereals with folic acid should be considered to secure a sufficient intake of folic acid in all fertile women.

Adolescent↗