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  • 1
    Keywords: THERAPY ; PATIENT ; TRIALS ; AGE ; REPRODUCIBILITY ; POSTMENOPAUSAL WOMEN ; REQUIRING PROLONGED OBSERVATION ; RECALL ; COLLABORATIVE REANALYSIS ; SEX-HORMONES
    Abstract: BACKGROUND: Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. METHODS: Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. FINDINGS: Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p〈0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p〈0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p〈0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p〈0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p〈0.01 for both comparisons). INTERPRETATION: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. FUNDING: Cancer Research UK.
    Type of Publication: Journal article published
    PubMed ID: 23084519
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  • 2
    Keywords: THERAPY ; HEALTH ; WOMEN
    Abstract: BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. METHODS: Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with 〈5 years of use (RR 1.43, 95% CI 1.31-1.56; p〈0.0001). Combining current-or-recent use (any duration, but stopped 〈5 years before diagnosis) resulted in an RR of 1.37 (95% CI 1.29-1.46; p〈0.0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p〈0.0001), being definitely increased only for the two most common types, serous (RR 1.53, 95% CI 1.40-1.66; p〈0.0001) and endometrioid (1.42, 1.20-1.67; p〈0.0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1.25, 95% CI 1.07-1.46, p=0.005). INTERPRETATION: The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. FUNDING: Medical Research Council, Cancer Research UK.
    Type of Publication: Journal article published
    PubMed ID: 25684585
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  • 3
    Keywords: CANCER ; THERAPY ; INFORMATION ; COHORT ; DISEASE ; incidence ; RISK ; RISK-FACTORS ; BREAST ; BREAST-CANCER ; DESIGN ; AGE ; WOMEN ; PROSPECTIVE COHORT ; smoking ; cancer risk ; UNITED-STATES ; ALCOHOL ; ALCOHOL-CONSUMPTION ; CONSUMPTION ; BIRTH COHORT ; POSTMENOPAUSAL WOMEN ; MASS INDEX ; ORAL-CONTRACEPTIVE USE ; REQUIRING PROLONGED OBSERVATION ; METAANALYSIS ; HORMONAL FACTORS ; ANTHROPOMETRIC MEASURES ; EPITHELIAL OVARIAN
    Abstract: BACKGROUND: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. METHODS AND FINDINGS: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p〈0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p〈0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p〈0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. CONCLUSIONS: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. Please see later in the article for the Editors' Summary.
    Type of Publication: Journal article published
    PubMed ID: 22606070
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters B 260 (1991), S. 6-10 
    ISSN: 0370-2693
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0711
    Keywords: Follicular fluid ; Oocyte ; Meiosis ; Progesterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the effect of low molecular weight fractions of human follicular fluid (FF1) on rat oocyte meiosis and progesterone secretion by the granulosa cells. Steroid-free FF1 extracts were filtered through Sephadex G50 gel. One highly retarded fraction was obtained (GF-3), which was either used for testing or further purified by filtration on Sephadex G10, the G10-3 fraction of which was used for experiments. The GF-3 and G10-3 fractions of FF1 inhibited (in a dose-dependent and reversible manner) meiosis of isolated rat oocytes during a 4-h culture. Similarly treated fractions of serum had no effect. The inhibition was not abolished by ether extraction, trypsin treatment, heating to 56° C for 1 h or boiling for 5 min, whereas heating to 105° C for 18 h decreased the effect. Gonadotropin-stimulated progesterone secretion by cumulus and mural granulosa cells was also dose-dependently and reversibly inhibited by the GF-3 fractions. Our results confirm those obtained in earlier studies on porcine oocyte maturation inhibitor (OMI).
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1420-908X
    Keywords: Key words: CD9 — Cell-interaction — Flow cytometry — Eosinophils — Platelets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: The redistribution of CD9 in peripheral blood eosinophils was investigated with respect to the interaction with platelets during in vitro activation, and whether this interaction exerts influence on eosinophil adhesion properties.¶Materials and Methods: Flow cytometry was used to investigate the CD9 expression in purified eosinophils or eosinophils from different whole blood preparations, with or without platelets present. To confirm an eosinophil/platelet interaction fluorescence microscopy was used, and to demonstrate release/shedding of CD9 molecules a biosensor technique was performed.¶Results: Our results show that both intracellular and surface expression of CD9 decrease upon in vitro activation in the absence of platelets, a phenomenon probably caused by release/shedding of soluble forms of CD9 and not due to intracellular degradation. Increased expression of CD9 on eosinophils, stimulated in the presence of platelets, is partly a result of interacting platelets, judged by the increase in platelet specific marker CD61. In our adhesion assay a significant increase in eosinophil adhesion properties to fibronectin was obtained when eosinophils were PMA stimulated and interacting with platelets, as compared to activated eosinophils without platelets.¶Conclusions: Our findings, that CD9 expression on eosinophils is dynamically regulated, support our previous suggestion that CD9 may be a useful activity marker and that platelet interaction acts on eosinophil adhesion.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1612-4766
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Description / Table of Contents: Zusammenfassung Der KiefernholznematodeBursaphelenchus xylophilus (Steiner undBuhrer) Nickle ist wiederholt in Finnland und Schweden in Importen von Koniferenhackschnitzeln aus Nordamerika gefunden worden. Diese Funde waren der Anlaß zu Einfuhrbeschränkungen und Untersuchungen über Verbreitung und Biologie derBursaphelenchus-Arten. Das Vorkommen von Nematoden dieser Gattung in Schweden wurde inventiert. Es ist bekannt, daß der Kiefernholznematode von Cerambyciden der GattungMonochamus auf neue Wirstbäume und Brutholz überführt wird. Ausgehend von dem Vorkommen der vermuteten Vektoren wurden im Frühjahr 1988 für die Nematoden-Inventierung in Süd- und Mittelschweden Proben von Kiefernholz mit Befall vonMonochamus-Arten eingesammelt. Aus diesem Holz schlüpften 59 Exemplare vonM. sutor L. und 2M. galloprovincialis Ol. In 14 dieserM. sutor von 6 Standorten und in beidenM. galloprovincialis wurden Nematoden der GattungBursaphelenchus gefunden, die der ArtB. mucronatus Mamiya und Enda ähnlich sind. Dies sind die ersten Funde von Nematoden desB. mucronatus-Typs inM. galloprovincialis und das erste Mal, daß über das Vorkommen von solchen Nematoden inM. sutor in Europa berichtet wird.
    Notes: Abstract A national research program was initiated in 1988 in Sweden to provide more information on the distribution and bionomics ofBursaphelenchus species. As a result of the intimate association known to occur between the pinewood nematodeB. xylophilus (Steiner andBuhrer) Nickle and its insect vectors a survey was directed to Scots pine wood (Pinus sylvestris L.) in whichMonochamus species were breeding. A total of 59M. sutor L. and twoM. galloprovincialis Ol. emerged from the collected material. Fourteen specimens of theM. sutor and bothM. galloprovincialis specimens containedBursaphelenchus nematodes which resembled the speciesB. mucronatus Mamiya andEnda. To our knowledge this is the first record of theB. mucronatus-type nematodes inM. galloprovincialis and the first finding of such nematodes inM. sutor in Europe.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: specificity of IgE binding to a human basophil-like cell line (KU812) was studied by flow cytometry. Four IgE myeloma proteins, representing both light-chain types, one chimeric IgE protein, and polyclonal serum IgE blocked the direct binding of FITC-labeled IgE(DES) myeloma protein to KU812 cells in a dose-dependent and nearly equimolar way. Although not as efficiently as human IgE (from five to eight times less on a molar basis), both rat and mouse IgE blocked IgE(DES)-FITC binding to KU812 cells. In sharp contrast, all four human IgG subclasses, both IgA subclasses, and IgM myeloma proteins, as well as monomeric and heat-aggregated polyclonal human IgG, were unable to block significantly IgE(DES)-FITC binding to KU812 cells (≤0.5/0 on a molar basis). The cytophilic epitope on IgE was heat-susceptible (56 °h), lost after reduction alkylation, and resident in the papain-derived Fcɛ -fragment, but not in the papain-derived F(ab') 2ɛ.- and Fcɛ-fragments nor in the pepsin-derived F(ab')2ɛ- and Fcɛ.'-fragments. Washing and displacement experiments indicated that a major part of IgE reacted with high affinity to KU812 cells. The results indicate that the binding of IgE to KU812 cells is highly specific and involves the classical high-affinity FcɛRI-receptor. Although the density of receptors is low, this human cell line offers a unique model to study IgE/FcɛRI interactions.
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 49 (1994), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The prevalence and specificity of naturally occurring human IgA anti-IgE autoantibodies (a-E Ab) were studied by ELISA with anti-IgA monoclonal antibodies (mAb) and a purified myeloma IgE as solid-phase protein, i.e., IgE-DES(κ). Such detected IgA a-E Ab were common among adults, and significantly increased geometric means (GM) were found in patients with atopy (P= 0.006; n= 41; GM = 79.3 arbitrary units (AU)/ml) and filariasis (P= 0.02; n= 41; GM = 75.9 AU/ml), as compared with nonatopic controls (n= 42; GM = 48.8 AU/ml). No such difference was observed between age-matched nonatopic (n= 22; GM = 36.7 AU/ml) and atopic (n= 22; GM = 38.6 AU/ml) children. Children had significantly (P= 0.001) lower IgA a-E Ab concentrations than adults, probably as a result of age, because IgA a-E Ab concentrations and age of children were significantly correlated (n= 44; P〈0.05; rs= 0.30). IgA a-E Ab concentrations were very low in cord serum (n= 32; median 〈0.1 AU/ml). Sex did not influence IgA a-E Ab concentrations in any study group. The specificity of IgA a-E Ab in nine sera was studied by ELISA inhibition assay using IgE-DES myeloma as solid-phase protein and inhibitory proteins of the IgG, IgM, IgD, and IgE classes, including five different IgE myeloma proteins, as well as three enzymatic fragments of IgE-DES. The inhibitions indicated that all IgA a-E Ab tested reacted in a low-affinity reaction with determinants restricted to IgE-DES, i.e., the solid-phase protein. These epitopes were heat-resistant (2 h; 56°C) and located in the Fabɛ-DES fragment. No isotype-specific IgA a-E Ab were found because none of the four other IgE proteins were inhibitory. Subclass typing indicated that most IgA a-E Ab belonged to the IgA 1 subclass. It is unlikely, for reasons of restricted specificity, low affinity, and common prevalence, that such IgA 1 a-E Ab are connected with IgE-mediated disorders. The study also raises questions on the definition of anti-IgE antibodies.
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 43 (1988), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cord serum IgE was assayed by particle counting immunoassay (PACIA) in an unselected series of European newborns (n = 190; geom mean = 0.37 IU/ml) and a cutoff limit established (≥ 1.20 IU/ml) for prediction of atopy. At control follow-up by questionnaire 18 months after birth, 38 infants (20.0%) had developed definite (9.5%) or probable (10.5%) atopy with a significant predominance of boys (P 〈 0.03). Infants with a positive immediate family history (IFH) had a higher risk of developing atopy (P 〈 0.0025) and also had a higher incidence of elevated cord IgE (P 〈 0.02) than infants with a negative IFH. Maternal atopy influenced cord IgE levels significantly (P 〈 0.00005), whereas paternal atopy did not (P= 0.23). No fetal IgE antibodies against five common allergens could be demonstrated in 36 cord sera tested. Breast-feeding for 3 months was not sufficient to prevent atopic symptoms. The predictive value of cord IgE was high since 26 of 36 newborns (positive predictive value = 72.2 %) with elevated cord IgE had developed atopic symptoms before follow-up. Of the 38 infants who developed atopic symptoms, 26 had elevated cord IgE (sensitivity = 68.4%) compared to only 10 (6.6%) of the 152 atopy-free infants (P 〈 0.00005). The data indicate that elevated cord IgE as determined by PACIA is a good predictor of early-onset atopy, better than family history (P 〈 0.008), and that primarily maternal atopy seems to affect fetal IgE synthesis.
    Type of Medium: Electronic Resource
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