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Biomedical subjects

P Bischof

Publications and source records attributed to P Bischof.

At least 55 records · Page 3Linked to original sources
PubMed1998

Modulation of human chorionic gonadotrophin bioactivity during the first trimester of pregnancy.

The objective of this study was to evaluate the bioactivity of human chorionic gonadotrophin (HCG) during first trimester pregnancy. This was done by means of a retrospective analysis of sera from patients with first trimester normal intrauterine and ectopic pregnancies. Serum samples were obtained from 38 women with amenorrhoea of <10 weeks. From these, 19 had a normal intrauterine pregnancy (IUP) and 19 an ectopic pregnancy (EP). Cases were allocated to either low serum immunoreactive HCG (HCGi), intermediate HCGi or high HCGi concentrations (HCGi <5000 mUI/ml, between 5000 and 40,000 mIU/ml and >40,000 mIU/ml respectively). HCGi and oestradiol were measured by enzyme immunoassays and bioactive HCG by the mouse Leydig cell bioassay. All results were analysed by analysis of variance and unpaired Student's t-test. There was a significant difference between bioactive to immunoreactive HCG ratios (b/i ratio) between the subgroups of low, intermediate and high HCGi concentrations. Lower b/i ratios were found when HCGi concentrations were high (HCG b/i mean +/- SEM: high subgroup, 0.33 +/- 0.07 versus low subgroup: 1.50 +/- 0.12; P < 0.0001). Furthermore, the b/i ratios were inversely correlated with oestradiol (P < 0.0001) and HCGi (P < 0.0001) concentrations but not with gestational age. There was no difference in the b/i ratios when comparing IUP with EP. It is concluded that, in first trimester pregnancies, there is a likely modulation of HCG bioactivity which is inversely correlated with HCGi and oestradiol concentration. The underlying mechanisms and their physiological relevance remain to be elucidated.

Animals↗
PubMed1998

Is there a role for leptin in human reproduction?

Leptin is a protein product from the obesity gene (ob gene). It has been shown that leptin significantly correlates with body mass index in humans. In contrast to the obesity of genetically obese (ob/ob) mice, human obesity is not generally caused by gene mutations. It is possible that human obesity results from central leptin resistance. Leptin can serve as a metabolic cue in the neuronal activation of gonadotropin releasing hormone (GnRH) at the end of the prepubertal period. The concentration of leptin is higher in pubertal girls than pubertal boys, and it is supposed that sexual dimorphism might be established in the prepubertal period or even in earlier developmental phases. This dimorphism could be explained by a suppressive action of androgens on leptin. Decreased leptin levels were found in undernourished women of reproductive age, mainly presenting with oligo- or amenorrhea. Leptin concentrations fluctuate according to the phase of the menstrual cycle. It is suggested that the complex relationship of leptin with other hormones, such as insulin, can have etiopathogenetic importance in some enigmatic reproductive disturbances such as the polycystic ovary syndrome. Recent findings of leptin in non-adipose tissue of the placenta could indicate its potential role in developmental physiology and human reproduction.

Animals↗
PubMed1997

Expression of stromelysin-3 in the human placenta and placental bed.

Human placentation is mediated by fetal trophoblastic cells which penetrate into the decidualized uterine endometrium. Trophoblast invasion requires the precisely regulated secretion of specific proteinases able to degrade the endometrial basement membranes and extracellular matrix. To document further the involvement of these proteinases during human placentation, we evaluated in vivo the expression of stromelysin-3, a member of the metalloproteinase family, during the first and third trimesters of pregnancy, by means of immunohistochemistry, in situ hybridization and Northern blot analysis. Human extravillous trophoblasts invading the maternal decidua produced stromelysin-3 during both, the first and third trimesters of pregnancy, but to a lesser extent during the latter. In floating villi, stromelysin-3 expression was restricted to the syncytiotrophoblasts that line intervillous vascular spaces. In conclusion, stromelysin-3 is expressed by differentiated, non-proliferative villous and extravillous trophoblastic cells in early and late placental beds and villi, and its pattern of expression evolves during pregnancy. Our observations suggest that stromelysin-3 could play a role in human placentation.

Blotting, Northern↗
PubMed1997

Distribution of type-I interferon-receptors in human first trimester and term placental tissues and on isolated trophoblast cells.

PROBLEM: Type-I interferon (IFN) is the protein recognizing pregnancy in ruminants. Although IFN is secreted in early pregnancy, its role is not still clear in other species. Like other cytokines, IFN exerts its biological functions through specific membrane receptors. We have investigated the potential action of IFN in human pregnancy by studying the distribution of the receptors in the human placenta. METHOD: Reactivity to monoclonal antibodies (mAbs) to the type-I IFN-receptor (R) was analyzed by immunohistochemistry in human placental tissues and in cytospins of first trimester trophoblast cells. RESULTS: Type-I IFN-R immunoreactivity was observed mostly in first trimester villous cytotrophoblasts and in the cytotrophoblast cell columns. Trophoblast in the decidua, the epithelium of the uterine glands, and most of the isolated trophoblast cells were also immunoreactive. CONCLUSION: The expression of type-I IFN-R in the highly proliferating and migrating trophoblast suggests that this cytokine has a role in trophoblast growth and invasion.

Antibodies, Monoclonal↗
PubMed1996

CA 125 in seminal plasma: correlation with semen parameters.

Ovarian cancer marker CA 125 was measured in human seminal plasma, and the concentrations ranged between 22 and 1149 U/ml, and between 39 and 4711 U/ejaculate. This very high patient-to-patient variability was in contrast to a much lower within-patient variability, which was comparable to that of other semen parameters. No significant differences in CA 125 concentration were found in seminal plasma from normospermic patients, patients with male factors, vasectomized men, and in aliquots of samples which led to a pregnancy, via artificial insemination or in-vitro fertilization. The seminal plasma CA 125 concentration was not correlated with sperm count, motility and morphology. In contrast, seminal plasma CA 125 concentrations correlated with the age of the patient (P < 0.001) and inversely with the volume of the ejaculate (P < 0.001). These correlations were independent of each other. CA 125 did not correlate with the prostatic marker zinc, but did do so with the seminal vesicle marker fructose and the epididymal marker carnitine.

Adult↗
PubMed1996

CA 15-3: a multicentre evaluation of automated and manual tests.

The introduction of a new and automated CA 15-3 immunoassay (IMx Abbott) prompted us to compare the analytical performance of this new test with established tests from CIS ELSA, Sorin, and Boehringer Mannheim in a multicentre study. CA 15-3 measurements in blood samples of breast tumour patients, comparison of intra- and inter-assay variation, dilution linearity, and lower limit of detection are described. The study showed improved precision for the automated over the manual test systems (intra-assay variation: IMx < 5%, CIS ELSA 4-9%, ES 300 < 3% and ETI Sorin > 10%; inter-assay variation: IMx < or = 8%, CIS ELSA < or = 19%, ES 300 < or = 9% and ETI Sorin < or = 27%). Results on patients' samples (n = 101 to 184) showed highly comparable results; IMx vs CIS ELSA site 1: r = 0.950; IMx vs CIS ELSA site 2: r = 0.998; IMx vs ES 300: r = 0.980; IMx vs ETI Sorin: r = 0.931. Slopes of regression lines varied from 0.666 for IMx vs ETI Sorin to 0.988 for IMx vs CIS ELSA (site 1, where heparin plasma was used instead of serum as recommended by the manufacturer found to be only slightly dependent on assay ranges analysed by statistical procedures applied. Despite good correlations between methods, it is recommended that samples collected in the follow-up of disease and at higher CA 15-3 concentrations are analysed by the same test; a changeover to another test is not encouraged.

Automation↗
PubMed1995

Clinical validation of the new ELSA-CA 125 II assay: report of a European multicentre evaluation.

The ELSA-CA 125 II is a second-generation radioimmunoassay for the quantification of CA 125 in serum. In a multicentre study involving 49 follow-ups of patients with ovarian cancers, and 880 other patients, 2.8% of healthy persons, 25% of 149 patients with benign gynaecological diseases and 39% of 82 patients with benign non-gynaecological diseases had CA 125 levels above 35 U/ml. Using the 35 U/ml cut-off, sensitivities among epithelial ovarian cancers were found to be 85% in serous tumors, 41% in mucinous tumors and 83% in other types. During follow-up of patients with serous ovarian cancers, we observed an equivalent behaviour of both assays--first- and second-generation--with the clinical evolution. We also compared results obtained with other assays commercially available; these were significantly different when a polyclonal antibody was used in the sandwich assay.

Adolescent↗
PubMed1995

Evaluation of infertility.

The most important goal of fertility investigation is to identify the cause(s) of infertility and to prescribe adequate therapy. The couple should be treated as a single unit as each partner contributes a share to the infertility potential of the couple. Evaluation should begin with the taking of a detailed history and a complete physical examination of both partners, which may point the investigation in a particular direction. However, other pertinent fertility factors should not be overlooked. A standardized and comprehensive approach to the investigation of infertility is proposed and is presented as a series of flow charts.

Algorithms↗
PubMed1995

Gelatinase and oncofetal fibronectin secretion is dependent on integrin expression on human cytotrophoblasts.

Collagenolytic activity of cytotrophoblasts is stimulated by glycoproteins of the extracellular matrix and since this stimulation can possibly occur through integrins, we measured the gelatinolytic activity of villous and extravillous cytotrophoblasts according to the type of integrins expressed on these cells. Cytotrophoblasts were isolated from legal abortions, immunopurified with anti-CD45, separated according to their expression of histocompatibility-linked antigen (HLA)-G, alpha 6 or alpha 5 integrin subunits and cultured for 5 days on plastic or agarose. Fetal fibronectin, human chorionic gonadotrophin (HCG) and the gelatinolytic activity were measured in the culture supernatants. Following immunopurification with anti-CD45, the gelatinolytic activity of cytotrophoblasts was significantly higher than before, indicating that contaminating lymphomyeloid cells secreted gelatinolytic inhibitors. HLA-G positive cells secreted significantly more gelatinases than HLA-G negative cells but their HCG secretion was similar. Compared to alpha 5 positive cells, alpha 6 positive cytotrophoblasts secreted significantly more gelatinases, significantly less fibronectin but similar amounts of HCG. We conclude that during trophoblast invasion, extravillous cytotrophoblasts (HLA-G positive) expressing the alpha 6 integrin subunit represent the invasive population of cells (high gelatinase and low fibronectin secretion). When expression of the alpha 5 integrin subunit is turned on, their invasive behaviour ceases and they secrete low amounts of gelatinases and high concentrations of fibronectin.

Abortion, Induced↗
PubMed1995

Effect of leukemia inhibitory factor on human cytotrophoblast differentiation along the invasive pathway.

PROBLEM: Leukemia inhibitory factor (LIF) is a pleiotropic secreted cytokine that was shown to be essential for blastocyst implantation in mice. Since it is well documented that LIF is produced by the human endometrium, we wondered if this cytokine was capable of modulating the invasive behaviour of human cytotrophoblastic cells (CTB). METHODS: CTB were isolated and purified from first trimester abortions, separated or not into cells bearing a laminin or a fibronectin receptor (alpha 6 beta 4 or alpha 5 beta 1 respectively) using specific monoclonal antibodies and magnetic particles. RESULTS: We observed that rhLIF inhibited the secretion of gelatinases and of hCG by CTB but remained without effects on the secretion of fetal fibronectin (fFN). These effects were exerted on different CTB subsets: although rhLIF inhibited the secretion of gelatinases by alpha 6 positive cells, it stimulated the fFN secretion by alpha 5 positive cells. The inhibitory effect of rhLIF on the secretion of hCG was mainly due to its effect on the hCG secretion of alpha 5 positive CTB. CONCLUSIONS: Taken together these results suggest that in vitro LIF inhibits the differentiation of CTB towards an invasive phenotype by inhibiting the secretion of metalloproteinases, by increasing the deposition of fFN into the extracellular matrix and by inhibiting the differentiation of CTB into syncytium.

Cell Differentiation↗
PubMed1995

Metalloproteinase secretion by endometrial leukocyte subsets.

PROBLEM: Human endometrium contains up to 40% leukocytes. Since their function is unclear, we cultured these cells separately to analyze their proteolytic potential in vitro. METHOD: Endometrium was obtained from hysterectomies or from first trimester abortion. After collagenase digestion, the different leukocyte subsets (CD56, CD3, CD19, CD16, CD45) were immuno-separated and cultured. Gelatine zymography and a quantitative type IV gelatinase assay were run on all culture supernatants. RESULTS: On zymography, all subtypes of endometrial leukocytes released gelatinases. The 72-kDa gelatinase was absent from peripheral leukocyte supernatants, whereas it was secreted by all endometrial leukocytes. The 92-kDa gelatinase was present in all culture supernatants. Large granular lymphocytes (CD56+, LGL) expressed the highest type VI gelatinase activity as compared to all other leukocytes. This activity increased during the cycle in LGL and T cells but remained unchanged in glandular and stromal cells. CONCLUSIONS: Endometrial leukocytes, particularly LGL, secrete significant amounts of gelatinases.

Adult↗
PubMed1995

[Prediction of prematurity by oncofetal fibronectin. Prospective cohort study].

OBJECTIVE: To evaluate the association between cervical oncofoetal fibronectin and prematurity as well as the interval between sampling and delivery in symptomatic women. METHODS: Cervical fibronectin was measured with an immunoassay in a cohort of 64 women at the University Hospital of Geneva. Subjects with positive and negative fibronectin were then compared using the relative risk and the incidence rate ratio of premature delivery as well as the survival tables. Performance of the test to predict premature delivery or delivery within one week of the test were expressed in terms of sensitivity, specificity, predictive values and likelihood ratios with their 95% confidence intervals. RESULTS: Thirty-four percent of women delivered prematurely. The presence of fibronectin was significantly associated with premature delivery and with a shorter interval to delivery. The likelihood ratio for a positive test was 2.6(95% CI: 1.45-4.66). A negative test had a 100% predictive value to exclude delivery within one week of the test. CONCLUSION: Oncofoetal fibronectin appears to be the best marker currently available to predict premature delivery. A randomized trial is needed to confirm its clinical usefulness.

Adult↗
PubMed1995

Importance of matrix metalloproteinases in human trophoblast invasion.

Human cytotrophoblast cells are invasive by virtue of their ability to secrete metalloproteinases (MMP) capable of digesting the extracellular matrix of the endometrium. It is the aim of the present study to determine which of the known MMP is responsible for this invasive behavior and to see to what extent endometrial secretions can modulate this enzymatic activity. Under our experimental conditions, first-trimester cytotrophoblast cells invade matrigel; this invasive behavior is inhibited by phenanthroline (an inhibitor of MMP) and by a polyclonal antibody to the 92-kDa gelatinase but not to other MMP. Since cytotrophoblast cells cultured in vitro secrete the 92-kDa gelatinase, and since adhesion to a substrate increases their gelatinolytic activity, it is believed that cytotrophoblast cells invade their surrounding matrix by binding to it and by increasing their secretion of 92-kDa gelatinase which then digests the collagen type IV of their micro-environment. This process of invasion is controlled by secretions from decidual cells (but not from non-decidualized stromal cells) since conditioned medium from decidual cells inhibits the activity of the 92-kDa gelatinase released from cytotrophoblast cells.

Animals↗
PubMed1994

Clinical significance of invisible or partially visible luteinizing hormone.

It is well known that luteinizing hormone (LH), like many other glycoproteins, is heterogeneous and presents several circulating isoforms. Recently, new sensitive immunometric assays measuring intact LH were developed. These assays have been found to underestimate or to be incapable of recognizing LH in some patients. This study was undertaken to determine the prevalence of such cases and to define their clinical characteristics. We compared three LH assays using as capture antibodies either a monoclonal antibody that reacts exclusively with intact LH (ES 600 Boehringer, Stratus Baxter) or a monoclonal antibody against the beta subunit of LH (IMX Abbott). In 17% of 90 patients tested, ES 600 measured > 50% lower LH concentrations when compared with the IMX. Moreover, in two cases LH was not detectable by ES 600 or Stratus, whereas it was normal with the IMX. We found another five such cases and discuss here the clinical data and results of different hormone measurements in these seven cases of 'invisible LH'. Although bioactive LH (mouse Leydig cell assay) was normal, the existence of low or even undetectable LH was clinically confusing and led to expensive complementary investigations such as gonadotrophin-releasing hormone analogue tests and magnetic resonance imaging. The uses and limitations of these assays are illustrated by different clinical situations in which the results of the different assays have been misleading.

Antibodies, Monoclonal↗
PubMed1994

Investigations on the cell type responsible for the endometrial secretion of complement component 3 (C3).

It has been shown that rat and human endometria have the capacity to produce complement component 3 (C3). In rats, endometrial C3 is an oestrogen-dependent protein produced and secreted by glandular cells. The cell responsible for the synthesis and secretion of human endometrial C3 has not been clearly defined. Our study was aimed at answering this question. Samples of endometrium obtained from hysterectomies were either immunostained for C3 or digested with collagenase; then the stromal and glandular cells were separated and immunopurified (or not) with an antibody to CD45 coupled to magnetic beads to eliminate the endometrial lymphomyeloid cells. Cells were cultured for 2 weeks and C3 measured in the medium by an in-house radioimmunoassay. Glandular as well as stromal cells stained positively for C3 and released C3 in vitro. The release of C3 from both cell types could be inhibited by cycloheximide. Epithelial cells produced significantly more C3 than stromal cells, and endometrial C3 production was higher for both cell types when these were obtained from secretory as compared to proliferative endometria. Lymphomyeloid cells were possibly a source of C3 since after immunoadsorption of these cells, the remaining stromal or glandular cells produced significantly less C3. We conclude that endometrial stromal, glandular and lymphomyeloid cells all produce C3.

Adult↗