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Biomedical subjects

P Bischof

Publications and source records attributed to P Bischof.

At least 19 recordsLinked to original sources
PubMed1992

Peripheral CA 125 levels in patients with uterine fibroids.

CA 125, a marker of ovarian cancer, is also increased in otherwise normal women suffering from, for example, pelvic inflammatory disease, endometriosis and adenomyosis. The tissues suspected of producing CA 125 in normal women include the endometrium, the ovary and the peritoneum. This study was based on the hypothesis that uterine myomata would distend the peritoneum covering the uterus and thereby increase the peripheral levels of CA 125. To verify this hypothesis we measured CA 125 by an immunoradiometric assay in eight normal women every second day throughout the cycle and in 26 women with uterine fibroids before and after hysterectomy and at 8 and 12 weeks during gonadotrophin releasing hormone (GnRH) analogue therapy. In normal women no difference was observed between CA 125 levels in the follicular phase or in the luteal phase of the cycle. Over one-third (10/26) of the patients with uterine fibroids had increased (greater than 90th centile of the controls) levels of CA 125 before GnRH therapy or hysterectomy. Removal of the uterus or administration of GnRH significantly decreased peripheral concentrations of CA 125 to levels below those observed in normal women. Furthermore, a significant positive correlation was observed between the levels of CA 125 and the volume of myomata as assessed by ultrasound. We conclude that in those cases of uterine fibroids where CA 125 is increased, monitoring this parameter during GnRH therapy is a good indirect measurement of regression of myomata.

Adult↗
PubMed1991

Squamous-cell carcinoma antigen (SCC-A) values related to clinical outcome of pre-invasive and invasive cervical carcinoma.

The serum concentration of squamous-cell carcinoma antigen (SCC-A), a subfraction of tumour antigen, was determined by RIA from healthy donors (control group) and from patients with malignant cervical disease. Ninety-six percent (173/180) of the healthy patients had squamous-cell carcinoma antigen serum levels below 2 ng/ml. Ten of 70 (14.3%) patients with CIN III, 53.8% (34/62) of patients with invasive squamous-cell carcinoma stage I, 85.8% (30/35) with stage II and 96.5% (27/28) with stage III/IV had squamous-cell carcinoma antigen serum levels above 2 ng/ml. We observed that 22.5% (11/49) of patients with a tumour volume below 10 ml and 92.6% of patients with a tumour volume greater than 10 ml had squamous-cell carcinoma antigen levels above 2 ng/ml (p less than 0.005). SCC-A was correlated with recurrence or progressive disease in 90.0% of cases. Other risk factors such as depth of invasion, microscopic parametrial involvement, lymphatic and/or vascular space permeation and histological grade were not correlated with squamous-cell carcinoma antigen. Furthermore, this marker increased 4.3 +/- 2.7 months before clinical evidence of recurrence or progressive disease. We conclude that serial serum levels of squamous-cell carcinoma antigen provide a means for early detection of recurrence or progressive disease. This tumour marker might also be useful for monitoring the treatment effects and has some prognostic value.

Antigens, Neoplasm↗
PubMed1991

Expression of extracellular matrix-degrading metalloproteinases by cultured human cytotrophoblast cells: effects of cell adhesion and immunopurification.

In vitro, invasion of basement membrane by human trophoblast can be blocked by metalloproteinase inhibitors. The purpose of our study was to characterize these enzymes by zymography, to define their cellular origin. First-trimester cytotrophoblast cells were prepared according to the method of Kliman et al. Half of the cell suspension was further purified with an antibody to leukocyte common antigen (CD45). Cytotrophoblast cells (immunopurified or not) were incubated in Dulbecco's modified Eagle's medium on different matrices. Progesterone, total human chorionic gonadotropin, and free beta-human chorionic gonadotropin were measured in the supernatant by radioimmunoassay or enzyme immunoassays. Secreted (in the medium) and cell-bound proteases were characterized by zymography on sodium dodecyl sulfate-polyacrylamide gels containing gelatin. Cytotrophoblast cell preparations contained 12% to 34% leukocyte common antigen-positive cells before and 0% after immunopurification. Large zones of digested matrices were observed after 48 hours of culture on Matrigel or rat tail collagen but not on agarose. Cells secreted progesterone, human chorionic gonadotropin, and free beta-human chorionic gonadotropin in vitro, but no difference was observed among cells grown on different matrices or between immunopurified and nonimmunopurified cells. By zymography, seven gelatin-degrading enzymes were seen in culture supernatants and five of them were present in cell lysates. The molecular weights of these proteases ranged from 59 to 230 kd. Immunopurification eliminated three of these enzymes, so they were clearly produced by bone marrow-derived cells (leukocyte common antigen positive) contaminating the cytotrophoblast cell preparation. Cells grown on Matrigel express a unique 59 kd gelatinase that was not seen in the supernatants of cells grown on other matrices. Zymography in the presence of inhibitors showed that these enzymes were neutral metalloproteinases, which might be responsible for the observed extracellular matrix degradation.

Cell Adhesion↗
PubMed1991

Comparison of a rapid, quantitative and automated assay for urinary luteinizing hormone (LH), with an LH detection test, for the prediction of ovulation.

The prediction of ovulation is necessary for oocyte aspiration in a spontaneous cycle and can be reliably achieved only by measuring luteinizing hormone (LH). Since radioimmunoassays of LH take too long for repeated measurements on the same day, we evaluated the possibility of adapting a rapid and fully automated assay of serum LH for use with urine samples. The study group comprised spontaneously ovulating women (38 cycles) who requested artificial insemination. Their serum oestradiol (E2) levels, ultrasound profile (US) and thrice daily urinary LH levels were determined from day 10 of their menstrual cycle. These patients were followed until US signs of follicular rupture were recorded. In all patients, a well-defined LH peak was measured in the urine. This peak lasted 12-15 h and was followed in 35 cycles (no US available for 3) by follicular rupture 9-51 h later. The data were grouped according to the time of the LH peak on day 0. Patients experiencing an LH peak between 0300 h and 0700 h on day 0 had significantly lower levels of E2 on day 0 compared to those with an LH peak between 2200 h and midnight. This is due to the fact that in the patients with an LH peak between 0300 h and 0700 h, E2 levels were already decreasing (from day 1 to day 0), whereas in those with the LH peak between 2200 h and midnight E2 levels were still increasing on the morning of day 0. We conclude that the 30-min IMX LH assay is a reliable, rapid and readily acceptable method for measuring urinary LH and for the prediction of ovulation.

Adult↗
PubMed1991

The presence of pregnancy-associated plasma protein-A in human corpora lutea: cellular and subcellular distribution and dependence on reproductive state.

Pregnancy-associated plasma protein-A (PAPP-A) is a high-molecular-weight glycoprotein primarily secreted by syncytiotrophoblasts of human placenta. It is not known, however, whether human CL of menstrual cycle or pregnancy also contain this protein. Therefore, light and electron microscope immunocytochemical studies were undertaken to investigate the presence, cellular and subcellular distribution, and dependence of luteal PAPP-A content on reproductive state. Human CL from early, mid, and late luteal phases and from term pregnancies immunostained specifically for PAPP-A. Immunostaining was found in large luteal cells (17-30 microns) but not in small luteal cells (7-16 microns) or in nonluteal cells in any of the reproductive states. Immunostaining was not found in negative control tissues, i.e. human liver or bovine CL of pregnancy. As expected however, term-pregnancy human placenta used for a positive control tissue immunostained intensely for PAPP-A. The luteal immunostaining was highest in early luteal phase, decreased progressively from early to mid and from mid to late luteal phases, and then disappeared in corpora albicantia. The relative intensity of immunostaining in early luteal phase human CL was similar to that in term-pregnancy human placenta and higher than in term-pregnancy human CL. The immunogold particles due to PAPP-A were primarily associated with secretory granules of large luteal cells. A small number of gold particles were also found in rough endoplasmic reticulum and cytoplasm. In conclusion, human CL contain immunoreactive PAPP-A. The luteal content varies with reproductive state, with the highest amount found in early luteal phase CL.(ABSTRACT TRUNCATED AT 250 WORDS)

Corpus Luteum↗
PubMed1990

Extracellular matrix influences hormone and protein production by human chorionic villi.

Increasing evidence confirms that the extracellular matrix greatly influences cell behaviour and function. Collagen and fibrin are in contact with trophoblast throughout pregnancy. To investigate whether these two matrices influence hormone production by the trophoblast, explants from first-trimester chorionic villi were cultured for up to 30 days either a) in medium with agitation, b) embedded in type-I collagen (three-dimensional gels), or c) embedded in fibrin (three-dimensional gels). The supernatant culture medium was changed every 48 h and tested by radioimmunoassay for hCG, progesterone and pregnancy-associated plasma protein A. In addition, after 3, 7, 15, and 30 days of culture villi were fixed and studied by light and electron microscopy. Embedding in the extracellular matrix showed higher and longer-lasting production rates of all measured products and superior structural preservation as compared to cultures with agitation. Collagen matrix proved to be superior to fibrin. As established by several tests, this difference was neither due to thrombin used to polymerize fibrinogen, nor to differences in the diffusion rates through the two different matrices used. We conclude that extracellular matrix, particularly collagen, influences the synthesis of trophoblastic products. Embedding of the villous explants in three-dimensional gels constitutes a new method for long-term cultures of chorionic villi.

Chorionic Gonadotropin↗
PubMed1990

CA 125 is an excretory product of human endometrial glands.

The present investigation was undertaken to study the cellular localization and kinetics of synthesis of CA 125 in the endometrium. CA 125 was localized by immunohistochemistry to the infranuclear region of epithelial cells during the proliferative phase and to the apical luminal border during the secretory phase. In gestational endometrium, both the cytoplasm and the apical luminal border of epithelial cells were intensely positive. No staining was seen in endometrial stromal cells during the normal cycle or in decidualized endometria. Results obtained from in vitro cultures of separated glandular and stromal cells were similar to those obtained by immunohistochemistry. That is, epithelial cells released between 5 and 25 times more CA 125 into the culture medium than did stromal cells. The release of CA 125 was highest in epithelial and stromal cells obtained during the early secretory phase. CA 125 concentrations were markedly elevated in endometrial aspirations obtained during the secretory phase or in endometria with crumbling stroma compared to plasma levels. Plasma levels of CA 125 were slightly elevated during menses. These results suggest that CA 125 is an exocrine product of endometrial epithelial cells. Plasma levels of CA 125 may be of endometrial origin only when the membrane barriers, which normally prevent its entry into the circulation, are damaged.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1990

Pregnancy-associated plasma protein-A-induced inhibition of human leukocyte elastase: an artifact.

Pregnancy-associated plasma protein A (PAPP-A), was reported to be an inhibitor in many in vitro systems. Since it was shown that the inhibition of coagulation and complement activity attributed to PAPP-A was in fact due to a contamination by heparin occurring during the purification process, we undertook the present study to see whether the reported PAPP-A-induced inhibition of human leukocyte elastase (HLE) could also be attributed to heparin contamination. PAPP-A was purified from maternal pregnancy EDTA plasma by a method which was previously shown to eliminate contaminating heparin: this preparation was inactive in the HLE assay. But PAPP-A isolated by heparin-Sepharose chromatography, or a PAPP-A-free washing of the heparin-Sepharose column were both inhibitors of HLE. Furthermore the inactive PAPP-A preparation, when incubated with the PAPP-A-free washing of the heparin-Sepharose column, yielded a high molecular weight preparation which inhibited HLE. It is concluded that PAPP-A is not an inhibitor of HLE and that the inhibition of HLE previously attributed to PAPP-A was due to contaminating heparin.

Chromatography, Gel↗
PubMed1989

Immunoregulatory activity in supernatants from cultures of normal human trophoblast cells of the first trimester.

Supernatants from isolated trophoblast cell cultures (trophoblastic fluid) derived from first-trimester human placentas were assessed for immunoregulatory activity. Trophoblastic fluid at different days of culture consistently inhibited the blast transformation of allogenic lymphocytes. This suppressor effect had no apparent correlation with biosynthesis of human chorionic gonadotropin by trophoblast cells, since this hormone was secreted into the culture fluid only for the initial 3 days. However, the culture fluids of such purified trophoblast cells contained an immunosuppressive factor, pregnancy-associated plasma protein A, which was measurable throughout the culture period of 8 days. The presence of pregnancy-associated plasma protein A in significant amounts in trophoblastic fluid collected at daily intervals indicated a continuous secretion ability of pregnancy-associated plasma protein A by trophoblast cells in culture parallel to the suppressive immunoregulatory effect of the fluid. Such immunosuppressive effect was absent in the culture fluids of control BeWo malignant trophoblast cells; the BeWo cell culture fluids had markedly reduced levels of pregnancy-associated plasma protein A. The culture supernatant of normal trophoblast cells of placentas from first-trimester pregnancy activated in vitro the generation of a population of suppressor lymphocytes. This effect is generally considered responsible for immunologic tolerance. Therefore demonstration of immunosuppressive effects and the presence of relatively high levels of pregnancy-associated plasma protein A in trophoblastic fluid indicate that such proteins secreted by the trophoblast cells may be important in the local immunoregulatory processes of the fetal allograft.

Cells, Cultured↗
PubMed1989

Three pregnancy proteins (PP12, PP14, and PAPP-A): their biological and clinical relevance.

The three pregnancy proteins, PP12, PP14, and PAPP-A, reviewed here are all produced by the endometrium under the influence of progesterone. Their production is low during the secretory phase and increases dramatically after decidualization and pregnancy. PP12 and PP14 are synthesized by the epithelial cells and PAPP-A is synthesized by the stromal cells. Reflecting perhaps the relative abundance of stromal cells, PAPP-A concentrations increase progressively to term, whereas the levels of PP12 and PP14 level off and even decline after the 20th week of gestation. These proteins are also found in nonpregnant subjects in extrauterine sites: follicles, follicular fluid, luteal cells, and fallopian tubes, and in males, in seminal vesicles and seminal fluid. PP12 has been found in several forms of cancer, although not with sufficient frequency to make it a useful tumor marker. The biologic function of these proteins is still subject to speculation, but they do reflect the biosynthetic capacity of decidualized endometrium, and especially PP14 may find clinical application in the management of infertility patients.

Carrier Proteins↗
PubMed1989

Are pregnancy-associated plasma protein-A (PAPP-A) and CA 125 measurements after IVF-ET possible predictors of early pregnancy wastage?

Pregnancy-associated plasma protein-A (PAPP-A), a macromolecular glycoprotein of placental origin, was reported to be depressed in established ectopic pregnancies. CA 125 is a known marker for ovarian cancer found to be elevated during the first trimester of pregnancy and in women with pelvic inflammatory disease. The present study investigated the usefulness of these parameters to predict the outcome of pregnancy in asymptomatic patients with a positive pregnancy test after in-vitro fertilization and embryo transfer (IVF-ET). Blood samples (n = 159) were obtained at different periods of time post-ET from 39 women, 21 of whom experienced a normal pregnancy, 12 had an intrauterine abortion and six had an ectopic pregnancy. PAPP-A and CA 125 were measured by radioimmunoassays. From day 30 onwards in normal pregnancies, PAPP-A was significantly increased over non-pregnant controls. In the spontaneous abortion group, the levels of PAPP-A were significantly lower than in normal pregnancy but higher than in non-pregnant controls. In ectopic pregnancy, PAPP-A remained at the level of non-pregnant controls throughout the entire observation period. CA 125 was significantly increased in all types of pregnancy. However, in two cases of hyperstimulation followed by a normal pregnancy and in four cases of ectopic pregnancy with signs of peritoneal irritation (hydrosalpinx, ruptured ectopic or salpingitis) the levels of CA 125 were 15-50 times higher than in normal pregnancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗
PubMed1989

Plasma levels of SP1-like immunoreactive material (SP1) and progesterone throughout pregnancy and following RU 486-induced early abortion in the cynomolgus monkey (Macaca fascicularis).

A human-SP1 immunoassay was used to detect SP1-like material (SP1) in the plasma of cynomolgus monkeys. In 27 females remaining non-pregnant during a mating period of 4 months, SP1 was occasionally detected at a mean concentration of 2.5 ng/ml. In 14 non-pregnant females of subsequent proven fertility, SP1 was detected 20 days following unfertile mating at a mean concentration of 4.8 ng/ml in 86% of cycles. At day 20 of proven pregnancies, SP1 was at 12 ng/ml in 93% of these animals. SP1 levels during pregnancy increased in two steps, a slow rise between days 20 and 50, followed by an abrupt rise between days 50 and 60 and afterwards a plateau at 600 ng/ml. Seven other pregnant monkeys received 10 mg/kg of the antiprogestin RU 486 at 28 days. Four aborted and the others continued their gestation. SP1 was always dramatically depressed by this treatment; in animals with abortion failure, it remained at a low concentration for 3 months, then the normal concentration range was recovered. The assay of SP1-like material does not allow early diagnosis of pregnancy, however, it remains interesting as a follow-up parameter after 60 days. Also, antiprogestins appear to be useful tools to analyse the metabolism of SP1.

Abortion, Induced↗
PubMed1989

Pregnancy-associated plasma protein-A in pregnant cynomolgus monkeys (Macaca fascicularis): radioimmunoassay, normal levels, effect of RU 486, and preliminary characterization.

Pregnancy-associated plasma protein-A (PAPP-A) is a human macromolecular glycoprotein produced by the trophoblast and possibly by the decidua. Its biological function is unknown, but in vitro, PAPP-A has been reported to be an inhibitor of granulocyte elastase. The present study was undertaken to see if pregnant cynomolgus monkeys could be an animal model sufficiently close to the human situation to study the physiology of PAPP-A. An antiserum to pregnant cynomolgus plasma was raised in rabbits. After adsorption with normal monkey plasma, this antiserum was used together with radioiodinated human PAPP-A to develop an heterologous radioimmunoassay for measurements of monkey PAPP-A. On polyacrylamide gel electrophoresis, it was shown that this polyspecific-antiserum bound the same molecular species of radioiodinated human PAPP-A as the available anti-human PAPP-A antiserum. The concentrations of cynomolgus PAPP-A (cPAPP-A) throughout pregnancy follow the same pattern as human PAPP-A (hPAPP-A) with an almost exponential increase up to term. The doubling time of cPAPP-A was similar to that of hPAPP-A. After RU 486-induced abortion or after spontaneous abortion, the levels of cPAPP-A decreased, with an apparent half-life of 2-3 days. Preliminary characterization of cPAPP-A revealed that although cPAPP-A was only immunologically related to hPAPP-A, it was biochemically very similar: they had the same PI and the same molecular weight, and both PAPP-As bound heparin. It is concluded that pregnant cynomolgus monkeys are a good model to study the physiology of PAPP-A.

Abortifacient Agents↗
PubMed1989

Immunological heterogeneity of pregnancy-associated plasma protein-A (PAPP-A). Effects on the radioimmunoassay of PAPP-A.

Pregnancy-associated plasma protein-A (PAPP-A) is a macromolecular glycoprotein produced by the trophoblast during pregnancy. Because the presence of PAPP-A in non-pregnant females is controversial, we re-evaluated our own radioimmunoassay technique for PAPP-A in the light of new observations about its immunological heterogeneity. Irrespective of the antibody (Geneva anti-PAPP-A or Dako anti-PAPP-A) the use of EDTA pregnancy plasma instead of pregnancy serum as a standard yielded different slopes of the standard curves and estimated significantly different amounts of PAPP-A in test samples. Moreover, highly purified tracers, isolated from maternal EDTA pregnancy plasma or pregnancy serum also produced significantly different results. So that the use of a tracer purified from EDTA plasma and EDTA pregnancy plasma as a standard will yield measurable levels of PAPP-A in non-pregnant female serum whereas the use of a tracer purified from maternal pregnancy serum and maternal pregnancy serum as a standard will not detect PAPP-A in the same samples. We conclude that, irrespective of the antiserum used, but depending on the biological origin of the tracer and the standard, different results will be obtained. PAPP-A is clearly immunologically heterogeneous, and the immunorecognition of PAPP-A will depend on whether or not blood coagulation has taken place.

Blotting, Western↗
PubMed1989

["Insitutom RC": a new instrument for valve incision in in-situ vein bypass].

The "in situ" bypass technique was first used by Cartier in 1960. It has only slowly gained acceptance among vascular surgeons. In part this can be explained by the lack of an easy and reliable method to render vein valves incompetent. The instruments most widely used for this purpose have been developed by Hall, Gruss and Leather ("Valve Stripper", "Insitucut" and "Valve Cutter", respectively). Based on theoretical considerations and practical experience, we have developed a new instrument for the incision of vein valves: the Insitutom RC. Unlike other instruments, it allows rotation control of the cutting blade and thus enables the surgeon to incise the valve cusps more precisely and reliably.

Arteriovenous Shunt, Surgical↗
PubMed1988

In vitro effects of pregnancy-associated plasma protein-A: artifacts due to heparin.

Pregnancy-associated plasma protein-A (PAPP-A) has been reported to inhibit elastase activity, lymphoblastogenesis, complement activity, and thrombin-induced coagulation of fibrinogen. Since some of these results are controversial, we reevaluate here the effects of PAPP-A in these last two systems. By molecular sieve chromatography, PAPP-A immunoreactivity and inhibitory activity on thrombin and complement were dissociated. A PAPP-A-free washing of the heparin-Sepharose column used during the purification of PAPP-A showed inhibitory activities similar to those of purified PAPP-A. Furthermore, a preparation of PAPP-A that had not been submitted to heparin-Sepharose chromatography during purification was not active in either assays. Thus, the anticoagulant and anti-complement effects previously attributed to PAPP-A were due to a contaminant of low molecular mass. We believe that this contaminant is probably heparin. A protocol to eliminate free and PAPP-A-bound heparin is presented herein, and implications for other previously reported in vitro effects of PAPP-A are discussed.

Blood Coagulation Tests↗
PubMed1988

Absence of immunoreactive luteinizing hormone following gonadotropin-releasing hormone agonist therapy in women with endometriosis.

Pituitary desensitization following infusion of gonadotropin-releasing hormone (GnRH) is measurable if bioactivity instead of immunoreactivity is considered. We hypothesized that GnRH agonist therapy induces the same kind of desensitization, but that radioimmunoassays (RIA) for gonadotropins based on polyclonal antibodies cannot show this effect because they recognize inactive fragments of gondadotropins. To test this hypothesis we measured luteinizing hormone (LH) with two different assays: one RIA was based on a polyclonal rabbit anti-hLH, while the other one was an immunoradiometric assay (IRMA) based on 2 different mouse monoclonal anti-hLH. LH measurements were performed on plasma samples obtained from 13 women with laparoscopically proven endometriosis and treated with microcapsules of the GnRH agonist D-Trp6-GnRH (Ferring) once a month. The correlation between LH measurements with both assays in 36 control plasma samples and in another 13 samples obtained before treatment in women with endometriosis was excellent (r = 0.959). In contrast, in women treated with GnRH agonist, the RIA yielded values ranging from undetectable to 12 mIU/ml, whereas 60 out of 66 values were undetectable with the IRMA. We conclude that the monoclonal anti-hLH antibodies in the IRMA either recognize an epitope close to the active site and/or do not recognize the biologically inactive LH fragments which are known to be produced during GnRH agonist therapy. Thus, monoclonal-antibody-based IRMA provide a new and interesting clinical tool to follow the effects of therapies which desensitize the gonadotropic function of the pituitary.

Antibodies, Monoclonal↗