Search PubMed⌕ Search

Biomedical subjects

P Bischof

Publications and source records attributed to P Bischof.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1987

Serum CA 125 in epithelial ovarian cancer. A longitudinal study.

Plasma levels of CA 125 were determined in 113 patients with ovarian cancer of epithelial origin. Of these, 69 patients had CA 125 measured before the first laparotomy and 84.6% of them had a CA 125 level greater than 35 U/ml. In 87 of the 113 patients whose tumour was producing CA 125, a good correlation was observed between the CA 125 levels and the clinical follow-up: 95.7% of the patients in remission had levels less than 35 U/ml, whereas all the patients with no change or with a progressive disease had levels greater than 35 U/ml. Furthermore in recurrent disease the levels of CA 125 were also increased (greater than 35 U/ml) in 92.3% of the patients. Thus, CA 125 measurements at regular intervals are of great clinical value in following the evolution of a tumour or the success of a therapy, but unfortunately do not allow detection of an ovarian tumour at an early stage.

Adenocarcinoma↗
PubMed1987

The disappearance rate of Schwangerschaftsprotein 1 in normal and pathological pregnancies.

In six women with a normal vaginal delivery at term, in 12 women who had a suction curettage between 6 and 12 weeks gestation and in eight women with an ectopic pregnancy, the post-partum or the post-surgery decline in radioimmunoassayable SP1 was faster during the first 24 h after surgery or delivery than later, so that two half-lives were calculated. The first 'half-life' of about 20 h (0-24 h after delivery or surgery) was of the same order of magnitude in all groups studied and corresponded well to previously published values. The mean second 'half-life' (greater than 24 h after delivery or surgery) was significantly longer in term (72.2 h) and in ectopic pregnancies (64.1 h) than in first trimester pregnancies (45.5 h). These results might indicate that the metabolism of SP1 either changes during pregnancy or that the changing SP1 beta/SP1 alpha ratio during pregnancy markedly influences the levels of SP1 as measured by radioimmunoassay.

Adult↗
PubMed1987

Regulation of prolactin production by progestin, estrogen, and relaxin in human endometrial stromal cells.

Human decidua synthesizes and secretes PRL. We identified the PRL synthesized in endometrial stromal cells and investigated the effect of medroxyprogesterone acetate (MPA), estradiol (E2), porcine relaxin (RLX), and RU486, an antiprogestin, on PRL production by stromal cells from non-pregnant endometrium in primary culture. Stromal cells were isolated from proliferative and secretory endometria and individually cultured in nutrient medium or medium supplemented with different hormone(s). The immunoreactive PRL isolated from culture medium of hormone-stimulated stromal cells was identified and compared to pituitary PRL. Bio-Gel elution pattern and mol wt analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblotting showed that PRL produced by stromal cells had properties identical to those of pituitary PRL. In addition, PRL mRNA was identified in hormone-stimulated stromal cells using human pituitary PRL cDNA as a hybridization probe. Analysis of mRNA by Northern blotting showed that the size of PRL mRNA isolated from stromal cells was indistinguishable from that of PRL mRNA in human decidua and pituitary tissue. These results indicated that PRL measured in culture medium was synthesized de novo by stromal cells. The PRL content in culture medium was quantitated by RIA. The PRL production rate in stromal cells cultured without hormones ranged from 6-10 ng/day.mg cell protein. After 4-5 days of incubation with RLX or MPA alone, the PRL production rate increased about 2- to 3-fold over the control value. E2 alone had either no effect or slightly decreased the stromal cell PRL production rate. Stromal cells responded to 0.02 microM MPA, and the maximal response was at 0.1-1 microM MPA. A further increase in PRL production was found when stromal cells were treated with a combination of MPA and E2 and MPA, E2 and RLX. In the presence of MPA or MPA and E2, 0.1 ng/ml relaxin increased the PRL production rate. A potent progestin antagonist, RU486, inhibited PRL production in stromal cells treated with MPA, MPA and E2, or MPA and RLX. These results indicate that endometrial PRL production is regulated by the combined effects of steroid hormones (progestin and estrogen) and a peptide hormone (relaxin).

Cells, Cultured↗
PubMed1987

[Pregnancy proteins].

This review article summarizes our knowledge about three proteins associated to human pregnancy: placental protein 12 and 14 (PP12, PP14) and pregnancy-associated plasma protein-A (PAPP-A). These have in common their origin since all three seem to be produced by the pregnant endometrium (although not exclusively). Two of these proteins (PP12, PP14) have been described independently by many authors and are thus known, under many different names. For each protein their biochemical properties, their origin and regulation, their biological properties, as well as potential clinical applications, are discussed in detail. The clinical applications of PP12, PP14 and PAPP-A measurements are not only limited to uterine pathologies but also include cancer (tumour markers) and pregnancy (hydatidiform moles and extra-uterine pregnancies). This review is the first complete and comparative study of these three proteins, but many more questions are asked than solved. This is essentially due to the fact that human endometrial proteins is a rather new subject.

Endometrium↗
PubMed1986

In vitro production of pregnancy-associated plasma protein-A (PAPP-A) by trophoblastic cells.

Pregnancy-associated plasma protein-A (PAPP-A) a high molecular weight glycoprotein, is found in high concentration in the maternal circulation during pregnancy. Immunohistochemically, PAPP-A can be localized in the trophoblast and in the decidua. Short term cultures of trophoblastic and decidual explants produce PAPP-A in vitro. It was thus of interest to see if long term cultures of primary monolayers of human trophoblast cells were capable of producing PAPP-A. Under our in vitro conditions, trophoblastic monolayers were producing both PAPP-A and beta hCG. During the first 3 days of culture PAPP-A levels increased in the medium whereas beta hCG levels decreased. The production of both proteins could be inhibited by cycloheximide. These results strongly suggest that the trophoblast is a source of PAPP-A in vivo.

Cells, Cultured↗
PubMed1986

Progesterone dependence and extratrophoblastic origin of pregnancy-associated plasma protein-A (PAPP-A) in early pregnancy.

Pregnancy-associated plasma protein-A (PAPP-A) is a macromolecular glycoprotein produced in increasing concentration as pregnancy advances. PAPP-A is not specific to pregnancy since measurable levels have been found in non-pregnant females and in males. In non-pregnant females, PAPP-A is probably produced by the endometrium. The origin of PAPP-A in pregnant women is still controversial. In-vitro trophoblast and decidual explants both produce PAPP-A. So far, it is not known if the same applies to the in-vivo situation and to what extent these two tissues contribute to the circulating levels of PAPP-A. This study compares the circulating concentrations of PAPP-A and beta-hCG and progesterone in different pathological situations. In hydatidiform moles, beta-hCG levels are very high demonstrating an intense trophoblastic activity, whereas PAPP-A levels remain in the normal range. With spontaneous abortions, beta-hCG levels decline to very low values whereas PAPP-A continues to increase. These observations furnish indirect evidence for a major contribution to circulating PAPP-A levels by extratrophoblastic sites. Furthermore, PAPP-A levels decrease after administration of an anti-progesterone (RU486) either in-vivo or in-vitro. This is considered as a proof that PAPP-A levels in early pregnancy are progesterone dependent.

Abortifacient Agents, Steroidal↗
PubMed1986

Binding of pregnancy-associated plasma protein-A (PAPP-A) to placental subfractions.

Pregnancy-associated plasma protein-A (PAPP-A) has been shown to exert immunosuppressive effects both on complement and on lymphoblastogenesis. It was of interest to see whether this protein could bind to syncytiotrophoblast microvillous membranes since these represent the effective interface between fetal tissue and the immunocompetent mother. Placental subfractions were prepared according to established techniques. PAPP-A was purified from different sources (pregnancy serum and plasma, retroplacental serum, placental extracts) and labelled with radioactive iodine. It could be shown that radioactive PAPP-A, irrespective of its biological origin was primarily binding to brush border membrane preparations but that significant binding was also seen with plasma membrane preparations. The binding was specific since alpha 2-macroglobulin (a structurally related protein to PAPP-A) was unable to displace bound radioactive PAPP-A. Scatchard plot representation of the data indicated that the affinity of PAPP-A for its binding site was of the same order of magnitude as reported for the insulin or GnRH receptors of the trophoblast (Ka 2 10(7)-2.5 10(8) M-1). These results are in agreement with the immunohistochemical localization of PAPP-A on the trophoblast providing that the small binding to plasma membrane preparations is due to contamination.

Cell Membrane↗
PubMed1986

Trophoblastic and decidual response to RU486: effects on human chorionic gonadotrophin, human placental lactogen, prolactin and pregnancy-associated plasma protein-A production in vitro.

RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha- (prop-1-ynyl)-oestra-4,9-dien-3-one] a potent progesterone antagonist, was shown to induce abortions in humans. Human chorionic gonadotrophin (HCG) and pregnancy-associated plasma protein-A (PAPP-A) decreased after RU486 administration, but it was not clear whether these effects were due to RU486 or secondary to trophoblast damage. To answer this question we tested the in-vitro effects of RU486 on short-term cultures of trophoblastic and decidual explants. It was observed that RU486 induced a significant inhibition of the trophoblastic production rate of beta HCG and PAPP-A but not human placental lactogen. This effect could be overcome by addition of progesterone (for PAPP-A and beta HCG) or cortisol (for beta HCG). Decidual prolactin (Prl) or PAPP-A secretions were also inhibited by RU486. Progesterone antagonized these effects, whereas cortisol was ineffective. These results suggest that PAPP-A is a progesterone-dependent protein and that the abortifacient effect of RU486 in humans could at least partially be due to an inhibition of the production of HCG and/or PAPP-A.

Abortifacient Agents↗
PubMed1986

Immunohistochemical localization of pregnancy-associated plasma protein-A in the male genital tract.

Pregnancy-associated plasma protein-A (PAPP-A) has been found in seminal fluid at concentrations 10-20 times higher than in plasma. This observation prompted us to undertake a morphological study of the male genital tract with the aid of the immunoperoxidase technique. Immunoreactive cells were found among the Leydig cell population, as well as among the epithelium of the rete testis, the head of the epididymis and the seminal vesicles. The relatively small number of weakly staining epithelial cells leaves open the question of whether PAPP-A is excreted by these cells or whether an active transfer mechanism - possibly in the seminal vesicles - is at work, the Leydig cells increasing the plasma concentration locally, by secretion of PAPP-A into the circulation.

Animals↗
PubMed1986

Cancer antigen 125 is produced by human endometrial stromal cells.

Cancer antigen 125 (CA125) is an antigenic determinant defined by a murine monoclonal antibody and is present on the surface of some ovarian tumours. Using an immunoradiometric assay CA125 immunoreactivity was found in amniotic fluid and decidual extracts, hence the possibility of an endometrial origin of CA125 in pregnant and non-pregnant women was investigated. First-trimester decidual explants produced CA125 in vitro and cycloheximide significantly reduced the concentration of CA125 both in the medium and in the tissue. CA125 was also produced in primary culture of human endometrial stromal cells, its concentration in the medium being significantly higher with cells obtained during the proliferative and early secretory phases compared to those obtained during the late secretory phases. Medroxyprogesterone acetate (MPA, 1 mumol/l) induced a significant inhibition of CA125 production. This effect could be blocked by oestradiol (E2, 36 nmol/l) or the antiprogesterone RU486 (10 mumol/l). In women with endometriosis, the circulating levels of CA125 increased with the severity of the disease and were found to be significantly higher when compared to those of healthy volunteers. Gonadotrophin-releasing hormone or Danatrol therapy significantly reduced the CA125 levels. The endometrium, decidualized or not, seem to be capable of producing CA125, and this production is evidently correlated with endometrial cell growth and/or activity.

Antibodies, Monoclonal↗
PubMed1986

Pulsatile secretion of pregnancy-associated plasma protein-A (PAPP-A) in non-pregnant women.

No changes in PAPP-A levels could be detected when plasma samples were obtained every second day throughout the entire menstrual cycle in three healthy women. But when measured every 30 min throughout 12 consecutive hours, in four healthy women, PAPP-A followed a pulsatile pattern which may originate in the endometrium since no PAPP-A pulses were detected in a long-term hysterectomized woman, or in two men. The pulses were not related to levels of oestradiol, progesterone, FSH or LH.

Adult↗
PubMed1986

In vitro release of pregnancy-associated plasma protein-A (PAPP-A) by human endometrial cells.

Evidence has now accumulated to sustain the idea that pregnancy-associated plasma protein-A (PAPP-A) is not pregnancy specific: it can be localized immunohistochemically in nonpregnant human endometrium. Thus, it was of interest to see if a primary cell culture of human endometrial cells was capable of producing PAPP-A. Immunoreactive PAPP-A-like material was detected in the culture medium of glandular as well as stromal cells. The presence of PAPP-A in endometrial culture medium was specific and could not be attributed to a nonspecific protease effect on the tracer used in radioimmunoassay. The production rate of PAPP-A by stromal cells could be enhanced by the addition of medroxyprogesterone acetate (MPA). Estradiol (E2) alone or in combination with MPA did not modify the production rate of PAPP-A. The production rate of PAPP-A by glandular cells remained unchanged after treatment with MPA and/or E2. These results confirm that in nonpregnant women PAPP-A is a progesterone-dependent protein produced by the endometrium.

Cells, Cultured↗
PubMed1986

Growth hormone response to thyrotropin-releasing hormone in children and adolescents: a reappraisal.

In normal subjects, thyrotropin-releasing hormone (TRH) is not involved in the control of growth hormone secretion. Paradoxical growth hormone (GH) responses to TRH have been described in acromegalic subjects and, recently, in some constitutionally tall children. To confirm this finding, we have examined the GH response to combined LHRH-TRH tests performed to assess the pituitary function of children with GH deficiency, tall stature before and during bromocriptine therapy, precocious or delayed puberty as well as in a group of patients of average height and normal bone age. Unlike prolactin, the GH "response" to TRH, in children followed longitudinally, is particularly heterogeneous with an unpredictable pattern of secretion in repeated tests. Over 90% of children display peaks of GH (greater than or equal to 5 ng/ml), of which 38% occur twice during the test period. Amplitude and frequency of GH peaks appear to be independent of height, chronological age or bromocriptine therapy. Secretory rate estimated by integrated surface area increases in parallel to sex steroids impregnation. The pattern of GH secretory episodes, the increase in mean GH secretion in parallel to the production of gonadal sex steroids and the failure of bromocriptine to affect GH secretion in constitutionally tall children allow to speculate that what is measured after TRH injection is normal spontaneous GH rhythm rather than a direct effect of TRH on GH secretion.

Adolescent↗
PubMed1986

Pregnancy-associated plasma protein-A concentrations in men with testicular and prostatic tumors.

Pregnancy-associated plasma protein-A (PAPP-A) is a macromolecular glycoprotein produced during pregnancy by the trophoblast and the decidua. It is not specific to pregnancy, since immunoreactive PAPP-A is in the circulation of normal women and men and in seminal fluid. Immunohistochemically, PAPP-A is localized in some Leydig cells, in the epididymis, in the rete testis, and in seminal vesicles. This study was conducted to learn whether circulating levels of PAPP-A can be used as a marker for the monitoring of human testicular cancer. PAPP-A was increased only in certain nonseminomatous germ cell tumor [malignant teratoma undifferentiated (MTU) + seminoma, malignant teratoma intermediate (MTI)], but the overlap with the normal values was too big for PAPP-A to have any clinical significance. After orchidectomy or prostatectomy, PAPP-A decreased but the levels were were similar to those of normal men. In men, PAPP-A can be produced by certain nonseminomatous germ cell tumors, but its origin in disease-free males is probably not the testis or the prostate.

Adenoma↗