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Biomedical subjects

P Bischof

Publications and source records attributed to P Bischof.

At least 109 records · Page 6Linked to original sources

Serum protein binding of diazepam and propranolol in the feto-maternal unit from early to late pregnancy.

Paired samples of maternal and fetal serum were obtained in 65 pregnancies between 13 and 41 weeks gestation. Concentrations of albumin, alpha 1-acid glycoprotein (alpha 1-AGP) and free fatty acids (FFA) were estimated in all samples and the in-vitro binding of diazepam and propranolol was estimated. The free fraction of diazepam in fetal serum was very high in early gestation and decreased with advancing gestation to reach maternal values around the 30th week. After 35 weeks gestation, values were generally lower in fetal than in maternal serum. Fetal serum binding of diazepam correlated with fetal albumin levels and gestational age. The ratio of the fetal/maternal free diazepam fraction correlated negatively with the fetal/maternal serum albumin concentration ratio. The maternal/fetal free diazepam fraction ratio correlated positively with gestational age. The free fraction of propranolol in fetal serum was higher than in maternal serum in early pregnancy and decreased with advancing gestation but always remained higher than the maternal values. The fetal/maternal free propranolol fraction ratio was negatively correlated with the fetal/maternal alpha 1-AGP serum concentration ratio. The maternal/fetal free propranolol fraction ratio was positively correlated with gestational age. Serum protein binding of propranolol was correlated with serum albumin concentrations in fetal samples but not in maternal samples. Serum FFA concentrations were not correlated with serum protein binding except for maternal serum binding of diazepam. For toxicological reasons it is advisable to monitor maternal blood for free concentrations of drugs that exhibit concentration-dependent protein binding or which can be displaced from binding sites by other drugs or endogenous compounds such as FFA.

Adolescent↗

Placental protein 5 (PP5) inhibits thrombin-induced coagulation of fibrinogen.

The effect of Placental Protein 5 (PP5) on thrombin-induced coagulation of diluted fibrinogen is described. In contrast to previous reports which failed to demonstrate antithrombin-like activity for PP5 on synthetic substrates, we show in this study that PP5 inhibits thrombin activity in a dose-dependent manner. PP5 acts thus in a very similar way to antithrombin III (ATIII). Although PP5 binds to heparin, it does not show any heparin-cofactor activity. Whereas catalytic amounts of heparin accelerate greatly the inhibitory effect of ATIII, no accelerating effect of heparin on PP5 could be observed under the same conditions. In spite of its anti-thrombin activity, PP5 cannot be considered as a pregnancy-analogue of ATIII, as it lacks the heparin-cofactor activity.

Antithrombin III↗

Longitudinal study of CEA and CA125 in ovarian cancer.

Carcinoembrionic antigen (CEA) and cancer antigen 125 (Ca125) levels were measured at regular intervals over a 24-month period in 19 patients with proven ovarian cancers. In 91.5% of the cases with recurrent or progressive disease, Ca125 levels were increased whereas only 34% of these patients had increased CEA levels. Furthermore, reduction of the tumoral mass was associated with a decrease of Ca125 levels in all patients. It is proposed that determination of Ca125 levels in ovarian cancer might provide a valuable prognostic tool for the assessment of the evolution of the disease.

Aged↗

Interaction of pregnancy-associated plasma protein-A (PAPP-A) with coagulation: a bioassay for PAPP-A.

The observation that pregnancy-associated plasma protein A (PAPP-A) concentrations are higher in plasma compared to serum obtained from the same patient, together with fact that PAPP-A binds to heparin, prompted us to study the interaction between PAPP-A and the clotting system. It was determined that pure PAPP-A inhibits thrombin-induced coagulation of citrated plasma. The presence of antithrombin III (AT III) was necessary since PAPP-A had no inhibitory effect on coagulation of AT III-depleted plasma. The effect of PAPP-A is thus similar to that of heparin. This property of PAPP-A was used to develop a bioassay. Thrombin-induced polymerization of purified fibrinogen was measured in a spectrophotometer. AT III is a weak inhibitor of polymerization, but its effect is magnified in the presence of PAPP-A or heparin. The residual thrombin activity, when plotted against the concentration of PAPP-A, gives a linear relationship. The assay conditions developed allow maximal sensitivity and reproducibility. The kinetics of inhibition due to PAPP-A and heparin was first order. With this bioassay, activities of PAPP-A molecules isolated by the same technique from different fetomaternal compartments were compared.

Antithrombin III↗

Urodynamic and clinical assessment of the Lyodura sling operation for urinary stress incontinence.

A Lyodura sling operation for urinary stress incontinence was performed on 36 patients. The success rate was 89%, when success was defined as absence of objective urine loss at coughing or straining, with full bladder in the upright position and during a Urilos test, at least 6 months after surgery. Full urodynamic assessment, including urethral rest and stress profiles, were performed before, and 6 months after, surgery. Success of the operation depended mainly on enhancement of urethral pressure transmission. Functional length of the urethra and maximal urethral pressure did not influence the success rate. The procedure is especially suitable in patients with some degree of uterine or vaginal prolapse.

Cough↗

Mating is random.

Human leukocyte antigen (HLA) typing was undertaken in 151 unrelated blood donors and in 35 normal couples having at least two living children. We compared observed and expected sharing of HLA antigens at four loci in normal couples. We also compared the observed sharing in couples with the expected sharing in unrelated blood donors if taken two by two and with the sharing observed after 1000 "synthetic matings" of normal couples. No statistically significant difference in HLA sharing appeared between these groups. Furthermore no differences were observed in the probabilities of sharing individual HLA antigens among the different groups. We thus conclude that the observed HLA sharing in normal couples is governed by chance alone and that mating is random in our population.

Female↗

Long-term results of GnRH analogue (Buserelin) treatment in girls with central precocious puberty.

The GnRH analogue Buserelin was given for one year to six girls with central precocious puberty in a daily subcutaneous dose of 20 micrograms/kg/day. A decrease of plasma estradiol and vaginal maturation index to prepubertal values was obtained in 5 out of 6 cases. Bone maturation decreased and final predicted adult height improved significantly. This analogue of GnRH appears to be an effective medication for gonadotropin dependent precocious puberty in girls.

Buserelin↗

[Reproduction and immune factors in the male].

Sperm antigenicity is demonstrated by the formation of sperm antibodies following vasectomy and by the possible occurrence of hypersensitivity reactions in women to seminal fluid. It may be that immunosuppressor factors in seminal plasma, as well as certain placental hormones, could explain the fact that sperm are not rejected immunologically in the female genital tract. The role of these different immune factors in male infertility and in the pathogenesis of AIDS is discussed.

Acquired Immunodeficiency Syndrome↗

[Reproduction and immune factors in women. Pregnancy, habitual abortion and HLA histocompatibility].

Immune tolerance of the mother towards the fetus, which is like an allograft, may be explained partially by the presence of immunosupressor factors produced by the placenta. The maternal production of antibodies against trophoblastic antigens would seem equally necessary to prevent the fetus being rejected by cytotoxic maternal lymphocytes. Where there is marked histocompatibility between partners the protecting antibodies are absent and that gives rise to repeated abortions. This hypothesis is discussed as well as the rationale of treatments that are aimed at increasing maternal production of protective antibodies in cases of habitual abortion.

Abortion, Habitual↗

In vitro production of pregnancy-associated plasma protein A by human decidua and trophoblast.

Immunohistochemical techniques and direct measurements of pregnancy-associated plasma protein A (PAPP-A) have demonstrated the presence of PAPP-A in trophoblast and decidua. The purpose of the present study was to investigate the possibility that these tissues are capable of producing PAPP-A in vitro. Trophoblast and decidua were obtained from term deliveries and from legal surgical terminations of pregnancy (7 to 12 weeks). In addition to trophoblast and decidua, myometrium was also obtained during two hysterectomies in the first trimester of pregnancy. Tissues were incubated in medium 199 at 37 degrees C under an oxygen/carbon dioxide atmosphere. Media containing either pregnancy-associated serum or non-pregnancy-associated serum were changed after 8 hours of incubation in medium 199 alone. In addition to PAPP-A, human placental lactogen (hPL) and prolactin (Prl) were measured in homogenates and media by radioimmunoassays in order to confirm the viability of the cultured tissues. Addition of pregnancy-associated serum to the media induced a significant release of PAPP-A from trophoblast and decidua when compared to that in control cultures. Non-pregnancy-associated serum had no effect. Myometrium did not release any measurable PAPP-A into the medium even in the presence of pregnancy-associated serum. Cycloheximide added to pregnancy-associated serum significantly inhibited the release of PAPP-A from trophoblast and decidua. These last tissues, irrespective of the culture condition, released significantly more PAPP-A as well as hPL and Prl than was initially present in the tissue. These data demonstrate that PAPP-A is released in vitro by trophoblast and decidua (but not by myometrium) and that this release can be magnified by a factor present only in pregnancy-associated serum. The release of PAPP-A, hPL, and Prl is considered as a de novo production since concentration of these proteins are higher in media and tissues after incubation compared to concentrations initially present in the tissue before culture and since cycloheximide significantly inhibits the release of PAPP-A, Prl, and hPL from the cultured tissues.

Culture Media↗

The disappearance rate of pregnancy-associated plasma protein-A (PAPP-A) after the end of normal and abnormal pregnancies.

PAPP-A is a macromolecular glycoprotein associated with human pregnancy. In vitro, PAPP-A is produced by explant cultures of trophoblast and decidua. The present work was undertaken to see if the presence of decidua had any effect on the disappearance rate of PAPP-A after removal of the placenta either by surgery or by spontaneous delivery. PAPP-A was measured before and at different times after a normal delivery (n = 6), after a termination of early pregnancy (n = 11) and after surgery for ectopic pregnancy (n = 8). The half life of PAPP-A after normal delivery (52.9 +/- 25.8 h, SD) was significantly (p less than 0.03) less than after a first trimester termination (93.9 +/- 41.6 h). After surgery for ectopic pregnancy in patients with curetted decidua, PAPP-A disappeared significantly faster (p less than 0.005) then in patients with intact decidua (84.1 +/- 17.8 vs 241.2 +/- 81.5 h). These results indicate that PAPP-A continues to be produced by the decidua after removal of the trophoblast in early pregnancy.

Abortion, Legal↗

Pregnancy-associated plasma protein-A (PAPP-A): concentration in uterine fluid and immunohistochemical localization in the endometrium.

Pregnancy-associated plasma protein-A (PAPP-A) was localized immunohistochemically in the endometrium and measured in uterine fluid of non-pregnant women. The variations of PAPP-A concentrations in uterine fluid during the menstrual cycle paralleled those found in the endometrium. In patients receiving hormone therapy there was a significant correlation between the uterine fluid PAPP-A concentration and the progestogen to oestrogen potency ratio of the hormonal treatment. The presence of PAPP-A in the uterine fluid cannot simply be explained by blood contamination or cell damage. These results are interpreted as indirect evidence for an exocrine as well as an endocrine secretion of PAPP-A by the endometrium which might be influenced by hormones.

Adult↗

Histochemical localization of pregnancy-associated plasma protein A in fetal, infant, and adult organs and comparison between antisera.

Histochemical localization of pregnancy-associated plasma protein A (PAPP A) was performed on various genital and extragenital organs from fetuses, infants, and adults. Three types of PAPP A reactive cells were found: endocrine, epithelial, and hematopoietic cells. Positive endocrine organs included the decidua and the fetal adrenal and Leydig cells. Positive epithelial cells were found in actively proliferating tissues, such as fetal renal tubules, fetal intestinal mucosa, and adult proliferative endometrial glands. In bone marrow, red cell precursors were PAPP A positive. Comparison of a commercially available antiserum with one raised in our own laboratory revealed significant differences in histochemical staining. The biological relevance of these findings remains to be determined.

Adult↗

Circulating beta-2-microglobulin levels during pregnancy and their possible relationship with feto-maternal histocompatibility.

Plasma beta 2 microglobulin (beta 2m) levels have been measured by radioimmunoassay in normal pregnant women, in two successive pregnancies of a woman who shares HLA antigens with her husband, in normal twin pregnancies, in toxemic pregnancies and in hydatidiform moles. During normal pregnancy, plasma beta 2m levels decrease reaching a minimum at week 14 and increase thereafter to a maximum at week 34. In the two successive pregnancies of the one patient with HLA compatibility, beta 2m concentrations were significantly lower than in normal pregnancies. Women with monozygotic twins had significantly less beta 2m than women with heterozygotic twins. Toxemic patients bearing female fetuses had also statistically lower beta 2m levels than toxemic women with male fetuses. Patients suffering from hydatidiform moles had beta 2m levels in the range of normal pregnant patients. Since circulating beta 2m is produced by lymphocytes one might assume that low beta 2m levels reflect a reduced activity of lymphocytes. The results presented here allow to propose a hypothesis which will have to be verified that reduced beta 2m levels are associated with an increased feto-maternal histocompatibility.

Adult↗

Pregnancy-associated plasma protein-A (PAPP-A) and immunosuppressive activity in split ejaculates.

Pregnancy-associated plasma protein-A (PAPP-A) and phytohemagglutinin (PHA)-induced lymphocyte transformation were measured in split ejaculates of 17 normal volunteers. The concentration of PAPP-A was identical in both fractions of the ejaculate but the first fraction was twice as immunosuppressive as the second fraction. The origin of PAPP-A in men as well as its possibility of being an immunosuppressor is discussed.

Ejaculation↗

Pregnancy-associated plasma protein-A (PAPP-A) inhibits thrombin-induced coagulation of plasma.

Concentrations of immunoreactive PAPP-A have been found significantly lower in the serum as compared to heparin or EDTA plasma from the same patients. After coagulation significant amounts of PAPP-A remain associated with the clot. Purified PAPP-A inhibits thrombin induced coagulation of plasma. This inhibition cannot be attributed to a direct effect of PAPP-A on thrombin. It is exerted via an activation of endogenous antithrombin III since the inhibitory effect of PAPP-A on thrombin induced coagulation in a euglobulin system can be observed only if antithrombin III is added. The fact that protamine sulphate is capable of neutralizing the inhibitory effects of PAPP-A made us postulate that PAPP-A, like heparin, possesses strongly acidic residues which bind to protamine.

Animals↗