Biomedical subjects

H Bohn

Publications and source records attributed to H Bohn.

At least 19 recordsLinked to original sources

PubMed1999

Isolation and sequence analysis of a cDNA encoding human placental tissue protein 13 (PP13), a new lysophospholipase, homologue of human eosinophil Charcot-Leyden Crystal protein.

Expression of placental tissue protein 13 (PP13) in different human tissues was investigated by chemiluminescence Western blot analysis using monospecific anti-PP13 serum. In term placentae we detected a 16 kDa single protein band immunochemically identical to the purified PP13 antigen. After investigation of 26 types of human fetal and adult tissue, PP13 was also found in certain other normal and tumorous tissue extracts. It is not secreted into circulation as we could not find PP13 in sera of pregnant women. A full length cDNA with 578 bp insert was isolated by screening a human placental cDNA library with anti-PP13 serum. The open reading frame of the cDNA encodes for a 139-residue-long protein with a predicted molecular mass of 16.118 kDa, identical to the previously isolated and characterized PP13 antigen described in 1983. By alignment search of the protein databank PP13 is highly homologous (69 per cent) to the 16.5 kDa human eosinophil Charcot-Leyden Crystal protein, a unique dual-function lysophospholipase, a member of the beta-galactoside binding S-type animal lectin superfamily. Northern blot analysis revealed a 600 bp PP13 mRNA, detected only in placental tissue from 16 types of human healthy adult tissue. Lysophospholipase activity of PP13 was confirmed by(1)H and(31)P nuclear magnetic resonance (NMR) measurements.

Adult↗

PubMed1998

Cloning and sequence analysis of cDNAs encoding human placental tissue protein 17 (PP17) variants.

Using monospecific anti-PP17 serum with chemiluminescence Western-blot analysis, we detected different molecular-mass variants of human soluble placental tissue protein 17 (PP17) in different normal adult and fetal human tissues besides term placenta. 13 cDNAs with three different insert lengths encoding PP17 variants were isolated by screening a human placental cDNA library. Sequence analysis of the shortest clones showed that the inserts contain the same open reading frame encoding PP17a variant (28,129 kDa) consisting of 251 residues, which is identical to the previously isolated and characterised PP17 antigen described in 1983. The ubiquitous PP17b variant is encoded by longer clones and contains 434 residues with a predicted molecular mass of 47,208 kDa. Compared to normal conditions, these newly discovered PP17 variants are overexpressed in cervix carcinoma tissue, as are their three different-size messenger RNAs in HeLa cell line. Increased amounts of PP17b are secreted into the circulation in cervix carcinoma patients. We also observed a typical elevation in serum levels of PP17 variants during healthy pregnancy. An alignment search of the protein databank showed that PP17a and PP17b are homologous to adipose tissue differentiation and lipid-droplet-associated proteins: human adipophilin, mouse adipose differentiation-related protein and rat perilipin A and B.

Amino Acid Sequence↗

PubMed1998

Glycodelins.

Glycodelins are 28 to 30-kD glycoproteins synthesized in various glands, notably those of the male and female reproductive organs. Depending on the site of origin, the same protein backbone is glycosylated in different ways, yielding glycodelins with different biological actions. Thus, human endometrium-derived glycodelin-A is temporally expressed in the latter half of the menstrual cycle, consists of unique sialylated and fucosylated lacdiNAc oligosaccharide sequences, and inhibits sperm-egg binding. By contrast, glycodelin-S from seminal vesicles has no such oligosaccharide sequences and no contraceptive activity. Glycodelin-A also has potent immunosuppressive properties, and its chemically modified forms inhibit transmission of HIV in vitro. Studies are reviewed suggesting that glycoforms dictate the function of human glycodelins, and that some of the oligosaccharide recognition sites present in the human gametes and immune cells have converged.

Alpha-Globulins↗

PubMed1996

The role of factor XIIIa in the mesenchymatogenesis of the human placenta: an immunohistochemical analysis.

Human placentas from normal pregnancies [9], interrupted pregnancies due to congenital anomalies of the fetuses [7] and legal abortions [9] were examined immunohistochemically using monoclonal antiserum for factor XIIIa. Hofbauer cells of the chorionic villi were strongly positive for factor XIIIa. Deeper staining in early pregnancy reflects the greater numbers of Hofbauer cells in this period of gestation. Our findings support the hypothesis that the presence of factor XIIIa in the Hofbauer cells promotes the maturation of the chorionic villi.

Chorionic Villi↗

PubMed1995

Immunohistochemical localization of pregnancy-related placental protein 4 in human placenta, umbilical cord and adult human female genital tissues.

Placental protein 4 (PP4) is a soluble placental tissue protein which was isolated from human placenta. The aim of the present study was to demonstrate the localization of cells containing PP4 in human placenta and in various female genital tissues under normal conditions. PP4 immunoreactive structures were demonstrated by using the peroxidase-antiperoxidase immunohistochemical technique. The samples were obtained from normal human placenta, umbilical cord, uterine cervix, endometrium, ovary and vulva. The most differentiated trophoblastic cells, the syncytiotrophoblasts, as well as the intermediate trophoblast cells contained PP4. PP4 immunoreactivity was present in umbilical cord as well. Occasionally PP4 was detected in normal ovarian, endometrial or vulvar tissue samples. Cervix and myometrium were free of PP4 immunoreactive material. PP4 staining was cytoplasmic. Our findings indicate that PP4 cannot be considered specific for the placenta since it is present in some human adult tissues as well.

Annexin A5↗

PubMed1995

Cardiovascular actions of the furoxan CAS 1609, a novel nitric oxide donor.

1. This study examines the cardiovascular effects of CAS 1609 (4-hydroxymethyl-furoxan-3-carboxamide) in vitro as well as in vivo in various animal models. 2. CAS 1609 relaxed guinea-pig pulmonary artery strips without endothelium with IC50-values of 0.9 microM (phenylephrine contracted) and 15 microM (KCl-depolarized). This effect was inhibited by oxyhaemoglobin. In these arteries CAS 1609 significantly increased (+192%) guanosine 3':5'-cyclic monophosphate levels, which indicates that the compound acts as a donor of nitric oxide (NO). 3. In the anaesthetized pig, CAS 1609 (0.3-1.0 mg kg-1, i.d.) significantly lowered blood pressure and left ventricular end-diastolic pressure. Left ventricular contractility was slightly reduced and heart rate remained almost unchanged. 4. In anaesthetized dogs, i.v. or i.d. administration of CAS 1609 (0.3-3.0 mg kg-1) decreased, in a dose-related fashion, preload and afterload of the heart, cardiac output, left ventricular work and myocardial oxygen consumption. This haemodynamic profile is similar to that of known NO-donors. 5. In anaesthetized dogs with acute heart failure due to intracoronary injection of microspheres, CAS 1609 (0.3 mg kg-1, i.v.) improved the haemodynamic condition and reduced mortality by 80%. 6. In conscious dogs, oral treatment with a dose of 0.5 mg kg-1 given twice daily at 07 h 00 min and 19 h 00 min (each dose had a duration of action > or = 12 h) for 5 days showed no signs of tolerance to the haemodynamic effects of the drug. 7. All these data indicate that CAS 1609 is a potent, long-lasting orally active donor of NO, devoid of tolerance development.

Administration, Oral↗

PubMed1994

Antiischemic effects of pirsidomine, a new nitric oxide donor.

The antiischemic effect of pirsidomine (CAS 936 (3-(cis-2,6-dimethylpiperidino)-N-(4-methoxybenzoyl))-sydnon imine), a new nitric oxide donor, was investigated in a model of myocardial infarction in the dog. Dogs were anaesthetised, thoracotomized, and the left descending coronary artery was occluded for 6 h. Pirsidomine was given intraduodenally (i.d.) at the dose of 1.0 mg/kg to 11 dogs 30 min prior to coronary occlusion. Eleven dogs received the solvent i.d. and served as controls. Pirsidomine administration completely prevented the increase in left ventricular end-diastolic pressure and pulmonary artery pressure induced by the coronary occlusion and resulted in a marked decrease in systolic and diastolic blood pressure, cardiac output, left ventricular contractility, left ventricular work and left ventricular oxygen consumption. Additionally, pirsidomine completely prevented the occlusion-induced increase in flow in the non-occluded circumflex coronary artery. Regional blood flow measurements (with radioactive microspheres) revealed that pirsidomine induced a significant reduction in blood flow in the non-ischemic areas (both epi- and endocardial) but in the course of the ischemia, significantly increased flow in the ischemic epicardial areas. Infarct-size (triphenyltetrazolium chloride technique) in control dogs was 45% of the area at risk, but only 26% (P < 0.05) in pirsidomine-treated dogs. Thus, pirsidomine had a marked antiischemic effect in this model. This was probably due to the hemodynamic unloading of the heart as well as to redistribution of blood from the non-ischemic to the ischemic areas of the myocardium.

Animals↗

PubMed1994

Immunohistochemical localization of pregnancy-related placental protein 4 in nontumorous tissues and in gynecological tumors.

The aim of the study was to demonstrate the localization of placental protein 4 (PP4) in different nontumorous and tumorous tissues originating from the female genital tract. PP4 immunoreactivity was demonstrated using the peroxidase-antiperoxidase immunohistochemical technique. Tissue samples were obtained from the cervix and body of the uterus, ovary, vulva and from gestational trophoblastic tumors. PP4-positive cells were present in nontumorous tissues with various pathologic findings, and in many but not all benign gynecological tumors. Similar numbers of PP4-positive cells were located in malignant and benign gynecological tumors; however, PP4 staining intensity was greater in the malignant lesions. PP4-positive cells were found in hydatidiform moles and in choriocarcinoma. PP4 was distributed mainly in the cytoplasm, but it was also bound to the cell membrane. We conclude from these studies that PP4 is located in a variety of benign and malignant cells of the female genital tract and that these cells may be the source of plasma PP4 found in patients with these conditions.

Female↗

PubMed1993

New NO-donors with antithrombotic and vasodilating activities, II: 3-alkyl-N-nitroso-5-sydnone imines.

Fifteen 3-alkyl-, four 3-cycloalkyl-N-nitroso-5-sydnone imines and five 3-alkyl-N-nitro-5-sydnone imines were synthesized and their ability to inhibit platelet aggregation induced by collagen (Born-test) was studied in vitro. Dependent on the chemical structure, the IC50-values for the inhibition of platelet aggregation were in the range of 0.2-140 mumol/L. It is suggested that this scale reflects different binding properties of the nitrosimines with respect to the platelet membrane. Highest activities were observed for the 3-hexyl (2f) and the 3-cyclohexyl (2p) derivative. Three nitrimines (3e, 3f, 3i) also showed IC50 values below 10 mumol/L. For the nitrosimines 2a, 2f, and 2m antithrombotic activity was demonstrated in vivo. They inhibited laser induced arterial thrombosis in anesthetized rats up to 70% two h after oral administration. In conscious renal-hypertensive dogs, the decrease in systolic blood pressure and left ventricular enddiastolic pressure suggests an antianginal activity of the compound 2a similar to that of molsidomine (M). The smoother onset and the longer duration of action of the new compound as compared to M could be a significant advantage of 2a in the therapy of angina pectoris.

Animals↗

PubMed1993

The development of an enzyme immunoassay for placental tissue protein 17 (PP17) and its clinical significance.

We developed an enzyme immunoassay (EIA) for placental protein 17 (PP17) using avidin biotin binding, and measured the serum-PP17 levels of 37 healthy men, 103 nonpregnant women, 48 pregnant women, and 86 patients with gynecologic malignancies. The mean level was 12.8 ng/ml in healthy men and 44.2 ng/ml in nonpregnant women (p < 0.05). The calculated upper limit of normal was 97.8 ng/ml (mean + 2 sigma). The serum PP17 concentration was remarkedly reduced postmenopausally. Pregnant women showed a mean serum level of 19.2 ng/ml, which was significantly lower than that of nonpregnant women. Immunoserological results strongly suggest that PP17 is produced far more in the normal endometrium than in the placentae and decidua. Patients with gynecologic malignancies had obviously lower mean serum PP17 levels (8.3-19.9 ng/ml) than those found in healthy nonpregnant women. Measurement of the serum PP17 concentration might be useful in distinguishing gynecologic malignancies from various normal conditions.

Biomarkers, Tumor↗

PubMed1993

Levels of alpha2 pregnancy-associated glycoprotein in maternal circulation during pregnancy in the mink.

This is the first demonstration of alpha 2-pregnancy-associated glycoprotein (alpha 2-PAG) in the mink. Mink alpha 2-PAG exhibits complete immunological cross reaction with dog alpha 2-PAG when analysed in assays employing antisera against canine alpha 2-PAG raised in rabbits. Alpha 2-PAG was quantitated by rocket immunoelectrophoresis in heparin plasma samples obtained from the peripheral circulation of mink during the breeding season. The plasma levels recorded in male mink were significantly lower (23 AU/ml) than the levels recorded in females at any stage of the breeding period. Very early in the breeding season and 2 weeks after delivery the alpha 2-PAG levels were high (> 200 AU/ml) in the circulation of the female mink. Like alpha 2-PAG in the pregnant bitch, mink alpha 2-PAG concentrations reach a local maximum in mid-pregnancy, and a local minimum at term.

Animals↗

PubMed1992

Cardiovascular effects of the new nitric oxide donor, pirsidomine. Hemodynamic profile and tolerance studies in anesthetized and conscious dogs.

The hemodynamic profile of pirsidomine, a new donor of NO (nitric oxide), was evaluated in dogs. In anesthetized dogs, the intravenous or intraduodenal administration of pirsidomine (0.3-10 mg/kg) decreased dose relatedly the preload and afterload of the heart, total peripheral resistance, cardiac output, left ventricular work and myocardial oxygen consumption. In conscious renal-hypertensive dogs, oral administration of pirsidomine (1.0-10 mg/kg) caused a marked and sustained decrease in systolic blood pressure and left ventricular end-diastolic pressure, which was accompanied by a slight and transient increase in heart rate and contractility. The diastolic blood pressure was affected less than in anesthetized dogs. Similar hemodynamic effects were obtained with M1 (3-(1-(2,6-dimethylpiperidino))-sydnonimine; 0.3-1 mg/kg), the main metabolite of pirsidomine, and with the known NO donor, isosorbide-5-mononitrate (IS-5-MN; 2-10 mg/kg). Tolerance development after repeated administration of pirsidomine and IS-5-MN was also investigated. In anesthetized dogs, repeated intraduodenal administrations of pirsidomine did not attenuate the response whereas tolerance occurred with hemodynamically equieffective doses of IS-5-MN. In conscious dogs, long term oral treatment, three times daily every 8th h for 5 days, revealed tolerance to IS-5-MN, slight or no tolerance to pirsidomine, and no cross-tolerance between the two agents. The results indicate that pirsidomine possesses an antianginal hemodynamic profile similar to that of its main metabolite, M1, and of IS-5-MN. This suggests a common mode of action via the release of NO.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

The immunohistochemical localization of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in human and cynomolgus monkey placentae.

New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated by avidin-biotin immunoperoxidase technique in the human and cynomolgus monkey placentae, decidua and umbilical cords. In human early placentae, MP2 A, B, C, and E were localized mainly in the membrane of villous syncytiotrophoblasts and cytotrophoblasts. Histiocytes in the villous stroma were positive for MP2 A, B, D, and E. In human term placentae, obvious positive staining for MP2 A, B, C, and E was observed in the membrane of villous syncytiotrophoblasts, in the amniotic epithelium, and in the umbilical cord sheath. Histiocytes in the villous stroma were positive for MP2 A, B, C, E, and especially for MP2 D. Importantly, MP2 A, C, and E were positive in polymorphonuclear neutrophils, since most of these common antigens are also carcinoma-associated, suggesting clinical usage of MP2 proteins as a new tumor marker. In the cynomolgus monkey placentae, similar immuno-staining results were obtained. The monkey can thus serve as a experimental model for the investigation of the placental proteins.

Amnion↗

PubMed1992

Immunohistochemical and ultrastructural investigation of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in gynecologic neoplasms.

New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated immunohistochemically by avidin-biotin immunoperoxidase technique and immunoelectron microscopy in various gynecologic neoplasms and normal gynecologic tissues. MP2 A and MP2 B were not specific for malignant tumors. MP2 C was present in 67-100% of ovarian carcinomas, 100% of benign dermoid cysts, and 77% of endometrial carcinomas. Except for endocervical adenocarcinomas, MP2 D was hardly detectable in gynecologic malignancies. Although MP2 E was hardly detectable in benign gynecologic tumors, this protein was present in ovarian carcinomas, uterine squamous carcinomas, endocervical adenocarcinomas, and endometrial adenocarcinomas. These results suggest a possible clinical application of these MP2 proteins as a new tumor marker for gynecologic malignancies.

Biomarkers, Tumor↗

PubMed1991

Identity between the placental protein PP10 and the specific plasminogen activator inhibitor of placental type PAI-2.

The highly specific plasminogen activator inhibitor of placental type, PAI-2, occurs in the placenta in a low molecular mass form of 46.6 kDa, and in pregnancy plasma in a (possibly glycosylated) high molecular mass form of 60 kDa. Extensive knowledge is available about the functional properties of PAI-2 as a plasminogen activator inhibitor and about its molecular biology and regulation. Of the several placenta proteins (PP) isolated, one of them, PP10, has a molecular mass of 48 kDa and its occurrence in malignancy and in complications during pregnancy has been the topic of a number of studies, though its properties and physiological significance are unknown. The present findings constitute evidence of immunological identity between PP10 and PAI-2. The sections of the amino acid sequence of PP10 analysed here were found to have identical counterparts in the sequence of the low molecular mass form of PA1-2, but in several preparations PP10 was found to occur in an inactive two-chain form due to cleavage of an Arg-Thr bond, the two peptide chains being linked to each other by a disulphide bridge. The cleavage site is identical to that observed in the reaction between PAI-2 and urokinase. The results make it possible to coordinate and correlate the findings of many separate studies and our own observations on PP10 and PAI-2.

Amino Acid Sequence↗

PubMed1991

Isolation and characterization of five new soluble placental tissue proteins (PP22, PP23, PP24, PP25, PP26).

Five new soluble placental tissue proteins (PP22, PP23, PP24, PP25, PP26) were isolated to purity from saline extracts of human term placentas and characterized by their physico-chemical properties. Specific antisera to the new proteins were obtained by immunizing animals with the corresponding purified proteins. They were used to detect and quantitate the new proteins in extracts of placentas and other human tissues by immunochemical methods such as gel diffusion tests. The immunohistochemical localization of the new proteins as well as measurement of their concentrations in body fluids by sensitive radioimmunoassays are presently under investigation.

Animals↗

PubMed1991

Isolation and characterization of membrane-associated placental proteins.

Membrane-associated proteins (MPs) of the human term placenta (afterbirth) were obtained by extracting the insoluble part of the tissue with solubilizing agents, after the soluble material had been removed by washing with saline. The insoluble residue was subsequently exhaustively extracted first with the nonionic detergent Triton X-100 and then with 6 M urea. In the Triton extract eleven new different membrane-associated antigens could be detected by immunochemical methods; they were designated as MP2A to MP2L. One of these proteins (MP2C) was found to be immunochemically identical with the already described soluble placental protein PP21 [3]. MP1 another antigen detected in the Triton extract later was identified as heart stable alkaline phosphatase. In the urea extract eight different membrane-associated antigens could be identified by immunochemical methods; they were designated as MP3 to MP10. MP3 later was found to be immunochemically identical with laminin. All these membrane-associated proteins have now been isolated to purity and characterized by their physico-chemical properties. Specific antisera to the new proteins were obtained by immunizing animals with the corresponding purified proteins. They were used to detect and quantitate the new proteins in extracts of placentas and other human tissues by immunochemical methods such as gel diffusion tests. The immunocytochemical localization of the new proteins as well as measurement of their concentrations in body fluids by sensitive radioimmunoassays or enzyme immunoassays are presently under investigation.

Adult↗

PubMed1991

Immunochemically detected placental proteins and their biological functions.

During the last 20 years a systematic search for proteins occurring in human term placenta (afterbirth) has been performed in our laboratory. As a result more than 30 soluble placental proteins and at least 20 different solubilized antigens apparently derived from the placental membranes have been identified by immunochemical methods in extracts from human term placentas. Most of these proteins have already been isolated to purity and characterized by their physicochemical parameters. Specific antisera to these proteins were obtained by immunizing animals with the corresponding purified proteins. They were used detect and localize these antigens by immunochemical methods in the placenta and in other human tissues. Sensitive immunochemical assays have been developed to exactly quantitate the new proteins in body fluids and to find out the diagnostic significance of measurement of these proteins in pregnant women and in patients with tumors and other diseases. Another aim was to elucidate the biological functions of our immunochemically detected proteins. The results obtained thus far are reported.

Female↗