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Biomedical subjects

H Bohn

Publications and source records attributed to H Bohn.

At least 91 records · Page 5Linked to original sources
PubMed1985

Synthesis of placental protein 12 by human decidua.

The synthesis and secretion of placental protein 12 (PP12) were studied in tissue culture using explants of decidua, amnion, chorion, and placenta from seven full term pregnancies. The total amounts of PP12 in media and tissues were measured by RIA, and new protein synthesis and secretion by decidual explants were demonstrated by the incorporation of [35S]methionine into PP12 after 20 h of incubation with 12.5 microCi/ml [35S]methionine. Cycloheximide was used to study the effect of a protein synthesis inhibitor on the secretion of PP12 by decidua. Significantly more PP12 (P less than 0.001) was released into the medium from decidual explants than from chorion and amnion explants throughout the experimental period of 24 h. When incubated under identical conditions, placental explants released no detectable PP12. In decidual tissues and their culture media, the total amount of PP12 was 127.4% higher after incubation than before incubation (P less than 0.001). No increase was found when chorion and amnion were cultured. The addition of cycloheximide into cultures decreased the total amount of PP12 in the decidua and in its culture medium by more than 50%, indicating that one part of PP12 in decidua was performed and another part was newly synthesized. Decidual explants incorporated [35S]methionine into immunoprecipitable PP12 indicating new PP12 synthesis. In gel filtration, 77% of decidual [35S] PP12 eluted in the same position as purified PP12. In sodium dodecyl sulfate polyacrylamide gel electrophoresis, the migration mobility of [35S]PP12 was identical with that of purified PP12. Our results clearly demonstrate that PP12 is a decidual rather than a placental protein.

Culture Media↗
PubMed1985

[New cardiovascular acting 2-aryl-2-imidazolinyl-acetic acids. Synthesis and pharmacologic effects].

The syntheses of new 2-aryl-2-imidazolinyl-acetic acids and esters are reported together with pharmacological results concerning structure-activity relationship. In contrast to the already known but inactive N(1)-alkylated derivatives of 2-arylamino-2-imidazolines the new compounds with an aryl acetic acid substitution in N(1) position of the imidazoline nucleus show the bradykardic activity of the exocyclic alkylated clonidine derivatives such as alinidine. The majority of these new substances reduce blood pressure and heart rate in anesthetized rats significantly with a long duration of action. 2-[2-(2,6-Dichloro-phenylamine)-2-imidazoline-1-yl]-2-(2-thienyl)- acetic acid 8a is the most potent compound. Blood pressure is lowered by 30-40 mmHg and heart rate by 175 beats/min with a duration of action greater than 60 min. The effect is weakened if the thienyl radical is replaced by other heterocycles or if the 2,6-dichlorphenyl group is replaced by a hydrogen atom. The variation of the substituents in the phenyl nucleus shows that the 2,6-dichlorphenyl structure is the optimum substitution pattern, as in the case of clonidine. In the series comprising the 2-[2-(2,6-dichlorphenylamino)-2-imidazoline-1-yl]-2-phenyl acetic acids (8j-8n) the incorporation of different substituents into the phenyl nucleus in the 2-position results in derivates of different activity. The esters 9a-9c show a faster onset of action as compared to the corresponding carboxylic acid 8a. The most interesting effect of compound 8a in normotensive conscious dogs is a strong and long-lasting decrease in heart rate accompanied by a moderate LVP dp/dtmax decrease, weak lowering of blood pressure and slight increase in LVEDP. After blocking beta-receptors by atenolol the compound 8a still reduces heart rate. Results in ganglion-blocked and pithed rats indicate a presynaptic and postsynaptic alpha 2-agonistic effect. A decrease in sympathetic tone as well as an increase in vagal activity in conscious dogs are considered as possible causes for bradycardic activity. Unlike alinidine, however, compound 8a does not affect directly sinus node function. The bradycardic effect of compound 8a which results in a decrease in oxygen consumption is supposed to be the cause of the reduction of infarct size in anesthetized dogs by 28%.

Acetates↗
PubMed1985

New pregnancy and placental proteins and their possible diagnostic significance.

In our laboratory a large number of, for the most part, new proteins have been detected by immunochemical methods in extracts from human term placentae: namely 3 pregnancy proteins (SP1, SP2 and SP3), around 40 soluble placental tissue proteins (PPs) and at least 11 different solubilized, apparently membrane-associated, tissue proteins. A great deal of the new proteins has been already isolated to purity and characterized. The treatise gives an overview of what is known of the physico-chemical properties and of the possible biological role of these proteins as well as of their occurrence in tissues and body fluids. It also summarizes the possible diagnostic significance of detection and measurement of these proteins on the one hand in pregnant women, on the other hand in patients with tumours and other diseases, as far as this has been already investigated.

Amniotic Fluid↗
PubMed1984

Pregnancy-specific beta-1 glycoprotein (SP-1) in breast carcinoma. Pathologic and clinical considerations.

Ectopic production of placental proteins by a variety of nontrophoblastic epithelial tumors is well recognized. Pregnancy-specific beta-1 glycoprotein (SP-1), a recently described placental protein, has been detected both in the serum and tumors of patients with breast carcinoma. To assess the significance of SP-1 in breast carcinoma, we stained 139 cases of primary breast carcinoma for SP-1 using the immunoperoxidase technique. Overall, 55 (40%) of breast cancers were positive for SP-1; focal positivity was also noted in normal breast epithelium and fibrocystic disease. Both intraductal (32%) and infiltrating duct (43%) carcinomas were more often positive than either in situ (5%) or infiltrating (26%) lobular carcinomas. SP-1 positivity in tumors of infiltrating duct morphology less than 3 cm in diameter, correlated highly (P less than 0.01) with the presence of axillary lymph node metastases. The presence of SP-1 in normal breast epithelium and fibrocystic disease and the low rate of positivity in lobular carcinoma casts doubt on the usefulness of SP-1 as a tumor marker. However, these findings suggest that immunopositivity for SP-1 in small infiltrating duct carcinomas may be an indicator of poor prognosis.

Breast Neoplasms↗
PubMed1984

Serum levels of placenta-specific tissue protein 12 (PP12) in pregnancies complicated by pre-eclampsia, diabetes or twins.

PP12 is one of the recently discovered soluble tissue antigens of the placenta. During normal pregnancy maternal serum PP12 levels rise during the first 18 weeks reaching a mean peak value of 139.9 +/- 40.26 micrograms/l; after that there is a fall to a mean value of 111.9 +/- 42.39 micrograms/l between 28 and 40 weeks. Significantly higher mean serum PP12 levels were found in the third trimester in two high risk pregnancy groups (281.09 +/- 117.08 micrograms/l in pre-eclamptic toxaemia and 203.71 +/- 73.77 micrograms/l in diabetes) while serum PP12 levels remained normal (114.94 +/- 58.06 micrograms/l) in twin pregnancy. The increase of serum PP12 concentration in toxaemia and in diabetes may be of considerable diagnostic significance.

Female↗
PubMed1984

The content of placental protein 12 in decidua and fetal membranes is greater than in placenta.

Radioimmunoassay, gel filtration and sodium dodecyl sulphate-polyacrylamide gel electrophoresis were used to study the content and properties of placental protein 12 (PP12) in the placenta, decidua and fetal membranes. The tissues were obtained from early pregnancy in 12 cases, and after normal term delivery in eight cases in seven of which chorion and amnion laeve were also studied. There was more PP12 in decidua and fetal membranes than in placenta. The decidua/placenta ratio of PP12 content ranged from 2 to 1154 (mean 193, SEM 66). These results suggest that PP12 is a decidual rather than placental protein.

Adolescent↗
PubMed1984

Human preovulatory follicular fluid, luteinized cells of hyperstimulated preovulatory follicles, and corpus luteum contain placental protein 12.

RIA gel filtration, isoelectric focusing; and immunoperoxidase staining were employed to study the occurrence and physicochemical characteristics of placental protein 12 (PP12) in the human ovary, corpus luteum, and preovulatory follicular fluid. Fluid aspirated from 75 follicles from 22 women hyperstimulated for in vitro fertilization contained 6-230 micrograms/liter PP12-like immunoreactive material. The dose-response curves of follicular fluid PP12, amniotic fluid PP12, and purified human placental PP12 were parallel in the PP12 RIA. In gel filtration, follicular fluid PP12 eluted in the same volume as purified PP12. The isoelectric point of follicular fluid PP12 was 4.9 and that of purified placental PP12 4.6-4.7. A positive correlation was found between follicular fluid estradiol and PP12, progesterone and PP12, and follicular fluid volume and PP12 concentrations. By immunoperoxidase staining, PP12 was not detectable in unstimulated ovarian tissue before ovulation. In hyperstimulated preovulatory follicles biopsied in connection with follicle aspiration, PP12 was found in the granulosa cells which were luteinized (n = 3), whereas in those hyperstimulated follicles (n = 5) with no luteinization, no PP12 was found either. PP12 was seen in all corpora lutea (n = 5) from unstimulated menstrual cycles. These results show that the occurrence of PP12 is not limited to the placenta. The correlation between follicular fluid steroid and PP12 levels and the findings by immunoperoxidase staining suggest that PP12 is related to endocrine phenomena of the ovary, possibly to the luteinization process.

Chromatography, Gel↗
PubMed1984

The immunocytochemical location of two membrane-associated placental tissue proteins in human and cynomolgus monkey placentae.

Using the PAP technique, the location of two new membrane-associated placental tissue proteins, MP1 and PP4 was studied in the placenta, its membranes, decidua and umbilical cord of human and cynomolgus monkeys. The results were the same throughout pregnancy. MP1 was located in the syncytiotrophoblast and trophoblastic cells of the reflected chorion. Other placental tissue components (cytotrophoblast, amnion, decidua, and umbilical cord) were negative. At present, MP1 appears to be specific for trophoblast. PP4 was located in the syncytiotrophoblast. Furthermore clear positive staining for PP4 was found in the villous cytotrophoblast, reflected and basal chorion, amnion, umbilical cord and decidua. In addition, PP4 was positive in some granulocyte-like blood cells in the intervillous space. Immunocytochemically, the most positive staining for both proteins was observed in the membrane of villous syncytiotrophoblastic cells. The findings in the placenta of cynomolgus monkeys were similar to those in women. The monkey could, thus, serve as a model for the investigation of these new membrane-associated placental tissue proteins.

Animals↗
PubMed1984

Detection and localization of placental protein 14-like protein in human seminal plasma and in the male genital tract.

The concentration of PP14 in seminal plasma was determined by radioimmunoassay. The levels were 13-362 mg/liter in normospermic specimens (n = 36), 10-252 mg/liter in samples from 46 infertile men (oligo-, astheno-, terato- or necrospermia), and 30-233 mg/liter in 7 vasectomized men. No significant difference was found in the PP14 levels in the groups examined. Low PP14 levels (13-25 micrograms/liter) were detected in male sera. In RIA, serial dilutions of seminal plasma and purified PP14 gave parallel dose-response curves. In tandem-crossed immunoelectrophoresis, seminal plasma PP14 showed a reaction of identity with PP14 purified from human term placenta. The isoelectric point of seminal plasma PP14 was 5.2-5.4 and that of early maternal serum PP14 was 4.8-4.9. In the normospermic group a moderate negative correlation (p less than 0.05) was found between the volume of seminal plasma and the PP14 level, whereas the correlation was positive (p less than 0.05) in the infertile group. There also was a negative correlation (p less than 0.05) between the percentage of motile spermatozoa and PP14 concentration. No correlation was observed between the sperm count or age of men and PP14 level in seminal plasma. The origin of seminal plasma PP14 is not from the testes, as the levels in vasectomized and nonvasectomized men were similar. By immunoperoxidase staining, PP14 was detected in the epithelium of seminal vesicles but not in the testis.

Adult↗
PubMed1983

The radioimmunoassay of human placental protein 14 (PP14).

The development and validation of a radioimmunoassay for the measurement of human placental protein 14 in maternal serum is described. The mean concentration of this protein in serum from 22 normal pregnant women showed a decline during the third trimester from 120 micrograms/l at 27 weeks gestation to 65 micrograms/l at term. Serum samples from 16 patients with intra-uterine growth retardation tended to contain lower concentrations of placental protein 14, these results reaching significance at weeks 36-38 of gestation. Of seven patients with pre-eclampsia from whom two or more blood samples were taken, four showed increases in concentration of this protein as pregnancy proceeded, compared with the normal pattern of decreasing values.

Blood Specimen Collection↗
PubMed1983

Purification of pregnancy-specific beta 1-glycoprotein with a monoclonal antibody immunoadsorbent.

Hybrid cell lines secreting monoclonal antibodies against pregnancy-specific beta 1-glycoprotein (SP1) were produced by fusion of a mouse myeloma cell line with spleen cells from BALB/c mice immunized with purified placental SP1. The clones were further grown intraperitoneally in mice, and the ascites fluids contained anti-SP1 antibodies in high titers. One of the monoclonal antibodies was coupled to cyanogen-bromide-activated Sepharose and used for affinity chromatography of SP1 using late pregnancy serum as starting material. The purification of SP1 by means of immunoadsorption utilizing monoclonal antibodies offers remarkable advantages compared with the purification procedures used so far.

Animals↗
PubMed1983

Concentration of placental protein 10 (PP10) in maternal serum and amniotic fluid throughout normal gestation and in pregnancy complicated by fetal growth retardation.

PP10, a new placental glycoprotein, was studied by a specific and sensitive double-antibody radioimmunoassay in maternal serum and other body fluids throughout pregnancy. The mean value of serum PP10 in healthy nonpregnant individuals was approximately 10 microU/l. During normal pregnancy it rose to 3,500 microU/l. The rate of rise was obtained from 78 normal pregnancies with 279 single assay values from weeks 6-40. The shape of the curve resembled that for other placental proteins (HPL, SP1). PP10 levels in amniotic fluid were measured in 145 samples from weeks 13-55 of normal pregnancies and at term. The mean concentration was 500 microU/l until week 18 and then rose slowly. Cord blood contained only trace amounts. PP10 was not found in maternal urine. The concentration in maternal serum and amniotic fluid was higher in twin pregnancies than in singleton pregnancies. In 46 cases with low birth weights the PP10 levels in maternal serum were significantly lower than normal. Simultaneous measurements of PP10 and E3, HPL and SP1 were made in 17 individual follow-up's. PP10 was comparable with E3 and appeared to be better than HPL and SP1 in predicting intrauterine fetal growth retardation.

Amniotic Fluid↗
PubMed1983

Levels of placenta-specific tissue protein 12 (PP12) in serum during normal pregnancy and in patients with trophoblastic tumour.

A sensitive radioimmunoassay method has been developed to measure soluble placental protein 12. Using this method trace amounts of PP12 have also been detected in the sera of healthy non-pregnant subjects (24.0 +/- 6.15 micrograms/l). During normal pregnancy serum PP12 levels rose rapidly reaching a peak value of 139.90 +/- 40.26 micrograms/l at 18 weeks. Serial determinations of PP12 have been made in 31 patients with trophoblastic tumours (16 hydatidiform moles, 10 invasive moles and five choriocarcinomas). It has been found that in patients with hydatidiform and invasive moles its initial values are extremely high (342.9 +/- 257.9 micrograms/l and 279.3 +/- 103.1 micrograms/l, respectively), much exceeding the non-pregnant and normal pregnant values. After evacuation of hydatidiform moles serum-PP12 rapidly fell to the upper limit of normal at 21-28 days, and to normal values at 8-12 weeks after operation. In patients with invasive mole requiring chemotherapy the rate of fall of PP12 level was slower. In patients with choriocarcinoma serum-PP12 levels were moderately raised (59-132 micrograms/l) and followed the clinical course of the disease. Serum-PP12 levels would seem to be of less value in monitoring patients with trophoblastic tumours than other tumour-markers (hCG, and SP1).

Choriocarcinoma↗
PubMed1983

Serum levels of placental protein 10 (PP10) in women with breast cancer and genital carcinoma and in healthy male and female subjects.

PP10, a recently characterized glycoprotein from human placenta, was studied using a specific double-antibody radioimmunoassay in the serum of about 100 volunteers and 200 cancer patients. Elevated levels (greater than 20 nU/ml) were found in 87% of patients with primary breast cancer, in 100% of those with primary genital tumours and in 78% of patients with recurrent disease. PP10 was also measured in tumour extracts and in some patients with benign tumours. The serum concentration decreased within a few weeks after removal of the tumour. There were no significant correlations of the PP10 level with age, tumour size, histological grading or lymph node involvement. Sequential determinations of PP10 during cytostatic therapy sometimes showed rising levels accompany the development of metastases. PP10 can be regarded as a tumour associated protein and a tumour marker in gynaecological practice.

Age Factors↗
PubMed1983

Immunologic and biological properties and clinical significance of placental proteins PP5 and PP12.

Among the number of newly isolated placental proteins, PP5 and PP12 share some common characteristics: Both are present in the syncytiotrophoblast of normal placenta and hydatidiform mole, but less frequently, if at all, in choriocarcinoma. The levels in heparinized plasma of both proteins are lower than those in serum, and both are heat-labile. The function of PP12 is completely unknown, whereas PP5 appears to be related to the blood coagulation and fibrinolytic systems at the placental site through its antiplasmin activity. Many exciting avenues of research have been opened to uncover the biological role of these proteins in fetal development and cancer. We are pursuing this research with the immediate goal of assessing the role of PP12 in the blood coagulation system and of studying the expression of both proteins in various forms of cancer.

Amniotic Fluid↗
PubMed1983

Purification and characterization of two new soluble placental tissue proteins (PP13 and PP17).

Two new soluble placental tissue proteins (PP13 and PP17) have been isolated and characterized. PP13 has an electrophoretic mobility the same as that of albumin, an isoelectric point in the range 4.7-4.8 and a sedimentation coefficient of 3.1 S. Its molecular weight was found to be 30 000. PP13 appears to be composed of two identical subunits which are held together by disulfide bonds. PP17 has an electrophoretic mobility in between the beta 1- and alpha 2-globulins, an isoelectric point in the range 5.2-5.3 and a sedimentation coefficient of 2.7 S. Its molecular weight was determined to be 30 300 by ultracentrifugation and 38 000 by SDS-polyacrylamide gel electrophoresis. PP17 apparently consists of a single peptide chain. The amino acid and carbohydrate compositions of these proteins also have been determined. Immunochemical methods were used to detect and quantitate the new proteins in extracts of placental and other human tissues as well as in body fluids. From one human term placenta an average of 3.7 mg PP13 and 2.5 mg PP17 could be extracted. In concentrated extracts of other human tissues and in body fluids, these proteins could not be detected, at least not in concentrations higher than 1 mg/dl. The immunohistochemical localization of these proteins as well as measurement of their concentrations in body fluids by sensitive radioimmunoassays are presently under investigation.

Amino Acids↗
PubMed1982

Physicochemical studies of pregnancy-specific beta 1-glycoprotein: unusual ultracentrifugal and circular dichroic properties.

The molecular properties of native and modified pregnancy-specific beta 1-glycoprotein (SP1) from human placenta were evaluated by sedimentation equilibrium, gel electrophoresis, and circular dichroic measurements. Native SP1 contained 6.2% N-acetylneuraminic acid (NANA), 5.8% galactose (Gal), 13% N-acetylglucosamine, 6.5% mannose, and 1.1% fucose but no detectable N-acetylgalactosamine. Treatment with mixed exoglycosidases and alpha-mannosidase removed 79% of the carbohydrate including all of the NANA and Gal. The intensity of the circular dichroic spectrum of SP1 in the far ultraviolet was quite low with a positive maximum at 235 nm and a negative maximum at 215 nm. The 235-nm band was lost upon treatment with reducing agents or with guanidinium chloride (GdmCl), but not by treatment with neuraminidase. Treatment of SP1 with neuraminidase, or with mixed exoglycosidases and alpha-mannosidase, resulted in decreases of the apparent molecular weight obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Neither exposure of SP1 to GdmCl nor its reduction and alkylation resulted in the appearance of subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partial specific volume of SP1 determined experimentally by comparing sedimentation equilibrium profiles in H2O and D2O was 0.695 +/- 0.007 mL/g. The molecular weight of SP1 in 6 M GdmCl (in the presence or absence of reducing agents) by equilibrium sedimentation was 42 300 +/- 400. In the absence of denaturing agents, SP1 existed in the form of aggregates (at least as high as trimeric SP1) that dissociated only slowly upon dilution. The presence of these aggregates may contribute to the reported molecular heterogeneity of SP1.

Alkylation↗