Search PubMed⌕ Search

Biomedical subjects

H Bohn

Publications and source records attributed to H Bohn.

At least 37 records · Page 2Linked to original sources
PubMed1991

Secretory endometrial protein PP14 in women with early pregnancy bleeding.

The decidualized endometrium produces secretory proteins of which secretory endometrial protein PP14 is the major product during the first trimester of pregnancy. The protein is secreted into the uterine lumen as well as into the peripheral blood. The purpose of this study was to examine whether decidual function, evaluated by the serum concentration of PP14, was different in women with early pregnancy bleeding compared to normal pregnant women. A reference range for serum PP14 was established on the basis of single samples from 236 normal pregnant women with ultrasonically confirmed gestational age. All the women were delivered of a normal child at term. The study comprised 128 pregnant women admitted because of vaginal bleeding between 6 and 18 weeks gestation. At ultrasonography, intrauterine fetal heart activity was either present or was confirmed at a subsequent examination. No difference was found in the serum level of PP14 compared to that in normal pregnancies, but women with vaginal bleeding and depressed PP14 levels appeared to have a 5-fold higher risk of preterm delivery than women with bleeding and normal PP14 levels.

Adult↗
PubMed1991

CAS 936, a novel syndnonimine with direct vasodilating and nitric oxide-donating properties: effects on isolated blood vessels.

Organic nitrates and sydnonimines exert their vasorelaxant activity by a common mechanism of action, i.e., release of nitric oxide (NO) and stimulation of the soluble guanylate cyclase of vascular smooth muscle cells. We wished to investigate the vasodilating activity of the novel sydnonimine CAS 936 in guinea pig isolated pulmonary arteries without endothelium. CAS 936 had no effect on contractions induced by norepinephrine (NE) or by the PGF2 alpha-analogue U46 619, but induced a longlasting relaxation of potassium depolarized arteries and of A23 187-contracted vessels. This effect was concentration-dependent (IC50 approximately 16 microM). Oxyhemoglobin and methylene blue had no inhibitory effect on CAS 936, whereas they inhibited the relaxations induced by SIN-1, a sydnonimine which acts by releasing NO. These results suggest that the vasodilating activity of CAS 936 is not related to NO. On the other hand, in vivo metabolites of CAS 936 inhibited NE- and U46 619-induced contractions. Oxyhemoglobin inhibited this effect. Therefore, we conclude that the CAS 936 molecule possesses a vasodilating activity of its own, whereas the metabolites may function as NO donors. The primary target of the intrinsic vasodilating activity of CAS 936 is very likely the vascular smooth muscle cell membrane. To determine which mechanism of action (NO unrelated or NO related) contributes mainly to the in vivo effects of CAS 936, studies of the metabolic fate of CAS 936 may be crucial.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Placental protein 4 as a possible tumor marker in ovarian tumors.

Placental protein 4 (PP-4), a recently characterized glycoprotein from human placenta, was studied using a specific double-antibody radioimmunoassay in sera of 130 volunteers, 76 ovarian tumor patients and in ovarian tumor cyst fluid and ascites of 21 patients. Elevated levels (greater than 3 micrograms/l) were found in 45 of 52 ovarian cancer patients (86.5%). PP-4 levels correlated significantly with staging. 31 patients with malignant ovarian tumor were monitored on 2-9 occasions during 5-82 weeks. Rising or falling levels of PP-4 correlated with progression or regression of disease in 25 of 31 instances (80.6%). Elevated levels were found in 10 of 24 benign and borderline ovarian tumors. Elevated PP-4 level does not indicate malignancy in each case. PP-4 can be regarded as tumor-associated antigen and an tumor marker in oncological practice.

Adenocarcinoma, Papillary↗
PubMed1991

Initial experience with placental protein 4 (PP-4) as tumor marker in cervical and endometrial cancer.

PP-4, a recently characterized glycoprotein from human placenta was studied using a specific double-antibody radioimmunoassay in sera of 130 volunteers, 74 cervical cancer patients and 43 endometrial cancer patients. Elevated levels (greater than 3 micrograms/l) were found in 35 (47.3%) cervical cancer patients and in 18 (41.9%) endometrial cancer patients. Degree of elevation were not correlated with clinical stage, histology, and histological degree of differentiation. 36 patients with cervical cancer and 20 patients with endometrial cancer were monitored on two to seven occasions during four to 50 weeks. Rising, remaining unchanged of falling levels of PP-4 correlated with progression, stabilization or regression of disease 55.5% in patients with cervical and 65.0% in patients with endometrial cancer. During and some months after external telecobalt irradiation therapy wide range of PP-4 levels were observed in some patients. The study suggest that PP-4 can be regarded as a tumor associated protein which most likely can serve as tumor marker in cervical and endometrial cancer.

Annexin A5↗
PubMed1990

Concentration of placental protein 19 in body fluid and placental tissues.

Placental protein 19 (PP19) is one of the new placental tissue proteins identified in extracts from human term placenta by Bohn and Winkler. We measured the PP19 concentration in body fluids and placental tissue by radioimmunoassay; the minimum detectable dose of standard was 1.5 ng/ml. Although ethylene diamine tetraacetic acid (EDTA-2K) inhibited the immunoreaction between PP19 (225/242) and anti-PP19 antibody (632 ZA), the PP19 concentration did not differ between serum and heparin and sodium citrate plasmas. The serum PP19 concentration was increased by hemolysis. In blood cell fractions separated by the Ficoll-Paque/Macrodex method, polymorphonuclear leukocyte fraction contained the highest PP19 concentration. The circulating serum PP19 concentration was 4.5 +/- 1.1 ng/ml (mean +/- standard deviation) in the proliferative phase (n = 8) and 5.1 +/- 1.6 ng/ml in the secretory phase (n = 7) for nonpregnant women, and 4.6 +/- 2.2 ng/ml from men (n = 12). Seminal plasma (n = 8) contained 212.2 +/- 99.7 ng/ml. The maternal serum PP19 concentration in 291 normal pregnancies increased from 6.2 ng/ml (median) at 6-7 weeks of gestation to 34.1 ng/ml at 38-39 weeks. The mean PP19 concentration was higher in amniotic fluid and retroplacental blood, but lower in umbilical cord blood than that in circulating maternal serum. In hydatidiform mole, vesicular fluid contained high PP19 concentration (1154.6 +/- 659.5 ng/ml), although these maternal serum concentration was not statistically higher than normal range. The chorionic villous trophoblast contained more PP19 than decidua, chorion, and amnion. These results suggest that PP19 has an extraplacental source, even though the chorionic villous trophoblast may be the main source throughout pregnancy.

Adult↗
PubMed1990

Enzyme immunoassay for placental protein 4 (PP4) and its possible diagnostic significance in patients with genital tract cancer.

We have established an enzyme immunoassay for placental protein 4 (PP4), by using avidin-biotin binding reaction, and set its normal range below 10.9 ng/ml (mean + 2 sigma). Throughout the menstrual cycle, the serum PP4 profile was similar to that of serum progesterone. In the follicular and ovulatory phase, PP4 remained relatively low, with the mean levels of 1.5 ng/ml and 1.8 ng/ml, respectively. In the luteal phase, the mean level was 3.2 ng/ml. In normal pregnancy, serum PP4 levels were low irrespective of gestational age, with a mean level of 3.0 ng/ml. There was only one case in which the serum PP4 level over 10.9 ng/ml. Mean serum PP4 levels and the frequencies of elevated serum PP4 levels were respectively 6.3 ng/ml and 11% in patients with benign ovarian neoplasms, 4.7 ng/ml and 6% in patients with endometriosis, and 5.5 ng/ml and 18% in patients with uterine myomata. The frequency of raised PP4 levels was 48% and the mean value was 13.3 ng/ml in patients with endometrial carcinoma, and the values were 44% and 13.4 ng/ml respectively in patients with cervical carcinoma. In patients with ovarian malignancy, the respective values were 15% and 7.0 ng/ml. The results did not relate to clinical stages of disease (FIGO), while the frequencies of elevated serum PP4 in patients with uterine carcinoma was over 40% in stage I diseases. Compared with other tumor markers such as carcino-embryonic antigen (CEA), tissue polypeptide antigen (TPA) and cancer antigen 125 (CA125), PP4 seems to be more promising as a marker of endometrial carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Annexin A5↗
PubMed1990

Cloning and prokaryotic expression of a biologically active human placental aldose reductase.

cDNA clones coding for human aldose reductase (AR) were isolated by antibody screening of a placental lambda gt11 cDNA library. The cDNA comprises the entire coding region and has a total length of 1,394 bp. The sequence deduced from the open reading frame encodes a protein of 316 amino acids and its amino acid composition is identical to the placental protein 9 (PP9), whose isolation and characterization were described by Bohn et al. (1982). The amino acid sequence of the placental human AR shows high homology to the rat AR; both proteins belong to the same protein superfamily as human liver AR, frog lens rho-crystallin, and bovine lung prostaglandin F synthase. Northern blot hybridization analysis revealed a size for the AR mRNA of approximately 1,500 bases. In addition to the full-length cDNA, one lambda gt11 clone was isolated which carries a putative intron of 597 bp at nucleotide position 754, corresponding to amino acid position 247. Expression of the AR cDNA in Escherichia coli resulted in the synthesis of a protein with a molecular weight of approximately 35 kD which can be immunoprecipitated specifically with antiserum raised against PP9. Despite the absence of a typical signal sequence, the human aldose reductase is partially translocated into the periplasm of the E. coli cells, where it is present in an enzymatically active form.

Aldehyde Reductase↗
PubMed1990

Cloning and expression of a cDNA encoding human placental protein 11, a putative serine protease with diagnostic significance as a tumor marker.

The placental protein 11 (PP11) can act as a tumor marker because of its specific association with various forms of cancer. A lambda gt11 cDNA library prepared from human placenta was screened with a polyclonal anti-PP11 antiserum. Out of 10(6) independent clones, only one clone reacted with the anti-PP11 antiserum. The isolated cDNA coded only for the carboxy-terminal part of PP11 and was subsequently used to rescreen a lambda gt10 placental cDNA library. Two cDNA clones out of 10(6) screened were identified encoding the entire protein of 369 amino acids, including a typical hydrophobic signal sequence of 18 amino acids. Expression of the PP11 cDNA coding sequence in Escherichia coli resulted in the synthesis of a protein with the expected size which can be specifically immunoprecipitated with anti-PP11 antiserum. Fractionation experiments revealed that two forms of the protein are present in the bacterial cell: a higher-molecular-weight form of approximately 42 kD in the cytoplasm and a smaller-molecular-weight form of approximately 42 kD in the periplasm. This result indicates that PP11 can be synthesized in E. coli and is process by removal of the hydrophobic signal sequence. Both the placental and the processed recombinant PP11 protein exhibit a protease activity.

Amino Acid Sequence↗
PubMed1990

Elevated sera levels of SP-1 induced by chemotherapy in patients with metastatic gestational trophoblastic diseases.

6 patients with invasive mole and 5 patients with choriocarcinoma were treated from 1983 till 1986. Serum samples were analyzed by simultaneous determining of pregnancy-specific beta-1-glycoprotein (SP-1) using enzyme-linked immunosorbent assay (ELISA) and beta subunit of human chorionic gonadotropin (beta-hCG) using Serono radioimmunoassay kit. In 2 patients with metastatic gestational trophoblastic disease (MGTD) SP-1 peaks were found during chemotherapy. In patients with MGTD with normalized beta-hCG levels a repeated, temporary elevation of isolated SP-1 levels was observed within some months following chemotherapy. After the last isolated peak of SP-1 the pulmonary metastases disappeared. This phenomenon was interpreted as a consequence of the oncolytic process in the affected tissue. In 1 patient with nonmetastatic choriocarcinoma SP-1 ELISA pseudoreaction was found. To recognize these pseudoreactions, a control plate with nonimmunized rabbit IgG was used, simultaneously with SP-1 determinations.

Adolescent↗
PubMed1989

Time-resolved immunofluorometric assay for placental protein 14.

A sandwich-type solid phase time-resolved immunofluorometric assay (IFMA) was developed for endometrial protein PP14 (placental protein 14). The assay utilizes affinity-purified polyclonal antibodies for coating the microtiter wells and for labelling with europium (III) chelate. Maintaining specificity, the 0.6 micrograms/l sensitivity of IFMA is over 25 times higher than that of RIA. The immunofluorometric method enables detection and accurate quantitation of PP14 in all those samples in which PP14 is undetectable by RIA. The method is suitable for quantitative measurement of low PP14 levels in serum of postmenopausal and fertile-aged women and men, as well as in follicular fluid. At 14-16 micrograms/l, which is the sensitivity of radioimmunoassay, the intra-assay variation of IFMA is 6.6% and inter-assay variation 11.4%. In postmenopausal women the PP14 levels are 12.7-56.7 micrograms/l, in fertile-aged women 13.7-113.4 micrograms/l, and in men 3.1-53.1 micrograms/l. The levels in preovulatory follicular fluid are 1.2-20.5 micrograms/l. It is concluded that PP14 IFMA is highly sensitive, accurate and suitable for measurement of protein levels undetectable by other currently available methods.

Amniotic Fluid↗
PubMed1989

Pregnancy-specific beta 1-glycoprotein: cDNA cloning, tissue expression, and species specificity of one member of the PS beta G family.

Pregnancy-specific beta 1-glycoprotein (PS beta G) is a heterogeneous product of the human syncytiotrophoblast, closely related to the CEA-NCA multigene family. In the present study, immunoscreening was carried out with anti-PS beta G antibodies to isolate cDNA sequences from a placental lambda gt11 expression library. One 1847-bp cDNA clone comprising the major portion of the coding sequence of a putative 48-kd peptide was sequenced and characterized. Hybridization of human genomic DNA to the PS beta G sequence revealed a complex pattern of restriction fragments, a finding well in agreement with the assumption that there are several independent PS beta G genes. A variable PstI band was found in human DNA. Transfer blot analysis of human placental RNA identified transcript of 2.2kb and 1.7kb that appear transiently with increasing levels of expression during gestation. No hybridization of PS beta G cDNA to human RNA from liver, kidney, heart, thyroid, and ovary was observed. In analyses of placental RNA from mouse, goat, sheep, and cow, no corresponding transcripts could be detected, and DNA hybridization under low-stringency hybridization conditions resulted in very faint cross-reacting bands, presumably indicating sequences that were scarcely related. However, PS beta G-specific DNA sequencies with similar restriction patterns were found in primates. These results are compatible with the assumption of late evolutionary development of certain PS beta G sequences.

Animals↗
PubMed1989

Comparative study of placental protein 19, human chorionic gonadotrophin and pregnancy-specific beta 1-glycoprotein as immunohistochemical markers for extravillous trophoblast in pregnancy and trophoblastic disease.

PP19, a new placental tissue protein, has alpha 1-beta 1 electrophoretic mobility, a molecular weight of 36,500 and 3.9% carbohydrate. To study immunocytochemical PP19 localization in extravillous trophoblast, we obtained formalin-fixed specimens from extravillous tubal pregnancy at gestational weeks (GW) 7-9 (12 blocks); four early intrauterine pregnancies at GW 7-13 (12 blocks); four late pregnancies at GW 28-38 complicated with intramural uterine myoma, placenta increta and abruptio placenta (8 blocks); four invasive complete moles (9 blocks); and seven primary and metastatic gestational choriocarcinomas (12 blocks). Immunohistochemical staining was done for PP19, pregnancy-specific beta 1-glycoprotein (SP1) and human chorionic gonadotrophin (hCG) using the indirect-labeled antibody method [purified PP19 (Lot no. 225/242) and antibody against PP19 (Lot no. 632ZA) prepared by H. Bohn, antibodies against hCG (Behringwerke, Marburg, FRG) and SP1 (Dakopatts, Copenhagen, Denmark)]. In both early and late intrauterine pregnancies, the extravillous syncytiotrophoblastic cell (XST) showed positive staining for hCG and SP1 in the cytoplasm, as well as for PP19, which stained more intensively in the nucleus than in the cytoplasm. The three proteins were not seen in the evtravillous cytotrophoblastic cell (XCT) in the trophoblastic cell column and shell. The interstitial cytotrophoblast-like cell (ICT), which infiltrated into the decidua and myometrium, and their blood vessels, was immunoreactively positive for PP19 but negative for hCG and SP1 with the exception of SP1-positive ICT in the myometrium in late pregnancy. XST and ICT in the endosalpinx of tubal pregnancy stained for all three proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1989

Circulating levels of placental protein 12 and chorionic gonadotrophin following RU 38486 and gemeprost for termination of first trimester pregnancy.

First trimester termination of pregnancy was successfully induced in ten patients with RU 38486 followed 2 days later by a prostaglandin (Gemeprost) pessary. Human chorionic gonadotrophin (HCG) values remained unaltered until after the abortion. The levels of placental protein 12 (PP12) showed an immediate and significant fall following RU 38486, then rose to values substantially higher than those at the initial visit after 2 days. These findings show that RU 38486 has a direct inhibitory effect on tissues producing PP12 and confirm the progesterone dependency of this protein.

Abortifacient Agents↗
PubMed1989

Immunochemical measurement and immunohistochemical detection of membrane-associated placental tissue protein 1.

Using the avidin-biotin binding system, an enzyme immunoassay procedure was developed to measure the membrane-associated placental tissue protein 1 (MP1) in serum. The standard curve covered the range from 10 to 1000 ng/ml of MP1. The intra- and inter-assay coefficient of variations (C.Vs) were less than 5 and 10%, respectively. Recoveries of MP1 added to serum ranged between about 96 and 101%. The MP1 serum level was over 10 and under 112 ng/ml in non-pathological men, and under 240 ng/ml in non-pathological women. The MP1 level in the ovulatory phase was higher than in other phases of the menstrual cycle. In pregnancies during 6-39 weeks, the MP1 level ranged from 10 to 540 ng/ml, and it increased during the third trimester of gestational age. In benign gynecologic diseases, the MP1 concentration in serum ranged from 10 to 215 ng/ml. The MP1 levels in benign diseases were compared with those in ovarian malignancies, in endometrial carcinoma, and in uterine cervical cancer. The immunohistochemical location of MP1 was detected in the cell membrane of ovarian cystadenocarcinoma.

Female↗
PubMed1989

Synthesis of polypeptides by the cervix of the baboon (Papio anubis).

Administration of oestradiol to ovariectomized baboons caused the epithelium of the cervix to differentiate into tall columnar cells that were ciliated or secretory. Administration of progesterone in the presence or absence of oestradiol altered the appearance of the lining epithelium, suggesting a decrease in secretory activity. Fluorographs of media from cultures of tissue from steroid-treated animals reflected changes in polypeptide biosynthesis which correlated with the morphological observations: 6 polypeptides (Mr 88,000-37,000; pI 5.5-6.0) were observed in all treatment groups and, except for relative changes in intensity, these polypeptides were electrophoretically similar to those synthesized by the endometrium. A new group of low molecular weight polypeptides (Mr 23,000-20,000, pI greater than 8.0-5.5) and a basic protein (Mr 160,000) were synthesized and released in the oestradiol-dominated animal. These polypeptides were distinct to the cervical mucosa since they were not observed in the endometrium or oviduct. Progesterone suppressed the synthesis of the low molecular weight acidic polypeptides (Mr 23,000-20,000; pI 6.1-5.5) but maintained the synthesis of the basic polypeptides (Mr 23,000-20,000; pI greater than 8). Treatment with progesterone +/- oestradiol did not appear to induce the synthesis of any new major polypeptides in the cervical epithelium. These results suggest that oestradiol induces the synthesis of a group of cervix-specific polypeptides and progesterone antagonizes the action of oestradiol in the baboon cervix.

Animals↗
PubMed1989

Oxygen and oxidation promote the release of nitric oxide from sydnonimines.

The antianginal effect of sydnonimines is believed to be due to the release of nitric oxide (NO) from inactive prodrugs. The first step in the transformation of the sydnonimine SIN-1 is the hydroxyl ion-dependent conversion to SIN-1A that occurs almost immediately at neutral pH. However, the subsequent process of NO release from SIN-1A is not yet understood. Therefore, the spontaneous degradation of SIN-1A in aqueous solutions was studied by chemical and pharmacological means. Measurement of the oxygen content of a freshly prepared SIN-1A solution revealed a rapid decrease of the oxygen concentration. The oxygen-consuming process was accompanied by a decrease in SIN-1A concentration and a progressive formation of NO and SIN-1C. SIN-1A was stable under nitrogen, labile under air, and very unstable under pure oxygen. Thus, oxygen is an important reactant in the decomposition of SIN-1A. The question of whether or not oxygen is essential for NO release was studied by investigating the effect of other oxidants. The oxidants potassium hexacyanoferrate, cupric sulfate, and lead tetraacetate augmented the conversion of SIN-1A to SIN-1C and increased the relaxing effect on isolated pulmonary arteries used to bioassay NO. Therefore, an oxidative process is essential for the release of NO from sydnonimines.

Biological Assay↗