Search PubMed⌕ Search

Biomedical subjects

H Bohn

Publications and source records attributed to H Bohn.

205 records · Page 12Linked to original sources

Placental protein 12 (PP12): factors affecting levels in late pregnancy.

The circulating concentration of placental protein 12 was measured by radioimmunoassay in 109 pregnant women. The effect on the serum PP12 level of temperature, repeat freezing and thawing, and day-to-day and diurnal variation were assessed and the post partum changes of levels were studied. On average, PP12 levels in plasma are about one-half of those in serum in the same individual. PP12 immunoreactivity is destroyed by heating but not by repeated freezing and thawing. Changes in serum PP12 levels at various times of day showed a significant and consistent diurnal variation (F = 7.21; d.f.24; 96; P less than 0.001). The peak mean (+/- s.e.m.) value at 0800 h (80.8 +/- 8.7 ng/ml) was 41 per cent higher than the 24-h mean (P less than 0.05), and the nadir concentration at 1400 h (40.4 +/- 5.4 ng/ml) was 29 per cent lower than the 24-h mean (P less than 0.025). There is also considerable day-to-day variation (up to 72 per cent) in serum PP12 levels. If serum samples are taken at 0700 h, there is a slight negative correlation between PP12 concentration and placental weight (P less than 0.05), but not between PP12 level and birthweight of the child. In term pregnancy, the levels taken at 0700 h are higher (163.7 +/- 12.4 ng/ml) than at 0900 to 1300 h (115.7 +/- 11.4 ng/ml, P less than 0.001). The PP12 level is not affected by labour.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

Immunochemical and biochemical relationship between human pregnancy-associated secreted endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG) and the soluble placental proteins 12 and 14 (PP12 and PP14).

Two proteins, pregnancy-associated endometrial alpha 1- and alpha 2-globulins (alpha 1- and alpha 2-PEG), synthesized de novo and secreted by the human endometrium and decidua during pregnancy, have been demonstrated to be immunochemically related to the soluble placental proteins PP12 and PP14 isolated from term placenta. However, although these immunochemically similar endometrially- and placentally-derived proteins differ in their reported biochemical properties, in this report we have demonstrated that PP12 and PP14 are biochemically identical to alpha 1- and alpha 2-PEG with respect to subunit size. We conclude that these placental proteins are derived from the endometrium by de novo synthesis, and we suggest that the localization of these proteins to the placenta reflects either absorption, specific binding or processing by the trophoblast. The significance of clinical studies involving PP12 and PP14 measurement must therefore be reassessed in the light of their exclusive endometrial origin.

Abortion, Therapeutic↗

Molecular cloning and characterization of placental tissue protein 18 (PP18a)/human mitochondrial branched-chain aminotransferase (BCATm) and its novel alternatively spliced PP18b variant.

Five different insert-length cDNAs encoding for soluble placental tissue protein 18 (PP18) variants were isolated by screening a human placental cDNA library using monospecific anti-PP18 serum. Sequence analysis of the longest clone showed that the insert contains an open reading frame encoding for a 392 residue-long protein with a 27 amino acid mitochondrial targeting sequence. The mature protein-designated PP18a-is 41.264 kDa consisting of 365 residues and is identical to the previously isolated and characterized PP18 antigen described in 1985. We also found a new, alternatively spliced cDNA encoding for a 300 residue-long, 33.776 kDa protein, which was designated PP18b. Alignment search of the protein databank showed that PP18a is almost entirely identical to the human mitochondrial branched-chain aminotransferase, while PP18b is its newly discovered splicing variant. We detected the two PP18 variants in normal adult and fetal human tissues besides the mitochondrial (only PP18a) and cytosolic (only PP18b) fractions of term placenta with chemiluminescence Western blot analysis. The 41 kDa PP18a variant was expressed ubiquitously, while the 33 kDa PP18b variant was found in smaller amounts in nearly all tissues. Trace amounts of the variants were present in the sera of non-pregnant healthy controls, as well as in pregnant women, but there was no real change in serum levels during pregnancy. In conclusion, PP18 variants are not specific for the placenta. Aminotransferase activity of placental origin PP18 antigens was verified by structural analysis and by a coupled branched-chain aminotransferase/glutamate dehydrogenase assay.

Alternative Splicing↗

Cloning and sequencing of human oncodevelopmental soluble placental tissue protein 17 (PP17): homology with adipophilin and the mouse adipose differentiation-related protein.

Using a monospecific anti-PP17 antiserum, we detected 4 different molecular-weight PP17 immunoreactive proteins (31,500 kD PP17a, 48, 000 kD PP17b, 60,900 kD PP17c and 74,000 kD PP17d) in different normal adult and fetal human tissues, and in term placenta, by chemiluminescence Western blot analysis. These proteins are overexpressed in cervix carcinoma tissue. Furthermore, increased amounts of PP17b are secreted into the circulation in cervix carcinoma patients; after radical surgery, PP17b serum levels are decreased, and the protein probably has an oncodevelopmental significance. cDNAs were isolated from a human placental cDNA library with the monospecific anti-PP17 antiserum. Sequence analysis of the clones showed that they encode for the 251 residue long PP17a variant, which is identical to the previously isolated and characterized PP17 antigen described in 1983. An alignment search of the protein databank showed that PP17a is homologous to human adipophilin and mouse adipose differentiation-related protein. PP17c turned out to be a dimer of PP17a, while PP17b and PP17d immunoreactive proteins recently detected on Western blots require further investigations.

Adult↗

Is placental tissue protein 17b/TIP47 a new factor in cervical cancer genesis?

We identified novel members of the placental tissue protein 17 (PP17) protein family which consists of different-size variants of PP17; cDNAs of PP17a and PP17b variants have also been cloned and sequence analyzed. By Western-blot analysis in cervical carcinoma tissues we found overexpression of PP17b. Compared to healthy controls a mean five-fold increase in the amount of PP17b was also detected in the sera of untreated cervical carcinoma patients, which declined after radical operations. In our recent findings, in sera of inoperable cervical carcinoma patients, we also found elevated PP17b levels which did not change after irradiation. By Northern-blot analyses we confirmed PP17b overexpression in cervical carcinoma tissues and also the alternative splicing of PP17 mRNAs in various normal human tissues. Presently, the amino acid sequence of TIP47--a mannose-6-phosphate receptor cargo selection device--turned out to be identical to that of PP17b. Due to its oncodevelopmental function, PP17b/TIP47 is more than likely to be connected to HSV-2 infection, which is probably one of the main etiopathogenic agents of cervical carcinoma along with the HPV virus, and may open a new trend in the research of pathological processes in human uterine cervical cancer.

Blotting, Northern↗

Overexpression of placental tissue protein 17b/TIP47 in cervical dysplasias and cervical carcinoma.

In our previous Western- and Northern-blot investigations, high over-expression of placental protein 17b/TIP47 was detected in extracts of human cervical carcinoma tissues compared to normal conditions of the cervical tissue. PP17b serum levels were also elevated in untreated cervical carcinoma patients compared to healthy controls. In the present study, the expression pattern of PP17 proteins was investigated in various cervical dysplasias and in cervical carcinoma tissue specimens by the streptavidin-biotin immunoperoxidase technique using PP17-specific antiserum. In normal third-trimester human placentas, which served as positive controls, mainly cytoplasmic PP17 immunostaining of syncytiotrophoblasts and chorionic trophoblasts was observed. Normal human uterine cervical squamous and glandular epithelia were negative or weakly positive, while in low grade dysplasias (CIN I-II) only the cytoplasms of dysplastic cells were weakly positive or positive; in high grade dysplasias (CIN III/ISC) cytoplasms of the dysplastic cells were strongly positive. Normal and superficial cells in the differentiated zones were negative in all tissue specimens. In cases of invasive epithelial cervical carcinomas, small basal-type tumour cells were mostly negative whilst cells with squamous differentiation were strongly positive for PP17. Our hypotheses for this newly detected phenomenon are briefly discussed.

Adult↗