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Biomedical subjects

M Heikinheimo

Publications and source records attributed to M Heikinheimo.

At least 73 records · Page 4Linked to original sources

Prediction of fetal alcohol syndrome by maternal alpha fetoprotein, human placental lactogen and pregnancy specific beta 1-glycoprotein.

No diagnostic measures exist for the fetal alcohol syndrome (FAS). Therefore, maternal serum alpha-fetoprotein (AFP), human placental lactogen (HPL) and pregnancy specific beta-1-glycoprotein (SP 1) were followed in 35 pregnant problem drinkers and 14 abstinent control women throughout pregnancy. Thirteen women gave birth to infants with FAS. These women had low levels of AFP and SP 1, but the levels of HPL were normal. Low AFP predicted FAS correctly in 59% with a relative risk of 2.46. Low SP 1 predicted FAS in 56% of the cases with FAS, and a relative risk was 3.29. HPL assay was useless in the detection of FAS. Low AFP and SP 1 may reflect primary or secondary effects of ethanol abuse in pregnancy and appear useful in predicting FAS. These tests can be recommended for routine use in the antenatal care of drinking women.

Adult↗

Oncoplacental protein SP1--a constitutive and inducible late differentiation marker of the human myelomonocytic lineage.

The oncoplacental protein SP1 is found in large quantities in human placenta, amniotic fluid, and pregnancy serum. Low levels have been reported in association with malignancy but also in healthy nonpregnant individuals. By indirect immunofluorescence, fluorescence-activated cell sorting, and immunoprecipitation we here demonstrate the presence of SP1 both on the surface and in the cytoplasm of human granulocytes but not in earlier myeloid progenitor cells in bone marrow. Lymphocytes did not contain the protein, and only trace amounts could be found in the cytoplasm of blood monocytes. A major glycoprotein with an apparent mol wt of 90,000 was obtained by immunoprecipitation of surface-labeled granulocytes. Cultivated blood monocytes, while adhering to surfaces or forming multinuclear giant cells, displayed a strong membrane and cytoplasmic expression of SP1. Treatment of the myeloid leukemia cell line ML-2 with tetraphorbol acetate (TPA) strongly induced SP1 in the membrane and cytoplasm as revealed by immunofluorescence and polyacrylamide gel electrophoresis (PAGE) of immunoprecipitates from lysates of surface radiolabeled cells. The induction of synthesis of SP1 in TPA-treated cells was confirmed by immunoprecipitation from lysates of cells metabolically labeled with 35S-methionine. Human lymphoblastoid and erythroleukemic cell lines did not express SP1 either before or after induced differentiation. Thus SP1 provides a late differentiation marker for the myelomonocytic lineage and is strongly induced during macrophage differentiation or by TPA treatment of ML-2 cells.

Cell Differentiation↗

Cytoskeletal markers and specific protein production in cells cultured from human first and third trimester placentae.

In primary, short-term cultures derived from first and third trimester placentae, 60 to 90 and 70 to 95%, respectively, of the total cell population positively stain for cytokeratin intermediate filaments, typical of epithelial, i.e. trophoblastic cells. The rest of the cells express only vimentin intermediate filaments and thus are of mesenchymal origin. Only the cytokeratin-positive cells express human chorionic gonadotropin (hCG), whereas both the epithelial and the mesenchymal cells stain positively for pregnancy-specific beta-1-glycoprotein (SP1). Cytokeratin-negative and vimentin-positive cell overgrowth is observed in cultures derived from first and early third trimester placentae. The cells constituting the monolayer thus formed are of fetal origin as evidenced by the expression of Y-body in over 80% of them. The cultured cells synthesize and secrete hCG and SP1. The activity of these trophoblast-specific functions is inversely proportional to the gestational age of the placenta. Production of specific proteins and expression of intermediate filaments are proposed as criteria for defining the nature and origin of placental cells in primary, short-term cultures.

Chorionic Gonadotropin↗

Alpha-fetoprotein, human placental lactogen, and pregnancy-specific beta 1-glycoprotein in pregnant women who drink: relation to fetal alcohol syndrome.

To determine the usefulness of the assays of maternal serum alpha-fetoprotein, human placental lactogen, and pregnancy-specific beta 1-glycoprotein in prenatal diagnosis of fetal alcohol syndrome, these proteins were followed in 35 problem drinkers (greater than 100 gm of ethanol weekly) and in 14 abstinent women throughout gestation. Thirteen women gave birth to infants with fetal alcohol syndrome, and these women had low levels of alpha-fetoprotein and pregnancy-specific beta 1-glycoprotein but levels of human placental lactogen were normal. Low alpha-fetoprotein correctly predicted fetal alcohol syndrome in 59% with a relative risk of 2.46. Low pregnancy-specific beta 1-glycoprotein predicted fetal alcohol syndrome in 56%, and a relative risk was 3.29. Low alpha-fetoprotein and pregnancy-specific beta 1-glycoprotein may reflect primary or secondary effects of ethanol abuse in pregnancy and appear to be useful in predicting fetal alcohol syndrome.

Adult↗

Effect of concomitant food intake on absorption kinetics of erythromycin in healthy volunteers.

The steady state absorption of erythromycin from enteric-coated pellets of erythromycin base was compared with that from enteric-coated tablets in a randomized, two-way cross-over study in 24 healthy adult volunteers. A higher mean individual peak concentration (p less than 0.01), and a greater mean area under the serum concentration-time (0-8 h) curve (AUC, p less than 0.01) was produced by the enteric-coated pellets, when the preparations were administered 1 hour before breakfast. No significant differences in the kinetic parameters between the two preparations were observed when they were taken during a non-standardized breakfast, as concomitant food intake was found to reduce both the peak levels and the AUC-values (p less than 0.01) produced by the pelleted preparation.

Adult↗

Evidence for the presence of oncoplacental SP1-like protein in normal nonpregnant serum.

To seek the pregnancy-specific beta 1-glycoprotein (SP1) in nonpregnant serum, normal human serum was applied to immunoadsorbent containing monoclonal anti-SP1 antibodies. SP1 eluted with 8 M urea was further analyzed by sodium dodecyl sulfate-gel electrophoresis and immunoblotting. A SP1-positive band with the same electrophoretic mobility as purified placental SP1 was found. The results suggest that serum from normal nonpregnant subjects contains material closely related to the placental protein SP1. The mean serum concentrations of SP1 were similar in men and women, ranging from 1.1-3.4 ng/ml.

Electrophoresis, Polyacrylamide Gel↗

Human chorionic gonadotrophin and pregnancy-specific beta-1-glycoprotein in predicting pregnancy outcome and in association with early pregnancy vomiting.

Serum concentrations of human chorionic gonadotrophin (HCG) and pregnancy-specific beta 1-glycoprotein (SP1) were measured in 99 women between the 6th and 10th gestational week, before the onset of pregnancy-threatening complications. The markers failed to predict threatening abortion appearing 9-112 days after sampling (n = 11), regardless of whether the pregnancy continued (n = 2) or ended with abortion (n = 9). Normal HCG and SP1 values were observed in 4 women who subsequently had preterm delivery. 14 women with daily vomiting had higher mean serum concentrations of HCG (p less than 0.01) and SP1 (p less than 0.05) than 12 women of the same gestational duration without nausea or vomiting. Our results thus show that random single HCG or SP1 determinations have minimal clinical value in predicting the failure of pregnancy and that early pregnancy vomiting seems to be associated with raised serum HCG and SP1 concentrations.

Abortion, Spontaneous↗

Amniotic fluid human chorionic gonadotropin in late pregnancy: elevated levels in toxemia with intrauterine growth retardation.

Amniotic fluid human chorionic gonadotropin (hCG) was studied by radioimmunoassay in 88 normal pregnancies and in 48 pregnancies with toxemia either with or without intrauterine growth retardation, between 34 and 41 weeks. In normal pregnancy, no significant change in the hCG level was observed from 34 to 41 weeks, with the logarithmic mean value being 522 mU/ml. The hCG levels in amniotic fluid were markedly elevated in toxemia (logarithmic mean 1,079 mU/ml), especially when associated with intrauterine growth retardation (logarithmic mean 2,056 mU/ml). Since in intrauterine growth retardation without maternal disease the hCG levels were normal (logarithmic mean 657 mU/ml), toxemia itself may be the factor that causes elevated levels of hCG in amniotic fluid.

Amniotic Fluid↗

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↗

Alkaline phosphatase activity in amniotic fluid in pregnancies with fetal disorders.

Alkaline phosphatase (ALP) activity was determined in 255 amniotic fluid samples collected by amniocentesis between 15 and 39 weeks of gestation. The samples were originally used for chromosomal analysis and/or alpha-fetoprotein measurements. The mean ALP activity in early amniotic fluid from pregnancies with fetal trisomy 18 and 21 syndromes was half of that found in the controls. Highly elevated ALP activity (over 10 times the median level) was found in 14 samples. Two of these pregnancies had normal outcome. Three samples were from pregnancies with intrauterine fetal death. Fetal disorders, including abdominal wall defect (four cases), Meckel's syndrome (two), hydrops fetalis syndrome (two) and genital anomaly (one), were observed in nine cases. Moderately elevated ALP activity (over three times the median) was found in 10 cases, including five pregnancies with a preterm labour shortly after the sample collection. The results indicate that elevated ALP activity in the third trimester amniotic fluid is often associated with fetal disorders.

Alkaline Phosphatase↗

Monoclonal antibodies against pregnancy-specific beta 1-glycoprotein (SP1) in immunohistochemistry and radioimmunoassay.

Monoclonal mouse antibodies against pregnancy-specific beta-1-glycoprotein (SP1) have been studied for their suitability in immunoperoxidase staining and radioimmunoassay methodologies. These antibodies were useful in staining normal placentas, hydatidiform moles, invasive moles and choriocarcinomas. They showed good specificity, with minimal background staining, and will thus be superior to conventional polyclonal antisera in immunohistochemistry. However, the presently tested monoclonal anti-SP1 antibodies were found not to be suitable for radioimmunoassay.

Animals↗

Reactivity of amniotic fluid alpha-fetoprotein with concanavalin A-sepharose in pre-natal diagnosis of fetal malformations.

The proportion of concanavalin A-non-reactive alpha-fetoprotein was determined in 215 amniotic fluid samples from second trimester pregnancies. the median percentage for concanavalin A-non-binding alpha-fetoprotein was 35.5% at the 15th week and 32.2% at the 18th gestational week. Nineteen of the 23 pregnancies with various fetal malformations showed highly elevated total alpha-fetoprotein levels. In this group, the value for non-reactive alpha-fetoprotein was below the normal range in 12 out of 13 samples collected at 15-17 weeks of pregnancy and in four out of six samples at 18-19 weeks. Four pathological pregnancies had only moderately elevated total alpha-fetoprotein levels (5.3-7.9 SD above the mean) and two of these samples had a low percentage of the concanavalin A-non-binding fraction. The amniotic fluid alpha-fetoprotein concentration was between 3 and 5 SD and over 5 SD above the mean in four and seven normal pregnancies, respectively. The concanavalin A-fractionation classified correctly 10 out of these 11 cases. The results indicate that the determination of the proportion of concanavalin A-non-binding alpha-fetoprotein is a useful supplementary test to the total alpha-fetoprotein assay.

Amniocentesis↗

Pregnancy-specific beta 1-glycoprotein-like material in human cerebrospinal fluid.

Human cerebrospinal fluid (CSF) from 34 unselected neurological patients was studied for pregnancy-specific beta 1-glycoprotein (SP1) activity because of the recent finding of SP1 production by cultured glial cells. An organic central nervous system lesion was diagnosed in 9 patients, but not in the other 25. Low levels of SP1 immunoreactivity were found in CSF by RIA, and the adsorption of anti-SP1 antiserum with concentrated CSF abolished the positive immunohistochemical staining of placental tissue obtained with the unadsorbed antiserum. By means of immunoadsorption using monoclonal anti-SP1 antibodies, it was possible to isolate SP1 immunoreactive material from CSF and to demonstrate that it had the same electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as purified placental SP1. These results show that CSF contains SP1-like material that is closely related, if not identical, to placental SP1. The amount of SP1 in CSF has no direct correlation to an organic central nervous system lesion or to abnormality of the CSF.

Adenocarcinoma↗

Cells from normal brain and gliomas synthesize pregnancy-specific beta 1-glycoprotein-like material in vitro.

The synthesis of pregnancy-specific beta 1-glycoprotein (SP1) was studied in normal brain-derived and malignant glial-cell cultures. The normal brain-derived and glioma cells were found to contain SP1 when studied by radioimmunoassay and by the triple-bridge immunoperoxidase technique. The active synthesis of SP1 by these brain-derived cells was confirmed by metabolic labelling and subsequent immune precipitation of the culture medium. The SP1-like material produced by the brain-derived cells had the same molecular weight as purified placental SP1.

Brain↗

Cultured human syncytiotrophoblasts synthesize pregnancy-specific beta-1-glycoprotein (SP1).

The synthesis of pregnancy-specific beta-1-glycoprotein (SP1) was studied in human syncytiotrophoblast cultures from first trimester placentas. Incorporation of 35S-methionine into SP1 was demonstrated by immunoprecipitation and polyacrylamide gel electrophoresis. In double diffusion the precipitation line of neosynthesized SP1 gave a reaction of complete immunological identity with maternal serum SP1. By indirect immunofluorescence intracellular SP1 was localised in the perinuclear region of the cells. The average rate of SP1 release into culture fluid was 600 ng/mg protein in 24 hours. On a molar basis the release of SP1 was 10 times less than that of human chorionic gonadotrophin (hCG). Our results demonstrate, for the first time, that cultured human syncytiotrophoblasts synthesis SP1 immunologically indistinguishable from placental SP1.

Cells, Cultured↗