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Biomedical subjects

K Isaka

Publications and source records attributed to K Isaka.

At least 37 records · Page 2Linked to original sources

[Development of the monoclonal antibody to cultured uterine endometrial adenocarcinoma cells (EI)].

A new monoclonal antibody (Moab), 3H2, was produced by immunizing Balb/C mouse with EI, a newly established human cell line from moderately differentiated endometrial adenocarcinoma of the uterus. The molecular weight of the Moab 3H2-defined antigen was 36,000 daltons, and suggests that the epitope of the Moab 3H2-defined antigen was protein moiety. Moab 3H2 was of the IgG1, subclass. Using formalin-fixed, paraffin-embedded human tissues and immunohistochemical techniques (ABC method), Moab 3H2 has demonstrated reactivity, Moab 3H2 reacted with well and moderately differentiated endometrial adenocarcinoma of the uterus, but did not react with poorly differentiated endometrial adenocarcinoma of the uterus, Moab 3H2 did not react with other tissues, malignant or normal, except ovarian clear cell adenocarcinoma, suggesting that Moab 3H2 reacts with well and moderately differentiated endometrial adenocarcinoma of the uterus with high specificity. To analyze the epitope of the Moab 3H2-defined antigen, it should be useful to make clear the function of carcinogenesis, differentiation and growth of endometrial adenocarcinoma of the uterus.

Adenocarcinoma↗

[Establishment and characterization of the new cell line (EI) from a human endometrial adenocarcinoma].

A moderately-differentiated endometrial adenocarcinoma cell line(EI) was established from a surgical specimens obtained from a 55-year-old woman with endometrial carcinoma. This cell line could be transplanted to nude mice, where the cells showed the same histological type as the primary tumor. The doubling time of the cell line was 50.5 hours; the saturation density was 7.5 x 104 cells/cm2; the plating efficiency was 46%. This cell line was determined to produce TPA, but not other tumor markers, such as CA125 or CEA. Neither estrogen receptor, nor progesterone receptor was detected from the culture cell or the primary tumor. Chromosome analysis revealed that cells examined were all 46,XX, + 8,t(14q14q), and only cells with this karyotype were thought to be able to grow. From these results, it was suggested that a gene on No. 8 chromosome would be involved in the carcinogenesis of endometrial adenocarcinoma. Thus this cell line was thought to be useful for the clarification of gene conversion during the process of development of endometrial adenocarcinoma.

Adenocarcinoma↗

[mRNA expression and protein localization of placental tissue protein 11, 12, 19 in gynecologic malignant tumors].

In recent years, the localization and function of placental tissue proteins (PPs), extracted by Bohn et al., have been extensively studied, the genetic code has been identified for each of the PPs. The present study was carried out to clarify the mRNA expression and protein localization of PP11, PP12, PP19 at the cell level and also to define PP19 the nature of which has remained obscure. PP19 was said to be placenta-derived S-100P. PP11 mRNA was not expressed in cytotrophoblast-derived normal placental tissue or endometrium-derived normal cells, but was expressed in syncytiotrophoblast-derived normal placental tissue, and in choriocarcinoma and endometrial adenocarcinoma, suggesting its involvement in carcinogenesis. PP12 mRNA was expressed in cytotrophoblast-derived normal placental tissue or endometrium-derived normal cells, but was not expressed in syncytiotrophoblast-derived normal placental tissue, choriocarcinoma or endometrial adenocarcinoma, suggesting that this protein serves in the function of normal cells. PP19 mRNA was expressed in the squamous epithelial cells of the uterine cervix and the villous cells, PP19 was localized in more differentiated regions, where cells tended toward keratinization, in both normal and dysplastic uterine cervices. In squamous cell carcinoma, PP19 was localized in more differentiated cells with a large cytoplasm. PP19 mRNA was not expressed in normal endometrial glands, but was detected in endometrial adenocarcinoma, suggesting its involvement in cell differentiation in cervical epitherial cells.

Base Sequence↗

Beneficial effect of intravenous taurine infusion on electroretinographic disorder in taurine deficient rats.

We investigated the effect of intravenous taurine infusion on the electroretinogram (ERG) of taurine-deficient rats produced by treatment with guanidinoethyl sulfonate (GES), a taurine transport inhibitor. Mother rats were fed a taurine-free diet and given drinking water containing 1% GES from 2 weeks of gestation to weaning. The same feeding conditions were applied to male offspring after weaning. Both ERG measurement and continuous infusion of taurine at a dose of 10, 30 or 100 mg/animal/day were performed for 3 weeks from 7 to 10 weeks of age. GES-treatment reduced a- and b-wave amplitudes to 50% of the control levels and also increased b-wave latencies. Intravenous infusion of taurine improved these ERG abnormalities in a dose-dependent manner. Taurine concentrations in plasma, eyes and brain were also decreased by treatment with GES, and dose-dependent recovery was observed after infusion with taurine, although the concentrations of other amino acids were not affected by GES-treatment and infusion of taurine. Observations of morphological changes revealed that the retinal damage in GES-treated animals was decreased by taurine infusion. These results indicate that the changes in ERG and retinal structure observed in taurine deficiency are improved by intravenous infusion of taurine.

Amino Acids↗

A three-dimensional method for calculating currents induced in bodies by extremely low-frequency electric fields.

A user-friendly, numerical program has been developed to permit the calculation of induced currents in modeled bodies of human and infrahuman subjects. The program is based on a charge-simulation method (CSM), and it takes into account the three-dimensional (3-D) character of the extremely-low-frequency (ELF) electric field and of the models to be exposed. The principle of the method is to simulate a 3-D object, for example, an animal model, by a combination of several parts (blocks) having simple geometric forms such as a sphere, a cylinder, or a cone. This approach permits easy preparation of input data on the dimensions of the blocks and their positions in a 3-D arrangement. Other input data, such as the coordinates of the contour points and the imaginary values of charges inside objects, which are necessary in the calculations by CSM, are produced automatically by selecting an appropriate "level" for each block, according to its importance. To simulate parts having irregular shapes, special blocks may be added. In one series of experiments, induced currents were calculated for a baboon model in various postures: standing upright, positioned on four legs, and sitting on the floor. Calculated currents, the total induced current in particular, agreed very well with experimental values. Local currents in parts of the baboon models were more variable, ranging from 5% to 17% of measured values in the case of induced currents in the head. Some problems with this method, such as the effect of the dimensions of blocks or the choice of block levels, are discussed.

Animals↗

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↗

ELF electromagnetic environment in power substations.

This paper presents a theoretical analysis of electromagnetic environments in power substations in service. A new analytical method is developed and applied to magnetic field calculations in 187-kV and 66-kV substations. Experimental results verify that the method offers a good prediction of the magnetic field profiles in the substations except for the areas where localized field sources exist. The analytical results show that the magnetic field strength depends to a great extent on how the load powers distribute on individual lines and buses, that the magnetic fields in substations have a three-dimensional characteristic, and that the predominant field component depends on the position of interest. Moreover, it is suggested that objects placed in substations are exposed not only to magnetic fields of high strength in comparison to those in houses or near the distribution networks but also to fields with several percent of harmonic distortion.

Electromagnetic Fields↗

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↗

Characteristic differences in immunohistochemical localization of new placental proteins (PP1, PP19, PP21) in the human placenta.

The immunohistochemical localization in the human placenta of new placental proteins PP1, PP19, and PP21 was clarified using modified indirect enzyme-labeled antibody method and compared with that of pregnancy-specific beta 1-glycoprotein (SP1). The major results are as follows: positive staining for PP1 was seen at the nucleus and cytoplasm of villous cytotrophoblasts, the X cells at the basal plate, and of chorionic trophoblasts, while the decidua cells and amnion were not stained. PP19 was characteristically seen in the nucleus and cytoplasm of syncytiotrophoblasts. X cells in basal plate, chorionic trophoblasts, and maternal leukocytes. The villous cytotrophoblasts, decidua cells, and amnion were not stained. PP21 localization was found at the microvilli and basal membrane of syncytiotrophoblasts and at the cytotrophoblast plasma membrane of the chorionic villus in early gestation. In late gestation, increased staining was seen at the syncytiotrophoblast microvilli and the villous basement membrane, and moderate staining at plasma membrane of the amniotic epithelium and chorionic trophoblasts. SP1 was found only at the syncytiotrophoblast cytoplasm of chorionic villi. Studies using these four placental proteins simultaneously may therefore provide a new key learning about unknown metabolic functions of trophoblasts.

Basement Membrane↗

Placental protein 21. Localization in human placenta and concentrations in the body fluids of men and nonpregnant and pregnant women.

The immunohistochemical localization of placental protein 21 (PP21) was marked in the syncytial brush border and basal membrane during the 1st and 2nd trimesters of pregnancy and also in the chorionic epithelial brush border and basement membrane at term. A weaker stain was found in the cell membranes of amniotic epithelial and chorionic trophoblast cells. Neither heparin nor changes in temperature significantly influenced PP21 concentration. Relatively high serum PP21 concentrations were measured during the follicular and luteal phases in healthy nonpregnant women and in healthy men whose seminal plasma also showed a high PP21 concentration. Serum PP21 levels in normal pregnancy rose from a median of 29.1 ng/ml at 6-7 weeks of gestation to 82.0 ng/ml at 36-37 weeks of gestation. Although maternal urine showed low PP21 levels during pregnancy, amniotic fluid PP21 levels were higher at 7-21 weeks of gestation than at term. Cord blood sera showed almost the same PP21 concentration as maternal sera, but retroplacental blood showed much higher levels. Maternal serum PP21 levels in hydatidiform mole patients did not differ from the normal pregnancy range, although their molar vesicular fluids contained higher PP21 concentrations. These results suggest an extraplacental source for PP21.

Adult↗

Serum concentration of placental proteins (PP5 and PP10) in toxemia of pregnancy as related to intrauterine growth retardation.

Maternal serum concentrations of placental proteins 5 (PP5) and 10 (PP10) were measured by radioimmunoassay in 568 samples obtained from 308 healthy pregnant women and 63 women having toxemia of pregnancy. Below-normal PP5 values were more widely distributed in the mild than in the severe toxemia group, while the incidence of above-normal PP5 values was found only in the severe toxemia group. The incidence of below-normal PP10 values was higher in the severe than in the mild toxemia group. Our study thus suggests that simultaneous measurement of PP5 and PP10 concentrations in maternal serum in toxemia of pregnancy is a useful monitoring technique for predicting progressive pathological change and placental dysfunction related to IUGR.

Female↗

Diagnostic reliability of simultaneous measurements of beta human chorionic gonadotropin and pregnancy-specific beta-1-glycoprotein in serum of patients with trophoblastic disease.

Serum levels for beta-human chorionic gonadotropin (beta-hCG) and pregnancy-specific beta 1-glycoprotein (SP1) in patients with trophoblastic disease were measured by radioimmunoassay and enzyme-linked immunosorbent assay. The beta-hCG:SP1 ratios were below 1.0 in all 22 cases of complete hydatidiform mole and in 8 of 9 cases of partial hydatidiform mole. Two (10.5%) of 19 cases of invasive mole involving metastasis had ratios that rose above 1.0 during chemotherapy. Ratios ranged from 1.6 to 29 in 11 of 15 cases of choriocarcinoma before chemotherapy. The remaining 4 cases, diagnosed within 3 months of antecedent pregnancy, had ratios below 0.99. Thus, the difference between choriocarcinoma and nonchoriocarcinoma beta-hCG:SP1 ratios may be due to trophoblastic differentiation based on the developmental stage and with trophoblast age, or due to the mass and potential activity of trophoblastic cells.

Choriocarcinoma↗

Binding of pregnancy-associated plasma protein-A (PAPP-A) to placental subfractions.

Pregnancy-associated plasma protein-A (PAPP-A) has been shown to exert immunosuppressive effects both on complement and on lymphoblastogenesis. It was of interest to see whether this protein could bind to syncytiotrophoblast microvillous membranes since these represent the effective interface between fetal tissue and the immunocompetent mother. Placental subfractions were prepared according to established techniques. PAPP-A was purified from different sources (pregnancy serum and plasma, retroplacental serum, placental extracts) and labelled with radioactive iodine. It could be shown that radioactive PAPP-A, irrespective of its biological origin was primarily binding to brush border membrane preparations but that significant binding was also seen with plasma membrane preparations. The binding was specific since alpha 2-macroglobulin (a structurally related protein to PAPP-A) was unable to displace bound radioactive PAPP-A. Scatchard plot representation of the data indicated that the affinity of PAPP-A for its binding site was of the same order of magnitude as reported for the insulin or GnRH receptors of the trophoblast (Ka 2 10(7)-2.5 10(8) M-1). These results are in agreement with the immunohistochemical localization of PAPP-A on the trophoblast providing that the small binding to plasma membrane preparations is due to contamination.

Cell Membrane↗

Synthesis of placental protein 12 by decidua from early pregnancy.

The synthesis and secretion of placental protein 12 (PP12) by early pregnancy decidua and trophoblast were studied in vitro from tissues obtained by curettage during elective termination of pregnancy (weeks 8-14). The tissue explants were incubated in Ham's F-10 medium for a 27-h period, and the PP12 levels in media and tissue homogenates were measured by RIA. De novo synthesis of PP12 was assessed by measuring the incorporation of radioactivity into PP12 after 20 h of incubation of tissues with 20 microCi/ml [35S]methionine. PP12 from the culture medium was immunoprecipitated with anti-PP12(A) antiserum, and the immunoprecipitate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The initial tissue content of PP12 was 10- to 72-fold higher in decidua than in trophoblast. The total amount of radioimmunoassayable PP12 released into medium by decidual explants during the 27-h incubation period together with that present in the tissues at the end of incubation exceeded the initial tissue content by 242.7 +/- 63.7% (mean +/- SE). Only small amounts of PP12 were detected in media from trophoblast cultures. During the first 7 h of incubation, inclusion of cycloheximide had no effect on PP12 release by decidual explants in three of four experiments. Between 7 and 27 h, the amount of PP12 released by cycloheximide-treated tissues was 20.0 +/- 7% of that released by control tissues (P less than 0.01). Cycloheximide had no effect on PP12 release by trophoblasts. Decidual explants incorporated [35S]methionine into PP12, but trophoblasts did not. In sodium dodecyl sulfate-gel electrophoresis, the newly synthesized PP12 comigrated with the major band of purified PP12 corresponding to mol wt 29,000. These data clearly confirm that PP12 is a protein of decidual rather than trophoblastic origin, and indicate that decidua from early pregnancy has the ability to synthesize it.

Decidua↗

Levels of placental protein 10 (PP 10) in maternal serum in normal and pathologic pregnancies.

Concentrations of placental protein 10 (PP 10) were measured by radioimmunoassay and found to be detectable but very low in nonpregnant women and in men. In an assay of 223 samples from normal pregnancies, the mean PP 10 level was 2.7 +/- 1.0 ng/ml (mean +/- SD) at 6 to 7 weeks of gestation. The level of PP 10 in maternal sera increased gradually as pregnancy progressed to a high of 40.2 +/- 19.0 ng/ml at 38 to 39 weeks, followed by a slight decrease to 28.9 +/- 15.6 ng/ml at 40 to 41 weeks. The coefficients of variation were 8.6 to 16.2% in diurnal variation and 10.3 to 34% in day-to-day variation. Relatively lower PP 10 levels were observed in maternal sera in threatened abortion with poor prognosis, toxemia of pregnancy, intrauterine fetal death and placenta previa.

Abortion, Threatened↗