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T Maruo

Publications and source records attributed to T Maruo.

At least 145 records · Page 8Linked to original sources
PubMed1987

The role of thyroid hormone as a biological amplifier of the actions of follicle-stimulating hormone in the functional differentiation of cultured porcine granulosa cells.

To characterize thyroid hormone action on the ovary, the direct effects of T4 or T3 were investigated in vitro using a monolayer culture system of porcine granulosa cells. Monolayer cultures were maintained for 6 days in 4% serum-supplemented medium in the absence or presence of porcine FSH (20 ng/ml), with or without graded doses of T4 or T3. Combined treatment with FSH and T4 (10(-7) M) induced morphological alternation resembling epithelioid cells, while FSH alone or T4 alone failed to bring about the epithelioid morphology. Concomitant treatment with FSH and T4 (10(-7) M) markedly increased FSH-stimulated induction of [125I]iodo-human CG binding to cultured granulosa cells obtained from small follicles. The combined treatment with FSH and T4 (10(-7) M) also resulted in a significant increase in progesterone and estrogen secretion by the cultured cells relative to treatment with FSH alone. Increases in progesterone, 17 beta-estradiol, and estrone secretion caused by the combined treatment with FSH and T4 (10(-7) M) were further augmented in response to the addition of exogenously provided substrate pregnenolone, testosterone, and androstenedione, respectively. Furthermore, aromatase activity assessed by the release of [3H]water from [1 beta-3H, 4-14C]androstenedione was significantly higher in cells treated concomitantly with FSH and T4 (10(-7) M) than that in cells treated with FSH alone. All the stimulatory effects of T4 (10(-7) M) on the morphological and functional differentiation of cultured granulosa cells were also found in combined treatment with FSH and T3 (10(-9) M). Either treatment with higher or lower concentrations of T4 or T3 gave attenuated effects, and T4 or T3 alone without FSH was incapable of exhibiting these stimulatory effects. These findings suggest that thyroid hormones synergize with FSH to exert direct stimulatory effects on granulosa cell functions, including morphological differentiation, LH/human CG receptor formation and steroidogenic enzyme (3 beta-hydroxysteroid dehydrogenase and aromatase) induction. Hence, decreases in ovarian functions during the states of hypo- or hyperthyroidism may account for diminished responsiveness of the granulosa cells to FSH.

Animals↗
PubMed1987

Induction of differentiated trophoblast function by epidermal growth factor: relation of immunohistochemically detected cellular epidermal growth factor receptor levels.

The effects of epidermal growth factor (EGF) on the production and secretion of hCG and human placental lactogen (hPL) by cultured placental tissues were investigated in relation to immunohistochemical measurements of cellular EGF receptor levels in the placenta. Explants of trophoblastic tissues obtained from normal early and term placentas were cultured in the presence or absence of EGF (100 ng/mL) with or without processing inhibitors (bacitracin, 1 mg/mL; colchicine, 100 microM; chloroquine, 100 microM) for 5 days, with EGF present for the first 2 days. Addition of EGF to the medium increased the release of hCG, hCG alpha, and hPL by the cultured early placental tissues. This EGF-stimulated hCG, hCG alpha, and hPL release was markedly inhibited by concomitant treatment with processing inhibitors. The time course of EGF effects indicated that the EGF-stimulated increase in hCG alpha secretion required a lag period of approximately 1 day, whereas significant increases in hCG and hPL secretion became apparent only after 3 days of EGF treatment. By contrast, in term placental tissues EGF stimulated only hCG alpha and hPL release, with a lag period of approximately 3 days. A possible direct action of EGF on the cultured placental tissues was reinforced by the immunohistochemical demonstration of EGF receptors in the placenta. When determined using the avidin/biotin immunoperoxidase method with monoclonal antibody to the mouse EGF receptor, EGF receptors were found predominantly on the syncytiotrophoblasts. Immunohistochemical measurements of cellular EGF receptor levels in the syncytiotrophoblasts revealed remarkably higher levels in early placenta compared to those in midterm and term placentas. Since EGF is likely to interact with its receptor, the lesser biological effects of EGF in cultures of term placental tissues may be due to the lower cellular EGF receptor levels in term placenta. These results demonstrate that EGF, via its receptors on the syncytiotrophoblasts, stimulates the release of both hCG and hPL in normal early placenta. They also suggest that EGF may play a significant role in the induction and regulation of the differentiated function of trophoblasts.

Cells, Cultured↗
PubMed1987

Differential effects of dibutyryl cyclic AMP and epidermal growth factor on the synthesis and secretion of human chorionic gonadotropin and its subunits by trophoblastic and non-trophoblastic cells.

The effects of dibutyryl cyclic adenosine 3',5'-monophosphate (cAMP) and epidermal growth factor (EGF) on the synthesis and secretion of human chorionic gonadotropin (hCG) and its subunits by normal and malignant trophoblasts as well as by non-trophoblastic cells were investigated in vitro. The explants of normal early placental tissues, choriocarcinoma cell line BeWo and non-trophoblastic tumor cell line CaSki from epidermoid carcinoma of the cervix, respectively, were cultured in the presence or absence of dibutyryl cAMP or EGF. The addition of either dibutyryl cAMP (1 mM) or EGF (100 ng/ml) caused significant increases in the synthesis and secretion of hCG and its subunits in cultures of normal and malignant trophoblasts, but had no stimulatory effect on hCG beta synthesis and secretion in culture of non-trophoblastic cell line CaSki that secretes predominantly hCG beta-like material. The magnitude of the stimulatory effects of dibutyryl cAMP and EGF on hCG (alpha,beta) synthesis and secretion by BeWo cells was much greater than that observed in normal trophoblasts. The time course of these stimulatory effects indicated that EGF-stimulated increase in hCG synthesis and secretion required a lag period longer than that for the dibutyryl cAMP-stimulated increase. These results suggest that there were no differences in normal and malignant trophoblasts in the mechanism for the stimulatory regulation of hCG (alpha, beta) synthesis and secretion, but immunoreactive hCG beta synthesis and secretion in non-trophoblastic tumor cells are regulated by a mechanism different from that in trophoblastic cells.

Bucladesine↗
PubMed1987

Discordant induction of tumor-associated antigen, TA-4 and chorionic gonadotropin beta in cultured cervical carcinoma cells.

The CaSki cell line derived from an epidermoid carcinoma of the uterine cervix produces and releases two types of tumor-associated antigen. One is a eutopic antigen, TA-4 and the other is an ectopic antigen, hCG beta-like material. The aim of the present investigation was to elucidate a possible difference in the induction mechanism of production of TA-4 and hCG beta-like material in the CaSki cells in relation to cellular differentiation and gene modulation. The exposure to epidermal growth factor (EGF, 100ng/ml) for two days greatly increased TA-4 production by the cultured CaSki cells without affecting cell growth and immunoreactive hCG beta production. The EGF-stimulated increase in TA-4 production required a lag period of approximately 24 hours. The exposure to sodium butyrate (2.5mM) stimulated immunoreactive hCG beta production by the cells, but decreased TA-4 production. The stimulatory effect of sodium butyrate on immunoreactive hCG beta production occurred only during the exposure to the agent. These discrepant effects of EGF and sodium butyrate on the production of TA-4 and hCG beta-like material by the CaSki cells suggest that a fundamental difference exists in the induction mechanism for the expression of these two types of tumor-associated antigen in cervical squamous carcinoma cells.

Antigens, Neoplasm↗
PubMed1987

[Prediction of the recurrence of squamous cell carcinoma of the uterine cervix by monitoring serum TA-4].

In this study, serum TA-4 and CEA in 21 recurrent cases were examined in relation to the pretreatment levels and recurrent lesions. The positive serum rate on recurrence was 66.7% in TA-4, 23.8% in CEA, and the mean serum level was 22.2 +/- 38.2 ng/ml in TA-4, while 4.8 +/- 9.2 ng/ml in CEA. In cases with local and intrapelvic recurrence, the positive serum rate was 61.5% in TA-4, 15.4% in CEA, and the mean serum level was 9.4 +/- 12.1 ng/ml in TA-4, and 4.3 +/- 10.2 ng/ml in CEA. In the cases in which there was distant recurrence, the serum positive rate was 75.0% in TA-4, 37.5% in CEA, and the mean serum level was 43.1 +/- 55.7 ng/ml in TA-4 and 5.7 +/- 7.7 ng/ml in CEA. In the cases whose serum pretreatment levels were positive, the positive serum rate on recurrence was 100% in TA-4 and 40.0% in CEA, while in the cases whose serum pretreatment levels were negative, the positive serum rate on recurrence was 40.0% in TA-4 and 9.1% in CEA. In 61.9% of the recurrent cases, the increase in serum TA-4 preceded the appearance of clinical signs, while the increase in serum CEA preceded it in only 19.0% of the recurrent cases. The mean leading time for tumor markers in the diagnosis of recurrence was 77.9 days in TA-4 and 60.0 days in CEA. It is therefore concluded that serum TA-4 monitoring after treatment is able to be used in predicting the recurrence of squamous cell carcinoma of the uterine cervix.

Antigens, Neoplasm↗
PubMed1986

[Selective augmentation of cellular hCG alpha mRNA levels and immunoreactive hCG alpha secretion by 17 beta-estradiol in the normal placenta].

In order to elucidate a possible self-regulation for hCG synthesis in placenta, effects of estradiol on hCG production and secretion were evaluated by culturing early placental tissue in the presence or absence of estradiol. The cellular level of mRNAs encoding hCG (alpha, beta) and hPL were estimated by mean grain count per syncytial nucleus on the placental sections hybridized in situ with labeled cDNA probes corresponding to these mRNAs. Immunoreactive hCG, hCG alpha and hPL in the media and explanted tissues were measured by the homologous RIAs. Addition of estradiol at concentration of 1 approximately 10 ng/ml into the medium caused an increase in the cellular levels of hCG alpha mRNA after 24-hour cultured, and exhibited significant increases in immunoreactive hCG alpha levels in the media and explanted tissues after 72-hour culture. The addition of estradiol neither affected the cellular levels of mRNA encoding hCG beta and hPL nor immunoreactive hCG and hPL levels in the media and tissues. The appropriated concentration of estradiol (1 approximately 10 ng/ml) used in above experiments was found to be similar to the tissue concentration in normal placenta. These findings suggest that the physiological concentration of estradiol selectively stimulates hCG alpha synthesis and secretion by normal placenta. Thus, estradiol in placenta may be a factor responsible for the increase of hCG alpha in maternal serum and placental tissue with the progress of gestation.

Chorionic Gonadotropin↗
PubMed1986

Production of tumor-associated antigen, TA-4, by the CaSki cervical carcinoma cell line.

Previous Japanese studies described the purification of TA-4 from homogenates of tumor tissues excised from squamous cell carcinomas of the uterine cervix, and the development of a radioimmunoassay to detect TA-4 in sera of patients with this disease. The aim of the present investigation was to determine if TA-4 was produced by the CaSki cell line, established in culture ten years ago from epidermoid carcinoma of the uterine cervix. The radioimmunoassay detected the TA-4 antigen in the CaSki cells, but not in cell lines derived from either choriocarcinoma or breast carcinoma. The TA-4 concentration in the CaSki cell lysate exceeded that in the CaSki culture fluid by more than twentyfold, and exceeded the concentration of human chorionic gonadotropin beta-like immunoreactive material by nearly two orders of magnitude. Antiserum to TA-4 was used to immunoprecipitate biosynthetically labeled TA-4 from CaSki cultures that had been incubated with [3H]leucine. After electrophoresis and autoradiography, the immunoprecipitated material showed a major band corresponding in apparent molecular weight (48,000 daltons) to TA-4 originally isolated from squamous cell carcinoma tumors. It is concluded that the CaSki cell line constitutes an ideal model with which to investigate the biosynthesis and regulation of TA-4, and a source for large-scale production of TA-4 for characterization studies as well as development of clinical diagnostic reagents.

Antigens, Neoplasm↗
PubMed1986

Differential modulation of chorionic gonadotropin (CG) subunit messenger ribonucleic acid levels and CG secretion by progesterone in normal placenta and choriocarcinoma cultured in vitro.

The ability of progesterone to modulate the production and secretion of human CG (hCG) in both normal placenta and choriocarcinoma was compared by culturing explants of each trophoblastic tissue in the presence or absence of progesterone. The cellular level of messenger RNAs (mRNAs) encoding hCG alpha, hCG beta, and human placental lactogen (hPL) were quantitatively estimated by mean grain count per syncytial nucleus on the tissue sections hybridized in situ with labeled complementary DNA probes corresponding to these mRNAs. Immunoreactive hCG, hCG alpha, and hCG beta in the media and explanted tissues were measured by the homologous RIAs, and hPL was assayed by hPL-RIA kit. Addition of progesterone at concentrations of 5-20 micrograms/ml into the culture of normal early placenta caused a decrease in the cellular levels of hCG alpha mRNA and hCG beta mRNA after a 24-h culture, and exhibited a decline in immunoreactive hCG and hCG alpha levels released into the media together with a decrease in immunoreactive hCG alpha and hCG beta levels in the explanted tissues after a 48-h culture. The addition of progesterone neither affected the cellular levels of hPL mRNA nor immunoreactive hPL levels in the media and tissues. On the other hand, addition of 17 beta-estradiol at concentrations similar to those used with progesterone did not alter the levels of immunoreactive hCG and hCG alpha in the media or explanted placental tissues, while lower concentrations (1-10 ng/ml) of 17 beta-estradiol caused an increase in immunoreactive hCG alpha levels in the media and cultured tissues. These findings suggest that the suppressive effect observed with progesterone is not likely to be a toxic effect of steroid, but is rather selective on hCG production and secretion by normal placenta. Thus, progesterone may be a factor responsible for the inhibitory regulation of hCG production and secretion by normal placenta. However, in contrast to normal placenta, the choriocarcinoma culture in vitro did not respond to progesterone. The steroid was without significant effect on the cellular levels of hCG alpha mRNA and hCG beta mRNA, and on the levels of immunoreactive hCG and hCG alpha in the media and explanted tissues. These results suggest that the inhibitory regulation of hCG production and secretion in choriocarcinoma is different from that in normal early placenta.

Choriocarcinoma↗
PubMed1986

[Relationship between serum levels and immunohistological tissue levels of CA 125 and CEA in epithelial ovarian cancers: its implications for tumor cell type specificity].

Tissue localization and serum levels of CA125 and CEA in patients with epithelial ovarian tumors were examined. In patients with serous cystadenocarcinoma, "high CA125 and low CEA" was a characteristic feature in the serum, while in patients with mucinous cystadenocarcinoma, "low CA125 and high CEA" was generally found in the serum. Tissue localization of CA125 was strongly positive in serous cystadenocarcinoma associated with high serum CA125 levels, and negative in serous tumors showing normal serum CA125 levels. In mucinous cystadenocarcinoma, CA125 staining was positive with a minimum intensity. Immunostaining of CEA was strongly positive in mucinous cystadenocarcinoma associated with high serum CEA levels and was negative in mucinous tumors showing normal serum CEA levels. Tissue localization of CEA in serous cystadenocarcinoma was negative. There was a good correlation between serum CA125 and immunohistochemical tissue levels of CA125 in serous cystadenocarcinoma, and the same between serum CEA and immunohistochemical tissue levels of CEA in mucinous cystadenocarcinoma. These results demonstrate that in epithelial ovarian tumors CA125 has a relatively higher tumor cell type specificity for serous cystadenocarcinoma, whereas CEA does for mucinous cystadenocarcinoma.

Adult↗
PubMed1986

[Efficacy evaluation of aztreonam for suppurative otitis media].

Preclinical and clinical studies were performed to evaluate usefulness and safety of aztreonam (AZT) in the treatment of acute otitis media, acute exacerbation of chronic otitis media and chronic otitis media and the following results were obtained. MICs for P. aeruginosa, P. mirabilis and P. inconstans isolated from the patients with suppurative otitis media were 1.56 micrograms/ml, less than or equal to 0.025 micrograms/ml and less than or equal to 0.025 micrograms/ml respectively in their peaks. In the intravenous injection of 1 g, AZT concentration in the mastoid cell mucosa was 7.52 micrograms/g on average and serum concentration 51.6 micrograms/ml sufficiently suggesting clinical efficacy of AZT. In the clinical trial by administering AZT 1-2 g/day for the patients with suppurative otitis media, effective rates were 2/3 (66.7%) for acute otitis media, 16/22 (72.7%) for acute exacerbation of chronic otitis media, 21/34 (61.8%) for chronic otitis media and 6/7 (85.7%) for cholesteatoma of the middle ear. Elimination rate of single Gram-negative pathogens was 82.1% in the bacteriological studies of AZT. As for abnormal laboratory findings, 7 cases showed GOT, GPT elevations. However, they were in minor degree and transient. Side effect was not noted except 1 case of flushing with itching. It was considered from the above results that AZT is a highly useful antibiotic for suppurative otitis media.

Adult↗
PubMed1985

[The biocellular effect of thyroid hormone on functional differentiation of porcine granulosa cells in culture].

To elucidate if the thyroid hormone acts directly on the ovary, the biocellular effect of L-thyroxine (T4) on porcine granulosa cells cultured in vitro was investigated. Monolayer cultures of porcine granulosa cells obtained from small (1 approximately 2 mm), medium (3 approximately 5 mm) or large (6 approximately 11 mm) follicles were carried out in the presence of porcine FSH (100 ng/ml). Concomitant treatment with T4 promoted FSH-dependent morphological luteinization, i.e. alteration of immature granulosa cells obtained from small follicles to epithelioid form. T4 also increased FSH-stimulated induction of hCG/LH receptor on immature granulosa cells. Furthermore, T4 augmented FSH-mediated production of progesterone and estradiol by immature granulosa cells cultured in vitro. The concentration of T4 to produce the maximal stimulatory effect was 10-7 M, demonstrating that optimal concentration of thyroid hormone is required for the expression of this stimulatory action. Since T4 alone demonstrated no effect on the differentiation of porcine granulosa cells and all the stimulatory effect of T4 seems to have a permissive action on FSH-induced granulosa cell luteinization. Although insulin showed a similar effect on porcine granulosa cells, no stimulation of estradiol production by porcine granulosa cells was observed with insulin in the culture system used in this study. These results suggest that the thyroid hormone acts directly on the ovary and plays an important role in modifying the FSH-dependent cellular differentiation of immature granulosa cells.

Animals↗
PubMed1985

[Selective inhibition of synthesis and secretion of hCG by progesterone and its correlation with hCG (alpha, beta) mRNA levels].

In order to elucidate the inhibitory regulation of hCG synthesis, the dynamics of the synthesis and secretion of hCG was investigated by culturing explants of trophoblastic tissues from early placenta and choriocarcinoma in the presence and absence of progesterone, and these results were then compared to those of hPL. The dynamics of mRNAs encoding hCG (alpha, beta) and hPL was assessed by grain counts in the tissue sections hybridized in situ with labelled cDNA probes corresponding to these mRNAs. In the control culture of early placenta, hCG, hCG alpha and hPL in the medium showed marked increases compared to the initial tissue levels, whereas hCG, hCG alpha and immunoreactive hCG beta in the tissue explants remained constant. Progesterone suppressed the secretion of hCG and hCG alpha by placental tissue after 48-hour culture in a dose-response manner and simultaneously decreased the tissue level of immunoreactive hCG beta. However, neither hPL secretion nor hPL tissue level were decreased by progesterone. The in situ hybridization revealed that grain counts for hCG alpha-mRNA and hCG beta-mRNA in the sections prepared from placenta cultured with progesterone were decreased compared to those prepared without progesterone, whereas grain counts for hPL-mRNA remained unchanged. In culture of explants from chorio-carcinoma, no inhibition of synthesis and secretion of hCG by progesterone was found. From these results it will be concluded that progesterone inhibits hCG synthesis through the inhibition of hCG alpha-mRNA and hCG beta-mRNA accumulation and that regulation of hCG synthesis in choriocarcinoma is different from that in the normal placenta.

Choriocarcinoma↗
PubMed1985

Tumor-associated antigen, TA-4, in the monitoring of the effects of therapy for squamous cell carcinoma of the uterine cervix. Serial determinations and tissue localization.

The level of tumor-associated antigen (TA-4) was determined in the serum and tumor tissue of patients with squamous cell carcinoma of the cervix by radioimmunoassay and immunoperoxidase techniques. Using an arbitrary limit of 2.5 ng/ml of serum, positive values were observed in 5.5% of healthy controls and 53.6% of patients with cervical squamous carcinoma. The mean value and incidence of elevation of serum TA-4 increased significantly with advancing disease stage. There was, however, no significant increase in serum TA-4 in the early stages of disease. Elevated TA-4 in serum rapidly fell to normal within 72 hours after radical surgery, but remained elevated if complete excision could not be performed. In case of radiotherapy, TA-4 levels in serum and tumor tissue often increased during the administration of the initial 2000 rad, and subsequently declined after the administration of a total of more than 4000 rad. The decline of serum TA-4 to normal observed during radiotherapy was found to be closely correlated with the disappearance of viable cancer cells in histopathologic specimens from the cervix. Immunohistochemical TA-4 staining was present in large cell nonkeratinizing carcinoma, but not in small cell nonkeratinizing carcinoma. These results indicate that the expression of TA-4 antigen in cervical squamous carcinoma is related to differentiation of the tumor cells and that serum TA-4 determination, despite its limitation for early diagnosis, provides a potential means for monitoring the effects of individual therapy for cervical squamous cell carcinoma.

Antigens, Neoplasm↗
PubMed1985

Antigonadotropic actions of GnRH agonist on ovarian cells in vivo and in vitro.

GnRH and its agonists have recently been shown to inhibit a variety of reproductive functions, in addition to its well-known gonadotropin releasing action in the pituitary. In order to determine the inhibitory mechanism and the site of action of these peptides in ovary, the direct actions of an agonistic analogue [D-Leu6, des-Gly-NH2] GnRH ethylamide on hypophysectomized immature rat ovaries in vivo and on rat luteal cells as well as porcine granulosa cells incubated in vitro were investigated. 125I-Labeled GnRH agonist, when injected to immature female rats, bound specifically not only to pituitary but also to ovaries. GnRH agonist inhibited hCG stimulation of progesterone production and ovarian weight augmentation in hypophysectomized immature female rats in vivo. FSH-stimulated induction of ovarian LH/hCG receptors and ovarian weight gain in diethylstilbestrol (DES)-treated hypophysectomized immature female rats were also suppressed by GnRH agonist. Moreover, treatment with GnRH agonist inhibited hCG-stimulated progesterone production by rat luteal cells incubated in vitro. In short time incubation of porcine granulosa cells obtained from medium follicles, the capacity and affinity of LH/hCG receptors were not affected by GnRH agonist. However, in long term culture of porcine granulosa cells obtained from small follicles, concomitant treatment with GnRH agonist markedly inhibited the induction of LH/hCG receptors stimulated by FSH and insulin. It may be possible that GnRH agonist prevents the differentiation of granulosa cells and subsequent acquisition of LH/hCG receptors, but has no effect on the LH/hCG receptors already induced. On the other hand, GnRH agonist delayed hCG-stimulated accumulation of cyclic AMP in porcine granulosa cells obtained from medium follicles. This delay of cyclic AMP accumulation may be responsible for the inhibition of progesterone production by ovarian cells. These findings suggest that GnRH agonist acts directly on ovarian cells and inhibits the action of FSH and LH/hCG, independently.

Animals↗