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T Maruo

Publications and source records attributed to T Maruo.

At least 19 recordsLinked to original sources

[Biology of trophoblast and its endocrinological profiles].

The trophoblast of human placenta is composed of syncytiotrophoblast (S-cell) and cytotrophoblast (C-cell). C-cell displays proliferative properties, while S-cell displays little potential for proliferation. A close similarity between cytologic localization of myc product and [3H]thymidine labeling suggests that myc expression is linked to trophoblast proliferation. In situ hybridization with cDNA probes revealed that mRNA expression of hCG alpha and hCG beta are initiated before syncytial formation, whereas hPL mRNA is expressed only in fully differentiated S-cell. EGF and EGF receptor (EGF-R) in 4-5 weeks placenta were localized to C-cell, whereas EGF and EGF-R in 6-12 weeks placenta were localized to S-cell. Consistent with these findings, EGF exerted gestational age dependent dual action on early placenta: one was to stimulate trophoblast proliferation in 4-5 weeks placenta and the other was to stimulate differentiated trophoblast function in 6-12 weeks placenta. An optimal dose of thyroid hormone stimulated progesterone, estradiol, hCG and hPL production in early placental tissues. Furthermore, women with unfavorable outcome of threatened abortion had lower T4, T3, free T4 and free T3 levels, as compared to women with favorable outcome. These data imply a role for thyroid hormone in maintaining early pregnancy. On the other hand, progesterone selectively inhibited hCG (alpha, beta) mRNAs expression and decreased hCG secretion in normal placental tissues, whereas choriocarcinoma did not respond to progesterone. This suggests that inhibitory regulation of hCG synthesis in choriocarcinoma is different from normal placenta. Characterization of choriocarcinoma hCG revealed that there are striking differences in carbohydrate structures between normal hCG and choriocarcinoma hCG. Sialic acid content in choriocarcinoma hCG was extremely lower compared to that in normal hCG. The biochemical detection of the alteration in hCG sugar chains is useful for early diagnosis of choriocarcinoma.

Cell Differentiation

Immunohistochemical demonstration of elevated expression of epidermal growth factor receptor in the neoplastic changes of cervical squamous epithelium.

To evaluate epidermal growth factor (EGF) receptor expression in the neoplastic process of squamous cell epithelium of the uterine cervix, normal, premalignant, and malignant cervical tissues were examined for the presence of EGF receptor by the avidin-biotin immunoperoxidase techniques with a monoclonal antibody to EGF receptor. Although normal cervical epithelium did not show appreciable staining for EGF receptor, predominant staining for the receptor was observed in most dysplastic epithelia and carcinomas in situ. In invasive squamous carcinoma, there was a great difference in the immunohistochemically detected levels of EGF receptor among the histologic cell types. Large cell nonkeratinizing carcinoma and its keratinizing counterpart contained high levels of EGF receptor; small cell nonkeratinizing carcinoma lacked immunostainable EGF receptor. These results suggest that the elevated expression of EGF receptor may be involved in the initial stage of tumorigenesis of cervical squamous epithelium and that EGF receptor expression may be related to the differentiation or dedifferentiation of cervical squamous carcinoma cells.

Antibodies, Monoclonal

A novel change in cytologic localization of human chorionic gonadotropin and human placental lactogen in first-trimester placenta in the course of gestation.

Cytologic localization of human chorionic gonadotropin and human placental lactogen in developing human early placenta was analyzed by avidin-biotin immunoperoxidase techniques with an affinity-purified polyclonal antibody to beta-human chorionic gonadotropin carboxyl terminal peptide and a polyclonal antibody to human placental lactogen. In 4- to 5-week placentas human chorionic gonadotropin and human placental lactogen were found to be primarily localized to cytotrophoblasts, whereas in 6- to 12-week placentas these substances were exclusively localized to syncytiotrophoblast. We previously reported that a similar change in cytologic localization of epidermal growth factor and its receptor from cytotrophoblasts to syncytiotrophoblast in first-trimester placenta appeared between 5 and 6 weeks of gestation. Because epidermal growth factor was demonstrated to stimulate human chorionic gonadotropin and human placental lactogen production by early placental tissues, their simultaneous expression, as well as epidermal growth factor and its receptor in the cytotrophoblast of 4- to 5-week placenta and in the syncytiotrophoblast of 6- to 12-week placenta, implies that human chorionic gonadotropin and human placental lactogen production by first-trimester placenta may be regulated in an autocrine manner, wherein epidermal growth factor may serve as the signal. These findings suggest that in very early placenta, before 6 weeks of gestation, no sequential expression of human chorionic gonadotropin and human placental lactogen closely linked to syncytia formation may exist and that both can be expressed in the cytotrophoblast or undifferentiated stem cell of villous trophoblast in very early placenta.

Chorionic Gonadotropin

A role for thyroid hormone in the induction of ovulation and corpus luteum function.

We have previously demonstrated that thyroid hormone synergizes with follicle-stimulating hormone (FSH) to exert stimulatory effects on granulosa cell differentiation and function, suggesting that it plays a physiological role in amplifying FSH-mediated differentiation of granulosa cells. The adequate differentiation of these cells, followed by normal follicle development, is indispensable for ovulation and subsequent corpus luteum formation. Thus, in the present studies, the clinical implications of thyroid hormone in the induction of ovulation and corpus luteum function were investigated. Serum levels of total 3,5,3'-triiodothyronine (T3) and total thyroxine (T4) as well as free T3 and T4 were significantly lower in patients with weight loss amenorrhea compared to normal cycling women. Although no ovulation was induced by clomiphene therapy when the serum T3 levels were less than 80 ng/dl, the rate of ovulation induced by clomiphene increased in parallel with the augmentation of serum T3 levels. This suggests that an adequate circulating level of thyroid hormone is one of the factors responsible for successful induction of ovulation by clomiphene citrate. Furthermore, the short luteal phase and insufficient progesterone secretion observed in patients with subclinical hypothyroxinemia were not improved by clomiphene therapy alone, but were improved markedly by combined treatment with thyroid hormone replacement and clomiphene citrate. These data imply that concomitant clomiphene treatment with thyroid hormone replacement therapy is of a great value not only for ovulation induction, but also for the treatment of luteal-phase defect in patients with subclinical hypothyroxinemia.

Adolescent

Gestational age-dependent dual action of epidermal growth factor on human placenta early in gestation.

In order to better understand the role of epidermal growth factor (EGF) in the regulation of placental growth and function, effects of EGF on proliferative activity and differentiated function of trophoblast were examined. Explants from very early (4-5 week) placentas and early (6-7 week, 8-9 week, 10-12 week) placentas were respectively cultured under a serum-free condition in the absence or presence of EGF (100 micrograms/L) for the first 48 h, and the cultures were continued for subsequent 72 h without EGF. The proliferative potential and differentiated function of trophoblast were assessed by immunohistochemical Ki-67 staining and by determining the ability to secrete human CG (hCG) and human placental lactogen (hPL), respectively. Quantitative estimates of proliferative activity based on mean percentage of Ki-67 positive nuclei showed that EGF stimulated proliferative potential of cytotrophoblast in very early (4-5 week) placental explants. The EGF stimulation of trophoblast proliferation was apparent at a 12-h EGF-treated period. By contrast, early (6-12 week) placental explants did not respond to EGF with increase in trophoblast proliferation. Instead, in early placental explant culture EGF stimulated hCG and hPL secretion with a lag period of 72 h, whereas very early placental explants did not respond to EGF with increase in hCG and hPL secretion. These results suggest that EGF exerts gestational age-dependent dual action on the first-trimester placenta: one is to stimulate trophoblast proliferation in 4-5 week placenta and the other is to stimulate differentiated trophoblast function in 6-12 week placenta.

Cell Division

The role of maternal thyroid hormones in maintaining early pregnancy in threatened abortion.

To evaluate a possible role of thyroid hormones in maintaining early pregnancy, serum levels of thyroid hormones, TSH and thyroxine-binding globulin (TBG) in 32 patients with a clinical diagnosis of threatened abortion were compared between two groups of patients with favorable and unfavorable pregnancy outcome. Serum levels of T4, T3, free T4 and free T3 levels determined at the onset of clinical signs of threatened abortion were found to be significantly lower in patients (N = 11) who subsequently aborted compared to patients (N = 21) who did not. Serum TSH levels did not differ between the two groups. Serum TBG levels in the patients who subsequently aborted were lower compared to patients with favorable pregnancy outcome. Furthermore, serum levels of T4 and T3 at the onset of threatened abortion in patients who subsequently did not abort were significantly higher compared to levels before pregnancy, whereas little increase in serum T4 and T3 levels relative to the pregnant levels was observed at the onset of clinical signs in the patients who subsequently aborted. These data imply a possible role of thyroid hormones in maintaining early pregnancy, and suggest that maternal serum level of thyroid hormone may be one of the endocrine factors responsible for the outcome of threatened abortion.

Abortion, Threatened

Increase in the expression of thyroid hormone receptors in porcine granulosa cells early in follicular maturation.

Thyroid hormone has been demonstrated to synergize with FSH to exert stimulatory effects on the differentiation of porcine granulosa cells. In order to further characterize the nature of thyroid hormone action on granulosa cells, the presence of triiodothyronine (T3) receptors in the nuclei of porcine granulosa cells was examined, and qualitatively and quantitatively compared during follicular maturation. Then, comparative abilities of granulosa cells from varying follicle stages to respond to T3 were assessed in terms of FSH-induced LH/hCG receptor formation and progesterone secretion. Furthermore, the expression of erb-A was analyzed using Northern blot hybridization of porcine granulosa cell RNA with a v-erb-A probe. Binding experiments with [125I]T3 showed that granulosa cell nuclei obtained from small follicles had a greater ability to bind [125I]T3 compared to those from large follicles. Scatchard analysis revealed the presence of nuclear T3 receptors with a single class of binding sites. There was little difference in the affinity of the T3 receptors during follicular maturation. By contrast, the number of the T3 receptors was higher in small follicle granulosa cells compared to that in large follicle granulosa cells. Thus, the increased T3 binding to small follicle granulosa cells relative to large follicle granulosa cells appears to be attributable to the increased number of the nuclear T3 receptors rather than to a change in the affinity. The magnitude of the stimulatory effects of T3 on granulosa cell functions was maximal in small follicle granulosa cells, but negligible in large follicle granulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Effects of epidermal growth factor on the proliferation and differentiation of procine granulosa cells cultured in vitro].

Various growth factors are likely to be involved in the proliferation and differentiation of granulosa cells. Our previous studies revealed that insulin, insulin-like growth factor (IGF-I) and thyroid hormone each act as a biological amplifier of the action of FSH in the ovary. This study was undertaken to elucidate a possible direct effect of epidermal growth factor (EGF) on granulosa cell functions using the procine model. Porcine granulosa cells obtained from small, medium and large follicle, were cultured in the presence or absence of FSH and IGF-I, with or without EGF. EGF stimulated the proliferation of granulosa cells from small follicles, but did not affect the proliferation of granulosa cells from large follicles. In culture of granulosa cells obtained from large follicles. EGF inhibited the secretion of estradiol, and increased the secretion of progesterone by cultured cells. Scatchard analysis of 125I-EGF binding revealed that there is a single type of EGF receptor (EGF-R) in granulosa cells and that the number of EGF-R increases as the follicle matures. In Sephadex G-75 column chromatography of the medium following 5-day culture of porcine granulosa cells, an elution peak of immunoreactive EGF was found in the fraction similar to the elution of 125I-hEGF. These results suggested that EGF is produced by granulosa cells which contain abundant EGF-R. Thus, EGF is likely to act in an autocrine manner to stimulate the proliferation of less mature granulosa cells and to increase progesterone production by mature granulosa cells in association with an inhibitory action on estradiol production. These dual actions of EGF on granulosa cell function are of great interest.

Animals

[The role of signal transduction systems in the regulation of production and secretion of TA-4 by cultured cervical epidermoid carcinoma cells (CaSki)].

The CaSki cell line derived from an epidermoid carcinoma of the uterine cervix produces and releases a tumor associated-antigen, TA-4. The authors have already reported that EGF stimulated the production and secretion of TA-4 by the CaSki cells. EGF receptor is known to be one of the proteins phosphorylated by C-kinase. In order to elucidate a possible role of signal transduction systems (cAMP-A-kinase, diacyglycerol-C-kinase and Ca(2+)-calmodulin) in the regulation of TA-4 production and secretion by human cervical epidermoid carcinoma cells, the effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on TA-4 production and secretion by CaSki cells were evaluated. TA-4 in the cultured cells and media were measured with a SCC RIA-Kit. The addition of PMA or Ca2+ ionophore to the medium caused increases in the cellular levels of TA-4 and TA-4 levels in the medium in a dose-dependent manner shortly after the addition. Combined treatment with PMA and Ca2+ ionophore did not cause additive increases in TA-4 levels in the cells and medium compared to the treatment with PMA alone or Ca2+ ionophore alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm

[The role of signal transduction systems in the regulation of the production and secretion of hCG (alpha, beta) by cultured human choriocarcinoma cells (BeWo)].

The BeWo cell line, derived from choriocarcinoma, produces and releases human chorionic gonadotropin (hCG) and its alpha- and beta-subunits. The authors have already reported that cAMP and EGF stimulated the production and secretion of hCG and its subunits by cultured BeWo cells. Therefore, in order to elucidate the role of signal transduction systems (cAMP-A-kinase system, DG-C-kinase system and Ca(2+)-calmodulin system) in the regulation of hCG (alpha, beta) synthesis by human choriocarcinoma cells, effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on hCG (alpha, beta) production and secretion by BeWo cells cultured in a serum-free condition were evaluated. Immunoreactive hCG alpha, hCG beta and hCG in the media and cultured cells were measured by each homologous RIA for hCG alpha, hCG beta and hCG, respectively. Addition of CT at a concentration of 100 ng/ml into the medium caused extreme increases in the cellular levels of hCG alpha, hCG beta and hCG together with remarkable increases in hCG alpha, hCG beta and hCG levels in the medium. This stimulatory effect of CT was first observed on the increase of hCG alpha levels in cultured BeWo cells and medium at 3h, then observed on the increase of hCG beta levels at 6h and was last detectable on the increase of hCG levels in the cultured cells and medium at 12h. Addition of PMA at a concentration of 100 ng/ml into the medium caused an increase in the cellular and medium levels of hCG alpha, hCG beta and hCG shortly (3h) after the exposure to PMA. Addition of A23187 at a concentration of 100 ng/ml into the medium caused a slight increase in hCG alpha levels in the medium at 6h without accompanying the increase in those cellular levels. When added together, PMA potentiated the stimulatory effect of CT on hCG alpha, hCG beta and hCG levels in the cultured BeWo cells and medium, while PMA did not potentiate the effect of A23187 in this experimental condition. These findings suggest that cAMP-A-kinase system plays a major role in the signal transduction of hCG (alpha, beta) synthesis and secretion by BeWo choriocarcinoma cells, and that DG-C-kinase system interacts synergistically with cAMP-A-kinase system in the regulation of hCG (alpha, beta) synthesis and secretion by BeWo cells. Ca(2+)-calmodulin system appears to participate in the regulation of hCG alpha secretion without affecting the synthesis of hCG (alpha, beta) in BeWo cells.

Calcimycin

Cytologic localization of epidermal growth factor and its receptor in developing human placenta varies over the course of pregnancy.

Cytologic localization of epidermal growth factor and its receptor in developing human placenta was analyzed by avidin-biotin immunoperoxidase techniques with a polyclonal antibody to epidermal growth factor and a monoclonal antibody to its receptor. In 4- to 5-week placenta, epidermal growth factor and its receptor were found to be almost exclusively localized to cytotrophoblasts, whereas in 6- to 12-week placentas they were predominantly localized to syncytiotrophoblasts. These findings suggest that both are initially expressed in cytotrophoblasts in very early placenta before 6 weeks' gestation and thereafter expressed in syncytiotrophoblasts in 6- to 12-week placentas. Their simultaneous expression in the cytotrophoblast of 4- to 5-week placentas and in the syncytiotrophoblast of 6- to 12-week placentas implies that epidermal growth factor may act in an autocrine manner in first-trimester placentas. By contrast, in second- and third-trimester placentas, epidermal growth factor was mainly localized to cytotrophoblasts, whereas its receptor was predominantly localized to syncytiotrophoblasts. These findings imply that epidermal growth factor may act in a paracrine fashion in second- and third-trimester placentas. The dynamic change in cytologic localization of epidermal growth factor and epidermal growth factor receptor in developing human placentas may reflect the change in a possible role of epidermal growth factor in the course of fetoplacental development.

Epidermal Growth Factor

Vascular reactivity in normal and abnormal gestation.

Preeclampsia is characterized by enhanced pressor responsiveness to angiotensin II. This report summarizes studies by our laboratory to investigate possible roles for calcium, sodium, membrane pumps, and the vasoactive hormones, atrial natriuretic peptide (hANP) and endothelin, in modulating the change in vascular reactivity characteristic of preeclampsia. Urinary calcium excretion, 1 alpha-25(OH)2D3 levels, and serum free calcium levels were all decreased, whereas parathyroid hormone levels and intraplatelet calcium concentrations were increased in women with preeclampsia. Erythrocyte sodium content was elevated, while red blood cell membrane Na-K-ATPase activity was decreased in patients with severe disease. Preeclamptics also had elevated levels of hANP, which failed to increase further when saline was infused or when blood pressure was increased transiently with angiotensin II administration. Finally, endothelin levels that are reduced in normal gestation, were increased in preeclampsia. While the cause of increased vascular reactivity is still unclear, there appear to be changes in the intracellular cation environment, combined with loss of compensating mechanisms, both at the membrane and humoral level, as well as enhanced concentrations of a potent vasoconstrictor in blood; all which lead to increases in vasoreactivity and blood pressure in preeclampsia.

Atrial Natriuretic Factor

Thyroid hormone as a biological amplifier of differentiated trophoblast function in early pregnancy.

Direct effects of T3 or T4 on the trophoblast function were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from normal early and term placentas were cultured with or without graded doses of T3 or T4 for 5 days in a serum-free condition. Addition of T3 (10(-8) mol/l) resulted in the maximum increase in daily secretion of progesterone, estradiol-17 beta as well as hCG alpha, hCG beta, hCG and hPL by cultured early placental tissues. Increases in progesterone and estradiol-17 beta secretion caused by the addition of T3 were further augmented in response to concomitant addition of pregnenolone and testosterone, respectively, suggesting that T3 (10(-8) mol/l) enhances 3 beta-hydroxysteroid dehydrogenase and aromatase activity in the placenta. These stimulatory effects of T3 (10(-8) mol/l) on the trophoblast endocrine function were also found with the use of T4 (10(-7) mol/l). Addition of higher or lower concentrations of T3 or T4 gave attenuated effects. These results suggest that the optimal concentration of thyroid hormone is needed for it to exert its maximally stimulatory action on trophoblast endocrine function. Unlike early placental tissues, cultured term placental tissues did not respond to the addition of T3 or T4 with increased endocrine activity. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of placental trophoblasts, followed by diminished expression of trophoblast endocrine function.

Chorionic Gonadotropin

Changes in causes of visual handicaps in Tokyo.

Newly registered visually handicapped patients at the Tokyo Metropolitan Rehabilitation Center for the Physically and Mentally Handicapped were studied in 1968 (when the facility was opened), 1978, and 1988. Examinations were carried out by the same physicians and diagnoses were made by uniform criteria. Since approximately 10% of the total population of Japan lives in Tokyo, the statistics on the causes of visual handicaps in this area deserve to be reported. The changes observed over the past twenty years are as follows: There were few changes in the percentages of high myopia, retinal degeneration and senile cataract. The percentages of corneal opacity, retinopathy of prematurity, congenital cataract and optic atrophy decreased, while those of diabetic retinopathy, glaucoma and retinal macular degeneration increased. Advances in medical treatment and the shift into an aging society in Japan are responsible for these changes observed.

Adolescent

[Modification of endocrine function of trophoblasts by thyroid hormone].

Direct effects of L-triiodothyronine(T3) on placental endocrine function were investigated in vitro with an organ culture system for human placental tissues. Explants of trophoblastic tissues obtained from early and term placentas were cultured with or without graded doses of T3 in a serum-free condition. The addition of an optimal concentration of T3(10(-3) M T3) stimulated daily secretion of progesterone and estradiol from cultured early placental tissues by acting at the level of 3 beta-hydroxysteroid dehydrogenase and aromatase enzyme activity, together with the enhancement of hCG(alpha, beta) and hPL secretion. The addition of higher or lower concentrations of T3 gave attenuated effects and the addition of an excessive concentration of T3(10(-3) M T3) resulted in remarkable inhibition of progesterone and estradiol secretion by cultured early placental tissues. These results suggest that the optimal concentration of thyroid hormone acts as a biological amplifier of endocrine function of cultured trophoblasts obtained from early placentas. Unlike the early placental tissues, cultured term placental tissues did not respond to the addition of graded doses of T3 with increased endocrine function. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of the trophoblast, followed by diminished endocrine function of early placental trophoblasts.

Chorionic Gonadotropin

Long-term results after strabismus surgery.

The results of surgery after 4 years' or more postoperative follow-up have been evaluated in a total of 1031 cases (575 esotropia, 456 exotropia). There is a difference in the angle of strabismus 1 month after surgery and 4 years after surgery. Based on these findings, the results of strabismus surgery must be evaluated after a sufficient amount of time has passed. The angle of strabismus to be aimed at, to provide best binocular vision and patient satisfaction, should be in the range of -2 +7 degree for esotropia and +2 -10 degree for exotropia, regardless of the patient's age at surgery.

Age Factors

Penetration of fleroxacin into maxillary sinus mucosa and palatine tonsil.

Ten patients undergoing tonsillectomy or operation on the maxillary-antrum were given 200 mg fleroxacin orally 1-2 h before surgery. The concentration of fleroxacin in maxillary sinus mucosa (mean 2.61 mg/kg) was similar to that in serum samples collected simultaneously (mean 2.46 mg/l); and similar results were obtained with tonsillar tissue (mean 3.27 mg/kg; simultaneous serum samples, mean 2.84 mg/l).

Anti-Infective Agents