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O Tanizawa

Publications and source records attributed to O Tanizawa.

At least 109 records · Page 6Linked to original sources
PubMed1992

[Analysis of circulating thyroid-stimulating activities in pregnant women with Graves' disease: differential measurement of activities induced by TSH receptor antibody and hCG].

Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and this aggravation is associated with postpartum relapse of thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), is responsible for this early aggravation, the respective TSA due to TSAb or hCG were evaluated with a sensitive cAMP accumulation assay using FRTL-5 cells. TSA, which was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG level, but was abolished completely by the pretreatment of serum samples with the solid-phase hCG antibody coupled with Sepharose-4B. Total TSA in the model samples of mixture of Graves' and pregnant sera (Gr + Preg), was reduced by the pretreatment with the solid-phase antibody, just corresponding with the reduction in hCG-induced TSA. Total TSA in early pregnant sera in 15 patients with Graves' disease, decreased significantly but was still positive even by the pretreatment with the hCG antibody. Pregnancy-associated changes in TSA was examined serially in a patient with Graves' disease, and hCG-induced TSA increased predominantly along with the serum thyroid hormone in early aggravation period. These data indicate that (1) the respective TSA due to TSAb or hCG can be differentially measured by using the solid-phase hCG antibody and (2) hCG plays an important role for aggravation of Graves' thyrotoxicosis in early pregnancy.

Animals↗
PubMed1991

Involvement of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vitro.

Although transforming growth factor (TGF) alpha and epidermal growth factor (EGF) receptor (EGFR) autocrine mechanism is widely demonstrated in many kinds of cancers, its biological significances still remain circumstantial. We critically assessed the significance of this mechanism on the growth of an ovarian cancer cell line. Northern blot analysis in polyadenylated RNA isolated from cells by using 32P-labeled pre-TGF alpha, EGRF, and prepro-EGF complementary DNAs as probes revealed that pre-TGF alpha and EGFR but not prepro-EGF gene transcripts were expressed in the cell. TGF alpha and EGFR but not EGF proteins were observed by immunocytochemical stainings, using monoclonal antibodies against human TGF alpha, EGFR, and EGF, respectively. This cell line possessed a class of high affinity EGF receptor by 125I-EGF binding studies; Kd being 2.9 x 10(-10) M and Bmax to be 7.7 x 10(4) sites/cell. As much as 1.12 +/- 0.14 ng (SD; n = 3)/10(7) cells/24 h of TGF alpha was secreted in the conditioned media. These results suggested the expression of a TGF alpha/EGFR autocrine mechanism in this cell line. We, therefore, assessed the biological significance of this mechanism on the growth of this cell line in serum-free monolayer cell cultures. Although 0.1, 1.0, and 10 nM concentrations of TGF alpha did not show significant growth promotion, monoclonal antibodies against TGF alpha and EGFR but not EGF significantly inhibited cell growth. All these data suggested the biological importance of a TGF alpha/EGFR autocrine mechanism on the growth of this cell line in vitro.

Antibodies, Monoclonal↗
PubMed1991

Importance of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vivo.

We have elucidated the importance of a transforming growth factor (TGF) alpha and epidermal growth factor receptor autocrine mechanism on the growth of a human ovarian serous cystadenocarcinoma-derived cell line (SHIN-3) in vitro. In this study, we studied the biological significance of this autocrine mechanism in vivo using female athymic nude (nu/nu) mice. We measured the mouse plasma epidermal growth factor and TGF alpha levels by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Plasma epidermal growth factor concentrations were remarkably decreased by sialoadenectomy (Sx): 410 +/- 65 (SE) pg/ml (n = 10) in intact animals; and undetectable in Sx mice (n = 5). Plasma TGF alpha levels were 90 and 40 pg/ml in intact and in Sx animals, respectively. Ten million SHIN-3 cells inoculated into nu/nu mice formed tumors in 100% of mice, and tumors grew progressively. Implantabilities and tumor growth rates of inoculated cells were not affected by Sx and even by Sx and anti-mouse epidermal growth factor antibody treatment. However, anti-TGF alpha monoclonal antibody (mAb) administered to SHIN-3 cell-inoculated Sx animals drastically reduced the tumor growth. Although 10(7) SHIN-3 cells formed tumors in this group, tumor growth was significantly inhibited by 10 micrograms of anti-TGF alpha mAb given 3 times a week, and growth inhibitions were more by 20 micrograms of anti-TGF alpha mAb. Moreover, as aggressive tumor growth as that in Sx animals was resumed by the cessation of anti-TGF alpha mAb treatments. All these data suggested the biological importance of a TGF alpha/epidermal growth factor receptor autocrine mechanism on the growth of this cell line in vivo.

Animals↗
PubMed1991

Evidence for the involvement of transforming growth factor alpha and epidermal growth factor receptor autocrine growth mechanism in primary human ovarian cancers in vitro.

We examined 35 primary human ovarian adenocarcinomas for the presence of epidermal growth factor (EGF) receptor (EGFR) in plasma membranes from cancer tissues by using 125I-EGF as a ligand. Specific 125I-EGF bindings were observed in 20 (57%) of these 35 cases. Scatchard analysis showed a class of high affinity EGF receptor: Kd 5.0 +/- 1.0 x 10(-10) M; Bmax, 83.3 +/- 12.1 fmol/mg protein (mean +/- SE, n = 20). Northern analysis in polyadenylated RNA from 15 EGFR(+) cancers using pretransforming growth factor alpha (pre-TGF alpha), prepro-EGF complementary DNA, and pE7, a complementary DNA clone of human EGFR, as probes revealed that pre-TGF alpha and EGFR mRNAs but not prepro-EGF mRNA were expressed in all cases examined. Immunocytochemical studies using monoclonal antibodies (mAbs) against TGF alpha, EGF, and EGFR showed that TGF alpha and EGFR but not EGF proteins were present on ovarian cancer cells in all cases. These data suggested a possible TGF alpha/EGFR autocrine mechanism in EGFR(+) ovarian cancers. We, therefore, examined the biological significance of this autocrine mechanism by using primary monolayer cell cultures. In primary cultures from EGFR (+) cancers, TGF alpha added to the culture medium stimulated the [3H]thymidine incorporation dose dependently. Moreover, the addition of mAbs against TGF alpha and EGFR but not EGF inhibited [3H]thymidine incorporation dose dependently in EGFR(+) cancer cells. On the other hand, in primary cultures from EGFR(-) cancers, TGF alpha and anti-TGF alpha, -EGFR, and -EGF mAbs did not show any effects on [3H]thymidine incorporation. All these results suggested the possible crucial role of a TGF alpha/EGFR autocrine growth mechanism in primary human ovarian cancers which express EGFR.

Adenocarcinoma↗
PubMed1991

K-ras activation in premalignant and malignant epithelial lesions of the human uterus.

We previously reported (Cancer Res., 50:6139-6145, 1990) a significant frequency of activating point mutations in codon 12 of the K-ras oncogene in endometrial adenocarcinomas of the uterine corpus (series 1). To further define the role of ras activation in the development of endometrial adenocarcinoma, we surveyed cystic, adenomatous, and atypical hyperplasias of uterine endometrium and additional cases of endometrial and cervical carcinoma (series 2) for the presence of activating mutations in cellular protooncogenes of the ras family. Polymerase chain reaction was performed from deparaffinized sections of formalin-fixed paraffin-embedded tissue. We screened for point mutations in codons 12, 13, and 61 of the K-, H-, and N-ras genes by dot blot hybridization analysis with mutation-specific oligomers. Mutations in K-ras were also confirmed by direct genomic DNA sequencing. Of 19 endometrial adenocarcinomas in series 2, point mutations in ras genes were found in 7 tumors. Six contained single-base substitutions, five in codon 12 of K-ras and one in codon 12 of N-ras. The seventh tumor contained two different point mutations in codon 12 of K-ras. In one endometrial adenocarcinoma, tumor cells with point mutations in K-ras were predominantly localized to a portion that had a more aggressive histological pattern. In endometrial hyperplasia, K-ras mutations, one in codon 12 and one in codon 13, were found in 2 of 16 hyperplasias histologically classified as atypical and clinically considered premalignant. None of 6 adenomatous hyperplasias and none of 12 cystic hyperplasias, the latter of which is considered clinically benign, contained any detectable ras mutations. No mutations in H-ras were detected in either carcinomas or hyperplastic tissue.

Adenocarcinoma↗
PubMed1991

The biological effects of macrophage-colony-stimulating factor induced by progestin on growth and differentiation of endometrial adenocarcinoma cells.

Progestins have biological effects of regression and differentiation on human endometrial adenocarcinoma. We investigated the effects of progestin on the induction of macrophage-colony-stimulating factor (M-CSF) and its receptor messenger RNAs in the human endometrial adenocarcinoma cell line Ishikawa which has receptors for both estrogen and progesterone. Poly(A)+RNA extracted from Ishikawa cells cultured with or without synthetic progestin R5020 was subjected to Northern blot hybridization using M-CSF and c-fms cDNA probes. The expression of M-CSF mRNA in Ishikawa cells increased about 2.3 times following treatment with R5020 at 10(-7) M. Induction of M-CSF mRNA by R5020 was antagonized by anti-progestin RU486 in a dose-dependent manner. However, c-fms mRNA, coding the M-CSF receptor, was expressed constitutively in Ishikawa cells and its expression was not affected by hormonal treatment. We further examined the biological effects of M-CSF on endometrial cancer cells. Colony formation of Ishikawa cells in soft agar, which represents anchorage-independent cell growth, was inhibited by M-CSF treatment. On the other hand, accumulation of glycogen granules in cytoplasm detected by periodicacid-Schiff staining was observed in Ishikawa cells treated with M-CSF. These results indicate that M-CSF, whose gene expression was enhanced by progestin, suppressed growth and induced differentiation of endometrial adenocarcinoma cells. These effects of M-CSF on endometrial cancer cells are similar to those of progestins, so the effects of progestins on these cells are, at least in part, probably mediated by M-CSF in an autocrine or paracrine manner.

Adenocarcinoma↗
PubMed1991

Superoxide anion increases intracellular pH, intracellular free calcium, and arachidonate release in human amnion cells.

We determined the effects of superoxide anion, produced by addition of xanthine oxidase to hypoxanthine, on the intracellular pH (pHi) and intracellular free calcium concentration ([Ca2+]i) and release of arachidonate in human cultured amnion cells. Superoxide anion induced a prompt increase of pHi and subsequent increase of [Ca2+]i. The evoked pHi was inhibited by pretreatment with anion channel blockers but not affected by omission of extracellular Na+ or addition of amiloride. The increase of [Ca2+]i was inhibited significantly by the absence of extracellular calcium or by the addition of a calcium channel blocker, cobalt. NH4Cl, which can generally increase pHi, also increased [Ca2+]i of amnion cells. But the increase of [Ca2+]i induced by the NH4Cl was significantly less than that induced by the amount of superoxide anion causing a similar increase in pHi. These results show that superoxide anion, crossed through anion channel in membrane, increased [Ca2+]i at least partially via increase of pHi and that the calcium mobilization was dependent on both extracellular and intracellular sources. Superoxide anion induced the release of arachidonate in a dose-dependent manner and this induction was inhibited by omission of extracellular calcium. These data suggest that the release of arachidonate was dependent on the increase of [Ca2+]i. We also determined the viability of cells in the presence of superoxide anion by flow cytometry. Superoxide anion at the levels used in these experiments did not change the percentage of viable cells. These findings suggested that superoxide anion may regulate biological functions in amnion cells via pHi, [Ca2+]i mobilization, and the release of arachidonate without damaging the cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

Length of the human umbilical cord in multiple pregnancy.

The factors controlling the length of the human umbilical cord are uncertain. In the generally accepted 'tension theory', the length of the umbilical cord is proposed to increase the tensile force on it in the uterus. The greatest tensile force is supposed to be fetal movement. If this is so, the length of the umbilical cord should be shorter in multiple pregnancy than in single pregnancy. To examine this possibility we measured the umbilical cord lengths in 3314 singleton births, 82 twins births (164 infants), and 11 triplet or quadruplet births (35 infants). The cord lengths in multiple pregnancies (twins 51.3 cm, triplets and quadruplets 50.1 cm) tended to be shorter than that in singleton pregnancies (57.2 cm). However, no significant difference was found in the ratio of the umbilical cord length to the infant body weight in these groups. Therefore, we conclude that an important factor in determining the cord length is the size of the infant.

Body Weight↗
PubMed1991

Effects of nocturnal hyperprolactinemia on ovarian luteal function and galactorrhea.

To determine the effects of nocturnal hyperprolactinemia on luteal function and galactorrhea we studied six diurnal normoprolactinemic women with regular menstrual cycles. The diurnal serum levels of prolactin (PRL), luteinizing hormone (LH) and progesterone (Prog) and the nocturnal PRL levels at 1 h intervals were determined throughout the first menstrual cycle. Four of the women were nocturnally normoprolactinemic and two showed nocturnal hyperprolactinemia and low luteal progesterone values. In the second menstrual cycle, they were given metoclopramide (10 mg) at midnight before sleep every day, and their serum levels of PRL, LH and Prog were determined by the same protocol as in the first cycle. During treatment with metoclopramide, all the women showed nocturnal hyperprolactinemia, but their diurnal PRL levels remained within the normal range. Low luteal Prog values were observed in all of them and the peak LH levels decreased in all four nocturnally normoprolactinemic women. They had galactorrhea but neither of the nocturnally hyperprolactinemic women had galactorrhea. These results suggest that nocturnal hyperprolactinemia is a cause of luteal insufficiency and galactorrhea.

Adult↗
PubMed1991

Purification of gonadotropes and intracellular free calcium oscillation. Effects of gonadotropin-releasing hormone and interleukin 6.

The intracellular free calcium concentration ([Ca2+]i) in single gonadotropes was measured with a calcium-sensitive fluorescent dye indo-1 or fura-2 and a digital imaging fluorescence microscopic system to determine how interleukin-6 (IL-6) increases release of gonadotropins. IL-6 induced an increase in the basal [Ca2+]i or the amplitude of spontaneous oscillation of [Ca2+]i in gonadotropes in a mixed population. Gonadotropin-releasing hormone (Gn-RH) induced a biphasic increase in [Ca2+]i, a transient increase, and then a prolonged increase. These effects were inhibited by the absence of extracellular calcium or pretreatment with calcium channel blockers, cobalt or nifedipine. Next, purified gonadotropes were prepared by fluorescence-activated cell sorting and argon laser treatment of the cells. Gonadotropes labeled with anti-luteinizing hormone antibody were sorted by fluorescence-activated cell sorting and then cultured as monolayers for 24-48 h. In this way, gonadotropes were concentrated from 5-10% to 70-85% from whole pituitary cells. After relabeling with anti-luteinizing hormone antibody, 100% purified gonadotropes were obtained by killing other types of cells with an argon laser. Gonadotropin-releasing hormone induced almost the same responses of [Ca2+]i in the purified cell population as in the mixed cell population, but IL-6 did not affect [Ca2+]i in the purified gonadotropes. These results suggest that IL-6 affects calcium mobilization in gonadotropes indirectly via paracrine pathways.

Animals↗
PubMed1991

Immunodetection of sialyl-Tn antigen in normal, hyperplastic and cancerous tissues of the uterine endometrium.

The expression of sialyl-Tn antigen (STn) in normal, hyperplastic and neoplastic tissues of the uterine endometrium was examined by immunoperoxidase staining of formalin-fixed, paraffin-embedded samples using the monoclonal antibody TKH-2, directed toward the STn structure (NeuAc 2-6GalNac 1-O-serine or threonine). STn was expressed in 13 of 18 normal postovulatory endometria with an increasing staining intensity and incidence in the late secretory phase. It was consistently absent in 10 proliferative endometria. None of 5 cystic, 4 adenomatous or 12 atypical hyperplasias expressed STn, but areas of severe cytological atypia in 3 atypical hyperplasias showed faint expression. STn expression was detected in 36 of 43 adenocarcinomas. Although the extent of staining varied from a few to most of the cancer cells, general staining was observed throughout the cytoplasm of cancer cells with increased staining of the luminal surface and frequent positive staining of intraluminal mucin. Thus, it is clear that STn is selectively expressed in cancer cells and shows restricted expression in normal and hyperplastic endometrial tissues. STn may be an early marker of malignant transformation and has potential for use as a diagnostic aid in the surgical pathology of the uterine endometrium.

Adenocarcinoma↗
PubMed1991

Short-term treatment with 17-beta estradiol enhances spontaneous [3H] dopamine release from cultured rat tuberoinfundibular neurons.

The effects of 17-beta estradiol (E2) on spontaneous [3H] dopamine ([3H]DA) release was investigated using primary cultured cells from the tuberoinfundibular region of rat hypothalamus, which includes DA neurons. [3H] DA uptake by the neurons in the presence of E2 at 10(-8) mol/l was similar to that by control cells. Pretreatment with E2 at 10(-9) mol/l or more resulted in dose-dependent increase in spontaneous [3H] DA release from the cultured hypothalamic cells. The spontaneous [3H] DA release reached almost a plateau on pretreatment with E2 at 10(-9) mol/l for 6 hours. Pretreatment with 1 nM E2 also enhanced DA release induced by 10 microM ionophore A23187. These results indicate that estrogen stimulates tuberoinfundibular DA neuronal activity.

Animals↗
PubMed1991

The interferon family stimulates the secretions of prolactin and interleukin-6 by the pituitary gland in vitro.

The effects of interferon-alpha, interferon-beta 1 and interferon-gamma on the secretions of prolactin (PRL) and interleukin-6 by primary cultured rat anterior pituitary cells were examined. These three interferons caused dose-dependent increases in PRL secretion within 30 min, and dose-dependent stimulation of interleukin-6 were weaker than the effects of interleukin-1 and tumor necrosis factor-alpha. These results suggest that interferons regulate PRL secretion from the pituitary gland, and that there may be a pathway in which interferons stimulate PRL secretion through interleukin-6 release.

Analysis of Variance↗
PubMed1991

The enhanced production of placental interleukin-1 during labor and intrauterine infection.

The purpose of this study was to determine the effect of labor and chorioamnionitis in interleukin-1 production by human placenta. We studied the activity of the placenta to produce interleukin-1 with an enzyme immunoassay by culturing tissue blocks. The placental tissue obtained after labor produced a larger amount of interleukin-1 than placental tissue obtained before labor. All the placental tissues produced more interleukin-1 beta than interleukin-1 alpha. The placentas with labor and chorioamnionitis produced about seventeenfold more interleukin-1 than placentas with labor only. We immunohistochemically identified interleukin-1--producing cells in the placenta and found that syncytiotrophoblasts produced both interleukin-1 alpha and interleukin-1 beta, while Hofbauer cells produced only interleukin-1 beta. In vitro analysis of the trophoblast activities to produce interleukin-1 revealed that microbial byproducts enhanced interleukin-1 production, possibly inducing accumulation of interleukin-1 receptor-positive cells at the sites of inflammation. In addition to stimulation of prostaglandin biosynthesis and labor, the placental interleukin-1 may act as an inflammatory mediator, leading to systemic and local changes at fetomaternal interface and activating fetomaternal immune systems against intrauterine infection.

Chorioamnionitis↗
PubMed1991

Application of gene amplification by polymerase chain reaction to genetic analysis of molar mitochondrial DNA: the detection of anuclear empty ovum as the cause of complete mole.

To investigate the pathogenesis of complete hydatidiform mole (complete mole), we employed a newly developed gene amplification method by polymerase chain reaction (PCR) for the restriction fragment length polymorphism (RFLPs) analysis of extranuclear DNA (mitochondrial DNA) of complete mole. Whole cellular DNA was extracted from six molar tissues and from peripheral blood mononuclear cells of parents. Two hyperpolymorphic regions of mitochondrial DNA, a 1.5-kb-long fragment and a 1.9-kb-long fragment, were selectively amplified from the extracted DNA by the PCR method. The amplification products amounted to over 10 micrograms after 30 cycles of PCR. The PCR products were digested with endonucleases (HaeIII, HinfI, AluI, and TaqI) and then electrophoresed on agarose gel. The electrophoretic pattern of digested DNA showed that the RFLPs of molar mitochondrial DNA coincided with those of the patient, indicating that the mitochondrial DNA of complete mole was inherited from the ovum. As it has been identified that the intranuclear DNA of complete mole is transmitted only from the spermatozoa, our results verify that complete mole results from the fertilization of an anuclear "empty" ovum with normal sperm at the molecular level.

Base Sequence↗
PubMed1991

Neutralizing effect of sodium thiosulfate on antitumor efficacy of cisplatin for human carcinoma xenografts in nude mice.

The present study was designed to examine the antitumor efficacy of combination chemotherapy with sodium thiosulfate (STS) and cis-diamminedichloroplatinum (CDDP) using a murine model. Xenograft tumors of the endometrial adenocarcinoma cell line responded well to intraperitoneal chemotherapy with CDDP in nude mice. However, addition of STS to CDDP treatment canceled the antitumor effect of CDDP. Such a finding was obtained in mice injected subcutaneously with STS even 72 hr after treatment with CDDP. On the other hand, alleviation of CDDP-induced side effects by administration of STS was not observed in mice treated by several modalities of combination chemotherapy with STS and CDDP. Thus, addition of STS to CDDP treatment reduced CDDP's antitumor efficacy with only minimal alleviation of side effects, suggesting that it would provide no benefit in patients treated with CDDP.

Adenocarcinoma↗
PubMed1991

Analysis of immunoregulatory activity of a choriocarcinoma-derived factor: specific suppression of proliferative process of cell-mediated immune responses including LAK cell generation.

The immunosuppressive activity of a JEG-3 choriocarcinoma-derived factor in human IL-2-dependent T cell responses has been studied, together with its effect on IL-2-independent T cell responses induced by 10 nM TPA. The factor completely suppressed the IL-2-independent proliferative responses of T cells but failed to suppress antigenic expression of activation-associated CD 25 molecules. Further studies examined the effect of the factor on LAK cell generation induced by rIL-2. Recombinant IL-2-induced LAK cell proliferation was observed on Day 4 and Day 5, but not on Day 3. As the factor suppressed the responses of LAK cell proliferation, we tested whether it blocked the generation of Day 3, Day 4 and Day 5 LAK cells. The addition of the factor failed to suppress the generation of Day 3 LAK cells, while it partially suppressed the lytic activity of Day 4 LAK cells and completely suppressed that of Day 5 LAK cells. The data suggest the presence of a heterogeneous pattern for LAK cell generation; one without proliferation, but the other requiring proliferation, to acquire killer activity. Taken together with the evidence that the factor failed to suppress NK activity, the choriocarcinoma-derived factor suppressed only the proliferative events of immunocompetent cells, but inhibited neither their activation nor the differentiation events. This immunosuppressive factor might be involved in the prevention of host-mediated rejection of choriocarcinoma cells or maternal rejection of the fetus.

Choriocarcinoma↗