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Biomedical subjects

N Terada

Publications and source records attributed to N Terada.

413 records · Page 23Linked to original sources

Effect of sex hormones on eosinophilic inflammation in nasal mucosa.

We examined the effects of sex hormones on the functions of eosinophils. Treatment of eosinophils with beta-estradiol significantly enhanced the eosinophil adhesion to human mucosal microvascular endothelial cells (HMMEC), and eosinophils stimulated by a combination of beta-estradiol and progesterone showed significant induced degranulation. On the other hand, testosterone significantly reduced the eosinophil adhesion to HMMEC and eosinophil viability. The experiments from the series of studies might provide a partial explanation for the aggravation of asthma and some forms of rhinitis that occurs during pregnancy.

Adult↗

Cytotoxic activity of normal mouse serum on mouse tumor cells in vitro.

Cytotoxic effects of normal mouse serum on mouse tumor cells were investigated in vitro. When FE melanoma cells of C57BL/6 mouse origin, were cultured in medium containing 1% fetal calf serum (FCS) and 10-30% C57BL/6 mouse serum, number of viable FE cells markedly decreased after a little increase in their number, indicating cell death of FE cells in culture with mouse serum. Phase-contrast microscopic examination showed appearance of fatty degeneration in FE cells after 24 h, and an increase in cell death after 48 h. Electron microscopic examination, and agarose gel electrophoresis of DNA at 72 h of culture showed that their cell death occurred as necrosis. This cytotoxic effect of mouse serum was also found in culture of combinations of C57BL/6 mouse serum and C57BL/6 mouse melanoma cells (G6 cells), and BALB/c mouse serum and various BALB/c mouse tumor cells (G-5 and G-1 liver tumor cells, and Colon 26 cells). Furthermore, sera of BALB/c and B10D2 mice also showed the cytotoxic effect on FE cells. The cytotoxic effect of mouse serum was not ascribed to complement activity because all mouse sera were treated at 56 degrees C for 30 min before use, and this heat treatment completely abolished complement activity, and because serum of C5-deficient mice also showed the cytotoxic effect. This cytotoxic activity was stable at heat treatment at 100 degrees C for 10 min, and was in a serum fraction of molecular weights more than 30,000 dalton. The present results show that normal mouse serum has a factor(s) inducing fatty degeneration and necrosis of mouse tumor cells.

Animals↗

Expression of cytokines enhancing the osteoclast activity, and parathyroid hormone-related protein in prostatic cancers before and after endocrine therapy: an immunohistochemical study.

Cytokines, interleukin (IL)-1alpha, IL-1beta, IL-3, IL-6, macrophage colony stimulating factor (M-CSF) and tumor necrosis factor-alpha (TNF-alpha) as well as parathyroid hormone-related protein (PTHrP) have been shown to enhance the osteoclast activity. To investigate mechanisms of the development of bone metastasis of prostatic cancers, expression of these cytokines and PTHrP was examined immunohistochemically in prostatic cancers of patients administered no prior therapy or endocrine therapy. All cytokines and PTHrP were stained in the cytoplasm of the epithelium of non-cancerous prostatic glands, and IL-3 and IL-6 were stained in the cytoplasm of smooth muscle cells besides epithelial cells of non-cancerous prostatic glands. Incidences of positivity of staining in prostate cancers of patients administered no prior therapy were 100% for IL-1alpha, IL-1beta, IL-6, M-CSF and TNF-alpha, 20% for IL-3, and 80% for PTHrP. Incidence of prostatic cancers stained positively for IL-1alpha and IL-1beta decreased significantly in patients administered endocrine therapy, but those for IL-3, IL-6, M-CSF, TNF-alpha and PTHrP did not change significantly. The present results suggest that prostatic cancers produce various cytokines, IL-1alpha, IL-1beta, IL-3, IL-6, M-CSF and TNF-alpha, as well as PTHrP, and that expression of these cytokines and PTHrP except IL-1alpha and IL-1beta is not under androgen control. Cytokines and PTHrP produced by prostatic cancers may play a role in the development of bone metastasis of prostatic cancers.

Aged↗

Inhibition by interleukin 18 of osteolytic bone metastasis by human breast cancer cells.

Effects of interleukin (IL)-18 on experimental bone metastasis of human breast cancer cells, MDA-231 cells, in nude mice were investigated. In addition, effects of IL-18 on subcutaneous growth of MDA-231 cells were examined. Bone metastasis was produced by an intracardiac injection of MDA-231 cells. Twenty eight days after the cell injection, severe osteolytic bone metastasis was examined by X-ray radiography, and both non-osteolytic and osteolytic bone metastases were examined microscopically. IL-18 (1 microgram/mouse) was injected intraperitoneally according to protocols A and B. In protocol A, IL-18 was injected daily from day 7 after an intracardiac or subcutaneous injection of cells, and in protocol B, it was injected daily for 7 days each before and after the cell injection. In protocol A, IL-18 injections significantly suppressed both the incidence of osteolytic bone metastasis detected by X-ray radiography (about 80% vs. about 20% for the control group vs. the treatment group) and the number of its foci/mouse (1.6 vs. 1 for the control group vs. the treatment group). However, they did not cause significant effects on either the incidence of bone metastasis detected microscopically or the number of its foci/mouse. In protocol B, IL-18 injections caused no significant effects on either the incidence of osteolytic bone metastasis detected by X-ray radiography or the number of its foci/mouse. They caused no significant effects on the incidence of bone metastasis detected microscopically, but significantly decreased the number of its foci/mouse (about 2.0 vs. about 1 for the control group vs. the treatment group). In both protocols A and B, IL-18 injections produced no significant effect on the tumor take and subsequent growth of tumors after a subcutaneous injection of the cancer cells. Since in protocol A, IL-18 appears to have exerted its action after establishment of metastasis by cancer cells to the bone marrow, the effects of IL-18 found in Protocol A indicate that IL-18 inhibited osteolytic growth at bone metastatic sites of breast cancers. On the other hand, since in protocol B IL-18 is likely to have functioned around the time when lodging of cancer cells and early development of metastasis occur in the bone marrow, the effects of IL-18 found in Protocol B indicate that the cytokine also suppresses an early stage of bone metastasis of breast cancers, although, this effect was less apparent than the effect on osteolytic growth. Therefore, IL-18 may be useful for suppression of osteolytic bone metastasis which is a serious problem in patients of advanced breast cancers.

Animals↗

Comparison of sensitivities of uterine cells in their proliferation responding to epidermal growth factor and estrogen between neonatal and postneonatal mice.

The uteri of mice up to 20 days after birth show estrogen-independent growth, although their growth is accelerated by estrogen, while the growth of the uteri of mice after 20 days completely depends on estrogen. In the present study, we compared the sensitivities of uterine cells in their proliferation responding to epidermal growth factor (EGF) and diethylstilbestrol (DES) between 5-day-old and 25-day-old ovariectomized mice. A single subcutaneous injection of EGF at doses of 0.25 and over 0.25 microgram/g body weight (BW) increased 3H-thymidine uptake by the whole uterus dose-dependently in both 25-day-old and 5-day-old mice, and a maximal increase in the 3H-thymidine uptake was attained at a dose of 1 microgram/g BW of EGF in both mice. A single subcutaneous injection of DES at 0.001 and over 0.001 microgram/g BW increased 3H-thymidine uptake by the whole uterus dose-dependently in both 25-day-old and 5-day-old mice, and a maximal increase was attained at 0.004 microgram/g BW of DES in both mice. EGF and DES increased labeling indices of both the epithelium and stroma in both 25-day-old and 5-day-old mice. The present results suggest that sensitivities of uterine cells of neonatal mice in their proliferation responding to EGF and DES are similar to those of postneonatal mice.

Age Factors↗

Castration induces apoptosis in the male accessory sex organs of Fas-deficient lpr and Fas ligand-deficient gld mutant mice.

The role of the Fas ligand-Fas system in castration-induced apoptosis in the epithelia of the ventral prostate (VP), seminal vesicle (SV), coagulating gland (CG) and epididymis (Ep) was investigated using lpr/lpr, and gld/gld mutant mice which are deficient in Fas and Fas ligand, respectively. The degree of apoptosis in the epithelium was quantitatively estimated by an apoptotic index (a percentage of apoptotic cells). The weights (mg/10 g body weight) of the VP, SV, CG and Ep of lpr/lpr and gld/gld mice were similar to those of normal +/+ mice and castration decreased the weights of the VP, SV, CG and Ep in these three kinds of mice to similar levels. Castration also increased the apoptotic indices in these organs reaching maximum on days 2-6 after castration. There was no significant difference in the apoptotic index of these organs among +/+, lpr/lpr and gld/gld mice on days 0-8 after castration. Agarose gel electrophoresis of DNAs extracted from the VP, SV, CG and Ep of +/+, lpr/lpr and gld/gld mice on day 4 after castration showed a ladder pattern. The present results suggest that the Fas ligand-Fas system plays little role in castration-induced apoptosis in the mouse male accessory sex organs such as the VP, SV, CG and Ep.

Animals↗

Enhancement by androgen of the angiogenic ability of androgen-responsive Shionogi carcinoma 115.

The effects of various steroids on the induction of angiogenesis by androgen-responsive Shionogi carcinoma 115 (SC115) were investigated by implanting a piece of a SC115 tumor tissue into a rabbit cornea together with a pellet containing each steroid (250 micrograms) and by examining neovascularization from the limbus. SC115 tumor tissues induced neovascularization in 42% corneas in the absence of steroids, and in 31, 63, 80 and 4% in the presence of estradiol-17 beta, progesterone, testosterone and dexamethasone, respectively. Only testosterone significantly increased the percentage of corneas with neovascularization, while dexamethasone significantly decreased it. Testosterone itself induced no neovascularization, and dexamethasone also inhibited neovascularization induced by acidic fibroblast growth factor. The present results suggest that androgen increases the secretion of an angiogenic factor(s) by an androgen-responsive SC115 tumor, while dexamethasone inhibits angiogenesis induced by the angiogenic factor(s).

Animals↗

Stimulation by estrogen and progesterone of the in vivo growth of transformed murine Leydig cells only at the limited early phase of growth.

B-1 F is a cell line established from estrogen-responsive murine Leydig cell tumor and maintained in vitro. We investigated the effects of steroid hormones on the growth of tumors produced by the inoculation of B-1 F cells into mice. When tumor tissues were transplanted into castrated male mice, injections of estradiol-17 beta (E2) or progesterone shortened the period before tumors became palpable, but did not affect the growth rates of tumors after tumors became palpable. Injections of E2 or progesterone from the time when tumors became palpable did not affect the growth of tumors, and the discontinuation of injections of E2 or progesterone during the middle growth phase showed no effect on the growth of tumors. E2 or progesterone also did not increase the mitotic indices of tumors after they became palpable. E2 and progesterone did not stimulate the proliferation of dispersed tumor cells in vitro. The present results suggested that steroid hormones might exert their actions only at the limited early phase of growth of transplanted steroid hormone-responsive tumors in vivo.

Animals↗

Effects of 30-m nitrox saturation dive on the immune system in man.

Hyperbaria reportedly affects the immune system, but the role of psychological factors arising from confinement has not been taken into consideration. We investigated the immune changes in 4 subjects exposed to a 9-day simulated 30-m (400-kPa) nitrogen-oxygen (nitrox) saturation dive, and compared the results with those of our previous study that showed immune and mood changes in normobaric confinement. Blood samples were taken before, during, and after the dive or confinement, and activated with an anti-CD2 agonistic antibody. The percentages of granulocytes, natural killer (NK) cells, and cells positive for CD69, an early activation marker, were analyzed by flow cytometry. Reduction of CD69 expression percentage was observed under both hyperbaric and normobaric conditions. Percentages of innate immune cells, such as granulocytes and NK cells decreased or remained mostly unchanged, contrasting with our previous study, which demonstrated increases in both percentages coordinate with mood improvement. We conclude that these changes may have been triggered by suppression of sympathetic nerve activity that occurs in 30-m nitrox saturation hyperbaria.

Adult↗

Clinical value of deconvolution analysis in radionuclide renal study.

Deconvolution analysis was applied to radionuclide renal study. The purpose of this study was to clarify the underlying renal physiology that determines the shape and values of the transfer function. Analysis of the renal models revealed that the initial height of the transfer function is the ratio of the radioactivity extracted by the kidney to that in the input function. In addition, the shape of the transfer function displayed the distribution of the transit times and enabled us to evaluate the percentage of nephrons having a particular transit time. Based on the relation between the input and output function, a new method for measuring GFR or ERPF was developed in which the input function was corrected by the plasma radioactivity at 5 min after injection of the tracer. As one of the advantages of the transfer function, it was proved clinically that the contribution of the blood background is automatically eliminated from the amplitude of the transfer function. From these findings, our method for the measurement of GFR was considered superior to that proposed by Gates and highly useful for routine radionuclide renal study.

Glomerular Filtration Rate↗

Establishment and characterization of human vaginal malignant melanoma xenotransplants.

Human vaginal malignant melanoma represents rare gynecological malignancies of poor prognosis. We have established a melanoma tumor line in nude mice, designated Mela-1, and have examined the histological and biological characteristics of this tumor. The Mela-1 tumor has preserved the histological, histochemical and biological characteristics of malignant melanoma even after 20 passages. Tumor cells are of epitheloid shape varying in size. An ultrastructural study revealed that the tumor cells were characterized by the presence of cells with deeply indented nuclei, and both types of melanosomes, eumelanosomes and pheomelanosomes, in various stages of maturation with vesiculo-globular bodies in the cytoplasm. Melanin analysis of the tumor indicated the Mela-1 tumor to be pheomelanic. Immunohistochemical examinations revealed that the Mela-1 cells were stained positively by melanoma-associated antibody (NKI/C3) and by antibodies for S-100 protein and vimentin, and negatively for keratin and CEA. The levels of AFP, CA125 and CEA in sera of tumor-bearing mice were within normal range. The 5-S-cysteinyldopa level in sera of tumor-bearing mice correlated well with the size of the tumor. Chromosomal analysis showed the human karyotype with great heterogeneity and a modal number of 102 chromosomes. Thus the Mela-1 tumor will be useful in establishing the biological characteristics in the search for an effective treatment of human malignant melanoma of the vagina.

Animals↗

No inhibitory effects of danazol estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins.

The effects of danazol on estrogen production by rat ovaries were investigated. Hypophysectomized immature female rats were injected daily with 2.5 or 5 IU of pregnant mare serum gonadotropin (PMS) and simultaneously daily given vehicle only or danazol (100 mg/kg body weight) for 14 days. Danazol did not decrease the activities of 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, 17, 20-lyase and aromatase in the ovaries of rats stimulated by 5IU of PMS. Danazol also did not decrease the activities of 3 beta-hydroxysteroid dehydrogenase and aromatase, and the production of aromatizable androgens (androstenedione plus testosterone) from progesterone in the ovaries of rats stimulated by 2.5 IU of PMS. In accordance with these results, danazol did not reduce the level of estradiol-17 beta in the sera of rats stimulated by 2.5 and 5 IU of PMS. The present results suggest that danazol does not inhibit estrogen production by the rat ovary through its direct action on the ovary.

Animals↗

Effects of antiallergic drugs on the proliferation of estrogen-sensitive mouse Leydig cell line.

The proliferation of B-1F cells established from an estrogen-sensitive mouse Leydig cell tumor is negatively regulated by leukotrienes, whose production is suppressed by the addition of estrogen. Disodium cromoglycate, tranilast, repirinast, tazanolast and pemirolast potassium are used as therapeutic agents for allergic diseases. They are known to inhibit the release of chemical mediators such as histamine and leukotrienes from peripheral leukocytes. It is therefore of interest to determine whether these drugs affect the proliferation of B-1 F cells. The drugs in the culture medium stimulated the proliferation of B-1F cells to various extents. The results suggest that chronic administration of these drugs to the patients with allergic diseases may possibly enhance the proliferation of some kinds of tumor cells, resulting in the change from latent to clinical tumors, although there are significant differences between in vitro cultured animal cells and in vivo humans.

Animals↗

Effects of prolactin and estrogen on cell proliferation of the mouse liver induced by partial hepatectomy.

Estrogen or prolactin suppresses mouse hepatocellular tumorigenesis induced by carcinogens through inhibition of the growth of preneoplastic hepatocytes. In the present study, we investigated whether estrogen or prolactin inhibits proliferation of normal hepatocytes as well as preneoplastic hepatocytes in mice. The proliferation of mouse hepatocytes was induced by partial hepatectomy, and DNA synthesis of the liver was evaluated by measurement of 5-[125I]iododeoxyuridine ([125I]IdUrd) uptake/mg liver DNA after an injection of [125I]IdUrd into mice. For acute treatment with estrogen or prolactin, estradiol-17 beta (E2) (1 micrograms) or ovine prolactin (140 micrograms) was injected into ovariectomized mice twice a day from the day of partial hepatectomy. For chronic treatment with estrogen, ovariectomized mice received implants of E2 pellets containing 100 micrograms E2 40 days before partial hepatectomy, and for chronic treatment with prolactin, hyperprolactinemia was induced by pituitary graft under the renal capsule of ovariectomized mice 40 days before partial hepatectomy or by daily injections of perphenazine (150 micrograms/day) beginning 40 days before partial hepatectomy. The acute treatment with either estrogen or prolactin did not affect the hepatocyte proliferation induced by partial hepatectomy. Chronic hyperprolactinemia induced by the pituitary graft or by injections of perphenazine, and the chronic treatment with E2 pellets did not suppress either basal or partial hepatectomy-induced proliferation of hepatocytes. The present results show that acute and chronic treatments with estrogen or prolactin do not inhibit proliferation of mouse normal hepatocytes, and suggest that the effects of estrogen and prolactin on proliferation of mouse hepatocytes are different from those on proliferation of preneoplastic hepatocytes.

Animals↗

Expression of Fas and Fas ligand in the testes and testicular germ cell tumors: an immunohistochemical study.

The Fas-Fas ligand system plays a crucial role in the production of a signal for apoptosis in the immune system. In the present study, expression of Fas and Fas ligand in the testes and testicular germ cell tumors was examined immunohistochemically. Expression of both Fas and Fas ligand was found on Leydig cells, Sertoli cells, and germ cells in the testis, and on epithelial cells in the epidydimal duct. Expression of both Fas and Fas ligand was also found in all 23 seminomas, 8 embryonal carcinomas, and 3 yolk sac tumors which were examined in this study. Western blot analysis after sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under a reducing condition with tissues of the thymus, the testis, and a seminoma showed a single major band bound to the antibody for Fas or Fas ligand at the position of molecular weight slightly more than 47.5 kilodalton. Since both Fas and Fas ligand are expressed on normal testicular cells, and on cells of testicular germ cell tumors, the Fas-Fas ligand system in these cells seems to play a role other than producing a signal for apoptosis.

Adult↗

Apoptosis in prostatic adenocarcinomas; a study of relationship to Ki-67 and Bcl-2 protein expression.

BACKGROUND: Tissue samples from patients with prostatic adenocarcinoma (PCA) were examined for relationship between apoptosis and expression of Ki-67 and bcl-2 protein. MATERIALS AND METHODS: Prostatic tissue was obtained from 29 prostatic cancer patients with no prior therapy. The number of apoptotic cells (apoptotic index; AI) and the percentage of Ki-67 stained cells (Ki-67 labeling index; LI) were compared with the expression of bcl-2 which was evaluated by the proportion and intensity of tumor cell immunostaining. RESULTS: Both AI and LI of moderately and poorly differentiated PCAs were significantly higher than those of well differentiated PCAs. There was a significant correlation between AI and LI. Bcl-2 protein was expressed less in moderately and poorly differentiated PCAs than in well differentiated PCAs. Moreover, there was no correlation between the bcl-2 protein expression and the AI. CONCLUSIONS: The results suggest that, in PCAs, the degree of apoptosis is correlated with the cellular proliferation, and that expression of bcl-2 protein is not a critical factor that determines the degree of apoptosis.

Adenocarcinoma↗

Maternal or umblical venous levels of nitrite/nitrate during pregnancy and at delivery.

OBJECTIVE: This study was intended to measure serum concentrations of nitrite plus nitrate as an index of nitric oxide synthesis, in the maternal vein during pregnancy, just after a spontaneous delivery and at the puerperium, and at an elective cesarean section, and in the umblical vein and artery. METHODS: Maternal venous sera, and umblical venous and arterial sera were collected, and serum concentrations of nitrite/nitrate were measured by an automated procedure based on the Greiss reaction after reduction of nitrate to nitrite. RESULTS: Compared to a serum concentration of nitrite/nitrate at the first trimester (12-13 weeks of pregnancy), a serum concentration of nitrite/nitrate slightly increased at the second trimester (27-28 weeks), and became maximal at the third trimester (35-36 weeks), followed by a significant decrease near the term (38-40 weeks). A serum concentration of nitrite/nitrate slightly increased just after a spontaneous delivery with labor pains, and at the puerperium to levels slightly more than that at the first trimester. Serum concentrations of nitrite/nitrate in the umblical vein and artery did not differ. They were significantly higher than a serum concentration of nitrite/nitrate in the maternal vein just after a spontaneous delivery with labor pains but not at an elective cesarean section without labor pains. CONCLUSION: A decrease in maternal serum levels of nitrite/nitrate near term may support a hypothesis that NO is one of factors responsible for the maintenance of uterine quiescence during pregnancy. Moreover, the present results suggest that NO plays some role in the feto-placental circulation during a spontaneous delivery.

Adult↗