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Biomedical subjects

H Inano

Publications and source records attributed to H Inano.

At least 37 records · Page 2Linked to original sources
PubMed1995

Chemoprevention by dietary dehydroepiandrosterone against promotion/progression phase of radiation-induced mammary tumorigenesis in rats.

When pregnant rats received whole body irradiations with 260 cGy gamma-ray at day 20 of pregnancy, and were then implanted with a diethylstilbestrol (DES) pellet for an experimental period of 1 year under feeding of a control diet, a high incidence (96.2%) of mammary tumors was observed. Administration of dietary 0.6% dehydroepiandrosterone (DHEA) together with DES implantation significantly decreased the incidence (35.0%) of mammary tumors. The first appearance of palpable tumors in the DHEA-fed group was 4.5 months later than that in the control group. For clarification of the mechanism of the chemopreventive action, we measured hormone levels in the serum of DHEA-fed rats. In the DHEA diet rats, the concentration of estradiol-17 beta exceeded, by approximately 6-fold, that in the control rats, while the levels of progesterone and prolactin were decreased by 30 and 45%, respectively. Interestingly, DHEA feeding prevented DES-induced hypertrophy of pituitary glands and DES-induced high level of prolactin in pituitary glands detected by immunohistochemical studies, but stimulated the development of mammary glands more than that in control rats treated with DES alone. These findings suggest that DHEA has a potent preventive activity against the promotion/progression phase of radiation-induced mammary tumorigenesis. The mechanism of chemoprevention by change of endocrinological environment is discussed.

Animals↗
PubMed1995

Estradiol-17 beta as an initiation modifier for radiation-induced mammary tumorigenesis of rats ovariectomized before puberty.

This investigation evaluated the roles of estradiol-17 beta, progesterone and prolactin in the initiation of mammary tumorigenesis by irradiation. Sixty day old Wistar-MS rats ovariectomized bilaterally at 23 days of age were injected daily with olive oil, estradiol-3-benzoate (E2B), progesterone or haloperidol for 14 days, and were then irradiated with gamma-rays (260 cGy) on the morning following the last injection. Diethylstilbestrol pellets were administered by implantation 30 days after the irradiation. Following treatment with E2B, the incidence of mammary tumors was increased 2.2-fold, in comparison with that in the corresponding control rats. Bilateral ovariectomy before puberty caused the mammary glands of adult rats to atrophy, and a low degree of differentiation with long narrow ducts was observed in whole mounts. The DNA synthesis in the mammary glands and serum prolactin level of E2B-treated rats were markedly increased and the terminal ducts showed distinctly increased differentiation into terminal end buds and alveolar buds with prolactin receptors. When progesterone, another ovarian hormone, or haloperidol, a dopamine antagonist in adenohypophysis, was injected into the rats under estrogen-free conditions, neither expression of prolactin receptors nor stimulation of DNA synthesis was observed in the mammary glands, and the incidence of mammary tumors induced by irradiation was lower than that observed in rats treated with E2B. Combined treatment with E2B and progesterone resulted in a reduction in the incidence of mammary tumors and in serum prolactin levels compared with those in E2B alone, in spite of the synergistic effects on prolactin receptor concentration and DNA synthesis by the two hormones. On the other hand, concurrent administration of haloperidol did not reduce the E2B-induced tumor incidence or prolactin concentration in serum. Many of the mammary tumors which developed in the ovariectomized rats were of the ER(-)PgR(-) type. The incidence of development of ER(+)PgR(+) tumors was increased by treatment with E2B before the irradiation, and no ER(-)PgR(-) tumors were observed in this group. Our results suggest that estrogen is a direct or indirect sensitizer for tumor initiation by radiation, and is also one of the regulatory factors for hormone dependence of radiation-induced mammary tumors.

Animals↗
PubMed1994

Susceptibility of lactating rat mammary glands to gamma-ray-irradiation-induced tumorigenesis.

Lactating rats of the Wistar-MS strain were irradiated with 260 cGy of gamma rays 21 days after parturition (day 21). Diethylstilbestrol (DES) pellets were implanted one month after termination of nursing and were allowed to remain for one year. A significantly higher incidence (96.4%) of mammary tumors was observed in these rats irradiated during late lactation than in virgin irradiated animals (30.4%). A control group of lactating animals irradiated during late lactation but not treated with DES was also observed for one year; the final incidence of mammary tumors in this group was 35.3%. The latency period was shortest in the DES-treated group irradiated during late lactation. Histological examination showed that the mammary glands of lactating rats were highly developed, with alveoli filled with milk. Five days after weaning, there was degeneration of alveolar tissue, concomitant with a marked decrease in the concentration of estrogen and prolactin receptors. A considerable amount of epithelial tissue remained in the mammary glands during the process of atrophy. When the rats were irradiated 5 days after weaning, and then were treated with DES for one year, the incidence of mammary tumors was 73.3%, significantly higher than that in virgin irradiated rats. However, this incidence was not significantly different from that in animals irradiated during late lactation. These results suggested that the induction of mammary tumors by gamma irradiation before or after weaning was more dependent upon the stage of differentiation in mammary glands than upon the proliferative activity of epithelial cells, and that DES is essential as a promoter for radiation-induced mammary tumorigenesis.

Animals↗
PubMed1994

Scanning electronmicroscopic morphometry of emphysema in humans.

We quantitated the holes in alveolar walls in 11 nonemphysematous lungs and in 11 lungs with mild emphysema, all of which were removed at surgery. We found that in the nonemphysematous lungs, 94.1% of the holes were smaller than 10 microns in diameter and only 0.2% were larger than 20 microns. In the lung parenchyma distant from emphysema, both the maximum diameter of the holes and the diameter of alveoli increased. In the parenchyma between emphysema, the areas of alveolar walls represented by holes also increased, as did the average hole area and number of holes per alveolus. We found that alveolar holes in the regions between emphysema correlated better with pulmonary function tests than did those in regions distant from emphysema. The maximum diameter of holes and the number of holes per alveolus correlated with functional residual capacity, residual volume, closing capacity expressed as a proportion of total lung capacity (CC/TLC), and static recoil pressure of the lung at TLC. Emphysema correlated with CC/TLC and with the transpulmonary pressure at 90% TLC. Bronchiolar lesions were not related to pulmonary function tests. Our data provide support for the hypothesis that the tissue surrounding emphysematous lesions contributes to loss of recoil.

Functional Residual Capacity↗
PubMed1993

Promotive effects of diethylstilbestrol, its metabolite (Z,Z-dienestrol) and a stereoisomer of the metabolite (E,E-dienestrol) in tumorigenesis of rat mammary glands pregnancy-dependently initiated with radiation.

Wistar-MS rats received whole body irradiation with 260 cGy gamma-rays at day 20 of pregnancy and then were treated with diethylstilbestrol (DES), E,E-dienestrol (E,E-DIES) or Z,Z-dienestrol (Z,Z-DIES) for 1 year. DES administration caused the highest incidence of mammary tumors with a concomitant reduction of gain in body weight. When E,E-DIES or Z,Z-DIES in pellet form was implanted, the incidence of tumors was significantly lower than that observed in rats treated with DES. To clarify the increased susceptibility to mammary tumorigenesis after DES administration we measured hormone levels in the serum of rats implanted with pellets containing derivatives of the synthetic estrogens. The serum prolactin concentration was significantly increased by DES administration. When E,E-DIES or Z,Z-DIES pellets were implanted the prolactin level was markedly reduced to 4.5% and 0.7% of that observed in DES-treated rats, respectively. In addition, the serum concentrations of estradiol-17 beta and progesterone in rats with Z,Z-DIES pellets were higher than those of rats with DES or E,E-DIES pellets. A large number of DES-induced mammary tumors were positive for both estrogen and progesterone receptors, but no tumors negative for both receptors were obtained. The findings suggest that DES acts directly on radiation-initiated mammary cells via binding with estrogen receptors and/or stimulates the secretion of prolactin from the pituitary glands.

Adenocarcinoma↗
PubMed1992

Influence of the estrous cycle at gamma-ray exposure on radiation-induced mammary tumorigenesis in virgin rats.

Wistar rats received whole body irradiation with 260 cGy gamma-rays at 10 a.m. of individual phases of their estrous cycle and then had diethylstilbestrol pellets implanted for 1 year. When the radiation was given during di-estrus II, the highest incidence (73.3%) of mammary tumorigenesis was observed, and mean latency until the first tumor appearance was 8.5 +/- 0.7 months. Also, rats irradiated on estrus had significantly lower incidence (35.3%) of mammary tumors than those irradiated on pro-estrus and di-estrus II, but there was no significant difference in latency period. Iball's indices of total mammary tumors, fibroadenoma plus adenocarcinoma, were 14.3 +/- 0.9, 28.8 +/- 2.1, 23.3 +/- 0.8 and 12.2 +/- 0.2 in rats irradiated during di-estrus I, di-estrus II, pro-estrus and estrus respectively. The percentage of adenocarcinomas was comparatively uniform (25.0 to 34.8%) throughout the various phases of the estrous cycles. Also, Iball's indices calculated from adenocarcinoma indicated no significant differences between all groups. From our results, the highest incidence of mammary tumors arose in rats after irradiation at di-estrus II with minimum level of prolactin in serum. We discuss different mechanisms of radiation-induced and chemical-carcinogen-induced tumorigenesis of mammary glands.

Adenocarcinoma↗
PubMed1992

Effect of zymosan-activated plasma on the deformability of rabbit polymorphonuclear leukocytes.

Intravascular infusion of inflammatory mediators causes a sudden neutropenia due to the sequestration of polymorphonuclear leukocytes (PMN) within the microvasculature of the lung and other organs. This sequestration could be due to a decrease in the ability of PMN to deform and pass through the narrow capillary bed. The purpose of this study was to determine if the complement fragments present in zymosan-activated plasma (ZAP) caused a rapid stiffening of PMN. The PMN deformability was determined by measuring the pressure required to pass PMN through a polycarbonate filter containing 5-micron pores at a constant flow rate as well as the extraction of PMN compared with red blood cells and 125I-labeled albumin by the filter. The role of the cytoskeleton in PMN deformation was examined in studies where F-actin formation was inhibited using cytochalasin B or microtubule assembly was inhibited using colchicine. The results showed that treatment with ZAP induced a rapid decrease in PMN deformability. Inhibiting the formation of F-actin made the unstimulated PMN more deformable and reduced the stiffening induced by ZAP. In contrast, inhibition of microtubule reassembly did not alter either normal deformability or the ZAP-induced decrease in deformability. In vivo, colchicine increased normal PMN margination but did not inhibit the rapid sequestration of PMN induced by infusion of ZAP. These studies indicate that ZAP induces a rapid decrease in PMN deformability that is mediated through the cytoskeleton. They suggest that this decrease is due to the polymerization of F-actin.

Actins↗
PubMed1992

Administration of alpha 1-proteinase inhibitor ameliorates bleomycin-induced pulmonary fibrosis in hamsters.

The effect of alpha 1-proteinase inhibitor (alpha 1Pi) administration on the acute lung injury and subsequent fibrosis induced by bleomycin (BLM) was examined in hamsters. Pulmonary lesions were quantitatively reduced in alpha 1Pi-administered BLM-treated (BLM-alpha 1Pi) animals compared with animals treated by BLM alone (BLM-control) at both 7 days (acute stage) and 30 days (fibrotic stage) after BLM treatment. Analysis of intraalveolar cells from bronchoalveolar lavage (BAL) fluid revealed that neutrophils and lymphocytes were significantly decreased in the BLM-alpha 1Pi animals at 7 days after BLM treatment and that 30 days after BLM treatment macrophages as well as neutrophils and lymphocytes were remarkably decreased in the BLM-alpha 1Pi animals. The elastase activity in supernatants of BAL fluid during 7 days following BLM treatment was detected, but there was no difference between the two groups. In vitro studies on neutrophil responsiveness to stimulation of BAL fluid at 3 days after BLM treatment revealed noticeable chemotaxis and generation of superoxide anion of isolated neutrophils, but alpha 1Pi did not show any inhibitory effects on neutrophil responsiveness. We suggest that alpha 1Pi administration ameliorates pulmonary fibrosis preceded by acute lung injury induced by BLM treatment in hamsters and that the inhibitory effects of alpha 1Pi on lung injury may not be brought about by altered elastase activity, chemotaxis, or superoxide generation in neutrophils. Alternative mechanisms are discussed.

Animals↗
PubMed1991

Biosynthesis of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one in the ovaries of grey mullet (Mugil cephalus) during induced ovulation by carp pituitary homogenates and an LHRH analogue.

Three female mullets received a priming injection of carp pituitary homogenate followed by a resolving injection of an LHRH analogue 24 hr later. Ovarian biopsies were obtained just prior to the first injection (phase I), 24 hr after the first injection (i.e., immediately before the second injection, phase II), and 8 hr after the second injection (phase III). Two fish (Nos. 1 and 3) spawned approximately 12 hr after the second injection. Serum levels of testosterone increased to some extent during phase II in all of the fish. Testosterone levels decreased abruptly during phase III in both fish Nos. 1 and 3. In contrast the concentration of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-diOHprog) was undetectable in phases I and II, and increased dramatically during phase III in the same fish. In fish No. 2, which did not spawn, neither the decrease of testosterone nor the increase of 17 alpha,20 beta-diOHprog was observed. Ovarian tissues of all the fish were pooled in each phase and incubated with 14C-labeled progesterone or 17 alpha-hydroxyprogesterone to investigate steroid metabolism. During phases I and II progesterone was converted to 17 alpha-hydroxyprogesterone, androstenedione, and testosterone. During phase III, production of these steroids decreased drastically, and in turn, synthesis of 20 beta-hydroxy-4-pregnen-3-one and 17 alpha,20 beta-diOHprog was induced. Using 17 alpha-hydroxyprogesterone as a substrate, androstenedione and testosterone were produced during phases I and II, whereas they decreased considerably during phase III. This was followed by the production of 17 alpha,20 beta-diOHprog as the major metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Pregnancy-dependent initiation in tumorigenesis of Wistar rat mammary glands by 60Co-irradiation.

Pregnant Wistar rats received whole body irradiation with 260 cGy gamma-rays at days 7, 14 and 20 of pregnancy and then were treated with diethylstilbestrol (DES) for 1 year. The highest incidence (92.9%) for tumorigenesis of mammary glands was observed in the rats irradiated in late pregnancy. Histological examination showed that tumors were classified as fibroadenoma and adenocarcinoma. To determine the reasons for specific induction of mammary tumors by irradiation in late pregnancy, hormone concentrations in serum and estrogen receptors in mammary glands during pregnancy were measured. Concentrations of estradiol, progesterone, 11-deoxycorticosterone and placental lactogen at day 20 were higher than at days 7 and/or 14, but no difference was observed in the concentrations of prolactin and thyroid-stimulating hormone during pregnancy. The estrogen receptor in mammary glands at day 20 was indicated to have the highest affinity and the highest binding capacity during pregnancy. Normal mammary glands at day 20 were suggested to have more abundant epithelial cells in the mammary lobes than those at days 7 and 14. The data suggest that the critical requirements for the initiation of tumorigenesis by gamma-rays are dependent upon the differentiated state of mammary glands exposed to various hormones, and that the concentration and persistence of the synthetic estrogen (DES) are necessary for the promotion of tumorigenesis of the irradiated mammary glands.

Animals↗
PubMed1990

Serum thymic factor as a radioprotective agent promoting survival after X-irradiation.

Serum thymic factor (FTS, zinc-free thymulin) protected mice from death after whole-body X-irradiation. It was significantly radioprotective even when administered after irradiation, but it was more effective when administered both before and after irradiation. The protective effect appears to be due to the enhancement of hematologic recovery in the animals.

Animals↗
PubMed1990

Steroidogenesis in the testes and the adrenals of adult male rats after gamma-irradiation in utero at late pregnancy.

Pregnant rats were irradiated with 2.1 Gy gamma-ray of 60Co at day 20 of gestation. Seventy days after birth, the body weight of the fetally irradiated male pups was significantly lower than the control. The testes, ventral prostates and seminal vesicles were atrophied by irradiation, whereas no decreased weight of the adrenals was observed. Histological examination of the testes of the irradiated rats revealed a complete disappearance of germinal cells. Sertoli cells and Leydig cells appeared normal, and no apparent histological difference was observed in the adrenals between the control and the irradiated rats. Activities of microsomal delta 5-3 beta-hydroxysteroid dehydrogenase (HSD) + isomerase, 17 alpha-hydroxylase/C17,20-lyase, 17 beta-HSD and 7 alpha-hydroxylase per pair of testes were decreased in the irradiated rats (36-86% of the control). In contrast, no decreased activity of 20 alpha-HSD in the cytosol fraction was observed by irradiation. No decreased activity of adrenocortical enzymes, such as delta 5-3 beta-HSD + isomerase, 21-hydroxylase, 11 beta-/18-hydroxylase and 5 alpha-reductase, was also observed in the irradiated group. Concentrations of LH, FSH, TSH, prolactin, testosterone, progesterone and aldosterone in serum were measured by radioimmunoassay. Only the FSH concentration was significantly increased by the irradiation, while no difference was found in the concentration of other hormones. It was concluded that irreversible damage was induced in spermatogenesis and androgen production by the fetal irradiation, whereas corticoidogenesis was not affected.

Adrenal Glands↗
PubMed1990

Reasons for reduced activities of 17 alpha-hydroxylase and C17-C20 lyase in spite of increased contents of cytochrome P-450 in mature rat testis fetally irradiated with 60Co.

Pregnant rats received whole body irradiation with 2.6 Gy gamma-ray from a 60Co source at Day 20 of gestation. When pups were 4 months old, activities of electron transport system and steroid monooxygenase in tests were assayed. The content of total cytochrome P-450 in the irradiated testes had increased to 170% of that in non-irradiated rats, but NADPH-cytochrome P-450 reductase activity had reduced to 36% of the control. Also, amounts of cytochrome b5 in testicular microsomal fraction were decreased markedly after irradiation, but no significant change of NADH-cytochrome b5 reductase activity was observed in the treated pups. Because both 17 alpha-hydroxylase and C17-C20 lyase activities tended to be decreased by fetal irradiation, testosterone production from progesterone and 17 alpha-hydroxyprogesterone was reduced to about 30% of the control. From these results, it has been suggested that the testicular cytochrome P-450 is radioresistant but steroid monooxygenase activities are reduced after the fetal irradiation. We propose that the discrepancy arises from the marked decrement of NADPH-cytochrome P-450 reductase activity.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Morphologic changes in the airways induced by recurrent exposure of acetylcholine in the guinea pig.

The morphologic changes in peripheral airways of guinea pigs derived from asthmalike breathing induced by acetylcholine (Ach) exposure were studied. In the Ach-exposed animals, the smooth muscle in the respiratory units (alveolar mouth of the alveolar duct) as well as in the peripheral airways was increased. The internal and external diameters of the peripheral airways were not significantly different between Ach-exposed and control animals. In addition, the Ach-exposed animals had higher specific diaphragm weights (diaphragm to body weight). We conclude that recurrent asthmalike breathing brings about increased smooth muscle, but the increased muscle contributes little to airway dimensions. We speculate that an increased airway wall thickness inside the outermost layer of smooth muscle may play a role in increasing airway reactivity.

Acetylcholine↗
PubMed1990

[The relationship between alveolar apertures and alveolar size and smoking history in humans, and experimental studies on air pollutants].

Using surgical specimens from patients with lung tumor, alveolar apertures and alveolar sizes were quantitatively assessed using scanning electron microscopy. Compared with smoking habits, increased apertures, defined as alveolar destruction were observed in patients smoking more than 35 years, whereas alveolar size was increased in patients, with a 15-year smoking history. Experimental studies with exposure to NO2, O3 and H2SO4 mist showed that exposure of NO2 and H2SO4 could induce epithelial injury such as disappearance of cilia in the central airways.

Adult↗
PubMed1989

Affinity labeling of cofactor-binding region of human placental estradiol 17 beta-dehydrogenase by periodate-oxidized NADP+ (o-NADP+).

Periodate-oxidized NADP+ (o-NADP+), an analogue of the cofactors, is a reversible inhibitor of estradiol 17 beta-dehydrogenase in human placenta. Mode of the inhibition by o-NADP+ appeared to be competitive type (Ki = 0.84 microM) against NAD+ and non-competitive type (Ki = 1.13 microM) against estradiol, respectively. Treatment of the estradiol 17 beta-dehydrogenase with o-NADP+ resulted in time-dependent loss of the enzyme activity. The inactivation exhibited pseudo-first order kinetics (t1/2 = 15 min) and was protected by NAD+ and NADP+. On the other hand, periodate-oxidized ATP inactivated slightly the estradiol 17 beta-dehydrogenase. These results indicate that the residue(s) of lysines is located near the cofactor-binding region of estradiol 17 beta-dehydrogenase of human placenta.

17-Hydroxysteroid Dehydrogenases↗
PubMed1989

Biosynthetic pathways of testosterone and estradiol-17 beta in slices of the embryonic ovary and testis of the chicken (Gallus domesticus).

To elucidate synthetic pathways of testosterone and estradiol-17 beta in embryonic gonads of the chicken, metabolism of various 14C-labeled steroids in slices of the left ovaries and paired testes of 15- and 9-day-old chicken embryos was examined. (1) Fifteen-day-old chicken embryos: From pregnenolone, more 17 alpha-hydroxypregnenolone was produced than progesterone in the ovary, while more progesterone was produced than 17 alpha-hydroxypregnenolone in the testis. From 17 alpha-hydroxypregnenolone, however, only dehydroepiandrosterone was detected as a product in both gonads. Dehydroepiandrosterone was converted mainly into androstenedione and its 5 beta-reduced derivatives by both gonads. Progesterone was converted into 5 beta-pregnane-3,20-dione more than into 17 alpha-hydroxyprogesterone by both gonads. Both gonads metabolized 17 alpha-hydroxyprogesterone, androstenedione, and testosterone predominantly into their corresponding 5 beta-reduced steroids, while production of androstenedione from 17 alpha-hydroxyprogesterone and of testosterone from androstenedione was limited. Estradiol-17 beta was produced from androstenedione and testosterone only by the ovary. (2) Nine-day-old chicken embryos: From pregnenolone, production of progesterone and 17 alpha-hydroxypregnenolone was similar in the ovary. On the other hand, in the testis, more progesterone was produced than 17 alpha-hydroxypregnenolone from pregnenolone. For delta 4-3-oxo steroids, strong activity of 5 beta-reductase was demonstrated in both gonads. From these results, both delta 4- and delta 5-pathways are involved in the formation of testosterone and then finally of estradiol-17 beta by the embryonic gonads of the chicken, and relative preference for the pathway seems to depend on sexes and embryonic ages. In addition, it is suggested that steroidogenesis in these embryonic gonads is characterized by marked activity of 5 beta-reductase, irrespective of sexes or ages.

17-alpha-Hydroxypregnenolone↗