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Biomedical subjects

A Miyamoto

Publications and source records attributed to A Miyamoto.

At least 19 recordsLinked to original sources
PubMed2003

Effect of local interaction of reactive oxygen species with prostaglandin F(2alpha) on the release of progesterone in ovine corpora lutea in vivo.

Prostaglandin (PG) F(2alpha) is implicated in the process of luteal regression in many species, and has been shown to increase the generation of reactive oxygen species. In this study, the role of reactive oxygen species in the local regulatory mechanisms of functional luteolysis in the ewe was examined. In Experiment 1, we studied local effects of hydrogen peroxide (H(2)O(2)) and its interaction with PGF(2alpha) on P secretion in ovine corpus luteum (CL) in vivo. For this purpose, a microdialysis system (MDS) was used, where only the cells surrounding the capillary membrane in the microenvironment of the CL are exposed to these factors, and the P secretory ability of the CL is maintained as if intact. The study used a multiple CL model to implant the MDS, enabling us to examine in parallel several experimental infusions into the MDS implanted in different CLs (one MDS line per CL) developed after superovulation in one ewe. On Day 8 after GnRH treatment, the MDS were implanted into multiple CL in both ovaries of six ewes. A 4-h infusion with PGF(2alpha) (10(-6)M) at 8-12 h slightly increased P release during infusion, while a 4-h infusion with H(2)O(2) (10(-3)M) at 20-24 h decreased P release at 27-38 h. A pre-infusion with PGF(2alpha) for 4h at 8-12h, followed by infusion of H(2)O(2) at 20-24 h rapidly decreased the P release at 20-40 h (P<0.05); this decrease occurred 7h earlier than in the CL treated with H(2)O(2) alone. In Experiment 2, by utilizing the MDS we also applied free radical scavengers to examine their possible weakening effect on the inhibition of P secretion in the microenvironment within the regressing CL induced by PGF(2alpha) treatment. On Day 8 after estrus, the MDS were implanted into the CL (single CL model, two MDS lines per CL). Infusion of free radical scavengers, superoxide dismutase (SOD;50mg/ml)+catalase (CAT; 10mg/ml), at 0-28 h first increased P release until 12 h (P<0.05), and consequently delayed the decrease in P release until 30 h after administration of PGF(2alpha) i.m. (P<0.05). The present results support the concept that the leading pathway from PGF(2alpha) induces an increase of reactive oxygen species in luteolysis in the ewe.

Animals↗
PubMed2003

Expression of 11beta-hydroxysteroid dehydrogenases in bovine follicle and corpus luteum.

In glucocorticoid target organs, local concentrations of active glucocorticoid are determined by the relative expression of two 11beta-hydroxysteroid dehydrogenases (HSDs): bi-directional 11beta-HSD type1 (11HSD1) that mainly activates cortisone to cortisol, and dehydrogenase 11beta-HSD type2 (11HSD2) that inactivates cortisol to cortisone. In this study, we examined the expression of mRNA encoding these two 11beta-HSDs in bovine granulosa cells harvested from preovulatory follicles and corpora lutea (CL). Ovaries were obtained from Holstein cows at a local slaughterhouse. Follicles larger than 10 mm in diameter and CL were dissected and follicular fluid and granulosa cells were taken. Corpora lutea were weighed and their stages were morphologically assessed (stage I, days 1-4; stage II, days 5-10; stage III, days 11-17; stage IV, days 8-20). Follicles were classified into four groups according to their hormonal status (oestradiol (E(2)): progesterone (P(4))>1: oestrogen active; E(2):P(4)<1: oestrogen inactive) and stage of the oestrous cycle (luteal or follicular phase). Total RNA was extracted with phenol-chloroform and subjected to a semi-quantitative RT-PCR for 11HSD1, 11HSD2 and beta-actin. Concentrations of steroids in follicular fluid were determined by an enzyme immunoassay. In granulosa cells, only 11HSD1 mRNA was detected. There was a negative correlation between the expression of 11HSD1 and the concentration of cortisol in follicular fluid (P<0.05), indicating 11HSD1 may act as a dehydrogenase in the bovine follicle. Both types of 11beta-HSDs were expressed in CL. The levels of mRNA for both isozymes were high in stage I and II, and were decreased in stage III CL. In stage IV CL, the expression of 11HSD2 but not 11HSD1 mRNA increased. These results indicate that the bovine granulosa cells and CL express 11HSD1 and 11HSD2, and they may play an important physiological role in the bovine ovary through modulating the local glucocorticoid environment.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

Local changes in blood flow within the preovulatory follicle wall and early corpus luteum in cows.

Haemodynamic changes are involved in the cyclic remodelling of ovarian tissue that occurs during final follicular growth, ovulation and new corpus luteum development. The aim of this study was to characterize the real-time changes in the blood flow within the follicle wall associated with the LH surge, ovulation and corpus luteum development in cows. Normally cyclic cows with a spontaneous ovulation (n = 5) or a GnRH-induced ovulation (n = 5) were examined by transrectal colour and pulsed Doppler ultrasonography to determine the area and the time-averaged maximum velocity (TAMXV) of the blood flow within the preovulatory follicle wall and the early corpus luteum. Ultrasonographic examinations began 48 h after a luteolytic injection of PGF(2alpha) analogue was given at the mid-luteal phase of the oestrous cycle. Cows with spontaneous ovulation were scanned at 6 h intervals until ovulation occurred. Cows with GnRH-induced ovulation were scanned just before GnRH injection (0 h), thereafter at 0.5, 1, 2, 6, 12, 24 h and at 24 h intervals up to day 5. Blood samples were collected at the same time points for oestradiol, LH and progesterone determinations. Cows with both spontaneous and GnRH-induced ovulation showed a clear increase in the plasma concentration of LH (LH surge) followed by ovulation 26-34 h later. In the colour Doppler image of the preovulatory follicle, the blood flow before the LH surge was detectable only in a small area in the base of the follicle. An acute increase in the blood flow velocity (TAMXV) was detected at 0.5 h after GnRH injection, synchronously with the initiation of the LH surge. At 12 h after the LH surge, the plasma concentrations of oestradiol decreased to basal concentrations. The TAMXV remained unchanged after the initial increase until ovulation, but decreased on day 2 (12-24 h after ovulation). In the early corpus luteum, the blood flow (area and TAMXV) gradually increased in parallel with the increase in corpus luteum volume and plasma progesterone concentration from day 2 to day 5, indicating active angiogenesis and normal luteal development. Collectively, the complex structural, secretory and functional changes that take place in the ovary before ovulation are closely associated with a local increase in the blood flow within the preovulatory follicle wall. The result of the present study provides the first visual information on vascular and blood flow changes associated with ovulation and early corpus luteum development in cows. This information may be essential for future studies involving pharmacological control of blood flow and alteration of ovarian function.

Animals↗
PubMed2002

Bovine retained placenta: hormonal concentrations in fetal and maternal placenta.

The aim of this study was to evaluate the relationship between the occurrence of retention of the fetal membranes (RFM) and the hormonal concentrations of progesterone, estradiol-17beta, prostaglandin E(2) (PGE(2)), prostaglandin F(2alpha) (PGF(2alpha)), oxytocin (OT), oxytocin receptor (OT-R), endothelin-1 and angiotensin II (Ang II) in the placental tissues of cattle. Parturition was induced in nine Holstein cows by a single injection of PGF(2alpha) on Day 274 of gestation. Six out of nine cows in the induced group did not release the fetal membranes within 12 h after parturition and served as the RFM group, and the remaining three cows in that group, which released their fetal membranes within 12 h, served as the non-RFM group. Five other cows calved spontaneously and served as controls. The placental tissues were collected immediately (0 h) and at 6 h after parturition. The hormonal concentrations were measured by enzyme immunoassay in maternal and fetal placental tissues from RFM, non-RFM and control cows. There were no differences in P4 and E2 concentrations among the RFM, non-RFM and control groups. The mean PGF(2alpha) concentration of the RFM group was lower than those of the non-RFM and control groups in the maternal part of the placenta. In maternal tissues, the OT and OT-R concentrations in the RFM group were lower than those at 0 and 6 h after parturition in the non-RFM group. Additionally, the Ang II concentration of the RFM group in both the maternal and fetal parts of placental tissues tended to be higher than those of the other groups. In conclusion, the present results suggest that ET-1 and Ang II may play differential tissue-specific roles in the placental unit that may amplify the local endocrinological cascade involving OT, OT-R and PGF(2alpha) interactions which are necessary for normal placental separation in the cow.

Animals↗
PubMed2002

The cooperative action of angiotensin II with subluteolytic administration of PGF2alpha in inducing luteolysis and oestrus in the cow.

There is evidence that the potent vasoconstrictor angiotensin II (Ang II) regulates luteal functions. In the present study, the effect of an intraluteal injection of Ang II alone or in combination with pretreatment with a subluteolytic i.m. dose of PGF(2alpha) on the concentration of plasma progesterone, corpus luteum regression and duration of the oestrous cycle was investigated. Cows were assigned randomly to receive an intraluteal injection of either: (i) 500 microl saline 30 min after i.m. administration of saline (control, n = 7); (ii) 500 microl saline 30 min after i.m. administration of a subluteolytic dose (125 microg) of a PGF(2alpha) analogue (1/4 PGF(2alpha), n = 5); (iii) 2 mg Ang II in 500 microl saline 30 min after i.m. administration of saline (Ang II, n = 5); or (iv) 2 mg Ang II in 500 microl saline 30 min after i.m. administration of a subluteolytic dose (125 microg) of the PGF(2alpha) analogue (1/4 PGF(2alpha)/Ang II, n = 6) on day 12 of the oestrous cycle. There were no significant changes in plasma progesterone concentrations in the control, 1/4 PGF(2alpha) or Ang II treatment groups. Treatment with 1/4 PGF(2alpha)/Ang II decreased plasma progesterone concentration, and induced luteolysis and oestrus. The onset of oestrus in cows treated with full-dose (500 microg) PGF(2alpha) (3.1 +/- 0.2 (mean +/- SEM) days after treatment) was significantly earlier than that in cows treated with 1/4 PGF(2alpha)/Ang II (4.8 +/- 0.2 days after treatment) (P < 0.05). The results from the present study demonstrate that an intraluteal injection of Ang II after i.m. administration of a subluteolytic dose of PGF(2alpha) analogue induces luteolysis and oestrus. Thus, these results support the contention that Ang II is directly correlated with the process of luteal regression in cows.

Angiotensin II↗
PubMed2001

Mutant of LolA, a lipoprotein-specific molecular chaperone of Escherichia coli, defective in the transfer of lipoproteins to LolB.

The outer membrane-specific lipoproteins of Escherichia coli are released from the inner membrane as a water-soluble complex with LolA and then transferred to the outer membrane receptor, LolB. LolA thus plays a critical role in the sorting and outer membrane localization of lipoproteins. To dissect the LolA function, the highly conserved residues were subjected to random mutagenesis, followed by selection for a growth defect. LolA(R43L), one of mutants thus constructed, possessed Leu in place of Arg at position 43 and caused accumulation of the LolA(R43L)-lipoprotein complex in the periplasm. LolA(R43L) was as active as wild-type LolA as to the release of lipoproteins from spheroplasts. In marked contrast, the transfer of lipoproteins from LolA(R43L) to LolB was completely inhibited, indicating that Arg at position 43 of LolA is involved in the lipoprotein transfer reaction.

Amino Acid Sequence↗
PubMed2001

Plasma and pituitary concentrations of gonadotropins (FSH and LH) in minke whales (Balaenoptera acutorostrata) during the feeding season.

This study investigated plasma and pituitary concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and steroid hormones (progesterone: P4, testosterone:T, estradiol-17beta: E2) by enzyme-immunoassay (EIA) in minke whales (Balaenoptera acutorostrata) captured during the feeding season (December to March) in the Antarctic Ocean. Plasma FSH and LH levels in female minke whales were higher (P <0.05) than in male whales. Although the pituitary weight was not significantly different between male and female whales, pituitary FSH and LH levels were higher in females than in males (P<0.01) and mature whales than immature whales (P<0.05). Plasma levels of FSH, T and E2 were not significantly different between immature and mature male whales, but plasma LH and pituitary FSH and LH levels were higher (P<0.05) in mature than in immature whales. In both immature and mature whales regardless of gender, pituitary FSH and LH levels were correlated significantly (r=0.69: P<0.01). In mature male whales, plasma T and E2 levels (r=0.60: P<0.01), and testis weight and plasma T levels (r=0.46: P <0.05) were correlated. In immature female whales, plasma FSH and LH levels were highly correlated (r=0.68: P<0.001), but were not for mature female whales. The results show that gender and maturity influence gonadal and pituitary function of minke whales during the feeding season.

Age Factors↗
PubMed2001

Ligand-induced signaling in the absence of furin processing of Notch1.

Notch is a conserved cell surface receptor that is activated through direct contact with neighboring ligand-expressing cells. The primary 300-kDa translation product of the Notch1 gene (p300) is cleaved by a furin-like convertase to generate a heterodimeric, cell-surface receptor composed of 180- (p180) and 120- (p120) kDa polypeptides. Heterodimeric Notch is thought to be the only form of the receptor which is both present on the cell surface and able to generate an intracellular signal in response to ligand. Consistent with previous reports, we found that disruption of furin processing of Notch1, either by coexpression of a furin inhibitor or by mutation of furin target sequences within Notch1 itself, perturbed ligand-dependent signaling through the well-characterized mediator of Notch signal transduction, CSL (CBF1, Su(H), and LAG-1). Yet contrary to these reports, we could detect the full-length p300 Notch1 product on the cell surface. Moreover, this uncleaved form of Notch1 could suppress the differentiation of C2C12 myoblasts in response to ligand. Taken together, these data support our previous studies characterizing a CSL-independent Notch signaling pathway and identify this uncleaved isoform of Notch as a potential mediator of this pathway. Our results suggest a novel paradigm in signal transduction, one in which two isoforms of the same cell-surface receptor could mediate two distinct signaling pathways in response to ligand.

Animals↗
PubMed2001

Growth hormone, but not luteinizing hormone, acts with luteal peptides on prostaglandin F2alpha and progesterone secretion by bovine corpora lutea in vitro.

Prostaglandin F2alpha (PGF2alpha) is a major physiological luteolysin in the cow. However, injection of PGF2alpha before day 5 (day 0 = estrus) of the estrous cycle dose not induce luteolysis. On the other hand, the early corpus luteum (CL) actively produces PGF2alpha. This indicates that luteal PGF2alpha may play a key role in the refractoriness to PGF2alpha injected during the early luteal phase when angiogenesis is active in the CL. Thus, this study aimed to investigate the possible interaction between pituitary hormones and local factors (luteal peptides) on secretion of PGF2alpha and progesterone (P) by the early bovine CL, and to evaluate the effect of growth hormone (GH) as well as its interactions on production of PGF2alpha in the developing CL. A RT-PCR analysis revealed that mRNA for GH receptor in CL was fully expressed from early in the luteal phase throughout the estrous cycle, while luteinizing hormone (LH) receptor mRNA was expressed less by the early and regressing CL than those at mid or late luteal phases (P < 0.05). For the stimulation test, an in vitro microdialysis system (MDS) was used as a model. Each bovine early CL (days 3-4) was implanted with the MDS, and maintained in an organ culture chamber. The infusion of GH, insulin-like growth factor-I (IGF-I) and oxytocin (OT) increased (P < 0.05) PGF2alpha and P release. In contrast, LH had no effect (P > 0.05) on PGF2alpha secretion and little effect on P release. Unexpectedly, there was no distinct interaction between pituitary hormones and luteal peptides on secretion of PGF2alpha and P. These results indicate that GH is a more powerful stimulator of PGF2alpha and P production in the early bovine CL than LH and suggest that GH and luteal peptides, IGF-1 and OT, contribute to maintenance of elevated PGF2alpha production in the developing bovine CL.

Animals↗
PubMed2001

The role of different X-inactivation pattern on the variable clinical phenotype with Rett syndrome.

A gene for Methyl-CpG binding protein 2 (MECP2), which locates Xq28, was recently found to be responsible for Rett syndrome. Although mutational analyses of MECP2 in Rett syndrome have been extensively analyzed, the mechanism(s) by which variable clinical phenotype occurred between affected monozygotic twins or sisters have not been clarified. We hypothesized that the difference of X-inactivation pattern might explain this phenomenon. With the method based on methylation-specific PCR, we analyzed polymorphic trinucleotide repeat in the human andorogen receptor gene mapped on Xq11.2-12, using DNA samples derived from previously described monozygotic twins and sisters together with their parents. Their clinical phenotypes were reported to be significantly different between siblings. We found that (1) maternally derived allele is predominantly active than paternally derived one in three out of four patients analyzed, (2) remaining one twin patient, whose ratio of active paternal allele is almost the same level as maternal allele, showed far much severe phenotype when compared with her counterpart. Together with the finding that most of the alleles with de novo mutation are from paternal X chromosome in sporadic cases, the existence of a mechanism that suppresses mutated paternal allele activation, resulting skewed X-inactivation to make clinical phenotype milder, might be speculated. Thus, when this mechanism fails to work sufficiently by an unknown reason, severer clinical phenotype could occur.

Adult↗
PubMed2001

Preeclamptic serum enhances endothelin-converting enzyme expression in cultured endothelial cells.

Increased vascular sensitivity to vasoconstrictors, such as angiotensin II and epinephrine, is observed in preeclampsia (PE). Recently, it was suggested that abnormal endothelial function might contribute to the pathophysiologic changes in PE. We investigated vasoconstrictor (angiotensin II and epinephrine)-induced endothelin-1 (ET-1) release from human umbilical vein endothelial cells incubated with sera from women with PE compared with normotensive pregnant and nonpregnant women. Moreover, inositol 1,4,5-trisphosphate production and endothelin-converting enzyme (ECE) expression in human umbilical vein endothelial cells were also evaluated. There were no significant differences in ET-1 release without vasoconstrictors among the three groups (nonpregnant, normotensive pregnant, and PE). No significant differences in basal inositol 1,4,5-trisphosphate production and ECE expression without vasoconstrictors were detected among the three groups. Vasoconstrictor-induced ET-1 release was significantly increased by PE sera. No significant difference was detected in vasoconstrictor-induced inositol 1,4,5-trisphosphate production among the three groups. However, ECE expression after incubation with vasoconstrictor was significantly increased by PE sera. Our results suggest that ET-1 release from endothelial cells may contribute to the increased vascular sensitivity to vasoconstrictors observed in PE, and that vasoconstrictor-induced ET-1 release may be related to enhanced ECE expression.

Adult↗
PubMed2001

Endothelin receptor mediating contraction of isolated bovine coronary artery.

We studied endothelin (ET) receptors and their subtypes on isolated bovine coronary arteries. Endothelin receptors that mediated contraction of isolated bovine coronary artery were characterized by the use of antagonists and agonists. Contractions induced by the nonselective agonist ET-1 (10-10-10-7 M) were not affected by the removal of the endothelium (pEC50: 8.52, maximal contraction: 105% of that induced by 60 mM KCl). BQ-123 (3 x 10-7 M) antagonized contractions of endothelium-denuded coronary rings induced by low concentrations of ET-1 (10-10 or 10-9 M), but potentiated the contractions induced by higher concentrations of ET-1 (3 x 10-8 and 10-7 M). BQ-788 (10-6 M) potentiated contractions induced by ET-1 (3 x 10-10 and 10-7 M). In the presence of BQ-788 (10-6 M), BQ-123 (3 x 10-8-3 x 10-6 M) concentration - dependently inhibited contractions induced by ET-1 (3 x 10-10 and 10-7 M) (pA2: 6.61). Sarafotoxin S6b (10-9-3 x 10-7 M) evoked contractions in the denuded coronary artery (pEC50: 8.49, maximal contraction: 139% of 60 mM KCl). The BQ-123 caused a concentration-dependent rightward shift of contractions induced by sarafotoxin S6b (pA2: 7.89). The present study indicates that ET-1 and sarafotoxin S6b contract the isolated bovine coronary artery by stimulating ETA receptors on smooth muscle cells, and that ETB receptors might suppress the ET-1-induced contractions.

Animals↗
PubMed2001

Stimulatory and synergistic effects of luteinising hormone and insulin like growth factor 1 on the secretion of vascular endothelial growth factor and progesterone of cultured bovine granulosa cells.

Vascular endothelial growth factor (VEGF) is the most important factor in the regulation of angiogenesis. Associated with luteinisation and formation of corpus luteum (CL) are alterations in luteal vascularity. The aim of the study was to test under in vitro conditions the stimulation of VEGF and progesterone (P) secretion of bovine granulosa cells by LH, IGF1 (insulin like growth factor) or by factors known to be produced by luteinised granulosa cells or in the early CL. Localisation of VEGF protein in preovulatory follicle and early CL were achieved by immunohistochemistry. LH and IGF1 stimulated dose dependently and significantly P and VEGF when tested alone. Both hormones added simultaneously had clear additive and even more interesting far greater (synergistic) effects on P with LH (0.1 ng/ml) plus 5 or 10 ng IGF1. In contrast, VEGF was stimulated only additively with 0.1 ng/ml of LH plus 5 or 10 ng IGF1. But with the higher dose of LH (1 ng/ml) additionally to the additive effect a tendency for a synergistic action (which was significant with 1 ng LH plus 5 ng IGF1/ml) was observed. Endothelin, oxytocin, progesterone, atrial natiuretic peptide, angiotensin II, prostaglandin F2 alpha alpha, prostaglandin E2, cortisol, fibroblast growth factor 1 and 2 and growth hormone showed no effect neither on P nor on VEGF. Tumour necrosis factor alpha (TNF alpha) stimulated (P < 0.05) VEGF with 10 or 100 ng/ml but not P. TPA (12-0 tetra decaenoyl-phorbol-13-acetate) or Ca2+ ionophore did not show a stimulatory effect in contrast to forskolin which increased P and VEGF secretion dose dependently. The VEGF protein was localised in follicle (granulosa cells, theca cells and some endothelial cells) and early (about 24 h after ovulation) CL (granulosa-lutein cells and endothelial cells). The same signalling pathway by stimulation of cAMP production and proteinkinase A activation for luteinisation and neo-vascularisation demonstrates a close temporal and spatial relationship of these normal physiological processes.

Animals↗
PubMed2001

Angiotensin II and atrial natriuretic peptide in the cow oviductal contraction in vitro: direct effect and local secretion of prostaglandins, endothelin-1, and angiotensin II.

Angiotensin II (Ang II) and atrial natriuretic peptide (ANP) may be involved in local regulation of the oviductal contraction during the estrous cycle. Thus, the in vitro effects of Ang II and ANP on the secretion and contraction of bovine oviduct during the follicular, postovulatory, and luteal phases were investigated. An in vitro microdialysis system (MDS) was utilized to determine the intraluminal release of prostaglandins (PGs), Ang II, and endothelin-1 (ET-1) from the bovine oviducts as well as to observe the effect of Ang II and ANP on the local secretion of these substances. The basal release of PGs, ET-1, and Ang II was higher (P < 0.05) during the follicular and postovulatory phases than during the luteal phase. Stimulation by infusion of Ang II (10(-6) M) or ANP (10(-7) M) into the MDS was carried out for 4 h between 4 and 8 h of incubation. In the oviducts from the follicular and postovulatory phases, the infusion of ANP increased the release of Ang II, but not of ET-1. Infusion of Ang II stimulated the release of ET-1. Both Ang II and ANP increased PGE(2) and PGF(2alpha) release. In the contraction study, direct administration of Ang II (10(-7) M) or ANP (10(-8) M) into the medium during the follicular and postovulatory phases increased the amplitude of oviductal contraction. In contrast, these substances did not show any effect in the contraction and secretion of oviducts from cows during the midluteal phase. These results indicate that during the periovulatory period, Ang II and ANP stimulate the contractile amplitude of the oviduct in vitro. In addition to their direct action on oviductal contraction, Ang II may activate oviductal secretion of ET-1 and PGs. Likewise, ANP stimulates oviductal secretion of PGs and Ang II. Hence, the overall results suggest the existence of a functional endothelin-angiotensin-ANP system in the bovine oviduct during the periovulatory period, which may regulate the oviductal contraction to ensure maximum efficiency of gamete/embryo transport through the oviduct.

Angiotensin II↗
PubMed2001

Estradiol-17beta is produced in bovine corpus luteum.

The aim of this study was to investigate the expression of cytochrome P450 aromatase (aromatase) mRNA, its activity, and estradiol-17beta (estradiol) secretion in bovine corpus luteum (CL) during the estrous cycle. Expression of aromatase mRNA was examined in CL at the early, mid, late, and regressed luteal stages by using a reverse transcription-polymerase chain reaction. Aromatase mRNA was detected in all luteal stages examined, although aromatase expression was significantly lower during the early and regressed luteal phases compared to the mid and late luteal phases. Moreover, cultured midluteal cells clearly converted exogenous [(3)H]androstenedione into estradiol, and an aromatase inhibitor significantly inhibited this conversion. To characterize the local release of estradiol within the CL during the estrous cycle, an in vitro microdialysis system (MDS) of CL was conducted. Estradiol in MDS perfusate was confirmed by a reverse-phase high-performance liquid chromatography in combination with enzyme immunoassays. Basal release of estradiol from microdialyzed CL did not change during the estrous cycle. Additionally, when freshly prepared midluteal cells were exposed to estradiol (10(-14) to 10(-9) M), estradiol stimulated prostaglandin (PG) F(2alpha) secretion (P < 0.05), although it did not affect progesterone and oxytocin secretion. The overall results indicate that estradiol is produced locally in bovine CL throughout the estrous cycle, and they suggest that estradiol plays a role in regulating PGF(2alpha) production in CL as an autocrine/paracrine factor.

Androstenedione↗
PubMed2001

Appraisal of transarterial immunoembolization for hepatocellular carcinoma: a clinicopathologic study.

Recurrence of hepatocellular carcinoma (HCC) is frequent, even after apparently curative resection. Preoperative transcatheter arterial chemoembolization (TAE) does not improve disease-free survival after hepatic resection. We previously reported the potential usefulness of transarterial immunoembolization (TIE), a newly developed arterial embolization technique using OK-432 and fibrinogen, as preoperative treatment. In this study, we further investigated the effect of TIE by histologic examination of the resected specimens and compared it with conventional TAE in a prospective nonrandomized manner. Thirty-nine patients underwent TIE (n = 17) or TAE (n = 22) before curative hepatectomy for HCC. Transarterial immunoembolization was performed according to the standard protocol using OK-432, fibrinogen, and thrombin. Histologic changes in cancerous and noncancerous liver tissues were examined at different stages after TIE. Histologic grading of cancer cell injury according to the modified Shimosato criteria (Grades 0-IV, in increasing order of severity of cell injury) and postoperative disease-free survival were compared between the two groups. Based on the results of histopathology, TAE was more effective than TIE against the main tumor. In contrast, TIE was significantly more effective than TAE against extracapsular invasion and intrahepatic metastasis. Disease-free survival after hepatectomy tended to be better in patients pretreated with TIE than TAE. Postoperative tumor recurrences in the TIE group (n = 4) occurred in the nontreatment regions, whereas tumor recurrences in TAE group developed mostly (8 of 11 patients) in treated liver regions. Based on results of histologic examination, TIE seems to be more effective than conventional TAE against extracapsular invasion and intrahepatic metastasis. Data for disease-free survival and recurrence site suggest TIE may be a useful preoperative treatment.

Antineoplastic Agents↗
PubMed2001

Endothelium-dependent relaxation in response to low concentrations of bradykinin is enhanced by phosphoramidon, bosentan and BQ-123 in bovine coronary arteries in vitro.

An endothelin (ET)-converting enzyme inhibitor phosphoramidon (10 microM), an ET(AB)-receptor antagonist bosentan (10 microM) and an ET(A)-receptor antagonist BQ-123 (1 microM) potentiated endothelium-dependent relaxation of bovine coronary arteries in response to bradykinin (BK) at femtomolar to picomolar concentrations, but not at nanomolar concentrations. BQ-788 (3 microM), an ET(B)-receptor antagonist, showed no significant effects on fM-nM BK-induced relaxation. These results suggest that the endothelium-dependent relaxation of isolated bovine coronary arteries induced by very low concentrations of BK is partly regulated by a complex mechanism involving the ET(A)-receptor antagonism.

Animals↗