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Biomedical subjects

Y Yoshimura

Publications and source records attributed to Y Yoshimura.

At least 235 records · Page 13Linked to original sources
PubMed1996

Involvement of angiotensin II in the process of gonadotropin-induced ovulation in rabbits.

In the present study we investigated the role of angiotensin II (Ang II) receptor subtypes in gonadotropin-induced ovulation, oocyte maturation, and ovarian steroidogenesis and prostaglandin (PG) production in in vitro-perfused rabbit ovaries. The addition to the perfusate of PD123319, a nonpeptide Ang II antagonist with a high affinity for AT2 receptors, inhibited hCG-induced ovulation in a dose-dependent manner, whereas CV-11974, a nonpeptide AT1 receptor antagonist, had no effect. The majority of ovulated ova and follicular oocytes resumed meiotic maturation in response to hCG; and PD123319, but not CV-11974, significantly inhibited hCG-induced oocyte maturation. The addition of both Ang II receptor antagonists to the perfusate had no significant effect on the concentration of progesterone in the perfusate of hCG-treated ovaries, whereas PD123319 inhibited the hCG-stimulated production of estradiol. The production of PGE2 and PGF2 alpha was significantly increased at 6 h in hCG-treated ovaries compared with ovaries before hCG administration. PD123319 inhibited the hCG-stimulated production of PGs by perfused rabbit ovaries in a dose-dependent manner, indicating that hCG-induced PG synthesis is mediated, at least in part, via the activation of AT2 receptors. Ovulatory efficiency in ovaries perfused with or without PD123319 in the presence of hCG was significantly correlated with PG production by perfused rabbit ovaries 12 h after exposure to hCG (r = 0.6553 for PGE2, p < 0.001; r = 0.4758 for PGF2 alpha, p < 0.05). In conclusion, Ang II exerts complex and coordinated control on at least two distinct aspects in the normal ovulatory process, ovulation and oocyte maturation. Ang II produced locally by gonadotropin exposure may be a part of a novel intraovarian paracrine or autocrine control mechanism that operates via the AT2 receptor in the ovary.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1996

Relationship of cigarette smoking to blood pressure and serum lipids and lipoproteins in men.

1. The relationship of cigarette smoking to blood pressure and serum lipids and lipoproteins was studied in 7608 men, ranging from 40 to 59 years of age. Analyses were performed separately for non-drinkers and drinkers. 2. After adjusting age and body mass index (BMI) in non-drinkers and age, BMI and alcohol intake in drinkers in forward stepwise multiple regression analysis, there was a dose-dependent negative relationship between cigarette smoking and diastolic blood pressure (DBP) and high density lipoprotein cholesterol (HDL-C), regardless of drinking habit. There was a dose-dependent positive relationship between cigarette smoking and the ratio of total cholesterol (TC) to HDL-C (TC:HDL-C) in non-drinkers, but not in drinkers. There was a dose-dependent negative relationship between cigarette smoking and TC and a positive relationship between cigarette smoking and triglycerides (TG) in drinkers, but not in non-drinkers. 3. After matching age and BMI in non-drinkers, subjects who smoked more than 30 cigarettes/day had significantly lower mean values of systolic blood pressure (SBP; 4.3%; P < 0.05), DBP (3.0%; P < 0.01) and HDL-C (15.5%; P < 0.01) and higher mean values of TC:HDL-C (25.0%; P < 0.01), TG (46.8%; P < 0.01) and beta-lipoprotein (12.0%; P < 0.01) than non-smokers. In drinkers, after matching age, BMI, and alcohol intake, subjects who smoked more than 30 cigarettes/day had significantly lower mean values of SBP (2.8%; P < 0.05), DBP (4.8%; P < 0.01), HDL-C (17.3%; P < 0.01) and TC (4.4%; P < 0.01) and higher mean values of TC:HDL-C (15.4%; P < 0.01) and TG (45.1%; P < 0.01) than non-smokers. 4. Although the results are somewhat variable, the present study reveals that cigarette smoking is negatively associated with SBP and DBP and unfavourably associated with lipids and lipoproteins, regardless of drinking habit.

Adult↗
PubMed1996

Physiological role of insulin-like-growth-factor-binding protein-4 in human folliculogenesis.

Insulin-like growth factor (IGF)-I and IGF-II, and their binding proteins (IGFBPs) have been demonstrated to play important roles in follicular development as intraovarian regulators. Previous studies have demonstrated that the follicular fluid of atretic follicles contains high levels of IGFBP-2 and IGFBP-4, which are known to inhibit the action of IGFs. In this study, we identified IGFBP-4 protease activity in the follicular fluid of developing but not atretic follicles. To elucidate the regulation mechanism of IGFBP-4 proteolytic activity in the ovary, cultured luteinized granulosa cells (GCs) were incubated with various hormones, and proteolyzed IGFBP-4 in the medium was analyzed. IGFBP-4 proteolytic activity was increased when GCs were incubated with IGFs, estradiol or follicle-stimulating hormone (FSH) but not with testosterone. We also showed that IGFBP-4 inhibited IGF-1-induced estradiol release by GCs while proteolyzed IGFBP-4 did not. These results suggest that human luteinized GCs produce IGFBP-4 protease, and that FSH and IGFs may stimulate folliculogenesis by modulating IGFBP-4 degradation in the ovary.

Cells, Cultured↗
PubMed1996

Insulin-like growth factor binding protein-3 inhibits gonadotropin-induced ovulation, oocyte maturation, and steroidogenesis in rabbit ovary.

The effects of insulin-like growth factor binding proteins (IGFBPs) on human CG (hCG)-induced oocyte maturation, ovulation, steroidogenesis, and intrafollicular plasminogen activator (PA) activity were investigated in rabbit ovaries perfused in vitro. The addition of IGFBP-3, but not IGFBP-1, to the perfusate dose dependently inhibited hCG-induced ovulation, whereas ovulation failed to occur in any ovaries perfused with medium or IGFBP-3 alone. IGFBP-3 (100 ng/ml) significantly inhibited the resumption of meiosis in ovulated ova and follicular oocytes in hCG-treated ovaries, as well as the hCG-stimulated production of estradiol (E2), but not progesterone, by the perfused ovaries. Intrafollicular PA activity increased significantly within 1 h after exposure to hCG, reaching a maximum at 4 h; IGFBP-3 significantly inhibited hCG-stimulated intrafollicular PA activity. The blockade of hCG-induced ovulation by IGFBP-3 correlated with the reduction in intrafollicular PA activity. Treatment with hCG induced a 2.5-fold increase in intrafollicular IGF-I messenger RNA levels at 4 h. Although ovulation failed to occur in ovaries treated with IGF-I (100 ng/ml) in the absence of gonadotropin, IGF-I significantly increased the mean diameter of preovulatory follicles and stimulated the resumption of meiosis in follicular oocytes. These effects of IGF-I on follicular growth and oocyte maturation were significantly inhibited by IGFBP-3 (100 ng/ml). Furthermore, IGFBP-3 significantly inhibited the IGF-I-stimulated production of E2. In conclusion, IGFBP-3, but not IGFBP-1, blocked the stimulatory effects of hCG in the ovulatory process. These findings suggest that IGFBP-3 may contribute to the regulation of intrafollicular PA activity during follicular development and ovulation evoked by gonadotropin exposure, at least in part, via neutralizing endogenously produced IGF-I.

Animals↗
PubMed1996

Angiotensin II induces ovulation and oocyte maturation in rabbit ovaries via the AT2 receptor subtype.

The present study was undertaken to investigate the role of angiotensin II (Ang II) in ovulation and ovarian steroidogenesis and prostaglandin (PG) production via the Ang II receptors in rabbit ovaries. In in vitro perfused rabbit ovaries, PD123319, a selective nonpeptide antagonist for AT2 receptors, reduced the Ang II-induced ovulation in a dose-dependent manner, whereas CV-11974, a selective nonpeptide antagonist for AT1 receptor, did not affect the Ang II-induced ovulation. Ang II also significantly stimulated the meiotic maturation of ovulated ova and follicular oocytes in the absence of gonadotropin. The addition of PD123319 at 10 (-6) M to the perfusate significantly inhibited the Ang II-induced oocyte maturation. Ang II did not stimulate the production of progesterone by perfused rabbit ovaries but significantly stimulated the production of estradiol (E2) and PGs. When PD123319 at 10(-6) M was added to the perfusate 30 min before the onset of Ang II administration, the Ang II-stimulated production of E2 and PGs was significantly blocked. Saralasin, a peptide analog of Ang II, inhibited the specific binding of [125I] iodo-[Sar1, Ile8] Ang II to rabbit ovarian membranes in a concentration-dependent manner, yielding an inhibitory constant (IC50) value of 1.58 x 10(-9) M. PD123319 and CV-11974 also inhibited the binding of [125I]iodo-[Sar1, Ile8] Ang II; however, PD123319 and CV-11974 were 15 and 40 times less potent than saralasin, respectively. Autoradiographic study revealed that an intense localization of Ang II receptors in the rabbit ovaries was present in the granulosa cell layers and the stroma of the preovulatory follicles. AT2 receptors were predominantly located in granulosa cells, whereas AT1 receptors were more concentrated in the stroma and thecal cell layers. In summary, Ang II induced ovulation and oocyte maturation and stimulated the production of E2 and PG by perfused rabbit ovary in vitro via the AT2 receptor. Thus, locally produced Ang II may be part of a novel intraovarian paracrine or autocrine control mechanism during the ovulatory process.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1996

Expression of beta 1 integrins in human endometrial stromal and decidual cells.

The present study was undertaken to investigate the expression of beta1 integrins in human endometrium and decidua using flow cytometry, immunohistochemistry, and immunoprecipitation. Fluorescence-activated flow cytometry demonstrated the greater expression of the beta 1, alpha 1, alpha 2, and alpha 5 subunits of the beta1 integrin family in cultured stromal cells from the midsecretory phase, than in those of the early proliferative phase. The addition of estradiol (E2) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of beta1 integrins in vitro. The immunohistochemical distribution of beta1 integrins demonstrated predominantly glandular epithelial staining in the proliferative phase, and mesenchymal and glandular staining in the midsecretory phase. Flow cytometry also demonstrated the expression of the beta 1, alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 subunits of beta 1 integrin family in cultured decidual cells, and the enriched-fraction of prolactin (PRL)-producing decidual cells isolated by Percoll gradients showed high levels of beta 1, integrins expression. Immunohistochemistry confirmed the beta 1 integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. Autoradiography of immunoprecipitate subjects to SDS-PAGE revealed three major polypeptides with molecular weights of 130 kDa (beta 1 subunit), 165 kDa (alpha 2 subunit), and 210 kDa (alpha 1 subunit) under reducing conditions. In summary, the present study demonstrated that endometrial stromal and decidual cells expressed beta1 integrin subunits at their surfaces. The expression exhibited a variability throughout the menstrual cycles, being predominantly detected in the secretory phase, and was maintained highly in the decidua. Thus, beta 1 integrins in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation.

Abortion, Therapeutic↗
PubMed1996

In vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine.

The in vitro and in vivo antitumor activity of a novel nucleoside, 4'-thio-2'-deoxy-2'-methylidenecytidine (4'-thio-DMDC), was examined. 4'-Thio-DMDC inhibited the growth of various cell lines established from human solid cancers, particularly the growth of lung and bladder carcinomas and melanomas. 4'-Thio-DMDC exhibited potent antitumor activity against subcutaneously implanted murine sarcoma S-180 and human fibrosarcoma HT-1080 xenografts. It was shown that 4'-thio-DMDC suppressed cell growth by inhibiting cellular DNA synthesis, and phosphorylation of the 5'-position of its deoxyribose by deoxycytidine kinase was needed for its antitumor activity. 4'-Thio-DMDC is a poor substrate for cytidine deaminase, thus it is a promising agent for the treatment of malignant solid tumors because it will not be converted into its inactive uridine form.

Animals↗
PubMed1996

Ovariectomy-evoked increase in gonadotropin releasing hormone receptor parallels its messenger RNA level, but does not correlate with stimulated gonadotropin release.

The amount of gonadotropin releasing hormone receptor (GnRH-R) in the anterior pituitary changes during the rat estrous cycle; in addition, it is chronically increased for several weeks in response to ovariectomy. The present study was undertaken to investigate these changes in relation to the concentrations of GnRH-R mRNA, gonadotropins and luteinizing hormone-beta (LH-beta) subunit in serum and the pituitary gland, as well as hypothalamic GnRH. GnRH-R concentrations on the day of estrus were significantly lower than that at diestrus (30% lower during 2 d), its mRNA decreased even further (by 60%), but there were no significant changes in gonadotropin. Ovariectomy increased GnRH-R significantly (by 30% during 2 wk) in parallel with receptor mRNA and with pituitary LH and LH-beta, but induced an earlier increase in serum gonadotropins. Our results suggest that transcriptional activity is more intimately linked to the number of GnRH-R in the long-term increase after ovariectomy than in the short-term change during the estrous cycle, and that the increased GnRH-R is not a major factor in ovariectomy-stimulated gonadotropin release.

Animals↗
PubMed1996

Proliferation of granulosa and thecal cells in germinal disc and non-disc regions during follicular growth in Japanese quail (Coturnix coturnix japonica): bromodeoxyuridine incorporation in situ.

Proliferation of granulosa and thecal cells was analysed during ovarian follicular growth in laying Japanese quail. The birds were injected intraperitoneally with bromodeoxyuridine (BrdU) 10 or 4 h before ovulation, that is, before or after a preovulatory LH surge, respectively, and incorporation of BrdU by follicular tissues was detected immunocytochemically. Cells labelled with BrdU were seldom seen in the most immature follicles in the ovarian cortex, whereas many granulosa and thecal cells were labelled with BrdU in medium-sized white yolky follicles (approximately 13.3% and 14.4% in granulosa and theca layers, respectively). Ten and four hours before ovulation, the granulosa cells in the germinal disc and non-disc regions of the third largest yellow yolky follicle (F3) were labelled with BrdU (approximately 8.4% and 9.4% in germinal disc; 6.1% and 9.0% in the non-disc region), but only those in the germinal disc region were labelled (approximately 5.4% and 4.0%) in the largest yellow yolky follicle (F1). The percentage of thecal cells labelled with BrdU 4 h before ovulation was significantly higher than the percentage labelled 10 h before ovulation, and was higher in F3 (approximately 11.7%) than in F1 follicles (approximately 5.4%) 4 h before ovulation. These results show that proliferation of granulosa and thecal cells occurs in both germinal disc and non-disc regions in growing follicles, but when a follicle matures proliferation is reduced and in the case of granulosa cells it is restricted to the germinal disc region.

Animals↗
PubMed1996

[Histological effects of short term endocrine therapy on prostatic cancer].

BACKGROUND: The objective of this study is to investigate the pathological changes which occurred in prostatic cancer shortly after the commencement of endocrine therapy. METHODS: Fourty-three patients underwent radical prostatectomy immediately after the short term endocrine therapy (treatment period was within one month) and the histological pictures of operative specimens were compared to those obtained from the pretreatment biopsy specimens. RESULTS: Degenerative changes of cancer cells, such as nuclear and cytoplasmic vacuole, collapse of the cytoplasm and the appearance of naked hyperchromatic nucleus were noticed after the short term endocrine therapy. Especially in the cases which were histologically evaluated to be poorly differentiated in the biopsy specimens, not only degenerative changes but also destruction of cancer nests caused by cell death were observed. The histological effects affected by short term endocrine treatment had no relation to the prognosis, but in the cases of stage D2, the pathological grade judged by post-therapeutic specimens were found to be useful for the prediction of prognosis. CONCLUSION: Endocrine therapy induces remarkable pathological changes in prostatic cancer within a very short time after beginning treatment.

Aged↗
PubMed1996

Disposition of the new angiotensin II receptor antagonist candesartan cilexetil in rats and dogs.

The disposition of candesartan cilexetil (CAS 145040-37-5, TCV-116) was studied after oral administration of 14C-labeled drug to rats and dogs. Candesartan cilexetil was absorbed from the small intestine and hydrolyzed completely to the pharmacologically active metabolite M-I during absorption process. In the plasma of these animals, an appreciable amount of M-I was present with no detectable concentration of unchanged drug. The M-I concentration in rat plasma attained a peak (Cmax, 0.280 microgram/ml) 2.3 h (Tmax after dosing and then declined with an apparent half-life (t1/2) of 3.8 h. In dogs, Tmax, Cmax, and t1/2 of M-I were 1.3 h, 0.012 microgram/ml, and 4.3 h, respectively. The bioavailabilities of M-I in rats and dogs were 28 and 5%, respectively. M-I was distributed widely in the tissues including the blood vessels as target tissues, was metabolized partially to the glucuronide and M-II, and was eliminated predominantly into the feces via biliary excretion. The elimination of M-I from the blood vessels was slower than that from the plasma. The sustained antihypertensive effect of this drug seemed to be due to the slow elimination of M-I from the blood vessels. With daily oral dosing for 14 days, no appreciable amounts of drug-related compounds were accumulated in rat body.

Angiotensin II↗
PubMed1996

[One-year outcome of panic disorder].

In this study we investigated the one-year outcome of panic disorder. The subjects were 169 panic disorder patients (69 males, 100 females; mean age 36.5 years), who attended the outpatient clinic of the Department of Psychiatry, Showa University Hospital, from September to December 1993. The outcome study was performed from October to December 1994. Patients who were being treated at Showa University Hospital during the outcome study were interviewed in person, and those who were not were interviewed by telephone. The one-year outcome of 100 patients (32 interviewed in person and 68 interviewed by telephone; 37 males, 63 females; mean age 39.5 years) was assessed. That of the remaining 69 patients was not assessed because they did not provide informed consent or had moved during the last year. The patients who were assessed (N = 100) were older and exhibited less severe phobic avoidance on their first visit to the clinic than those who were not assessed (N = 69). The frequency of panic attacks, and the severity of phobic avoidance and anticipatory anxiety decreased significantly between the time of the patients' first visit to the clinic and the time of the outcome study. Panic attacks, phobic avoidance and anticipatory anxiety disappeared in 27.0%, 32.9% and 13.6% and decreased in frequency or severity in 61.8%, 62.0% and 61.4% of the cases, respectively. Seventy-three patients felt that the severity of their panic disorder symptoms decreased between the time of the outcome study and the time of their first visit to the clinic, 20 felt that it had not changed and 7 felt that it had increased worse. The phobic avoidance and anticipatory anxiety at the time of the patients' first visit to the clinic were more severe, and the Global Assessment of Functioning Scale score was lower in the case of the former group of patients than in that of the latter two groups.

Adolescent↗
PubMed1996

Heart rate response and perceived exertion during twenty consecutive karate sparring matches.

This study investigated the changes in heart rate (HR) and perceived exertion ratings (RPE) of 20 consecutive karate sparring matches each of 2 minutes duration. The resting and maximal HR (HRmax) responses to the maximal treadmill test were 69.8 +/- 2.9 beats.min-1 and 198.5 +/- 8.2 beats.min-1, respectively. The resting HR before the 20 sparring matches was 83.5 +/- 11.3 beats min-1. The mean HR during the 20 sparring matches was 191.8 +/- 9.4 beats.min-1 which was equal to 96.7 +/- 4.2% of HRmax. At the end of the 20 sparring matches, the mean RPE obtained was 19 +/- 2. The results of this study suggest that the subjects could continue the 20 sparring matches for about 40 minutes at the intensity close to the HRmax.

Adult↗