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Biomedical subjects

Y Yoshimura

Publications and source records attributed to Y Yoshimura.

At least 217 records · Page 12Linked to original sources

Role of oxygen-derived free radicals in free growth retardation induced by ischemia-reperfusion in rats.

We investigated the involvement of oxygen-derived free radicals in the pathogenesis of the intrauterine growth retardation (IUGR) induced in Sprague-Dawley rats by ischemia-reperfusion. On day 17 of gestation, rats received saline, superoxide dismutase (SOD, 50,000 U/kg), catalase (CAT, 50,000 U/kg), or SOD + CAT subcutaneously 1 h before induction of 30 min of ischemia of the right uterine horn. On day 21 the placental level of lipid peroxides was significantly increased (P < 0.001 vs. sham-operated group) and IUGR was induced (P < 0.001 vs. left horn) in the saline-treated group n = 6). Pretreatment with SOD + CAT (n = 6) significantly inhibited the increase in placental lipid peroxides and prevented IUGR. The effect of ischemia-reperfusion on uterine blood flow, with or without pretreatment with radical scavengers, was investigated in separate experiments by laser-Doppler flowmetry. The induction of hypoperfusion 3 h after ischemia (blood flow -40 +/- 5%, n = 6, P < 0.05) was blocked by pretreatment with SOD + CAT (n = 6). Results indicate that oxygen-derived free radicals may be important in the development of postischemic uteroplacental hypoperfusion and of ischemia-reperfusion-induced IUGR in the rat.

Animals↗

Osmolarity in renal medulla of transgenic mice regulates transcription via 5'-flanking region of canine BGT1 gene.

Betaine is a major compatible osmolyte accumulated in the mammalian kidney medulla and in Madin-Darby canine kidney cells in response to hypertonicity. The accumulation is the result of an increase in maximal velocity of the Na(+)- and Cl-coupled betaine transporter designated BGT1. We have previously cloned the canine BGT1 gene and identified a tonicity-responsive enhancer element (TonE) in its 5'-flanking region. Here we report studies of transgenic mice that have in their genome 2.4 kb of the 5'-flanking region of the canine BGT1 gene in front of a chloramphenicol acetyl-transferase (CAT) reporter. Expression of CAT mRNA was detected only in the renal medulla and was increased by experimental manipulations that increase the tonicity of the renal medulla and decreased by manipulations that decrease medullary tonicity. We conclude that the 2.4-kb 5'-flanking region of the BGT1 gene mediates an increase in transcription in response to hyperosmolarity in the renal medulla.

Animals↗

Effects of a thromboxane synthetase inhibitor (OKY-046) in an ischemia-reperfusion model of intrauterine growth retardation in Sprague-Dawley rats.

We investigated the effects of thromboxane (TX) A2 in rats with ischemia-reperfusion-induced intrauterine growth retardation. A saline solution or OKY-046, a selective TXA2 synthetase inhibitor, was injected into the caudal vein of pregnant rats on gestation day 17 before the induction of 60-min uteroplacental ischemia. The fetuses and placentas were delivered and examined on gestation day 21. Blood from the uterine vein of the occluded horn shortly after uteroplacental ischemia was collected, and plasma concentrations of TXB2 and 6-keto-prostaglandin (PG) F1 alpha were determined in the other rats on gestation day 17. Treatment with OKY-046 prevented the ischemia-induced reduction in the fetal body and placental weights. The ratio of 6-keto-PGF1 alpha to TXB2 was significantly increased in the OKY-046-treated group. We conclude that the action of TXA2 might play a salient role in our model.

6-Ketoprostaglandin F1 alpha↗

Comparison of bactericidal effects of commonly used antiseptics against pathogens causing nosocomial infections. Part 2.

Opportunistic infections caused by gram-negative rods (GNR), conventionally regarded as organisms with low or no pathogenicity, and intractable infections caused by various resistant organisms pose a great problem now. In view of this, we determined the bactericidal effects of 5 commonly used disinfectants using as the test strains Xanthomonas maltophilia and Serratia marcescens, chosen among other GNR since they often cause nosocomial infections. Regarding the bactericidal activities against X. maltophilia and S. marcescens, both sensitive strains and resistant strains were killed within 20 s of exposure to povidone-iodine and sodium hypochlorite. With chlorhexidine, 1 strain each of both species was not killed within 10 min of exposure at a concentration of 0.2%. Both sensitive strains and resistant strains of X. maltophilia were killed within 20 s of exposure to benzalkonium at 0.02%, while a concentration of 0.1% was required for benzalkonium to kill S. marcescens within 20 s. With Tego-51, both sensitive strains and resistant strains of X. maltophilia were killed within 20 s at 0.02%, while 1 strain of S. marcescens was not killed within 20 s at a concentration of 0.1%. In the use of disinfectants, comparative bactericidal effects of various disinfectants against clinical isolates should be taken into consideration.

Anti-Infective Agents, Local↗

Effects of nitric oxide on ovulation and ovarian steroidogenesis and prostaglandin production in the rabbit.

Evidence supports the involvement of nitric oxide (NO) in ovarian physiology. The present study was undertaken to investigate the role of the NO/NO synthase (NOS) systems in ovulation, oocyte maturation, ovarian steroidogenesis, and PG production using in vitro perfused rabbit ovaries. The addition of the NOS inhibitors, aminoguanidine hemisulfate salt (AG) and N-omega-nitro-L-arginine methyl ester (L-NAME), to the perfusate inhibited the ovulation induced by hCG in a dose-dependent manner, whereas D-NAME had no significant effect. Neither AG nor L-NAME affected the hCG-induced meiotic maturation of the ovulated ova. The exogenous administration of the NO generator, sodium nitroprusside (NP), induced follicle rupture in the absence of gonadotropin, but did not induce oocyte maturation. Inhibition of endogenous NOS by AG and L-NAME resulted in a significant elevation in the production of estradiol (E2), but not of progesterone, stimulated by hCG. The concomitant administration of NP significantly reduced the AG-stimulated production of E2 by ovaries perfused in the presence of hCG, which suggests that NO down-regulates ovarian E2 synthesis. Ovarian production of PGE2 and PGF2alpha in response to hCG was significantly blocked by L-NAME, and exogenous administration of NP stimulated the production of PGs in the absence of gonadotropin. Significant correlations were observed between the ovulatory efficiencies and the production of PGs by rabbit ovaries perfused with or without L-NAME. In conclusion, the ovarian NO/NOS system is involved in follicle rupture during the ovulatory process. NO may induce follicle rupture in rabbit ovaries at least in part by the stimulation of PG production.

Animals↗

A therapeutic role of prolactin supplementation in ovarian stimulation for in vitro fertilization: the bromocriptine-rebound method.

In a prospective randomized study, we examined whether a novel method of ovarian stimulation, the bromocriptine-rebound method, improves in vitro fertilization (IVF) outcomes compared with the conventional long protocol using GnRH agonist and human menopausal gonadotropin (hMG). Ovulatory women with previous failed IVF-embryo transfer using the long protocol were prospectively assigned to either the bromocriptine-rebound method (group 1, 82 cycles) or the long protocol (group 2, 80 cycles). The bromocriptine-rebound method was the same as the long protocol, except that bromocriptine was administered daily from day 4 of the preceding cycle until 7 days before hMG stimulation. The numbers of follicles, fertilized oocytes, and embryos with superior morphology were higher in group 1 than in group 2. The rates of clinical pregnancy and live birth delivery per cycle were significantly higher in group 1 (38% and 33%, respectively) than in group 2 (21% and 19%, respectively). The mean concentration of serum PRL during hMG administration was significantly higher in group 1 than group 2. A significant correlation between the number of superior embryos and PRL concentrations was observed in group 1, but not in group 2. Next, we performed a retrospective study to investigate how the bromocriptine-rebound method exerts its beneficial effects. In the initial IVF with the long protocol, the mean concentration of serum PRL during hMG administration and the expression of PRL receptor (PRLr) messenger ribonucleic acid (mRNA) in granulosa cells were significantly higher in nonpregnant patients than in pregnant ones. When IVF was repeated with the bromocriptine-rebound method in the nonpregnant patients, the expression of PRLr mRNA decreased significantly. In conclusion, the bromocriptine-rebound method enhances embryonic development and the rate of live birth delivery in patients with previous failed IVF using the long protocol. We hypothesize that in the nonpregnant patients using the long protocol, the serum PRL concentration and PRLr mRNA expression are increased to compensate for poor postreceptor responsiveness of granulosa cells to PRL during oocyte maturation. The bromocriptine-rebound method may improve oocyte maturation in such patients by restoring postreceptor responsiveness of granulosa cells to PRL during the hypoprolactinemic period and increasing the PRL concentration by a rebound phenomenon after discontinuation of bromocriptine.

Adult↗

Effects of sexual maturation and gonadal steroids on the localization of IgG-, IgM- and IgA-positive cells in the chicken oviduct.

The effects of sexual maturation and gonadal steroids on the localization of immunoglobulin-positive cells in chicken oviducts were studied. Oviductal tissues were collected from laying hens and chicks treated with stilboestrol (DES, an analogue of oestrogen) or progesterone. Paraffin wax sections of the tissues were immunostained for IgG, IgM and IgA, and the frequency of cells staining positive was examined using an image analysis system. Some of the cells in the mucosal epithelium and plasma cell-like cells in the stroma of the oviduct stained positive for IgG, IgM or IgA. In the mucosal epithelium of laying hens, there was a significantly greater number of IgG-positive (IgG+) cells in the shell gland than in the infundibulum, magnum and isthmus, more IgM+ cells in the magnum than in the infundibulum, and more IgA+ cells in the magnum than in the other segments of the oviduct with the exception of the vagina. The frequency of IgG+ and IgM+ cells in the mucosal epithelium of all oviductal segments and IgA+ cells in the magnum, isthmus and vagina was significantly higher in laying hens than in immature birds. In the subepithelial stroma of laying hens, there was a significantly greater population of IgG+ cells in the infundibulum and vagina than in the magnum and isthmus, more IgM+ cells in the infundibulum than in the magnum, and more IgA+ cells in the uterovaginal junction and vagina than in the magnum and isthmus. The frequency of IgG+, IgM+ and IgA+ cells in the subepithelium of infundibulum, uterovaginal junction and vagina was significantly greater in laying hens than in immature birds. The number of IgM+ cells in all oviductal segments and of IgA+ cells in the magnum of the mucosal epithelium of the chicks treated with DES increased significantly compared with those of control chicks. In addition, the number of IgG+ cells in the shell gland and vagina and of IgM+ cells in the vagina of the stroma of DES-treated birds were increased. Treatment of immature birds with progesterone had no effect on the localization of Ig+ cells in the oviduct except for a decrease in the number of IgM+ cells in the shell gland. These results suggest that the local immunity in the oviduct develops during sexual maturation, possibly under the control of oestrogen.

Animals↗

Heart rate, blood lactate responses and ratings of perceived exertion to 1,000 punches and 1,000 kicks in collegiate karate practitioners.

The purpose of this study was: 1) to investigate the responses of heart rate (HR), blood lactate and ratings of perceived exertion (RPE) to 1,000 punches and 1,000 kicks in collegiate highly skilled (BB Group) and novice (WB Group) karate practitioners; and, 2) to compare RPE obtained from the subjects to RPE expected by their coaches. The mean values of HR, percent of maximal HR (% HRmax), percent of maximal HR reserve (% MHRR), blood lactate and RPE in 1,000 punches for the BB Group were 102.5 +/- 14.8 beats. min-1, 53.1 +/- 8.5%, 27.1 +/- 12.7%, 0.8 +/- 0.2 mmol.1-1 and 12.2 +/- 1.2 respectively, and for the WB Group were 116.1 +/- 17.9 beats. min-1, 58.1 +/- 7.7%, 35.2 +/- 13.3%, 1.2 +/- 0.6 mmol.1-1 and 12.8 +/- 1.2, respectively. Likewise, the mean values in 1,000 kicks for the BB Group were 127.4 +/- 12.4 beats. min-1, 66.0 +/- 8.0%, 47.0 +/- 12.5%, 1.3 +/- 0.4 mmol.1-1 and 14.2 +/- 1.2, respectively, and for the WB Group were 137.0 +/- 14.4 beats.min-1, 70.1 +/- 7.4%, 52.0 +/- 12.8%, 2.4 +/- 0.8 mmol. 1-1 and 16.3 +/- 1.5, respectively. These responses to 1,000 punches and 1,000 kicks were moderate, and the RPE for 1,000 punches in both BB and WB Groups and for 1,000 kicks in the BB Group were significantly lower than the RPE expected by their coaches.

Adult↗

Integrins: expression, modulation, and signaling in fertilization, embryogenesis and implantation.

Normal morphogenesis and differentiation depend on the coordination of cell-cell and cell extracellular matrix (ECM) interactions. Integrins are a class of adhesion molecules that participate in the cell-cell and cell-substratum interactions and are present on essentially all human cells. All mammalian eggs express integrins at their surface, and the integrin alpha 6 beta 1 serves as a sperm receptor, mediating sperm-egg binding. In addition, certain integrin moieties appear to be regulated to within the cycling endometrium; the expression of beta 1 integrins in the early proliferative phase is restricted to the glandular epithelium, whereas stromal cells in the midsecretory phase also express beta 1 integrins. The expression of beta 1 integrins increases at the time of implantation and remains high in decidua during early pregnancy. A disruption of the integrin expression is associated with certain types of infertility in women. The apical surface of the mural trophectoderm does indeed possess functional integrins, and trophoblast interactions with ECM proteins depend largely on the integrin family of adhesion receptors. Thus, integrins play particularly important roles in fertilization and embryogenesis, including the process of implantation.

Animals↗

[Bacterial culture of the anterior chest skin for prophylaxis in cardiovascular operations: prospective study in two civilian hospitals].

Mediastinitis after median stermotomy is a significant complication for a cardiovascular surgery. Prospective study of bacterial cultures of the anterior chest skin in cardiac and aortic surgery was performed with the comparison of two civilian hospitals. There were many ABPC-resistant bacteria including 26 to 67 percent of Staphylococcus epidermidis (SE). ABPC could not be chosen for the first drug of prophylaxis. Although there was a few CEZ-resistant SE, the efficacy of first-generation cephalosporins was acceptable in this series. If methicillin-resistant Staphylococcus aureus (MRSA) is detected in patient's preoperative bacterial cultures, vancomycin should be selected for prophylaxis. In patients with poor risk who required emergent cardiac surgery, combinational use of an first-generation cephalosporin and an amikacin or a minocycline should be recommended in our data.

Adult↗

Studies on the metabolism of the new antidiabetic agent pioglitazone. Identification of metabolites in rats and dogs.

Metabolic studies of pioglitazone (CAS 105355-27-9, AD-4833), a new agent, in rats and dogs using liquid chromatography/tandem mass spectrometry and 1H-nuclear magnetic resonance led to characterization of the following metabolites; the parent compound, (+/-)-5-(p-hydroxybenzyl)-2-4-thiazolidinedione (M-I), (+/-)-5-[p-[2-(5-ethyl-2-pyridyl)-2-hydroxyethoxy]benzyl] -2,4-thiazolidinedione (M-II), (+/-)- 5-[p-[2-(5-acetyl-2-pyridyl)ethoxy]benzyl]2,4-thiazolidinedione (M-III), (+/-)-5-[p-[2-[5-(1-hydroxyethyl)-2- pyridyl]ethoxy]benzyl]-2,4-thiazolidinedione (M-IV), (+/-)-5-[p-[2-(5- carboxymethyl-2-pyridyl)ethoxy]- benzyl]-2,4-thiazolidinedione (M-V), and (+/-)-5-[p-[2-(5-carboxy-2- pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione (M-VI). Pioglitazone is considered to be metabolized by cleavage of aliphatic C-O bond to lead to M-I, hydroxylation of aliphatic methylene groups to form M-II and M-IV, oxidation of M-IV to give M-III, oxidation of the ethyl group to form M-V, and oxidative loss of the terminal carbon to lead to M-IV. Furthermore, part of metabolites exist as conjugated form. Among the conjugates, M-IV conjugated with sulfuric acid and M-V conjugated with taurine were identified.

Administration, Oral↗

Disposition of the new antidiabetic agent pioglitazone in rats, dogs, and monkeys.

The disposition of pioglitazone (CAS 105355-27-9, AD-4833) was studied after oral administration to rats, dogs, and monkeys using 14C-labeled drug. After oral dosing, pioglitazone was well absorbed from the gastrointestinal tract at an extent of 96, 95, and 90% in rats, dogs, and monkeys, respectively. In rats, the concentration of pioglitazone in plasma reached a peak (Cmax 0.71 micrograms/ml) at 4 h (tmax) after dosing and declined with a half-life (t1/2) of 2.6 h. In dogs, tmax, Cmax and t1/2 were 0.5 h 0.32 micrograms/ml and 2.1 h, and those for monkeys were 4.3 h, 0.43 micrograms/ml and 5.3 h, respectively. The drug was metabolized mainly to M-I to M-VI including the pharmacologically active metabolites (M-II, III and IV). The pharmacologically active compounds (total of the unchanged compound and the above three active metabolites) accounted for 87, 71, and 73% of the radioactivity in plasma of rats, dogs and monkeys, respectively. The radioactivity was widely distributed in tissues after oral administration to rats, and decreased to the very low concentration within 24 to 72 h after dosing. Radioactivity dose was almost completely excreted in urine and feces.

Administration, Oral↗

[Transurethral balloon laser thermotherapy for benign prostatic hyperplasia].

Between April 1994 and March 1995, transurethral balloon laser thermotherapy (TUBAL-T) using Prostalase was performed on 53 patients with benign prostatic hyperplasia. Clinical efficacy was evaluated at 3 months after TUBAL-T. The mean international prostate symptom score (I-PSS) decreased from 21.5 at baseline to 11.3 after 3 months (p < 0.0001). Irritative (the sum of items 1, 2, 4 and 7 of I-PSS) decreased by 55%, while obstructive symptoms (the sum of items 3, 5 and 6 of I-PSS) by 45%. However, other objective parameters such as maximum flow rate, voided volume, percent postvoid residual volume and prostate volume showed no significant change (7.8 to 7.2 ml/s, 130 to 147 ml, 33 to 28% and 39.7 to 41.0 ml, respectively). In conclusion, significant improvement after TUBAL-T was observed for subjective symptoms, especially irritative symptoms, but not for objective parameters.

Aged↗

[A case of transient cortical blindness due to reversible ischemic neurological deficit (RIND) after caesarean section under lumbar anesthesia].

We report a case of 31-year-old woman with pregnant toxicosis, who developed transient blindness after caesarean section under lumbar anesthesia. The patient was hypoxic due to atelectasis when she developed blindness, but she had no ophthalmologic abnormalities. MRI depicted abnormal high intensity areas (HIA) with T 2-weighted images (T 2 WI) in the occipital lobes and the basal ganglia. CT could not detect any of these MRI findings. The patient regained her vision four days after the onset. The HIA disappeared in a follow up MRI (T 2 WI) two weeks after the onset. The patient was diagnosed as cortical blindness due to RIND. Although most of the transient cortical blindness are accompanied with pregnant toxicosis with hypertension, there are some cases without pregnant toxicosis. We stress the importance of maintaining the blood pressure within the normal range in patients with hypertension who undergo surgery under spinal anesthesia.

Adult↗

Candesartan cilexetil: a review of its preclinical pharmacology.

Candesartan is a highly potent, long-acting and selective angiotensin II type 1 (AT1) receptor blocker. It is administered orally as the inactive prodrug candesartan cilexetil which is rapidly and completely converted to candesartan during gastrointestinal absorption. In vitro studies have shown that candesartan acts as an insurmountable angiotensin II receptor antagonist, binding tightly to and dissociating slowly from the AT1 receptor. The above characteristics are thought to contribute to the marked and long-lasting antihypertensive effects of candesartan cilexetil in several animal models of hypertension. These included rodent models of renal hypertension in which candesartan cilexetil also demonstrated efficacy equivalent to or greater than enalapril. In other animal models, candesartan cilexetil reduced the incidence of stroke, renal dysfunction and renal disease while reducing cardiac and vascular hypertrophy. Furthermore, candesartan cilexetil conferred some protection against cerebral and renal damage at a dose that had no blood pressure-lowering effect. In toxicity and general pharmacology studies, candesartan cilexetil was shown to possess a 'clean' profile with a large safety margin. Also it did not potentiate chemical- or autocoid-induced cough or anaphylactoid reactions.

Angiotensin Receptor Antagonists↗

[Antinociceptive activity of intracisternal clonidine in the mouse].

The antinociceptive activities of clonidine have been determined against three qualitatively different noxious stimuli in the mouse. The methods used to evaluate this activity were selected to include tests which employ different types of noxious stimuli, i.e. heat (hot plate), chemical (acetic acid-induced writhing) and mechanical (tail pinch). Test drug and control treatments were given by cisternal injection in a dose volume of 10 microliters.mouse-1. The results presented here show that clonidine has potent antinociceptive properties against several types of noxious stimuli. Clonidine produced steep dose-response lines in all tests. The response to the writhing assays were completely inhibited by 1.0 microgram.mouse-1 of clonidine. In contrast in both the hot plate and tail pinch assay, however, clonidine did not produce a consistent antinociceptive effect at a dose of 200 micrograms.mouse-1. Utilizing these three different types of assays, the rank order of antinociceptive potency for clonidine in different noxia was the writhing >> hot plate > tail pinch. It was concluded from these results that clonidine has potent antinociceptive properties against chemical visceral stimuli.

Adrenergic alpha-Agonists↗

Synthesis of 2'-deoxy-2'-fluoro-4'-thioarabinonucleosides using the Pummerer rearrangement and their biological evaluation.

Searching for more effective antineoplastic and antiviral agents, we have prepared various 2'-deoxy-2'-fluoro-4'-thioarabinonucleosides. The glycosylation reaction of persilylated pyrimidine bases with a 4-thiosugar derivative was performed using SnCl4 as a catalyst. The same reaction between purines and the 4-thiosugar, catalyzed by TMSOTf, gave the corresponding purine 4'-thionucleosides. Pyrimidine derivatives (e.g., 5-ethyluracil, 5-iodouracil, and 5-iodocytosine) showed potent anti-HSV-1 activities, and guanine and 2,6-diaminopurine derivatives showed marked anti-HCMV activities.

Antimetabolites, Antineoplastic↗

Effect of a low-calcium environment on EGF inducible AP-1 binding activity in osteoblastic MC3T3-E1 cells.

In the mouse osteoblastic cell line MC3T3-E1, the signaling response of DNA-binding protein induced by the treatment of epidermal growth factor (EGF) was examined using electrophoretic mobility shift assay. EGF increased the binding activity in nuclear extracts of MC3T3-E1 cells to TPA-responsive element (TRE). Competition experiments revealed that the binding activity to AP-1 site in the nuclear extracts of EGF treated MC3T3-E1 cells was entirely inhibited by unlabeled AP-1 consensus oligonucleotide. The DNA-binding activity of AP-1 by EGF in nuclear extracts of MC3T3-E1 cells cultured under a low calcium environment was more increased.

Animals↗