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Biomedical subjects

Y Yoshimura

Publications and source records attributed to Y Yoshimura.

At least 271 records · Page 15Linked to original sources

Disposition of DN-2327, a new anxiolytic, in rats, dogs, and monkeys.

The disposition of DN-2327 after oral dosing of 14C-labeled DN-2327 ([14C]DN-2327) to rats, dogs and monkeys was studied. DN-2327 was absorbed from the small intestine after oral administration. In the plasma of these animals, a small amount of unchanged compound and M-I were detected, with M-II (a pharmacologically active metabolite) as a major component. The concentration of the unchanged compound in rat plasma attained a peak (Cmax 0.002 microgram/ml), then declined, with a half-life (t1/2) of 3 h. Tmax, Cmax and t1/2 of DN-2327 in dogs and monkeys were 0.6 h, 0.332 microgram/ml and 1.5 h, and 2.3 h, 0.036 microgram/ml and 6.2 h, respectively. About 60, 75 and 48% of the radioactivity dosed was absorbed in rats, dogs and monkeys, respectively, whereas the bioavailability in rats, dogs and monkeys was less than 1, 34 and 10%, respectively, indicating that DN-2327 had been subjected to the first pass effect. In rats given [14C]DN-2327 orally, the radioactivity was distributed widely in various tissues, including the brain. In the brain regions, DN-2327 and M-II were distributed and M-II was major component, indicating that the pharmacological effects of DN-2327 may depend largely on M-II. In these animals, [14C]DN-2327 was excreted in feces via bile mostly as metabolites. During repeated oral administration, DN-2327 and its metabolites did not accumulate in rat tissues, except in the kidney.

Administration, Oral↗

Atretic changes of follicular wall caused by destruction of the germinal disc region of an immature preovulatory follicle in the chicken: an electron microscope study.

The germinal disc of the female gamete and its overlying follicular wall (the germinal disc region) is hypothesized to play an important role in the regulation of follicular growth. The role of the germinal disc region in follicular growth in chickens was investigated by destroying the germinal disc region or an area opposite the germinal disc (control) of the second largest follicle 22-23 h before ovulation of the F1 follicle, by localized freezing with solid CO2. Structural changes of the follicular wall (non-frozen region) were observed by electron microscopy 10-20 h after the destruction of the germinal disc region. Development of the inner structure of mitochondria in granulosa cells and accumulation of lipid droplets in thecal cells were observed in follicles 15 h after destruction of the germinal disc region. Twenty hours after destruction of the germinal disc region, follicles showed early signs of atresia (bursting atresia). Degenerative changes in follicles, including hydrolysis by lysosomal enzymes, were present in thecal fibroblast-like cells. Control follicles, in which an area opposite the germinal disc region was frozen 20 h before examination, had no degenerative features. These results provide further evidence that the germinal disc region is required for follicular growth.

Animals↗

Effects of luteinizing hormone and follicle-stimulating hormone on the progesterone receptor induction in chicken granulosa cells in vivo.

Progesterone receptor (PR) is increased in the granulosa cells prior to ovulation. In order to investigate the factors that induce PR in granulosa cells, we examined whether the PR is induced in granulosa cells by the injection of chickens with ovine luteinizing hormone (oLH) or porcine follicle-stimulating hormone (pFSH) by Western blot analysis. In the oLH-stimulated birds, PR of 79 kDa and 110 kDa were recognized in the granulosa cells of the largest follicle, whereas a PR of 110 kDa was observed in those of the smaller follicles (the second and third largest follicles). No immunoreaction product was observed in the granulosa cells of both the largest and the smaller follicles in pFSH-stimulated birds. In the control birds that were injected with saline, no immunoprecipitate was recognized in the granulosa cells of the largest or smaller follicles. These results suggest that LH may be involved in the induction of PR in the granulosa cells prior to ovulation.

Animals↗

[Perioperative management of a patient with severe bronchial asthma attack].

We report an anesthetic management for Miles' operation in a 50-year-old female who had frequent severe bronchial asthmatic attacks prior to surgery. Because the surgical field was in the lower abdomen, we selected spinal anesthesia combined with epidural anesthesia. For spinal anesthesia, 15 mg of hyperbaric tetracaine with epinephrine was used. Moreover, 3 ml of 2% mepivacaine with epinephrine was injected via an epidural catheter, and then analgesia up to Th 6 was obtained. In order to prevent an asthmatic attack during surgery, the following cares were taken: (1) administration of moisturized oxygen by nebulizer via a nasal canula, (2) intravenous administration of steroid, (3) addition of epinephrine to the local anesthetics, and (4) sedation by music. The surgery was completed safely without asthmatic attacks. Postoperatively, pain control with buprenorphine was managed with a continuous extradural infusion. The patient was discharged 50 days after surgery, and was in a favorable condition without bronchial asthmatic attacks.

Anesthesia, Epidural↗

[Regulatory system and physiological significance of local factors in the ovary during follicular development and maturation].

The concept of classical endocrine control of ovarian function has now been extended to a more complex regulator system, including paracrine and autocrine modulating mechanisms. Among many factors, locally produced intraovarian insulin-like growth factors (IGFs) and the binding proteins (IGFBPs) and renin-angiotensin system (RAS) have been shown to play an important role in the control of folliculogenesis and ovulation. Growth hormone (GH) amplified gonadotropin actions in the process of follicular development and ovulation, at least in part, stimulating ovarian IGF-I production. IGF-I as well as IGFBPs were produced by ovarian granulosa cells. IGF-I acted synergistically with gonadotropins in the stimulation of a variety of granulosa cell functions, including estradiol (E2) and progesterone production and plasminogen activator (PA) activity. Furthermore, rabbit ovarian cells and rat granulosa cells possessed specific IGF type I receptors. The biological effects of IGF-I, including intrafollicular PA activities and ovarian steroidogenesis, were modulated by a family of IGFBPs in a complex manner. In the ovary IGFBP-3 appeared to neutralize the actions of gonadotropin and IGF-I, probably via its ability to sequester IGF-I, in the process of follicular growth, oocyte maturation, and ovulation. A functional local RAS is also known to exist in the ovary. Angiotensin II (Ang II) at 2-h intervals induced oocyte maturation, ovulation, and the production of E2 and prostaglandins (PGs) in the in vitro perfused rabbit ovaries in the absence of gonadotropin. In addition, the intrafollicular Ang II content and renin-like activity were enhanced during the ovulatory process by exposure to hCG, and the concomitant addition of saralasin inhibited hCG-induced ovulation in a dose-dependent manner. Captopril, an inhibitor of angiotensin converting enzyme, significantly inhibited the resumption of meiosis in the ovulated ova and follicular oocytes stimulated by hCG. Autoradiographic study revealed that AT2 receptors were predominantly located in granulosa cells, whereas AT1 receptors were more concentrated in the stroma and the thecal layers. Ang II-stimulated production of E2 and PGs and ovulation were significantly blocked by PD123319, a selective nonpeptide antagonist for AT2 receptors. The increase in ovarian IGF-I synthesis by exposure to hCG or GH induced the stimulation of intrafollicular PA activities. IGFBP-3 blocked the stimulatory effects of gonadotropin in the ovulatory process by neutralizing endogenously produced IGF-I, resulting in reduced intrafollicular PA activities. The increase in intrafollicular PA activities significantly stimulated the generation of Ang II in the preovulatory follicles by an activation of prorenin to renin and/or by the direct cleavage of angiotensinogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin II↗

[A case of adult Wilms' tumor with vena caval involvement].

The patient was a 35-year-old female with the chief complaint of macrohematuria. Computerized tomographic (CT) scan, ultrasonography and magnetic resonance imaging (MRI) revealed the presence of a large and inhomogeneous mass in the left kidney, and a tumor thrombus growing in the inferior vena cava. Angiography also showed a hypervascular tumor in the left kidney. The chest X-ray and CT scan demonstrated multiple metastatic lesions in the bilateral lungs. Radical nephrectomy and thrombectomy was performed under the diagnosis of left renal tumor with its invasion of inferior vena cava. Pathological findings revealed that this tumor was nephroblastoma, and its type was clear cell sarcoma of the kidney (CCSK). The patient received chemotherapy according to National Wilms' Tumor Study (NWTS) IV chemotherapeutic drug regimen. In general, CCSK is known to have poor prognosis. However, doxorubicin has been reported to have a relatively good antitumor effect for CCSK. However, in this case, the evaluation after the first course of chemotherapy was progressive disease, because some new lesions appeared, although most old pulmonary metastatic lesions were reduced.

Adult↗

[Effects of the maturity of human oocytes on fertilization and embryonic development: application of oocyte maturation in medium containing follicle-stimulating hormone].

A total of 2,145 oocytes from 355 IVF cycles were classified as overmature (O), mature (M), transitional (T), immature (I) and abnormal (A) according to the morphology of the corona radiata. The rates of fertilization (%F) and embryonic development (%D) per oocyte were the highest in the M group, and decreased significantly with the decreasing maturity of the oocytes (T and I) and were the lowest in the A group. Decreases in %F and %D were also observed in the O group. %F and %D were significantly higher in oocytes with a polar body (PB) than without a PB. Mature oocytes classified according to the morphology of the corona radiata had significantly higher %F and %D than those classified according to the morphology of the cumulus oophorus. %F and %D were increased when T-oocytes without a PB and I-oocytes were matured in vitro for 18-24 hours in medium supplemented with FSH. A normal female baby was delivered, following IVF-ET of two T-oocytes matured in vitro with FSH.

Adult↗

[The accuracy of computed tomography and magnetic resonance imaging in evaluating the extent of endometrial carcinoma].

The present study was designed to determine the accuracy of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in evaluating the extent of the tumor in 36 patients with endometrial carcinoma. The CT and MRI findings were compared with the microscopic pathologic characteristics in all cases. Linear regression analysis for measurements of residual normal myometrium revealed significant positive correlations (p < 0.001) between MRI (r = 0.861) and CT (r = 0.826) findings and pathologic evaluation. Thirty-six patients were divided into two groups according to our previous CT and MRI criteria: the superficial myometrial invasion group and advanced tumor group. In MRI findings, higher incidences of deep (> or = 1/2) myometrial invasion (p < 0.001), vessel permeation (p < 0.05) and cervical involvement (p < 0.05) were observed in the advanced group. In CT findings, deep myometrial invasion (p < 0.001) was observed in the advanced group. The incidence of extrauterine extension of the tumor did not differ significantly between CT and MRI findings. The accuracy figures for cervical involvement evaluated by CT and MRI were 83% and 86%, respectively. In four of 6 patients, in whom an intact Junctional zone (j-zone) was detected by MRI, the tumor was localized in the endometrium. The remaining 2 patients had only superficial myometrial invasion histologically. In all 16 patients, in whom the j-zone was interrupted in MRI findings, myometrial invasion was confirmed pathologically.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrial Neoplasms↗

[Postoperative bronchial stenosis associated with IAA complex and transendoscopic resection of intrabronchial granulation].

Problem with stenosis of the left bronchus was encountered in a patient with type B interrupted aortic arch complex after the arch reconstruction and pulmonary artery banding. Bronchoscopic study disclosed the intraluminal granulation of left bronchus and transendoscopic resection of the granulation successfully relieved the stenosis and brought the patient to full recovery.

Airway Obstruction↗

[A novel method of ovarian stimulation for in vitro fertilization (bromocriptine-rebound method) increases developmental potential of oocytes and pregnancy rate].

A novel method of ovarian stimulation for IVF is reported. Endocrine-normal ovulatory women with a history of unsuccessful IVF attempts by means of a long protocol of a GnRH agonist/hMG regimen (L regimen) were studied. Ovaries were stimulated by the three regimens described below. The bromocriptine-rebound (BR) regimen consisted of bromocriptine (B) 2.5mg/day administered daily beginning on day 4 of the preceding cycle and buserelin acetate administered beginning in early high phase. Administration of B was discontinued in the low phase of the IVF cycle and daily administration of hMG was begun 7 days later. HCG was administered when dominant follicles reached 16-18 mm in diameter. The bromocriptine-continuous (BC) regimen was the same as the BR regimen, except that B was administered until the administration of hCG. The L regimen was the same as the BR regimen, except that no B was administered. The pregnancy rate per oocyte retrieval was significantly higher on the BR regimen (56% in 70 cycles) than the L regimen (33% in 46 cycles), and lowest on the BC regimen (29% in 7 cycles). The rate of fertilization and cleavage per oocyte and the proportion of morphologically-good embryos were significantly higher on the BR regimen (59.1% and 57.3%, respectively) than the L regimen (46.3% and 48.0%, respectively), and lowest on the BC regimen (49.0% and 41.7%, respectively). Serum PRL concentrations (ng/ml) at the time hMG was started were 14.9 +/- 1.5, 7.9 +/- 1.7 and 2.5 +/- 0.7 on the BR, L and BC regimens, respectively. The results of this study show that the BR regimen increases the developmental potential of oocytes and the pregnancy rate, probably because of increasing serum PRL levels to within the normal range.

Adult↗

Mitral valve repair using continuous warm blood cardioplegia.

To achieve satisfactory mitral valve repair, we applied continuous warm blood cardioplegia to seven children with congenital heart disease associated with mitral valve insufficiency. All patients had mild to moderate mitral valve regurgitation before the operation. The competency of the mitral valve was assessed by injecting test solution into the left ventricle through the mitral valve orifice with the heart beating under warm blood perfusion into the aortic root proximal to the cross-clamp. Repair of the mitral valve was performed under normothermic cardiac arrest with continuous antegrade perfusion of warm blood cardioplegia. In all patients, these two procedures could be alternated with ease and safety simply by varying the potassium concentration of cardioplegia. While satisfactory valve repair was obtained with the initial procedure in 4 cases, repair was repeated twice in two and three times in one. There were no operative deaths and no complications directly related to the procedure. Postoperative echocardiography demonstrated good mitral valve function with none to trivial regurgitation in six patients (86%). Continuous warm blood cardioplegia is a useful and safe tool for mitral valve repair.

Child↗

A facile synthesis of 4'-thio-arabinonucleosides as potential antiviral agents from D-glucose.

As potential antiviral agents, 4'-thio-arabinonucleosides were synthesized. Methyl 3-O-benzyl-xylo-furanoside, readily obtained from D-glucose, was converted to 1,4-anhydro-4-deoxy-4-thio-arabinitol. The protection of hydroxyl groups and the Pummerer rearrangement, followed by Lewis acid induced glycosylation afforded 4'-thio-arabinonucleosides. The compounds showed anti HSV-1 activity.

Antiviral Agents↗

A novel synthesis of antineoplastic 4'-thionucleosides using D-glucose as a chiral synthon.

We have synthesized 2'-deoxy-2'-methylene-4'-thiocytidine as a potential antineoplastic agent. Isopropylidene-3-O-benzylxylose, readily obtained from D-glucose in 5 steps, was converted to 1,4-anhydro-4-deoxy-4-thio-arabinitol. After manipulation at 2-position, unique Pummerer type glycosylation at the alpha-position of sulfoxides gave the target compound. Antineoplastic effect of this compound is also reported.

Antineoplastic Agents↗

Isolation and characterization of cDNA clones specifically expressed in testicular germ cells.

We have cloned cDNAs involved in germ cell-specific expression. For this, a subtracted cDNA library was generated by subtracting cDNAs derived from supporting cells of mutant testis from wild-type testis cDNAs. Detailed analyses of mRNA expression revealed that the genes corresponding to the cloned cDNAs were exclusively expressed in testes and were developmentally controlled.

Actin Depolymerizing Factors↗

Chromosome mapping of the human (RECA) and mouse (Reca) homologs of the yeast RAD51 and Escherichia coli recA genes to human (15q15.1) and mouse (2F1) chromosomes by direct R-banding fluorescence in situ hybridization.

We mapped the human (RECA) and mouse (Reca) homologs of the yeast RAD51 and Escherichia coli recA genes to human and mouse chromosomes by direct R-banding fluorescence in situ hybridization. This gene was assigned to human chromosome 15q15.1 and to mouse chromosome 2F1, respectively. This is the first report on the precise localization of this gene to human and mouse chromosomes. This gene was mapped to a region on human chromosome 15q15.1 and mouse 2F1 that is believed to be a conserved syntenic group.

Animals↗

Histological changes of implanted collagen material during bone induction.

Studies were made on the fate of implanted material during bone induction. Mixtures of 1 mg of crude bone morphogenetic protein (BMP), or bovine serum albumin as a control, and 1.5 mg of bovine collagen, were pressed into discs and implanted under the fascia of the rectus abdominus muscle of rats. The tissues with implants were fixed 7, 10, and 14 days later and examined histologically. On day 7 after implantation, the implant was surrounded and invaded by alkaline phosphatase-positive cells. New bone and cartilage were seen at the periphery of the implant. In the regions of calcified cartilage and bone, these osteogenic matrices were intermixed with the implant. The mineral deposits were seen by electron microscopy not only on the osteogenic matrices but also on the implanted collagen. On day 14, the bone had spread to the center of the implant. No osteogenesis or chondrogenesis was seen in control implants. It was concluded that the calcification occurred on the implanted collagen during bone induction, and that it was related to successive bone formation and remodeling.

Alkaline Phosphatase↗

Fully mechanized latex immunoassay for serum lipoprotein(a).

We have developed a fully automated system to quantify lipoprotein(a) (Lp(a)) in human serum, based on the latex-enhanced turbidimetric immunoassay by application of the Immuno Chemistry Analyzer 501X. This assay was carried out with undiluted serum and was able to detect at Lp(a) levels higher than 4.0 mg/l. When judged to be out of range of the calibration (> 600 mg/l), the sample was automatically re-tested after automatic 10-fold dilution. Within-run C.V.s ranged from 1.9 to 2.1% and between-run C.V.s from 2.7 to 3.9%. Results by the present method were in good agreement with those by the in-house ELISA (r = 0.978) and the commercial ELISA (r = 0.990). The distribution of Lp(a) levels in sera from 508 healthy donors was highly skewed; the mean and median were 158 mg/l and 105 mg/l, respectively.

Adolescent↗