PubMed HealthSearch

Biomedical subjects

Y Yoshimura

Publications and source records attributed to Y Yoshimura.

At least 55 records · Page 3Linked to original sources

Input-specific induction of long-term depression in Ca(2+)-chelated visual cortex neurons.

An input-dependent increase in postsynaptic Ca2+ may play a role in long-term potentiation (LTP) of synaptic transmission while no or subthreshold increase in Ca2+ is associated with long-term depression (LTD) in the developing visual cortex. To see whether LTD is induced only at tetanized synapses, a Ca(2+)-chelator was injected into layer 2/3 neurons in cortical slices from young rats, and excitatory postsynaptic potentials (EPSPs) of these cells, after test stimulation of the white matter and layer 1/2, were observed before and after tetanic stimulation of the former site. The chelator injection led to LTD of EPSPs at tetanized synapses, but no changes were seen at non-tetanized synapses. These results suggest that tetanic inputs induce LTD at tetanized synapses when they are associated with no or subtle increase in postsynaptic Ca2+.

Animals

One-stage repair of blepharophimosis.

Congenital blepharophimosis is a congenital anomaly characterized by abnormalities in the area of the eyes, including bilateral ptosis, shortening of the horizontal fissure of the lid, expansion of the intercanthal distance, and epicanthus inversus. The condition is subject to autosomal-dominant heredity and is said to occur more frequently in Orientals than in Occidentals. Over the past 9 years, we have surgically treated 11 cases of congenital blepharophimosis using a procedure in which levator resection and medial canthoplasty are performed in one stage. It has been commonly believed that when levator resection and medial canthoplasty are performed at the same time, tension in the eyelid becomes too strong to achieve favorable results; therefore, the standard procedure has been to divide the operation into two stages. In all 11 cases we experienced, however, it was possible to obtain good results with a single-stage operation.

Child, Preschool

Reconstruction of the entire upper eyelid area with a subcutaneous pedicle flap based on the orbicularis oculi muscle.

Lagophthalmos caused by trauma or inflammation may damage the cornea and, if not adequately treated, may result in loss of eyesight. Hence surgical intervention is required at the earliest possible stage. We have developed a subcutaneous pedicle flap elevated from the temporozygomatic area and rotated 180 degrees around a small pedicle base that contains the orbicularis oculi muscle. With this flap, the entire upper eyelid can be reconstructed as an aesthetic unit in one stage so that the result is satisfactory not only functionally, but also cosmetically. The operative procedure is presented along with case reports.

Adult

Treatment effects of GnRH agonist on the binding of estrogen and progesterone, and the histological findings of uterine leiomyomas.

The changes in the histology and steroid hormone binding capacity of the uterine leiomyomas treated with; GnRH agonists (GnRHa buserelin acetate in, 900 micrograms/day for 16 weeks) were investigated. The occurrence of hyaline degeneration in the myometrium was significantly higher in the GnRHa-treated group than in the control group, and the grade of hyaline degeneration was more advanced in the GnRHa group. After the GnRHa treatment, the Bmax of the estrogen receptor increased significantly in the leiomyomas and myometrium. The Bmax of progesterone receptors in the myometrium decreased significantly and the reduction rates of leiomyomas (% of the initial volumes) measured by MRI correlated (r = 0.775) with the Bmax of progesterone receptors. In summary, GnRHa caused hyaline degeneration of the uterine leiomyomas which were responsible for the shrinkage. The shrunk leiomyomas have the potential for regrowth in response to estrogen as they still have high concentrations of the estrogen receptors.

Adult

Effect of bupivacaine on muscle tissues and new bone formation induced by demineralized bone matrix gelatin.

Heterotopic bone formation induced by demineralized bone matrix gelatin (BMG) in bupivacaine-HCl-treated skeletal muscle was examined histologically. BMG was obtained by dehydrating diaphyseal shafts of femora and tibiae of male, 4-week-old Sprague-Dawley (SD) rats, cutting it into chips, and demineralizing and extracting the chips with various solutions. The BMG was implanted into the rectus abdominis muscle of male, 5-week-old SD rats, bupivacaine-HCl was injected at the same site, and the resulting plaques of tissues were examined histologically on days 5, 10, 15 and 20 after BMG implantation. Heterotopic bone formation occurred in all animals. The bupivacaine-treated group had more degenerated and injured muscle fibers, and more osteocytes than the control group. Electron microscopy showed that the basement membrane of muscle fibers was discontinuous and that many mononucleated cells resembling activated satellite cells were present on day 5. Many fibroblasts, undifferentiated mesenchymal cells and myogenic cells were seen in the area around the BMG. In new bones there were few osteocytes on day 10, but their numbers were increased on days 15 and 20 after implantation, especially in the bupivacaine-treated group. The population of osteocytes that increased rapidly may have included mononucleated cells similar to activated satellite cells.

Abdominal Muscles

Possible contribution of prolactin in the process of ovulation and oocyte maturation.

The present study was undertaken to evaluate the effects of PRL in the process of ovulation and oocyte maturation. In the first experiment, using an in vitro perfused rabbit ovary model, the addition of PRL to the perfusate inhibited hCG-induced ovulation in a dose-related fashion, without any reduction in progesterone synthesis. In a subsequent experiment, PRL directly inhibited both the degeneration and decomposition of surface epithelial cells and the disruption of connective tissue at the apex of the follicle wall. Furthermore, PRL inhibited hCG-stimulated plasminogen activator (PA) activity in mature follicles in a dose-related fashion. In the final experiment, we demonstrated conditions in which rabbit oocytes matured in vitro acquire competence for early embryonic development. PRL, as well as gonadotropins and estradiol, was an important constituent in the process of oocyte maturation, promoting embryonic development. These results suggest that the preovulatory environment of PRL within the follicle may influence the process of ovulation and oocyte maturation.

Animals

Effects of prolactin on fertilization and cleavage of human oocytes.

The effects of PRL on fertilization and cleavage of human oocytes and subsequent pregnancy were studied. Forty-five patients (47 cycles) with euprolactinemic normal menstrual cycles undergoing in vitro fertilization (IVF) for the treatment of tubal infertility were selected for this study. The patients were divided into three groups dependent upon their mean serum PRL concentrations for the 3 days prior to oocyte retrieval; hypoprolactinemic (less than 10 micrograms/l), euprolactinemic (10-30 micrograms/l) and hyperprolactinemic cycles (greater than or equal to 30 micrograms/l). Multiple follicular development was induced with hMG, and 10 patients were randomized to receive bromocriptine beginning with the previous menstrual cycle. In the hypoprolactinemic cycle group, the fertilization rate was significantly lower than in the hyperprolactinemic cycle group, and the cleavage rate was significantly lower than in the other groups. The fertilization rates and the cleavage rates in the hyperprolactinemic cycle group were higher than those in the euprolactinemic cycle group; however, these differences were not statistically significant. While the pregnancy rates in the euprolactinemic cycle group were higher than in the other two groups, the numbers were too small for meaningful statistical comparison. The present study demonstrates that below normal concentrations of PRL have deleterious effects on IVF outcome. These data suggest that PRL may play a beneficial stimulatory role in oocyte maturation and the acquisition of developmental capacity.

Adult

Localization of progesterone receptors in pre- and postovulatory follicles of the domestic hen.

Progesterone may act locally to modulate follicular maturation and ovulation in the domestic hen. The distribution of progesterone receptors (PR) in the pre- and postovulatory follicles was determined in hens by immunocytochemistry and Western blot analysis. Monoclonal antibodies to chicken PR, PR6, and PR 13, were used. PR were localized in nuclei of theca externa fibroblasts and germinal epithelial cells in stigma and nonstigma regions of the third largest preovulatory follicle (F3). In the largest preovulatory follicle (F1), PR were present in theca externa fibroblasts, germinal epithelial cells, and also in granulosa cells and some of the theca interna fibroblasts in the stigma and nonstigma region. Twenty-four hours after ovulation, PR in the fibroblasts of the theca externa of the postovulatory follicle (POF) were remarkably reduced, but the amount of PR in the granulosa cells was similar to that observed in the F1. A high density of PR was also found in the fibroblasts, arterial wall, and smooth muscle fibers in the loose connective tissue of pre- and postovulatory follicles. Western blot analysis indicated that PR in the granulosa and theca tissue were identical in molecular weight to PR in the shell gland. Western blot analysis also confirmed the changes in the amounts of PR in the pre- and postovulatory follicles as determined by immunocytochemistry. The relative amounts of PR in the granulosa cells as determined by Western blot analysis was F2 less than F1 = POF, and in theca tissue was F2 = F1 greater than POF. The presence of PR in specific ovarian tissues suggests that these tissues are target tissues for progesterone and that progesterone may have a role in regulating follicular maturation and ovulation through receptor-mediated pathways.

Animals

Involvement of leukotriene B4 in ovulation in the rabbit.

The present study was undertaken to assess the effects of lipoxygenase products on ovulation, oocyte maturation, and steroid production in the perfused rabbit ovary preparation. Ovulatory efficiency was significantly reduced when rabbit ovaries were perfused with human CG (hCG) plus nordihydroguaiaretic acid (NDGA) at 10(-5) or 10(-6) M, as compared to contralateral hCG-treated controls. The addition of NDGA to the perfusate inhibited hCG-induced ovulation in a dose-related manner. The percentage of ovulated ova and follicular oocytes achieving germinal vesicle breakdown did not differ significantly between NDGA-treated ovaries and contralateral controls. Leukotriene B4 (LTB4) production by the perfused rabbit ovaries reached its maximum 6 h after exposure to hCG and then declined. The addition of NDGA at 10(-5) M significantly inhibited hCG-stimulated LTB4 production by rabbit ovaries throughout the entire perfusion periods. The ovulatory efficiency in ovaries treated with hCG alone or with hCG plus NDGA correlated significantly with LTB4 production by perfused rabbit ovaries 6 h after exposure to hCG (alpha = 0.8893, P less than 0.01). Furthermore, the addition of LTB4 at 100 ng/ml to the perfusate reversed the inhibitory effects of NDGA on hCG-induced ovulation. However, exposure to NDGA affected neither progesterone nor estradiol production elicited by hCG administration. These results suggest that NDGA may block hCG-induced ovulation in vitro, probably via the inhibition of LTB4 production by rabbit ovaries.

Animals

Changes in convulsion susceptibility of lidocaine by alteration of brain catecholaminergic functions.

Influences of the manipulation of brain catecholaminergic neuronal activity on the incidence of lidocaine-induced convulsions in mice were studied and compared with those of pentylenetetrazol (PTZ)-induced convulsions. alpha-Methyl-p-tyrosine (alpha-MPT) decreased both brain noradrenaline (NA) and dopamine (DA) levels, and disulfiram decreased the NA level and increased the DA level. The incidence of lidocaine-induced convulsions was decreased by treatments with alpha-MPT and disulfiram, while that of PTZ was increased by either treatment. The incidence of lidocaine-induced convulsions was slightly, but not significantly increased by L-dihydroxyphenylalanine (L-DOPA), although the brain DA level was increased by L-DOPA. Methamphetamine and desipramine increased the incidences of lidocaine-induced convulsions. These results may suggest that brain catecholaminergic neurons, differing from their role in inhibiting control of PTZ-seizure, act to facilitate lidocaine-induced convulsions.

Animals

Uptake of nicotinamide by rat pancreatic beta cells with regard to streptozotocin action.

Exposure of rat pancreatic beta cells in monolayer culture to 2 mmol streptozotocin (STZ)/l for 1 h followed by thorough washing inhibited their uptake of [14C]nicotinamide and [3H]2-deoxyglucose [( 3H]2-DG) to about 50% and also reduced the intracellular ATP concentration to 50% of that in control cells. These changes were not due to a lethal cytotoxic effect of STZ, because cell viability, as estimated by succinic dehydrogenase activity, was 90% of that of control cells. Oligomycin and carbonylcyanide-m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, caused a dose-dependent decrease in intracellular ATP concentration while maintaining high cell viability. These ATP-depleted cells showed a decrease in insulin release and an inhibition of the uptake of [14C]nicotinamide and [3H]2-DG in a dose-dependent manner. Therefore oligomycin and CCCP reproduced the same effects as those found in beta cells treated with STZ. These results suggest that the uptake of nicotinamide and 2-DG by beta cells might be regulated by their intracellular ATP concentration. The decreased uptake of nicotinamide in ATP-depleted beta cells caused by STZ might explain the lack of protective effect of nicotinamide against STZ cytotoxicity when administered after the latter. Furthermore, the radiotracer experiments demonstrated that the transport of nicotinamide by intact beta cells was inhibited in a dose-dependent manner by 2-DG and vice versa, i.e. the transport of 2-DG was inhibited by nicotinamide. These findings suggest the existence of a common transport mechanism in beta cells responsible for the uptake of nicotinamide and 2-DG, the transport of which is known to occur by facilitated diffusion.

Adenosine Triphosphate

The ultrastructure of cartilage formation from neonatal skeletal muscle in vitro.

Histological changes in cultured neonatal skeletal muscle tissue at the early stage of cartilage induction by syngeneic insoluble bone matrix gelatin (BMG) containing bone morphogenetic protein were examined by light and electron microscopy. Minced skeletal muscle was cultured on hemicylindrical pieces of BMG for 14 days. Chondroblasts first appeared in the crevices of the BMG on Day 7 of the culture, and cartilage tissue was seen to fill the crevices completely by Day 10. The main findings in this work are as follows: 1) the activation of satellite cells and necrosis of myonuclei; 2) the migration of satellite cells from the basement membrane; 3) fibroblasts with increased numbers of organelles between degenerated muscle fibers closely resembling the migratory satellite cells; 4) the migration of the spindle-shaped cells into the crevices of the BMG; and 5) change of the spindle-shaped cells to chondroblasts. These findings suggest that neonatal skeletal muscles, which appear more mature than embryonic muscles, also have a chondrogenetic potential when grown on BMG, and that chondroblasts originate from the spindle-shaped cells which are thought to result from migratory satellite cells as well as fibroblasts.

Animals

Oxygen dependence of lipid peroxidation in mice.

Peroxidation of lipids in serum and tissues of mice placed in low or high levels of oxygen was examined. After exposure to 100% oxygen for 3 h, no significant differences were observed between control and exposed mice. However, exposure to 100% oxygen for 6 h resulted in a decrease in oxygen consumption, an increase in lipid peroxides in tissues and serum, and the formation of hydroxyl radicals in tissues and serum. At low concentrations of oxygen (14% or 16%), a decrease in oxygen consumption, peroxidation of lipids and formation of hydroxyl radicals also were observed. Damage to mice was great with the lower oxygen concentrations of oxygen. There was a close correlation between the consumption of oxygen lipid peroxidation, formation of hydroxyl radicals.

Animals

Architecture of implanted bone matrix gelatin influences heterotopic calcification and new bone formation.

Heterotopic bone formation in skeletal muscle induced by compacted demineralized bone matrix gelatin (BMG) was studied histologically and biochemically. BMG was obtained by dehydrating diaphyseal shafts of femora and tibiae of 4-week-old male Sprague-Dawley rats, cutting the bone into chips, and demineralizing and extracting the chips with various solutions. The BMG was treated with 4 M guanidine-HCl, and compacted BMG was prepared by centrifugation. The compacted BMG was implanted into the rectus abdominis muscle of 5-week-old male Sprague-Dawley rats. The resulting specimens were examined histologically, and their alkaline phosphatase activity and the calcium content of the tissues were measured 3, 5, 7, 10, and 15 days after implantation. The BMG (separated BMG) with 75- to 500-microns particle sizes were implanted into control rats. The results showed that calcification, alkaline phosphatase activity, and bone formation were suppressed by implantation of the compacted BMG and that scarcely any vascularization occurred. Calcification, vascularization, and alkaline phosphatase activity were related and were indispensable for bone formation. In the control group, bone formation was observed at sites of high activity of alkaline phosphatase and well-developed vascularization. These results suggested that compacting of BMG suppressed vascularization, decreased calcification, and consequently reduced the induction of bone formation.

Alkaline Phosphatase

Localization of progesterone receptors in the shell gland of laying and nonlaying chickens.

The aim of the present study was to localize the progesterone receptor (PR) in the shell gland of the chicken and to determine if the localization and the amount of PR in the shell gland change with egg laying activity. White Leghorn hens laying regularly or out of lay for more than 2 wk were used. Localization of PR in the shell gland was done by immunocytochemistry. The amount of PR in the shell gland mucosal tissues was measured by Western blot analysis. Monoclonal antibodies to the chicken PR, PR6, and PR13 were used in both experiments. The PR were present in the nuclei of the surface epithelial cells, tubular gland cells, stromal fibroblasts, and smooth muscle cells in the arterial wall and myometrium of laying hens. The PR were localized in the same tissues of the shell gland of nonlaying hens as in laying hens. However, the density of PR-positive cells in nonlaying hens was greater, possibly because the tissues were atrophied. Western blot analysis indicated that the amount of PR was greater in nonlaying hens than in laying hens when equal amounts of proteins were used, whereas the molecular weights of PR of laying and nonlaying hens were identical. These results suggest that progesterone acting through its receptor may regulate the secretory activity of the surface epithelium and tubular gland cells for shell formation and the contractile activity of the myometrium. Moreover, once the cells of the shell gland differentiate and become responsive to progesterone, these cells maintain this responsiveness even during the nonlaying period.

Animals

Studies on condensed-heterocyclic azolium cephalosporins. I. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- alkoxyiminoacetamido]-3-(imidazo[1,2-a]pyridinium-1-yl)methyl-3- cephem-4-carboxylates.

In our study of the structure-activity relationships of cephalosporins bearing quaternary ammonium groups at the 3 position, we postulated that delocalization of the azolium positive charge would lead to an expanded antibacterial spectrum and increased activity. Since quaternization of condensed-heterocyclic compounds such as imidazo[1,2-a]pyridine gives positive charge delocalization, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporin derivatives (1-53) bearing various (imidazo[1,2-a]pyridinium-1-yl)methyl moieties at the 3 position were prepared and their antibacterial activity was determined. As expected, these cephalosporins exhibited potent activity against both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. These results imply that imidazo[1,2-a]pyridine is a quite useful substituent for improving antibacterial activity and spectrum. The structure-activity studies revealed that a favorable substituent on the imidazo[1,2-a]pyridine is the cyano radical at the 6 position of the ring, and ethoxyimino or 1-carboxy-1-methylethoxyimino groups are suitable for the alkoxyimino substituent. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- ethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2-a]pyridinium -1-yl)methyl-3-cephem-4-carboxylate (45) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-(1- carboxy-1-methylethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2- a] pyridinium-1-yl)methyl-3-cephem-4-carboxylate (49) showed good antibacterial activity.

Cephalosporins

Studies on condensed-heterocyclic azolium cephalosporins. II. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3-(condensed- heterocyclic azolium)methyl-3-cephem-4-carboxylates.

From our series of studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]ceph alosporins containing imidazo[1,5-a]pyridinium, imidazo[1,2-b]pyridazinium, imidazo[1,2-a]pyrimidinium, imidazo[1,2-c]pyrimidinium, and pyrazolo[1,5-a]pyridinium methyl groups at the 3 position. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3- (imidazo[1,5-a]pyridinium-2-yl) (1), (imidazo[1,2-b]pyridazinium-1-yl) (2), and (pyrazolo[1,5-a]-pyridinium-1-yl) (3)methyl-3-cephem-4-carboxylates showed potent antibacterial activity and broad antibacterial spectrum. The antibacterial activity of these cephalosporins (1 approximately 3) was superior to that of ceftazidime (CAZ). These results imply that the delocalization of the positive charge of the imidazo[1,5-a]pyridinium, pyrazolo[1,5-a]pyridinium and imidazo[1,2-b]pyridazinium groups leads to an expanded antibacterial spectrum and increased activity and that these condensed-heterocyclic compounds as well as imidazo[1,2-a]pyridine are effective moieties for improving antibacterial activity and spectrum.

Cephalosporins