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Biomedical subjects

Y Yoshimura

Publications and source records attributed to Y Yoshimura.

At least 361 records · Page 20Linked to original sources

Protein kinase C mediates gonadotropin-releasing hormone agonist-induced meiotic maturation of follicle-enclosed rabbit oocytes.

The present study was undertaken to determine the effects of a protein kinase C inhibitor, staurosporine, on gonadotropin-releasing hormone agonist (GnRHa)-induced oocyte maturation and follicular prostaglandin (PG) production, and the response to direct activators of protein kinase C using rabbit mature follicle culture. Treatment of mature follicles with GnRHa (buserelin and leuprolide acetate) neither stimulated nor inhibited cAMP accumulation in both the follicle and oocyte. Exposure to staurosporine at 10(-6) M 60 or 15 min before GnRHa (buserelin) administration reduced significantly the meiotic maturation of follicle-enclosed oocytes induced by GnRHa at 10(-7) M. However, staurosporine addition coincident with the agonist or thereafter did not inhibit meiotic maturation. Staurosporine suppressed GnRHa-induced meiotic maturation in a dose-dependent manner, whereas hCG-stimulated oocyte maturation was not inhibited. Similarly, staurosporine administered 60 min before exposure to GnRHa suppressed GnRHa-stimulated PG production by mature follicles. The active phorbol esters, 10(-6) M 12-0-tetra-decanoyl phorbol 13-acetate (TPA) and 10(-6) M 4 beta-phorbol 12,13-didecanoate (4 beta-PDD) stimulated meiotic maturation whereas the biological inactive isomer, 4 alpha-PDD, did not. The kinetics of germinal versicle breakdown of follicle-enclosed oocytes in the presence of active phorbol esters paralleled that of GnRHa-treated oocytes. Furthermore, the concomitant addition of staurosporine at 10(-6) M to the culture medium inhibited significantly (p less than 0.05) TPA-induced meiotic maturation. These data demonstrate that GnRHa stimulated both the meiotic maturation of follicle-enclosed oocytes and follicular PG formation via a mechanism other than the cAMP-mediated process.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

Long-term depression is induced in Ca2+/calmodulin kinase-inhibited visual cortex neurons.

To elucidate a role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in induction of long-term potentiation (LTP), KN-62, a selective inhibitor for CaMKII, was injected into layer 2/3 neurons of sliced visual cortex obtained from young rats. Tetanic stimulation (5 Hz, 1 min) applied to the white matter after the KN-62 injection induced long-term depression (LTD) of excitatory postsynaptic potentials (EPSPs) evoked by test stimulation of the white matter in 9 of the 14 cells tested. However, EPSPs evoked by test stimulation of the non-tetanized site were not changed, indicating that the induction of LTD was input-specific. Simultaneously, recorded field potentials which were derived from neurons with intact CaMKII showed LTP. These results suggest that postsynaptic CaMKII plays a role in the induction of LTP/LTD in visual cortex.

Animals↗

Effect of antacid on absorption of the quinolone lomefloxacin.

The effect of antacid on the absorption of lomefloxacin (LFLX) in humans was studied. When LFLX was orally administered concomitantly with aluminum- and magnesium-containing antacids under fasting conditions, its level in plasma decreased by one-half and its area under the concentration-time curve was reduced by 40% compared with the levels observed after treatment with LFLX alone. The urinary recovery value also decreased by 40%. No such effects were noted after coadministration of LFLX and a nonmetallic antacid. This study confirmed the existence of chelate complexes of LFLX with Al3+ and Mg2+ and examined the chelating strength. The stability constants of LFLX with Al3+ and Mg2+ were measured and compared with those of ofloxacin and norfloxacin; little difference was observed among them. LFLX was found to bind more strongly with Al3+ than with Mg2+. Further, the existence of chelate formation was proven by 13C-nuclear magnetic resonance spectroscopy. The decrease in the LFLX level in plasma in humans could be explained by a reduced absorption of the Al(3+)- and Mg(2+)-LFLX chelate complexes.

Adult↗

Possible involvement of lipoxygenase products in human corpora lutea.

The present study was undertaken to determine the ability of cultured luteal cells from human corpora lutea to secrete progesterone (P4) and prostaglandins (PGs), and to assess the effects of the products of the lipoxygenase pathway on luteal P4 production. Luteal cells responded to human chorionic gonadotropin (hCG) with a significant increase (2- to 7-fold) in P4 production. Arachidonic acid significantly stimulated PGE2 synthesis by luteal cells in a dose-dependent manner. Both basal PGE2 production and the responsiveness to arachidonic acid were maintained for 8 days. In contrast, both PGF2 alpha and 6-keto-PGF1 alpha production abruptly declined as the culture proceeded. However, the addition of hCG did not further stimulate the accumulation of the 3 PGs assayed. In the subsequent experiment, 5-hydroxyeicosatetraenoic acid (5-HETE) and the reaction products of soybean lipoxidase of arachidonic acid (AA-LIP) were utilized for evaluating the involvement of the lipoxygenase pathway in luteolysis. The addition of 5-HETE dose-dependently inhibited P4 production by the cultured luteal cells. Although treatment with either arachidonic acid or lipoxidase alone had no effect on P4 production, AA-LIP significantly reduced P4 production in the presence or absence of hCG. These results suggest that the products of the lipoxygenase as well as of the cyclo-oxygenase pathway may be important in regulating the life span and function of human corpora lutea.

Adult↗

Role of corpus luteum function in embryo implantation.

The present study was undertaken to evaluate the role of corpus luteum function in the implantation process of cryopreserved embryos. Six patients with tubal infertility were studied, with a total of 27 fresh embryos being replaced following controlled ovarian hyperstimulation and in vitro fertilization. These embryo transfers failed to produce pregnancy. From the patients, 22 supernumerary embryos were cryopreserved and 10 viable frozen-thawed embryos were transferred in a subsequent natural cycle, resulting in 2 pregnancies. In 1 of the pregnancies, the serum concentrations of estradiol (E2) and progesterone (P4) in the midluteal phase were 29 pg/ml and 5.6 ng/ml, respectively. These values were considered to be below the physiological range. These data suggest that a pregnancy can be achieved in spite of low circulating E2 and P4 levels during the luteal phase, which are generally indicative of the luteal phase defect.

Adult↗

Stimulatory role of cyclic adenosine monophosphate as a mediator of meiotic resumption in rabbit oocytes.

The present study was undertaken to assess the role of alterations of intraoocyte cAMP concentrations in the meiotic maturation of isolated and follicle-enclosed oocytes. In isolated oocyte culture, the intracellular cAMP content of denuded oocytes declined within 15 min of incubation, whereas the cAMP content of cumulus-enclosed oocytes did not change substantially for 1.5 h of incubation, and then declined abruptly. Commitment to meiotic maturation was preceded by reduced concentrations of intraoocyte cAMP. Forskolin inhibited the spontaneous maturation of cumulus-enclosed oocytes in a dose-dependent manner. However, this inhibition was attenuated as the duration of incubation increased. Forskolin significantly stimulated the intracellular cAMP content of denuded and cumulus-enclosed oocytes, but intraoocyte cAMP returned to pretreatment values within 4 h. The decline in intraoocyte cAMP was followed by the meiotic maturation of isolated oocytes. In in vitro perfused rabbit ovaries, exposure to forskolin at 10(-4) M, as well as to 50 IU human CG, accelerated the meiotic maturation of follicle-enclosed oocytes. The intraoocyte cAMP content increased significantly within 30 min and reached its maximum 2 h following exposure to forskolin. Thereafter, cAMP decreased abruptly and returned to pretreatment levels by 6 h. These alterations of intraoocyte cAMP contents following exposure to forskolin paralleled those observed in human CG-treated ovaries. The decline in cAMP content of follicle-enclosed oocytes was followed by their meiotic maturation. In conclusion, the sustained elevation of intraoocyte cAMP levels inhibits the initiation of meiotic maturation in isolated and follicle-enclosed oocytes. Within the follicle, resumption of meiosis is triggered via a transient increase in intraoocyte cAMP, but commitment to meiosis must await the decline of intraoocyte cAMP.

Animals↗

Characterization of thyroidal membrane-bound Mg-adenosinetriphosphatase activated by trypsin or poly-L-lysine.

The Mg-adenosinetriphosphatase (ATPase) in the thyroidal NaI-treated microsome fraction was activated by treatment with basic polyamino acids or trypsin, but not with acidic polyamino acids and basic proteins such as lysozyme and ribonuclease. The enzyme kinetics showed that the activation of trypsin or poly-L-lysine was due to an increase in the maximal velocity of the hydrolyzing reaction without a change in the affinity of the enzyme for its substrate. A break at about 25 degrees C was observed in the Arrhenius plots of Mg-ATPase in the trypsin- or poly-L-lysine treated preparations, but there was no break in the control preparation. These results suggest that the activating effect of trypsin or poly-L-lysine on Mg-ATPase activity in the thyroidal NaI-treated microsome fraction is related to the lipid environment surrounding the enzyme molecule in the thyroid cell membrane.

Animals↗

Possible involvement of leukotrienes in human luteal function.

The present study was undertaken to assess the ability of human corpora lutea to produce leukotriene B4 (LTB4). The maximum capacity of luteal cells to secrete progesterone was attained on day 4, and both the basal production and the responsiveness to hCG decreased thereafter. In contrast, the production of LTB4 by cultured luteal cells was significantly reduced on day 4, but increased thereafter. The basal concentration of LTB4 produced by luteal cells varied from 75 to 590 pg/10(5) cells/2 days. LTB4 production appeared to decrease concomitantly with increased-progesterone production in cultured luteal cells. Exposure to hCG decreased significantly LTB4 production by cultured luteal cells on day 4. An inhibitor of the lipoxygenase pathway, nordihydroguaiaretic acid (NDGA), inhibited LTB4 production in a dose-dependent manner. However, NDGA did not affect basal progesterone production by the cultured luteal cells. A significant inverse relationship existed between the accumulation rates of progesterone and LTB4 in the luteal cells. Furthermore, the addition of LTB4 inhibited progesterone production in a dose-dependent manner in both the presence and absence of hCG. In conclusion, LTB4 could be synthesized by human corpora lutea in vitro, and correlated inversely with the secretion rates of progesterone. These data suggest that LTB4 produced locally in the corpus luteum may be an important regulator in human luteal regression.

Adult↗

Induction of meiotic maturation of follicle-enclosed oocytes of rabbits by a transient increase followed by an abrupt decrease in cyclic AMP concentration.

The involvement of cyclic adenosine monophosphate (cAMP) in mammalian oocyte maturation was assessed using cultures of rabbit cumulus-oocyte complexes and perfused rabbit ovaries. Rabbit cumulus-oocyte complexes were cultured in Brackett's medium with or without forskolin at 10(-4), 10(-5) or 10(-6) mol l-1 for 3-6 h. At 3 or 4 h spontaneous meiotic maturation was significantly (P < 0.05) inhibited by forskolin at 10(-4) mol l-1. With prolonged incubation, spontaneous maturation progressed despite exposure to forskolin. In the second experiment ovaries were perfused for 12 h with forskolin (10(-4), 10(-5) or 10(-6) mol l-1) or medium alone. Neither ovulation nor degeneration of follicular oocytes occurred in any perfused ovary. The percentage of follicular oocytes achieving germinal vesicle breakdown was significantly (P < 0.001) increased in response to forskolin in a dose-related manner. In an additional experiment, ovaries were perfused with forskolin at 10(-4) mol l-1. A significant increase in the cAMP content in the follicle was observed within 30 min, but the ability to produce cAMP in response to forskolin decreased as the duration of perfusion was increased. Intraoocyte cAMP increased significantly within 30 min and reached its maximum 2 h after exposure to forskolin. Thereafter, cAMP levels in the oocytes decreased abruptly. This drop in intraoocyte cAMP concentration was followed by the resumption of meiosis. The alterations of intraoocyte cAMP contents following exposure to hCG in vivo paralleled those observed in the ovaries perfused with forskolin. These data suggest that a transient, but not continuous, increase in cAMP concentration after the gonadotrophin surge may be required to initiate oocyte maturation.

Animals↗

Studies on condensed-heterocyclic azolium cephalosporins. III. Synthesis and antibacterial activity of 7 beta-[2-(2-amino-5-substituted-thiazol-4-yl)-2 (Z)-alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl-3-cephem-4- carboxylates.

As a part of our research on the synthesis of cephalosporins bearing condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus, we describe herein the synthesis of 7 beta-[2-(2-amino-5-halogeno-, methylthio-, methylsulfinyl-, methylsulfonyl- and sulfothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporins and their antibacterial activity. Among the compounds prepared, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido]-3-(imidazo[1,5-a]-pyridinium-1-yl)methyl-3-cephem -4-carboxylate (14) showed good antibacterial activity against both Staphylococcus aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, whereas the antibacterial activity against other Gram-negative bacteria was a slightly lower than that of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(im ida zo [1,2-a]pyridinium (I-1) and imidazo[1,5-a]pyridinium (I-4)-1-yl)methyl-3-cephem-4-carboxylates.

Anti-Bacterial Agents↗

Studies on condensed-heterocyclic azolium cephalosporins. IV. Synthesis and antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)- alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl cephalosporins including SCE-2787.

The synthesis and in vitro antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetami do] cephalosporins bearing various condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus are described. The thiadiazolyl cephalosporins showed good antibacterial activity against both Gram-positive and Gram-negative bacteria and the MICs of the thiadiazolyl cephalosporins against Pseudomonas aeruginosa was more potent than that of the corresponding 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3- (condensed-heterocyclic azolium)methyl cephalosporins. Also, the thiadiazolyl cephalosporins bearing (imidazo[1,2-b]-pyridazinium-1-yl)methyl groups at the 3 position showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Among the cephalosporins tested, 7 beta-[2-(5- amino-1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido]-3-(imidaz o[1,2- b]pyridazinium-1-yl)methyl-3- cephem-4-carboxylate (4, SCE-2787) which exhibited the most potent antibacterial activity and the broadest antibacterial spectrum was selected as a parenteral cephalosporin candidate for further biological evaluation.

Cephalosporins↗

Studies on condensed-heterocyclic azolium cephalosporins. V. Synthesis and antibacterial activity of 3-(condensed-triazolo-pyridinium, -pyrimidinium, and -pyridazinium)-methyl cephalosporins.

As a part of our 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)-methoxyiminoacetamido] cephalosporins (1-16, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido] cephalosporins (17,18) and 7 beta-[2-(5-amino- 1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido) cephalosporins (19-23) containing a variety of condensed-heterocyclic triazolium methyl groups at the 3 position in the cephalosporin nucleus. These cephalosporins exhibited potent antibacterial activity, and it appears that condensed-heterocyclic triazolium as well as condensed-heterocyclic imidazolium rings are effective moieties for improving antibacterial activity and the spectrum of activity. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(5- methyl[1,2,3]triazolo-[1,5-alpha]pyridinium-1-yl)methyl-3-cephem-4- carboxylate (9) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3-(6- methoxy[1,2,4]triazolo[1,5-alpha]pyridinium-1-yl)methyl-3-cephem-4- carboxylate (11) showed good antibacterial activity.

Cephalosporins↗

Recording the bladder electromyogram for bladder activity evaluation during post-operative urinary urgency.

When the intravesical pressure cannot be measured because of continuous drainage, bladder electromyography is an alternative means of evaluating the functional condition of the urinary bladder. However, many problems that accompany this procedure have not been solved. In the present study we tried bladder electromyography with a newly-developed carbon fiber electrode in a patient who underwent an open prostatectomy. It was helpful in recognizing the relationship between urinary urgency and the spasmic activity of the vesicular detrusor muscle.

Aged↗

[AFP producing gastric cancer manifested by metastasis to the tentorium cerebelli; case report and review of the literature].

We report a case of AFP producing gastric cancer manifested by metastasis to the tentorium cerebelli. A 66-year-old male patient was admitted with dysarthria, occipital headache and nausea on May 1, 1990. Neurological examination revealed signs of increased intracranial pressure and the right-sided cerebellar hemispheric signs. CT and MRI showed a round tumor shadow 3cm in diameter, which originated in the right-side tentorium cerebelli and grew in the posterior fossa. Tumor stains fed by the right tentorial artery were recognized by angiography. Serum AFP level was 503.5ng/ml. The patient underwent an operation under general anesthesia in the prone position. The tumor was totally removed via the suboccipital transtentorial approach. Histological examination revealed AFP producing adenocarcinoma. The patient was found to have a gastric cancer after neurosurgical operation, and underwent subtotal gastrectomy by surgeons. Serum AFP level was 254.5ng/ml after removal of metastatic brain tumor, and 5.0ng/ml after subtotal gastrectomy.

Adenocarcinoma↗

[Effects of propentofylline (HWA285) on recovery of brain function following total cerebral ischemia (TCI) in dogs].

We examined the effects of a xanthine derivative, propentofylline, on recovery of brain function following TCI in 23 adult mongrel dogs. TCI was produced by clamping ascending aorta with aortoatrial bypass formation. The dogs were divided into 3 groups: preischemic administration (0.3 mg.kg-1.min-1, 30 min), post-ischemic administration (0.5 mg.kg-1.min-1, 6h) and control. The progress of recovery of EEG, respiration, reflexes, motor functions, arousal state and behavior were observed for 7 days after TCI and the latter 5 functions were analysed using neurologic deficit score (NDS). Propentofylline shortened the time necessary for reappearance of EEG after the starting of recirculation but could not improve the NDS.

Animals↗

[Visualization of the intravesical urine stream].

Although many urodynamic techniques have been used to evaluate the function of the lower urinary tract, the principles of these measurements are only based on a relationship between flow rate and pressure. In addition to these measurements, the intravesical urine stream would provide useful information on urodynamics. We have experimentally attempted to visualize the urine stream in a bladder using transrectal ultrasound examination. Since an air-particle is a good target for ultrasound visualization, we instillated a 10% glycerine solution into the bladder for the maintenance of air-particles. Before instillation, this glycerine solution was strongly shaken so that air-particles were kept in the solution. The urine stream was successfully observed throughout the whole process of voiding. In video-recording analysis, the velocity of urine stream was measured by tracing some air-particles. The velocity of urine stream was approximately 28.4 cm/sec in the body and increased to 116.6 cm/sec at the bladder neck. Thus, the urine stream was accelerated toward the urethra during voiding. Therefore, it seems that visualization of the urine stream offers a new parameter for evaluation of urodynamic studies.

Humans↗