Biomedical subjects
T Aono
Publications and source records attributed to T Aono.
Activation of K+ channels by ritodrine hydrochloride in uterine smooth muscle cells from pregnant women.
This study investigated the mechanism of activation of K+ channels by ritodrine hydrochloride in human myometrial smooth muscle cells. The patch-clamp technique was used for recording single channel currents. Ritodrine (10(-5) M) activated two types of K+ channels in cultured uterine smooth muscle cells from pregnant women: the Ca(2+)-activated K+ (KCa) channel and the ATP-sensitive K+ (KATP) channel. Forskolin (10(-4) M), an activator of adenylate cyclase, and protein kinase A activated the KCa channel. In addition, 10(-4) M GTP activated the KCa channel in inside-out patches using a pipette containing 10(-5) M ritodrine. The KATP channel was activated by protein kinase A, but not by 10(-4) M GTP. The beta-adrenoceptor agonist ritodrine activates two types of K+ channels: the KCa channel via direct gating by GTP-binding proteins and possibly via cAMP-dependent phosphorylation, and the KATP channel possibly via cAMP-dependent phosphorylation. These mechanisms partially explain the relaxing effect of ritodrine hydrochloride.
Effect of lysophosphatidic acid on the preimplantation development of mouse embryos.
The effect of lysophosphatidic acid (LPA) on the preimplantation development of mouse embryos was examined. The blastocyst rates from 2-cell and 4-cell stage embryos were significantly higher in the presence of LPA at the pronuclear stage. However, the blastocyst rate from 4-cell stage embryos was significantly lower when LPA was added to the medium at the 4-cell stage than when it was added at the pronuclear stage. Furthermore, pretreatment of pronuclear stage embryos with pertussis toxin suppressed LPA-induced embryo development, suggesting that it is probably mediated by a Gi-protein-linked receptor.
Enhanced gastric acid secretion induced by gastrin can be suppressed by glucose injected into the portal vein in rats.
Gastric acid secretion induced by tetragastrin was examined after glucose injection into the portal vein in rats. The enhancement of acid secretion caused by gastrin was inhibited by glucose injection into the portal vein, and the acid response was dose dependent. The acid response due to portal glucose injection was not reproduced when the hepatic vagal branch was sectioned. These findings suggest that the portal glucose signal modulates gastric acid secretion controlled by gastrin.
[Maternal plasma beta-endorphin levels during labor in relation to maternal obesity].
The relationship between maternal plasma levels of beta-endorphin (beta-Ep) during labor and various obstetrical factors was investigated in 115 healthy pregnant women. beta-Ep was determined by radioimmunoassay using double-antibody RIA kit (INCSTAR Corporation, Stillwater, M'S.). The results were as follows: (1) The primiparous women showed a significant increase of maternal plasma levels of beta-Ep at delivery compared with the multiparous women. In addition, the group of women whose Bishop's score at the onset of labor was 5 points or less showed a significant increase of maternal plasma levels of beta-Ep at delivery compared with that in the group of women whose Bishop's score was 6 points or more. (2) The increase in maternal plasma levels of beta-Ep during the first and the second stage of labor was significantly higher in obese women (pre-pregnancy BMI > or = 24) than in normal weight women (pre-pregnancy BMI < 24). In normal weight women in pre-pregnancy, the group of women whose weight gain during pregnancy was 11kg or more showed a significantly higher increase of beta-Ep compared with that in the group of women whose weight gain was less than 11 kg. These results suggest that a stressful delivery caused a significant increase of maternal plasma levels of beta-Ep during labor. Moreover, obesity and marked weight gain during pregnancy caused a remarkable increase in beta-Ep probably due to latent dystocia.
Glucose signal in the nucleus of the vagus nerve modulates the cyclicity of gastric motility in rats.
The cyclicity and intensity of gastric motility were examined following glucose injection into the nucleus of the vagus nerve (X) or into the nucleus of the solitary tract (SOL) in anesthetized rats. Enhanced gastric motility caused by insulin administration was influenced by 4 mM glucose (500 nl) injected into the X; glucose provoked a shift in the cyclicity power spectrum without any change in intensity. The peak power spectrum shifted from 4.0-5.0 cpm to 2.0-3.0 cpm, but not significant change in the cyclicity power spectrum was seen when the same dose of glucose was injected into the SOL. It was also noted that the power spectrum response to 4 mM glucose injection into the X was not modified when 4 mM glucose was injected into the SOL simultaneously. The results suggest that the medullary glucose signal in the X differentially modulates the cyclicity of gastric motility independent of the SOL.
Major hepatectomy and pancreatoduodenectomy for advanced carcinoma of the biliary tract.
Seven patients with advanced carcinoma of the extrahepatic biliary tract, including two with cancer of the gallbladder, underwent major hepatectomy with concomitant pancreatoduodenectomy. The mean hepatic volume resected was 64 (range 35-81) per cent. Postoperative complications occurred in all patients and accounted for two hospital deaths. Two patients with gallbladder carcinoma survived without recurrence for 22 and 58 months. Three of five patients with bile duct cancer survived operation, although all three subsequently died from recurrent disease at 8, 10 and 27 months. Combined major hepatectomy and pancreatoduodenectomy may be appropriate in selected patients with advanced cancer of the gallbladder. Further evaluation is necessary before this approach can be recommended for those with advanced bile duct carcinoma.
Liver regeneration is enhanced by omeprazole in rats following partial hepatectomy.
The effect of omeprazole on liver regeneration was studied in rats following partial (65 per cent) hepatectomy. Omeprazole 0.2 mg/kg increased the relative liver weight (weight of liver as a proportion of body-weight) and mitotic index (P < 0.05). There was no difference in food and water intake. The serum gastrin concentration was significantly higher in animals receiving omeprazole 0.2 mg/kg than in controls (P < 0.05). Omeprazole administration induced an increase in the level of serum alkaline phosphatase (P < 0.05) but had no effect on serum albumin, glutamic-pyruvic transaminase and total bilirubin levels. Omeprazole stimulates liver regeneration after partial hepatectomy and this regeneration may be mediated by gastrin.
Detection of varicella-zoster virus DNA in blood of children with varicella.
The nested polymerase chain reaction was used to detect varicella zoster virus (VZV) DNA in 67 samples of peripheral blood mononuclear cells (PBMC) from 39 otherwise healthy children with varicella. Eleven were during the incubation period and 56 were after appearance of rash. VZV DNA was detected in two of eight (25%) PBMC at the early phase of the incubation period (day -14 to -11). The rate of the detection increased to 67% in -5 to -1 days prior to the onset of the rash and 46% in 0-4 days after the onset. It declined gradually with time and was undetectable in patients after 15 days from the clinical onset. The serum antibody determined with the fluorescent antibody to membrane antigen was first detected in the samples on day 2 and subsequently increased to 100% rapidly. In conclusion, VZV DNA cannot be detected usually in PBMC of healthy children except in varicella.
Immunoglobulin binding factor: a new tumor marker for prostatic tumors.
Human seminal plasma contains an immunoglobulin gamma binding factor (IgBF) with an estimated molecular weight of 16 kD under reducing condition. IgBF was detected only in the prostate, including benign prostatic hypertrophy (BPH) and neoplasm. The present study was performed to determine whether IgBF is a useful prostatic marker. Serum IgBF levels were measured in patients with prostatic tumors and in control patients without tumor by radioimmunoassay. Serum prostatic-specific antigen (PSA), the standard prostatic marker, was also determined. Serum IgBF levels in patients with prostate cancer were significantly higher than those in age-matched controls (P < 0.05). Also, patients with BPH tended to have elevated IgBF levels than the controls, although the values were not statistically significant. In control patients, serum IgBF levels increased with advancing age. There was no correlation between serum levels of IgBF and PSA in patients with prostate cancer. Using cut-off level at 28.5 ng/ml (2 S.D. above the mean IgBF level of age-matched control), the sensitivities were 41.2% (7/17) for prostate cancer, 23.1% (6/26) for BPH, and 5.6% (1/18) for control patients. In conclusion, serum IgBF is a useful marker in the diagnosis of patients with prostatic tumor, and in evaluating the course of treatment.
Mating pheromone-induced expression of the mat1-Pm gene of Schizosaccharomyces pombe: identification of signalling components and characterization of upstream controlling elements.
Transcription of the mat1-Pm gene of Schizosaccharomyces pombe controlling entry into meiosis is stimulated by the mating pheromone, M-factor. We have studied its expression by monitoring beta-galactosidase activity in cells carrying a plasmid-borne mat1-Pm/lacZ fusion construct. Stimulation required the M-factor receptor (Map3) and other proteins (Gpa1, Byr1, Byr2 and Spk1) thought to be involved in propagating the pheromone signal within the cell. Mutational activation of gpa1 encoding an alpha subunit of the receptor-coupled heterotrimeric G protein causes full expression of mat1-Pm even in the absence of pheromone, suggesting that Gpa1 is a key signal transmitter. Furthermore, an activated ras1val17 mutant exhibited a much stronger level of induction than wild-type cells, though full expression needs M-factor treatment. Deletion analysis of the mat1-Pm promoter region identified a stretch of 21 bp that is shown to play a critical role in controlling expression. This region lies just upstream of a TATA-like box and contains a TR-box (TTCTTTGTTY) motif which is the recognition site of a putative transcription factor Ste11. Point mutations in the TR-box motif abolished the expression of mat1-Pm/lacZ. Almost no expression of mat1-Pm was detected in a ste11 deletion mutant, whereas overproduction of Ste11 greatly increased the expression.
Expression of glutathione S-transferase-pi in human ovarian cancer as an indicator of resistance to chemotherapy.
Expression of glutathione S-transferase-pi (GST-pi) was examined immunohistochemically in relation to the response to chemotherapy with cisplatin in 61 patients with primary ovarian cancer who had not received any chemotherapy before surgery. GST-pi were detected in the cancer tissues of 33 patients (54.1%). Of 28 clinically measurable lesions after surgery, 10 of the 11 tumors (90.9%) showing positive GST-pi staining were drug resistant (no change or progressive disease), whereas 6 of the 17 tumors (35.3%) showing negative staining were drug resistant. This difference in the response rates of the two groups was significant (P < 0.005). The survival period of patients with GST-pi-positive tumors was also significantly shorter than that of those with GST-pi-negative tumors (P < 0.005). These data strongly suggest that GST-pi expression in tumor cells is related to drug resistance of patients with epithelial ovarian cancer and is a useful marker of a poor prognosis.
An interaction between glucose and estrogen in gastric acid secretion in the lateral hypothalamic area of female rats.
Gastric acid outputs caused by glucose injection into the lateral hypothalamic area (LHA) were examined in insulin hypoglycemia with or without estradiol-17 beta (EST) administration in bilaterally ovariectomized (OV) female rats. The basal level of acid output was higher in OV rats without EST than in OV rats with EST. When acid response was expressed as the percentage change, glucose injection into the LHA decreased acid output in a dose-dependent fashion in OV rats, while, in OV rats with EST, glucose injection into the LHA also reduced acid output without dose dependency. It was also noted that the threshold concentration of glucose that induced an acid response was lower in OV rats without EST than in OV rats with EST. These findings suggest that glucose-sensitive neurons responsible for gastric acid secretion can be modulated by estrogen at the LHA level.
Enhanced hepatic portal blood flow induced by prostaglandin E1 following liver transplantation in pigs.
Portal venous blood flow (PVF), hepatic arterial blood flow (HAF), and systemic arterial pressure (SAP) were examined after prostaglandin E1 (PGE1) was injected into the vena cava superior (VCS) of liver-transplanted pigs. The injection of PGE1 at 0.2 micrograms/kg/min for 2 min on the day of transplantation and 3 days later produced an increase in PVF without causing any change in HAF or SAP, the response in PVF being dose-dependent. However, no reliable change in PVF, HAF, or SAP was seen when the same dose of PGE1 was administered 7 days after transplantation. Furthermore, no significant difference was noted among the values for PVF and total hepatic blood flow (THF) during the experimented days, although the HAF value had increased markedly 3 days after transplantation. These findings suggest that PGE1 is effective in increasing PVF in the liver transplanted condition; however, the hepatic circulatory improvement attributed to this agent would be limited to the first few days following transplantation.
Successful freezing of unfertilized mouse oocytes and effect of cocultures in oviducts on development of in vitro fertilized embryos after thawing.
PURPOSE: To establish a freeze-thawing method for unfertilized oocytes with a high success rate, we examined several conditions for freeze-thawing. The effects of EDTA and cocultures in oviducts on the development of embryos fertilized in vitro after thawing were also studied. RESULTS: In the first experiment, unfertilized oocytes that were frozen in 1.5 M dimethylsulfoxide (DMSO) supplemented with 0.2 M sucrose by a slow freeze-thawing method showed the best results (fertilization rate, 71.9%; blastocyst rate per frozen oocyte, 18.8%). The proportion of embryos that developed to blastocysts was significantly higher when DMSO was added at 4 degrees C than at room temperature (39.4 vs 19.4%; P < 0.01). The addition of EDTA (10 microM) to the culture medium did not promote embryo development after fertilization in vitro. However, the rate of development of in vitro fertilized embryos to blastocysts after thawing was significantly higher when the embryos were cultured in oviducts in vitro than the rates in control cultures and those cultured with EDTA (blastocyst rate from fertilized oocytes, 71.4 vs 51.0 and 52.8%, respectively; P < 0.01). CONCLUSION: Unfertilized mouse oocytes can be cryopreserved successfully by a slow freeze-thawing method with the addition of 1.5 M DMSO and 0.2 M sucrose at low temperatures, and coculture with oviducts enhances the development of embryos that are fertilized in vitro after thawing.
Releases of oxytocin and prolactin during breast massage and suckling in puerperal women.
The responses of prolactin (PRL) and oxytocin (OT) to suckling and breast massage were examined in lactating women. The suckling group showed increase in frequency of pulsatile release of OT and increase of the plasma PRL level. In contrast, the breast massage group showed a significant, but not a pulsatile increase in the plasma OT level and no increase in the plasma PRL level. These findings suggest that suckling causes both milk production and milk ejection, while breast massage causes only ejection of milk already stored in acini, and that prolactin release is not related to increase of the oxytocin level itself, but to its pulsatile release.
Interaction of glucose signals between the nucleus of the vagus nerve and the portal vein area in the regulation of gastric motility in rats.
Intragastric pressures were examined after glucose injection into the nucleus of the vagus nerve (X) of the medulla oblongata or into the portal vein (PV) or both in bilaterally adrenalectomized rats. Ten mM glucose (500 nl) injected into the X or into the PV (25 microliters) decreased gastric pressure associated with insulin-hypoglycemia. Simultaneous injection of glucose into the X and PV produced a reduction in gastric pressure in an additive manner. In addition, a significant fall in gastric pressure was seen when an ineffective concentration of glucose was injected into the X and PV simultaneously. The results suggest that the X and PV signals interact with each other to inhibit gastric motility.
Mechanism of anovulation in hyperprolactinemic amenorrhea determined by pulsatile gonadotropin-releasing hormone injection combined with human chorionic gonadotropin.
OBJECTIVE: To clarify the mechanism of anovulation in hyperprolactinemic anovulatory women by subcutaneous (SC) pulsatile GnRH injection. DESIGN: Prospective clinical study. SETTING: Studies were made on at the Department of Obstetrics and Gynecology, the University of Tokushima, School of Medicine. PATIENTS: Six hyperprolactinemic (group 1) and 7 normoprolactinemic (group 2) anovulatory patients were studied. INTERVENTIONS: After examinations of pulsatile secretion of LH, the GnRH test, thyrotropin-releasing hormone test and estrogen test, pulsatile GnRH treatment (20 micrograms/2 hours SC) was performed. Two protocols were tested on each patient. In the non-hCG protocol, GnRH treatment was continued until ovulation. In the hCG protocol, 5,000 IU of hCG was injected to induce ovulation when follicles were fully mature. MAIN OUTCOME MEASURE: The rates of follicular maturation and ovulation, serum E2 and P in the two groups. RESULTS: Pulsatile LH secretion was impaired in both groups. LH release 48 hours after estrogen injection was impaired in group 1 but not in group 2. Follicles matured on pulsatile GnRH treatment in all cycles in both groups. However, with the non-hCG protocol, ovulation occurred in only 17% of group 1, but in 89% of group 2. With the hCG protocol ovulation occurred in all cycles in both groups. CONCLUSIONS: The main cause of anovulation is impaired gonadotropin pulsatility and derangement of the estrogen-positive feedback effect on LH secretion in hyperprolactinemic patients, their ovarian response to gonadotropin being well maintained. Subcutaneous pulsatile GnRH therapy combined with hCG can be used as an alternative to bromocriptine treatment for induction of ovulation in these patients.