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Biomedical subjects

K Sengoku

Publications and source records attributed to K Sengoku.

At least 37 records · Page 2Linked to original sources

Mouse/human sequence divergence in a region with a paternal-specific methylation imprint at the human H19 locus.

We have identified a region with characteristics of a paternal-specific methylation imprint at the human H19 locus. This region, extending from -2.0 kb upstream to the start of transcription, is heavily methylated in sperm and on the paternal allele in somatic cells. This methylation was preserved during pre-implantation. Structural analysis revealed the presence of CpG islands and a large direct repeat with a 400 bp sequence reiterated several times, but no significant sequence homology to the corresponding region of the mouse H19 gene. These findings could suggest a role for secondary DNA structure in genomic imprinting across the species, and they also present a puzzling aspect of the evolution of the H19 regulatory region in human and mouse.

Alleles↗

Involvement of protein kinases in platelet activating factor-induced acrosome reaction of human spermatozoa.

The involvement of protein kinases in platelet activating factor (PAF)-induced acrosome reaction of human spermatozoa was investigated using specific inhibitors of protein kinase A (PKA), protein kinase C (PKC) and protein tyrosine kinase (PTK). PAF (10(-9)-10(-11) M) treatment of spermatozoa enhanced the acrosome reaction in a dose-dependent manner (32 +/- 4% at 10(-9) M, 28 +/- 4% at 10(-10) M and 24 +/- 3% at 10(-11) M respectively). When spermatozoa were preincubated with PKA, PKC and PTK inhibitor (KT5720, calphostin C and genistein) for 15 min prior to addition of PAF, there was a significantly reduced acrosome reaction induced by PAF, but complete inhibition was not observed. On the other hand, combined use of three inhibitors completely inhibited PAF-induced acrosome reaction to levels of non-treated samples. These results suggest that the induction of the acrosome reaction by PAF treatment may involve the activation of PKA, PKC and PTK signalling pathways, and that interaction between these pathways may regulate complex mechanisms of PAF-induced acrosome reaction.

Acrosome↗

The role of superoxide dismutase in the human ovary and fallopian tube.

OBJECTIVES: To investigate the localization of manganese superoxide dismutase (Mn-SOD) and copper-zinc superoxide dismutase (Cu, Zn-SOD) in the human ovary and fallopian tube, and to examine the role of superoxide radicals and SODs in the human ovulatory process. METHODS: Using immunohistochemical methods, we studied the localization of SODs in 22 human ovaries, in 18 fallopian tubes, and in aspirated granulosa cells. We measured, by enzyme-linked immunosorbent assay, the concentrations of SODs in follicular fluid taken from 94 IVF patients. RESULTS: Mn-SOD was found in granulosa, in theca and luteal cells and in fallopian tubes. Cu, Zn-SOD was localized in theca and luteal cells. The concentration of Cu, Zn-SOD in follicular fluid in the high-progesterone group (11.3 + 4.2 ng/ml) was significantly less than in the low-progesterone group (24.5 + 19.5) (p < 0.05). CONCLUSION: Mn-SOD and Cu, Zn-SOD have different localizations and actions in human ovaries and fallopian tubes. The superoxide radical-SOD system might play an important role in ovulation and in the luteal function of the human ovary.

Body Fluids↗

Plasma membrane block to polyspermy in human oocytes and preimplantation embryos.

The existence and time course of the human plasma membrane block to polyspermy were investigated by an in vitro fertilization assay using zona pellucida-free unfertilized oocytes, pronuclear oocytes and embryos. In the time course study using a high sperm concentration (10(5) spermatozoa ml-1), the number of penetrating spermatozoa at 30 and 60 min after insemination were 1.3 +/- 0.3 and 2.9 +/- 0.4, respectively. By 2 h after insemination, spermatozoa penetration reached a maximum. A lower maximum number of penetrating spermatozoa was observed at a low sperm concentration (10(4) spermatozoa ml-1), but the number of penetrating spermatozoa still reached a maximum by 2 h after insemination. A reinsemination experiment demonstrated that the number of penetrating spermatozoa was not significantly different between control and reinseminated oocytes, while sperm penetration was not observed in the oocyte beyond the two-cell stage. Furthermore, the number of binding spermatozoa decreased after fertilization and most of the four-cell stage embryos displayed no sperm binding. These results suggest that the plasma membrane block plays an important role in the prevention of polyspermy in the human oocyte, and that the plasma membrane block may involve permanent changes in the binding or fusion ability of spermatozoa in the oolemma after fertilization.

Blastocyst↗

The use of zona-free aged unfertilized human oocytes as a predictor for successful subzonal insemination.

OBJECTIVE: To examine the reliability of the zona-free aged (1 day old) human unfertilized oocyte sperm penetration assay for assessing sperm fertilizing ability and to determine the predictive value of this assay for subsequent subzonal insemination (SUZI) outcomes. DESIGN: A total of 253 unfertilized oocytes from total fertilization failure patients and from good fertilization rate (> 70%) patients in standard IVF were inseminated with donors' spermatozoa, and penetration rates were compared in each group. Two hundred seventy-two unfertilized oocytes from total fertilization failure, poor fertilization (< 30%), and normal fertilization (> 30%) were inseminated with husbands' spermatozoa, and penetration rates were compared between the three groups. In 29 patients, the results of the zona-free assay performed in previous IVF were compared with the fertilization rates of subsequent SUZI. RESULTS: In the zona-free assay using donors' spermatozoa, there was no difference in penetration rates between the two groups (109/122, 89.3% versus 114/131, 87.0%). Penetration rates using partners' spermatozoa were positively correlated with fertilization rates in standard IVF (total fertilization failure 34/75, 45.3%; poor fertilization 56/77, 72.7%; normal fertilization 108/120, 90.0%). There was a significant difference in fertilization rates after SUZI between the patients with negative and positive penetration in zona-free assay (4/53, 7.5%, versus 54/174, 31.0%). CONCLUSION: The zona-free human oocyte assay may primarily reflect sperm fertilizing ability. This asssay also could be a reliable predictor for subsequent SUZI outcome.

Cellular Senescence↗

[Four cases of noncardiac surgery after PTCA].

Malignant tumors were detected in four patients who had been hospitalized for acute myocardial infarction and/or postinfarction angina. All of them underwent curative operations after successful percutaneous transluminal coronary angioplasty (PTCA). Operations performed were partial colectomy on the first patient, low anterior rectal resection on the second patient, left pulmonary upper lobectomy on the third patient and partial colectomy with cholecystectomy on the fourth patient. There were no complications in the perioperative periods except the first patient in which postoperative electrocardiogram showed transient peaked T wave in leads II, III, AVf, V5 and V6. Forty six days after colectomy (55 days after PTCA), the first patient underwent emergency PTCA for restenosis. Prior PTCA, as well as CABG, is considered to have decreased cardiac complications in patients with ischemic heart disease. But when a non-cardiac operation should be done after PTCA, we should take restenosis into consideration.

Aged↗

Evaluation of transvaginal color Doppler sonography, transvaginal sonography and CA 125 for prediction of ovarian malignancy.

OBJECTIVES: To evaluate the efficacy of color Doppler ultrasonography as the predictor of malignant ovarian tumors and to compare the results with CA 125 levels and ultrasonographic morphological patterns. METHODS: We compared color Doppler ultrasound with sonographic findings and serum CA 125 levels for predicting ovarian malignancy in 16 patients with malignant and 12 patients with benign ovarian tumors. RESULTS: There was a significant difference in pulsatility index (PI) value of ovarian vessel between benign and malignant tumors (2.42 +/- 0.67 for benign and 1.35 +/- 0.78 for malignant, respectively, P < 0.01). The specificity of morphological findings and CA 125 was lower than that of PI measurements, but sensitivity was not different between the three methods. In addition, the combination of color Doppler and CA 125 or morphological assessments resulted in a sensitivity of 100% and a negative predictive value of 100%, respectively. CONCLUSION: PI measurements by transvaginal color Doppler ultrasound combined with CA 125 levels or morphological findings could be an accurate and appropriate screening method for ovarian tumors.

Adult↗

A randomized prospective study of gonadotrophin with or without gonadotrophin-releasing hormone agonist for treatment of unexplained infertility.

The use of gonadotrophin-releasing hormone agonist (GnRHa) in combination with human menopausal gonadotrophin (HMG) for ovulation induction has been advocated for the treatment, particularly by in-vitro fertilization (IVF) of various types of infertility. The present study was designed to compare the clinical efficacy of HMG alone with a short protocol of GnRHa/HMG for treatment of unexplained infertility. A total of 91 couples with unexplained infertility were randomly assigned to one of two treatments; either HMG with intra-uterine insemination (IUI) (45 patients, 62 cycles) or GnRHa/HMG with IUI (46 patients, 69 cycles) treatments. Progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration were significantly higher in HMG (1.5 +/- 0.9 ng/ml) versus GnRHa/HMG (0.8 +/- 0.6 ng/ml; P < 0.05) cycles. Furthermore, GnRHa suppressed the occurrences of premature luteinization (GnRHa/HMG 5.8% and HMG 24.2% respectively). However, there were no significant differences in HMG dose requirements, plasma oestradiol concentrations or follicular development on the day of HCG administration between the two groups. Nor were any significant differences found in the pregnancy rates between the two treatment protocols (GnRHa/HMG 13.0% and HMG 11.3% respectively). Our results suggest no beneficial effect of GnRHa/HMG compared to HMG alone for the treatment of unexplained infertility, based on pregnancy rates.

Adult↗

[Basic and clinical studies on biapenem (L-627) in obstetrics and gynecology].

UNLABELLED: We investigated biapenem (BIPM, L-627) a newly carbapenem antibiotic, for its antibacterial activity, tissue penetration, clinical efficacy and bacteriological effect in obstetric and gynecological infections, and obtained the following results. 1. Antibacterial activity: MICs of L-627 against 149 strains isolated from 80 patients in this clinical trial were examined and compared with those of imipenem (IPM) and ceftazidime (CAZ). The MIC50 and MIC90 of L-627 against the isolates were 0.2 and 12.5 micrograms/ml, respectively. Those of IPM were 0.2 and 6.25 micrograms/ml, respectively. The antibacterial activity of L-627 was quite similar to that of IPM, and was superior to that of CAZ. 2. Tissue and retroperitoneal fluid penetration: The peak levels in venous and uterine arterial sera were 24.0 and 26.2 micrograms/ml, respectively, after 300 mg drip infusion. The peak levels in the uterine or adnexal tissues were 2.39-9.60 micrograms/g, and 0.2 microgram/g of L-627 was detected at 275 minutes after administration. Peak levels in retroperitoneal fluid were 8.7 +/- 1.7 micrograms/ml at 1 hour after the completion of 30 minutes drip infusion (300 mg) and 7.9 +/- 0.2 micrograms/ml at 30 minutes after 300 mg 60 minutes drip infusion (300 mg). These levels expected the MICs against main pathogenic organisms. 3. CLINICAL RESULTS: L-627 was given to the following 144 patients (No. of analytical subjects) at a daily dose of 0.3-1.2 g for 2-13 days: intrauterine infections (54), adnexitis (36), parametritis (17), pelvic peritonitis (27), bartholins abscess (6) and other infections (4). The clinical efficacy was 93.1% (134/144) and the eradication rate against isolated organisms was 88.7% (110/124). Side effects were observed in 2 patients: eruption (1) and vomiting with numbness of the tongue (1). Abnormal change in laboratory test results included increase in eosinophils in 1, increase in GOT, GPT and gamma-GTP in 1 and increase in GPT and A1-P in 1, but all of these abnormalities were very mild and withdrawal of the drug was not required. Our results suggest that this drug is useful in the treatment of gynecological infections.

Adolescent↗

[A cytogenetic study of human oocytes unfertilized in in-vitro fertilization (IVF)].

A total of 260 unfertilized human oocytes obtained in our IVF program were studied cytogenetically, by a gradual fixation-air drying method proposed by Mikamo and Kamiguchi (1983). The oocytes were obtained from 72 cycles of 52 patients (mean age 32.1). Indications for these patients were 26 cases of tubal factor, 13 of male infertility, 2 of endometriosis and 11 of unexplained infertility. Ovulation induction was performed by hMG-hCG administration with GnRHa pretreatment. Of the 260 unfertilized oocytes, 183 displayed metaphase II and 149 were karyotyped accurately. There were 5 diploids (3.4%), 9 structural anomalies (6.0%) and 15 aneuploids (10.1%) including 8 hyperhaploids (5.4%) and 7 hypohaploids (4.7%). One hundred and twenty-two oocytes out of 149 (81.9%) were found to be normal haploids [23,X]. In 9 aneuploids, 5 showed the loss or gain of monads (so-called predivision), while 4 showed the loss or gain of dyads (so-called nondisjunction). Twenty-three oocytes out of 149 (15.4%) had one or more split dyads. (so-called nondisjunction). Twenty-three oocytes out of 149 (15.4%) had one or more split dyads. Our results were compared with those obtained in previous studies, and the importance of the chromosome preparation method in evaluating aberration frequencies was stressed. Causal mechanisms of aneuploidy, diploidy and structural anomaly were also discussed.

Adult↗

Effects of platelet activating factor on human sperm function in vitro.

The direct effects of platelet activating factor (PAF) and the specific PAF receptor antagonist, CV-3988, on the fertilizing ability of human spermatozoa were investigated. PAF (10(-7)-10(-11) M) increased the human sperm penetration rates in a sperm penetration assay at all doses > 10(-11) M. In contrast, treatment of the spermatozoa with 10(-5) CV-3988 caused a significant decrease in human sperm penetration of zona-free hamster oocytes and adversely affected sperm motility after 24 h of incubation. This suppression was reversed by the addition of PAF. The acrosome reaction was also enhanced by PAF treatment of spermatozoa but this effect was not observed in calcium-free medium. While 10(-5) M CV-3988 decreased the acrosome reaction, the inhibition was also reversed by the addition of PAF. These results suggest that PAF may have a direct role in the fertilizing capacity of human spermatozoa. These findings also suggest that PAF may have a clinical application in an in-vitro fertilization programme.

Acrosome↗

[Pharmacokinetic and clinical studies of flomoxef in the perinatal period].

Pharmacokinetic and clinical studies on flomoxef (FMOX) in the perinatal period were carried out and following results were obtained 1. The pharmacokinetic parameter T1/2's of FMOX in maternal serum, umbilical cord serum and amniotic fluid in mothers after single intravenous injection of 1 g (n = 46) and 2 g (n = 34) were 1.11, 9.24, 9.24 hours and 2.54, 12.49, 12.49 hours, respectively. Cmax's and Tmax's of umbilical cord serum and amniotic fluid were 12.71, 11.77 micrograms/ml and 0.57, 3.35 hours upon single dose of 1 g i.v., and 35.17, 12.37 micrograms/ml and 0.32, 3.42 hours upon single dose of 2 g i.v., respectively. 2. Clinical usefulness were evaluated in 93 cases including were various infections in pregnancy and puerperal period. In pregnancy cases, clinical efficacy rate was 95.5% (21/22), and 100% in puerperal period. Bacteriological response rate was 84.6% (eradicated: 29, decreased: 4, unchanged: 2, replaced: 4 and unknown: 8 cases). No severe side effects nor clinical laboratory test results were observed in any cases. From above basic and clinical results, we conclude that FMOX is a useful and safe agent for various infections in pregnancy and puerperal period.

Adult↗

[Two cases of male infertility with pathological dilatation of ejaculatory duct].

Two cases of male infertility with pathological dilatation of ejaculatory duct are reported. In both cases, the dilatated wall of the ejaculatory duct was incised at the vermontanum with a cold knife endoscopically. After the incision, the findings of semen analysis of one case improved markedly and his wife became pregnant. In another case, semen analysis was not improved. Transurethral incision seemed to be a useful modality for the treatment of pathological dilatation of ejaculatory duct.

Adult↗

Effects of platelet activating factor on mouse sperm function.

Platelet activating factor (PAF) has been implicated in a variety of reproductive processes. This study was designed to investigate the effect of PAF and the specific PAF receptor antagonist, CV-3988, on capacitation and the acrosome reaction in mouse spermatozoa using an in vitro fertilization (IVF) system. When spermatozoa were preincubated for 30 min in medium containing PAF (10(-7) to 10(-11) M), a significant increase in the fertilization rate with both cumulus-free and zona-free oocytes was observed. In contrast, treatment of the spermatozoa with 10(-5) M CV-3988 caused a significant decrease in both sperm motility and fertilization rates with zona-intact and zona-free oocytes. This suppression was reversed by the addition of PAF. Furthermore, the acrosome reaction was enhanced by PAF treatment of spermatozoa in a dose-dependent manner. This stimulation of the acrosome reaction by PAF required the presence of calcium ions in the medium. While 10(-5) M CV-3988 inhibited the acrosome reaction, the inhibition was also reversed by the addition of PAF. These results suggest that PAF can stimulate not only the capacitation process but also the acrosome reaction, both of which are dependent on extracellular calcium.

Acrosome↗

[Role of oxygen radical and superoxide dismutase in ovulation in the rat].

We studied the effect of Cu,Zn-superoxide dismutase (SOD) and Mn-SOD, which are specific scavenging enzymes of the superoxide anion radical, on ovulation and examined the localization of SOD in rat ovaries. The results were as follows. 1) The number of ova in the Cu,Zn-SOD (8 mg x 4) administrated group (27.8 +/- 5.4 : p less than 0.01) was significantly reduced compared to the control group (49.0 +/- 3.3). Similarly, the number of ova in the Mn-SOD (2 mg x 2) administrated group (16.9 +/- 7.6 : p less than 0.01) was significantly reduced compared to the control (52.9 +/- 6.3). 2) In the rat ovary, Cu,Zn-SOD examined by the immunohistological method was found to be localized in the granulosa cells of mature Graafian follicles, growing follicles, primordial follicles and epithelial cells of the fallopian tubes. Mn-SOD was localized in the external theca cells of mature Graafian follicles and the corpus luteum. The activity of SOD estimated by the modified nitroblue tetrazolium method was consistent with the immunohistological localization of both SODs. We considered that oxygen radicals and SODs play an important role in rat ovulation, and Cu,ZN-SOD and Mn-SOD have a different localization and action in the rat ovary.

Animals↗

The effect of platelet activating factor on ovulation.

The mechanism of ovulation has been compared to an inflammatory reaction. Platelet activating factor (PAF) is an important mediator of inflammation as it may induce the production of prostaglandins and lysosomal enzyme. We evaluated the potential role of PAF in PMSG-HCG induced ovulation using CV3988, a specific PAF receptor antagonist in a superovulated ICR mice (9-12 weeks old). CV3988 blocked the ovulation in a dose dependent manner, and the significant reduced ovulatory efficiency was observed at more than 500 micrograms dose (p less than 0.001). The ovulatory efficiency reduced by CV3988 was reversed by PAF in a dose dependent manner. In vitro fertilization (IVF) rate of follicular oocytes with treatment of CV3988 was not different from that of ovulated ova without treatment. These results suggest that PAF may be involved in the ovulation process but the presence of PAF may not be essential for the fertilization of the ova as IVF.

Animals↗

[Study on flomoxef in the perinatal period].

The placental passage and the the therapeutic efficacy of flomoxef (FMOX, 6315-S) were studied in patients in the perinatal period. A summary of the obtained results is as follows: 1. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid obtained upon one-shot intravenous injections to 12 patients were compared with those obtained upon 1 hour drip infusions to 9 patients. It was found that the former means of administration gave higher concentrations that the latter. 2. Concentrations of FMOX in maternal serum, umbilical cord serum and amniotic fluid at 1 to 6 hours after administration through either method were all higher than MIC80's of recognized bacteria. 3. Clinical efficacies were evaluated in 10 patients with puerperal intrauterine infection, 7 patients with endometritis, 2 patients with pyelonephritis and 1 patient each with endo-cervicitis, amniotic fluid infection, mastitis and perineal wound infection. Clinical efficacies were excellent in 5 patients (21.7%), good in 17 patients (73.9%) and poor in 1 patient (4.4%), thus the overall efficacy rate was 95.7%. 4. Eradication of causative bacteria were obtained in all 8 cases tested, hence the eradication rate was 100%. 5. Mild diarrhea in 1 patient was the only side effect observed. No abnormal clinical laboratory test results were found in any patients.

Adult↗

[Transvaginal ultrasonographic findings and hCG levels in early intrauterine pregnancies].

The correlation of transvaginal ultrasound (TVU) findings with serial hCG determinations was evaluated during early pregnancy in 60 patients. In these patients, the time of ovulation was accurately determined by ultrasonic monitoring of follicular rupture. The results were as follows. 1) A gestational sac less than 6 mm in diameter was identified in 22 of 38 cases (57.9%) in 4 weeks gestation, and the mean number of cycle days for detection of the GS was 34.1 +/- 2.5. On the other hand, fetal heart movement was detected as early as 43.0 +/- 2.8 days from the last menstrual period. 2) A good linear relationship was found between the gestational age and size of the gestational sac and size of the fetus. 3) A gestational sac was identified in one of 10 cases (10.0%) with hCG levels below 1,000 mIU/ml (1st IRP), 5 of 6 with levels of 1,000-2,000 mIU/ml, and all 15 cases with levels above 2,000 mIU/ml. These results suggested that TVU could significantly improve the detection of gestational sacs, and result in a lower hCG threshold than previously established with transabdominal sonography. Furthermore, our findings derived from patients in which the date of ovulation could be accurately determined by ultrasound should be useful in further studies of early fetal development.

Chorionic Gonadotropin↗