Biomedical subjects

Koichiro Shimoya

Publications and source records attributed to Koichiro Shimoya.

At least 19 recordsLinked to original sources

PubMed2006

Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain.

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.

Animals↗

PubMed2006

A decrease of cell proliferation by hypothermia in the hippocampus of the neonatal rat.

Hypothermia is a potential therapy for cerebral hypoxic ischemic injury of not only adults but also neonates. However, the side effects of hypothermia in the developing brain, where a massive amount of neurogenesis occurs, remain unclear. We investigated the proliferation of neural progenitor cells by systemic application of the thymidine analog 5-bromodeoxyuridine (BrdU) in neonatal rats in a severe hypothermic environment. The rat pups were divided into two groups, a hypothermia group (30 degrees C: n=10) and a normothermia group (37 degrees C: n=10). After the pups were placed for 21 h in each environment, 100 mg/kg/day of BrdU was injected intraperitoneally to label dividing cells, and then the pups were sacrificed at 24 h. We examined the number of BrdU-labeled cells in the subventricular zone of the periventricle and the subgranular zone of the dentate gyrus. In the hypothermic environment, BrdU-labeled cells significantly decreased in number in the dentate gyrus, but not in the periventricular region. Thus, the severe hypothermic environment induced a decrease of neurogenesis in the neonatal rat. These observations are noteworthy regarding clinical hypothermia therapy following cerebral hypoxic ischemic injury during the perinatal period.

Aging↗

PubMed2006

Long-term neuroprotective effects of carbon dioxide on neonatal rat hypoxic-ischemic brain injury: an experimental study of skilled motor tasks.

OBJECTIVE: This study was undertaken to investigate the long-term effect of hypercapnia on neonatal hypoxic-ischemic brain injury, we tested its effect in a neonatal rat hypoxia-ischemia model. STUDY DESIGN: The rats were subjected to unilateral carotid artery ligation and exposure to 8% oxygen for 30 minutes. Six percent carbon dioxide was administered to the neonatal rats during unilateral hypoxia-ischemia, and the motor function and neurologic outcomes were determined 3 months later. RESULTS: Significant motor functional improvement was observed in the hypercapnic animals, as judged by the Montoya staircase test. The unilateral brain injury was significantly ameliorated in the hypercapnic animals, and this amelioration was well correlated with the motor functional performance. Cerebral blood flow during hypoxia-ischemia, monitored by laser Doppler flowmetry, was better preserved in the hypercapnic animals. CONCLUSION: Our results suggest that mild hypercapnia during hypoxia-ischemia may provide long-lasting motor functional as well as neurologic protection for immature brains, possibly by increasing cerebral blood flow during hypoxia.

Animals↗

PubMed2006

Mouse model of human infertility: transient and local inhibition of endometrial STAT-3 activation results in implantation failure.

Embryo implantation involves a series of biochemical reactions and its failure is an important therapeutic target of infertility treatment. We established an infertile mouse model using transient and local suppression of signal transducer and activator of transcription-3 (STAT-3) activity by STAT-3 decoy transfer into the uterine cavity during implantation, resulting in <30% implantation. This infertility is caused by suppression of decidualization, which is indispensable for implantation, and independent of progesterone. These conditions may mimic clinically unexplained infertility. Our results suggest that STAT-3 could be a useful target for diagnosis and therapy of human implantation failure.

Animals↗

PubMed2006

Simple and highly efficient method for transient in vivo gene transfer to mid-late pregnant mouse uterus.

Up- and down-regulation of various genes in the placenta, decidua and amnion has been reported during the mid-late period of pregnancy and in pregnancy-related complications, such as preeclampsia and preterm labor. However, whether this gene regulation at the feto-maternal interface directly influences the physiology/pathophysiology of disease remains unknown. In order to study this problem, transient gene transfer into the pregnant uterus at mid-late term would be a useful tool. We injected exogenous plasmid entrapped using a commercially available Hemagglutinating Virus of Japan Envelope (HVJ-E) vector system (GenomONE Neo, Ishihara Sangyo) into the extra-amniotic space of the upper part of the pregnant mouse uterus on day 14.5 post-coitus (p.c.). Luciferase activity driven by the cytomegalovirus promoter was detectable for 3 days after transfection in the upper, middle and lower part of the uterus. beta-Galactsidase activity was localized in the basal lamina of the placenta, the decidual membrane and the fetal membrane. Exogenous plasmid was not transmitted to the fetus. The course of pregnancy was not disturbed by this procedure; rupture of membranes, intrauterine fetal growth restriction and preterm birth were not observed. Thus, we demonstrated that this transient gene transfer method is highly efficient and minimally invasive, and expect that this procedure will be a useful tool to analyze the pathophysiology of pregnancy-related disorders.

Animals↗

PubMed2006

The effects of repeated corticosteroid administration on the neurogenesis in the neonatal rat.

OBJECTIVE: The purpose of this study is to clarify the effects on the brain including neurogenesis pretreated with repeated doses of dexamethasone in the neonatal rat. STUDY DESIGN: The 4-day-old Sprague Dawley rats were pretreated with 4 different regimens, namely, single administration of dexamethasone, 2-dose administration, 3-dose administration, and saline administration as a control. Concurrently, bromodeoxyuridine (BrdU), which was incorporated into the dividing cells, was administered. We examined body weight, brain weight, and the number of BrdU-labeled cells in the subventricular zone (SVZ), the subgranular zone (SGZ), and the cortex. RESULTS: Both the body and brain weight of the rats pretreated with dexamethasone were significantly decreased compared with those given saline. Quantitative analysis of BrdU-labeled cells revealed the significant dose-dependent decreases in the SVZ, the SGZ, and the cortex with the dexamethasone treatment. CONCLUSION: We concluded that the decreases in neurogenesis caused by repeated antenatal corticosteroid therapy might result in the adverse effects on the size of the head at birth.

Aging↗

PubMed2006

Prospective study of non-closure or closure of the peritoneum at cesarean delivery in 124 women: Impact of prior peritoneal closure at primary cesarean on the interval time between first cesarean section and the next pregnancy and significant adhesion at second cesarean.

AIM: The aim of this study was to evaluate the effect of non-closure of the peritoneum at cesarean delivery on postoperative complications and the interval time to the next pregnancy, and to investigate the incidence of adhesion following cesarean and the association between adhesion formation and peritoneal closure. METHODS: One hundred and twenty four women scheduled for cesarean section were randomized to either closure of both the visceral and parietal peritoneum (C-group, n = 70) or non-closure (NC-group, n = 54). At repeated cesarean, the levels and extent of adhesion, operating time, and any complications were examined. RESULTS: There was no difference in the incidence of postoperative complications at the first cesarean section. The operating time of the C-group was significantly longer than that of the NC-group. The frequency of analgesic use was significantly higher in the C-group. The time interval from cesarean section to the next pregnancy in the NC-group was significantly shorter than that in the C-group. There are no significant differences between the rates of complications in the C-group and the NC-group at repeated cesarean. The incidence of adhesion in the C-group was significantly higher than that in the NC-group (P < 0.05). The mean total operating time and the mean interval time for skin incision to delivery in the C-group were significantly longer than those in the NC-group (P < 0.05 and P < 0.001, respectively) at repeated cesarean section. CONCLUSIONS: Non-closure of the peritoneum at cesarean delivery appears to have no adverse effect on postoperative recovery, it also decreases the number of analgesic doses and shortens the operating time and may be more desirable in achieving a next pregnancy. The present study demonstrated that surgical peritoneal closure resulted in more advanced adhesion formation. The practice of non-closure of the peritoneum should be performed at cesarean.

Adult↗

PubMed2006

Reduction of aquaporin-8 on fetal membranes under oligohydramnios in mice lacking prostaglandin F2 alpha receptor.

AIM: To investigate the association between aquaporin-8 (AQP-8: a water channel protein) expression in fetal membranes and oligohydramnios during near-term and postdate pregnancy, we set up an oligohydramnios model using prostaglandin F2 alpha receptor (FP)-deficient mice. METHODS: Pregnant FP-deficient mice from 14 to 21 gestational days (GD) were killed to measure the amniotic fluid volume (AFV), and fetal membranes were collected for the analysis of aquaporin-8 expression. RESULTS: The AFV was highest at 14 GD, and was significantly decreased to 28% and 0% at 20 GD and 21 GD, respectively, compared with the volume at 14 GD. Immunohistochemistry and immunoblot analysis showed that aquaporin-8 was expressed in the basal component of fetal membranes, and that the protein level was significantly decreased to 60% at 20 GD compared with that at 14 GD. CONCLUSIONS: We demonstrated that AQP-8 expression in the fetal membrane was decreased at post term in FP-deficient mice. Our findings suggest that aquaporin-8 in fetal membranes may be involved in the regulation of AFV, especially when oligohydramnios occurs.

Amniotic Fluid↗

PubMed2006

Rapid detection of trisomy 21 by gene dosage analysis using quantitative real-time polymerase chain reaction.

AIM: Rapid detection of fetal aneuploidy helps inform a mother's choice about the course of her pregnancy. Obtaining results by fluorescent in situ hybridization (FISH) requires more than 24 h, and thus a more rapid method is needed. METHODS: Conventional G-banding and FISH for chromosome 21 were performed for cultured amniocytes. Genomic DNA was extracted from uncultured amniocytes obtained from 23 patients. TaqMan polymerase chain reaction (PCR) primers were designed to amplify the potassium voltage gated channel gene on chromosome 21q22.12 and the ribosomal phosphoprotein gene on 18q21.1. Quantitative real-time PCR was performed for these two gene fragments and the differences of the threshold cycle (Ct) of the two genes (Ct 18-Ct 21) were calculated for each sample. RESULTS: G-banding revealed that 19 patients had a normal karyotype and four had trisomy 21. FISH resulted in one case of a false positive. The Delta Ct values (Ct 18-Ct 21) of trisomy 21 patients were significantly higher than the values of individuals with normal karyotypes (P < 0.001) and there was no overlapping. CONCLUSIONS: Fetal trisomy 21 is rapidly detectable by gene dosage analysis from amniocytes using quantitative real-time PCR.

Amniotic Fluid↗

PubMed2006

Mid-second trimester measurement of fetal nasal bone length in the Japanese population.

AIM: We carried out a preliminary study to compare the nasal bone length (NBL) and biparietal diameter/NBL (BPD/NBL) ratio between the Japanese and white populations. METHODS: Three hundred and fifty nine (359) singleton fetuses of healthy Japanese couples were examined from June 2004 to October 2005. NBL was measured by the strict midsagittal section. The reference range of NBL was established from cross-sectional data between 15 and 25 weeks' gestation. RESULTS: The success rate of obtaining reliable NBL was 93% (333/356). There were 330 fetuses (93%) available for constructing a reference range from the population. The median NBL increased from 3.2 mm at 15 weeks' to 7.6 mm at 25 weeks' gestation. The median of BPD/NBL ratio was 9.01. CONCLUSIONS: We demonstrated that NBL was significantly shorter and BPD/NBL was significantly greater in the Japanese population than those in the white and black populations.

Adolescent↗

PubMed2006

Spontaneous rupture of uterine surface varicose veins in pregnancy: a case report.

BACKGROUND: Spontaneous rupture of uterine surface varicose veins is rare but may become a serious complication of pregnancy. CASE: A 40-year-old woman, gravida 2, para 0-0-1-0, presented with worsening generalized abdominal pain after occasional nausea, vomiting and diarrhea over the previous 2 days. After a 4-hour observation period, sudden onset of severe, prolonged fetal heart rate decelerations was recognized along with frequent uterine contractions. Emergency cesarean section was performed under a tentative diagnosis of placental abruption. A live, female infant weighing 1,730 g was delivered and had Apgar scores of 5 and 9 at 1 and 5 minutes, respectively. Intraoperatively, approximately 500 mL of hemoperitoneum was present, and multiple bleeding sites from varicose veins on the posterior uterine surface were detected. Because the maternal vital signs became unstable and hemostasis was difficult, hysterectomy was performed and blood transfusion administered. CONCLUSION: Although very rare, hemoperitoneum should be included in the differential diagnosis when a pregnant woman experiences acute-onset, severe abdominal pain, even without an episode of abdominal trauma.

Adult↗

PubMed2005

Secretory leukocyte protease inhibitor levels in cervicovaginal secretion of elderly women.

OBJECTIVE: Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. The aim of the present study was to examine whether there is an association between the SLPI concentration in the cervicovaginal secretion (CS) and vaginal complaints of post-menopausal women. METHODS: Uterine cervix tissues and CS of peri- or post-menopausal women were obtained. SLPI was assayed by ELISA. To determine the level of SLPI mRNA and the localization of SLPI protein in the uterine cervix, we performed RT-PCR and immunochemical staining, respectively. RESULTS: The levels of SLPI in the CS of post-menopausal women with vaginal complaints were significantly lower that those of post-menopausal women without vaginal complaints. The levels of SLPI in the CS of post-menopausal women were lower that those of peri-menopausal women and post-menopausal women treated with hormone replacement therapy. Positive staining was observed in epithelial cells of the cervix of elderly women, however, the intensity was weaker than that in peri-menopausal women. Positive staining was also observed in gland cells of the cervix of peri-menopausal women, but not in those of post-menopausal women. SLPI transcripts were detected in the cervix of post-menopausal women. The treatment of post-menopausal women with vaginal estrogen increased the concentrations of SLPI in CS of post-menopausal women. CONCLUSIONS: The present findings suggest that the decreased amount of SLPI in the CS of post-menopausal women might be one of the causes of the symptoms of post-menopausal women and contribute to the immunodefense mechanisms of the elderly women.

Aged↗

PubMed2005

In vivo gene transfer into the mouse uterus: a powerful tool for investigating implantation physiology.

In vivo transient transfection of cDNA into uterine endometrium during the implantation period provides great opportunities to analyse the physiology/pathophysiology of implantation at the molecular level. We review here methodologies which have been applied for this purpose. Viral vectors are widely used for in vivo gene therapy models; however, there is no successful example of gene transfer into the uterus using such vectors. Cationic liposome-based technologies have produced some successful results, causing alterations in implantation physiology. We applied a haemagglutinating virus of Japan envelope (HVJ-E) vector system and showed that the transfection efficiency was much higher than that of methods based on cationic liposome. Commercial HVJ-E vector (GenomONE-Neo) is now also available. Several successful examples of in vivo gene transfer revealed that calcitonin, Hoxa 10 and NF kappaB play important roles in determining the efficiency or timing of implantation. Based on this knowledge, we should further analyse the pathophysiology of human implantation failure using human materials.

Abortion, Spontaneous↗

PubMed2005

Elevated expression of N-acetylglucosaminyltransferase V in first trimester human placenta.

In early pregnancy, placental trophoblast cells rapidly grow and invade into maternal uterine tissue. N-Acetylglucosaminyltransferase V (GnT-V) and its product, beta1-6-GlcNAc branching glycan, are known to correlate with tumor invasion and metastasis. Since the placentation process resembles invasion of cancer cells, we examined the expression of beta1-6-GlcNAc branching glycan and GnT-V in human placenta. Placentas derived from the first trimester contained a larger amount of beta1-6-GlcNAc branching glycan, detected by leukoagglutinating phytohemagglutinin lectin blotting, than those at term. Immunohistochemical study revealed that beta1-6-GlcNAc branching glycans and GnT-V protein were localized in the trophoblast layer. Both protein expression and the enzyme activity of GnT-V in first trimester placentas were higher than those at term. These results suggest that GnT-V would contribute to placentation in the early phase of pregnancy, possibly regulating the process of invasion of trophoblast cells.

Agglutinins↗

PubMed2005

Tension-free vaginal tape procedure with manual-tapping method: a potentially useful technique.

AIM: Stress urinary incontinence (SUI) is accompanied by pelvic organ prolapse (POP) in many cases. We investigate a procedure to adjust the level of suspension of the mid-urethra using tension-free vaginal tape (TVT) under general anesthesia at the time of POP repair surgery. METHODS: Preliminary examination carried out prior to this study showed that the pressure stress applied by a surgeon is less than half of that induced using the cough-stress method: the manual-tapping method (MTM) showed an average intravesical urinary leak point pressure (IULPP) of 21.4 mmHg (range 19-23 mmHg), when the cough-stress method demonstrated an average IULPP >52.4 mmHg (range 45-58 mmHg; n = 3). An attempt was made to predict postoperative SUI by packing sponge gauze into the manually replaced vagina preoperatively. If SUI appeared, TVT was added to the repair operation for POP in those patients (n = 11). Lastly, the MTM was used to decide the level of urethral suspension during the TVT procedure following POP repair surgery under general anesthesia (n = 11). RESULTS: Eleven patients underwent the TVT procedure combined with POP repair surgery. The mean postoperative follow-up period was 23.8 months (range 9-40 months). There was no case of post-surgical ischuria. One patient showed a cystocele during the postoperative course. However, all other patients were relieved from the symptoms of POP, and none complained of SUI following the procedure. CONCLUSION: The MTM seems to be a more appropriate indicator by which to adjust the level of urethral suspension during the TVT procedure than the conventional method, particularly under general anesthesia. To prevent and cure perioperative SUI, the MTM as a TVT procedure combined with POP repair surgery under general anesthesia is a useful procedure.

Aged↗

PubMed2004

Surgical reinforcement of support for the vagina in pelvic organ prolapse: concurrent iliococcygeus fascia colpopexy (Inmon technique).

To reinforce the support of the vagina, concurrent use of iliococcygeus fascia colpopexy with the McCall culdeplasty was scheduled for primary uterine prolapse. Forty-five women with primary uterine prolapse without stress urinary incontinence were treated by McCall culdeplasty alone or McCall culdeplasty plus iliococcygeus fascia colpopexy for suspension of the upper portion of the vagina. Recurrence of vaginal support defects were carefully followed for 15-50 months. Additional iliococcygeus fascia colpopexy did not change with the axis of the vagina obtained by McCall culdeplasty, although it prolonged total operation time by 32 min and increased blood loss by 94 ml. Two cases (8.3%) had postoperative vaginal defects in the group undergoing combined procedures and seven recurrent cases (33.3%) were observed in the group undergoing McCall culdeplasty alone. The durability of the combined procedures was superior to that of the modified McCall culdeplasty alone by Kaplan-Meier analysis. These results suggest that iliococcygeus fascia colpopexy is reasonably safe and strengthens not only the attachment of the upper part of the vagina but also that of the anterolateral vaginal wall.

Aged↗

PubMed2004

Alteration of the timing of implantation by in vivo gene transfer: delay of implantation by suppression of nuclear factor kappaB activity and partial rescue by leukemia inhibitory factor.

Nuclear factor kappaB (NF-kappaB) is activated in the murine endometrium during implantation period [Am. J. Reprod. Immunol. 51 (2004) 16]. Transient transfection of IkappaBalpha mutant (IkappaBalphaM) cDNA into the mouse uterine cavity using hemagglutinating virus of Japan envelope vector suppressed uterine NF-kappaB activity less than half of that observed in control on days 3.5 and 4.5 p.c. IkappaBalphaM cDNA transfection led to significant delay of implantation. After IkappaBalphaM cDNA transfection, LIF mRNA expression in the uterus was significantly suppressed on days 3.5 and 4.5 p.c. Co-transfection of LIF cDNA with IkappaBalphaM cDNA in the uterus partially rescued the delay of implantation induced by suppression of NF-kappaB activity. Taken together, these findings indicate that NF-kappaB activation determines the timing of the implantation, at least in part, via control of LIF expression.

Animals↗

PubMed2004

Idarubicin administered during pregnancy: its effects on the fetus.

Acute myeloblastic leukemia, subtype M1, was diagnosed in a 39-year-old G2P1 Japanese woman at 21 weeks' gestation. Remission-induction polychemotherapy, including daunorubicin, performed for one cycle, did not lead to remission. Second-line chemotherapy, including idarubicin, performed for one cycle, was administrated during the early third trimester of pregnancy. Septic shock occurred due to severe myelosuppression. An emergent cesarean section was performed in response to a nonreassuring pattern of the fetal heart rate and a rapid decrease in fetal amniotic fluid. The neonate delivered at 32 weeks' gestation showed no signs of cardiac failure but did show signs of transient myelosuppression, hepatopathy, and elevated creatine kinase. Complete remission was established with idarubicin including chemotherapy.

Adult↗