Masaji Nagaishi

Chromosome abnormalities identified in 347 spontaneous abortions collected in Japan

Objective: We determined the incidence of specific chromosome abnormalities in this Japanese population so that comparisons could be made to the incidence of chromosome abnormalities reported for other populations.

Surgical procedure to conserve the uterus for future pregnancy in patients suffering from massive adenomyosis

The treatment for severe adenomyosis has usually been hysterectomy, because there is no line of demarcation between diseased and normal tissue. Yet many such women wish to retain their uterus and some even wish to bear children. This report evaluates the efficacy of a new method of adenomyomectomy, where adenomyotic tissues are radically excised and the uterine wall is reconstructed by a triple-flap method, without overlapping suture lines, to prevent uterine rupture in subsequent pregnancies. This is a prospective case series followed for 10 years from June 1998 to August 2008 of 104 women with severe adenomyosis verified histologically and with magnetic resonance imaging. There was a dramatic reduction in both dysmenorrhoea and hypermenorrhoea and all patients returned to having normal menstrual cycles. Of 26 women who wished to conceive, 16 became pregnant, 14 (53.8%)went to term and delivered a healthy baby and there were no cases of uterine rupture. Adenomyosis symptoms recurred in only four out of 104 cases. The procedure thus resulted in a dramatic reduction in symptoms and allowed over half of women who wished to conceive to go to term without uterine rupture.

Transplacental effects of allopurinol on suppression of oxygen free radical production in chronically instrumented fetal lamb brains during intermittent umbilical cord occlusion

Objective. To evaluate the transplacental effect of allopurinol, which acts as a xanthine oxidase inhibitor and free radical scavenger, on inhibiting the production of superoxides during intermittent partial umbilical cord occlusion. Methods. Using four chronically instrumented fetal lambs, ewes received 400 mg allopurinol over a period of two hours. Concentrations of allopurinol and oxypurinol in blood samples from mothers and fetuses and fetal brain microdialysis perfusate were measured by HPLC. In another three cases the production of superoxide during intermittent umbilical cord occlusion was studied by measurement of chemiluminescence in perfusate before and after administration of Allopurinol. Results. (i) Allopurinol concentration in mothers had reached equilibrium by 30 min after starting administration and maintained a concentration about 6 μg/ml. Allopurinol concentration in fetuses increased gradually and reached 2.25 ± 0.54 μg/ml at 120 min; (ii) Oxypurinol concentration in both mothers and fetuses increased during administration of allopurinol; (iii) Concentrations of allopurinol and oxypurinol in the perfusates reached 0.32 ± 0.12 μg/ml, 0.53 ± 0.22 μg/ml at 120min respectively; and (iv) Administration of allopurinol significantly suppressed superoxide production during intermittent partial umbilical cord occlusion. Conclusion. These results demonstrated a good transfer of allopurinol from mother to fetus and suggested the possibility of intrauterine treatment to inhibit fetal brain damage resulting from increased oxygen free radicals.

Expression of Functional Chemokine Receptors of Human Placental Cells

PROBLEM: Chemokine receptors of placental trophoblasts possibly act as co‐receptors or alternative receptors of maternal–fetal infection by HIV. To clarify their possible expression and the physiological roles of chemokines on human placentae, we studied chemokine/chemokine receptor expression and the effects of exogenous chemokines on choriocarcinoma cell lines.
 MATERIALS AND METHODS: Placental samples were obtained from 13 placentae of various gestational ages. Villous tissue was mechanically dissected from samples. Trophoblasts were enriched by anti‐human chorionic gonadotropin (hCG)‐coated magnetic beads. Human choriocarcinoma cell lines (JAR, BeWo, JEG‐3) were maintained in RPMI 1640 media supplemented with 10% FCS. Expression of chemokine receptors was studied by RT‐PCR. The effects of MIP‐1α, RANTES, MCP‐1 on hCG production were estimated by EIA. Effects of chemokines on proliferation of choriocarcinoma cell lines were examined by MTT assay.
 RESULTS: We observed mRNA expression of CCR‐1, 2, 3, 4, 5 and CXCR‐1, 2, 4 in 1st trimester placental villi, CCR‐1, 2, 4 and CXCR‐1, 2, 4 in 2nd trimester placental villi, CCR‐1, 2, 4 and CXCR‐4 in 3rd trimester placental villi. Using MACS enriched trophoblasts, we observed identical results. A choriocarcinoma cell line BeWo expressed CCR‐1, 3, 4 and CXCR‐1, 2, 4 while JEG‐3 and JAR expressed CCR‐1, 3, 4, 5 and CXCR‐1, 2, 4. Expression of the CCR‐5 and CXCR‐4 protein in choriocarcinoma cell lines and MACS‐enriched trophoblats were confirmed by flow cytometry. Chemokine MCP‐3, MIP‐1α, RANTES mRNA were expressed by the 1st, 2nd and 3rd trimester placental samples and the three choriocarcinoma cell lines examined. MCP‐1 was expressed by 1st and 2nd trimester placental villi. Administration of chemokines up‐regulated proliferation (10−1–10 ng/mL) and hCG production (10−1–10−2ng/mL) of the three choriocarcinoma cell lines examined.
 CONCLUSIONS: Our results suggest possible roles of chemokines/chemokine receptors on placental physiology and their involvement in HIV transmission as alternative receptors.

Changes of expression of glucose transporters in the fetal lamb brain after MCI-186 administration to the maternal circulation with 10-min persistent umbilical cord occlusion.

Objective. To evaluate the effect of MCI-186 (3-methyl-1-phenyl-2-pyrazoline-5-one), a potent hydroxyl radical scavenger, administered to the maternal circulation following umbilical cord occlusion in regard to glucose transporter (GLUT) expression. Materials and methods. Fourteen instrumented lambs were prepared. In three cases, a 10-min persistent umbilical cord occlusion was performed; 30 min after the insult, fetal brains were extirpated (Group A). Four cases had a 10-min occlusion (Group B) and four cases had 10-min occlusion and were administered MCI-186 to the maternal circulation (Group C). Three days following the insult, the fetal brains were extirpated. The remaining three cases had a sham operation (Group D). Brain tissue sections were stained at the locations of GLUT-1, -3 and -5 and were evaluated by two pathologists. Results. The expression of GLUT-1 and -3 significantly increased in the basal ganglia, hippocampi and periventricular region of Group B when compared with that of Group A. The expression of GLUT-1 and -3 in three regions of Group B were significantly higher than that of Group C and D. GLUT-5 was recognised only in Group B. Conclusion. On the basis of expression of GLUT, the protective effect of MCI-186 on brain injury resulting from hypoxia/ischemia-reperfusion is documented.

The Production of Hydroxyl Radicals in the Fetal Lamb Brain Resulting from Occlusion of the Umbilical Circulation and the Transplacental Effect of MCI-186 to Inhibit Hydroxyl Radical Production

The present study evaluated hydroxyl radical production in fetal lamb brain during and after umbilical cord occlusion and examined the effects of injecting MCI-186 (3-metyl-1-phenyl-2-pyrazolin-5-one; Edaravone), a hydroxyl radical scavenger, into the maternal circulation. In 11 chronically instrumented lambs, intermittent total umbilical cord occlusions 1 min out of every 3 min for 1 h and 10-min persistent total umbilical cord occlusion were performed with brain microdialysis using 5 mM of sodium salicylate. In the remaining four lambs, 60 mg of MCI-186 was administered into the maternal circulation from shortly before the end of 10-min persistent total umbilical cord occlusion. Concentrations of 2,3-dihydroxy-benzoic acid (2,3-DHBA), produced by hydroxyl radical reactions with sodium salicylate, were measured in perfusate by HPLC. Concentration of 2,3-DHBA in perfusate was 23.05 ± 10.95 nM before umbilical cord occlusion. Levels of 2,3-DHBA tended to increase slightly during and after intermittent umbilical cord occlusion, and were significantly increased by the end of 10-min occlusion (40.06 ± 21.36 nM) and after occlusion (93.74 ± 29.17 nM). Infusion of MCI-186 suppressed 2,3-DHBA concentration to 29.35 ± 14.95 nM after occlusion. Administration of MCI-186 into the maternal circulation reduces hydroxyl radical production induced by umbilical cord occlusion in the fetal lamb brain.

MCI-186 administered to the maternal circulation inhibits fetal brain injury resulting from total umbilical cord occlusion in the chronically instrumented fetal lamb

Objective. To evaluate the transplacental effects of MCI-186 (edaravone), a potent hydroxyl radical scavenger, administered to the maternal circulation to inhibit fetal brain injury caused by umbilical cord occlusion. Methods. Nine chronically instrumented lambs were prepared. In three cases, 10-min persistent total umbilical cord occlusion (group A) was performed. Another three cases underwent occlusion and were administered 60 mg of MCI-186 through the maternal femoral vein prior to the end of occlusion (group B). The remaining three cases underwent sham operation (group C). On day 3 after insult, fetal brains were extirpated. Paraffin-embedded brain tissue sections were stained with hematoxylin and eosin, Bodian, Kluver–Barrera, and TUNEL. Neuronal cellular damage was evaluated by two pathologists blinded to the experimental conditions. Results. Group A displayed numerous cells with eosinophilic condensation of nuclear chromatin and proliferation of microglia in the hippocampus and basal ganglia. TUNEL-positive cells were observed in the periventricular area. Group B showed microglial proliferations, but no marked changes. No pathological changes were apparent in group C. Conclusions. MCI-186 administered to the maternal circulation could inhibit fetal brain injury resulting from hypoxia-reperfusion induced by umbilical cord occlusion.

A Novel Treatment for Cervical and Cesarean Section Scar Pregnancies by Transvaginal Injection of Absolute Ethanol to Trophoblasts: Efficacy in 19 Cases

STUDY OBJECTIVE To evaluate the efficacy of a nonsurgical treatment for cervical pregnancy (CP) and cesarean section scar pregnancy (CSP). DESIGN Retrospective clinical study (Canadian Task Force classification III). SETTING Private assisted reproductive technology practice. PATIENTS Nineteen women with CP (n = 16) or CSP (n = 3), including 6 patients with positive fetal heartbeat. INTERVENTION Transvaginal local injection of absolute ethanol (AE) into the hyperechoic ring (lacunar space) around the gestational sac under ultrasound guidance. MEASUREMENTS AND MAIN RESULTS Serum beta-human chorionic gonadotropin (β-hCG) was measured at frequent intervals, and ultrasound and/or magnetic resonance imaging was used to observe the gestational sac. In 9 patients, the serum β-hCG level was effectively reduced with a single AE injection at 2 hours. In the remaining 10 patients, the level decreased but then increased in 4 and slowly decreased in the other 6; all of these 10 patients required 2 to 5 repeat AE injections. In all patients, serum β-hCG level was reduced by 50% within 3 days and decreased to <10% of the initial level within 14 days. In 18 patients (95%), the level was decreased to 1.0 mIU/mL within 40 days. Seven patients were treated on an outpatient basis. Twelve patients received no anesthesia. Five patients subsequently became pregnant, and each had a live birth. There was no recurrent CP or CSP. The procedure was successful in all 19 patients. CONCLUSION This procedure is an effective treatment for CP or CSP that could be used in place of conventional surgical interventions and medical treatment using MTX.