Characterization of Urate Transport System in JAR and JEG-3 Cells, Human Trophoblast-derived Cell Lines

Urate (uric acid) is the major inert end product of purine metabolism in humans. Since it is water soluble, it requires a membranous protein called transporter for its permeation across the plasma membrane. Increased blood urate level is often seen in preeclampsia, but its precise mechanism remains unknown. Syncytiotrophoblasts function as a barrier between maternal blood and fetal one so called “blood-placental barrier”. So far, the expression of several urate transporters was identified in these cells, but it is still unclear about their contribution to urate handling in blood-placental barrier. In this study, we investigated the expression of urate transporters and the properties of ［14C］urate transport in both JAR and JEG-3, human choriocarcinoma cells as a model of human placenta. Conventional PCR analysis revealed that both JAR and JEG-3 cells express strongly breast cancer resistance protein (BCRP/ABCG2) mRNA. Uptake of ［14C］urate by these cells is time-dependent with Na＋- and Cl－-independent and voltage-insensitive manner and is not inhibited by benzbromarone, a representative renal urate transport inhibitor. Then, we focused on BCRP which shows strong mRNA expression and found that these cells have urate efflux property that is sensitive to fumitremorgin C (FMC), a BCRP inhibitor. These results suggest that BCRP is one of the important components for urate handling in human placenta in pathophysiological condition such as preeclampsia

Retrorectal epidermoid cyst with unusually elevated serum SCC level, initially diagnosed as an ovarian tumor

Retrorectal epidermoid cyst is one of the developmental cysts which arise from remnants of embryonic tissues. We report a rare case of retrorectal epidermoid cyst, initially diagnosed as an ovarian tumor. Serum SCC value as tumor marker was elevated to the high level. Laparoscopy revealed ovaries, uterus and other pelvic organs were all normal. This tumor existed in the retroperitoneal cavity and compressed the rectum. Later, complete tumor resection was performed by laparotomy. Histological study revealed the epithelium of this tumor consisted of only squamous cells without atypia, and the diagnosis of this tumor was retrorectal epidermoid cyst. Retrorectal epidermoid cyst is very rare, and difficult to diagnose before surgery. However, if we have-knowledge of developmental cysts, and by careful digital examination and image diagnosis, a differential diagnosis can be made

Efficacy and Complications of Emergent Transcatheter Arterial Embolization for the Management of Intractable Uterine Bleeding

Objective：Transcatheter arterial embolization（TAE）, including uterine artery embolization（UAE）, is effective for the management of obstetric and gynecologic hemorrhage. Some adverse effects have been reported with TAE, such as amenorrhea, endometrial trauma, and subsequent infertility. Herein we report the efficacy and complications of emergent TAE for the management of severe intractable uterine bleeding at our institute.Methods：From 2010 to 2019, thirty-eight patients underwent emergent TAE for intractable uterine bleeding. We evaluated the efficacy and complications of TAE, including a change in menstruation, fertility, and pregnancy outcomes in perinatal patients（group A；n＝23）, and in patients with gynecologic hemorrhage（group B；n＝15）.Results：In group A, 7 cases of retained placenta, 4 cases of postpartum hemorrhage, 2 cases of placenta accrete, 2 cases of uterine artery pseudoaneurysm, 2 cases of cervical pregnancy, 1 case of cesarean scar pregnancy, and 5 cases of unexplained hemorrhage were included. The median age of the group A was 37. In group B, 4 cases of uterine artery pseudoaneurysm, 2 cases of uterine arteriovenous malformation, 3 cases of uterine fibroids, 1case of adenomyosis, and 5 cases of unexplained hemorrhage were included. The median age of the group B was 39. The first attempt at TAE successfully controlled hemorrhage in 33 of 38 patients （86.8％）without major complications, and the remaining 5 patients required an additional attempt at TAE to control hemorrhage. One patient（2.6％）had transient buttock pain and foot ischemia. Among the 33 patients who had adequate follow-up care, all patients resumed regular menstruation. The median time to resume regular menstruation after TAE was 3 months （range, 1-13 months）in group A（n＝20）and 1 month（range, 1-6 months）in group B（n＝13）. Four of patients had 6 pregnancies in total：3 full-term live births, 2 missed abortions, and 1 artificial abortion. Among the 13 patients who desired pregnancy, 3（23％）conceived spontaneously.Conclusions：This retrospective study showed that emergent TAE may be effective and safe in treating intractable uterine bleeding with a high success rate. Ovarian and endometrial function were preserved based on the relatively early return of menstruation. Further prospective investigations with large number of patients are needed to confirm the preservation of ovarian function, fertility, and pregnancy outcome in reproductive-aged women

Clinical Evaluation of Breech Deliveries Over a Fifteen-Year Period at a Hospital in Ota, Japan

Objective : To examine the characteristics and perinatal outcome of pregnancies with breech presentation. Methods : Breech deliveries were divided into four groups : primipara vaginal delivery group (PV-multipara vaginal delivery group (MV-G), planned cesarean section group (PC-G), and emergency cesarean section group (EC-G). The maternal age, gestational week, neonatal birth weight, and Apgar score were compared.Results : There were no significant differences in maternal age, gestational week as well as neonatal birth weight among the four groups. An Apgar score at 1 minute of less than 6 points was seen in 0%, 11.1%, 15.3%, and 20% of the PC, MV, PV and EC-Gs, respectively. (PV-G and PC-G were compared to obtain p < 0.05) Although, no neonate in this study had an Apgar score at 5 minutes of less than 6 points.Conclusion : There was no significant difference of perinatal outcome between vaginal delivery and cesarean section for breech presentation at term

TISSUE POLYPEPTIDE SPECIFIC ANTIGEN (TPS) AS A TUMOR MARKER FOR GYNECOLOGIC MALIGNANCIES : A COMPARATIVE STUDY WITH TISSUE POLYPEPTIDE ANTIGEN (TPA), CANCER ANTIGEN 125 (CA125) AND SQUAMOUS CELL CARCINOMA-ASSOCIATED ANTIGEN (SCC)

1957年共同研究者により各種腫瘍組織混合抽出液より精製されたtissue polypeptide antigen (TPA)はその後cytokeratins 8, 18, 19との交差反応が見られ,一種の細胞構築蛋白であることが判明している。最近Bjurk・lundはTPAをマウスに免疫しcytokeratinと交差しない単クローン抗体M3を得た。同抗体を使用して組み立てられたimmunoradiometrical assay (IRMA)を用いてspecific TPA (TPS)を各種婦人科癌患者血清にて測定し,従来のTPA, cancer antigen 125 (CA 125)およびsquamous cell carcinoma-associated antigen (SCC)と比較し,その臨床的有用性と限界を検討した。A new immunoradiometrical assay (IRMA) for a tissue polypeptide specific antigen (TPS) has recently been established using a monoclonal antibody (M 3) against purified tissue polypeptide antigen (TPA). With the use of this IRMA, we measured serum TPS levels in 68 patients with benign gynecologic diseases and in 71 patients with gynecologic malignancies before treatment. Eleven gynecological cancer patients who showed the positivity for TPS before the treatment were followed up by monitoring the serum TPS levels. Tissue polypeptide antigen (TPA), cancer antigen 125 (CA 125) or squamous cell carcinoma-associated antigen (SCC) were also measured in these patients. The present study first described the clinical usefulness and weakness of TPS as a tumor marker for gynecologic malignancies by making a comparison with TPA, CA 125 or SCC

Conventional IVF デノ long protocol ニオケル hCG トウヨビ ノ ケッチュウ progesterone チ ト ニンシン セイセキ ニ ツイテ

Long protocol(L)下でのconventional IVF(cIVF)において,hCG 切り替え日の血中progesterone(P)値とcIVF における種々の因子及び妊娠成績との関係について検討した.不妊外来を受診した患者で,L 下でcIVF を施行された486 例,706 周期を対象とした.hCG 切り替え日の血中P 値と血中estradiol(E2)値,総hMG 投与量,採卵数,正常受精(2PN)発生数,2PN 発生率,良好胚(G1)胚数,G1 胚発生率,子宮内膜厚(EM),leaf pattern の有無,妊娠率等との関係について検討した.P 値とE2 値,採卵数,2PN 発生数,G1胚数との間には,有意な正の相関関係が認められた(P<0.01).2PN 発生率との間には有意な負の相関関係が認められた(P<0.01).子宮内膜におけるleaf patternの有無を見ると,leaf( +)の群ではleaf( &#8722;)の群に比べ有意にP 値が低かった(P<0.01).また,P 値レベル別での妊娠率,多胎率,流産率の比較では,P 値2.1&#8722;2.5 ng/ml で妊娠率が有意に高かった(P<0.05).P 値レベルは,E2 値,採卵数,2PN 発生数およびG1 胚発生数と相関している.これらのことから,P 値レベルは卵胞成熟および卵のquality を示す一つのシグナルとなり得ることが明らかになった.一方,P 値レベルが子宮内膜の肥厚や妊娠率に影響していないことも判明した.Objectives:The aim of this study was to evaluate thecorrelation between serum progesterone (P) levels on theday of hCG administration and various factors includingpregnancy outcome in a conventional IVF( cIVF) long protocolstimulation.Material and methods:Seven hundred six IVF cyclesusing a long protocol with GnRH agonist and hMG involving486 patients were studied. This study retrospectivelyevaluated the correlation of serum P levels on the day ofhCG administration with serum estradiol (E2) levels, totaldose of hMG, number of oocytes retrieved, number of normalfertilized oocytes, normal fertilized oocytes rate, numbersof high quality oocytes (G1), G1 rate, endometrialthickness, presence of endometrial leaf pattern and pregnancyoutcome in cIVF.Results:A significant positive correlation was observedbetween serum P levels on the day of hCG administrationand serum E2 levels, number of oocytes retrieved, numberof normal fertilized oocytes and numbers of G1,( p<0.01).A significant negative association was observed betweenserum P levels on the day of hCG administration and normalfertilized oocytes rate( p<0.01).Serum P levels on the day of hCG administration of theleaf( +) group( presence of endometrial leaf pattern) wassignificantly low in comparison with that of the leaf (&#8722;)group( p<0.01).Among the six groups, the pregnancy ratein P levels from 2.1 to 2.5 ng/ml was significantly high incomparison with others.Conclusion:A significant positive correlation was observedbetween serum P levels on the day of hCG administrationand E2 levels, number of oocytes retrieved, numberof normal fertilized oocytes and numbers of G1. Among thesix groups, the pregnancy rate in P levels from 2.1 to 2.5ng/ml was significantly high in comparison with others. Accordingto two above-mentioned results, we conclude thatan appropriate P levels is important for oocyte maturation

シキュウガン

子宮癌は頸癌と体癌よりなる.近年頸癌はヒトパピローマウイルス(HPV)が,発癌の要因であることがほぼ確立された.上皮内癌を含めた罹患率は20代で大幅な伸びを示し,性活動の活発化にともなうHPV感染の関与とされ,検診の実施年齢も20歳以上に引き下げられた.欧米では予防ワクチンの大規模臨床試験が進行中である.進行癌でも米国臨床試験の報告から,化学療法併用放射線治療がほぼ標準治療になって来ている.体癌は罹患率が約3倍に増加している.これは高齢者の増加,ライフスタイルの変化による.体癌の治療は手術以外の治療に確立されたものはない,補助療法は欧米では放射線治療,本邦では化学療法が一般的である.まだ中間解析の報告ではあるが,進行癌での比較試験では,化学療法群が無病生存率,最終生存率いずれにおいても化学療法の優位が報告された.現在,頸癌,体癌とも日本婦人科腫瘍学会が治療ガイドラインを作成中であるが,国内での臨床研究のさらなる基盤整備が必要である.Uterine carcinoma is cervical and endometrial cancer. Recently, epidemiologic studies demonstrate that the major risk factor for development of cervical cancer is HPV infection. Incident rate of cervical cancer has been increasing in twenties. Ministry of health, labour and welfare recommend that official cancer screening tests starts more than twenty. In Europe and America, Randomized phase III control trials of prophylactic vaccine therapy for preventing HPV is doing. Based on clinical trials, concurrent cisplatin-based chemotherapy with radiation has been standard treatment of patient with advanced cervical cancer. Endometrial cancer is increased in change of our Japanese life stile. Operation is only established therapy in patient with endometrial cancer Adjuvant radiation therapy is standard treatment in US. Nevertheless, adjuvant chemotherapy is standard in Japan. A randomized phase III study comparing radiation therapy versus chemotherapy in patient with advanced endometrial cancer is now going. In Preliminary data of this trial, chemotherapy was higher progression free and all over survival rate than radiation therapy. After all, we should be made the guidelines for cervical and endometrial cancer as soon as possible. Thus, we need improvement of the system for clinical trials

TT ウイルス ボシ カンセン ノ コウホウシテキ, ゼンホウシテキ ケンキュウ : トクニ ボシ カンセン ヨウシキ ト シュウサンキ ニオケル リンショウテキ イギ ニツイテ

近年同定され,輸血後肝炎との関連が示唆されているTTV について,その母子感染の自然史と周産期における臨床的意義について後方視的,前方視的に検討した.HBV 及びHCV が検出されない妊婦(前方視的研究;NBCPW 群)におけるTTV DNA 陽性率は19.0%(37/195)であり,このうちsAST/sALT 値が110 U/L を超える例は皆無であった.HBV あるいはHCV キャリア妊婦(後方視的研究;BCCPW 群)ではTTV DNA 陽性率は25.0%(21/84)である.このうちsAST/sALT 値が110U/L を超える例は23.8%(5/21)に達し,この5 例はTTV 単独キャリアではなく,HBV 又はHCV との重複キャリアであった.NBCPW 群の出生児(14 名)におけるTTV DNA 陽転率は57.1%であり,このうちsAST/sALT 値が110 U/L を超えた例は無かった.BCCPW 群の出生児(21 名)におけるTTV DNA 陽転率は42.9%であり,このうちsAST/sALT 値が110 U/L を超えた児は2 名(22.2%)で,この2 名はHCV キャリアでもあった.TTV DNA 陽転化した総数17 名の出生児は全員生後18 ヶ月時点までTTV DNA 陽性が持続しており,脱キャリア化は認められていない.また,キャリア化児におけるTTV DNA 出現時期および哺育方法より経胎盤感染,経産道感染および経唾液感染は否定的であり,経母乳感染の可能性が強く示唆される結果であった.また,キャリア妊婦及びキャリア化児における肝機能異常は母子共々TTV 単独キャリアでは認められず,TTV 感染の周産期における臨床的インパクトは低いと思われる.The natural history of mother-to-child transmission(MTCT) of the TT virus (TTV) was investigated retroandprospectively.Serum TTV DNA was detected in 37 out of the 195( 19.0%) pregnant women without both HBV and HCV in theirsera (NBCPW) and 21 out of the 84 (25.0 %) pregnantwomen with HBV and/or HCV (BCCPW). In the lattergroup, 5 out of the 21( 23.8%) TTV carrier pregnant womenshowed repeatedly sAST and/or sALT levels over110U/L, but none of the former group did.With informed consent (IC), 14 (NBCPW) and 21 (BCCPW)infants were followed from birth up to 18 months ofage by receiving tests for serum TTV DNA and levels ofsAST and sALT. Eight out of the 14 infants (57.1 %, NBCPW)and 9 out of the 21 infants( 42.9%, BCCPW) developedTTV carrier-state, and all of these 17 carrier infantsmaintained serum TTV DNA-positive through the followupperiods. No infants (NBCPW) showed elevated serumlevels (>110 U/L) of AST or ALT during the follow-upperiods, but 2 out of the 9 infants( 22.2%, BCCPW) showedsAST or sALT levels higher than 110 U/L, and these 2 infantswere found to be in HCV carrier-state.None of the infants developed a TTV-positive resultwithin 1 month after birth, and thereafter 11.8 % (2/17)developed carrier-state in 3 months, 47.1 % in 6 months,82.4 % in 12 months. These findings may exclude the intrauterineor trans-vaginal infection as a mode of TTVMTCT. On the other hand, all carrier infants with one exceptionwere raised by breast feeding, which was rich inTTV. Both carrier pregnant women and children, who wereneither HBV nor HCV carriers, showed no abnormal liverfunction through the follow-up periods.Thus, we conclude that TTV MTCT occurs highly, but itis not so significant practically

シュウサンキ リョウイキ ニオケル Gガタ カンエン ウイルス ノ リンショウテキ イギ : オナジ フラビ ウイルス カ ニ ゾクスル Cガタ カンエン ウイルス ト ヒカク シテ

HBV, HCV 同様血清肝炎を惹起する可能性を示唆されているHGV の(1)妊婦における検出率,(2)母子感染の自然史,そのリスクファクター及びキャリア化児の予後,(3)キャリア妊婦及びキャリア化児における肝機能を前方視的に調査し,同ウイルスの周産期における臨床的意義を同じフラビウイルス科に属するHCV と比較検討した.対象は1996&#12316;2004 年に当科を受診した妊婦3,738 名(HGV),4,023 名(HCV)とキャリア妊婦の出生児14 名(HGV),24 名(HCV)である.HGV RNA は RT-PCR 法(定性)k,real-time PCR(定量)及びcycle-sequence 法(genome sequence)により,HGV-E2 抗体はELISA 法を用いて,またHCV RNA はnested RT-PCR(定性),real- time PCR(定量)により,またHCV-Ab は2nd 及び3rd generation EIA を用いて測定した.対象児の血清サンプルは臍帯血から最長119 ヶ月まで定期的に検査に供された.妊婦におけるHGV RNA, HCV RNA の検出率は各々0.64%(24/3,738),0.60%(24/4,023)であり両者に有意差を認めなかった(p=0.7984).HGV-E2 抗体の検出率は4.4%(82/1,858)であり,HGV RNA とHGV-E2 抗体は相互排他的であった.HGV RNA 単独陽性妊婦で肝機能異常は見られなかった.出生児におけるHGV RNA,HCV RNA 陽性はそれぞれ64.3%(10/16),12.5%(3/24)に認められ,両ウイルス陽性児とも経膣分娩症例であり,キャリア妊婦のviral loads はそれぞれ107 及び105 copies/ml 以上の症例であった.HGV 母子感染と推測された4 組の母子ペア血清を用いたHGV RNA シークエンス相同性の検討では各母子間で100%の一致率が得られ,HGV 母子感染の直接的証拠が得られた.キャリア化した9 名の児のうち1名が肝機能異常(sALT 値>110 U/L)を呈したが,これはHCV との重複感染例であった.フォローアップ中にHCV では約16.7%がキャリア化後3 年以内に脱キャリア化したが,HGV キャリア児ではRNA 陰性化は少なくとも最長約10 年間のフォローアップ期間中には皆無であった.妊婦のHGV 及びHCV 保有率(キャリア率)はほぼ同等であり,一方母子感染率は前者が後者の約5.1 倍に達し,母子感染がHGV キャリアの主たる供給源であることが示唆された.HGV およびHCV 母子感染では,キャリア妊婦の血中viral loads 及び経膣分娩がリスクファクターであることが示された.さらに,同じフラビウイルス科に属しながら,HGV はHCV とは異なり,肝傷害性が殆ど無いことが判明した.The epidemiology and natural history of mother-to-childtransmission( MTCT) of hepatitis G virus( HGV) were investigatedto evaluate potential clinical significance of HGVin perinatal periods. The data was discussed by comparisonwith those of a well-known flavivirus, hepatitis C virus(HCV).During the periods from 1996 to 2006, 3,738 pregnantwomen received screening tests for HGV RNA and 4,023pregnant women received screening tests for HCV Antibodies(Ab). HGV RNA-positive pregnant women weretested for HGV-E2 Ab and HCV Ab-positive pregnantwomen were tested for HCV RNA. HGV- and HCV RNApositivewomen underwent the measurement of viral loadswith use of real-time PCR. With informed consent, 14 infantsborn to HGV carrier mothers and 24 infants born toHCV carrier mothers were followed from birth to 19months of age by receiving the measurement of serumHGV- or HCV RNA and sAST/sALT levels.HGV RNA was detected in 0.64 % (24/3,738) of thewomen tested and HCV RNA was detected in 0.60 %(24/4,023) of the women tested. HGV-E2 Ab was detectedin 4.4 % and mutually exclusive with HGV RNA. Nine ofthe 14 infants born to HGV carrier mothers( 64.3%) and 3of 24 infants born to HCV carrier mothers (12.5 %) developedHGV and HCV carrier-states respectively. The homologyof HGV RNA sequences was perfectly identical betweenthe 4 paired sera of mother-child.Both of vaginal delivery mode and maternal viral loads atdelivery (HGV>107, HCV>105 copies/ml) were suggestedas one of risk factors for MTCT. The elevation of sAST/sALT levels (>110 U/L) in the HGV and HCV carrier infantswere 7.1%( 1/9) and 66.7%(2/3) respectively. However,one HGV carrier infant with elevated sAST/sALTlevels was found to be a HCV carrier.We conclude that HGV MTCT occurs very frequently,but HGV is not so significant in perinatal periods comparedwith another flavivirus, HCV