研究者詳細 - 真里谷　奨

論文 - 真里谷　奨

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The age-related required number of zygotes estimated from prior clinical studies of preimplantation genetic testing for aneuploidy (PGT-A).

Tasuku Mariya, Takeshi Sugimoto, Takema Kato, Toshiaki Endo, Hiroki Kurahashi

Systems biology in reproductive medicine 69 ( 1 ) 1 - 7 2023年01月 [国際誌]

Women who are undergoing preimplantation genetic testing for aneuploidy (PGT-A) often wish to know how many eggs will be required to optimize the chances of a live birth. However, no precise data on this can yet be provided during genetic counseling for this procedure. On the basis of PGT-A data from related studies and current databases, we have estimated that the number of zygotes required for a 50% chance of a live birth is 8 at age 40 but increases markedly to 21 at age 43. PGT-A markedly reduces the miscarriage rate per embryo transfer but does not alleviate the extremely high number of zygotes required for a live birth in women of an advanced maternal age. Detailed genetic counseling will therefore be desirable prior to undergoing this procedure.

DOI PubMed

Letrozole increases preantral follicle growth and decreases estradiol production without impairing follicle survival.

Fukiko Kasuga-Yamashita, Tsuyoshi Baba, Sachiko Nagao, Yuya Fujibe, Miyuki Morishita, Yoshika Kuno, Tasuku Mariya, Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Tsuyoshi Saito

Journal of ovarian research 15 ( 1 ) 136 - 136 2022年12月 [国際誌]

BACKGROUND: Letrozole has been reported to be effective in treating anovulation, preventing ovarian hyperstimulation syndrome (OHSS), and retrieving oocytes in breast cancer patients. However, the role and mechanism of letrozole in follicular development remain unclear. RESULTS: We treated mouse preantral follicles with various treatments; we found no significant difference in follicle survival rates in the letrozole (LET) group compared with the control group, but the average diameter of follicles in the LET group tended to be larger (CTRL vs. LET 30, p = 0.064; CTRL vs. LET 100, p = 0.025). The estradiol concentrations in culture media of the LET group were significantly lower than those observed in the control group (CTRL vs. LET 30, p = 0.038; CTRL vs. LET 100, p = 0.025). We further found a marked increase in follicle-stimulating hormone receptor (FSHR) gene expression in response to letrozole treatment (CTRL vs. LET 30, p = 0.075; CTRL vs. LET 100, p = 0.034). This result suggested that increased FSHR expression promotes follicle development. Letrozole inhibited aromatase activity, but the effect was limited. Letrozole did not significantly reduce vascular endothelial growth factor (VEGF) gene expression. CONCLUSIONS: Letrozole may promote follicle development by increasing the expression of FSHR. Letrozole may be useful for fertility preservation of patients with estrogen-dependent cancers such as breast cancer and various other cancers. Whether letrozole has a direct effect in reducing OHSS requires further investigation.

DOI PubMed

Maple syrup urine disease due to a paracentric inversion of chr 19 that disrupts BCKDHA: A case report.

Katsuyuki Yokoi, Yoko Nakajima, Yuta Sudo, Tasuku Mariya, Rie Kawamura, Makiko Tsutsumi, Hidehito Inagaki, Tetsushi Yoshikawa, Tetsuya Ito, Hiroki Kurahashi

JIMD reports 63 ( 6 ) 575 - 580 2022年11月 [国際誌]

Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder of branched-chain amino acid metabolism caused by mutations in BCKDHA, BCKDHB, and DBT that encode the E1α, E1β, and E2 subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Various MSUD-causing variants have been described; however, no structural rearrangements in BCKDHA have been reported to cause the classic MSUD phenotype. Here, we describe the classic patient with MSUD with compound heterozygous pathogenic variants in BCKDHA: a missense variant (NM_000709.3:c.757G > A, NP_000700.1:p.Ala253Thr) and a paracentric inversion disrupting Intron 1 of BCKDHA, which was identified by whole-genome sequencing and validated by fluorescence in situ hybridization. Using the sequence information of the breakpoint junction, we gained mechanistic insight into the development of this structural rearrangement. Furthermore, the establishment of junction-specific polymerase chain reaction could facilitate identification of the variant in case carrier or future prenatal/preimplantation tests are necessary.

DOI PubMed

Target enrichment long-read sequencing with adaptive sampling can determine the structure of the small supernumerary marker chromosomes.

Tasuku Mariya, Takema Kato, Takeshi Sugimoto, Syunsuke Miyai, Hidehito Inagaki, Tamae Ohye, Eiji Sugihara, Yukako Muramatsu, Seiji Mizuno, Hiroki Kurahashi

Journal of human genetics 67 ( 6 ) 363 - 368 2022年01月 [国際誌]

Structural analysis of small supernumerary marker chromosomes (sSMCs) has revealed that many have complex structures. Structural analysis of sSMCs by whole genome sequencing using short-read sequencers is challenging however because most present with a low level of mosaicism and consist of a small region of the involved chromosome. In this present study, we applied adaptive sampling using nanopore long-read sequencing technology to enrich the target region and thereby attempted to determine the structure of two sSMCs with complex structural rearrangements previously revealed by cytogenetic microarray. In adaptive sampling, simple specification of the target region in the FASTA file enables to identify whether or not the sequencing DNA is included in the target, thus promoting efficient long-read sequencing. To evaluate the target enrichment efficiency, we performed conventional pair-end short-read sequencing in parallel. Sequencing with adaptive sampling achieved a target enrichment at about a 11.0- to 11.5-fold higher coverage rate than conventional pair-end sequencing. This enabled us to quickly identify all breakpoint junctions and determine the exact sSMC structure as a ring chromosome. In addition to the microhomology and microinsertion at the junctions, we identified inverted repeat structure in both sSMCs, suggesting the common generation mechanism involving replication impairment. Adaptive sampling is thus an easy and beneficial method of determining the structures of complex chromosomal rearrangements.

DOI PubMed

Twin pregnancy with untyped Ehlers-Danlos syndrome requiring prompt genetic testing: A case report.

Shiori Ogawa, Tasuku Mariya, Yuya Fujibe, Marie Ogawa, Keiko Ikeda, Miyako Mizukami, Yoshika Kuno, Aki Ishikawa, Shinichi Ishioka, Akihiro Sakurai, Tsuyoshi Saito

Case reports in women's health 33 e00384 2022年01月 [国際誌]

Ehlers-Danlos syndrome is a rare genetic disorder that presents with a variety of pathologies depending on the disease type. Among them, vascular Ehlers-Danlos syndrome requires extremely careful management as there have been many reports of fatal perinatal complications such as uterine rupture. Although hypermobile Ehlers-Danlos syndrome is less likely to cause fatal complications, symptoms such as arthralgia, hip dislocation, and depression may be seen throughout pregnancy. We report here a case of twin pregnancy in which Ehlers-Danlos syndrome was first suspected at 19 weeks of gestation. Vascular Ehlers-Danlos syndrome could not be ruled out based on family medical history, making it difficult to determine the perinatal management strategy. Prompt genetic testing did however rule out the vascular type and the patient was diagnosed with hypermobile Ehlers-Danlos syndrome from the clinical symptoms, enabling us to manage the pregnancy safely until 34 weeks of gestation.

DOI PubMed

Radical Vaginal Trachelectomy.

Tsuyoshi Saito, Motoki Matsuura, Masato Tamate, Masahiro Iwasaki, Tasuku Mariya

Surgery journal (New York, N.Y.) 7 ( Suppl 2 ) S103-S107 2021年12月 [国際誌]

Recently, radical vaginal hysterectomy (RVH) has developed into laparoscopically assisted radical vaginal hysterectomy (LARVH), which is associated with the laparoscopical procedure, and it is applied as radical vaginal trachelectomy and semi-radical vaginal hysterectomy. LARVH is indicated for patients with stage IB1 and IIA1 cervical carcinoma, especially those with a tumor size of less than 2 cm, because the cardinal ligaments cannot be resected widely. Although RVH that is associated with laparoscopic pelvic lymphadenectomy is the most used surgical procedure, radical trachelectomy may be performed either abdominally or vaginally (laparoscopic or robotic). One report found that the pregnancy rate was higher in patients who underwent minimally invasive or radical vaginal trachelectomy than in those who underwent radical abdominal trachelectomy.

DOI PubMed

A screening assistance system for cervical cytology of squamous cell atypia based on a two-step combined CNN algorithm with label smoothing.

Yuta Nambu, Tasuku Mariya, Shota Shinkai, Mina Umemoto, Hiroko Asanuma, Ikuma Sato, Yoshihiko Hirohashi, Toshihiko Torigoe, Yuichi Fujino, Tsuyoshi Saito

Cancer medicine 11 ( 2 ) 520 - 529 2021年11月 [国際誌]

BACKGROUND: Although many cervical cytology diagnostic support systems have been developed, it is challenging to classify overlapping cell clusters with a variety of patterns in the same way that humans do. In this study, we developed a fast and accurate system for the detection and classification of atypical cell clusters by using a two-step algorithm based on two different deep learning algorithms. METHODS: We created 919 cell images from liquid-based cervical cytological samples collected at Sapporo Medical University and annotated them based on the Bethesda system as a dataset for machine learning. Most of the images captured overlapping and crowded cells, and images were oversampled by digital processing. The detection system consists of two steps: (1) detection of atypical cells using You Only Look Once v4 (YOLOv4) and (2) classification of the detected cells using ResNeSt. A label smoothing algorithm was used for the dataset in the second classification step. This method annotates multiple correct classes from a single cell image with a smooth probability distribution. RESULTS: The first step, cell detection by YOLOv4, was able to detect all atypical cells above ASC-US without any observed false negatives. The detected cell images were then analyzed in the second step, cell classification by the ResNeSt algorithm, which exhibited average accuracy and F-measure values of 90.5% and 70.5%, respectively. The oversampling of the training image and label smoothing algorithm contributed to the improvement of the system's accuracy. CONCLUSION: This system combines two deep learning algorithms to enable accurate detection and classification of cell clusters based on the Bethesda system, which has been difficult to achieve in the past. We will conduct further research and development of this system as a platform for augmented reality microscopes for cytological diagnosis.

DOI PubMed

Next-generation sequencing of 16S rRNA for identification of invasive bacterial pathogens in a formalin-fixed paraffin-embedded placental specimen: a case report of perinatal fulminant Streptococcus pyogenes infection.

Tasuku Mariya, Toyotaka Sato, Yuya Fujibe, Manami Ishido, Hiroshi Shimada, Terufumi Kubo, Yoko Nagai, Wataru Arai, Suguru E Tanaka, Kyota Ashikawa, Yoshiyuki Sakuraba, Shinichi Ishioka, Shin-Ichi Yokota, Tsuyoshi Saito

Medical molecular morphology 54 ( 4 ) 374 - 379 2021年07月 [国内誌]

Intrauterine infection is one of the most important causes of maternal death. In perinatal emergency, we often miss an opportunity to obtain culture specimens. In this study, we tried to examine whether we investigated whether bacteria causing infection can be detected from a formalin-fixed paraffin-embedded (FFPE) placental specimen. We examined the placenta from a maternal invasive infection that resulted in infectious abortion at 18 weeks of gestation. The case was diagnosed by acute fever and abdominal pain, and the patient was cured after 3 weeks of intensive antimicrobial treatment. Four Streptococcus pyogenes strains were isolated from vaginal fluid and blood cultures of the patient. All of the strain types were emm1/ST28. We amplified the V1-V2 region of 16S rRNA from an FFPE placental specimen and sequencing was performed using a next-generation sequencer (NGS). Taxonomic analysis was then performed for sequenced data. We succeeded in detecting causative pathogens from the FFPE placenta: 69.1% of the predominantly identified bacteria were S. pyogenes and other small populations of bacteria were detected. Our results revealed the utility of NGS for 16S rRNA analysis of an FFPE placenta. This method may reveal previous perinatal invasive infections of unknown origin retrospectively.

DOI PubMed

Effectiveness of cross double mcdonald cerclage for intractable bleeding from a cervical varix in pregnant women

Yuya Fujibe, Tasuku Mariya, Masahito Mizuuchi, Shinichi Ishioka, Tsuyoshi Saito

Gynecology and Minimally Invasive Therapy ( Wolters Kluwer Medknow Publications ) 10 ( 3 ) 177 - 180 2021年07月

Cervical varix during pregnancy is a rare condition, and standard management for bleeding from a varix has not been established. We performed cross double cervical cerclage and effectively stopped bleeding. A 41-year-old female had a twin pregnancy. The development of a cervical varix was observed during pregnancy and bleeding from ruptured varix started at 20 weeks of gestation. We performed surgical hemostasis by cervical cerclage. In the first cerclage, we could not stop the bleeding from the varix. For further restriction of blood supply to the cervical varix, we performed a second cerclage in a crossed position on a deeper side of the vagina than the first cerclage. Then the bleeding completely stopped and there was no bleeding until delivery. The 'cross double McDonald cerclage' performed in our patient may be a useful modified cerclage method for stopping intractable bleeding from the cervix during pregnancy.

DOI

子宮温存している若年発症子宮体部腺肉腫の2例

寺田倫子, 松浦基樹, 野藤五沙, 西村庸子, 真里谷奨, 玉手雅人, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 63回 292 - 292 2021年07月

Increased cervical Chlamydia trachomatis and syphilis infections in Japanese females of reproductive age in the late 2010s: Possible cause.

Satoshi Shimano, Tasuku Mariya, Tsuyoshi Saito

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2021年05月 [国際誌]

From 2000 to 2019, Japan's reproductive-age population gradually declined by 24%. In comparison, the Chlamydia trachomatis infection rate increased from 2016, with the syphilis infection rate increasing more sharply from 2014. Since 2013, the numbers of foreign tourists to Japan have also increased. From 2011 to 2018, the rate of increase in tourists was 5.02 times, while the rate of increase in syphilis patients was higher at 22.4 times. The lack of a one-to-one relationship between foreign tourists and syphilis cases suggests that cases of syphilis were transmitted to others. Although the prevalence of syphilis in the tourists' home countries (Korea in 2014 and China in 2013) was 20-30 times higher than that in Japan, the Japanese sex industry did not discriminate against foreign tourists, leading to increased STI infections in Japanese female sex workers. Indeed, from 2017 to 2018, a history of working in the sex industry for six months was identified as a risk factor for syphilis. The rise in Chlamydia trachomatis infections has lagged behind that of syphilis by two years, with the rate of increase lower. We suspect the difference in increasing rates of syphilis and chlamydial infections is due to the different methods of infection: syphilis can be transmitted by light physical contact, such as a kiss, whereas chlamydia requires close sexual contact, such as oral sex or sexual intercourse. Regardless, examinations and infection control are necessary to prevent the spread of STIs in Japan due to inbound tourists.

DOI PubMed

Does Radical trachelectomy (RT) during pregnancy have higher obstetrical and oncological risks than RT before pregnancy?

Shota Shinkai, Shinichi Ishioka, Tasuku Mariya, Yuya Fujibe, Miseon Kim, Masayuki Someya, Tsuyoshi Saito

( Research Square Platform LLC ) 2021年03月

Abstract Purpose Radical trachelectomy (RT) with pelvic lymphadenectomy has become a new treatment option for young patients with uterine cervical cancer stages 1A2–1B1 who desire the preservation of their fertility. However, the application of RT for pregnant patients is still controversial. We comparatively studied both obstetrical and oncological outcomes of pregnant patients who underwent vaginal RT during pregnancy and those who underwent vaginal RT before pregnancy. Methods Both obstetrical and oncological results of eight patients who underwent vaginal RT with pelvic lymphadenectomy during pregnancy in our institute between 2010 and 2020 (Group A), and ten pregnant patients who underwent vaginal RT with pelvic lymphadenectomy before pregnancy during the same period (Group B) were reviewed based on their medical charts. Results There were no significant differences in blood loss, surgical time, or surgical completeness between Group A and Group B. Nor were there significant differences in obstetrical outcomes between the two groups. However, two of the eight patients in Group A had recurrence of the cancer. None of the patients in Group B has shown any signs of recurrence thus far. Conclusion Vaginal RT during pregnancy does not affect the obstetrical prognoses of patients with early invasive uterine cervical cancer, and it might be a tolerable treatment modality for them. However, oncologically, it should be performed carefully as there is a risk of recurrence.

DOI

Common iliac artery dissection as a complication of common iliac artery balloon occlusion for placenta percreta: A case report.

Kimihito Saito, Tasuku Mariya, Yuya Fujibe, Masato Saito, Naoki Hirokawa, Shinichi Ishioka, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 47 ( 3 ) 1172 - 1177 2021年03月 [国際誌]

A 37-year-old pregnant woman who had undergone three previous cesarean sections was diagnosed as having placenta percreta. We decided to perform cesarean hysterectomy with bilateral common iliac artery balloon occlusion (CIABO). The duration of surgery was 2 h and 2 min and total estimated blood loss was 2600 mL. Surgery was completed without any surgical complications, but the pulse oximeter waveform of the left leg became undetectable during surgery. We immediately performed angiography after closure of laparotomy and found abnormal pooling of contrast media at the left common iliac artery in the region in which the balloon was positioned. We made a diagnosis of left common iliac artery dissection caused by CIABO. We performed emergent revascularization by intravascular stenting. We conclude that CIABO can cause common iliac artery dissection by mechanical stimulation of the inflated balloon. Careful intraoperative evaluation of limb ischemia and preparation of intravascular treatment is needed for a safe procedure.

DOI PubMed

Less correlation between mismatch repair proteins deficiency and decreased expression of HLA class I molecules in endometrial carcinoma: a different propensity from colorectal cancer.

Tasuku Mariya, Terufumi Kubo, Yoshihiko Hirohashi, Junko Yanagawa, Yuta Tabuchi, Kazuhiko Matsuo, Kiyoshi Furumura, Rena Morita, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Tadashi Hasegawa, Tsuyoshi Saito, Toshihiko Torigoe

Medical molecular morphology 54 ( 1 ) 14 - 22 2021年03月 [国内誌]

Mismatch repair protein deficiency (dMMR) is a favorable prognostic factor in colorectal cancer. It is also associated with aberrant expression of HLA class I molecules, which are required for cytotoxic T lymphocyte-mediated cancer immunotherapy. Because dMMR is frequently also found in endometrial cancers (ECs), we retrospectively investigated the expression of mismatch repair proteins and HLA class I molecules in 127 EC patients. In this study, EC patients being treated in our hospital were recruited from 2005 to 2009 and observed until December 2017. Lesion specimens were evaluated via immunohistochemistry for MSH6 and PMS2 (mismatch repair proteins) and HLA class I molecules. Expression of these molecules was statistically related to clinical and pathological factors and prognosis. dMMR was detected in 33 patients and did not correlate with the expression level of HLA class I molecules (P = 0.60). On the other hand, unexpectedly, multivariate analysis revealed that intact expression of HLA class I molecules was associated with p53 overexpression (P = 0.004). Neither dMMR nor decreased expression of HLA class I molecules were prognostic factors. These results are inconsistent with previous findings for colorectal cancer. A distinctive local tissue immune microenvironment would underlie the discrepancy in the results between EC and colorectal cancer.

DOI PubMed

Umbilical cyst associated with patent urachus that spontaneously disappeared: A case report.

Yuya Fujibe, Tasuku Mariya, Masahito Mizuuchi

Prenatal diagnosis 41 ( 3 ) 384 - 385 2021年02月 [国際誌]

DOI PubMed

ERα increases endometrial cancer cell resistance to cisplatin via upregulation of BAG3.

Shuetsu Abe, Masahiro Iwasaki, Shutaro Habata, Tasuku Mariya, Masato Tamate, Motoki Matsuura, Seiro Satohisa, Tsuyoshi Saito

Oncology letters 21 ( 1 ) 20 - 20 2021年01月 [国際誌]

Endometrial cancer is a leading cause of cancer-associated mortality in women and has a poor prognosis in advanced stages. Our previous study revealed that BCL-2-associated athanogene 3 (BAG3) may contribute to enhancing cell viability through downregulation of microRNA (miR)-29b in endometrial cancer cell lines. In addition, a relationship between estrogen receptor α (ERα) and BAG3 was recently reported in several cancer cell types. The present study investigated the relationship between ERα and BAG3 in endometrial cancer cell lines. The results demonstrated that exogenous ERα overexpression enhanced BAG3 expression in the EMTOKA endometrial cancer cell line, which does not endogenously express ERα, but had no effect on BAG3 expression levels in the Ishikawa cell line, which does endogenously express ERα. In addition, ERα overexpression suppressed miR-29b expression and enhanced the expression of Mcl-1, a mediator situated downstream of BAG3, in EMTOKA cells, but not Ishikawa cells. ERα overexpression also enhanced EMTOKA, but not Ishikawa, endometrial cancer cell viability in the presence of cisplatin. These findings suggested that ERα may contribute to enhancing endometrial cancer cell resistance to anticancer agents through BAG3 overexpression.

DOI PubMed

骨盤解剖学をCadaver Surgery Trainingで理解する混合研究の試み

玉手雅人, 松浦基樹, 阿部秀悦, 西村庸子, 常松梨沙, 寺田倫子, 真里谷奨, 岩崎雅宏, 金尾祐之, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 311 - 311 2021年01月

Deep Learning(YOLOv3)を用いたリアルタイム婦人科細胞診断支援システム設計の試み

真里谷奨, 新開翔太, 松浦基樹, 郷久晴朗, 岩崎雅宏, 南部優太, 藤野雄一, 淺沼広子, 廣橋良彦, 鳥越俊彦, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 278 - 278 2021年01月

島野敏司, 真里谷奨, 長井陽子, 芦川享大, 荒井渉, 斎藤豪

臨床と微生物 ( (株)近代出版 ) 48 ( 1 ) 041 - 045 2021年01月

ERα発現および非発現子宮体癌細胞株に於けるBAG3発現および増殖能との関連

阿部秀悦, 岩崎雅宏, 幅田周太朗, 真里谷奨, 小川万梨絵, 郷久晴朗, 齋藤豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 ) 39 ( 1 ) 285 - 285 2021年01月

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