記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Remote antenatal checkups were conducted on the northernmost island of Japan to reduce the burden of hospital visits among pregnant women. This study aims to investigate the effectiveness and safety of remote antenatal checkups for pregnant women living on a remote island. METHODS: This observational study included singleton pregnancies on Rebun Island between October 2020 and September 2022. General surgeons conducted medical interviews and performed fetal sonography using an obstetrician videoconference system at the main central hospital. The primary outcomes were the degrees of physical, mental, and economic burdens of hospital visits and the levels of anxiety and satisfaction with remote antenatal checkups as assessed using a questionnaire survey. Moreover, we investigated the incidence of adverse perinatal events, including maternal death, fetal death, neonatal death, severe neonatal neurological disorders, and other obstetric complications. RESULTS: This study included 16 out of 22 pregnant women from Rebun Island who visited the central hospital. No adverse perinatal events occurred as a result of the remote antenatal checkups. One pregnant woman had gestational diabetes, whereas the others had no obstetric complications. The participants underwent a median of two remote antenatal checkups. According to a questionnaire survey, 90.0%, 80.0%, and 70.0% of the pregnant women perceived improvements in their physical, mental, and economic burdens, respectively. Although 70.0% of the participants experienced anxiety regarding remote antenatal checkups before the introduction, all were satisfied after delivery. CONCLUSIONS: Remote antenatal checkups effectively reduced the burden of hospital visits for pregnant women, who reported high levels of satisfaction. Furthermore, antenatal checkups were safely conducted on remote islands.

DOI： 10.31662/jmaj.2022-0195

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Multimorbidity is defined as the coexistence of two or more chronic physical or psychological conditions within an individual. The association between maternal multimorbidity and adverse perinatal outcomes such as preterm delivery and low birth weight has not been well studied. Therefore, this study aimed to investigate this association. METHODS: We conducted a prospective cohort study using data from the Japan Environment and Children's Study of pregnant women between 2011 and 2014. Those with data on chronic maternal conditions were included in the study and categorised as having no chronic condition, one chronic condition or multimorbidities. The primary outcomes were the incidence of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Adjusted logistic regression was performed to estimate ORs (aORs) and 95% CIs. RESULTS: Of the 104 062 fetal records, 86 885 singleton pregnant women were analysed. The median maternal age and body mass index were 31 years and 20.5 kg/m2, respectively. The prevalence of pregnant women with one or more chronic conditions was 40.2%. The prevalence of maternal multimorbidity was 6.3%, and that of PTB, LBW, and SGA were 4.6%, 8.1%, and 7.5%, respectively. Pre-pregnancy underweight women were the most common, observed in 15.6% of multimorbidity cases, followed by domestic violence from intimate partner in 13.0%. Maternal multimorbidity was significantly associated with PTB (aOR 1.50; 95% CI 1.33-1.69), LBW (aOR 1.49; 95% CI 1.35-1.63) and SGA (aOR 1.33; 95% CI 1.20-1.46). CONCLUSION: Maternal multimorbidity was associated with adverse perinatal outcomes, including PTB, LBW and SGA. The risk of adverse perinatal outcomes tends to increase with a rise in the number of chronic maternal conditions. Multimorbidity becomes more prevalent among pregnant women, making our findings important for preconception counselling.

DOI： 10.1136/bmjopen-2022-069281

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study aimed to document the complication status of infants with orofacial clefts born between 2011 and 2014 in Japan. This was a descriptive study using data from the Japan Environment and Children's Study. Among 103 060 pregnancies, 248 infants with orofacial clefts were included (livebirth, 239; stillbirth, 4; miscarriage, 5). The items of interest were complication status of orofacial clefts: isolated (typical orofacial clefts only); multi-malformed (orofacial clefts with unrelated major defects); syndromic (orofacial clefts with a syndrome or a chromosomal defect). Regarding the cleft subtypes, of 248 infants with orofacial clefts, 104 had cleft lip with cleft palate (CLP) (41.9%), 68 had cleft lip without cleft palate (CL) (27.4%), 58 had cleft palate without cleft lip (CP) (23.4%), and 18 were nonclassified (7.3%). In infants with CLP, the proportions of isolated, multi-malformed, and syndromic phenotypes were 73.1%, 15.4%, and 11.5%, respectively. In infants with CL, the proportions were 79.4%, 16.2%, and 4.4%, respectively. In infants with CP, the proportions were 69.0%, 13.8%, and 17.2%, respectively. The most frequently associated congenital anomaly was congenital heart disease. In infants with syndromic CLP, 41.7% had trisomy 13. In infants with syndromic CP, 80.0% had the Pierre Robin sequence. Congenital heart disease could be the most frequently associated congenital anomaly. The most frequently associated syndrome could be trisomy 13 in those with CLP and Pierre Robin sequence in those with CP.

DOI： 10.1111/cga.12496

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当区分：責任著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Urinary cotinine concentration (UCC) reflects smoking status. However, in pregnant women, its association with adverse birth outcomes related to fetal growth is not widely known. Thus, we aimed to explore this relationship by focusing on dose-response relationships. We investigated 86,638 pregnant women enrolled between 2011 and 2014 in a prospective cohort study in Japan and observed three birth outcomes (preterm birth, low birth weight, and small-for-gestational age). We measured UCC in the second or third trimester, and categorized the participants using cut-off values (negative cotinine concentration, passive cotinine concentration, and active cotinine concentration corresponding to non-smokers, passive smokers, and active smokers, respectively). Logistic regression analyses were conducted to evaluate the risks, and dose-response relationships were visualized using restricted cubic spline curves. Analyses based on self-reported smoking status were also performed. We found that in low active and highly active cotinine concentrations, the adjusted odds ratios (aORs) of birth outcomes were significantly increased (preterm birth, 1.24 [95% CI 1.06-1.46], 1.39 [95% CI 1.19-1.62]; low birth weight, 1.40 [95% CI 1.24-1.58], 2.27 [95% CI 2.05-2.53]; small-for-gestational age, 1.35 [95% CI 1.19-1.52], 2.39 [95% CI 2.16-2.65]). Restricted cubic spline curves demonstrated risk elevations in the active cotinine concentration range. Our research revealed dose-response relationships between UCC during pregnancy and the risks of preterm birth, low birth weight, and small-for-gestational age. Measurement of UCC to ascertain smoking status during pregnancy may be a useful approach for predicting the risks of these birth outcomes.

DOI： 10.1016/j.envres.2022.114302

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: We aimed to grasp the actual working hours of Japanese obstetricians and gynecologists (OB/GYN doctors) as accurately as possible, using the same method of the Ministry of Health, Labour, and Welfare (MHLW). METHODS: The time study targeted OB/GYN doctors working at 10 universities nationwide including Niigata University and 21 institutions which take a role of perinatal care in Niigata prefecture. Working hours per week were calculated based on the following categories: regular and overtime work inside the hospital, work outside the hospital, self-improvement, education, research, and others. Data on weekly working hours were converted to yearly data for analyses. RESULTS: A time study of 10 universities nationwide revealed that 30% of doctors work overtime for more than 1860 h even if they do not include on-call shifts in their working hours. In 21 institutions in Niigata, physicians in Niigata University worked more overtime than other hospitals. It became clear that community health care was supported by dispatching physicians working at university. Furthermore, the results of simulations predicted the pessimistic situation of perinatal medical care in Niigata. CONCLUSIONS: Our study showed the possibility to exist much more OB/GYN doctors who work more than 1860 h of overtime work per year than the data presented by the MHLW based on nation-wide survey in 2019. The fact that the working hours at the side jobs had a great influence on the increase in overtime work of physicians in University was the same result as the report of MHLW published in 2021.

DOI： 10.1111/jog.15230

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The extremes of maternal pre-pregnancy body mass index (BMI) are known to be risk factors associated with obstetric and adverse perinatal outcomes. Among Japanese women aged 20 years or older, the prevalence of underweight (BMI < 18.5 kg/m2) was 11.5% in 2019. Maternal thinness is a health problem caused by the desire to become slim. This study aimed to investigate the association between the severity of maternal low pre-pregnancy BMI and adverse perinatal outcomes, including preterm birth (PTB), low birth weight (LBW), and small-for-gestational age (SGA). METHODS: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant individuals between 2011 and 2014. Pre-pregnancy BMI was categorized as severe-moderate underweight (BMI < 16.9 kg/m2), mild underweight (BMI, 17.0-18.4 kg/m2), low-normal weight (BMI, 18.5-19.9 kg/m2), high-normal weight (BMI, 20.0-22.9 kg/m2), overweight (BMI, 23.0-24.9 kg/m2), and obese (BMI ≥ 25.0 kg/m2). The high-normal weight group was used as the reference for statistical analyses. Adjusted logistic regression was performed to evaluate the association between pre-pregnancy BMI and PTB, LBW, and SGA. RESULTS: Of 92,260 singleton pregnant individuals, the prevalence was 2.7% for severe-moderate underweight, 12.9% for mild underweight, and 24.5% for low-normal weight. The prevalence of adverse outcomes was 4.6% for PTB, 8.1% for LBW, and 7.6% for SGA. The adjusted odds ratios (aORs) for PTB were 1.72 (95% confidence interval [CI], 1.46-2.03) for severe-moderate underweight and 1.26 (95% CI, 1.14-1.39) for mild underweight. The aORs of LBW were 2.55 (95% CI, 2.27-2.86) for severe-moderate underweight, 1.64 (95% CI, 1.53-1.76) for mild underweight, and 1.23 (95% CI, 1.16-1.31) for low-normal weight. The aORs of SGA were 2.53 (95% CI, 2.25-2.84) for severe-moderate underweight, 1.66 (95% CI, 1.55-1.79) for mild underweight, and 1.29 (95% CI, 1.21-1.38) for low-normal weight. CONCLUSIONS: A dose-response relationship was found between the severity of low pre-pregnancy BMI and PTB, LBW, and SGA. Even low-normal BMI (18.5-19.9 kg/m2) increased the risk of LBW and SGA. This study provides useful information for pre-conception counseling in lean individuals.

DOI： 10.1186/s12884-022-04418-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The cervical cytology of our patient transformed from squamous cell carcinoma to negative for intraepithelial lesion or malignancy, possibly due to the graft-versus-tumor effect following allogeneic stem cell transplantation.

DOI： 10.1002/ccr3.4835

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although cytology-based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing for cervical screening increases detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV-positive women to avoid over-referral to colposcopy may be setting specific. As Japan requires data that have been generated domestically to modify screening guidelines, we conducted a 3-year prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to evaluate the potential role of HPV16/18 partial genotyping and cytology for primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology and HPV testing were carried out. Women with abnormal cytology or HPV16/18 positivity underwent colposcopy. Those with 12 other high-risk (hr) HPV types underwent repeat cytology after 6 months. Primary study endpoints were detection of high-grade cervical disease defined as CIN2/CIN3 or greater as determined by consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV 16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively. HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2) adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity declined with increasing age. This is the first Japanese study to investigate the role of partial genotyping and cytology in an HPV-based screening program. Results should help policy-makers develop guidelines for future cervical screening programs and management of cervical abnormalities based on HPV genotype.

DOI： 10.1111/cas.13608

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To identify epidemiologic risk factors and investigate whether the characteristics of removed ovarian tissue during surgery influence the recurrence of endometriomas. DESIGN: Retrospective cohort study. SETTING: Medical university hospital. POPULATION: 248 women with endometriomas. METHODS: All women who had a minimum of 2 years of follow-up after the laparoscopic excision of endometriomas were analysed retrospectively. Specimens were analysed histologically. MAIN OUTCOME MEASURES: Sixteen epidemiologic variables were analysed as possible risk factors for recurrence. The association between the characteristics of removed ovarian tissue (the thickness of the cyst wall, the thickness of ovarian tissue, and the morphological features) and endometrioma recurrence was investigated. RESULTS: The cumulative incidence of endometriomas reached 42% at 60 months after surgery. We identified only a younger age at surgery as a risk factor, and postoperative pregnancy as a preventive factor. There were no differences in the mean thickness of the cyst wall and the removed ovarian tissue between patients with and without recurrence. No statistically significant associations were found between the morphologic characteristics of removed cyst wall, ovarian tissue, graded on a semi-quantitative basis, and recurrence. CONCLUSIONS: These results suggest that the rate of endometrioma recurrence had a significant relation to patient age and postoperative pregnancy; however, there was no association between the histological characteristics of the excised tissue and recurrence.

DOI： 10.1111/aogs.12051

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Diagnosis of lymph node metastasis is a critical issue in the treatment of cervical cancer. Many studies describing sentinel node navigation surgery (SNNS) for examination of node status have been reported in the past decade. In this study, the feasibility of node status diagnosis by SNNS, including intraoperative frozen section diagnosis, in patients with early and advanced cervical cancer was evaluated. PATIENTS AND METHODS: Fifty-eight cervical cancer patients with early and advanced stage disease were enrolled. All patients were treated with backup pelvic lymphadenectomy after SNNS. To detect sentinel lymph nodes (SLNs), radioactive material and/or blue dye were used as tracers. Lymph nodes confirmed as SLNs were immediately sent to pathologists and diagnosed by frozen section intraoperatively. RESULTS: A total of 118 and 16 SLNs were pathologically investigated in early and advanced stage cervical cancer, respectively. The detection rate of SLNs in the early and advanced stages was 94.7% and 66.7%, respectively, whereas the detection rate using 1 or 2 tracers was 62.5% and 90%, respectively. The false-negative rate and negative predictive value was 0% and 100% for all stages. Pathological diagnosis by frozen section was completed within 30 minutes in all cases. CONCLUSIONS: Our data demonstrate that SNNS in cervical cancer is a promising procedure for patients with early stage (up to Ib1) disease, especially patients with small tumor diameter (<2.0 cm). However, SNNS raises several points for discussion before it can be established as a practical clinical procedure or as part of a subsequent radical hysterectomy.

DOI： 10.1111/IGC.0b013e3181a83d65

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Follicular thyroid cancer (FTC) is known to metastasize to distant sites via hematogenous spread; however, the underlying pathways that contribute to metastasis remain unknown. Recent creation of a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta (TRbeta(PV/PV) mouse) that spontaneously develops thyroid cancer with metastasis similar to humans has provided new opportunities to study contributors to FTC metastasis. This study evaluates the role of gelsolin, an actin-regulatory protein, in modulating the metastatic potential of FTC. Gelsolin was previously found by cDNA microarray analysis to be down-regulated in TRbeta(PV/PV) mice as compared with wild-type mice. This study found an age-dependent reduction of gelsolin protein abundance in TRbeta(PV/PV) mice as tumorigenesis progressed. Knockdown of gelsolin by small interfering RNA resulted in increased tumor cell motility and increased gelsolin expression by histone deacetylase inhibitor (trichostatin A) led to decreased cell motility. Additional biochemical analyses demonstrated that gelsolin physically interacted with TRbeta1 or PV in vivo and in vitro. The interaction regions were mapped to the C terminus of gelsolin and the DNA binding domain of TR. The physical interaction of gelsolin with PV reduced its binding to actin, leading to disarrayed cytoskeletal architectures. These results suggest that PV-induced alteration of the actin/gelsolin cytoskeleton contributes to increased cell motility. Thus, the present study uncovered a novel PV-mediated oncogenic pathway that could contribute to the local tumor progression and metastatic potential of thyroid carcinogenesis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Thyroid hormone (T3) is critical for growth, differentiation, and maintenance of metabolic homeostasis. Mice with a knock-in mutation in the thyroid hormone receptor alpha gene (TRalpha1PV) were created previously to explore the roles of mutated TRalpha1 in vivo. TRalpha1PV is a dominant negative mutant with a frameshift mutation in the carboxyl-terminal 14 amino acids that results in the loss of T3 binding and transcription capacity. Homozygous knock-in TRalpha1(PV/PV) mice are embryonic lethal, and heterozygous TRalpha1(PV/+) mice display the striking phenotype of dwarfism. These mutant mice provide a valuable tool for identifying the defects that contribute to dwarfism. Here we show that white adipose tissue (WAT) mass was markedly reduced in TRalpha1(PV/+) mice. The expression of peroxisome proliferator-activated receptor gamma (PPARgamma), the key regulator of adipogenesis, was repressed at both mRNA and protein levels in WAT of TRalpha1(PV/+) mice. Moreover, TRalpha1PV acted to inhibit the transcription activity of PPARgamma by competition with PPARgamma for binding to PPARgamma response elements and for heterodimerization with the retinoid X receptors. The expression of TRalpha1PV blocked the T3-dependent adipogenesis of 3T3-L1 cells and repressed the expression of PPARgamma. Thus, mutations of TRalpha1 severely affect adipogenesis via cross talk with PPARgamma signaling. The present study suggests that defects in adipogenesis could contribute to the phenotypic manifestation of reduced body weight in TRalpha1(PV/+) mice.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

HOX genes encode transcription factors that function to establish basic body pattern during embryogenesis and maintain the function of specific organs in the adult. Recent studies have demonstrated that HOX genes are also involved in oncogenesis in a range of malignancies. To elucidate whether HOX genes contribute to ovarian carcinogenesis, we created an expression profile of HOX genes using ovarian derived materials from surgical samples and epithelial ovarian cancer cells derived from five different cell lines. Real-time quantitative RT-PCR assay indicated overexpression of 14 HOX genes in clusters A and B but only 2 genes in clusters C and D. Of the 16 HOX genes, overexpression of paralogs of HOX3, HOX4 and HOX7 is seen in cluster A and B, and of HOX13 in all paralogs. In addition, HOXB7, HOXA13 and HOXB13 showed high levels of overexpression in cancer cells and tissues whereas no or little expression was observed in normal controls. To examine whether overexpressed HOX genes regulate invasion of ovarian cancer cells directly, we introduced an antisense DNA fragment of overexpressed HOXB7 and HOXB13, and HOXC5 that did not show overexpression into SKOV3 cells by electroporation. Antisense introduction followed by chemoinvasion assay using matrigel chamber demonstrated that SKOV3 cells introduced an antisense of each HOXB7 and HOXB13 showed 85% and 50% reduction of invasion ability compared to the parental SKOV3 cells, respectively. In contrast, antisense of HOXC5 introduced cells showed no significant difference of the invasion ability. These results suggest an important role of overexpressed HOX genes, especially for invasive characteristics of ovarian cancer cells.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The phosphatidylinositol 3-kinase/AKT pathway is crucial to many cell functions, and its dysregulation in tumors is a common finding. The molecular basis of follicular thyroid cancer metastasis is not well understood but may also be influenced by AKT activation. We previously created a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta gene (TRbetaPV mouse) that spontaneously develops thyroid cancer and distant metastasis similar to human follicular thyroid cancer. In this study, we investigated whether our mouse model exhibits similar AKT activation as human follicular thyroid cancer. Western blot analysis on thyroids from both wild-type and TRbeta(PV/PV) mice revealed elevation of activated AKT in TRbeta(PV/PV) mice. Immunohistochemistry and confocal microscopy reveal activated AKT in both the thyroid and metastatic lesions of TRbeta(PV/PV) mice. Whereas all three AKT isoforms were overexpressed in primary tumors from TRbeta(PV/PV) mice in the cytoplasm of thyroid cancer cells, only AKT1 was also found in the nucleus, matching the localization of activated AKT in a pattern similar to human follicular thyroid cancer. In the metastases, all AKT isoforms correlated with phosphorylated AKT nuclear localization. We created primary thyroid cell lines derived from TRbeta(PV/PV) mice and found reduction of phosphorylated AKT levels or AKT downstream targets diminishes cell motility. Activated AKT is common to both human and mouse follicular thyroid cancer and is correlated with increased cell motility in vitro and metastasis in vivo. Thus, TRbeta(PV/PV) mice could be used to further dissect the detailed pathways underlying the progression and metastasis of follicular thyroid carcinoma.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The etiology and genetic alterations of follicular thyroid carcinoma are not well understood. By targeting a mutation (PV) into the thyroid hormone receptor beta gene (TRbetaPV mouse), we created a knock-in mutant TRbeta(PV/PV) mouse that spontaneously develop follicular thyroid carcinoma with progression to metastasis similar to human follicular thyroid carcinoma. This mouse model provides a valuable tool to ascertain the nature and the extent of genomic rearrangements that occur during carcinogenesis of the thyroid. Spectral karyotyping analysis (SKY) of seven cell lines derived from thyroid tumors developed in TRbeta(PV/PV) mice showed that all of them had abnormal karyotypes, with chromosome number ranging from near-diploid (39-42 chromosomes) to hypotetraploid (63-79 chromosomes). These seven cell lines also exhibited a variety of structural chromosomal aberrations, including common recurrent translocations and deletions. This SKY analysis shows that the development and progression of follicular thyroid carcinoma in knock-in TRbeta(PV/PV) mutant mice comprise recurrent structural and numerical genomic changes, some of which mimic those described in human thyroid cancer.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have created a knockin mutant mouse by targeting a mutation (PV) into the thyroid hormone receptor beta gene (TRbetaPV mouse). TRbetaPV/PV mice, but not TRbetaPV/+ mice, spontaneously develop follicular thyroid carcinoma. To identify other genetic changes in the TRbeta gene that could also induce thyroid carcinoma, we crossed TRbetaPV mice with TRbeta-/- mice. As TRbetaPV/- mice (mutation of one TRbeta allele in the absence of the other wild-type allele) aged, they also spontaneously developed follicular thyroid carcinoma through the pathological progression of hyperplasia, capsular and vascular invasion, anaplasia, and eventually metastasis to the lung, but not to the lymph nodes. The pathological progression of thyroid carcinoma in TRbetaPV/- mice was indistinguishable from that in TRbetaPV/PV mice. Analyses of the expression patterns of critical genes indicated activation of the signaling pathways mediated by TSH, peptide growth factors (epidermal growth factor and fibroblast growth factor), TGF-beta, TNF-alpha, and nuclear factor-kappaB, and also suggested progressive repression of the pathways mediated by the peroxisome proliferator-activated receptor gamma. The patterns in the alteration of these signaling pathways are similar to those observed in TRbeta(PV/PV) mice during thyroid carcinogenesis. These results indicate that in the absence of a wild-type allele, the mutation of one TRbeta allele is sufficient for the mutant mice to spontaneously develop follicular thyroid carcinoma. These results provide, for the first time, in vivo evidence to suggest that the TRbeta gene could function as a tumor suppressor gene. Importantly, these findings present the possibility that TRbeta could serve as a novel therapeutic target in thyroid cancer.

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Resistance to thyroid hormone (RTH) is caused by mutations of the thyroid hormone receptor beta (TRbeta) gene. To understand the transcriptional program underlying TRbeta mutant-induced phenotypic expression of RTH, cDNA microarrays were used to profile the expression of 11,500 genes in a mouse model of human RTH. RESULTS: We analyzed transcript levels in cerebellum, heart and white adipose tissue from a knock-in mouse (TRbetaPV/PV mouse) that harbors a human mutation (referred to as PV) and faithfully reproduces human RTH. Because TRbetaPV/PV mice have elevated thyroid hormone (T3), to define T3-responsive genes in the context of normal TRbeta, we also analyzed T3 effects in hyperthyroid wild-type gender-matched littermates. Microarray analysis revealed 163 genes responsive to T3 treatment and 187 genes differentially expressed between TRbetaPV/PV mice and wild-type littermates. Both the magnitude and gene make-up of the transcriptional response varied widely across tissues and conditions. We identified genes modulated in T3-dependent PV-independent, T3- and PV-dependent, and T3-independent PV-dependent pathways that illuminated the biological consequences of PV action in vivo. Most T3-responsive genes that were dysregulated in the heart and white adipose tissue of TRbetaPV/PV mice were repressed in T3-treated wild-type mice and upregulated in TRbetaPV/PV mice, suggesting the inappropriate activation of T3-suppressed genes in RTH. CONCLUSIONS: Comprehensive multi-tissue gene-expression analysis uncovered complex multiple signaling pathways that mediate the molecular actions of TRbeta mutants in vivo. In particular, the T3-independent mutant-dependent genomic response unveiled the contribution of a novel 'change-of-function' of TRbeta mutants to the pathogenesis of RTH. Thus, the molecular actions of TRbeta mutants are more complex than previously envisioned.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hormone replacement therapy (HRT) is not successful or is contraindicated for the treatment of climacteric symptoms in some patients. To investigate whether certain herbal formulas of traditional Chinese medicine (Kampo in Japanese) could be used as an alternative treatment, a longitudinal 'before and after' comparative study was carried out in 18 Japanese women, and the results were compared with those of 16 women who underwent HRT. Kampo improved all the climacteric symptoms. In contrast, improvement of cold limbs, sleeping disorders, shoulder stiffness/lumbago, and fatigue in the HRT group was either not significant or of limited extent. In addition, the serum level of estradiol in postmenopausal women was raised by the combined use of two Kampo formulas. These results suggest that Kampo may be considered an alternative to HRT for the treatment of climacteric symptoms, but vigorous monitoring for potential side effects of increased estrogen levels in some postmenopausal patients is needed.

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Constitutive overexpression of matrix metalloproteinases (MMPs) is frequently observed in malignant tumors. MMPs are a family of zinc endopeptidases consisting of at least 20 different members. In particular, MMP-2 and MMP-9 are reported to be closely associated with invasion and metastasis in several cancers. We investigated whether expression of MMP-2 and MMP-9 is associated with invasion ability of seven cervical cancer cells by administration of o-phenanthroline as MMP inhibitor. In two cell lines, Siha and Caski, MMP-2 mRNA and protein were expressed at high levels. After treatment with o-phenanthroline, the rate of invasion in these two cell lines was significantly decreased. In contrast, in the other two cell lines, HT-3 and Caski, high levels of MMP-9 mRNA and protein were expressed but there was no decrease in the rate of invasion in these cells after treatment with o-phenanthroline. The data suggest that expression level of MMP-2 mRNA may regulate with invasion ability of cervical cancer.

PubMed

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総ページ数：530p  

CiNii Books

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総ページ数：xi, 313p   記述言語：日本語  

CiNii Books

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総ページ数：x, 324p   記述言語：日本語  

CiNii Books

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記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

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記述言語：日本語   出版者・発行元：北海道産科婦人科学会  

漿液性子宮内膜上皮内癌(serous endometrial intraepithelial carcinoma:SEIC)は,子宮体部漿液性癌の前駆病変と考えられており,間質浸潤がみられなくても周囲に浸潤癌を伴うことや経卵管的播種をきたすことがあり,子宮外進展を来したものは予後不良とされている。今回我々は,子宮頸部細胞診異常から発見され,手術療法によってSEICと診断された症例を経験したので報告する。症例は58歳。2妊1産,53歳閉経。前医にて検診目的で実施した子宮頸部細胞診でAGC,子宮頸部組織診でLSIL/CIN1,子宮内膜組織診で漿液性癌の診断となったため子宮体癌として精査加療目的で当科初診となった。多発子宮筋腫のため内膜の評価は画像でも困難だったが当科の子宮内膜組織診でも漿液性癌と診断され,腹式単純子宮全摘出術,両側付属器摘出術,大網部分切除術,骨盤および傍大動脈リンパ節郭清術を施行した。最終病理組織診断はSEIC,pT1aN0M0(UICC 8th),腹水細胞診陽性であった。術後補助療法を勧めたが希望されず経過観察としていた。術後1年6ヵ月で多発リンパ節転移及び腹膜播種を認め,化学療法を開始したが開始後4ヵ月で無症候性血尿の増悪を認め,膀胱浸潤の診断となりレジメン変更を行ったが治療効果は認められず,術後2年9ヵ月で原病死に至った。婦人科検診を契機に発見された無症状のSEICの1例を経験した。腺系細胞の異常を認めた場合には,SEICの存在も念頭に,早期の診断及び治療に結びつけることが重要と認識した。今後,さらに術後治療も含め,その有用性も併せて検討していきたい。(著者抄録)

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記述言語：日本語   出版者・発行元：北海道産科婦人科学会  

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記述言語：日本語   出版者・発行元：北海道産科婦人科学会  

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記述言語：日本語   出版者・発行元：(公社)全国大学保健管理協会  

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記述言語：日本語   出版者・発行元：(一社)日本女性医学学会  

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記述言語：日本語   出版者・発行元：(一社)日本生殖医学会  

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記述言語：日本語   出版者・発行元：(一社)日本生殖医学会  

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記述言語：日本語   出版者・発行元：(一財)日本漢方医学教育振興財団  

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記述言語：日本語   出版者・発行元：(株)メディカルドゥ  

先天性筋強直性ジストロフィー(congenital myotonic dystrophy:CDM)は筋強直性ジストロフィー1型の最重症型であり,CDMの児の両親のどちらかが病的バリアントをもつ。他覚的には発症しているが,自覚症状のない例に対する遺伝学的検査は発症前診断に相当すると考えられ,予防法・治療法のない疾患では心理・社会的問題が大きく,検査前に遺伝医療部門での専門的な遺伝カウンセリングが必須である。今回遺伝学的に確定診断されたCDMの児の両親に対して遺伝医療の専門家による遺伝カウンセリングが行われないまま遺伝学的診断を行い,どのように告知するかが問題となった事例を経験した。結果告知前に遺伝カウンセリングを行ったことで告知を受容できた例を報告する。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本東洋医学会  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

＜文献概要＞Point 骨盤内炎症性疾患(PID)は,頻回に罹患する患者も認め,診断や治療が遅れると,不妊や異所性妊娠などのリスクが高くなる病気であり,慢性的に骨盤痛が残ることもある.早期に,かつ正確に診断して,治療に結びつけることが必要である.本疾患に関しては,医療者側も正しく理解している方が多いとはいえず,早期の診断・治療につなげるためにも理解を深めることが必要である.

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00525&link_issn=&doc_id=20230405130077&doc_link_id=10.34433%2Fog.0000000197&url=https%3A%2F%2Fdoi.org%2F10.34433%2Fog.0000000197&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：金原出版(株)  

＜文献概要＞医師の働き方改革関連法遵守に向けて様々な意見や提案があるが,国全体の考えとは別に地域ごとの現状を踏まえた方向性も探索し,実行に移していかなければ乗り越えることができないものと推測する。今回,筆者が暮らす北海道の現状ならびに産婦人科医療の推移と予測から,働き方改革の議論を契機とした今後目指していく北海道の産婦人科医療提供の姿を記述した。機能分化・連携,集約化・重点化の推進に関しては個々の医療機関レベルでの努力には限界があり,地域医療構想と連動した取り組みなどが重要である。産婦人科医師の増加,地域住民の意識改革が必要と考えられる。

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J00642&link_issn=&doc_id=20210415040100&doc_link_id=%2Fae4shond%2F2021%2F0084s1%2F101%2F0434-0437%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4shond%2F2021%2F0084s1%2F101%2F0434-0437%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：福井県産婦人科医会  

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記述言語：日本語   出版者・発行元：(一社)日本思春期学会  

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記述言語：日本語   出版者・発行元：北海道医師会  

北海道における平成30年間の産婦人科医療の経緯を解析し、令和10年頃の状況を予測した。北海道関連の人口統計資料、日本産科婦人科学会、日本産婦人科医会資料、北海道産婦人科医会、北海道産科婦人科学会名簿をもとにした。北海道の人口は2010年において550万人で人口減少が加速し、2018年度は529万人になっていた。国立社会保障・人口問題研究所推計では、2040年には419万人、2060年には308万人と予測されており、2030年度の出生数は2万人前後と推測され、分娩施設数も2030年度には60施設に減少するものと推測された。平成20年ころの北海道の出生数は4万人から平成30年は3万人と減少しており、さらに分娩施設数が減少(集約化)する反面、分娩施設に所属している医師数が256名から320名と増加していることから、医師一人当たりの分娩に対する負担量は軽減されている可能性があると考えられた。

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記述言語：日本語   出版者・発行元：(有)フジメディカル出版  

産婦人科領域のさまざまな疾患に対し漢方薬が用いられている。漢方薬が産婦人科臨床で多用されていることは、歓迎すべきことである。しかしながら、西洋薬に比べ漢方薬は作用や副作用が穏やかな印象がもたれており、副作用には注目が集まりにくい。けれども、漢方薬にも重大な副作用があり漫然と使用することは非常に危険であるため注視する必要がある。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J06513&link_issn=&doc_id=20180625140005&doc_link_id=%2Fal1wohef%2F2018%2F000502%2F006%2F0086-0091%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fal1wohef%2F2018%2F000502%2F006%2F0086-0091%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：産婦人科漢方研究会  

月経周期に合わせ周期的に増悪・寛解を繰り返す月経疹に対し、小青竜湯が奏功した1例を報告する。月経疹は、estrogen、progesteroneに対するアレルギー反応がその発症機序として想定されており、ホルモン分泌の変化に合わせ増悪・寛解を繰り返し、難治であることも少なくない。症例は29歳。19歳時に膨疹初発、その後も黄体期に全身性の紅色膨疹を周期的に生じるようになり副腎皮質ステロイドを定期内服していたが、呼吸苦を伴うほどに重症化して入院加療を要することもあった。小青竜湯内服開始後は内服ステロイドの減量が可能となり、重症化することなく経過している。月経疹の本態は、progesteroneやestrogenに対する自己抗体が産生されることで発症する自己免疫性蕁麻疹であると考えられている。一方、小青竜湯はchemical mediator遊離抑制作用などによりI型をはじめとするアレルギー反応を抑制するとの報告が多数あり、本症例も小青竜湯の抗アレルギー作用により月経疹が軽快したものと考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：産婦人科漢方研究会  

平成13年度「医学教育モデル・コア・カリキュラム」のガイドラインに基づき医学教育の現場で和漢薬に関する教育が導入され,漢方療法を卒前に学ぶ医療者が増えてきている.産婦人科領域においても漢方薬は頻用されており,当科では漢方を主体とした講義時間を設け,医学生に産婦人科の医療で使用する漢方薬の役割を教育している.これらの教育の影響もあり漢方療法に興味を抱く学生が増えている.彼らが,産婦人科領域で将来働いてもらうように教育の充実・活動の場を提供することは,私たち産婦人科医師の重要な仕事の一つと考える.しかしながら,漢方医学教育の課題の一つとして,教育者の不足が挙げられる.旭川医大においても教育者の不足,講義時間の確保など多数の問題を抱えており学外講師の応援や漢方診療に取り組む医師(他科も含めて)と協力しながら対応しているのが現状である.当大学の漢方関連の卒前教育状況,学生の意識調査結果ならびに当科における漢方関連の医学生との活動を報告する.(著者抄録)

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

漢方の観点からみると妊娠中は血虚や陰虚になりやすく、それに伴い様々な症状が出現する。これら妊娠中の諸症状に対し、西洋薬単独よりも漢方薬の使用もしくは併用で症状がさらに改善することはよく知られている。妊娠中に使用される漢方薬は、古典からもわかるように地道な臨床集積から有効性が認められ副作用の少ないものが現在まで残っている。今回、妊娠中の漢方治療について、おもな使用法と注意点を中心に記述する。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J00525&link_issn=&doc_id=20141031060009&doc_link_id=%2Fae4sanke%2F2014%2F008111%2F010%2F1347-1354%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fae4sanke%2F2014%2F008111%2F010%2F1347-1354%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本糖尿病・妊娠学会  

耐糖能異常合併妊娠では妊娠中の厳格な血糖コントロールにおいて、血糖値の目標下限値は70mg/dlとされているが、低血糖が母児へ与える影響については不明な点が多い。動物実験では妊娠初期の低血糖が胎児奇形や発育遅滞に影響するといった報告もある。今回われわれは、非妊娠時より低血糖発作を繰り返した症例で、2度の妊娠管理を経験した。症例は19歳ごろより空腹時の脱力感を自覚し、21歳で随時血糖値24mg/dlの低血糖発作を発見され、2007年1月当科紹介初診。低血糖の入院精査にて、インスリノーマや内分泌疾患などは否定し、75gブドウ糖負荷試験(OGTT)にて血糖値は0分値65mg/dl、60分値122mg/dl、120分値65mg/dlであり、インスリン値からも反応性低血糖症と診断した。αグルコシダーゼ阻害薬を開始したが、挙児希望のため内服を中止し、2007年10月(22歳)に第1子の妊娠判明。妊娠19週2日に食後血糖値66mg/dl、HbA1c 4.6%、40～50mg/dlの低血糖発作を繰り返しており、補食や分割食で対応していた。妊娠25週5日の75g OGTTでは0分値78mg/dl、60分値154mg/dl、120分値112mg/dl。5分割食として低血糖発作を予防し、妊娠40週1日で2420g、低出生体重児でSFD(small for date)の女児を出産。25歳時には第2子の妊娠判明、HbA1c 5.4%であり、妊娠初期から5分割食を指示し、重篤な低血糖発作はなく経過。妊娠37週4日で2754g、AFD(appropriate for date)の女児を出産。母体体重は第1子妊娠中には約11kg、第2子妊娠中には約8kgの増加であった。2児ともに奇形や明らかな新生児合併症はなく、その後の発育も順調である。本症例では、胎児発育に影響を与えるその他の要因を認めず、2回の異なる妊娠経過から、妊娠中の繰り返す低血糖は児の発育遅延に関係する可能性が考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2014&ichushi_jid=J03986&link_issn=&doc_id=20140905450025&doc_link_id=https%3A%2F%2Fasahikawa-med.repo.nii.ac.jp%2Frecords%2F5053&url=https%3A%2F%2Fasahikawa-med.repo.nii.ac.jp%2Frecords%2F5053&type=%E6%97%AD%E5%B7%9D%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%EF%BC%9A%E6%97%AD%E5%B7%9D%E5%8C%BB%E7%A7%91%E5%A4%A7%E5%AD%A6%E5%AD%A6%E8%A1%93%E6%88%90%E6%9E%9C%E3%83%AA%E3%83%9D%E3%82%B8%E3%83%88%E3%83%AA_AMCoR&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80003_3.gif

記述言語：日本語   出版者・発行元：日本更年期と加齢のヘルスケア学会((NPO)更年期と加齢のヘルスケア)  

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開催年月日： 2024年1月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年8月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年6月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2023年6月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2010年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京  

開催年月日： 2010年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：札幌  

開催年月日： 2010年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：鹿児島  

開催年月日： 2010年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：金澤  

開催年月日： 2010年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：富山  

開催年月日： 2009年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京  

開催年月日： 2008年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京  

開催年月日： 2006年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催年月日： 2006年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：京都  

開催年月日： 2006年8月

記述言語：日本語   会議種別：口頭発表（一般）