In Japan, the governmental recommnendation of HPV vaccine has been suspended since June 2013, due to media reports of alleged adverse vaccination events. Although evidence of effectiveness and safety ...of the HPV vaccine has been universally demonstrated, and the medical and academic organizations across Japan have requested the resumption of the government's recommendation, the Japanese government has not changed their official stance towards the HPV vaccine. Under the current suspension of the national government's recommendation, one local government Isumi City started sending a leaflet containing information of cervical cancer and HPV vaccine, but not recommendation for the vaccine, to the tagted girls born in the fiscal year (FY) 2003. The cumulative vaccination rate of them reached 10.07% (14/139), which was significantly higher than that (0.00%) for girls born in FY 2002 who did not receive such a leaflet (p < 0.001). We sincerely ask the national government to change their stance towards the HPV vaccine. We also strongly suggest that, in the meantime, local governments immediately begin to provide an appropriate information of cervical cancer and HPV vaccine to the targeted girls and their parents in a way similar to what Isumi City has now shown to be effective.
Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA ...sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using pairedend massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring.
Human papillomavirus (HPV) vaccine has been used to prevent chronic HPV infection, which accounts for cervical cancer. Japanese Ministry of Health, Labor and Welfare (MHLW) conducted an HPV ...vaccination campaign in 2010 and the Obstetrical Gynecological Society of Osaka initiated a multicenter, prospective cohort study in Osaka, Japan - OCEAN (Osaka Clinical resEArch of HPV vacciNe) study - to investigate the oncogenic HPV prevalence and the long-term protection rate of HPV vaccine. A total of 2814 participants were enrolled on their visit for HPV vaccination between 12 and 18 years old. Among them, 102 participants received HPV/Pap co-test as primary cancer screening at the age of 20-21. We compared the prevalence in two groups (the vaccinated and the unvaccinated group). HPV infection ratio was significantly lower in the vaccinated group compared to the unvaccinated (12.9% vs. 19.7%; p = .04). In particular, HPV 16 and 18 were not detected in the vaccinated group, while 4.9% of participants in the unvaccinated group were infected (p = .001), suggesting that vaccination provided effective protection against high-risk types of HPV. The cross-protection effect of HPV vaccines was also observed against HPV 31, 45, and 52. Although HPV vaccines were not contributed to the reduction of cervical intraepithelial neoplasia 1 (CIN) (p = .28), CIN2 or worse was not observed in vaccinated group. Our research showed that at the age of 20-21, HPV vaccine inhibited the infection of high-risk HPV and had impacted on the development to CIN2 or worse in Japan.
Women born between 1994 and 1999 achieved high vaccination rates for human papillomavirus (HPV); they are now reaching the age of cervical cancer screening programs in Japan. In this study, we aimed ...to investigate the health awareness of HPV-vaccinated and unvaccinated women and to create tailored leaflets recommending cervical cancer screening for each. Surveys on the cancer screening rates for HPV-vaccinated and unvaccinated women aged 20 and 21 have demonstrated that the rate was significantly higher (
< 0.01) in vaccinated (6.2%) than in unvaccinated women (3.1%). Next, interviews and Internet questionnaires clarified that there was a trend that vaccinated women have a better health consciousness than the unvaccinated ones, and that in unvaccinated women, their willingness to receive cervical cancer screening was significantly enhanced by the fear of developing cancer. Finally, in a prospective study, the increase in the screening rate for both vaccinated and unvaccinated groups after they read tailored leaflets, from 6.4% to 7.4% and from 3.9% to 5.1%, respectively, was not statistically significant compared to the groups provided with a standard reminder letter. Cervical cancer control measures might be enhanced by recommending cervical cancer screening in ways better tailored to HPV vaccination status.
Aim
The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and intervillous and decidual pathology in patients with pregnancy loss was investigated.
Methods
We ...performed a cross‐sectional study on 243 patients presenting with pregnancy loss for the degree of intervillous fibrin and thrombosis (IT), and decidual fibrin and thrombosis (DT) and determined their MTHFR C677T genotypes. Overall differences in age, body mass index (BMI), gravidity, parity, number of pregnancy losses and gestational period when the pathologic samples were obtained, also were determined.
Results
There were no significant differences in age, BMI, gravidity, parity, number of pregnancy losses and gestational period, relative to MTHFR C677T genotype (TT vs CT vs CC). There were significantly more T allele carriers and TT genotype patients among patients with severe IT (odds ratio OR 1.653, P = 0.033 and OR 2.246, P = 0.032, respectively) and those with severe IT and decidual thrombosis (OR 2.602, P = 0.012 and OR 3.375, P = 0.035, respectively). The CC genotype was protective against the four studied pathologic grades.
Conclusion
To our knowledge, this is the first study showing that the MTHFR C677T TT genotype and T allele are associated with severe intervillous and decidual pathologies in patients with pregnancy loss. Differences in pathologic grades of MTHFR C677T TT genotype could support the hypothesis that further periconceptional treatment for pregnancy loss could be customized depending on single nucleotide polymorphisms.
Placental mesenchymal dysplasia (PMD) is a rare placental vascular anomaly which resembles partial molar pregnancy by 2‐D ultrasonography. It is challenging but clinically important to distinguish ...between them in order to avoid unnecessary termination of pregnancy. A patient was referred to our centre at 13 weeks of gestation and 2‐D ultrasound of the placenta showed a widespread vesicular pattern mixed with normal appearing placenta. Amniotic fluid volume was normal, and the fetus appeared to be an appropriate size for gestation without obvious structural abnormalities. 3‐D reconstruction imaging of the placenta showed a large multi‐cystic area arising from the chorionic plate which was adjacent to normal‐appearing placenta. 3‐D imaging rendered with ‘inversion mode’ revealed multiple fluid‐filled structures with different sizes and appearances. Her serum hCG level was slightly elevated. All findings taken together, we suspected PMD rather than partial molar pregnancy. Histological examinations of the placenta after termination at 15 weeks confirmed the diagnosis.
Objective The objective of this study was to investigate the potential value of ADAM12 (A disintegrin and metalloprotease) in first-trimester screening for trisomy 21 and other major chromosomal ...abnormalities. Study Design The concentration of ADAM12 was measured at 11-13 weeks in cases of trisomy 21 (n = 49), trisomy 18 (n = 28), trisomy 13 (n = 20), Turner syndrome (n = 29), triploidy (n = 10), and euploid pregnancies (n = 272). The levels of ADAM12, expressed as multiples of median (MoM), were compared in cases and controls and were assessed for association with free β-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A). Results The median ADAM12 value in trisomy 21 (0.961 MoM) was not significantly different from the euploid fetuses (1.013 MoM), but in trisomy 18 (0.697 MoM), trisomy 13 (0.577 MoM), triploidy (0.426 MoM), and Turner syndrome (0.747 MoM), the levels were significantly lower. In both the euploid and aneuploid pregnancies, there was a significant association between ADAM12 and free β-hCG and PAPP-A. Conclusion Maternal serum ADAM12 concentration at 11-13 weeks of gestation is unlikely to be useful in first-trimester screening for chromosomal abnormalities because in trisomy 21 the levels are not significantly different from normal, and in the other chromosomal defects, there is a significant association between ADAM12 and the traditional biochemical markers of free β-hCG and PAPP-A.
Placenta growth factor (PlGF) is a placental angiogenic factor. Metal-responsive transcription factor (MTF)-1 was reported to take part in the hypoxic induction of PlGF in RAS-transformed mouse ...fibroblasts. We contrarily showed that PlGF mRNA and protein levels decreased under hypoxia in a choriocarcinoma BeWo cell line derived from trophoblast. In this report, we examined whether hypoxia-dependent regulation of the PlGF gene in these cells also depends on MTF-1. We analyzed the effect of hypoxia on MTF-1 expression, and it was revealed to be decreased. Moreover, MTF-1 small interfering RNA treatment decreased PlGF mRNA level. To investigate the transcription of PlGF under hypoxia, we cloned promoter region of the human PlGF. Promoter deletion analysis suggested that triple repeats of metal-responsive element located between −511 and −468 bp in the promoter are important for the hypoxic regulation of PlGF. Treatment with MTF-1 small interfering RNA resulted in the significant decreased luciferase activity in PlGF reporter constructs. Chromatin immunoprecipitation showed the binding of the MTF-1 protein to the promoter region. We examined MTF-1 immunoreactivity in trophoblasts of term placental tissue from patients with normal pregnancies and preeclampsia, which represents a condition of placental hypoxia. Immunoreactivity of the MTF-1 protein was decreased in placentas from pregnant women with preeclampsia when compared with those from normal pregnant women. Taken together, these findings suggest that MTF-1 is involved in hypoxia-dependent regulation of PlGF in trophoblast-derived cells.
Hypoxia down-regulates placenta growth factor via decreasing metal transcription factor-1 in trophoblast-derived BeWo cells.
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