Antibody responses after BNT162b2 vaccination in Japanese geriatric intermediate care facilities.

Background: To evaluate antibody responses against the primary series of vaccination of severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2] vaccines in the staff and residents of Japanese geriatric intermediate care facilities. Methods: All subjects (159 staff and 96 residents) received two doses of the BNT162b2 mRNA vaccine 3 weeks apart. Baseline data of subject were collected using a structured form. Serum samples were collected three times: before vaccination, 3 weeks after the first dose, and 4 weeks after the second dose, and anti-receptor binding domain of the spike protein of SARS-CoV-2 [anti-RBD] IgG was measured using two immunoassays. Results: After the second dose, geometric mean titers [GMT] of anti-RBD with both the Abbott and Roche assay were significantly lower in residents than staff (2282 AU/mL vs. 8505 AU/mL, and 258 U/mL vs. 948 U/mL, respectively). Multivariate analysis of characteristics affecting antibody responses (≥1280 AU/mL for Abbott and > 210 U/mL for Roche) showed lower odds ratios [ORs] for older age (adjusted OR per 10 year increase [aOR] = 0.62, 95 % confidence interval [95 %CI]; 0.38-1.02), steroid usage (aOR = 0.09, 95 %CI; 0.01-0.60) and regular nonsteroidal anti-inflammatory drugs [NSAIDs] usage (aOR = 0.16, 95 %CI; 0.03-0.88). Conclusions: Elderly people and steroid and NSAID users had lower antibody responses following the second vaccine dose.

Hypertensive disorders of pregnancy by oocyte donation pregnancy in Japanese women aged 40 years or older: a single-center retrospective cohort study.

This study aimed to examine the incidence of hypertensive disorders of pregnancy (HDP) among Japanese women with oocyte donation pregnancy (ODP) aged 40 years or older and estimate whether the women with ODP were more likely to develop HDP than those with autologous oocyte pregnancy (AOP) and spontaneous pregnancy (SP). In our study (N = 1361), the proportions of women who developed HDP were 20.5%, 12.8%, and 7.6% for ODP, AOP, and SP, respectively. After adjustment of covariables, the women with ODP were more likely to develop HDP than those with AOP or SP.

Management of the occiput posterior presentation: a single institute experience.

AIM: We have examined the risk factors and management processes of the persistent occiput posterior (pOP) position by analyzing medical records from our hospital. MATERIAL AND METHODS: Medical records and delivery notes from January 2007 to December 2009 were reviewed and 103 patients were identified as having the pOP position during active labor. A total of 1054 patients who had occiput anterior (OA) deliveries were used as control. RESULTS: There was no significant difference in population background between the pOP and control groups. Fifty-eight (56%) cases of pOP were identified before the birth of the fetal head whereas 45 were found to be in pOP at the birth. Among these cases identified as pOP before the birth, 30 (52%) patients underwent an attempt to rotate pOP to OA manually. A total of 14 (47%) attempts were successful and delivered OA vaginally. Of 16 cases whose attempts failed, five (31%) had cesarean delivery and 11 had vaginal OP delivery. The overall cesarean rate in this group was 16.7%. Twenty-eight patients who did not have any corrective intervention had a significantly higher rate of cesarean section (60.7%, P<0.001 by χ(2) analysis). The advanced head station and the wider dilatation resulted in a successful manual rotation. CONCLUSIONS: Attempts to correct pOP by manual rotation have better results when the head is in the mid-pelvis. Also, posture change reduces cesarean section rate. The current data suggest attempts to correct pOP to OA reduce cesarean section rate.

Clinical management and outcome of pregnancies complicated by previous abruption.

OBJECTIVES: We studied the clinical management and prognosis of pregnant women with a history of abruption, as well as the associated risk factors. METHODS: We reviewed the cases of 23 patients with a history of abruption and 66 patients with abruption. RESULTS: The recurrence rate of abruption was 4.3%. Intentional care prolonged gestational age in most patients. Although the incidence of abruption was low (0.44%), the consequences could be perinatal death and maternal disseminated vascular coagulation (DIC). CONCLUSION: To prevent abruption recurrence, careful monitoring during hospitalization is important. Both clinical findings and transabdominal echography are useful in diagnosing abruption.

Evidence-based guidelines for treatment of cervical cancer in Japan: Japan Society of Gynecologic Oncology (JSGO) 2007 edition.

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.

Sequential changes in genome-wide DNA methylation status during adipocyte differentiation.

DNA methylation is an epigenetic mark on the mammalian genome. There are numerous tissue-dependent and differentially methylated regions (T-DMRs) in the unique sequences distributed throughout the genome. To determine the epigenetic changes during adipocyte differentiation, we investigated the sequential changes in DNA methylation status of 3T3-L1 cells at the growing, confluent, postconfluent and mature adipocyte cell stages. Treatment of 3T3-L1 cells with 5-aza-2'-deoxycytidine inhibited differentiation in a stage-dependent manner, supporting the idea that formation of accurate DNA methylation profile, consisting of methylated and unmethylated T-DMRs, may be involved in differentiation. Analysis by methylation-sensitive quantitative real-time PCR of the 65 known T-DMRs which contain NotI sites detected 8 methylations that changed during differentiation, and the changes in the patterns of these methylations were diverse, confirming that the differentiation process involves epigenetic alteration at the T-DMRs. Intriguingly, the dynamics of the methylation change vary depending on the T-DMRs and differentiation stages. Restriction landmark genomic scanning detected 32 novel T-DMRs, demonstrating that differentiation of 3T3-L1 cells involves genome-wide epigenetic changes by temporal methylation/demethylation, in addition to maintenance of a static methylated/demethylated state, and both depend on differentiation stage.

Cell type-specific methylation profiles occurring disproportionately in CpG-less regions that delineate developmental similarity.

Our previous studies using restriction landmark genomic scanning (RLGS) defined tissue- or cell-specific DNA methylation profiles. It remains to be determined whether the DNA sequence compositions in the genomic contexts of the NotI loci tested by RLGS influence their tendency to change with differentiation. We carried out 3834 methylation measurements consisting of 213 NotI loci in the mouse genome in 18 different tissues and cell types, using quantitative real-time PCR based on a Virtual image rlgs database. Loci were categorized as CpG islands or other, and as unique or repetitive sequences, each category being associated with a variety of methylation categories. Strikingly, the tissue-dependently and differentially methylated regions (T-DMRs) were disproportionately distributed in the non-CpG island loci. These loci were located not only in 5'-upstream regions of genes but also in intronic and non-genic regions. Hierarchical clustering of the methylation profiles could be used to define developmental similarity and cellular phenotypes. The results show that distinctive tissue- and cell type-specific methylation profiles by RLGS occur mostly at NotI sites located at non-CpG island sequences, which delineate developmental similarity of different cell types. The finding indicates the power of NotI methylation profiles in evaluating the relatedness of different cell types.

[A case of advanced clear cell carcinoma of the endometrium that responded remarkably to neoadjuvant chemotherapy of combination carboplatin plus weekly paclitaxel].

Clear cell carcinoma of the endometrium is a very rare and highly malignant neoplasm that accounts for less than 5% of endometrial carcinoma. Survival of patients in the advanced stage is poor, and the treatment of choice is not clear. We report the case of a 62-year-old woman who had Stage IVb advanced clear cell carcinoma of the endometrium with multiple lung metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy of combination carboplatin (CBDCA) (AUC 5, day 1) plus weekly paclitaxel (PTX) (70 mg/m(2), day 1, 8, 15). After 3 courses of chemotherapy, the uterine tumor was obviously reduced, and lung metastases had disappeared. Therefore, she underwent the operation. The current case suggests that combination CBDCA plus weekly PTX is effective against advanced clear cell carcinoma of the endometrium.

Estradiol-induced ezrin overexpression in ovarian cancer: a new signaling domain for estrogen.

We have for the first time exposed estrogen's role in the epithelial ovarian cancer (OVCA) metastatic cascade and discovered that it is related to the induction of ezrin over-expression. 17beta Estradiol (E2) was administered to SKOV3 (ERalpha>beta) and DOV13 (ERalpha

[A case of synchronous double cancer responding to UFT--dermoid cyst with secondary malignant transformation and uterine endometrial adenocarcinoma].

We report here a case of synchronous dermoid cyst with secondary malignant tumor and uterine endometrial adenocarcinoma that responded to UFT. A 35-year-old female complained of abdominal fullness and visited our hospital. She had an abdominal mass which was newborn-head size. We performed right salpingo-oophorectomy and partial omentectomy. The pathological findings were dermoid cyst with secondary malignant transformation. After the operation she had underwent cyclic chemotherapy with CDDP, CPA, THP and 5-FU. After three cycles of chemotherapy, a uterine recurrence was suspected from her uterine endocervical smear test. Then we performed a second operation, but radical surgery was impossible due to the presence of multiple metastases to pelvic lymph nodes. The pathological findings were primary uterine endometrial adenocarcinoma, not metastasis from dermoid cyst with secondary malignant tumor. After the second operation, she was treated with oral UFT (400 mg/day), as she refused chemotherapy and radiotherapy. Two months after the start of UFT, the tumor markers were reduced remarkably, and the patient maintained good QOL throughout the treatment without serious adverse events. We conclude that UFT might be benefical in the treatment of advanced gynecologic cancer.

Arabidopsis Cys2/His2-type zinc-finger proteins function as transcription repressors under drought, cold, and high-salinity stress conditions.

ZPT2-related proteins that have two canonical Cys-2/His-2-type zinc-finger motifs in their molecules are members of a family of plant transcription factors. To characterize the role of this type of protein, we analyzed the function of Arabidopsis L. Heynh. genes encoding four different ZPT2-related proteins (AZF1, AZF2, AZF3, and STZ). Gel-shift analysis showed that the AZFs and STZ bind to A(G/C)T repeats within an EP2 sequence, known as a target sequence of some petunia (Petunia hybrida) ZPT2 proteins. Transient expression analysis using synthetic green fluorescent protein fusion genes indicated that the AZFs and STZ are preferentially localized to the nucleus. These four ZPT2-related proteins were shown to act as transcriptional repressors that down-regulate the transactivation activity of other transcription factors. RNA gel-blot analysis showed that expression of AZF2 and STZ was strongly induced by dehydration, high-salt and cold stresses, and abscisic acid treatment. Histochemical analysis of beta-glucuronidase activities driven by the AZF2 or STZ promoters revealed that both genes are induced in leaves rather than roots of rosette plants by the stresses. Transgenic Arabidopsis overexpressing STZ showed growth retardation and tolerance to drought stress. These results suggest that AZF2 and STZ function as transcriptional repressors to increase stress tolerance following growth retardation.

[Concurrent weekly nedaplatin-based radiotherapy for high risk, recurrent and advanced cervical cancer].

Advanced cervical cancer has been predominantly treated with a combination of external beam and brachytherapy in Japan. Recent studies suggest concurrent use of cisplatin and radiation treatment has superior disease control to radiation only treatment. We have conducted a phase I pilot study of concurrent use of weekly nedaplatin (30 mg/m2) and sequential external beam and brachytherapy in advanced stage or recurrent uterine cervical cancer patients (n = 6). All patients completed the treatment without serious complications. Five patients had complete responses and one a partial response. The average AUC of nedaplatin after one administration was 5.0 micrograms/ml.hr. The therapeutic index was 2. We concluded that concurrent use of weekly nedaplatin and radiation is well tolerated by Japanese women, and may well be an excellent therapeutic modality for selected cases of advanced or recurrent cervical cancer.

Ezrin, a membrane-cytoskeletal linking protein, is highly expressed in atypical endometrial hyperplasia and uterine endometrioid adenocarcinoma.

We previously demonstrated that ezrin transcription was required for in vitro invasion and was involved in the acquisition of metastatic potential in endometrial cancer cells. In order to determine the functional role of ezrin in endometrial cancer, we examined ezrin protein expression in 20 cancerous and 33 non-cancerous tissues by immunohistochemistry and Western blot analysis. The specimens included 20 uterine endometrioid adenocarcinomas (UEC), seven simple endometrial hyperplasias (sH), seven complex endometrial hyperplasias (cH), seven atypical endometrial hyperplasias (aH), and 12 samples of normal endometrium (NE). Tissues of primary (P) and metastatic (M) lesions of endometrial cancers were obtained from five patients. Ezrin was specifically expressed in UEC and its precursor lesions. Ezrin expression was significantly higher in aH (P<0.05) and UEC (P<0.001) compared with NE, sH, and cH. In addition, ezrin was significantly highly expressed in M compared with P (P<0.05). Ezrin expression was associated with neither clinical stage nor histopathologic grade of UEC. In immunohistochemistry, ezrin was localized in the membrane of metastasized cancer cells, although ezrin was mainly distributed in the cytoplasm of most cancer cells and some endometrial hyperplastic cells. On Western blot analysis, ezrin was also detected in both cytosolic and membrane fractions in aH and UEC, whereas ezrin was detected in only cytosolic fraction in sH and cH. These data suggest that expression and subcellular distribution of ezrin protein play an important role in development and progression of UEC.

[A case of advanced ovarian carcinosarcoma that responded remarkably to neoadjuvant chemotherapy of combined CPT-11 and CDDP].

Carcinosarcoma of the ovary is a very rare and highly malignant neoplasm that accounts for less than 1% of ovarian neoplasms. Survival of patients with advanced stage cancer is poor and the best treatment is not clear. We report the case of a 60-year-old woman who had Stage IV advanced heterogeneous ovarian carcinosarcoma with lung and liver metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy of combination CPT-11 (60 mg/m2, day 1, 15) and CDDP (60 mg/m2, day 1). Tumor markers of CA125 and LDH decreased remarkably to the normal level after 3 and 4 courses of chemotherapy, respectively. After 7 courses of chemotherapy, the ovarian tumor was obviously reduced, and the lung and liver metastases had disappeared. The patient was then able to undergo surgery. The current case suggests that combination CPT-11 and CDDP is effective against advanced ovarian carcinosarcoma.