Unmutated Immunoglobulin M Can Protect Mice from Death by Influenza Virus Infection

To elucidate the role of class switch recombination (CSR) and somatic hypermutation (SHM) in virus infection, we have investigated the influence of the primary and secondary infections of influenza virus on mice deficient of activation-induced cytidine deaminase (AID), which is absolutely required for CSR and SHM. In the primary infection, AID deficiency caused no significant difference in mortality but did cause difference in morbidity. In the secondary infection with a lethal dose of influenza virus, both AID−/− and AID+/− mice survived completely. However, AID−/− mice could not completely block replication of the virus and their body weights decreased severely whereas AID+/− mice showed almost complete prevention from the reinfection. Depletion of CD8+ T cells by administration of an anti-CD8 monoclonal antibody caused slightly severer body weight loss but did not alter the survival rate of AID−/− mice in secondary infection. These results indicate that unmutated immunoglobulin (Ig)M alone is capable of protecting mice from death upon primary and secondary infections. Because the titers of virus-neutralizing antibodies were comparable between AID−/− and AID+/− mice at the time of the secondary infection, a defect of AID−/− mice in protection of morbidity might be due to the absence of either other Ig classes such as IgG, high affinity antibodies with SHM, or both

Plasma Oxytocin Concentrations During and After Gestation in Japanese Pregnant Women Affected by Anxiety Disorder and Endometriosis

[Background] Oxytocin has a key role in mother-infant bonding, maternal care, social interaction, and stress-related psychiatric disorders. However, the factors determining oxytocin concentrations during and after pregnancy such as medical history related to nursing or parental behavior are unknown. To elucidate these, we analyzed the relationships between oxytocin concentrations during and after pregnancy, and medical history assessed in the Japan Environment and Children’s Study (JECS). [Methods] We then selected the pregnant women with a medical history of anxiety disorder and endometriosis as cases and pregnant women without medical history as controls adjusting the cohort for age and parity for a nested case-control study, after which 162 women remained for analysis. We evaluated 162 pregnant women from JECS using answers provided in a questionnaire and by measuring plasma oxytocin concentration by ELISA during the first (T1) and second (T2) trimesters of pregnancy, and after childbirth (T3). [Results] Oxytocin concentration increased in a time dependent manner, consistent with previous reports. There were weak negative correlations between oxytocin concentration at T1 and the mother’s age and height, but no correlation with other factors. The mean oxytocin concentrations of pregnant women with a history of an anxiety disorder (n = 7) and endometriosis (n = 13) were significantly lower than those of pregnant women with no such history at T2 and T3. [Conclusion] These results suggest that oxytocin concentrations during and after pregnancy were affected by a past history of anxiety disorder and endometriosis. This is the first study of the relationship between oxytocin concentration and endometriosis. To elucidate the molecular mechanisms, further study is needed

A Case Report of an Accessory and Cavitated Uterine Mass Treated with Total Laparoscopic Hysterectomy

Accessory and Cavitated Uterine Mass (ACUM) is a condition defined by the presence of a non-communicating uterine mass close to the insertion of the round ligament. ACUM is a rare M?llerian anomaly found in young women and is diagnosed by the presents of a central cavity in the uterus, lined by functional endometrium, and surrounded by a ring of smooth muscle. In most cases, surgical treatment is recommended due to severe dysmenorrhea. Herein, we present a case of a woman with severe dysmenorrhea since adolescence which was not relieved with any form of hormonal treatment. ACUM was suspected preoperatively based on MRI findings, and she was treated with total laparoscopic hysterectomy. A uterine mass was found at the insertion of the right round ligament during surgery. All her symptoms improved after resection

Schizencephaly and Porencephaly Due to Fetal Intracranial Hemorrhage: A Report of Two Cases

Schizencephaly and porencephaly are extremely rare types of cortical dysplasia. Case 1: Prenatal magnetic resonance imaging (MRI) showed wide clefts in the frontal and parietal lobes bilaterally. On postnatal day 3, MRI T2-weighted images showed multiple hypointensities in the clefts and ventricular walls, suggestive of hemosiderosis secondary to intracranial hemorrhage. Case 2: Prenatal MRI showed bilateral cleft and cyst formation in the fetal cerebrum, as well as calcification and hemosiderosis indicative of past hemorrhage. T2-weighted images showed hypointensities in the same regions as the calcification, corresponding with hemosiderosis due to intracranial hemorrhage on postnatal day 10. Thus, prenatal MRI was useful for diagnosing schizencephaly and porencephaly. Schizencephaly and porencephaly were thought to be due to fetal intracranial hemorrhage, which, in the porencephaly case, may have been related to a mutation of COL4A1

Comparison of Total Laparoscopic Hysterectomy with Abdominal Total Hysterectomy in Patients with Benign Disease: A Retrospective Cohort Study

Background: The present study aimed to determine whether total laparoscopic hysterectomy (TLH) is being implemented safely and appropriately compared with abdominal total hysterectomy (ATH) in our hospital. Methods: We retrospectively reviewed clinical records of 102 patients who underwent total hysterectomy for benign gynecological disease at Japanese Red Cross Yamaguchi Hospital from January 2017 to August 2018. We examined periods of hospital stay, operation time, blood loss, weight of the uterus, frequency of perioperative complications, and the duration from the first visit to the date of surgery. P < 0.05 was considered to be statistically significant indicated statistical significance. Results: TLH and ATH were performed in 55 (53%) and 47 (46%) cases, respectively. The TLH group had significantly longer total operation time [133 (82-205) min vs. 87 (57-155) min, P < 0.0001], lesser blood loss [5 (5-35) g vs. 100 (10-820) g, P < 0.0001], shorter hospital stay [7 (5-14) days vs. 10 (9-26) days, P < 0.0001], and lighter uterine weight [206 (27-658) g vs. 554 (79-2284) g, P < 0.0001] than the ATH group. The frequency of perioperative complications did not differ between the two groups (3.5% vs. 8.0%, P = 0.4103). Conclusion: TLH had a longer operation time and a lesser excised uterine weight, but it had less intraoperative blood loss, shorter hospital stay, and no difference in perioperative complication frequency when compared with ATH

Is Adjuvant Chemotherapy Necessary in Patients with Early Endometrial Cancer?

Background: We investigated whether there was a difference in prognosis between patients with stage IA endometrial cancer with and without lymphovascular space invasion. Methods: We enrolled patients with stage IA (pT1aN0M0) endometrial cancer admitted to our hospital from 2009 to 2018. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy. We immunopathologically evaluated the presence or absence of lymphovascular space invasion in the tumor tissue using hematoxylin and eosin, Elastica-van Gieson, and podoplanin staining. We analyzed disease-free and overall survival and calculated patients’ survival distribution using the Kaplan–Meier method and log-rank test. The multivariate analysis was performed to determine the prognostic factors. Results: A total of 116 patients were included. The median age of the patients was 57 (range, 30–78) years, and the histological subtype revealed 98 and 18 cases of types 1 and 2, respectively. The median follow-up period was 71.9 (range, 10.8–149) months, and the 3-year disease-free and 3-year overall survival rates were 94% and 99%, respectively. The disease-free and overall survival rates were significantly shorter in type 2 patients than in type 1 patients (type 2 vs. type 1; 77% vs. 97%, P < 0.01, 94% vs. 100%, P = 0.014, respectively). The univariate and multivariate analyses showed that there were no significant differences in disease-free survival between the lymphovascular space invasion-positive and -negative groups among type 1 cases. Conclusion: There was no difference in prognosis between patients with stage IA and type 1 endometrial cancer with and without lymphovascular space invasion

Efficacy of Norethisterone in Patients with Ovarian Endometrioma

Endometriosis is a chronic inflammatory disorder associated with pelvic pain and infertility. Because surgical and medical therapies control symptoms, but it is hard to cure completely endometriosis, long term of pharmacologic management is necessary. Norethisterone (NET), one of progestins, has safety profile and advantage that allow long-term use. In this preliminary report, we showed the efficacy of NET in 6 patients with endometriosis. The size of ovarian endometrioma was decreased after treatment with NET for 6 months, and all patients were relieved from dysmenorrhea pain within 6 months, suggesting that NET would be a suitable medication to treat endometriosis

Endometrial Cancer Arising in Adenomyosis That Could Not Be Diagnosed by Endometrial Biopsy: A Case Report

Uterine adenomyosis is an estrogen-dependent tumor and one of the most common benign diseases in sexually mature women. The frequency of endometrial cancer associated with adenomyosis has been reported to be 18%–66%. On the other hand, endometrial cancer arising in adenomyosis (EC-AIA) is extremely rare. EC-AIA is now considered a different entity from and has a worse prognosis than endometrial cancer with adenomyosis (EC-A). In the present study, we report a case of endometrial cancer with adenomyosis in which endometrial biopsy failed to provide a definitive diagnosis. A 63-year-old female patient presented with endometrial thickening. Endometrial cytology was positive, and magnetic resonance imaging (MRI) showed small lesions suggestive of endometrial cancer with shallow invasion and adenomyosis. However, an endometrial biopsy showed only metaplasia, and careful follow-up was initiated. Subsequent endometrial cytology showed enlarged and round nuclei, uniform chromatin distribution, no thickening of nuclear margins, and abundant cytoplasm appearing in a sheet-like arrangement, suggesting atypical cells of endometrial glands with metaplasia. Three suspicious positive results and one positive result were observed, but repeated biopsies did not lead to the diagnosis of malignancy. The patient underwent diagnostic hysterectomy 19 months after the initial visit. The postoperative histopathological diagnosis was stage IA endometrial cancer (endometrioid carcinoma G1). This case of endometrial cancer associated with adenomyosis was difficult to diagnose. Our findings demonstrate that EC-AIA should be considered even if no lesions were detected by endometrial biopsy

SR-16234, a Novel Selective Estrogen Receptor Modulator for Pain Symptoms with Endometriosis: An Open-label Clinical Trial

[Background]SR-16234 is a selective estrogen receptor modulator (SERM) structurally different from approved SERM and has been reported to have estrogen receptor (ER) α antagonistic activity and strong affinity with a weak partial agonistic activity to ERβ receptor. SR-16234 showed strong inhibitory effects on transplanted endometrial cysts in the endometriosis model of rat and mouse. In this clinical trial, efficacy and safety of SR-16234 have been evaluated in endometriosis patients. [Methods]This trial was an open-label single arm clinical trial. Ten patients with dysmenorrhea and pelvic pain associated with endometriosis and adenomyosis were enrolled in this trial, and received 40 mg of SR-16234 once daily for 12 weeks. The primary endpoint was the visual analogue scale (VAS) of pelvic pain. The secondary endpoints included dysmenorrhea score, pelvic pain score, objective observations (stiffness of Douglas’ pouch, limitation of uterine movement, size of ovarian chocolate cysts, thickness of endometrium, and serum CA125 concentration) and safety. [Results]After oral administration of SR-16234 40 mg for 12 weeks, there were statistically significant decreases in pelvic pain VAS, total pelvic pain score, total dysmenorrhea score, stiffness of Douglas’ pouch, limitation of uterine movement compared with the baseline values. [Conclusion]The present trial suggested that a selective estrogen receptor modulator could be used for treatment of pain associated with endometriosis for the first time