BALB/c-Fcgr2b−/−Pdcd1−/− mouse expressing anti-urothelial antibody is a novel model of autoimmune cystitis

We report the impact of anti-urothelial autoantibody (AUAb) on urinary bladder phenotype in BALB/c mice deficient of the FcγRIIb and PD-1. AUAb was present in serum samples from approximately half of the double-knockout (DKO) mice, as detected by immunofluorescence and immunoblots for urothelial proteins including uroplakin IIIa. The AUAb-positive DKO mice showed degeneration of urothelial plaque and umbrella cells, along with infiltration of inflammatory cells in the suburothelial layer. TNFα and IL-1β were upregulated in the bladder and the urine of AUAb-positive DKO mice. Voiding behavior of mice was analyzed by the Voided Stain on Paper method. 10-week-old and older AUAb-positive DKO mice voided significantly less urine per void than did wild type (WT) mice. Furthermore, administration of the AUAb-containing serum to WT mice significantly reduced their urine volume per void. In summary, this report presents a novel comprehensive mouse model of autoimmune cystitis

Xenoantigen, an αGal epitope-expression construct driven by the hTERT-promoter, specifically kills human pancreatic cancer cell line

BACKGROUND: We previously reported the usefulness of the αGal epitope as a target molecule for gene therapy against cancer. To induce cancer cell specific transcription of the αGal epitope, an expression vector which synthesizes the αGal epitope under the control of a promoter region of the human telomerase reverse transcriptase (hTERT), NK7, was constructed. METHODS: NK7 was transfected into a human pancreatic carcinoma cell line, MIA cells, and telomerase-negative SUSM-1 cells served controls. Expression of the αGal epitope was confirmed by flow cytometry using IB4 lectin. The susceptibility of transfected MIA cells to human natural antibodies, was examined using a complement-dependent cytotoxic cross-match test (CDC) and a flow cytometry using annexin V. RESULTS: The αGal epitope expression was detected only on the cell surfaces of NK7-transfected MIA cells, i.e., not on naive MIA cells or telomerase negative SUSM-1 cells. The CDC results indicated that MIA cells transfected with NK7 are susceptible to human natural antibody-mediated cell killing, and the differences, as compared to NK-7 transfected telomerase negative SUSM-1 cells or telomerase positive naïve MIA cells, were statistically significant. The flow cytometry using annexin V showed a higher number of the apoptotic cells in NK-7 transfected MIA cells than in naïve MIA cells. CONCLUSIONS: The results suggest that αGal epitope-expression, under the control of the hTERT-promoter, may be useful in cancer specific gene therapy

Change of Bone Mechanical Strength in Rats after Spinal Cord Injury over a Short Term

This study investigated the time-course of changes in bone mechanical strength in rats with spinal cord injury (SCI). Sixty-four male Wistar rats underwent spinal cord transection at the thoracic nerve. Control rats underwent a sham procedure (SHAM). Animals were sacrificed at day 1, 4, 7 and 14 after operation. The mechanical strength of the left femur and tibia was measured by the three-point bending strength test. The bones were dried, weighed and burned to ash. A specimen of right tibia was prepared and examined under a microscope. Bone mechanical strength, dry bone weight, and ash content of the femur and tibia in SCI rats were significantly lower than those in SHAM animals. Dry bone weight and ash content began to decrease from the 4th day after SCI and reached their lowest at day 7 after operation. Bone mechanical strength had reduced significantly by the 14th day. Gaps and spaces were observed in the trabecular area at the same time. After SCI, calcified cartilage decreased and the reduction of bone mass occurred rapidly. Moreover, a decline of bone mechanical strength is caused within 2 weeks. Thus, SCI led to the atrophy of bone and caused the reduction of mechanical strength at an early stage. It is thus necessary to prevent bone loss after SCI immediately

Obstructive azoospermia as an unusual complication associated with herniorrhaphy of an omphalocele: a case report

<p>Abstract</p> <p>Introduction</p> <p>Iatrogenic damage to the seminal tract is one of the causes of obstructive azoospermia, which can be an indication for reconstruction surgery. We present a case of obstructive azoospermia as an unusual complication after neonatal herniorrhaphy of an omphalocele.</p> <p>Case presentation</p> <p>A 30-year-old Japanese man was diagnosed with obstructive azoospermia. He had undergone herniorrhaphy of an omphalocele immediately after birth. Reconstruction surgery of both seminal tracts was performed to pursue the possibility of naturally achieved pregnancy. Intra-operative findings demonstrated that both vasa deferentia were interrupted at the internal inguinal rings, although the abdominal end of the right vas leading to the seminal vesicle was found in the abdominal cavity. The discharge from the stump of the testicular end had no sperm, although the right epididymal tubules were dilated with motile sperm. Therefore, we performed right-sided vasovasostomy in the internal inguinal ring and ipsilateral epididymovasostomy simultaneously.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first report describing obstructive azoospermia as an unusual complication of herniorrhaphy of an omphalocele. It is important to pay attention to the existence of seminal tracts in such surgery as well as in inguinal herniorrhaphy.</p

Assessment of energy expenditure using doubly labeled water, physical activity by accelerometer and reported dietary intake in Japanese men with type 2 diabetes: A preliminary study

The aim of the present study was to determine the total energy expenditure, physical activity and dietary intake of men with type 2 diabetes mellitus and control participants without type 2 diabetes mellitus who were matched for age and body mass index. The participants in the present study were 12 well‐controlled type 2 diabetes mellitus patients and 10 controls, aged 40–75 years, with a body mass index <30 kg/m2. Total energy expenditure under free‐living conditions was assessed using the doubly labeled water method, and physical activity was measured using a triaxial accelerometer. Dietary intake was assessed using a self‐recorded food intake diary during the measurement period. Participants were instructed to record their dietary intake over 3 days, including 2 weekdays. Total energy expenditure was not significantly different between the groups (P = 0.153), nor were energy (P = 0.969) or macronutrient intakes. In conclusion, when age and body mass index are matched, total energy expenditure and self‐reported energy intake are not significantly different between type 2 diabetes mellitus patients and healthy controls

Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity

BACKGROUND: Recently, the concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged. Chronic uterine inflammation is a known cause of implantation failure and is associated with high matrix metalloproteinase (MMP) activity in uterine cavity flushing. MMP activity of women with RIF has been reported to be higher than that of fertile women. In the present retrospective study we evaluated the efficacy of treatment for high MMP activity in the uterine cavity of patients with RIF. METHODS: Of the 597 patients recruited to the study, 360 patients underwent MMP measurements and 237 patients did not (control group). All patients had failed to become pregnant, despite at least two transfers of good-quality embryos. Gelatinase MMP-2 and MMP-9 activity in uterine flushing fluid was detected by enzymology (MMP test). All samples were classified into two groups (positive or negative) based on the intensity of the bands on the enzyme zymogram, which represents the degree of MMP activity. Patients who tested positive on the initial test were treated for 2 weeks with a quinolone antibiotic and a corticosteroid, and subsequently underwent a second MMP test. Negative results on the second MMP tests after treatment and subsequent rates of pregnancy and miscarriage were used to evaluate the efficacy of treatment. Data were analyzed by the Mann–Whitney U-test and the chi-square test. RESULTS: Of the patients who underwent the MMP test, 15.6% had positive results (high MMP activity). After treatment, 89.3% of patients had negative results on the second MMP test. These patients had a significantly better pregnancy rate (42.0%) than the control group (26.6%), as well as a lower miscarriage rate (28.5% vs 36.5%, respectively). CONCLUSIONS: A 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity

大型核融合試験施設におけるメガワットミリ波ジャイロトロン発振器周辺の電磁環境調査

将来のエネルギー源として開発が進められている磁場閉じ込め方式の核融合研究では，高温プラズマの生成や制御，プラズマ加熱及び計測のために大電力高周波発振機器が利用されている．本論文では，核融合科学研究所の大型ヘリカル装置で使用されているメガワットミリ波ジャイロトロン発振器(周波数: 77 GHz，最大出力: 1～1.5 MW/2秒)を対象とし，作業従事者の安全管理を目的に，ホーンアンテナを用いて機器周辺での電磁環境を定点調査した．その結果，77 GHz発振器からおよそ30 m離れた場所で観測された漏洩電界の周波数は，77 GHzが最も強く，そこから数GHz離れた両側の周波数領域にも微弱なスプリアススペクトルが確認された．また，同じ場所で，数十秒から数百秒の発振運転に伴う漏洩電界(最大実効値: 数V/m)が観測された．電界の漏洩箇所は，ジャイロトロン発振器を構成する接地電位の電子ビームコレクターと，その他の部位とを電気的に絶縁するために具備された窒化ケイ素製絶縁部と推定された．本研究により，大型核融合試験施設におけるメガワットジャイロトロン発振器周辺のミリ波帯での漏洩電界の実態を初めて明らかにした

Development and validation of prediction model for incident overactive bladder: The Nagahama study.

OBJECTIVES We aimed to develop models to predict new-onset overactive bladder in 5 years using a large prospective cohort of the general population. METHODS This is a secondary analysis of a longitudinal cohort study in Japan. The baseline characteristics were measured between 2008 and 2010, with follow-ups every 5 years. We included subjects without overactive bladder at baseline and with follow-up data 5 years later. Overactive bladder was assessed using the overactive bladder symptom score. Baseline characteristics (demographics, health behaviors, comorbidities, and overactive bladder symptom scores) and blood test data were included as predictors. We developed two competing prediction models for each sex based on logistic regression with penalized likelihood (LASSO). We chose the best model separately for men and women after evaluating models' performance in terms of discrimination and calibration using an internal validation via 200 bootstrap resamples and a temporal validation. RESULTS We analyzed 7218 participants (male: 2238, female: 4980). The median age was 60 and 55 years, and the number of new-onset overactive bladder was 223 (10.0%) and 288 (5.8%) per 5 years in males and females, respectively. The in-sample estimates for C-statistic, calibration intercept, and slope for the best performing models were 0.77 (95% confidence interval 0.74-0.80), 0.28 and 1.15 for males, and 0.77 (95% confidence interval 0.74-0.80), 0.20 and 1.08 for females. Internal and temporal validation gave broadly similar estimates of performance, indicating low optimism. CONCLUSION We developed risk prediction models for new-onset overactive bladder among men and women with good predictive ability

COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naïve major depressive disorder: a diffusion tensor imaging study

We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, and white matter changes in patients with major depressive disorder (MDD) and healthy subjects using diffusion tensor imaging (DTI). We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years) and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years). Using DTI analysis with a tract-based spatial statistics (TBSS) approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects). In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05). No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association between the COMT gene Val158Met and the white matter abnormalities found in the temporal lobe of patients with MDD