Long-term single cell bioluminescence imaging with C-3 position protected coelenterazine analogues.

Bioluminescence is a powerful imaging modality for monitoring biological phenomena both in vitro and in vivo. Bioluminescence imagin (BLI) is becoming a seamless imaging technology covering the range from cells to organs of small animals. Long-term imaging at the single cell level would lead to a true understanding of the dynamics of life phenomena. This work presents a long-term single cell bioluminescence imaging technology accomplished with C-3 position protected furimazines (FMZs), a CTZ analogues, which generate intense blue emission when paired with a highly stable engineered luciferase, Nanoluc. Four types of FMZs protected at the C-3 position have been synthesized. The type and steric bulkiness of the protection group strongly contributed to storage stability and the kinetics of the bioluminescence reactions of the analogues in human living cells. In particular, two developed FMZ analogues resulted in significantly longer bioluminescence emission with higher S/N ratio than FMZ at single cell level. Long-term bioluminescence single cell imaging technology with the developed FMZ analogues will lead to seamless imaging in the range from cells to organs of small animals.

Elimination of a spiral wave pinned at an obstacle by a train of plane waves: Effect of diffusion between obstacles and surrounding media.

In excitable media such as cardiac tissue and Belousov-Zhabotinsky reaction medium, spiral waves tend to anchor (pin) to local heterogeneities. In general, such pinned waves are difficult to eliminate and may progress to spatio-temporal chaos. Heterogeneities can be classified as either the absence or presence of diffusive interaction with the surrounding medium. In this study, we investigated the difference in the unpinning of spiral waves from obstacles with and without diffusive interaction, and found a profound difference. The pacing period required for unpinning at fixed obstacle size is larger in case of diffusive obstacles. Further, we deduced a generic theoretical framework that can predict the minimal unpinning period. Our results explain the difference in pacing periods between for the obstacles with and without diffusive interaction, and the difference is interpreted in terms of the local decrease of spiral wave velocity close to the obstacle boundary caused in the case of diffusive interaction.

Current status of cervical cytology during pregnancy in Japan.

In Japan, uterine cancer screening during pregnancy is subsidized by public funds. We examined the current status of the results of cervical cytology conducted during pregnancy in Japan. We requested 2,293 obstetrical facilities to provide information on cervical cytology in pregnant women who delivered between October 2018 and March 2019. A total of 1,292 obstetrical facilities responded, with valid information on a total of 238,743 women. The implementation rate of cervical cytology during pregnancy was 86.8% in Japan. The prevalence of abnormal cervical cytology during pregnancy was 3.3% in total and 4.9% using a spatula/brush with liquid-based cytology (LBC). The prevalence of positive high-risk human papillomavirus (HPV) in teenagers with atypical squamous cells of undetermined significance (ASC-US) was significantly higher than women of other ages (p < 0.01). Because HPV vaccine coverage has dropped to less than 1% in Japan, a further study with various conditions will be needed to improve the accuracy of cervical cancer screening during pregnancy.

[A case of ascending colon cancer with unresectable distant metastases treated by systemic chemotherapy].

The patient, a male in his 70s, was referred to this hospital by his neighborhood doctor with what was said to be impaired hepatic function. Detailed examinations revealed a circumferential ascending colon cancer, diffuse hepatic metastases scattered over both liver lobes, and lymph node metastases in the left axilla. With the primary lesion-induced symptoms of stenosis controllable, the patient began systemic chemotherapy by mFOLFOX6 without a resection of the primary lesion. After completing a 10-course treatment, the patient underwent surgery to resect the primary lesion in preparation for bevacizumab treatment. In the postoperative systemic chemotherapy, FOLFIRI and mFOLFOX6 were administered concomitantly with bevacizumab. After a total of 19 courses, the patient's systemic condition gradually deteriorated. He eventually died of cancer one year and seven months after diagnosis of the primary lesion or one year and one month subsequent to the resection of the primary lesion. No consensus has been reached on the necessity to resect the primary lesion in patients with advanced colorectal cancer who also have unresectable distal metastases. Systemic chemotherapy, nevertheless, can provide tumor control on both primary and metastatic lesions and could become a treatment option in the future.

Oscillation and synchronization in the combustion of candles.

We investigate a simple experimental system using candles; stable combustion is seen when a single candle burns, while oscillatory combustion is seen when three candles burn together. If we consider a set of three candles as a component oscillator, two oscillators, that is, two sets of three candles, can couple with each other, resulting in both in-phase and antiphase synchronization depending on the distance between the two sets. The mathematical model indicates that the oscillatory combustion in a set of three candles is induced by a lack of oxygen around the burning point. Furthermore, we suggest that thermal radiation may be an essential factor of the synchronization.

The reduction in pigment epithelium-derived factor is a sign of malignancy in ovarian cancer expressing low-level of vascular endothelial growth factor.

BACKGROUND: Angiogenesis is a critical factor in the progression of solid tumors and metastasis. The aim of this study was to characterise the roles of angiogenic and anti-angiogenic factors on ovarian cancer. METHODS: The expression levels of vascular endothelial growth factor (VEGF, angiogenic factor) and pigment epithelial growth factor (PEDF, anti-angiogenic factor) were measured by real-time polymerase chain reaction and Western blotting in ovarian tumors. Microvessel density (MVD) was evaluated by the total microvessel length in high-power field of tumor tissue preparations. RESULTS: MVD correlated with tumor malignancy. The tissues with the highest expression levels of VEGF (VEGF-H) were malignant tumors. The VEGF expression levels in some malignant tumors (VEGF-L) were as low as that in benign tumors. Therefore, the expression of PEDF was examined. The PEDF expression levels in VEGF-L malignant tumors were significantly lower than those in benign tumors. On the other hand, the PEDF expression levels in VEGF-H malignant tumor tissues were not significantly different from those in benign tumors. CONCLUSION: The reduction in PEDF expression levels may be, in part, responsible for tumor malignancy in VEGF-L ovarian tumors. Furthermore, PEDF may be a useful marker of malignancy in VEGF-L ovarian tumors.

Unpinning of a spiral wave anchored around a circular obstacle by an external wave train: common aspects of a chemical reaction and cardiomyocyte tissue.

It is well known that spiral waves are often stabilized by anchoring to a local heterogeneity ("pinning") and that such pinned waves are rather difficult to eliminate. In the present report, we show that pinned spiral waves can be eliminated through collision with a wave train arriving from the outer region, as confirmed in experiments on the Belousov-Zhabotinsky (BZ) reaction as well as in cardiomyocyte tissue culture. A numerical simulation using the Oregonator, a mathematical model for the BZ reaction, provides the parameter area for successful unpinning. The scenario of unpinning is discussed in terms of the dispersion relation of the wave train by taking into account the curvature effect of the excitation wave.

Current status of Neisseria gonorrhoeae cervicitis in pregnant women in Japan.

We evaluated the current prevalence of gonococcal cervicitis among pregnant women in institutes that either do or do not routinely screen for gonococcal infection in Japan. We requested 2,330 obstetrical facilities to provide information on Neisseria gonorrhoeae cervicitis in pregnant women. A total of 1,876 (80.5%) of them responded. The universal screening test for gonococcal cervicitis, involving nucleic acid amplification for all pregnant women, was performed in 281 institutes (13.9% of institutes across Japan). The total rate of pregnant women with gonococcal cervicitis was 1.3% in the institutes performing the screening test during pregnancy, while it was only 0.2% (p < 0.01) in those not performing it. This suggests that 84% of infected women may have been missed in the institutes that do not routinely perform the screening test for gonococcal cervicitis. It may be time to examine the cost-effectiveness of providing gonococcal screening for all pregnant women in Japan.

The role of Mac-1 (CD11b/CD18) in osteoclast differentiation induced by receptor activator of nuclear factor-kappaB ligand.

Multinuclear osteoclasts are derived from CD11b-positive mononuclear cells in bone marrow and in circulation. FACS sorting experiments showed impaired osteoclastogenesis in RAW264.7 cells with low CD11b expression. Neutralizing antibodies and siRNA against CD11b inhibited osteoclastogenesis induced by RANKL. Although primary cultured mouse bone marrow macrophages expressed CD11a and CD11b, osteoclastogenesis induced by M-CSF and RANKL was inhibited in the presence of anti-CD11b or anti-CD18 but not anti-CD11a antibodies. Furthermore, anti-CD11b antibodies inhibited NFATc1 expression induced by M-CSF and RANKL in BMMs. These findings suggest, at least partly, an important role of CD11b in osteoclastogenesis.

Mathematical approach to unpinning of spiral waves anchored to an obstacle with high-frequency pacing.

Spiral waves are observed in wide variety of reaction-diffusion systems. Those observed in cardiac tissues are important since they are related to serious disease that threatens human lives, such as atrial or ventricular fibrillation. We consider the unpinning of spiral waves anchored to a circular obstacle on excitable media using high-frequency pacing. Here, we consider two types of the obstacle; i.e., that without any diffusive interaction with the environment, and that with diffusive interaction. We found that the threshold frequency for success in unpinning is lower for the obstacle with diffusive interaction than for the one without it. We discuss the threshold frequency based on the angular velocity of a chemical wave anchoring the obstacle.

Novel unsymmetrically pi-elongated porphyrin for dye-sensitized TiO2 cells.

A novel naphthyl-fused zinc porphyrin carboxylic acid has been synthesized and employed successfully in a dye-sensitized TiO2 solar cell, with a power conversion efficiency of 4.1%, which is improved by 50% relative to the unfused porphyrin reference cell.

Survival versus collapse: abrupt drop of excitability kills the traveling pulse, while gradual change results in adaptation.

Excitable media show changes in their basic characteristics that reflect temporal changes in the environment. In the photosensitive Belousov-Zhabotinsky (BZ) reaction, excitability is decreased by illumination. We found that a traveling pulse failed to propagate when a certain level of light intensity was switched on abruptly, but the pulse continued propagating when the light intensity reached the same level gradually. We investigated the mechanism of adaptation of pulse propagation to the change in light intensity using two mathematical models, the Oregonator model (a specific model for the photosensitive BZ reaction), and the FitzHugh-Nagumo model (a generic model for excitable media). The appearance of a characteristic such as adaptation is shown to be a general feature for a traveling pulse in excitable media.

Influence of obesity on the short-term outcome of laparoscopic colectomy for colorectal cancer.

PURPOSE: Obesity has been generally associated with increased surgical risk. However, data on the outcome of laparoscopic colectomy in obese and non-obese patients are controversial. The aim of this study is to assess the short-term outcome of laparoscopic colectomy for colorectal cancer (CRC) in obese patients as compared with non-obese patients. MATERIALS AND METHODS: Sixty-nine patients who underwent laparoscopic anterior resection for CRC during the past six years were retrospectively evaluated. The patients with CRC involving the sigmoid or rectosigmoid colon and subjected to intracorporeal anastomosis were included in this study. They were divided into three groups according to body mass index (BMI): obese (BMI >/= 28.0 kg/m(2)), pre-obese (BMI: 25.0-27.9 kg/m(2)) and non-obese (BMI < 25.0 kg/m(2)). RESULTS: Nine patients (13.0%) were obese, 11 patients (15.9%) were pre-obese and 49 patients (71.1%) were non-obese. Patient characteristics, such as age, gender, tumor location, previous laparotomy, were similar among the three groups. There were no significant differences in operative time, blood loss, intraoperative complications and conversion rates. Postoperative complications and duration of postoperative hospital stay were also similar among the three groups. However, two of the three patients in the pre-obese group had to be operated on again due to incarceration of the small bowel into a port site. CONCLUSIONS: Laparoscopic colectomy can be safely performed in obese patients with short-term results similar to those obtained in non-obese and pre-obese patients.

Current status of syphilis in pregnant women in Japan.

We examined the current status of syphilis-infected pregnant Japanese women, according to the results of syphilis screening and confirmation tests of women who gave birth in Japan between October, 2015 and March, 2016. We requested 2458 obstetrical facilities to provide information of syphilis screening tests and 78.1% of them responded. Considering the response rate and the rate of implementation of confirmation tests, the number of syphilis-infected pregnant Japanese women was estimated to be 250 (1/4022) per year.

Current Proportion of Women Receiving Perinatal Psychosocial or Psychological Intervention in Japan.

BACKGROUND: In this study, we examined the current status of psychosocial or psychological intervention for women during pregnancy and the postpartum period in Japan. METHODS: We estimated the number of women receiving perinatal psychosocial or psychological intervention in Japan. On December 2015, we requested 2,462 obstetrical facilities that are members of the Japan Association of Obstetricians and Gynecologists (JAOG) to provide information on women who received psychosocial or psychological intervention during pregnancy, the hospitalization period for childbirth and the puerperal 1 month in 2014. A total of 1,305 (53.0%) of the 2,462 obstetrical facilities responded with valid information on a total of 515,373 women, accounting for approximately 52% of all deliveries that occurred in Japan during the study period. RESULTS: The number of women who received psychosocial or psychological intervention during pregnancy, the hospitalization period for childbirth and the puerperal 1 month were 4,843 (0.94%), 4,791 (0.93%) and 3,015 (0.59%), respectively. In total, 8,743 women (1.70%) received psychosocial or psychological intervention in 2014. CONCLUSION: Considering the response rate, the number of women requiring perinatal psychosocial or psychological intervention was estimated to be 16,000 per year in Japan.

[Incongruous homonymous quadrantanopia due to suprasellar calcificated lesions].

A 53 year-old woman with a history of tuberculous meningitis at 3 years of age incidentally found a right incongruous homonymous quadrantanopia in ophthalmologic check-up. On magnetic resonance imaging and helical computed tomography, the left optic tract was obscured by suprasellar calcified lesions. The left internal carotid artery was diffusely narrowed and occluded at its terminal portion as demonstrated by cerebral angiography. The calcificated lesions were diagnosed to derive from old tuberculous meningitis on the basis of her history, their location and the association of vascular occlusive changes. Incongruous homonymous hemianopsia due to optic tract damage is usually caused by tumor or aneurysm. Its occurrence by calcified inflammatory lesions has never been reported previously. The present case is considered of value in this respect.

Establishment of the T-cell large granular lymphocyte leukemia cell line MOTN-1 carrying natural killer-cell antigens.

A novel interleukin-2 (IL-2) dependent leukemia cell line MOTN-1 was established from the peripheral blood of a 63-year-old woman with T-cell large granular lymphocyte (LGL) leukemia in chronic phase. Primary peripheral blood leukemia cells were CD3+, CD5+, CD7+, CD56+, CD94+, CD161+, TcRalphabeta+, and HLA-DR+. The immunoprofile of the established cell line MOTN-1, however, showed CD3-, CD5-, CD7+, CD56+, CD94+, CD159+, CD161+, TcRalphabeta- and HLA-DR+; the MOTN-1 cells were cytoplasmatically positive for CD3varepsilon and the products of the T-cell receptor (TcR) genes beta and gamma. While the TcRbeta and TcRgamma genes were rearranged, the TcRdelta gene was found to be deleted. DNA fingerprinting and chromosome analysis identifying the t(2;6)(q?23;q?21) and t(12;18)(q13;q?22) alterations demonstrated the authenticity and the malignant nature of the cell line. The scientific significance of MOTN-1 lies in (1) the rarity of this type of leukemia cell lines, (2) the co-expression of various T- and natural killer (NK)-cell-associated markers, and (3) its unique chromosomal aberrations.

Simultaneous determination of metabolites of trimethylbenzenes, dimethylbenzylmercapturicacid and dimethylhippuric acid, in human urine by solid-phase extraction followed by liquid chromatography tandem mass spectrometry.

We describe a novel method for the determination of three kinds of dimethylbenzylmercapturic acids (DMM) and six kinds of dimethylhippuric acids (DMH), found in urine as metabolites of trimethylbenzenes, based on liquid chromatography/electrospray ionization tandem mass spectrometry. A solid-phase extraction procedure was used for the extractions of DMM and DMH from a urine sample, and the separation was performed on a reversed-phase C(30) column. The analytes were ionized by electrospray in the positive-ion mode. Operating in the multiple reaction monitoring mode, the linearity of the relative mass spectrometric responses to the internal standard versus analyte concentrations were established in the range 0.1-100 ng ml(-1). The extraction procedure was rapid and the relative standard deviations were below 5%. The detection limits of DMM and DMH in the urine by the proposed method were in the ranges 0.26-0.41 and 0.42-2.0 ng l(-1), respectively. Furthermore, DMM and DMH were detected in a urine sample from an individual who did not suffer from occupational exposure to trimethylbenzenes, by using this method.

Current status of HTLV-1 carrier in Japanese pregnant women.

We examined the current status of human T-cell leukemia virus type 1 (HTLV-1) carrier in Japanese pregnant women, according to the results of HTLV-1 screening and confirmation tests of women who gave birth in Japan in 2011. We requested 2642 obstetrical facilities to provide information of HTLV-1 tests and 71.3% of them responded. Considering the response rate and the rate of implementation of confirmation tests, the number of HTLV-1 carrier in Japanese pregnant women was estimated to be 1620 (0.16%) per year.