Remedy for improving ICC prognosis

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is still poor, and the 5-year survival rate in patients undergoing radical surgery (R0) is less than one-third. Since the prognosis depends mainly on tumor factors, so early diagnosis is necessary. To extend the survival time of these patients with a poor prognosis, cases of long-term survival were examined based on the results of our experiences and the literature. It was found that the hepatitis virus was highly involved in the carcinogenesis of ICC, and patients who were infected with hepatitis virus had rather good survival

Pathological study of pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): effects of lowered serum zinc level on the toxicity

Introduction. We have previously reported that Asian sand dust (ASD) induced acute and chronic inflammatory changes in the lung of mice. Zinc (Zn) is reported to influence inflammation and wound healing. The purpose of the study was to assess the effects of lowered serum Zn levels on the lung toxicity induced by ASD. Material and methods. Mice that were fed diets containing normal (group 1) or low (group 2) content of Zn for 8 weeks were intratracheally instilled with 3.0 mg of ASD, followed by sacrifice at 24 hours, 2 weeks, and 1, 2 and 3 months after instillation. Paraffin sections of lung tissues were stained by hematoxylin and eosin and by immunohistochemistry to detect tumor necrosis factor (TNF) and interleukin (IL)-1β as well as inflammasome (NALP3), autophagy (LC-3) and lysosome (LAMP-1) markers. Selected samples of lung tissue were examined by electron microscopy. Results. Following histological examination of the lung, similar patterns of inflammatory changes were observed in mice with normal and low serum Zn concentrations; however, they were more prominent and persistent in mice with low serum Zn level. These changes were both purulent (acute) and pyogranulomatous (chronic) in nature. In the lung lesions of group 2 mice the changes within the cytoplasmic vacuoles of enlarged ASD-containing macrophages (Mo) were clearly visible. The macrophages expressed TNF and IL-1β, and semi-quantitative analysis revealed a larger number of TNF-positive Mo in mice with normal level of serum Zn and a larger number of IL-1β-positive Mo in mice with low level of serum Zn. Decreased positive LC-3 staining and dilated lysosomes containing ASD particles were observed in the cytoplasm of Mo in mice with low serum Zn concentration. Conclusions. These findings suggest that low serum zinc concentration may induce the modulation of cytokine expression and lysosomal malfunction by phagocytotic and/or autophagic mechanisms, and may result in interstitial pyogranulomatous inflammation in the lungs of mice treated with ASD

Membrane Fouling Potentials of an Exoelectrogenic Fouling-Causing Bacterium Cultured With Different External Electron Acceptors

Integrated microbial fuel cell (MFC) and membrane bioreactor (MBR) systems are a promising cost-effective and energy-saving technology for wastewater treatment. Membrane fouling is still an important issue of such integrated systems in which aeration (oxygen) is replaced with anode electrodes (anodic respiration). Here, we investigated the effect of culture conditions on the membrane fouling potential of fouling-causing bacteria (FCB). In the present study, Klebsiella quasipneumoniae strain S05, which is an exoelectrogenic FCB isolated from a MBR treating municipal wastewater, was cultured with different external electron acceptors (oxygen, nitrate, and solid-state anode electrode). As results, the fouling potential of S05 was lowest when cultured with anode electrode and highest without any external electron acceptor (p < 0.05, respectively). The composition of soluble microbial products (SMP) and extracellular polymeric substances (EPS) was also dependent on the type of electron acceptor. Protein and biopolymer contents in SMP were highly correlated with the fouling potential (R2 = 0.73 and 0.81, respectively). Both the fouling potential and yield of protein and biopolymer production were significantly mitigated by supplying electron acceptors sufficiently regardless of its types. Taken together, the aeration of MBR could be replaced with solid-state anode electrodes without enhancement of membrane fouling, and the anode electrodes must be placed sufficiently to prevent the dead spaces in the integrated reactor

分子内結合が調節するJRABのLIMドメインによるアクチン細胞骨格の再編成

JRAB/MICAL-L2 is an effector protein of Rab13, a member of the Rab family of small GTPase. JRAB/MICAL-L2 consists of a calponin homology domain, a LIM domain, and a coiled-coil domain. JRAB/MICAL-L2 engages in intramolecular interaction between the N-terminal LIM domain and the C-terminal coiled-coil domain, and changes its conformation from closed to open under the effect of Rab13. Open-form JRAB/MICAL-L2 induces the formation of peripheral ruffles via an interaction between its calponin homology domain and filamin. Here, we report that the LIM domain, independent of the C-terminus, is also necessary for the function of open-form JRAB/MICAL-L2. In mechanistic terms, two zinc finger domains within the LIM domain bind the first and second molecules of actin at the minus end, potentially inhibiting the depolymerization of actin filaments (F-actin). The first zinc finger domain also contributes to the intramolecular interaction of JRAB/MICAL-L2. Moreover, the residues of the first zinc finger domain that are responsible for the intramolecular interaction are also involved in the association with F-actin. Together, our findings show that the function of open-form JRAB/MICAL-L2 mediated by the LIM domain is fine-tuned by the intramolecular interaction between the first zinc finger domain and the C-terminal domain

Measuring sleep quality and autonomic nervous function

The purpose of this study was to determine the relationship between quality of sleep and autonomic nervous functioning in healthy adult Japanese women using three measures, namely, the Pittsburgh Sleep Quality Index (PSQI) for subjective assessment of sleep quality, actigraphy for objective assessment of sleep, and heart rate variability using high frequency and low frequency domains. Participants were 31 healthy women in their 20s to 40s who met the selection criteria, including having normal monthly menstrual periods. Participants were categorized as good or poor sleepers according to their PSQI score. Median correlation coefficients of activity count and high frequency were −0.62 (range −0.43 to −0.84) for good sleepers and −0.45 (range 0.003 to −0.64) for poor sleepers. Good sleepers showed a significantly higher correlation of activity count and high frequency (Z=−2.11, P<0.05). Median correlation coefficients of activity count and low frequency/high frequency were 0.54 (range 0.29–0.73) for good sleepers and 0.41 (range 0.11–0.63) for poor sleepers. The PSQI, actigraphy data, and heart rate variability results showed positive correlations between sleep time as measured by PSQI and duration of inactivity as measured by actigraphy (r=0.446, P<0.05) and sleep time as measured by actigraphy (r=0.377, P<0.05), and a negative correlation between sleep time as measured by PSQI and the correlation coefficients of activity count and high frequency (r=−0.460, P<0.01). These results support the finding that sleep-wake rhythms can be monitored efficiently with actigraphy, providing accurate data that can support the diagnosis of sleeping disorders. Furthermore, actigraphy data were associated with heart rate variability and PSQI findings, but only in subjects who were poor sleepers. Actigraphy is an accurate, efficient, rapid, and inexpensive test for determining objective and subjective sleeping problems, and can also be used in clinical tests for sleep assessment

JRAB shifts “dancing style” of cell clusters

In fundamental biological processes, cells often move in groups, a process termed collective cell migration. Collectively migrating cells are much better organized than a random assemblage of individual cells. Many molecules have been identified as factors involved in collective cell migration, and no one molecule is adequate to explain the whole picture. Here we show that JRAB/MICAL-L2, an effector protein of Rab13 GTPase, provides the “law and order” allowing myriad cells to behave as a single unit just by changing its conformation. First, we generated a structural model of JRAB/MICAL-L2 by a combination of bioinformatic and biochemical analyses and showed how JRAB/MICAL-L2 interacts with Rab13 and how its conformational change occurs. We combined cell biology, live imaging, computational biology, and biomechanics to show that impairment of conformational plasticity in JRAB/MICAL-L2 causes excessive rigidity and loss of directionality, leading to imbalance in cell group behavior. This multidisciplinary approach supports the concept that the conformational plasticity of a single molecule provides “law and order” in collective cell migration

Heart Disease, Other Circulatory Diseases, and Onset of Major Depression among Community Residents in Japan: Results of the World Mental Health Survey Japan 2002-2004

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95%Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.</p

Measuring sleep quality and autonomic nervous function

The purpose of this study was to determine the relationship between quality of sleep and autonomic nervous functioning in healthy adult Japanese women using three measures, namely, the Pittsburgh Sleep Quality Index (PSQI) for subjective assessment of sleep quality, actigraphy for objective assessment of sleep, and heart rate variability using high frequency and low frequency domains. Participants were 31 healthy women in their 20s to 40s who met the selection criteria, including having normal monthly menstrual periods. Participants were categorized as good or poor sleepers according to their PSQI score. Median correlation coefficients of activity count and high frequency were −0.62 (range −0.43 to −0.84) for good sleepers and −0.45 (range 0.003 to −0.64) for poor sleepers. Good sleepers showed a significantly higher correlation of activity count and high frequency (Z=−2.11, P<0.05). Median correlation coefficients of activity count and low frequency/high frequency were 0.54 (range 0.29–0.73) for good sleepers and 0.41 (range 0.11–0.63) for poor sleepers. The PSQI, actigraphy data, and heart rate variability results showed positive correlations between sleep time as measured by PSQI and duration of inactivity as measured by actigraphy (r=0.446, P<0.05) and sleep time as measured by actigraphy (r=0.377, P<0.05), and a negative correlation between sleep time as measured by PSQI and the correlation coefficients of activity count and high frequency (r=−0.460, P<0.01). These results support the finding that sleep-wake rhythms can be monitored efficiently with actigraphy, providing accurate data that can support the diagnosis of sleeping disorders. Furthermore, actigraphy data were associated with heart rate variability and PSQI findings, but only in subjects who were poor sleepers. Actigraphy is an accurate, efficient, rapid, and inexpensive test for determining objective and subjective sleeping problems, and can also be used in clinical tests for sleep assessment

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: An Extensive Study Containing More Benign Lesions

Introduction: The Japan Lung Cancer Society (JLCS) and the Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma (JLCS-JSCC system). Prior to the proposal, the Papanicolaou Society of Cytopathology (PSC) had proposed a revised reporting system (PSC system), which comprises the “neoplastic, benign neoplasm, and low-grade carcinoma” category (N-B-LG category), in addition to the 4 categories of the JLCS-JSCC system. This study aimed to evaluate the interobserver agreement of the JLCS-JSCC system with an additional dataset with more benign lesions in comparison with the PSC system. Methods: We analyzed 167 cytological samples, which included 17 benign lesions, obtained from the respiratory system. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the JLCS-JSCC system and PSC system. Results: The interobserver agreement was moderate in the JLCS-JSCC (k = 0.499) and PSC (k = 0.485) systems. Of the 167 samples, 17 samples were benign lesions: 7 pulmonary hamartomas, 5 sclerosing pneumocytomas, 2 squamous papillomas, one solitary fibrous tumor, one meningioma, and one lymphocytic proliferation. There were diverse sample types as follows: 11 touch smears, 3 brushing smears, 2 aspirations, and one sputum sample. Fourteen samples (82.3%) were categorized into “negative” or “atypical” by more than half of the observers in the JLCS-JSCC system. Conversely, 3 samples were categorized as “suspicious” or “malignant” by more than half of the observers in the JLCS-JSCC system. On the other hand, 11 samples (64.7%) were categorized into the N-B-LG category by more than half of the observers in the PSC system. Conclusions: The concordance rate in the JLCS-JSCC system was slightly higher than that in the PSC system; however, the interobserver agreement was moderate in both the JLCS-JSCC and PSC systems. These results indicate that both the JLCS-JSCC and PSC systems are clinically useful. Therefore, both systems are expected to have clinical applications. It may be important to integrate the 2 systems and construct a universal system that can be used more widely in clinical practice