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Prognosis of breast cancer patients has been improved along with the progress in cancer therapies. However, cancer therapeutics-related cardiac dysfunction (CTRCD) has been an emerging issue. For early detection of CTRCD, we examined whether native T1 mapping and global longitudinal strain (GLS) using cardiac magnetic resonance (CMR) and biomarkers analysis are useful.We prospectively enrolled 83 consecutive chemotherapy-naïve female patients with breast cancer (mean age, 56 ± 13 yrs.) between 2017 and 2020. CTRCD was defined based on echocardiography as left ventricular ejection fraction (LVEF) below 53% at any follow-up period with LVEF10% points decrease from baseline after chemotherapy. To evaluate cardiac function, CMR (at baseline and 6 months), 12‑lead ECG, echocardiography, and biomarkers (at baseline and every 3 months) were evaluated.A total of 164 CMRs were performed in 83 patients. LVEF and GLS were significantly decreased after chemotherapy (LVEF, from 71.2 ± 4.4 to 67.6 ± 5.8%; GLS, from -27.9 ± 3.9 to -24.7 ± 3.5%, respectively, both P 0.01). Native T1 value also significantly elevated after chemotherapy (from 1283 ± 36 to 1308 ± 39 msec, P 0.01). Among the 83 patients, 7 (8.4%) developed CTRCD. Of note, native T1 value before chemotherapy was significantly higher in patients with CTRCD than in those without it (1352 ± 29 vs. 1278 ± 30 msec, P 0.01). The multivariable logistic regression analysis revealed that native T1 value was an independent predictive factor for the development of CTRCD [OR 2.33; 95%CI 1.15-4.75, P = 0.02].These results indicate that CMR is useful to detect chemotherapy-related myocardial damage and predict for the development of CTRCD in breast cancer patients.

There are no evidence-based reports on the proper duration of antimicrobial therapy following video-assisted thoracoscopic surgery debridement (VATS-D) in thoracic empyema (TE) or complicated parapneumonic effusion (PPE). This study aimed to investigate the optimal duration of antimicrobial therapy after VATS-D.Between January 2011 and December 2019, 33 patients corresponding to American College of Chest Physicians (ACCP) category 3 or 4 undergoing VATS-D were included. The times until the body temperature (BT) was confirmed to be less than 37.5 °C and 37.0 °C, white blood cell count (WBC) less than 10,000/μl, segmented neutrophils (seg) less than 80%, and C-reactive protein (CRP) level less than 25% of the preoperative value were retrospectively analyzed.The median time from the onset of TE/PPE to surgery was 13 days. The median durations of preoperative and postoperative antibiotic use were five and seven days, respectively. Major complications occurred in four cases (three and one cases of respiratory failure and cerebral infarction, respectively). The median postoperative hospital stay was 14 days. Recurrence or progression to chronic empyema was seen in four cases. The median numbers of days until the conditions were met were three days for BT 37.5 °C, six days for BT 37.0 °C, four days for WBC10,000, seven days for seg80% and seven days for CRP25%.The proper duration of antimicrobial therapy after VATS-D for TE/PPE is approximately three to seven days. Urgent VATS-D may shorten the total antibiotic usage.

Objective Transglutaminase (TGM)2 and peroxisome proliferator-activated receptor (PPAR)γ are thought to participate in the pathogenesis of nasal polyp formation in cystic fibrosis (CF). We herein investigated expressions of cystic fibrosis transmembrane conductance regulator (CFTR), TGM2, PPARγ and isopeptide bonds, a reaction product of TGM, in non-CF nasal polyps. Methods Nasal polyps and inferior turbinates were collected from chronic rhinosinusitis patients without CF during transnasal endoscopic sinonasal surgery. Expressions of CFTR, TGM2, isopeptide bonds and PPARγ were examined by fluorescence immunohistochemistry and quantitative RT-PCR. Expression of CFTR was also analyzed by Western blot. Results Immunohistochemical fluorescence of the nasal polyp was significantly lower for CFTR and PPARγ, and significantly higher for TGM2 and isopeptide bonds than that of the turbinate mucosa. Lower expression of CFTR in the nasal polyp than in the turbinate mucosa was also observed in Western blot. Expression of PPARG mRNA was significantly lower in the nasal polyp than in the turbinate mucosa, whereas expressions of CFTR mRNA or TGM2 mRNA did not differ between the two tissues. Immunohistochemical fluorescence for CFTR showed significant negative correlation with that for TGM2 and isopeptide bonds, and significant positive correlation with that for PPARγ. The fluorescence for TGM2 was positively correlated with that for isopeptide bonds and negatively correlated with that for PPARγ. The fluorescence for isopeptide bonds tended to be negatively correlated with that for PPARγ. Conclusions These results suggest a possible role of the CFTR-TGM2-PPARγ cascade in the pathogenesis of nasal polyp formation in non-CF patients as in CF patients.

Introduction Takotsubo syndrome (TTS) is triggered mostly by physical and/or emotional stress that is processed in stress-associated brain regions, including the amygdala. However, it remains unclear whether such stress-induced brain activity is associated with TTS onset. Methods and results We acquired brain [18F]-2-fluoro-deoxy- d -glucose (18F-FDG) positron emission tomography in 4 TTS patients (44–82 yrs., 3 women) on days 2–4 (acute phase) and days 29–40 (recovery phase) after diagnosis of TTS was made by coronary angiography and left ventriculogram. The 18F-FDG uptake was measured globally and also in the pre-defined regions of interest of the bilateral amygdala on the common Montreal Neurological Institute space; all 18F-FDG images were normalized using automated image pre-processing. Amygdalar activity was calculated by dividing the 18F-FDG uptake of the amygdala by the global brain uptake. Left ventriculograms showed that apical ballooning was typical at diagnosis and was then relieved in the recovery phase. Amygdalar activity in the acute phase (0.872 ± 0.032) was higher than in the recovery phase (0.805 ± 0.037) (P = 0.013). Conclusions We report here 4 cases of TTS showing higher amygdalar activity in the acute phase as compared with the recovery phase, suggesting that increased stress-induced neurobiological activity is associated with TTS onset.

Cerebral palsy is more common among preterm infants than among full-term infants. Although there is still no clear evidence that fetal heart rate monitoring effectively reduces cerebral palsy incidence, it is helpful to estimate the timing of brain injury leading to cerebral palsy and the causal relationship with delivery based on the fetal heart rate evolution patterns. Understanding the relationship between the timing and the type of brain injury can help to identify preventive measures in obstetrical care.This study aimed to examine the relationship between the timing of insults and the type of brain injury in preterm infants with severe cerebral palsy.This longitudinal study was based on a nationwide database for cerebral palsy. The data of infants with severe cerebral palsy (equivalent to levels 3-5 of the Gross Motor Function Classification System-Expanded and Revised), born between 2009 and 2014 at 28 to 33 weeks of gestation, were included. The intrapartum fetal heart rate evolution patterns were evaluated by 3 obstetricians blinded to clinical information other than gestational age at birth, and these were categorized after agreement by at least 2 of the 3 reviewers into (1) continuous bradycardia, (2) persistently nonreassuring (prenatal onset), (3) reassuring-prolonged deceleration, (4) Hon's pattern (intrapartum onset), (5) persistently reassuring (pre- or postnatal onset), and (6) unclassified. Infant brain magnetic resonance imaging findings at term-equivalent age were assessed by a pediatric neurologist blinded to the background details, except for gestational age at birth and corrected age at image acquisition, and these were categorized as (1) basal ganglia-thalamus, (2) white matter, (3) watershed cortex or subcortex, (4) stroke, (5) normal, and (6) unclassified based on the predominant site involved. The risk factors for the basal ganglia-thalamus group were compared with those of the combined white matter and watershed injuries group.Among 1593 infants with severe cerebral palsy, 231 were born at 28 to 33 weeks of gestation, and 140 met the eligibility criteria. Fetal heart rate evolution patterns were categorized as bradycardia (17% [24]); persistently nonreassuring (40% [56]); reassuring-prolonged deceleration (7% [10]); reassuring-Hon (6% [8]); persistently reassuring (7% [10]); and unclassified (23% [32]). Cerebral palsy was presumed to have an antenatal onset in 57% of infants and to have been caused by intrapartum insult in 13% of infants. Magnetic resonance imaging showed that 34% (n=48) of infants developed basal ganglia-thalamus-dominant brain injury. Of the remaining 92 infants, 43% (60) showed white matter injuries, 1% (1) showed watershed injuries, 4% (5) showed stroke, 1% (1) had normal findings, and 18% (25) had unclassified findings. Infants with continuous bradycardia (adjusted odds ratio, 1033.06; 95% confidence interval, 15.49-68,879.92) and persistently nonreassuring fetal heart rate patterns (61.20; 2.09-1793.12) had a significantly increased risk for basal ganglia-thalamus injury.Severe cerebral palsy was presumed to have an antenatal onset in 57% of infants and to have been caused by intrapartum insult in only 13% of infants born at 28 to 33 weeks of gestation. Although the white matter-watershed injury was predominant in the study populations, severe acute hypoxia-ischemia may be an important prenatal etiology of severe cerebral palsy in preterm infants.

Although depressive symptoms increased mortality and hospitalization in chronic heart failure (CHF) patients, the underlying mechanism remains unclear. The aim of this study was to investigate whether an alteration in hippocampal perfusion, which is the neural substrate of depressive symptoms, is associated with changes in cardiac structures and/or functions in CHF patients.We used baseline data of 70 CHF patients (66.8 ± 8.9 yrs, 32.5% women), including cerebral blood flow (CBF) in the hippocampus, geriatric depression scale (GDS) scores and echocardiographic parameters, in the Brain Assessment and Investigation in Heart Failure Trial (B-HeFT) (UMIN000008584). Echocardiography was repeated at 3.1 ± 0.5 years after the baseline evaluation. We first tested voxel-wise regression model with hippocampal CBF as dependent variable and each of echocardiographic parameter change as independent variable, adjusted for age and sex. Structural equation modeling was used to test a mediation effect of cognitive test scores on associations between hippocampal perfusion and changes in cardiac structures and/or functions.Baseline anterior hippocampal CBF was negatively correlated with changes in left ventricular posterior wall thickness (PWT) (P 0.05 with family-wise error corrections). An existence of depressive symptoms was positively correlated with the baseline anterior CBF and negatively with the PWT changes (P 0.05, both). There were both direct effects of the baseline anterior hippocampal CBF on PWT thinning and effects mediated through the depressive symptoms (P 0.05, both).This study provides the first evidence that the alteration in hippocampal perfusion may lead to changes in cardiac structures via increase in depressive symptoms in CHF patients.

Although cardiac troponin and natriuretic peptide have been shown to decrease after balloon pulmonary angioplasty (BPA) with improved right ventricular afterload in chronic thromboembolic pulmonary hypertension (CTEPH), biomarkers to evaluate the effects of BPA independently of heart failure status remain to be developed.In 39 consecutive CTEPH patients including 31 who underwent BPA, we measured plasma levels of cyclophilin A (CyPA), which we demonstrated is secreted from pulmonary vascular smooth muscle cells in response to mechanical stretch and hypoxia.CyPA levels were elevated in CTEPH patients (12.7, IQR: 7.6-16.0) compared with 8 thromboembolic controls with a history of venous thromboembolism (4.9, IQR: 2.4-11.2) or 18 healthy controls (4.1, IQR: 2.4-6.8) (both p0.05) and were linearly correlated with mean pulmonary arterial pressure (r=0.50, p = 0.0003) and pulmonary vascular resistance (r=0.32, p= 0.026). BPA reduced CyPA levels and tended to lower brain-type natriuretic peptide (BNP) levels (p0.01 and p = 0.07). When comparing the changes in CyPA before and after BPA in the two subgroups with higher (≥35pg/mL) and normal (35pg/mL) BNP at baseline, CyPA decreased both in patients with higher BNP and those with normal BNP (both p0.05). In contrast, BNP decreased only in patients with higher BNP (p0.05). Also, CyPA decreased both in patients with lower (25 kg/mCyPA could be a useful biomarker to evaluate the effects of BPA even in patients with normal BNP or high BMI.

Alzheimer's disease (AD) has a long preclinical phase during which beta-amyloid accumulates in the brain without cognitive impairment. However, the pattern of brain network alterations in this early stage of the disease remains to be clarified. In this study we examined the relationships between regional brain network indices and beta-amyloid deposits. Twenty-four elderly subjects with the APOE4 allele underwent both a 1.5-Tesla magnetic resonance imaging (MRI) scan and a positron emission tomography (PET) scan using [18F]Florbetapir. We computed network metrics such as the degree, betweenness centrality, and clustering coefficient, and examined the relationships between the beta-amyloid accumulation and these regional brain network connectivity metrics. We found a significant positive correlation between the global standardized uptake value ratio (SUVR) of [18F]Florbetapir and the betweenness centrality in the left parietal region. However, there were no significant correlations between the SUVR score and other network indices or the regional gray matter volume. Our data suggest a relationship between the beta-amyloid accumulation and the regional brain network connectivity in subjects at risk of AD. The brain connectome may provide an adjunct biomarker for the early detection of AD.

The interfacial bonding strength between carbon nanotubes (CNTs) and the metal matrix in CNT/metal composites can be increased by depositing metal or metal oxide particles onto the CNT surface. In this study, the effect of the supported amorphous Al2O3 nanoparticles on the tensile strength of individual multi-walled CNTs (MWCNTs) synthesized by chemical vapor deposition has been investigated in situ by scanning electron microscopy. The average tensile strength of MWCNTs with supported amorphous Al2O3 nanoparticles was slightly higher than that of the as-grown MWCNTs, which could be attributed to the interactions between the supported materials and the CNT defect sites.

To evaluate whether the extent of perfusion defects assessed by examining lung perfused blood volume (PBV) images is a stronger estimator of the clinical severity of chronic thromboembolic pulmonary hypertension (CTEPH) compared with other computed tomography (CT) findings and noninvasive parameters.We analyzed 46 consecutive patients (10 men, 36 women) with CTEPH who underwent both dual-energy CT and right-heart catheter (RHC) examinations. Lung PBV images were acquired using a second-generation dual-source CT scanner. Two radiologists independently scored the extent of perfusion defects in each lung segment employing the following criteria: 0, no defect, 1, defect in50% of a segment, 2, defect in ≥50% of a segment. Each lung PBV score was defined as the sum of the scores of 18 segments. In addition, all of the following were recorded: 6-min walk distance (6MWD), brain natriuretic peptide (BNP) level, and RHC hemodynamic parameters including pulmonary artery pressure (PAP), right ventricular pressure (RVP), cardiac output (CO), the cardiac index (CI), and pulmonary vascular resistance (PVR). Bootstrapped weighted kappa values with 95% confidence intervals (CIs) were calculated to evaluate the level of interobserver agreement. Correlations between lung PBV scores and other parameters were evaluated by calculating Spearman's rho correlation coefficients. Multivariable linear regression analyses (using a stepwise method) were employed to identify useful estimators of mean PAP and PVR among CT, BNP, and 6MWD parameters. A p value0.05 was considered to reflect statistical significance.Interobserver agreement in terms of the scoring of perfusion defects was excellent (κ=0.88, 95% CIs: 0.85, 0.91). The lung PBV score was significantly correlated with the PAP (mean, rho=0.48; systolic, rho=0.47; diastolic, rho=0.39), PVR (rho=0.47), and RVP (rho=0.48) (all p values0.01). Multivariable linear regression analyses showed that only the lung PBV score was significantly associated with both the mean PAP (coefficient, 0.84, p0.01) and the PVR (coefficient, 28.83, p0.01).The lung PBV score is a useful and noninvasive estimator of clinical CTEPH severity, especially in comparison with the mean PAP and PVR, which currently serve as the gold standards for the management of CTEPH .

Arginine vasopressin (AVP) synthesis in the hypothalamo-neurohypophysial system (HNS) is up-regulated by kainic acid (KA)-induced seizure in rats. However, it remains unknown whether a subconvulsive dose of KA affects the HNS. Here we examined the effects of subcutaneous (s.c.) administration of a low dose of KA (4 mg/kg) on the gene expressions of the AVP, oxytocin (OXT) and neuronal nitric oxide synthase (nNOS) in the supraoptic (SON) and paraventricular nuclei (PVN) of the rat hypothalamus, using in situ hybridization histochemistry. The expression of the AVP gene in the SON and PVN was judged to be up-regulated in KA-treated rats in comparison with saline-treated rats as controls. Next, the expression of the OXT gene was significantly increased in the SON at 6-24h and in the PVN at 6 and 12h after s.c. administration of KA. Finally, the expression of the nNOS gene was significantly increased in the SON and PVN at 3 and 6h after s.c. administration of KA. These results suggest that up-regulation of the gene expressions of the AVP, OXT and nNOS in the rat hypothalamus may be differentially affected by peripheral administration of a subconvulsive dose of KA.

Postcardiac injury syndrome (PCIS) occurs following a pericardial or myocardial injury. On the other hand, PCIS following cardiac catheter intervention is rare and can be difficult to diagnose because of its delayed onset. A 24-year-old man underwent radiofrequency ablation (RFA) for paroxysmal atrial fibrillation and suffered from general fatigue and left-sided pleural effusion three months after the procedure. His symptoms and effusion were effectively treated within a month by administrating nonsteroidal anti-inflammatory drugs. However, seven months later, he developed left-sided chest pain and low-grade fever. Computed tomography showed a thickening of the parietal pleura and reccurence of the pleural effusion. Pleural biopsy by video-assisted thoracoscopy demonstrated chronic pleuritis with a non-necrotizing granulomatous reaction. Given the previous RFA, and in the absence of infection or malignant disease, he was diagnosed with PCIS and treated with colchicine.

Objective The banding pattern of Streptococcus mutans strains generated using repetitive extragenic palindromic PCR (rep-PCR) with enterobacterial repetitive intergenic consensus (ERIC) primers has been shown previously. In the present study, the sequencing and analysis of gene sequences of the 6 most intense and commonly occurring amplicons from S. mutans serotype c was investigated. Methods The sequences of the amplicons from S. mutans serotype c strain by using rep-PCR with ERIC1R and ERIC2 primers were compared to the whole genome sequence of S. mutans UA159 and NN2025 strains. Results The amplicons were found to contain partial gene sequences coding for proteins such as the hypothetical protein, glucan binding protein A, putative methylated-DNA-protein-cysteine S-methyltransferase, putative d-3-phosphoglycerate dehydrogenase, putative excinuclease ABC (subunit A) and putative GTP-binding protein. The locations of 5 of the 6 amplicons were found to be assembled downstream in the UA159 genome. The coding direction of the amplicons in the NN2025 genome was in reverse orientation relative to that in the UA159 strain, except in the 2170-bp amplicon. Conclusions The repeating sequence elements of ERIC in S. mutans serotype c are located on one side of the genome and have less frequency and similarity compared to those in enterobacteria.

We investigated the removal of bacteriophages by adsorption on commercially available powdered activated carbon (N-PAC, median diameter >10 μm) and super-powdered activated carbon (S-PAC, median diameter 0.7–2.8 μm). N-PACs failed to remove the virus in Milli-Q water buffered with 100 μM Ca 2+ , but some S-PACs successfully removed it under the same condition. Three factors contributed substantially to virus removal: a smaller electrophoretic repulsive force between the virus and the PAC particles, a large proportion of pores 20–50 nm in diameter, and a greater hydrophobicity of the virus surface.

Objectives We conducted a prospective bacteriological survey to investigate antibiotic resistance-related genetic characteristics and the turnover of nasopharyngeal Streptococcus pneumoniae carriage in healthy children in day-care centers (DCCs). Methods A total of 363 nasopharyngeal mucus samples were collected from children aged 0 to 6 years attending two DCCs in the summer of 2004 (n = 181) and the following winter (n = 182). We obtained 157 S. pneumoniae isolates and analyzed them by antibiotic susceptibility testing, PCR assay for the penicillin-binding protein (PBP) genes and macrolide-resistance gene, and pulsed-field gel electrophoresis (PFGE). Results The overall carriage rate was 43.3% (157/363). The percentages of penicillin-intermediately resistant S. pneumoniae (PISP) strains, penicillin-resistant S. pneumoniae (PRSP) strains, erythromycin-intermediately resistant S. pneumoniae strains and erythromycin-resistant S. pneumoniae strains were 35.7% (56/157), 0.6% (1/157), 1.9% (3/157), and 69.4% (109/157), respectively. The percentages of S. pneumoniae strains with the pbp mutation(s) and mefA and/or ermB gene(s) were 92.4% (145/157) and 71.3% (112/157), respectively. Fifty strains with different PFGE patterns were obtained from among the 157 isolates. Thirteen strains were observed in both seasons, but only one of these strains was isolated from the same carrier. Twenty-one strains (42.0%) were isolated from two or more children, and 17 of these were each isolated from children attending the same DCC. Conclusions These results indicate the spread of S. pneumoniae, particularly those with antibiotic-resistance genes, and the vigorous genetic turnover and substantial horizontal transmission of this pathogen in healthy children attending DCCs in Japan.

A novel model of network artificial chemistry (NAC) in which molecular agents with assembler programs move through the network is presented. By the execution of the agent programs, nodes rewire edges according to their own types (either hydrophilic or hydrophobic), and as a consequence, a global topological structure is created in the network. Using numerical experiments equipped with three agent types (centrosome, hydrogen, and van der Waals), it is demonstrated that the revised NAC is able to emulate the organization of a pseudo-lattice structure between hydrophilic nodes, repulsion between hydrophilic and hydrophobic nodes, and the division of a network cell actualized as a hydrophilic cluster.

We explore cellular and molecular mechanisms of nasal adjuvant of a combination of a plasmid encoding the Flt3 ligand cDNA (pFL) and CpG oligodeoxynucleotides (CpG ODN). The double DNA adjuvant given with OVA maintained prolonged OVA-specific secretory IgA (S-IgA) Ab responses in external secretions for more than twenty-five weeks after the final immunization. Further, both Th1- and Th2-type cytokine responses were induced by this combined adjuvant regimen. The frequencies of plasmacytoid DCs (pDCs) and CD8+ DCs were significantly increased in nasopharyngeal-associated lymphoreticular tissue (NALT) of mice given the combined adjuvant. Importantly, when we examined adjuvanticity of pFL plus CpG ODN in 2-year-old mice, significant levels of mucosal IgA Ab responses were also induced. These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for the development of an effective mucosal vaccine for the elderly.

Photodecomposition processes of 2-, 3-, and 4-methylaniline cations induced by a moderately intense (∼10 11 W/cm 2 ) visible nanosecond laser field and an intense (∼10 15 W/cm 2 ) UV femtosecond laser field have been investigated using a tandem mass spectrometer. Highly unsaturated fragment cations such as C 6 H 2 + and C 6 H 3 + are dominantly produced by the nanosecond laser, while less unsaturated smaller fragment cations such as C 3 H 3 + , C 4 H 4 + , and C 5 H 5 + are produced mainly by the femtosecond laser. Ab initio calculations have also been performed to estimate the stable geometrical structures of C 6 H 2 + and C 6 H 3 + and those of possible intermediate ring compounds for discussing the photodecomposition pathways in intense laser fields.

Background & Aims: The follicle-associated epithelium (FAE) plays key roles in antigen uptake and subsequent induction of mucosal immunity. In this study, we examined whether M-cell targeting using a protein antigen (Ag) delivery system would induce oral tolerance instead of enhancement of Ag-specific mucosal antibody (Ab) responses. Methods: Mice were fed different doses of a recombinant protein sigma 1 of reovirus genetically conjugated to ovalbumin (OVA-pσ1), pσ1 only, or phosphate-buffered saline (PBS) before oral challenge with OVA plus cholera toxin as mucosal adjuvant. OVA-specific Ab and CD4-positive (CD4+) T-cell responses were determined. Results: A low dose of OVA-pσ1 reduced anti-OVA Ab and CD4+ T-cell responses in both mucosal and systemic lymphoid tissues. OVA/MHC I-Ad tetramer staining showed that the numbers of OVA-specific CD4+ T cells were significantly reduced in lamina propria of mice fed OVA-pσ1 than those fed pσ1 only or PBS only. In fact, Foxp3 expressing CD25+ CD4+ T cells were markedly increased in this tissue. Nonetheless, CD25+ CD4+ T cells from the spleen, mesenteric lymph nodes, and Peyer's patches of orally tolerized mice showed increased transforming growth factor β1 (TGF-β1) and interleukin-10 (IL-10) production compared with nontolerized mice. Conclusions: These results show that an FAE M-cell targeting protein Ag delivery system facilitates oral tolerance induction because of a reduction in Ag-specific CD4+ T cells and increased levels of TGF-β1 and IL-10 producing, CD25+ CD4+ regulatory T cells in both systemic and mucosal lymphoid tissues.

Orexin-A and -B (identical to hypocretin-1 and -2) are hypothalamic neuropeptides that regulate appetite and arousal. Orexins-producing neurons project their axons to various brain regions, including the olfactory bulb. In the present study, to understand the relationship between orexins and olfaction, we investigated the distribution of the orexin-A- and -B-immunoreactive (ir) fibers in the rat olfactory bulb and the contents of orexin-A and -B in the rat olfactory bulb after food deprivation for 48 h by using immunohistochemistry and radioimmunoassay, respectively. Both orexin-A- and -B-ir fibers are similarly wide spread from the glomerular layer of the olfactory bulb where the terminals of the peripheral olfactory nerves make synapses with the mitral cells or the tufted cells, to the piriform cortex. Dense orexin-A- and -B-ir fibers were observed mainly in the granular cell layer and anterior olfactory nucleus. The contents of orexin-A and -B (pg/10 mg wet weight tissue) in fed rats (mean ± S.E.M., n = 6) were 2.72 ± 0.24 and 6.31 ± 0.63, respectively. Fasting for 48 h significantly reduced the contents of orexin-B, but not orexin-A. Orexins in the rat olfactory bulb may be involved in not only olfactory system but also energy balance.

Summary Background Eikenella corrodens ( E. corrodens ) is a Gram-negative facultative anaerobic bacillus that originally was thought to be an attenuated and indigenous bacterium. In recent years, a number of reports have documented that E. corrodens can be a potential pathogen not only in immunocompromised patients but also in hosts with normal immunity. We herein study E. corrodens infections of the head and neck encountered in our department. Methods Twenty-two consecutive patients treated in our department for E. corrodens infections of the head and neck were retrospectively analyzed. Microbial specimens were subjected to light microscopic examination, aerobic culture using chocolate and sheep blood agar media, and anaerobic culture using Brucella HK agar medium. Cultured bacteria were subjected to antimicrobial susceptibility tests by means of the broth microdilution method. Results There were 16 males and 6 females with an average age of 29.9years. Two patients had malignancy, while the other patients had no particular risk factors or underlying diseases. Infected sites were the ear in 6 cases, pharynx in 12 cases (tonsil in 10 cases), paranasal sinuses in 3 cases, and salivary gland in 1 case. Seventeen patients suffered polymicrobial infections. Staphylococcus and Streptococcus were the most frequently detected pathogens coexisting with E. corrodens , and mixed infections of E. corrodens and Streptococcus milleri group bacteria were prone to form abscesses. Isolated E. corrodens was susceptible to third-generation cephems (MIC90=0.15–0.25μg/ml), carbapenems (MIC90≦0.15μg/ml), and new quinolones (MIC90≦0.15μg/ml), and resistant to oxacillin (MIC90>8μg/ml), cefazolin (MIC90>4μg/ml), macrolides (MIC90=4–8μg/ml), and clindamycin (MIC90>4μg/ml). Conclusions E. corrodens infections of the head and neck occur most frequently in the tonsil even in hosts with normal immunity. Coexistence with Streptococcus milleri group bacteria and the use of ineffective antibiotics can be exacerbating factors. First-choice drugs for E. corrodens infections should be third-generation cephems, carbapenems, or new quinolones.

We have obtained several charge-transfer complexes of CnDTP-TTF ( n = 5,6). The C5DTP-TTF salts are the κ -type semiconductor with high room-temperature conductivities, whereas β′′ -(C6DTP-TTF) 2 (GaCl 4 ) 0.66 shows the metallic behavior down to 40 K. In order to improve the conductivity by increasing the bandwidth, we have applied a pressure and synthesized a series of the selenium analogues, C n DTP-STF ( n = 5,6). In this report, crystal structures and conducting behaviors of C n DTP-TTF salts, and the attempt of increasing the bandwidths are described.

A new series of RDT-EDO-TTF [R = C5, C6, C7, C8; (cis-l,2-cycloalkylene-l,2-dithio)ethylenedioxytetrathiafulvalene and R = Bz; (benzodithio)ethylenedioxytetrathiafulvalene] donors containing cycloalkylene or benzene, and ethylenedioxy groups as a source of the steric hindrance and the intermolecular hydrogen bonds has been synthesized. The charge transfer (CT) salts, β″-(RDT-EDO-TTF)2(PF6)x (R = C5, C6, C7, C8, and Bz), have the similar β″-type donor arrangement due to the intermolecular hydrogen-bonded network (CH…O) in the two-dimensional (2D) plane. The C6DT-EDO-TTF molecule containing the flexible cyclohexylene group affords the 2:1 salts, which shows the metallic behaviors down to 1.3 K with a variety of resistivities at room temperature, 3.0 × 10−3∼5.0 × 10−2 ohm cm. On the other hand, the BzDT-EDO-TTF donor with the fixed functional benzo group gives the non-stoichiometry complexes, which exhibit the similar metallic behavior down to 1.3 K with the largest RRR = 40∼115 among the RDT-EDO-TTF salts.

This study attempts to investigate the development of sensorineural hearing loss following a head blow without skull fracture in association with physiological and histopathologic changes in an experimental animal model. With the head in a freely movable position, albino guinea pigs were given a single blow to the occipital region by a head blow device. At 1, 7, and 14 days after the blow, the animals’ auditory brainstem response (ABR) and cochlear microphonics (CM) were examined, and both the temporal bone and brain stem were observed by light and electron microscopy. The ABR threshold was unchanged at day 1, was significantly increased at day 7, and was fully recovered at day 14. The I–V and I–II interpeak latencies were significantly prolonged at days 1 and 7, and wave I latency was significantly prolonged at day 7 only. These latencies were recovered to normal limits at day 14. On the other hand, no significant change in CM versus the control group was observed at any point in the measurements. Histopathologically, no abnormal finding was seen at the light microscopic level. However, at the electron microscopic level, there were some injuries to the eighth nerve. At day 1, the lamellar structure of the myelin sheath was irregular, and the periaxonal space was expanded; at day 7, the myelin sheath was disintegrated. At day 14, however, these changes were partially reversed. These results suggest that sensorineural hearing loss following a head blow in this model is attributed to dysfunction of the eighth nerve rather than to cochlear impairment.

A new series of CnDT-EDO-TTF [n=5, 6, 7, 8; (cis-1,2-cycloalkylene-1,2-dithio)ethylenedioxytetrathiafulvalene] donors containing cycloalkylene and ethylenedioxy groups as a source of intermolecular hydrogen bonds and the steric hindrance has been synthesized. The charge transfer (CT) salts, β″-(CnDT-EDO-TTF)2(PF6)x (n=5, 6, 7, 8), have the similar β″-type donor arrangements owing to the intermolecular hydrogen-bonded network (CH⋯O) in the two-dimensional (2D) plane. The steric hindrance of cycloalkylene groups enlarges the intermolecular distance in the order from n=5, 6, 7, to 8 salt. The calculated bandwidth, however, decreases in the different order from n=8, 5, 7, to 6 salt in consideration of the 2D interactions. All salts, β″-(CnDT-EDO-TTF)2(PF6)x, show a metallic feature down to 1.5 K, and the temperature dependences indicate the negative chemical pressure effect from n=8, 5, 7, to 6 salt in the same order of the calculated bandwidth.

Magnetization measurements of hexagonal La2Ni7 were performed in magnetic fields of up to 15 T . In 54 K K , a field-induced metamagnetic transition was found to occur from an antiferromagnetic (AF) state to a ferromagnetic (F) state. At T K , successive metamagnetic transitions occur from an antiferromagnetic state via an intermediate state to a ferromagnetic state. The magnetization processes were successfully analyzed by using Landau-type free energy assuming a F state and two types of AF state.

The symmetric (s-) and unsymmetric (us-) BEDT-STF (=bis(ethylenedithio)diselenadithia-fulvalene) salts were prepared, and their crystal structures and electrical resistivities were investigated. Four us-BEDT-STF salts have the positional disorder of the Se atoms in the STF framework in crystals, whereas three s-BEDT-STF salts have no disorder. When κ-(us-BEDT-STF)2GaCl4 and κ-(cis-s-BEDT-STF)2GaCl4 are compared, the latter without the positional disorder of the Se atoms is more conductive than the former one with the disorder.

Organic superconductors have been usually obtained by the bandwidth control of antiferromagnetic insulator. In order to find another parameter to control the electronic state, the band filling control has been applied to obtain the carrier-controlled organic conductors. As a result, the systematic band filling control for four kinds of organic conductors has been succeeded. The obtained crystals were (a) 2:1 salts, λ-ET 2 (GaCl 4 1− ) 1− x (CoCl 4 2− ) x [ET=bis(ethylenedithio)tetrathiafulvalene], doping to the antiferromagnetic insulator, (b) 2:1 salts, δ′-ET 2 (GaCl 4 ) 1− x (CoCl 4 ) x , doping to the non-magnetic insulator, (c) 3:1 salts, α-ET 3 (CoCl 4 ) 1− x (GaCl 4 ) x (TCE), doping to the charge ordered salt, and (d) 3:2 salts, β′-ET 3 (CoCl 4 ) 2− x (GaCl 4 ) x , doping to the half-filled band insulator. For both 2:1 salts, (a) and (b), the semiconducting behaviors have transferred to relatively conductive semiconducting ones by doping. The largest change of transport property is observed for (d) β′-phase from semiconducting behavior of parent material to metallic ones [β′-ET 3 (CoCl 4 ) 2− x (GaCl 4 ) x ( x =0.88, 0.66)] down to 140 and 100 K, respectively. These systematic band filling control suggests that the doping to the 1/2-filled band insulator is most effective.

We studied the sleep effect, the carry over effect (sleepiness) on polysomnography (PSG), the sleep propensity test (SPT), the subjective sleep rating scale for the ultra short acting hypnotics triazolam and short acting hypnotics brotizolam. Ten healthy male volunteers were used for double blind crossover design by randomized allocation with a single oral administration. Informed consent was obtained from all subjects. Placebo (PL), triazolam (TL, 0.125 mg), triazolam (TH, 0.25 mg) and brotizolam (BR, 0.25 mg) were administered at 11 p.m. PSG was recorded from 11 p.m. to 7 a.m. in the next morning. Then, Stanford Sleepiness Scale (SSS) and Kwansei Gakuin Sleepiness Scale (KSS) were checked before 8 a.m., and SPT was recorded at 8:00–8:20 a.m. In PSG of total sleep, TH decreased the frequency of stage shifts significantly ( p p p p

Laminin is a major component of the extracellular matrix. The laminin gamma1 chain is the least variant component of the laminin heterotrimeric assembly. The laminin gamma1 chain gene (LAMC1) expression is induced by several factors, including transforming growth factor-beta (TGF-beta). LAMC1 promoter contains a highly conserved transcriptional element, bcn-1. We screened cDNA libraries with the yeast one-hybrid system to identify transcriptional factors that are recognized by the bcn-1 motif. Using this strategy we isolated the basic helix-loop-helix/leucine zipper (bHLHzip) E-box-binding transcription factor, TFE3. Until now, the E-box was the only element known to recruit the bHLHzip transcription factors. Although the bcn-1 element only remotely resembles the E-box sequence, we show that TFE3 binds and activates the bcn-1 element. TFE3 cooperates with Smad proteins in the activation of the LAMC1 promoter in cells, an effect that is critically dependent not only on the bcn-1 element but also on one of the Smad-binding elements (SBE). The cooperative induction of the LAMC1 promoter and the endogenous LAMC1 gene by TFE3 and Smad3 is augmented by the TGF-beta signaling pathway. Thus, the bcn-1 is a novel TFE3-dependent TGF-beta target element that regulates LAMC1 gene expression.

In order to search and clarify the mechanism of organic superconductors, it is of importance to control the electronic state systematically and elucidate the electronic phase diagram. In organic conductors, bandwidth control is usually applied to change the electronic states from insulating, superconducting, to metallic state. By the chemical bandwidth control with introducing Se atoms, the antiferromagnetic insulator, λ-ET 2 GaCl 4 , newly prepared, shifts to the semiconductor, λ-(us-BEDT-STF) 2 GaCl 4 , and superconductor, λ-BETS 2 GaCl 4 . It is clarified that λ-type organic superconductor has been obtained by the chemical bandwidth control of the antiferromagnetic insulator. In this paper, our recent successful results of band filling control in organic conductors are also reported.

SummaryAlthough patients with atrial fibrillation (AF) have an increased risk of embolic stroke, some clinicians hesitate to provide anticoagulation therapy for these patients during electroconvulsive therapy (ECT), which is widely applied for the treatment of intractable depression, bipolar disorder, and catatonic schizophrenia, because of potential intracerebral hemorrhage. We report on a 77-year-old female depressive patient with AF treated with aspirin but not on anticoagulation therapy because of poor compliance who developed embolic stroke 1 day after the last ECT. The CHADS2 score of this patient was 2 and included the age and hypertension. The present case suggests that anticoagulation therapy should be considered for patients with obvious risks of embolic stroke when they are subjected to ECT.

Objective: Sinusitis is frequently associated with cleft lip and palate. The present study was performed in an attempt to investigate maxillary sinus development in relation to the occurrence of sinusitis in cleft patients. Methods: Forty-seven consecutive patients with cleft lip and alveolus with or without cleft palate underwent computed tomographic scans of the maxilla. The cross-sectional area of the maxillary sinus at the level of the zygomatic arch was measured, and the soft tissue density shadow of the sinus was scored on a 4-point scale. Results: The cross-sectional area of the sinus was significantly smaller in the child group (10 years or less) than in the adolescent group (11–20 years, P

The heterogeneous nuclear ribonucleoprotein (hnRNP) K, a component of the hnRNP particles, appears to be involved in several steps of regulation of gene expression. To gain insight into mechanisms of K protein action, we performed two-hybrid screens using full-length hnRNP K as a bait. Several novel protein partners were identified, including Y-box-binding protein (YB-1), splicing factors 9G8 and SRp20, DNA-methyltransferase, hnRNP L, and hnRNP U. In vitro binding studies and co-immunoprecipitation from cellular extracts provided evidence for direct interaction between hnRNP K and YB-1. Two distinct domains in YB-1 were responsible for binding to K protein. Each protein was able to transactivate transcription from a polypyrimidine-rich promoter; however, this effect was reduced when K and YB-1 proteins were coexpressed suggesting a functional interaction between these two proteins.

The effects of bradykinin (BK) and histamine on transepithelial ion transport in primary cultures of gerbil middle ear epithelium were investigated. Lysyl-bradykinin (lys-BK) elicited a transient increase in short-circuit current ( I sc ) when added to apical or basolateral surfaces. Lys-BK had a larger effect than BK or des-arg 9 -BK on both epithelial surfaces. Histamine induced a transient increase in I sc only when added to the basolateral surface. Mepyramine, an H 1 histamine antagonist, greatly reduced the histamine-induced I sc . The H 2 and H 3 histamine antagonists were both ineffective for inhibiting the I sc responses to histamine. Diphenylamine-2-carboxylate or 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, Cl − channel blockers, significantly blocked the I sc responses to lys-BK or histamine. The Ca 2+ -mobilizing action of lys-BK and histamine was also investigated in single middle ear epithelial cells. BK and histamine induced an increase in the intracellular Ca 2+ concentration. 1,2-Bis-(2-aminophenoxy)ethane- N , N , N ′, N ′-tetraacetic acid-acetoxymethyl ester, a calcium chelator, greatly reduced the increase in the I sc responses to lys-BK or histamine. These data indicate that BK and histamine activate intracellular Ca 2+ -dependent mechanisms, leading to apical Cl − secretion in the cultured gerbil middle ear epithelium via B 2 BK receptors and H 1 histamine receptors.

Regeneration of plasma ultrafiltrate is a significant step towards the development of wearable artificial kidneys (WAK). Monolayers of Madin–Darby canine kidney (MDCK) cells were grown on inner surface of cellulose diacetate hollow fibers contained in mini-filters. Eight such devices were tested as bioartificial tubules for regeneration of peritoneal dialysis effluent (PD drainage) from a patient. PD drainage was perfused at a rate of 25 μl min−1, under 50 mm Hg hydraulic pressure and ultrafiltrate was produced from apical to basal direction of the cells. Cell-uncovered membranes (n=8) were also similarly tested as controls. Hydraulic permeability of the cell-uncovered membranes was 0.49±0.06 μl min−1, whereas that of the cell-covered membranes (experimental) was 0.28±0.04 μl min−1 (P

Physiological and pharmacological characteristics of the globular substance, a precursor of otoconia, are not well understood. In the present study, we investigated the variations and regulation of internal pH (pHi) of the globular substance of the guinea-pig inner ear. The otoconial membrane was dissected out from the utricular macula and loaded with the pH-sensitive fluorophore, carboxyseminaphthorhodafluor-1. Dynamic changes of fluorescence were directly observed under a confocal laser scanning microscope, and pHi was calculated from dual emission ratio. In the NaCl standard solution buffered with 5 mM HEPES/Tris at pH 7.4, the pHi of the globular substance varied from 6.26 to 8.55 with an average of 7.21 (n = 270). Exposure to 25 mM NH+4 induced a rapid increase of the pHi followed by a slow relaxation. The, wash-out of NH+4 caused a prompt and pronounced acidification followed by a gradual pHi recovery to the initial level. This gradual pHi recovery was significantly inhibited by the absence of external Na+, indicating the presence of an external Na(+)-dependent H+ extrusion mechanism. This pHi recovery was also inhibited by 1 mM amiloride and 10 microM 3-amino-N-(aminoiminomethyl)-6-[ethyl(2-propyl)amino]pyrazine-2-ca rboxamide. These results suggest the presence of an Na(+)-H+ exchanger in the globular substance of the guinea pig. However, HCO3(-)-transporting mechanisms were not determined. The working hypothesis for the otoconial formation is discussed.

Histochemical and biochemical studies have shown that the otoconial membrane, as well as the tectorial membrane and the cupula, contains glycoproteins and proteoglycans. However, uronic acids, which are essential elements of glycosaminoglycans (GAGs), have not so far been directly detected or quantitatively measured in inner ear samples. In the present study, we quantitatively analyzed the glucuronic acid (GlcA) content of the otoconial membrane of the guinea pig by methanolysis combined with reversed-phase high-performance liquid chromatography (RP-HPLC). The utricular otoconial membrane was treated with thermolysin to separate the supernatant (OM-sup; gelatinous layer) and precipitate (OM-ppt; otoconia). The samples were then subjected to methanolysis followed by brief TFA hydrolysis, incubated with 1-phenyl-3-methyl-5-pyrazolone for labeling, and then analyzed by RP-HPLC coupled with the detection of UV absorbance at 245 nm. The GlcA contents of OM-sup and OM-ppt were 2.1 and 5.8 pmol/100 ng protein, respectively. Based on this result, GlcA-containing GAGs estimated as (GlcA+monosulfo-N-acetylhexosamine)n would be 1.0% of protein in OM-sup and 2.61% of protein in OM-ppt, indicating that this type of glycoconjugate is a minor component in both fractions. It is, accordingly, presumed that both the gelatinous layer and otoconia of the otoconial membrane have totally different properties from those of the tectorial membrane and cartilaginous matrix, which contain abundant GAGs.

In fibrous dysplasia (FD) involving the paranasal sinuses, the initial clinical presentation is related to sinus obstruction, visual disturbance, facial asymmetry, and nasal obstruction. FD is characterized by changes of the normal bone to an isomorphous fibrous tissue and poorly formed woven b0ne.l Although clinical and radiographic features provide important information, the diagnosis of FD requires a biopsy to differentiate it from other fibro-osseous diseases.z-5 The treatment of FD is controversial and ranges from total and radical resection to conservative excision to alleviate and prevent symptoms.3,6-8 Total excisional surgery of the involved bone often accompanies secondary deformity, significant risks of morbidity, and probable mortality.3,g-12 Subtotal surgical resection of FD in advanced cases is recommended to alleviate or ameliorate symptoms. Endoscopic sinus surgery (ESS) is an established surgical treatment for chronic sinusitis.13 Expanded indications for ESS include repair of blow-out fractures, resection of inverted papilloma, and orbital decompression.14-16 An endoscopic approach provides a deep biopsy specimen with minimal surgical morbidity.2J7 We report three cases of FD treated successfully with ESS. ESS led to the establishment of

This paper describes a new approach to determine specifications of the graphical user interface (GUI) for supervisory-control systems. Conventionally specifications of the GUI are determined by making a protype with prototyping tools to check GUI behavior. However, conventional prototyping tools have the following problems, (1) it takes time to define behavior of the prototype because designers need to recognize functions at each GUI object before describing behaviour of the object, (2) it is difficult to develop the GUI because the tools provide only limited information about behaviour such as MOTIF widgets, and sometimes require user to program, (3) the tools do not make any documents which are necessary for later maintenance. We have solved these problems with the following three techniques, (1) the picture-based prototyping technique allows designers to describe the GUI by drawing sequences of images based on the operator’s interface, (2) the multiple views technique generates views automatically to extract specifications such as functions of objects from the sequences of drawn images so that programmers can make programming code for the GUI based on the specifications, (3) the document generator technique outputs the specifications as documents in the specified format. These techniques allow designers to describe behaviors of the GUI rapidly and flexibly without any programming and to obtain the necessary specifications and documents.

Lewis acid-mediated nucleophilic alkylation of the chiral [6,3a,4]oxadiaza-indano[5,4-α]isoquinoline derivatives with various organometallic reagents leads to highly enantioselective synthesis of 1-alkyl substituted tetrahydroisoquinolines. This methodology was applied to the asymmetric synthesis of (−)-salsolidine and (+)- O -methylarmepavine.

Portal vein branch occlusion induces atrophy of occluded hepatic lobes, concomitantly associated with the complementary hypertrophy of unoccluded lobes. In this context, selective embolization of the portal vein branch supplying the area to be resected has been performed prior to extended hepatectomy to reduce the risk of postoperative liver failure. However, carcinoma of the hepatic hilus is often associated with obstructive jaundice. At present it is still obscure whether cholestatic hepatocytes can also respond well to the proliferation stimuli caused by the portal vein branch embolization. To clarify this point, we made a rat model of portal vein branch ligation in combination with cholestasis. As an indicator of proliferation, we determined the activity of DNA polymerase alpha and the mitotic index. The results demonstrate that, even in the cholestatic liver, the expression of DNA polymerase alpha in unoccluded lobes was induced by contralateral portal vein branch ligation. The maximal degree of DNA polymerase alpha induction in the cholestatic liver was similar to that in the noncholestatic liver, i.e., fivefold above that in the resting liver. The level of DNA polymerase alpha activity correlated well with the mitotic index in the same tissue. Furthermore, the cell proliferation after the portal vein branch occlusion is not suppressed by the preceding external biliary drainage, which had been shown to suppress the liver regeneration after partial hepatectomy. From these results, it is concluded that portal vein branch ligation induces liver cell proliferation in unoccluded lobes, irrespective of the presence of cholestasis.

We report here measurements of the photo-luminescence spectra and the time response of the σ-conjugated polymer, poly(methylphenylsilane), film at 2 K. The site-selective luminescence and the time response are discussed in terms of the exciton band model and localized states in disordered system.

Biological characteristics of the globular substance, which is considered to be a precursor of otoconia, were investigated by means of confocal laser scanning microscopy. The shape of the globular substance was a complete sphere, 3–10 μm in diameter. Its surface stained positively with both rhodamine 123 and DiOC 6 (3), implying similarity to intracellular organelles, whereas no fluorescence was seen when stained with chlortetracycline, a membrane-associated Ca 2+ dye. Meanwhile, this substance showed very little affinity for six kinds of lectins, indicating the lack of a surface structure of carbohydrates. The fluorescence of fluo-3 in the globular substance increased markedly after the application of ionomycin. But this was completely inhibited by the depletion of external Ca 2+ . This reaction suggests that the surface of the globular substance exhibits characteristics of a biological membrane and that the influx of external Ca 2+ occurs through membrane-combined ionomycin. Internal free Ca 2+ concentration varied from 1.1×10 −9 to 1.6×10 t-4 M, the geometric mean being 3.3×10 −7 M, which is higher than normal resting level of intracellular Ca 2+ concentration but lower than the calcium content of the globular substance estimated by X-ray microanalysis in previous studies.

Nucleophilic addition of carbon nucleophiles and metal hydride reagents to hydrazonium salts modified by optically active 2-substituted pyrrolidine auxiliaries leads to highly enantioselective synthesis of 1-substituted tetrahydroisoquinolines. This methodology was applied to asymmetric synthesis of the title isoquinoline alkaloids.