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Background: Trappin‐2/pre‐elafin is an endogenous inhibitor of human neutrophil elastase involved in inflammation, innate immunity and vascular remodelling, which consist of the complex pathological process of systemic sclerosis (SSc). Objectives: To clarify the potential role of trappin‐2 in SSc. Methods: Serum trappin‐2 levels were determined by enzyme‐linked immunosorbent assay in 51 SSc and 18 healthy subjects. Trappin‐2 expression was evaluated in SSc lesional skin and cultured endothelial cells treated with FLI1 siRNA by immunohistochemistry, reverse transcription‐real‐time PCR and/or immunoblotting. Friend leukaemia virus integration 1 (Fli1) binding to the PI3 promoter was assessed by chromatin immunoprecipitation. Results: Since serum trappin‐2 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction, SSc patients with normal renal function were analysed. Although serum trappin‐2 levels were comparable between diffuse cutaneous SSc, limited cutaneous SSc and control subjects, the prevalence of digital ulcers or elevated right ventricular systolic pressure (RVSP) was significantly higher in SSc patients with elevated serum trappin‐2 levels than in those with normal levels. Furthermore, serum trappin‐2 levels were significantly increased in SSc patients with digital ulcers or elevated RVSP compared to those without. Moreover, serum trappin‐2 levels positively correlated with RVSP values in SSc patients. Importantly, trappin‐2 expression was enhanced in small vessels of SSc lesional skin. In cultured endothelial cells, trappin‐2 expression was elevated by gene silencing of FLI1 at mRNA and protein levels and Fli1 occupied the PI3 promoter. Conclusions: Endothelial trappin‐2 up‐regulation partially due to Fli1 deficiency can be associated with the development of SSc vasculopathy. [ABSTRACT FROM AUTHOR]

SUMMARY: In this paper, we present a novel flexible sensor array manufacturing process that involves transfer printing methods using a chip mounter with a vacuum collet. We successfully transfer‐printed continuously very fragile microelectromechanical systems (MEMS)‐based 5‐mm‐long, 1‐mm‐wide, 5‐μm‐thick high‐aspect‐ratio ultrathin PZT (1.9 μm)/Si (3 μm) strain sensors onto a polyimide based flexible printed‐circuit (FPC) substrate with etched Cu wiring. Then, we connected the sensors to the Cu wiring by printing insulating and conductive pastes using a screen printer. The output voltage based on the deformation behavior of the test plate was generated from the flexible piezoelectric strain sensor array attached to the plate. Therefore, the developed piezoelectric sensor array is capable of easily performing the distribution measurement of the strain leading to damage such as cracks. [ABSTRACT FROM AUTHOR]

Abstract: Background/Purpose: The relationships between the skin components and these mechanical roles are still unclear. To clarify these relationships, we investigated spatial mapping of the mechanical behavior of cultured skin equivalents (SEs) using optical coherence tomography (OCT)‐based straingraphy. Methods: We built a strain relaxation test system combined with OCT and developed an algorithm that could visualize a time‐dependent strain distribution, named dynamic‐optical coherence straingraphy (D‐OCSA). Using this system, we analyzed how the spatial mechanical changes in the SEs depended on the culture duration. For quantitative analysis of viscoelastic behavior, we defined a relaxation attenuation coefficient of strain rate, which indicates the ratio of viscosity and elasticity in the Klevin‐Voight model. Results: By culturing for 4 days in comparison to culturing for 1 day, the strain relaxation attenuation coefficient of the whole skin, especially at the region of the dermal‐epidermal junction (DEJ), significantly increased in the negative direction. In tissue slices taken for microscopy, several cracks were observed in the SEs cultured for 4 days. Conclusion: This study is the first to provide quantified evidence that the DEJ is a dynamically specialized region. An OCT‐based straingraphy system (D‐OCSA) would be beneficial for evaluating the quality of SEs, as well as functional analysis of their mechanics. [ABSTRACT FROM AUTHOR]

Background Antimicrobial peptides have attracted much attention as a member of disease-associated molecules in systemic sclerosis (SSc), which is pathologically characterized by immune abnormalities, vasculopathy and tissue fibrosis. Objective To investigate the potential contribution of one of the antimicrobial peptide psoriasin to the development of SSc. Methods Psoriasin expression in the skin samples and sera derived from SSc patients and its correlation with clinical parameters were analysed. Psoriasin expression was evaluated by immunohistochemistry with skin samples from SSc patients and healthy controls. Serum levels of psoriasin were determined by enzyme-linked immunosorbent assay in 51 SSc patients and 19 healthy controls and assessed for the association with clinical symptoms. Results The expression of psoriasin was elevated in the epidermis of SSc lesional skin. Serum psoriasin levels were higher in SSc patients, especially in diffuse cutaneous SSc patients with disease duration of <6 years, than in healthy controls. With respect to clinical association, SSc patients with interstitial lung disease, telangiectasia and pitting scars had significantly augmented levels of serum psoriasin than those without each of these symptoms. In the subgroup of patients with interstitial lung disease, the elevation of serum psoriasin levels was associated with higher ground-glass opacity scores. Furthermore, serum psoriasin levels were decreased after the treatment with intravenous cyclophosphamide pulse as compared to baseline values. Conclusion Our findings indicate a possible contribution of psoriasin to the development of clinical symptoms associated with vascular and epithelial abnormalities and inflammation in SSc, further supporting the roles of antimicrobial peptides in the SSc pathogenesis. [ABSTRACT FROM AUTHOR]

Aims To test the hypothesis that treatment with a sodium-glucose co-transporter-2 inhibitor would reverse ventricular repolarization heterogeneity, a predictor of cardiovascular mortality, in people with Type 2 diabetes. Methods We retrospectively analysed changes in indices of ventricular repolarization before and after treatment with a sodium-glucose co-transporter-2 inhibitor in 46 people with Type 2 diabetes. Results Sodium-glucose co-transporter-2 inhibitor treatment reduced HbA1c concentration [62±13 mmol/mol (7.7±1.2%) vs 59±16 mmol/mol (7.5±1.4%)], body weight (77.8±13.9 vs 74.7±12.5 kg) and systolic blood pressure (133±18 vs 126±12 mmHg) in the study participants. Heart rate and QTc interval were not changed by sodium-glucose co-transporter-2 inhibitor treatment, but QTc dispersion was significantly reduced (median, 48.8 vs 44.2 ms). Sodium-glucose co-transporter-2 inhibitor treatment reversed QTc dispersion more in participants who had larger QTc dispersion before the treatment. Changes in systolic blood pressure (Spearman's ρ= 0.319; P=0.031), but not in HbA1c concentration, were correlated with changes in QTc dispersion after sodium-glucose co-transporter-2 inhibitor treatment. Conclusions The findings suggest that sodium-glucose co-transporter-2 inhibitor treatment reverses ventricular repolarization heterogeneity in people with Type 2 diabetes, independently of its effect on glycaemic control. The favourable effect on ventricular repolarization heterogeneity could be the mechanism by which empaglifozin reduced cardiovascular events in a recent study. [ABSTRACT FROM AUTHOR]

Background and purpose Few studies have examined why some patients with dementia stop attending medical consultations. We conducted a retrospective study to investigate factors associated with discontinuous clinic attendance. Methods Participants were 988 patients with dementia from university hospital (UH) clinics and affiliated local hospital (LH) clinics. We compared continuous and discontinuous attenders on cognitive and affective functions and activities of daily living (ADL), and also compared UH and LH patients (UH: continuous, n = 176; discontinuous, n = 207; LH: continuous, n = 418; discontinuous, n = 187). Results The total annual rate of discontinuation was 8.0%, and the mean period of attendance before discontinuation was 2.2 ± 2.4 years (UH, 2.8 ± 3.0; LH, 1.5 ± 1.3, P < 0.01). Scores for the Mini-Mental State Examination, Hasegawa Dementia Scale - Revised, Geriatric Depression Scale, apathy scale, Abe's behavioral and psychological symptoms of dementia (BPSD) score, and ADL were significantly worse in the discontinuous group than the continuous group for both UH and LH patients ( P < 0.01). The best predictor of discontinuation was ADL decline (UH and LH) and Abe's BPSD score (UH). The most common reason for discontinuation was returning to the family doctor (39.1% for UH), and cessation of hospital attendance at their own discretion (35.3% for LH). Conclusions We identified the main reasons for discontinuation of attendance as returning to the family doctor and cessation of hospital attendance at their own discretion. The best predictors of discontinuation were ADL decline and worsening BPSD. There were significant differences in discontinuation between UH and LH patients with dementia. [ABSTRACT FROM AUTHOR]

Background: This study marks the first epidemiological evaluation of the prevalence and burden of chronic neuropathic pain (NeP) in an Asian population. The objective of this nationwide cross-sectional study was to identify the characteristics of individuals with NeP, detect the NeP features that affect their quality of life (QOL), and demonstrate the negative effects of NeP on social and daily living as well as comorbidities including depression, anxiety and sleep disorders.Methods: We mailed a cross-sectional, population-based epidemiological survey to a random nationwide sample of 10,000 Japanese adults over 20 years old.Results: The response rate was 54.4% (2445 men, 2992 women; mean age, 53.4 years). Prevalence of chronic pain was 16.6%, and prevalence of NeP was 3.2% as detected by the PainDETECT. Participants with NeP showed significantly lower quality of life according to scores on the EuroQol-5 Dimensions scale (p < 0.001), higher levels of psychological distress on the Kessler 6-item psychological distress scale (p < 0.001), poorer sleep quality (p < 0.001), and more workdays lost (p < 0.001) than did participants without NeP. Linear regression modelling showed that widespread pain, thermal hyperalgesia and pressure-induced pain had strong associations with lower QOL, with regression coefficients of -0.046 (p < 0.001), -0.038 (p < 0.001), and -0.040 (p < 0.001), respectively.Conclusions: This study is the first to report the prevalence of NeP in an Asian population using a validated questionnaire. This study provides compelling evidence that chronic NeP is more strongly associated with poorer QOL, mental health and social well-being than CP without a neuropathic component.Significance: This population-based nationwide epidemiological study revealed the prevalence, characteristics, and negative effects of chronic pain with neuropathic components in Asian society. The prevalence of neuropathic pain was 3.2% with PainDETECT. [ABSTRACT FROM AUTHOR]

Background Facial skin pigmentation is one of the most prominent visible features of skin aging and often affects perception of health and beauty. To date, facial pigmentation has been evaluated using various image analysis methods developed for the cosmetic and esthetic fields. However, existing methods cannot provide precise information on pigmented spots, such as variations in size, color shade, and distribution pattern. The purpose of this study is the development of image evaluation methods to analyze individual pigmented spots and acquire detailed information on their age-related changes. Methods To characterize the individual pigmented spots within a cheek image, we established a simple object-counting algorithm. First, we captured cheek images using an original imaging system equipped with an illumination unit and a high-resolution digital camera. The acquired images were converted into melanin concentration images using compensation formulae. Next, the melanin images were converted into binary images. The binary images were then subjected to noise reduction. Finally, we calculated parameters such as the melanin concentration, quantity, and size of individual pigmented spots using a connected-components labeling algorithm, which assigns a unique label to each separate group of connected pixels. Results The cheek image analysis was evaluated on 643 female Japanese subjects. We confirmed that the proposed method was sufficiently sensitive to measure the melanin concentration, and the numbers and sizes of individual pigmented spots through manual evaluation of the cheek images. The image analysis results for the 643 Japanese women indicated clear relationships between age and the changes in the pigmented spots. Conclusion We developed a new quantitative evaluation method for individual pigmented spots in facial skin. This method facilitates the analysis of the characteristics of various pigmented facial spots and is directly applicable to the fields of dermatology, pharmacology, and esthetic cosmetology. [ABSTRACT FROM AUTHOR]

Background: There were several reports suggesting α-adrenoceptor antagonists are effective to treat neuropathic pain. The aims of this study were as follows: (1) to introduce drug delivery system for dorsal root ganglion (DRG) neurons; (2) to elucidate the effects of α-adrenoceptor antagonists in acute, subacute or chronic phase and (3) to determine which subtype of adrenoceptor was mainly involved.Method: We used 130 male Sprague-Dawley rats. After root constriction, rats received three local injections of α-adrenoceptor antagonists around DRG. We administered the non-selective α-adrenoceptor antagonist phentolamine for 3 consecutive days from day 0, 4 or 11 after the surgery, and the α1-adrenoceptor antagonist prazosin, the α1-adrenoceptor antagonist silodosin, the more preferred α1-adrenoceptor than prazosin and the α2-adrenoceptor antagonist yohimbine for 3 consecutive days from day 0 after the surgery.Results: Phentolamine and yohimbine continually attenuated pain behaviour. Prazosin at high dose attenuated pain behaviour, however, prazosin at low dose did not attenuate pain behaviour every experimental day. Silodosin had no analgesic effect. Phentolamine injections from day 4 after surgery attenuated pain behaviour that had been established on the 3rd experimental day until the 28th post-operative day, although effect of phentolamine wore off. Phentolamine injections from day 11 after surgery temporarily attenuated pain behaviour that had been established on the 3rd, 7th and 10th experimental days.Conclusions: This study showed α-adrenoceptor antagonists could suppress pain behaviour via α2-adrenoceptor in acute phase and temporary attenuate pain behaviour in chronic phase. These findings presented potentials sympathetic nerve blockade contributed to treat neuropathic pain. [ABSTRACT FROM AUTHOR]

ABSTRACT The total mercury content of Quaternary sediments over the last 1.1 Ma from IODP Site U1308 drilled in the North Atlantic Ocean has changed, varying with periodicities of 100 000 and 41 000 years. The Hg content of the sediment increased during glacial periods, associated with increases in ice-rafted debris (IRD), and correlates positively with the total organic carbon (TOC) content and inversely with the absolute abundance of surface-dwelling nannoplankton species. TOC/total nitrogen ratios and δ13Corg values of TOC indicate that the TOC deposited during glacial periods was marine and associated with increased Hg deposition. These observations suggest that marine Hg is incorporated into the organic matter produced by deep-dwelling phytoplankton in the lower photic zone. Mercury- and IRD-bearing icebergs flowed out to this area during glacial periods melt, increasing the Hg content of photic water, and depositing IRD on the ocean floor, where increased marine Hg during glacial periods was consumed by deep-dwelling phytoplankton. Therefore, the change in the sediment Hg content from the North Atlantic Ocean is controlled by climatic change and can be used as a chemical indicator of Northern Hemisphere ice sheet variability. [ABSTRACT FROM AUTHOR]

Background and purpose: The influence of metabolic syndrome (MetS) on cognitive and affective functions in patients with Alzheimer's disease (AD) was examined. Methods: A total of 570 AD patients were divided into two subgroups depending on waist circumference (WC) (normal versus achieving Japanese diagnostic criteria of MetS). Afterwards, the AD control subgroup was defined as those normal WC patients with no vascular risk factors (VRFs). The AD with MetS (AD-MetS) subgroup was defined as the MetS WC group who had two or more VRFs to qualify as having MetS. Cognitive and affective functions, insulin resistance, vascular endothelial function and white matter changes between AD-MetS and AD controls were compared. Results: Scores on the Mini-Mental State Examination, Hasegawa Dementia Score -- Revised, Frontal Assessment Battery and Montreal Cognitive Assessment were worse in the AD-MetS group than in AD controls, but the difference was not significant. Some analyses were conducted twice, once including all patients and once including only late-elderly patients. Scores on the Geriatric Depression Scale were found to be significantly higher for AD-MetS than for AD controls (all ages, late-elderly), as were those for apathy (late-elderly). Furthermore, both the homeostasis model assessment of insulin resistance and reactive hyperemia index scores were significantly worse in AD-MetS than in AD controls, whilst white matter changes showed a tendency to be worse. Conclusions: Greater cognitive and affective decline occurs in patients with AD-MetS than in those without. Further, insulin resistance and vascular endothelial dysfunction are strongly correlated with AD-MetS before pathological white matter changes can be observed. [ABSTRACT FROM AUTHOR]

Background and purpose: A novel TYPE of prion disease associated mainly with autonomic-sensory polyneuropathy was reported by us previously. Methods: Here the autopsy pathology for patient 1 (the sister) and the clinical characteristics of her younger brother (patient 2) are newly reported. Polymerase chain reaction based restriction fragment length polymorphism analysis of the prion protein gene (PRNP) was performed on both patients and their father (normal control). Results: Polymerase chain reaction based restriction fragment length polymorphism analysis revealed a 2-bp deletion (CT) in codon 178 that causes an additional variable 25 amino acids at the C terminal, from the mutation site to the premature stop codon at codon 203, in both patients 1 and 2 but not in their father. The autopsy of patient 1 showed remarkable prion protein (PrP) deposits in the sympathetic ganglion and peripheral nerves, correlated to her severe autonomic sensory failure. PrP deposits were also found in the central nervous system and peripheral organs such as the heart, lung, stomach, jejunum, ileum, colon, urinary bladder and adrenal gland. The symptoms and biopsy findings of patient 2 were nearly the same as those reported previously for patient 1. His cognitive function was well preserved, but autonomic functions were severely impaired. His biopsied samples showed PrP deposits in the sural nerve and nerve plexuses of the stomach and colon. Conclusion: The present unique 2-bp deletion (CT) in codon 178 induced a 'PrP systemic deposition disease' such as pan-autonomic failure, sensory neuropathy and mild cognitive impairment with a specific pathology. [ABSTRACT FROM AUTHOR]

The band gap of and disordered structure in Li8SiN4 (lattice constant: a = 10.148 Å, c = 9.567 Å) are studied by optical absorption, photoacoustic spectroscopy, X-ray diffraction, and Raman scattering spectroscopy. Li8SiN4 is a semiconductor with a band gap of 2.4 eV, suggesting the transition from the N-2p valence band to the conduction band mainly consisting of Si-3s and/or -3p orbitals. A broad Raman peak is observed at 586 cm-1, indicating the homogenously random distribution of Li and Si atoms. Li8SiN4 crystallizes in a superstructure of eight face-centered N sublattices. In each sublattice, one Li and one Si atom are randomly and diagonally occupied at two tetrahedral sites next to N, while six Li atoms reside at the other sites next to N. The possible locations of one remaining Li atom are also discussed. Li8SiN4 is a direct transition, which is slightly larger than the d-d electron transitions in the typical cathode materials LiMn2O4 and LiCoO2. For a 5 × 5 mm2 sized lithium secondary battery with the Li8SiN4 + acetylene black cathode/propylene carbonate + LiClO4 electrolyte/Li anode structure, the capacity for the discharge current of 10 µA is between 2.44 µAh/cm2 and 3.56 µAh/cm2 for a potential range between 2.8 V and 3.8 V. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Background and Purpose: The ω-3 polyunsaturated fatty acids exert antinociceptive effects in inflammatory and neuropathic pain; however, the underlying mechanisms remain unclear. Docosahexaenoic acid-induced antinociception may be mediated by the orphan GPR40, now identified as the free fatty acid receptor 1 (FFA1 receptor). Here, we examined the involvement of supraspinal FFA1 receptor signalling in the regulation of inhibitory pain control systems consisting of serotonergic and noradrenergic neurons.Experimental Approach: Formalin-induced pain behaviours were measured in mice. Antinociception induced by FFA1 receptor agonists was examined by intrathecal injections of a catecholaminergic toxin, 5-HT lowering drug or these antagonists. The expression of FFA1 receptor protein and c-Fos was estimated by immunohistochemistry, and the levels of noradrenaline and 5-HT in the spinal cord were measured by LC-MS/MS.Key Results: FFA1 receptors colocalized with NeuN (a neuron marker) in the medulla oblongata and with tryptophan hydroxylase (TPH; a serotonergic neuron marker) and dopamine β-hydroxylase (DBH; a noradrenergic neuron marker). A single i.c.v. injection of GW9508, a FFA1 receptor agonist, increased the number of c-Fos-positive cells and the number of neurons double-labelled for c-Fos and TPH and/or DBH. It decreased formalin-induced pain behaviour. This effect was inhibited by pretreatment with 6-hydroxydopamine, DL-p-chlorophenylalanine, yohimbine or WAY100635. Furthermore, GW9508 facilitated the release of noradrenaline and 5-HT in the spinal cord. In addition, GW1100, a FFA1 receptor antagonist, significantly increased formalin-induced pain-related behaviour.Conclusion and Implications: Activation of the FFA1 receptor signalling pathway may play an important role in the regulation of the descending pain control system. [ABSTRACT FROM AUTHOR]

Background and Purpose The ω-3 polyunsaturated fatty acids exert antinociceptive effects in inflammatory and neuropathic pain; however, the underlying mechanisms remain unclear. Docosahexaenoic acid-induced antinociception may be mediated by the orphan GPR40, now identified as the free fatty acid receptor 1 ( FFA1 receptor). Here, we examined the involvement of supraspinal FFA1 receptor signalling in the regulation of inhibitory pain control systems consisting of serotonergic and noradrenergic neurons. Experimental Approach Formalin-induced pain behaviours were measured in mice. Antinociception induced by FFA1 receptor agonists was examined by intrathecal injections of a catecholaminergic toxin, 5-HT lowering drug or these antagonists. The expression of FFA1 receptor protein and c- Fos was estimated by immunohistochemistry, and the levels of noradrenaline and 5-HT in the spinal cord were measured by LC- MS/ MS. Key Results FFA1 receptors colocalized with Neu N (a neuron marker) in the medulla oblongata and with tryptophan hydroxylase ( TPH; a serotonergic neuron marker) and dopamine β-hydroxylase ( DBH; a noradrenergic neuron marker). A single i.c.v. injection of GW9508, a FFA1 receptor agonist, increased the number of c- Fos-positive cells and the number of neurons double-labelled for c- Fos and TPH and/or DBH. It decreased formalin-induced pain behaviour. This effect was inhibited by pretreatment with 6-hydroxydopamine, DL-p-chlorophenylalanine, yohimbine or WAY100635. Furthermore, GW9508 facilitated the release of noradrenaline and 5-HT in the spinal cord. In addition, GW1100, a FFA1 receptor antagonist, significantly increased formalin-induced pain-related behaviour. Conclusion and Implications Activation of the FFA1 receptor signalling pathway may play an important role in the regulation of the descending pain control system. [ABSTRACT FROM AUTHOR]

Background and purpose Diabetes mellitus ( DM) is associated with a decline in cognitive and affective functions. Methods In all, 182 outpatients with DM were investigated for associations of cognitive and affective functions with diabetes-related factors and cerebral white matter abnormalities. In addition, the difference in cognitive decline of age-matched late elderly normal subjects and DM patients was investigated. Results The present study revealed that cognitive and affective functions declined in some DM patients. Furthermore, the decline in these functions was unrelated to fasting blood sugar level but was related to glycosylated hemoglobin (HbA1c) and insulin resistance. Poor HbA1c control was associated with a significant decline in the 'calculation' subscale and insulin resistance for 'naming', 'read list of letters' and 'delayed recall' Montreal Cognitive Assessment (Mo CA) subscale scores. Magnetic resonance imaging scans showed that both periventricular hyperintensity ( PVH) and deep white matter hyperintensity were associated with Mini Mental State Examination ( MMSE) and Mo CA scores, but only PVH was related to homeostasis model assessment of insulin resistance scores. Compared with age-matched late elderly normal subjects, 'orientation to time' and 'registration' MMSE subscales declined in late elderly DM patients. Conclusions These results suggest that cognitive and affective decline in DM patients was mostly related to glucose control and insulin resistance, whilst amongst late elderly subjects the impairment of 'attention' and 'orientation' were characteristic features of DM patients. [ABSTRACT FROM AUTHOR]

Background and purpose Spinocerebellar ataxia type 36 ( SCA36), also called Asidan, is an autosomal-dominant neurodegenerative disorder identified as a hexanucleotide GGCCTG repeat expansion in the first intron 1 of the NOP56 gene. In the present study, for the first time an autopsy sample from an Asidan patient was examined and cytoplasmic inclusions and ( GGCCUG) n repeat RNA foci were detected. Methods Hematoxylin and eosin staining, immunohistochemical staining, as well as fluorescence in situ hybridization were used to investigate the cytoplasmic inclusions of ubiquitin and p62 and the ( GGCCUG) n repeat RNA foci. Results The present study showed both ubiquitin- and p62-positive inclusions in the cytoplasm of the inferior olivary nucleus of the Asidan patient, ( GGCCUG) n RNA foci in neuronal nuclei of the cerebrum, cerebellum, inferior olive, spinal cord and temporal muscle, and three types of RNA foci, i.e. single small, multiple small and giant. Of interest is that the giant RNA foci, nearly 10 μm in diameter, that were detected in Purkinje cells, spinal motor neurons and most frequently in the inferior olivary nucleus, may be responsible for pivotal clinical symptoms of Asidan. Conclusions The present study is the first report to show neuronal cytoplasmic inclusion bodies and giant RNA foci in an Asidan patient. The relationships between the giant RNA foci and neurodegeneration have yet to be studied. [ABSTRACT FROM AUTHOR]

Introduction The number of infused CD34+ cells is crucial to the success of peripheral blood stem cell transplantation ( PBSCT). Here, we present, for the first time, a new method of enumerating hematopoietic progenitor cells ( HPCs) for PBSCT. Method This novel method is based on hemolysis and chemical staining, followed by flow cytometry-based optical detection, conducted using an automated hematology analyzer ( XN series, Sysmex). CD34+ cells and HPCs were compared in 76 granulocyte colony-stimulating factor (G- CSF)-mobilized blood or apheresis samples taken from healthy donors ( n = 18) or patients undergoing autologous PBSCT ( n = 6). Results There was a strong correlation between the numbers of HPCs and CD34+ cells ( R2 = 0.958). The expected total number of HPCs in the final products, which was estimated from HPCs in pre-apheresis PB or mid-apheresis products, also correlated well with the total number of CD34+ cells in the final products. The change in HPCs in PB closely resembled that of CD34+ cells during mobilization. Experiments using immunomagnetic beads suggested that the majority of CD34+ cells existed in HPCs, and vice versa. Conclusion Hematopoietic progenitor cells may serve as surrogates for CD34+ cells in PBSCT. However, further investigations are required to verify this. [ABSTRACT FROM AUTHOR]

The surface structure of polycrystalline wustite was observed by means of scanning tunnel microscopy (STM). Wustite (Fe1- xO) samples were prepared from oxidation of iron plates under different oxygen partial pressures. The non-stoichiometry numbers (1- x) of Fe1- xO were 0.912, 0.901 and 0.887, respectively. Fe1- xO surface is composed of many terraces like stairs. The planes are covered with mesh. The mesh size is about 1.3 nm, corresponding to the double lattice constant of Fe1- xO, and independent of x. There are some depressions in the mesh randomly distributed and the mesh around the depressions is deformed. [ABSTRACT FROM AUTHOR]

With 6 figures and 2 tables Soybean Kunitz trypsin inhibitor (SKTI) is extensively studied for its biological function, anti-nutritional feature, transgenic insect-resistant breeding and as a genetic marker for tracing the origin and dissemination of soybeans. In this study, SKTI was revealed to exist with a high level of polymorphism at its single locus in the genus Glycine subgenus Soja. We investigated 5612 individual plants of Chinese wild soybean for polymorphic variation and geographical distribution of SKTI in China. As a result, five new variants were detected. These variants were Tibi7, Tih, Tii, Tij and Tik. Together with the known variants at this locus, the sum surprisingly has accounted up to at least eight electrophoretically distinguishable variants at this locus in Chinese wild soybean. This strongly suggests that Chinese wild soybean has high level of polymorphism at SKTI locus, and this protein has high mutability in the phylogenetic history of SKTI. The geographical pattern of the polymorphism indicated that the variability of SKTI abounded in Northeast China and Tib allele existed with high frequency in the southeastern littoral of China. [ABSTRACT FROM AUTHOR]

In this study, we regenerated skin and its appendages by transplanting cultured normal dermal fibroblasts, into which morphogen genes had been introduced. We cultured normal dermal fibroblasts obtained from Fisher 344 rats on the surface of hydroxyapatite beads, and then adsorbed them onto the surface of a collagen sponge, which was transplanted into a full-thickness skin defect prepared on the backs of rats. Before transplantation, genes were introduced into the dermal fibroblasts via adenovirus vector (ad)-bone morphogenetic protein 2 and ad-wingless int 3 genes in addition to fibroblast growth factor-2 protein. By Week 4, the appearance of follicle germs or primitive hair germs was observed only in the ad-bone morphogenetic protein 2+ad-wingless int 3 combined with the fibroblast growth factor-2 protein group. By Week 16, in that same group, hair follicles having mature pilosebaceous systems with equally spaced localization had formed in the ulcer wound. [ABSTRACT FROM AUTHOR]

Background: Lafutidine is a unique histamine H2-receptor antagonist (H2RA) that has a sensitizing effect on capsaicin-sensitive afferent neurons (CSAN). This effect may make lafutidine useful for the treatment of burning mouth syndrome (BMS). Methods: To evaluate the efficacy and safety of lafutidine in patients with oral burning sensation, a randomized controlled trial was performed. Patients who had been receiving other H2RAs with no sensitizing effect on CSAN were randomly assigned to receive lafutidine 10 mg twice daily for 12 weeks, instead of the previous H2RAs, plus gargling with azulene sulfonate sodium (ASS) (lafutidine group, n = 36) or to continue to receive the previous H2RAs plus ASS gargling (control group, n = 35). The intensity of burning sensation was scored by means of a visual analog scale (VAS). Results: Thirty-four patients in the lafutidine group and 30 in the control group completed the study. In the lafutidine group, the rate of improvement in the VAS score as compared with the baseline value was significant after 4, 8, and 12 weeks of treatment ( P < 0.05). The improvement rate was consistently higher in the lafutidine group than in the control group; the differences between the groups were significant ( P < 0.05) after 4, 8, and 12 weeks of treatment. Only two mild abdominal adverse events occurred in the lafutidine group, but neither required the termination of treatment. Conclusion: Oral lafutidine is very safe and effective for reducing the intensity of oral burning sensation and may therefore be a viable option for the treatment of BMS. [ABSTRACT FROM AUTHOR]

BACKGROUND: A study of Asian-American students suggested a positive association between inactive ALDH2*2 and susceptibility to hangover. A biomarker for moderate-to-heavy drinking in persons with inactive aldehyde dehydrogenase-2 (ALDH2) is increased mean corpuscular volume (MCV). METHODS: Associations between hangover and ALDH2 genotype, alcohol flushing, and MCV were examined for 251 Japanese workers (139 men, 112 women). RESULTS: Inactive ALDH2*1/2*2 heterozygotes drank less alcohol than active ALDH2*1/2*1 homozygotes (p < 0.0001), but the frequency of hangover did not significantly differ between the two groups for either gender. The amount of drinking reported to lead to hangover was significantly less for male and female ALDH2*1/2*2 heterozygotes than for their ALDH2*1/2*1 homozygous counterparts (p < 0.005). The proportion of men who had hangover three times or more during the past year increased significantly with increased daily alcohol consumption in men with the ALDH2*1/2*2 genotype (p = 0.0002) but not in those with the ALDH2*1/2*1 genotype. For men who usually consumed <44 g of ethanol/day, the median amount of drinking before hangover was significantly lower for ALDH2*1/2*2 men than for ALDH2*1/2*1 men reporting the same level of consumption. Hangover occurred with consistently high frequency among ALDH2*1/2*1 men, regardless of their daily consumption. Similar findings were observed in a comparison of men who never flushed and those who reported current or former flushing, a surrogate marker of inactive ALDH2. Assessment of hangover risk by quartiles of MCV showed that men with MCV of > or =96 had a significantly higher risk of hangover than did men with MCV of <91 (odds ratio = 5.56; 95% confidence interval = 1.69-18.25). CONCLUSIONS: Inactive heterozygous ALDH2, alcohol flushing, and increased MCV were positively associated with hangover susceptibility in Japanese workers, suggesting that acetaldehyde is etiologically linked to the development of hangover. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a multifactorial disease in which the genes of the major histocompatibility complex (MHC) play a key role. Recently, non-human leukocyte antigen (non-HLA) genes in the class III region of this complex have been presumed to be associated with type 1 diabetes by linkage analyses. We investigated the possibility of the inhibitor of κB-like ( IKBL, also known as ‘ NFKBIL1’) gene as one of these candidates. We carried out a case-control study of 124 patients with type 1 diabetes and 330 healthy control subjects. The haplotypes of the IKBL promoter, i.e., PA (−263A, −63T), PB (−263A, −63A), PC (−263G, −63T), were assigned by the single-nucleotide polymorphisms at positions −263 and −63 from the transcription start site. The frequency of the wild-type haplotype, PA, was elevated, while that of the variant-type haplotype, PC, was lower in patients than controls. In two-locus analyses with HLA-DRB1 alleles, the PA haplotype showed linkage disequilibrium with the DRB1* 0405 allele and the PC haplotype with the DRB1* 1502 allele. A notable observation was that the PC haplotype was significantly associated with protection in the DRB1* 1502-negative population. Our study indicates the first evidence of a possible independent association between type 1 diabetes and polymorphisms in the promoter of the IKBL gene. [ABSTRACT FROM AUTHOR]

Background: In vitro culture systems have been used to study the physiological and pathological characteristics of human mast cells. However, there are some differences in proliferation and maturation of mast cells between fetal bovine serum (FBS)-containing and serum-deprived cultures. Accordingly, we attempted to identify circulating factor(s) affecting the development of human mast cells. Methods: We measured the serum levels of retinol and several cytokines. To elucidate the antiproliferative effects of the serum, a retinoic acid receptor (RARα ) antagonist and neutralizing antibodies against cytokines were used. Results: Similar to FBS, human serum dose-dependently suppressed the growth of tryptase[sup +] cells from CD34[sup +] cord blood cells or 20-week cultured mast cells under stimulation with stem cell factor (SCF). The serum-mediated inhibition might be based on a decline in proliferation rate. Among inhibitors for mast cell growth, retinol and transforming growth factor (TGF)-β 1 were present at high levels in human serum. In contrast with anti-TGF-β 1 antibody, an RARα antagonist counteracted the serum-induced suppression of human mast cell proliferation. Conclusions: Our results suggest that retinol and its derivatives act as a circulating regulator for human mast cell growth. The RARα antagonist may be a useful tool to obtain higher numbers of mast cells in FBS-containing cultures. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increased mean corpuscular volume (MCV) is common in alcohol abusers and alcoholics. MCV is higher in Japanese heavy drinkers with inactive aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/2*2 than among those with active ALDH2 encoded by ALDH2*1/2*1. Inactive ALDH2 dramatically increases blood acetaldehyde levels after alcohol intake. Because moderate and heavy drinkers with ALDH2*1/2*2 have very high risks for esophageal cancer, MCV might serve as an indicator of these high-risk drinkers. METHODS: In this investigation of the association of red cell values with the ALDH2 genotype and possible confounding factors, the drinking, smoking, and dietary habits reported on a structured questionnaire by 163 Japanese working men were subjected to multivariate analyses. RESULTS: Aging, lower body mass index (BMI), more alcohol consumption, and more smoking were positively associated with increased MCV. Among moderate to heavy drinkers (>or=9 units/week; 1 unit = 22 g of ethanol), both MCV and mean corpuscular hemoglobin were higher and the red cell count was lower in those with ADLH2*1/2*2 than in those with ALDH2*1/2*1. Multiple linear regression analysis after adjustment for age, BMI, and smoking revealed that a positive relationship between the amount of drinking and MCV but inverse relationships for drinking and red cell count, as well as hemoglobin and hematocrit values, were significantly stronger for men with ALDH2*1/2*2 than for those with ALDH2*1/2*1, demonstrating a gene-environment interaction. Drinking accounted for 19.9% of interindividual MCV variance among men with ALDH2*1/*2*2 but for only 1.3% of variance among those with ALDH2*1/2*1. Age, BMI, drinking, and smoking accounted for 52.1 and 34.7% of the variation among those with ALDH2*1/2*2 and ALDH2*1/2*1, respectively. Macrocytosis (MCV >or=100.0 fl) was observed in 18 subjects (11.0%), and use of macrocytosis as a biomarker of moderate to heavy drinkers with ALDH2*1/2*2 had a sensitivity of 54.5% (6 of 11) and a specificity of 92.1% (140 of 152). CONCLUSIONS: Alcohol-related red cell value changes associated with inactive ALDH2 in Japanese men suggest the importance of acetaldehyde's role in increasing MCV and the potential for using MCV as a marker for high-risk drinkers for esophageal cancer. [ABSTRACT FROM AUTHOR]

One of the most striking features of neurons in the mature peripheral nervous system is their ability to survive and to regenerate their axons following axonal injury. To perform a comprehensive survey of the molecular mechanisms that underlie peripheral nerve regeneration, we analyzed a cDNA library derived from the distal stumps of post-injured sciatic nerve which was enriched in non-myelinating Schwann cells using cDNA microarrays. The number of up- and down-regulated genes in the transected sciatic nerve was 370 and 157, respectively, of the 9596 spotted genes. In the up-regulated group, the number of known genes was 216 and the number of expressed sequence tag (EST) sequences was 154. In the down-regulated group, the number of known genes was 103 and that of EST sequences was 54. We obtained several genes that were previously reported to be involved in regeneration of the injured neurons, such as cathepsin D, ninjurin 1, tenascin C, and co-receptor for glial cell line-derived neurotrophic factor family of trophic factors . In addition to unknown genes, there seemed to be a lot of annotated genes whose role in nerve regeneration remains unknown. [ABSTRACT FROM AUTHOR]

Summary Eminoplasty using T-shaped titanium miniplate was performed on 15 joints in nine patients suffering from recurrent dislocation of the temporomandibular joint with several general complications. After the conventional pre-auricular approach to the zygomatic arch and eminence, the bent over miniplate was inserted anteriorly against the articular eminence and fixed to the zygomatic arch with miniscrews to limit the over-movement of the condyle. In one case, the miniplate fractured, but no recurrence of dislocation was observed. In another case, it was possible to evaluate the mandibular movement by Sirognathograph analysis, which proved satisfactory function of the joints. [ABSTRACT FROM AUTHOR]

BackgroundAlthough interleukin (IL)-4 and IL-5 have been demonstrated to play a critical role in the pathophysiology of allergic diseases such as allergic rhinitis, the mechanism that causes the predominance of Th2 lymphocytes has yet to be clarified. Thymus and activation-regulated chemokine (TARC) has been known to facilitate the recruitment, activation and development of Th2 polarized cells, leading investigators to suggest a role for TARC in the development of Th2 responses. ObjectiveTo gain a better understanding of the role of TARC in the pathogenesis of allergic rhinitis we investigated the cellular sources of this chemokine in nasal mucosa. In addition, the effect of cytokines on TARC production has been investigated. MethodsThe expression of TARC in human nasal mucosa was assessed by immunohistochemistry. To study the effect of cytokines on TARC production, epithelial cells, endothelial cells and fibroblasts, isolated from inferior nasal mucosa samples, were stimulated by a variety of cytokines including IL-4, IL-13, tumour necrosis factor (TNF)-α and interferon (IFN)-γ. ResultsEpithelial cells in nasal mucosa in subjects with allergic rhinitis expressed higher signal level than those in non-allergy patients. Combined stimulation with IL-4 and TNF-α, as well as IL-13 and TNF-α, synergistically induced TARC expression in epithelial cells. Furthermore, the amount of TARC induced by these cytokines was higher in epithelial cells obtained from patients with allergic rhinitis than in those from non-allergic patients. ConclusionThese results demonstrate a crucial role of nasal epithelial cells in the expression of TARC, and that Th2 cytokine IL-4 and IL-13 may promote Th2 responses by inducing TARC production from epithelial cells. [ABSTRACT FROM AUTHOR]

Describes serial levels of interleukins (IL)-4, IL-5 and IL-13 serum eosinophil cationic protein and blood and urine eosinophil derived neurotoxin (EDN) in a patient with Chrug-Strauss syndrome treated by oral prednisolone. Clinical findings; Relationship between IL-13 and EDN and nonspecific biologic inflammatory marker levels.

Objectives: Advanced glycation end products (AGE) are present in amyloid deposits in beta2-microglobulin amyloidosis, and it has been postulated that glycation of beta2-microglobulin may be involved in fibril formation. The aim of this paper was to ascertain whether AGE occur in amyloid deposits in familial amyloidotic polyneuropathy (FAP).Setting: Department of Medicine, Umeå University Hospital and First Department of Internal Medicine, Kumamoto University School of Medicine.Design: The presence of AGE was sought immunohistochemically and biochemically in amyloid-rich tissues from patients with FAP.Subjects: Biopsy specimens from nine patients and 10 controls were used for the immunohistochemical analysis. For amyloid preparation, vitreous samples from three FAP patients were used.Results: Immunohistochemical studies using a polyclonal anti-AGE antibody revealed positive immunoreactivity in intestinal materials, but the pattern of reactivity was unevenly distributed; it was often present in the border of amyloid deposits, or surrounding them. Non-amyloid associated immunoreactivity was also observed in a few regions of the specimens, although the AGE-positive structures were situated in areas containing amyloid deposits. Western blotting of purified amyloid from the vitreous body of FAP patients revealed a significant association of AGE with amyloid fibrils.Conclusion: The immunoreactivity for the AGE antibody suggests that AGE may be involved in fibril formation in FAP. [ABSTRACT FROM AUTHOR]

We performed a 5 year longitudinal study of cycloplegic refraction in a cohort of 350 Japanese schoolchildren from 6 to 11 years of age in a rural area of southwestern Japan. The spherical refraction was measured under cycloplegia with an infrared autorefractometer. The grouped data from 350 right eyes showed leptokurtic frequency distributions, and the median was +0.91 D at age 6 yrs, shifted towards emmetropia with increasing age and reached +0.34 D at age 11 years. The prevalence of myopia of -1.0 D or more was 0.3%, 0.6%, 2.0%, 2.6%, 2.9%, and 4.9% from age 6 to 11 years. and the prevalence of myopia of more than -2.0 D was less than 1% at age 6-9 years and thereafter increased up to 6.0% at age 11 years. Linear regression analysis for the longitudinal refractive data revealed that 247 (70.6%) of the 350 eyes exhibited first-order linear decrease in hyperopia or increase in myopia with an average annual change of -0.15 D/year, 14 (4%) showed second-order curvilinear change. and 89 (25.4%) remained unchanged. In the eyes with linear change, there was a significant relationship between the refraction at age 6 years and the rate of subsequent change such that the less hyperopic or emmetropic at age 6 years, the larger the change. The refraction at birth was estimated by extrapolation of the linear regression analysis results, implying that 88% of newborns have hyperopia of +1.0 D or greater and myopia is rare. These results indicate the current state of refraction in Japanese schoolchildren of a rural area. [ABSTRACT FROM AUTHOR]

Background: The pathogeneses of allergic rhinitis and bronchial asthma are believed to be closely mutually related because of the similar dynamics of allergy‐inducing cells and molecules and clinical overlap. In this study, we compared these diseases in the dynamics of cell apoptosis‐regulating molecules. Methods: Allergic rhinitis patients (n=36), bronchial asthma patients (n=22), and healthy subjects (n=32) were subjected to measurement of serum (soluble Fas) (sFas) levels during the stable and attack disease phases by a sandwich enzyme‐linked immunosorbent assay. Results: Serum sFas levels in patients with allergic rhinitis during the attack phase were significantly lower (P<0.0001) than those in healthy individuals. There were no differences between them during the attack and stable disease phases. In contrast, serum sFas levels in patients with bronchial asthma during the attack phase were higher (P<0.0005) than those in healthy individuals. Interestingly, the levels during the attack phase were lower (P<0.002) than those during the stable phase. Conclusions: Our results suggest a different pathogenesis for allergic rhinitis and bronchial asthma at the cell apoptosis‐linked step. [ABSTRACT FROM AUTHOR]

This study analysed the effect of Schistosoma japonicum egg antigens (SEA) on the activation of lymphocytes from naive mice. T cells were found to be unaffected by SEA. B cells, however, were activated by SEA without participation of adherent cells such as macrophages. B-cell activating factor(s) in SEA were distributed into a fraction of Mr 120,000 and a fraction of Mr 650,000 by gel filtration. However, a fraction of Mr 120,000 demonstrated thc presence of a limited number of components by polyacrylamide gel electrophoresis (PAGE) under non-denaturing conditions. These activating factor(s) were destroyed by peroxidase oxidation, heat treatment, chymotrypsin and trypsin digestion. These results indicate that the B-cell activating factor(s) in SEA contain both carbohydrate and protein. IgM antibodies were detected in the culture supernatant of SEA-activated B cells after 48 hr in culture, but IgG antibodies were undetected in culture. These antibodies did not react with SEA but reacted with sheep, horse, mouse red blood cells, carbonic anhydrase and autoantigens in myelinated nerve fibres of cerebrum as well as luminal surface and parietal cells of the stomach of naive mice. Thus our data demonstrated that SEA directly stimulates naive B cells to produce antibodies against heterophile and autologous antigens. [ABSTRACT FROM AUTHOR]

We examined the mechanisms of disturbed T-lymphocyte function that occurred during Schistosoma japonicum infection of BALB/c mice from the viewpoint of the interleukin cascade reaction. Each point of the interleukin cascade reaction was examined. First, IL-1 production by adherent peritoneal or spleen cells, as a source of macrophages, was normal or rather enhanced during the infection, the values being 100-180% of the control. Secondly, proliferative response to exogenous IL-1 of thymocytes from S. japonicum-infected mice progressively decreased during 3-7 weeks of infection. Thirdly, IL-2 production of S. japonicum-infected mice was significantly inhibited, even at 2 weeks of infection, and the activity was 10-20% of the control at 5-8 weeks of infection. Diminished IL-2 production was not caused by suppressive factors, such as PGE2 or suppressor macrophages, or a decrease in the number of IL-2-producing T cells. Finally, the response to exogenous IL-2 in S. japonicum-infected mice was suppressed markedly by 4 weeks of infection, and the responsiveness was reduced to 20% of the control at 8 weeks of infection. The mechanisms of disturbances in T-cell functions in S. japonicum-infected mice are discussed. [ABSTRACT FROM AUTHOR]

Background Recent studies have revealed that interleukin (IL)-13, as well as IL-4, causes de novo surface expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells of the umbilical vein and accelerates selective eosinophil migration. However, its role in allergic rhinitis remains to be clarified. Of particular interest is whether IL-13 upregulates VCAM-1 expression in human mucosal microvascular endothelial cells (HMMECs), to which eosinophils adhere in nasal mucosa. Methods To understand the potential role of IL-13 in eosinophilic inflammation in nasal mucosa, we examined the effects of IL-13 on the adhesiveness between HMMECs and eosinophils. Results IL-13 increased VCAM-1 expression in HMMECs, the adhesiveness of endothelial cells to eosinophils, and the transendothelial migration. On the other hand, IL-13 decreased the adhesiveness of eosinophils to HMMECs, and, as a result, accelerated eosinophil infiltration. Those effects are more potent than was those of IL-4. In addition, we also report that the amount of IL-13 in nasal mucosa was higher than that of IL-4. Conclusions These results strongly indicate that IL-13, as well as IL-4, may be important in eosinophilic inflammation in the nasal mucosa. [ABSTRACT FROM AUTHOR]

We investigated whether the amount of antigen has an effect on the systemic and local levels of soluble ICAM-1 (sICAM-1 ) in patients with pollinosis, and assessed its biologic significance. The levels of subjective symptoms and sICAM-1 in sera and nasal epithelial lining fluids (ELF) from 14 subjects with pollinosis (allergic group) and eight healthy subjects (control group) were measured from pre- to postseason in 1993 (total pollen count: 10854/cm²) and 1994 (total pollen count: 415/cm²), and the results were compared with each other among the four groups. The levels of subjective symptoms and sICAM-1 in ELF from the allergic group significantly increased during the season in both 1993 and 1994. However, there was a significant difference (P<0.01) between the levels of those in 1993 and those in 1994 during the season. The levels of sICAM-1 in sera from the allergic group were significantly upregulated during the seasons and postseasons only in 1993, and there was a significant difference (P<0.05) between the levels in 1993 and those in 1994 during the postseason. We conclude that amount of pollen has an influence on the local and systemic levels of sICAM-1, as well as the scores of subjective symptoms, in patients with seasonal allergic rhinitis. [ABSTRACT FROM AUTHOR]