Axonal TDP-43 aggregates in sporadic amyotrophic lateral sclerosis.

AIMS: Axonal aggregates of phosphorylated (p-) transactive response DNA-binding protein 43 kDa (TDP-43) in sporadic amyotrophic lateral sclerosis (sALS) were examined in relation to propagation of the protein in the nervous system. METHODS: Brains and spinal cords of Japanese patients with sALS and control subjects were examined immunohistochemically using formalin-fixed paraffin-embedded specimens with special reference to the topographical distribution, microscopic features, presynaptic aggregates, and correlation between the aggregates in axons and the clinical course. RESULTS: (i) Aggregates of p-TDP-43 were frequently present in axons of the hypoglossal and facial nerve fibres and the spinal anterior horn cells. (ii) Aggregates of p-TDP-43 in the axons showed two characteristic microscopic features - dash-like granuloreticular aggregates (GRAs) and massive aggregates (MAs). (iii) MAs were surrounded by p-neurofilaments, but p-neurofilament immunnoreactivity decreased at the inside of axons with GRAs. (iv) Patients showing MAs and GRAs had a relatively shorter clinical course than patients without the aggregates. (v) Some neurones in the red nucleus in patients were surrounded by synapses containing p- and p-independent (i)-TDP-43, and almost all neurones had lost their nuclear TDP-43 immunoreactivity; 17% of those neurones in the red nucleus also had TDP-43-immunopositive neuronal cytoplasmic inclusions, but no postsynaptic p-TDP-43 deposition was evident. CONCLUSIONS: There are two types of axonal p-TDP-43 aggregates, MAs and GRAs, located predominantly in the facial and hypoglossal nuclei and anterior horn cells. These aggregates may influence the function of neurones, and presynaptic aggregates of the protein induce loss of p-i-TDP-43 in the nuclei of postsynaptic neurones.

Pressure-induced valence crossover and novel metamagnetic behavior near the antiferromagnetic quantum phase transition of YbNi_{3}Ga_{9}.

We report electrical resistivity, ac magnetic susceptibility, and x-ray absorption spectroscopy measurements of intermediate valence YbNi_{3}Ga_{9} under pressure and magnetic field. We have revealed a characteristic pressure-induced Yb valence crossover within the temperature-pressure phase diagram, and a first-order metamagnetic transition is found below P_{c}∼9 GPa where the system undergoes a pressure-induced antiferromagnetic transition. As a possible origin of the metamagnetic behavior, a critical valence fluctuation emerging near the critical point of the first-order valence transition is discussed on the basis of the temperature-field-pressure phase diagram.

Compact, highly efficient ytterbium doped bismuthate glass waveguide laser.

Laser slope efficiencies close to the quantum defect limit and in excess of 78% have been obtained from an ultrafast laser inscribed buried channel waveguide fabricated in a ytterbium-doped bismuthate glass. The simultaneous achievement of low propagation losses and preservation of the fluorescence properties of ytterbium ions is the basis of the outstanding laser performance.

Association of clinical oral health status with self-rated oral health and GOHAI in Japanese adults.

OBJECTIVE: The objective of this study was to investigate clinical oral health status relationships that affect quality of life (using the 12-item General Oral Health Assessment Index (GOHAI)) and self-rated oral health in a community of Japanese residents. METHODS: 459 residents of Yokote City, Japan aged 40-55 years had oral health examinations and completed self-administered questionnaires collecting data on age, gender, GOHAI items and self-rated oral health. Linear regression analysis was performed with GOHAI or self-rated oral health as a dependent variable and gender, age and indicators of oral health status as independent variables. RESULTS: The GOHAI indicated 42.7% of subjects were concerned about the appearance of their teeth, 30.1% were worried about teeth problems and 27.5% concerned about sensitive teeth. Analyses showed that gender, decayed teeth, oral dryness and missing teeth were significantly associated with variation in GOHAI scores, and that gender, decayed teeth, oral dryness and oral hygiene were significantly associated with variation in self-rated oral health. CONCLUSION: This study revealed that in this sample of Japanese adults aged 40-55 years, decayed teeth and oral dryness affected both GOHAI and self-rated oral health, whereas missing teeth affected GOHAI and oral hygiene affected self-rated oral health. Subjects did not recognise periodontal disease as a quality of life impacting condition or as a health problem.

Relationship of smoking and smoking cessation with oral health status in Japanese men.

BACKGROUND AND OBJECTIVE: Smoking has been associated with the number of natural teeth a person has and with the likelihood of periodontitis. The purpose of this study was to determine the relationships between the number of teeth present and periodontal diseases with smoking habits in a cohort of Japanese men. MATERIAL AND METHODS: The study group comprised 1088 men, 40-75 years of age. Oral examinations were conducted in dental clinics. Information on smoking status and on oral health behavior was collected from self-administered questionnaires. The relationship between oral health status and smoking status was estimated using adjusted odds ratios. RESULTS: Compared with those whom had never smoked, the odds ratios of having more than eight missing teeth and having periodontitis, among current smokers, were 1.67 and 1.74, respectively. In those who had stopped smoking for 11 years or longer, there was no increase in the odds ratio of having more than eight missing teeth and periodontitis, compared with those whom had never smoked. CONCLUSION: Smoking has a positive association with missing teeth and periodontitis. However, smoking cessation is beneficial for oral health. The odds of having more than eight missing teeth, or of having periodontitis, in those who had never smoked was similar to that of individuals who reported that they had stopped smoking for 11 years or more.

Gastric hyposecretion in esophageal squamous-cell carcinomas.

Recently, gastric fundic atrophy is reported to be an independent risk factor for esophageal squamous-cell carcinoma (ESCC). The aim of this study is to investigate the acid secretory level in ESCC in a case-control study. From April 2004 to March 2008, 100 consecutive subjects with early ESCC and 100 age- and sex-matched asymptomatic controls were prospectively enrolled. Gastrin-stimulated acid output was assessed by endoscopic gastrin test. Conditional regression analyses were used to adjust for other potential confounders. Multivariate analyses revealed a strong association between profound hypochlorhydria and ESCC with odds ratio (95% confidence interval): 6.0 (1.9-18.4). The association remained significant after adjusting for the effect of gastric atrophy as a covariate. The association became stronger as the ESCC developed more distal site of the esophagus. This study indicates that profound hypochlorhydria is a strong independent risk factor for ESCC even after adjusting for the influence of gastric atrophy.

An 8-month-old boy with congenital fibromuscular dysplasia presenting with shock caused by sudden renal hemorrhage.

Fibromuscular dysplasia (FMD) is a non-atheromatous, non-inflammatory, multifocal segmental angiopathy. FMD is the most common cause of pediatric renovascular hypertension. Aneurysmal formation of the main renal artery and distal branches is a rare complication of FMD in infancy. We report an 8-month-old boy with FMD presenting with shock caused by sudden renal hemorrhage that necessitated removal of one kidney. A diagnosis of renovascular hypertension resulting from intimal type FMD with aneurysmal formation was made on the basis of the presence of hypertension, elevation of PRA and aldosterone activity, pathological findings and the results of renal angiography. Our findings suggest that it is therefore necessary to consider FMD with aneurysmal formation as a possible cause of hypertension and renal hemorrhage in infants.

Relationship between the acid-inhibitory effects of two proton pump inhibitors and CYP2C19 genotype in Japanese subjects: a randomized two-way crossover study.

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Brillouin gain-coefficient measurement for bismuth-oxide-based photonic crystal fiber under significant beam reflection at splicing points.

We investigate a six-air-hole bismuth-oxide-based photonic crystal fiber (Bi-PCF) in terms of Brillouin characteristics. One huge challenge in measuring the Brillouin properties of the Bi-PCF is the nonnegligible beam reflection at the splicing points, which can be attributed to the mirroring effect caused by different refractive indices of silica and bismuth fibers. To solve the problem we propose a method that is based on the combination of a pump-probe beat lock-in scheme and a normalized gain curve-fitting technique. Using this method, successful characterization of Brillouin properties for a 1.16-m-long Bi-PCF is experimentally demonstrated. With the measured Brillouin gain coefficient and the known chi((3)) nonlinearity parameters, the Kerr nonlinearity figure-of-merit (F(nl-SBS)), including the stimulated Brillouin scattering-caused pump-power limit, is also estimated for the Bi-PCF.

Direct condensation of carboxylic acids with alcohols catalyzed by Hafnium(IV) salts.

In order to promote atom efficiency in synthesis and to avoid the generation of environmental waste, the use of stoichiometric amounts of condensing reagents or excess substrates should be avoided. In esterification, excesses of either carboxylic acids or alcohols are normally needed. We show that the direct condensation of equimolar amounts of carboxylic acids and alcohols can be achieved with the use of hafnium(IV) salts, such as commercially available hafnium(IV) chloride and hafnium(IV) tert-butoxide. The present method can be applied to direct polyesterification and may be suitable for large-scale operations.

Rebamipide, a cytoprotective drug, increases gastric mucus secretion in human: evaluations with endoscopic gastrin test.

We have previously developed a rapid, simple endoscopic method for evaluating gastrin-stimulated maximal acid output (the endoscopic gastrin test, EGT). In EGT, gastric fluid newly secreted over 10 min after gastrin stimulation is collected under direct endoscopic visualization. In this study, employing the EGT, we evaluated the effect of rebamipide, a cytoprotective anti-ulcer drug, on gastric mucus secretion. In ten Helicobacter pylori-negative healthy volunteers, gastric juice was collected by EGT prior to and after 4-week administration of rebamipide. The collected gastric juice was subjected to analysis for gastric mucus output. Total gastric mucin output was significantly increased by 53% by rebamipide administration from 3.2 +/- 1.2 mg hexose/10 min to 4.9 +/- 2.2 mg hexose/10 min (P < 0.01). Further analysis by ion-exchange chromatography revealed that rebamipide administration induced a specific increase in acidic mucin rich in sialic acid. Applying EGT, this study demonstrated that rebamipide administration increased gastric mucus secretion in human.

Relationship of smoking and smoking cessation with number of teeth present: JPHC Oral Health Study*.

BACKGROUND: Smoking is associated with the number of teeth. The purpose of this study was to determine the relationship of number of teeth with smoking and smoking cessation. METHODS: Subjects included 547 males aged between 55 and 75 years. Oral examinations were conducted in 2005. Smoking status information was collected from questionnaire surveys conducted in 1990, 1995, 2000, and 2005. The relationship between having more than eight missing teeth and smoking status was estimated with adjusted odds ratio. RESULTS: Comparing with never smokers, odds ratios of having more than eight missing teeth among current and former smokers were 1.96 and 1.86, respectively. The odds ratios in those who had stopped smoking for

Disruption of gastric barrier function by luminal nitrosative stress: a potential chemical insult to the human gastro-oesophageal junction.

OBJECTIVE: The human gastro-oesophageal junction is exposed to abundant amounts of luminal reactive nitrogen oxide species (RNOS) derived from the enterosalivary re-circulation of dietary nitrate. The aim of this study is to investigate the direct effects of luminal RNOS on the adjacent gastric barrier function using an ex vivo chamber model. METHODS: A chamber model in which the rat gastric mucosal membrane was mounted between the two halves of a chamber was designed to simulate the microenvironment of the lumen and the adjacent mucosa of the gastro-oesophageal junction. On the mucosal side of the chamber, RNOS were generated by the acidification of physiological concentrations of sodium nitrite. The epithelial barrier function was evaluated by electrophysiological transmembrane resistance, and membrane permeability with [3H]mannitol flux. The expression of occludin was evaluated by immunohistochemistry and immunoblotting. Dinitrosyl dithiolato iron complex (DNIC) was also measured by means of electron paramagnetic resonance spectroscopy to confirm the diffusion of RNOS from the mucosal lumen into the mounted mucosa. RESULTS: The administration of acidified nitrite to the mucosal lumen caused both a decrease in transmembrane resistance and an increase in epithelial permeability, suggesting a disturbance of the gastric barrier function. These changes were accompanied by a derangement of the expression of occludin. The diffusion of luminal RNOS into the mounted membrane was confirmed by showing the generation of DNIC within the tissue. CONCLUSIONS: Simulating the microenvironment of the human gastro-oesophageal junction, this study demonstrated that RNOS generated luminally at the human gastro-oesophageal junction can derange the barrier function of the adjacent tissue by disrupting the tight junction.

Nanoparticles synthesis using supercritical fluid technology - towards biomedical applications.

Supercritical fluid (SCF) technology has become an important tool of materials processing in the last two decades. Supercritical CO(2) and H(2)O are extensively being used in the preparation of a great variety of nanomaterials. The greatest requirement in the application of nanomaterials is its size and morphology control, which determine the application potential of the nanoparticles, as their properties vary significantly with size. Although significance of SCF technology has been described earlier by various authors, the importance of this technology for the fabrication of inorganic and hybrid nanomaterials in biomedical applications has not been discussed thoroughly. This review presents the nanomaterial preparation systematically using SCF technology with reference to the processing of biomedical materials. The basic principles of each one of the processes have been described in detail giving their merits and perspectives. The actual experimental data and results have been discussed in detail with respect to the selected nanomaterials for biomedical applications. The SCF synthesis of nanoparticles like phosphors, magnetic materials, carbon nanotubes, etc. have been discussed as they have potential applications in bio-imaging, hyperthermia, cancer therapy, neutron capture therapy, targeted drug delivery systems and so on. The more recent approach towards the in situ surface modification, dispersibility, single nanocrystal formation, and morphology control of the nanoparticles has been discussed in detail.

Neural activities of tactile cross-modal working memory in humans: an event-related potential study.

In the present study, we examined the neural mechanisms underlying cross-modal working memory by analyzing scalp-recorded event-related potentials (ERPs) from normal human subjects performing tactile-tactile unimodal or tactile-auditory cross-modal delay tasks that consisted of stimulus-1 (S-1, tactile), interval (delay), and stimulus-2 (S-2, tactile or auditory). We hypothesized that there would be sequentially discrete task-correlated changes in ERPs representing neural processes of tactile working memory, and in addition, significant differences would be observed in ERPs between the unimodal task and the cross-modal task. In comparison to the ERP components in the unimodal task, two late positive ERP components (LPC-1 and LPC-2) evoked by the tactile S-1 in the delay of the cross-modal task were enhanced by expectation of the associated auditory S-2 presented at the end of the delay. Such enhancement might represent neural activities involved in cross-modal association between the tactile stimulus and the auditory stimulus. Later in the delay, a late negative component (LNC) was observed. The amplitude of LNC depended on information retained during the delay, and when the same information was retained, this amplitude was not influenced by modality or location of S-2 (auditory S-2 through headphones, or tactile S-2 on the left index finger). LNC might represent the neural activity involved in working memory. The above results suggest that the sequential ERP changes in the present study represent temporally distinguishable neural processes, such as the cross-modal association and cross-modal working memory.

Analysis of synchrony demonstrates that the presence of "pain networks" prior to a noxious stimulus can enable the perception of pain in response to that stimulus.

Our previous study has shown that directed attention to a painful stimulus is associated with increased synchrony between electrocorticographic (ECoG) oscillations in pain-related cortical structures. We now test the hypothesis that the synchrony or functional connectivity of this pain network differs between events during which pain is or is not perceived (pain or non-pain events) in response to a noxious cutaneous laser stimulus. ECoG recordings were made through subdural electrodes implanted in a patient for the treatment of epilepsy. The patient was instructed that the stimulus could be painful or non-painful on any given presentation. Synchrony between ECoG signals at different sites was measured during the pre-stimulus interval, and the difference in the number of sites with significant pre-stimulus synchrony was compared between pain and non-pain events. Pre-stimulus synchrony was more common during pain versus non-pain events among electrodes overall, and in the subset of electrodes at which laser-evoked potentials (LEPs) were recorded. This difference between pain and non-pain events was also significant for the subset of electrodes over medial cortex, including anterior cingulate cortex (ACC), but not for subsets of electrodes over the superior and inferior convexity, including primary somatosensory (S1) and parasylvian cortex (PS), respectively. These results suggest that dynamic changes in the functional connectivity between ACC and other cortical regions enable the perception of pain in response to noxious stimuli.

Masticatory ability and functional tooth units in Japanese adults.

The purposes of this study were (i) to examine the relationship between the number of natural teeth and the number of functional tooth units in Japanese adults, (ii) to evaluate how functional tooth units relate to subjective masticatory ability and (iii) to determine the minimum number of natural teeth and functional tooth units needed to maintain adequate self-assessed chewing function. A self-administered questionnaire was given and dental examination was conducted for 2164 residents aged 40 to 75 years. Counts were made on the number of functional tooth units of natural teeth (n-functional tooth units), the sum of natural teeth and artificial teeth on implant-supported and fixed prostheses (nif-functional tooth units) and the sum of natural teeth and artificial teeth on implant-supported, fixed and removable prostheses (total-functional tooth units). The average number of natural teeth, n-functional tooth units and nif-functional tooth units decreased with age, but these were often replaced by functional tooth units from artificial teeth on removable prostheses. Total-functional tooth units in 50-59 year old people were slightly lower compared with those in other age groups. Subjects who reported that they could chew every food item on an average had 23.4 total natural teeth, 12.6 posterior natural teeth, 7.6 n-functional tooth units, 8.6 nif-functional tooth units and 10.4 total-functional tooth units, and subjects without chewing difficulties had fewer functional tooth units from removable prostheses. Maintaining 20 and more natural teeth and at least eight nif-functional tooth units is important in reducing the likelihood of self-assessed chewing difficulties.

Thrombin-induced exposure and prostacyclin inhibition of the receptor for factor VIII/von Willebrand factor on human platelets.

The receptor for Factor VIII/von Willebrand factor (F. VIIIVWF) is readily available on circulating platelets. We have found that the stimulation of platelets with traces of thrombin at concentrations that are generated physiologically (0.008 U-0.05 U/ml) induced concentration-dependent binding of 125I-labeled F. VIIIVWF in a steady-state system. The binding induced by thrombin was specific because it was inhibited by a 100-fold molar excess of unlabeled F. VIIIVWF factor, by rabbit monospecific antibody against Factor VIII, and was not inhibited by an excess of fibrinogen or fibronectin. Binding induced by thrombin required metabolically active platelets, in contrast to a system with ristocetin that also prompted binding to glutaraldehyde-treated platelets. The thrombin effects on binding of 125I-F. VIIIVWF was not observed when platelets were washed with EDTA-containing buffers; EDTA and EGTA both inhibited thrombin-induced binding. Platelet membrane glycoproteins were required because enzymatic stripping od them from the platelet surface with chymotrypsin reduced binding 2.5-5.0-fold. Prostacyclin, in the concentration range of 1 to 50 nM, had two distinct effects on the receptor for F. VIIIWVF: (a) it prevented exposure of this receptor when added 10 min before thrombin, and (b) it reversed the binding of 125I-F. VIIIVWF to the platelet receptor when added 30 min after thrombin and the ligand, ie., when binding was at equilibrium. The dual effect of prostacyclin on the receptor for F. VIIIVWF was reproduced by dibutyryl cyclic AMP.

Four-wave mixing based widely tunable wavelength conversion using 1-m dispersion-shifted bismuth-oxide photonic crystal fiber.

We demonstrate widely tunable wavelength conversion based on four-wave mixing using a dispersion-shifted bismuth-oxide photonic crystal fiber (Bi-PCF). A 1-meter-long Bi-PCF is used as the nonlinear medium for wavelength conversion of a 10 Gb/s non-return-to-zero (NRZ) signal. A 3- dB working range of the converted signal over 35 nm is obtained with around 1-dB power penalty in the bit-error-rate measurements.

Psychophysics of CNS pain-related activity: binary and analog channels and memory encoding.

The forebrain neuronal system signaling pain has been poorly characterized. The pain pathway afferent to the thalamus may be a labeled line consisting of neurons in the pain-signaling pathway to the brain (spinothalamic tract, STT) that respond only to painful stimuli. It has recently been proposed that the STT contains a series of analog-labeled lines, each signaling a different aspect of the internal state of the body (interoception), for example, visceral/cold/itch sensations. In this view, pain is the unpleasant emotion produced by disequilibrium of the internal state. The authors now show that stimulation of an STT receiving zone (thalamic principal somatic sensory nucleus, ventral caudal) in awake humans produces two different exteroceptive responses. The first is a binary response signaling the presence of painful stimuli. The second is an analog response in which nonpainful and painful sensations are graded with intensity of the stimulus. Such stimulation can evoke both the sensory and emotional components of previously experienced pain. These results illustrate the diverse functions of human pain signaling pathways.