Brain acetylcholinesterase activity in FTDP-17 studied by PET.
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Biomedical subjects
Publications and source records attributed to K Fukushi.
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Nanofiltration (NF) is considered as one of the most promising separation technologies to obtain a very good-quality permeate in water and wastewater treatment. A submerged NF membrane bioreactor (NF MBR) using polyamide membranes was tested for a long-term operation and the performance of the NF MBR was compared with that of a microfiltration MBR (MF MBR). Total organic carbon (TOC) concentration in the permeate of the NF MBR ranged from 0.5 to 2.0 mg/L, whereas that of the MF MBR showed an average of 5 mg/L. This could be explained by the tightness of the NF membrane. Although the concentration of organic matter in the supernatant of the NF MBR was higher than that in the permeate due to high rejection by the NF membrane, the NF MBR showed excellent treatment efficiency and satisfactory operational stability for a long-term operation.
This study evaluates the performance of nanofiltration membrane bioreactor (NF MBR) systems using cellulose triacetate (CA) and polyamide (PA) membranes. The results indicated that both NF membranes could produce high quality permeate in the submerged NF MBR system. In addition, hollow fiber CA membranes exhibited the capability of higher permeate productivity than PA membranes. However, to obtain high quality permeate for a long-term operation, CA membranes should be maintained using an appropriate method, such as chlorine disinfection, in order to control the membrane biodegradation. The results demonstrated that PA membranes were capable of producing higher quality permeate for a long period than CA membranes. In order to enhance the practicability of PA membranes in submerged NF MBR systems, it is required that the membranes should have the lowest possible intrinsic salt rejection.
The presence of pathogenic microorganisms in municipal waste sludge may create a serious outbreak of water borne diseases if the sludge is used for agricultural purpose. An attempt to decrease the number of pathogenic microorganisms, Salmonella spp. using a simulated acid-phase anaerobic digester was tested in a laboratory-scale batch experiment. Reduction of Salmonella spp. was demonstrated in a mixture of sludge and organic acid, simulating an acid digester of a two-phase anaerobic digestion process. A high concentration of organic acid at a pH value of 5.5-6.0 prevents a decrease in Salmonella spp. concentration. Almost complete destruction of Salmonella spp. is observed within two days if the pH value is maintained below 5.5.
The presence of pathogenic microorganisms in municipal waste sludge may create a serious outbreak of water borne diseases if the sludge is used for agricultural purpose. An attempt to decrease the number of pathogenic microorganisms, Salmonella spp. using a simulated acid-phase anaerobic digester was tested in a laboratory-scale batch experiment. Reduction of Salmonella spp. was demonstrated in a mixture of sludge and organic acid, simulating an acid digester of a two-phase anaerobic digestion process. A high concentration of organic acid at a pH value of 5.5-6.0 prevents a decrease in Salmonella spp. concentration. Almost complete destruction of Salmonella spp. is observed within two days if the pH value is maintained below 5.5.
The primary transmitter deficit is cholinergic in Alzheimer's disease (AD), and the amygdala receives a major cholinergic projection from the nucleus basalis of Meynert (Ch4), which may play an important role in the retention of affective conditioning and/or memory consolidation. We measured brain acetylcholinesterase (AChE) activity in 54 patients with AD and in 22 normal controls by positron emission tomography and N-[(11)C]methylpiperidin-4-yl acetate to characterize the cholinergic pathology in AD. The k(3) values were calculated as an index of AChE activity in a three-compartment model analysis using the metabolite-corrected arterial input function. The k(3) values were highly significantly reduced by 20% in the cerebral neocortex (P <0.0001 in the two-tailed t test), 14% in the hippocampus (P <0.001), and 33% in the amygdala (P <0.0001) in AD patients compared with normal controls. The k(3) values were significantly correlated with the Mini-Mental State Examination scores in both the cerebral cortex (P <0.001) and the amygdala (P <0.05) in AD patients, supporting the cholinergic hypothesis of cognitive dysfuncion in AD. Further studies are required, however, to elucidate the specific role of the cholinergic deficit in the amygdala in the emotional and behavioral symptoms in AD.
Experiments were carried out to isolate metal removing bacteria from activated sludge culture and test the metal removal capability of isolated bacteria. Two concentrations of copper solution (CuCl2) used to select the copper-tolerance level of each isolate were 0.05 mM and 2.5 mM. Experimental data showed that isolates could be obtained by using non-selective medium (NSM) in the presence of copper. The isolates were displayed on agar plates with diverse colonial morphological characteristics. A maximum uptake of 81 mg/g dry cell mass was observed at an initial copper concentration of 50 mg/l. The minimum uptake was 9 mg/g dry cell mass. Copper uptake efficiency by isolates from NSM with 0.5 mM CuCl2 was significantly different with those from NSM with 2.5 mM CuCl2.
Acetylcholinesterase (AChE) activities in the brain of three patients with AD were measured once before and once during donepezil treatment (5 mg/d in two patients, 3 mg/d in one patient) using PET and N-[11C]methylpiperidin-4-yl acetate. Donepezil reduced k(3) values, an index of AChE activity, in the cerebral cortex by 39 +/- 5%. All patients showed some degree of symptomatic improvement, and it was concluded that this improvement was likely caused by improved cholinergic activity by inhibition of AChE in the brain.
To evaluate organic pollution in water, we did preliminarily studies on high-throughput characterization of organic pollution in water using microchip-based capillary electrophoresis (CE) with laseer-induced fluorescence (LIF) detection. The applied voltage was investigated to control the gated valve injection and CE separation for conventional cross type microchips using a self-made personal computer (PC)-based controller as the voltage supply. We obtained high-throughput data for the reproducible separation of fluorescein isothiocyanate (FITC)-labeled river-water samples using a zwitter-ion based buffer solution to avoid adsorption of the labeled sample onto the channel of a microchip made from quartz glass. We used real samples from the Hino River that flows into Lake Biwa, from ten sampling points and obtained several reproducible peaks in different separation patterns for each sample within 2 min. We successfully demonstrated high-throughput characterization of dissolved organic carbon (DOC) in environmental water using the microchip.
N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) is a radiotracer that has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET) using a standard compartment model analysis and a metabolite-corrected arterial input function. In the current study, the authors evaluated the applicability of a simple kinetic analysis without blood sampling, namely shape analysis. First, the authors used computer simulations to analyze factors that affect the precision and bias of shape analysis, then optimized the shape analysis procedure for [11C]MP4A. Before shape analysis execution, the later part of dynamic PET data except for the initial 3 minutes were smoothed by fitting to a bi-exponential function followed by linear interpolation of 8 data points between each of adjacent scan frames. Simulations showed that shape analysis yielded estimates of regional metabolic rates of [11C]MP4A by AChE (k3) with acceptable precision and bias in brain regions with low k3 values such as neocortex. Estimates in regions with higher k3 values became progressively more inaccurate. The authors then applied the method to [11C]MP4A PET data in 10 healthy subjects and 20 patients with Alzheimer's disease (AD). There was a highly significant linear correlation in regional k3 estimates between shape and compartment analyses (300 neocortical regions, [shape k3] = 0.93 x [NLS k3], r = 0.89, P < 0.001). Significant reductions in k3 estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral cortices in patients with AD as compared with controls were observed when using shape analysis (P < 0.013, two-tailed t-test), although these reductions (17% to 20%) were somewhat less than those obtained by compartment analysis (22% to 27%). The sensitivity of shape analysis for detecting neocortical regions with abnormally low k3 in the 20 patients with AD (92 out of 200 regions, 46%) also was somewhat less than compartment analysis (136 out of 200 regions, 68%). However, taking its simplicity and noninvasiveness into account, the authors conclude that quantitative measurement of neocortical AChE activity with shape analysis and [11C]MP4A PET is practical and useful for clinical diagnosis of AD.
N -[(11)C]methylpiperidin-4-yl acetate ([(11)C]MP4A) is an acetylcholine analog. It has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET). [(11)C]MP4A is specifically hydrolyzed by AChE in the brain to a hydrophilic metabolite, which is irreversibly trapped locally in the brain. The authors propose a new method of kinetic analysis of brain AChE activity by PET without arterial blood sampling, that is, reference tissue-based linear least squares (RLS) analysis. In this method, cerebellum or striatum is used as a reference tissue. These regions, because of their high AChE activity, act as a biologic integrator of plasma input function during PET scanning, when regional metabolic rates of [(11)C]MP4A through AChE (k(3); an AChE index) are calculated by using Blomqvist's linear least squares analysis. Computer simulation studies showed that RLS analysis yielded k(3) with almost the same accuracy as the standard nonlinear least squares (NLS) analysis in brain regions with low (such as neocortex and hippocampus) and moderately high (thalamus) k(3) values. The authors then applied these methods to [(11) C]MP4A PET data in 12 healthy subjects and 26 patients with Alzheimer disease (AD) using the cerebellum as the reference region. There was a highly significant linear correlation in regional k(3) estimates between RLS and NLS analyses (456 cerebral regions, [RLS k(3) ] = 0.98 x [NLS k(3) ], r = 0.92, P < 0.001). Significant reductions were observed in k(3) estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral neocortices (P < 0.001, single-tailed t-test), and hippocampus (P = 0.012) in patients with AD as compared with controls when using RLS analysis. Mean reductions (19.6%) in these 6 regions by RLS were almost the same as those by NLS analysis (20.5%). The sensitivity of RLS analysis for detecting cortical regions with abnormally low k 3 in the 26 patients with AD (138 of 312 regions, 44%) was somewhat less than NLS analysis (52%), but was greater than shape analysis (33%), another method of [(11)C]MP4A kinetic analysis without blood sampling. The authors conclude that RLS analysis is practical and useful for routine analysis of clinical [(11)C]MP4A studies.
The number of novel man-made hazardous substances produced by industries is increasing year after year, resulting in conventional discharge standards ineffective to preserve the natural ecological environment. A novel index, ecological co-inhabitance index (ECI), was proposed in order to evaluate the river ecosystem sensitively. The river benthic community with a high value of ECI is formed in the healthy ecosystem where benthic animals can share resources in the river environment efficiently, keep the ecosystem functioning, and give the least adverse effect to lower reaches of the river. In order to clarify the characteristic of ECI, the relationship between ECI and water quality in the river was investigated using the data on benthic animals obtained from 17 various rivers. Results of this investigation indicated that ECI could synthetically evaluate the river environment without a bias toward a specific water quality. Moreover, ECI had the significant correlation coefficients with diversity index, biotic index and pollution index at significance level 0.05, respectively. Therefore, ECI is a promising index for managing the river ecosystem.
There is a great difficulty in virus enumeration in sewage sludge because viruses in sludge are firmly captured by sludge solids. In order to determine the precise number of viruses in sludge, an enhanced virus recovery method with a combination of an enzyme and a cation exchange resin (CER) was developed. Test viruses were seeded to a sample sludge obtained from a municipal wastewater treatment plant, and the sludge were incubated with various eluents. The quantity of eluted viruses in the liquid phase was then measured by the plaque assay technique. Using the eluent containing only water, CER, and CER with enzyme exhibited 0%, 19% and 39% of virus recovery, respectively. While the conventional USEPA method exhibited a virus recovery of 21%. Furthermore, viruses eluted by the eluent containing the CER and the lysozyme included not only surface-attached viruses but also solids-embedded viruses.
Six copper-binding microbial proteins were isolated from activated sludge cultures grown on media containing copper at various concentrations. Molecular weights among isolated proteins were ranged from 1.3k to 1 74k dalton. Isolated proteins were compared for their copper binding capabilities. Proteins isolated from cultures grown in the presence of copper in the growth media exhibited higher copper binding capabilities than those isolated from the culture grown in the absence of copper. The highest metal uptake of 61.23 (mol copper/mol protein) was observed by a protein isolated from a culture grown with copper at a concentration of 0.25 mM. This isolated protein (CBP2) had a molecular weight of 24k dalton. Other protein exhibited copper binding capability of 4.8-32.5 (mol copper/mol protein).
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Analytical conditions of pH, surfactants, and additives were investigated for the simultaneous separation of bisphenol A and alkylphenols by micellar electrokinetic chromatography. Reproducibility of migration time was improved at higher pH (pH 8.0). When five surfactants having linear alkyl chains or four bile salts were used, the separation of hydrophobic phenols and 4-nonylphenol isomers was not achieved. In order to improve the separation, the use of additives with sodium dodecyl sulfate solution was investigated. The separation of hydrophobic phenols was improved by the addition of organic solvents, however, isomers were not separated. Their separation was achieved by the addition of beta- or gamma-cyclodextrin.
The ability to analyze samples with disparate levels of analyte and matrix ions is among the important benefits defining the practical utility of modern capillary electrophoresis. To compensate for the sensitivity limitations regarding trace-level inorganic anions, a number of on-line approaches that should offer an improved S/N ratio in direct UV detection were examined. The novel use of reversed pre-electrophoresis (at the applied voltage opposite to the separation voltage) made it possible to efficiently remove the most part of high chloride levels from the sample and hence to lower the background signal and to inject increased quantities of fast analyte anions. Specifically, by taking these advantages the sensitivity response of iodide was improved by a factor of 5 over normal CE mode. Using isotachophoretic sample stacking, a two-fold increase in detectability was obtained for moderately mobile anions, nitrate and nitrite, that corresponds to the minimum detectable concentrations close to their natural occurrences in seawater. Furthermore, field-amplified sample injection at increased electrolyte-to-sample matrix concentration ratios enabled the maximum S/N enhancement, with detection limits at the level of 10(-6) M and lower in the presence of > or = 5 x 10(4)-fold molar excess of chloride.
We describe capillary zone electrophoresis (CZE) for the simultaneous determination of bromide, nitrite and nitrate ions in seawater. Artificial seawater was adopted as the carrier solution to eliminate the interference of high concentrations of salts in seawater. The artificial seawater was free from bromide ion to enable the determination of bromide ion in a sample solution. For the purpose of reversing the electroosmotic flow (EOF), 3 mM cetyltrimethylammonium chloride (CTAC) was added to the carrier solution. A 100 microm ID (inside diameter) capillary was used to extend the optical path length. The limits of detection (LODs) for bromide, nitrite, and nitrate ions were 0.46, 0.072, and 0.042 mg/L (as nitrogen), respectively. The LODs were obtained at a signal to noise ratio (S/N) of 3. The values of the relative standard deviation (RSD) of peak area for these ions were 1.1, 1.5, and 0.97%. The RSDs of migration time for these ions were 0.61, 0.69, and 0.66%. Artificial seawater samples containing various concentrations of bromide, nitrite, and nitrate ions were analyzed by the method. The error was less than +/-12% even if the concentration ratio of bromide ion to nitrite or nitrate ion was 20-240. The proposed method was applied to the determination of bromide, nitrite, and nitrate ions in seawater samples taken from the surface and the seabed. These ions in other environmental waters such as river water and rainwater samples were also determined by ion chromatography (IC) as well as this method.