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Biomedical subjects

K S Chen

Publications and source records attributed to K S Chen.

At least 19 recordsLinked to original sources

Behavioral phenotypes of amyloid-based genetically modified mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative affliction of the elderly, presenting with progressive memory loss and dementia and terminating with death. There have been significant advances in understanding the biology and subsequent diagnosis of AD; however, the furious pace of research has not yet translated into a disease-modifying treatment. While scientific inquiry in AD is largely centered on identifying biological players and pathological mechanisms, the day-to-day realities of AD patients and their caregivers revolve around their steady and heartbreaking cognitive decline. In the past decade, AD research has been fundamentally transformed by the development of genetically modified animal models of amyloid-driven neurodegeneration. These important in vivo models not only replicate some of the hallmark pathology of the disease, such as plaque-like amyloid accumulations and astrocytic inflammation, but also some of the cognitive impairments relevant to AD. In this article, we will provide a detailed review of the behavioral and cognitive deficits present in several transgenic mouse models of AD and discuss their functional changes in response to experimental treatments.

Alzheimer Disease↗

Video-assisted laparoscopic procedures in peritoneal dialysis.

BACKGROUND: Although laparoscopy is commonly adopted for the diagnosis and management of various medical or surgical problems, its use for patients with peritoneal dialysis has seldom been addressed. This retrospective study analyzes the indications and clinical effects of this procedure. METHODS: A retrospective chart was drawn up and a videotape review performed for 18 laparoscopic procedures involving 198 patients receiving peritoneal dialysis on a long-term basis at our dialysis unit from May 1992 to June 2002. The clinical and demographic parameters in this study included gender, age, underlying renal diseases, duration of peritoneal dialysis before laparoscopy, indications of laparoscopic intervention, laparoscopic findings, time of operation, laparoscopic procedures, postoperative complications, mortality, and catheter results. RESULTS: A total of 18 laparoscopic procedures were performed in 17 uremia patients, with indications including catheter malfunction in five cases, preimplantation evaluation of peritoneal space in three cases, evaluation of the etiology underlying intractable peritonitis in nine cases, and verification of the cause for dialysate leakage in one case. Four (80%) of the five catheter malfunctions were successfully corrected, including one case of catheter migration and three cases of omental wrapping, whereas correction failed in the remaining case because of severe bowel adhesion. New catheter placement after adhesiolysis was successful in all three cases of preimplantation peritoneal evaluation (100%). Of the nine patients whose peritonitis episodes were evaluated, two were found to have secondary peritonitis, two had fungal peritonitis; one had tuberculous peritonitis and four had bacterial peritonitis. In the case of persistent exit-site dialysate leakage, laparoscopy showed a penetrating injury of the abdominal wall, raising a strong suspicion of iatrogenic injury during the tunneling maneuvers in initial catheter placement. Two conversions to laparotomy were performed: one to repair the penetrating injury and the other to save the life of a patient threatened by severe fungal peritonitis with abdominal cocoon formation. The laparoscopic procedures lasted 20 to 150 min (average, 50 min). Despite one instance of postoperative hydrocele, there was no operative mortality. CONCLUSIONS: The analytical results of this study demonstrate that the current video-assisted laparoscopic technique is an effective means for managing several problems related to peritoneal dialysis such as catheter malfunction, preimplantation evaluation, location of the source of the dialysate leak, and assessment of the causes for peritonitis. Thus, this technique should always be considered when the these problems arise.

Adolescent↗

Motorcycle emissions and fuel consumption in urban and rural driving conditions.

This work reports sampling of motorcycle on-road driving cycles in actual urban and rural environments and the development of representative driving cycles using the principle of least total variance in individual regions. Based on the representative driving cycles in individual regions, emission factors for carbon monoxide (CO), hydrocarbons (HC), nitrogen oxides (NO(x)=NO+NO(2)) and carbon dioxide (CO(2)), as well as fuel consumption, were determined using a chassis dynamometer. The measurement results show that the representative driving cycles are almost identical in the three largest cities in Taiwan, but they differ significantly from the rural driving cycle. Irrespective of driving conditions, emission factors differ insignificantly between the urban and rural regions at a 95% confidence level. However, the fuel consumption in urban centers is approximately 30% higher than in the rural regions, with driving conditions in the former usually poor compared to the latter. Two-stroke motorcycles generally have considerably higher HC emissions and quite lower NO(x) emissions than those of four-stroke motorcycles. Comparisons with other studies suggest that factors such as road characteristics, traffic volume, vehicle type, driving conditions and driver behavior may affect motorcycle emission levels in real traffic situations.

Air Pollutants↗

Source profiles and ozone formation potentials of volatile organic compounds in three traffic tunnels in Kaohsiung, Taiwan.

Twenty-five volatile organic compounds (VOCs) up to C10 were measured using Carbotrap multibed thermal adsorption tubes during the morning and afternoon rush hours on four different days in all three traffic tunnels in Kaohsiung, Taiwan. A gas chromatograph (GC) equipped with a flame-ionization detector (FID) was then used to analyze the VOCs. The analytical results show that VOC concentrations increase with traffic flow rate, and emission profiles in the three tunnels are mostly in the range C2-C6. In addition to the traffic conditions and vehicle type, the pattern of emissions in each tunnel was also influenced by other factors, such as vehicle age, nearby pollution sources, and the spatial or temporal variation of VOCs in the urban atmosphere. The ozone formation potential (OFP) in each tunnel was assessed based on the maximum incremental reactivities of the organic species, demonstrating that OFP increases with traffic flow rate. Vehicle distribution influences the contributions of organic group to OFP in a tunnel. Meanwhile, when ranked in descending order of contribution to OFP in all tunnels, the organic groups followed the sequence olefins, aromatics, and paraffins.

Air Pollutants↗

Impaired eyeblink conditioning and decreased hippocampal volume in PDAPP V717F mice.

We examined heterozygous transgenic (Tg) mice that overexpress V717F amyloid precursor protein (APP) for delay eyeblink conditioning (EBC) and hippocampal volume with magnetic resonance imaging (MRI). Platelet-derived APP mice were significantly impaired on EBC relative to wild type (WT) litter-mate controls. T2-weighted spin echo images (62.5 x 125 x 500 microm) of the same mice were acquired under anesthesia using a 9.4T magnet. Tg mice had hippocampal to brain volume ratios that were significantly smaller than WT controls (31% smaller in the rostral dorsal hippocampus, 13-22% smaller among equal dorsal-ventral thirds of a caudal section). These results indicate that overexpression of APP or beta amyloid profoundly affects learning and memory and hippocampal volume. The results also indicate that eyeblink conditioning and quantitative MRI in mice may be useful assays to follow the progression of disease-related changes, and to test the effectiveness of potential therapeutics against Alzheimer's disease.

Alzheimer Disease↗

Measurement and three-dimensional modeling of airflow and pollutant dispersion in an undersea traffic tunnel.

Airflow and pollutant dispersion in a cross-harbor traffic tunnel were experimentally and numerically studied. Concentrations of the gaseous pollutants CO, NOx, and total hydrocarbons (THC) at three axial locations in the tunnel, together with traffic flow rate, traffic speed, and types of vehicle were measured. Three-dimensional (3D) turbulent flow and dispersion of air pollutants in the tunnel were modeled and solved numerically using the finite volume method. Traffic emissions were modeled accordingly as banded line sources along the tunnel floor. The results reveal that cross-sectional concentrations are nonuniformly distributed and that concentrations rise with downstream distance. The piston effect of vehicles alone can provide 9-23% dilution of air pollutants in the tunnel, compounded to a 23-74% dilution effect according to the ventilation condition.

Air Movements↗

Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome.

Mutations in myosin XVA are responsible for the shaker 2 ( sh2) phenotype in mice and nonsyndromic autosomal recessive profound hearing loss DFNB3 on chromosome 17p11.2. We have ascertained seven families with profound congenital hearing loss from Pakistan and India with evidence of linkage to DFNB3 at 17p11.2. We report three novel homozygous mutations in MYO15A segregating in three of these families. In addition, one hemizygous missense mutation of MYO15A was found in one of eight Smith-Magenis syndrome (del(17)p11.2) patients from North America who had moderately severe sensorineural hearing loss.

Abnormalities, Multiple↗

On the pyrolysis kinetics of scrap automotive tires.

Pyrolysis kinetics of scrap tires of passenger car and truck have been investigated thermogravimetrically under heating rates of 5, 10, 20 and 30K/min and temperature range 373-1273K in nitrogen. The results show that the initial reaction temperatures are 482-521K for the tire of passenger car and 458-511K for truck tire. Both tires exhibit similar behaviors that the initial reaction temperature decreases, but reaction range and reaction rate increase when heating rate is increased. The overall rate equation for each tire can be modeled satisfactorily by a simple one equation from which the kinetic parameters such as the activation energy (E), the pre-exponential factor (A), and the reaction order (n) of unreacted material based on Arrhenius form are determined using Friedman's method. The results show that two tires behave similarly and the average kinetic parameters of two tires are E = 147.95 +/- 0.21kJ/mol, A = (6.295 +/- 1.275)x10(10)min(-1), and n = 1.81 +/- 0.18. The predicted rate equations compare fairly well with the measured data.

Incineration↗

BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major components of plaque, beta-amyloid peptides (Abetas), are produced from amyloid precursor protein (APP) by the activity of beta- and gamma-secretases. beta-secretase activity cleaves APP to define the N-terminus of the Abeta1-x peptides and, therefore, has been a long- sought therapeutic target for treatment of AD. The gene encoding a beta-secretase for beta-site APP cleaving enzyme (BACE) was identified recently. However, it was not known whether BACE was the primary beta-secretase in mammalian brain nor whether inhibition of beta-secretase might have effects in mammals that would preclude its utility as a therapeutic target. In the work described herein, we generated two lines of BACE knockout mice and characterized them for pathology, beta-secretase activity and Abeta production. These mice appeared to develop normally and showed no consistent phenotypic differences from their wild-type littermates, including overall normal tissue morphology and brain histochemistry, normal blood and urine chemistries, normal blood-cell composition, and no overt behavioral and neuromuscular effects. Brain and primary cortical cultures from BACE knockout mice showed no detectable beta-secretase activity, and primary cortical cultures from BACE knockout mice produced much less Abeta from APP. The findings that BACE is the primary beta-secretase activity in brain and that loss of beta-secretase activity produces no profound phenotypic defects with a concomitant reduction in beta-amyloid peptide clearly indicate that BACE is an excellent therapeutic target for treatment of AD.

Alzheimer Disease↗

Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset.

During the innate immune response to infection, monocyte-derived cytokines (monokines), stimulate natural killer (NK) cells to produce immunoregulatory cytokines that are important to the host's early defense. Human NK cell subsets can be distinguished by CD56 surface density expression (ie, CD56(bright) and CD56(dim)). In this report, it is shown that CD56(bright) NK cells produce significantly greater levels of interferon-gamma, tumor necrosis factor-beta, granulocyte macrophage-colony-stimulating factor, IL-10, and IL-13 protein in response to monokine stimulation than do CD56(dim) NK cells, which produce negligible amounts of these cytokines. Further, qualitative differences in CD56(bright) NK-derived cytokines are shown to be dependent on the specific monokines present. For example, the monokine IL-15 appears to be required for type 2 cytokine production by CD56(bright) NK cells. It is proposed that human CD56(bright) NK cells have a unique functional role in the innate immune response as the primary source of NK cell-derived immunoregulatory cytokines, regulated in part by differential monokine production.

Antigens, CD↗

Petal-like apatite formed on the surface of tricalcium phosphate ceramic after soaking in distilled water.

In the present study six types of tricalcium phosphate ceramic were prepared and soaked in distilled water for different periods to investigate whether a surface apatite layer was formed on TCP ceramics or not. X-ray diffractometry (XRD) and Fourier-transformed infrared (FTIR) spectrometer were used to examine the changes in crystalline phases and functional groups of TCP ceramics for different soaking periods. Calcium and phosphate ions released from TCP ceramics during soaking were recorded by atomic absorption analysis and ion-coupled plasma. Results revealed that alphaTCP, alphaTCP/betaTCP mixture (alphabetaTCP) and betaTCP ceramic were gradually dissolved. There was no apatite layer formed on their surface after being immersed in distilled water for different durations of time. Mg-TCP ceramic, tricalcium phosphate doped with Mg ions, exhibited a lower dissolution rate than the other types of TCP ceramics. Apatite crystals were also not formed on the surface of Mg-TCP ceramic when immersed in distilled water. Tribasic calcium phosphate, prepared from wet precipitation method, was converted to betaTCP/HAP (HbetaTCP) or alphaTCP/betaTCP/HAP (HalphabetaTCP) crystalline composition at different sintering temperatures (1,150 degrees C and 1,300 degrees C). The surface apatite layer did not appear on HbetaTCP ceramic after soaking. We observed that petal-like apatite was formed on the HalphabetaTCP ceramic surface after being immersed for 2 weeks. alphaTCP phase of HalphabetaTCP ceramic was not directly converted to apatite during soaking. The surface apatite layer formed on the HalphabetaTCP ceramic surface was due to the precipitation of the calcium and phosphate ions released from alphaTCP dissolution. HAP, which existed in the structure of HalphabetaTCP ceramic, plays a role as apatite-precipitating seed to uptake calcium and phosphate ions. TCP ceramics which lacked alphaTCP and HAP content neither converted to apatite nor formed surface apatite on their surfaces during immersion.

Apatites↗

Design and evaluation of drug-loaded wound dressing having thermoresponsive, adhesive, absorptive and easy peeling properties.

In order to develop a novel unique wound dressing, a combination of self-adhesive Eudragit E film with antibacterial drug-loaded poly (N-isopropyl-acrylamide) (PNIPAAm) microgel beads was designed. The result indicates that the tack property of Eudragit E film increased with an increase of the PNIPAAm microgel beads added, but there was no significant difference between the dried PNIPAAm microgel beads with or without adsorbing drug. In addition, the peel strength of Eudragit E film initially decreased with the addition of PNIPAAm microgel beads, but increased to a maximum value when PNIPAAm microgel beads were added from 4% to 7.6%. then decreased again after 7.6%. The optimal concentration of PNIPAAm microgel beads was 7.6% (w/v) which had better tack and peel adhesive properties. The water uptake ratio of Eudragit E film containing PNIPAAm microgel beads was found to be temperature-dependent, suggesting that the Eudragit E film containing PNIPAAm microgel beads enabled to absorb the wound fluid. Eudragit E film containing PNIPAAm microgel beads with or without adsorbing drug had significantly reduced peel strength after 12 h-immersion in solution. All these results suggest that a novel drug-loaded wound dressing has been developed by binding a self-adhesive Eudragit E film with an antibacterial drug-loaded PNIPAAm microgel beads to achieve thermo-responsive, adhesive, absorptive and easy peeling functions.

Acrylic Resins↗

Determination of source contributions to ambient PM2.5 in Kaohsiung, Taiwan, using a receptor model.

Ambient particulates of PM2.5 were sampled at three sites in Kaohsiung, Taiwan, during February and March 1999. In addition, resuspended PM2.5 collected from traffic tunnels, paved roads, fly ash of a municipal solid waste (MSW) incinerator, and seawater was obtained. All the samples were analyzed for twenty constituents, including water-soluble ions, organic carbon (OC), elemental carbon (EC), and metallic elements. In conjunction with local source profiles and the source profiles in the model library SPECIATE EPA, the receptor model based on chemical mass balance (CMB) was then applied to determine the source contributions to ambient PM2.5. The mean concentration of ambient PM2.5 was 42.69-53.68 micrograms/m3 for the sampling period. The abundant species in ambient PM2.5 in the mass fraction for three sites were OC (12.7-14.2%), SO4(2-) (12.8-15.1%), NO3- (8.1-10.3%), NH4+ (6.7-7.5%), and EC (5.3-8.5%). Results of CMB modeling show that major pollution sources for ambient PM2.5 are traffic exhaust (18-54%), secondary aerosols (30-41% from SO4(2-) and NO3-), and outdoor burning of agriculture wastes (13-17%).

Agriculture↗

Combustion modeling and performance evaluation in a full-scale rotary kiln incinerator.

This work summarizes the results of numerical investigations and in situ measurements for turbulent combustion in a full-scale rotary kiln incinerator (RKI). The three-dimensional (3D) governing equations for mass, momentum, energy, and species, together with the kappa - epsilon turbulence model, are formulated and solved using a finite volume method. Volatile gases from solid waste were simulated by gaseous CH4 distributed nonuniformly along the kiln bed. The combustion process was considered to be a two-step stoichiometric reaction for primary air mixed with CH4 gas in the combustion chamber. The mixing-controlled eddy-dissipation model (EDM) was employed to predict the conversion rates of CH4, O2, CO2, and CO. The results of the prediction show that reverse flows occur near the entrance of the first combustion chamber (FCC) and the turning point at the entrance to the second combustion chamber (SCC). Temperature and species are nonuniform and are vertically stratified. Meanwhile, additional mixing in the SCC enhances postflame oxidation. A combustion efficiency of up to 99.96% can be achieved at approximately 150% excess air and 20-30% secondary air. Reasonable agreement is achieved between numerical predictions and in situ measurements.

Air Pollution↗

Fluconazole disk diffusion test with methylene blue- and glucose-enriched Mueller-Hinton agar for determining susceptibility of Candida species.

A 25-microg fluconazole disk diffusion test using a Mueller-Hinton agar plate containing 2% glucose and 5 microg of methylene blue/ml (GM-MH) was compared to the macrodilution reference method for 210 Candida species. The GM-MH agar plate was read at 24 h. The predictive values of disks with susceptible, intermediate, and resistant results on the GM-MH agar plate at 24 h were 97.1, 56.3, and 76.5%, respectively.

Antifungal Agents↗

Organic esters of plasticizers affecting the water absorption, adhesive property, glass transition temperature and plasticizer permanence of eudragit acrylic films.

The materials used in film coating technology are very important tools for pharmaceutical applications. The effects of four organic esters used as plasticizers (triacetin, diethyl phthalate (DEP), dibutyl phthalate (DBP) and tributyl citrate (TBC)) on the water absorption behavior and adhesive property of Eudragit films and on the glass transition temperature (T(g)) and plasticizer permanence of Eudragit E film were investigated. The results indicate that the water absorption of these Eudragit films was dependent on the type of Eudragit polymers and plasticizers used. Eudragit E film plasticized with triacetin showed a slight water absorption, but when plasticized with DEP, DBP or TBC did not. All Eudragit RL films showed significant uptake of water, but Eudragit RS films exhibited a lesser degree of water absorption. The adhesion (tack value) of all Eudragit films was markedly increased when the concentration of plasticizer was greater than 25%. Eudragit E film exhibited a greater adhesiveness than the Eudragit RL or RS film, particularly with higher plasticizer concentration. Weight loss of the Eudragit E film plasticized with triacetin or DEP was more pronounced with aging, but when plasticized with DBP or TBC weight loss was not seen. The results indicate that TBC may be the best choice of plasticizer for Eudragit film, particularly for the Eudragit E film.

Acrylic Resins↗

Preparation of betaTCP/HAP biphasic ceramics with natural bone structure by heating bovine cancellous bone with the addition of (NH(4))(2)HPO(4).

In this study, the calcined bovine bone (CBB)-removing the organic substance by a burning process-with addition of different quantities of ammonium phosphate [(NH(4))(2)HPO(4)] (AP) was heated to a high temperature to transform its crystalline phase constitution from hydroxyapatite (HAP) into a tricalcium phosphate (TCP)/HAP biphasic structure. Results revealed that the CBB without AP appeared to be mainly composed of an HAP type pattern when heated to 1300 degrees C. After adding doped AP to CBB, the HPO(4)(2-) ions of AP condensed into P(2)O(7)(4-) ions at temperatures of 400-600 degrees C. P(2)O(7)(4-) ions reacted with the OH(-) ions of HAP to form betaTCP at temperatures up to 600 degrees C. The conversion reaction of HAP to betaTCP finished at around 900 degrees C. With increasing AP in the CBB, HAP gradually converted into different phase compositions of TCP/HAP or TCP at high temperature. Mechanical testing results showed that there was no significant difference in sintered CBB with different quantities of AP. By heating calcined bovine cancellous bone with different quantities of AP, we obtained different crystalline phase compositions of bioceramics with a natural porous structure.

Animals↗

The value of gallium-67 and thallium-201 whole-body and single-photon emission tomography images in dialysis-related beta 2-microglobulin amyloid.

The aim of this study was to investigate the value of gallium-67 and thallium-201 whole-body and single-photon emission tomography (SPET) images in long-term dialysis patients in whom dialysis-related beta 2-microglobulin amyloid (beta 2-MA) was clinically suspected. Twenty-three patients who had received dialysis for at least 10 years were included in the study. A technetium-99m methylene diphosphonate (MDP) whole-body scan was performed in all of the patients. If there was any MDP accumulation in the articular and/or peri-articular region, 67Ga and 201Tl whole-body and SPET images were then acquired. If any 67Ga and/or 201Tl uptake was observed, a CT-guided biopsy was done. In those patients who had articular and/or peri-articular uptake of 99mTc MDP, 67Ga and/or 201Tl and who were pathologically proven to have beta 2-MA, 99mTc MDP, 67Ga and 201Tl whole-body scans and SPET were carried out again, both 3 months and 1 year after initiation of treatment. This served to evaluate the therapeutic effect and allowed comparison with the clinical findings. Of the 23 patients, eight had abnormal 99mTc MDP uptake. Among these eight, six had intense 99mTc MDP, 67Ga and 201Tl uptake in the articular and peri-articular regions before medication. Three months after the start of treatment, there were very marked decreases in uptake on both the 67Ga and 201Tl scans but less obvious changes in uptake of 99mTc-MDP. In comparison with the other clinical manifestations such as limitation in range of motion, the more the painful disability improved, the less was the uptake on both 67Ga and 201Tl scans. There were virtually no differences in uptake pattern between the three scans of each radiopharmaceutical obtained for each patient in both 3 months and 1 year after initial of treatment. It is concluded that 99mTc-MDP whole-body bone scan can both detect active and pre-existing inactive deposits of beta 2-MA. 67Ga and 201Tl scans are helpful to differentiate active from inactive deposits of beta 2-MA and to evaluate the therapeutic effect on these patients. SPET images are usually needed to distinguish articular and periarticular lesions from bone lesions.

Amyloid↗