[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
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Journal Article↗
Biomedical subjects
J M Yang
Publications and source records attributed to J M Yang.
Characterization and adsorption properties of eggshells and eggshell membrane.
The objective of this work was to study the chemical and physical characterization of eggshell and eggshell membrane particles prepared from the hen eggshell waste. Under the characterization measurements investigated, it was found that the pore structures of the two biomaterials belong to a typical Type II, indicating that they should be basically characteristic of nonporous materials or materials with macropores or open voids. Further, the chemical composition of the resulting eggshell particle was strongly associated with the presence of carbonate minerals from the Fourier transform infrared (FTIR) spectra. In contrast to the resulting eggshell membrane particle, the presence of functional groups of amines and amides was observable because of its chemical composition of fibrous proteins. From the isotherm data of methylene blue at 25 degrees C, the Freundlich model yielded a somewhat better fit than the Langmuir model. The adsorption isotherms revealed the eggshell biosorbents could only uptake the basic dye of less than 1.0mg/g in aqueous medium, which was attributed to their poor pore properties.
Adsorption↗
The effect of xenobiotic exposure on spontaneous autoimmunity in (SWR x SJL)F1 hybrid mice.
F1 hybrids of SWR (H-2(q)) and SJL (H-2(s)) mice spontaneously develop a lupuslike condition in an age-dependent manner, and these two H-2 haplotypes also confer susceptibility to induction of systemic autoimmunity by heavy metals such as mercury, silver, and gold with anti-fibrillarin antibodies (AFA) as marker. The aim of this study was to determine how the mixing of two susceptible genomes might influence expression of idiopathic and induced autoimmunity over a period of 14 mo of exposure to mercury and silver. Spontaneous autoimmunity first appeared as antinuclear antibodies (ANA) in females at 10 wk of age and in males at 10 mo of age, and was followed by development of anti-chromatin antibodies. Antibodies to double-stranded DNA developed in 60% of males and 20% of females. Thirty percent of males and 10% of females developed a coarsely speckled ANA pattern associated with high titers of anti-Sm antibodies. Glomerular immune complex (IC) deposits and a proliferative glomerulonephritis were seen at 17 mo of age. The F1 hybrids treated with metals showed no exaggeration of spontaneous autoimmunity. However, the metals suppressed the spontaneous development of anti-Sm and antichromatin antibodies. The metal-induced AFA, linked to the H-2(s) and H-2(q) haplotype, reached a maximum after 3-4 mo of treatment and then declined; 33% of the silver-treated hybrids finally became AFA-negative, despite continuous treatment. The decline in ANoA during metal treatment is contrary to the situation in metal-treated SJL mice. This indicates that dominant SWR background genes suppressed induction of certain autoimmune traits in the (SWR x SJL)F1 hybrid mice.
Age Factors↗
Tob is a potential marker gene for the basal layer of the epidermis and is stably expressed in human primary keratinocytes.
BACKGROUND: Epidermis consists of multiple layers, from the proliferating basal layer to terminal differentiated cornified layers, and these layers are defined by differentiation status. Tob gene product is known to be a member of the BTG antiproliferative protein family. We investigated the expression pattern of Tob gene product to understand the possible role in differentiation of keratinocytes and epidermis. OBJECTIVES: In this study, we examined the expression of Tob gene product in the primary cultured human keratinocytes and in the in vivo epidermis. METHODS: The expression of Tob gene product was assessed by Western blotting analysis. Cellular localization of Tob was detected using the green fluorescent protein-tagged Tob cDNA expression construct. In vivo expression of Tob gene product in the epidermis was determined by immunohistochemistry with paraffin sections. RESULTS: Tob family members are degraded by the ubiquitine-proteasome system triggered by the growth signal. Tob is stably and abundantly expressed in primary cultured human keratinocytes. Furthermore, the expression of Tob in the keratinocytes persists during the differentiation induced by calcium; however, it was not detected in primary cultured fibroblasts. Also, the subcellular localization of Tob is mainly in the cellular membrane in the primary human keratinocytes. We evaluated Tob expression in normal skin, oral mucosa and different diseases, such as psoriasis, X-linked ichthyosis and squamous cell carcinoma (SCC). Using immunohistochemical analysis, we observed that Tob was selectively expressed in the basal layer of X-linked ichythyosis and the hyperproliferative basal layer of psoriasis and oral mucosa as well as in normal epidermis. In SCC, the expression of Tob gene product was relatively decreased. CONCLUSIONS: Tob is stably expressed in primary human keratinocytes and it is specifically expressed in the basal layer of in vivo epidermis.
Blotting, Western↗
Broad energy spectrum of laser-accelerated protons for spallation-related physics.
A beam of MeV protons, accelerated by ultraintense laser-pulse interactions with a thin target foil, is used to investigate nuclear reactions of interest for spallation physics. The laser-generated proton beam is shown (protons were measured) to have a broad energy distribution, which closely resembles the expected energy spectrum of evaporative protons (below 50 MeV) produced in GeV-proton-induced spallation reactions. The protons are used to quantify the distribution of residual radioisotopes produced in a representative spallation target (Pb), and the results are compared with calculated predictions based on spectra modeled with nuclear Monte Carlo codes. Laser-plasma particle accelerators are shown to provide data relevant to the design and development of accelerator driven systems.
Journal Article↗
Magnifying endoscopy in gastritis of the corpus.
Endoscopic diagnosis of Helicobacter pylori infection, before biopsies and serological tests are performed, is possible through careful analysis of the network of superficial vessels in patients with gastritis. At standard endoscopy, a regular arrangement of the collecting venules (RAC) is visible as numerous minute red points in the corpus of the noninfected stomach, and is not visible in H. pylori gastritis. Magnifying endoscopy provides more precise information concerning the collecting venules, the network of capillaries surrounding the gastric pits, the swelling of the surface epithelium between pits, and the enlargement and destruction of the pits. The magnified appearance is classified as Z-0 (noninfected stomach) or as Z-1 to Z-3 for successive degrees of mucosal damage in the infected stomach. Histological controls confirm the reliability of the endoscopic classification. Magnifying endoscopy also proves helpful in the assessment of completeness of eradication of H. pylori.
Gastric Mucosa↗
Polymorphisms of the prion protein gene (PRNP) in Chinese domestic sika deer (Cervus nippon hortulorum).
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Amyloid↗
Analysis of genes responding to ultraviolet B irradiation of HaCaT keratinocytes using a cDNA microarray.
BACKGROUND: Ultraviolet (UV) B irradiation causes many important biological changes in skin, which lead to pathophysiological alterations of the homeostatic environment. OBJECTIVES: To gain more insight into the molecular events provoked by UVB irradiation, we performed cDNA microarray analysis. METHODS: Immortalized HaCaT keratinocytes were irradiated with a high cytotoxic dose of UVB (50 mJ cm(-2)), and total RNA was isolated. Fluorescently labelled probes were prepared by reverse transcription and were hybridized with cDNA microarray slides made using 840 cDNA clones. RESULTS: Time-course cDNA microarray analysis revealed the global gene expression profile after UVB exposure. Of 840 genes tested, 192 genes showed changes in their expression levels at one or more of four time points. The genes were clustered into four groups according to their expression patterns in a self-organizing maps analysis. Classification of these genes into nine functional categories revealed that UVB irradiation affected several biological processes. The genes that were first upregulated and then returned to normal levels included several genes related to the inhibition of cell growth and the proteasome pathway. Conversely, the expressions of many genes involved in the cytoskeleton, signal transduction, metabolism and transcription were first downregulated or unchanged and then upregulated later, reflecting the recovery of UVB-damaged cellular activities. CONCLUSIONS: These results demonstrate the complexity of the transcriptional profile of the UVB response, and provide a basis for the global characterization of UV-regulated gene expression.
Adult↗
The effect of inlet velocity profile on the bifurcation COPD airway flow.
The effect of inlet velocity profile on the flow features in obstructed airways is investigated in this study. In reality, the inlet velocity distributions on such models, which are extracted from medial branches of natural human lung, should be neither uniform, nor symmetric parabolic, but skewed-parabolic due to having been skewed by the upper carina ridges. Four different three-dimensional three-generation models based on the 23 generations model of Weibel have been considered, respectively. The fully three-dimensional incompressible laminar Navier-Stokes equations and continuity equation have been solved using CFD solver on unstructured tetrahedral meshes. To reduce the complexity of the simulations, only one Reynolds number of 900 was used in this calculation. Four types of inlet boundary conditions, namely uniform, parabolic, positive-skewed parabolic (skewed to the positive x-direction), and negative-skewed parabolic, were imposed on the obstructed airway models, which were considered to be obstructed at either the second generation or the third generation airways, respectively. The results show that the inlet velocity profile has significant influence on the flow patterns, mass distributions, and pressure drops in either the symmetric model, or the three obstructed models. The three generation airways may not be enough to study the bifurcation flow in chronic obstructive pulmonary disease (COPD) airways, and a four-generation or more airway model is necessary to get better predictive results.
Computer Simulation↗
Characterization of proton and heavier ion acceleration in ultrahigh-intensity laser interactions with heated target foils.
Proton and heavy ion acceleration in ultrahigh intensity ( approximately 2 x 10(20) W cm(-2) ) laser plasma interactions has been investigated using the new petawatt arm of the VULCAN laser. Nuclear activation techniques have been applied to make the first spatially integrated measurements of both proton and heavy ion acceleration from the same laser shots with heated and unheated Fe foil targets. Fe ions with energies greater than 10 MeV per nucleon have been observed. Effects of target heating on the accelerated ion energy spectra and the laser-to-ion energy conversion efficiencies are discussed. The laser-driven production of the long-lived isotope (57 )Co (271 days) via a heavy ion induced reaction is demonstrated.
Journal Article↗
Silica adsorbent prepared from spent diatomaceous earth and its application to removal of dye from aqueous solution.
The objective of this work is to study the activation regeneration of spent diatomaceous earth (SDE) for the preparation of silica adsorbents using thermal regeneration and acid/alkaline activation methods. Under the experimental conditions investigated, it was found that the alkaline activation method carried out by sodium hydroxide under controlled conditions is significantly superior to other heat and activation methods. The porosities of solids thus obtained are over 0.2, indicating that they are basically mesoporous. The optimal porous material thus prepared was used as a mineral adsorbent for methylene blue at 25 degrees C. The adsorption equilibrium revealed that the silica adsorbent can take up over 50 mg/g at relatively low concentrations in aqueous medium from the fittings of Langmuir and Freundlich isotherms with high correlations. On the other hand, the adsorption kinetic of methylene blue under various adsorbent dosages can be well described with a pseudo-second-order reaction model.
Journal Article↗
A multicenter trial of the efficacy and safety of 0.03% tacrolimus ointment for atopic dermatitis in Korea.
BACKGROUND: Atopic dermatitis is a chronically relapsing, common inflammatory skin disease, which significantly affects quality of life negatively in many respects. Topical steroids are the mainstay of atopic dermatitis treatment but they carry the risk of local side effects. A topical formulation of tacrolimus, a macrolide calcineurin inhibitor, has recently been developed. OBJECTIVE: To evaluate the efficacy and safety of 0.03% tacrolimus ointment for the treatment of moderate to severe atopic dermatitis in Korea. METHODS: An open, non-comparative, multi-center study with 4 weeks' follow-up was performed. A total of 180 patients (aged 2-57 years old) were enrolled. Tacrolimus ointment (0.03%) was applied to all involved areas twice daily. Efficacy was evaluated by an investigator's global assessment, the eczema area and severity index score, and by the patient's assessment of pruritus and clinical response at baseline, and after weeks 1, 2 and 4. Dermatology life quality index (DLQI), children's DLQI (CDLQI) and toddler's DLQI were assessed at baseline and at week 4. The safety assessment included monitoring all adverse events and clinical laboratory values. RESULTS: All efficacy parameters were improved. The mean EASI (eczema area and severity index) score was 19.7 at baseline and reduced to 8.0 at the end of the study. Moderate improvement was observed by the investigator's global assessment after 4 weeks' treatment. A marked decrease of pruritus was observed, and mild or moderate improvement was observed by patients' global assessments after the treatment period. Significant benefits in terms of quality of life in adults and children with atopic dermatitis were obtained. The most common adverse events associated with tacrolimus treatment were transient skin burning sensation (45.3%) and pruritus (41.6%) at the site of application. CONCLUSION: 0.03% tacrolimus ointment should be considered effective and safe in both Korean children and adults with moderate to severe atopic dermatitis.
Administration, Cutaneous↗
Adsorption of paraquat on the physically activated bleaching earth waste from soybean oil processing plant.
A series of regeneration experiments with physical activation were carried out on bleaching earth waste from the soybean refining process in a rotary reactor. The influence of activation parameters on the spent clay by varying the holding time of 1 to approximately 4 hours and temperature of 700 to approximately 900 degrees C was determined. The variations of pore properties as well as the change of chemical characteristics in the resulting solids were also studied. Results showed that the resulting samples were type IV with hysteresis loops corresponding to type H3 from nitrogen adsorption-desorption isotherms, indicating slit-shaped mesoporous characteristics. However, the regenerated clays had smaller surface areas (70 to approximately 117 m2/g) than that (245 m2/g) of fresh bleaching earth. Under the physical activation conditions investigated, the holding time of 1 hour and temperature of 700 degrees C were found to be optimal conditions for producing mesoporous clay with physical activation. The adsorption of paraquat on regenerated sample was also evaluated. The isotherm showed that the regenerated sample still had a high affinity for this herbicide. Thus, the regeneration of this agro-industrial waste is one option for utilizing the clay resource, and it may be used for water treatment applications to remove organic contaminants.
Adsorption↗
Blockade of alpha1-adrenoceptors and cardiac depressant effect by a newly synthetic antihypertensive drug, DL-017 of quinazoline derivative.
The electromechanical effects of 3-[[4-(2-methoxy phenyl)piperazin-1-yl]methyl]-5-(methylthio)-2,3-dihydroimidazo[1,2-c]quinazoline (DL-017), a newly synthesized quinazoline-derived antihypertensive agent, on mammalian cardiac tissues were evaluated. In driven canine Purkinje fibers, DL-017 decreased twitch tension, the maximal rate of upstroke of the action potential (Vmax), and intracellular Na+ activity (a(i)Na) in a concentration-dependent manner. The action potential duration was decreased in canine Purkinje fibers but increased in guinea pig papillary muscles. In guinea pig ventricular papillary muscles, phenylephrine in the presence of 1 microM propranolol increased the twitch tension in a concentration-dependent manner. At 10 microM, phenylephrine significantly decreased a(i)Na and shortened the action potential duration. DL-017 at 0.01 microM inhibited these phenylephrine-induced effects and shifted the concentration-dependent curve to the right. In sinoatrial nodes, DL-017 inhibited pacemaker activity, involving decreases in the slope of diastolic depolarization and Vmax and an increase in a delay of repolarization. These results suggest that, in addition to blockade of alpha1-adrenoceptors and Na+ channels, DL-017 reduces cardiac excitability and contractility in association with inhibition of slow inward Ca2+ and outward K+ channels. Since two order higher concentrations are required, the contribution of DL-017 to cardiac depressant from blockade of ionic channels seems to be less important when this compound is clinically used as an antihypertensive drug.
Action Potentials↗
Interactions of 1-methyl-4-phenylpyridinium and other compounds with P-glycoprotein: relevance to toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
The vesicular monoamine transporter 2 (VMAT2) has sequence homology with bacterial multidrug transporters which in turn share homology with mammalian P-glycoprotein (P-GP). Both VMAT2 and P-GP can detoxify cells. 1-Methyl-4-phenylpyridinium (MPP(+)), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is a substrate for VMAT2 that has several structural features in common with P-GP substrates and inhibitors. The present studies investigated whether P-GP is responsible for the elimination of MPP(+) from the brain. Additionally, VMAT2 and P-GP are inhibited by many of the same compounds. Thus we also investigated whether VMAT2 inhibitors could block P-GP in vitro and vice versa whether P-GP inhibitors could block VMAT2 mediated transport of [3H]-DA into synaptic vesicles. In mice treated with MPTP and a P-GP inhibitor (quinidine, trans-flupentixol or cyclosporine A), the elimination of MPP(+) from the striatum was significantly delayed. However, in experiments using various cell lines expressing either mouse or human P-GP, MPP(+) did not reverse the P-GP mediated resistance to vincristine, suggesting that MPP(+) is a poor substrate for P-GP. Additional experiments were performed using mdr1a/b double knockout mice which lack functional P-GP encoded by these two genes. Data from mdr1a/b knockout mice treated with MPTP also suggest that MPP(+) is not extruded from the brain by P-GP. In other studies, we demonstrated that the VMAT2 inhibitors tetrabenazine and Ro 4-1284 inhibit P-GP and that the P-GP inhibitors trans-flupentixol and quinidine inhibit VMAT2. Thus, several new drugs can be added to the list of compounds that are able to inhibit both VMAT2 and P-GP, providing further evidence of the similarity between these two transporters.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Efficient evolutionary algorithm for the thin-film synthesis of inhomogeneous optical coatings.
We propose an efficient evolutionary approach for the thin-film synthesis of inhomogeneous optical coatings. The proposed approach consists of global and local strategies by integration of decreasing-based mutations and self-adaptive mutations by means of family competition and adaptive rules. Numerical results indicate that the proposed approach performs robustly and is competitive with other approaches. Our approach, although somewhat slower, is flexible and can easily be adopted to other application domains. Our approach is also able to generate homogeneous solutions with two materials available.
Journal Article↗
Synergistic apoptosis induced by bacterial endotoxin lipopolysaccharide and high glucose in rat microglia.
The present study investigates whether bacterial lipopolysaccharide (LPS) in the presence of increased levels of glucose induced synergistic cytotoxicity in primary cultured microglia. Significant cytotoxicity was only observed while the concentrations of LPS were increased to 10 microg/ml. D-glucose concentration-dependently (25-125 mM) generated cytotoxicity. Synergistic apoptosis of microglia was seen by LPS in the presence of increased levels of D-glucose. This synergistic cytotoxicity was attenuated by the use of superoxide dimutase and catalase, suggesting the involvement of oxidative free radicals. Collectively, the present results suggest that increased ambient levels of glucose rendered microglia vulnerable to LPS insults, and led to a synergistic apoptosis. The findings here may be important in certain patho-physiological implications in which hyperglycemia exacerbated the ambient functions contributed by microglia, and may provide new insight into a novel therapeutic intervention.
Animals↗
Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin.
Glioblastoma multiforme is the most treatment-resistant brain tumor. Elongation factor-2 (EF-2) kinase (calmodulin kinase III) is a unique protein kinase that is overexpressed in glioma cell lines and in human surgical specimens. Several mitogens activate this kinase and inhibitors block mitogen activation and produce cell death. Geldanamycin (GA) is a benzoquinone ansamycin antibiotic that disrupts Hsp90-protein interactions. Because EF-2 kinase is chaperoned by Hsp90, we investigated the effects of GA on the viability of glioma cells, the expression of EF-2 kinase protein, and the interaction between Hsp90 and EF-2 kinase. GA was a potent inhibitor of the clonogenicity of four glioma cells lines with IC(50)s ranging from 1 to 3 nM. 17-allylamino-17-demethoxygeldanamycin (17-AAG), a less toxic and less potent derivative of GA, inhibited the clonogenicity of glioma cells with IC(50) values of 13 nM in C6 cells and 35 nM in T98G cells. Treatment of cell lines for 24-48 h of GA or 17-AAG disrupted EF-2-kinase/Hsp90 interactions as measured by coimmunoprecipitation, resulting in a decreased amount of recoverable kinase in cell lysates. The ability of GA to inhibit the growth of glioma cells was abrogated by overexpressing EF-2 kinase. In addition, 17-AAG significantly inhibited the growth of a glioma xenograft in nude mice. These studies demonstrate for the first time the activity of GAs against human gliomas in vitro and in vivo and suggest that destruction of EF-2 kinase may be an important cytotoxic mechanism of this unique class of drug.
Animals↗