Search PubMed⌕ Search

Biomedical subjects

C K Wang

Publications and source records attributed to C K Wang.

At least 19 recordsLinked to original sources

Transient regulatory T-cells: a state attained by all activated human T-cells.

CD4(+)CD25(+)FOXP3(+) regulatory T-cells (T(regs)) form an important arm of the immune system responsible for suppressing untoward immune responses. T(regs) can be thymically derived or peripherally induced, even from CD4(+)CD25(-)FOXP3(-) T-cells. FOXP3 expression and in vitro suppressive activity are considered unique hallmarks of this dedicated and stable lineage of regulatory cells. Here we show that virtually all human CD4(+)CD25(-)FOXP3(-) T-cells and CD8(+)CD25(-)FOXP3(-) T-cells attain a transient FOXP3(+)CD25(+) state during activation. In this state of activation, these cells possess the classic phenotype of T(regs), in that they express similar markers and inhibit in vitro proliferation of autologous CD4(+)CD25(-) T-cells. This state is characterized by suppressed IFN-gamma production and robust TNF-alpha and IL-10 production. Interestingly, the great majority of the activated cells eventually downregulate FOXP3 expression, with a concomitant drop in suppressive ability. Our results show that, in humans, FOXP3 expression and T(reg) functionality are not exclusive features of a stable or unique lineage of T-cells but may also be a transient state attained by almost all T-cells. These results warrant caution in interpreting human studies using FOXP3 and suppressive activity as readouts and suggest that attempts to induce "T(regs)" may paradoxically result in induction of effector T-cells, unless stability is confirmed.

Cell Lineage↗

alpha-Synuclein promoter RsaI T-to-C polymorphism and the risk of Parkinson's disease.

Increased alpha-synuclein expression may be involved in the pathogenesis of Parkinson's disease (PD). We investigated the association of Rep1 microsatellite and RsaI T-to-C substitution in the alpha-synuclein promoter region with the risk of PD by a case-control study. The RsaI C/C genotype and C allele were found less frequently in PD patients than in controls. A reduced risk of the Rep1-RsaI 0-C haplotype (OR = 0.57, 95% CI = 0.36-0.90) with PD was evident. The quantitative real-time PCR study showed that the alpha-synuclein mRNA expression was increased (although not significantly) in PD patients with RsaI T/T genotype or Rep1-RsaI 0-T haplotype as compared to T/C genotype or 0-C haplotype. Reporter constructs containing the RsaI C allele drove significantly lower transcriptional activity compared with the RsaI T allele in both IMR32 and 293 cells. The findings suggest that the RsaI T-to-C substitution may have a functional relevance to the susceptibility to PD.

Adult↗

Examining the effect of length/width ratio on the hydro-dynamic behaviour in a DAF system using CFD and ADV techniques.

Dissolved air flotation (DAF) is a solid-liquid separation system that uses fine bubbles rising from the bottom to remove particles in water. In this study, we investigated the effect of L/W(L; length, W; width) on the hydrodynamic behavior in a DAF system using CFD (computational fluid dynamics) and ADV (acoustic Doppler velocimetry) technique. The factual full-scale DAF system, L/W ratio of 1:1, was selected and various UW ratio conditions (2:1, 3:1,4:1 and 5:1) were simulated with CFD. For modelling, 2-phase (gas-liquid) flow equations for the conservation of mass, momentum and turbulence quantities were solved using a Eulerian-Eulerian approach based on the assumption that a very small particle is applied in the DAF system. Also, for verification of CFD simulation results, we measured the actual velocity at some points in the full-scale DAF system with the ADV technique. Both the simulation and the measurement results were in good accordance with each other. We concluded that the L/W ratio and outlet geometry play an important role for flow pattern and fine bubble distribution in the flotation zone. In the ratio of 1:1, the dead zone is less than those in other cases. On the other hand, in the ratio of 5:1, the fine bubbles were more evenly distributed.

Waste Disposal, Fluid↗

Detection of quantitative trait loci affecting milk production traits on bovine chromosome 6 in a Chinese Holstein population by the daughter design.

Fourteen microsatellite markers with a coverage of 63.5 cM on bovine chromosome 6 were selected, and 26 sire families with 2,260 daughters were analyzed for mapping quantitative trait loci (QTL) affecting 5 milk production traits in a Chinese Holstein population. In the analyses across 26 families and within the largest significant families with a one-QTL model fitted, a QTL near BMS470 was detected that affected fat yield at the 5% experiment-wide significance level. When a 2-QTL model was fitted in the across-family analysis, it was found that there might exist 2 QTL affecting the 3 yield traits, although the exact or empirical thresholds for the significance testing were unknown. In all analyses, the results for milk yield and protein yield were generally consistent, which might have resulted from the same genetic background for milk and protein yield.

Animals↗

Interactions between the cytomegalovirus promoter and the estrogen response element: implications for design of estrogen-responsive reporter plasmids.

We aimed to produce an estrogen-responsive reporter plasmid that would permit monitoring of estrogen receptor function in the uterus in vivo. The plasmid pBL-tk-CAT(+)ERE was induced by estrogen in bovine endometrial stromal cells. When the CAT gene was replaced by the secreted alkaline phosphatase SeAP, the resulting construct pBL-tk-SeAP(+)ERE remained estrogen responsive. However when the tk promoter was replaced by the cytomegalovirus (cmv) promoter, the resulting plasmid (pBL-cmv-SeAP(+)ERE) was not estrogen responsive. Inhibition of ERE function was not due to an effect in trans or due to lack of estrogen receptor. It was not due to an interaction between the cmv promoter and the SeAP gene. cmv promoter function was dependent on NF-kappaB, and mutagenesis in the NF-kappaB sites reduced basal reporter expression without imparting responsiveness to estrogen. A mutation in the TATA box also failed to impart estrogen responsiveness. Modeling of DNA accessibility indicated the ERE was inserted at a site accessible to transcription factors. We conclude that the cmv promoter inhibits ERE function in cis when the two sequences are located in the same construct, and that this effect does not involve an interaction between cmv and reporter gene, NF-kappaB sites or the TATA box, or DNA inaccessibility.

Animals↗

DNA haplotype analysis of CAG repeat in Taiwanese Huntington's disease patients.

We studied the expanded CAG repeat and adjacent CCG repeat in 53 Huntington's disease (HD) patients and 172 unrelated normal subjects matched to the patients for ethnic origin. The range of the CAG repeat varied from 38 to 109 in the HD patients and from 10 to 29 in the control group. A significant negative correlation was found between the age at onset and the CAG expansion, with no significant influence of the adjacent CCG repeat on the age at onset by multiple regression analysis. Allelic association using CCG repeat and 2 flanking dinucleotide repeat markers within 150 kb of the HD gene revealed linkage disequilibrium for 2 of 3 markers. Haplotype analysis of 24 HD families using these markers identified 3 major haplotypes underlying 87.5% of HD chromosomes. The data suggested frequent haplotypes in the Taiwanese population on which one or more mutational events leading to the disease occurred.

Alleles↗

Compound dual radiation action theory for 252Cf brachytherapy.

The existing dosimetry protocol that uses the concept of RBE for 252Cf brachytherapy contains large uncertainties. A new formula has been developed to correlate the biological effect (i.e. cell survival fraction) resulting from a mixed n + gamma radiation field with two physical quantities and two biological quantities. The formula is based on a pathway model evolved from that of the compound-dual-radiation-action (CDRA) theory, previously proposed by Rossi and Zaider. The new model employs the recently published data on radiation-induced DNA lesions. The new formula is capable of predicting quantitatively the synergistic effect caused by the interactions between neutron events and gamma ray events, and it is intended to be included into a new dosimetry protocol for future 252Cf brachytherapy.

Algorithms↗

A case study of dissolved air flotation for seasonal high turbidity water in Korea.

A DAF (Dissolved-Air-Flotation) process has been designed considering raw water quality characteristics in Korea. Although direct filtration is usually operated, DAF is operated when freshwater algae blooms occur or raw water turbidity becomes high. Pre-sedimentation is operated in case when the raw water turbidity is very high due to rainstorms. A main feature of this plant is that the operation mode can be changed (controlled) based on the characteristics of the raw water to optimize the effluent quality and the operation costs. Treatment capacity (surface loading rate) and efficiency of DAF was found to be better than the conventional sedimentation process. Moreover, low-density particles (algae and alum flocs) are easily separated while the removal of them by sedimentation is more difficult. One of the main concerns for DAF operation is a high raw water turbidity. DAF is not adequate for raw water, which is more turbid than 100 NTU. In order to avoid this problem, pre-sedimentation basins are installed in the DAF plant to decrease the turbidity of the DAF inflow. For simulation of the actual operation, bench and full-scale tests were performed for highly turbid water conditions. Consequently, it is suggested that pre-sedimentation with optimum coagulation prior to DAF is the appropriate treatment scheme.

Air↗

Utero-tubal transfer of mouse embryos.

A successful embryo transfer depends on the quality of the transferred embryos, recipients, and the transfer techniques. Among these, transfer techniques are often the limiting factor because transfer methodologies and personal skills vary. Suboptimal embryo transfer procedures can compromise transgenic experiments (pronuclear microinjection and gene targeting) and critical steps of mouse colony maintenance (embryo cryopreservation and mouse line rederivation). Here we present an efficient and simple procedure utilizing specific designs to improve the transfer quality. A 100% implantation rate is observed after the utero-tubal embryo transfer, which indicates that the modified method successfully prevents the embryos from flowing out of the punctured hole during embryo transfer. We believe this alternative methodology is able to fulfill the need of high efficiency of animal production.

Animals↗

Bone-directed expression of Col1a1 promoter-driven self-inactivating retroviral vector in bone marrow cells and transgenic mice.

Gene therapy of bone would benefit from the availability of vectors that provide stable, osteoblast-specific expression. This would allow bone-specific expression of Col1a1 cDNAs for treatment of osteogenesis imperfecta. In addition, such a vector would restrict expression of secreted therapeutic proteins to the bone-synthesizing regions of the bone marrow after ex vivo transduction of marrow stromal cells and reintroduction of the cells into patients. Retrovirus vectors stably integrate into target cell genomes; however, long-term regulated expression from internal cellular promoters has not been consistently achieved. In some cases this is due to a stem cell-specific mechanism for transcriptional repression of retroviruses. We evaluated the ability of self-inactivating ROSA-derived vectors containing a bone-directed 2.3-kb rat Col1a1 promoter to display osteoblast-specific expression. In vitro expression was examined in bone marrow stromal cell cultures induced to undergo osteoblastic differentiation. In vivo expression was evaluated in chimeric mice derived from transduced embryonic stem cells. The results indicate that self-inactivating retrovirus vectors containing the Col1a1 promoter are not permanently inactivated in embryonic stem cells and are specifically expressed in osteoblasts in vivo and in vitro. Thus these vectors should be useful for bone-directed gene therapy.

Animals↗

Inhibitory effect of betel quid on the volatility of methyl mercaptan.

Betel quid, a popular natural masticatory in Taiwan, is mainly composed of fresh areca fruit, Piper betle (leaf or inflorescence), and slaked lime paste. People say that halitosis disappears during betel quid chewing. In this study, the removal of mouth odor during betel quid chewing was discussed by using a model system which measured its inhibition on the volatility of methyl mercaptan. Results showed that crude extracts of betel quid (the mixture of areca fruit, Piper betle, and slaked lime paste) and extracts of the mixture of areca fruit and slaked lime paste exhibited marked effects on the volatility of methyl mercaptan, and the inhibition function increased when increasing amounts of slaked lime paste were added. The same condition (increased inhibition) was also found by replacing the slaked lime paste with alkaline salts (calcium hydroxide, potassium hydroxide, or sodium hydroxide). Areca fruit, the major ingredient of betel quid, contained abundant phenolics. However, the crude phenolic extract of areca fruit did not show any inhibitory activity on the volatility of methyl mercaptan. Great inhibitory activity occurred only when the crude phenolic extract of areca fruit was treated with alkali. Further studies by using gel filtration determined that the effect probably came from the oxidative polymerization of phenolics of areca fruit after alkaline treatment.

Areca↗

Goal orientations, self-determination and pupils' discipline in physical education.

In this study, we examined the patterns of goal orientations, perceived competence, reasons for behaving well and self-reported discipline in school physical education among 511 pupils from years 8 and 9 (mean age 14.2 years). Cluster analyses were conducted on two randomly split subsamples to identify homogeneous groups of pupils on these measures of achievement motivation and discipline. Three meaningful clusters emerged for the first subsample, which were then cross-validated for the second subsample. One group of pupils revealed low scores on task and ego orientations, perceived competence and feelings of self-determination about their behaviour in lessons. These perceptions were related to lower ratings of discipline in physical education than pupils who scored more highly on these variables. The highest discipline scores were reported by pupils with high task and ego orientations, perceived competence and feelings of autonomy. The results are useful for teachers and other physical activity leaders in enhancing motivation and disciplined behaviour in young people. Promoting more self-determined reasons for being disciplined, for example, could lead to more orderly classes.

Adolescent↗

Functions of the upstream and proximal steroidogenic factor 1 (SF-1)-binding sites in the CYP11A1 promoter in basal transcription and hormonal response.

The CYP11A1 gene encodes P450scc (cholesterol side-chain cleavage enzyme), which catalyzes the first step for the synthesis of steroids. Expression of CYP11A1 is controlled by transcription factor SF-1 (steroidogenic factor 1). Two functional SF-1-binding sites, P and U, located at -40 and -1,600 regions of the CYP11A1 gene, have been identified, but their exact functions with respect to basal activation vs. cAMP response have not been dissected. We have addressed this question by examining the ability of the mutated human CYP11A1 promoter to drive LacZ reporter gene expression in transgenic mouse lines. The activity of the mtP mutant promoter was greatly reduced, indicating the importance of the P site. Mutation of the upstream U site also resulted in reduced reporter gene expression, but some residual activity remained. This residual reporter gene activity was detected in the adrenal and gonad in a tissue-specific manner. ACTH and hCG can stimulate LacZ gene expression in the adrenals and testes of transgenic mice driven by the wild-type but not the mtU promoter. These results indicate that the upstream SF-1-binding site is required for hormonal stimulation. Our experiments demonstrate the participation of both the proximal and the upstream SF-1-binding sites in hormone-responsive transcription.

Adrenal Glands↗

Biodistribution and radiation dosimetry of the dopamine transporter ligand.

UNLABELLED: 18F-labeled 2 beta-carbomethoxy-3beta-(4-chlorophenyl)-8-(-2-fluoroethyl)nortropane ([18F]FECNT) is a recently developed dopamine transporter ligand with potential applications in patients with Parkinson's disease and cocaine addiction. METHODS: Estimates of the effective dose equivalent and doses for specific organs were made using biodistribution data from 16 Sprague-Dawley rats and nine rhesus monkeys. PET images from two rhesus monkeys were used to calculate the residence time for the basal ganglia. The computer program MIRDOSE3 was used to calculate the dosimetry according to the methodology recommended by MIRD. RESULTS: The basal ganglia were the targeted tissues receiving the highest dose, 0.11 mGy/MBq (0.39 rad/mCi). The effective dose equivalent was 0.018 mSv/MBq (0.065 rem/mCi), and the effective dose was 0.016 mSv/MBq (0.058 rem/mCi). CONCLUSION: Our data show that a 185-MBq (5-mCi) injection of [18F]FECNT leads to an estimated effective dose of 3 mSv (0.3 rem) and an estimated dose to the target organ or tissue of 19.4 mGy (1.93 rad).

Animals↗

Allelopathic effect of Acorus tatarinowii upon algae.

Besides competing with algae for light and mineral nutrients (i.e. N, P, etc.), the root system of Acorus tatarinowii excretes some chemical substances, which injure and eliminate alga cells, to inhibit the growth of the algae. When the algae cells were treated in "A. tatarinowii water", some of the chlorophyll a were destroyed and the photosynthetic rate of algae decreased markedly and the ability of alga cells to deoxidize triphenyltetrazolium chloride (TTC) reduced greatly. Then alga cells turned from bright red to bluish green under fluorescence microscope. These showed that the allelopathic effects of A. tatarinowii on algae were obvious and planting A. tatarinowii can control some green algae. The experiment on the extractions of the secretions of the root system showed that the inhibitory effect had a concentration effect. If the concentration of the root secretion was below 30 microliters/disc, the inhibitory rate was negative; if it was over 45 microliters/disc, the inhibitory rate was positive. This proved that the influence of the root secretion on the same acceptor was a kind of concentration effect. When the concentration of the root secretion was low, it promoted the growth of algae; when the concentration reached a definite threshold value, it restrained the growth of algae. In present case, the threshold value was between 30 microliters/disc and 45 microliters/disc.

Acorus↗

Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model.

The lifespan of human fibroblasts and other primary cell strains can be extended by expression of the telomerase catalytic subunit (hTERT). Since replicative senescence is accompanied by substantial alterations in gene expression, we evaluated characteristics of in vitro-aged dermal fibroblast populations before and after immortalization with telomerase. The biological behavior of these populations was assessed by incorporation into reconstituted human skin. Reminiscent of skin in the elderly, we observed increased fragility and subepidermal blistering with increased passage number of dermal fibroblasts, but the expression of telomerase in late passage populations restored the normal nonblistering phenotype. DNA microarray analysis showed that senescent fibroblasts express reduced levels of collagen I and III, as well as increased levels of a series of markers associated with the destruction of dermal matrix and inflammatory processes, and that the expression of telomerase results in mRNA expression patterns that are substantially similar to early passage cells. Thus, telomerase activity not only confers replicative immortality to skin fibroblasts, but can also prevent or reverse the loss of biological function seen in senescent cell populations.

Catalytic Domain↗