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Y Lee

Publications and source records attributed to Y Lee.

At least 37 records · Page 2Linked to original sources

Sp1-associated activation of macrophage inflammatory protein-2 promoter by CpG-oligodeoxynucleotide and lipopolysaccharide.

Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that is important in recruiting neutrophils to inflammatory sites. Our previous reports demonstrated that lipopolysaccharide (LPS) or CpG-oligode-oxynucleotide (CpG-ODN) rapidly induce MIP-2 gene expression in the macrophage cell line, RAW 264.7. Here, we show that the DNA sequence of the MIP-2 promoter between -114 and +14 is sufficient for strong promoter activity in LPS- or CpG-ODN-stimulated RAW 264.7 cells. Importantly, comprehensive mutant analysis reveals that an Sp1 element in the promoter region between -114 and -94 is essential for synergistic MIP-2 promoter activation by NF-kappaB and c-Jun regardless of the presence of an AP-1 site. By combining deletion or site-specific mutant analysis with immunocomplex assays, we also confirmed that Sp1 mediates the recruitment of transcription factors NF- kappaB and c-Jun in LPS- or CpG-ODN-treated RAW 264.7 cells. Several lines of experimental evidence imply that the Sp1-binding element is an important determinant of MIP-2 promoter activity, and that NF-kappaB, c-Jun and Sp1 can functionally cooperate to elicit maximal activation of the promoter.

Animals↗

The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain. Cyclooxygenase (COX) enzyme is of particular interest because it is the major target of NSAIDs. Although NSAIDs are remarkably effective in the management of pain and inflammation, their use is limited by several adverse effects including gastrointestinal bleeding and ulceration, impaired renal function, and inhibition of platelet aggregation. Discovery of a second cyclooxygenase, COX-2, led to the hypothesis that NSAID side effects could be decreased, as the inhibition of COX-2 is more directly implicated in ameliorating inflammation while the inhibition of COX-1 is related to adverse effects in the GI tract. This stimulated the development of selective COX-2 inhibitors (coxibs) that are better tolerated than nonselective NSAIDs but comparable in analgesic efficacy. This article provides an overview on the therapeutic use of selective COX-2 inhibitors for relief of acute pain, largely based on clinical trials in patients undergoing the surgical removal of impacted third molars, with focus on analgesic efficacy and the potential safety associated with their use compared to dual COX-1/COX-2 inhibitors.

Acute Disease↗

Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition.

AIMS/HYPOTHESIS: Leptin has been shown to activate AMP-activated protein kinase (AMPK), an enzyme that regulates the activities of key enzymes of lipid synthesis and metabolism. We assess here (i) whether AMPK activity is diminished in rodents deficient in leptin or the leptin receptor, and (ii) the effects of treating the diabetes-prone, leptin-receptor-deficient Zucker Diabetic Fatty (ZDF) rat with an AMPK activator. METHODS: AMPK activity and related parameters were measured in muscle and or liver of fa/fa and ZDF rats and ob/ob mice. We also explored the effect of treatment with the AMPK activator 5-aminoimidazole 4-carboxamide 1-beta-D ribofuranoside (AICAR) (7.4 mmol/l, on Monday, Wednesday and Friday for 15 weeks, beginning at 7 weeks of age) on the phenotype of the ZDF rat. RESULTS: AMPK activity was diminished in muscle and/or liver of fa/fa (leptin-receptor-deficient, non-diabetic) and ZDF (leptin-receptor-deficient, diabetes-prone) rats and ob/ob mice (leptin-deficient). ZDF rats that had free access to food became hyperglycaemic (22.2 mmol/l) and hyperphagic after 2 to 5 weeks and remained so during the remainder of the study. Treatment of ZDF rats with AICAR prevented the development of diabetes, as well as increases of triglyceride content in liver, muscle and the pancreatic islets. It also attenuated the morphological abnormalities observed in the islets of untreated rats. Rats diet-matched with the AICAR-treated animals developed diabetes of intermediate severity and showed decreases in triglyceride content in the islets, but not in liver or muscle. CONCLUSIONS/INTERPRETATION: The results indicate that a deficiency of leptin or the leptin receptor is associated with a decrease in AMPK activity in muscle and/or liver. They also suggest that treatment with an AMPK activator prevents the development of diabetes and ectopic lipid accumulation in the ZDF rat.

Adenylate Kinase↗

A1 and A2 transitions in superfluid 3He in 98% porosity aerogel.

Superfluid 3He in high porosity aerogel is the system in which the effects of static impurities on a p-wave superfluid can be investigated in a systematic manner. We performed shear acoustic impedance measurements on this system (98% porosity aerogel) in the presence of magnetic fields up to 15 T at the sample pressures of 28.4 and 33.5 bars. We observed the splitting of the superfluid transition into two transitions in high fields in both bulk and liquid in aerogel. The field dependence of the splitting in aerogel resembles that of the bulk superfluid 3He caused by the presence and growth of the A1 phase. Our results provide the first evidence of the A1 phase in superfluid (3)He/aerogel.

Journal Article↗

Interfacial pinning in the superfluid 3He A-B transition in aerogel.

Continuous-wave NMR studies of 3He in the presence of 99.3% porosity silica aerogel at 34.0 bars and in a magnetic field of 28.4 mT reveal a first-order phase transition between A-like and B-like superfluid phases on both warming and cooling. NMR spectra show that the phases on warming are the same as the phases on cooling, and the interface between them is found to be strongly pinned, even close to T(c,aero). The observed behavior is consistent with spatial variation of pinning strengths within the aerogel.

Journal Article↗

PDE6 is an effector for the Wnt/Ca2+/cGMP-signalling pathway in development.

Wnt signalling in development operates via members of the Frizzleds, G-protein-coupled receptors that bind specific Wnt ligands and mediate signalling via distinct pathways. The Wnt/Ca(2+)/cGMP pathway mediated by Frizzled-2 was discovered recently. Activation of this pathway leads to increased intracellular concentrations of Ca(2+) and decreased intracellular concentrations of cGMP. The nature of the phosphodiesterase responsible for this Frizzled-2-mediated effect on cGMP levels was identified based on three separate criteria: (i) sensitivity to selective enzyme inhibitors, (ii) behaviour on chromatographic separation, and (ii) isolation by two-dimensional gels in tandem with direct mapping by MS of tryptic digests of the activity. On the basis of results from these three analyses, the cGMP-specific phosphodiesterase, PDE6, is demonstrated to be an effector for the Wnt/Ca(2+)/cGMP signalling pathway of development, which is mediated by Frizzled-2.

Animals↗

Bench-scale assessment of the effectiveness of an anaerobic selector in controlling filamentous bulking.

A laboratory scale sequencing batch reactor (SBR) was used to assess the ability of an anaerobic selector to control filamentous growth in an activated sludge plant experiencing bulking problems. The SBR was operated under a sequence of 60 min anaerobic followed by 120 min of aerobic period at 20 degrees C, with a total solids retention time (SRT) of 4 d and a hydraulic retention time (HRT) of 8 h. The apparent soluble organic carbon (SOC) removal from the liquid phase averaged 18% during the anaerobic period, which is significantly less than the 80-90% removal generally considered to be required to suppress the growth of filamentous bacteria. The anaerobic selector was, however, able to control sludge bulking, resulting in an average sludge volume index (SVI) below 140 ml g(-1). The true amount of the SOC uptake was masked by simultaneous hydrolysis of particulate organic matter during the anaerobic period, a process which should be considered in future studies and comparisons.

Bacteria, Anaerobic↗

Mechanical stretch activates type 2 cyclooxygenase via activator protein-1 transcription factor in human myometrial cells.

The uterus is subject to stretch throughout pregnancy, which, in the presence of progesterone, is a potent stimulus for uterine growth. However, in the absence of progesterone or when stretch is excessive, as in multiple pregnancy, it may provoke the onset of labour. We have investigated the effect of stretch on prostaglandin synthesis in primary human uterine myocytes [non-pregnant (NP), pregnant not in labour (NL) and pregnant in labour (L)]. The cells were grown on flexible bottom culture plates and subjected to 1 or 6 h static stretch. Expression of type 2 cyclooxygenase (COX-2) mRNA was similar in samples obtained from NP and L groups and both were significantly greater than those found in the NL group. Stretch of cells from all groups resulted in increased COX-2 mRNA expression. In further studies carried out on cells taken from the NL group, 6 h of stretch resulted in increased COX-2 protein levels and, in the media, increases in prostaglandin (PG) I(2) metabolite and PGE(2) concentrations and a reduction in the concentration of PGF(2)alpha metabolites. After stretch, EMSA studies showed increased activator protein-1 (AP-1) nuclear protein DNA binding activity but not of nuclear factor kappaB. These data demonstrate that stretch of human myocytes results in increased COX-2 activity and suggest that this may occur through activation of the AP-1 system.

Adult↗

Evaluation of Cryptosporidium parvum oocyst recovery efficiencies from various filtration cartridges by electrochemiluminescence assays.

AIMS: To evaluate four types of filtration cartridges for their capacities, efficiency for capture and release of Cryptosporidium parvum oocysts for detection. METHODS AND RESULTS: Filtration cartridges included in this evaluation were IDEXX Filta-Max, Gelman Envirochek HV, Corning CrypTest, and Filterite Sigma+. Various dosages of C. parvum oocysts were spiked into water samples with a wide range of turbidity (10-50 NTU). Electrochemiluminescence assays were employed to enumerate viable or total number of C. parvum oocysts in these eluates. Among the cartridges tested, Filta-Max consistently showed higher oocyst recovery efficiency, especially with large volume, highly turbid water samples. CONCLUSIONS: Filta-Max filter is the best performer because of its higher oocyst recovery efficiency. SIGNIFICANCE AND IMPACT OF THE STUDY: The overall sensitivities of various C. parvum oocyst detection assays in water samples can be improved if highly efficient oocyst recovery filtration cartridges such as Filta-Max are incorporated in sample preparation.

Animals↗

Enrichment of gene-coding sequences in maize by genome filtration.

Approximately 80% of the maize genome comprises highly repetitive sequences interspersed with single-copy, gene-rich sequences, and standard genome sequencing strategies are not readily adaptable to this type of genome. Methodologies that enrich for genic sequences might more rapidly generate useful results from complex genomes. Equivalent numbers of clones from maize selected by techniques called methylation filtering and High C0t selection were sequenced to generate approximately 200,000 reads (approximately 132 megabases), which were assembled into contigs. Combination of the two techniques resulted in a sixfold reduction in the effective genome size and a fourfold increase in the gene identification rate in comparison to a nonenriched library.

Chromosomes, Plant↗

Effects of predation and ORP conditions on the performance of nitrifiers in activated sludge systems.

Effects of changing oxidation-reduction potential (ORP) and grazing of protozoa on nitrifiers in activated sludge systems was investigated. This study used sequencing batch reactors which were acclimated under aerobic and alternating anoxic/aerobic conditions, with and without inhibition of protozoa, the predatory microorganisms. The feed used was a synthetic wastewater containing beef and yeast extracts as a carbon source. It was found that the biomass, determined by mixed liquor volatile suspended solids (MLVSS) in the reactors, was significantly affected by predation while ORP (aerobic and alternating anoxic/aerobic conditions) has no impact on the MLVSS regardless of the presence or absence of predation. However, the nitrification rates in the reactors show completely different trends indicating that the ORP of the system has a significant impact on the rates while predation does not. It was found that nitrification rates in alternating reactors were almost double the rates in the aerobic reactors, both with and without predatory inhibition. The decay rate of autotrophic bacteria (b(A)) in aerobic reactors was determined by tracking the decrease of the maximum nitrification rate under both anoxic and aerobic starvation conditions. The b(A) in alternating anoxic/aerobic reactors was also determined under alternating starvation conditions. It was found that, in any case, the alternating anoxic/aerobic autotrophic biomass b(A) was much smaller that the b(A) of aerobic biomass determined under aerobic and anoxic starvation conditions. The alternating anoxic/aerobic b(A) was 62.1% less than the aerobic biomass b(A) under aerobic starvation and 40.2% less for the aerobic biomass starved under anoxic conditions. No statistically significant differences in b(A) were observed between reactors with or without the inhibition of predators.

Animals↗

Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone.

Prostate adenocarcinoma is associated with the formation of osteoblastic metastases in bone. It is hypothesized that osteoclastogenesis is a critical component in the development of skeletal metastases. These findings, however, were generally noted in predominantly osteolytic lesions. The pathophysiology of osteoblastic lesions remains unknown but the type of bone lesion formed may be influenced by the cytokines produced by prostate tumors. To test this theory, we implanted PC-3 and LAPC-9 cells into the tibias of SCID mice. These mice were sacrificed at 1, 2, 4, 6, and 8 weeks after implantation and histologic analysis was performed on these tibias. PCR analysis was also performed on bulk tumors. The results showed that the PC-3 implanted tibias developed pure osteolytic lesions while the LAPC-9 implanted tibias developed pure osteoblastic lesions on radiographs. Analysis of tibias after injection with PC-3 cells revealed progressive osteolytic lesions with abundant osteoclast activity at 2 weeks and destruction of the proximal tibia at 6 weeks after cell implantation. In contrast, the LAPC-9 cells formed osteoblastic lesions six weeks after cell injection. There were rare osteoclasts prior to the establishment of the osteoblastic lesions but greater osteoclast activity was noted with remodeling of the osteoblastic lesion 8 weeks after implantation of the tumor cells. PCR analysis revealed that PC-3 cells produced RANKL, IL-1, and TNF-alpha, which are associated with osteoclastogenesis. In contrast, LAPC-9 cells produced osteoprotegerin, which blocks osteoclast production and no detectable levels of RANKL or IL-1 and only minimal amounts of TNF-alpha were noted. These cells secreted BMP-2, -4, -6, and IL-6, which are associated with bone formation. These results suggest that the role of the osteoclast in the development of a metastatic lesion is variable depending on the phenotype of the prostate cancer cells, and that tumor-induced osteolysis may not be required for osteoblastic metastases.

Animals↗

Near-field imaging of surface plasmon on gold nano-dots fabricated by scanning probe lithography.

We obtained scanning near-field optical microscopy images to study the excitation of surface plasmons on metallic dots fabricated using scanning probe lithography. Gold nano-dots were fabricated by applying electric voltages to conducting probes installed in an atomic force microscope using the mechanism of field-induced diffusion and nano-oxidation plus Au-coating. High spatial resolution of scanning near-field optical microscopy revealed a 'bifold' pattern of surface plasmon mode on fabricated Au dots in the polarization direction of incident light. We found that scanning near-field optical microscopy imaging combined with scanning probe lithography is able to provide a systematic study of surface plasmon excitation on nano-metallic structures.

Aluminum↗

Sequence analysis of a rainbow trout cDNA library and creation of a gene index.

Expressed sequence tag (EST) projects have produced extremely valuable resources for identifying genes affecting phenotypes of interest. A large-scale EST sequencing project for rainbow trout was initiated to identify and functionally annotate as many unique transcripts as possible. Over 45,000 5' ESTs were obtained by sequencing clones from a single normalized library constructed using mRNA from six tissues. The production of this sequence data and creation of a rainbow trout Gene Index eliminating redundancy and providing annotation for these sequences will facilitate research in this species.

Animals↗

Modification of ASM No.1 for a submerged membrane bioreactor system: including the effects of soluble microbial products on membrane fouling.

In this study, a mathematical model for the submerged membrane bioreactor (SMBR) was developed by combining the activated sludge model (ASM) with a membrane resistance-in-series model. Some modifications were introduced to make ASM to be suitable for describing the characteristics of SMBR. A set of the 1st-order differential equations was established for 13 dependent variables relevant to particles and soluble matters. Performing model simulations for various conditions, the time when a membrane would be fouled could be predicted as well as the effluent quality. From simulation results, F/M ratio and SRT can be considered as major factors of the soluble microbial products (SMP) concentration in a reactor and it is clear that SMP can play an important role in membrane fouling and water quality simultaneously. The model would be very helpful in optimizing operation conditions as well as in designing an optimal SMBR system.

Bioreactors↗

Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

Alternative Splicing↗