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Biomedical subjects

J Cho

Publications and source records attributed to J Cho.

At least 37 records · Page 2Linked to original sources

The TIGR Gene Indices: analysis of gene transcript sequences in highly sampled eukaryotic species.

While genome sequencing projects are advancing rapidly, EST sequencing and analysis remains a primary research tool for the identification and categorization of gene sequences in a wide variety of species and an important resource for annotation of genomic sequence. The TIGR Gene Indices (http://www.tigr.org/tdb/tgi. shtml) are a collection of species-specific databases that use a highly refined protocol to analyze EST sequences in an attempt to identify the genes represented by that data and to provide additional information regarding those genes. Gene Indices are constructed by first clustering, then assembling EST and annotated gene sequences from GenBank for the targeted species. This process produces a set of unique, high-fidelity virtual transcripts, or Tentative Consensus (TC) sequences. The TC sequences can be used to provide putative genes with functional annotation, to link the transcripts to mapping and genomic sequence data, to provide links between orthologous and paralogous genes and as a resource for comparative sequence analysis.

Animals↗

Evaluation of chondromalacia of the patella with axial inversion recovery-fast spin-echo imaging.

The purpose of our study was to assess the accuracy of inversion recovery-fast spin-echo (IR-FSE) imaging for the evaluation of chondromalacia of the patella. Eighty-six patients were included, they underwent magnetic resonance (MR) examination and subsequent knee arthroscopy. Medial and lateral facets of the patella were evaluated separately. Axial images were obtained by using IR-FSE (TR/TE/TI = 3000/25/150 msec; echo train length, 8; 4-mm thickness; 12-cm field of view; 512 x 256 matrix; two, number of excitations) with a 1.5-T MR machine. MR interpretation of chondromalacia was made on the basis of the arthroscopic grading system. Of a total of 172 facets graded, arthroscopy revealed chondromalacia in 14 facets with various grades (G0, 158; G1, 1; G2, 3; G3, 6; G4, 4). Sensitivity, specificity, and accuracy in the chondromalacia grades were 57.1%, 93.0%, and 90.1%, respectively. There was one false-negative case (G4) and 11 false-positive cases (G1, eight; G2, two; G3, one). Sensitivity and specificity corrected by one grade difference were improved to 85.7% and 98.1%, respectively. When cartilage changes were grouped into early (corresponding to grade 1 and 2) and advanced (grade 3 and 4) diseases, sensitivity and specificity of the early and advanced diseases were 75% and 94% and 80% and 99%, respectively. IR-FSE imaging of the knee revealed high specificity but low sensitivity for the evaluation of chondromalacia of the patella.

Adolescent↗

Cleaning strategies for flux recovery of an ultrafiltration membrane fouled by natural organic matter.

One of the most common problems encountered in water treatment applications of membranes is fouling. Natural organic matter (NOM) represents a particularly problematic foulant. Membranes may be fouled by relatively hydrophilic and/or hydrophobic NOM components, depending on NOM characteristics, membrane properties, and operating conditions. To maximize flux recovery for an NOM-fouled ultrafiltration membrane (NTR 7410), chemical cleaning and hydraulic rinsing with a relatively high cross-flow velocity were investigated as cleaning strategies. The modification of the membrane surface with either an anionic or a cationic surfactant was also evaluated to minimize membrane fouling and to enhance NOM rejection. Foulants from a hydrophobic NOM source (Orange County ground water (OC-GW)) were cleaned more effectively in terms of permeate flux by acid and caustic cleanings than foulants from a relatively hydrophilic NOM source (Horsetooth surface water (HT-SW)). An anionic surfactant (sodium dodecyl sulfate (SDS)) was not effective as a cleaning agent for foulants from either hydrophobic or hydrophilic NOM sources. High ionic strength cleaning with 0.1 M NaCl was comparatively effective in providing flux recovery for NOM-fouled membranes compared to other chemical cleaning agents. Increased cross-flow velocity and longer cleaning time influenced the efficiency of caustic cleaning, but not high ionic strength cleaning. The membrane was successfully modified only with the cationic surfactant; however, enhanced NOM rejection was accompanied by a significant flux reduction.

Acids↗

The anatomical and computational basis of the rat head-direction cell signal.

As a rat navigates through space, neurons called head-direction (HD) cells provide a signal of the rat's momentary directional heading. Although partly guided by landmarks, the cells also show a remarkable ability to track directional heading based on angular head movement. Theoretical models suggest that the HD cells are linked together to form an attractor network, and that cells which signal angular velocity update the directional setting of the attractor. Recently, cell types similar to those required theoretically have been discovered in the lateral mammillary and dorsal tegmental nuclei. Lesion and anatomical data suggest these nuclei might constitute the postulated attractor-path integration mechanism, and that they provide the HD cell signal to cortical areas where it has been observed.

Animals↗

Implementation of a forearm support to reduce the amount of irradiated lung and heart in radiation therapy of the breast.

We compared simulator images of medial tangential fields taken in two positions: (1) with the ipsilateral arm abducted, holding a 'L-bar' armrest and (2) with both arms extended above the head in a forearm support. The average maximum heart distance as well as the central lung distance decreased significantly by 3.4 (SE 0.9) and 4.7 (SE 1.1) mm, respectively, when the new forearm support was used. The estimated normal tissue complication probability for excess cardiac mortality decreased by on average 3.1% (SE 1.3%). For some patients, a greater amount of the axilla was included in the field. We recommend the use of the forearm support during breast cancer treatment with tangential fields to decrease the amount of heart and lung inside the fields.

Breast Neoplasms↗

The continuous monitoring of field water samples with a novel multi-channel two-stage mini-bioreactor system.

Toxicity monitoring of field water samples was performed using a novel multi-channel two-stage mini-bioreactor system and genetically engineered bioluminescent bacteria for the continuous monitoring and classification of the toxicity present in the samples. The toxicity of various samples spiked with known endocrine disrupting chemicals and phenol was also investigated for system characterization. The field samples used in this study were obtained from two different sites on a monthly basis--from a drinking water treatment plant, referred to as site N, and from a stream near a dam which is currently being constructed, referred to as site T. These samples were either pumped or injected into the second mini-bioreactors to initiate the toxicity test. Most of the samples did not show any specific toxicity. However, one sample showed to have, based upon the detection results, and was deemed toxic. The samples spiked with phenol showed possible responses in the DPD2540 and TV1061 channels, indicating the occurrence of both membrane and protein damage due to phenol. In the tests using an endocrine disrupting chemical, bisphenol A, DNA damage was detected in the DPD2794 channel with a concentration of 2 ppm. Finally, a simple but novel early warning protocol that can be used in a drinking water reservoir and a suspected place where effluents of toxic materials enter the water sourse was suggested with a schematic diagram. In conclusion, this system showed good feasibility for use as a toxicity monitoring system in the field and as an early warning system, indicating if effluents are toxic.

Bacteria↗

Head direction, place, and movement correlates for cells in the rat retrosplenial cortex.

The retrosplenial cortex is strongly connected with brain regions involved in spatial signaling. To test whether it also codes space, single cells were recorded while rats navigated in an open field. As in earlier work (L. L. Chen, L. H. Lin, C. A. Barnes, & B. L. McNaughton, 1994; L. L. Chen, L. H. Lin, E. J. Green, C. A. Barnes, & B. L. McNaughton, 1994), the authors found head direction cells with properties similar to those in other areas. These cells were slightly anticipatory. Another cell type fired to particular combinations of location, direction, and movement, which suggested that they may fire whenever the rat approaches a particular location, using a particular locomotor behavior. The remaining cells could not be clearly categorized but also showed a significant correlation with one or more of the spatial-movement variables examined. The fact that the retrosplenial cortex contains spatial and movement-related signals and is connected with the motor cortex suggests that it may play a role in path integration or navigational motor planning.

Animals↗

Central beta-amyloid peptide-induced peripheral interleukin-6 responses in mice.

beta-Amyloid peptides (Abetas) share with lipopolysaccharide, a potent pro-inflammatory agent, the property of stimulating glial cells or macrophages to induce various inflammatory mediators. We recently reported that central administration of lipopolysaccharide induces peripheral interleukin-6 responses via both the central and peripheral norepinephrine system. In this study, the effect of intracerebroventricular injection of various synthetic Abetas on plasma interleukin-6 levels was examined in mice. Abeta(1-42) dose-dependently increased plasma interleukin-6 levels: 'aged' Abeta(1-42) was more effective than fresh, whereas Abeta(42-1) had no effect. 'Aged' Abeta(1-42) (205 pmol/mouse i.c.v.)-induced plasma interleukin-6 peaked at 2 h post injection, which is earlier than the peak time of the Abeta(1-42)-induced brain interleukin-6, tumor necrosis factor-alpha and interleukin-1beta levels, which was 4, 4 and 24 h, respectively. Among various peripheral organs, Abeta(1-42) (205 pmol/mouse i.c.v.) significantly increased interleukin-6 mRNA expression in lymph nodes and liver. Abeta(1-42) (205 pmol/mouse i.c.v.) significantly increased norepinephrine turnover in both hypothalamus and spleen. Either central or peripheral norepinephrine depletion effectively inhibited the Abeta(1-42)-induced peripheral interleukin-6 response. Pretreatment with prazosin (alpha(1)-adrenergic antagonist), yohimbine (alpha(2)-adrenergic antagonist), and ICI-118,551 (beta(2)-adrenergic antagonist), but not with betaxolol (beta(1)-adrenergic antagonist), inhibited Abeta(1-42)-induced plasma interleukin-6 levels. These results demonstrate that centrally administered Abeta(1-42) effectively induces the systemic interleukin-6 response which is mediated, in part, by central Abeta(1-42)-induced activation of the central and the peripheral norepinephrine systems.

Amyloid beta-Peptides↗

Targeting dexamethasone to Kupffer cells: effects on liver inflammation and fibrosis in rats.

Kupffer cells (KC) play an important role in the pathogenesis of inflammatory liver diseases leading to fibrosis. Anti-inflammatory drugs are only effective when administered at high doses that may cause side effects. Therefore, dexamethasone coupled to mannosylated albumin (Dexa(5)-Man(10)-HSA) was designed by us to selectively deliver this anti-inflammatory drug to the KC. The effectiveness of Dexa(5)-Man(10)-HSA was studied both in organ cultures and fibrosis induced by bile duct ligation (BDL) in rats. Dexa(5)-Man(10)-HSA accumulated in livers of both healthy and fibrotic rats (67% +/- 5% and 70% +/- 9% of the dose, respectively) and uptake was found almost exclusively in KC. Active dexamethasone was liberated from its carrier, because Dexa(5)-Man(10)-HSA could effectively inhibit nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) release in endotoxin-activated liver slices. In vivo, however, this was associated with increased collagen I and III depositions and enhanced tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression. This was accompanied by a decreased influx of reactive oxygen species (ROS) producing cells in the livers of BDL animals treated with Dexa(5)-Man(10)-HSA as compared with untreated BDL rats. Dexa(5)-Man(10)-HSA treatment also replenished the depleted glycogen stores in hepatocytes of BDL livers. In conclusion, our studies showed selective delivery of dexamethasone to KC with Dexa(5)-Man(10)-HSA. This conjugate reduced intrahepatic ROS in vivo and TNF-alpha production in vitro and prevented glycogen depletion in vivo, indicating effective pharmacologic targeting. Dexa(5)-Man(10)-HSA, however, also accelerated fibrogenesis, which was paralleled by TIMP-1 mRNA induction. Targeting of dexamethasone to KC provides evidence for a dual role of this cell type in fibrogenesis of BDL rats.

Animals↗

Immunostimulatory DNA mediates inhibition of eosinophilic inflammation and airway hyperreactivity independent of natural killer cells in vivo.

BACKGROUND: Immunostimulatory DNA sequences (ISS) inhibit eosinophilic inflammation and airway hyperreactivity in mouse models of asthma. In vitro ISS activate natural killer (NK) cells to secrete IFN-gamma, and this cytokine is hypothesized to contribute to the antiallergic effect of ISS in vivo. OBJECTIVE: We investigated whether ISS activation of NK cells is important in mediating the reduction in airway hyperreactivity and the antieosinophilic effect of ISS in vivo. METHODS: We assessed whether ISS modulated the development of eosinophilic airway inflammation and airway hyperreactivity to methacholine in ovalbumin (OVA)-sensitized and OVA allergen-challenged mice pretreated with an antibody to deplete NK cells. RESULTS: Mice sensitized and challenged with OVA had significant bronchoalveolar lavage and lung eosinophilia, as well as airway hyperresponsiveness. ISS induced significant inhibition of bronchoalveolar lavage and lung eosinophilia, as well as airway hyperresponsiveness, in OVA-sensitized mice pretreated before OVA challenge with an NK cell-depleting antibody (NK(-) mice), as well as in mice pretreated with a control non-NK cell-depleting antibody (NK(+) mice). The NK cell-depleting antibody inhibited ISS-induced IFN-gamma production by spleen cells. CONCLUSION: These studies demonstrate that depletion of NK cells has no significant effect on ISS-mediated inhibition of airway eosinophilia and airway hyperresponsiveness in vivo, suggesting that non-NK cells and cytokines other than IFN-gamma derived from NK cells mediate the majority of the ISS-inhibitory effect on eosinophilic inflammation and airway hyperresponsiveness in vivo.

Adjuvants, Immunologic↗

Sequence evaluation of four pooled-tissue normalized bovine cDNA libraries and construction of a gene index for cattle.

An essential component of functional genomics studies is the sequence of DNA expressed in tissues of interest. To provide a resource of bovine-specific expressed sequence data and facilitate this powerful approach in cattle research, four normalized cDNA libraries were produced and arrayed for high-throughput sequencing. The libraries were made with RNA pooled from multiple tissues to increase efficiency of normalization and maximize the number of independent genes for which sequence data were obtained. Target tissues included those with highest likelihood to have impact on production parameters of animal health, growth, reproductive efficiency, and carcass merit. Success of normalization and inter- and intralibrary redundancy were assessed by collecting 6000-23,000 sequences from each of the libraries (68,520 total sequences deposited in GenBank). Sequence comparison and assembly of these sequences was performed in combination with 56,500 other bovine EST sequences present in the GenBank dbEST database to construct a cattle Gene Index (available from The Institute for Genomic Research at http://www.tigr.org/tdb/tgi.shtml). The 124,381 bovine ESTs present in GenBank at the time of the analysis form 16,740 assemblies that are listed and annotated on the Web site. Analysis of individual library sequence data indicates that the pooled-tissue approach was highly effective in preparing libraries for efficient deep sequencing.

Animals↗

RESOURCERER: a database for annotating and linking microarray resources within and across species.

Microarray expression analysis is providing unprecedented data on gene expression in humans and mammalian model systems. Although such studies provide a tremendous resource for understanding human disease states, one of the significant challenges is cross-referencing the data derived from different species, across diverse expression analysis platforms, in order to properly derive inferences regarding gene expression and disease state. To address this problem, we have developed RESOURCERER, a microarray-resource annotation and cross-reference database built using the analysis of expressed sequence tags (ESTs) and gene sequences provided by the TIGR Gene Index (TGI) and TIGR Orthologous Gene Alignment (TOGA) databases [now called Eukaryotic Gene Orthologs (EGO)].

Animals↗

Oxidation of polycyclic aromatic hydrocarbons by ozone in the presence of sand.

A series of soil slurry experiments was performed to investigate the characteristics of PAHs removal by ozone in various conditions. Gaseous ozone was bottled into the aqueous phase in the presence of soil contaminated by PAHs. The effects of soil media, OH radical scavengers, ozone dosage, and humic acid were examined at the given experimental conditions. There exists a substantial difference in the removal of PAH according to the types of soil media tested. Baked sand showed the highest removal efficiency compared to the others. The descending order of removal rate was: BS > S > GB. This is considered to be due to the OH radical effect produced by catalytic reactions of ozone with the reactive site on the and. This is qualitatively proved by the experiment of scavenging OH radicals using tert-butanol. The comparison of half-lives of ozone in sand and glass bead columns further supports this hypothesis. It was found that about 22% of enhancement of phenanthrene destruction was accomplished by OH radicals produced by the catalytic ozone decomposition. The rate of ozone consumption for the phenanthrene oxidation was obtained as 1.88 mg/mgO3/min.

Catalysis↗

Angular velocity and head direction signals recorded from the dorsal tegmental nucleus of gudden in the rat: implications for path integration in the head direction cell circuit.

When a rat navigates through space, head direction (HD) cells provide an ongoing signal of the rat's directional heading. It is thought that these cells rely, in part, on angular path integration of the rat's head movements. This integration requires that the HD cell system receive information about angular head movements and that this information be combined with the current directional signal, to generate the next "predicted" direction. Recent data suggest that the dorsal tegmental nucleus (DTN) may play a critical role in helping to generate the HD cell signal. To test this, recordings were made from cells in the DTN in freely moving rats. The following cell types were found: (a) "classic" HD cells, (b) angular velocity cells, and (c) cells that fired as a function of both head direction and angular velocity. Thus, DTN cells exhibit firing characteristics that are critical to the neural circuit hypothesized for generation of the HD cell signal.

Acceleration↗

In vitro and in vivo studies of AT-1362, a newly synthesized and orally active inhibitor of thrombin.

AT-1362 was found to be a potent, selective, and competitive inhibitor of thrombin, with a Ki value of 6.7 nM. In a rat model of venous thrombosis induced by partial stasis and endothelial disruption, the ID(50) values (a dose required to obtain 50% inhibition of thrombus formation over each vehicle group) of AT-1362 and argatroban were 0.03 mg/kg i.v. plus 0.5 microg/kg/minute and 0. 13 mg/kg i.v. plus 8.7 microg/kg/minute, respectively, and the antithrombotic effect of AT-1362 without prolongation of bleeding time lasted for 2 hours and disappeared 4 hours after oral administration of 30 mg/kg. In the rat tail transection model, the BT(2) values (a dose causing two-fold prolongation of the bleeding time over each vehicle group) of AT-1362 and argatroban were 0.56 mg/kg i.v. plus 9.3 microg/kg/minute and 1.1 mg/kg i.v. plus 73.3 microg/kg/minute, respectively. The reduction of thrombus formation and the prolongation of bleeding time were correlated with an ex vivo activated partial thromboplastin time (APTT) for both drugs. AT-1362 at 0.3 mg/kg i.v. plus 5 microg/kg/minute and argatroban at 0.6 mg/kg i.v. plus 40 microg/kg/minute significantly (p<0.05 and p<0.01, respectively) improved the vessel patency in a FeCl(2)-induced carotid artery thrombosis model in rats. These results suggest that AT-1362 may be a potent antithrombotic agent for the treatment of thrombotic diseases.

Administration, Oral↗

RNA aptamers that specifically bind to a 16S ribosomal RNA decoding region construct.

RNA-RNA recognition is a critical process in controlling many key biological events, such as translation and ribozyme functions. The recognition process governing RNA-RNA interactions can involve complementary Watson-Crick (WC) base pair binding, or can involve binding through tertiary structural interaction. Hence, it is of interest to determine which of the RNA-RNA binding events might emerge through an in vitro selection process. The A-site of the 16S rRNA decoding region was chosen as the target, both because it possesses several different RNA structural motifs, and because it is the rRNA site where codon/anticodon recognition occurs requiring recognition of both mRNA and tRNA. It is shown here that a single family of RNA molecules can be readily selected from two different sizes of RNA library. The tightest binding aptamer to the A-site 16S rRNA construct, 109.2-3, has its consensus sequences confined to a stem-loop region, which contains three nucleotides complementary to three of the four nucleotides in the stem-loop region of the A-site 16S rRNA. Point mutations on each of the three nucleotides on the stem-loop of the aptamer abolish its binding capacity. These studies suggest that the RNA aptamer 109.2-3 interacts with the simple 27 nt A-site decoding region of 16S rRNA through their respective stem-loops. The most probable mode of interaction is through complementary WC base pairing, commonly referred to as a loop-loop 'kissing' motif. High affinity binding to the other structural motifs in the decoding region were not observed.

Aminoglycosides↗

Specific binding of Hoechst 33258 to site 1 thymidylate synthase mRNA.

The translational initiator codon in thymidylate synthetase (TS) mRNA is located in a stem-loop structure with a CC bubble. TS is an important target for anticancer drugs. Aminoglycoside antibiotics have been shown to specifically bind to TS mRNA site 1 constructs and, furthermore, specific binding requires the non-duplex CC bubble region. It is shown here that DNA intercalating agents and DNA minor groove-binding drugs also bind to a TS mRNA site 1 construct. This binding is competitive with aminoglycosides, suggesting that the binding sites overlap. Hoechst 33258 binds with a dissociation constant of 60 nM, a value significantly lower than the approximately 1 microM values found for aminoglycosides. Footprinting and direct binding studies show that the CC bubble is important for binding of the Hoechst compound. However, the exact structure of the bubble is unimportant. Interestingly, mutations in regions adjacent to the bulge also affect binding. These studies point to the important role of non-duplex RNA structures in binding of the DNA minor groove binder Hoechst 33258.

Anti-Bacterial Agents↗

Col2-GFP reporter marks chondrocyte lineage and chondrogenesis during mouse skeletal development.

Mice were generated in which a Col2-GFP transgene serves as a reporter for the chondrocyte lineage and for chondrogenesis in live embryos and newborn pups. Cells actively engaged in chondrogenesis were identified by confocal optical sectioning within their native environments in embryos and in thick tissue slices. Chondrocytes exhibiting GFP fluorescence were purified from rib cages by high-speed cell sorting of crude cell suspensions. Intensity of fluorescence correlated with biosynthesis of procollagen II in these cells. The use of these mice and their cells provides a novel approach for studying chondrocyte differentiation and chondrogenesis during skeletal development.

Animals↗