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Biomedical subjects

H Tang

Publications and source records attributed to H Tang.

At least 55 records · Page 3Linked to original sources

Metabolic disorder in myocardiac intracellular free calcium after thermal injury.

Cutaneous burn trauma causes functional inhibition of the heart, but the mechanism is unclear. Using a high dissociation constant (K(D)) calcium indicator TF-BAPTA and 19F MR spectroscopy, the relationship between the changes of cytosolic free calcium and cardiac function after burn trauma was examined. Sprague-Dawley rats received scald (43% TBSA) or sham burns. Twenty-four hours later, the hearts were excised and perfused by the Langendorff method with a modified phosphate-free Krebs-Henseleit bicarbonate buffer. Left ventricular developed pressure (LVDP) was recorded through a catheter attached to an intraventricular balloon. At the same time, 31P and 19F nuclear magnetic resonance (NMR) spectroscopy was perforined before and after TF-BAPTA loading. LVDP of the heart from burned rats was 40% less than in sham burn rats (65+/-6 vs 110+/-12 mmHg, P<0.01). Cytosolic free calcium increased about four-fold in those hearts from the burn group compared to the sham burn group (0.807+/-0.192 vs 3.891+/-0.929 microM). Loading TF-BAPTA in those hearts only caused about a 15-20% decrease in LVDP. PCr/Pi ratio also decreased significantly with this loading, but ATP signals were not affected. In conclusion, the inhibition of cardiac contractility caused by burn trauma correlated with the overload of cytosolic free calcium in the heart.

Adenosine Triphosphate↗

Recognition of engineered tRNAs with an extended 3' end by Exportin-t (Xpo-t) and transport of tRNA-attached ribozymes to the cytoplasm in somatic cells.

Our recent analysis indicates that the cytoplasmic localization of tRNA-attached ribozymes (tRNA-Rz) is critical for its high-level intracellular activity, suggesting that mature mRNAs in the cytoplasm are more accessible to ribozymes than pre-mRNAs in the nucleus (Kato et al. J. Biol. Chem. 2001, 276, 15378-15385; Kuwabara et al. Nucleic Acids Res. 2001, 29, 2780-2788). Although studies in Xenopus oocytes led to the proposal that only correctly processed mature tRNAs are exported from nuclei in a RanGTP-dependent manner (Lund and Dahlberg Science 1998, 282, 2082-2085), our tRNA-Rz with an extended 3' end can also be exported to the cytoplasm in somatic cells. Xpo-t/RanGTP bound to tRNA-attached ribozymes in vitro and in somatic cells, with recognition basically resembling the recognition of mature tRNAs. In contrast, no binding to tRNA-attached ribozymes occurred in Xenopus oocytes. The injection of a nuclear extract of Xenopus oocytes together with tRNA-attached ribozymes inhibited the export of tRNA-attached ribozymes but not mature tRNAs in somatic cells, suggesting the existence of an inhibitor(s) of the Xpo-t-dependent export pathway. Moreover, the inhibitor(s) appears responsible for a proofreading mechanism that operates in oocytes.

Active Transport, Cell Nucleus↗

Anti-CD11a ameliorates disease in the human psoriatic skin-SCID mouse transplant model: comparison of antibody to CD11a with Cyclosporin A and clobetasol propionate.

The present study assesses the applicability of human skin-SCID (severe combined immunodeficiency) mouse chimeras in testing antipsoriatic therapeutics. Three agents were examined: (1) a monoclonal antibody to the alpha subunit of leukocyte function associated antigen-1 integrin (CD11a); (2) Cyclosporin A; and (3) clobetasol propionate (Temovate), a potent topical corticosteroid used clinically in the treatment of psoriasis. Skin transplanted to SCID mice from normal human volunteers or from psoriatic lesional skin was allowed to heal for 3 to 5 weeks before application of test reagents. During this period, psoriatic skin, which was 3.8-fold thicker than the corresponding normal skin before transplantation, maintained its phenotype (ie, increased epidermal thickness, rete ridges with blunted ends, and intralesional presence of T lymphocytes). Transplanted normal human skin, however, underwent a hyperplastic response during this period, resulting in a 2.4-fold increase in epidermal thickness. After the healing period, animals transplanted with normal or psoriatic skin were treated for 14 days by daily intraperitoneal injection of either Cyclosporin A or a monoclonal antibody to human CD11a, or by topical application of clobetasol propionate. At the end of the treatment period, the mice were killed and the tissue evaluated morphometrically for changes in epidermal thickness and immunohistologically for the presence of T lymphocytes. Both Cyclosporin A and anti-CD11a reduced the epidermal thickness of transplanted psoriatic skin, whereas neither reagent significantly reduced the thickness of transplanted normal skin. T lymphocytes were detected in the skin from treated animals; there did not seem to be any reduction in the number of T lymphocytes. Clobetasol propionate reduced the epidermal thickness of both normal and psoriatic skin. These data indicate that, in this model, therapies directed against pathophysiologic mechanisms that contribute to psoriasis can be distinguished from treatments that block epidermal hyperplasia occurring as a consequence of xenografting. Our observations provide evidence for the activity of anti-CD11a in an animal model of human psoriasis.

Administration, Topical↗

A new estimator of significance of correlation in time series data.

Many expression array experiments monitor gene activity as an organism goes through some biological process. It is desirable to find genes with similar expression patterns in the resulting time series data. We propose a new simulation approach that assesses the statistical significance of similarity scores between expression patterns. The simulation takes into account the dependence between columns of data.

Cell Cycle↗

Simultaneous modelling of metabolic, genetic and product-interaction networks.

The creation of cell models from annotated genome information, as well as additional data from other databases, requires both a format and medium for its distribution. Standards are described for the representation of the data in the form of Document Type Definitions (DTDs) for XML files. Separate DTDs are detailed for genetic, metabolic and gene product-interaction networks, which can be used to hold information on individual subsystems, or which may be combined to create a whole cell DTD. In the execution of this work, a fifth DTD was also created for a metabolite thesaurus, which allows incorporation of metabolite synonyms and generic nomenclature data into the models. A gene-regulation classification scheme was also created, to facilitate incorporation of gene regulatory information in an efficient manner. The work is described with particular reference to the metabolic network of Escherichia coli, which contains 808 individual enzymes. The assignment of confidence levels to these data, through the use of Gene Ontology evidence codes, is highlighted. In silico investigations may now be performed using the mathematical simulation workbench, DBsolve, which incorporates the facility to introduce data directly from XML.

Computational Biology↗

Fragment assembly with double-barreled data.

For the last twenty years fragment assembly was dominated by the "overlap - layout - consensus" algorithms that are used in all currently available assembly tools. However, the limits of these algorithms are being tested in the era of genomic sequencing and it is not clear whether they are the best choice for large-scale assemblies. Although the "overlap - layout - consensus" approach proved to be useful in assembling clones, it faces difficulties in genomic assemblies: the existing algorithms make assembly errors even in bacterial genomes. We abandoned the "overlap - layout - consensus" approach in favour of a new Eulerian Superpath approach that outperforms the existing algorithms for genomic fragment assembly (Pevzner et al. 2001 InProceedings of the Fifth Annual International Conference on Computational Molecular Biology (RECOMB-01), 256-26). In this paper we describe our new EULER-DB algorithm that, similarly to the Celera assembler takes advantage of clone-end sequencing by using the double-barreled data. However, in contrast to the Celera assembler, EULER-DB does not mask repeats but uses them instead as a powerful tool for contig ordering. We also describe a new approach for the Copy Number Problem: "How many times a given repeat is present in the genome?". For long nearly-perfect repeats this question is notoriously difficult and some copies of such repeats may be "lost" in genomic assemblies. We describe our EULER-CN algorithm for the Copy Number Problem that proved to be successful in difficult sequencing projects.

Algorithms↗

Realizations of fast 2-D/3-D image filtering and enhancement.

This paper proposes a novel algorithm for multidimensional image enhancement based on a fuzzy domain enhancement method, and an implementation of a recursive and separable low-pass filter. Considering a smoothed image as a fuzzy data set, each pixel in an image is processed independently, using fuzzy domain transformation and enhancement of both the dynamic range and the local gray level variations. The algorithm has the advantages of being fast and adaptive, so it can be used in real-time image processing applications and for multidimensional data with low computational cost. It also has the ability to reduce noise and unwanted background that may affect the visualization quality of two-dimensional (2-D)/three-dimensional (3-D) data. Examples for the applications of the algorithm are given for mammograms, ultrasound 3-D images, and photographic images.

Algorithms↗

Replication of the wild type and a natural hepatitis B virus nucleocapsid promoter variant is differentially regulated by nuclear hormone receptors in cell culture.

A natural hepatitis B virus (HBV) variant associated with seroconversion from HBeAg to anti-HBe antibody contains two nucleotide substitutions (A1764T and G1766A) in the proximal nuclear hormone receptor binding site in the nucleocapsid promoter. These nucleotide substitutions prevent the binding of the retinoid X receptor alpha (RXR alpha)-peroxisome proliferator-activated receptor alpha (PPAR alpha) heterodimer without greatly altering the efficiency of binding of hepatocyte nuclear factor 4 (HNF4) to this recognition sequence. In addition, these nucleotide substitutions create a new binding site for HNF1. Analysis of HBV transcription and replication in nonhepatoma cells indicates that RXR alpha-PPAR alpha heterodimers support higher levels of pregenomic RNA transcription from the wild-type than from the variant nucleocapsid promoter, producing higher levels of wild-type than of variant replication intermediates. In contrast, HNF4 supports higher levels of pregenomic RNA transcription from the variant than from the wild-type nucleocapsid promoter, producing higher levels of variant than of wild-type replication intermediates. HNF1 can support variant virus replication at a low level but is unable to support replication of the wild-type HBV genome. These observations indicate that the replication of wild-type and variant viruses can be differentially regulated by the liver-specific transcription factors that bind to the proximal nuclear hormone receptor binding site of the nucleocapsid promoter. Differential regulation of viral replication may be important in the selection of specific viral variants as a result of an antiviral immune response.

Amino Acid Sequence↗

Amino acid-induced translation of TOP mRNAs is fully dependent on phosphatidylinositol 3-kinase-mediated signaling, is partially inhibited by rapamycin, and is independent of S6K1 and rpS6 phosphorylation.

Vertebrate TOP mRNAs contain an oligopyrimidine tract at their 5' termini (5'TOP) and encode components of the translational machinery. Previously it has been shown that they are subject to selective translational repression upon growth arrest and that their translational behavior correlates with the activity of S6K1. We now show that the translation of TOP mRNAs is rapidly repressed by amino acid withdrawal and that this nutritional control depends strictly on the integrity of the 5'TOP motif. However, neither phosphorylation of ribosomal protein (rp) S6 nor activation of S6K1 per se is sufficient to relieve the translational repression of TOP mRNAs in amino acid-starved cells. Likewise, inhibition of S6K1 activity and rpS6 phosphorylation by overexpression of dominant-negative S6K1 mutants failed to suppress the translational activation of TOP mRNAs in amino acid-refed cells. Furthermore, TOP mRNAs were translationally regulated by amino acid sufficiency in embryonic stem cells lacking both alleles of the S6K1 gene. Inhibition of mTOR by rapamycin led to fast and complete repression of S6K1, as judged by rpS6 phosphorylation, but to only partial and delayed repression of translational activation of TOP mRNAs. In contrast, interference in the phosphatidylinositol 3-kinase (PI3-kinase)-mediated pathway by chemical or genetic manipulations blocked rapidly and completely the translational activation of TOP mRNAs. It appears, therefore, that translational regulation of TOP mRNAs, at least by amino acids, (i) is fully dependent on PI3-kinase, (ii) is partially sensitive to rapamycin, and (iii) requires neither S6K1 activity nor rpS6 phosphorylation.

Alleles↗

[Effective factors of flocculation-DAF pilot process treating water with low temperature and low turbidity from Miyun reservoir].

The hydraulic parameters in coagulation, flocculation and flotation units of DAF pilot process were systematically investigated when employing flocculants AS and PAC respectively. In general, the available parameters for PAC are more favorable in DAF process. For PAC as a flocculant during DAF run, the favorable coagulation rapid mixing time is 15 s, the flocculant mixing time is no less than 5 minutes. However for AS, the corresponding time values are greater than 30 s and more than 7.5 minutes respectively. The available coagulation mixing intensity is 300-1000 s-1. The available flocculation mixing intensity (average G) is 40-140 s-1, and the GT (average) value is greater than 2 x 10(4). Both equal-speed mixing and two or three stages mixing could provide slight better turbidity removal. For MJ model nozzle, the suitable recycle ratio is 5.0%-8.3% at dispersed pressure of 2.5-3.3 kg.cm2. The detention time and hydraulic intensity in contact zone of DAF tank have important effects on DAF turbidity removal.

Flocculation↗

[Characterization of speciation distribution of IPF-PFSi].

The preparation and speciation distribution characteristic of a new kind of inorganic polymer flocculant(IPF)-PFSi were investigated in detail by the combination of direct and indirect speciation analysis methods. The experimental results show that the speciation distribution of PFSi is decided significantly with basicity, kinds of silica and Si/Fe ratio. Among them, the basicity is one of the main factors. SilicaA and silicaB exhibit a similar effect, while silicaC has limited effect on the hydrolysis of Fe(III). The typical speciation distribution and transformation property of PFCl changes limitedly with the introduction of silica species.

Chlorides↗

[Cytotoxic T lymphocyte activity induced by genetic immunization with NV-HC/NS].

OBJECTIVE: To investigate the immunoprophylactic and immunotherapeutic effects of DNA vaccine (NV-HC/NS(3)) after inoculation of mice by target tumor loading technique. METHODS: Before or after inoculation with NV-HC/NS(3) intramuscularly, BALB/c mice in the experimental group were planted with target tumor cells (SP2/0-NS(3)), which were derived from BALB/c mice and stably transfected with the recombinant plasmid NV-HC/NS(3). Tumor growth and survival rate of the mice immunized with NV-HC/NS(3) were compared with those in the control group. RESULTS: Tumor mass grew well in all mice in the control group in a few days, while no visible tumor mass growth in 40% mice immunized with NV-HC/NS(3) could be seen. The survival rate and life span of mice in the experimental group were significantly longer than those in the control group. CONCLUSIONS: Specific immune activity could be induced by immunization with NV-HC/NS(3). Such effects are immunoprophylactic and immunotherapeutic.

Animals↗

[Antisense RNA for urokinase receptor inhibits the invasiveness and metastasis of lung carcinoma].

OBJECTIVE: To inhibit invasion and metastasis of human lung carcinoma cell line 95D by antisense RNA for urokinase receptor (uPAR). METHODS: Antisense RNA expression plasmid for uPAR was introduced into the highly metastatic human lung carcinoma cells 95D. Modified Boyden's chamber was used to detect the invasion ability, and nude mice were used to determine metastasis. RESULTS: Two transfected clones were found to integrate the antisense expression plasmid into genomic DNA and to express antisense RNA for uPAR. Antisense RNA blocked the uPAR expression in the transfected clones. The evident reductions of the invasiveness of antisense clones were observed by comparison with control cells, 95D cells and cells transfected with pcDNA3 vector. The metastatic potential of these two antisense clones decreased significantly in comparison with the controls (P < 0.05). CONCLUSIONS: The results suggest that antisense RNA for uPAR inhibits uPAR expression and leads to a decrease of metastatic potential of 95D cells. Antisense RNA technique may have a valuable application in anti-metastatic therapy of human lung carcinoma.

Animals↗

[An experimental study on the change in cardiac sympathetic neuroelectrophysiology in severely scalded rats during early postburn stage].

OBJECTIVE: To investigate the mechanism and the rule of the change in cardiac sympathetic neuroelectrophysiology in severely scalded rats during early postburn stage, so as to explore the relationship between the change and postburn severe cardiac injury. METHODS: Forty-four Sprague-Dawley rats were randomly divided into normal (n = 6), sham injury (n = 8) and scalded (n = 20) groups. The rats in scalded group were inflicted by 30% TBSA III degree burn on the backs. The electric discharge activity of cardiac sympathetic nerve was observed and recorded by neuroelectrophysiological technique. The changes in ECG and myocardial mechanic indices were simultaneously observed. RESULTS: The activity of efferent cardiac sympathetic nerve increased immediately after scalding, but that of the afferent nerve increased obviously after about 90s incubation period. The activity of efferent nerve further increased after the increase of afferent activity, and this increase in both efferent and afferent nerves lasted for about 3 hours and decreased evidently thereafter. The change of afferent nerve was earlier than that of efferent nerve. The average electric discharge activity of cardiac sympathetic nerve increased with obvious fluctuation, which exhibited intermittent burst pattern at 1 PBH in some rats, in which frequent ventricular extrasystole appeared accompanying with the simultaneous increase in electric discharge burst in 4 rats. The postburn LVDP and +/- dp/dtmax in rats decreased significantly. CONCLUSION: The activities of both efferent and afferent cardiac sympathetic nerve increased dramatically in the early postburn stage. The change in efferent nerve activity could be affected to some degree by that of afferent nerve. This implied that the increase of the neuroelectrophysiological activity of cardiac sympathetic nerve might be one of the causes of early severe postburn cardiac injury.

Animals↗

[A study on the myocardial contractile function and intracellular free calcium in scalded rats].

OBJECTIVE: To explore the relationship between postburn myocardial function and intracellular free calcium concentration. METHODS: Sprague-Dawley (SD) rats were employed as the model in which 7 were inflicted with 43% TBSA degree scalding (S group) and 7 as sham scalding control group (C group). The hearts of the injured rats were isolated and perfused in vitro by Langendorff method after 24 postburn hours (PBHs). The hearts were connected to a cardiac function monitor, and the dynamic changes in left ventricular develop pressure (LVDP) were continuously monitored. The cardiac 19F and 31P NMR spectroscopy was determined before and after and TF-BAPTA was added to the perfusate. RESULTS: When compared with those in C group, the LVDP of scalded rat heart decreased by 40% (P < 0.01), and the myocardial cytoplasmic free calcium concentration was four times above that in C group (P < 0.01). After TF-BAPTA was taken by myocytes, cardiac LVDP only decreased by 15% to 20%, and the PCr/Pi ratio decreased, while there was no change in ATP. CONCLUSION: Myocardial contractile function could be inhibited after burn injury, which might be related to the increase of myocardial cytoplasmic free calcium concentration.

Animals↗