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Biomedical subjects

Z Tu

Publications and source records attributed to Z Tu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Recognition of sentences in noise by normal-hearing listeners using simulations of speak-type cochlear implant signal processors.

To assess whether more channels are needed to understand speech in noise than in quiet, we processed speech in a manner similar to that of spectral peak-like cochlear implant processors and presented it at a +2-dB signal-to-noise ratio to normal-hearing listeners for identification. The number of analysis filters varied from 8 to 16, and the number of maximum channel amplitudes selected in each cycle varied from 2 to 16. The results show that more channels are needed to understand speech in noise than in quiet, and that high levels of speech understanding can be achieved with 12 channels. Selecting more than 12 channel amplitudes out of 16 channels did not yield significant improvements in recognition performance.

Adult↗
PubMed2000

Rat hepatocellular apoptosis induced by glycodeoxycholate.

OBJECTIVE: To explore the relationship between glycodeoxycholate (GDC) and rat hepatocellular apoptosis. METHODS: GDC was used to treat rat hepatocytes cultured in vitro and the apoptotic cells were observed and analyzed with light microscope, transmission electron microscope, TUNEL in situ hybridization, DNA agarose gel electrophoresis and flow cytometry. RESULTS: When rat hepatocytes were incubated with GDC (final concentration of 100 micromol/L) for 2h, apoptotic hepatocytes were observed with light and transmission electron microscope, and TUNEL in situ hybridization. When the hepatocytes were incubated with GDC (final concentration of 50, 100, 150 micromol/L, respectively) for 2h, or with GDC (final concentration of 100 micromol/L) for 2, 4, 6, 8h, respectively, agarose gel electrophoresis of the hepatocytes DNA demonstrated the typical ladder patterns. CONCLUSION: GDC with final concentration of 50, 100, 150 micromol/L could induce rat hepatocellular apoptosis.

Animals↗
PubMed2000

[Protein expression of human progesterone receptor isoforms A and B in uterine leiomyoma].

OBJECTIVE: To investigate the role of two isoforms of human progesterone receptor A (hPR-A) and B (hPR-B) in the development of uterine leiomyoma, their distribution and expression in leiomyoma were detected. METHODS: The tissues of leiomyoma and normal myometrium from 30 uteri, which were excised for leiomyoma, were used for the localization and quantification of protein of the two isoforms. Immunohistochemistry and Western blot were applied respectively. RESULTS: Both hPR-A and hPR-B were nuclear receptors. Concentrations of hPR-(A + B) and hPR-A in leiomyoma were higher than those in normal myometrium (295,796 +/- 90,856, 256,275 +/- 98,560; P = 0.042, P = 0.000,563). Both isoforms were presented in leiomyoma and normal myometrium, with a consistent dominance of hPR-B over hPR-A. More expression of hPR-A was found during secretive phase than proliferative phase, not only in leiomyoma but also in normal myometrium (P = 0.037, P = 0.024). CONCLUSIONS: The development of uterine leiomyoma seems to be related with the progesterone receptor isoforms, especially hPR-A.

Adult↗
PubMed1999

Sphingosine 1-phosphate-induced cell rounding and neurite retraction are mediated by the G protein-coupled receptor H218.

Sphingosine 1-phosphate (SPP) is a lipid second messenger that also acts as a first messenger through the G protein-coupled receptor Edg-1. Here we show that SPP also binds to the related receptors H218 and Edg-3 with high affinity and specificity. SPP and sphinganine 1-phosphate bind to these receptors, whereas neither sphingosylphosphorylcholine nor lysophosphatidic acid compete with SPP for binding to either receptor. Transfection of HEK293 cells with H218 or edg-3, but not edg-1, induces rounded cell morphology in the presence of serum, which contains high levels of SPP. SPP treatment of cells overexpressing H218 cultured in delipidated serum causes cell rounding. A similar but less dramatic effect was observed in cells overexpressing Edg-3 but not with Edg-1. Cell rounding was correlated with apoptotic cell death, probably as a result of loss of attachment. Nerve growth factor-induced neuritogenesis in PC12 cells was inhibited by overexpression of H218 and to a lesser extent Edg-3. SPP treatment rapidly enhanced neurite retraction in PC12 cells overexpressing Edg-1, Edg-3, or H218. Thus, H218, and possibly Edg-3, may be the cell surface receptors responsible for cell rounding and neurite retraction induced by SPP. Moreover, the identification of these two additional SPP receptors indicates that a family of highly specific receptors exists that mediate different responses to SPP.

Animals↗
PubMed1999

MosquI, a novel family of mosquito retrotransposons distantly related to the Drosophila I factors, may consist of elements of more than one origin.

A novel family of non-long-terminal-repeat (non-LTR) retrotransposons, named MosquI, was discovered in the yellow fever mosquito, Aedes aegypti. There were approximately 14 copies of MosquI in the A. aegypti genome. Four of the five analyzed MosquI elements were truncated at the 5' ends while one of them, MosquI-Aa2, was full-length. All five MosquI elements ended with 4-10 TAA tandem repeats, as the Drosophila I factors do. Interestingly, MosquI elements were often found near genes and other repetitive elements. The 6,623-bp MosquI-Aa2 contained two open reading frames (ORFs) flanked by a 404-bp 5' untranslated region and a 326-bp 3' untranslated region. The two ORFs code for nucleocapsids, endonuclease, reverse transcriptase, and RNase H domains. Although overall structural and sequence comparisons suggest that MosquI is highly similar to the Drosophila I factors, phylogenetic analysis based on the reverse transcriptase domains of 40 non-LTR retrotransposons indicate that MosquI and I factors are likely paralogous elements which may have been separated before the split between the ancestors of mollusca and arthropoda. Pairwise comparisons between the four truncated MosquI elements showed 96.7%-99.5% identity at the nucleotide level, while comparisons between the full-length MosquI-Aa2 and the truncated copies showed only 80.2%-81.8% identity. These comparisons and preliminary phylogenetic analyses suggest that the full-length and truncated MosquI elements may belong to two subfamilies originating from two source genes that diverged a long time ago. In contrast to the defective I factors in Drosophila melanogaster, which are likely very old components of the genome, the truncated MosquI elements seem to have been recently active. Finally, the genomic distribution and evolution of MosquI elements are analyzed in the context of other non-LTR retrotransposons in A. aegypti.

Aedes↗
PubMed1999

Genomic and evolutionary analysis of Feilai, a diverse family of highly reiterated SINEs in the yellow fever mosquito, Aedes aegypti.

Five short interspersed repetitive elements (SINEs) were found fortuitously in the introns of a steroid hormone receptor AaHR3-2 gene of the yellow fever mosquito, Aedes aegypti, constituting a novel family of tRNA-related SINEs named Feilai. In addition, nine other Feilai elements were found in currently available sequences in Ae. aegypti, six of which were also near genes. Approximately 5.9 x 10(4) copies of Feilai were present in Ae. aegypti, equivalent to 2% of the entire genome. An additional 35 Feilai elements were isolated from a genomic library. Of the total 49 Feilai elements, 20 were full-length. Sequence comparisons and phylogenetic analyses of the full-length elements strongly suggest that there are at least two subfamilies within the Feilai family. There is a high degree of conservation within the two subfamilies. However, sequence divergence between the subfamilies, along with the presence of highly degenerate Feilai elements, suggests that Feilai is likely a diverse family of SINEs that has existed in Ae. aegypti for a long time. Many Feilai elements were closely associated with other transposons, especially with fragments of non-LTR retrotransposons and miniature inverted-repeat transposable elements. The 500-bp sequences immediately flanking a Feilai element were highly A + T-rich, which is consistent with the fact that no Feilai has been found in the coding regions of genes. It is likely that the highly reiterated and interspersed Feilai elements are partially responsible for the pattern of short-period interspersion of the Ae. aegypti genome. The evolutionary relationship between Feilai and the Ae. aegypti genome is likely complex.

Aedes↗
PubMed1999

On the number of channels needed to understand speech.

Recent studies have shown that high levels of speech understanding could be achieved when the speech spectrum was divided into four channels and then reconstructed as a sum of four noise bands or sine waves with frequencies equal to the center frequencies of the channels. In these studies speech understanding was assessed using sentences produced by a single male talker. The aim of experiment 1 was to assess the number of channels necessary for a high level of speech understanding when sentences were produced by multiple talkers. In experiment 1, sentences produced by 135 different talkers were processed through n (2 < or = n < or = 16) number of channels, synthesized as a sum of n sine waves with frequencies equal to the center frequencies of the filters, and presented to normal-hearing listeners for identification. A minimum of five channels was needed to achieve a high level (90%) of speech understanding. Asymptotic performance was achieved with eight channels, at least for the speech material used in this study. The outcome of experiment 1 demonstrated that the number of channels needed to reach asymptotic performance varies as a function of the recognition task and/or need for listeners to attend to fine phonetic detail. In experiment 2, sentences were processed through 6 and 16 channels and quantized into a small number of steps. The purpose of this experiment was to investigate whether listeners use across-channel differences in amplitude to code frequency information, particularly when speech is processed through a small number of channels. For sentences processed through six channels there was a significant reduction in speech understanding when the spectral amplitudes were quantized into a small number (< 8) of steps. High levels (92%) of speech understanding were maintained for sentences processed through 16 channels and quantized into only 2 steps. The findings of experiment 2 suggest an inverse relationship between the importance of spectral amplitude resolution (number of steps) and spectral resolution (number of channels).

Acoustic Stimulation↗
PubMed1999

Primary choledochorrhaphy after common bile duct exploration.

AIM: To prove further the safety of primary closure of the common bile duct. METHOD: Twenty patients among 99 common bile duct explorations underwent primary closure. Pre- and postoperative liver function test, ultrasound and intraoperative cholangiography data, operation time, postoperative complications and the length of postoperative stay were recorded. RESULTS: Nineteen patients did not suffer any biliary complication. One had bile leakage and bile peritonitis, and another had duodenal leakage. One case was complicated by gastric ulcer perforation. The mean postoperative hospital stay except for the 2 patients with complications was 8.72 +/- 0.75 days. Preoperative abnormal liver function tests recovered within 2-3 weeks after the operation. Postoperative ultrasound scan of the biliary tract within 2 months revealed no stenosis and residual stone. CONCLUSION: Primary common bile duct closure is a safe alternative to routine biliary drainage in selected patients.

Adult↗
PubMed1999

Identification and functional analysis of novel human melanocortin-4 receptor variants.

Inactivation of the melanocortin-4 receptor (MC4-R) by gene-targeting results in mice that develop maturity-onset obesity, hyperinsulinemia, and hyperglycemia. These phenotypes resemble common forms of human obesity, which are late-onset and frequently accompanied by NIDDM. It is not clear whether sequence variation of the MC4-R gene contributes to obesity in humans. Therefore, we examined the human MC4-R gene polymorphism in 190 individuals ascertained on obesity status. Three allelic variants were identified, including two novel ones, Thr112Met and Ile137Thr. To analyze possible functional alterations, the variants were cloned and expressed in vitro and compared with the wild-type receptor. One of the novel variants, Ile137Thr, identified in an extremely obese proband (BMI 57), was found to be severely impaired in ligand binding and signaling, raising the possibility that it may contribute to development of obesity. Furthermore, our results also suggest that sequence polymorphism in the MC4-R coding region is unlikely to be a common cause of obesity in the population studied, given the low frequency of functionally significant mutations.

Adolescent↗
PubMed1999

[Glycodeoxycholic acid changes the membrane fluidity and superoxides of lipids in hepatocytes].

OBJECTIVES: To explore the mechanisms of hepatocyte injury caused by glycodeoxycholic acid (GDCA) through studies on the roles of GDCA to membrane fluidity and superoxides of lipids of hepatocyte. METHODS: GDCA was used to treat hepatocytes of rat cultured in vitro and changes in cell membrane fluidity and malondialdehyde(MDA) were observed. RESULTS: In the presence of GDCA (final concentration of 250 mumol/L), the concentration of hepatocyte MDA of GDCA increased significantly (P < 0.001) and membrane fluidity decreased (P < 0.02) after culture of 1 or 4 hours. ALT was directly related to MDA and fluorescence polarization (P), r was 0.945 and 0.986, respectively. CONCLUSION: GDCA can induce the increase of MDA and decrease of fluidity of hepatocyte membrane, and finally cause hepatocyte injury.

Animals↗
PubMed1999

[The genotype of vac A gene of Helicobacter pylori (Hp) and its correlation with the gastroduodenal diseases associated with Hp].

OBJECTIVE: To analyze the expression of vac A gene of Helicobacter pylori (Hp) isolated from Chinese patients and to find out the relationship between the genotype of Hp vac A and the gastroduodenal diseases associated with Hp. METHODS: Clones of Hp obtained from patients with gastroduodenal diseases were cultured and mRNA extraction was performed with reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: 92% of the strains isolated in Shanghai (China) was found to be s1/m2. Strains expressing s1/m1 forms were obtained in 4 cases. s2 form was not found. CONCLUSION: The overwhelming majority of strains isolated from Shanghai patients expresses s1/m2 from. The s1/m2 genotype is dispersed in all of the gastroduodenal diseases associated with Hp.

Adolescent↗
PubMed1998

Identification of an important cysteine residue in human glutamate-cysteine ligase catalytic subunit by site-directed mutagenesis.

Glutamate-cysteine ligase (GLCL) catalyses the rate-limiting step in glutathione biosynthesis. To identify cysteine residues in GLCL that are involved in its activity, eight conserved cysteine residues in human GLCL catalytic subunit (hGLCLC) were replaced with glycine residues by PCR-based site-directed mutagenesis. Both recombinant hGLCLC and hGLCL holoenzyme were expressed and purified with a baculovirus expression system. The activity of purified hGLCL holoenzyme with the mutant hGLCLC-C553G was 110+/-12 micromol/h per mg of protein compared with 370+/-20 micromol/h per mg of protein for the wild-type. Holoenzymes with hGLCLC-C52G, -C248G, -C249G, -C295G, -C491G, -C501G or -C605G showed activities similar to the wild type. The Km values of hGLCL containing hGLCLC-C553G were slightly lower than those of the wild type, indicating that the replacement of cysteine-553 with Gly in hGLCLC did not significantly affect substrate binding by the enzyme. hGLCLC-C553G was more easily dissociated from hGLCLR than the wild-type hGLCLC. GLCL activity increased by 11% after hGLCLC-C553G was incubated with an equimolar amount of purified hGLCL regulatory subunit (hGLCLR) at room temperature for 30 min, but increased by 110% after wild-type hGLCLC was incubated with hGLCLR for 10 min. These results indicate that cysteine-553 in hGLCLC is involved in heterodimer formation between hGLCLC and hGLCLR.

Amino Acid Substitution↗
PubMed1998

Sphingosine-1-phosphate in cell growth and cell death.

Recent evidence suggests that branching pathways of sphingolipid metabolism may mediate either apoptotic or mitogenic responses depending on the cell type and the nature of the stimulus. While ceramide has been shown to be an important regulatory component of apoptosis induced by tumor necrosis factor alpha and Fas ligand, sphingosine-1-phosphate (SPP), a further metabolite of ceramide, has been implicated as a second messenger in cellular proliferation and survival induced by platelet-derived growth factor, nerve growth factor, and serum. SPP protects cells from apoptosis resulting from elevations of ceramide. Inflammatory cytokines stimulate sphingomyelinase, but not ceramidase, leading to accumulation of ceramide, whereas growth signals also leading to accumulation of ceramide, whereas growth signals also stimulate ceramidase and sphingosine kinase leading to increased SPP levels. We propose that the dynamic balance between levels of sphingolipid metabolites, ceramide, and SPP, and consequent regulation of different family members of mitogen-activated protein kinases (JNK versus ERK), is an important factor that determines whether a cell survives or dies.

Animals↗
PubMed1998

Expression and characterization of human glutamate-cysteine ligase.

Glutamate-cysteine ligase (GLCL) catalyzes the rate-limiting step in glutathione biosynthesis. GLCL comprises regulatory (GLCLR) and catalytic (GLCLC) subunits. To understand better the structure-function relationship of GLCL subunits and holoenzyme, human GLCLR and GLCLC genes were inserted into the baculovirus genome. Recombinant hGLCLR andhGLCLC were produced in cells infected with recombinant baculoviruses, and homogeneous hGLCL subunits and holoenzyme were purified from cell lysates with a Ni-NTA resin. Purified recombinant hGLCL holoenzyme was catalytically more active than hGLCLC with L-glutamate, L-alpha-aminobutyrate, and ATP as substrates. The selectivity of purified hGLCL holoenzyme for L-glutamate, L-alpha-aminobutyrate, or L-cysteine was significantly higher than for hGLCLC. Glutathione was a noncompetitive inhibitor for both hGLCL holoenzyme and hGLCLC. hGLCLC was more sensitive to inhibition by glutathione than hGLCL holoenzyme. Deletion of the first 25 amino acid residues at the amino terminus of GLCLC dramatically decreased GLCL activity, indicating that the amino terminus of GLCLC is required for full catalytic activity. Expressed and purified hGLCL provides a useful tool to investigate glutathione biosynthesis in vitro.

Animals↗
PubMed1998

Purification and characterization of rat kidney sphingosine kinase.

Sphingosine kinase catalyzes the formation of the bioactive sphingolipid metabolite sphingosine 1-phosphate, which plays important roles in numerous physiological processes, including growth, survival, and motility. We have purified rat kidney sphingosine kinase 6 x 10(5)-fold to apparent homogeneity. The purification procedure involved ammonium sulfate precipitation followed by chromatography on an anion exchange column. Partially purified sphingosine kinase was found to be stabilized by the presence of high salt, and thus, a scheme was developed to purify sphingosine kinase using sequential dye-ligand chromatography steps (since the enzyme bound to these matrices even in the presence of salt) followed by EAH-Sepharose chromatography. This 385-fold purified sphingosine kinase bound tightly to calmodulin-Sepharose and could be eluted in high yield with EGTA in the presence of 1 M NaCl. After concentration, the calmodulin eluate was further purified by successive high pressure liquid chromatography separations on hydroxylapatite, Mono Q, and Superdex 75 gel filtration columns. Purified sphingosine kinase has an apparent molecular mass of approximately 49 kDa under denaturing conditions on SDS-polyacrylamide gel, which is similar to the molecular mass determined by gel filtration, suggesting that the active form is a monomer. Sphingosine kinase shows substrate specificity for D-erythro-sphingosine and does not catalyze the phosphorylation of phosphatidylinositol, diacylglycerol, ceramide, DL-threo-dihydrosphingosine, or N,N-dimethylsphingosine. However, the latter two sphingolipids were potent competitive inhibitors. With sphingosine as substrate, the enzyme had a broad pH optimum of 6.6-7.5 and showed Michaelis-Menten kinetics, with Km values of 5 and 93 microM for sphingosine and ATP, respectively. This study provides the basis for molecular characterization of a key enzyme in sphingolipid signaling.

Animals↗
PubMed1998

Up-regulation of glutamate-cysteine ligase gene expression by butylated hydroxytoluene is mediated by transcription factor AP-1.

Several regulatory elements, including AP-1 and NF-kappa B, are present in the 5'flanking region of the human glutamatex-cysteine ligase (EC 6.3.2.2, gamma-glutamyl-cysteine synthetase) catalytic subunit (GLCLC) gene. In this study, we investigated the role of redox-sensitive transcription factors in the regulation of GLCLC gene expression in LLC-PK1 cells that were exposed to the antioxidant butylated hydroxytoluene (BHT). Exposure of LLC-PK1 cells to 100 microM BHT induced expression of transcription factor AP-1, as demonstrated by an electrophoretic mobility shift assay. Peak AP-1 induction occurred after 3 h of incubation with BHT, BHT increased luciferase gene expression in cells that were transfected with a luciferase reporter vector containing an AP-1 element upstream of a SV40 promoter. Northern analysis showed that transcription of GLCLC gene in cells after incubation with BHT was increased 30% compared with control cells. Cellular glutathione concentrations were also significantly increased in cells exposed to BHT. In contrast, exposure of LLC-PK1 cells to 100 microM BHT did not alter expression of the transcription factor NF-kappa B. These results show that induction of transcription factor AP-1 by BHT is involved in transactivation of GLCLC gene expression.

Antioxidants↗
PubMed1998

Sphingoid base 1-phosphate phosphatase: a key regulator of sphingolipid metabolism and stress response.

The sphingolipid metabolites ceramide and sphingosine-1-phosphate are second messengers with opposing roles in mammalian cell growth arrest and survival; their relative cellular level has been proposed to be a rheostat that determines the fate of cells. This report demonstrates that this rheostat is an evolutionarily conserved stress-regulatory mechanism that influences growth and survival of yeast. Although the role of sphingosine-1-phosphate in yeast was not previously examined, accumulation of ceramide has been shown to induce G1 arrest and cell death. We now have identified a gene in Saccharomyces cerevisiae, LBP1, that regulates the levels of phosphorylated sphingoid bases and ceramide. LBP1 was cloned from a yeast mutant that accumulated phosphorylated long-chain sphingoid bases and diverted sphingoid base intermediates from sphingolipid pathways to glycerophospholipid biosynthesis. LBP1 and its homolog, LBP2, encode very hydrophobic proteins that contain a novel-conserved sequence motif for lipid phosphatases, and both have long-chain sphingoid base phosphate phosphatase activity. In vitro characterization of Lbp1p shows that this phosphatase is Mg2+-independent with high specificity for phosphorylated long-chain bases, phytosphingosine and sphingosine. The deletion of LBP1 results in the accumulation of phosphorylated long-chain sphingoid bases and reduced ceramide levels. Moreover, deletion of LBP1 and LBP2 results in dramatically enhanced survival upon severe heat shock. Thus, these phosphatases play a previously unappreciated role in regulating ceramide and phosphorylated sphingoid base levels in yeast, and they modulate stress responses through sphingolipid metabolites in a manner that is reminiscent of their effects on mammalian cells.

Amino Acid Sequence↗