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Biomedical subjects

W Jiang

Publications and source records attributed to W Jiang.

At least 271 records · Page 15Linked to original sources
PubMed1995

Mental stress-induced ischemia in the laboratory and ambulatory ischemia during daily life. Association and hemodynamic features.

BACKGROUND: The purpose of this study was to determine the correspondence of mental stress-induced ischemia in the laboratory with ambulatory ischemia and to assess the relationship between hemodynamic responses to mental stress and the occurrence of ischemia. Although exercise testing is usually used to elicit myocardial ischemia, ischemia during daily life usually occurs at relatively low heart rates and in the absence of strenuous physical exercise. Mental stress has been shown to trigger ischemic events in the laboratory at lower heart rates but at blood pressures comparable to exercise. We therefore compared the extent to which mental stress and exercise testing identify patients who develop ischemia out of hospital. METHODS AND RESULTS: One hundred thirty-two patients with documented coronary disease and recent evidence of exercise-induced myocardial ischemia underwent 48-hour ambulatory monitoring and radionuclide ventriculography during exercise and mental stress testing. Patients who displayed mental stress-induced ischemia in the laboratory were more likely to exhibit ischemia during daily life (P < .021). Furthermore, patients who exhibited ischemia during ambulatory monitoring displayed larger diastolic blood pressure (P < .006), heart rate (P < .039), and rate-pressure product responses (P < .018) during mental stress. CONCLUSIONS: Among patients with prior positive exercise stress tests, mental stress-induced ischemia, defined by new wall motion abnormalities, predicts daily ischemia independent of exercise-induced ischemia. Exaggerated hemodynamic responses during mental stress testing also identify individuals who are more likely to exhibit myocardial ischemia during daily life and mental stress.

Activities of Daily Living↗
PubMed1995

Cross-talk between the histidine protein kinase VanS and the response regulator PhoB. Characterization and identification of a VanS domain that inhibits activation of PhoB.

VanS is a two-component transmembrane sensory kinase that, together with its response regulator VanR, activates the expression of genes responsible for vancomycin resistance in Enterococcus faecium BM4147. In this report, we demonstrate that the cytoplasmic domain of VanS (including residues Met95 to Ser384) is capable of high level activation (> 500 fold) of the Escherichia coli response regulator PhoB in vivo in the absence of its signaling kinases PhoR, CreC (PhoM), or acetyl phosphate synthesis. In vitro experiments carried out on the purified proteins confirmed that the activation is due to efficient cross-talk between VanS and PhoB, since phospho-VanS catalyzed transfer of its phosphoryl group to PhoB with approximately 90% transfer in 5 min at a 1:4 VanS/PhoB stoichiometry. However, the rate of transfer was at least 100-fold slower than that observed between phospho-VanS and VanR. The in vivo activation of PhoB was used as a reporter system to identify peptide fragments of VanS capable of interfering with activation by VanS(Met95-Ser384), in order to identify an interaction domain. A library of plasmids encoding fragments of VanS(Met95-Ser384) was constructed using transposon mutagenesis, and a subpopulation of these plasmids encoded peptides that interfered with activation of PhoB by VanS(Met95-Ser384). A minimal size fragment (Met95-Ile174) was shown to be both necessary and sufficient for potent inhibition (85%) of this activation.

Amino Acid Sequence↗
PubMed1995

Relative importance of electrode placement over number of channels in transient myocardial ischemia detection by Holter monitoring.

To compare the efficacy of 3-channel ambulatory electrocardiographic monitoring (Holter monitoring) with 2-channel Holter monitoring in the detection of transient myocardial ischemia (TMI), channels CM2, CM5, and modified II were studied. Sixty patients with documented coronary artery disease underwent 48-hour Holter monitoring during their normal daily life, followed by exercise stress testing in the laboratory monitored by means of radionuclide ventriculography and standard 12-lead electrocardiography. Analysis revealed that 3-channel Holter monitoring identified 24 patients with a total of 205 TMI episodes and a total ischemic burden of 371.00 mV-min. By itself, CM2 would have detected only 3 patients (13% of the TMI population), 6 TMI episodes (3% of the total TMI episodes), and a 2.4 mV-min ischemic burden (0.7% of the total ischemic burden). Modified II alone would have identified 17 patients (71% of the TMI population), 160 TMI episodes (78% of the total TMI episodes), and 307.24 mV-min of the ischemic burden (82% of the total ischemic burden). The combination of CM5/modified II identified 23 patients (96% of the TMI population), 201 TMI episodes (98% of the total TMI episodes), and 370.44 mV-min of the ischemic burden (98% of the total ischemic burden). These findings suggest that the electrode placement is more important than the absolute number of channels in the detection of TMI by Holter monitoring.

Electrocardiography↗
PubMed1995

Antisense to cyclin D1 inhibits growth and reverses the transformed phenotype of human esophageal cancer cells.

The cyclin D1 gene is amplified and overexpressed in a significant fraction of human esophageal tumors, and several other types of human cancer, but the functional significance of this overexpression has not been established. To further address the roles of cyclin D1 in growth control and tumorigenesis, we have overexpressed an antisense cyclin D1 cDNA construct, either constitutively or inducibly, in the HCE7 human esophageal cancer cell line in which cyclin D1 is amplified and expressed at high levels. The expression of antisense cyclin D1 led to decreased expression of cyclin D1 at both mRNA and protein levels, and this was associated with a marked inhibition of cell proliferation. Antisense cyclin D1 expressing cells displayed a decreased plating efficiency, increased doubling time, decreased saturation density, increased cell size, decreased cyclin D1-associated in vitro kinase activity, decreased anchorage-independent growth, and a loss of tumorigenicity in nude mice. These findings provide direct evidence that the overexpression of cyclin D1 in certain tumor cells contributes to their abnormal growth and tumorigenicity. The ability to revert the transformed phenotype of these cells with antisense cyclin D1 suggests that cyclin D1 may be a useful target in cancer therapy.

Cell Adhesion↗
PubMed1995

Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron organization, localization to chromosome bands 9q22.2-q22.3, and mutation screening in subjects with fructose-1,6-bisphosphatase deficiency.

Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate. Deficiency of fructose-1,6-bisphosphatase is associated with fasting hypoglycemia and metabolic acidosis because of impaired gluconeogenesis. We have cloned and characterized the human liver fructose-1,6-bisphosphatase gene (FBP1). FBP1, localized to chromosome bands 9q22.2-q22.3 by fluorescence in situ hybridization, consists of seven exons that span > 31 kb, and the six introns are in the same position as in the rat gene. FBP1 was screened for mutations in two subjects with fructose-1,6-bisphosphatase deficiency. Four nucleotide substitutions were identified, two of which were silent mutations in the codons for Ala-216 (GCT-->GCC) and Gly-319 (GGG-->GGA). The other substitutions were in intron 3, a C-->T substitution 7 nucleotides downstream from the splice donor site, and in the promoter region, an A-->T substitution 188 nucleotides upstream from the start of transcription. These nucleotide substitutions were also found in normal unaffected subjects and thus are not the cause of fructose-1,6-bisphosphatase deficiency in the two subjects studied. The molecular basis of hepatic fructose-1,6-bisphosphatase deficiency in these subjects remains undetermined but could result from unidentified mutations in the promoter that decrease expression or from mutations in another gene that indirectly lead to decreased fructose-1,6-bisphosphatase activity.

Amino Acid Sequence↗
PubMed1995

The receptor DEC-205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing.

Dendritic cells and thymic epithelial cells perform important immunoregulatory functions by presenting antigens in the form of peptides bound to cell-surface major histocompatibility complex (MHC) molecules to T cells. Whereas B cells are known to present specific antigens efficiently through their surface immunoglobins, a comparable mechanism for the capture and efficient presentation of diverse antigens by dendritic cells and thymic epithelial cells has not previously been described. We show here that their antigen-presentation function is associated with the high-level expression of DEC-205, an integral membrane protein homologous to the macrophage mannose receptor and related receptors which are able to bind carbohydrates and mediate endocytosis. DEC-205 is rapidly taken up by means of coated pits and vesicles, and is delivered to a multivesicular endosomal compartment that resembles the MHC class II-containing vesicles implicated in antigen presentation. Rabbit antibodies that bind DEC-205 are presented to reactive T-cell hybridomas 100-fold more efficiently than rabbit antibodies that do not bind DEC-205. Thus DEC-205 is a novel endocytic receptor that can be used by dendritic cells and thymic epithelial cells to direct captured antigens from the extracellular space to a specialized antigen-processing compartment.

Amino Acid Sequence↗
PubMed1995

Stable overexpression of cyclin D1 in a human mammary epithelial cell line prolongs the S-phase and inhibits growth.

Amplification and/or increased expression of cyclin D1 occurs in an appreciable fraction of primary human breast carcinomas and several other types of human cancer. In addition, overexpression of cyclin D1 in rodent fibroblasts enhances growth and malignant transformation. The present study demonstrates that the extent of amplification and expression of cyclin D1 varies widely amongst a series of cell lines established from normal human mammary epithelium or human breast carcinomas. The HBL-100 mammary epithelial cell line did not display amplification or increased expression of cyclin D1. We used retrovirus-mediated transduction to obtain derivatives of this cell line that stably expressed relatively high levels of an exogenous cyclin D1 cDNA. These derivatives displayed an increased doubling time, decreased saturation density, decreased cloning efficiency, decreased anchorage-independent growth, an increased fraction of cells in the S-phase, and decreased tumorigenicity. Thus, increased expression of cyclin D1 in this cell line markedly inhibits rather than enhances growth, which may be due to the prolongation of S-phase.

Breast↗
PubMed1995

Overexpression of the yeast MCK1 protein kinase suppresses conditional mutations in centromere-binding protein genes CBF2 and CBF5.

We find that overexpression in yeast of the yeast MCK1 gene, which encodes a meiosis and centromere regulatory kinase, suppresses the temperature-sensitive phenotype of certain mutations in essential centromere binding protein genes CBF2 and CBF5. Since Mck1p is a known serine/threonine protein kinase, this suppression is postulated to be due to Mck1p-catalyzed in vivo phosphorylation of centromere binding proteins. Evidence in support of this model was provided by the finding that purified Mck1p phosphorylates in vitro the 110 kDa subunit (Cbf2p) of the multimeric centromere binding factor CBF3. This phosphorylation occurs on both serine and threonine residues in Cbf2p.

Fungal Proteins↗
PubMed1995

The structural genes, MEP1A and MEP1B, for the alpha and beta subunits of the metalloendopeptidase meprin map to human chromosomes 6p and 18q, respectively.

Meprins are cell membrane, oligomeric metalloendopeptidases composed of two distinct but evolutionarily related subunits, alpha and beta. The structural genes for the meprin subunits, Mep-1 alpha and Mep-1 beta, have been previously mapped to chromosomes 17 and 18, respectively, of the mouse genome. We now report the localization of MEP1A and MEP1B in the human genome. MEP1A mapped to the short arm of chromosome 6 by the use of radiation and somatic cell hybrids. More specifically, it is localized between the centromere and GSTA2 in 6p11-p12. MEP1B mapped to chromosome 18, by the use of somatic cell hybrids, in 18q12.2-q12.3, proximal to the TTR/PALB gene. As in the mouse genome, the two homologous human structural genes for alpha and beta (50% identical on the cDNA level) are unlinked. These new markers on human chromosomes 6 and 18 extend the region of known linkage homology with mouse chromosomes 17 and 18, respectively, and provide new molecular access to regions of the human genome.

Animals↗
PubMed1995

Characterization of polymorphic forms of fluconazole using Fourier transform Raman spectroscopy.

Detailed Fourier transform Raman spectra of fluconazole have been recorded and the main spectral features of fluconazole have been assigned to its vibrational modes. Two different polymorphic forms of fluoconazole were identified in two spectral regions, 150-1700 cm-1 and 2700-3200 cm-1, respectively. The FT-Raman results agree well with those of differential scanning calorimetry and X-ray powder diffractometry. The combination of definiteness with easy sample handling makes FT-Raman spectroscopy a valuable technique for the analysis of polymorphs.

Calorimetry, Differential Scanning↗
PubMed1995

Immunogenic properties of rabbit haemorrhagic disease virus structural protein VP60 expressed by a recombinant baculovirus: an efficient vaccine.

We have constructed a recombinant baculovirus containing the gene encoding the structural protein VP60 from the Spanish field isolate AST/89 of rabbit haemorrhagic disease virus (RHDV). Infection of cultured Spodoptera frugiperda Sf9 cells with this recombinant virus resulted in the production of high yields of VP60 protein which did not seem to assemble to form virus like particles, but was antigenically similar to the corresponding viral protein obtained from purified virions. A VP60-dose study showed that the recombinant protein was able to elicit a protective response in rabbits against a nasal challenge with 100 LD50 of RHDV. The effective dose able to protect 50% of the animals in the absence of adjuvant was found to be 10-25 micrograms of recombinant VP60.

Animals↗
PubMed1995

Design of a selectable reporter for the detection of mutations in mammalian simple repeat sequences.

To study the mutator phenotype characteristic of tumors showing widespread replication errors at simple DNA repeat sequences (RER+), we designed a selectable reporter system for the detection of such mutations in mammalian cells. A hygromycin B phosphotransferase gene was rendered out-of-frame by the insertion of a (CA)13 dinucleotide repeat tract immediately following the ATG start codon, and subcloned into a retroviral expression vector containing a G418 (neo) selectable marker. Following transduction of this construct into cultured cells, clonal neo+ cell lines were established and then tested for their ability to form colonies in hygromycin B-containing medium. Using this system, we found that the HCT116, LS174T and LS180 human colon carcinoma cell lines acquire hygromycin resistance (hygr) at a 100-fold higher frequency than the HT29, SW480, DLD-1 and HCT15 human colon carcinoma and NIH3T3 fibroblast cell lines, and at a 25-fold higher rate than the Rat 6 embyro fibroblast cell line. DNA sequence analysis indicated that frameshift mutations had occurred within the CA dinucleotide repeat tract in HCT116 cells that became hygr. Thus, the mutation rates at simple repeated sequences in mammalian cell lines can be readily determined and studied using this system.

3T3 Cells↗
PubMed1995

Reduced virulence of Candida albicans mutants affected in multidrug resistance.

Disruption of a multidrug resistance gene (CaMDR1) in Candida albicans resulted in mutant strains that colonized mouse kidneys to very high levels but were markedly reduced in their virulence. No obvious differences in several properties related to colonization and dissemination were noted among MDR+ or mdr- strains. These results suggest that specific fungal efflux pumps play a role in fungal pathogenicity.

ATP-Binding Cassette Transporters↗
PubMed1995

Molecular cloning, mapping, and regulation of Pho regulon genes for phosphonate breakdown by the phosphonatase pathway of Salmonella typhimurium LT2.

Two pathways exist for cleavage of the carbon-phosphorus (C-P) bond of phosphonates, the C-P lyase and the phosphonatase pathways. It was previously demonstrated that Escherichia coli carries genes (named phn) only for the C-P lyase pathway and that Enterobacter aerogenes carries genes for both pathways (K.-S. Lee, W. W. Metcalf, and B. L. Wanner, J. Bacteriol. 174:2501-2510, 1992). In contrast, here it is shown that Salmonella typhimurium LT2 carries genes only for the phosphonatase pathway. Genes for the S. typhimurium phosphonatase pathway were cloned by complementation of E. coli delta phn mutants. Genes for these pathways were proven not to be homologous and to lie in different chromosomal regions. The S. typhimurium phn locus lies near 10 min; the E. coli phn locus lies near 93 min. The S. typhimurium phn gene cluster is about 7.2 kb in length and, on the basis of gene fusion analysis, appears to consist of two (or more) genes or operons that are divergently transcribed. Like that of the E. coli phn locus, the expression of the S. typhimurium phn locus is activated under conditions of Pi limitation and is subject to Pho regulon control. This was shown both by complementation of the appropriate E. coli mutants and by the construction of S. typhimurium mutants with lesions in the phoB and pst loci, which are required for activation and inhibition of Pho regulon gene expression, respectively. Complementation studies indicate that the S. typhimurium phn locus probably includes genes both for phosphonate transport and for catalysis of C-P bond cleavage.

Aminoethylphosphonic Acid↗
PubMed1995

Intracellular interference of tick-borne flavivirus infection by using a single-chain antibody fragment delivered by recombinant Sindbis virus.

A single-chain antibody fragment that identifies a neutralizing epitope on the envelope protein of louping ill and some other tick-borne flaviviruses was previously expressed in soluble form from bacteria and shown to be functionally active in vitro. To see whether or not the single-chain antibody could bind and inactivate infectious virus in vivo, we have used recombinant Sindbis virus as a delivery vehicle for intracellular expression of the antibody fragment. The variable genes and interchain linker encoding the single-chain antibody were cloned into a double subgenomic Sindbis virus expression vector to generate recombinant Sindbis virus. Infection with this recombinant Sindbis virus provided high-level cytoplasmic expression of the antibody fragment in mammalian cells. We demonstrate (i) that the antibody fragment was antigen binding and (ii) that louping ill virus infectivity was significantly reduced in the presence of intracellular antibody expressed by the superinfecting recombinant Sindbis virus.

Animals↗