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Biomedical subjects

D Wang

Publications and source records attributed to D Wang.

At least 145 records · Page 8Linked to original sources
PubMed2001

Characterization of volatile organic compounds in smoke at experimental fires.

Significant associations between firefighting and cancer have been reported; however, studies finding toxic products of combustion at municipal fires have been limited by (1) technical difficulties encountered at the scene of working fires, (2) the lack of a coherent sampling strategy, and (3) the absence of verified sampling methods. The objective of the present study was to characterize the presence of volatile organic compound (VOC) combustion products in fire smoke. Air samples from experimental fires burning various materials commonly found at structural fires were collected into evacuated Summa canisters and analyzed for 144 target VOCs using cryogenic preconcentration and gas chromatography/mass spectroscopy (GC/MSD) methodology. The resulting chromatograms were characterized by a small number of predominant peaks, with 14 substances (propene, benzene, xylenes, 1-butene/2-methylpropene, toluene, propane, 1,2-butadiene, 2-methylbutane, ethylbenzene, naphthalene, styrene, cyclopentene, 1-methylcyclopentene, isopropylbenzene) being found in proportionately higher concentrations in all experimental fires and accounting for 65% (SD = +/-12%) by mass of total measured VOCs. Benzene, toluene, 1,3-butadiene, naphthalene, and styrene were found at higher concentrations than most other VOCs and increased with the time of combustion together with increasing levels of carbon monoxide. Benzene was found in the highest concentrations, with peak levels ranging from 0.6 ppm to 65 ppm, while the levels of 1,3-butadiene, styrene, and naphthalene peaked at 0.1, 0.4, and 3 ppm, respectively. This study revealed that there were no new or novel, toxic nonpolar VOCs resulting from the burning of common building materials. This is important in view of the studies that have found associations between firefighting and various forms of cancer.

Beds↗
PubMed2001

Stromal inhibition of megakaryocytic differentiation correlates with blockade of signaling by protein kinase C-epsilon and ERK/MAPK.

Contact with bone marrow stromal cells maintains normal and leukemic hematopoietic progenitors in an undifferentiated state. Recently, stromal contact has been shown to diminish the yield of megakaryocytes in cultures of primary human hematopoietic stem cells. This inhibition may explain the poor megakaryocytic engraftment frequently observed after bone marrow transplantation. In the current study, stromal co-culture is shown to render K562 cells refractory to megakaryocytic induction. This stromal inhibition correlated with the selective down-regulation in K562 cells of protein kinase C-epsilon (PKC-epsilon), which has recently been implicated in regulation of megakaryocytic lineage commitment. In addition, the stromal inhibition correlated with inactivation of the ERK/MAPK pathway, which has also been implicated in promoting megakaryocytic development. Forced expression of PKC-epsilon by retroviral transduction was insufficient to reverse the stromal blockade of ERK/MAPK signaling or of megakaryocytic induction. Thus stromal interruption of ERK/MAPK signaling occurred independently of PKC-epsilon levels and correlated more closely with megakaryocytic blockade. These findings provide potential mechanisms for stromal inhibition of hematopoietic differentiation and possibly for the poor megakaryocytic engraftment seen after bone marrow transplantation.

Bone Marrow Cells↗
PubMed2001

Dissociation of Pax-5 from KI and KII sites during kappa-chain gene rearrangement correlates with its association with the underphosphorylated form of retinoblastoma.

The KI and KII sites play a crucial role in kappa-chain gene rearrangement, which was investigated in mice deficient for these sites. Previously, we found that Pax-5 can bind to the KI and KII sites; however, the function of Pax-5 in kappa-chain gene rearrangement has not been investigated. Here, we have used an in vitro culture system in which differentiation from pre-B cells to immature B cells is induced by removing IL-7. We showed that, after the induction of differentiation, Pax-5 dissociated from the KI and KII revealed by EMSA analyses, and this dissociation occurred specifically at the KI and KII sites, but not at the Pax-5 binding site, in the CD19 promoter because of a lower binding affinity of Pax-5 for the KI and KII sites. During differentiation induced by removing IL-7, the underphosphorylated form of retinoblastoma preferentially associated with Pax-5, which caused dissociation of Pax-5 from KI and KII sites. These results suggest that the dissociation of Pax-5 from the KI and KII sites is important in the induction of kappa-chain gene rearrangement.

Amino Acid Motifs↗
PubMed2001

Determination and comparison of competitive isotherms by rectangular pulse method and frontal velocity analysis method.

Two different approaches, the rectangular pulse method and a new method, the frontal velocity analysis method are applied to the determination of competitive isotherms for two systems on ODS-silica. Both sets of experimental data are found to fit well to the competitive-Langmuir isotherm equation. The data obtained from the rectangular pulse method and the frontal velocity analysis method are in general agreement with each other and the best coefficients of the competitive isotherms obtained with the two methods are close. This shows that the simpler and easier method, the frontal velocity analysis method can be used to determine binary competitive isotherms.

Adsorption↗
PubMed2001

Allylstannylation of carbon-carbon and carbon-oxygen unsaturated bonds via a radical chain process.

In the presence of a radical initiator, allyltributylstannanes bearing an electron-withdrawing group at the beta-position smoothly reacted with electron-deficient terminal alkenes to give allylstannylated products in good yields. The stannyl group was introduced into the terminal carbon with high regioselectivity. The allylstannylation of homochiral 8-phenylmenthyl acrylate proceeded with moderate to good diastereoselectivity. Terminal and electron-deficient internal alkynes as well efficiently underwent the radical-initiated allylstannylation in an anti addition mode. The reaction of terminal alkynes showed the same regioselectivity as that of terminal alkenes. The present radical reaction was applicable to allylation of aromatic aldehydes and ketones.

Journal Article↗
PubMed2001

Different processes are involved in human brain for shape and face comparisons.

Fifteen subjects participated in a matching task of visual stimuli. Two sequentially presented stimuli in a pair were the same shape (shape match), different shapes (shape mismatch), same human face (face match) or different faces (face mismatch). All four kinds of stimulus pairs were of equal probability. The shape mismatch pairs elicited a negative event-related potential component N270 (Peak latency: 262.1+/-16.5 ms, P4) after the second stimulus onset, while the face mismatch evoked N270 with longer peak latency (301.2+/-19.8 ms, P4) and N450. There exists a specific system for mismatch processing of a complex stimulus (face) in the human brain.

Cerebral Cortex↗
PubMed2001

Transformation of sib-pair values for the Haseman-Elston method.

The squared sib-pair phenotype difference (SQD) has been used as a dependent variable in the Haseman-Elston (H-E) regression quantitative-trait locus (QTL) linkage method, but it has been shown that the SQD does not make full use of linkage information. In this study, we examine the efficiency of SQD in H-E regression compared to other proposed functions of the sib-pair phenotypes. A new function of sib-pair phenotypes, the product of pair values corrected with family mean (PCF), is shown to have desirable properties in many realistic situations. Consistent results were obtained using a combination of large-sample analytic approximations, simulation, and analyses of quantitative-trait data from Genetic Analysis Workshop 10. The advantages of PCF are further improved in the presence of family-specific effects arising from environmental factors or when additional QTLs influence the trait. All of the phenotype functions are incorporated in our new, freely available linkage-mapping program MULTIGENE 1.0 for the PC environment.

Chromosome Mapping↗
PubMed2001

MOT1-catalyzed TBP-DNA disruption: uncoupling DNA conformational change and role of upstream DNA.

SNF2/SWI2-related ATPases employ ATP hydrolysis to disrupt protein-DNA interactions, but how ATP hydrolysis is coupled to disruption is not understood. Here we examine the mechanism of action of MOT1, a yeast SNF2/SWI2-related ATPase that uses ATP hydrolysis to remove TATA binding protein (TBP) from DNA. MOT1 function requires a 17 bp DNA 'handle' upstream of the TATA box, which must be double stranded. Remarkably, MOT1-catalyzed disruption of TBP-DNA does not appear to require DNA strand separation, DNA bending or twisting of the DNA helix. Thus, TBP-DNA disruption is accomplished in a reaction apparently not driven by a change in DNA structure. MOT1 action is supported by DNA templates in which the handle is connected to the TATA box via single-stranded DNA, indicating that the upstream duplex DNA can be conformationally uncoupled from the TATA box. Combining these results with proposed similarities between SNF2/SWI2 ATPases and helicases, we suggest that MOT1 uses ATP hydrolysis to translocate along the handle and thereby disrupt interactions between TBP and DNA.

Adenosine Triphosphatases↗
PubMed2001

Molecular determinants for Csk-catalyzed tyrosine phosphorylation of the Src tail.

Phosphorylation of a critical tail tyrosine residue in Src modulates its three-dimensional structure and protein tyrosine kinase activity. The protein tyrosine kinase Csk is responsible for catalyzing the phosphorylation of this key Src tyrosine residue, but the detailed molecular basis for Src recognition and catalysis is poorly understood. In this study, we investigate this phosphorylation event using purified recombinant Csk and Src proteins and mutants. It was shown that the apparent k(cat) and K(m) values for Csk phosphorylation of catalytically impaired Src (dSrc) are similar to the parameters for Csk-catalyzed phosphorylation of the Src family member Lck. The SH3 (Src homology 3) and SH2 (Src homology 2) domains of dSrc were fully dispensable with respect to rapid phosphorylation, indicating that the catalytic domain and tail of dSrc are sufficient for the high efficiency of dSrc as a substrate. Of the eight Src tail residues examined, only the fully conserved Glu (Y-3 position) and Gln (Y-1 position) investigated by alanine scanning mutagenesis caused large reductions (10--40-fold) in dSrc substrate efficiency. The Y-3 Glu requirement was stringent as conservative replacements with Asp or Gln were no better than Ala whereas replacement of the Y-1 Gln with Ile was readily tolerated. Interestingly, en bloc replacement of the tail with a seven amino acid consensus sequence derived from a peptide library analysis was no better than the wild-type sequence. Surprisingly, the dSrc Y527F protein, although not a Csk substrate, enhanced Csk-catalyzed phosphorylation of dSrc. These results and other data suggest that Src dimerization (or higher order oligomerization) is important for high-efficiency Csk-catalyzed phosphorylation of the Src tail.

Amino Acid Substitution↗
PubMed2001

Regional differences in integrin expression: role of alpha(5)beta(1) in regulating smooth muscle cell functions.

There is increasing evidence to suggest that coronary smooth muscle cells (SMCs) differ from noncoronary SMCs. As integrin adhesion molecules regulate many SMC functions, we hypothesized that differences in integrin expression on coronary and noncoronary SMCs may account for cellular differences. Analysis of integrin expression on freshly isolated porcine coronary and noncoronary SMCs revealed that coronary SMCs express significantly less alpha(5)beta(1) than noncoronary SMCs, whereas the expression of total beta(1) and that of alpha(v)beta(3) are similar. Consistent with these findings, coronary SMCs demonstrated significantly less adhesion to fibronectin, compared with carotid artery SMCs. As alpha(5)beta(1)-mediated signaling has been associated with cellular proliferation, the effects of differential alpha(5)beta(1) expression on cell proliferation were examined by comparing primary coronary and carotid artery SMC proliferation. Coronary SMC growth was significantly lower than that of carotid artery SMCs when plated on fibronectin or type I collagen. Blocking alpha(5)beta(1) function on carotid artery SMCs produced a significant decrease in cellular proliferation, resulting in growth similar to that of coronary SMCs. Furthermore, blocking alpha(5)beta(1), but not alpha(v)beta(3), inhibited loss of alpha-smooth muscle actin in proliferating SMCs. Proliferating coronary SMCs were found to upregulate alpha(5)beta(1) expression, further indicating a role for alpha(5)beta(1) in SMC growth. These results suggest that dissimilar alpha(5)beta(1) integrin expression may mediate regional differences in phenotype of vascular SMCs.

Animals↗
PubMed2001

Clinical evaluation of a new recombinant antigen-based cytomegalovirus immunoglobulin M immunoassay in liver transplant recipients.

BACKGROUND: Human cytomegalovirus (CMV) is a significant cause of morbidity and mortality among transplant recipients. Monitoring transplant recipients by CMV IgM serology has been questioned by several studies due to the reported insensitivity of serologic tests relative to antigen detection methods. METHODS: In this retrospective study, we have evaluated the performance of the new recombinant antigen-based Abbott AxSYM CMV IgM assay and compared it with CMV culture technique in a cohort of 40 liver transplant recipients who did not receive antiviral prophylaxis. RESULTS: The sensitivity, specificity, and positive and negative predictive values for detection of CMV disease by the AxSYM CMV IgM assay were 90.0%, 60.0%, 69.2%, and 85.7%, respectively, and by culture the values were 100%, 55.0%, 69.0%, and 100%, respectively. Detection of CMV IgM occurred before or at the time of CMV disease in only R+ recipients. CONCLUSION: Although this assay is a sensitive test for CMV-specific IgM, detection of CMV IgM preceded detection of virus by culture in patients only when the liver transplant recipient was CMV immune before transplantation (R+).

Antibodies, Viral↗
PubMed2001

Isolation and characterization of senescence-induced cDNAs encoding deoxyhypusine synthase and eucaryotic translation initiation factor 5A from tomato.

Full-length cDNA clones encoding deoxyhypusine synthase (DHS) and eucaryotic initiation factor 5A (eIF-5A) have been isolated from a cDNA expression library prepared from tomato leaves (Lycopersicon esculentum, cv. Match) exposed to environmental stress. DHS mediates the first of two enzymatic reactions that activate eIF-5A by converting a conserved lysine to the unusual amino acid, deoxyhypusine. Recombinant protein obtained by expressing tomato DHS cDNA in Escherichia coli proved capable of carrying out the deoxyhypusine synthase reaction in vitro in the presence of eIF-5A. Of particular interest is the finding that DHS mRNA and eIF-5A mRNA show a parallel increase in abundance in senescing tomato flowers, senescing tomato fruit, and environmentally stressed tomato leaves exhibiting programmed cell death. Western blot analyses indicated that DHS protein also increases at the onset of senescence. It is apparent from previous studies with yeast and mammalian cells that hypusine-modified eIF-5A facilitates the translation of a subset of mRNAs mediating cell division. The present study provides evidence for senescence-induced DHS and eIF-5A in tomato tissues that may facilitate the translation of mRNA species required for programmed cell death.

Aging↗
PubMed2001

Triplex targeting of human PDGF-B (c-sis, proto-oncogene) promoter specifically inhibits factors binding and PDGF-B transcription.

Human c-sis/PDGF-B proto-oncogene has been shown to be overexpressed in a large percentage of human tumor cells establishing a growth-promoting, autocrine growth circuit. Triplex forming oligonucleotides (TFOs) can recognize and bind sequences in duplex DNA, and have received considerable attention because of their potential for targeting specific genomic sites. The c-sis/PDGF-B promoter contains a unique homopurine/homopyrimidine sequence (SIS proximal element, SPE), which is crucial for binding nuclear factors that provoke transcription. In order to develop specific transcriptional inhibitors of the human c-sis/PDGF-B proto-oncogene, 20 potential TFOs targeting part or all of the SPE were screened by gel mobility analysis. DNase I footprinting shows that the TFOs we designed can form a sequence-specific triplex with the target. Protein binding assays demonstrate that triplex formation inhibits nuclear factors binding the c-sis/PDGF-B promoter. Both transient and stable transfection experiments demonstrate that the transcriptional activity of the promoter is considerably inhibited by the TFOs. We propose that TFOs represent a therapeutic potential to specifically diminish the expression of c-sis/PDGF-B proto-oncogene in various pathologic settings where constitutive expression of this gene has been observed.

Base Sequence↗
PubMed2001

Choroid plexus epithelial cells in adult rats show structural alteration but not apoptosis following an exposure to hypobaric hypoxia.

The choroid plexus in adult rats was examined for any structural alteration or apoptotic cell death following a high altitude exposure which leads to the development of hypobaric hypoxia due to reduced oxygen tension in the atmospheric air. Caspase-3 (a protease which mediates apoptosis) immunoreactivity was absent in the choroid plexus epithelial cells in the control rats and following altitude exposure; Bcl-2 (anti-apoptotic protein) and Bax (pro-apoptotic protein) immunoreactivity were upregulated at 3 h-2 days following the altitude exposure when compared to the controls but not in longer surviving rats. At the ultrastructural level, glycogen particles and vacuoles were observed in some epithelial cells at 7 days following the altitude exposure. It is suggested that transient exposure to high altitude may not cause much damage to the choroid plexus epithelial cells except for some structural alteration which may be due to altered metabolism of the cells in response to hypobaric hypoxia.

Age Factors↗
PubMed2001

A potential role for protein kinase C-epsilon in regulating megakaryocytic lineage commitment.

Multiple studies have shown that intracellular signal transduction by the protein kinase C (PKC) family participates in the initiation of megakaryocyte differentiation. In this study, multiple approaches addressed the functional contributions by specific PKC isozymes to megakaryocytic lineage commitment of two independent cell lines, K562 and human erythroleukemia (HEL). Pharmacologic profiles of induction and inhibition of megakaryocytic differentiation in both cell lines suggested a role for the calcium-independent novel PKCs, in particular PKC-epsilon. In transfection studies, the isolated variable domain of PKC-epsilon selectively blocked exogenous activation of the megakaryocyte-specific alpha IIb promoter. Constitutively active mutants of PKC-epsilon, but not of other PKC isozymes, cooperated with the transcription factor GATA-1 in the activation of the alpha IIb promoter. The functional cooperation between GATA-1 and PKC-epsilon displayed dependence on cellular milieu, as well as on the promoter context of GATA binding sites. In aggregate, the data suggest that PKC-epsilon specifically participates in megakaryocytic lineage commitment through functional cooperation with GATA-1 in the activation of megakaryocytic promoters.

Carbazoles↗
PubMed2001

Determination of pKa values of anthraquinone compounds by capillary electrophoresis.

In this paper, the dissociation constants (pKa1, pKa2) of five anthraquinones were determined from the relation between the effective mobility at different pH values and the buffer pH value, which was derived from the basic electrophoresis theory and the dissociation equilibrium of a binary acid. In addition, the changes of pKa values of the five compounds were also investigated when organic modifiers were added to the buffer system.

Anthraquinones↗
PubMed2001

Autosomal dominant glut-1 deficiency syndrome and familial epilepsy.

Glut-1 deficiency syndrome was first described in 1991 as a sporadic clinical condition, later shown to be the result of haploinsufficiency. We now report a family with Glut-1 deficiency syndrome affecting 5 members over 3 generations. The syndrome behaves as an autosomal dominant condition. Affected family members manifested mild to severe seizures, developmental delay, ataxia, hypoglycorrhachia, and decreased erythrocyte 3-O-methyl-D-glucose uptake. Seizure frequency and severity were aggravated by fasting, and responded to a carbohydrate load. Glut-1 immunoreactivity in erythrocyte membranes was normal. A heterozygous R126H missense mutation was identified in the 3 patients available for testing, 2 brothers (Generation 3) and their mother (Generation 2). The sister and her father were clinically and genotypically normal. In vitro mutagenesis studies in Xenopus laevis oocytes demonstrated significant decreases in the transport of 3-O-methyl-D-glucose and dehydroascorbic acid. Xenopus oocyte membranes expressed high amounts of the R126H mutant Glut-1. Kinetic analysis indicated that replacement of arginine-126 by histidine in the mutant Glut-1 resulted in a lower Vmax. These studies demonstrate the pathogenicity of the R126H missense mutation and transmission of Glut-1 deficiency syndrome as an autosomal dominant trait.

3-O-Methylglucose↗