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Biomedical subjects

F Wang

Publications and source records attributed to F Wang.

At least 271 records · Page 15Linked to original sources
PubMed1999

Study on relationship between carbon disulfide exposure and symptoms and signs of nervous system in workers.

The relationship between carbon disulfide (CS2) and the symptoms and signs of nervous system in rayon workers was investigated. In a cross sectional study of CS2-exposed workers from the viscose industry and controls, data on neurological symptoms and clinical neurological examination were evaluated. The exposed subjects includes 326 workers and 105 workers from the same factory, without exposure to CS2 or to any other neurotoxic agents, served as controls. The median exposure to CS2(8 h time weighted) in the low-level exposure group was 4.6 mg/m3, and 18.3 mg/m3 in high-level exposure group. Non-conditional multiple logistic regression analysis was employed for evaluating statistical differences by using SAS software. In the analysis, age, sex, work time, body mass index (BMI), smoking and drinking habits, educational background and marriage status were controlled. The odds ratio (OR) significantly increased of some symptoms in workers exposed to CS2 at levels below 10 mg/m3, as compared to controls. The dose-effect relationship between the exposure to CS2 and the symptoms of nervous system was demonstrated. In terms of neurological parameters, no other abnormal change but that in temperature sensitivity was observed in workers exposed to CS2. In conclusion, the influence of low level CS2 on nervous system of workers should not be ignored.

Carbon Disulfide↗
PubMed1999

Diffusion distances of known iron complexes in model systems.

Diffusion distances (abbreviated d's), the distances between the sites of generation of presumed hydroxyl radicals (*OH) by low molecular weight forms of Fe and the site of their reaction with substrate, were measured for three model systems for cellular DNA of varying degrees of complexity. Two d's for Fe complexed with each of ethylene diamminetetraaccetic acid (FeEDTA) and nitrilotriacetic acid (FeNTA) were measured for generation of malondialdehyde-type products (MDA) from deoxyribose and of single-strand breaks (SSBs) in the plasmid pBR322. The closer d's for pBR322 SSB generation (5-6 nm) were considerably greater than the d's for MDA generation in the deoxyribose assay (2-3 nm). This is consistent with charge-charge interactions playing an important role in defining d. The d's for FeNTA, FeEDTA, and other Fe species generating SSBs in isolated Ehrlich ascites tumor cell nuclei ranged from 2.1 to 14 nm. Charge-charge interactions, Fe-ligand-specific interactions, and binding to nuclear components were concluded to be important factors affecting d in isolated nuclei. Other factors related to nuclear structure may also play a role.

Animals↗
PubMed1999

Formation of phosphatidic acid and subclasses of phosphatidylethanol in human neutrophils upon interleukin-8 stimulation.

Previous studies showed that interleukin-8 (IL-8) stimulates phospholipase D hydrolysis of phosphatidylcholine to generate phosphatidic acid in human neutrophils. Phosphatidylcholine in these cells contains diacyl, alkylacyl and alkenylacyl subclasses. No studies have examined phospholipase D hydrolysis of the three subclasses of phosphatidylcholine in interleukin-8-stimulated neutrophils. We used a non-radioactive but very sensitive method to assess the relative distribution of the subclasses in phosphatidylethanol, which is derived from phospholipase D activity in ethanol-exposed neutrophils. We present evidence that the relative abundance of diacyl and alkylacyl subclasses in phosphatidylethanol is similar to that in phosphatidylcholine. Alkenylacyl subclass was also detectable in the phosphatidylethanol fraction, albeit as a minor subclass. Our findings suggest that phospholipase D catalyses the hydrolysis of diacyl, alkylacyl and alkenylacyl subclasses of phosphatidylcholine in neutrophils upon IL-8 stimulation.

Chromatography, Thin Layer↗
PubMed1999

Fourier transform ion cyclotron resonance mass spectrometric detection of small Ca(2+)-induced conformational changes in the regulatory domain of human cardiac troponin C.

Troponin C (TnC), a calcium-binding protein of the thin filament of muscle, plays a regulatory role in skeletal and cardiac muscle contraction. NMR reveals a small conformational change in the cardiac regulatory N-terminal domain of TnC (cNTnC) on binding of Ca2+ such that the total exposed hydrophobic surface area increases very slightly from 3090 +/- 86 A2 for apo-cNTnC to 3108 +/- 71 A2 for Ca(2+)-cNTnC. Here, we show that measurement of solvent accessibility for backbone amide protons by means of solution-phase hydrogen/deuterium (H/D) exchange followed by pepsin digestion, high-performance liquid chromatography, and electrospray ionization high-field (9.4 T) Fourier transform Ion cyclotron resonance mass spectrometry is sufficiently sensitive to detect such small ligand binding-induced conformational changes of that protein. The extent of deuterium incorporation increases significantly on binding of Ca2+ for each of four proteolytic segments derived from pepsin digestion of the apo- and Ca(2+)-saturated forms of cNTnC. The present results demonstrate that H/D exchange monitored by mass spectrometry can be sufficiently sensitive to detect and identify even very small conformational changes in proteins, and should therefore be especially informative for proteins too large (or too insoluble or otherwise intractable) for NMR analysis.

Amino Acid Sequence↗
PubMed1999

Sequencing of gel-isolated proteins using microblotter capillary liquid chromatography-electrospray mass spectrometry.

Enzymatic digests of proteins isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) were separated by capillary high-performance liquid chromatography (HPLC). The column eluate was split to an electrospray mass spectrometer on one side and to both a UV detector and a microblotter on the other side. Using the microblotter, the peptides eluted from the column were collected directly onto a polyvinylidene difluoride (PVDF) membrane for Edman sequencing. Thus, a peptide mass map from the mass spectrometric analysis and a prepared PVDF membrane for subsequent Edman sequencing were generated in a single experiment. The addition of molecular mass information to the blotted LC eluate is useful for determining the most important peaks to undergo Edman sequencing. Coupling the capillary HPLC with a microblotter to electrospray mass spectrometry provides an integrated system for separation, collection, and structural analysis of protein digests. It provides high levels of sensitivity, recovery, and convenience for protein characterization. Proteins loaded onto SDS-PAGE at low picomole levels can be analyzed by the new integrated system.

Amino Acid Sequence↗
PubMed1999

Tumour cells engineered to secrete interleukin-15 augment anti-tumour immune responses in vivo.

We examined the effect of interleukin-15 (IL-15) gene transfer into tumour cells on the host's anti-tumour response. In BALB/c mice IL-15 producing Meth-A cells (Meth-A/IL-15) underwent complete rejection, in a response characterized by massive infiltration of CD4+ T-cells and neutrophils. In contrast, Meth-A cells transfected with vector alone (Meth-A/Neo) grew rapidly. Moreover, rechallenged parental cells also were rejected in association with CD8* T-cell infiltration. However, in nude mice there was no drastic difference between Meth-A/IL-15 and Meth-A/Neo cells. These results demonstrate that IL-15-secreting tumour cells can stimulate local and systemic T-cell-dependent immunity and therefore may have a potential role in cancer therapy.

Animals↗
PubMed1999

The risk of angiosarcoma following primary breast cancer.

Lymphangiosarcoma of the upper extremity is a rare and aggressive tumour reported to occur following post-mastectomy lymphoedema (Stewart-Treves syndrome). Haemangiosarcoma, a related rare tumour, has occasionally been reported to occur in the breast following irradiation. We conducted a case-control study using the University of Southern California-Cancer Surveillance Program, the population-based cancer registry for Los Angeles County, to evaluate the relationship between invasive female breast cancer and subsequent upper extremity or chest lymphangiosarcoma and haemangiosarcoma together referred to as angiosarcoma. Cases were females diagnosed between 1972 and 1995 with angiosarcoma of the upper extremity (n = 20) or chest (n = 48) who were 25 years of age or older and residing in Los Angeles County when diagnosed. Other sarcomas at the same anatomic sites were also studied. Controls were females diagnosed with cancers other than sarcoma during the same time period (n = 266,444). Cases and controls were then compared with respect to history of a prior invasive epithelial breast cancer. A history of breast cancer increased the risk of upper extremity angiosarcoma by more than 59-fold (odds ratio [OR] = 59.3, 95% confidence interval [95% CI] = 21.9-152.8). A strong increase in risk after breast cancer was also observed for angiosarcoma of the chest and breast (OR = 11.6, 95% CI = 4.3-26.1) and for other sarcomas of the chest and breast (OR = 3.3, 95% CI = 1.1-1.7).

Adult↗
PubMed1999

Risk factors for psychopathology among Chinese children.

The present study was designed to examine the family environment and child characteristics associated with psychopathology among Chinese children. A large epidemiological sample of 1695 children aged 6-11 was drawn from 12 elementary schools in Linyi Prefecture of China. Parents completed the Child Behaviour Checklist, the Family Environment Scale, and a self-administered questionnaire including a number of items with regard to family, parental, and child characteristics. Results indicated that the overall prevalence of child psychopathology was 17.2%. Logistic regression analyses showed that a number of family and parental, as well as prenatal, perinatal and postnatal risk factors had significant association with child psychopathology. The most notable risks were derived from poor parental rearing with regard to the child's misbehaviour, low birthweight, and poor marital relations of the parents after controlling for other factors. These findings are consistent with previously reported risk factors for child psychopathology, highlighting the importance of family and early childhood intervention as a measure to prevent child psychopathology in China.

Child↗
PubMed1999

Multiple radon entry modeling in a house with a cellar.

Combining a computational fluid dynamics (CFD) model and a multi-zonal model, a study was carried out on radon entry through the complex substructure of a house with a cellar. The uniqueness of the radon entry problem in this type of house was due to the involvement of two radon entry routes to two chambers: the cellar and the living area of the house. Soil gas carrying radon was driven through the two routes by two coupled disturbance pressures in the chambers. The effects of temperature differences were considered as another driving force for the radon entry. Examined in this study were the effects of the geometry of the substructure, air permeability of the soil, air-tightness of the cellar shell, and cellar ventilation on radon entry to both the cellar and the living area. The ground floor covering on top of the soil outside a cellar wall increased radon entry through this wall by about 68%, as radon built up to a very high level under the covering. The effect of cellar ventilation was found as follows: the cellar ventilation created a layer of airflow in the soil under the ground floor; the flow passed over a crack in the ground floor, the entry route to the living area, diluting the radon in the area. Hence, the soil gas entering the living area carried less radon. Cellar ventilation seems more effective in reducing radon entry to the living area in a more permeable soil and leaky cellar shell; a moderate cellar ventilation condition achieved 77% reduction in radon entry to the area. When permeability of these two materials was lower and soil radon content remained the same, the chances of radon entry was also lower; hence, the indoor radon level was lower and no radon control was needed. When such soil contains high radon concentration, other mitigation measures must be sought.

Air Pollutants, Radioactive↗
PubMed1999

Gating of cystic fibrosis transmembrane conductance regulator chloride channels by adenosine triphosphate hydrolysis. Quantitative analysis of a cyclic gating scheme.

Gating of the cystic fibrosis transmembrane conductance regulator (CFTR) involves a coordinated action of ATP on two nucleotide binding domains (NBD1 and NBD2). Previous studies using nonhydrolyzable ATP analogues and NBD mutant CFTR have suggested that nucleotide hydrolysis at NBD1 is required for opening of the channel, while hydrolysis of nucleotides at NBD2 controls channel closing. We studied ATP-dependent gating of CFTR in excised inside-out patches from stably transfected NIH3T3 cells. Single channel kinetics of CFTR gating at different [ATP] were analyzed. The closed time constant (tauc) decreased with increasing [ATP] to a minimum value of approximately 0.43 s at [ATP] >1.00 mM. The open time constant (tauo) increased with increasing [ATP] with a minimal tauo of approximately 260 ms. Kinetic analysis of K1250A-CFTR, a mutant that abolishes ATP hydrolysis at NBD2, reveals the presence of two open states. A short open state with a time constant of approximately 250 ms is dominant at low ATP concentrations (10 microM) and a much longer open state with a time constant of approximately 3 min is present at millimolar ATP. These data suggest that nucleotide binding and hydrolysis at NBD1 is coupled to channel opening and that the channel can close without nucleotide interaction with NBD2. A quantitative cyclic gating scheme with microscopic irreversibility was constructed based on the kinetic parameters derived from single-channel analysis. The estimated values of the kinetic parameters suggest that NBD1 and NBD2 are neither functionally nor biochemically equivalent.

3T3 Cells↗
PubMed1999

Dissociated insulin and islet amyloid polypeptide secretion from isolated rat pancreatic islets cocultured with human pancreatic adenocarcinoma cells.

Abnormal insulin and islet amyloid polypeptide (IAPP) secretion are usually seen in patients with exocrine pancreatic cancer. The beta-cell dysfunction is a characteristic of the glucose intolerance found in pancreatic cancer patients. The effects of pancreatic cancer cells on insulin and IAPP secretion from beta cells are unclear. In this study, isolated rat pancreatic islets were cocultured with two human pancreatic adenocarcinoma cell lines (Panc-1 and HPAF) and a human colonic adenocarcinoma cell line (HT-29). As a control, islets were incubated in the absence of malignant cells. The accumulation of insulin and IAPP in culture media was measured by radioimmunoassay. Output of insulin and IAPP was decreased in islets cocultured with each malignant cell line. Molar ratio of secreted IAPP and insulin (IAPP/insulin) was increased in the islets cocultured with Panc-1 or HPAF cells, but not HT-29 cells. The decreased insulin and IAPP secretion were partly recovered after Panc-1, HPAF, or HT-29 cells were removed. The IAPP/insulin ratio was normalized after the removal of Panc-1 or HPAF cells. This study indicates that insulin and IAPP secretion are altered by the human adenocarcinoma cells investigated. The impairment induced by pancreatic adenocarcinoma cells is associated with a hypersecretion of IAPP relative to insulin on a molar basis.

Adenocarcinoma↗
PubMed1999

The NS5A protein of hepatitis C virus partially inhibits the antiviral activity of interferon.

The non-structural protein 5A (NS5A) of some hepatitis C virus (HCV) isolates has been implicated in the inhibition of the antiviral activity of interferon (IFN). In the present study, the possible inhibitory effects of NS5A from two isolates of HCV subtype 1b, HCV-1bJk and M094AJk, and their chimeric form on the antiviral activity of IFN were examined. HCV-1bJk and M094AJk are categorized as IFN resistant and IFN sensitive, respectively, based on the sequences of the IFN-sensitivity determining region (ISDR). When encephalomyocarditis virus was used as a challenge virus, NS5A was shown to eliminate the antiviral activity of IFN, with inhibition being more prominent with HCV-1bJk NS5A than with M094AJk NS5A. Moreover, the inhibition was significantly weaker in cells expressing a chimeric NS5A that had a short stretch of 49 amino acids (aa 2209-2257), including the ISDR sequence, from M094AJk in the backbone of the HCV-1bJk sequence than in cells expressing the original NS5A from HCV-1bJk. These results suggest an important role for the 49 aa sequence, including the ISDR, in the inhibition of IFN-mediated antiviral activity. On the other hand, only a slight reduction of IFN antiviral activity by HCV-1bJk NS5A was observed when vesicular stomatitis virus was used as a challenge virus, and barely any reduction was observed when Japanese encephalitis virus was used. These results may reflect differential importance of each of the IFN-mediated signalling pathways in conferring resistance against different viruses.

3T3 Cells↗
PubMed1999

Redox imbalance differentially inhibits lipopolysaccharide-induced macrophage activation in the mouse liver.

Endotoxemia is accompanied by significant changes in the reductive-oxidative (redox) balance of critical target organs. Redox stress has been shown to regulate the expression of proinflammatory genes that are induced by endotoxic lipopolysaccharide (LPS) in vitro; however, much less is known about the effects of redox imbalance on LPS-induced gene expression in vivo. To assess the effects of redox stress on inflammatory responses in endotoxemia, mice were treated with either diethyl maleate (DEM), a glutathione-depleting agent, or buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, and challenged with LPS. While serum tumor necrosis alpha (TNF-alpha) responses and the appearance of TNF-alpha-positive Kupffer cells in the liver were virtually eliminated by DEM or BSO treatment, the expression of both CD14 and inducible NO synthase (iNOS) by Kupffer cells was unaffected by glutathione depletion. By contrast, LPS-induced hepatocyte and hepatic sinusoidal endothelial cell iNOS expression was significantly inhibited in DEM-treated mice. Hepatocyte iNOS induced by recombinant mouse TNF-alpha was also inhibited by DEM treatment. These results indicate that the effects of oxidative stress in this organ are cell type specific and suggest that both the production and the action of TNF-alpha are substantially influenced by the redox state of the liver during endotoxemia.

Animals↗
PubMed1999

Strong selective pressure for evolution of an Epstein-Barr virus LMP2B homologue in the rhesus lymphocryptovirus.

Latent membrane protein 2B (LMP2B) is expressed during latent Epstein-Barr virus (EBV) infection, but little is known about its role. The goal of this study was to determine whether an LMP2B homologue is conserved in the rhesus monkey lymphocryptovirus (LCV). Both rhesus LCV LMP2A and LMP2B genes were cloned and sequenced. The rhesus LCV LMP2B gene is positionally conserved, and the EBNA-2 responsiveness and the bidirectional nature of the LMP1-LMP2B promoter have also been functionally conserved. However, this region of the genome encoding the LMP1, LMP1-LMP2B promoter, and LMP2B first exon demonstrates the most dramatic nucleotide sequence divergence between human and nonhuman LCV observed to date. Evolution of the rhesus LCV LMP2B promoter and transcript despite the dynamic nature of this genomic region reflects strong selective pressure for a yet-to-be-identified LMP2B function.

Amino Acid Sequence↗
PubMed1999

Evolution of two types of rhesus lymphocryptovirus similar to type 1 and type 2 Epstein-Barr virus.

Rhesus monkeys and other nonhuman Old World primates are naturally infected with lymphocryptoviruses (LCV) that are closely related to Epstein-Barr virus (EBV). A rhesus LCV isolate (208-95) was derived from a B-cell lymphoma in a simian immunodeficiency virus-infected rhesus macaque. The EBNA-2 homologues from 208-95 and a previous rhesus LCV isolate (LCL8664) were polymorphic on immunoblotting, so the EBNA-2 genes from these two rhesus LCV were cloned, sequenced, and compared. The EBNA-2 genes have 40% nucleotide and 41% amino acid identities, and the differences are similar to those between the type 1 and type 2 EBV EBNA-2. Sequence from a portion of the LMP1 gene which is extremely divergent among different LCV was virtually identical between the 208-95 and LCL8664 strains, confirming a common rhesus LCV background. Thus, the EBNA-2 polymorphism defines the presence of two different rhesus LCV types, and both rhesus LCV types were found to be prevalent in the rhesus monkey population at the New England Regional Primate Research Center. The existence of two rhesus LCV types suggests that the selective pressure for the evolution of two LCV types is shared by human and nonhuman primate hosts.

Amino Acid Sequence↗
PubMed1999

Mechanisms that regulate Epstein-Barr virus EBNA-1 gene transcription during restricted latency are conserved among lymphocryptoviruses of Old World primates.

Epstein-Barr virus (EBV), the only known human lymphocryptovirus (LCV), displays a remarkable degree of genetic and biologic identity to LCVs that infect Old World primates. Within their natural hosts, infection by these viruses recapitulates many key aspects of EBV infection, including the establishment of long-term latency within B lymphocytes, and is therefore a potentially valuable animal model of EBV infection. However, it is unclear whether these LCVs have adopted or maintained the same mechanisms used by EBV to express essential viral proteins, such as EBNA-1, in the face of cell-mediated repression of EBV gene expression that occurs upon establishment of the asymptomatic carrier state. To address this issue, we determined whether the endogenous LCVs of baboon (Cercopithecine herpesvirus 12) and rhesus macaque (Cercopithecine herpesvirus 15) have the functional equivalent of the EBV promoter Qp, which mediates exclusive expression of EBNA-1 during the restricted programs of EBV latency associated with the carrier state. Our results indicate that (i) both the baboon and rhesus macaque LCVs have a genomic locus that is highly homologous to the EBV Qp region, (ii) key cis-regulatory elements of Qp are conserved in these LCV genomes and compose promoters that are functionally indistinguishable from EBV Qp, and (iii) EBNA-1 transcripts identical in structure to EBV Qp-specific EBNA-1 mRNAs are present in nonhuman LCV-infected cells, demonstrating that these Qp homologs are indeed utilized as alternative EBNA-1 promoters. These observations indicate that the molecular mechanisms which regulate EBV gene expression during restricted latency have been conserved among the LCVs. The contribution of these mechanisms to viral persistence in vivo can now be experimentally tested in nonhuman primate models of LCV infection.

Animals↗
PubMed1999

Inhibition of antigen presentation by the glycine/alanine repeat domain is not conserved in simian homologues of Epstein-Barr virus nuclear antigen 1.

Most humans and Old World nonhuman primates are infected for life with Epstein-Barr virus (EBV) or closely related gammaherpesviruses in the same lymphocryptovirus (LCV) subgroup. Several potential strategies for immune evasion and persistence have been proposed based on studies of EBV infection in humans, but it has been difficult to test their actual contribution experimentally. Interest has focused on the EBV nuclear antigen 1 (EBNA1) because of its essential role in the maintenance and replication of the episomal viral genome in latently infected cells and because EBNA1 endogenously expressed in these cells is protected from presentation to the major histocompatibility complex class-I restricted cytotoxic T-lymphocyte (CTL) response through the action of an internal glycine-alanine repeat (GAR). Given the high degree of biologic conservation among LCVs which infect humans and Old World primates, we hypothesized that strategies essential for viral persistence would be well conserved among viruses of this subgroup. We show that the rhesus LCV EBNA1 shares sequence homology with the EBV and baboon LCV EBNA1 and that the rhesus LCV EBNA1 is a functional homologue for EBV EBNA1-dependent plasmid maintenance and replication. Interestingly, all three LCVs possess a GAR domain, but the baboon and rhesus LCV EBNA1 GARs fail to inhibit antigen processing and presentation as determined by using three different in vitro CTL assays. These studies suggest that inhibition of antigen processing and presentation by the EBNA1 GAR may not be an essential mechanism for persistent infection by all LCV and that other mechanisms may be important for immune evasion during LCV infection.

Alanine↗