Biomedical subjects

Z Wang

Publications and source records attributed to Z Wang.

At least 235 records · Page 13Linked to original sources

PubMed2001

An Arabidopsis mutant cex1 exhibits constant accumulation of jasmonate-regulated AtVSP, Thi2.1 and PDF1.2.

Jasmonates (JA) act as a regulator in plant growth as well as a signal in plant defense. The Arabidopsis vegetative storage protein (AtVSP) and plant defense-related proteins thionin (Thi2.1) and defensin (PDF1.2) have previously been shown to accumulate in response to JA induction. In this report, we isolated and characterized a novel recessive mutant, cex1, conferring constitutive JA-responsive phenotypes including JA-inhibitory growth and constitutive expression of JA-regulated AtVSP, Thi2.1 and PDF1.2. The plant morphology and the gene expression pattern of the cex1 mutant could be phenocopied by treatment of wild-type plants with exogenous JA, indicating that CEX1 might be a negative regulator of the JA response pathway.

Adenosine Triphosphatases↗

PubMed2001

Highly stereoselective hydrocarbation of terminal alkynes via Pt-catalyzed hydrosilylation/Pd-catalyzed cross-coupling reactions.

[reaction: see text]. The formal addition of an aryl-H or alkenyl-H bond across a terminal alkyne has been accomplished by the combination of platinum-catalyzed hydrosilylation followed by palladium-catalyzed cross-coupling. The use of the t-Bu3P-Pt(DVDS) catalyst in combination with tetramethyldisiloxane gave excellent regio- and stereoselectivity with a number of alkyne substrates. Subsequent, fluoride-promoted cross-coupling proceeded in high yield and stereospecificity for a variety of aryl halides.

Journal Article↗

PubMed2001

Detection of soluble urokinase receptor by immunoradiometric assay and its application in tumor patients.

It has recently been found that tumor cells express large amounts of urokinase receptor (uPAR) on their surface and that the blood soluble uPAR (suPAR) level in cancer patients is increased. However, the significance of suPAR in tumor progression is still unclear. To investigate the significance of suPAR in evaluating clinical status of solid tumor patients, an immunoradiometric assay (IRMA) based on using two monoclonal antibodies (McAbs) to different epitopes of uPAR was established to determine the serum levels of suPAR in normal individuals and solid tumor patients. The detectable range of this suPAR IRMA was 1.95-500 microg/l. The affinity constant was 4.75x10(9) l/mol. The mean rate of recovery was 101.3%, and the mean coefficients of variation for intra- and interassay were 6.40+/-2.57% (mean+/-S.D., n = 11) and 10.48+/-2.65% (n = 5), respectively. The serum suPAR levels were 2.71+/-1.12 microg/l in 62 normal individuals, 3.71+/-1.69 microg/l in 30 patients with benign tumors, and 5.82+/-2.27 microg/l in 124 patients with malignant tumors. The serum suPAR levels of these two types of tumor patients were increased in comparison with that of normal individuals (P values less than.01 and.001). The extent of their increase in malignant tumors was much greater than in benign tumors (P < .001). The serum suPAR levels of patients with malignant tumors were correlated with tumor invasion, metastasis, and surgical intervention. Our data suggest that IRMA for suPAR could be a sensitive and specific assay and that the serum suPAR level would be a valuable index for evaluating the condition and prognosis of tumor patients in clinic.

Adolescent↗

PubMed2001

Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells.

Apoptosis induction may be a mechanism mediating the anticancer activity of selenium. Our earlier work indicated that distinct cell death pathways are likely involved in apoptosis induced by the CH3SeH and the hydrogen selenide pools of selenium metabolites. To explore the role of caspases in cancer cell apoptosis induced by selenium, we examined the involvement of these molecules in the death of the DU-145 human prostate carcinoma cells induced by methylseleninic acid (MSeA), a novel penultimate precursor of the putative critical anticancer metabolite CH3SeH. Sodium selenite, a representative of the genotoxic selenium pool, was used as a reference for comparison. The results show that MSeA-induced apoptosis was accompanied by the activation of multiple caspases (caspase-3, -7, -8, and -9), mitochondrial release of cytochrome c (CC), poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation. In contrast, selenite-induced apoptotic DNA fragmentation was observed in the absence of these changes, but was associated with the phosphorylation of c-Jun-NH2-terminal kinase 1/2 and p38 mitogen-activated protein kinase/stress-activated protein kinase 2. A general caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone, blocked MSeA-induced cleavage of procaspases and PARP, CC release, and DNA nucleosomal fragmentation, but did not prevent cell detachment. Furthermore, PARP cleavage and caspase activation were confined exclusively to detached cells, indicating that MSeA induction of cell detachment was a prerequisite for caspase activation and apoptosis execution. This process therefore resembled "anoikis," a special mode of apoptosis induction in which adherent cells lose contact with the extracellular matrix. Additional experiments with irreversible caspase inhibitors show that MSeA-induced anoikis involved caspase-3- and -7-mediated PARP cleavage that was initiated by caspase-8 and probably amplified through CC-caspase-9 activation and a feedback activation loop from caspase-3. Taken together, the data support a methyl selenium-specific induction of DU-145 cell apoptosis that involves cell detachment as a prerequisite (anoikis) and is executed principally through caspase-8 activation and its cross-talk with multiple caspases.

Anoikis↗

PubMed2001

Ontogeny of brain-derived neurotrophic factor gene expression in the forebrain of prairie and montane voles.

Brain-derived neurotrophic factor (BDNF) plays an important role in normal brain development. In the present study, we examined the ontogenetic pattern of BDNF gene expression in both monogamous prairie voles (Microtus ochrogaster) and promiscuous montane voles (M. montanus); two closely related microtine rodents that differ in life strategy and social behavior. In both species, BDNF mRNA showed an early appearance and a transient expression in a regionally specific manner. In the dentate gyrus and CA3 region of the hippocampus, BDNF mRNA was found neonatally, increased gradually during development, and reached a peak at weaning, followed by a subsequent decline to the adult level. In the paraventricular nucleus of the hypothalamus, levels of BDNF mRNA persisted until weaning, followed by a significant increase to the adult levels at 3 months of age. BDNF mRNA also demonstrated a species-specific developmental pattern. In the cingulate cortex, BDNF mRNA labeling displayed a transient increase in the second and third postnatal weeks followed by a subsequent decrease to the adult level in prairie voles, but persisted throughout the course of development in montane voles. In general, montane voles achieved an adult pattern of BDNF mRNA expression earlier than did prairie voles. Together, these data indicate that BDNF may function differently in infant and adult brains, and that the two species of voles differ in the ontogenetic pattern of BDNF mRNA expression in a regional-specific manner, which may be associated with their different life strategy and brain and behavioral development.

Animals↗

PubMed2001

[Cloning of liver cancer-related gene HCCA2 and association of that gene with liver cancer].

OBJECTIVE: To study and clone novel liver cancer-related genes and to explore the molecular basis of hepatocarcinogenesis. METHODS: mRNA differential display polymerase chain reaction (DDPCR) was used to clone several gene fractions that were highly expressed in hepatocarcinoma tissues and not expressed or lowly expressed in paracarcinoma tissue. A full-length cDNA of one of such genes was obtained by screening the placenta cDNA library. The expression of this novel gene in 43 pairs of human hepatocellular carcinoma and paracarcinoma tissue was analyzed by Northern blotting. RESULTS: A full-length cDNA of liver cancer-related gene HCCA2 that was widely distributed in normal tissues and not expressed in liver tissue. The positive expression rate of this gene was 79% (34/43) in hepatocellular carcinoma tissue. Its expression was associated with the completeness of the tumor envelop and the expression of KI-67 PROTEIN (P < 0.01). CONCLUSION: The novel gene HCCA2 may be related with the infiltration and proliferation of liver cancer.

Blotting, Northern↗

PubMed2001

Preparation of polycyclic systems by sequential 5-exo-digonal radical cyclization, 1,5-hydrogen transfer from silicon, and 5-endo-trigonal cyclization.

Radicals of type 1 undergo 5-exo diagonal cyclization, and the resulting vinyl radical abstracts hydrogen from silicon to afford a silicon-centered radical. This radical closes in a 5-endo trigonal manner to generate radicals of type 4, which are reduced (4 --> 5) by stannane, except when the starting acetylene carries a terminal trimethylstannyl group. In this case, radicals 4 expel trimethylstannyl radical to afford vinyl silanes 6. The stereochemical outcome of the radical cascade 1 --> 5 is controlled by the stereochemistry of the oxygen-bearing carbon in 1 (see starred atom). The sequence can be initiated by carbon-, alpha-substituted carbon-, oxyacyl-, and carbamoyl radicals and generates a silicon-containing ring fused onto a carbocycle or heterocycle. Numerous examples are described, as well as a number of transformations of the final cyclization products, especially their response to n-Bu(4)NF and to BF(3).OEt(2), reagents that cleave the newly formed carbon-silicon bond.

Journal Article↗

PubMed2001

Recombinant measles viruses expressing heterologous antigens of mumps and simian immunodeficiency viruses.

We have genetically engineered a panel of recombinant measles viruses (rMVs) that express from various positions within the MV genome either the HN or F surface glycoproteins of mumps virus (MuV) or the env, gag or pol proteins from simian immunodeficiency virus (SIV). All rMVs were rescued from the respective antigenomic plasmid constructs; progeny viruses replicated comparably to the progenitor Edmonston B MV, but showed slight propagation retardation, which was dependent on the size and nature of the expressed proteins and on the genomic position of the inserts. All transgenes except that encoding mumps F glycoprotein were faithfully maintained and expressed even after virus amplification by 10(20). Our results suggest possible applications of rMVs as live-attenuated, multivalent vaccines against retroviruses such as SIV and HIV as well as other pathogens more distantly related to MV than MuV.

Animals↗

PubMed2001

The cyclin-dependent kinase inhibitor (CDKI) flavopiridol disrupts phorbol 12-myristate 13-acetate-induced differentiation and CDKI expression while enhancing apoptosis in human myeloid leukemia cells.

Interactions between the cyclin-dependent kinase inhibitor (CDKI) flavopiridol (FP) and phorbol 12-myristate 13-acetate (PMA) were examined in U937 human leukemia cells in relation to differentiation and apoptosis. Simultaneous, but not sequential, exposure of U937 cells to 100 nM FP and 10 nM PMA significantly increased apoptosis manifested by characteristic morphological features, mitochondrial dysfunction, caspase activation, and poly(ADP-ribose) polymerase cleavage while markedly inhibiting cellular differentiation, as reflected by diminished plastic adherence and CD11b expression. Enhanced apoptosis in U937 cells was associated with an early caspase-independent increase in cytochrome c release and accompanied by a substantial decline in leukemic cell clonogenicity. Moreover, PMA/FP cotreatment significantly increased apoptosis in HL-60 promyelocytic leukemia cells and in U937 cells ectopically expressing the Bcl-2 protein. In U937 cells, coadministration of FP blocked PMA-induced expression and reporter activity of the CDKI p21WAF/CIP1 and triggered caspase-mediated cleavage of the CDKI p27KIP1. Coexposure to FP also resulted in a more pronounced and sustained activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase cascade after PMA treatment, although disruption of this pathway by the mitogen-activated protein kinase kinase 1 inhibitor U0126 did not prevent potentiation of apoptosis. FP accelerated PMA-mediated dephosphorylation of the retinoblastoma protein (pRb), an event followed by pRb cleavage culminating in the complete loss of underphosphorylated pRb (approximately Mr 110,000) by 24 h. Finally, gel shift analysis revealed that coadministration of FP with PMA for 8 h led to diminished E2F/pRb binding compared to the effects of PMA alone. Collectively, these findings indicate that FP modulates the expression/activity of multiple signaling and cell cycle regulatory proteins in PMA-treated leukemia cells and that such alterations are associated with mitochondrial damage and apoptosis rather than maturation. These observations also raise the possibility that combining CDKIs and differentiation-inducing agents may represent a novel antileukemic strategy.

Apoptosis↗

PubMed2001

Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene.

ITP and dITP exist in all cells. dITP is potentially mutagenic, and the levels of these nucleotides are controlled by inosine triphosphate pyrophosphatase (EC ). Here we report the cloning, expression, and characterization of a 21.5-kDa human inosine triphosphate pyrophosphatase (hITPase), an enzyme whose activity has been reported in many animal tissues and studied in populations but whose protein sequence has not been determined before. At the optimal pH of 10.0, recombinant hITPase hydrolyzed ITP, dITP, and xanthosine 5'-triphosphate to their respective monophosphates whereas activity with other nucleoside triphosphates was low. K(m) values for ITP, dITP, and xanthosine 5'-triphosphate were 0.51, 0.31, and 0.57 mm, respectively, and k(cat) values were 580, 360, and 640 s(-1), respectively. A divalent cation was absolutely required for activity. The gene encoding the hITPase cDNA sequence was localized by radiation hybrid mapping to chromosome 20p in the interval D20S113-D20S97, the same interval in which the ITPA inosine triphosphatase gene was previously localized. A BLAST search revealed the existence of many similar sequences in organisms ranging from bacteria to mammals. The function of this ubiquitous protein family is proposed to be the elimination of minor potentially mutagenic or clastogenic purine nucleoside triphosphates from the cell.

Amino Acid Sequence↗

PubMed2001

Na+-Ca2+ exchanger remodeling in pressure overload cardiac hypertrophy.

Perturbations of Ca(2+) metabolism are central to the pathogenesis of cardiac hypertrophy. The electrogenic Na(+)-Ca(2+) exchanger mediates a substantial component of transmembrane Ca(2+) movement in cardiac myocytes and is up-regulated in heart failure. However, the role of the exchanger in the pathogenesis of cardiac hypertrophy is poorly understood. Thoracic aortic banding in mice induced 50-60% increases in heart mass and cardiomyocyte size. Despite the absence of myocardial dysfunction, steady-state NCX1 transcript and protein levels were increased to an extent similar to that reported in heart failure. As recent studies indicate that calcineurin is critical to the expression of Na(+)-Ca(2+) exchanger genes, we inhibited calcineurin with cyclosporin. Calcineurin inhibition blunted the increases in NCX1 transcript and protein levels and eliminated the increases in heart mass and cell volume normally associated with pressure overload. To examine the functional significance of these changes, we measured Na(+)-Ca(2+) exchanger current in two independent ways. Surprisingly, exchanger current density was decreased in hypertrophied myocytes, and this down-regulation was eliminated by calcineurin inhibition. Together, these data reveal a role for Na(+)-Ca(2+) exchanger current in the electrical remodeling of hypertrophy and implicate calcineurin signaling therein. In addition, these data suggest the Na(+)-Ca(2+) exchanger is functionally regulated in hypertrophy.

Action Potentials↗

PubMed2001

[Carcinogenicity of bile from cholecystolithiasis patients].

OBJECTIVE: To study the carcinogenicity of bile from cholecystolithiasis patients and the relationship between cholecystolithiasis and gallbladder carcinoma (GBC). METHODS: The bile from 18 cholecystolithiosis patients was examined by Ames test and two-stage cell transformation assay. RESULTS: The bile from cholecystolithiosis patients could significantly promote the formation of BALB/c3T3 cell transformation (P = 0.0233). The bile from symptomatic patients was much more active in tumor promotion than that from asymptomatic patients (P < 0.05). CONCLUSION: The bile in cholecystolithiasis patients exhibits a tumor-promoter activity, which may account for the high incidence of GBC among cholecystolithiasis patients.

3T3 Cells↗

PubMed2001

Photophysical process of hexadecyl 4-biphenylamino benzoate.

The photophysical properties of hexadecyl 4-biphenylamino benzoate (HBAB), the molecule of which possesses a polar end composed of donor (triphenylamino group) and acceptor (ester group) and a long non-polar alkyl tail, have been carefully studied in different conditions. The results show that the twisted intramolecular charge transfer (TICT) emission is given in polar solvents at room temperature and intramolecular charge transfer (ICT) emission is given at 77 K. These can be supported by the solvent effect, temperature effect and the quenching process.

Acetates↗

PubMed2001

Sperm protein 17 is a novel cancer-testis antigen in multiple myeloma.

Various studies have demonstrated the aberrant expression of normal testicular proteins in neoplastic cells. These proteins collectively form the new class of tumor antigens called cancer-testis (CT) antigens. Their selective normal tissue expression makes them ideal antigens for immune targeting of the malignant disease. In this study, the expression of a spermatozoa protein, Sp17, in multiple myeloma was investigated. It was found that Sp17 is detectable in tumor cells from 12 of 47 (26%) myeloma patients. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis detected Sp17 transcripts and proteins, respectively. Northern blot analysis and RT-PCR demonstrated that Sp17 transcripts were detected only in normal testis, supporting its tissue specificity. Since a high proportion of normal individuals develop antibodies against Sp17 following vasectomy, Sp17 is likely to be a highly immunogenic protein in vivo. Sp17 is therefore a novel member of the CT antigen family and should be an ideal target for immunotherapy of multiple myeloma.

Antigens, Neoplasm↗

PubMed2001

Pronociceptive actions of dynorphin maintain chronic neuropathic pain.

Whereas tissue injury increases spinal dynorphin expression, the functional relevance of this upregulation to persistent pain is unknown. Here, mice lacking the prodynorphin gene were studied for sensitivity to non-noxious and noxious stimuli, before and after induction of experimental neuropathic pain. Prodynorphin knock-out (KO) mice had normal responses to acute non-noxious stimuli and a mild increased sensitivity to some noxious stimuli. After spinal nerve ligation (SNL), both wild-type (WT) and KO mice demonstrated decreased thresholds to innocuous mechanical and to noxious thermal stimuli, indicating that dynorphin is not required for initiation of neuropathic pain. However, whereas neuropathic pain was sustained in WT mice, KO mice showed a return to baselines by post-SNL day 10. In WT mice, SNL upregulated lumbar dynorphin content on day 10, but not day 2, after injury. Intrathecal dynorphin antiserum reversed neuropathic pain in WT mice at post-SNL day 10 (when dynorphin was upregulated) but not on post-SNL day 2; intrathecal MK-801 reversed SNL-pain at both times. Opioid (mu, delta, and kappa) receptor density and G-protein activation were not different between WT and KO mice and were unchanged by SNL injury. The observations suggest (1) an early, dynorphin-independent phase of neuropathic pain and a later dynorphin-dependent stage, (2) that upregulated spinal dynorphin is pronociceptive and required for the maintenance of persistent neuropathic pain, and (3) that processes required for the initiation and the maintenance of the neuropathic pain state are distinct. Identification of mechanisms that maintain neuropathic pain appears important for strategies to treat neuropathic pain.

Animals↗

PubMed2001

Synthesis of the C8-deoxyguanosine adduct of the food mutagen IQ.

[structure: see text] The C8-2'-deoxyguanosine adduct of the food mutagen 2-amino-3-methylimadazo[4,5-f]-quinoline (IQ) has been synthesized. The key step is a palladium-catalyzed N-arylation of a suitably protected 8-bromo-2'-deoxyguanosine derivative.

Biotransformation↗

PubMed2001

Safety and immunogenicity trial in adult volunteers of a human papillomavirus 16 L1 virus-like particle vaccine.

BACKGROUND: Studies in animal models have shown that systemic immunization with a papillomavirus virus-like particle (VLP) vaccine composed of L1, a major structural viral protein, can confer protection against subsequent experimental challenge with the homologous virus. Here we report results of a double-blind, placebo-controlled, dose-escalation trial to evaluate the safety and immunogenicity of a human papillomavirus (HPV) type 16 (HPV16) L1 VLP vaccine in healthy adults. METHODS: Volunteers were given intramuscular injections with placebo or with 10- or 50-microg doses of HPV16 L1 VLP vaccine given without adjuvant or with alum or MF59 as adjuvants at 0, 1, and 4 months. All vaccine recipients were monitored for clinical signs and symptoms for 7 days after each inoculation. Immune responses were measured by an HPV16 L1 VLP-based enzyme-linked immunosorbent assay (ELISA) and by an HPV16 pseudovirion neutralization assay. The antibody titers were given as the reciprocals of the highest dilution showing positive reactivity in each assay. All statistical tests were two-sided. RESULTS: The prevaccination geometric mean ELISA titer for six seropositive individuals was 202 (range, 40--640). All vaccine formulations were well tolerated, and all subjects receiving vaccine seroconverted. Serum antibody responses at 1 month after the third injection were dose dependent in recipients of vaccine without adjuvant or with MF59 but were similar at both doses when alum was the adjuvant. With the higher dose, the geometric means of serum ELISA antibody titers (95% confidence intervals) to purified VLP 1 month after the third injection were as follows: 10,240 (1499 to 69 938) without adjuvant, 10,240 (1114 to 94 145) with MF59, and 2190 (838 to 5723) with alum. Responses of subjects within each group were similar. Neutralizing and ELISA antibody titers were highly correlated (Spearman correlation =.85), confirming that ELISA titers are valid proxies for neutralizing antibodies. CONCLUSIONS: The HPV16 L1 VLP vaccine is well tolerated and is highly immunogenic even without adjuvant, with the majority of the recipients achieving serum antibody titers that were approximately 40-fold higher than what is observed in natural infection.

Adjuvants, Immunologic↗

PubMed2001

Characterization and identification of a "mystery" oil spill from Quebec (1999).

This paper describes a case study in which advanced chemical fingerprinting and data interpretation techniques were used to characterize the chemical compositions and determine the source of an unknown spilled oil from Quebec. On 28 February 1999, significant amounts of oil was reported on the river banks of St. Laurence River in front of a company named "Thermex" (in a town - Beauharnois, Quebec, about 50 km northwest of Montreal). The spilled oil was suspected to be released from a nearby factory. In response to this specific site investigation needs, a tiered analytical approach using GC-MS and GC-flame ionization detection was applied. A variety of diagnostic ratios of "source-specific marker" compounds, in particular isomers of biomarkers and alkylated series of polycyclic aromatic hydrocarbons within the same alkylation groups, were determined and analyzed. The hydrocarbon analysis results reveal the following: (1) the spilled oil is very "specific", and is significantly different from most crude oils in chemical composition; (2) the oil in samples come from the same source, however, the spill sample 2569 was identified to contain a small amount (approximately 10%) of diesel; (3) the spilled oil was relatively "fresh", its chemical composition has not undergone significant alteration yet; (4) the spilled oil showed unusually high concentration of the US Environmental Protection Agency priority polycyclic aromatic hydrocarbons (PAHs). The "Pyrogenic Index" values were determined to be as high as 0.11-0.13, significantly higher than crude oils (<0.010) and heavy Bunker type fuels (0.015-0.060). This indicates significant contribution of PAH composition from pyrogenic components; (5) biomarkers were also detected, but their concentrations were unusually low in comparison to most crude oils.

Chromatography, Gas↗