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Biomedical subjects

X Wang

Publications and source records attributed to X Wang.

At least 433 records · Page 24Linked to original sources

Integrating water-quality management and land-use planning in a watershed context.

The spatial relationships between land uses and river-water quality measured with biological, water chemistry, and habitat indicators were analyzed in the Little Miami River watershed, OH, USA. Data obtained from various federal and state agencies were integrated with Geographic Information System spatial analysis functions. After statistically analyzing the spatial patterns of the water quality in receiving rivers and land uses and other point pollution sources in the watershed, the results showed that the water biotic quality did not degrade significantly below wastewater treatment plants. However, significantly lower water quality was found in areas downstream from high human impact areas where urban land was dominated or near point pollution sources. The study exhibits the importance of integrating water-quality management and land-use planning. Planners and policy-makers at different levels should bring stakeholders together, based on the understanding of land-water relationship in a watershed, to prevent pollution from happening and to plan for a sustainable future.

Agriculture↗

Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase.

Hypertrophy is an adaptive response of the heart to myocardial injury or hemodynamic overload that may progress and contribute to cardiac decompensation and eventually to heart failure. The signaling pathways controlling this response in the cardiac myocyte are poorly understood. A data mining effort of a human failed heart cDNA library was undertaken in an effort to identify novel signaling molecules involved in cardiac hypertrophy. This effort identified a novel kinase (MLK7) homologous to the mixed lineage kinase family of proteins. The mixed lineage kinases are mitogen-activated protein kinase kinase kinases (MAPKKKs) which activate stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase pathways. They contain a catalytic domain with homology to both serine/threonine and tyrosine-specific kinases and a dual leucine zipper. MLK7 is identical to leucine zipper and sterile-alpha motif protein kinase (ZAK) through the leucine zipper domain but has a completely divergent COOH-terminus and shares approximately 40% homology with the other MLKs overall. Expression of MLK7 mRNA is most abundant in skeletal muscle and heart, with expression restricted to the cardiac myocyte. The recombinant histidine tagged MLK7 expressed and purified from insect cells exhibited serine/threonine kinase activity in vitro with myelin basic protein as substrate. When expressed in cardiac myocytes, MLK7 activated SAPK/JNK1, and ERK and p38 to a lesser extent. Additionally, MLK7 altered fetal gene expression and increased protein synthesis in cardiac myocytes. These data suggest that MLK7 is a new member of the mixed lineage kinase family that modulates cardiac SAPK/JNK pathway and may play a role in cardiac hypertrophy and progression to heart failure.

Adult↗

Active specific immunotherapy of malignant melanoma and peptide mimics of the human high-molecular-weight melanoma-associated antigen.

The realization that tumor cells utilize multiple mechanisms to escape from immune recognition and destruction has stimulated interest in developing and applying immunotherapeutic strategies which target both humoral and cellular immunity to malignant cells. As a result, the tumor-associated antigens (TAA) used as targets have to be expressed on the cell surface membrane of malignant cells. Furthermore, since most of the TAA used for active specific immunotherapy are self-antigens, a challenge facing tumor immunologists is to develop strategies which are effective in breaking tolerance to self-antigens. This chapter describes one strategy which relies on the use of peptide mimics of the human high-molecular-weight melanoma-associated antigen (HMW-MAA) as immunogens to implement active specific immunotherapy in patients with malignant melanoma. These mimics, which are isolated from phage display peptide libraries by panning with anti-HMW-MAA monoclonal antibodies, are expected to induce both humoral and cellular anti-HMW-MAA immunity.

Animals↗

The relationship of CyclinD1 and estrogen receptor expression in the process of proliferation and metastasis in breast neoplasm.

The role of CyclinD1 and estrogen receptor (ER) in the process of proliferation and metastasis of breast neoplasm and their relationship were studied. The expression levels of CyclinD1 and ER in the tissue samples were detected by using flow cytometry and L SAB immunohistochemistry staining, respectively. The results showed that CyclinD1 and ER expression levels in breast cancer were significantly higher than in benign breast neoplasm (P < 0.05). The CyclinD1 expression levels in stage I was much lower than in stages II, III, IV (P < 0.05). The positive rate of ER was not related with tumor size, lymph node metastasis and TNM stage (P > 0.05), but the CyclinD1 expression level in ER (+) group was significantly higher than in ER (-) group (P < 0.05). It was concluded that CyclinD1 expression level might be obviously related with the proliferation and metastasis of breast neoplasm and ER.

Adenocarcinoma↗

An experimental study on the regulation of expression of Th2 cytokines from T lymphocytes by protein kinase C in asthma.

To explore the regulatory role of protein kinase C (PKC) in the expression of Th2 cytokines, interleukin-4 (IL-4) and interleukin-5 (IL-5) by T lymphocytes in asthma. T lymphocytes were isolated and purified from blood and bronchial alveolus lavage fluid (BALF) of each guinea pig of normal control group and asthmatic group and from peripheral blood of the asthmatic patients and normal controls, and were stimulated with PKC accelerant phorbol 12-myristate 13-acetate (PMA) and inhibitor Ro31-8220. The expression of IL-4 and IL-5 mRNA and protein was detected by using in situ hybridization staining and ELISA respectively. The expression of IL-4 and IL-5 mRNA and protein of asthmatic T lymphocytes stimulated with PMA was significantly higher than that of asthmatic T lymphocytes stimulated without PMA respectively (P < 0.01) and that of normal T lymphocytes stimulated with PMA respectively (P < 0.01). The expression of IL-4 and IL-5 mRNA and protein of asthmatic T lymphocytes stimulated with PMA and Ro31-8220 was significantly lower than that of asthmatic T lymphocytes stimulated only with PMA respectively (P < 0.01). It was concluded that PKC might participate in regulating the expression of IL-4 and IL-5 in asthmatic T lymphocytes, and the activation of PKC in T lymphocytes might play an important role in the pathogenesis of asthma.

Adult↗

Lack of association between alpha2-macroglobulin polymorphisms and Alzheimer's disease.

This study was undertaken to investigate the role of two alpha2-macroglobulin (A2M) polymorphisms, an intronic 5-bp deletion and Ile1000Val, in the development of Alzheimer's disease (AD) and to evaluate the interaction between the apolipoprotein E (APOE) and A2M polymorphisms. The A2M polymorphisms were screened by using polymerase-chain-reaction-based assays in 555 white late-onset AD cases and 446 controls. The gentoype distributions of the 5-bp deletion and Ile1000Val polymorphisms were comparable between cases and controls (P = 0.158 and P = 0.148, respectively). Likewise, there was no significant difference in allele frequencies of each polymorphism among cases and controls (P = 0.361 and P = 0.062, respectively). The stratification of data by APOE*4 status also did not yield any significant association. In conclusion, we observed no association between either the intronic deletion polymorphism or the Ile1000Val polymorphism of A2M and AD in our case-control cohort.

Aged↗

Epitope mapping of human herpesvirus-7 gp65 using monoclonal antibodies.

Human herpesvirus (HHV)-7 encodes a unique 65-kDa heparin-binding glycoprotein, designated gp65. This molecule is thought to play a role in virus attachment and entry. To obtain reagents to map the structure and function of HHV-7 gp65, we produced monoclonal antibodies to this molecule. Ten monoclonal antibodies reacting with gp65 on ELISA were subdivided in four groups on the basis of their isotype and differential reactivity with (i) native versus denatured forms of gp65, and (ii) mature (virion-associated) versus immature (cell-associated) forms of the molecule. We were able to map the binding epitopes for eight of these ten antibodies, and these were found to cluster to one site on gp65 (amino acids 239-278); within this region, the antibodies reacted with at least three distinct domains (244-251, 255-262, 263-278). The reasons for the apparent immunodominance of this region are uncertain. Taken together, this panel of antibodies constitutes an extensive and well-characterized set of HHV-7 specific antibodies that may have utility for future analyses of the structure/function of gp65, and for studies on the virus life cycle.

Amino Acid Sequence↗

Identification of three missense mutations in the peroxisome proliferator-activated receptor alpha gene in Japanese subjects with maturity-onset diabetes of the young.

We screened the protein-coding region of the peroxisome proliferator-activated receptor alpha gene (PPARA) and the flanking intron sequences for mutations in 57 unrelated Japanese subjects with maturity-onset diabetes of the young (MODY). We found three missense mutations, designated P22R, D140Y, and V227A. The D140Y and V227A mutations were found at similar frequencies in MODY and in nondiabetic Japanese subjects, suggesting that they were unlikely to be pathogenic. The P22R mutation was found in a single female subject with MODY. Two of her four siblings, all of whom were diagnosed with diabetes before age 35 years, also inherited the P22R mutation. However, two other diabetic siblings had not inherited the mutant allele, implying that the P22R mutation was not the cause of MODY in this family. Variation in the coding region of PPARA is unlikely to be a major cause of MODY in Japanese people.

Adult↗

Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells.

The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment.

Animals↗

PKA-dependent phosphorylation of cardiac myosin binding protein C in transgenic mice.

OBJECTIVE: To investigate the physiological role of cAMP-dependent protein kinase A (PKA)-mediated, cardiac myosin binding protein C (MyBP-C) phosphorylation. METHODS: A cardiac MyBP-C cDNA lacking nine amino acids, which contained a phosphorylation site, was made, and subsequently used to generate multiple lines of transgenic mice. Upon confirming that a partial replacement of endogenous protein with transgenic protein occurred, the biochemical and physiological consequences were studied. PKA-dependent phosphorylation assays were used to estimate the phosphorylation states of major cardiac PKA substrates. Myofibril Mg-ATPase activities were also measured. Isolated working heart and whole animal exercise studies were used to measure the physiological changes. RESULTS: Transgenic mice displayed a compensatory response, with PKA-mediated phosphorylation of both troponin I and phospholamban showing significant increases. The remaining endogenous cardiac MyBP-C also showed increased phosphorylation levels. Maximal Mg(2+)-ATPase activity was increased. Significant functional changes at both the whole organ and whole animal levels also occurred. Parameters reflecting cardiac contractility and relaxation increased about 22 and 25%, respectively, in the mutant relative to wild type mice (n=5, P<0.001). In young adults the capacity for stress exercise, quantitated using an exercise treadmill regimen, was substantially enhanced (n=6, P<0.01). CONCLUSIONS: Cardiac MyBP-C phosphorylation plays an important physiological role and that the protein's degree of phosphorylation is coordinated with the phosphorylation levels of other proteins within the contractile apparatus.

Animals↗

Effects of homocysteine on murine splenic B lymphocyte proliferation and its signal transduction mechanism.

OBJECTIVE: Elevated plasma homocysteine (Hcy) levels have been defined as an increased risk of atherosclerosis. However, the mechanisms that Hcy induces the development of atherosclerosis are not fully understood. Therefore, effect of Hcy on B lymphocyte proliferation and its cellular mechanism were examined in normal and hyperhomocysteinemia ApoE-knockout mice. METHODS: Mouse B lymphocytes were incubated with Hcy, related compounds and/or antioxidants and/or inhibitors of PKC, p38 MAPK, NF-kappaB in the presence or absence of lipopolysaccharide. DNA synthesis, production of reactive oxygen species was measured. RESULTS: Hcy (0.1-3.0 mM) and other compounds with thiol (-SH), such as cysteine and glutathione significantly increased resting and lipopolysaccharide-induced B lymphocyte proliferation. ApoE-knockout mice with hypercysteinemia (plasma Hcy levels were 20.3+/-2.9 vs. 2.6+/-0.6 microM in control, P<0.05) had a significant promotion of B cell proliferation in response to lipopolysaccharide. Hcy also increased intracellular reactive oxygen species production. Radical scavengers reduced Hcy-induced B lymphocyte proliferation. The promotion of Hcy was significantly inhibited by inhibitors of PKC (calphostin C and RO-31-8220), p38 MAPK (SB 202190 and PD 169316) and NF-kappaB (pyrrolidine dithiocarbamate). CONCLUSIONS: The reactive oxygen species generated by thiol (-SH) auto-oxidation of Hcy are essential, and PKC, p38 MAPK and NF-kappaB are involved in the Hcy-induced B lymphocyte proliferation. Hyperhomocysteinemia may increase B lymphocyte susceptibility to inflammatory progression of atherosclerotic lesions.

Analysis of Variance↗

Optimal decolorization and kinetic modeling of synthetic dyes by Pseudomonas strains.

Pseudomonas spp were isolated from an anaerobic-aerobic dyeing house wastewater treatment facility as the most active azo-dye degraders. Decolorization of azo dyes and non-azo dyes including anthraquinone, metal complex and indigo was compared with individual strains and a bacterial consortium consisting of the individual strain and municipal sludge (50 50wt). The consortium showed a significant improvement on decolorization of two recalcitrant non-azo dyes, but little effect on the dyes that the individual strains could degrade to a great or moderate extent. Decolorization of Acid violet 7 (monoazo) by a Pseudomonas strain GM3 was studied in detail under various conditions. The optimum decolorization activity was observed in a narrow pH range (7-8), a narrow temperature range (35-40 degrees C), and at the presence of organic and ammonium nitrogen. Nitrate had a severe inhibitory effect on azo dye decolorization: 10 mg/L led to 50% drop in decolorization activity and 1000 mg/L to complete activity depression. A kinetic model is established giving the dependence of decolorization rate on cell mass concentration (first-order) and dye concentration (half order). The rate increased with temperature from 10 to 35 C, which can be predicted by Arrhenius equation with the activation energy of 16.87 kcal/mol and the frequency factor of 1.49 x 10(11) (mg L)1/2/g DCM min.

Coloring Agents↗

Sorption and cosorption of organic contaminant on surfactant-modified soils.

Three kinds of soils were modified with the cationic surfactants, hexadecyltrimethylammonium (HDTMA) bromide and tetramethylammonium (TMA) bromide to increase their sorptive capabilities. Sorption of chlorobenzene in simulated groundwater by these soils was investigated. HDTMA-modified soil has a higher ability to sorb chlorobenzene from simulated groundwater than unmodified soil. TMA-modified soil did not show the superiority. HDTMA thus can be used to modify soil to improve its sorption capability. Cosorption of chlorobenzene in simulated groundwater in the absence or presence of nitrobenzene and dichloromethane on HDTMA-modified soil was also investigated. Nitrobenzene facilitated sorption of chlorobenzene on all HDTMA-modified soil. Dichloromethane did not influence the sorption of chlorobenzene by HDTMA-modified soil. The results suggest that HDTMA-modified soil is a highly effective sorbent for chlorobenzene and multiple organic compounds did not impede the uptake of chlorobenzene.

Adsorption↗

Acute toxicity of substituted phenols to Rana japonica tadpoles and mechanism-based quantitative structure-activity relationship (QSAR) study.

Acute 12 h and 24 h lethal toxicity (12 h-LC50 and 24 h-LC50) of 31 substituted phenols to Rana japonica tadpoles was determined. Results indicate that toxicity of phenols to tadpoles varied only slightly with length of exposure and the 12-h test could serve as surrogate of the 24-h test. A mechanism-based quantitative structure-activity relationship (QSAR) method was employed and 1-octanol/water partition coefficient (log K(ow))-dependent models were developed to study different modes of toxic action. Most phenols elicited their response via a polar narcotic mechanism and an excellent logK(ow)-dependent model was obtained. Soft electrophilicity and pro-electrophilicity were observed for some phenols and a good log K(ow)-dependent model was also achieved. Additionally, the significant dissociation of carboxyl on benzoic acid derivatives sharply reduced their toxicity. A statistically robust QSAR model was developed for all studied compounds with the combined application of log K(ow), energy of lowest unoccupied orbital (E(lumo)), heat of formation (HOF) and the first-order path molecular connectivity dices (1chi(p)).

Animals↗

Specific association of 36Cl with low molecular weight humic substances in soils.

Soils initially contaminated with 36Cl in the chloride form were subjected to solid-liquid extractions using a variety of reagents including deionised water and 1 M sodium hydroxide (NaOH). 1 M NaOH was found to result in the greatest recovery of 36Cl from the soils, a result which provided initial evidence that radioactive chlorine became attached to humic substances present naturally within the soils. Deionised water and 1 M NaOH extracts were subjected to analysis involving separation by gel filtration chromatography (GFC). It was found that 36Cl in 1 M NaOH extracts associated preferentially with low molecular weight (LMW) fractions of humic substances whereas, in deionised water extracts, 36Cl appeared to be present exclusively in the chloride form. Previous literature evidence, mainly from highly organic forest soils, suggests that conversion of stable chlorine from chloride to organic forms can occur as a result of biological action. The present paper also presents good evidence for the specific attachment of stable chlorine (37Cl) to a LMW humic fraction, again demonstrated using GFC separation. Current risk assessments of the deep geological disposal of solid radioactive wastes containing 36Cl typically assume a very low degree of sorption based on the notion that the predominant environmental species of radiochlorine is chloride. This paper concludes with a brief discussion on the implications of organochlorine formation in the biosphere for assessment of the radiological impact of deep geological disposal of solid radioactive wastes.

Adsorption↗

Effects of redox potential and pH value on the release of rare earth elements from soil.

Equilibrium release experiments were conducted under three different pH values of 3.5, 5.5 and 7.5 as well as three redox potentials of 400, 0 and -100 Mv to investigate the influence of redox potential and pH value on the La, Ce, Gd and Y release of from the simulated-REEs-accumulation (SRA) soil. Oxygen and nitrogen were allowed to flow into soil suspension to adjust redox potential to a preset value, and 1 mol/l HCl or 1 mol/l NaOH solutions were added into the soil suspension to keep pH at a preset value. Results indicated that La, Ce, Gd and Y release increased gradually with the decrease of pH value or Eh, and the influence of redox potential on Ce was more remarkable than on La, Gd and Y. At the same time. It was observed that La, Ce, Gd and Y releases were positively correlated with the release of Fe and Mn, indicating that La, Ce, Gd and Y releases might originate from dissolution of Fe-Mn oxyhydroxides under reduction and low pH conditions. Moreover, it was found that alteration of pH value and redox potential might affect the change of La, Ce, Gd and Y species in the soil. The contents of La, Ce, Gd and Y in exchangeable fraction and Fe-Mn oxide fraction in the solid phase from soil suspension separation decreased with the decline of pH value and redox potential. Multiple stepwise regression analysis showed that exchangeable fraction and Fe-Mn oxide fraction predominately contributed to the La, Ce, Gd and Y release. Low pH value and redox potential were more favorable to La, Ce, Gd and Y releases following the change of their species. The La, Ce, Gd and Y contents in exchangeable fraction and Fe-Mn oxide fraction are the main contributors to their release.

Biological Availability↗

Validation of germination rate and root elongation as indicator to assess phytotoxicity with Cucumis sativus.

Germination rate and root elongation, as a rapid phytotoxicity test method, possess several advantages, such as sensitivity, simplicity, low cost and suitability for unstable chemicals or samples. These advantages made them suitable for developing a large-scale phytotoxicity database and especially applicable for developing quantitative structure-activity relationship (QSAR) to study mechanisms of phytotoxicity. In this paper, the comparative inhibition of germination rate and root elongation of Cucumis sativus by selected halogen-substituted phenols and anilines were determined. The suitability of germination rate and root elongation as phytotoxicity endpoints was evaluated. Excellent reproducibility and stability of germination rate and root elongation in the control test, relatively greater sensitivity and similar dose-response relations for all tested compounds were observed. These results together with those of a 2-day test were used to demonstrate the suitability of this phytotoxicity test method. A QSAR was developed for the phytotoxicity mode of action of the tested compounds to C sativus seeds. Models that combined the logarithm of 1-octanol/water partition coefficient (log Kow) and the energy of the lowest unoccupied molecular orbital (Elumo) were developed for both germination rate inhibition and root elongation inhibition. The results of these studies indicate that phytotoxicity of substituted phenols and anilines to C. sativus seeds could be explained by a polar narcosis mechanism. This paper will promote the application of germination rate and root elongation method and the development of large-scale phytotoxicity database, which will provide the fundamental data for QSAR and ecological risk assessment of organic pollutants.

Biomarkers↗

Structural characterization of phosphorylated chitosan and their applications as effective additives of calcium phosphate cements.

Chitosan was phosphorylated by P2O5 in methanesulfonic acid and the product as water-soluble phosphorylated chitosan (P-chitosans) was then characterized by phosphorus elemental analysis, IR and 31P-NMR spectroscopy. Two calcium phosphate cement (CPC) systems, i.e. (1) monocalcium phosphate monohydrate (MCPM) and calcium oxide (CaO) in 1 M phosphate buffer (pH = 7.4) and (2) dicalcium phosphate dihydrate (DCPD) and calcium hydroxide [Ca(OH)2] in 1 M Na2HPO4 solution, were chosen to improve their mechanical properties by the addition of water-soluble P-chitosans with various values for molecular weight, degree of deacetylation (DD) and degree of substitution (DS). The results show that the compressive strength (CS) and Young's modulus of both CPC formulations after setting were obviously increased and setting time was slightly prolonged by adding water-soluble P-chitosan to the liquid phases. When a suitable amount of P-chitosan was used, two improved CPC formulations were obtained with much better mechanical properties while the setting times were not longer than 15 min. The enhancement of compressive strength was due to high Ca2+-binding ability of phosphorylated chitosan, which could tightly bind the newly formed hydroxyapatite (HA) particles together by polymeric chains. It was noted that excessive addition of P-chitosan would lead to slow setting or no setting at all. The hardened CPC samples containing P-chitosan were characterized via X-ray diffraction spectra and scanning electron microscopy. Their leaching experiment was also carried out. The results indicated that P-chitosan-forced calcium phosphate cements have some good characteristics for clinical applications.

Bone Cements↗