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Biomedical subjects

W Zhang

Publications and source records attributed to W Zhang.

At least 415 records · Page 23Linked to original sources
PubMed2000

Segregation analysis of esophageal cancer in a moderately high-incidence area of northern China.

In order to explore the mode of inheritance of esophageal cancer in a moderately high-incidence area of northern China, we conducted a pedigree survey on 225 patients affected by esophageal cancer in Yangquan, Shanxi Province. Segregation analysis was performed using the REGTL program of S.A.G.E. The results showed that Mendelian autosomal recessive inheritance of a major gene that influences susceptibility to esophageal cancer provided the best fit to the data. In the best-fitting recessive model, the frequency of the disease allele was.2039. There was a significant sex effect on susceptibility to the disease. The maximum cumulative probability of esophageal cancer among males with the AA genotype was 100%, but, among females, it was 63.5%. The mean age at onset for both men and women was 62 years. The age-dependent penetrances for males with the AA genotype by the ages of 60 and 80 years were 41.6% and 95.2%, respectively, whereas, for females, they were 26.4% and 60.5%, respectively. Incorporating environmental risk factors-such as cigarette smoking, pipe smoking, alcohol drinking, eating hot food, and eating pickled vegetables-into the models did not provide significant improvement of the fit of the models to these data. The results suggest a major locus underlying susceptibility to esophageal cancer with sex-specific penetrance.

Adult↗
PubMed2000

Photolysis of ((3-(Trimethylsilyl)propoxy)phenyl)phenyliodonium salts in the presence of 1-naphthol and 1-methoxynaphthalene

Direct photolysis of ((3-trimethylsilylpropoxy)phenyl)phenyliodonium salts with different counteranions (Cl(-), SbF(6)(-), and B(C(6)F(5))(4)(-)) in methanol leads to products by both heterolytic and homolytic processes. In the presence of 1-naphthol and 1-methoxynaphthalene, products formed by a heterolytic reaction disappear, suggesting an electron-transfer process occurs between excited 1-naphthol/1-methoxynaphthalene and the iodonium salts. In the case of 1-methoxynaphthalene, three phenylated methoxynaphthalene isomers are produced. These are produced as radical coupling products from the phenyl radical and 1-methoxynaphthalene radical cation.

Journal Article↗
PubMed2000

Novel chiral bisoxazoline ligands with a biphenyl backbone: preparation, complexation, and application in asymmetric catalytic reactions

Novel C(2)-symmetric chiral bisoxazoline ligands 1 were easily prepared from enantiomerically pure 2-amino alcohols and achiral 2, 2'-biphenyldicarboxylic acid via the corresponding amide and mesylate as intermediates. Since these ligands bear only two ortho-substituents on the biphenyl backbone, the biphenyl axis is not fixed, and the two diastereomers of these ligands exist in equilibrium in solution. Interestingly, when the ligands 1 were coordinated with a metal ion, only one of the two possible diastereomer complexes, an (S,aS,S)-complex, can be formed depending on the combination of the ligand and the metal ion. Thus, copper(I) afforded only the (S,aS,S)-complexes with all ligands 1, while zinc(II), palladium(II), and silver(I) afforded the (S,aS, S)-complexes as the sole product only with 1b, which has a bulky tert-butyl group on the oxazoline ring, and a mixture of the two diastereomer complexes with 1a,c,d. The copper(I)-catalyzed asymmetric cyclopropanation of styrene with diazoacetate proceeded successfully with these ligands and good to excellent enantioselectivities were afforded.

Journal Article↗
PubMed2000

ProFound: an expert system for protein identification using mass spectrometric peptide mapping information.

We describe the protein search engine "ProFound", which employs a Bayesian algorithm to identify proteins from protein databases using mass spectrometric peptide mapping data. The algorithm ranks protein candidates by taking into account individual properties of each protein in the database as well as other information relevant to the peptide mapping experiment. The program consistently identifies the correct protein(s) even when the data quality is relatively low or when the sample consists of a simple mixture of proteins. Illustrative examples of protein identifications are provided.

Algorithms↗
PubMed2000

Conserved amino acids in metal-binding motifs of PDE3A are involved in substrate and inhibitor binding.

The activity of phosphodiesterase (PDE)3A requires divalent cations. Putative metal-binding sites are expected at 2 highly conserved metal-binding motifs, HXXXH(X)(25)E. A functional truncated recombinant PDE3A containing the catalytic domain (PDE3Atriangle up1) and mutant proteins were expressed in a baculovirus/Sf9 cell system. All the mutant proteins had decreased catalytic efficiency (k(cat)/K(m)). Mutants H752A, H756A, and E825A had k(cat) of less than 0.0008 s(-1) to 0.0475 s(-1) compared to PDE3Atriangle up1, with 1.86 second(-1), with unchanged K(m). Although E866A had a k(cat) of 0.235 s(-1), the K(m) for cyclic adenosine monophosphate (cAMP) was increased 11-fold and the K(i) for cyclic guanosine monophosphate (cGMP) was 27-fold higher than PDE3Atriangle up1. The K(i) of H836A for cGMP was 177-fold higher than that of PDE3Atriangle up1. The K(m) for E971A was 5-fold higher than PDE3Atriangle up1. These results suggest that the cAMP and cGMP binding sites are overlapping, but not identical, involving both common and different amino acids. Mutants E825A, H836A, and E866A showed low activity in a metal ion-free assay; however, their enzymatic activities were increased 4- to 10-fold in buffers containing Mn(2+), Mg(2+), or Co(2+). This observation indicates that conserved amino acids in the second metal-binding motif might not be involved in binding divalent cations but may serve other functions such as substrate or inhibitor binding in PDE3A.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

Reaction of reducing hydroxyl radical adducts of pyrimidine nucleotides with riboflavin and flavin adenine dinucleotide (FAD) via electron transfer: a pulse radiolysis study.

Using the techniques of pulse radiolysis with time-resolved spectrophotometric detection, it has been demonstrated that the interaction of reducing OH radical adducts of dCMP, TMP and UMP with riboflavin (RF) and flavin adenine dinucleotide (FAD) does proceed via an electron transfer reaction. From buildup kinetics of radical species, the rate constants of electron transfer from reducing OH adducts of pyrimidines to RF and FAD have been determined, respectively. It could be deduced that RF and FAD would reduce the probability of repair of the damaged DNA in the presence of enzymes and antioxidants, accordingly RF and FAD might have a radiosensitization effect on DNA damage.

DNA↗
PubMed2000

[Rapid determination of the ozone in water].

A new potassium iodide--N, N-diethy1-1,4-phenylen-ediammonium sulfate (DPD) spectrophotometry method for the determination of the ozone in water was established. The method was based on the quantitative reaction between the ozone and potassium iodide in buffered solution(pH 3.35): O3 + 2I- + 2H+-->O2 + I2 + H2O. Iodine could react with DPD regent and produce pink color. Its absorption was determined at 510 nm with spectrophotometer. The range of direct determination was 0-1.00 mg/L. Beer's law was obeyed in this range. The detection limit was 0.01 mg/L. The relative standard deviations were from 1.2% to 2.7% (n = 10). The recoveries were from 98.6% to 106.6%. Water samples were determined with both this method and iodimetry. The results were comparable. The method was applied to the determination of the ozone in water sample with satisfactory results. It was practical and reliable.

Ozone↗
PubMed2000

[Arthroscopic meniscus plasty of the discoid cartilage of the knee joint].

From 1989 to 1998, arthroscopic discoid lateral meniscus plasty was performed in twenty-eight patients(thirty-one joints), and evaluated in a short follow-up term. The mean age was 21.5(6-42) years. The average follow-up period lasted 8.4 months. The results were assessed by the Ikeuchi's grading, 87.1% joints had excellent and good results, including all incomplete types and 77.8% complete type of discoid meniscus. It is suggested that arthroscopic meniscus plasty plays an important role in the treatment of discoid meniscus of knee, and should be performed possibly as soon as the disease was diagnosed by arthroscopic examination.

Adolescent↗
PubMed2000

Event-related brain potentials elicited by a number discrimination task.

To study the number cognition process, we recorded event-related potentials (ERPs) in 14 subjects when they were indicating whether a number pair was the same or not. The two numbers given in sequence were either the same (condition 1) or different (condition 2). After 270 ms following the onset of the second stimulus in condition 2, a negative component N270 was recorded on the scalp with the most negative amplitude at the central and occipital areas. Hemispheric asymmetry was not observed in the potential. This negative component is considered to reflect the mismatching process for numbers in the brain.

Adult↗
PubMed2000

qBrain-2, a POU domain gene expressed in quail embryos.

We isolated a quail class III POU domain gene, qBrain-2, which was cloned from a cDNA library of E5 embryos. Northern blot and in situ hybridization analyses showed that qBrain-2 was expressed in developing central nervous system and adult brain. Moreover, qBrain-2 transcripts showed a dynamic distribution in embryonic central nervous system. Its transcripts were dominantly detected in the ventricular zone of the developing brain and spinal cord, but rarely in the differentiated region of mantle zone as well as the non-neuronal roof plate and floor plate. This suggests that qBrain-2 is involved in proliferation and differentiation of the neuroepithelial cells of quail central nervous system.

Amino Acid Sequence↗
PubMed2000

Familial juvenile hyperuricemic nephropathy: localization of the gene on chromosome 16p11.2-and evidence for genetic heterogeneity.

Familial juvenile hyperuricemic nephropathy (FJHN), is an autosomal dominant renal disease characterized by juvenile onset of hyperuricemia, gouty arthritis, and progressive renal failure at an early age. Using a genomewide linkage analysis in three Czech affected families, we have identified, on chromosome 16p11.2, a locus for FJHN and have found evidence for genetic heterogeneity and reduced penetrance of the disease. The maximum two-point LOD score calculated with allowance for heterogeneity (HLOD) was 4.70, obtained at recombination fraction 0, with marker D16S3036; multipoint linkage analysis yielded a maximum HLOD score of 4.76 at the same location. Haplotype analysis defined a 10-cM candidate region between flanking markers D16S501 and D16S3113, exhibiting crossover events with the disease locus. The candidate interval contains several genes expressed in the kidney, two of which-uromodulin and NADP-regulated thyroid-hormone-binding protein-represent promising candidates for further analysis.

Adolescent↗
PubMed2000

Regulation of expression of the human beta-1,2-N-acetylglucosaminyltransferase II gene (MGAT2) by Ets transcription factors.

Oncogenic transformation of fibroblasts by the src oncogene has long been known to cause an increase in the size of cell-surface protein-bound oligosaccharides, owing primarily to increased N-glycan branching mediated by increased beta-1,6-N-acetylglucosaminyltransferase V (GnT V) activity. The src-responsive element of the GnT V promoter was localized to Ets-binding sites and the promoter was transcriptionally stimulated by both ets-1 and ets-2 expression [Buckhaults, Chen, Fregien and Pierce (1997) J. Biol. Chem. 272, 19575-19581; Kang, Saito, Ihara, Miyoshi, Koyama, Sheng and Taniguchi (1996) J. Biol. Chem. 271, 26706-26712]. Because GnT V action requires the prior action of beta-1,2-N-acetylglucosaminyltransferase II (GnT II) and the human GnT II promoter contains four putative Ets-binding sites [Chen, Zhou, Tan and Schachter (1998) Glycoconj. J. 15, 301-308], GnT II might also be under oncogenic control via Ets transcription factors. We now report that co-transfection into HepG2 or COS-1 cells of either ets-1 or ets-2 expression plasmids together with chimaeric GnT II promoter-chloramphenicol acetyltransferase plasmids results in a 2-4-fold stimulation of promoter activity. Mobility-shift assays and South-Western blots localized the functional Ets-binding site to one of the four putative sites on the GnT II promoter. The GnT II promoter, unlike the GnT V promoter, is not activated by either src or neu. Therefore although both promoters are stimulated by a member of the Ets family of transcription factors, the functional role of this Ets transcriptional control seems to be different for the two genes.

Animals↗
PubMed2000

Terminal osseous dysplasia with pigmentary defects maps to human chromosome Xq27.3-xqter.

We have identified a four-generation family with 10 affected females manifesting one or more of the following features: osseous dysplasia involving the metacarpals, metatarsals, and phalanges leading to brachydactyly, camptodactyly, and other digital deformities; pigmentary defects on the face and scalp; and multiple frenula. There were no affected males. We performed X-inactivation studies on seven affected females, using a methylation assay at the androgen receptor locus; all seven demonstrated preferential inactivation of their maternal chromosomes carrying the mutation, and two unaffected females showed a random pattern. These findings indicate that this disorder is linked to the X chromosome. To map the gene for this disorder, we analyzed DNA from nine affected females and five unaffected individuals, using 40 polymorphic markers evenly distributed throughout the X chromosome. Two-point and multipoint linkage analyses using informative markers excluded most of the X chromosome and demonstrated linkage to a region on the long arm between DXS548 and Xqter. A maximum LOD score of 3.16 at recombination fraction 0 was obtained for five markers mapping to Xq27.3-Xq28. The mapping data should facilitate the identification of the molecular basis of this disorder.

Abnormalities, Multiple↗
PubMed2000

Epitope randomization redefines the functional role of glutamic acid 110 in interleukin-5 receptor activation.

Sequence randomization through functional phage display of single chain human interleukin (IL)-5 was used to investigate the limits of replaceability of the Glu(110) residues that form a part of the receptor-binding epitope. Mutational analysis revealed unexpected affinity for IL-5 receptor alpha chain with variants containing E110W or E110Y. Escherichia coli-expressed Glu(110) variants containing E110W in the otherwise sequence-intact N-terminal half, including a variant with an E110A replacement in the sequence-disabled C-terminal half, were shown by their CD spectra to be folded into secondary structures similar to that of single chain human IL-5 (scIL-5). Biosensor kinetics analysis revealed that (E110W/A5)scIL-5 and (E110W/A6)scIL-5 had receptor alpha chain binding affinities similar to that of (wt/A5)scIL-5. However, (E110W/A6)scIL-5 had a significantly reduced bioactivity in TF-1 cell proliferation compared with both (wt/A5)scIL-5 and (E110W/A5)scIL-5, and this activity reduction was disproportionately greater than the much smaller effect of Glu(110) mutation on receptor binding affinity. The marked and disproportionate decrease in TF-1 proliferation observed with (E110W/A6)scIL-5 suggests a role for Glu(110) in the biological activity mediated by the signal transducing receptor betac subunit of the IL-5 receptor. This is also consistent with the lack of stimulation of JAK2 phosphorylation by the (E110W/A6)scIL-5 mutant in recombinant 293T cells, as compared with the concentration-dependent stimulation seen for scIL-5. The results reveal the dispensability of charge in the Glu(110) locus of IL-5 for receptor alpha chain binding and, in contrast, its heretofore underappreciated importance for receptor activation.

Epitopes↗
PubMed2000

Blocking of CD44-hyaluronic acid interaction prolongs rat allograft survival.

BACKGROUND: Lymphocyte activation and infiltration into a transplanted organ is an integral component of the rejection process. Graft infiltration of lymphocytes requires adhesion of leukocytes to the endothelium, diapedesis, and transmigration. One of several proteins involved in this process is CD44, which is known to interact with endothelial hyaluronan (HA). Blockade of cell-matrix and cell-cell interactions have been used extensively for modulation of immune responses and graft rejection. Based on these observations, we evaluated the effects of blocking CD44-HA interactions in a transplantation model. METHODS: We used a low molecular weight hyaluronic acid formulation (LMWHA) for the treatment of rat renal and cardiac allograft recipients. LMWHA was administered intraperitoneally at 0.5-5 mg/kg for 5-10 days after transplantation with or without a subtherapeutic dose of cyclosporine. RESULTS: LMWHA monotherapy prolonged allograft survival significantly, but only for a few days. In combination with low-dose cyclosporine, long-term survival of allografts was observed in some of recipients. CONCLUSION: Further definition of the underlying mechanism of LMWHA therapy may provide a rationale for the development of novel, nontoxic, nonimmunogenic immunotherapies.

Animals↗
PubMed2000

A simplified procedure for the preparation of MHC/peptide tetramers: chemical biotinylation of an unpaired cysteine engineered at the C-terminus of MHC-I.

Recently, a powerful approach for the detection of MHC/peptide-specific T cells has been made possible by the engineering of soluble-tetrameric MHC/peptide complexes, consisting of singly biotinylated MHC/peptide molecules bound to fluorescent-labeled streptavidin. These tetrameric molecules are thought to compensate for the low affinity and relative fast dissociation rate of the TCR/MHC-peptide interaction by increasing the avidity of this interaction, thus allowing the stable binding of MHC/peptide tetramers to TCR expressing cells. Here we describe a new more simplified procedure for obtaining MHC/peptide tetramers using the well-characterized H-2K(b)/VSV system. This procedure consists of the incorporation of an unpaired cysteine residue at the C-terminus of the H-2K(b) molecule, allowing site-specific biotinylation by a -SH-specific biotinylating reagent. The H-2K(b)/VSV tetramers bound only to hybridomas expressing H-2K(b)/VSV-specific TCRs. When coated on a plate, these tetramers were able to induce IL-2 release by those hybridomas. Furthermore, H-2K(b)/VSV tetramers bound to CTL populations obtained from mice immunized with VSV-peptide. The specificity of the binding was further refined by studying cross-recognition of VSV by CTL populations obtained from mice immunized with single amino acid substituted VSV peptide variants. H-2K(b)/VSV tetramers bound only to those CTL populations that cross-reacted with the wild-type VSV peptide. Our method provides a simple, efficient and inexpensive procedure for making MHC/peptide tetramers, a highly specific and very useful reagent with a number of important applications in basic and clinical T cell research.

Biotinylation↗