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Biomedical subjects

X Wang

Publications and source records attributed to X Wang.

At least 397 records · Page 22Linked to original sources
PubMed2001

In vivo substrates and the contribution of the common phospholipase D, PLDalpha, to wound-induced metabolism of lipids in Arabidopsis.

The common plant phospholipase D (PLD), PLDalpha, has been proposed to be involved in wound-induced production of jasmonic acid. To better understand the role(s) of PLDalpha in the wound response, detailed lipid analysis was carried out to determine the in vivo substrates and the contribution of PLDalpha in wound-induced lipid metabolism in Arabidopsis thaliana. Mechanical wounding of Arabidopsis leaves resulted in significantly less hydrolysis of phosphatidylcholine (PC) in PLDalpha-deficient than in wild-type plants. Hydrolysis of phosphatidylethanolamine, phosphatidylglycerol (PG), and phosphatidylinositol within 30 min of wounding was not significantly different in PLDalpha-deficient and wild-type leaves. Phosphatidic acid (PA) levels increased rapidly in wild-type and, to a lesser extent, in PLDalpha-deficient plants. The acyl composition of the PA generated by wounding suggests that the major in vivo substrate of PLD in wild-type leaves was PC, and that PG hydrolysis accounted for 10-15% of the wound-induced PA in wild-type leaves. Comparison of the acyl compositions of the wound-induced PA of wild-type and PLDalpha-deficient leaves indicated that PLDalpha hydrolyzed PG more readily than other PLD isoforms did. Wounding produced substantial increases in free linoleic and linolenic acids in wild-type plants, whereas PLDalpha-deficient plants showed only a slight increase in linoleic acid and no significant increase in linolenic acid. These results demonstrate that PLDalpha and at least one other PLD isoform, as well as other hydrolytic enzymes, are active in mechanically wounded Arabidopsis leaves, and PLDalpha is involved in wound-induced metabolism of polyunsaturated fatty acids.

Arabidopsis↗
PubMed2001

MDM2 and MDMX can interact differently with ARF and members of the p53 family.

Members of the p53 family of transcription factors have essential roles in tumor suppression and in development. MDM2 is an essential regulator of p53 that can inhibit the transcriptional activity of p53, shuttle p53 out of the nucleus, and target p53 for ubiquitination-mediated degradation. Little is known about the interaction and selectivity of different members of the p53 family (p53, p63, and p73) and the MDM2 family (MDM2 and MDMX). Here we show that the transcriptional activities of p53 and p73, but not that of p63, were inhibited by both MDM2 and MDMX. Consistent with these, we found that MDMX can physically interact with p53 and p73, but not with p63. Moreover, ectopically expressed MDM2 and MDMX could induce alterations in the subcellular localization of p73, but did not affect the subcellular localization of p53 and p63. Finally, we demonstrate that while ARF can interact with MDM2 and inhibit the regulation of p53 by MDM2, no interaction was found between ARF and MDMX. These data reveal that significant differences and selectivity exist between the regulation of different members of the p53 family by MDM2 and MDMX.

ADP-Ribosylation Factors↗
PubMed2001

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗
PubMed2001

Transforming growth factor-beta signaling in cancer.

Transforming growth factor (TGF-beta) is a multifunctional polypeptide implicated in the regulation of a variety of cellular processes including growth, differentiation, apoptosis, adhesion, and motility. Abnormal activation or inhibition of these TGF-beta regulated processes is implicated in many diseases, including cancer. Cancers can develop through selective exploitation of defects in TGF-beta signaling that occur at several different levels in the pathway. The TGF-beta signal transduction cascade is initiated when TGF-beta binds to transmembrane receptors. The TGF-beta receptors then phosphorylate and activate Smad proteins, which transduce the signal from the cytoplasm to the nucleus. In the nucleus, Smads can bind directly to DNA and cooperate with other transcription factors to induce transcription of TGF-beta target genes. Mutations in target genes, Smads, or the TGF-beta receptor are associated with certain human cancers.

DNA-Binding Proteins↗
PubMed2001

Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes.

Using cDNA expression cloning, a cDNA encoding a novel human melanoma Ag, MART-2 (melanoma Ag recognized by T cells-2), recognized by HLA-A1-restricted CD8(+) T cells from tumor-infiltrating lymphocytes (TIL1362) was isolated from an autologous melanoma cell line, 1362 mel. Homologous sequences to the cDNA had been registered in the EST database. This gene encoded an uncharacterized protein expressed ubiquitously in most normal and cancer cells. A mutation (A to G transition) was found in the cDNA obtained from the1362 mel melanoma cell line in the sequences encoding the phosphate binding loop (P-loop) that resulted in loss of the ability to bind GTP. Transfection of NIH-3T3 with the mutated MART-2 did not result in the development of significant foci. By screening 36 various cancer cell lines using single-strand conformation polymorphism, a possible mutation in the P-loop of MART-2 was found in one squamous cell lung cancer cell line, EBC1. The T cell epitope for TIL1362, FLEGNEVGKTY, was identified to be encoded by the mutated sequence of the MART-2 Ag. The mutation substituted glycine in the normal peptide with glutamic acid at the third amino acid of the epitope, which is an important primary anchor amino acid for HLA-A1 peptide binding. The normal peptide, FLGGNEVGKTY, was not recognized by TIL1362, suggesting that this T cell response was specific for the autologous tumor. Although transforming activity was not detected in the NIH-3T3 assay, MART-2 with the mutation in the P-loop may be involved in the generation of melanoma through a loss of GTP binding activity.

3T3 Cells↗
PubMed2001

[Effects of vasoactive peptides on the development of restenosis].

OBJECTIVE: To investigate the effects of several vasoactive peptides on the development of restenosis. METHODS: The model of balloon angioplasty to the rat aorta was prepared and used to study the changes of endothelin (ET), angiotensin II (A II), calcitonin gene-related peptide (CGRP) and adrenomedullin (Adm) in the plasma and aorta tissues, with radioimmuno-assay. (3)H-TdR incorporation and intima/media ratio of aortic tissue were measured after angioplasty. In cultured vascular smooth muscle cells, effects of these peptides on the proliferation of VSMC were evaluated with (3)H-TdR incorporation. Effects of these peptides on the expression of hypertension-related gene (HRG-1) in aorta tissue and cultured VSMC from SHR and WKY rats were studied by semi-quantitative RT-PCR. RESULTS: After angioplasty, the levels of ET and A II in the plasma and/or aorta tissue were significantly increased, with VSMC proliferation. On day 10 after angioplasty, the levels of ET in the plasma and tissue were increased by 69% and 124% respectively, compared with the that in the control group (P < 0.01); and the levels of aortic A II were increased by 80% (P < 0.01). Antiserum against ET and angiotensin converting enzyme (ACE) inhibitors could obviously inhibit the proliferation of VSMC and neointima formation. Compared with the sham group on day 3 after angioplasty, the CGRP levels in plasma and aorta tissue were increased by 64% and 89% respectively (P < 0.01); the Adm levels in the plasma and aorta tissue were increased by 129% and 102% respectively (P < 0.01). On day 10, intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima formation induced by balloon aortic injury with the inhibitory rate of 66% and 79%, respectively, (P < 0.01). ET and A II attenuated the expression of HRG-1 in the aorta, thus activating mitogen activated protein kinase (MAPK). CGRP and Adm potentiated the expression of HRG-1, thus inhibiting the activity of MAPK. CONCLUSIONS: ET and A II stimulate the proliferation of injured intima, and CGRP and Adm have an anti-hyperplasia effects after angioplasty. That these peptides are suggested to be involved in the regulation of proliferation of VSMC and to affect the developing of vascular restenosis, by means of regulating the expression of HRG-1 and MAPK activities.

Adrenomedullin↗
PubMed2001

Inhibitors of p38 MAP kinase increase the survival of transplanted dopamine neurons.

Fetal cell transplantation therapies are being developed for the treatment of a number of neurodegenerative disorders including Parkinson's disease [10-12,21,22,24,36,43]. Massive apoptotic cell death is a major limiting factor for the success of neurotransplantation. We have explored a novel protein kinase pathway for its role in apoptosis of dopamine neurons. We have discovered that inhibitors of p38 MAP kinase (the pyridinyl imidazole compounds: PD169316, SB203580, and SB202190) improve survival of rat dopamine neurons in vitro and after transplantation into hemiparkinsonian rats. In embryonic rat ventral mesencephalic cultures, serum withdrawal led to 80% loss of dopamine neurons due to increased apoptosis. Incubation of the cultures with p38 MAP kinase inhibitors at the time of serum withdrawal prevented dopaminergic cell death by inhibiting apoptosis. In the hemiparkinsonian rat, preincubation of ventral mesencephalic tissue with PD169316 prior to transplantation accelerated behavioral recovery and doubled the survival of transplanted dopamine neurons. We conclude that inhibitors of stress-activated protein kinases improve the outcome of cell transplantation by preventing apoptosis of neurons after grafting.

Animals↗
PubMed2001

HIV-1 envelope is a neutral antagonist to CXCR4 in T-cells.

The chemokine receptor CXCR4 is the principal coreceptor for X4 strains of HIV-1. We show that gp120 is unable to induce interactions between CXCR4 and G-protein in T-cells, but antagonized the agonist effect of SDF-1alpha, the natural ligand for CXCR4. Gp120 had ten times lower affinity for CXCR4 than CD4, implying that a substantial role for cellular CD4 may be to facilitate binding of the viral envelope to CXCR4. Binding of gp120 to CXCR4 was neither regulated by guanine nucleotides, nor affected by divalent cations, was temperature independent and bound to a homogenous population of CXCR4, which is characteristic for an antagonist to a G-protein coupled receptor. In contrast, SDF-1alpha binds to two affinity states of CXCR4 in T-cell membranes, which are modulated by guanine nucleotides. Binding of SDF-1alpha to CXCR4 was highly temperature dependent. Thus, the interaction of CXCR4 with HIV-1 viral envelope and chemokine exhibits fundamental differences.

Cations↗
PubMed2001

Gene expression profile changes in initiation and progression of squamous cell carcinoma of esophagus.

Tumorigenesis is a complex process involving multiple genes. As a step toward understanding the complicated changes between normal and malignant cells, this report focused on gene expression profile variations among normal and abnormal esophageal epithelium tissues. The cDNA microarray approach was used to investigate gene expression profiles of 5 different stages during initiation and progression of esophageal cancer. According to pathological characteristics, these 5 stages were normal, dysplasia I (mild dysplasia), dysplasia II (moderate dysplasia), carcinoma in situ (CIS) and squamous cell carcinoma of esophagus (SCC). Comparing and analyzing those gene expression profiles, we observed that the expression levels of many genes changed in dysplasia I and some known tumor-related genes were over-expressed or under-expressed in all 4 abnormal stages. Using principle component analysis we identified a set of genes that may play an important role in tumor development. Hybridization data were confirmed by semi-quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. These results suggest that cDNA microarray technology is a useful tool to discover genes frequently involved in esophageal neoplasia and provides novel clues to diagnosis, early detection and intervention of SCC.

Carcinoma in Situ↗
PubMed2001

The critical stage of pinealectomy surgery after which scoliosis is produced in young chickens.

STUDY DESIGN: Stages of the surgical procedure for pinealectomy in chickens were identified. Groups of chickens were selected for each stage. Scoliosis development was identified from radiographs. OBJECTIVES: To determine the critical stage of surgery for pinealectomy after which scoliosis develops in young chickens. SUMMARY OF BACKGROUND DATA: Pinealectomy in young chickens consistently produces scoliosis in young chickens that has many characteristics similar to those seen in patients with adolescent idiopathic scoliosis. The mechanism behind this phenomenon remains unknown. METHODS: Five distinct stages in the pinealectomy surgery were identified. Groups of chickens were selected to undergo surgery to represent these five stages. Scoliosis was determined from weekly radiographs. RESULTS: Cutting the pineal stalk was identified as the critical stage in the surgery after which scoliosis developed. The incidence of scoliosis did not increase after more extensive surgery in which the pineal bulb was removed from the skull. This stage was also correlated with a significant reduction of serum melatonin levels. CONCLUSIONS: Cutting the pineal stalk was identified as the critical stage of pinealectomy surgery after which scoliosis may develop. This stage was also correlated with the significant reduction of average serum melatonin levels. These results allow the focus of attention into the mechanism behind this phenomenon to center on the consequences of cutting the pineal stalk rather than total removal of the pineal gland.

Animals↗
PubMed2001

Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation.

A reduced-intensity preparative regimen consisting of melphalan and a purine analog was evaluated for allogeneic transplantation in 86 patients who had a variety of hematologic malignancies and were considered poor candidates for conventional myeloablative therapies because of age or comorbidity. Seventy-eight patients received fludarabine 25 mg/m(2) daily for 5 days in combination with melphalan 180 mg/m(2) (n = 66) or 140 mg/m(2) (n = 12). Eight patients received cladribine 12 mg/m(2) continuous infusion for 5 days with melphalan 180 mg/m(2). The median age was 52 years (range, 22-70 years). Disease status at transplantation was either first remission or first chronic phase in 7 patients, untreated first relapse or subsequent remission in 16 patients, and refractory leukemia or transformed chronic myelogenous leukemia in 63 patients. Nonrelapse mortality rates on day 100 were 37.4% for the fludarabine/melphalan combination and 87.5% for the cladribine/melphalan combination. The median percentage of donor cells at 1 month in 75 patients was 100% (range, 0%-100%). The probability of grade 2-4 and 3-4 acute graft-versus-host disease was 0.49 (95% CI, 0.38-0.60) and 0.29 (95% CI, 0.18-0.41), respectively. Disease-free survival at 1 year was 57% for patients in first remission or chronic phase and 49% for patients with untreated first relapse or in a second or later remission. On multivariate analysis the strongest predictor for disease-free survival was a good or intermediate risk category. In summary, fludarabine/melphalan combinations are feasible in older patients with associated comorbidities, and long-term disease control can be achieved with reduced-intensity conditioning in this population.

Acute Disease↗
PubMed2001

Dinuclear and heteropolynuclear complexes containing Mo2(4+) units.

The quadruply bonded compound Mo2(DpyF)4 (1), where DpyF- is the anion of N,N'-di(2-pyridyl)formamidine, has been prepared by ligand substitution reactions of Mo2(OOCCF3)4 and either the neutral ligand, HDpyF, at ambient temperature or its lithium salt, LiDpyF, under refluxing conditions. An X-ray structural analysis shows that 1 has a paddlewheel structure with a [symbol: see text] distance of 2.1108(6) A. Reaction of 1 with CoCl2 in methanol produces the paramagnetic compound [Mo2Co(DpyF)4][CoCl4].2MeOH (2). The Co(II) atom in the cation [Mo2Co(DpyF)4]2+ resides on a low-spin hexacoordinate environment (S = 1/2) with a Co...Mo separation of 2.979(6) A, suggesting there is no direct bonding interaction between the Co and Mo atoms. The Mo-Mo distance of 2.1096(5) A is similar to that in 1. Reaction of 1 and CuCl in methanol yields [Mo2Cu4(DpyF)4Cl2][CuCl2]2.2MeOHxEt2O (3). In the cation there are two copper atoms on each side of the Mo2 core. Each is coordinated to two pyridyl nitrogen atoms of the cis DpyF- ligands and loosely bridged to the other by a chloride ion. As a result, the Cu(I) atoms are not aligned with the Mo2 unit. The Cu to Mo separations are in the range 3.003(1)-3.015(1) A, and the Mo-Mo distance of 2.127(1) A is comparable to those in 1 and 2.

Journal Article↗
PubMed2001

Cloning and characterization of full-length human ribosomal protein L15 cDNA which was overexpressed in esophageal cancer.

The aim of this investigation was trying to identify the genes differentially expressed in esophageal cancer. By combining suppression subtractive hybridization (SSH) with reverse Northern high density blots, a gene named EC45 was obtained, which dramatically overexpressed in 70% esophageal cancer (18/26). EC45 was mapped to 3p12-3p11.2 by radiation hybrid mapping (RH mapping). The putative full length EC45 cDNA (1987 bp) was identified by cDNA libraries screening of esophageal cancer. EC45 encoded 204 amino acids, and it shared a 100% similarity with ribosomal protein L15 (635 bp, mRNA) in ORF, but no similarity in 5' UTR or 3' UTR. Northern blot panel of multiple adult human normal tissues showed EC45 distributed in almost normal tissues tested. All these data suggested that EC45, encoding ribosomal protein L15 and overexpressing in esophageal cancer might play a possible role in carcinogenesis of esophagus.

Amino Acid Sequence↗
PubMed2001

Effects of histone acetylation on the solubility and folding of the chromatin fiber.

The folding ability of chromatin fractions containing approximately identical nucleosome numbers and the same linker histone composition, but with different extents of core histone acetylation, were analyzed by analytical ultracentrifugation. It was found that the acetylated fractions consistently exhibited a relatively small but significantly lower extent of compaction than that of their native nonacetylated counterparts. This was regardless of the extent of the size distribution heterogeneity of the fractions analyzed. Furthermore the acetylated chromatin fibers exhibited an enhanced solubility in both NaCl and MgCl(2), which is neither the result of a differential binding affinity of the linker histones to chromatin nor of an alteration in the relative amounts of the histone H1 variants.

Acetylation↗
PubMed2001

Interactions between yeast iso-1-cytochrome c and its peroxidase.

Isothermal titration calorimetry was used to study the formation of 19 complexes involving yeast iso-1-ferricytochrome c (Cc) and ferricytochrome c peroxidase (CcP). The complexes comprised combinations of the wild-type proteins, six CcP variants, and three Cc variants. Sixteen protein combinations were designed to probe the crystallographically defined interface between Cc and CcP. The data show that the high-affinity sites on Cc and CcP coincide with the crystallographically defined sites. Changing charged residues to alanine increases the enthalpy of complex formation by a constant amount, but the decrease in stability depends on the location of the amino acid substitution. Deleting methyl groups has a small effect on the binding enthalpy and a larger deleterious effect on the binding free energy, consistent with model studies of the hydrophobic effect, and showing that nonpolar interactions also stabilize the complex. Double-mutant cycles were used to determine the coupling energies for nine Cc-CcP residue pairs. Comparing these energies to the crystal structure of the complex leads to the conclusion that many of the substitutions induce a rearrangement of the complex.

Alanine↗
PubMed2001

Discrete targeting signals direct Pmp47 to oleate-induced peroxisomes in Saccharomyces cerevisiae.

Pmp47 is a peroxisomal membrane protein consisting of six transmembrane domains (TMDs). We previously showed that the second matrix loop containing a basic cluster of amino acids is important for peroxisomal targeting, and similar basic targeting motifs have been found in other peroxisomal membrane proteins. However, this basic cluster by itself targets to peroxisomes very poorly. We have developed a sensitive quantitative localization assay based on the targeting of Pmp47-GFP fusion proteins to identify the important elements of the basic cluster and to search for other targeting information on Pmp47. Our data suggest that side-chain structure and position as well as charge are important for targeting by the basic cluster. Analysis of other regions of Pmp47 indicates that all TMDs except TMD2 can be eliminated or substituted without significant loss of targeting. TMD2 plus an adjacent cytoplasmic-oriented sequence is crucial for targeting. Cytoplasmic-oriented sequences from two other peroxisomal membrane proteins, ScPex15p and ScPmp22, could partially substitute for the analogous sequence in Pmp47. Targeting with high fidelity to oleate-induced peroxisomes required the following elements: the cytoplasmic-oriented sequence and TMD2, a short matrix loop containing a basic cluster, and a membrane-anchoring TMD.

Amino Acid Sequence↗
PubMed2001

Formation of Monolayer Lipid Membranes in Water and Ethanol from Bolaamphiphiles.

Three single-chain bolaamphiphiles containing two salicylidene units per molecule as the rigid segment were synthesized. Their aggregation behavior in water and ethanol has been studied. They can form monolayer membranes not only in water solution but also in pure ethanol. The presence of a relatively short methylene chain as a spacer at the center of the molecule has a dramatic influence on the morphology of the aggregates formed. Copyright 2001 Academic Press.

Journal Article↗