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W Xu

Publications and source records attributed to W Xu.

At least 451 records · Page 25Linked to original sources
PubMed1995

Crystal structure of a paired domain-DNA complex at 2.5 A resolution reveals structural basis for Pax developmental mutations.

The 2.5 A resolution structure of a cocrystal containing the paired domain from the Drosophila paired (prd) protein and a 15 bp site shows structurally independent N-terminal and C-terminal subdomains. Each of these domains contains a helical region resembling the homeodomain and the Hin recombinase. The N-terminal domain makes extensive DNA contacts, using a novel beta turn motif that binds in the minor groove and a helix-turn-helix unit with a docking arrangement surprisingly similar to that of the lambda repressor. The C-terminal domain is not essential for prd binding and does not contact the optimized site. All known developmental missense mutations in the paired box of mammalian Pax genes map to the N-terminal subdomain, and most of them are found at the protein-DNA interface.

Amino Acid Sequence↗
PubMed1995

Eosin, a potent inhibitor of the plasma membrane Ca pump, does not inhibit the cardiac Na-Ca exchanger.

The Na-Ca exchanger and the sarcolemmal/plasma membrane (SL(PM)) Ca pump are the two major pathways for Ca transport to the extracellular space in many cells. In cardiac myocytes, the Na-Ca exchanger appears to be responsible for a greater portion of this Ca flux [Bassani, R. A., et al. (1992) J. Physiol. 453, 591-608]. However, the respective contributions of these two transporters are not as well-defined in all tissues (e.g., smooth muscle). We propose that eosin (tetrabromofluorescein) may be a useful tool for quantitatively determining the proportion of Ca transported by the Na-Ca exchanger vs the SL(PM) Ca pump in various cells. Eosin is the most potent inhibitor known for the SL(PM) Ca pump (IC50 approximately 0.3 microM in red blood cell inside-out vesicles); unlike the Na/K and H/K pumps, eosin does not compete with ATP for the SL(PM) Ca pump [Gatto, C., & Milanick, M. A. (1993) Am. J. Physiol. 264, C1577-C1586]. In the present study, we have shown that eosin was a potent inhibitor of the cardiac SL(PM) Ca pump (IC50 approximately 1 microM); in contrast, eosin (< or = 20 microM) did not inhibit the cardiac Na-Ca exchanger. In experiments where Ca was being transported by both the SL(PM) Ca pump and the Na-Ca exchanger simultaneously, eosin effectively eliminated the Ca pump-mediated transport. In addition, we show that eosin can permeate the human red cell membrane; cell permeability is an attractive feature for using eosin in whole cell studies. We conclude that eosin can be used for determining the role that the SL(PM) Ca pump plays in whole cell Ca homeostasis.

Animals↗
PubMed1995

Glucose-6 phosphate dehydrogenase mutations and haplotypes in various ethnic groups.

Mutations that produce glucose-6-phosphate dehydrogenase (G6PD) deficiency have been identified in samples from patients with hemolytic disease in the United States, and in G6PD-deficient samples from Greece, the Canary Islands, the Czech and Slovak Republics, South China, and in samples from the Coriell Cell Repository. Eight new mutations are described. Particularly unusual were a nonsense mutation ("G6PD Georgia"1284A), a deletion of six bases ("G6PD Stony Brook" 724-729 del) coding for two amino acids, and a deletion of the invariant dinucleotide ApG at the 3' acceptor splice site in the highly conserved sequence between intron 10 and exon 11 ("G6PD Varnsdorf"). In addition, five new missense point mutations were identified: "G6PD Cleveland"820A creates a deduced AA 274 Glu-->Lys; "G6PD West Virginia"910T AA 303 Val-->Phe; "G6PD Fushan"1004A, AA 335 Ala-->Asp; "G6PD Olomouc"1141C AA 381 Leu-->Phe; and "G6PD Praha"1166G AA 389 Glu-->Gly. All of the new mutations except for "G6PD Fushan"1004A were found in patients with hereditary nonspherocytic hemolytic anemia. A coincidental finding in the case of G6PD "West Virginia" was a C-->T transition at nucleotide 1,191. This silent mutation, Asn-->Asn, appears to be rare. Haplotype analysis of mutations in samples from the Canary Islands and South China agreed with previous findings.

Anemia, Hemolytic↗
PubMed1995

Absence of linkage between human obesity and the mouse agouti homologous region (20q11.2) or other markers spanning chromosome 20q.

Mutant alleles of the agouti gene cause obesity in the mouse and the homologous gene in humans has been mapped to chromosome 20q11.2. An allelic variant of the agouti gene could account for obesity in humans and we tested this hypothesis by genotyping 210 sibling pairs from 45 families segregating an obesity phenotype. Using sibling pair linear regression analysis, evidence for linkage between obesity and markers flanking the agouti locus and other markers spanning chromosome 20q was assessed. We found no correlation between identity-by-descent at these markers and obesity differences within pairs. In the mouse, obesity caused by mutations of the agouti gene develops later in life, so a subset of families with adult-onset obesity were also tested for linkage, with negative results. Although it is not possible to exclude alleles of the agouti gene as a contributor to obesity in humans, the absence of positive linkage in this study suggests that either the agouti gene has small effects or the allele frequency is low.

Age of Onset↗
PubMed1995

Growth regulation and cellular changes during differentiation of human prostatic cancer LNCaP cells as induced by T lymphocyte-conditioned medium.

Human prostatic epithelial cells from an androgen-dependent LNCaP cell line were examined in response to conditioned medium (CM) derived from phytohemagglutinin (PHA)-stimulated lymphocytes. Addition of CM caused a greater than 70% reduction of cell proliferation by cell counting and cell cycle. These cells showed G1 phase arrest and the clonogenicity was reduced. The growth-modulating effect was dose-dependent and not due to cell lysis or apoptosis. The binding of androgen to androgen receptor on these cells showed approximately 50% reduction, underlining a proliferation reduction mechanism. The prostate-specific antigen (PSA) was downregulated to approximately 75% during the process. Cell morphology showed dendritic processes extending from cytoplasm and other neuroendocrine cell characteristics. The expression of several cytoskeleton and intracellular proteins increased as determined by immunostaining on slides and by ELISA procedures. These included vimentin, correlating to cell shape changes, cytokeratins 8 and 18, associated with differentiated cell types of prostate epithelia, and neuron-specific enolase and serotonin, associated with neuroendocrine cells. From these cellular changes, we can infer that the cell growth was modulated along with induction of terminal differentiation. Activated T cells were demonstrated to be important in providing the modulating activity. This growth modulator was semipurified and had an estimated molecular weight 13,000 to 24,000 Da. The activity was determined to be distinct from TGF, TNF, and some commonly known lymphokines. The interaction between lymphoid and prostatic cells in growth and development is described.

Biomarkers↗
PubMed1995

Characterization of measles viruses isolated after measles vaccination.

Seven measles virus (MV) strains were isolated from children who developed clinical signs of fever and rash 3-9 days after measles vaccination. The nucleotide sequence of the H gene, the molecular size of the H protein, the haemadsorption activity on African green monkey red blood cells, and antigenicity as determined by virus neutralization revealed that one strain was of the vaccine type and the remaining six were the wild virus type. Isolation of the virus directly from patients suspected of a vaccine-induced side-reaction and subsequent characterization of such isolated virus may be useful in differentiation between vaccine-induced side-reactions and natural measles.

Antibodies, Monoclonal↗
PubMed1995

Flourishing health work in China.

Great achievements have been made in China's medical and health work over the past 44 years. China now has become one of the leaders among the developing countries in respect of people's health conditions and health care service, and some of the fields have reached an advanced level. China owes its flourishing health work to the policy of 'put prevention first, rely on the progress of science and technology, strengthen rural health work, and give equal emphasis to both traditional Chinese and western medicine'. 'Health for all by the year of 2000' has been set as a strategic goal in China, and will be accomplished through increased governmental investment in health work and constant reforms of the medical systems.

China↗
PubMed1995

Arabidopsis TCH4, regulated by hormones and the environment, encodes a xyloglucan endotransglycosylase.

Adaptation of plants to environmental conditions requires that sensing of external stimuli be linked to mechanisms of morphogenesis. The Arabidopsis TCH (for touch) genes are rapidly upregulated in expression in response to environmental stimuli, but a connection between this molecular response and developmental alterations has not been established. We identified TCH4 as a xyloglucan endotransglycosylase by sequence similarity and enzyme activity. Xyloglucan endotransglycosylases most likely modify cell walls, a fundamental determinant of plant form. We determined that TCH4 expression is regulated by auxin and brassinosteroids, by environmental stimuli, and during development, by a 1-kb region. Expression was restricted to expanding tissues and organs that undergo cell wall modification. Regulation of genes encoding cell wall-modifying enzymes, such as TCH4, may underlie plant morphogenetic responses to the environment.

Amino Acid Sequence↗
PubMed1995

Identification of a candidate c-mos repressor that restricts transcription of germ cell-specific genes.

The c-mos proto-oncogene is specifically expressed in female and male germ cells. Previous studies identified a negative regulatory element (NRE) upstream of the c-mos promoter that suppresses c-mos transcription in transfected NIH 3T3 cells. In this study, we used gel shift assays to detect proteins in nuclear extracts of NIH 3T3 cells that bind to the c-mos NRE in a sequence-specific manner. One protein was found to bind to a region of the NRE which was shown by site-directed mutagenesis to be required for suppression of c-mos transcription. This factor was present in nuclear extracts of several somatic cell lines and tissues but not in male germ cells in which c-mos is transcribed, suggesting that it is a somatic cell repressor of c-mos transcription. The binding site of the candidate repressor within the c-mos NRE consists of sequences related to putative NREs identified in two other male germ cell-specific genes (encoding protamine 2 and phosphoglycerate kinase 2). The c-mos repressor bound and could be UV cross-linked to these protamine 2 and phosphoglycerate kinase 2 gene sequences as a protein with an apparent molecular mass of approximately 30 kDa. The repressor binding site is also conserved in two other germ cell-specific genes (encoding testis-specific cytochrome c and heat shock-like protein 70), suggesting that the c-mos repressor may be generally involved in suppressing transcription of germ cell-specific genes in somatic cells.

3T3 Cells↗
PubMed1995

Congenital erythropoietic porphyria: identification and expression of 10 mutations in the uroporphyrinogen III synthase gene.

To investigate the molecular basis of the phenotypic heterogeneity in congenital erythropoietic porphyria, the mutations in the uroporphyrinogen III synthase gene from unrelated patients were determined. Six missense (L4F, Y19C, V82F, V99A, A104V, and G225S), a nonsense (Q249X), a frameshift (633insA), and two splicing mutations (IVS2+1 and IVS9 delta A + 4) were identified. When L4F, Y19C, V82F, V99A, A104V, 633insA, G225S, and Q249X were expressed in Escherichia coli, only the V82F, V99A, and A104V alleles expressed residual enzymatic activity. Of note, the V82F mutation, which occurs adjacent to the 5' donor site of intron 4, resulted in approximately 54% aberrantly spliced transcripts with exon 4 deleted. Thus, this novel exonic single-base substitution caused two lesions, a missense mutation and an aberrantly spliced transcript. Of the splicing mutations, the IVS2+1 allele produced a single transcript with exon 2 deleted, whereas the IVS9 delta A+4 allele was alternatively spliced, approximately 26% being normal transcripts and the remainder with exon 9 deleted. The amount of residual activity expressed by each allele provided a basis to correlate genotype with disease severity, thereby permitting genotype/phenotype predictions in this clinically heterogeneous disease.

Adolescent↗
PubMed1995

Growth attenuation in a human prostate cell line mediated by a phorbol ester.

Human prostatic cancer cells JCA-1 were induced with a phorbol ester 12-o-tetradecanoylphorbol-13-acetate (TPA), and cell growth differentiation were analyzed. Within hours of exposure to TPA, cell proliferation decreased and reached approximately 80% reduction after 3 days, as determined by [3H]thymidine incorporation and cell counting. Cell cycle analysis revealed a blocking of cells entering into the replicating S and G2M phases from the G1 phase. The TPA induced cells had a reduced growth rate but remained viable. The growth-modulating activity of TPA was similarly observed with LNCaP cells. Agarose gel electrophoresis of the chromosomal DNA from induced cells exhibited a non-fragmented pattern excluding the possibility of cell apoptosis. In parallel to the growth reduction, the TPA induced cells became larger in size showing dendrite like cytoplasmic extensions. Furthermore, JCA-1 cells treated with TPA acquired the expression of cytokeratin 18 and increased the expression of actin and vimentin by 300%. These results indicate an induced growth reduction accompanied by cellular differentiation of the prostatic cancer cells.

Cell Cycle↗
PubMed1995

[Enzyme-linked immunoadsorbent assays for myelin basic protein and antibodies to myelin basic protein in serum and CSF of patients with diseases of the nervous system].

Simplified enzyme-linked immunoadsorbent assays (ELISA) for myelin basic protein (MBP) and antibodies to myelin basic protein (Anti-MBP) have been used to test 337 patients with diseases of the nervous system including 36 compressive diseases (CMP), 33 multiple sclerosis (MS), 34 cerebrovascular diseases (CVD), 31 inflammatory diseases of central nervous system (ID), 161 epilepsy (EP) and 42 other nervous diseases (OND). Comparison of results among various groups indicates that serum mean MBP values of CMP, MS, CVD, ID and EP groups are significantly higher than those of OND group and normal control (P < 0.01). The serum mean MBP value of 33 acute trauma patients with spine fracture and paraplegia, the majority of CMP group, is the highest compared with MS group (P < 0.05), CVD, ID and EP groups (P < 0.01). CSF mean MBP value of 15 CVD patients is markedly greater than that of OND group (P < 0.05). No statistically significant differences are found in serum MBP values between OND group and normal control, and in serum and CSF Anti-MBP values among six groups by using our method.

Autoantibodies↗
PubMed1995

Treatment of intracranial germinoma.

In 31 patients with intracranial germinoma who received radiotherapy, 15 were operated on, and 13 were treated with CSF shunt (7) and external ventricular drainage (6). After radiotherapy, clinical symptoms were improved in 93.5% of the patients. Follow-up of 16 patients for 2 to 14 years showed better results. We consider that initial treatment with radiotherapy may be appropriate for germinomas because of its high radiosensitivity. If hydrocephalus developed, external ventricular drainage combined with radiotherapy was performed, but shunting operation might be avoided because of potential peritoneal seedings of germinomas. In addition to chemotherapy, re-irradiation is an effective method for recurrent germinoma.

Adolescent↗
PubMed1995

[Correlation study of allelic gene deletion of nm23-H1 and human colorectal carcinoma metastasis].

In recent years, a tumor suppressor gene nm23 has been found to be associated with decreased tumor metastatic potential. Allelic deletion, mutation and low expression of this gene has been correlated with tumor metastatic potential in a number of tumors. There are two known isotypes of human nm23 gene, named nm23-H1 and nm23-H2. We examined DNA from 23 cases of colorectal carcinomas and their corresponding normal mucosa using Southern blot hybridization with nm23-H1 cDNA probe. Five cases with allelic deletion of nm23-H1 gene were found, with allelic deletion rate of 57. 1% (4/7) in cases with metastasis to lymph node, liver or other organs, and 6.2% (1/16) in cases without metastases (P < 0.005). There is no correlation between allelic deletion and tumor size, location or differentiation. This result indicates that nm23-H1 gene plays an important role in the metastasis of colorectal carcinoma.

Alleles↗
PubMed1995

[Involvement of opioid peptides in corticofugal modulation of pain].

The effect of opioid peptides on corticofugal modulation of nociceptive response in thalamic ventrobasal nucleus (VB) produced by cortical sensorimotor area II (Sm II) was observed. Single unit activities of VB neurons were extracellularly recorded by glass microelectrodes. The results showed that the nociceptive responses of VB neurons were attenuated at 0-7.5 minutes after stimulating Sm II (n = 14, P < 0.05). The inhibitory effect of stimulation of Sm II was reduced after ventriculer microinjection of 20ul of naloxone (n = 9), while marked inhibition was shown at 0-2.5 minutes after stimulating Sm II in the saline control group (n = 9, P < 0.05). There was a statistical difference at 0-2.5 minutes after stimulating Sm II between the two groups (P < 0.05). These studies suggest that opioid peptides might be involved in corticofugal modulation of pain.

Animals↗