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Biomedical subjects

W Xu

Publications and source records attributed to W Xu.

At least 397 records · Page 22Linked to original sources
PubMed1997

[The decrease of gastric mucosal blood flow in obstructive jaundice under stress].

OBJECTIVE: To investigate the cause of decrease of gastric mucosal blood flow (GMBF) in obstructive jaundice under stress. METHODS: With common bile duct ligation (CBDL) in Wistar rats under cold restraint stress, GMBF and the content of Endothelin-1, Angiotensin-II, H2, alpha 1 receptor in gastric mucosa were measured. Before stress anti-ET-1 serum, Enalapril, Cimentidine and Phetolamins were administrated, and the change of GMBF was studied. RESULTS: GMBF was significantly decreased in CBDL in stress than those in control subjects. The content of ET1 and Ang-II was significantly increaced, the density of H2 and alpha 1 receptor was significantly decreased. Before stress antagonist was administrated, and GMBF was significantly increased. CONCLUSION: GMBF was decreased by increased ET, Ang-II and decreased H2, alpha 1 receptor in CBDL, under stress. Antagonist improved gastric mucosal blood flow. They had protection from gastric mucosa.

Angiotensin II↗
PubMed1997

[Antagonistic effect of orphanin FQ on morphine analgesia in rat brain].

The discovery of a novel receptor-opioid receptor-like (ORL) receptor (1994) and its endogenous ligand-Orphanin FQ (OFQ) (1995) represented a new approach in the study of opioids and anti-opioids in CNS. Based on the high homology of ORL receptor and OFQ with their opioid family counterparts, as well as the high expression of ORL receptor mRNA and protein in the brain areas associated with nociception, the effect of OFQ on morphine induced analgesia in the rat brain was further investigated. The results showed that: (1) Intracerebroventricular (i.c.v.) injection of OFQ reversed the stress analgesia induced by i.c.v. injection of normal saline, which seems to be mediated by endogenous opioid peptides. (2) I.c.v. injection of OFQ dose-dependently antagonized morphine-induced analgesia dose-dependently. (3) I.c.v. injection of antisense oligodeoxynucleotide for the gene encoding ORL receptor to block the expression of ORL receptor in the CNS potentiated the analgesia induced by cumulative injection of morphine. The results suggest that OFQ seems to play a role of anti-opioid peptide in the rat brain.

Analgesics, Opioid↗
PubMed1996

Functional effects of mutating the closing GxA base-pair of a conserved hairpin loop in 23 S ribosomal RNA.

Recently, Draper and co-workers solved the structure of a hexanucleotide hairpin loop that is conserved in large subunit ribosomal RNAs. (In Escherichia coli, the hexanucleotide consists of nucleotides 1093 to 1098, in the GTPase center of 23 S rRNA.) A major feature of that structure is a G1093xA1098 base-pair that closes the loop. Our laboratory reported previously the isolation of the mutation G1093A and its characterization as a suppressor of UGA mutations and a cause of temperature-conditional lethality. For the work reported here, we asked whether G1093A causes its phenotypes precisely because it is part of the G1093/A1098 base-pair. Using oligonucleotide-directed site-specific mutagenesis, we introduced base substitutions at nucleotides 1093 and 1098 into a plasmid-borne ribosomal RNA operon (rrnB). Each mutant plasmid was then tested for the two mutant phenotypes, nonsense suppression and temperature-dependent growth inhibition. Our results indicate that mutations at 1093 do not cause the mutant phenotypes because G1093 is part of the G1093xA1098 base-pair. We discuss alternative avenues to the observed mutant phenotypes and, in particular, present a model in which a specific interaction of the loop is involved in peptide chain termination.

Base Composition↗
PubMed1996

Grafting on nude mice of living skin equivalents produced using human collagens.

Autologous epidermal transplantation for human burn management is an example of a significant breakthrough in tissue engineering. However, the main drawback with this treatment remains the fragility of these grafts during and after surgery. A new human bilayered skin equivalent (hSE) was produced in our laboratory to overcome this problem. The aim of the present work was to study skin regeneration after hSE grafting onto nude mice. A comparative study was carried out over a period of 90 days, between anchored bovine skin equivalent, hSE and hSE+, the latter containing additional matrix components included at concentrations similar to those in human skin in vivo. The addition of a dermal layer to the epidermal sheet led to successful graft take, enhanced healing, and provided mechanical resistance to the grafts after transplantation. In situ analysis of the grafts showed good ultrastructural organization, including the deposition of a continuous basement membrane 1 week after surgery.

Animals↗
PubMed1996

Anti-peptide aptamers recognize amino acid sequence and bind a protein epitope.

In vitro selection of nucleic acid binding species (aptamers) is superficially similar to the immune response. Both processes produce biopolymers that can recognize targets with high affinity and specificity. While antibodies are known to recognize the sequence and conformation of protein surface features (epitopes), very little is known about the precise interactions between aptamers and their epitopes. Therefore, aptamers that could recognize a particular epitope, a peptide fragment of human immunodeficiency virus type I Rev, were selected from a random sequence RNA pool. Several of the selected RNAs could bind the free peptide more tightly than a natural RNA ligand, the Rev-binding element. In accord with the hypothesis that protein and nucleic acid binding cusps are functionally similar, interactions between aptamers and the peptide target could be disrupted by sequence substitutions. Moreover, the aptamers appeared to be able to bind peptides with different solution conformations, implying an induced fit mechanism for binding. Just as anti-peptide antibodies can sometimes recognize the corresponding epitope when presented in a protein, the anti-peptide aptamers were found to specifically bind to Rev.

Amino Acid Sequence↗
PubMed1996

The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase.

The identity of the maturation inducer capable of mediating the differentiation of human myeloid leukemic HL-60 calls to terminal monocytic cells was investigated. One of such inducers from T cells was purified as a 54.3-kD peptide. The amino acid sequence of a tryptic peptide and the enzyme cleavage sites revealed 100% homology to neuroleukin or phosphoglucose isomerase (PGI). Neuroleukin mediates differentiation of neurons and is homologous to PGI, which catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate. The 54.3-kD inducer was shown to have PGI enzymatic activity. Separately purified PGI by substrate-elution exhibited identical specificity as the maturation inducer for HL-60 cell differentiation. They mediated a reduction of proliferating S and G2M cells, and the mature monocytic calls acquired complement receptors, phagocytic capacity, and adherence morphology. The magnitude of differentiation was dosage dependent on the inducer, with a bell-shaped curve. At the excess dose range cells did not undergo differentiation and remained in a proliferating cycle. Abnormally elevated PGI enzyme activities were detected in the plasma of acute myelogenous leukemia patients. Whether they represent an excess of the differentiation regulator in patients and are important in leukemogenesis remain to be investigated.

Aged↗
PubMed1996

Molecular cloning and structural organization of the human inducible nitric oxide synthase gene (NOS2).

Previously, we reported the isolation and molecular cloning of human inducible nitric oxide synthase gene (NOS2) sequences from human chromosome 17 cosmid libraries. Here we describe the further characterization and sequencing of the NOS2 gene. The genomic structure of the NOS2 gene was determined from two overlapping cosmid clones, namely, pcos4A and pcos20. the NOS2 open reading frame is encoded by 27 exons, with translation initiation and termination in exon 2 and exon 27, respectively. These results differ from the previously reported organization of the iNOS gene, where 26 exons were reported for the genomic structure of NOS2.

Alternative Splicing↗
PubMed1996

The molecular role of the common gamma c subunit in signal transduction reveals functional asymmetry within multimeric cytokine receptor complexes.

The specific signal transduction function of the gamma c subunit in the interleukin (IL) 2, IL-4, IL-7, IL-9, and IL-15 receptor complexes remains undefined. The present structure-function analyses demonstrated that the entire cytoplasmic tail of gamma c could be functionally replaced in the IL-2 receptor (IL-2R) signaling complex by a severely truncated erythropoietin receptor cytoplasmic domain lacking tyrosine residues. Heterodimerization of IL-2R beta with either gamma c or the truncated erythropoietin receptor chain led to an array of specific signals normally derived from the native IL-2R despite the substitution of Janus kinase JAK2 for JAK3 in the receptor complex. These findings thus suggest a model in which the gamma c subunit serves as a common and generic "trigger" chain by providing a nonspecific Janus kinase for signaling program initiation, while signal specificity is determined by the unique "driver" subunit in each of the gamma c- containing receptor complexes. Furthermore, these results may have important functional implications for the asymmetric design of many cytokine receptor complexes and the evolutionary design of receptor subfamilies that share common trigger or driver subunits.

Cells, Cultured↗
PubMed1996

Dietary beta-alanine results in taurine depletion and cerebellar damage in adult cats.

We have used the taurine analogue, beta-alanine, to perturb the taurine concentrations in taurine-supplemented and taurine-deprived adult cats. By using 5% beta-alanine in the drinking water for 20 weeks, both groups of cats had greatly reduced brain taurine concentrations. Taurine-supplemented cat brain accumulated relatively small amounts of beta-alanine whereas taurine-deprived cats accumulated large amounts of beta-alanine. The cerebellum of cats treated with beta-alanine had a number of pathological changes compared with similar cats drinking water alone. The changes were more severe in the taurine-deprived cats, and included reduced numbers of granule and Purkinje cells, with many of those remaining appearing pyknotic and dying. Long swollen fibers were seen in the white matter, resembling Rosenthal fibers described in some human cerebellar diseases. There was also prominent gliosis. Using antibodies to beta-alanine and taurine, beta-alanine was localized in Purkinje cell soma and dendrites, in Golgi II cells, and in some granule cells, especially in taurine-deprived cats treated with beta-alanine. Taurine appears to have been virtually eliminated from Purkinje and granule cells, and concentrated in Golgi II cells and glia. We conclude that beta-alanine is responsible for these neurotoxic pathological changes.

Administration, Oral↗
PubMed1996

Molecular basis of congenital erythropoietic porphyria: mutations in the human uroporphyrinogen III synthase gene.

Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of the fourth enzyme in the heme biosynthetic pathway, uroporphyrinogen III synthase (URO-synthase). To date, 17 mutations have been described including 11 missense, one nonsense, two mRNA splicing defects, one deletion and two coding region insertions. Most mutations have been identified in one or a few unrelated families with the exception of C73R and L4F which occurred in 29.6% and 9.3% of the 54 mutant alleles studied, respectively. Interestingly, analysis of the mutant alleles identified only 83% of the causative mutations, suggesting that about 20% of the mutations causing CEP lie elsewhere in the gene. Of note, mutation V82F, resulting from a G to T transversion of the last nucleotide of exon 4, caused both a missense mutation and an aberrantly spliced RNA transcript. Prokaryotic expression of the mutant URO-synthase alleles identified those with significant residual activity, thereby permitting genotype/phenotype predictions for this clinically heterogeneous disease.

Adolescent↗
PubMed1996

Identification of the rat epididymis-secreted 4E9 antigen as protein E: further biochemical characterization of the highly homologous epididymal secretory proteins D and E.

Epididymis-secreted proteins D and E have been purified to homogeneity and partially characterized, and it is shown that monoclonal antibody (MAb) 4E9 (raised against a detergent extract of rat caudal epididymal sperm [Moore et al., 1994: Mol Reprod Dev 37(2):181-194]) recognizes protein E, but not protein D. The molecular weight of protein D (approximately 30 kD) is approximately 2 kD lower than protein E (approximately 32 kD). The NH2-terminus of each protein is blocked; however, microsequencing of internal peptides confirms earlier reports of significant sequence identity between the two proteins. High performance liquid chromatography tryptic peptide mapping showed peak differences between the two proteins, but it was not possible to obtain amino acid sequence in the peaks that were different. The epitope for MAb 4E9 was localized in the blocked NH2-terminus-CNBr peptide derived from protein E. The epitope was destroyed by protease treatment of protein E. Removal of N-linked oligosaccharides did not destroy the epitope for MAb 4E9 and did not affect the molecular weight difference between the proteins.

Amidohydrolases↗