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Biomedical subjects

N Xu

Publications and source records attributed to N Xu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Comprehensive linkage map of bovine chromosome 27.

The results of genotypic data contributed to the International Society for Animal Genetics (ISAG) Bovine Chromosome 27 Workshop are presented. Eight laboratories contributed 23 261 informative meioses from 44 loci. Eighteen loci were typed by at least two laboratories and were used to construct a consensus linkage map. Twenty-one loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 66.9 cM. The sex-averaged comprehensive map was 75.5 cM, while the female and male maps were 73.1 and 63.7 cM, respectively. Five loci were excluded from the analysis because of ambiguous position in the linkage group and a low LOD score (less than 2.0). Average distance between loci in the comprehensive map was 1.98 cM.

Animals↗
PubMed2001

Comprehensive linkage map of bovine chromosome 11.

The results of genotypic data contributed to the International Society of Animal Genetics (ISAG) Bovine Chromosome 11 (BTA11) Workshop are presented. Six laboratories contributed a total of 26 199 informative meioses from 80 loci. Thirty-six loci were typed by at least two independent laboratories and were used to construct a consensus linkage map of the chromosome. The remaining loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 128.9 cM. The female consensus map was 101.2 cM, while the male consensus map was 129.8 cM. The comprehensive sex-averaged map was 134.2 cM and the average genetic distance between loci was 1.72 cM.

Animals↗
PubMed2001

Sustained and therapeutic delivery of factor IX in nude haemophilia B mice by encapsulated C2C12 myoblasts: concurrent tumourigenesis.

This study reports the generation of an immunodeficient murine model for haemophilia B, obtained by breeding factor IX-deficient mice with an immunodeficient mouse strain, and use of this mouse model to evaluate the long-term efficacy and safety of a gene therapy strategy for treating haemophilia B. Nude haemophilic mice were implanted with biocompatible microcapsules enclosing recombinant myoblasts secreting human factor IX. The activated partial thromboplastin time (APTT) of plasma of mice thus treated was invariably shortened 3 weeks after microcapsule implantation, and remained shortened for at least 77 days. Shortening of the APTT of the haemophilia mice coincided with the appearance of human factor IX in mice plasmas (up to 600 ng mL(-1) on day 77), and normalization of the tail-bleeding time. Thus, the microencapsulated myoblasts reversed the clinical phenotype of haemophilia B. In contrast, plasmas of immunocompetent haemophilic mice similarly implanted with microcapsules only showed a transient shortening of APTT, and coincident transient delivery of human factor IX antigen. Rapid disappearance of human factor IX from plasmas of immunocompetent mice also coincided with production of antibodies to the human transgene. Significantly, 86% of the nude haemophilia mice developed tumours of myoblast origin. Thus, while this study revealed the feasibility of this gene therapy approach to treat severe haemophilia B, it also highlights the importance of using safer cell lines to prevent tumour development.

Animals↗
PubMed2001

A comparison of tailpipe, dilution tunnel, and wind tunnel data in measuring motor vehicle PM.

Comparison between particle size distributions recorded directly at the tailpipes of both diesel and gasoline vehicles and measurements made using a conventional dilution tunnel reveals two problems incurred when using the latter method for studying particle number emissions. One is the potential for particulate matter (PM) artifacts originating from hydrocarbon material stored in the transfer hose connecting the tailpipe to the dilution tunnel, and the other is the particle coagulation (as well as condensation and chemical changes) that occurs during the transport. Both are potentially generic to current PM emissions measurement practices. The artifacts typically occur as a nanoparticle mode (10-30 nm) that is 2-4 orders of magnitude larger than what is present in the vehicle exhaust and can easily be mistaken for a similar mode that can arise from the nucleation of hydrocarbon or SO4(2-) components in the exhaust under appropriate dilution rates. Wind tunnel measurements are in good agreement with those made directly from the tailpipe and substantiate the potential for artifacts. They reveal PM levels for the recent model port fuel injection (PFI) gasoline vehicles tested that are small compared with the ambient background particle level during steady-state driving. The PM emissions recorded for drive cycles such as the Federal Test Procedure (FTP) and US06 occur primarily during acceleration, as has been previously noted. Light-duty diesel vehicle emissions normally exhibit a single lognormal mode centered between 55 and 80 nm, although a nonartifact nanoparticle mode in some cases appears at a 70-mph cruise up a grade.

Air Movements↗
PubMed2001

Protein kinase C-delta regulates thrombin-induced ICAM-1 gene expression in endothelial cells via activation of p38 mitogen-activated protein kinase.

The procoagulant thrombin promotes the adhesion of polymorphonuclear leukocytes to endothelial cells by a mechanism involving expression of intercellular adhesion molecule 1 (ICAM-1) via an NF-kappaB-dependent pathway. We now provide evidence that protein kinase C-delta (PKC-delta) and the p38 mitogen-activated protein (MAP) kinase pathway play a critical role in the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells. We observed the phosphorylation of PKC-delta and p38 MAP kinase within 1 min after thrombin challenge of human umbilical vein endothelial cells. Pretreatment of these cells with the PKC-delta inhibitor rottlerin prevented the thrombin-induced phosphorylation of p38 MAP kinase, suggesting that p38 MAP kinase signals downstream of PKC-delta. Inhibition of PKC-delta or p38 MAP kinase by pharmacological and genetic approaches markedly decreased the thrombin-induced NF-kappaB activity and resultant ICAM-1 expression. The effects of PKC-delta inhibition were secondary to inhibition of IKKbeta activation and of subsequent NF-kappaB binding to the ICAM-1 promoter. The effects of p38 MAP kinase inhibition occurred downstream of IkappaBalpha degradation without affecting the DNA binding function of nuclear NF-kappaB. Thus, PKC-delta signals thrombin-induced ICAM-1 gene transcription by a dual mechanism involving activation of IKKbeta, which mediates NF-kappaB binding to the ICAM-1 promoter, and p38 MAP kinase, which enhances transactivation potential of the bound NF-kappaB p65 (RelA).

Cells, Cultured↗
PubMed2001

Versatile role for hnRNP D isoforms in the differential regulation of cytoplasmic mRNA turnover.

An important emerging theme is that heterogeneous nuclear ribonucleoproteins (hnRNPs) not only function in the nucleus but also control the fates of mRNAs in the cytoplasm. Here, we show that hnRNP D plays a versatile role in cytoplasmic mRNA turnover by functioning as a negative regulator in an isoform-specific and cell-type-dependent manner. We found that hnRNP D discriminates among the three classes of AU-rich elements (AREs), most effectively blocking rapid decay directed by class II AREs found in mRNAs encoding cytokines. Our experiments identified the overlapping AUUUA motifs, one critical characteristic of class II AREs, to be the key feature recognized in vivo by hnRNP D for its negative effect on ARE-mediated mRNA decay. The four hnRNP D isoforms, while differing in their ability to block decay of ARE-containing mRNAs, all potently inhibited mRNA decay directed by another mRNA cis element that shares no sequence similarity with AREs, the purine-rich c-fos protein-coding region determinant of instability. Further experiments indicated that different mechanisms underlie the inhibitory effect of hnRNP D on the two distinct mRNA decay pathways. Our study identifies a potential mechanism by which cytoplasmic mRNA turnover can be differentially and selectively regulated by hnRNP D isoforms in mammalian cells. Our results support the notion that hnRNP D serves as a key factor broadly involved in general mRNA decay.

3T3 Cells↗
PubMed2001

Elevated expression of proprotein convertases alters breast cancer cell growth in response to estrogen and tamoxifen.

Two proprotein convertase cDNAs, PC1 and furin, were stably transfected into the human breast cancer cell line MCF-7. The PC1 or furin over-expressing cells possessed an altered morphology. When grown in vitro in a serum-free medium, the population doubling time of the convertase-transfected cells was twice that of wild-type (WT) cells. High concentrations of estradiol stimulated the growth of all three cell types to a similar extent; however, at low concentrations of estradiol, the convertase-transfected cells grew more slowly than WT cells. In athymic nude mice implanted with 5 mg estradiol pellets, the growth of tumors of convertase-transfected MCF-7 cells was stimulated to a degree similar to that of WT MCF-7 tumors. However, in mice implanted with lower-dose (1.5 mg) estradiol pellets, the tumors of PC1- or furin-transfected MCF-7 cells grew approximately five times slower than those of WT MCF-7 cells. In mice implanted with tamoxifen pellets, tumors of PC1- or furin-transfected MCF-7 cells regressed approximately five times slower than the WT tumors. This study shows that the over-expression of proprotein convertases confers a greater estrogen dependency and anti-estrogen resistance on human breast cancer cells.

Animals↗
PubMed2001

[An experimental study on the release of endotoxin from gram negative bacteria induced by antibiotics].

OBJECTIVE: To explore the characteristics and possible mechanism of LPS released from Gram negative bacteria induced by antibiotics, so as to improve clinical management of endotoxemia and sepsis. METHODS: Cultures containing PA103 subtype of Pseudomonas aeruginosa (PA) and E coli 25922 subtype of E coli were treated with four kinds of antibiotics as Imipenam (IMP), ceftazidime (CTZ), amikacin (AMN) and pefloxacine (PFX) in four concentrations of 0.5, 1, 5 and 10 MIC for 8 hours. The changes in the bacterial quantity and morphology and the supernatant levels of free LPS of the culture media were observed at different time points. RESULTS: All the four kinds of antibiotics could kill the tested bacteria in similar degree, but lead to the different types of morphological changes of the bacteria. In detail, IMP could convert the bacteria into spherical shape, while CTZ and PFX made the bacteria to filamentous shape. But AMN could induce lysis of bacterial thallus. Under same condition, the ability of different kinds and concentrations of antibiotics to induce LPS release ranked as CTZ > PFX > IMP > AMN, 0.5MIC > 1MIC > 5MIC > 10MIC. Along with the prolongation of the action time, the LPS release increased. Furthermore, PA103 released less endotoxin than E. coli after the action of antibiotics. CONCLUSION: All of the four antibiotics, i,e, IMP, CTZ, AMN and PFX could induce PA103 and E coli 25922 to release different levels of LPS, which was related to bacterial morphological changes. The LPS release from the bacteria was correlated to the antibiotics applied, concentrations, action time and the bacterial features. Antibiotics with less ability of inducing LPS release were recommended for clinical management of the sepsis and/or septic shock caused by Gram negative bacteria.

Amikacin↗
PubMed2000

NMR structure and mutagenesis of the third Bir domain of the inhibitor of apoptosis protein XIAP.

The inhibitor of apoptosis proteins (IAPs) regulate the caspase family of cysteine proteases, which play an important role in the execution of programmed cell death. Human X-linked inhibitor of apoptosis protein (XIAP) is a potent inhibitor of caspases-3, -7, and -9. Here we show that the Bir3 domain is the minimal region of XIAP that is needed for potent caspase-9 inhibition. The three-dimensional structure of the Bir3 domain of XIAP, determined by NMR spectroscopy, resembles a classical zinc finger and consists of five alpha-helices, a three-stranded beta-sheet, and a zinc atom chelated to three cysteines and one histidine. The structure of the Bir3 domain is similar to that of the Bir2 domain of XIAP but differs from the previously determined structure of the Bir3 domain of MIHB. Based on site-directed mutagenesis, we have identified the regions of the Bir3 domain of XIAP that are important for inhibiting caspase-9. Despite the structural similarities of the Bir2 and Bir3 domain of XIAP, a different set of residues were found to be critical for inhibiting the individual caspases. These results suggest that XIAP inhibits caspase-3 and caspase-9 in a different manner.

Amino Acid Sequence↗
PubMed2000

A mechanism for translationally coupled mRNA turnover: interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex.

mRNA turnover mediated by the major protein-coding-region determinant of instability (mCRD) of the c-fos proto-oncogene transcript illustrates a functional interplay between mRNA turnover and translation. We show that the function of mCRD depends on its distance from the poly(A) tail. Five mCRD-associated proteins were identified: Unr, a purine-rich RNA binding protein; PABP, a poly(A) binding protein; PAIP-1, a poly(A) binding protein interacting protein; hnRNP D, an AU-rich element binding protein; and NSAP1, an hnRNP R-like protein. These proteins form a multiprotein complex. Overexpression of these proteins stabilized mCRD-containing mRNA by impeding deadenylation. We propose that a bridging complex forms between the poly(A) tail and the mCRD and ribosome transit disrupts or reorganizes the complex, leading to rapid RNA deadenylation and decay.

Amino Acid Sequence↗
PubMed2000

beta(2)-Integrin blockade driven by E-selectin promoter prevents neutrophil sequestration and lung injury in mice.

Interaction of CD11/CD18 beta(2) integrins on polymorphonuclear leukocytes (PMNs) with their counterreceptor, intercellular adhesion molecule-1, on the surface of vascular endothelial cells is a critical event mediating stable PMN adhesion and migration across the pulmonary vascular endothelial barrier. Neutrophil inhibitory factor (NIF), a 41-kDa glycoprotein isolated from the canine hookworm (Ancylostoma caninum), binds to the I domain of CD11a and CD11b and inhibits beta(2) integrin-dependent PMN adhesion. We describe a novel strategy using the endothelial cell-specific E-selectin promoter to induce NIF expression in an inflammation-specific manner in pulmonary vascular endothelial cells. A construct containing NIF cDNA driven by the inducible endothelial cell-specific E-selectin promoter (pESNIF) was transfected into human pulmonary artery endothelial cells (HPAECs). Lipopolysaccharide challenge (known to activate E-selectin) resulted in NIF mRNA and protein expression in transfected HPAECs. NIF expression induced by the E-selectin promoter prevented PMN adhesion to the activated HPAECs, whereas PMNs adhered avidly to activated HPAECs in the absence of NIF expression. To address the utility of this approach in conditionally preventing in vivo PMN sequestration, we injected mice intravenously with cationic liposomes containing the pESNIF construct. Analysis of lung tissue showed that intraperitoneal challenge of Escherichia coli resulted in NIF expression. Inflammation-specific NIF expression induced by the E-selectin promoter prevented lung PMN sequestration and vascular injury induced by E coli challenge. These studies suggest the feasibility of conditionally blocking beta(2) integrin function at sites where the endothelium is activated and thereby of locally preventing PMN activation and migration responses that lead to tissue inflammation.

Animals↗
PubMed2000

Novel rapidity dependence of directed flow in high-energy heavy-Ion collisions

For high-energy nucleus-nucleus collisions, we show that a combination of space-momentum correlations characteristic of radial expansion, together with the correlation between the position of a nucleon in the nucleus and its stopping, results in a very specific rapidity dependence of directed flow: a reversal of sign in the midrapidity region. We support our argument by RQMD model calculations for Au+Au collisions at sqrt[s] = 200A GeV.

Journal Article↗
PubMed2000

Reversibility of increased microvessel permeability in response to VE-cadherin disassembly.

We determined the role of vascular endothelial (VE)-cadherin complex in regulating the permeability of pulmonary microvessels. Studies were made in mouse lungs perfused with albumin-Krebs containing EDTA, a Ca(2+) chelator, added to study the VE-cadherin junctional disassembly. We then repleted the perfusate with Ca(2+) to restore VE-cadherin integrity. Confocal microscopy showed a disappearance of VE-cadherin immunostaining in a time- and dose-dependent manner after Ca(2+) chelation and reassembly of the VE-cadherin complex within 5 min after Ca(2+) repletion. We determined the (125)I-labeled albumin permeability-surface area product and capillary filtration coefficient (K(fc)) to quantify alterations in the pulmonary microvessel barrier. The addition of EDTA increased (125)I-albumin permeability-surface area product and K(fc) in a concentration-dependent manner within 5 min. The permeability response was reversed within 5 min after repletion of Ca(2+). An anti-VE-cadherin monoclonal antibody against epitopes responsible for homotypic adhesion augmented the increase in K(fc) induced by Ca(2+) chelation and prevented reversal of the response. We conclude that the disassembled VE-cadherins in endothelial cells are mobilized at the junctional plasmalemmal membrane such that VE-cadherins can rapidly form adhesive contact and restore microvessel permeability by reannealing the adherens junctions.

Adherens Junctions↗
PubMed2000

Temporal arteritis and fever: report of a case and a clinical reanalysis of 360 cases.

The purposes of this article are to report a case with temporal arteritis (TA) and to summarize and reanalyze the cases of temporal arteritis associated with fever in published articles for understanding better the clinical features of TA. A case with biopsy-proven TA is reported. The publications with TA and fever were searched by using MEDLINE in English from 1966 to 1999. Three hundred sixty cases of temporal arteritis associated with fever were reanalyzed. The results showed that a case of biopsy-proven TA with typically clinical manifestation was initially misdiagnosed and that the reanalysis of 360 cases revealed that the common clinical findings at presentation were abnormal temporal arteries, headache, low fever, loss of weight, polymyalgia rheumatica, jaw claudication, vision disorder, arthralgis or myalyias, and ear pain and that the uncommon clinical findings at presentation were high fever, malaise, anorexia, breast pain, transient ischemic attack/stroke, cough, mental disorder, diarrhea, and uterine prolapse, etc. Laboratory findings were the range of erythrocyte sedimentation rate (ESR) 14 to 149 with a mean of 97.0 mm/hr, white blood cells being normal or increased in the range of 10.9 to 22.9 x 10(9)/L, hemoglobin level 7 to 16 g/dL, the platelets count increased to 785 x 10(9)/L, and microscopic hematuria. The diagnosis was made by a combination of clinical features, an increased ESR, a response to steroids, and, most specifically, temporal artery biopsy. The initial diagnosis was misdiagnosed in 38.2% of patients. In conclusion, the features of TA associated with fever have not been widely appreciated yet. TA is a common cause of fever of unknown origin (FUO) in the elderly. TA should be considered when patients complain of common and uncommon manifestations. An elevated ESR will aid in the diagnosis of TA, and temporal artery biopsy will provide certainty.

Adult↗
PubMed1999

A novel human apolipoprotein (apoM).

A novel human apolipoprotein designated apolipoprotein M (apoM) is described. The unique N-terminal amino acid sequence of apoM was found in an approximately 26-kDa protein present in a protein extract of triglyceride-rich lipoproteins (TGRLP). The isolated apoM cDNA (734 base pairs) encoded a 188-amino acid residue-long protein, distantly related to the lipocalin family. The mRNA of apoM was detected in the liver and kidney. Western blotting demonstrated apoM to be present in high density lipoprotein (HDL) and to a lesser extent in TGRLP and low density lipoproteins (LDL). The first 20 amino acid residues of apoM constituted a hydrophobic segment with characteristic features of a signal peptide. This was retained in the mature protein because of the lack of a signal peptidase cleavage site. In vitro translation in the presence of microsomes demonstrated translocation of apoM over the membrane and glycosylation but no signal peptide cleavage. The in vitro translated product remained associated with the microsomes after treatment with carbonate at pH 11, demonstrating that apoM is an integral protein. This finding suggests that apoM is linked to the single phospholipid layer of lipoproteins with a hydrophobic signal anchor. In conclusion, a novel human apolipoprotein, the function of which remains to be determined, is described.

Adult↗