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J Xu

Publications and source records attributed to J Xu.

At least 253 records · Page 14Linked to original sources
PubMed2001

Extraction of the aortic and pulmonary components of the second heart sound using a nonlinear transient chirp signal model.

The objective of this paper is to adapt and validate a nonlinear transient chirp signal modeling approach for the analysis and synthesis of overlapping aortic (A2) and pulmonary (P2) components of the second heart sound (S2). The approach is based on the time-frequency representation of multicomponent signals for estimating and reconstructing the instantaneous phase and amplitude functions of each component. To evaluate the accuracy of the approach, a simulated S2 with A2 and P2 components having different overlapping intervals (5-30 ms) was synthesized. The simulation results show that the technique is very effective for extracting the two components, even in the presence of noise (-15 dB). The normalized root-mean-squared error between the original A2 and P2 components and their reconstructed versions varied between 1% and 6%, proportionally to the duration of the overlapping interval, and it increased by less than 2% in the presence of noise. The validated technique was then applied to S2 components recorded in pigs under normal or high pulmonary artery pressures. The results show that this approach can successfully isolate and extract overlapping A2 and P2 components from successive S2 recordings obtained from different heartbeats of the same animal as well from different animals.

Animals↗
PubMed2001

Structural and thermodynamic analysis of the binding of solvent at internal sites in T4 lysozyme.

To investigate the structural and thermodynamic basis of the binding of solvent at internal sites within proteins a number of mutations were constructed in T4 lysozyme. Some of these were designed to introduce new solvent-binding sites. Others were intended to displace solvent from preexisting sites. In one case Val-149 was replaced with alanine, serine, cysteine, threonine, isoleucine, and glycine. Crystallographic analysis shows that, with the exception of isoleucine, each of these substitutions results in the binding of solvent at a polar site that is sterically blocked in the wild-type enzyme. Mutations designed to perturb or displace a solvent molecule present in the native enzyme included the replacement of Thr-152 with alanine, serine, cysteine, valine, and isoleucine. Although the solvent molecule was moved in some cases by up to 1.7 A, in no case was it completely removed from the folded protein. The results suggest that hydrogen bonds from the protein to bound solvent are energy neutral. The binding of solvent to internal sites within proteins also appears to be energy neutral except insofar as the bound solvent may prevent a loss of energy due to potential hydrogen bonding groups that would otherwise be unsatisfied. The introduction of a solvent-binding site appears to require not only a cavity to accommodate the water molecule but also the presence of polar groups to help satisfy its hydrogen-bonding potential. It may be easier to design a site to accommodate two or more water molecules rather than one as the solvent molecules can then hydrogen-bond to each other. For similar reasons it is often difficult to design a point mutation that will displace a single solvent molecule from the core of a protein.

Amino Acid Substitution↗
PubMed2001

The evaluation of multiple surrogate endpoints.

Surrogate endpoints are desirable because they typically result in smaller, faster efficacy studies compared with the ones using the clinical endpoints. Research on surrogate endpoints has received substantial attention lately, but most investigations have focused on the validity of using a single biomarker as a surrogate. Our paper studies whether the use of multiple markers can improve inferences about a treatment's effects on a clinical endpoint. We propose a joint model for a time to clinical event and for repeated measures over time on multiple biomarkers that are potential surrogates. This model extends the formulation of Xu and Zeger (2001, in press) and Fawcett and Thomas (1996, Statistics in Medicine 15, 1663-1685). We propose two complementary measures of the relative benefit of multiple surrogates as opposed to a single one. Markov chain Monte Carlo is implemented to estimate model parameters. The methodology is illustrated with an analysis of data from a schizophrenia clinical trial.

Antipsychotic Agents↗
PubMed2001

Dynamic and heterogeneous mutations to fluconazole resistance in Cryptococcus neoformans.

Infections with the human pathogenic basidiomycetous yeast Cryptococcus neoformans are often treated with fluconazole. Resistance to this antifungal agent has been reported. This study investigated the patterns of mutation to fluconazole resistance in C. neoformans in vitro. The MIC of fluconazole was measured for 21 strains of C. neoformans. The MICs for these 21 strains differed (0.25 to 4.0 microg/ml), but the strains were selected for this study because they exhibited no growth on plates of yeast morphology agar (YMA) containing 8 microg of fluconazole per ml. To determine their mutation rates, six independent cultures from a single original colony were established for each of the 21 strains. Each culture was then spread densely on a YMA plate with 8 microg of fluconazole per ml. A random set of putative mutants was subcultured, and the MIC of fluconazole was determined for each mutant. The 21 strains evinced significant heterogeneity in their mutation rates. The MICs of the putative mutants ranged widely, from their original MIC to 64 microg of fluconazole per ml. However, for this set of 21 strains, there was no significant correlation between the original MIC for a strain and the mutation rate of that strain; the MIC for the mutant could not be predicted from the original MIC. These results suggest that dynamic and heterogeneous mutational processes are involved in generating fluconazole resistance in C. neoformans.

Antifungal Agents↗
PubMed2001

Function-based selection and characterization of base-pair polymorphisms in a promoter of Escherichia coli RNA polymerase-sigma(70).

We performed two sets of in vitro selections to dissect the role of the -10 base sequence in determining the rate and efficiency with which Escherichia coli RNA polymerase-sigma(70) forms stable complexes with a promoter. We identified sequences that (i) rapidly form heparin-resistant complexes with RNA polymerase or (ii) form heparin-resistant complexes at very low RNA polymerase concentrations. The sequences selected under the two conditions differ from each other and from the consensus -10 sequence. The selected promoters have the expected enhanced binding and kinetic properties and are functionally better than the consensus promoter sequence in directing RNA synthesis in vitro. Detailed analysis of the selected promoter functions shows that each step in this multistep pathway may have different sequence requirements, meaning that the sequence of a strong promoter does not contain the optimal sequence for each step but instead is a compromise sequence that allows all steps to proceed with minimal constraint.

Base Sequence↗
PubMed2001

Prevalence of iron transport gene on pathogenicity-associated island of uropathogenic Escherichia coli in E. coli O157:H7 containing Shiga toxin gene.

Uropathogenc Escherichia coli (UPEC) CFT073 has a pathogenicity-associated island (PAI(CFT073)), which causes pyelonephritis and cystitis. Using PCR method, we found the prrA gene of PAI(CFT073) in E. coli O157:H7 EDL933. Further detailed PCR screening of 38 open reading frames, the right and left junction sequences of PAI(CFT073), revealed that it is the prrA-modD-yc73-fepC gene cluster but not the PAI(CFT073) present in E. coli O157:H7 EDL933. A rapid preliminary analysis suggested that the prrA-modD-yc73-fepC gene cluster of the PAI(CFT073), is present in 43 strains of E. coli O157:H7 containing Shiga toxin (Stx) gene but absent in 19 strains of E. coli O157:H7 without Stx gene. A strict co-occurrence of the prrA-modD-yc73-fepC gene cluster and Stx genes was observed, regardless of their origin. The prrA-modD-yc73-fepC gene cluster encode proteins probably involved in iron uptake system, which strongly suggests the importance of iron metabolism in the Stx-mediated virulence. In addition, the prrA-modD-yc73-fepC gene cluster may be used as a diagnostic marker to distinguish E. coli O157:H7 strains containing Stx gene from that without Stx gene, and possibly to quickly detect other pathogenic gram-negative bacteria containing the Stx gene.

Animals↗
PubMed2001

Induction of potent human immunodeficiency virus type 1-specific T-cell-restricted immunity by genetically modified dendritic cells.

A novel technology combining replication- and integration-defective human immunodeficiency virus type 1 (HIV-1) vectors with genetically modified dendritic cells was developed in order to induce T-cell immunity. We introduced the vector into dendritic cells as a plasmid DNA using polyethylenimine as the gene delivery system, thereby circumventing the problem of obtaining viral vector expression in the absence of integration. Genetically modified dendritic cells (GMDC) presented viral epitopes efficiently, secreted interleukin 12, and primed both CD4(+) and CD8(+) HIV-specific T cells capable of producing gamma interferon and exerting potent HIV-1-specific cytotoxicity in vitro. In nonhuman primates, subcutaneously injected GMDC migrated into the draining lymph node at an unprecedentedly high rate and expressed the plasmid DNA. The animals presented a vigorous HIV-specific effector cytotoxic-T-lymphocyte (CTL) response as early as 3 weeks after a single immunization, which later developed into a memory CTL response. Interestingly, antibodies did not accompany these CTL responses, indicating that GMDC can induce a pure Th1 type of immune response. Successful induction of a broad and long-lasting HIV-specific cellular immunity is expected to control virus replication in infected individuals.

Animals↗
PubMed2001

D(1) dopamine receptor regulation of NHE3 during development in spontaneously hypertensive rats.

To determine if the defective interactions among D(1)-like receptors, G proteins, and Na(+)/H(+) exchanger 3 (NHE3) are consequences of hypertension, we studied these interactions in rats, before (2--3 wk) and after (12 wk) the establishment of hypertension. To eliminate the confounding influence of second messenger action on D(1) receptor-NHE3 interaction, studies were performed in renal brush-border membranes (BBM) devoid of cytoplasmic second messengers. NHE3 activity increased with age in Wistar-Kyoto (WKY) rats (3 wk = 1.48 +/- 0.39, n = 13; 12 wk = 2.83 +/- 0.15, n = 16, P < 0.05) but not in spontaneously hypertensive rats (SHRs; 3 wk = 2.52 +/- 0.37, n = 11; 12 wk = 2.81 +/- 0.20, n = 16). D(1) receptor protein tended to decrease, whereas NHE3 protein tended to increase with age in both WKY and SHRs. However, the inhibitory effect of a D(1)-like agonist, SKF-81297, on NHE3 activity increased with age in WKY rats (3 wk = -40.7 +/- 5.3%, n = 10, 12 wk = -58.7 +/- 4.6%, n = 12, P < 0.05) but not in SHRs (3 wk = -27.6 +/- 5.9%, n = 11, 12 wk = -25.1 +/- 3.2%, n = 11). The decreased inhibitory effect of another D(1)-like agonist, fenoldopam, on NHE3 activity in SHRs was not caused by increased activity and binding of G beta gamma to NHE3 as has been reported in young WKY rats. G(s)alpha mediates, in part, the inhibitory effect of D(1)-like agonists on NHE3 activity. In WKY rats, fenoldopam increased G(s)alpha/NHE3 binding to the same extent in 2-wk-old (1.5-fold, n = 4) and adult (1.5-fold, n = 4) rats. In contrast, in SHRs, fenoldopam decreased the amount of G(s)alpha bound to NHE3 in 2-wk-old SHRs and had no effect in 4-wk-old and adult SHRs. These studies indicate that the decreased inhibitory effect of D(1)-like agonists on NHE3 activity in SHRs (compared with WKY rats) precedes the development of hypertension. This may be caused, in part, by a decreased interaction between G(s)alpha and NHE3 in BBM secondary to impaired D(1)-like receptor function.

Aging↗
PubMed2001

Molecular cloning, structure and expression of a novel nuclear RNA-binding cyclophilin-like gene (PPIL4) from human fetal brain.

The cyclophilins are members of a highly conserved, ubiquitous family, and play an important role in protein folding, immunosuppression by cyclosporin A (CsA), and infection of HIV-1 virions. Here we report that a novel member of the cyclophilin family, PPIL4, was cloned and identified during the large-scale sequencing analysis from a human fetal brain cDNA library. The PPIL4 gene encodes a protein which shares 96% amino acid identity with a protein encoded by a putative gene recently cloned from several different early stages of mouse embryo, and its homologues are found in several other organisms. According to bioinformatics analysis, the PPIL4 gene was found to be located in chromosome 6q24-->q25. Besides the PPIase motif, PPIL4 also has an RNA recognition motif (RRM), a pair of bipartite nuclear targeting sequences, and a lysine rich domain. RT-PCR analysis indicated that PPIL4 gene expression is abundant in kidney but has a ubiquitously low expression pattern in other human adult tissues.

Amino Acid Motifs↗
PubMed2001

Reduction and restoration of mitochondrial dna content after focal cerebral ischemia/reperfusion.

BACKGROUND AND PURPOSE: Oxidative damage of mitochondrial DNA (mtDNA) in the ischemic brain is expected after ischemia/reperfusion injury. A recent study demonstrated limited patterns of mtDNA deletion in the brain after ischemia/reperfusion. We studied the ischemia/reperfusion-induced global changes of mtDNA integrity and its restoration in a rat model of transient focal ischemia in vivo. METHODS: Changes in mtDNA content in the ischemic brain were assessed with the use of a rat stroke model featuring transient severe ischemia confined to the cerebral cortex of the right middle cerebral artery territory for 30 or 90 minutes. A new long polymerase chain reaction method, using mouse DNA as an internal standard, was applied to measure the relative content of intact rat mtDNA. Southern hybridization following alkaline gel electrophoresis was conducted in a parallel study to confirm long polymerase chain reaction results. RESULTS: A reduction in mtDNA content was found after ischemia for 30 and 90 minutes. The mtDNA was restored to near nonischemic levels 24 hours after 30- but not 90-minute ischemia. CONCLUSIONS: These results confirm that ischemia/reperfusion causes mtDNA damages. Restoration of the mtDNA content to nonischemic levels after 30-minute ischemia raises the possibility that mtDNA repair or repletion occurs after brief ischemia.

Animals↗
PubMed2001

Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice.

The differential regulation of pulmonary surfactant proteins (SPs) is demonstrated in a murine model of Aspergillus fumigatus (Af )-induced allergic airway inflammation and hyperresponsiveness. BALB/c mice were sensitized intraperitoneally and challenged intranasally with Af extract. Enzyme-linked immunosorbent assay analysis of serum immunoglobulin (Ig) levels in these mice showed markedly increased total IgE and Af-specific IgE and IgG1. This was associated with peribronchial/perivascular tissue inflammation, airway eosinophilia, and secretion of interleukin (IL)-4 and IL-5 into the bronchoalveolar lavage fluid (BALF). Functional analysis revealed that in comparison with nonsensitized mice, allergic sensitization and challenge resulted in significant increases in acetylcholine responsiveness. To analyze levels of SPs, the cell-free supernate of the BALF was further fractionated by high-speed (20,000 x g) centrifugation. After sensitization and challenges, the pellet (large-aggregate fraction) showed a selective downregulation of hydrophobic SPs SP-B and SP-C by 50%. This reduction was reflected by commensurate decreases in SP-B and SP-C messenger RNA (mRNA) expression of the lung tissue of these animals. In contrast, there was a 9-fold increase in SP-D protein levels in the 20,000 x g supernate without changes in SP-D mRNA. The increased levels of SP-D showed a significant positive correlation with serum IgE (r = 0.85, P < 0.001). Tissue mRNA and protein levels of SP-A in either the large- or the small-aggregate fractions were unaffected. Our data indicate that allergic airway inflammation induces selective inhibition of hydrophobic SP synthesis accompanied by marked increases in the lung collectin SP-D protein content of BALF. These changes may contribute significantly to the pathophysiology of Af-induced allergic airway hyperresponsiveness.

Animals↗
PubMed2001

Identification and association of polymorphisms in the interleukin-13 gene with asthma and atopy in a Dutch population.

Asthma and atopy are related conditions that may share similar genetic susceptibility. Linkage studies have identified a region on chromosome 5q that contains biologic candidates for both asthma and atopy phenotypes, including several proinflammatory cytokines. Interleukin (IL)-13, one of the candidate genes in the region, is directly involved in the regulation of immunoglobulin E and has been associated with both asthma and atopy. We sought to identify new polymorphisms in the IL-13 gene, and evaluated the involvement of a subset of these variants in asthma and atopy in a case-control study using probands and spouses from a Dutch asthma family study. IL-13 was sequenced in 20 probands and 20 unaffected spouses, and 10 polymorphisms were identified, four novel and six previously reported. Three single nucleotide (nt) polymorphisms (SNPs) were detected in the 5'-promoter region, two in intron 1, and five in exon 4. Only one of the exon 4 SNPs resulted in an amino-acid change (Arg130Gln). We analyzed three SNPs in IL-13 in an extended group of 184 probands and their spouses: one in the promoter region (-1111), the Arg130Gln (nt position 4257), and a 3' untranslated region SNP (nt position 4738). The most significant associations were observed to asthma (P = 0.005), bronchial hyperresponsiveness (P = 0.003), and skin-test responsiveness (P = 0.03) with the -1111 promoter. These results provide evidence that variation in the IL-13 gene is involved in the pathogenesis of asthma and atopy. Further investigation is required to determine which specific alleles or combination of alleles contribute to these phenotypes, and the possible downstream effects of the resulting change in IL-13 levels or activity.

Adult↗
PubMed2001

A novel method for enzyme immobilization: direct encapsulation of acid phosphatase in nanoporous silica host materials.

Immobilization of acid phosphatase (ACP) in mesoporous or, more generally, nanoporous silica has been accomplished via the sol-gel reactions of tetramethyl orthosilicate in the presence of ACP and of D-glucose (DG) as a nonsurfactant template, which is subsequently removed by water extraction after the formation of nanocomposite gels. Characterization of the silica host after the removal of DG shows that the pore size and volume generally increase with the DG content. At high DG contents, the silica hosts are nanoporous with interconnected nanoscaled pores/channels of regular diameter (e.g., 3.4 nm). Catalytic activity of ACP encapsulated in nanoporous hosts is significantly improved over that in microporous host prepared in the absence of DG. The apparent enzymatic activity at various pH values and substrate concentrations correlates well with the nanostructures of the host matrices. As the DG content is increased in the synthesis, the activity tends to increase. At a DG content of 42-60 wt%, the samples exhibit activities about triple that of the template-free control. These and other results from enzymatic kinetic studies suggest that the increase in the pore size and volume facilitates the transport of the substrate and product molecules in the host matrices, leading to the observed increase in activity. The thermal stability of ACP is remarkably improved upon immobilization. There is no detectable leakage of ACP from the host matrices and the biogels are reuseable. This study provides a useful protocol for the development of nanotechnology for various biocatalysts and biosensors.

Acid Phosphatase↗
PubMed2001

Feedback regulation of PRL secretion is mediated by the transcription factor, signal transducer, and activator of transcription 5b.

PRL secretion from the anterior pituitary gland is inhibited by dopamine produced in the tuberoinfundibular dopamine neurons of the hypothalamus. The activity of tuberoinfundibular dopamine neurons is stimulated by PRL; thus, PRL regulates its own secretion by a negative feedback mechanism. PRL receptors are expressed on tuberoinfundibular dopamine neurons, but the intracellular signaling pathway is not known. We have observed that mice with a disrupted signal transducer and activator of transcription 5b gene have grossly elevated serum PRL concentrations. Despite this hyperprolactinemia, mRNA levels and immunoreactivity of tyrosine hydroxylase, the key enzyme in dopamine synthesis, were significantly lower in the tuberoinfundibular dopamine neurons of these signal transducer and activator of transcription 5b-deficient mice. Concentrations of the dopamine metabolite dihydroxyphenylacetic acid in the median eminence were also significantly lower in signal transducer and activator of transcription 5b-deficient mice than in wild-type mice. No changes were observed in nonhypothalamic dopaminergic neuronal populations, indicating that the effects were selective to tuberoinfundibular dopamine neurons. These data indicate that in the absence of signal transducer and activator of transcription 5b, PRL signal transduction in tuberoinfundibular dopamine neurons is impaired, and they demonstrate that this transcription factor plays an obligatory and nonredundant role in mediating the negative feedback action of PRL on tuberoinfundibular dopamine neurons.

Animals↗
PubMed2001

The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts.

Giant cell tumour of bone (GCT) is a benign primary neoplasm of a bone characterised by distinctive clinical, radiological and pathological features. Females are slightly more often affected than males, and the majority of patients present between the ages of 20 and 50. GCT is locally aggressive and produces expansive and lytic lesions, most commonly in the epiphyses of long tubular bones. Histologically, it is composed of oval and spindle mononuclear cells, uniformly distributed amongst which are large multinucleated osteoclast-like giant cells. Although the term "Giant Cell Tumour" (and the erroneous historical term 'osteoclastoma') may imply that it is the multinucleated giant cells which are responsible for the proliferative capacity of the tumour, there is evidence that the stromal-like cells, the major component of the mononuclear cell population, represent the true neoplastic component of the neoplasm. The diagnosis and management of conventional GCT are often challenging and there is considerable current interest in its pathobiology. The precise histogenesis of GCT and the nature of its varying cellular constituents have remained a matter of some controversy. Factors influencing the clinical course and biological aggression of GCT are also unclear. In this selective review, the clinicopathological characteristics of GCT are summarised and current areas of interest in the study of the neoplasm are presented and discussed. Lastly, a hypothetical model of the mechanism of histogenesis and the biological behaviour of GCT is presented.

Animals↗
PubMed2001

Comparison of Diadegma insulare (Hymenoptera: Ichneumonidae) and Microplitis plutellae (Hymenoptera: Braconidae) as biological control agents of Plutella xylostella (Lepidoptera: Plutellidae): field parasitism, insecticide susceptibility, and host-searching.

Parasitism of Plutella xylostella (L.) third and fourth instars was evaluated in a cabbage field in Geneva, NY, in 1999. Over the entire season, average parasitism was 33.6% for third instars and 53.6% for fourth instars, and the main parasitoids were Diadegma insulare (Cresson) and Microplitis plutellae Muesbeck. In the early season, total parasitism was low, and mainly caused by D. insulare. However, later in the season, parasitism reached >80% for the fouth instars and 50% for the third instars. Our survey indicated that M. plutellae heavily parasitized P. xylostella, and provided higher parasitism rates than D. insulare in the late season. Comparison of these two species in laboratory bioassays indicated there were no significant differences in susceptibility to four insecticides commonly used in crucifer fields. For both parasitoids, an experience with P. xylostella on a damaged leaf increased their host-searching efficacy. Compared with M. plutellae, D. insulare was a better host-searcher both for the naive and the experienced adults. Although both parasitoids can cause high mortality rates of P. xylostella, D. insulare may be more suitable to be released in fields to enhance natural control against P. xylostella.

Animals↗
PubMed2001

Variation in susceptibility of Diadegma insulare (Hymenoptera: Ichneumonidae) to permethrin.

Six field populations of the parasitoid Diadegma insulare (Cresson) were collected from Mexico and the United States and tested for their susceptibility to permethrin by using a glass-vial residue bioassay. Significant differences existed in susceptibility, with one population significantly more susceptible than the other five. Susceptibility of D. insulare increased when they were reared for several generations in the greenhouse in the absence of selection. D. insulare was less suceptible to permethrin than the adult stage of its host, Plutella xylostella (L.), from a laboratory colony, but more susceptible than those hosts collected from a commercial field. Our data suggest that a field population of D. insulare appeared to increase its tolerance to permethrin much more slowly than P. xylostella.

Animals↗