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Biomedical subjects

Y Wu

Publications and source records attributed to Y Wu.

At least 73 records · Page 4Linked to original sources
PubMed2004

Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To assess longitudinal expression of a proliferation-inducing ligand (APRIL) in patients with systemic lupus erythematosus (SLE) and its correlation with B lymphocyte stimulator (BLyS) expression, serum anti-dsDNA titres, and clinical disease activity. METHODS: Sixty eight patients with SLE were longitudinally followed up for a median of 369 days. At each visit the physician assessed disease activity by SLEDAI, and blood was collected for determination of serum APRIL and BLyS levels and of blood APRIL and BLyS mRNA levels. Fifteen normal control subjects underwent similar laboratory evaluation. RESULTS: Dysregulation of APRIL was not as great as that of BLyS. Changes in serum levels of APRIL and BLyS over time were usually discordant, whereas blood levels of APRIL and BLyS mRNA strongly paralleled each other. Serum APRIL levels modestly, but significantly, inversely correlated with serum anti-dsDNA titres in anti-dsDNA positive patients analysed in aggregate. Moreover, serum APRIL levels modestly, but significantly, inversely correlated with clinical disease activity in all patients analysed in aggregate. CONCLUSION: Serum levels of APRIL and BLyS are differentially regulated. APRIL may serve as a down modulator of serological and/or clinical autoimmunity in patients with SLE. This may have important ramifications for BLyS targeted treatment, and it remains to be determined whether agents which neutralise only BLyS will be preferable to agents which neutralise both BLyS and APRIL.

Antibodies, Antinuclear↗
PubMed2004

Technical note: protein conjugate-based immunoassay of whole milk progesterone.

The objectives were to develop a novel protein conjugate-based ELISA test for whole milk progesterone with a dynamic range capable of fully profiling estrous cycles in the dairy cow and to study effects of whole milk medium on antibody binding to progesterone-protein conjugates. A series of progesterone-4-ovalbumin conjugates with different length intermediate linkers were applied as coating antigens in an ELISA format to determine antibody-binding performance in whole milk. Use of an 18-atom linker gave higher binding than use of a 4- or 11-atom linker at certain conjugate concentrations, but no further increase was observed with increasing linker length. An ELISA constructed with the 18-atom linker conjugate gave a detection limit of 0.089 ng/mL progesterone and correlated well to an established radioimmunoassay procedure (r = 0.94). The assay has the distinct advantages of a wide linear range (0.1 to 100 ng/mL), allowing full profiling of bovine estrous cycles, use of whole milk directly without extraction or prior dilution, and employing more easily purified protein conjugates as coating antigens compared with commercial progesterone-enzyme conjugate for milk ELISA assays.

Animals↗
PubMed2004

Acceptance and completion of hepatitis B vaccination among drug users in New York City.

Hepatitis B (HBV) vaccination rates remain low among drug users. We examined correlates of vaccine acceptance and completion in two ongoing prospective studies of young injecting and non-injecting drug users in New York City. Street recruited drug users were enrolled at one of two neighbourhood locations (Harlem and the Bronx) between 2000 and 2004 and completed risk behaviour questionnaires and HBV testing. Free HBV vaccination was offered. Among 1117 participants, 26.1% (275) had a previous HBV infection, 57.9% (610) were susceptible to HBV, and 16.0% (169) had serological evidence of previous vaccination. Of the 610 participants susceptible to HBV, 466 (76.4%) returned for their results and were offered vaccination; 53.9% (251) received at least one dose of the vaccine (acceptors). Correlates of vaccine acceptance included older age, public assistance as main income source, and being recruited in the Bronx. Daily crack users were significantly less likely to initiate the vaccine series. Among 240 vaccine acceptors, 98 (40.8%) completed all three doses. Daily injectors, Hispanics, and those recruited in Harlem were less likely to complete the vaccination series. HBV vaccination acceptance among drug users seems likely in programmes that are convenient and offer remuneration; however, extended efforts are needed to improve series completion.

Adult↗
PubMed2003

Phosphate ions in bone: identification of a calcium-organic phosphate complex by 31P solid-state NMR spectroscopy at early stages of mineralization.

Previous 31P cross-polarization and differential cross-polarization magic angle spinning (CP/MAS and DCP/MAS) solid-state NMR spectroscopy studies of native bone and of the isolated crystals of the calcified matrix synthesized by osteoblasts in cell culture identified and characterized the major PO(-3)(4) phosphate components of the mineral phase. The isotropic and anisotropic chemical shift parameters of the minor HPO(-2)(4) component in bone mineral and in mineral deposited in osteoblast cell cultures were found to differ significantly from those of brushite, octacalcium phosphate, and other synthetic calcium phosphates. However, because of in vivo and in vitro evidence that phosphoproteins may play a significant role in the nucleation of the solid mineral phase of calcium phosphate in bone and other vertebrate calcified tissues, the focus of the current solid-state 31P NMR experiments was to detect the possible presence of and characterize the phosphoryl groups of phosphoproteins in bone at the very earliest stages of bone mineralization, as well as the possible presence of calcium-phosphoprotein complexes. The present study demonstrates that by far the major phosphate components identified by solid-state 31P NMR in the very earliest stages of mineralization are protein phosphoryl groups which are not complexed with calcium. However, very small amounts of calcium-complexed protein phosphoryl groups as well as even smaller, trace amounts of apatite crystals were also present at the earliest phases of mineralization. These data support the hypothesis that phosphoproteins complexed with calcium play a significant role in the initiation of bone calcification.

Animals↗
PubMed2003

Molecular basis of passive stress relaxation in human soleus fibers: assessment of the role of immunoglobulin-like domain unfolding.

Titin (also known as connectin) is the main determinant of physiological levels of passive muscle force. This force is generated by the extensible I-band region of the molecule, which is constructed of the PEVK domain and tandem-immunoglobulin segments comprising serially linked immunoglobulin (Ig)-like domains. It is unresolved whether under physiological conditions Ig domains remain folded and act as "spacers" that set the sarcomere length at which the PEVK extends or whether they contribute to titin's extensibility by unfolding. Here we focused on whether Ig unfolding plays a prominent role in stress relaxation (decay of force at constant length after stretch) using mechanical and immunolabeling studies on relaxed human soleus muscle fibers and Monte Carlo simulations. Simulation experiments using Ig-domain unfolding parameters obtained in earlier single-molecule atomic force microscopy experiments recover the phenomenology of stress relaxation and predict large-scale unfolding in titin during an extended period (> approximately 20 min) of relaxation. By contrast, immunolabeling experiments failed to demonstrate large-scale unfolding. Thus, under physiological conditions in relaxed human soleus fibers, Ig domains are more stable than predicted by atomic force microscopy experiments. Ig-domain unfolding did not become more pronounced after gelsolin treatment, suggesting that the thin filament is unlikely to significantly contribute to the mechanical stability of the domains. We conclude that in human soleus fibers, Ig unfolding cannot solely explain stress relaxation.

Adaptation, Physiological↗
PubMed2003

A simplified approach to stem cell mobilization in multiple myeloma patients not previously treated with alkylating agents.

High-dose chemotherapy and autologous stem cell rescue is considered a standard part of initial therapy for patients with multiple myeloma. Therefore, potential transplant candidates are generally treated with dexamethasone-based programs rather than alkylating agents to avoid stem cell toxicity. The optimal mobilizing regimen for patients with multiple myeloma has not been defined. However, aggressive chemotherapy may result in excessive morbidity and cost in this older, immunocompromised population. We retrospectively examined our experience with a well-tolerated regimen of 1.5 g/m(2) cyclophosphamide on day -10 followed by 10 microg/kg G-CSF beginning on day -7 in 50 consecutive patients with multiple myeloma and no prior alkylating agent therapy. Median stem cell collection was 4.88 x 10(6) CD34+ cells/kg per apheresis and 44 patients collected >5 x 10(6) CD34+ cells/kg within 2 days. In 36 patients, more than 10 x 10(6) CD34+ cells/kg were collected including 33 patients who required 1-2 days of collection. One patient required hospitalization for fever/neutropenia and two required weekend apheresis. We conclude that 1.5 g/m(2) cyclophosphamide plus 10 microg/kg G-CSF is a safe, effective, highly predictable mobilizing program that uniformly provided enough stem cells for one transplant and enough stem cells for two transplants.

Adult↗
PubMed2003

CIR sand casting system for trans-tibial socket.

The authors have developed a trans-tibial socket fabrication system based on the "dilatancy" principle, a process that has been commonly used in forming wheelchair Seating. The CIR Sand Casting System replaces plaster of Paris with sand for forming both a negative sand mould and a positive sand model, which can be modified for either thermoplastic socket formation or resin lamination. Initial clinical trials suggest that fabrication times are approximately 90 minutes from patient evaluation and casting to dynamic alignment. Compatibility with all existing prosthetic components is retained. It is believed the CIR socket fabrication system may be a competitive alternative for prosthetic service providers in developing countries.

Amputation, Surgical↗
PubMed2003

Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis.

BACKGROUND: It has been shown that expression of the potent angiogenic factor, vascular endothelial growth factor (VEGF), and its receptors, flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), increased during the development of liver fibrosis. AIMS: To elucidate the in vivo role of interaction between VEGF and its receptors in liver fibrogenesis. METHODS: A model of CCl(4) induced hepatic fibrosis was used to assess the role of VEGFR-1 and VEGFR-2 by means of specific neutralising monoclonal antibodies (R-1mAb and R-2mAb, respectively). R-1mAb and R-2mAb were administered after two weeks of treatment with CCl(4), and indices of fibrosis were assessed at eight weeks. RESULTS: Hepatic VEGF mRNA expression significantly increased during the development of liver fibrosis. Both R-1mAb and R-2mAb treatments significantly attenuated the development of fibrosis associated with suppression of neovascularisation in the liver. Hepatic hydroxyproline and serum fibrosis markers were also suppressed. Furthermore, the number of alpha-smooth muscle actin positive cells and alpha1(I)-procollagen mRNA expression were significantly suppressed by R-1mAb and R-2mAb treatment. The inhibitory effect of R-2mAb was more potent than that of R-1mAb, and combination treatment with both mAbs almost completely attenuated fibrosis development. Our in vitro study showed that VEGF treatment significantly stimulated proliferation of both activated hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). VEGF also significantly increased alpha1(I)-procollagen mRNA expression in activated HSC. CONCLUSIONS: These results suggest that the interaction of VEGF and its receptor, which reflected the combined effects of both on HSC and SEC, was a prerequisite for liver fibrosis development.

Animals↗
PubMed2003

Induction of type-IIA secretory phospholipase A2 in animal models of acute lung injury.

The aim of this study was to evaluate the presence of type-II secretory phospholipase A2 (sPLA2-IIA) in alveolar space and its possible role in the destruction of surfactant in three rat models of acute lung injury. Alveolar instillation of either lipopolysaccaride or live Pseudomonas aeruginosa resulted in a significant increase in lung oedema and in a decrease in static compliance of the respiratory system together with alveolar-neutrophil influx as compared with healthy control rats. The upregulation of messenger ribonucleic acid and sPLA2-IIA by the lung was evident. This was associated with surfactant degradation and a decrease in large:small ratio of surfactant aggregates in bacteria-instilled rats. A negative correlation between compliance and sPLA2-IIA activity in bronchoalveolar lavage fluid was shown. By contrast, during alpha naphthylthiourea-induced injury, neither alveolar-neutrophil influx nor increase in sPLA2-IIA activity was observed. Additional experiments in rats treated with a specific inhibitor of type-II secretory phospholipase A2 activity (3 acetamine-1-benzyl-2 ethylindolyl-5 oxy; propane phosphonic acid (LY311727)) demonstrated no improvement in physiological parameters despite a biochemical effect, suggesting that its activity is only one of the multiple factors involved in the pathophysiology of lung injury.

Animals↗
PubMed2003

Leiocyclocin C and D, two cyclopeptides from Goniothalamus leiocarpus.

Two new cyclopeptides, leiocyclocin C (1) and D (2), were isolated from the seeds of Goniothalamus leiocarpus (Annonaceae). Their structures were determined as cyclo-(Gly1-Ser-Pro2-Tyr2-Gly2-Tyr1-Pro1-Pro3) and cyclo-(Gly1-Leu-Pro1-Gly2-Phe-Tyr-Pro2), respectively, by means of spectral and chemical methods.

Annonaceae↗
PubMed2002

New type of vortex pinning structure effective at very high magnetic fields.

We report on a new type of correlated nanometer-scale pinning structure observed in a melt-processed (Nd0.33Eu0.38Gd0.28)Ba(2)Cu(3)O(y) (NEG-123). It consists of NEG/Ba-rich clusters in the stoichiometric NEG-123 matrix forming a lamellar array with a period of a few nanometers. These lamellas appear within regular twins, thus representing their fine substructure-sometimes straight, sometimes wavy. This new material structure correlates well with the significant enhancement of pinning at high fields, represented by irreversibility field above 14 T at 77 K (B parallel c). We believe that the new pinning medium enables one to significantly broaden the limits for high-field applications.

Journal Article↗
PubMed2002

Protein kinase A phosphorylates titin's cardiac-specific N2B domain and reduces passive tension in rat cardiac myocytes.

beta-Adrenergic stimulation of cardiac muscle activates protein kinase A (PKA), which is known to phosphorylate proteins on the thin and thick filaments of the sarcomere. Cardiac muscle sarcomeres contain a third filament system composed of titin, and here we demonstrate that titin is also phosphorylated by the beta-adrenergic pathway. Titin phosphorylation was observed after beta-receptor stimulation of intact cardiac myocytes and incubation of skinned cardiac myocytes with PKA. Mechanical experiments with isolated myocytes revealed that PKA significantly reduces passive tension. In vitro phosphorylation of recombinant titin fragments and immunoelectron microscopy suggest that PKA targets a subdomain of the elastic segment of titin, referred to as the N2B spring element. The N2B spring element is expressed only in cardiac titins, in which it plays an important role in determining the level of passive tension. Because titin-based passive tension is a determinant of diastolic function, these results suggest that titin phosphorylation may modulate cardiac function in vivo.

Adrenergic beta-Agonists↗
PubMed2002

Measuring and optimizing the momentum aperture in a particle accelerator.

Particle motion in storage rings is confined by various aperture limits, the size of which restricts the performance of the ring in terms of injection efficiency, lifetime, etc. Intrabeam scattering makes particles sweep a large portion of the phase space, where their motion may eventually be resonantly or chaotically excited to large amplitudes leading to collision with the vacuum chamber. We report here the studies performed at the Advanced Light Source (ALS) on the on- and off-momentum particle motion that provides a good understanding of these limitations. Using off-momentum simulations and experiments together with frequency map analysis, we could precisely correlate beam loss areas with resonance locations. The very good agreement between simulations and experiments allowed us to provide guidance for avoiding these dangerous areas. This analysis results in predictive improvements of the momentum aperture, which actually led to a lifetime increase of 25% at the ALS for very high bunch charge.

Journal Article↗
PubMed2002

BDNF overexpression increases dendrite complexity in hippocampal dentate gyrus.

There is increasing evidence that brain-derived neurotrophic factor (BDNF) modulates synaptic and morphological plasticity in the developing and mature nervous system. Plasticity may be modulated partially by BDNF's effects on dendritic structure. Utilizing transgenic mice where BDNF overexpression was controlled by the beta-actin promoter, we evaluated the effects of long-term overexpression of BDNF on the dendritic structure of granule cells in the hippocampal dentate gyrus. BDNF transgenic mice provided the opportunity to investigate the effects of modestly increased BDNF levels on dendrite structure in the complex in vivo environment. While the elevated BDNF levels were insufficient to change levels of TrkB receptor isoforms or downstream TrkB signaling, they did increase dendrite complexity of dentate granule cells. These cells showed an increased number of first order dendrites, of total dendritic length and of total number of branch points. These results suggest that dendrite structure of granule cells is tightly regulated and is sensitive to modest increases in levels of BDNF. This is the first study to evaluate the effects of BDNF overexpression on dendrite morphology in the intact hippocampus and extends previous in vitro observations that BDNF influences synaptic plasticity by increasing complexity of dendritic arbors.

Animals↗
PubMed2002

Patterns of lung function in asymptomatic nonsmoking men and women in the People's Republic of China.

PURPOSE: To evaluate patterns of lung function in healthy, working Chinese men and women in different geographic areas of the People's Republic of China (PRC). METHODS: We conducted lung function tests on 2926 asymptomatic, never smoking Chinese men and women aged 35-56 years residing in or around Beijing and Guangzhou. Within each of these locations, separate urban and rural samples were recruited. RESULTS: Age and height adjusted lung function was greater in Beijing than in Guangzhou, and within each city for residents of rural vs. urban areas. Among women, estimated rates of lung aging were greater in Beijing than in Guangzhou, and in urban vs. rural areas. Both FEV(1) and FVC exhibited a curvilinear association with body mass index. CONCLUSIONS: Lung function data from this largely working cohort exhibited marked geographic and urban-rural differences in this never smoking, adult Chinese cohort. Such variation is not uncommon and may reflect differences in body size, diet, and environmental and occupational exposures across these different settings. Caution should be used in applying published reference equations to populations from different parts of the PRC.

Adult↗
PubMed2002

Study of beta-amyloid peptide (Abeta40) insertion into phospholipid membranes using monolayer technique.

beta-Amyloid peptide (Abeta), a normal constituent of neuronal and non-neuronal cells, has been proved to be the major component of extracellular plaque of Alzheimer's disease (AD). The interaction of Abeta with lipid membranes may be essential for its neurotoxicity. Our previous study revealed that membrane insertion may provide a possible pathway by which Abeta prevents itself from aggregation and fibril formation. In the present work we studied the membrane insertion of Abeta and the factors that affect its insertion ability using a monolayer approach. The results show that Abeta is surface active and can insert into lipid monolayers. When a high level of cholesterol is present, Abeta40 can insert into the phospholipid mixtures simulating physiological membrane composition. Acidic pH enhances Abeta insertion, while the effect of ionic strength is rather complex. Abeta insertion ability may be ultimately relative to cholesterol-rich domains in the monolayers, which indicates strong interaction between Abeta and cholesterol.

1,2-Dipalmitoylphosphatidylcholine↗