Biomedical subjects

Q Chen

Publications and source records attributed to Q Chen.

At least 91 records · Page 5Linked to original sources

PubMed2002

A novel sialyl Lewis(x) analogue attenuates ischemia reperfusion injury in rabbit lung.

BACKGROUND: We investigated the effects of OJ-R9545, a novel Sialyl Lewis x analogue, on lung ischemia-reperfusion (IR) injury using an in vivo rabbit model. METHODS: The left hilum of the lung was clamped for 110 minutes; the lung was then reperfused for 90 minutes. Either OJ-R9545 (10 mg/kg) or vehicle solution was administered from 10 minutes before reperfusion to 60 minutes after reperfusion in the OJ-R (+) and OJ-R (-) group (n = 6 in each group), respectively. The sham group (n = 3) underwent an identical procedure without ischemia. RESULTS: Arterial oxygen tensions in the OJ-R (+) group were superior to those in the OJ-R (-) group from 30 to 90 minutes after reperfusion (p < 0.05 and p < 0.01). Lung wet/dry weight ratio and myeloperoxidase activity after reperfusion in the OJ-R (+) group were both significantly lower than the corresponding figures in the OJ-R (-) group (p < 0.05). The intrapulmonary leukocytes were significantly reduced in the OJ-R (+) group compared with those in the OJ-R (-) group (p < 0.01). CONCLUSIONS: OJ-R9545 attenuates lung IR injury by preventing leukocyte infiltration into the lung.

Animals↗

PubMed2001

Orbital ordering in LaMnO3: estimates of structure factors and comparison of measurement methods.

This paper shows that the phenomenon of orbital ordering should be detectable by energy-filtered quantitative convergent-beam electron diffraction (QCBED). The structure factors of LaMnO(3) crystals are calculated using a non-spherical atomic scattering model of the Mn(3+) ion. Several low-order electron structure factors showed pronounced change with orbital ordering, in which the e(g)(1) electron orders in the 3d(3z(2) - r(2)) orbital leaving the 3d(x(2) - y(2)) unoccupied. In contrast, the X-ray structure factors showed very small change. Orbital order is important in transition-metal oxides, including colossal magnetoresistive manganite oxides. The calculations show that by using QCBED it is possible to measure the subtle changes in electron structure factors due to orbital ordering of the e(g)(1) electron of the Mn(3+) ion in an LaMnO(3) crystal. A comparison of methods for structure-factor measurement is given, including Bragg X-ray and gamma-ray diffraction, X-ray Pendellösung and critical-voltage methods. New measurements by QCBED of structure factors in rutile are compared with the Bragg X-ray values. These show that QCEBD can provide an accurate extinction-free measurement of low-order structure factors, which is extremely difficult or perhaps impossible when using other methods applied to real crystals.

Journal Article↗

PubMed2001

Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication.

SCF ubiquitin ligases target phosphorylated substrates for ubiquitin-dependent proteolysis by means of adapter subunits called F-box proteins. The F-box protein Cdc4 captures phosphorylated forms of the cyclin-dependent kinase inhibitor Sic1 for ubiquitination in late G1 phase, an event necessary for the onset of DNA replication. The WD40 repeat domain of Cdc4 binds with high affinity to a consensus phosphopeptide motif (the Cdc4 phospho-degron, CPD), yet Sic1 itself has many sub-optimal CPD motifs that act in concert to mediate Cdc4 binding. The weak CPD sites in Sic1 establish a phosphorylation threshold that delays degradation in vivo, and thereby establishes a minimal G1 phase period needed to ensure proper DNA replication. Multisite phosphorylation may be a more general mechanism to set thresholds in regulated protein-protein interactions.

Binding Sites↗

PubMed2001

Selective permeation of hydrogen peroxide through polyelectrolyte multilayer films and its use for amperometric biosensors.

A platinum electrode was coated with polyelectrolyte multilayer (PEM) films to prepare an amperometric hydrogen peroxide sensor which can be used in the presence of possible interferences such as ascorbic acid, uric acid, and acetaminophen. The PEM films were prepared on the surface of a Pt disk electrode by an alternate deposition of polycation and polyanion from the aqueous solutions through electrostatic force of attraction. The Pt electrodes coated with a poly(allylamine)/poly(vinyl sulfate) or poly(allylamine)/poly(styrenesulfonate) film were used successfully for detecting H2O2 selectively in the presence of the possible interfering agents. It was suggested that H2O2 can diffuse into the PEM film smoothly while the ascorbic acid, uric acid, and acetaminophen cannot penetrate the film by a size exclusion mechanism. On the other hand, the electrodes coated with PEM films containing poly(ethyleneimine) or poly(diallyldimethylammonium chloride) were not useful for the selective determination of H2O2. The results were rationalized based on the different permeability of the films due to the different molecular density or packing in the PEM films. The PEM film-coated electrode was useful for constructing glucose biosensors by coupling with glucose oxidase.

Acetaminophen↗

PubMed2001

Present-day crustal deformation in China constrained by global positioning system measurements.

Global Positioning System (GPS) measurements in China indicate that crustal shortening accommodates most of India's penetration into Eurasia. Deformation within the Tibetan Plateau and its margins, the Himalaya, the Altyn Tagh, and the Qilian Shan, absorbs more than 90% of the relative motion between the Indian and Eurasian plates. Internal shortening of the Tibetan plateau itself accounts for more than one-third of the total convergence. However, the Tibetan plateau south of the Kunlun and Ganzi-Mani faults is moving eastward relative to both India and Eurasia. This movement is accommodated through rotation of material around the eastern Syntaxis. The North China and South China blocks, east of the Tibetan Plateau, move coherently east-southeastward at rates of 2 to 8 millimeters per year and 6 to 11 millimeters per year, respectively, with respect to the stable Eurasia.

Journal Article↗

PubMed2001

Induction of alpha-synuclein aggregation by intracellular nitrative insult.

Brain lesions containing filamentous and aggregated alpha-synuclein are hallmarks of neurodegenerative synucleinopathies. Oxidative stress has been implicated in the formation of these lesions. Using HEK 293 cells stably transfected with wild-type and mutant alpha-synuclein, we demonstrated that intracellular generation of nitrating agents results in the formation of alpha-synuclein aggregates. Cells were exposed simultaneously to nitric oxide- and superoxide-generating compounds, and the intracellular formation of peroxynitrite was demonstrated by monitoring the oxidation of dihydrorhodamine 123 and the nitration of alpha-synuclein. Light microscopy using antibodies against alpha-synuclein and electron microscopy revealed the presence of perinuclear aggregates under conditions in which peroxynitrite was generated but not when cells were exposed to nitric oxide- or superoxide-generating compounds separately. alpha-Synuclein aggregates were observed in 20-30% of cells expressing wild-type or A53T mutant alpha-synuclein and in 5% of cells expressing A30P mutant alpha-synuclein. No evidence of synuclein aggregation was observed in untransfected cells or cells expressing beta-synuclein. In contrast, selective inhibition of the proteasome resulted in the formation of aggregates detected with antibodies to ubiquitin in the majority of the untransfected cells and cells expressing alpha-synuclein. However, alpha-synuclein did not colocalize with these aggregates, indicating that inhibition of the proteasome does not promote alpha-synuclein aggregation. In addition, proteasome inhibition did not alter the steady-state levels of alpha-synuclein, but addition of the lysosomotropic agent ammonium chloride significantly increased the amount of alpha-synuclein, indicating that lysosomes are involved in degradation of alpha-synuclein. Our data indicate that nitrative and oxidative insult may initiate pathogenesis of alpha-synuclein aggregates.

Ammonium Chloride↗

PubMed2001

Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma.

It has been reported that interferons (IFNs) may have antitumor activity in multiple myeloma (MM). The mechanism for their effect on MM, however, remains elusive. This study shows that IFN-alpha and -beta, but not -gamma, induce apoptosis characterized by Annexin V positivity, nuclear fragmentation and condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and NCI-H929), and in plasma cells from 10 patients with MM. Apo2 ligand (Apo2L, also TRAIL) induction was one of the earliest events following IFN administration in U266 cells. Treatment of these cells with TRAIL, but not with Fas agonistic antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in U266 cells was partially blocked by a dominant-negative Apo2L receptor, DR5, demonstrating the functional significance of Apo2L induction. This study shows that IFNs activate caspases and the mitochondrial-dependent apoptotic pathway, possibly mediated by Apo2L production. Thus, IFN-alpha and -beta induce cytochrome c release from mitochondria starting at 12 hours, with an amplified release seen at 48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release, whereas the late, amplified cytochrome c release coincides with changes in levels of Bcl-2, Bcl-X(L), and reduction of mitochondrial membrane potential. These results link the Apo2L induction and modulation of Bcl-2 family proteins to mitochondrial dysfunction. Furthermore, IFNs and Apo2L induce cell death of CD38(+)/CD45(-/dim) plasma cells, without significant effect on nonplasma blood cells, in a caspase and Bcl-2 cleavage-dependent manner. These results warrant further clinical studies with IFNs and Apo2L in MM.

Apoptosis↗

PubMed2001

A novel sugar-stimulated covalent switch in a sugar sensor.

The bgl sensory system is composed of a membrane-bound sugar sensor, BglF, and a transcriptional regulator, BglG. The sensor BglF has several enzymatic activities: in its nonstimulated state, it acts as BglG phosphorylase; in the presence of beta-glucoside in the growth medium, it acts as BglG dephosphorylase and as the beta-glucoside phosphotransferase. The same active site on BglF, Cys-24, is responsible for the phosphorylation of both the stimulating sugar and the BglG protein. BglF is composed of three domains, two hydrophilic and one hydrophobic. Our previous results suggested that catalysis of the sugar-stimulated functions depends on specific interactions between the B domain, which contains the active site cysteine, and the integral membrane C domain. We report here that the stimulating sugar triggers the formation of a disulfide bond between the active site cysteine and another cysteine in the membrane-embedded domain of BglF. Inability of a mutant BglF protein to form the disulfide bridge between the B and C domains correlates with its inability to catalyze the sugar-stimulated functions. The ability of the cysteine residue in BglF to bind covalently either to a phosphoryl group or to another cysteine residue, depending on the protein stimulation state, suggests a novel way to control signaling by alternative bond formation.

Bacterial Proteins↗

PubMed2001

Dynamic regulation of metabolism and respiration by endogenously produced nitric oxide protects against oxidative stress.

One of the many biological functions of nitric oxide is the ability to protect cells from oxidative stress. To investigate the potential contribution of low steady state levels of nitric oxide generated by endothelial nitric oxide synthase (eNOS) and the mechanisms of protection against H(2)O(2), spontaneously transformed human ECV304 cells, which normally do not express eNOS, were stably transfected with a green fluorescent-tagged eNOS cDNA. The eNOS-transfected cells were found to be resistant to injury and delayed death following a 2-h exposure to H(2)O(2) (50-150 microM). Inhibition of nitric oxide synthesis abolished the protective effect against H(2)O(2) exposure. The ability of nitric oxide to protect cells depended on the presence of respiring mitochondria as ECV304+eNOS cells with diminished mitochondria respiration (rho(-)) are injured to the same extent as nontransfected ECV304 cells and recovery of mitochondrial respiration restores the ability of nitric oxide to protect against H(2)O(2)-induced death. Nitric oxide also found to have a profound effect in cell metabolism, because ECV304+eNOS cells had lower steady state levels of ATP and higher utilization of glucose via the glycolytic pathway than ECV304 cells. However, the protective effect of nitric oxide against H(2)O(2) exposure is not reproduced in ECV304 cells after treatment with azide and oligomycin suggesting that the dynamic regulation of respiration by nitric oxide represent a critical and unrecognized primary line of defense against oxidative stress.

Adenosine Triphosphate↗

PubMed2001

Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1).

Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-beta. To test this hypothesis we compared the regulation of TGF-beta in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-beta(1) production in transgenic animals and macrophages were the major site of TGF-beta(1) production and deposition in these tissues. IL-13 also activated TGF-beta(1) in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-beta-binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-beta(1) activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13-induced fibrosis was also significantly ameliorated by treatment with the TGF-beta antagonist soluble TGFbetaR-Fc (sTGFbetaR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-beta(1) in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9-dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-beta pathway.

Animals↗

PubMed2001

Role of nonimmune IgG bound to PfEMP1 in placental malaria.

Infections with Plasmodium falciparum during pregnancy lead to the accumulation of parasitized red blood cells (infected erythrocytes, IEs) in the placenta. IEs of P. falciparum isolates that infect the human placenta were found to bind immunoglobulin G (IgG). A strain of P. falciparum cloned for IgG binding adhered massively to placental syncytiotrophoblasts in a pattern similar to that of natural infections. Adherence was inhibited by IgG-binding proteins, but not by glycosaminoglycans or enzymatic digestion of chondroitin sulfate A or hyaluronic acid. Normal, nonimmune IgG that is bound to a duffy binding-like domain beta of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) might at the IE surface act as a bridge to neonatal Fc receptors of the placenta.

Animals↗

PubMed2001

Limits on silicon nanoelectronics for terascale integration.

Throughout the past four decades, silicon semiconductor technology has advanced at exponential rates in both performance and productivity. Concerns have been raised, however, that the limits of silicon technology may soon be reached. Analysis of fundamental, material, device, circuit, and system limits reveals that silicon technology has an enormous remaining potential to achieve terascale integration (TSI) of more than 1 trillion transistors per chip. Such massive-scale integration is feasible assuming the development and economical mass production of double-gate metal-oxide-semiconductor field effect transistors with gate oxide thickness of about 1 nanometer, silicon channel thickness of about 3 nanometers, and channel length of about 10 nanometers. The development of interconnecting wires for these transistors presents a major challenge to the achievement of nanoelectronics for TSI.

Journal Article↗

PubMed2001

[Defective expression of B7.2 in B cell chronic lymphocytic leukemia B cells].

OBJECTIVE: To investigate the expression of B7.1 and B7.2 molecules in peripheral B cells of patients with chronic B cell lymphocytic leukemia (BCLL) and to study the relationship between B7.1 and B7.2 expression and pathogenic mechanism of BCLL. METHODS: Peripheral blood mononuclear cells (PBMC) were separated by Ficoll-Hypaque lymphocytes separation medium from 25 normal persons (normal control group) and 23 BCLL patients (BCLL group) which were further divided into two groups, phase 0-II group and phase III-IV group. Flow cytometry (FCM) was used to analyze the B7.1 and B7.2 expression in peripheral B cells after the mononuclear cells had been cultured for 24 hours in vitro. RESULTS: The B7.2 expression in B cells of BCLL patients was significantly lower than that in normal control group (P < 0.05). No statistically significant difference was found in the B7.1 expression and co-expression of B7.1 and B7.2 between the BCLL group and normal control group. The average B7.2 expression rates in patients of phase 0-II group and phase III-IV group were 25% +/- 17% and 17% +/- 8% respectively without statistically significant difference. CONCLUSION: The B7.2 expression in B cell of patients with BCLL is defective, which may be one of the pathogenic mechanisms of chronic BCLL and a major cause why the body fails to clear the BCLL cells via immunological means.

Adult↗

PubMed2001

Exogenous peptides presented by transporter associated with antigen processing (TAP)-deficient and TAP-competent cells: intracellular loading and kinetics of presentation.

This study investigates the differential capacity of TAP-deficient T2 cells, TAP-competent EBV cells, and immature and mature dendritic cells to present peptides to preformed CTL lines. It demonstrates that presentation of exogenous peptides involves peptide uptake and loading onto newly synthesized MHC class I molecules. This mechanism was best demonstrated for low affinity peptides in the presence of irrelevant peptides competing for HLA binding sites. Under these circumstances, inhibition of protein synthesis with cycloheximide or vesicular trafficking with brefeldin A significantly reduced the presentation of low affinity peptides. This was not restored by adding exogenous beta(2)-microglobulin to stabilize the MHC complex on the cell surface. In contrast, presentation of high affinity peptides was not sensitive to cycloheximide or brefeldin A, which suggests that different mechanisms may operate for presentation of high and low affinity peptides by TAP-competent cells. High affinity peptides can apparently compete with peptides in preloaded MHC class I molecules at the cell surface, whereas low affinity peptides require empty MHC molecules within cells. Accordingly, very high concentrations of exogenous low affinity peptides in conjunction with active MHC class I metabolism were required to allow successful presentation against a background of competing intracellular high affinity peptides in TAP-competent cells. These findings have implications for the design of peptide and protein-based vaccines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

The activation of dopamine D4 receptors inhibits oxidative stress-induced nerve cell death.

Oxidative stress is thought to be the cause of nerve cell death in many CNS pathologies, including ischemia, trauma, and neurodegenerative disease. Glutamate kills nerve cells that lack ionotropic glutamate receptors via the inhibition of the cystine-glutamate antiporter x(c)(-), resulting in the inhibition of cystine uptake, the loss of glutathione, and the initiation of an oxidative stress cell death pathway. A number of catecholamines were found to block this pathway. Specifically, dopamine and related ligands inhibit glutamate-induced cell death in both clonal nerve cell lines and rat cortical neurons. The protective effects of dopamine, apomorphine, and apocodeine, but not epinephrine and norepinephrine, are antagonized by dopamine D4 antagonists. A dopamine D4 agonist also protects, and this protective effect is inhibited by U101958, a dopamine D4 antagonist. Although the protective effects of some of the catecholamines are correlated with their antioxidant activities, there is no correlation between the protective and antioxidant activities of several other ligands. Normally, glutamate causes an increase in reactive oxygen species (ROS) and intracellular Ca(2+). Apomorphine partially inhibits glutamate-induced ROS production and blocks the opening of cGMP-operated Ca(2+) channels that lead to Ca(2+) elevation in the late part of the cell death pathway. These data suggest that the protective effects of apomorphine on oxidative stress-induced cell death are, at least in part, mediated by dopamine D4 receptors via the regulation of cGMP-operated Ca(2+) channels.

Animals↗

PubMed2001

Optimal alveolar oxygen concentration for cold storage of the lung.

BACKGROUND: Ischemia of the lung is different from that of solid organs because the lung contains gas in the alveoli. However, the optimal gas composition in the alveoli during cold storage remains uncertain. We investigated the relationship between the alveolar oxygen concentration and reperfusion injury. METHODS: The lungs inflated with 0% O2, 5% O2, room air, 50% O2, or 100% O2 were reperfused after 8 hR storage at 4 degrees C and pulmonary functions were measured for 120 min using an ex vivo rat lung model. The levels of high-energy phosphate and lipid peroxidation of the lung were analyzed after a PA flush, preservation, and reperfusion. Additionally, respiration of the mitochondria in the lungs was measured after preservation. RESULTS: The pulmonary functions were significantly superior in the 5% O2 group than those in the 0% O2, 50% O2, and 100% O2 groups. Pulmonary edema developed in the 0% O2, 50% O2, and 100% O2 groups, but not in the 5% O2 group. After preservation, the energy level in the lungs decreased only in the 0% O2 group. Although lipid peroxidation of the lungs did not increase in any group after preservation, significant increases were observed in the room air, 50% O2 and 100% O2 groups after reperfusion. State 3 and 4 ratios of the mitochondrial respiration significantly decreased in the lungs of the room air, 50% O2 and 100% O2 groups. CONCLUSIONS: Although the cold-preserved lungs require oxygen, hyperoxygenation induced mitochondrial dysfunction and increased lipid peroxidation and led to deleterious lung function after reperfusion. Therefore, hypoxic conditions that can maintain the energy level of the lung during cold storage would be optimal.

Adenine Nucleotides↗

PubMed2001

Indian hedgehog is an essential component of mechanotransduction complex to stimulate chondrocyte proliferation.

Indian hedgehog (Ihh), a member of the vertebrate hedgehog morphogen family, is a key signaling molecule that controls chondrocyte proliferation and differentiation. In this study, we show a novel function of Ihh. Namely, it acts as an essential mediator of mechanotransduction in cartilage. Cyclic mechanical stress greatly induces the expression of Ihh by chondrocytes. This induction is abolished by gadolinium, an inhibitor of stretch-activated channels. This suggests that the IHH gene is mechanoresponsive. The mechano-induction of Ihh is essential for stimulating chondrocyte proliferation by mechanical loading. The presence of an Ihh functional blocking antibody during loading completely abolishes the stimulatory effect of mechanical load on proliferation. Furthermore, Ihh mediates the mechanotransduction process in a bone morphogenic protein (BMP)-dependent and parathyroid hormone-related peptide-independent manner. BMP 2/4 are up-regulated by mechanical stress through the induction of Ihh, and BMP antagonist noggin inhibits mechanical stimulation of chondrocyte proliferation. This suggests BMP lies downstream of Ihh in mechanotransduction pathway. Our data suggest that Ihh may transduce mechanical signals during cartilage growth and repair processes.

Animals↗

PubMed2001

Glucose-induced toxicity in insulin-producing pituitary cells that coexpress GLUT2 and glucokinase. Implications for metabolic engineering.

We have shown that intermediate lobe (IL) pituitary cells can be engineered to produce sufficient amounts of insulin (ins) to cure diabetes in nonobese diabetic mice but, unlike transplanted islets, ILins cells evade immune attack. To confer glucose-sensing capabilities into these cells, they were further modified with recombinant adenoviruses to express high levels of GLUT2 and the beta-cell isoform of glucokinase (GK). Although expression of GLUT2 alone had negligible effects on glucose usage and lactate production, expression of GK alone resulted in approximately 2-fold increase in glycolytic flux within the physiological (3-20 mm) glucose range. GLUT2/GK coexpression further increased glycolytic flux at 20 mm glucose but disproportionately increased flux at 3 mm glucose. Despite enhanced glycolytic fluxes, GLUT2/GK-coexpressing cells showed glucose dose-dependent accumulation of hexose phosphates, depletion of intracellular ATP, and severe apoptotic cell death. These studies demonstrate that glucose-sensing properties can be introduced into non-islet cells by the single expression of GK and that glucose responsiveness can be augmented by the coexpression of GLUT2. However, in the metabolic engineering of surrogate beta cells, it is critical that the levels of the components be closely optimized to ensure their physiological function and to avoid the deleterious consequences of glucose-induced toxicity.

Adenosine Triphosphate↗