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Biomedical subjects

Y Qiu

Publications and source records attributed to Y Qiu.

At least 37 records · Page 2Linked to original sources
PubMed2004

Airway inflammation in children with difficult asthma: relationships with airflow limitation and persistent symptoms.

BACKGROUND: The effective management and development of new treatments for children with difficult asthma requires investigation of the underlying airway pathology and its relationships with persistent symptoms and airflow limitation. METHODS: The density of immunologically distinct inflammatory cells and cells expressing interleukin (IL)-4, IL-5, and RANTES was determined in paraffin-embedded endobronchial biopsy specimens from 27 children with difficult asthma (6-16 years) following treatment with systemic corticosteroids. Eleven non-asthmatic children (7-16 years) acted as controls. Reticular basement membrane (RBM) thickness was also recorded and forced expiratory volume in 1 second (FEV(1)) and exhaled nitric oxide (FE(NO)) measured, the latter in asthmatic children only. RESULTS: RBM thickness was greater in the asthmatic than the control group (median (range) 7.4 (3.1-11.1) v 5.1 (3.5-7.5) microm, p = 0.02). No other significant tissue difference was seen, nor was there a difference between asthmatic subjects with daily symptoms after systemic corticosteroids and those who became asymptomatic. CD4+ T lymphocyte density was higher in asthmatic subjects with persistent airflow limitation (post-bronchodilator FEV(1)<80% predicted) than in those without (9.1 (5.5-13.6) v 3.5 (0.6-34.9)%, p = 0.027). Analysing all asthmatic subjects together, there were negative correlations between CD4+ T lymphocytes and both pre-bronchodilator FEV(1) (r = -0.57 (95% CI -0.79 to -0.23), p = 0.002) and post-bronchodilator FEV(1) (r = -0.61 (95% CI -0.81 to -0.29), p<0.001). There were no significant correlations between FE(NO) and inflammatory cells of any type. CONCLUSION: In children with difficult asthma treated with systemic corticosteroids, persistent airflow limitation is associated with a greater density of CD4+ T lymphocytes in endobronchial biopsy specimens.

Adolescent↗
PubMed2003

An inhibitor of IkappaB kinase, BMS-345541, blocks endothelial cell adhesion molecule expression and reduces the severity of dextran sulfate sodium-induced colitis in mice.

OBJECTIVE: Inflammatory bowel diseases such as ulcerative colitis and Crohn's disease are characterized by chronic relapsing inflammation. The transcription of many of the proteins which mediate the pathogenesis in inflammatory bowel disease (e.g., TNFalpha, ICAM-1, VCAM-1) is NF-kappaB-dependent. IkappaB kinase is critical in transducing the signal-inducible activation of NF-kappaB and, therefore, represents a potentially promising target for the development of novel agents to treat inflammatory bowel disease and other inflammatory diseases. RESULTS: Here we show that BMS-345541, a highly selective inhibitor of IkappaB kinase, inhibited the TNFalpha-induced expression of both ICAM-1 and VCAM-1 in human umbilical vein endothelial cells at the same concentration range as cytokine expression is inhibited in monocytic cells (IC(50) congruent with 5 microM). Against dextran sulfate sodium-induced colitis in mice, BMS-345541 administered orally at doses of 30 and 100 mg/kg was effective in blocking both clinical and histological endpoints of inflammation and injury. CONCLUSION: This represents the first example of an inhibitor of IkappaB kinase with anti-inflammatory activity in vivo and indicates that inhibitors of IkB kinase show the promise of being highly efficacious in inflammatory disorders such as inflammatory bowel disease.

Animals↗
PubMed2003

Novel dynamic ccaling regime in hole-doped La2CuO4.

Only 3% hole doping by Li is sufficient to suppress the long-range three-dimensional (3D) antiferromagnetic order in La2CuO4. The spin dynamics of such a 2D spin liquid state at T<<J was investigated with measurements of the dynamic magnetic structure factor S(omega,q), using cold neutron spectroscopy, for single crystalline La2Cu0.94Li0.06O4. S(omega,q) peaks sharply at (pi,pi) and crosses over around 50 K from omega/T scaling to a novel low temperature regime characterized by a constant-energy scale. The possible connection to a crossover from the quantum critical to the quantum disordered regime of the 2D antiferromagnetic spin liquid is discussed.

Journal Article↗
PubMed2003

Inhibitors of 20-hydroxyeicosatetraenoic acid reduce renal vasoconstrictor responsiveness.

20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450-derived constrictor eicosanoid produced by the preglomerular vasculature where it contributes to regulation of tone. Removal of the tonic inhibitory influence of nitric oxide (NO) has been reported to increase renal 20-HETE release. Because inhibition of NO synthesis enhances responses to vasoconstrictor agents, we examined a contribution for increased 20-HETE generation. In the rat kidney perfused with Krebs' buffer, responses to U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy PGF2alpha), a thromboxane A2 mimetic, were compared before and after 50 microM L-nitroarginine (L-NA) to inhibit NO synthase. L-NA raised perfusion pressure (PP) from 79 +/- 3 to 190 +/- 7 mm Hg and enhanced constrictor responsiveness to U46619. U46619 (10, 30, 100, and 300 ng) increased PP by 7 +/- 1, 17 +/- 2, 50 +/- 7, and 67 +/- 7 mm Hg, respectively, before L-NA and 15 +/- 1, 37 +/- 7, 68 +/- 10, and 85 +/- 11 mm Hg, respectively, after L-NA, which did not increase 20-HETE efflux from the kidney. Nonetheless, an inhibitor of omega-hydroxylase, dibromododecencyl methylsulfonimide (DDMS), which reduced 20-HETE release, normalized the enhanced responsiveness to U46619. When PP was elevated with phenylephrine, vasoconstrictor responses to U46619 were similarly enhanced, an effect that was also prevented by DDMS. DDMS and an antagonist of 20-HETE, 20-HEDE [20-hydroxyeicosa-6(Z), 15(Z)-dienoic acid], also reduced vasoconstrictor responses to U46619 in the absence of elevation of PP. Because 20-HETE inhibits K+ channels, we examined the effects of K+ channel inhibitors on vasoconstrictor responses and showed that both tetraethylammonium (TEA) and charybdotoxin enhanced renal vasoconstrictor responses to U46619. However, the inhibitory effects of 20-HEDE on vasoconstrictor responses remained after treatment with TEA. These results support a role for 20-HETE vasoconstrictor responses but suggest an action independent of K+ channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2003

A comparative magnetoencephalographic study of cortical activations evoked by noxious and innocuous somatosensory stimulations.

We recorded somatosensory-evoked magnetic fields and potentials produced by painful intra-epidermal stimulation (ES) and non-painful transcutaneous electrical stimulation (TS) applied to the left hand in 12 healthy volunteers to compare cortical responses to noxious and innocuous somatosensory stimulations. Our results revealed that cortical processing following noxious and innocuous stimulations was strikingly similar except that the former was delayed approximately 60 ms relative to the latter, which was well explained by a difference in peripheral conduction velocity mediating noxious (Adelta fiber) and innocuous (Abeta fiber) inputs. The first cortical activity evoked by both ES and TS was in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side. The following activities were in the bilateral secondary somatosensory cortex (SII), insular cortex, cingulate cortex, anterior medial temporal area and ipsilateral SI. The source locations did not differ between the two stimulus modalities except that the dipole for insular activity following ES was located more anterior to that following TS. Both ES and TS evoked vertex potentials consisting of a negativity followed by a positivity at a latency of 202 and 304 ms, and 134 and 243 ms, respectively. The time course of the vertex potential corresponded to that of the activity of the medial temporal area. Our results suggested that cortical processing was similar between noxious and innocuous stimulation in SI and SII, but different in insular cortex. Our data also implied that activities in the amygdala/hippocampal formation represented common effects of noxious and tactile stimulations.

Adult↗
PubMed2003

Microanatomy of endoscope-assisted glabellar nasal keyhole approach.

OBJECTIVE: To make a study of the detailed microanatomy of endoscope-assisted glabellar nasal keyhole approach (GNKA) to be used clinically. METHODS: 10 dry adult Chinese skulls were measured and 10 perfused cadaveric heads were dissected to mimic the GNKA. RESULTS: Average distances between bilateral supraorbital foramen/incisure, supratrochlear incisure, medial orbital wall were 47.71+/-3.61 mm, 33.67+/-3.82 mm and 24.34+/-1.29 mm, respectively, in dry skulls. Average distance from nasion to medial inter-canthus line (ICL) was 10.31+/-1.02 mm in cadaveric heads. The nasion was 3.95+/-0.45 mm above the cribriform plate (CP) and the ICL is 6.25+/-0.71 mm below. With the assistance of endoscopes, GNKA can expose all extradural structures near the midline from the anterior skull base to the ventral brain stem corresponding to the clivus. The exposed clival dura was 19.18+/-1.44 mm in width and 25.44+/-1.25 mm in length. Intradural structures such as frontal base, parasellar area, longitudinal fissure and the third ventricle floor, can also be exposed. CONCLUSION: GNKA is a minimally invasive and effective anterior skull base approach. Determining the inferior margin of incision by ICL instead of nasion is more convenient and can expose the subcranial area better.

Adult↗
PubMed2003

Effects of diltiazem on platelet activation and cytosolic calcium during percutaneous transluminal coronary angioplasty.

AIMS: To evaluate effects of diltiazem on platelet hyper-reactivity in situations associated with endothelial injury and their possible relationship to cytosolic calcium concentration. METHODS: Blood samples were collected at seven time points from 35 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) who received combined diltiazem and aspirin/ticlopidine therapy or aspirin/ticlopidine therapy alone. Platelet expression of glycoprotein IIb/IIIa and P-selectin, production of thromboxane B(2), and cytosolic calcium concentration were measured, respectively, by whole blood flow cytometry, radioimmunoassay, and fluorospectrophotometry. The effects of diltiazem of different concentrations on expression of glycoprotein IIb/IIIa and P-selectin were also studied in vitro in blood samples from patients with chronic stable angina. RESULTS: Of the two treatments, aspirin/ticlopidine therapy did not prevent an acute increase of expression of glycoprotein IIb/IIIa and P-selectin and plasma thromboxane B(2) five minutes and 10 minutes after first inflation and 10 minutes after PTCA, whereas combined diltiazem and aspirin/ticlopidine therapy had a significant inhibitory effect. In the group receiving aspirin/ticlopidine therapy, there was a short term increase of platelet [Ca(2+)](i) immediately after PTCA which was significantly reduced by diltiazem treatment. Expression of glycoprotein IIb/IIIa and P-selectin was significantly inhibited in vitro by diltiazem in the concentration of 200 ng/ml or higher, but not 50 ng/ml. CONCLUSIONS: Combined diltiazem and aspirin/ticlopidine therapy significantly inhibited platelet activation that continued in the presence of conventional aspirin/ticlopidine treatment. Antiplatelet effects of diltiazem were probably a consequence of reduction of platelet [Ca(2+)](i) and may only be achieved in higher than therapeutic concentrations.

Aged↗
PubMed2002

Significant up-regulation of nestin protein in the neostriatum of MPTP-treated mice. Are the striatal astrocytes regionally activated after systemic MPTP administration?

We are interested in the possible role of central glial cells in pathogenesis of Parkinson's disease of mammals. Parkinsonism model was induced by systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and the reactive glial cells were examined by immunocytochemical visualization of nestin protein in the brains and spinal cords of C57 mice. Abundant nestin-like immunoreactivity was predominately found in the caudate putamen of MPTP-treated mice and about 481-fold of nestin-like immunoreactive cells increased compared with that of control animals, indicating that significant up-regulation of nestin protein occurred in these regions. Majority of nestin-like immunoreactive cells characterized with astrocytic profiles of multiple, radical and hypotrophic processes, and showed a distribution and dynamic patterns similar to that of glial fibrillary acid protein (GFAP)-immunoreactive cells in the caudate putamen. Double immunofluorescence confirmed that 100% of nestin-like immunoreactive cells exhibited GFAP-immunoreactivity while nestin/GFAP double-labeled cells constituted about 84% of total GFAP-immunoreactive cells in the caudate putamen, indicating these nestin-like immunoreactive cells belong to a reactive population of the astrocytes. On the other hand, no obvious changes of nestin- or GFAP-like immunoreactivities were detected in the globus pallidus, the substantia nigra and the ventral tegmental area after MPTP-treatment. The results have provided morphological evidence for the regional activation of astrocytic glial cells following systemic MPTP administration, suggesting that a large population of reactive striatal astrocytes might play an important role in initial pathogenesis or acute stage of Parkinson's disease in mammals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2002

Cerebral activation by the signals ascending through unmyelinated C-fibers in humans: a magnetoencephalographic study.

Cerebral processing of first pain, associated with A delta-fibers, has been studied intensively, but the cerebral processing associated with unmyelinated C-fibers, relating to second pain, remains to be investigated. This is the first study to clarify the primary cortical processing of second pain by magnetoencephalography, through the selective activation of C-fibers, by the stimulation of a tiny area of skin with a CO2 laser. In the hemisphere contralateral to the side stimulated, a one-source generator in the upper bank of the Sylvian fissure (secondary somatosensory cortex, SII) or two-source generators in SII and the hand area of the primary somatosensory cortex (SI) were the optimal configurations for the first component 1M. The onset and peak latency of the two sources in SI and SII were not significantly different. In the hemisphere ipsilateral to the stimulation, only one source was estimated in SII, and its peak latency was significantly (approximately 18 ms on average) longer than that of the SII source in the contralateral hemisphere. From our findings we suggest that parallel activation of SI and SII contralateral to the stimulation represents the first step in the cortical processing of C-fiber-related activities, probably related to second pain.

Adult↗
PubMed2002

Beta-turn formation by a six-residue linear peptide in solution.

A model peptide AAGDYY-NH2 (B1), which is found to adopt a beta-turn conformation in the TEM-1 beta-lactamase inhibitor protein (BLIP) in the TEM-1/BLIP co-crystal, was synthesized to elucidate the mechanism of its beta-turn formation and stability. Its structural preferences in solution were comprehensively characterized using CD, FT-IR and 1H NMR spectroscopy, respectively. The set of observed diagnostic NOEs, the restrained molecular dynamics simulation, CD and FT-IR spectroscopy confirmed the formation of a beta-turn in solution by the model peptide. The dihedral angles [(phi3, phi3) (phi4, phi4)] of [(-52 degrees, -32 degrees ) (-38 degrees, -44 degrees )] of Gly-Asp fragment in the model peptide are consistent with those of a type III beta-turn. In a conclusion, the conformational preference of the linear hexapeptide B1 in solution was determined, and it would provide a simple template to study the mechanism of beta-turn formation and stability.

Circular Dichroism↗
PubMed2002

Oestrogen-induced apoptosis in colonocytes expressing oestrogen receptor beta.

Epidemiological studies of postmenopausal hormone replacement therapy show a reduction in the risk of developing colon cancer, and animal studies using 17beta-oestradiol (E(2)) demonstrate a decreased incidence of chemically-induced colon cancer. Using the colon cancer cell line, COLO205, we found that E(2) induced a dose-dependent increase in DNA fragmentation and nuclear condensation, significant effects being seen at 10(-12 )mol/l. BSA-conjugated E(2), which cannot enter cells, was ineffective at inducing apoptosis in COLO205 cells, indicating that E(2) was not acting through a cell-membrane receptor. E(2) did not induce the morphological changes characteristic of differentiation. Using RT-PCR we found that the oestrogen receptor alpha (ERalpha) isoform was absent in the COLO205 cell line in contrast to CACO-2, LoVo and SW620 cells, but mRNAs for ERbeta1, -beta2, -beta5 and -beta6 isoforms were detected. Western immunoblotting results showed full-length ERbeta protein but no detectable ERalpha in COLO205 cells. In normal human colon tissue samples immunoreactive ERbeta was found but ERalpha was barely detectable. Expression of ERbeta was lost in some colon cancer specimens and reduced in others. We conclude that E(2), through ERbeta, at concentrations found during replacement therapy, may inhibit the development of colon cancer by inducing apoptosis.

Apoptosis↗
PubMed2001

Environment-sensitive hydrogels for drug delivery.

Environmentally sensitive hydrogels have enormous potential in various applications. Some environmental variables, such as low pH and elevated temperatures, are found in the body. For this reason, either pH-sensitive and/or temperature-sensitive hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors as well as drug delivery systems. Light-sensitive, pressure-responsive and electro-sensitive hydrogels also have the potential to be used in drug delivery and bioseparation. While the concepts of these environment-sensitive hydrogels are sound, the practical applications require significant improvements in the hydrogel properties. The most significant weakness of all these external stimuli-sensitive hydrogels is that their response time is too slow. Thus, fast-acting hydrogels are necessary, and the easiest way of achieving that goal is to make thinner and smaller hydrogels. This usually makes the hydrogel systems too fragile and they do not have mechanical strength necessary in many applications. Environmentally sensitive hydrogels for drug delivery applications also require biocompatibility. Synthesis of new polymers and crosslinkers with more biocompatibility and better biodegradability would be essential for successful applications. Development of environmentally sensitive hydrogels with such properties is a formidable challenge. If the achievements of the past can be extrapolated into the future, however, it is highly likely that responsive hydrogels with a wide array of desirable properties can be made.

Animals↗
PubMed2001

Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8(+) cells.

We wished to determine if the inflammatory cells surrounding the airway mucus-secreting glands in chronic bronchitis (CB) were associated with interleukin (IL)-4 and IL-5 mRNA expression and whether the CD8 T cell population expressed these cytokines. Digoxigenin-labeled IL-4 and IL-5 antisense RNA probes were used to detect gene expression in 11 asymptomic smokers (AS), 11 smokers with CB alone with normal lung function, and 10 smokers with chronic bronchitis and coexisting chronic obstructive pulmonary disease (CB+COPD; FEV(1)% of predicted of 43-77% and FEV(1)/ FVC of 51-68%). There were approximately three times as many IL-4 than IL-5 mRNA(+) cells. The highest number of IL-4 mRNA(+) cells were in the submucosal glands of the CB group with normal lung function (216/mm(2)), significantly higher than the values in either the AS (63/mm(2)) or the CB+COPD (87/mm(2)) groups, respectively (p < 0.01). There were similar group differences when the total numbers of inflammatory cells were compared. Accordingly, there was a positive correlation between the number of IL-4 mRNA(+) cells and the total number of inflammatory cells in both the subepithelium and glandular compartments (r = 0.60; p = 0.01 and r = 0.70; p = 0.02, respectively). There were no significant associations between the numbers of CD8(+) and IL-4 or IL-5 mRNA(+) cells. Of 1328 IL-4(+) and 1404 CD8(+) cells counted none was double labeled. Of 727 IL-5(+) and 1569 CD8(+) cells, none was double labeled. In contrast, as a positive control, 34% of tumor necrosis factor (TNF)-alpha(+) cells were also CD8(+) and 15% of CD8(+) cells were TNF-alpha positive. Thus, cells other than the CD8(+) phenotype produce IL-4 and IL-5 in CB. We conclude that there is increased inflammation and IL-4 gene expression in the mucus-secreting glands and the airway mucosa of smokers with bronchitis: both are lower in those with CB and coexisting COPD suggesting that airway inflammation in CB is reduced when airway obstruction develops.

Aged↗
PubMed2001

In vivo gene delivery via portal vein and bile duct to individual lobes of the rat liver using a polylysine-based nonviral DNA vector in combination with chloroquine.

The objective of this study was to evaluate a bifunctional synthetic peptide as a DNA vector for regional gene delivery to the rat liver by the portal vein and bile duct routes. The 31-amino-acid peptide (polylysine-molossin) comprises an amino-terminal chain of 16 lysines for electrostatic binding of DNA, and the 15 amino acid integrin-binding domain of the venom of the American pit viper, Crotalus molossus molossus. Initial in vitro evaluation demonstrated that polylysine-molossin/DNA complexes were much smaller (approximately 50-100nm versus 500-1300nm), more positively charged, and more stable in isotonic dextrose in comparisons with salt-containing solutions. However, polylysine-molossin/DNA complexes in any solution other than complete culture medium were ineffective for gene delivery in vitro. Vector localization studies demonstrated that both the portal vein and bile duct routes provided excellent access of polylysine-molossin/DNA complexes to the liver. However, complexes delivered by the portal vein were rapidly lost (<15 min) following re-establishment of the portal circulation, whereas complexes delivered by the bile duct persisted much longer. Polylysine-molossin/DNA complexes in various isotonic solutions were delivered to the right lateral lobes either by perfusion through a branch of the portal vein or by infusion into appropriate branches of the bile duct. Two or three hours before gene delivery, rats were given a single injection of chloroquine. We report that the polylysine-molossin vector is much more effective (>10-fold) when delivered by the bile duct route with all isotonic solutions evaluated, and that polylysine-molossin/DNA complexes in isotonic dextrose are much more effective (>10-fold) than complexes in salt-containing solutions.

Animals↗
PubMed2001

The carboxyl terminus of the granulocyte colony-stimulating factor receptor, truncated in patients with severe congenital neutropenia/acute myeloid leukemia, is required for SH2-containing phosphatase-1 suppression of Stat activation.

The G-CSF receptor transduces signals that regulate the proliferation, differentiation, and survival of myeloid cells. A subgroup of patients with severe congenital neutropenia (SCN) has been shown to harbor mutations in the G-CSF receptor gene that resulted in the truncation of the receptor's carboxyl-terminal region. SCN patients with mutations in the G-CSF receptor gene are predisposed to acute myeloid leukemia. The truncated receptors from SCN/acute myeloid leukemia patients mediate augmented and sustained activation of Stat transcription factors and are accordingly hyperactive in inducing cell proliferation and survival but are defective in inducing differentiation. Little is known about the molecular mechanisms underlying the negative role of the receptor's carboxyl terminus in the regulation of Stat activation and cell proliferation/survival. In this study, we provide evidence that SH2-containing phosphatase-1 (SHP-1) plays a negative regulatory role in G-CSF-induced Stat activation. We also demonstrate that the carboxyl terminus of the G-CSF receptor is required for SHP-1 down-regulation of Stat activation induced by G-CSF. Our results indicate further that this regulation is highly specific because SHP-1 has no effect on the activation of Akt and extracellular signal-related kinase1/2 by G-CSF. The data together strongly suggest that SHP-1 may represent an important mechanism by which the carboxyl terminus of the G-CSF receptor down-regulates G-CSF-induced Stat activation and thereby inhibits cell proliferation and survival in response to G-CSF.

Animals↗
PubMed2001

Breath sounds, asthma, and the mobile phone.

The sounds generated by breathing in asthma are widely accepted as an indicator of disease activity. We have investigated the use of a mobile phone and electronic signal transfer by e-mail and voice mail to study tracheal breath sounds in individuals with normal lung function and patients with chronic or exercise-induced asthma. Spectrograms from patients with active asthma and impaired lung function were significantly different from people without asthma (p<0.0001). Our results suggest that mobile phone recordings clearly discriminate tracheal breath sounds in asthma and could be a non-invasive method of monitoring airway diseases.

Adolescent↗
PubMed2001

Conduction velocity of the spinothalamic tract in humans as assessed by CO(2) laser stimulation of C-fibers.

We measured the conduction velocity (CV) of C-fibers in the spinothalamic tract (STT) following stimulation with a CO(2) laser using a new method. We delivered non-painful laser pulses to tiny areas of the skin overlying the vertebral spinous processes at different levels from the 7(th) cervical (C7) to the 12(th) thoracic (T12), and recorded cerebral evoked potentials in 11 healthy men. We used the term "ultra-late laser evoked potentials" (ultra-late LEPs), since the peak latency was much longer than that for conventional LEPs related to Adelta-fibers following painful laser stimulation (late LEPs). The mean CV of C-fibers in the STT was 2.2+/-0.6 m/s, which was significantly lower than the CV of the Adelta-fibers (10.0+/-4.5 m/s). This technique is novel and simple, and should be useful as a diagnostic tool for assessing the level of spinal cord lesions.

Adult↗