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Biomedical subjects

Q Zhang

Publications and source records attributed to Q Zhang.

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

Roles for gliotransmission in the nervous system.

Astrocytes were long referred to as passive cells in the central nervous system (CNS). However, the application of fluorescent Ca2+ indicators revealed their "Ca2+ excitability" in response to a variety of stimuli. Since then, evidence showing that astrocytes release chemical transmitters and can modulate synapses has led to a new integrative view of the astrocyte. While it is inarguable that astrocytes play essential roles in nervous system function, and that gliotransmission modulates synapses, a significant challenge lies in developing the appropriate experimental strategy to allow unequivocal identification of roles for gliotransmission in nervous system function.

Animals↗
PubMed2004

Quantitation of SU1 1248, an oral multi-target tyrosine kinase inhibitor, and its metabolite in monkey tissues by liquid chromatograph with tandem mass spectrometry following semi-automated liquid-liquid extraction.

SU11248 is a potent inhibitor of PDGFR, VEGFR, KIT, and Flt3, and is currently under Phase I clinical evaluation as an anticancer drug. A sensitive and specific analytical method for the quantitation of SU11248 and its metabolite in several monkey tissues (liver, kidney, brain and white fat) using LC-MS-MS following semi-automated liquid-liquid extraction (LLE) was developed and validated. Amounts of 50 mg of tissue were homogenized using an ultrasonic processor. After addition of the stable labelled internal standard (IS) and ammonium hydroxide (0.3%), samples were extracted with 2.5 ml of tert-butyl methyl ether. Following centrifugation, aliquots of 1.8 ml of the organic phase were transferred into a 96-well plate. The Packard Multiprobe II robotic liquid handler was used to perform all steps mentioned above. The organic phase was dried and the residue was reconstituted with 800 microl of 15 mM ammonium formate buffer solution (pH 3.25) using a Tomtec Quadra 96 workstation. Aliquots of 10 microl of the resulting solution were injected into the LC-MS-MS system. A Symmetry Shield C8 column (50 mm x 2.1 mm, 3.5 microm) was used to perform the chromatographic analysis. The mobile phase was 15 mM ammonium formate buffer solution (pH 3.25)-acetonitrile (74:26 (v/v)) with a flow-rate of 0.35 ml/min. Retention times of the metabolite and SU11248 were about 2.5 and 3.5 min, respectively. Total cycle time was 5 min. MS detection used the Applied Biosystems-MDS Sciex API 3000 with TurbolonSpray interface and multiple reaction monitoring (MRM) operated in positive ion mode. The method was validated for both compounds over the calibration range of about 2 and 2000 ng/g. The suitability and robustness of the method for in vivo samples were confirmed by analysis of monkey tissues from animals dosed with SU11248.

Animals↗
PubMed2004

Improved targeting of platinum chemotherapeutics. the antitumour activity of the HPMA copolymer platinum agent AP5280 in murine tumour models.

AP5280 is a novel N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound platinum (Pt) therapeutic designed to increase the therapeutic index relative to conventional, small-molecule platinum agents. The platinum-polymer construct accumulates in solid tumours on the basis of increased capillary permeability. The bound platinum moiety is present as an N,O-Pt chelate at the distal end of a tetrapeptide linker, glycine-phenylalanine-leucine-glycine, and the weight-average molecular weight (Mw) of the construct is 22 kDa. The antitumour activity and toxicity of AP5280 were assessed in the syngeneic murine B16F10 and Lewis lung tumour models, and in the human ovarian carcinoma 2008 and head and neck squamous carcinoma UMSCC10b xenograft models. The maximum tolerated dose (MTD) of AP5280 was 6-fold greater than that of carboplatin (CBDCA) in vivo. AP5280 was active in all four tumour models, and it displayed a higher therapeutic index than CBDCA in each of these tumour models. The antitumour effect of AP5280 given at 16% of its MTD was equivalent to that produced by a MTD of CBDCA. Thus, consistent with the design goal for this drug, and despite being less potent than CBDCA, AP5280 produced less systemic toxicity relative to its antitumour activity and thus has a greater therapeutic index. On the basis of the improved therapeutic index evidenced in these models, AP5280 has been advanced into clinical trials.

Acrylamides↗
PubMed2004

Acute mesenteric venous thrombosis: a better outcome achieved through improved imaging techniques and a changed policy of clinical management.

OBJECTIVE: To analyse and compare the results obtained from acute mesenteric venous thrombosis (MVT) patients before and after the change of the clinical management principle, to assess the factors responsible for the recent better outcome and determine the best management for this disease. MATERIALS AND METHODS: We retrospectively reviewed 41 patients treated for acute MVT admitted in our hospital between 1978 and 2003. Before 1995 (Group I), our policy was to perform surgery in patients with suspected acute MVT. After 1995 (Group II), we changed our policy to a medical approach when achievable. Each patient in this study was assessed for diagnosis, initial management (operative or non-operative), mortality, duration of hospitalisation, and outcome. RESULTS: There were 13 in Group I, 28 in Group II. The mean duration of diagnoses made after admission was 7.3 S.D. 2.6 days for patients in Group I, and 1.5 S.D. 1.2 days for those in Group II (p<0.01, Student's t-test). Eleven patients underwent operations and two patients received non-operative treatment initially in group I, the mortality was 39%; while nine patients underwent operations and 19 patients received non-operative management in group II, the mortality was 11% (p<0.05). No death occurred in the patients with initial non-operative management. The mean duration of hospitalisation was 26 S.D. 6.8 days in Group I and 12.6 S.D. 4.6 days in Group II (p<0.01, Student's t-test). No significant difference in 2-year survival rate between the two groups. CONCLUSION: Recent improvements in imaging techniques and better understanding of the aetiology have led to a dramatic change in the principle and policy of clinical management for acute MVT, which leads to a more favourable outcome of acute MVT.

Acute Disease↗
PubMed2004

Regulation of transgene expression in muscles by ultrasound-mediated hyperthermia.

Heat-sensitive transgene expression systems have been proposed recently for use in gene therapy to enable both spatial and temporal control of the gene activity. The transgene was put under the control of HSP-related promoters and could be turned on by external heat treatment. While the 'heat activation' phenomenon of the HSP-related promoters in vitro had been well documented, the detailed time response and temporal regulation profile in vivo were not fully understood. We reported here the regulation of transgene luciferase expression in vivo in muscles using a custom-built ultrasound-mediated hyperthermia instrument. The effects of different heating parameters and treatment regimens were evaluated. Optimal activation of gene expression was found at 39 degrees C. Significant tissue damage was observed at 41 degrees C and above, which directly correlated with the greatly reduced gene expression. The gene constructs remained stable and silent in muscle cells, and could be turned on at a later time without losing much activity. Repeated activation was also possible, but required heat treatment at a higher temperature to overcome thermotolerance.

Animals↗
PubMed2004

Muscle blood flow in response to concentric muscular activity vs passive venous compression.

AIM: To measure muscle blood flow (MBF) using photoplethysmography (PPG) following concentric muscular activity of the leg (active treatment) or passive venous compression (passive treatment) with or without venous obstruction. METHODS: In study A, blood flow in the anterior tibial muscle was measured in 15 healthy subjects with a mean age of 30 years. In study B, blood flow in the gastrocnemius muscle was measured in nine healthy subjects with a mean age of 34 years. Subjects performed concentric muscular activity in one leg. Passive venous compression by a venous foot pump was applied in the contralateral leg. RESULTS: MBF increased significantly following concentric muscular activity, but not following passive venous compression. MBF decreased in both legs when venous obstruction, induced by a thigh tourniquet, was applied. However, MBF was significantly higher following concentric muscular activity than passive venous compression. CONCLUSION: We conclude that concentric muscular activity produces higher MBF values than passive venous compression.

Adolescent↗
PubMed2004

Abnormally elevated intramuscular pressure impairs muscle blood flow at rest after exercise.

We used photoplethysmography (PPG) to measure the relative changes in the anterior tibial muscle blood flow (MBF) in response to exercise when intramuscular pressure (IMP) was elevated (the test leg) or when IMP was normal (the control leg). The elevated IMP was induced by applying venous obstruction of 40 mmHg or 65 mmHg (thigh tourniquet) of a casted leg in eight healthy subjects. Subjects performed dorsiflexion of both feet in sitting position with or without venous obstruction. IMP at rest after exercise increased to 39.4+/-7.9 mmHg or to 58.3+/-8.4 mmHg, respectively. MBF at rest before exercise was 100%. At rest after exercise, it increased to 184+/-52.6% in the test leg when IMP was 39.4 mmHg, and to 279+/-108.3% in the control leg. MBF at rest after exercise was 156+/-58.2% in the test leg when IMP was 58.3 mmHg and 303+/-95.3% in the control leg. The abnormally elevated IMP induced by venous obstruction of a casted leg reduced MBF at rest after exercise. PPG seems to be a suitable method to measure changes in MBF in response to exercise and in experimental conditions with abnormally elevated IMP.

Adult↗
PubMed2004

Mucosal immunology of vaccines against pathogenic nasopharyngeal bacteria.

The introduction of Haemophilus influenzae type b conjugate vaccines during the 1990s was followed by dramatic decreases both in the incidence of Haemophilus influenzae type b related invasive disease and in nasopharyngeal carriage of the organism. The extent of this effect has been influenced by the fact that Haemophilus influenzae type b conjugate vaccines reduce nasopharyngeal carriage and induce herd immunity. Based on the success of Haemophilus influenzae type b conjugate vaccines, chemical conjugation has been applied to the development of pneumococcal and meningococcal polysaccharide conjugate vaccines. Evidence has begun to accumulate that these new polysaccharide based conjugate vaccines can also reduce nasopharyngeal carriage and can induce immune responses at the local mucosal level, which may be responsible for these effects. This article reviews recent studies on mucosal immune responses induced by polysaccharide based vaccines and some protein vaccine antigens against several pathogenic nasopharyngeal bacteria, and discusses the mechanisms and functions of these immune responses that may help our understanding of mucosal immune responses to both immunisation and infection.

Antigens, Viral↗
PubMed2004

Multiscale simulations of carbon nanotube nucleation and growth: electronic structure calculations.

Several first-principles surface and bulk electronic structure calculations relating to the nucleation and growth of single-wall carbon nanotubes are described. Density-functional theory in various forms is used throughout. In the surface-related calculations, a 38-atom Ni cluster and several low-index Ni surfaces are investigated using pseudopotentials and plane-wave expansions. The energetic ordering of the sites for C atom adsorption is found to be the same, with the Ni(100) facet favored. The bulk diffusion coefficient of C in Ni as a function of cluster size and temperature is calculated from various molecular dynamics approaches. In another group of bulk-related calculations, Gaussian orbital basis sets are used to study a cluster or "flake" containing 14 C atoms. The flake is a segment of three hexagons from an "unrolled" carbon nanotube, with an armchair termination. The binding energies of C, Ni, Co, Fe, Cu, and Au atoms to it were calculated in an effort to gain insight into the mechanism for the high catalytic activity of Ni, Co, and Fe and the lack of it in Cu and Au. The binding energies of Cu and Au are about 1 eV less than those of the three catalytic elements. Similar methods are used to study the initial stages of nanotube growth within the context of classical nucleation theory. Finally, issues relating to the establishment of a fundamental catalytic mechanism are addressed.

Adsorption↗
PubMed2004

Asthma severity and medical resource utilisation.

Asthma represents a growing public health problem and the cost of asthma has been rising in many countries. The aim of this study was to estimate the direct and indirect cost of asthma among adult patients in Italy, and to assess the relationship between healthcare resource use and asthma severity according to the Global Initiative for Asthma (GINA) classification system. A multicentre cross-sectional study was conducted in 16 Italian hospital-based specialised asthma clinics. Data collection was based on self-administered questionnaires and took place during the period May 1-November 30, 1999, and 500 consecutive patients with asthma, aged 18-55 yrs, were enrolled during regularly scheduled visits. Direct costs (drugs, physician visits, emergency service use and hospitalisation), indirect costs (loss of paid workdays) and total costs were determined in euros (Euros) for 1999. Patients with more severe disease, as classified by the GINA guideline, exhibited more night-time and daytime symptoms and were more limited in performing normal daily activities. The mean total cost of asthma per patient per year was estimated to be Euros 1,260; drug costs accounted for 16%, physician costs 12%, emergency service and hospitalisation costs 20% and indirect costs 52% of the mean cost. Stratified by severity, the total annual cost per patient amounted to Euros 720, Euros 1,046, Euros 1,535 and Euros 3,328 for patients with intermittent, mild persistent, moderate persistent and severe persistent asthma, respectively. Asthma severity, as determined by the Global Initiative for Asthma classification, is significantly associated with symptoms, limitations in normal daily activities, asthma-related medical resource utilisation and both direct and indirect costs. Asthma control is not only a clinical but also an economic imperative.

Activities of Daily Living↗
PubMed2003

The genetic basis of stay-green in rice analyzed in a population of doubled haploid lines derived from an indica by japonica cross.

Delayed leaf-senescence, or stay-green, has been regarded as a desired characteristic for the production of a number of crops including rice. In this study, we analyzed the genetic basis of stay-green using a population of 190 doubled haploid lines from the cross between an indica parent Zhenshan 97 and a stay-green japonica parent Wuyujing 2. The population was tested in replicated field trials in 2 consecutive years, and six traits were defined to evaluate the stay-green characteristics. A genetic linkage map with 179 SSR (simple sequence repeat) marker loci was constructed. The software QTLMapper, based on a mixed linear model approach, was applied to detect QTLs, epistatic effects and their environmental interactions for these traits. A total of 46 main-effect QTLs was detected for the six traits that can be localized to 25 chromosomal regions. The individual effects of all the QTLs were small. Fifty digenic interactions were resolved that involved 66 loci distributed on all 12 chromosomes. Environmental interactions were detected for 18 of the main-effect QTLs and 14 of the epistatic interactions. Collectively, the epistatic effects and QTL by year interactions accounted for large proportions of the phenotypic variations. The results also showed that most of the stay-green traits were negatively correlated with yield and its component traits. The implications of the results in crop improvement were discussed.

Chromosome Mapping↗
PubMed2003

Coal-induced interleukin-6 gene expression is mediated through ERKs and p38 MAPK pathways.

In the present study, we have tested the ability of coal dust to stimulate kinase phosphorylation of activator protein-1 (AP-1) signal transduction pathways and production of interleukin-6 (IL-6) in both mouse epidermal JB6 and human lung epithelial A549 cells. Seven coal samples from three coalmine regions of Pennsylvania (PA), West Virginia (WV), and Utah (UT) with high, medium, and low prevalence of coal workers' pneumoconiosis (CWP), respectively, were investigated. Results from the present study indicate that three PA coals stimulated the mitogen-activated protein kinase (MAPK) family of extracellular signal-regulated kinases (ERKs) and p38 MAPK, but not c-Jun-NH2-terminal kinases (JNKs) in human lung A549 cells. The effects of three UT coals on the kinase phosphorylation were less as compared to those of the PA coals. Coal dusts from three coalmine regions induced IL-6 in a dose-dependent manner in both JB6 and A549 cells. Interestingly, levels of IL-6 in both cells treated with coals from three coalmine regions correlated well with CWP prevalence from that region. To assess the role of AP-1 pathways in coal-mediated transcriptional activation of IL-6, various inhibitors were used in cells treated with one PA coal, which induced a maximal response. It was found that the increase in IL-6 protein and mRNA by the PA coal was completely eliminated by the pretreatment of both cell types with PD98059, a specific MEK1 inhibitor, and SB202190, a p38 kinase inhibitor. Our results indicate that coal dust can stimulate IL-6 release from mouse epidermal JB6 cells and human lung epithelial A549 cells, and the coal-induced IL-6 increase may involve ERKs and p38 MAPK pathways.

Animals↗
PubMed2003

Genetic and physical mapping of a new gene for bacterial blight resistance in rice.

The inheritance of resistance for bacterial blight, caused by Xanthomonas oryzae pv. oryzae ( Xoo), was studied in Minghui 63, an elite restorer line for a number of widely used rice hybrids in China. A new dominant gene against a Chinese Xoo strain JL691 in both the seedling and adult stages was identified in Minghui 63 and designated as Xa26( t). Using a total of 477 highly susceptible individuals from an F(2) population, the Xa26( t) locus was mapped to a region of about 1.68 cM. This locus co-segregated with marker R1506 and was 0.21 cM from marker RM224 on one side and 1.47 cM from marker Y6855RA on the other side, in rice chromosome 11. A contig map, composed of five non-redundant bacterial artificial chromosome (BAC) clones and spanning approximately 500 kb in length, was constructed. Analysis of recombination events in the Xa26( t) region with the highly susceptible F(2) individuals anchored the gene locus to a region covered by three overlapped BAC clones. Assay of the lines showing a double crossover in marker loci flanking Xa26( t), in a population of recombinant inbred lines carrying Xa26( t), further delineated the gene to a 20-kb fragment. The Xa26( t) locus is tightly linked to another bacterial blight resistance gene locus, Xa4.

Chromosomes, Artificial, Bacterial↗
PubMed2003

Induction of interleukin-6 by coal containing bioavailable iron is through both hydroxyl radical and ferryl species.

Coal mining causes health problems, such as pneumoconiosis. We have previously shown that prevalence of pneumoconiosis in workers from various coalmine regions positively correlates with levels of bioavailable iron (BAI) in the coals from that region. In the present study, the nature of reactive oxygen species formed by BAI in the coals and its mechanisms of the induction of biological responses were investigated. Human lung epithelial cell line, A549 cells, were used to examine the induction of interleukin-6 (IL-6), a pro-inflammatory cytokine, which is known to play a crucial role in the development of pneumoconiosis. We found that levels of IL-6 protein as well as its mRNA were significantly increased in the cells treated for 24 h with 20 microg/cm2 of the BAI-containing Pennsylvania (PA) coal; for example we observed 6.7-fold increase in IL-6 protein. Levels of IL-6 protein in cells treated with the Utah (UT) coal containing low-BAI were only 1.9-fold of the control levels. The enhancing effect on the IL-6 by the PA coal was similar to that caused by hydrogen peroxide. Superoxide dismutase (SOD), catalase (CAT), and N-acetyl-L-cysteine (NAC) all had inhibitory effects on the PA coal-induced IL-6 formation. However, CAT had the least protective effect as compared to SOD and NAC. Our results indicate that BAI in the PA coal may induce IL-6 through both ferryl species (via iron autoxidation) and hydroxyl radicals (via the Fenton/Haber Weiss reactions).

Acetylcysteine↗
PubMed2003

Cytological evidence for preservation of mitochondrial and plastid DNA in the mature generative cells of Chlorophytum spp. (Liliaceae).

Following 4',6-diamidino-2-phenylindole staining of mature pollen grains of Chlorophytum comosum, fluorescence microscopy confirmed that cytoplasmic nucleoids (DNA aggregates) were present in the generative cells, which indicated the possibility of biparental cytoplasmic inheritance. Electron and immuno-electron microscopy showed that both plastids and mitochondria were present in the generative cells, and both organelles contained DNA. These results indicate that mitochondria and plastids of C. comosum have the potential for biparental inheritance. Similar results were obtained with mature pollen grains of C. chinense. Therefore, we conclude the coincident biparental inheritance for mitochondria and plastids in the members of the genus Chlorophytum.

DNA, Mitochondrial↗
PubMed2003

Detection and survival of Campylobacter in chicken eggs.

AIMS: Campylobacter jejuni, a food-borne human pathogen, is widespread in poultry; however, the sources of infection and modes of transmission of this organism on chicken farms are not well understood. The objective of this study was to determine if vertical transmission of C. jejuni occurs via eggs. METHODS AND RESULTS: Using a temperature differential method, it was shown that Campylobacter had limited ability to penetrate the eggshell. When C. jejuni was directly inoculated into the egg yolk and the eggs were stored at 18 degrees C, the organism was able to survive for up to 14 days. However, viability of C. jejuni was dramatically shortened when injected into the albumen or the air sac. When freshly laid eggs from Campylobacter-inoculated specific pathogen-free (SPF) layers were tested, C. jejuni-contamination was detected in three of 65 pooled whole eggs (5-10 eggs in each pool) via culture and PCR. However, the organism was not detected from any of the 800 eggs (80 pools), collected from the same SPF flock, but kept at 18 degrees C for 7 days before testing. Likewise, Campylobacter was not recovered from any of 500 fresh eggs obtained from commercial broiler-breeder flocks that were actively shedding Campylobacter in faeces. Also, none of the 1000 eggs from broiler breeders obtained from a commercial hatchery were positive for Campylobacter. CONCLUSIONS: These results suggest that vertical transmission of C. jejuni through the egg is probably a rare event and does not play a major role in the introduction of Campylobacter to chicken flocks. SIGNIFICANCE AND IMPACT OF THE STUDY: Control of Campylobacter transmission to chicken flocks should focus on sources of infection that are not related to eggs.

Animal Husbandry↗