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Biomedical subjects

Y Zhang

Publications and source records attributed to Y Zhang.

At least 253 records · Page 14Linked to original sources
PubMed2003

Simultaneous determination of N-butyramide-tacrine and tacrine in mouse plasma and brain homogenate by high-performance liquid chromatography with a simple gradient solvent system.

A novel reversed-phase HPLC method was developed for the simultaneous determination of tacrine (THA) and the newly synthesized prodrug (N-butyramide-THA, BTHA) in mouse plasma and brain homogenate. The assay involves deproteinisation and subsequent detection at 240 nm with a gradient solvent system. Retention times were 18.5 and 9.3 min for BTHA and THA, respectively. Average recoveries for the analytes were 80.7% (BTHA) and 76.6% (THA) from plasma, and 75.0% (BTHA) and 68.4% (THA) from brain homogenate. Linear responses were observed over a wide range (0.25-20 microg/ml for BTHA in plasma and in brain homogenate, 0.025-20 microg/ml for THA in both matrices). Both BTHA and THA degraded from the prodrug can be detected even 12 h after intravenous administration of BTHA, indicating that BTHA is a promising prodrug for brain targeting.

Animals↗
PubMed2003

Chronic fluoxetine differentially affects 5-hydroxytryptamine (2A) receptor signaling in frontal cortex, oxytocin- and corticotropin-releasing factor-containing neurons in rat paraventricular nucleus.

Differential adaptive changes in serotonin2A [5-hydroxytryptamine (5-HT)2A] receptor signaling during treatment may be one mechanism involved in the latency of therapeutic improvement with antidepressants, such as fluoxetine. We examined the effects of fluoxetine (2, 3, 7, 21, or 42 days) on hypothalamic 5-HT2A receptor signaling. The hormone responses to an injection of the 5-HT2A receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane HCl (DOI) were used as an index of hypothalamic 5-HT2A receptor function. Treatment with fluoxetine for 21 or 42 days produced diminished adrenocorticotropic hormone (ACTH) and oxytocin (but not corticosterone) responses to DOI injections (2.5 mg/kg i.p.; 15 min postinjection). Regulators of G protein signaling 4 and Galphaq protein levels in the hypothalamic paraventricular nucleus were not altered during fluoxetine treatment. Because previous studies indicate that treatment with fluoxetine for 21 days resulted in increased hormone responses to DOI when measured at 30 min after injection, we examined the effect of fluoxetine (21 days) on DOI-induced increase hormone levels at 15, 30, and 60 min after DOI injection. Fluoxetine decreased the oxytocin response at 15 but not at 30 min post-DOI injection, and potentiated the ACTH and corticosterone responses at 30 min post-DOI injection. For comparison, we examined the effect of fluoxetine on 5-HT2A receptor-mediated increase in phospholipase C (PLC) activity in the frontal cortex. 5-HT-stimulated, but not guanosine 5'-O-(3-thio)triphosphate-stimulated PLC activity was increased after 21 days of fluoxetine-treatment. Overall, these results indicate that chronic fluoxetine treatment can potentiate 5-HT2A receptor signaling in frontal cortex but differentially alters 5-HT2A receptor signaling in oxytocin-containing neurons and corticotropin-releasing factor-containing neurons in the paraventricular nucleus.

Animals↗
PubMed2003

Vasodilatory and electrophysiological actions of 8-iso-prostaglandin E2 in porcine coronary artery.

We examined the effects of several E-ring and F-ring isoprostanes on mechanical and electrophysiological activity in porcine coronary artery. Several isoprostanes evoked concentration-dependent contractions, with 8-iso-PGE2 being the most potent (-log EC50 of 6.9 +/- 0.1); this excitatory effect has been described in detail elsewhere and was not examined further here. 8-iso-PGE2 evoked dose-dependent relaxations in tissues preconstricted with the thromboxane A2-agonist U46619 (10(-6) M), with a negative log EC50 of 6.0 +/- 0.1 (n = 5). 8-iso-PGE1 and 8-iso-PGF2 beta also evoked relaxations (albeit with lower potency), whereas the other F-ring isoprostanes (8-iso-PGF1 alpha, 8-iso-PGF1 beta, and 8-iso-PGF2 alpha) were largely ineffective in this respect. The potency and efficacy of 8-iso-PGE2 in reversing tone were not dependent upon the concentration of U46619 used to preconstrict the tissues (10(-8) to 10(-6) M), indicating a lack of U46619-induced functional antagonism of these responses. 8-iso-PGE2 was able to completely relax tissues that had been denuded of endothelium (as indicated by loss of responsiveness to bradykinin). 8-iso-PGE2-evoked relaxations were markedly reduced by elevating the K+ equilibrium potential using 30 mM KCl and abolished by 60 mM KCl; they were also sensitive to charybdotoxin (10(-7) M) but not to 4-aminopyridine (1 mM). 8-iso-PGE2 also caused membrane hyperpolarization and augmentation of outward K+ current. We conclude that 8-iso-prostaglandin E2 acts directly on the smooth muscle to increase K+ conductance, leading to membrane hyperpolarization and vasodilation.

Animals↗
PubMed2003

Expression of the gamma-zein protein of maize in seeds of transgenic barley: effects on grain composition and properties.

A cDNA clone encoding the gamma-zein protein of maize was expressed in developing grain of barley using the starchy endosperm cell-specific promoter from the wheat Glu-1D-1 (HMW subunit 1Dx5) gene. Seven transgenic lines were recovered from 226 bombarded immature embryos, of which two were sterile and four tetraploid, while five were shown to express the gamma-zein protein based on western blotting. Southern blot analysis showed the presence of between about three and twelve transgene insertions. Detailed comparative studies of five null and five homozygous transformed sub-lines from transgenic line A showed that gamma-zein accounted for over 4% of the total prolamin fraction, corresponding to about 1.9% of the total grain N. Comparison of the proteins present in the gel protein fraction demonstrated that the gamma-zein was incorporated into polymers, as in maize. However, there was no effect on grain hardness measured using the Perten Single Kernel Characterisation System or on the vitreousness measured by visual inspection. This contrasts with the situation in maize where a clear association with vitreousness has been reported.

Gene Transfer Techniques↗
PubMed2003

Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVES: Based on their HLA association, both ankylosing spondylitis (AS) and rheumatoid arthritis (RA) seem to be T-cell-driven diseases in which the autoantigens remain to be defined. One possible autoantigen is the G1 domain of aggrecan, the major cartilage proteoglycan. In BALB/c mice immunized with this protein, spondylitis and erosive polyarthritis have been reported. Immune reactivity to the G1 has been described in patients with RA and AS in an earlier study. Using novel and more sensitive techniques and relevant controls we sought to define the role of G1 as an autoantigen more precisely and to extend the specific analyses to the peptide level. METHODS: Peripheral blood (PB) mononuclear cells (MNC) from 47 AS patients, 22 RA patients and 20 healthy normal controls were exposed in vitro for 6 h to the cartilage-derived autoantigens G1, human cartilage (HC) gp-39 and collagen II. Synovial fluid (SF) MNC from seven AS and four RA patients were similarly analysed. Furthermore, PB MNC of 15 AS and 10 RA patients were examined with overlapping 18-mer peptides covering the whole G1 protein to identify the immunodominant epitopes. T cells were stained by monoclonal antibodies directed against the surface markers CD4, CD69 and against the intracellular cytokines interferon-gamma (IFN gamma), tumour necrosis factor-alpha (TNF alpha), interleukin 4 (IL-4) and IL-10. The percentage of reactive T cells was quantified by flow cytometry. RESULTS: After antigen-specific stimulation with the G1 protein, the CD4+ T cells of 30 AS patients (61.7%) and of 12 RA patients (54.5%) secreted significant amounts of IFN gamma and TNF alpha, while, in contrast, only 10% of the normal controls showed a response (P < 0.05). The synovial CD4+ T cells of five AS (71.5%) and of all four RA patients showed antigen-specific responses to the G1. In contrast, stimulation with HC gp-39 and collagen II showed no significant IFN gamma and TNF alpha secretion of MNC in all groups. Several G1-derived T-cell epitopes were identified as immunodominant in PB MNC of AS and RA patients and were partly overlapping. CONCLUSIONS: These data show that a cellular immune response to G1 is present in most AS and RA patients. G1-immunodominant epitopes were identified. The relevance of this finding for the pathogenesis of AS and RA remains to be established.

Adipokines↗
PubMed2003

Deficiency of the cysteine protease cathepsin S impairs microvessel growth.

During angiogenesis, microvascular endothelial cells (ECs) secrete proteinases that permit penetration of the vascular basement membrane as well as the interstitial extracellular matrix. This study tested the hypothesis that cathepsin S (Cat S) contributes to angiogenesis. Treatment of cultured ECs with inflammatory cytokines or angiogenic factors stimulated the expression of Cat S, whereas inhibition of Cat S activity reduced microtubule formation by impairing cell invasion. ECs from Cat S-deficient mice showed reduced collagenolytic activity and impaired invasion of collagens type I and IV. Cat S-deficient mice displayed defective microvessel development during wound repair. This abnormal angiogenesis occurred despite normal vascular endothelial growth factor and basic fibroblast growth factor levels, implying an essential role for extracellular matrix degradation by Cat S during microvessel formation. These results demonstrate a novel function of endothelium-derived Cat S in angiogenesis.

Animals↗
PubMed2003

Glutathione S-transferase M1 and T1 genetic polymorphisms, alcohol consumption and breast cancer risk.

Alcohol consumption has been inconsistently associated with breast cancer risk. Recent studies suggest that genetic polymorphisms of glutathione S-transferases (GSTs) may modify this relation. To determine if breast cancer risk is associated with GSTM1 and GSTT1 genetic polymorphisms, and to evaluate the effect modification between GST genotypes and alcohol consumption in the risk of breast cancer, we conducted a case-control study in the state of Connecticut in the period 1998 and 2001. Cases were histologically confirmed, incident breast cancer patients in New Haven County, CT. Controls were randomly selected from women histologically confirmed to be without breast cancer. The study results show that, while GSTM1 genotypes were not associated with breast cancer risk, GSTT1-null genotype was associated with a significant 90% increased risk for postmenopausal women (OR=1.9, 95% CI 1.2-3.0). Analysis by GST genotypes and alcohol consumption shows that GSTM1A ever-drinking women had a 2.5-fold (OR=2.5, 95% CI 1.1-5.5) increased risk of breast cancer compared to the GSTM1A never-drinkers, and the risk increases with duration and daily amount of alcohol consumption. Postmenopausal women with GSTT1-null genotype, who consumed a lifetime of >250 kg of spirit-equivalents, had an almost seven-fold increased risk (OR=6.8, 95% CI 1.4-33.9), and drinking commencing at younger ages appears to carry a higher risk. An OR of 8.2 (95% CI 1.2-57.4) was observed for those with GSTM1A, and GSTT1-null genotypes who had consumed a lifetime of >250 kg of spirit-equivalents. In conclusion, alcohol consumption may increase breast cancer risk among those who carry susceptible GST genotypes.

Adolescent↗
PubMed2003

Investigation of the role of ANKH in ankylosing spondylitis.

OBJECTIVE: The ank/ank mouse develops a phenotype similar to ankylosing spondylitis (AS) in humans. ANKH, the human homolog of the mutated gene in the ank/ank mouse, has been implicated in familial autosomal-dominant chondrocalcinosis and autosomal-dominant craniometaphyseal dysplasia. This study was undertaken to investigate the role of ANKH in susceptibility to and clinical manifestations of AS. METHODS: Sequence variants were identified by genomic sequencing of the 12 ANKH exons and their flanking splice sites in 48 AS patients; variants were then screened in 233 patients and 478 controls. Linkage to the ANKH locus was assessed in 185 affected-sibling-pair families. RESULTS: Five single-nucleotide polymorphisms were identified within the coding region and flanking splice sites. No association between either susceptibility to AS or its clinical manifestations and these novel polymorphisms, or between disease susceptibility and 3 known promoter variants, was seen. No linkage between the ANKH locus and AS was observed. Multipoint exclusion mapping rejected the hypothesis of a locus of a magnitude lambda>/=1.4 (logarithm of odds score <-2) (equivalent to a genetic contribution of >10% to the AS sibling recurrence risk ratio) within this area contributing to AS. CONCLUSION: These findings indicate that ANKH is not significantly involved in susceptibility to or clinical manifestations of AS.

Adult↗
PubMed2003

The NuRD complex: linking histone modification to nucleosome remodeling.

ATP-dependent nucleosome remodeling and core histone tail modifications play important roles in chromatin function. Purification and characterization of the NuRD/Mi-2 complex, which possesses both nucleosome remodeling and histone deacetylase activities, suggests that ATP-dependent nucleosome remodeling and histone tail modification can be coupled. Recent studies indicate that NuRD is an integral part of the MeCP1 complex, suggesting that nucleosome remodeling and histone deacetylation play important roles in methylated DNA silencing. Studies in Caenorhabditis elegans have revealed important functions of the NuRD complex in embryonic patterning and Ras signaling. Accumulating evidence indicates that NuRD may regulate transcription of specific genes by interacting with specific transcriptional factors. In addition, it may also participate in genome-wide transcriptional regulation through an association with histone tails.

Animals↗
PubMed2003

Gene expression profile of cardiomyocytes in hypertrophic heart induced by continuous norepinephrine infusion in the rats.

Catecholamines play an important role in the development of cardiac hypertrophy. To observe cardiomyocyte-specific gene expression changes induced by catecholamines in vivo, left ventricular cardiomyocytes were isolated from male Sprague-Dawley rats after continuous infusion of norepinephrine (NE; 0.2 mg/kg per hour intravenously) for 0.5, 1, 2, 3 and 7 days. The gene expression profiles of these cells during different NE infusion stages were assessed by using a cDNA microarray, and the microarray data were further analyzed by a clustering method. Cardiac hypertrophy was induced upon continuous NE infusion, with the peak at 3 days. Meanwhile, manifest changes in gene expression profile within cardiomyocytes over the time course were revealed, most of the genes never having been reported to be involved in cardiac hypertrophy. The number of genes displaying differential expression also peaked at the middle stage of infusion (2-3 days), and the majority of the signaling molecules were found differentially expressed mainly at this stage, including phosphatidylinositol 3-kinase, calcium/calmodulin-dependent protein kinase II and non-receptor tyrosine kinases, etc. The tumor suppressor p53 was found up-regulated at very early (0.5 days) and late stages (7 days) of NE infusion. Self-organization clustering analysis revealed subsets of coordinate regulated genes. One set consisted of several enzymes involved in energy metabolism, including carnitine octanoyltransferase, ATP synthase subunit c, pancreatic lipase and glycogen phosphorylase, possessing a similar expression pattern with a rapidly elevated expression level at the early stage of NE infusion. This is the first study to provide transcriptional information for cardiomyocytes, a single cell type, in the heart during the development of cardiac hypertrophy in vivo, and may provide accurate clues to elaborate hypotheses about the evolution of this pathology.

Animals↗
PubMed2003

Relationship between the expression levels of CD61, CD63, and PAC-1 on platelet surface in peripheral blood and the transplanted kidney function.

OBJECTIVE: To analyze the relationships between the expression levels of CD61, CD63, and PAC-1 on the platelet surface and the incidences of acute rejection and tubular necrosis as well as the recovery of graft function after renal transplantation. METHODS: The expression levels of CD61, CD63, and PAC-1 on platelet surfaces were assayed by flow cytometry in 86 patients with different stages of uremia before and after transplantation. Patients were divided into three groups: 29 patients with normal graft function, 30 with acute rejection, and 27 with acute tubular necrosis. Patients with acute rejection were randomly assigned into groups treated with or without anticoagulants. RESULTS: The expression levels of CD61, CD63, and PAC-1 on platelet surfaces significantly increased (P <.05) among patients with acute rejection, as compared with those with normal graft function or acute tubular necrosis. Compared with controls, the expression levels of CD61, CD63, and PAC-1 were lower among acute rejection patients who, received anticoagulant therapy. The recovery time for graft function shorter and, the 1-year patients and graft survival rates higher. CONCLUSIONS: The pretransplant expression levels of CD61, CD63, and PAC-1 on platelet surface were significantly higher among patients with acute rejection, suggesting that this complication rather than acute tubular necrosis may be related to platelet activation. Patients with acute rejection displayed benefit from anticoagulant therapy.

Adult↗
PubMed2003

Immunological tolerance in chickens hatching from eggs injected with cell-associated herpesvirus of Turkey (HVT).

Cell-associated herpesvirus of turkeys (HVT) was inoculated in ovo at various stages of incubation. Chickens hatching from these eggs were tested for anti-HVT antibodies by several serologic procedures including enzyme-linked immunosorbent assay, indirect immunofluorescence assays, and western blot. Viremic chickens that remained free of detectable antibodies were considered tolerant to HVT. Chickens exposed to HVT at embryonation day 14 or earlier had 6-33% incidence of tolerance. Tolerant chickens developed persistent HVT viremia. A preliminary challenge experiment provided circumstantial evidence that tolerant to HVT may be associated with reduced resistance to virulent Marek's disease virus. Tolerance to HVT did not influence the ability of the chickens to produce antibodies against an extraneous antigen or respond to a T cell mitogen.

Animals↗
PubMed2003

Functional characterisation of the recombinant tumor necrosis factors in rainbow trout, Oncorhynchus mykiss.

Tumor necrosis factor (TNF) is a key mediator in regulating the inflammatory response. Previously two TNF genes have been cloned and sequenced from rainbow trout, Oncorhynchus mykiss. In this study, the mature peptides of the two TNF molecules were produced in bacteria, purified under native conditions and their bioactivities evaluated in vitro. Both trout rTNF1 and rTNF2 induced gene expression of a number of proinflammatory factors including IL1beta, TNF1, TNF2, IL8 and COX2 in freshly isolated head kidney leucocytes and the macrophage cell line RTS11. The stimulatory doses of both rTNFs were >or=10 ng/ml. Moreover, leucocyte migration and phagocytic activity were enhanced in vitro by the rTNFs in a dose dependent manner. Western blot analysis revealed the presence of multiple forms of rTNF structures including monomeric, dimeric and trimeric forms, suggesting that formation of a homotrimeric structure may be essential for the TNF bioactivities.

Adjuvants, Immunologic↗
PubMed2003

Biodiesel production from waste cooking oil: 1. Process design and technological assessment.

Four different continuous process flowsheets for biodiesel production from virgin vegetable oil or waste cooking oil under alkaline or acidic conditions on a commercial scale were developed. Detailed operating conditions and equipment designs for each process were obtained. A technological assessment of these four processes was carried out to evaluate their technical benefits and limitations. Analysis showed that the alkali-catalyzed process using virgin vegetable oil as the raw material required the fewest and smallest process equipment units but at a higher raw material cost than the other processes. The use of waste cooking oil to produce biodiesel reduced the raw material cost. The acid-catalyzed process using waste cooking oil proved to be technically feasible with less complexity than the alkali-catalyzed process using waste cooking oil, thereby making it a competitive alternative to commercial biodiesel production by the alkali-catalyzed process.

Catalysis↗