Biomedical subjects

F Ye

Publications and source records attributed to F Ye.

At least 19 recordsLinked to original sources

PubMed2014

Gene transfer of arginine kinase to skeletal muscle using adeno-associated virus.

In this study, we tested the feasibility of non-invasively measuring phosphoarginine (PArg) after gene delivery of arginine kinase (AK) using an adeno-associated virus (AAV) to murine hindlimbs. This was achieved by evaluating the time course, regional distribution and metabolic flux of PArg using (31)phosphorus magnetic resonance spectroscopy ((31)P-MRS). AK gene was injected into the gastrocnemius of the left hindlimb of C57Bl10 mice (age 5 weeks, male) using self-complementary AAV, type 2/8 with desmin promoter. Non-localized (31)P-MRS data were acquired over 9 months after injection using 11.1-T and 17.6-T Bruker Avance spectrometers. In addition, (31)P two-dimensional chemical shift imaging and saturation transfer experiments were performed to examine the spatial distribution and metabolic flux of PArg, respectively. PArg was evident in each injected mouse hindlimb after gene delivery, increased until 28 weeks, and remained elevated for at least 9 months (P<0.05). Furthermore, PArg was primarily localized to the injected posterior hindimb region and the metabolite was in exchange with ATP. Overall, the results show the viability of AAV gene transfer of AK gene to skeletal muscle, and provide support of PArg as a reporter that can be used to non-invasively monitor the transduction of genes for therapeutic interventions.

Animals↗

PubMed2006

Mapping the MRI voxel volume in which thermal noise matches physiological noise--implications for fMRI.

This work addresses the choice of the imaging voxel volume in blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). Noise of physiological origin that is present in the voxel time course is a prohibitive factor in the detection of small activation-induced BOLD signal changes. If the physiological noise contribution dominates over the temporal fluctuation contribution in the imaging voxel, further increases in the voxel signal-to-noise ratio (SNR) will have diminished corresponding increases in temporal signal-to-noise (TSNR), resulting in reduced corresponding increases in the ability to detect activation induced signal changes. On the other hand, if the thermal and system noise dominate (suggesting a relatively low SNR) further decreases in SNR can prohibit detection of activation-induced signal changes. Here we have proposed and called the "suggested" voxel volume for fMRI the volume where thermal plus system-related and physiological noise variances are equal. Based on this condition we have created maps of fMRI suggested voxel volume from our experimental data at 3T, since this value will spatially vary depending on the contribution of physiologic noise in each voxel. Based on our fast EPI segmentation technique we have found that for gray matter (GM), white matter (WM), and cerebral spinal fluid (CSF) brain compartments the mean suggested cubical voxel volume is: (1.8 mm)3, (2.1 mm)3 and (1.4 mm)3, respectively. Serendipitously, (1.8 mm)3 cubical voxel volume for GM approximately matches the cortical thickness, thus optimizing BOLD contrast by minimizing partial volume averaging. The introduced suggested fMRI voxel volume can be a useful parameter for choice of imaging volume for functional studies.

Artifacts↗

PubMed2006

Evolution of spin-wave excitations in ferromagnetic metallic manganites.

Neutron scattering results are presented for spin-wave excitations of three ferromagnetic metallic A1-xA'xMnO3 manganites (where A and A' are rare- and alkaline-earth-metal ions), which when combined with previous work elucidate the systematics of the interactions as a function of carrier concentration x, on-site disorder, and strength of the lattice distortion. The long-wavelength spin dynamics show only a very weak dependence across the series. The ratio of fourth to first neighbor exchange (J4/J1) that controls the zone boundary magnon softening changes systematically with x, but does not depend on the other parameters. None of the prevailing models can account for these behaviors.

Journal Article↗

PubMed2006

Interference of cyclosporine on glucose metabolism: potential role in chronic transplantation kidney fibrosis.

OBJECTIVES: To explore the fibrosis induction effects of cyclosporine (CsA) on renal tubular epithelial cells, as well as the potential mechanisms of CsA-mediated alterations of glucose metabolism in chronic allograft nephropathy (CAN). METHODS: The rat renal tubular epithelial cell line NRK-52E cells were cultured in medium with 50 mmol/L of D-glucose for 7, 14, or 28 days. The expression of TGF-beta1, CTGF, Smad3, and Smad7, which are involved in the fibrosis signal pathway, was detected by immunofluorescence and reverse-transcriptase polymerase chain reaction. Meanwhile, cells were cultured in various concentration of CsA in glucose-free medium for 24 hours followed by the addition of D-[3-(3)H]-glucose for 30 minutes; glucose uptake was detected by examining the radiation intensity. RESULTS: The expression of TGF-beta1, Smad3, Smad7, and CTGF of NRK-52E cells were up-regulated significantly (P < .05) after culture with 50 mmol/L glucose for 7 days compared with those in 25 mmol/L glucose. At 14 and 28 days, TGF-beta1 was slightly decreased compared with 7 days, but CTGF, Smad3, and Smad7 increased robustly (P < .05). CsA significantly stimulated glucose uptake at various concentrations, with an absorption peak at 60 minutes that decreased at 75 minutes. Furthermore, CsA may have dose-dependent effects on glucose uptake. CONCLUSION: High glucose concentrations may play an important role in the NRK-52E cell fibrosis during the CAN process due to an interference of CsA on glucose metabolism.

Animals↗

PubMed2006

Nuclear translocation of SMAD3 may enhance the TGF-beta/SMADS pathway in high glucose circumstances.

OBJECTIVES: Posttransplant diabetes mellitus is one of the most frequent complications after kidney transplantation. It is considered to be one cause of chronic allograft nephropathy. This study sought to investigate the effects of high glucose on the expression and nuclear translocation of Smad3, which is an important signal mediator involved in the fibrotic signal pathway. METHODS: The established rat renal mesangial cell line HBZY-1 was cultured in medium with various concentrations of glucose (4.5 mg/mL, 9.0 mg/mL, or 13.5 mg/mL), which was collected at 7, 14, or 21 days. The total expression of Smad3, including both inner and outer nucleus proteins was examined by Western blot analysis. The nuclear translocated Smad3, representing only the inner nucleus protein, was detected by immunofluorescence staining observed under a laser confocal scanning microscope. RESULTS: No significant difference in the total Smad3 expression was demonstrated by Western blot analysis among the three groups of HBZY-1 cells at various concentration of glucose after 7, 14, or 21 days. There was no fluorescence detected in the nucleus at day 7 by immunofluorescence staining; however, robust positive expression of Smad3 was detected at days 14 and 21. CONCLUSION: As a restricted Smads member, Smad3 protein might not be upregulated in the presence of high glucose. However, with prolonged culture time, Smad3 translocates from cytoplasm to nucleus, which may be a pivotal step in the fibrotic signal pathway.

Animals↗

PubMed2006

The C-terminal peptide of connective tissue growth factor blocks the full molecule binding to tubular epithelial cell.

OBJECTIVES: Interstitial fibrosis is a critical pathologic change in chronic allograft nephropathy. The cytokine connective tissue growth factor (CTGF, also CCN2) plays an important role in epithelial-mesenchymal transformation (EMT) of tubular epithelial cells to renal interstitial fibrosis. The hexadeca-peptide within the C-terminal of CTGF (named P2) contains the unique binding domain of CTGF to its potential receptor, integrin alphavbeta3. This study examined whether P2 bound preferentially to the receptor and served as an inhibitor of CTGF. METHODS: All studies used an established rat kidney tubular epithelial cell line NRK-52E. Chemically synthesized P2 was purified, and some of it labeled with FITC. The affinity of CTGF or P2 to NRK-52E cells was examined by a solid-phase cell adhesion assay. Competitive binding between P2 and CTGF to NRK-52E cells was examined with flow cytometric analysis. RESULTS: Both P2 and CTGF bound to the NRK-52E cells, mediating cell adhesion. When the cells were incubated in the mixture of P2 and CTGF, P2 bound to the cells preferentially. Furthermore, when cells were preincubated with excessive CTGF, it became difficult for subsequent P2 binding to occur. CONCLUSIONS: P2 and CTGF seemed to bind to cell membranes at the same binding domain. P2 competitively blocked CTGF binding, acting as a CTGF inhibitor.

Animals↗

PubMed2006

[Establishment of Z-HL16C cell line.].

BACKGROUND: To establish and study the nature and the application of Z-HL16C cell line. METHODS: The cell line was continuously passed, frozen stored and recovered. Its application was expanded and the cell type was identified. RESULTS: The cell line had an epithelial-cell-like shape, the size appeared uniform, the cell boundary was distinct. It has been continuously passed, frozen stored and recovered for ten years. Its recovery rate was about 90%. It has been proved to be sensitive to the tested viruses which were enteroviruses (Polio, Cox, Echo), influenza viruses, parainfluenzaviruses, adenoviruses, measles virus. This cell line has been identified as a cancerization cell. CONCLUSION: The cell line Z-HL16C has been stably established, it has a broad spectrum in sensitivity for culturing viruses.

Cell Line↗

PubMed2005

Fibroblast growth factors 7 and 10 are expressed in the human embryonic pancreatic mesenchyme and promote the proliferation of embryonic pancreatic epithelial cells.

AIMS/HYPOTHESIS: The fibroblast growth factor (FGF) family consists of 22 members. In rodents, several FGFs are expressed in the pancreas, where they participate in epithelial-mesenchymal interactions. Our objective was to describe the pattern of expression of FGFs in the human embryonic pancreas and to analyse their effect on pancreas development. METHODS: The expression of FGFs was analysed by RT-PCR. To investigate the cell types expressing FGF7 and FGF10, we separated epithelial from mesenchymal cells using immunomagnetic beads linked to E-cadherin antibodies and performed real-time PCR. The effect of FGF7 and FGF10 on proliferation of human embryonic pancreatic epithelial cells was evaluated in vitro by measuring BrdU incorporation. RESULTS: We found that different FGFs are expressed in the human embryonic pancreas, and we focused on FGF7 and FGF10. We defined a new approach to separating epithelial cells (containing the pancreatic progenitor cells) from mesenchymal cells. This allowed us to demonstrate that human embryonic pancreatic mesenchymal cells express both FGF7 and FGF10. We next demonstrated that FGF7 and FGF10 were able to induce the proliferation of the epithelial cells in vitro. CONCLUSION/INTERPRETATION: These findings indicate that it is now possible to efficiently separate human embryonic pancreatic epithelial from mesenchymal cells, an important step to characterize and expand progenitor cells. This method allowed us to demonstrate that human embryonic pancreatic mesenchyme expresses FGF7 and FGF10 that act on epithelial cells to activate their proliferation. Such growth factors could thus be used to expand human embryonic pancreatic epithelial cells.

Base Sequence↗

PubMed2002

Order parameter criticality of the d = 3 random-field Ising antiferromagnet Fe0.85Zn0.15F2.

The critical exponent beta=0.16+/-0.02 for the random-field Ising model order parameter is determined using extinction-free magnetic x-ray scattering for Fe0.85Zn0.15F2 in magnetic fields of 10 and 11 T. The observed value is consistent with other experimental random-field critical exponents, but disagrees sharply with Monte Carlo and exact ground state calculations on finite-sized systems.

Journal Article↗

PubMed2002

Alpha-glucosidase inhibition from a Chinese medical herb (Ramulus mori) in normal and diabetic rats and mice.

Alpha-glucosidase inhibitors are oral antidiabetic drugs. A traditional Chinese medical herb, Sangzhi (Ramulus mori), appears to have properties similar to those of alpha-glucosidase inhibitors. The effects of an aqueous extract of Shangzhi (SZ) were studied in normal and alloxan diabetic rats and mice, and these results compared with those for acarbose, an alpha-glucosidase inhibitor. In our grade-dose studies, SZ was found to lower and prolong the zenith of blood glucose concentration (ZBG) after sucrose or starch loading and stabilize blood glucose levels in fasting normal and alloxan diabetic mice. After 2 weeks of SZ administration with high-calorie chow or a normal diet, the fasting and non-fasting blood glucose concentrations in alloxan diabetic mice and rats were decreased. In alloxan rats, the blood fructosamine concentration was lowered. Results for acarbose and SZ were similar. These indicate that SZ has alpha-glucosidase inhibitory effects.

Alloxan↗

PubMed2001

Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity.

Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC(50) = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of 1a led to 1c, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of 1c with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC(50) of 1.2 nM in the Src enzymatic assay, an IC(50) of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

Animals↗

PubMed2001

6-Substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity.

A series of new 6-substituted-4-(3-bromophenylamino)quinazoline derivatives that may function as irreversible inhibitors of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases have been prepared. These inhibitors have, at the C-6 position, butynamide, crotonamide, and methacrylamide Michael acceptors bearing water-solublilizing substituents. These compounds were prepared by acylation of 6-amino-4-(3-bromophenylamino)quinazoline with unsaturated acid chlorides or mixed anhydrides. We show that attaching a basic functional group onto the Michael acceptor results in greater reactivity, due to intramolecular catalysis of the Michael addition and/or an inductive effect of the protonated basic group. This, along with improved water solubility, results in compounds with enhanced biological properties. We present molecular modeling and experimental evidence that these inhibitors interact covalently with the target enzymes. One compound, 16a, was shown to have excellent oral activity in a human epidermoid carcinoma (A431) xenograft model in nude mice.

Administration, Oral↗

PubMed2001

MEK (MAPKK) inhibitors. Part 2: structure-activity relationships of 4-anilino-3-cyano-6,7-dialkoxyquinolines.

A series of 4-anilino-3-cyano-6,7-dialkoxyquinolines with different substituents attached to the 4-anilino group has been prepared that are potent MEK (MAP kinase kinase) inhibitors. The best activity is obtained when a phenyl or a thienyl group is attached to the para-position of the aniline through a hydrophobic linker, such as an oxygen, a sulfur, or a methylene group. The most active compounds show low nanomolar IC(50)'s against MEK (MAP kinase kinase), and have potent growth inhibitory activity in LoVo cells (human colon tumor line).

Aniline Compounds↗

PubMed2001

Synthesis and Src kinase inhibitory activity of a series of 4-phenylamino-3-quinolinecarbonitriles.

Screening of a directed compound library in a yeast-based assay identified 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (2a) as a Src inhibitor. An enzymatic assay established that 2a was an ATP-competitive inhibitor of the kinase activity of Src. We present here SAR data for 2a which shows that the aniline group at C-4, the carbonitrile group at C-3, and the alkoxy groups at C-6 and C-7 of the quinoline are crucial for optimal activity. Increasing the size of the C-2 substituent of the aniline at C-4 of 2a from chloro to bromo to iodo resulted in a corresponding increase in Src inhibition. Furthermore, replacement of the 7-methoxy group of 2a with various 3-heteroalkylaminopropoxy groups provided increased inhibition of both Src enzymatic and cellular activity. Compound 25, which contains a 3-morpholinopropoxy group, had an IC(50) of 3.8 nM in the Src enzymatic assay and an IC(50) of 940 nM for the inhibition of Src-dependent cell proliferation.

Aniline Compounds↗

PubMed2001

Fluorescent microsphere-based readout technology for multiplexed human single nucleotide polymorphism analysis and bacterial identification.

Large-scale human genotyping requires technologies with a minimal number of steps, high accuracy, and the ability to automate at a reasonable cost. In this regard, we have developed a rapid, cost-effective readout method for single nucleotide polymorphism (SNP) genotyping that combines an easily automatable single-tube allele-specific primer extension (ASPE) with an efficient high throughput flow cytometric analysis performed on a Luminex 100 flow cytometer. This robust technique employs an ASPE reaction using PCR-derived target DNA containing the SNP and a pair of synthetic complementary capture probes that differ at their 3' end-nucleotide defining the alleles. Each capture probe has been synthesized to contain a unique 25-nucleotide identifying sequence (ZipCode) at its 5' end. An array of fluorescent microspheres, covalently coupled with complementary ZipCode sequences (cZipCodes), was hybridized to biotin-labeled ASPE reaction products, sequestering them for flow cytometric analysis. ASPE offers both an advantage of streamlining the SNP analysis protocol and an ability to perform multiplex SNP analysis on any mixture of allelic variants. All steps of the assay are simple additions of the solutions, incubations, and washes. This technique was used to assay 15 multiplexed SNPs on human chromosome 12 from 96 patients. Comparison of the microsphere-based ASPE assay results to gel-based oligonucleotide ligation assay (OLA) results showed 99.2% agreement in genotype assignments. In addition, the microsphere-based multiplex SNPs assay system was adapted for the identification of bacterial samples by both ASPE and single base chain extension (SBCE) assays. A series of probes designed for different variable sites of bacterial 16S rDNA permitted multiplex analysis and generated species- or genus-specific patterns. Seventeen bacterial species representing a broad range of gram-negative and gram-positive bacteria were analyzed within 16 variable sites of 16S rDNA sequence. The results were consistent with the published sequences and confirmed by direct DNA sequencing.

Alleles↗

PubMed2001

On the mechanism of the protective effects of nitroglycerin and nicorandil in cardiac anaphylaxis.

Previous investigations have shown that nitric oxide donors and nicorandil can suppress allergic reaction. In the present study, the protective effects of nitroglycerin and nicorandil on cardiac anaphylaxis were examined. Presensitized guinea-pig hearts challenged with specific antigen caused a marked decrease in coronary flow (CF), left ventricular pressure (LVP) and its derivatives (+/-dp/dtmax), increase in heart rate, and prolongation of P-R interval. Nitroglycerin (300 nM) or nicorandil (100 microM) markedly increased the content of calcitonin gene-related peptide (CGRP) concomitant with a significant improvement of the cardiac dysfunction and alleviation of the extension of P-R interval. Nicorandil at a concentration of 100 microM also inhibited the sinus tachycardia and histamine release. The protection afforded by nitroglycerin was abolished by glibenclamide, a blocker of ATP-sensitive potassium channels, or by CGRP8-37, the selective CGRP receptor antagonist, or by pretreatment with capsaicin, which depletes endogenous CGRP. The inhibitory effect of nicorandil on cardiac anaphylaxis was abolished only by glibenclamide but not by pretreatment with capsaicin. These results suggest that nitroglycerin and nicorandil possess a protection of cardiac anaphylactic injury. The present study also suggests that the protective effect of nitroglycerin may be related to stimulation of CGRP release and opening the KATP channel, and that the effect of nicorandil is mainly due to the activation of the KATP channel.

Anaphylaxis↗

PubMed2001

Differential expression of Tie-2 receptors and angiopoietins in response to in vivo hypoxia in rats.

In this study, we assessed the effects of in vivo hypoxia on the expression of Tie-2 receptors and angiopoietins in various organs of conscious rats and correlated these effects with the expression of hypoxia-inducible factor-1 (HIF-1). RT-PCR and Southern blotting were used to amplify mRNA expression of angiopoietin-1, -2, and -3, Tie-2, and HIF-1 alpha in tissues of normoxic and hypoxic (fraction of inspired oxygen of 9--10% for either 12 or 48 h) rats. Hypoxia provoked a decline in angiopoietin-1 mRNA and Tie-2 mRNA, protein, and phosphorylation levels in the lung, liver, cerebellum, and heart but not in the kidney and diaphragm. In comparison, hypoxia raised the levels of angiopoietin-2 mRNA in the cerebellum and angiopoietin-3 mRNA in the lung, kidney, and diaphragm. HIF-1 alpha mRNA was abundant in most organs of normoxic rats but was significantly induced in the kidney and diaphragm of hypoxic rats. We conclude that in vivo hypoxia exerts inhibitory effects on the activity of the angiopoietin-1/Tie-2 receptor pathway through reduction of angiopoietin-1 and upregulation of angiopoietin-2 and -3. Induction of angiopoietin-3 in the kidney and diaphragm of hypoxic rats could be mediated through the HIF-1 transcription factor.

Angiopoietin-1↗

PubMed2001

Effects of temperature and air pollutants on cardiovascular and respiratory diseases for males and females older than 65 years of age in Tokyo, July and August 1980-1995.

We studied exposures to higher daily maximum temperatures and concentrations of air pollutants in Tokyo during the summer months of July and August from 1980 to 1995 and their effects on hospital emergency transports for cardiovascular and respiratory diseases for males and females > 65 years of age. Cardiovascular diseases were angina, cardiac insufficiency, hypertension, and myocardial infarction. Respiratory diseases were asthma, acute and chronic bronchitis, and pneumonia. Except for pneumonia, daily maximum temperatures were not associated with hospital emergency transports. Increasing daily maximum temperatures, however, were associated with decreased hospital emergency transports for hypertension. Concentrations of nitrogen dioxide or particulate matter < or = 10 microm, however, were associated with daily hospital emergency transports for angina, cardiac insufficiency, myocardial infarction, asthma, acute and chronic bronchitis, and pneumonia. For cardiac insufficiency, hypertension, myocardial infarction, asthma, chronic bronchitis, and pneumonia, the expected daily number of emergency transports per million were greater for males than for females. For angina and acute bronchitis, there were no differences for the expected daily numbers of emergency transports per million between males and females.

Aged↗