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Biomedical subjects

M Yang

Publications and source records attributed to M Yang.

At least 37 records · Page 2Linked to original sources
PubMed2001

IL-13 induces airways hyperreactivity independently of the IL-4R alpha chain in the allergic lung.

The potent spasmogenic properties of IL-13 have identified this molecule as a potential regulator of airways hyperreactivity (AHR) in asthma. Although IL-13 is thought to primarily signal through the IL-13Ralpha1-IL-4Ralpha complex, the cellular and molecular components employed by this cytokine to induce AHR in the allergic lung have not been identified. By transferring OVA-specific CD4(+) T cells that were wild type (IL-13(+/+) T cells) or deficient in IL-13 (IL-13(-/-) T cells) to nonsensitized mice that were then challenged with OVA aerosol, we show that T cell-derived IL-13 plays a key role in regulating AHR, mucus hypersecretion, eotaxin production, and eosinophilia in the allergic lung. Moreover, IL-13(+/+) T cells induce these features (except mucus production) of allergic disease independently of the IL-4Ralpha chain. By contrast, IL-13(+/+) T cells did not induce disease in STAT6-deficient mice. This shows that IL-13 employs a novel component of the IL-13 receptor signaling system that involves STAT6, independently of the IL-4Ralpha chain, to modulate pathogenesis. We show that this novel pathway for IL-13 signaling is dependent on T cell activation in the lung and is critically linked to downstream effector pathways regulated by eotaxin and STAT6.

Adoptive Transfer↗
PubMed2001

Spatial-temporal imaging of bacterial infection and antibiotic response in intact animals.

We describe imaging the luminance of green fluorescent protein (GFP)-expressing bacteria from outside intact infected animals. This simple, nonintrusive technique can show in great detail the spatial-temporal behavior of the infectious process. The bacteria, expressing the GFP, are sufficiently bright as to be clearly visible from outside the infected animal and recorded with simple equipment. Introduced bacteria were observed in several mouse organs including the peritoneal cavity, stomach, small intestine, and colon. Instantaneous real-time images of the infectious process were acquired by using a color charge-coupled device video camera by simply illuminating mice at 490 nm. Most techniques for imaging the interior of intact animals may require the administration of exogenous substrates, anesthesia, or contrasting substances and require very long data collection times. In contrast, the whole-body fluorescence imaging described here is fast and requires no extraneous agents. The progress of Escherichia coli-GFP through the mouse gastrointestinal tract after gavage was followed in real-time by whole-body imaging. Bacteria, seen first in the stomach, migrated into the small intestine and subsequently into the colon, an observation confirmed by intravital direct imaging. An i.p. infection was established by i.p. injection of E. coli-GFP. The development of infection over 6 h and its regression after kanamycin treatment were visualized by whole-body imaging. This imaging technology affords a powerful approach to visualizing the infection process, determining the tissue specificity of infection, and the spatial migration of the infectious agents.

Administration, Oral↗
PubMed2001

Different classifications of UPOs in the parametrically different chaotic ISI series of a neural pacemaker.

Various interspike intervals (ISIs) in a series of spontaneous discharges of experimental neural pacemakers were identified as chaotic and as lying between stable period 2 and stable period 3. The method of So et al. for detection of unstable periodic orbits (UPOs) was applied to analyze two chaotic ISI series generated under the action of [Ca2+]o in different concentrations. In the chaotic ISI series near the stable period 2, an unstable period 2 orbit was detected. In the chaotic ISI series near the stable period 3, both an unstable period 2 orbit and an unstable period 3 orbit were detected. The location of the unstable period 2 orbit was close to that of the stable period 2 in the return map, while the location of the unstable period 3 orbit was close to that of the stable period 3. The results not only revealed the structures of various chaotic ISI series, but also indicated that the classification of UPOs could reflect the experimental control parameters at which the chaotic ISI series were generated. The previously discovered period adding bifurcation in the ISI series generated by experimental neural pacemakers [12] was further described in terms of the evolution of the period orbits.

Action Potentials↗
PubMed2001

A new locus for hereditary gingival fibromatosis (GINGF2) maps to 5q13-q22.

Gingival fibromatosis (GINGF) is an oral disorder characterized by enlargement of the gingiva. It occurs either as the sole phenotype or combined with other symptoms. Thus far, one GINGF locus has been mapped on chromosome 2, at 2p21, and a second possible locus has been mapped to 2p13. However, the genes responsible for this disorder have not been elucidated. We identified a four-generation Chinese GINGF family in which the disease manifests within 1 year after birth. After exclusion of the two known GINGF loci in this family, we performed a genome-wide search to map the chromosome location of the responsible gene. We identified a new locus, GINGF2, on chromosome 5q13-q22 with a maximum two-point lod score of 4.31 at D5S1721 (theta = 0.00). Haplotype analysis placed the critical region in the interval defined by D5S1491 and D5S1453. Within this region, calcium/calmodulin-dependent protein kinase IV (CAMK4) is a strong candidate.

Age of Onset↗
PubMed2001

G alpha 16 couples chemoattractant receptors to NF-kappa B activation.

The guanine nucleotide-binding regulatory protein alpha-subunit, Galpha(16), is primarily expressed in hemopoietic cells, and interacts with a large number of seven-membrane span receptors including chemoattractant receptors. We investigated the biological functions resulting from Galpha(16) coupling of chemoattractant receptors in a transfected cell model system. HeLa cells expressing a kappaB-driven luciferase reporter, Galpha(16), and the formyl peptide receptor responded to fMLP with a approximately 7- to 10-fold increase in luciferase activity. This response was accompanied by phosphorylation of IkappaBalpha and elevation of nuclear kappaB-DNA binding activity, indicating activation of NF-kappaB. In contrast to Galpha(16), expression of Galpha(q), Galpha(13), and Galpha(i2) resulted in a marginal increase in kappaB luciferase activity. A GTPase-deficient, constitutively active Galpha(16) mutant (Q212L) could replace agonist stimulation for activation of NF-kappaB. Furthermore, expression of Galpha(16) (Q212L) markedly enhanced TNF-alpha-induced kappaB reporter activity. The Galpha(16)-mediated NF-kappaB activation was paralleled by an increase in phospholipase C-beta activity, and was blocked by pharmacological inhibitors of protein kinase C (PKC) and by buffering of intracellular Ca(2+). The involvement of a conventional PKC isoform was confirmed by the finding that expression of PKCalpha enhanced the effect of Galpha(16), and a dominant negative PKCalpha partially blocked Galpha(16)-mediated NF-kappaB activation. In addition to formyl peptide receptor, Galpha(16) also enhanced NF-kappaB activation by the C5a and C3a receptors, and by CXC chemokine receptor 2 and CCR8. These results suggest a potential role of Galpha(16) in transcriptional regulation downstream of chemoattractant receptors.

Active Transport, Cell Nucleus↗
PubMed2001

Phosphorus limitation of nitrogen fixation by Trichodesmium in the central Atlantic Ocean.

Marine fixation of atmospheric nitrogen is believed to be an important source of biologically useful nitrogen to ocean surface waters, stimulating productivity of phytoplankton and so influencing the global carbon cycle. The majority of nitrogen fixation in tropical waters is carried out by the marine cyanobacterium Trichodesmium, which supplies more than half of the new nitrogen used for primary production. Although the factors controlling marine nitrogen fixation remain poorly understood, it has been thought that nitrogen fixation is limited by iron availability in the ocean. This was inferred from the high iron requirement estimated for growth of nitrogen fixing organisms and the higher apparent densities of Trichodesmium where aeolian iron inputs are plentiful. Here we report that nitrogen fixation rates in the central Atlantic appear to be independent of both dissolved iron levels in sea water and iron content in Trichodesmium colonies. Nitrogen fixation was, instead, highly correlated to the phosphorus content of Trichodesmium and was enhanced at higher irradiance. Furthermore, our calculations suggest that the structural iron requirement for the growth of nitrogen-fixing organisms is much lower than previously calculated. Although iron deficiency could still potentially limit growth of nitrogen-fixing organisms in regions of low iron availability-for example, in the subtropical North Pacific Ocean-our observations suggest that marine nitrogen fixation is not solely regulated by iron supply.

Atlantic Ocean↗
PubMed2001

Identification of a novel human fibroblast growth factor and characterization of its role in oncogenesis.

The fibroblast growth factor (FGF) family of signaling molecules has been implicated in normal developmental and physiological processes, as well as in human malignancy. Using a homology-based genomic DNA mining process, we identified a human gene encoding a novel member of the FGF family, that we designate FGF-20. The FGF-20 cDNA was isolated, and its sequence confirmed the gene prediction. FGF-20 is expressed in normal brain, particularly the cerebellum, and in some cancer cell lines. Recombinant FGF-20 protein induces DNA synthesis in a variety of cell types and is recognized by multiple FGF receptors. Ectopic expression of FGF-20 in NIH 3T3 cells renders the cells transformed in vitro and tumorigenic in nude mice. These results underscore the utility of mining genomic DNA databases and reveal FGF-20 to be a novel oncogene that may play a role in human cancer.

3T3 Cells↗
PubMed2001

Two-dimensional direct-reading fluorescence spectrograph for DNA sequencing by capillary array electrophoresis.

We report a compact, two-dimensional direct-reading fluorescence spectrograph and demonstrate its application to DNA sequencing by capillary array electrophoresis. The detection cuvette is based on sheath flow, wherein the capillaries terminate in a two-dimensional array in a fluid-filled chamber that is pressurized with buffer. A thin metal plate is located downstream from the capillaries. This barrier plate has an array of holes that precisely matches the location of the capillaries. Buffer flows through the holes, drawing analyte from the capillaries in a well-defined array of thin filaments. Fluorescence is excited in the upper chamber with an elliptically shaped laser beam. The bottom chamber is sealed with a glass window and drained from the side. Fluorescence is detected by imaging the illuminated sample streams through the holes in the barrier plate. A prism is used to disperse fluorescence from each sample across a CCD camera so that the emission spectrum is monitored simultaneously from each capillary. The instrument is demonstrated in a 32-capillary configuration but can be scaled to several thousand capillaries.

DNA↗
PubMed2001

Whole-body and intravital optical imaging of angiogenesis in orthotopically implanted tumors.

The development of drugs for the control of tumor angiogenesis requires a simple, accurate, and economical assay for tumor-induced vascularization. We have adapted the orthotopic implantation model to angiogenesis measurement by using human tumors labeled with Aequorea victoria green fluorescent protein for grafting into nude mice. The nonluminous induced capillaries are clearly visible against the very bright tumor fluorescence examined either intravitally or by whole-body luminance in real time. The orthotopic implantation model of human cancer has been well characterized, and fluorescence shadowing replaces the laborious histological techniques for determining blood vessel density. Intravital images of orthotopically implanted human pancreatic tumors clearly show angiogenic capillaries at both primary and metastatic sites. A quantitative time course of angiogenesis was determined for an orthotopically growing human prostate tumor periodically imaged intravitally in a single nude mouse over a 19-day period. Whole-body optical imaging of tumor angiogenesis was demonstrated by injecting fluorescent Lewis lung carcinoma cells into the s.c. site of the footpad of nude mice. The footpad is relatively transparent, with comparatively few resident blood vessels, allowing quantitative imaging of tumor angiogenesis in the intact animal. Capillary density increased linearly over a 10-day period as determined by whole-body imaging. Similarly, the green fluorescent protein-expressing human breast tumor MDA-MB-435 was orthotopically transplanted to the mouse fat pad, where whole-body optical imaging showed that blood vessel density increased linearly over a 20-week period. These powerful and clinically relevant angiogenesis mouse models can be used for real-time in vivo evaluation of agents inhibiting or promoting tumor angiogenesis in physiological microenvironments.

Animals↗
PubMed2001

Identification of protein kinase C isoforms involved in interferon-gamma-induced expression of inducible nitric oxide synthase in murine BV2 microglia.

Microglia are major inflammatory cells of the brain. It has been known that interferon-gamma (IFN-gamma) induces nitric oxide (NO)/inducible nitric oxide synthase (iNOS) in microglia, and that protein kinase C (PKC) mediates the action of IFN-gamma. In this study, we investigated isoforms of PKC that are involved in IFN-gamma-induced activation of microglia using BV2 murine microglial cells. NO release/iNOS expression in IFN-gamma -treated BV2 cells was reduced in the presence of PKC inhibitors (Gö 6976 and BIM), and by long-term pre-treatment (48 h) of cells with phorbol-12-myristate-13-acetate (PMA) or thymeleatoxin. PMA depleted alpha, beta, delta, and epsilon isoforms, and thymeleatoxin depleted alpha, beta, and epsilon isoforms although gamma, eta, iota, lambda, theta, mu, and zeta were also detected in these cells. Furthermore, IFN-gamma phosphorylated alpha and epsilon on their tyrosine residues. These results suggested that alpha and epsilon could be the major PKC isoforms involved in signaling pathways of IFN-gamma to induce NO/iNOS expression in BV2 microglia.

Animals↗
PubMed2001

[Surveillance of bacterial resistance in China (1998-1999)].

OBJECTIVE: To determine the rates of bacterial resistance of clinical isolates obtained from patients with hospital infections (HI) or community acquired infections (CAI) in the study wards of 13 hospitals located at different areas in China. METHODS: Susceptibility test was performed on 2 081 strains isolated from 13 hospitals, using standard plate dilution method according to the guidelines of NCCLS (1998). MIC(50) and MIC(90) were used to show the antibacterial activity of antimicrobial agents, and data of R%, I% and S% represent resistant, intermediate and susceptible rates of bacteria to antimicrobial agents tested. RESULTS: Among total 98 strains of S. aureus, 87 were isolated from patients with CAI and 11 were from HI patients. The incidence of methicillin resistant S.aureus (MRSA) from total infections caused by S. aureus was 27.55%, while the incidence of MRSA from HI patients was 81.82%, which was significantly higher than that (21.84%) from CAI patients. The rate of penicillin resistant S. pneumoniae (PRSP) (R% + I%) was 22.50%; the rate of R (MIC >/= 2 mg/L) was 2.5%, and most of PRSP strains was intermediate, with I% of 20%. No strains of S. aureus, neither strains of E. faecalis, nor of E. faecium were found resistant to vancomycin. The intermediate rate (I%) of E. faecalis and E. faecium to vancomycin was 3.23% and 3.77%, respectively. Cross resistance of E. coli to quinolones was present obviously, and more than 60% of E. coli strains were resistant to fluoroquinolones tested. CONCLUSION: Multi-drug resistance (MDR) of bacteria is a serious problem in China, including MDR of MRSA, PRSP, and enterobacteriaceae; and the resistant rate of enterobacterinceae is the highest up-to-date.

Anti-Bacterial Agents↗
PubMed2001

2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT.

We have examined the mutational basis of adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency (MIM 102600) in a patient of Polish origin who has been passing 2,8-dihydroxyadenine (DHA) stones since birth, but has considerable residual enzyme activity in lymphocyte extracts. The five exons and flanking regions of APRT were amplified by PCR and then sequenced. A single T insertion was identified at the intron 4 splice donor site (TGgtaa to TGgttaa:IVS4+2insT) in one allele from the proband, his mother, and brother. A G-to-T transversion in exon 5 (GTC-to-TTC:c.448G>T, V150F) was identified in the other allele, and this mutation was also present in one allele from the father and the paternal grandmother. Tru91 and AvaII digestions of PCR products spanning exons 4 and 5, respectively, confirmed the mutations. The mother was heterozygous for an intragenic TaqI site, but all other family members were homozygous for the presence of this site. IVS4+2insT, located on the allele containing the TaqI site, has been identified previously in several families from Europe, suggesting a founder effect, but the substitution in exon 5 is a novel mutation. IVS4+2insT is known to result in complete loss of enzyme activity, and our results suggest that V150F produces an enzyme that is nonfunctional in vivo but has considerable residual activity in vitro.

Adenine↗
PubMed2001

Transduction of liver cells by lentiviral vectors: analysis in living animals by fluorescence imaging.

Viral vectors based on lentiviruses, such as the human immunodeficiency virus, are able to transduce a broad spectrum of nondividing cells in vivo. This ability of lentiviral vectors makes them an attractive vehicle for gene transfer into the liver. In order to determine the requirements for efficient lentiviral gene transfer, we used a fluorescence imaging system, which allows the detection of cells and tissues that express fluorescent reporter genes (e.g., green fluorescence protein) in the living animal. We show that the latest generation of lentiviral vectors efficiently transduces the murine liver. Further analysis demonstrated that neither cell-cycle activation nor division of liver cells is a prerequisite for lentiviral gene transfer in vivo.

Animals↗
PubMed2001

Platelet-derived growth factor enhances granulopoiesis via bone marrow stromal cells.

Platelet-derived growth factor (PDGF), a growth factor for connective tissue cells, stimulates erythropoiesis and megakaryocytopoiesis in vitro but the effect of PDGF on granulocyte proliferation remains unknown. The effect of the recombinant human PDGF-BB isoform on granulopoiesis was investigated in this study. The results show that PDGF significantly stimulated murine colony-forming unit-granulocyte-monocyte (CFU-GM) proliferation in a dose-dependent manner (1 to 100 ng/mL) using murine bone marrow cells (n = 4). Maximum stimulation was obtained with 50 ng/mL of PDGF (P < .01). The effect of PDGF on murine CFU-GM proliferation was compared with that of interleukin (IL)-3, IL-6, granulocyte-monocyte colony-stimulating factor (GM-CSF), and acidic fibroblast growth factor (aFGF) at their optimal doses. The stimulating activity of PDGF was higher than that of aFGF but lower than that of IL-3, IL-6, or GM-CSF. There is no synergistic effect between PDGF and IL-3 or IL-6, but a significant enhancing effect was observed in IL-3 plus IL-6. PDGF also stimulated the growth of CFU-GM with CFU-megakaryocyte in the presence of bone marrow stromal cells. We also found that PDGF had similar a effect on human CFU-GM proliferation using bone marrow mononuclear cells (MNC). However, the increase in PDGF-stimulated CFU-GM proliferation was inhibited by anti-GM-CSF, anti-IL-3, and anti-IL-6 antibodies (n = 4), suggesting that endogenously produced GM-CSF, IL-3, and IL-6 may play a role in the PDGF-induced CFU-GM proliferation. Furthermore, PDGF (1 to 100 ng/mL) did not show any effect on CFU-GM proliferation when replacing bone marrow MNC with immunomagnetic selection-enriched CD34+ cells from human cord blood (n = 5; purity, 91% +/- 6.5%). This study indicates that PDGF may indirectly enhance CFU-GM proliferation by inducing the bone marrow stromal cells to produce GM-CSF, IL-3, or IL-6.

Adult↗