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Biomedical subjects

M Yang

Publications and source records attributed to M Yang.

At least 91 records · Page 5Linked to original sources
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↗
PubMed2001

Endocytosis in different lifestyles of protozoan parasitism: role in nutrient uptake with special reference to Toxoplasma gondii.

A fundamental property of any eukaryotic cell is endocytosis, that is the ability to take up external fluid, solutes and particulate matter into membrane-bound intracellular vesicles by various mechanisms. Toxoplasma gondii is an intracellular protozoan parasite of the phylum Apicomplexa with a wide geographical and host range distribution. Significant progress in studying the cell biology of this parasite has been accomplished over the last few years. Only recently endocytic compartments and endocytic trafficking have come to a closer dissection in T. gondii. In this review, we discuss the evidence for an endocytic compartment and present a model for an endocytic pathway in Toxoplasma against a background of endocytosis in kinetoplastida and the extensive insights gained from mammalian and yeast cells.

Animals↗
PubMed2001

Kinetics of phthalate reactions with ammonium hydroxide in aqueous matrix.

Common phthalate pollutants, such as dimethyl phthalate and diethyl phthalate found in aqueous environmental matrices react with ammonium hydroxide at ordinary temperatures exhibiting an overall reaction order in the range 1.3-1.4. While the reaction is of first order with respect to the phthalate, the order of reaction is fractional in ammonium hydroxide. The rate constants for the reactions of these two phthalates in alkaline waters at ambient temperatures are in the range 1.3 x 10(-4) and 8.5 x 10(-5) Lx/mol s. Under these conditions the estimated half-lives for dimethyl phthalate and diethyl phthalate at a concentration of each at 20 mg/L is 4.5 and 14 h, respectively. Other phthalates are expected to exhibit similar kinetics in their base hydrolysis with NH4OH. Thus, the presence of both the phthalate esters and ammonia or ammonium salts in the water under alkaline conditions may result in their self-removal by hydrolysis.

Ammonium Hydroxide↗
PubMed2001

Cue and context conditioning of defensive behaviors to cat odor stimuli.

Exposure of rats to a cat odor block in a previously familiarized situation was followed by three extinction days to the same or a different situation, and with or without an identical but odor-free block, and, testing in the original apparatus with an odor-free block (cue). Initial exposure produced risk assessment (stretch attend), avoidance of the block, and crouch/freeze with sniffing/head movements. Avoidance continued during extinction, but context-only exposed rats showed predominantly crouch/freeze with sniff/head movements, while rats exposed to the context+cue showed higher levels of stretch attend. During the test day, rats exposed to the cue during extinction showed reduced defensive responding compared to those not extinguished with the cue, but context extinction had less effect, possibly due in part to initial familiarization with the situation. These data indicate that both cue and context conditioning to cat odor did occur, and that the type of conditioned stimulus (context-only vs. context+cue) influenced the type of defensive behaviors elicited by this stimulus, although the all animals received the same conditioning protocol. Particular behaviors disappeared at different rates during extinction, with avoidance the most persistent. However, in this context there was no incentive for approach behaviors inconsistent with avoidance, and stretch attend behaviors could and did occur while subjects were located far from the block or the area in which it had been encountered. In addition, immobile crouch/freeze did not occur at higher than control levels, while the crouch/freeze activities that did increase incorporated sensory sampling in a relevant modality (sniffing/head movements). Thus, the behaviors seen to the conditioned stimulus appeared to reflect combinations of different defense strategies, appropriate to the type of conditioned stimulus and responsive to its extinction. Differences between these data and those from studies using fecal predator odorants suggest that the latter may not elicit a complete range of conditioned defenses.

Aggression↗
PubMed2001

Dynamics of aluminum speciation in forest-well drainage waters from the Rhode River watershed, Maryland.

This paper reports an investigation of the dynamics of aluminum (Al) speciation in the forest-well waters from study site 110 of the Rhode River watershed, a representative sub-unit of Chesapeake Bay. Seasonal changes of Al speciation are evaluated by a modified MINEQL computer model using chemical equilibrium calculation. It was found that Al-F and Al-Org complexes were the dominate forms, whereas toxic forms of Al3+ and Al-OH were not significant. This indicates that Al toxicity is not very serious in the Rhode River area due to the high concentrations of fluoride and organic materials, even though sometimes pH is very low (approximately 4). Increased H+ or some other associated factors may be responsible for the decline in fish and amphibian population on the watershed.

Acid Rain↗
PubMed2001

Effects of the CATCH physical education intervention: teacher type and lesson location.

BACKGROUND: Substantial differences exist in how and where physical education (PE) is conducted in elementary schools throughout the United States. Few effectiveness studies of large-scale interventions to improve PE have been reported. DESIGN: Multicenter randomized trial. SETTING/ PARTICIPANTS: The Child and Adolescent Trial for Cardiovascular Health (CATCH) was implemented in PE classes in 96 schools (56 intervention, 40 control) in four study centers: California, Louisiana, Minnesota, and Texas. INTERVENTION: The 2.5-year PE intervention consisted of professional development sessions, curricula, and follow-up consultations. MAIN OUTCOME MEASURES: Intervention effects on student physical activity and lesson context in PE were examined by teacher type (PE specialists and classroom teachers) and lesson location (indoors and outdoors). RESULTS: Differential effects by teacher type and lesson location were evidenced for both physical activity and lesson context. Observations of 2016 lessons showed that intervention schools provided more moderate-to-vigorous physical activity (p=0.002) and vigorous physical activity (p=0.02) than controls. Classroom teachers improved physical activity relatively more than PE specialists, but PE specialists still provided longer lessons and more physical activity. Classroom teachers increased lesson length (p=0.02) and time for physical fitness (p=0.03). CONCLUSIONS: The intervention improved PE of both specialists' and classroom teachers' lessons. States and districts should ensure that the most qualified staff teaches PE. Interventions need to be tailored to meet local needs and conditions, including teacher type and location of lessons.

Analysis of Variance↗
PubMed2001

Voltammetric biosensors for the determination of formate and glucose-6-phosphate based on the measurement of dehydrogenase-generated NADH and NADPH.

This paper describes the development of a modified electrode for the electrocatalytic oxidation of beta-nicotinamide adenine dinucleotide (beta-NADH) and beta-nicotinamide adenine dinucleotide phosphate (beta-NADPH) using electropolymerised 3,4-dihydroxybenzaldehyde (3,4-DHB). Two voltammetric biosensors using enzyme-immobilised membranes were constructed for the determination of formic acid and glucose-6-phosphate (G6P), respectively. The formic acid biosensor based on the combination of formate dehydrogenase (FDH)-modified membrane with 3,4-DHB-coated glassy carbon electrode is one to two orders more sensitive (LOD, 5.0x10(-5) M) than previously reported electrochemical biosensors. Similarly, lower detection limit (4.0x10(-5) M) for the measurement of G6P was achieved using glucose-6-phosphate dehydrogenase (G6PDH) in the presence of beta-NADP(+). The interference of uric acid and ascorbate was minimised by incorporating an additional membrane modified with uricase and ascorbate oxidase, respectively. The biosensing scheme developed in this study can be adopted universally with a number of dehydrogenases for the detection of different substrates.

Benzaldehydes↗
PubMed2001

Bone-targeted Src SH2 inhibitors block Src cellular activity and osteoclast-mediated resorption.

Src, a nonreceptor tyrosine kinase, is an important regulator of osteoclast-mediated resorption. We have investigated whether compounds that bind to the Src SH2 domain inhibit Src activity in cells and decrease osteoclast-mediated resorption. Compounds were examined for binding to the Src SH2 domain in vitro using a fluorescence polarization binding assay. Experiments were carried out with compounds demonstrating in vitro binding activity (nmol/L range) to determine if they inhibit Src SH2 binding and Src function in cells, demonstrate blockade of Src signaling, and lack cellular toxicity. Cell-based assays included: (1) a mammalian two-hybrid assay; (2) morphological reversion and growth inhibition of cSrcY527F-transformed cells; and (3) inhibition of cortactin phosphorylation in csk-/- cells. The Src SH2 binding compounds inhibit Src activity in all three of these mechanism-based assays. The compounds described were synthesized to contain nonhydrolyzable phosphotyrosine mimics that bind to bone. These compounds were further tested and found to inhibit rabbit osteoclast-mediated resorption of dentine. These results indicate that compounds that bind to the Src SH2 domain can inhibit Src activity in cells and inhibit osteoclast-mediated resorption.

Actins↗
PubMed2001

Utilization of quinolone drugs as monomers: characterization of the synthesis reaction products for poly(norfloxacin diisocyanatododecane polycaprolactone).

A broad spectrum antimicrobial agent, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid (norfloxacin), has been successfully incorporated as a monomer into a polyurethane backbone structure via a three-step polymerization of norfloxacin, diisocyanatododecane (DDI), and polycaprolactone diol (PCL). The reaction was catalyzed by dibutyltin dilaurate and carried out in dimethyl sulfoxide. The sequential order of monomer feeding had a strong influence on the polymerization behavior and final polymer structure. In the preferred reaction scheme norfloxacin is initially reacted with DDI to form an oligomer. This is followed by a second reaction where PCL is introduced in order to produce a drug polymer chain with higher molecular weight and degradable segments. Cross-linking of urea linkages between the norfloxacin and DDI segments was a particular concern and was minimized by feeding PCL into the reaction system immediately following the completion of the first step. Chain extension by 1,4-butanediol or ethylenediamine was shown to be an effective approach for increasing the molecular weight of the polymers.

Anti-Infective Agents↗