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Biomedical subjects

J L Yu

Publications and source records attributed to J L Yu.

At least 19 recordsLinked to original sources

Anxiolytic-like activity of the mGLU2/3 receptor agonist LY354740 in the elevated plus maze test is disrupted in metabotropic glutamate receptor 2 and 3 knock-out mice.

RATIONALE: (1S,2S,5R,6S)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) is a potent and selective agonist for group II metabotropic glutamate (mGlu2 and mGlu3) receptors, with anxiolytic-like activity in animal and human models, and efficacy in anxiety patients. However, the lack of mGlu2 or mGlu3 receptor specific agonists has prevented in vivo characterization of individual functions of these two receptors in mediating the anxiolytic-like effects of LY354740. OBJECTIVE: To utilize mGlu2 receptor and mGlu3 receptor knockout animals and the mGlu2/3 selective antagonist (2S,1'S,2'S)-2-(9-xanthylmethyl)-2-(2'-carboxycyclopropyl)glycine (LY341495) to further investigate the roles of mGlu2 and mGlu3 receptors in mediating the anxiolytic-like actions of LY354740 in a mouse model of anxiety [elevated plus maze (EPM) test]. METHODS: To confirm that mGlu2/3 receptors are responsible for anxiolytic-like activity in the EPM under these test conditions, mice were pretreated with LY341495 at 30 min prior to s.c. administered LY354740. Subsequently, saline vehicle or LY354740 was administered (s.c.) 30 min before the EPM testing in wild-type, mGlu2 receptor knockout, and mGlu3 receptor knockout mice. RESULTS: LY354740 reduced in a dose-dependent manner anxiety-related behavior on the EPM in wild-type mice with a maximally effective dose of 10--20 mg/kg s.c. Pretreatment with LY341495 potently prevented the anxiolytic-like effects of LY354740 (20 mg/kg, s.c.) in mice. Although the mGlu2 receptor knockout and mGlu3 receptor knockout mice were grossly normal, the anxiolytic-like activity of LY354740 (20 mg/kg, s.c.) was not evident in either mGlu2 or mGlu3 receptor knockout mice, when compared to their wild-type controls. CONCLUSIONS: The activation of both mGlu2 and mGlu3 receptors by LY354740 appears to be required for anxiolytic-like activity in the EPM test in mice. These studies serve as a foundation for additional studies on underlying circuits, brain structures, and receptor subtypes involved in the anxiolytic-like actions of mGlu receptor active agents, and the design of future drugs for anxiety disorders in humans.

Amino Acids↗

Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor.

Pre-synaptic metabotropic glutamate (mGlu) receptors modulate neuronal excitability by controlling glutamate and gamma-aminobutyric acid (GABA) release. The mGlu8 receptor is predominantly found in pre-synaptic terminals and its expression is highly restricted. To study the role of this receptor, mGlu8 receptor-deficient mice were generated. Here we report that naïve mGlu8 receptor-deficient mice showed increased anxiety-related behavior in the elevated plus maze in low illumination conditions (red light). Open arm avoidance and risk assessment behavior were both significantly increased in mutant mice. Increased stressfulness of the testing conditions abolished this behavioral difference. Fluorescent light or prior restraint stress decreased the open arm activity of wild-type mice, while the open arm activity of mutant mice was essentially unaffected, leading to similar values in both strains. The total number of arm entries or closed arm entries was not significantly different between strains, indicating that the lack of mGlu8 receptor does not affect locomotor activity. No gross behavioral changes, or changes in the function of the autonomic nervous system or somatomotor systems were observed in mutant mice. Moreover, no significant differences in seizure susceptibility were detected between strains. Our results suggest that mGlu8 receptor may play a role in responses to novel stressful environment.

Animals↗

Heterogeneous vascular dependence of tumor cell populations.

Cells within a tumor are highly heterogeneous with respect to a wide range of genotypic and phenotypic characteristics. The latter include such properties as growth, survival, invasion, and metastasis. We asked whether the degree to which individual tumor cells rely on a tumor's vasculature might also be heterogeneous. By adapting an intravital Hoechst 33342 staining technique, we labeled and isolated tumor cells based on their relative proximity to perfused vessels. Because tumor regions distal to the vasculature are likely hypoxic, we examined cells deficient for hypoxia-inducible factor-1alpha (HIF-1alpha), a transcription factor that has been shown to mediate hypoxia-induced responses, including apoptosis. Despite reduced vascularization in HIF-1alpha-/- embryonic stem cell-derived tumors, their growth in vivo was found to be accelerated relative to HIF-1alpha+/+ tumor counterparts. We hypothesized that this paradoxical observation is because of decreased apoptotic rate, resulting in diminished vascular dependence of HIF-1alpha-/- cells. Analysis of heterogeneous tumors established from mixtures of HIF-1alpha+/+ with HIF-1alpha-/- cells revealed that the proportion of cells expressing wild-type HIF-1alpha was increased in perivascular areas and decreased in distal tumor regions. Thus, cells expressing HIF-1alpha were found to be highly dependent on proximity to blood vessels for their growth and survival in vivo, whereas cells that had lost HIF-1alpha expression were much less so. Heterogeneity in angiogenesis dependence was also observed among cell subpopulations isolated from human melanoma xenografts. This potential for selection of less vascular-dependent tumor cell variants throughout the course of disease progression may have important implications for the long-term efficacy of anti-angiogenic therapy.

Animals↗

Acupuncture effects on reflex responses to mental stress in humans.

In animal studies, acupuncture has been shown to be sympathoinhibitory, but it is unknown if acupuncture is sympathoinhibitory in humans. Nineteen healthy volunteers underwent mental stress testing pre- and postacupuncture. Muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate during mental stress were compared pre- and postacupuncture. Control acupuncture consisted of acupuncture at nonacupoints and "no-needle" acupuncture. Acupuncture had no effect on resting MSNA, blood pressure, or heart rate. After real acupuncture, the increase in mean arterial pressure (pre- vs. postacupuncture 4.5 vs. 1.7 mmHg, P < 0.001), but not MSNA or heart rate, was blunted during mental stress. Similarly, following nonacupoint acupuncture, the increase in mean arterial pressure was blunted during mental stress (5.4 vs. 2.9 mmHg, P < 0.0003). No-needle acupuncture had no effect on these variables. In conclusion, acupuncture at traditional acupoints, nonacupoints, and no-needle acupuncture does not modulate baseline MSNA or MSNA responses to mental stress in normal humans. Acupuncture significantly attenuates the increase in blood pressure during mental stress. Needling nonacupoints, but not "no-needle" acupuncture, have a similar effect on blood pressure.

Acupuncture Therapy↗

Synthesis, characterization, and magnetic properties of carbon- and boron-oxide-encapsulated iron nanocapsules.

Carbon- and boron-oxide-encapsulated iron nanocapsules have been synthesized by arc discharge in methane (CH4) and diborane (B2H6) atmospheres respectively. The characterization and magnetic properties of carbon- and boron-oxide-encapsulated iron nanocapsules [abbreviated as Fe(C) and Fe(B) respectively] were investigated and compared. The structure of the Fe(B) nanocapsules is different from that of the Fe(C) nanocapsules. The Fe(C) nanocapsules consist of a crystalline graphite shell and a core of alpha-Fe and/or Fe3C. The Fe(B) nanocapsules consist of an amorphous boron-oxide layer and a core of Fe(B) solid solution, alpha-Fe, gamma-Fe, FeB, and/or Fe3B phases. The saturation magnetizations of both the Fe(C) and the Fe(B) nanocapsules below 300 K decrease monotonically with increasing temperature. The coercivities of the Fe(C) and Fe(B) nanocapsules are almost 2 orders of magnitude higher than that of bulk Fe. The temperature dependence of magnetization at high temperatures indicates the existence of some phase transformations.

Borohydrides↗

Study on antimicrobial susceptibility of bacteria causing neonatal infections: a 12 year study (1987-1998).

OBJECTIVE: The method of Manual of Clinical Microbiology was used to identify bacteria. We investigated the epidemiological characteristics of bacterial agents and their antimicrobial susceptibility as empirical treatment for neonatal infections. Disk diffusion tests were also done for antimicrobial susceptibility. RESULTS: From January 1987 to December 1998, 2,244 bacterial strains were isolated in our neonatal ward. The first three predominant species were Staphylococcus epidermidis (23.9%), Staphylococcus saprophyticus (19.9%) and Escherichia coli (12.6%) in group I (infections acquired outside of hospital). Escherichia coli, Klebsiella and Pseudomonas aeruginosa accounted for 18%, 15.2% and 12.6% respectively in group II (nosocomial infections). The sensitivity rates of those antimicrobials that are seldom used for newborns were found to be higher, while the resistant rates of the commonly used antimicrobial drugs have increased significantly. The resistant rates of bacterial isolate from group II to antimicrobial agents including penicillin and ampicillin were significantly higher than those isolated from group I (p<0.05)The sensitivity rate was 82.2% (717/833) by using amikacin only, when combined with penicillin, rose to 89%(741/833). CONCLUSIONS: Gram-negative bacteria were mainly responsible for nosocomial infections of neonates in our hospital. Infections acquired outside the hospital were mainly caused by Gram-positive bacteria. Nosocomial pathogens produced drug resistance easily. Combination of amikacin and penicillin can be recommended as the initial antibiotics for treatment of neonatal infections.

Anti-Bacterial Agents↗

High-frequency color flow imaging of the microcirculation.

The extension of ultrasound (US) color flow imaging (CFI) techniques to high frequencies (> 20 MHz) has the potential to provide valuable noninvasive tools for scientific and clinical investigations of blood flow in the microcirculation. We describe the development of a slow-scan CFI system operating in the 20-100-MHz range that has been optimized to image the microcirculation. The apparatus has incorporated elements of a previously reported pulsed-wave Doppler system and is capable of operating in either CFI or pulsed-wave mode. The performance of the CFI system was evaluated at a center frequency of 50 MHz using two PVDF transducers with -6-dB beam widths of 43 and 60 microm. The -6 dB-axial resolutions were estimated to be 66 and 72 microm, respectively. In vivo validation experiments conducted using the murine ear model demonstrated the detection of flow in vessels down to 15-20 microm in diameter with flow velocities on the order of mm per s. Further experiments examining experimental murine tumors confirmed the successful detection of flow in the tumor microcirculation.

Animals↗

Oncogenes and angiogenesis: signaling three-dimensional tumor growth.

Three-dimensional tumor growth is dependent on the perpetual recruitment of host blood vessels to the tumor site. This recruitment process (mainly via angiogenesis) is thought to be triggered, at least in part, by the very same set of genetic alterations (activated oncogenes, inactivated/lost tumor suppressor genes) as those responsible for other aspects of malignant transformation (e.g., aberrant mitogenesis, resistance to apoptosis). Potent oncogenes are able to deregulate expression of both angiogenesis stimulators and inhibitors in cancer cells. For example, mutant ras expression is associated with increased production of vascular endothelial growth factor (VEGF) and downregulation of thrombospondin-1 (TSP-1). Upregulation of VEGF and angiogenesis can also be induced by constitutive activation of other oncogenic proteins (e.g., EGFR, Raf, MEK, PI3K) acting at various levels on the Ras signaling pathway. The mode and the magnitude of such proangiogenic influences can be significantly modified by cell type (fibroblastic or epithelial origin), epigenetic factors (hypoxia, changes in cell density), and/or presence of additional genetic lesions (e.g., preceding loss of p16 or p53 tumor suppressor genes). Activated oncogenes (e.g., ras, src, HER-2) induce co-expression of angiogenic properties concomitantly with several highly selectable traits (increased mitogenesis, resistance to apoptosis), a circumstance that may accelerate selection of the angiogenic phenotype at the cell population level. On the other hand oncogene-induced reduction in growth requirements may also endow tumor cells with a diminished (albeit not abrogated) dependence on (close) proximity to blood vessels, i.e., with reduced vascular dependence. Thus, oncogenes can impact several interconnected aspects of cellular growth, survival, and angiogenesis. Experimental evidence suggests that, in principle, many of these properties (including angiogenesis) can be simultaneously suppressed (and tumor stasis or regression induced) by effective use of the specific oncogene antagonists and signal transduction inhibitors.

Animals↗

[Genescan for STR analysis and genetic distribution in a population sample from Han, China].

Genetic distributions for nine STR loci and Amelogenin locus were determined in a Chinese Han population based on DNA sequencing. The databanks in Chinese Population were generated by using Genescan, genotype and genetic distribution analysis. Allele frequency distribution was determined for 10 loci, such as D3S1358, VWA, FGA, Amelogenin, THO1, TPOX, CSF1PO, D5S818, D13S317 and D7S820. The results show significant differences between ethnic groups (African-American, US-Caucasian and Chinese Han) in the pattern of distribution as well as in the related frequency of the most common alleles of their STR loci. The probabilities of identity values for the population described in this section are 2.79 x 10(-10) (U.S-Caucasian), 1.23 x 10(-10) (African-American) and 0.5 x 10(-10) (Chinese Han). The results show the probability of Paternity Exclusion (PPE) values of 0.9998 (Chinese Han), 0.9996 (African-American) and 0.9994 (U.S-Caucasian). These results suggested that the nine STR loci and the Amelogenin locus are very useful for human identification, such as analyzing forensis casework, establishing DNA databanks, processing paternity test, evaluation linkage genetics, studying gene natural resources and monitoring bone marrow transplants.

Asian People↗

[Expression of single-chain Fv antibody for anti-beet necrotic yellow vein virus in Escherichia coli].

The heavy chains variable region gene (VH) of monoclonal antibody against beet necrotic yellow vein virus (BNYVV) was amplified from total DNA extracted from anti-BNYVV hybridoma cells by PCR. Sequencing showed that the VH belongs to mouse subgroup II(A) and contains 360 bp, which code one hundred and twenty amino acids. The VH and VL genes were inserted into a plasmid which contains a linker sequence for constructing scFv gene. The new vector named pTC scFv. The scFv was produced in Escherichia coli and appeared binding activity with BNYVV antigen by ELISA method.

Amino Acid Sequence↗

Binding of immobilized fibronectin by biliary drain isolates.

Occlusion of biliary stents, as the result of bacterial adhesion and colonization onto biliary stents, still remains a major problem. Biliary proteins, such as fibronectin (Fn) and vitronectin (Vn), have been presumed to be involved in the process of bacterial adhesion to biliary biomaterial. In the present study, Fn binding by 5 strains of E. coli isolated from biliary drains or from bile was studied. All strains did not bind detectable amounts of soluble Fn but bound to immobilized plasma Fn. Adhesion of four strains of E. coli to ovalbumin was reduced by periodate treatment of ovalbumin, but adhesion to Fn was unaffected. Adhesion was inhibited by mannose-containing saccharides, trypsin treatment of the protein, and protease treatment of the bacterial cells. Autoradiography showed that components of cell extracts from three E. coli strains bind 125I-Fn but not a 150 kD Fn fragment. The findings indicate that the adhesion of these bacteria to Fn is a protein-protein interaction, inhibited by D-mannose, and possibly mediated by fimbrial components.

Animals↗

Fibronectin exposes different domains after adsorption to a heparinized and an unheparinized poly(vinyl chloride) surface.

The adsorption of fibronectin to poly(vinyl chloride) catheters with end-point attached (EPA) heparin and tridodecylmethylammonium chloride-heparinized poly(vinyl chloride) was compared to that of unheparinized poly(vinyl chloride) using antibodies directed against four different domains of the protein. After perfusion of human plasma on the EPA-heparinized surface, the exposure of the N-terminal 29-kD fragment increased during the first 5 h of perfusion. Also, the exposure of the 30-kD gelatin-binding and 65-kD cell-binding fragments increased with time, but at a lower level. On the unheparinized catheter, low levels of antibodies bound to the different domains, and the binding showed little variation during the 5 h of plasma perfusion, indicating that the fibronectin molecule does not change configuration to a significant extent on this surface after the initial adsorption. When the EPA-heparinized surface was preabsorbed with human fibrinogen before incubation with fibronectin, significantly less of the 29-kD (fibrin-binding) domain was exposed, and the 30-kD domain was not exposed. Exposure of the 31- and 65-kD domains increased after preadsorption of fibrinogen to the surface. Since fibronectin has heparin-binding domains, it adsorbs differently to a heparinized versus an unheparinized surface. This will influence subsequent binding of other proteins to the surface, as well as potential binding of microbes. The use of antibodies to defined domains of the fibronectin molecule provides a powerful tool in studies of configurational changes of fibronectin after adsorption to different surfaces.

Adsorption↗

Fibronectin binding by Propionibacterium acnes.

Strains of Propionibacterium acnes, isolated from different kinds of orthopaedic and biomaterial-associated infections and from skin flora were shown to express binding of soluble as well as immobilized fibronectin. Among these 7 strains isolated from orthopaedic infections, 2 from breast prostheses, and 9 skin isolates, 2, 2, and 5 strains respectively bound immobilized fibronectin. The fibronectin binding was sensitive to protease and heat treatment, and was inhibited by a cell surface extract from one of the binding strains. In SDS-PAGE and autoradiography of cell surface extracts, a band corresponding to a MW of about 80 kD reacted with fibronectin and the 150 kD fragment of fibronectin. Binding to fibronectin and the 150 kD fragment of fibronectin could be inhibited with heparin. We thus present a first Fn binding protein of P. acnes, a surface exposed protein of 80 kD. None of the strains bound soluble collagen, and only one strain expressed weak binding of vitronectin and bone sialoprotein II.

Adhesins, Bacterial↗

Protein adsorption and bacterial adhesion to biliary stent materials.

Four biliary stents inserted for relief of jaundice in patients with biliary obstruction due to carcinoma of pancreatic head were examined for the adsorption of biliary proteins and bacterial colonization. Fibronectin and vitronectin (S-protein) were found to be the two main proteins adsorbed on the inner surface of the stents. Biliary isolates included Escherichia coli, Enterococcus faecalis, and Candida albicans. In vitro studies were performed to clarify the kinetics of biliary protein and bacterial adhesion. Biliary drains of polytetrafluorethylene, polyethylene, polyurethane, and rubber were placed in a flow cell and perfused with human bile at 37% C for 24 hr. The materials were subjected to either detection of adsorbed biliary proteins or perfusion with 3 H-labeled E. coli cells (1 X 10 6 cfu/ml). The results show that the adsorbed biliary proteins were detectable on the surface of biliary stents and able to enhance bacterial adhesion to the surface in the first 24 hrs after the exposure of stent materials to bile, and that both the adsorption of biliary proteins and the adhesion of bacterial cells were material- and strain-dependent. Furthermore, there was a clear correlation between the amount of adsorbed fibronectin and the number of adherent bacteria. The results indicate that, in the clinical situation, biliary proteins may be adsorbed on the surface of inserted stents within a short time after insertion, and some of them may be used by bacterial cells as receptors for adhesion to the surface, and thus involved in the process of bacterial adhesion.

Adsorption↗

A bacteriologic and scanning electron microscope study after implantation of foreign bodies in the biliary tract in rats.

BACKGROUND: Bacterial adherence to the stent surfaces, concomitant colonization, and possible stent blockage are the main complications after the use of biliary stents. The present study was assigned to investigate bacteriologic and morphologic changes in the biliary tract after the implantation of biliary drain materials. METHODS: Rubber and silicone pieces with a surface area of 1 cm2 were implanted into the biliary tract in rats after temporary obstruction of the common bile duct by the use of a mini-occluder. The animals were killed at 4, 8 and 14 weeks, respectively, after implantation, and the implants were retrieved, cultured, and examined by scanning electron microscopy (SEM). Bacterial culture and SEM were also performed on tissue samples obtained from the mucosal surface of the biliary tract. RESULTS: Bacterial colonization and biofilm formation were found on the surfaces of the implanted materials and on the mucosal surface of the biliary tract in animals with implants but not on the biliary tract mucosa in rats without implants. CONCLUSION: Foreign bodies implanted in the biliary tract facilitate bacterial adherence not only to the surface of the implants but also to the mucosal surface in the biliary tract.

Animals↗

Fibronectin on the surface of biliary drain materials--a role in bacterial adherence.

The present study deals with the demonstration of deposited fibronectin (Fn) on the surfaces of implanted biliary drain materials and the role of deposited Fn in promotion of bacterial adherence. Rubber pieces that had been implanted in the biliary tracts of rats for 4 weeks were retrieved and the following approaches employed for further investigations: (1) adherence of [methyl-3H]thymidine-labeled Escherichia coli to implanted and unimplanted rubber pieces; (2) blocking the adherence of radiolabeled bacteria with anti-Fn antibodies; (3) detection of deposited Fn by 125I-labeled anti-Fn IgG; and (4) immunoblotting of the surface eluate from implanted rubber pieces. The results show that in the presence of serum, plasma, or bile, the number of E. coli cells adherent to implanted rubber pieces was 10 times higher than that adherent to the unimplanted pieces (P < 0.001) and that the adherence was reduced by pretreatment of implanted pieces with anti-Fn antibodies. Furthermore, the implanted pieces appeared to have a high affinity for 125I-labeled rabbit anti-Fn IgG rather than the 125I-IgG without anti-Fn fraction. Fn was also found in the surface eluate of implanted pieces by immunoblotting of the eluate. The results in the present study suggest that Fn may be involved in implant-associated infections in the biliary tract.

Animals↗