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Biomedical subjects

K Yu

Publications and source records attributed to K Yu.

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

mTOR, a novel target in breast cancer: the effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer.

The mammalian target of rapamycin (mTOR) is a central regulator of G1 cell cycle protein synthesis that precedes commitment to normal cellular replication. We have studied the effect of cell cycle inhibitor-779 (CCI-779), a rapamycin ester that inhibits mTOR function, on the proliferation of a panel of breast cancer cell lines. Six of eight lines studied were sensitive (IC(50)< or = 50 nM) and two lines were resistant (IC(50)>1.0 microM) to CCI-779. Sensitive lines were estrogen dependent (MCF-7, BT-474, T-47D), or lacked expression of the tumor suppressor PTEN (MDA-MB-468, BT-549), and/or overexpressed the Her-2/neu oncogene (SKBR-3, BT-474). Resistant lines (MDA-MB-435, MDA-MB-231) shared none of these properties. CCI-779 (50 nM) inhibited mTOR function in both a sensitive and a resistant line. In nu/nu mouse xenografts, CCI-779 inhibited growth of MDA-MB-468 (sensitive) but not MDA-MB-435 resistant tumors. Treatment of sensitive lines with CCI-779 resulted in a decrease in D-type cyclin and c-myc levels and an increase in p27(kip-1) levels. There was good correlation between activation of the Akt pathway and sensitivity to CCI-779. Amplification of mTOR-regulated p70S6 kinase, which is downstream of Akt, may also have conferred CCI-779 sensitivity to MCF-7 cells. Taken together, the data suggest that mTOR may be a good target for breast cancer therapy, especially in tumors with Akt activation resulting from either growth factor dependency or loss of PTEN function.

Animals↗
PubMed2001

Survival of Escherichia coli O157:H7 on strawberry fruit and reduction of the pathogen population by chemical agents.

Survival of Escherichia coli O157:H7 was studied on strawberry, a fruit that is not usually washed during production, harvest, or postharvest handling. Two strains of the bacteria were tested separately on the fruit surface or injected into the fruit. Both strains of E. coli O157:H7 survived externally and internally at 23 degrees C for 24 h and at 10, 5, and -20 degrees C for 3 days. The largest reduction in bacterial population occurred at -20 degrees C and on the fruit surface during refrigeration. In all experiments, the bacteria inside the fruit either survived as well as or better than bacteria on the surface, and ATCC 43895 frequently exhibited greater survival than did ATCC 35150. Two strains of E. coli also survived at 23 degrees C on the surface and particularly inside strawberry fruit. Chemical agents in aqueous solution comprising NaOCl (100 and 200 ppm), Tween 80 (100 and 200 ppm), acetic acid (2 and 5%), Na3PO4 (2 and 5%), and H2O2 (1 and 3%) were studied for their effects on reduction of surface-inoculated (10(8) CFU/ml) E. coli O157:H7 populations on strawberry fruit. Dipping the inoculated fruit in water alone reduced the pathogen population about 0.8 log unit. None of the compounds with the exception of H2O2 exhibited more than a 2-log CFU/g reduction of the bacteria on the fruit surface. Three percent H202, the most effective chemical treatment, reduced the bacterial population on strawberries by about 2.2 log CFU/g.

Colony Count, Microbial↗
PubMed2001

[A study on city motor vehicle emission factors by tunnel test].

Applying the principle of tunnel test to run a typical across-river tunnel test in Guangzhou city, 48 h-online-monitor data include pollutant concentration, traffic activity and meteorological data were gained. The average motor vehicle emission factors of NOx, CO, SO2, PM10 and HC were calculated using mass balance which are 1.379, 15.404, 0.142, 0.637, 1.857 g/km. vehicle respectively. Based on that, combined emission factors of 8 types of city vehicles were calculated using linear regression. The result basically showed the character and level of motor vehicle emission in Chinese city.

Vehicle Emissions↗
PubMed2001

[Intraspinal implantation of genetically modified myoblasts with brain-derived neurotrophic factor gene in treating spinal cord injury in rats: neurophysiological study].

OBJECTIVE: To observe the value of gene therapy to spinal cord injury in vivo by transferring gene of brain-derived neurotrophic factor (BDNF) to rat myoblast with retroviral vector electrophysiologically. METHODS: Transection of spinal cord at the level of T9 was produced in 30 adult SD rats that were divided randomly into three groups: BDNF gene modified myoblast implantation (group A), myoblast implantation (group B), and no cell implantation as controls (group C). Three months after operation, whether the axon had regenerated and how the neural function was restored were observed, using the techniques of cerebral somatosensory evoked potential (CSEP) and motor evoked potential (MEP). RESULTS: Three months after injury, 3 rats in group A showed CSEP signals and 5 rats MEP signals, but no electrophysiological response was found in group B or group C. The amplitudes of the recovery of CSEP or MEP signals decreased and their latencies increased as compared with those before injury. The neural function of the spinal cord was greater in group A than in B and C. CONCLUSION: Treatment with genetically modified myoblasts producing BDNF can accelerate recovery from traumatic spinal cord injury in adult rats.

Animals↗
PubMed2001

Recording of spared motor evoked potentials and its augmentation by 4-aminopyridine in chronic spinal cord-injured rats.

OBJECTIVE: To research the direct electrophysiological evidence of discomplete spinal cord injury (SCI) and the effect of 4-aminopyridine on it. METHODS: Motor evoked potentials (MEPs), both spinal cord recorded MEPs (scMEPs) and extracellularly recorded MEPs (exMEPs) were recorded and characterized on a T13 epidural electrode (scMEPs) and an extracellular microelectrode (exMEPs) for 10 normal rats and 40 rats with lesions of various severity (sham, 35 g.cm force (gcf), 70 gcf, 100 gcf impact injury) at the T8-T9 cord using the Allen's drop model. The incline plane and Tarlov techniques were used to assess clinical neurological function. RESULTS: MEPs in the normal rats were elicited by applying transcortical suprathreshold stimulation consisting of 3-4 early negative peaks (N1, N2, N3 and N4) followed by several late waves. The N1 and N2 peaks were largest in the anterior and ventrolateral funiculus, respectively, which was indicative of extrapyramidal pathways. The 100 gcf impact injuries and the cord transection abolished the MEP distal to the lesion, whereas the 35 gcf injuries resulted in a latency shift and amplitude decrement of the MEP peaks. Eighteen of the 20 rats with 70 gcf-injuries showed clinical paraplegia. Among them, 7 rats had neurophysiological evidence of residual conduction pathways through the lesioned cord segment, such as the presence of N1 and N2 peaks in the scMEPs or exMEPs. After 4-aminopyridine (4-AP) administrations (1 mg/kg), the amplitude of the spared exMEP increased significantly and spread more widely. CONCLUSIONS: MEPs evoked by transcortical stimulation travel mostly in the extrapyramidal tract. MEP monitoring could provide an excellent method of detecting the functional integrity of the motor tracts after SCI, and could even detect spared motor fibers after discomplete SCI. Furthermore, the use of 4-AP or other K+ channel blocking agents may be a potential treatment for patients with chronic moderate to severe SCI.

4-Aminopyridine↗
PubMed2001

The preliminary experimental study of induced differentiation of embryonic stem cells into corneal epithelial cells.

PURPOSE: To study preliminarily induced differentiation of embryonic stem cells into corneal epithelial cells in vitro. METHODS: Murine embryonic stem cells were co-cultured with Rabbit limbal corneal epithelial cells in Transwell system to induce differentiation. Mophological and immunohistochemical examination were implemented. RESULTS: The induced cells from embryonic stem cells have an epithelial appearance. The cells formed a network and were confluent into film gradually after being co-cultured with rabbit limbal corneal epithelial cells for 24-96 hours. The cells ranged mosaic structure and localized together with clear rim. Most of the cells showed polygonal appearance. Transmission electron microscope showed lots of microvilli on the surface of induced cells and tight junctions between them. These epithelial-like cells expressed the corneal epithelial cell specific marker cytokeratin3/cytokeratin12. CONCLUSION: The potential mechanism of the differentiation of murine embryonic stem cells into corneal epithelial cells induced by limbal corneal epithelial cell-derived inducing activity is to be further verified.

Animals↗
PubMed2000

Loss of fibroblast growth factor receptor 2 ligand-binding specificity in Apert syndrome.

Craniosynostosis syndromes are autosomal dominant human skeletal diseases that result from various mutations in fibroblast growth factor receptor genes (Fgfrs). Apert syndrome (AS) is one of the most severe craniosynostosis syndromes and is associated with severe syndactyly of the hands and feet and with central nervous system malformations. AS is caused by specific missense mutations in one of two adjacent amino acid residues (S252W or P253R) in the highly conserved region linking Ig-like domains II and III of FGFR2. Here we demonstrate that these mutations break one of the cardinal rules governing ligand specificity of FGFR2. We show that the S252W mutation allows the mesenchymal splice form of FGFR2 (FGFR2c) to bind and to be activated by the mesenchymally expressed ligands FGF7 or FGF10 and the epithelial splice form of FGFR2 (FGFR2b) to be activated by FGF2, FGF6, and FGF9. These data demonstrate loss of ligand specificity of FGFR2 with retained ligand dependence for receptor activation. These data suggest that the severe phenotypes of AS likely result from ectopic ligand-dependent activation of FGFR2.

3T3 Cells↗
PubMed2000

Receptor engagement on cells expressing a ligand for the tolerance-inducing molecule OX2 induces an immunoregulatory population that inhibits alloreactivity in vitro and in vivo.

Increased survival of C57BL/6 renal allografts following portal vein donor-specific pretransplant immunization of C3H mice is associated with increased expression of the molecule OX2 seen on host dendritic cells, along with a marked polarization in cytokine production from lymphocytes harvested from the transplanted animals, with preferential production of IL-4, IL-10, and TGF-beta on donor-specific restimulation in vitro, and decreased production of IL-2, IFN-gamma, and TNF-alpha compared with non-portal vein-immunized control transplanted mice. The increased renal allograft survival and the altered cytokine production are abolished by infusion of anti-mouse OX2 mAb (3B6). Infusion of a soluble OX2:Fc immunoadhesin can itself produce significant prolongation of xeno- and allografts in mice. We have used FITC-conjugated OX2:Fc to characterize cells expressing a ligand (OX2L) for OX2, and provide evidence that subpopulations of LPS-stimulated splenic macrophages, Con A-activated splenic T cells, and the majority (>80%) of gammadeltaTCR(+) T cells express this ligand. We show below that F4/80(+), OX2L(+) splenic macrophages, admixed with OX2:Fc, represent a potent immunosuppressive population capable of causing more profound inhibition of alloreactivity in vitro or in vivo than that seen using either OX2:Fc or OX2(+) (or OX2L(+)) cells alone. Immunoregulation by this OX2L(+) population occurs in an MHC-restricted fashion.

Animals↗
PubMed2000

Characterization of a pituitary GnRH-receptor from a perciform fish, Morone saxatilis: functional expression in a fish cell line.

Gonadotropin-releasing hormones (GnRHs) bind to the specific receptor present on the gonadotrophs to activate the synthesis and release of gonadotropins (follicle stimulating hormone or FSH and luteinizing hormone or LH), which in turn control gonadal maturation, gametogenesis and gamete release. Perciform species have three endogenous GnRHs. The main objective of this study was to characterize the gonadotropin-releasing hormone receptor (GnRH-R) present in the pituitary of a perciform species, striped bass (Morone saxatilis) and demonstrate how it interacts with its potential ligand. In this study, a cDNA for GnRH-R from the pituitaries of striped bass was cloned. The cloned cDNA has an open reading frame (ORF) that codes for a 419 amino acids peptide. Like other G-protein coupled receptors including the non-mammalian GnRH-Rs, the peptide has seven putative transmembrane domains and a C-terminal tail. Comparative analysis of the amino acid sequence of striped bass (stb) GnRH-R shows 38-87% similarity with the known GnRH-Rs. A Northern blot analysis revealed a single GnRH-R transcript in the pituitary; however, its expression in various extrapituitary tissues was demonstrated by a reverse-transcription-PCR (RT-PCR). Functionally, upon induction by endogenous forms of GnRHs (seabream, chicken II and salmon GnRHs) and a mammalian GnRH-agonist, the recombinant stbGnRH-R mediated a reporter gene (luciferase) activity in a fish cell line (CHSE-214). A real-time relative quantitation method established that significantly higher (P<0.05) levels of stbGnRH-R mRNA were present in the pituitaries of striped bass with advanced stages of ovarian development, compared to the pituitaries of fish with less developed ovaries.

Amino Acid Motifs↗
PubMed2000

Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis despite continued expression of interferon gamma and nitric oxide synthase 2.

Tuberculosis is a major cause of death in much of the world. Current estimates are that one-third of the world's population is infected with Mycobacterium tuberculosis. Most infected persons control the infection but in many cases may not eliminate the organism. Reactivation of this clinically latent infection is responsible for a large proportion of active tuberculosis cases. A major risk factor for reactivation of latent tuberculosis is HIV infection, suggesting a role for the CD4(+) T cell subset in maintaining the latent persistent infection. In this study, we tested the requirement for CD4(+) T cells in preventing reactivation in a murine model of latent tuberculosis. Antibody-mediated depletion of CD4(+) T cells resulted in rapid reactivation of a persistent infection, with dramatically increased bacterial numbers in the organs, increased pathology in the lungs, and decreased survival. Although CD4(+) T cells are believed to be a major source of interferon (IFN)-gamma, expression of the gene for IFN-gamma in the lungs of CD4(+) T cell-depleted mice was similar to that in control mice. In addition, inducible nitric oxide synthase production and activity was unimpaired after CD4(+) T cell depletion, indicating that macrophage activation was present even during CD4(+) T cell deficiency. These data indicate that CD4(+) T cells are necessary to prevent reactivation but may have roles in addition to IFN-gamma production and macrophage activation in controlling a persistent tuberculous infection.

Animals↗
PubMed2000

Demand characteristics of residential substance abuse treatment programs.

PURPOSE: This study examined the objective demand characteristics of treatment programs in which substance abuse patients, or psychiatric patients, were residing. It also examined associations of objective demand with substance abuse patients' perceived expectations for functioning during treatment and patients' in-program participation. METHODS: A total of 994 patients living in 79 programs took part. RESULTS: When patients had a substance abuse rather than a psychiatric problem, objective demand was higher: program policies had higher requirements for functioning and more resident control; programs offered fewer health-treatment services; and the physical design provided fewer safety features and social-recreational aids. Compared to substance abuse patients in low-demand programs, patients in high-demand programs perceived the program to have higher expectations, in that the treatment climate exerted more press to develop relationships, set goals, and be organized. Patients in high-demand programs engaged more in self-initiated activities and participated more in treatment services and program-organized events. Substance abuse patients' activity and participation levels were determined jointly by the level of demand and by the expectations for patients' expressiveness and self-understanding of their personal problems. IMPLICATIONS: The findings illustrate the importance of considering objective indices of demand in conjunction with perceived expectations to improve patients' treatment outcomes.

Adult↗
PubMed2000

Volatile compounds from Escherichia coli O157:H7 and their absorption by strawberry fruit.

Volatile compounds emitted by cultures of two strains of the pathogenic bacterium Escherichia coliO157:H7 and a nonpathogenic strain of E. coli were trapped on Super-Q porous polymer and identified by GC-MS. The predominant compound produced by all three strains was indole with lesser amounts of other components including methyl ketones, 2-heptanone, 2-nonanone, 2-undecanone, and 2-tridecanone. The vapor-phase profiles of these strains were similar for most chemicals identified but differed with regard to ketones. Strawberry fruit was shown to be a suitable host for E. coli O157:H7 with the population of the bacterium either increasing or remaining stable after 3 days depending on inoculation level. Headspace analysis of the volatile compounds from inoculated fruit yielded no detectable quantity of indole. Strawberry fruit readily absorbed indole and other volatile compounds produced by the bacteria and in some cases metabolized the compounds to new volatile products. Thus, headspace "marker" compounds indicating possible bacterial contamination of fruit were largely removed from the vapor phase by the strawberries.

Absorption↗
PubMed2000

Relationship between the tertiary structures of mastoparan B and its analogs and their lytic activities studied by NMR spectroscopy.

Mastoparan B (MP-B), an antimicrobial cationic tetradecapeptide amide isolated from the venom of the hornet Vespa basalis, is an amphiphilic alpha-helical peptide. MP-B possesses a variety of biological activities, such as mast cells degradation histamine release, erythrocyte lysis and inhibition of the growth of gram-positive and gram-negative bacteria. In order to study the relationship between the structure and the biological activity of MP-B, we used four analogs by replacing amino acids with alanine. Tertiary structures of MP-B and its analogs in 2,2,2-trifluoroethanol (TFE)-containing aqueous solution have been determined by NMR spectroscopy and molecular modeling. The results indicate that [Ala4]MP-B and [Ala12]MP-B with higher hydrophobicity adopt a higher content of amphiphilic helical structures, and have better antimicrobial and hemolytic activities than MP-B. However, [Ala3]MP-B and [Ala9]MP-B with lower hydrophobicity have disordered structures. [Ala3]MP-B and [Ala9]MP-B have low antimicrobial activity and much less hemolytic activity relative to MP-B. It is likely that tryptophan residue in MP-B and appropriate hydrophobicity of MP-B to induce alpha-helical structure is essential for the antibacterial and hemolytic activity of MP-B. This study can aid understanding of the structure-activity relationship of MP-B and to design peptides to possess lytic activity.

Alanine↗
PubMed2000

Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice.

Members of the Mycobacterium tuberculosis group synthesize a family of long-chain fatty acids, mycolic acids, which are located in the cell envelope. These include the non-oxygenated alpha-mycolic acid and the oxygenated keto- and methoxymycolic acids. The function in bacterial virulence, if any, of these various types of mycolic acids is unknown. We have constructed a mutant strain of M. tuberculosis with an inactivated hma (cmaA, mma4) gene; this mutant strain no longer synthesizes oxygenated mycolic acids, has profound alterations in its envelope permeability and is attenuated in mice.

Animals↗
PubMed2000

Can semantic knowledge influence motion correspondence?

Semantic factors are presumed to have little influence on motion perception. Two experiments examined the effects of an object's semantic identity on motion correspondence using the Ternus paradigm. Motion correspondence was not influenced by whether the object depicted is typically moving or stationary, but it was influenced by the way(s) in which an object's components typically move relative to one another: perceived correspondence differed depending on whether the motion tokens constituted the feet of a person walking or the wheels of a car. Apparently, semantic knowledge can influence motion correspondence, although such influence is weak and may be restricted to certain types of semantic information. The adaptive significance of such restricted influences is considered.

Adult↗
PubMed2000

Tris(2,6-di-tert-butyl-4-methylphenolato-O)(triphenylphosphine oxide-O)samarium(III).

In the title complex, [Sm(C(15)H(23)O)(3)(C(18)H(15)OP)], the central metal atom is coordinated by three O atoms of the aryloxo ligands and by one O atom of the triphenylphosphine oxide molecule resulting in a distorted tetrahedral geometry. The Sm-O(Ar) distances (Ar is aryl) range from 2.122 (2) to 2.190 (2) A and the Sm-O(PPh(3)) bond length is 2.306 (2) A.

Journal Article↗
PubMed2000

A commercial preparation of catalase inhibits nitric oxide production by activated murine macrophages: role of arginase.

Catalase is widely used as a pharmacological probe to evaluate the role of hydrogen peroxide in antimicrobial activities of phagocytic cells. This report demonstrates that the ability of a commercial preparation of catalase to inhibit concomitantly macrophage antimycobacterial activity and production of reactive nitrogen intermediates can be attributed, at least in part, to the depletion of L-arginine by contaminating arginase. In experimental systems that employ pharmacological probes, the existence of nonspecific effects should be considered in data interpretation.

Animals↗