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Biomedical subjects

X Yu

Publications and source records attributed to X Yu.

At least 181 records · Page 10Linked to original sources

A new Drosophila APC homologue associated with adhesive zones of epithelial cells.

Adenomatous polyposis coli protein (APC) is an important tumour suppressor in the human colon epithelium. In a complex with glycogen synthase kinase-3 (GSK-3), APC binds to and destabilizes cytoplasmic ('free') beta-catenin. Here, using a yeast two-hybrid screen for proteins that bind to the Drosophila beta-catenin homologue, Armadillo, we identify a new Drosophila APC homologue, E-APC. E-APC also binds to Shaggy, the Drosophila GSK-3 homologue. Interference with E-APC function produces embryonic phenotypes like those of shaggy mutants. Interestingly, E-APC is concentrated in apicolateral adhesive zones of epithelial cells, along with Armadillo and E-cadherin, which are both integral components of the adherens junctions in these zones. Various mutant conditions that cause dissociation of E-APC from these zones also obliterate the segmental modulation of free Armadillo levels that is normally induced by Wingless signalling. We propose that the Armadillo-destabilizing protein complex, consisting of E-APC, Shaggy, and a third protein, Axin, is anchored in adhesive zones, and that Wingless signalling may inhibit the activity of this complex by causing dissociation of E-APC from these zones.

Adenomatous Polyposis Coli Protein↗

Role of mitogen-activated protein kinases in activation-induced apoptosis of T cells.

A member of the mitogen-activated protein (MAP) kinase family, Jun N-terminal kinase (JNK), has been implicated in regulating apoptosis in various cell types. We have investigated the requirement for another type of MAP kinase, extracellular signal-regulated protein kinase (ERK) in activation-induced cell death (AICD) of T cells. AICD is the process by which recently activated T cells undergo apoptosis when restimulated through the T-cell antigen receptor. Here we show that both JNK and ERK are activated rapidly upon T-cell receptor (TCR) ligation prior to the onset of AICD. A chemical inhibitor of ERK activation, PD 098059, inhibits ERK activation and apoptosis, while JNK activation is not inhibited. This suggests that JNK activation is not sufficient for apoptosis. TCR cross-linking induces expression of the apoptosis-inducing factor, Fas ligand (FasL), and its expression correlates with ERK activation. In addition, apoptosis induced by direct ligation of the Fas receptor by anti-Fas antibody is not associated with ERK activation and is not inhibited by PD 098059. These data suggest that ERK activation is an early event during T-cell apoptosis induced by antigen-receptor ligation, and is not involved in apoptosis per se but in the expression of FasL. MAP kinase family members may be similarly involved in inducing apoptosis signals in other cell types.

Animals↗

Pro- and anti-arrhythmic effects of a kappa opioid receptor agonist: a model for the biphasic action of a local hormone in the heart.

1. The effects of kappa opioid receptor stimulation on cardiac rhythm and the underlying signal pathways were investigated in the rat. 2. Stimulation of kappa opioid receptors with 40-50 mumol/L U50 488H, a selective kappa opioid receptor agonist, induced dysrhythmias and increased inositol 1,4,5-trisphosphate (IP3) production in rat isolated, perfused heart. The pro-arrhythmic effects of U50 488H were abolished by 5 mumol/L norbinaltorphimine (nor-BNI), a specific kappa opioid receptor antagonist. 3. The effect of U50 488H on cardiac dysrhythmia and IP3 production were abolished by 1 mmol/L neomycin and streptomycin, phospholipase C (PLC) inhibitors. 4. At 1 mumol/L, U50 488H, which itself has no effect on cardiac rhythm and IP3 production, significantly attenuated the potentiating effect of 1 mumol/L noradrenaline (NA) on dysrhythmias, which were induced by low flow in the isolated heart. The effects of U50 488H were abolished by 1 mumol/L nor-BNI. Cytosolic cAMP production was augmented by 1 mumol/L NA and this was significantly attenuated by 1 mumol/L U50 488H. 5. At 1 mumol/L, U50 488H also reduced [Ca2+]i oscillations induced by 0.5 mumol/L NA and 0.5 mumol/L forskolin, an activator of adenylate cyclase (AC). 6. In conclusion, U50 488H exerted pro- and anti-arrhythmic actions at high and lower concentrations, respectively. The former effect was mediated via the PLC/IP3 pathway, while the latter was mediated via the AC/cAMP pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Immunity to cross-reactive serotypes induced by pneumococcal conjugate vaccines in infants.

Infants were immunized with 1 of the 3 experimental pneumococcal conjugate vaccines that contain 6B and 19F but not 6A or 19A serotypes. Their sera were studied for the capacity to opsonize Streptococcus pneumoniae 6A, 6B, 19A, and 19F serotypes and the level of IgG antibody to the 4 serotypes. Significant increases were observed in the number of infants with detectable opsonophagocytic titers with 3 conjugate vaccines for 6B (vaccine) serotype but with only 2 vaccines for 6A (cross-reactive) serotype. Significant increases were observed with 2 conjugate vaccines for 19F serotype but with only 1 vaccine for 19A serotype. Thus, some conjugate vaccines may elicit cross-protection better than others. In addition, correlations between opsonophagocytic titers and IgG antibody levels by ELISA were high for 6B and 19F serotypes but low for 6A and 19A serotypes. Thus, ELISA may be an inadequate surrogate assay of vaccine response for cross-reactive serotypes.

Adult↗

A laminin and nerve growth factor-laden three-dimensional scaffold for enhanced neurite extension.

Agarose hydrogel scaffolds were engineered to stimulate and guide neuronal process extension in three dimensions in vitro. The extracellular matrix (ECM) protein laminin (LN) was covalently coupled to agarose hydrogel using the bifunctional cross-linking reagent 1,19- carbonyldiimidazole (CDI). Compared to unmodified agarose gels, LN-modified agarose gels significantly enhanced neurite extension from three-dimensionally (3D) cultured embryonic day 9 (E9) chick dorsal root ganglia (DRGs), and PC 12 cells. After incubation of DRGs or PC 12 cells with YIGSR peptide or integrin beta1 antibody respectively, the neurite outgrowth promoting effects in LN-modified agarose gels were significantly decreased or abolished. These results indicate that DRG/PC 12 cell neurite outgrowth promoting effect of LN-modified agarose gels involves receptors for YIGSR/integrin beta1 subunits respectively. 1,2-bis(10, 12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC(8,9)PC)-based lipid microcylinders were loaded with nerve growth factor (NGF), and embedded into agarose hydrogels. The resulting trophic factor gradients stimulated directional neurite extension from DRGs in agarose hydrogels. A PC 12 cell-based bioassay demonstrated that NGF-loaded lipid microcylinders can release physiologically relevant amounts of NGF for at least 7 days in vitro. Agarose hydrogel scaffolds may find application as biosynthetic 3D bridges that promote regeneration across severed nerve gaps.

Animals↗

Pneumococcal capsular polysaccharide preparations may contain non-C-polysaccharide contaminants that are immunogenic.

We measured the capacity to opsonize Streptococcus pneumoniae serotype 6B and estimated the concentration of immunoglobulin G anti-6B capsular polysaccharide (PS) antibodies in 25 pre- and postimmune sera from adults immunized with a pneumococcal PS vaccine. We first studied two postvaccination serum samples displaying less opsonophagocytic capacity than expected. The majority of anti-6B antibodies in the two samples reacted with the capsular PSs of several unrelated serotypes (2, 4, 9V, 19F, and 23F) and with the lysate of noncapsulated S. pneumoniae bacteria but not with C-PS. The non-type-specific antibodies accounted for at least one-half of anti-6B antibodies in 40% of prevaccination sera and 10% of postvaccination sera from adults. The non-type-specific antibodies could be demonstrated in the enzyme-linked immunosorbent assays (ELISAs) for pneumococcal antibodies to other serotypes (4, 9V, 18C, 19F, and 23F). The nonspecific antibodies appear to bind a contaminant(s) in the current preparations of capsular PS. ELISA for antibodies to pneumococcal capsules may not be serotype specific for some samples.

Adult↗

Visualization of protein-RNA interactions in cytoplasmic polyhedrosis virus.

Unlike the multiple-shelled organization of other Reoviridae members, cytoplasmic polyhedrosis virus (CPV) has a single-shelled capsid. The three-dimensional structures of full and empty CPV by electron cryomicroscopy show identical outer shells but differ inside. The outer surface reveals a T=1 icosahedral shell decorated with spikes at its icosahedral vertices. The internal space of the empty CPV is unoccupied except for 12 mushroom-shaped densities attributed to the transcriptional enzyme complexes. The ordered double-stranded RNA inside the full capsid forms spherical shells spaced 25 A apart. The RNA-protein interactions suggest a mechanism for RNA transcription and release.

Animals↗

Induction of apoptosis in murine coronavirus-infected cultured cells and demonstration of E protein as an apoptosis inducer.

We demonstrated that infection of 17Cl-1 cells with the murine coronavirus mouse hepatitis virus (MHV) induced caspase-dependent apoptosis. MHV-infected DBT cells did not show apoptotic changes, indicating that apoptosis was not a universal mechanism of cell death in MHV-infected cells. Expression of MHV structural proteins by recombinant vaccinia viruses showed that expression of MHV E protein induced apoptosis in DBT cells, whereas expression of other MHV structural proteins, including S protein, M protein, N protein, and hemagglutinin-esterase protein, failed to induce apoptosis. MHV E protein-mediated apoptosis was suppressed by a high level of Bcl-2 oncogene expression. Our data showed that MHV E protein is a multifunctional protein; in addition to its known function in coronavirus envelope formation, it also induces apoptosis.

Animals↗

Regulation of lymphocyte cell fate decisions and lymphomagenesis by BCL-6.

Genetic alterations of the BCL-6 gene in mice and man have established BCL-6 as a pivotal regulator of normal differentiation of B and T lymphocytes as well as one of the most frequently translocated oncogenes in human B cell lymphomas. As an oncogene, BCL-6 has not been easy to place into existing paradigms of cellular transformation. Rather, it is likely that the function of BCL-6 as a regulator of lymphocyte differentiation is subverted in BCL-6-induced lymphomas. The lymphomas in which BCL-6 is translocated are all suspected to arise from the germinal center B lymphocyte. Given the selective expression of BCL-6 protein in normal germinal center B lymphocytes and the requirement for BCL-6 in germinal center development, the functions of BCL-6 in normal and malignant B cells are probably intertwined. The BCL-6 protein is a potent transcriptional repressor which presumably controls lymphocyte differentiation and induces lymphomas by regulating the expression of key downstream target genes.

Animals↗

Interstitial brachytherapy using iridium-192 for malignant brain tumors: clinical results.

OBJECTIVE: To determine the effects and toxicity of interstitial brachytherapy using iridium-192 on brain malignant gliomas. METHODS: Between January 1992 and January 1995, 56 patients with anaplastic astrocytoma and glioblastoma multiforme were treated with stereotactic brachytherapy using temporary high-activity iridium-192 sources. RESULTS: The median survival for patients receiving brachytherapy was 28 months. The survival rates at 1, 2, 3 years were 92.8%, 83.9% and 71.4% respectively. CONCLUSIONS: Brachytherapy may improve the control of local tumor and prolong the survival, when used in deep malignant brain gliomas, by temporary implanted high doses of iridium-192 sources.

Adult↗

[Gene expression of beta-adrenoceptor signal transmitters in heart failure].

OBJECTIVE: To investigate the alteration in steady-state levels of messenger RNA(mRNA) of beta-adrenoceptor signal transmitters in heart failure. METHODS: The reverse transcription polymerase chain reaction (RT-PCR) was used to assess gene expression in small quantity of circulatory lymphocytes. With selected oligonucleotide primers, we used quantitative RT-PCR to amplify mRNAs encoding beta 2-adrenergic receptor(beta 2-AR), adenylate cyclase (AC), beta 2-adrenergic receptor kinase(beta-ARK), and beta-arrestin and cAMP response element binding protein (CREB) in 16 healthy subjects and 30 heart-failing patients. RESULTS: The alteration of gene expression in heart failure appeared to be selective, the steady-state levels of mRNA increased significantly involving AC and the transcription factor, CREB; decreased significantly involving membrane receptor, beta 2-AR; unchanged significantly involving phosphorylating factors of beta-AR uncoupling, beta-ARK and beta-arrestin. CONCLUSION: The aberrant gene expression of beta-adrenergic receptor might play an important role in the pathogenesis of heart failure.

Adenylyl Cyclases↗

Immunological characteristics of natural resistance in Microtus fortis to infection with Schistosoma japonicum.

OBJECTIVE: To explore the immunological characteristics of natural resistance to Schistosoma japonicum infection in Microtus fortis (MF) living in the Dongting Lake area. METHODS: Passive transfer of sera from uninfected laboratory bred MF (BMF) to albinao mice (AM) was performed to observe the acquired protection. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked immunoblotting (ELIB) methods were used to recognize 4 different life-cycle stage antigens of S. japonicum by sera from wild MF (WMF), BMF, BMF13 and BMF19. Tests were also performed on in vitro killing effect of sera and/or lymphocytes from BMF and WMF to schistosomulae; quantitative determination of C3 and C4 by immunoturbidometry, and interleukin-4 (IL-4) and antibodies to the 4 stage antigens in sera from WMF, BMF and infected BMF by ELISA. RESULTS: Compared with the control group, stool eggs per gram (EPG) of AM in the test group was significantly reduced by 81.54%, miracidium hatching rate, by 50.67%, liver egg counts, by 72.07%, the diameter of hepatic egg granuloma, by 70.39 microns. Western blotting probed with the 4 MF sera all revealed 7 specific bands for SSA, 3 for AWA and SEA, but none for CA antigens. The sera and/or lymphocytes from WMF and BMF gave obvious killing effects on schistosomulae with an adjusted death rate of 64.12%-78.83%. The levels of "natural antibodies" produced by MF to S. japonicum were in the following order: anti-SSA > anti-AWA > anti-SEA > anti-CA, all of which increased significantly after the infection. Serum levels of C3, C4 and IL-4 in uninfected BMF were significantly higher than those in AM. After infection, levels of C3 and C4 were further increased respectively by 72.83% and 295.49% in the 4th week and IL-4 by 303.83% in the 9th day. CONCLUSIONS: Immunological characteristics of innate resistance in M. fortis to S. japonicum infection were existed with no significant difference between WMF and BMF.

Animals↗

[DNA polymorphism of Vibrio cholera and other vibrios].

OBJECTIVE: To investigate the inherent characteristics of V. cholera and other vibrios and the association between them. METHODS: Polymerase chain reaction (PCR), DNA sequences analysis, randomly amplified polymorphic DNA (RAPD) and average linkage cluster analysis were used to study V. cholera including 3 strains of O139, 4 strains of E1 Tor biotype, 3 strains of classical and 3 other vibrios. RESULTS: V. cholera O139 contained the genomic sequences of CTX A2-B as well as O1 V. cholera, indicating that their homologous nucleotides was 96.9%-98.7%, and other vibrios did not contain CTX. O1 V. cholera and other vibrios were divided into 4 groups by RAPD: classical; O139 and E1 Tor; V. paraheamolyticus and V. vulnificus; and V. flluvialis. The O139 DNA fingerprints of RAPD were almost as same as E1 Tor biotype, whose average linkage cluster distance was 0, similar with classical biotype, whose average linkage cluster distance was 2.07, much different from V. paraheamolyticus and others with the average linkage cluster distance being 6.76-8.54. CONCLUSION: V. cholera and other vibrios are polymorphic in inherent characteristics. Being as same as the inherent characteristics of E1 Tor, O139 may evoluted from E1 Tor biotype. And also the inherent characteristics of V. parahemolytisus were as same as those of V. vulnificus.

DNA, Bacterial↗

[Influence of flavonoid of Astragalus membranaceus's stem and leaves on the function of cell mediated immunity in mice].

OBJECTIVE: To investigate the immune regulation of flavonoid of Astragalus membranaceus's stem and leaves (FAM). METHODS: Changes of total T cell count and subsets in mice were determined by monoclonal antibody assay before and after treatment with FAM, and the LAK activity was tested simultaneously by isotope technique. RESULTS: FAM could promote the proliferation of lymphocytes induced by ConA, raise the T cell count and regulate the T cell subsets disorder, elevate the LAK activity induced by IL-2. CONCLUSION: FAM possesses the effect of immune stimulation and immune regulation in treating immunosuppressive mice. This study provides the experimental basis for clinical application of FAM.

Adjuvants, Immunologic↗

[Effect of ginseng injection in treating congestive heart failure and its influence on thyroid hormones].

OBJECTIVE: To observe the effect of Ginseng injection on congestive heart failure (CHF) and its influence on thyroid hormones. METHODS: Fifty-four Patients of CHF were divided into two groups. On the basis of conventional treatment of western medicine, the Ginseng injection was given to the treated group additionally. Blood level of triiodothyronine (T3), thyroxine (T4), reverse triiodothyronine (rT3) and thyroid stimulating hormone (TSH) of all patients were determined before and after treatment by radioimmunoassay. RESULTS: There were significant difference between the treated group and the control group in cure rate and mean course of therapy. The levels of T3 and T4 of all patients were lower than those of the normal control before treatment, and rT3 were higher. Two weeks after treatment, T3 and T4 level in all patients increased significantly and rT3 level significantly decreased(P < 0.05, P < 0.01). CONCLUSION: Ginseng injection has a good effect on patients with CHF. It also has regulatory effect on thyroid hormones.

Adult↗

[Effects of humic acid on lipid peroxidation in arsenosis prevalent areas].

OBJECTIVE: To explore the causes of blackfoot disease in Taiwan. METHODS: Experiments to induce lipid peroxidation by arsenic and humic acid were made in vitro. Arsenic was determined for the water sampled from the arsenosis prevalent areas in Inner Mongolia and blackfoot disease prevalent areas in Taiwan and humic acid determined for the extracts of the coal rich in arsenic sampled from Guizhou Province in China by MDA-TBA colorimetry. RESULTS: Experiments found that humic acid could induce lipid peroxidation caused by sodium salt of unsaturated fatty acids in vitro in a weak and unstable manner, which could be promoted by 0.05 mmol/L of Fe(+ +) and not by 1 mmol/L As(2)O(3). The extent of lipid peroxidation caused depended on the sources, constituents and structure of humic acid samples, those from Inner Mongolia ranked the highest, those from Guizhou and Taiwan the medium and the commercial humic acid (Aldrich Co. in the US) the lowest. The experiments also found that lipid peroxidation caused by commercial humic acid presented a dynamic process in the existence of trace amount of iron, and humic acid could decompose the products of lipid peroxidation. CONCLUSION: The experiments suggested the relations of humic acid and arsenic to iron and other transition elements in the blackfoot disease prevalent areas and areas with an environment rich in arsenic and humic acid.

Arsenic Poisoning↗

[Electroencephalography and transcranial Doppler analysis in children with migraine].

Electroencephalogram(EEG) and transcranial Doppler(TCD) recordings were carried out in 25 children with migraine during ictal and interictal period. The results were that the abnormal rate of EEG and TCD was 85% and 72%, respectively; the positive rate of EEG provoked test was 60%; there was the single untypical epileptiform wave in the occipital in 3 patients by EEG. We conclude that EEG combined TCD examination in migraine can increase the correct rate of diagnosis and help to differ epilepsy from migraine.

Adolescent↗