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Biomedical subjects

J Zhu

Publications and source records attributed to J Zhu.

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

Serum of cytomegalovirus-infected mice induces monocyte chemoattractant protein-1 expression by endothelial cells.

Inflammation plays a central role in atherogenesis. It was hypothesized that infection of apolipoprotein E-deficient mice with murine cytomegalovirus (MCMV) increases serum levels of proinflammatory cytokines, which may induce "proatherosclerotic" changes in endothelial cells (ECs). Serum samples were collected from uninfected and infected mice. ELISA was used to determine cytokine serum levels and monocyte chemoattractant protein-1 (MCP-1) levels in the supernatant of mouse ECs incubated with serum-containing medium. Serum samples from infected mice induced MCP-1 expression by ECs. These serum samples contain interferon (IFN)-gamma, whereas IFN-gamma was undetectable in serum samples from uninfected mice. Preincubating infected mouse serum with anti-IFN-gamma monoclonal antibody significantly decreased serum-induced EC expression of MCP-1. Thus, MCMV infection increases IFN-gamma serum levels, such serum can induce MCP-1 in ECs, and the serum-induced MCP-1 expression is due, at least in part, to IFN-gamma. If these changes in EC function also occur in vivo in response to infection, they could exacerbate atherogenesis.

Animals↗
PubMed2001

Temporal profile of anti-ganglioside antibodies and their relation to clinical parameters and treatment in Guillain-Barré syndrome.

Elevated anti-ganglioside antibody levels mainly of anti-GM1 and anti-GD1a specificities have been reported in THE serum of patients with Guillain-Barré syndrome (GBS). The relevance of anti-ganglioside antibodies other than anti-GM1 and anti-GD1a IgG antibodies and the temporal profile of anti-ganglioside antibodies in GBS is less clear. We studied serum antibodies to GM1, GD1a, GD1b, GQ1b, sulfatide and cardiolipin of the IgM, IgG and IgA classes over the course of GBS in patients who were untreated or treated with high dose intravenous immunoglobulin (IvIg). Antibodies to GD1b, GQ1b, sulfatide and cardiolipin were not detected in the sera of the GBS patients examined in this study. Anti-GM1 IgG titers peaked around 40 days and anti-GD1a IgM around 90 days after GBS onset. Titers of anti-GM1 IgG antibodies decreased following IvIg treatment. Patients with antibody peaks, defined as fivefold or higher increase in antibody titer compared to the lowest antibody titer over the course of GBS, had higher disability scores during the first two weeks of GBS and a worse clinical outcome (anti-GM1 IgG and anti-GD1a IgM antibody peaks) and axonal damage (anti-GD1a IgM antibody peaks), compared to patients without peak antibody titers. Anti-GM1 IgG and anti-GD1a IgM antibodies are thus strongly associated with more severe- and predominantly axonal cases of GBS. The appearance of anti-GM1 IgG and anti-GD1a antibody peaks in the serum after the termination of the acute phase of GBS suggests that these antibodies are produced secondary to nerve damage in GBS. The data does not exclude the possibility that secondarily secreted anti-GM1 IgG and anti-GD1a IgM antibodies may themselves be biologically active and play a role in disease propagation and/or recovery from disease in some patients with GBS.

Antibodies↗
PubMed2001

Analysis of oxytetracycline, tetracycline, and chlortetracycline in water using solid-phase extraction and liquid chromatography-tandem mass spectrometry.

A method using liquid chromatography-tandem mass spectrometry has been developed for determination of trace levels of tetracycline antibiotics in ground water and confined animal feeding operation waste water. Oxytetracycline (OTC), tetracycline (TC), and chlortetracycline (CTC) were extracted from water samples using both polymeric and C18 extraction cartridges. The addition of a buffer containing potassium phosphate and citric acid improved tetracycline recoveries in lagoon water. Method detection limits determined in reagent water fortified with 1 microg l(-1) OTC, TC, and CTC were 0.21, 0.20, and 0.28 microg l(-1). Method detection limits in lagoon water samples fortified at 20 microg l(-1) for OTC, TC, and CTC were 3.6, 3.1, and 3.8 microg l(-1). Variability in recovery from laboratory fortified blanks ranged from 86 to 110% during routine analysis.

Chlortetracycline↗
PubMed2001

Determinants involved in Kv1 potassium channel folding in the endoplasmic reticulum, glycosylation in the Golgi, and cell surface expression.

Kv1.1 and Kv1.4 potassium channels are expressed as mature glycosylated proteins in brain, whereas they exhibited striking differences in degree of trans-Golgi glycosylation conversion and high cell surface expression when they were transiently expressed as homomers in cell lines. Kv1.4 exhibited a 70% trans-Golgi glycosylation conversion, whereas Kv1.1 showed none, and Kv1.4 exhibited a approximately 20-fold higher cell surface expression level as compared with Kv1.1. Chimeras between Kv1.4 and Kv1.1 and site-directed mutants were constructed to identify amino acid determinants that affected these processes. Truncating the cytoplasmic C terminus of Kv1.4 inhibited its trans-Golgi glycosylation and high cell surface expression (as shown by Li, D., Takimoto, K., and Levitan, E. S. (2000) J. Biol. Chem. 275, 11597-11602), whereas truncating this region on Kv1.1 did not affect either of these events, indicating that its C terminus is not a negative determinant for these processes. Exchanging the C terminus between these channels showed that there are other regions of the protein that exert a positive or negative effect on these processes. Chimeric constructs between Kv1.4 and Kv1.1 identified their outer pore regions as major positive and negative determinants, respectively, for both trans-Golgi glycosylation and cell surface expression. Site-directed mutagenesis identified a number of amino acids in the pore region that are involved in these processes. These data suggest that there are multiple positive and negative determinants on both Kv1.4 and Kv1.1 that affect channel folding, trans-Golgi glycosylation conversion, and cell surface expression.

Amino Acid Sequence↗
PubMed2001

Histopathological findings of cardiac conduction system of 150 Finns.

One hundred and fifty heart specimens were collected from the cases submitted for autopsy in the Department of Forensic Medicine in the University of Turku in March-May 1995 and May-July 1996, respectively. The cardiac conduction system (CCS) of these hearts were examined in order to find out the histopathological changes in the CCS of Finnish persons and their forensic pathological significance. There were 94 males and 56 females. Almost all age groups were included. The results revealed that in most of the persons the fibrous tissue and fatty tissue in the CCS increased with aging. In about half of the persons, there was deposition of calcium in the central fibrous body, pars membranacea, and the top of the musculature in the interventricular septum. In seven cases, the atrioventricular node (AVN), His bundle (HB) or bundle branches (RBB, LBB) were compressed by the calcium deposition. Hemorrhage, inflammation, amyloidosis, tumor, fatty infiltration and developmental malformations were observed in 31 cases. Twenty-eight cases died of myocardial infarct, among them, no involvement of the CCS could be observed. The authors concluded that routine examination of the CCS is helpful for revealing diseases of the CCS and improving the quality of forensic pathological diagnosis.

Adult↗
PubMed2001

p73 cooperates with DNA damage agents to induce apoptosis in MCF7 cells in a p53-dependent manner.

p73, a member of the p53 family, can induce apoptosis in cancer cells. Since p53-mediated apoptosis can be augmented by various cancer chemotherapeutic agents, it has been hypothesized that the status of the endogenous p53 gene in cancer cells is a key determinant in the outcome of cancer therapy. To determine whether p73 can sensitize cancer cells to apoptosis by DNA damage agents, several MCF7 adenocarcinoma cell lines that inducibly express p73 or p53 under a tetracycline-regulated promoter were generated. We found that at relevant physiological levels, p73, but not p53, is capable of sensitizing MCF7 cells to apoptosis induced by chemotherapeutic agents. In addition, we found that p73 can cooperate with the DNA damaging agent camptothecin to activate the initiator caspase 2. Furthermore, we found that p73 can cooperate with DNA damaging agents or p53 to induce some p53 target genes and activate their promoters. In contrast, in MCF7E6 cells that ectopically express the human papillomavirus E6 oncogene and are functionally p53-null, the ability of p73 to sensitize cells to apoptosis is abrogated. Taken together, these results suggest that a functional interaction between p53 and p73 in MCF7 cells leads to enhanced induction of apoptosis.

Adenocarcinoma↗
PubMed2001

Exacerbations of Bronchitis: bronchial eosinophilia and gene expression for interleukin-4, interleukin-5, and eosinophil chemoattractants.

Eosinophilia has been reported during exacerbations of bronchitis, but the mechanisms of tissue recruitment of eosinophils are unclear. We quantified eosinophils and the concurrent expression of cytokines and chemokines probably responsible for the tissue eosinophilia in bronchial biopsies obtained from three groups of nonatopic subjects: (1) healthy nonsmokers (n = 7; FEV1 % predicted = 108 +/- 4 [mean +/- SEM]); (2) nonasthmatic smokers with chronic bronchitis (CB) in a stable phase of their disease (n = 11; FEV1 % predicted: 75 +/- 5); and (3) nonasthmatic subjects with CB who sought medical advice for an exacerbation of their condition (n = 9; FEV(1) % predicted: 61 +/- 8). We applied anti-EG2 antibody and immunostaining to detect and count eosinophils. We performed in situ hybridization to visualize and enumerate cells expressing the genes for interleukin (IL)-4 and IL-5 and the eosinophil chemokines eotaxin, monocyte chemoattractant protein (MCP)-4, or regulated on activation, normal T-cell expressed and secreted (RANTES). We confirmed an increase in EG2-positive eosinophils in patients with CB in exacerbation. We found messenger RNA (mRNA) positivity for IL-4 and IL-5 in CB, but the between-group differences were not statistically significant. However, the numbers of lymphomononuclear cells expressing eotaxin mRNA were significantly greater in the smokers with CB than in the healthy nonsmokers without CB (p < 0.01). Following an exacerbation, RANTES expression was upregulated and this chemokine was strongly expressed in both the surface epithelium and in subepithelial lymphomononuclear cells: only RANTES showed a significant positive correlation with the increasing number of EG2-positive cells (r = 0.51; p < 0.03). In conclusion, an allergic profile of inflammation can also occur in CB: the marked upregulation of RANTES in the epithelium and subepithelium most likely accounts for the increased eosinophilia associated with an exacerbation of bronchitis.

Adult↗
PubMed2001

[Effect of endostatin gene transfer mediated by electric pulses into skeletal muscles on development of atherosclerotic plaques in mice].

OBJECTIVE: To investigate the effect of endostatin gene transfer mediated by electric pulses into skeletal muscles of mice upon the develpment of atherosclerotic plaques. METHODS: Eukaryotic expression plasmid of mouse endostatin was injected into the muscles of 2 groups of ApoE-deficient mice, group A at the age of 24 weeks, and group B at the age of 36 weeks (named therapy group as a whole). Gene transfer was mediated by electric pulses for ten times. Empty plasmid was used to mice at the same ages as controls. Twenty weeks later, blood-lipid was tested, and the aortas of the experimental animals were taken out to examine the areas of atherosclerotic plaques and count the endothelial cells and microvessels in the plaques. RESULTS: In the 24-week-aged group, the stenosis rate of aorta 16% +/- 4% before the experiment. Twenty weeks later, the stenosis rate was 56% +/- 14% among the control mice, and was 34% +/- 8% among the treated ones with an improvement rate of 54%. In the 36-week-aged group, the stenosis rate of aorta was 30% +/- 6% before the experiment. Twenty weeks after the begining of experiment, the stenosis rate was 64% +/- 12% among the control mice, and was 49% +/- 10% among the treated ones with an improvement rate of 44%. Twenty weeks after the begining of experiment, the endothelial cell count and microvessel appearance rate were less among the therapy group than among the controls. There was no significant difference in blood-lipid between the therapy group and the control group. CONCLUSION: Endostatin gene transfer into skeletal muscle effectively inhibits the development of atherosclerotic plaques.

Animals↗
PubMed2001

Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation.

Promyelocytic leukemia (PML) is the organizer of nuclear matrix domains, PML nuclear bodies (NBs), with a proposed role in apoptosis control. In acute promyelocytic leukemia, PML/retinoic acid receptor (RAR) alpha expression disrupts NBs, but therapies such as retinoic acid or arsenic trioxide (As2O3) restore them. PML is conjugated by the ubiquitin-related peptide SUMO-1, a process enhanced by As2O3 and proposed to target PML to the nuclear matrix. We demonstrate that As2O3 triggers the proteasome-dependent degradation of PML and PML/RARalpha and that this process requires a specific sumolation site in PML, K160. PML sumolation is dispensable for its As2O3-induced matrix targeting and formation of primary nuclear aggregates, but is required for the formation of secondary shell-like NBs. Interestingly, only these mature NBs harbor 11S proteasome components, which are further recruited upon As2O3 exposure. Proteasome recruitment by sumolated PML only likely accounts for the failure of PML-K160R to be degraded. Therefore, studying the basis of As2O3-induced PML/RARalpha degradation we show that PML sumolation directly or indirectly promotes its catabolism, suggesting that mature NBs could be sites of intranuclear proteolysis and opening new insights into NB alterations found in viral infections or transformation.

Adenosine Triphosphatases↗
PubMed2001

Identification of a novel, human multilymphoid progenitor in cord blood.

The earliest stages of lymphoid commitment from human pluripotent hematopoietic stem cells have not been defined. A clonogenic subpopulation of CD34(+)CD38(-) cord blood cells were identified that expressed high levels of the CD7 antigen and possessed only lymphoid potential. CD34(+)CD38(-)CD7(+) (CD7(+)) cells uniformly coexpressed CD45RA and HLA-DR; c-kit and Thy-1 expression was absent to low. Clonal analysis demonstrated that single CD7(+) cells could generate B cells, natural killer cells, and dendritic cells but were devoid of myeloid or erythroid potential. In contrast, control CD34(+)CD38(-)CD7(-) (CD7(-)) cells generated both lymphoid and myelo-erythroid cells. The lymphoid potential (generation of lymphoid progeny in bulk and single cell cultures) of CD7(+) cells was equivalent to that of the pluripotent CD7(-) cells. RNA expression studies showed that CD7(+) cells expressed PU.1 and GATA-3, but did not express Pax-5, terminal deoxynucleotide transferase, or CD3epsilon. In contrast to the previously described murine common lymphoid progenitor, the alpha chain of the receptor for interleukin-7 was not detected by fluorescence-activated cell sorting analysis or RNA polymerase chain reaction in CD7(+) cells. These studies identify a clonogenic lymphoid progenitor with both B-cell and natural killer cell lineage potential with a molecular profile that suggests a developmental stage more primitive than previously identified lymphoid progenitors. The CD7(+) phenotype distinguishes primitive human lymphoid progenitors from pluripotent stem cells, thus allowing the study of regulation of early human lymphopoiesis and providing an alternative to pluripotent stem cells for genetic manipulation and transplantation. (Blood. 2001;97:3683-3690)

ADP-ribosyl Cyclase↗
PubMed2001

Stat6 is necessary and sufficient for IL-4's role in Th2 differentiation and cell expansion.

IL-4 plays a critical role in the differentiation of TCR-stimulated naive CD4 T cells to the Th2 phenotype. In response to IL-4, the IL-4R activates a set of phosphotyrosine binding domain-containing proteins, including insulin receptor substrate 1/2, Shc, and IL-4R interacting protein, as well as Stat6. Stat6 has been shown to be required for Th2 differentiation. To determine the roles of the phosphotyrosine binding adaptors in Th2 differentiation, we prepared a retrovirus containing a mutant of the human (h)IL-4R alpha-chain, Y497F, which is unable to recruit these adaptors. The mutant hIL-4Ralpha, as well as the wild-type (WT) hIL-4Ralpha, was introduced into naive CD4 T cells. Upon hIL-4 stimulation, Y497F worked as well as the WT hIL-4Ralpha in driving Th2 differentiation, as measured by Gata3 up-regulation and IL-4 production. Furthermore, IL-4-driven cell expansion was also normal in the cells infected with Y497F, although cells infected with Y497F were not capable of phosphorylating insulin receptor substrate 2. These results suggest that the signal pathway mediated by Y497 is dispensable for both IL-4-driven Th2 differentiation and cell expansion. Both WT and Y497F hIL-4Ralpha lose the ability to drive Th2 differentiation and cell expansion in Stat6-knockout CD4 T cells. A constitutively activated form of Stat6 introduced into CD4 T cells resulted in both Th2 differentiation and enhanced cell expansion. Thus, activated Stat6 is necessary and sufficient to mediate both IL-4-driven Th2 differentiation and cell expansion in CD4 T cells.

Animals↗
PubMed2001

Critical sites for the interaction between IL-2Rgamma and JAK3 and the following signaling.

JAK3 is the only known protein tyrosine kinase associating with IL-2Rgamma. This interaction is supposed to be very important to IL-2 signaling. In order to identify the critical residues for these two molecular interactions and the following signal events, various mutants of gammac and JAK3 were constructed on the basis of computer analysis. The direct interaction was determined via the yeast two-hybrid system, while the signaling was analyzed with reporter genes under the control of the c-fos, c-myc, or tnf-beta promoters, respectively. Results showed that there are two key sites on gammac involved in this interaction and the following signal transduction: the critical one is E327 via electrostatic interaction, the other is L293 via hydrophobic interaction. As to JAK3, the data indicated that Y100 is important for the interaction with gammac. These results also document that the requirement for interaction between gammac and JAK3 is different to activate different signaling pathways mediated by gammac, such as c-fos, c-myc, and JAK-STAT.

Animals↗
PubMed2001

Photochemically removable silyl protecting groups.

Several o-phenol-containing alkoxyvinylsilanes were prepared and their photochemistry was investigated. These materials were prepared via hydrosilylation of the corresponding o-acetoxy arylacetylenes. Two major classes of photochemical processes were identified in these reactants: trans-->cis isomerization, leading to an intramolecular nucleophilic substitution process at silicon, and 1,5-silyl shift, leading to an unsymmetrical dialkoxysilane. The major outcome of this work is a novel class of photochemically removable protecting groups. Two alkyl substitutions on silicon, the dimethyl and diisopropyl, were examined. The latter is more stable and is preferred for protecting groups that must tolerate multiple steps or reagents. Protection of alcohols is generally performed starting with the arylethynyl acetate, which can be subjected to hydrosilylation, alcohol substitution, and acetate deprotection without isolation of intermediates. Two groups were studied in detail, the phenol and 2-naphthol vinyl silane derivatives. A variety of primary and secondary alcohols were protected with these reagents. These groups can be deprotected cleanly and in high yield by irradiation from 250 to 350 nm.

Acetylene↗
PubMed2001

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade enhances incidence and severity of experimental autoimmune neuritis in resistant mice.

Experimental autoimmune neuritis (EAN), an autoimmune inflammatory demyelinating disease of the peripheral nervous system, represents an animal model of the human Guillain-Barré syndrome. EAN can be induced by active immunization in several animals, including Lewis rats. In contrast, most strains of mice including the widely used C57BL/6 (B6) strain are reputedly resistant to the induction of EAN. In the present study, we demonstrate that in B6 mice, anti-CTLA-4 monoclonal antibody administration in conjunction with immunization with the P0 protein derived peptide 180-199 can induce clinical and pathological definite EAN. Upregulating effects of CTLA-4 blockade on initial and ongoing EAN are demonstrated. CTLA-4 blockade augmented cellular infiltration and enhanced demyelination in the target organ sciatic nerves as well as increased T cell proliferation in lymph node cells. Moreover, serum levels of IFN-gamma and IL-4 were increased. Thus, manipulation of CTLA-4/B7 costimulatory pathway by CTLA-4 blockade can promote autoreactivity and break the relative tolerance to peripheral autoantigen P0 in resistant B6 mice.

Abatacept↗