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Biomedical subjects

J Zhu

Publications and source records attributed to J Zhu.

At least 253 records · Page 14Linked to original sources
PubMed2000

Construction, phenotypic analysis, and immunogenicity of a UL5/UL29 double deletion mutant of herpes simplex virus 2.

A number of studies have shown that replication-defective mutant strains of herpes simplex virus (HSV) can induce protective immunity in animal systems against wild-type HSV challenge. However, all of those studies used viruses with single mutations. Because multiple, stable mutations provide optimal levels of safety for live vaccines, we felt that additional mutations needed to be engineered into a candidate vaccine strain for HSV-2 and genital herpes. We therefore isolated an HSV-2 strain with deletion mutations in two viral DNA replication protein genes, UL5 and UL29. The resulting double deletion mutant virus strain, dl5-29, fails to form plaques or to give any detectable single cycle yields in normal monkey or human cells. Nevertheless, dl5-29 expresses nearly the same pattern of gene products as the wild-type virus or the single mutant viruses and induces antibody titers in mice that are equivalent to those induced by single deletion mutant viruses. Therefore, it is feasible to isolate a mutant HSV strain with two mutations in essential genes and with an increased level of safety but which is still highly immunogenic.

Animals↗
PubMed2000

MCG10, a novel p53 target gene that encodes a KH domain RNA-binding protein, is capable of inducing apoptosis and cell cycle arrest in G(2)-M.

p53, a tumor suppressor, inhibits cell proliferation by inducing cellular genes involved in the regulation of the cell cycle. MCG10, a novel cellular p53 target gene, was identified in a cDNA subtraction assay with mRNA isolated from a p53-producing cell line. MCG10 can be induced by wild-type but not mutant p53 and by DNA damage via two potential p53-responsive elements in the promoter of the MCG10 gene. The MCG10 gene contains 10 exons and is located at chromosome 3p21, a region highly susceptible to aberrant chromosomal rearrangements and deletions in human neoplasia. The MCG10 gene locus encodes at least two alternatively spliced transcripts, MCG10 and MCG10as. The MCG10 and MCG10as proteins contain two domains homologous to the heterogeneous nuclear ribonucleoprotein K homology (KH) domain. By generating cell lines that inducibly express either wild-type or mutated forms of MCG10 and MCG10as, we found that MCG10 and MCG10as can suppress cell proliferation by inducing apoptosis and cell cycle arrest in G(2)-M. In addition, we found that MCG10 and MCG10as, through their KH domains, can bind poly(C) and that their RNA-binding activity is necessary for inducing apoptosis and cell cycle arrest. Furthermore, we found that the level of the poly(C) binding MCG10 protein is increased in cells treated with the DNA-damaging agent camptothecin in a p53-dependent manner. These results suggest that the MCG10 RNA-binding protein is a potential mediator of p53 tumor suppression.

Alternative Splicing↗
PubMed2000

Sequestration and inhibition of Daxx-mediated transcriptional repression by PML.

PML fuses with retinoic acid receptor alpha (RARalpha) in the t(15;17) translocation that causes acute promyelocytic leukemia (APL). In addition to localizing diffusely throughout the nucleoplasm, PML mainly resides in discrete nuclear structures known as PML oncogenic domains (PODs), which are disrupted in APL and spinocellular ataxia cells. We isolated the Fas-binding protein Daxx as a PML-interacting protein in a yeast two-hybrid screen. Biochemical and immunofluorescence analyses reveal that Daxx is a nuclear protein that interacts and colocalizes with PML in the PODs. Reporter gene assay shows that Daxx drastically represses basal transcription, likely by recruiting histone deacetylases. PML, but not its oncogenic fusion PML-RARalpha, inhibits the repressor function of Daxx. In addition, SUMO-1 modification of PML is required for sequestration of Daxx to the PODs and for efficient inhibition of Daxx-mediated transcriptional repression. Consistently, Daxx is found at condensed chromatin in cells that lack PML. These data suggest that Daxx is a novel nuclear protein bearing transcriptional repressor activity that may be regulated by interaction with PML.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Regulation of a voltage-sensitive release mechanism by Ca(2+)-calmodulin-dependent kinase in cardiac myocytes.

A role for Ca(2+)-calmodulin-dependent kinase (CamK) in regulation of the voltage-sensitive release mechanism (VSRM) was investigated in guinea pig ventricular myocytes. Voltage clamp was used to separate the VSRM from Ca(2+)-induced Ca(2+) release (CICR). VSRM contractions and Ca(2+) transients were absent in cells dialyzed with standard pipette solution but present when 2-5 microM calmodulin was included. Effects of calmodulin were blocked by KN-62 (CamK inhibitor), but not H-89, a protein kinase A (PKA) inhibitor. Ca(2+) current and caffeine contractures were not affected by calmodulin. Transient-voltage relations were bell-shaped without calmodulin, but they were sigmoidal and typical of the VSRM with calmodulin. Contractions with calmodulin exhibited inactivation typical of the VSRM. These contractions were inhibited by rapid application of 200 microM of tetracaine, but not 100 microM of Cd(2+), whereas CICR was inhibited by Cd(2+) but not tetracaine. In undialyzed myocytes (high-resistance microelectrodes), KN-62 or H-89 each reduced amplitudes of VSRM contractions by approximately 50%, but together they decreased VSRM contractions by 93%. Thus VSRM is facilitated by CamK or PKA, and both pathways regulate the VSRM in undialyzed cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Infection and atherosclerosis: potential roles of pathogen burden and molecular mimicry.

Infection has been implicated as a cause of atherosclerosis since the first half of the 19th century. Over the years, sporadic publications have appeared in the literature reflecting a persistent but relatively low level of research activity in this area. In the last decade, however, publications relating to this topic have increased markedly. And very recently, new epidemiological and mechanistic data relating infection to several different diseases, including atherosclerosis, have appeared, stimulating the emergence of important paradigm shifts in how we think about the causes of chronic disease. The following article reviews some of these newer concepts as they relate to a possible role of infection in atherosclerosis.

Arteriosclerosis↗
PubMed2000

Monoclonal antibody against vascular cell adhesion molecule-1 inhibits neointimal formation after periadventitial carotid artery injury in genetically hypercholesterolemic mice.

Vascular cell adhesion molecule (VCAM)-1 is induced in smooth muscle cells after arterial injury, in which it has been implicated in the recruitment of inflammatory cells to the site of injury. To investigate the effect of hypercholesterolemia on VCAM-1 induction after injury and the role of VCAM-1 in neointimal response to injury, we injured the carotid artery of wild-type and apolipoprotein E null (KO) mice fed normal and high cholesterol chow. We demonstrate a graded response of VCAM-1 induction as well as monocyte/macrophage infiltration by immunohistochemistry 3 days after injury that correlated with increasing circulating cholesterol levels. Three weeks after injury, KO mice fed high cholesterol chow (KO HC group) had a significantly greater neointimal formation compared with wild-type and KO mice fed normal chow (P<0.05). Inhibition of VCAM-1 function in the KO HC group by monoclonal antibody treatment significantly reduced monocyte/macrophage infiltration and neointimal formation. There was reduced alpha-actin expression in KO HC mice 7 days after injury that was partially inhibited by VCAM-1 antibody treatment. Cell migration in an in vitro injury model was partially inhibited by monoclonal VCAM-1 antibody treatment. We propose an additional role for VCAM-1 in smooth muscle cell activation and neointimal formation after injury.

Actins↗
PubMed2000

Effects of perinatal nicotine exposure on development of [3H]hemicholinium-3 binding sites in rat neonate brain.

In this study, [3H]hemicholinium-3 ([3H]HC-3) binding, which labels the presynaptic high affinity-choline transport sites, was examined in two brain regions, cerebral cortex and midbrain, of nicotine-treated and -untreated rat neonates. In nicotine-untreated neonates, [3H]HC-3 binding sites of cerebral cortex increased from 64 fmol/mg protein at postnatal day 7 to 142 fmol/mg protein at postnatal day 35. In nicotine-treated neonates, the development of [3H]HC-3 binding sites in cerebral cortex was significantly retarded, compared with control neonates on the 7th, 14th and 21st postnatal days. In parallel with this, the development of muscarinic receptor in cerebral cortex, which was detected by [3H]quinuclidinyl benzylate ([3H]QNB) binding, was also retarded by nicotine treatment. However, in midbrain, neither [3H]HC-3 nor [3H]QNB binding sites at postnatal day 14 was affected by nicotine treatment. These results strongly suggest that perinatal treatment with nicotine inhibits presynaptic and postsynaptic development of the cholinergic pathway in cerebral cortex but not in midbrain of rat neonate.

Animals↗
PubMed2000

Protective effect of Rolipram in experimental autoimmune neuritis: protection is associated with down-regulation of IFN-gamma and inflammatory chemokines as well as up-regulation of IL-4 in peripheral nervous system.

Rolipram, a phosphodiesterase type 4 inhibitor, is reported to have anti-inflammatory effects. It can markedly downregulate antigen-driven T cell proliferation and suppress TNF-(alpha and TNF-beta production in vitro and in vivo, which have led to its use in the treatment of a number of autoimmune disorders including experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN). EAN is a CD4+ T cell-mediated demyelinating autoimmune disease of peripheral nervous system (PNS) that represents an animal model for the study of the immunopathogenesis and immunotherapy of Guillain-Barré syndrome (GBS) in human. In the previous study, we reported that suppression of EAN by Rolipram was associated with down-regulated myelin antigen-induced T cell responses as well as downregulated IFN-gamma and TNF-alpha production. Here we report that EAN induced in Lewis rats by inoculation with the PNS P2 protein peptide 57-81 and Freund's complete adjuvant (FCA), was strongly suppressed by Rolipram administered twice daily intraperitoneally from day 9 post immunization (p.i.), i.e. after onset of clinical EAN to day 18 p.i. This clinical effect was associated with dose-dependent down-regulated production of IFN-gamma and the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha, MIP-2 and monocyte chemotactic protein-1(MCP-1) as well as up-regulated IL-4 production in sciatic nerve sections from Rolipram-treated EAN rats at maximum of clinical EAN, i.e. on day 14 p.i.. These findings suggest that Rolipram may be useful in certain T cell-dependent autoimmune diseases and inflammatory neuropathies. These observations call for further studies on the potential role of Rolipram in the treatment of autoimmune diseases.

Animals↗
PubMed2000

Losartan reduces collagen content and intimal thickening of iliac arteries after balloon injury in rabbits.

Intimal thickening and formation of extracellular matrix are parts of the repair process after vascular injury. Similar processes occur after coronary angioplasty. Prior studies have shown that losartan inhibits intimal thickening in rat carotid arteries following balloon injury. However, the effects of losartan in reducing the collagen content of arteries after balloon injury have not been examined. The objectives of this study were to determine the change in collagen content after balloon injury and to analyse the mechanisms of reduction of collagen content and intimal thickening. Losartan (15 mg/kg/d) was administered orally from six days before to eight weeks after balloon injury in rabbits. Collagen content was measured histologically by the use of circularly polarised images of picrosirius red-stained sections. Collagen content in arterial intima was found to be significantly lower in the losartan-treated group (n= 12) than in the control group (n= 12)(21.6% +/- 5.2% vs. 43.8% +/- 7.6%, p<0.01). Losartanreduced the collagen content in arterial intima by 50.7% area fraction compared with that of control. The morphological observation showed that the intimal area and intimal-to-medial area ratio in the losartan-treated group were significantly less than in the control group (0.27 +/- 0.13mm2 vs. 0.52 +/- 0.29 mm2,0.55 +/- 0.21 vs. 0.97 +/- 0.25, respectively, p<0.05). These data indicate that losartan reduces vascular collagen content and inhibits intimal thickening after balloon injury. The results also suggest that collagen accumulation in the intima may be an important factor in the development of the stenotic lesion and that the use of losartan may have therapeutic value to prevent stenosis after balloon injury.

Angiotensin II↗
PubMed2000

[The alpha-dissipation characteristic of human auricular points].

We researched into the dissipative characteristic of human auricular points in 40 cases of myopia. The logZ-logf curve of the dissipative characteristic of the otopoint is similiar to the dermal alpha-Dispersion in 1-100 kHz of the alternating electric field. The dissipative effect of the otopoint is generated mainly by the skin of the body surface. The characteristic frequency f0 has intimate relation to patholgic change, correlation coefficent r approximately 0.8. The f0 has characteristic reflecting pathologic change, P < 0.01. The relexation time tau signifies the space constructive characteristic of the tissue. So we suppose that the otopoint and its characteristic reflecting pathologic change essentially relate to the change of biological macromolecule conformation of the dermatic tissue under acupoint.

Acupuncture Points↗
PubMed2000

[An ADAA model and its analysis method for agronomic traits based on the double-cross mating design].

According to the double-cross mating design and using principles of Cockerham's general genetic model, a genetic model with additive, dominance and epistatic effects (ADAA model) was proposed for the analysis of agronomic traits. Components of genetic effects were derived for different generations. Monte Carlo simulation was conducted for analyzing the ADAA model and its reduced AD model by using different generations. It was indicated that genetic variance components could be estimated without bias by MINQUE(1) method and genetic effects could be predicted effectively by AUP method; at least three generations (including parent, F1 of single cross and F1 of double-cross) were necessary for analyzing the ADAA model and only two generations (including parent and F1 of double-cross) were enough for the reduced AD model. When epistatic effects were taken into account, a new approach for predicting the heterosis of agronomic traits of double-crosses was given on the basis of unbiased prediction of genotypic merits of parents and their crosses. In addition, genotype x environment interaction effects and interaction heterosis due to G x E interaction were discussed briefly.

Crosses, Genetic↗
PubMed2000

Cluster, function and promoter: analysis of yeast expression array.

Gene clusters could be derived based on expression profiles, function categorization and promoter regions. To obtain thorough understanding of gene expression and regulation, the three aspects should be combined in an organic way. In this study, we explored the possible ways to analyze the large-scale gene expression data. Three approaches were used to analyze yeast temporal expression data: 1) start from clustering on the expression profiles followed by function categorization and promoter analysis, 2) start from function categorization followed by clustering on expression profiles and promoter analysis, and 3) start from clustering on the promoter region followed by clustering on expression profiles. For clustering analysis on the time-series data, we developed a largest-first algorithm, which provide a mechanism for quality control on clusters. For promoter analysis, we developed a core-extension algorithm.

Algorithms↗
PubMed2000

[Genetic polymorphisms of eight STR loci in a Chinese Han population].

OBJECTIVE: To understand the allele structure and genetic polymorphism at eight STR loci in Chinese Han population and construct a preliminary database. METHODS: EDTA-blood specimens were collected from the unrelated individuals in Chengdu, China. The DNA samples were extracted with Chelex method and were amplified by PCR technique. The PCR products were analyzed by the PAG horizontal electrophoresis with discontinuous buffer system and by the approach of the automated fluorescence detection. RESULTS: Five STR loci consist of simple repeat motifs, while three STR loci contain complex repeat structures. The STR polymorphisms at all of the eight loci have been observed in Chinese Han population. According to the obtained data, the combined exclusion probability and the combined discrimination power for these STR markers in Chinese population are 0.9978 and 0.999 999 992, respectively. CONCLUSION: The obtained data are beneficial to understanding the population genetics of the eight STR loci in Chinese Han population. For forensic genetics, the obtained data can be used to calculate the probabilities dealing with the paternity test and the individual identification.

China↗
PubMed2000

[Polymorphisms of four STRs and their associations with IDDM in Chinese Han population].

OBJECTIVE: To obtain the polymorphic data of short tandem repeat(STR) loci of D15S657, D11S1369, D6S2420 and D6S503 in Chinese Han population and to study the association of these four STR loci with insulin-dependent diabetes mellitus(IDDM). METHODS: The polymorphisms of the four STRs were studied by polymerase chain reaction-polyacrylamide gel electrophoresis(PCR-PAGE) followed by direct sequencing of PCR products in 105 normal Chinese Hans and 48 patients with IDDM. RESULTS: Seven alleles at D15S657 locus, 5 alleles at D11S1369 locus, 7 alleles at D6S2420 locus and 4 alleles at D6S503 locus were found. No deviation from Hardy-Weinberg equilibrium was observed. The heterozygosities of these loci were 0. 7524, 0.6000, 0.6286, 0.6571 and the polymorphic information contents(PIC) 0.7616, 0.4430, 0.5345 and 0.5932, respectively. The allele frequencies of allele A(5) at D15S657 locus, allele A(5) at D11S1369 locus and allele A(4) at D6S2420 locus were increased significantly in patients with IDDM, compared to those in the control group. CONCLUSION: The four STRs, used as genetic markers, were suitable for case-control study, forensic medicine identification and population genetic study. There is an association between the polymorphisms of D15S657, D11S1369, D6S2420 and IDDM.

Adult↗
PubMed2000

[Genetic analysis on flowering and boll setting in upland cotton (Gossypium hirsutum L.). III. Genetic behavior at different developing stages].

An additive-dominant genetic model with genotype by environment interaction was employed to analyze the genetic behavior of flowering and fruiting at different development stages, with 2-year data from 4 x 4 diallel crosses. The results of variance analysis indicated that flowering and fruiting behaviors were mainly controlled by dominant effects at early period, but by additive effects later on. Compared with genetic main effects, GE interaction effects playeda minor role on the flowering and fruiting behavior. The analysis of covariance between average flower number, boll number at different development stages and total number of bolls showed that there were significant positive dominant correlation and negative or zero additive correlation before August 1st, but having the opposite results afterward. Interaction correlation existed during the whole period. It was found, by further analysis of conditional variances, that different development stages have diverse gene action intensity. The last ten days of July and the first-middle ten days of August had the highest gene action level. Time interval of investigation played a great role on exploring the law of gene action during the flowering and fruiting period; when selecting the time interval of investigation, it is necessary to contemplate the purpose of the experiment, environmental condition, investigating traits and developing period simultaneously.

Gossypium↗
PubMed2000

[Developmental genetic analysis of brown rice thickness of indica rice (Oryza sativa L.)].

Analysis of developmental genetic effects for brown rice thickness (BRT) trait in indica rice (Oryza sativa L.) at four different filling stages was conducted and a developmental genetic model and corresponding statistical approaches for quantitative traits of triploid endosperm in cereal crops was used. The results indicated that the diploid maternal plant, triploid endosperm and cytoplasmic genetic effects were important for BRT trait at all filling stages of rice and those effects were the major effect at initial medium, filling period and mature period respectively. The additive and dominance effects were the major effect alternatively at four filling stages of rice. Significant endosperm and maternal dominance effects for BRT suggest that the utilization of heterosis for BRT is viable. The results of conditional genetic variance components shown that the expression of new quantitative genes in endosperm, cytoplasm and maternal plant for BRT was found at most filling stages of rice. The gene expression was most active at the early filling stages, especially at the second stage (8-14 days after flowering). Near to mature period (22-28 days after flowering), however, the expression of genes decreased sharply and even closed. The phenomena that the genes expressed spasmodically, i.e. the net genetic effects equaled to zero in some filling stages were detected for some genetic effects. Dominance and cytoplasmic correlation coefficients were significant at 0.05 or 0.01 probability level in some filling stages meanwhile there were the most strong relationship between mature period and other periods for BRT.

Genetic Variation↗
PubMed2000

[Expression of recombinant human soluble Flt3 ligand and its in vitro effects on malignant hematopoietic cells].

OBJECTIVE: To express human soluble Flt3 ligand in a yeast expression system. Pichia pastoris, and investigate the effects of recombinant human soluble Flt3 ligand (rhFL) on the proliferation of malignant hematopoietic cells(MHC) and the effect of dexamethasone (DXM) on the expression of Flt3 receptor (Flt3R) and the rhFL induced proliferation of those cells. METHODS: An artificial gene for rhFL was synthesized by using favored genetic codons of the yeast Pichia pastoris. Flt3R was determined by flow cytometry. Proliferation of MHCs was measured by microculture tetrazolium (MTT) assay. RESULTS: 1. An expression vector, pPICZ alpha A-FL, was constructed and electroporated into Pichia pastoris. A yield of over 30 mg/L of yeast culture supernatant was obtained. The rhFL could stimulate the proliferation of Raji and HL-60 cells at concentrations of 10-100 ng/ml, but did not for most of other MHCs. 2. Flt3R was expressed in 5 of 18 MHC lines and the expression in leukemic blast cells was widespread and extremely heterogeneous. 3. The presence of the receptor on the surface of MHC did not necessarily imply a significant ligand-induced response, at least in terms of proliferation. By contrast, some Flt3R-negative MHC responded to rhFL. 4. DXM down-regulated the expression of Flt3R and inhibited the proliferation induced by rhFL in some MHC lines and fresh leukemia cell samples. CONCLUSION: A yield of 30 mg/L of rhFL was obtained. rhFL stimulated the proliferation of Raji, HL-60 cells and some fresh leukemia cells, which could be inhibited by DXM through down-regulation of Flt3R. A combination of FL and DXM might possibly serve to control hematopoietic defects in malignant hematopoietic diseases.

Antineoplastic Agents, Hormonal↗