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Biomedical subjects

Z Lu

Publications and source records attributed to Z Lu.

At least 109 records · Page 6Linked to original sources

Genome of lumpy skin disease virus.

Lumpy skin disease virus (LSDV), a member of the capripoxvirus genus of the Poxviridae, is the etiologic agent of an important disease of cattle in Africa. Here we report the genomic sequence of LSDV. The 151-kbp LSDV genome consists of a central coding region bounded by identical 2.4 kbp-inverted terminal repeats and contains 156 putative genes. Comparison of LSDV with chordopoxviruses of other genera reveals 146 conserved genes which encode proteins involved in transcription and mRNA biogenesis, nucleotide metabolism, DNA replication, protein processing, virion structure and assembly, and viral virulence and host range. In the central genomic region, LSDV genes share a high degree of colinearity and amino acid identity (average of 65%) with genes of other known mammalian poxviruses, particularly suipoxvirus, yatapoxvirus, and leporipoxviruses. In the terminal regions, colinearity is disrupted and poxvirus homologues are either absent or share a lower percentage of amino acid identity (average of 43%). Most of these differences involve genes and gene families with likely functions involving viral virulence and host range. Although LSDV resembles leporipoxviruses in gene content and organization, it also contains homologues of interleukin-10 (IL-10), IL-1 binding proteins, G protein-coupled CC chemokine receptor, and epidermal growth factor-like protein which are found in other poxvirus genera. These data show that although LSDV is closely related to other members of the Chordopoxvirinae, it contains a unique complement of genes responsible for viral host range and virulence.

Animals↗

The genome of turkey herpesvirus.

Here we present the first complete genomic sequence of Marek's disease virus serotype 3 (MDV3), also known as turkey herpesvirus (HVT). The 159,160-bp genome encodes an estimated 99 putative proteins and resembles alphaherpesviruses in genomic organization and gene content. HVT is very similar to MDV1 and MDV2 within the unique long (UL) and unique short (US) genomic regions, where homologous genes share a high degree of colinearity and their proteins share a high level of amino acid identity. Within the UL region, HVT contains 57 genes with homologues found in herpes simplex virus type 1 (HSV-1), six genes with homologues found only in MDV, and two genes (HVT068 and HVT070 genes) which are unique to HVT. The HVT US region is 2.2 kb shorter than that of MDV1 (Md5 strain) due to the absence of an MDV093 (SORF4) homologue and to differences at the UL/short repeat (RS) boundary. HVT lacks a homologue of MDV087, a protein encoded at the UL/RS boundary of MDV1 (Md5), and it contains two homologues of MDV096 (glycoprotein E) in the RS. HVT RS are 1,039 bp longer than those in MDV1, and with the exception of an ICP4 gene homologue, the gene content is different from that of MDV1. Six unique genes, including a homologue of the antiapoptotic gene Bcl-2, are found in the RS. This is the first reported Bcl-2 homologue in an alphaherpesvirus. HVT long repeats (RL) are 7,407 bp shorter than those in MDV1 and do not contain homologues of MDV1 genes with functions involving virulence, oncogenicity, and immune evasion. HVT lacks homologues of MDV1 oncoprotein MEQ, CxC chemokine, oncogenicity-associated phosphoprotein pp24, and conserved domains of phosphoprotein pp38. These significant genomic differences in and adjacent to RS and RL regions likely account for the differences in host range, virulence, and oncogenicity between nonpathogenic HVT and highly pathogenic MDV1.

Amino Acid Sequence↗

Genome sequence of a baculovirus pathogenic for Culex nigripalpus.

In this report we describe the complete genome sequence of a nucleopolyhedrovirus that infects larval stages of the mosquito Culex nigripalpus (CuniNPV). The CuniNPV genome is a circular double-stranded DNA molecule of 108,252 bp and is predicted to contain 109 genes. Although 36 of these genes show homology to genes from other baculoviruses, their orientation and order exhibit little conservation relative to the genomes of lepidopteran baculoviruses. CuniNPV genes homologous to those from other baculoviruses include genes involved in early and late gene expression (lef-4, lef-5, lef-8, lef-9, vlf-1, and p47), DNA replication (lef-1, lef-2, helicase-1, and dna-pol), and structural functions (vp39, vp91, odv-ec27, odv-e56, p6.9, gp41, p74, and vp1054). Auxiliary genes include homologues of genes encoding the p35 antiapoptosis protein and a novel insulin binding-related protein. In contrast to these conserved genes, CuniNPV lacks apparent homologues of baculovirus genes essential (ie-1 and lef-3) or stimulatory (ie-2, lef-7, pe38) for DNA replication. Also, baculovirus genes essential or stimulatory for early-late (ie-1, ie-2), early (ie-0 and pe-38), and late (lef-6, lef-11, and pp31) gene transcription are not identifiable. In addition, CuniNPV lacks homologues of genes involved in the formation of virogenic stroma (pp31), nucleocapsid (orf1629, p87, and p24), envelope of occluded virions (odv-e25, odv-e66, odv-e18), and polyhedra (polyhedrin/granulin, p10, pp34, and fp25k). A homologue of gp64, a budded virus envelope fusion protein, was also absent, although a gene related to the other category of baculovirus budded virus envelope proteins, Ld130, was present. The absence of homologues of occlusion-derived virion (ODV) envelope proteins and occlusion body (OB) protein (polyhedrin) suggests that both CuniNPV ODV and OB may be structurally and compositionally different from those found in terrestrial lepidopteran hosts. The striking difference in genome organization, the low level of conservation of homologous genes, and the lack of many genes conserved in other baculoviruses suggest a large evolutionary distance between CuniNPV and lepidopteran baculoviruses.

Animals↗

African swine fever virus multigene family 360 and 530 genes are novel macrophage host range determinants.

Pathogenic African swine fever virus (ASFV) isolates primarily target cells of the mononuclear-phagocytic system in infected swine and replicate efficiently in primary macrophage cell cultures in vitro. ASFVs can, however, be adapted to grow in monkey cell lines. Characterization of two cell culture-adapted viruses, MS16 and BA71V, revealed that neither virus replicated in macrophage cell cultures. Cell viability experiments and ultrastructural analysis showed that infection with these viruses resulted in early macrophage cell death, which occurred prior to viral progeny production. Genomic cosmid clones from pathogenic ASFV isolate E70 were used in marker rescue experiments to identify sequences capable of restoring MS16 and BA71V growth in macrophage cell cultures. A cosmid clone representing a 38-kbp region at the left terminus of the genome completely restored the growth of both viruses. In subsequent fine-mapping experiments, an 11-kbp subclone from this region was sufficient for complete rescue of BA71V growth. Sequence analysis indicated that both MS16 and BA71V had significant deletions in the region containing members of multigene family 360 (MGF 360) and MGF530. Deletion of this same region from highly pathogenic ASFV isolate Pr4 significantly reduced viral growth in macrophage cell cultures. These findings indicate that ASFV MGF360 and MGF530 genes perform an essential macrophage host range function(s) that involves promotion of infected-cell survival.

African Swine Fever Virus↗

Epidermal growth factor-induced tumor cell invasion and metastasis initiated by dephosphorylation and downregulation of focal adhesion kinase.

Upregulated epidermal growth factor (EGF) receptor (EGFR) expression and EGFR-induced signaling have been correlated with progression to invasion and metastasis in a wide variety of carcinomas, but the mechanism behind this is not well understood. We show here that, in various human carcinoma cells that overexpress EGFR, EGF treatment induced rapid tyrosine dephosphorylation of focal adhesion kinase (FAK) associated with downregulation of its kinase activity. The downregulation of FAK activity was both required and sufficient for EGF-induced refractile morphological changes, detachment of cells from the extracellular matrix, and increased tumor cell motility, invasion, and metastasis. Tumor cells with downregulated FAK activity became less adherent to the extracellular matrix. However, once cells started reattaching, FAK activity was restored by activated integrin signaling. Moreover, this process of readhesion and spreading could not be abrogated by further EGF stimulation. Interruption of transforming growth factor alpha-EGFR autocrine regulation with an EGFR tyrosine kinase inhibitor led to a substantial increase in FAK tyrosine phosphorylation and inhibition of tumor cell invasion in vitro. Consistent with this, FAK tyrosine phosphorylation was reduced in cells from tumors growing in transplanted, athymic, nude mice, which have an intact autocrine regulation of the EGFR. We suggest that the dynamic regulation of FAK activity, initiated by EGF-induced downregulation of FAK leading to cell detachment and increased motility and invasion, followed by integrin-dependent reactivation during readhesion, plays a role in EGF-associated tumor invasion and metastasis.

3T3 Cells↗

The change and significance of the Na+-K+-ATPase alpha-subunit in ouabain-hypertensive rats.

Ouabain has recently been identified as an endogenous Na+-K+ pump inhibitor having a close association with hypertension. However, some patients with hypertention do not show high levels of endogenous ouabain (EO), and patients with high EO levels do not necessarily suffer from hypertention. It is believed that the Na+-K+-ATPase activity in essential hypertension does not undergo homogenous change. The present study was designed, therefore, to investigate the expression and the significance of the Na+-K+-ATPase alpha-subunit isoforms in kidney tissue in ouabain-hypertensive rats. Ouabain was administered chronically to establish a model of ouabain-hypertensive rats. Biochemical analysis, cytobiology and sABC immunohistochemistry were they used to assay for expression of Na+-K+-ATPase alpha-subunit isoforms in kidney tissue. After the first week of receiving ouabain, 65% (n=13) of rats had hypertension. After the second week, the blood pressure of these 13 hypertensive rats was increased significantly compared to the baseline and control levels (p<0.05). The plasma renin activity was normal, and angiotensin II and aldosterone levels were increased significantly in these rats (p<0.05). But in the other 35% (n=7) of rats of the experimental group, there was no apparent increase in blood pressure after receiving ouabain. The plasma ouabain level in the non-hypertensive subgroup was significantly higher than that in the hypertensive subgroup, but the 86Rb intake and the number of 3H-ouabain binding sites did not decrease. The Na+-K+-ATPase activity showed non-homogeneous changes. In hypertensive rats, the expression levels of ouabain paralleled the degree of hypertension (r=0.88, p<0.05). The positive granules were mainly scattered in the cytoblastoma of the reticular zone of adrenal cortex. There were thus different levels of expression of Na+-K+-ATPase alpha-subunit isoforms in this model. In the hypertension subgroup the alpha1 was most strongly expressed, followed by the alpha2 and alpha3 isforms. But in the non-hypertensive subgroup the order was alpha3 > alpha2 > alpha1. The positive granular was mainly scattered in the convoluted tubules of the kidney. These results suggest that the high level of ouabain and the change of the Na+-K+-ATPase alpha-subunit isoforms may play a critical role in hypertension.

Adrenal Glands↗

Novel tumor-promoting property of tamoxifen.

The tumor-promoting phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) cooperates with c-Src overexpression to transform rat fibroblasts. TPA transforms c-Src-overexpressing cells by depleting the delta isoform of protein kinase C (PKCdelta). Tamoxifen, which has both estrogen-mimetic and estrogen-antagonist properties, has been widely used to improve the prognosis of breast cancer patients. However, with extended use, there is an increased risk for endometrial and other cancers that can be observed within 10 years of treatment. We report here that tamoxifen, similar to TPA, cooperates with c-Src overexpression to transform 3Y1 rat fibroblasts. Tamoxifen induced both DNA synthesis and anchorage-independent cell proliferation in c-Src-overexpressing, but not in parental, 3Y1 rat fibroblasts. Tamoxifen also induced an association between c-Src and PKCdelta that resulted in the tyrosine phosphorylation and down-regulation of PKCdelta. These phenotypes were not induced by estrogen, indicating that the effect of tamoxifen was in addition to any estrogen-mimetic effects. Thus, in addition to the hyperplasia-inducing capability of an estrogen-mimetic, tamoxifen has an additional tumor-promoting capability similar to that of TPA. The dual tumor-promoting capability of both estrogen- and TPA-mimetic properties for tamoxifen may contribute to the increased incidence of endometrial cancers observed in the relatively short exposure period of <10 years.

Animals↗

[The sieving performance of a new polyethersulfone hollow fiber plasma fractionation membrane].

Plasma fractionation membrane is very important in double filtration plasmapheresis. We studied a new polyethersulfone hollow fiber membrane plasma fractionator and evaluated the effect of time, transmembrane pressure (TMP) and mean shear rate on the sieving coefficient (SC) during membrane plasma fractionation. The sieving coefficients of various proteins reached their maximum values at 40 min at the plasma flow rate QI = 30 ml/min and plasma filtrated flow rate QF = 20 ml/min. The QF increased with the increase of TMP, and the point of the intersection of the curve of the QF vs. TMP and the SC vs. TMP was regarded as the ideal condition for plasma fractionation. The plasma filtrated rate PFR = QF/QI = 0.6-0.7. The TMP changed with the change of the mean shear rate, and the mean shear rate had little effect on the SC. The data is of significance to the application of plasma fractionation membrane.

Membranes, Artificial↗

[Anaerobic biological treatment of Lincomycin production wastewater].

The high-strength Lincomycin production wastewater containing toxic and refractory substances treated by lab-scale mesophilic UASB reactor was described. When the reactor was operated in influent COD 8000-14,000 mg/L and HRT 10 h, the volumetric loading rate and COD removal rate could reach 20-35 kg/(m3.d) and 50%-55%, respectively. The granular sludge might be formatted by using a bit longer acclimation time, adjusting and maintaining fairly high surface hydraulic loading rate of 0.2-0.4 m3/(m2.h), influent COD of 2000-3000 mg/L and sludge loading rate of 0.2-0.5 kg/(kg.d). The anaerobic kinetic constants of Vmax and Ks for the wastewater treatment were 1.3 d-1 and 8133 mg/L, respectively. The non-biodegradable substances accounted for about 30% of total COD, which was the important factor of relative low COD removal rate for the wastewater.

Anaerobiosis↗

Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1.

The phosphatidylinositol 3-kinase (PI3K) signaling pathway has inherent oncogenic potential. It is up-regulated in diverse human cancers by either a gain of function in PI3K itself or in its downstream target Akt or by a loss of function in the negative regulator PTEN. However, the complete consequences of this up-regulation are not known. Here we show that insulin and epidermal growth factor or an inactivating mutation in the tumor suppressor PTEN specifically increase the protein levels of hypoxia-inducible factor (HIF) 1alpha but not of HIF-1beta in human cancer cell lines. This specific elevation of HIF-1alpha protein expression requires PI3K signaling. In the prostate carcinoma-derived cell lines PC-3 and DU145, insulin- and epidermal growth factor-induced expression of HIF-1alpha was inhibited by the PI3K-specific inhibitors LY294002 and wortmannin in a dose-dependent manner. HIF-1beta expression was not affected by these inhibitors. Introduction of wild-type PTEN into the PTEN-negative PC-3 cell line specifically inhibited the expression of HIF-1alpha but not that of HIF-1beta. In contrast to the HIF-1alpha protein, the level of HIF-1alpha mRNA was not significantly affected by PI3K signaling. Vascular endothelial growth factor reporter gene activity was induced by insulin in PC-3 cells and was inhibited by the PI3K inhibitor LY294002 and by the coexpression of a HIF-1 dominant negative construct. Vascular endothelial growth factor reporter gene activity was also inhibited by expression of a dominant negative PI3K construct and by the tumor suppressor PTEN.

Androstadienes↗

Effects of ouabain and digoxin on gene expression of sodium pump alpha-subunit isoforms in rat myocardium.

OBJECTIVE: To compare the effects of ouabain and digoxin on the gene expression of sodium pump alpha-subunit isoforms in the myocardium of rats. METHODS: Normal Sprague-Dawley (SD) rats were injected with ouabain (20 micrograms.kg-1.d-1, i.p.), digoxin (32 micrograms.kg-1.d-1, i.p.) and normal saline (NS) once a day, respectively, and indirect systolic blood pressure was recorded once a week. Six weeks later, all of the rats were killed, and sodium pump alpha 1-, alpha 2-, and alpha 3-subunit mRNA levels in the myocardium were detected with the reverse transcription polymerase chain reaction (RT-PCR) method. RESULTS: The systolic blood pressure of the rats infused with ouabain increased significantly at the end of week 6 (132.6 +/- 9.0 mm Hg vs 115.7 +/- 8.2 mm Hg, P < 0.01), while no difference in blood pressure was found between the digoxin group and the NS group. The expression of sodium pump alpha-subunit isoforms in the ventricular myocardium was regulated by either ouabain or digoxin. Both ouabain and digoxin stimulated expression of the alpha 3-isoform, whereas alpha 2 was unchanged in those two groups. alpha 1-isoform expression decreased in the ouabain group and was unchanged in the digoxin group. CONCLUSIONS: These results suggest that both ouabain and digoxin could regulate sodium pump alpha-subunit isoform expression, which might be related to the physiological roles of endogenous ouabain and might be responsible for the difference in the pharmacological and toxicological effects of ouabain and digoxin, including their effects on blood pressure.

Animals↗

[Start-up of full-scale UASB reactors].

The UASB reactors treating high-temperature citric acid wastewater could be started up in the alternation of mesophilic and thermophilic ranges because the local climate changed greatly by seasons. The reactors were started up in mesophilic range, and the total efficiency of the two-stage reactors reached 77%-86%; when the temperature of reactors reached 44 degrees C-45 degrees C, the reactors were operated in thermophilic range, and the total efficiency of the two-stage reactors reached 84%-93%; the reactors were re-operated in mesophilic range after closing about 38 days, and the total efficiency of the two-stage reactors reached 82%-96%. The start-up in the alternation of mesophilic and thermophilic ranges of the full-scale UASB reactors and the characteristics of mesophilic and thermophilic granular sludge were reported in this paper.

Citric Acid↗

[Detection of HPV in human esophageal cancer in high-incidence area and its correlation with p53 expression].

OBJECTIVE: To investigate the association of HPV with the development of esophageal cancer (EC) in a high-incidence area of EC and to elucidate its correlation with p53 overexpression. METHODS: Thirty EC specimens were collected from Anyang, Henan. Four pairs of primers were designed to perform in situ hybridization (ISH) and in situ PCR(ISPCR). Immunohistochemical staining was used to detect p53. RESULTS: HPV L1, HPV-16-E6 and HPV-16-E7 was detected in 10.0%, 60.0% and 63.3% of the EC samples, respectively. The detection rate of HPV-18-E6 was low(6.7%) and no EBV was detected. Overexpression of p53 was identified in 73.3% EC. With ISH or ISPCR, HPV-16-E6 was positive in 53.3% of EC. CONCLUSION: The low detection rate of HPV L1 and high detection rate of HPV-16-E6 and E7 genes suggest that HPV may be partially lost when integrating into tumor cell genome, while E6 and E7 genes are intact. The results support a role of HPV-16 in the pathogenesis of EC in high incidence area. Although p53 mutation takes an important part in tumor pathogenesis, it is not consistent with the HPV existence in the EC cells.

Esophageal Neoplasms↗

[Detection of the expression of Smad4, transforming growth factor beta(1) and beta receptor II proteins in paraffin-embedded human pancreatic cancer tissues].

OBJECTIVE: To explore the relationships between Smad4, TGF beta1 and TbetaR II in the TGF-beta pathway and the possible mechanisms by which they effect pancreatic carcinoma. METHODS: The expression of Smad4, TGF beta1 and TbetaR II in paraffin embedded pancreatic carcinoma tissues was detected by using antibodies against Smad4, TGF beta1 and TbetaR II with EnVision immunohistochemistry. RESULTS: The positive rates of Smad4, TGF beta1 and TbetaR II were 58.93% (33), 66.07% (37) and 60.71% (34), respectively. The positive rates of the above three proteins in matched normal pancreatic tissues were 89.29% (50), 25.00% (14) and 25.00% (14) respectively. There was a significant relationship between the expression of TGF beta1, clinical stage and the metastasis of the tumor (P < 0.05). There was also a significant relationship between the expressions of TGF beta1 and TbetaR II (P < 0.05). CONCLUSIONS: The expression of Smad4 in pancreatic carcinoma tissue is significantly decreased but the expression of TGF beta1 and TbetaR II are increased. Smad4 may play an important role in the regulation of TGFbeta inducible gene expression and subsequent growth inhibition, but TGFbeta may also act in a Smad4-independent manner.

DNA-Binding Proteins↗

[Relative study of soluble syndecan-1 and prognosis of patients with multiple myeloma].

OBJECTIVE: To investigate the role of soluble syndecan-1 in the pathogenesis of human multiple myeloma (MM). METHODS: Serum level of soluble syndecan-1 of patients with MM and plasma cell leukemia was determined by ELISA. RESULTS: (1) The median serum soluble syndecan-1 concentrations of MM patients and controls were 111 ng/ml (41 - 6,300 mg/L) and 63 mg/L (10 - 163 mg/L), respectively (P < 0.005). (2) For 47 myeloma patients, increased serum syndecan-1 concentrations at diagnosis were associated with a poor prognosis. Patients with serum syndecan-1 levels below or above 166 mg/L had significantly different survival times (median > 48 months or < 18 months, respectively, P < 0.0001). (3) Serum soluble syndecan-1 levels were correlated with beta-2 microglobulin concentrations and the percentage of plasma cell. CONCLUSION: Serum levels of circulating soluble syndecan-1 correlated with tumor mass and may exert pleiotropic effects on myeloma cell behavior.

Humans↗

[Transconjunctival approach to the fractures of the orbital floor and infraorbital rim].

OBJECTIVE: To study the surgical approach to the orbital floor and infraorbital rim. METHOD: 15 cases of fractures of the orbital floor and infraorbital rim were treated with the transconjunctival approach. RESULT: All fractures of the orbital floor and infraorbital rim were repositioned and fixed through transconjunctival approach. Except for 1 case with mild canthal malposition, no other complication was observed. CONCLUSION: The transconjunctival approach can provide adequate exposure of the infraorbital rim and orbital floor without scar formation in the face.

Adolescent↗

[Different sampling method affects the voice assessment results for the patient with vocal polyp].

OBJECTIVE: In order to definitude the influence caused by the different sampling in voice assessment. METHOD: We comparing the results acquired by total section and subsection sampling. RESULT: The results acquired by subsection tended to normal more than those acquired by total section. CONCLUSION: Subsection sampling voice assessment might conceal the degree of the disease state of patients.

Adult↗