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Biomedical subjects

L Zhang

Publications and source records attributed to L Zhang.

At least 289 records · Page 16Linked to original sources
PubMed2001

[Expression of vascular endothelial growth factor in primary esophageal squamous cell carcinoma and its significance in angiogenesis and prognosis of the tumor].

OBJECTIVE: To study the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in primary esophageal squamous cell carcinoma and to clarify the association of VEGF expression with the angiogenesis and prognosis of this tumor. METHODS: VEGF expression and MVD in 82 specimens of primary esophageal squamous cell carcinoma, resected from Jan 1981 through May 1994, were examined by immunohistochemistry staining (SP method), using anti-VEGF polyclonal antibody and anti-factor VIII monoclonal antibody. The relationship between VEGF expression and MVD and postoperative survival of patient was analyzed. RESULTS: Fifty-two out of the eighty-two specimens of esophageal squamous cell carcinoma (63.4%) showed positive expression of VEGF. The median of MVD in tumor was 37/mm2 (9-150/mm2). There was a close correlation between MVD and VEGF expression (P = 0.001). The survival rate of patients with high MVD in the tumor was significantly lower than that of patients with low MVD (P = 0.017). The higher the level of expression of VEGF in tumor, the poorer prognosis for the patients (P = 0.000). CONCLUSION: In primary esophageal squamous cell carcinoma, angiogenesis is mediated mainly by VEGF. VEGF is associated with tumor progression and may increase the malignancy via angiogenesis. It may be used as an independent indicator for prognosis of esophageal squamous cell carcinoma.

Adult↗
PubMed2001

Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice.

Heme oxygenase (HO)-1 degrades the pro-oxidant heme and generates carbon monoxide and antioxidant bilirubin. We have previously shown that in response to hypoxia, HO-1-null mice develop infarcts in the right ventricle of their hearts and that their cardiomyocytes are damaged by oxidative stress. To test whether HO-1 protects against oxidative injury in the heart, we generated cardiac-specific transgenic mice overexpressing different levels of HO-1. By use of a Langendorff preparation, hearts from transgenic mice showed improved recovery of contractile performance during reperfusion after ischemia in an HO-1 dose-dependent manner. In vivo, myocardial ischemia and reperfusion experiments showed that infarct size was only 14.7% of the area at risk in transgenic mice compared with 56.5% in wild-type mice. Hearts from these transgenic animals had reduced inflammatory cell infiltration and oxidative damage. Our data demonstrate that overexpression of HO-1 in the cardiomyocyte protects against ischemia and reperfusion injury, thus improving the recovery of cardiac function.

Animals↗
PubMed2001

Migration of neutral solutes by double stepwise gradient elution in capillary electrochromatography.

Characteristics of electroosmotic flow (EOF) and the migration of neutral solutes under double stepwise gradient elution in capillary electrochromatography were studied systematically. EOF velocity proved to be the function of operation time changing with the introduction of the second mobile phase. Accordingly, the retention of components also changed. The migration of neutral solutes was studied under the following three situations; A, components eluted when the column was filled only with the first kind of mobile phase; B, solutes eluted still in the first kind of mobile phase while at that time two kinds of mobile phase coexisted in the column and C, samples eluted in the second kind of mobile phase. Equations to describe the retention times of components under these three kinds of conditions were deduced and applied to predict the retention times of 12 aromatic compounds. Relative errors between experimental and calculated values were below 5.0%, which proved the reliability of the equations. In addition, parameters that might affect the retention time of solutes, such as the transferring time of mobile phase vials, the capacity factors of components and EOF velocities two steps were studied systematically.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2001

[Microanatomical study of transcerebellomedullary fissure approach].

OBJECTIVE: To study the anatomy of structures on the way to the fourth ventricle of cerebrum via transcerebellomedullary fissure approach. METHODS: Ten cadaveric heads fixed with formalin and with their arteries and veins perfused with color latex were dissected with nicrosurgical anatomical skills to observe the structure of tela choroida, fourth ventricle roof, rhomboid fossa, and posterior inferior cerebellar artery (PICA) and its branches. RESULTS: Via the transcerebellomedullary fissure approach, any part of the rhomboid fossa can be reached by exposing and separating the tela choroida, inferior medullary velum, and nodule of vermis, and the dorsolateral part of pons and of medulla obligata can be reached by lateral recess. CONCLUSION: The fourth ventricle of cerebrum and the lateral parts of brainstem can be reached via transcerebellomedullary fissure approach through normal anatomical spaces. The tonsilomedullary and telovelotonsillar segments of PICA are the most important vessels in the transcerebellomedullary fissure approach.

Brain Stem↗
PubMed2001

Estrogen protects against beta-amyloid-induced neurotoxicity in rat hippocampal neurons by activation of Akt.

The cellular mechanisms underlying the neuroprotective effects of estrogen are only beginning to be elucidated. Here we examined the role of protein kinase B (Akt) activation in 17beta-estradiol (E2) inhibition of beta-amyloid peptide (31-35) (Abeta31-35)-induced neurotoxicity in cultured rat hippocampal neurons. Abeta31-35 (25-30 betaM) significantly decreased the total number of microtubule associated protein-2 positive cells (MAP2+). This decrease was significantly reversed by pre-treatment with 100 nM E2. Further, 100 nM E2 alone significantly increased the total number of protein kinase B and microtubule associated protein-2 positive cells compared with controls. Such E2-induced increases were inhibited by LY294002 (20 microM), a specific PI3-K inhibitor, as well as by tamoxifen, an estrogen receptor antagonist/selective estrogen receptor modulator. These results indicate that the neuroprotective effects of E2 may be mediated at least in part via estrogen receptor-mediated protein kinase B activation.

Alzheimer Disease↗
PubMed2001

Isolation and characterization of the human stearoyl-CoA desaturase gene promoter: requirement of a conserved CCAAT cis-element.

Stearoyl-CoA desaturase is the rate-limiting enzyme in the production of mono-unsaturated fatty acids. We have recently cloned and characterized the human Scd cDNA and SCD (the stearoyl-CoA desaturase structural gene) on chromosome 10, as well as the non-transcribed pseudogene on chromosome 17. In order to further define SCD regulation and function, we have isolated and characterized the promoter of the structural gene. Screening of chromosome-10-specific libraries resulted in the isolation of 4.1 kb of SCD sequence upstream of the translation start site. Binding sites for transcription factors critical for mouse Scd1 and Scd2 promoter activity, such as sterol-regulated-element-binding protein and nuclear factor Y, were present in the human SCD promoter (Scd is the mouse stearoyl-CoA desaturase gene). Deletion analysis in HaCaT keratinocytes identified a critical region for promoter activity between nts 496-609 upstream of the translation start site. Site-directed mutagenesis of binding sites in this region identified the CCAAT box as the critical cis-element for SCD promoter activity. An electrophoretic mobility-shift assay confirmed that this element binds nuclear proteins from HaCaT keratinocytes. The polyunsaturated-fatty-acid (PUFA) response element, previously identified in the promoters of mouse Scd1 and Scd2, was found to be conserved in the human SCD promoter, and contained the critical CCAAT cis-element. A minimal promoter construct including this region was responsive to fatty acids, with oleate and linoleate decreasing transcription and stearate increasing it. These studies indicate that CCAAT-box-binding proteins activate SCD transcription in cultured keratinocytes and that fatty acids modulate transcription, most likely through the conserved PUFA response element.

Amino Acid Sequence↗
PubMed2001

Hyaluronan synthase 3 overexpression promotes the growth of TSU prostate cancer cells.

Hyaluronan synthase 3 (HAS3) is responsible for the production of both secreted and cell-associated forms of hyaluronan and is the most active of the three isoforms of this enzyme in adults. In this study, the cDNA for human HAS3 was cloned and characterized. The open reading frame consisted of 1659 bp coding for 553 amino acids with a deduced molecular weight of about 63,000 and isoelectric pH of 8.70. The sequence of human HAS3 displayed a 53% identity to HAS1 and a 67% identity to HAS2. It also contained a signal peptide and six potential transmembrane domains, suggesting that it was associated with the plasma membrane. To evaluate the physiological role of human HAS3, expression vectors for this protein were transfected into TSU cells (a prostate cancer cell line), and the phenotypic changes in these cells were examined. The enhanced expression of hyaluronan in the transfected cells was demonstrated by dot blot analysis and ELISA. These cells were found to differ from their vector-transfected counterparts with respect to the following: (a) they grew at a faster rate in high (but not low) density cultures; (b) conditioned media from these cells stimulated the proliferation and migration of endothelial cells; (c) when placed on the chorioallantoic membrane of chicken embryos, these cells formed large, dispersed xenografts, whereas the control transfectants formed compact masses; and (d) when injected s.c. into nude mice, the xenografts formed by HAS3 transfectants were bigger than those formed by control transfectants. Histological examination of these xenografts revealed the presence of extracellular hyaluronan that could act as conduits for the diffusion of nutrients. In addition, they had a greater number of blood vessels. However, the HAS3-transfected TSU cells did not display increased metastatic properties as judged by their ability to form lung masses after i.v. injection. These results suggested that the HAS3-induced overexpression of hyaluronan enhanced tumor cell growth, extracellular matrix deposition, and angiogenesis but was not sufficient to induce metastatic behavior in TSU cells.

Allantois↗
PubMed2001

Superconductivity in 4 angstrom single-walled carbon nanotubes.

Investigation of the magnetic and transport properties of single-walled small-diameter carbon nanotubes embedded in a zeolite matrix revealed that at temperatures below 20 kelvin, 4 angstrom tubes exhibit superconducting behavior manifest as an anisotropic Meissner effect, with a superconducting gap and fluctuation supercurrent. The measured superconducting characteristics display smooth temperature variations owing to one-dimensional fluctuations, with a mean-field superconducting transition temperature of 15 kelvin. Statistical mechanic calculations based on the Ginzburg-Landau free-energy functional yield predictions that are in excellent agreement with the experiments.

Journal Article↗
PubMed2001

Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism.

The Ser/Thr kinase Raf-1 is a protooncogene product that is a central component in many signaling pathways involved in normal cell growth and oncogenic transformation. Upon activation, Raf-1 phosphorylates mitogen-activated protein kinase kinase (MEK), which in turn activates mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERKs), leading to the propagation of signals. Depending on specific stimuli and cellular environment, the Raf-1--MEK--ERK cascade regulates diverse cellular processes such as proliferation, differentiation, and apoptosis. Here, we describe a MEK--ERK-independent prosurvival function of Raf-1. We found that Raf-1 interacts with the proapoptotic, stress-activated protein kinase ASK1 (apoptosis signal-regulating kinase 1) in vitro and in vivo. Deletion analysis localized the Raf-1 binding site to the N-terminal regulatory fragment of ASK1. This interaction allows Raf-1 to act independently of the MEK--ERK pathway to inhibit apoptosis. Furthermore, catalytically inactive forms of Raf-1 can mimic the wild-type effect, raising the possibility of a kinase-independent function of Raf-1. Thus, Raf-1 may promote cell survival through its protein-protein interactions in addition to its established MEK kinase function.

Animals↗
PubMed2001

Electrically-assisted transdermal delivery of buprenorphine.

The objective of this study was to explore the electrically assisted transdermal delivery of buprenorphine. Oral delivery of buprenorphine, a synthetic opiate analgesic, is less efficient due to low absorption and large first-pass metabolism. While transdermal delivery of buprenorphine is expected to avoid the first-pass effect and thereby be more bioavailable, use of electrical enhancement techniques (iontophoresis and/or electroporation) could provide better programmability. Another use of buprenorphine is for opiate addiction therapy. However, a patch type device is subject to potential abuse as it could be removed by the addict. This abuse can be prevented if drug particles are embedded in the skin. The feasibility of doing so was investigated by electro-incorporation. Buprenorphine HCl (1 mg/ml) in citrate buffer (pH 4.0) was delivered in vitro across human epidermis via iontophoresis using a current density of 0.5 mA/cm(2) and silver-silver chloride electrodes. Electroporation pulses were also applied in some experiments. For electro-incorporation, drug microspheres or particles were driven into full thickness human skin by electroporation. It was observed that the passive transdermal flux of buprenorphine HCl was significantly enhanced by iontophoresis under anodic polarity. The effectiveness of electro-incorporation seemed inconclusive, with pressure also playing a potential role. Delivery was observed with electro-incorporation, but the results were statistically not different from the corresponding controls.

Administration, Cutaneous↗
PubMed2001

[The transcription and expression of IL-18 gene in HBV infectors].

OBJECTIVE: To evaluate the possible roles of interleukin 18 (IL-18) in hepatitis B virus (HBV) infection. METHODS: Peripheral blood lymphocytes from 3 groups of HBV infectors (including 15 asymptomatic carriers, 30 patients with chronic hepatitis, 12 patients with fulminant hepatitis) and 10 blood donors (as normal controls) were analyzed. The transcription and expression of IL-18 in PBMC were assessed by semi-quantitive reverse transcription polymerase chain reaction and flow cytometry. RESULTS: (1) There were significant differences in the transcription and expression levels of IL-18 between each group of HBV infectors. Interestingly, it was highest in fulminant hepatitis group, and lowest in asymptomatic carrier group. However there was no significant difference between chronic hepatitis and normal controls. The severity of disease was accompanied with the elevation of IL-18 production. (2) The severity degree of liver inflammation in chronic hepatitis was ccompanied with the elevation of IL-18 production. (3) The transcription and expression of IL-18 in chronic hepatitis B correlated with serum ALT positively (r = 0.54, P < 0.01; r = 0.63, P < 0.01). (4) There was a positive correlation in transcription and expression of IL-18 in each group of HBV infectors (asymptomatic carrier r = 0.980, P < 0.001; chronic hepatitis r = 0.910, P < 0.001; fulminant hepatitis r = 0.975, P < 0.001). CONCLUSION: IL-18 may take part in the host immunity against HBV,and relate to the inflammation degree of liver.

Female↗
PubMed2001

Interaction between aldolase and vacuolar H+-ATPase: evidence for direct coupling of glycolysis to the ATP-hydrolyzing proton pump.

Vacuolar H(+)-ATPases (V-ATPases) are essential for acidification of intracellular compartments and for proton secretion from the plasma membrane in kidney epithelial cells and osteoclasts. The cellular proteins that regulate V-ATPases remain largely unknown. A screen for proteins that bind the V-ATPase E subunit using the yeast two-hybrid assay identified the cDNA clone coded for aldolase, an enzyme of the glycolytic pathway. The interaction between E subunit and aldolase was confirmed in vitro by precipitation assays using E subunit-glutathione S-transferase chimeric fusion proteins and metabolically labeled aldolase. Aldolase was isolated associated with intact V-ATPase from bovine kidney microsomes and osteoclast-containing mouse marrow cultures in co-immunoprecipitation studies performed using an anti-E subunit monoclonal antibody. The interaction was not affected by incubation with aldolase substrates or products. In immunocytochemical assays, aldolase was found to colocalize with V-ATPase in the renal proximal tubule. In osteoclasts, the aldolase-V-ATPase complex appeared to undergo a subcellular redistribution from perinuclear compartments to the ruffled membranes following activation of resorption. In yeast cells deficient in aldolase, the peripheral V(1) domain of V-ATPase was found to dissociate from the integral membrane V(0) domain, indicating direct coupling of glycolysis to the proton pump. The direct binding interaction between V-ATPase and aldolase may be a new mechanism for the regulation of the V-ATPase and may underlie the proximal tubule acidification defect in hereditary fructose intolerance.

Animals↗
PubMed2001

Potential ionic mechanism for repolarization differences between canine right and left atrium.

Experimental and clinical evidence suggests a critical role for the left atrium (LA) in atrial fibrillation (AF). In animal models, repolarization is faster in the LA than in the right atrium (RA), leading to more stable reentry circuits with a shorter intrinsic period in the LA. The ionic mechanisms underlying LA-RA repolarization differences are unknown. Therefore, we evaluated ionic currents and action potentials (APs) with the whole-cell patch clamp in isolated canine atrial myocytes. The density of the rapid delayed rectifier current (I(Kr)) was greater in the LA (eg, 1.83+/-0.10 pA/pF at +20 mV) than in the RA (1.15+/-0.07 pA/pF, P<0.01; n=16 cells per group). The slow and ultrarapid delayed rectifier, the inward rectifier, L-type Ca(2+), and transient outward K(+) currents were all comparable in the LA and RA. There were no differences in kinetic or voltage-dependent properties of currents in LA versus RA. Western blots of ether-a-go-go-related gene (ERG) protein in three RA and corresponding LA regions showed significantly greater ERG expression in LA. AP duration (APD) was shorter in the LA versus RA in both isolated cells and multicellular preparations, and the effective refractory period (ERP) was shorter in the LA compared with the RA in vivo. Dofetilide had significantly larger APD- and ERP-increasing effects in the LA compared with RA, and LA-RA repolarization differences were eliminated by exposure to dofetilide. We conclude that LA myocytes have larger I(Kr) than do RA myocytes, contributing importantly to the shorter APD and ERP in LA. The larger LA I(Kr) may participate in the ability of the LA to act as a "driver region" for AF, with potentially important implications for understanding AF mechanisms and antiarrhythmic therapy.

Action Potentials↗
PubMed2001

Increased genetic damage in oral leukoplakia from high risk sites: potential impact on staging and clinical management.

BACKGROUND: Two staging systems for oral leukoplakias have been proposed to better predict prognosis. Although one system includes site as an independent determinant, its use is controversial. METHODS: Recent studies have shown that loss of heterozygosity (LOH) in oral premalignancies is associated with risk of progression. The authors analyzed 127 oral dysplasias for LOH on 3 chromosome arms (3p, 9p, and 17p). The lesions included 71 from the floor of mouth, ventrolateral tongue, and soft palate complex (designated high risk [HR] sites) and 56 from the rest of the oral cavity (low risk [LR] sites). RESULTS: Dysplasias from HR sites contained significantly higher LOH frequencies than LR sites (percentage with any loss, P = 0.0004; percentage with multiple losses, P = 0.0001; percentage loss on each of the arms, P < 0.05). Loss on 3p and/or 9p, a pattern associated with a 24-fold increased risk of progression (Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, Lovas J, et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res 2000;6:357-62) was more frequent among HR lesions (P = 0.0005). Loss of heterozygosity frequencies were elevated at HR sites among both genders and among smokers and nonsmokers. For different histologic groups, LOH frequencies were elevated for HR sites in mild dysplasias (P < 0.05) and moderate dysplasias (marginal significance, P = 0.06), but not in severe dysplasias/carcinoma in situ. CONCLUSIONS: Anatomic location of mild and moderate oral dysplasias in Western populations may be an important diagnostic indicator because lesions at HR sites have a greater tendency to include genetic alterations associated with elevated risk of progression.

Adult↗
PubMed2001

Development of a novel helicase assay using electrochemiluminescence.

DNA helicases are ubiquitous enzymes involved in DNA replication, recombination, and repair. These enzymes use the energy of ATP to unwind duplex DNA. A common approach to measure DNA helicase activity utilizes electrophoresis to visualize product formation in a gel. The present study develops a rapid helicase assay based on electrochemiluminescence. The assay is adaptable to rapid high-throughput screening for chemical inhibitors. The assay is applied to Escherichia coli DnaB. Three other technologies have also been applied to DnaB and are compared to results of the electrochemiluminescence-based assay.

Base Sequence↗
PubMed2001

Markers for carcinogenicity among butadiene-polymer workers in China.

We examined a spectrum of genotoxic and other outcomes in 41 butadiene-polymer production workers and 38 nonexposed controls, in China, to explore the role of butadiene in human carcinogenesis. Among butadiene-exposed workers, median air exposure was 2 ppm (6-h TWA), due largely to intermittent high-level exposures. Compared to unexposed subjects, butadiene-exposed workers had greater levels of hemoglobin N-(2,3,4-trihydroxybutyl)valine (THBVal) adducts (P<0.0001), and adduct levels tended to correlate, among butadiene-exposed workers, with air measures (P=0.03). Butadiene-exposed workers did not differ, however, from unexposed workers with respect to frequency of uninduced or diepoxybutane-induced sister chromatid exchanges, aneuploidy as measured by fluorescence in situ hybridization of chromosomes 1, 7, 8 and 12, glycophorin A variants or lymphocyte hprt somatic mutation. Also among the exposed, greater THBVal levels were not associated with increases in uninduced sister chromatid exchanges, aneuploidy, glycophorin A, or hprt mutations. Butadiene-exposed workers had greater lymphocyte (P=0.002) and platelet counts (P=0.07) and lymphocytes as a percent of white blood cells were moderately correlated with greater THBVal levels (Spearman's rho=0.32, P=0.07). Among butadiene-exposed workers, several serum cytokines correlated with THBVal adduct levels. Overall, the study demonstrated exposure to butadiene in these workers, by a variety of short-term and long-term measures, but did not show specific genotoxic effects, at the chromosomal or gene levels, related to that exposure.

Air Pollutants, Occupational↗