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Biomedical subjects

G Lu

Publications and source records attributed to G Lu.

At least 37 records · Page 2Linked to original sources
PubMed2001

Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver.

Human hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. In this work, we report on a comprehensive characterization of gene expression profiles of hepatitis B virus-positive HCC through the generation of a large set of 5'-read expressed sequence tag (EST) clusters (11,065 in total) from HCC and noncancerous liver samples, which then were applied to a cDNA microarray system containing 12,393 genes/ESTs and to comparison with a public database. The commercial cDNA microarray, which contains 1,176 known genes related to oncogenesis, was used also for profiling gene expression. Integrated data from the above approaches identified 2,253 genes/ESTs as candidates with differential expression. A number of genes related to oncogenesis and hepatic function/differentiation were selected for further semiquantitative reverse transcriptase-PCR analysis in 29 paired HCC/noncancerous liver samples. Many genes involved in cell cycle regulation such as cyclins, cyclin-dependent kinases, and cell cycle negative regulators were deregulated in most patients with HCC. Aberrant expression of the Wnt-beta-catenin pathway and enzymes for DNA replication also could contribute to the pathogenesis of HCC. The alteration of transcription levels was noted in a large number of genes implicated in metabolism, whereas a profile change of others might represent a status of dedifferentiation of the malignant hepatocytes, both considered as potential markers of diagnostic value. Notably, the altered transcriptome profiles in HCC could be correlated to a number of chromosome regions with amplification or loss of heterozygosity, providing one of the underlying causes of the transcription anomaly of HCC.

Carcinoma, Hepatocellular↗
PubMed2001

[Effects of inorganic arsenicals on the methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells].

OBJECTIVE: To study the effects of inorganic arsenicals on the methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells. METHODS: The methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells were measured by methylation-specific PCR (MSP) and RT-PCR methods. RESULTS: (1) The exposure of the BEP2D cells to sodium arsenite (0.016 approximately 2 micromol/L) or high-density sodium arsenate (80 approximately 160 micromol/L), but not low-density sodium arsenate (20 approximately 40 micromol/L), produced significant hypermethylation of p16 gene CpG islands in BEP2D cells. (2) The expressions of p16 gene in the groups of sodium arsenite and sodium arsenate at the test were lower than that of the control group, especially in the groups of sodium arsenite. CONCLUSIONS: Inorganic arsenicals alter the methylation patterns and the expression of p16 gene in BEP2D cells, which suggests that the hypermethylation of p16 gene CpG islands may be one of the mechanisms of carcinogenesis of inorganic arsenicals.

Arsenic↗
PubMed2001

The crystal structure of bar-headed goose hemoglobin in deoxy form: the allosteric mechanism of a hemoglobin species with high oxygen affinity.

The crystal structure of a high oxygen affinity species of hemoglobin, bar-headed goose hemoglobin in deoxy form, has been determined to a resolution of 2.8 A. The R and R(free) factor of the model are 0.197 and 0.243, respectively. The structure reported here is a special deoxy state of hemoglobin and indicates the differences in allosteric mechanisms between the goose and human hemoglobins. The quaternary structure of the goose deoxy hemoglobin shows obvious differences from that of human deoxy hemoglobin. The rotation angle of one alphabeta dimer relative to its partner in a tetramer molecule from the goose oxy to deoxy hemoglobin is only 4.6 degrees, and the translation is only 0.3 A, which are much smaller than those in human hemoglobin. In the alpha(1)beta(2) switch region of the goose deoxy hemoglobin, the imidazole ring of His beta(2)97 does not span the side-chain of Thr alpha(1)41 relative to the oxy hemoglobin as in human hemoglobin. And the tertiary structure changes of heme pocket and FG corner are also smaller than that in human hemoglobin. A unique mutation among avian and mammalian Hbs of alpha119 from proline to alanine at the alpha(1)beta(1 )interface in bar-headed goose hemoglobin brings a gap between Ala alpha119 and Leu beta55, the minimum distance between the two residues is 4.66 A. At the entrance to the central cavity around the molecular dyad, some residues of two beta chains form a positively charged groove where the inositol pentaphosphate binds to the hemoglobin. The His beta146 is at the inositol pentaphosphate binding site and the salt-bridge between His beta146 and Asp beta94 does not exist in the deoxy hemoglobin, which brings the weak chloride-independent Bohr effect to bar-headed goose hemoglobin.

Adaptation, Physiological↗
PubMed2001

Hepatic stellate cells contain the functional estrogen receptor beta but not the estrogen receptor alpha in male and female rats.

In an earlier study, we showed that estradiol (E2) inhibits proliferation and transformation in cultured rat hepatic stellate cells (HSCs) and that the actions of E2 are mediated through estrogen receptors (ERs). This study reports on an investigation of the cellular localization of ER subtypes ERalpha and ERbeta using immunohistochemistry in experimental fibrotic liver rats and of each ER subtype expression in cultured rat HSCs by evaluating the produced mRNA and protein. The results indicate that high levels of ERbeta expression and low or no levels of ERalpha expression were observed in normal and fibrotic livers and in quiescent and activated HSCs from both males and females. The specificity of E2-mediated antiapoptotic induction through the ERbeta was shown by dose-dependent inhibition by the pure ER antagonist ICI 182,780 in HSCs which were undergoing early apoptosis. These findings demonstrate for the first time that rat HSCs possess functional Erbeta, but not Eralpha, to respond directly to E2 exposure.

Animals↗
PubMed2001

Hydrogen-enhanced local plasticity in aluminum: an ab initio study.

Dislocation core properties of Al with and without H impurities are studied using the Peierls-Nabarro model with parameters determined by ab initio calculations. We find that H not only facilitates dislocation emission from the crack tip but also enhances dislocation mobility dramatically, leading to macroscopically softening and thinning of the material ahead of the crack tip. We observe strong binding between H and dislocation cores, with the binding energy depending on dislocation character. This dependence can directly affect the mechanical properties of Al by inhibiting dislocation cross-slip and developing slip planarity.

Journal Article↗
PubMed2001

The effect of interleukin-6 on the proliferation of prostate cancer cells in vitro and the modulation of this procedure.

The role of interleukin-6 (IL-6) in the growth of an androgen-independent prostate cancer cell line (PC-3 m) was defined and the effect of dexamethasone, which was previously shown to modulate IL-6/IL-6 receptor (IL-6R) on this procedure was investigated. By using a pretty sensitive and specific enzyme immunoassay (ELISA), it was found that PC-3 m produced certain IL-6, but there was no difference in IL-6 secretion between the group with or without dexamethasone treatment. It was also found that PC-3 m cells could not be stimulated to grow by exogenous IL-6 (P > 0.05), while it could be inhibited to grow by anti-IL-6 monoclonal antibody and dexamethasone with a dose-dependent fashion. Our observation indicated that IL-6 acted as an autocrine growth factor for PC-3 m, and dexamethasone could inhibit cell proliferation by a mechanism independent of its effect on IL-6 mRNA expression.

Androgens↗
PubMed2001

Photocatalytic degradation of dyes on a magnetically separated photocatalyst under visible and UV irradiation.

A novel kind of magnetically separable photocatalyst of TiO2/SiO2/gamma-Fe2O3 (TSF) is prepared. Scanning tunnel microscope (STM) and X-ray diffractometer (XRD) were used to characterize the structure of the photocatalyst. In the TSF photocatalyst, a TiO2 shell is for photocatalysis, a gamma-Fe2O3 core as a carrier is for separation by the magnetic field and a SiO2 membrane between the TiO2 shell and the gamma-Fe2O3 core is used to weaken the adverse influence of gamma-Fe2O3 on the photocatalysis of TiO2. Three kinds of dyes, Fluoresein, Orange II and Red acid G, were used to examine the photocatalytic activity of TSF. Due to strong UV adsorption of the gamma-Fe2O3, the photocatalytic activity of TSF was lower than that of the pure TiO2. Deducting the light absorption of the gamma-Fe2O3 particles, the photocatalytic activity of TSF was found to be higher than that of the P25 under UV irradiation. On the other hand, the photocatalytic activity of TSF under visible irradiation was much lower than that of the P25 TiO2 even deducting the visible light absorption of the gamma-Fe2O3 particles. Differences in the photocatalytic mechanisms under UV and visible irradiation lead to the differences in the photodegradation characteristics of dyes on TSF. The recycled TSF exhibited a good repeatability of photocatalytic activity.

Catalysis↗
PubMed2001

Synthesis and biodistribution of a new 99mTc nitrido complex for brain imaging.

Bis(N-isobutyl-dithiocarbamato) nitrido technetium-99m complex [99mTcN(IBDTC)2] (IBDTC: N-isobutyl dithiocarbamato) was synthesized by the reduction of 99mTcO4- into [99mTc = N]2+ with stannous chloride in the presence of succinic dihydrazide and propylenediamine tetraacetic acid, followed by the addition of sodium N-isobutyl dithiocarbamate dihydrate. The radiochemical purity of the complex was over 90% as measured by thin layer chromatography. It was stable over 6h at room temperature. Its partition coefficient indicated that it is a good lipophilic complex. Biodistribution in mice demonstrated that the complex accumulated in the brain with high uptake and good retention. The brain uptake (ID%/g) was 6.22, 5.45 and 3.88 and the brain/blood ratio was 1.51, 2.24, 1.84 at 5, 30 and 60 min post-injection, respectively. These results suggest potential usefulness of the complex as a brain perfusion imaging agent.

Animals↗
PubMed2001

Effects of idoxifene and estradiol on NF-kappaB activation in cultured rat hepatocytes undergoing oxidative stress.

BACKGROUND/AIMS: Idoxifene is a tissue-specific selective estrogen receptor modulator. Estradiol is a potent endogenous antioxidant, and nuclear factor kappaB (NF-kappaB) is a key transcription factor that induces multiple genes in response to inflammation or oxidative stress. The aim of this study was to explore the inhibitory effects of idoxifene and estradiol on NF-kappaB activation in hepatocytes in a state of oxidative stress. METHODS: Lipid peroxidation was induced in cultured rat hepatocytes by incubation with ferric nitrilotriacetate solution. NF-kappaB activity was evaluated by electrophoretic mobility shift assay. RESULTS: The oxidative stress-induced activation of NF-kappaB and degradation of IkappaB-alpha were maximal at 3-5 h, with an increase in lactate dehydrogenase (LDH) and malondialdehyde (MDA) secretion into the culture medium. Treatment with idoxifene and estradiol inhibited IkappaB-alpha degradation and NF-kappaB activation through the attenuation of hepatocyte oxidative bursts and decreased extracellular levels of LDH and MDA. In addition, idoxifene and estradiol inhibited lipid peroxidation in rat liver mitochondria. A potent NF-kappaB inhibitor, pyrrolidine dithiocarbamate, prevented NF-kappaB activation by inhibition of IkappaB-alpha degradation and decreased LDH and MDA levels, suggesting that NF-kappaB might be a regulator in a genetic response to increase oxidative stress-induced hepatic injury. CONCLUSIONS: These findings suggest that idoxifene and estradiol function as antioxidants and protect hepatocytes from inflammatory cell injury.

Animals↗
PubMed2001

Electron cryomicroscopy and bioinformatics suggest protein fold models for rice dwarf virus.

The three-dimensional structure of rice dwarf virus was determined to 6.8 A resolution by single particle electron cryomicroscopy. By integrating the structural analysis with bioinformatics, the folds of the proteins in the double-shelled capsid were derived. In the outer shell protein, the uniquely orientated upper and lower domains are composed of similar secondary structure elements but have different relative orientations from that of bluetongue virus in the same Reoviridae family. Differences in both sequence and structure between these proteins may be important in defining virus-host interactions. The inner shell protein adopts a conformation similar to other members of Reoviridae, suggesting a common ancestor that has evolved to infect hosts ranging from plants to animals. Symmetry mismatch between the two shells results in nonequivalent, yet specific, interactions that contribute to the stability of this large macromolecular machine.

Amino Acid Sequence↗
PubMed2001

Contrasting patterns of mitochondrial DNA and microsatellite introgressive hybridization between lineages of lake whitefish (Coregonus clupeaformis); relevance for speciation.

We performed a combined analysis of mitochondrial DNA (mtDNA) and microsatellite loci among lake whitefish (Coregonus clupeaformis) populations in order to assess the levels of congruence between both types of markers in defining patterns of genetic structuring, introgressive hybridization and inferring population origins in the hybrid zone of the St. John River basin. A second objective was to test the hypothesis that secondary contact between glacial lineages always resulted in the occurrence of sympatric dwarf and normal whitefish ecotypes. Fish were sampled from 35 populations and polymorphism was screened at mtDNA and six microsatellite loci for a total of 688 and 763 whitefish, respectively. Four lakes harbouring a single whitefish population of normal ecotype admixed with mtDNA haplotypes of different lineages were found. This confirmed that secondary contact between whitefish evolutionary lineages did not always result in the persistence of reproductively isolated ecotypes. Microsatellites further supported the definition of distinct glacial lineages by identifying lineage-specific allelic size groups. They also further supported the hypothesis that ecotypes originated from either a single founding lineage (sympatric divergence) or following secondary contacts between lineages (allopatric divergence), depending on the lake. In general, however, the pattern of population differentiation and introgressive hybridization observed at microsatellites was in sharp contrast with that depicted by mtDNA variation. Both factorial correspondence analysis and analysis of admixture proportion revealed a much more pronounced pattern of introgressive hybridization than depicted by mtDNA analyses. Variable levels of introgression indicated that environmental differences may be as important as the historical contingency of secondary contact in explaining the persistence of sympatric ecotypes and the differential pattern of introgressive hybridization among lakes. Whitefish populations from the St. John River basin hybrid zone represent a rare illustration of a continuum of both morphological and genetic differentiation within a given taxon, spanning from complete introgression to possibly complete reproductive isolation, depending on lakes. Thus, each lake may be viewed as a different temporal snapshot taken throughout the gradual process of speciation.

Animals↗
PubMed2001

In vitro phosphorylation of COOH termini of the epithelial Na(+) channel and its effects on channel activity in Xenopus oocytes.

Recent findings have suggested the involvement of protein phosphorylation in the regulation of the epithelial Na(+) channel (ENaC). This study reports the in vitro phosphorylation of the COOH termini of ENaC subunits expressed as glutathione S-transferase fusion proteins. Channel subunits were specifically phosphorylated by kinase-enriched cytosolic fractions derived from rat colon. The phosphorylation observed was not mediated by the serum- and glucocorticoid-regulated kinase sgk. For the gamma-subunit, phosphorylation occurred on a single, well-conserved threonine residue located in the immediate vicinity of the PY motif (T630). The analogous residue on beta(S620) was phosphorylated as well. The possible role of gammaT630 and betaS620 in channel function was studied in Xenopus laevis oocytes. Mutating these residues to alanine had no effect on the basal channel-mediated current. They do, however, inhibit the sgk-induced increase in channel activity but only in oocytes that were preincubated in low Na(+) and had a high basal Na(+) current. Thus mutating gammaT630 or betaS620 may limit the maximal channel activity achieved by a combination of sgk and low Na(+).

Animals↗
PubMed2001

Signaling events mediating the additive effects of oleic acid and angiotensin II on vascular smooth muscle cell migration.

Obese hypertensive patients with cardiovascular risk factor clustering and increased risk for atherosclerotic disease have increased plasma nonesterified fatty acid levels, including oleic acid (OA), and a more active renin-angiotensin-aldosterone system. Vascular smooth muscle cell (VSMC) migration and proliferation participate in the development of atherosclerotic plaque. OA and angiotensin (Ang) II induce synergistic mitogenic responses in VSMCs through sequential signaling pathways dependent on the activation of protein kinase C (PKC), oxidants (reactive oxygen species, ROS), and extracellular signal-regulated kinase (ERK) activation. We tested the hypotheses that (1) OA and Ang II have additive or synergistic effects on VSMC migration and (2) PKC, ROS, and mitogen-activated protein kinase are critical signaling molecules. OA at 100 micromol/L increases VSMC migration 60+/-10% over control (P:<0.001). Ang II (10(-)(9) mol/L) increases VSMC migration by 62+/-13% and 73% over control, respectively (P:<0.01). Coincubation of cells with OA and Ang II produces a nearly additive increase in VSMC cell migration at 107+/-20% (P:<0.01). Increases in VSMC migration induced by OA alone and combined with Ang II were reduced by PKC inhibition and downregulation. VSMC migration in response to OA alone and with Ang II was also inhibited by N:-acetyl-cysteine, MEK inhibition, and ERK antisense. VSMC migration in response to OA alone or combined with Ang II is dependent on activation of PKC, ROS, and ERK activation, further raising the possibility that increased plasma nonesterified fatty acids and an activated renin-angiotensin-aldosterone system in subjects with the risk factor cluster contribute to accelerated atherosclerosis through a PKC, ROS, and ERK-dependent signaling pathway.

Acetylcysteine↗
PubMed2001

[Malformed macrocephalous sperm with polytails and chromosomal aberrance].

OBJECTIVE: To investigate the relationship between sperm anomalies and chromosomal aberrance and to further understand the pathological changes of anomalous spermatozoa. METHODS: Light and electronic (SEM or TEM) microscopes were used for morphological analysis. Fluorescence in situ hybridization(FISH) with chromosome X-, Y-specific probes were used for aneuploidy detection in sperms of the patient. RESULTS: Ninety eight point seven five per cent of the Papanicolaou stained sperms were observed to be abnormal; 100% of the sperm heads were abnormal, measured under oil objective (1000 times); 60.25% of the sperms had two or more tails (the maximum being eight tails). SEM and TEM demonstrated that the heads contained a large amount of cytoplasmic structure, the surfaces of heads were uneven, the nuclei were of much irregular shape; besides aberrance in quantity, anomalies occurred with centromeres, mitochondria and flagella in the tails. The results of FISH showed that the aneuploidy rate of sex chromosomes was 61.41% which was parallel to the rate of polytails. CONCLUSION: Even though the chromosomes in somatic cells are normal, the chromosomes in anomalous sperms may be abnormal.

Adult↗
PubMed2001

[Study of a familial insertional translocation involving chromosomes 1 and 7 by using fluorescence in situ hybridization].

OBJECTIVE: To determine the karyotype of a case with a history of spontaneous abortion and terminal deletion by using of conventional G-banding method and search the cause of insertional translocation of chromosomal terminal region. METHODS: Fluorescence in situ hybridization (FISH) technique was performed to analyze the case by using whole chromosome 7 painting probe and subterminal probe of 7q36-->qter which was generated by chromosome microdissection technique. RESULTS: The case was a carrier with a very rare insertional translocation involving chromosomes 1 and 7. The region of chromosome 7q36-->qter was not inserted into chromosome 1. The abnormal chromosome was inherited from her mother. CONCLUSION: The present authors provided an experiment evidence that in this case the chromosome insertional translocation including the terminal region was still a three breakage rearrangement and the terminal deletion found by cytogenetics should be an interstitial deletion. Combining with chromosome microdissection, FISH technique is a powerful diagnostic method for detecting the chromosome structural abnormality.

Adult↗
PubMed2001

Population-based, case-control study of blood C-peptide level and breast cancer risk.

Insulin resistance has been suggested to be associated with an increased risk of breast cancer. Insulin sensitivity can be measured using blood C-peptide, a marker of insulin secretion. It is thus conceivable that blood C-peptide levels may be associated with breast cancer risk. To evaluate this hypothesis, we analyzed data from a subset (143 case-control pairs matched by age and status of menopause) of women who participated in the Shanghai Breast Cancer Study, a population-based, case-control study conducted in Shanghai during 1996-1998. Fasting blood samples were collected from study subjects to measure C-peptide levels. For cancer patients, the samples were collected before any cancer therapy. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals related to C-peptide levels. Breast cancer risk was increased with increasing levels of C-peptide (trend test, P = 0.01), with an odds ratio of 2.7 (95% confidence interval = 1.2-5.9) observed for the highest compared with the lowest tertile of C-peptide concentration after adjusting for body mass index and age at the first live birth. The risk was not altered after fully adjusting for other traditional risk factors for breast cancer. This positive association was observed in both pre and postmenopausal women and regardless of the levels of waist-to-hip ratio or body mass index. The results from this study were consistent with the insulin-resistance hypothesis for breast cancer and suggest that increased levels of C-peptide may contribute to the development of breast cancer.

Adult↗