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Biomedical subjects

X Hu

Publications and source records attributed to X Hu.

At least 55 records · Page 3Linked to original sources
PubMed2002

In vitro corrosion testing of PVD coatings applied to a surgical grade Co-Cr-Mo alloy.

Toxic effects and biological reaction of metallic corrosion and wear products are an important concern for metal on metal artificial joints. Corrosion tests were conducted to study the susceptibility to pitting and localized corrosion, with three coatings, CrN, TiN and DLC, applied to a wrought high carbon Co-Cr-Mo alloy substrate material. Corrosion testing involved the measurement of potential time transients during immersion in a physiological solution and cyclic polarization of specimen potentials into the transpassive range followed by reversal of the potential to scan in the cathodic direction to regain the rest potential E(rest). Resistance to pitting and localized corrosion was assessed by determining the transpassive breakdown potential E(bd) and if any hysteresis generated during the reverse cyclic scan may have caused crossover with the original anodic scan. Three different surface coating conditions were tested namely: (1) as-coated, (2) polished, and (3) indented to penetrate the coating by diamond pyramid hardness indentor. Results showed that all three coatings produced significant improvements in corrosion resistance compared to performance of the wrought cobalt alloy but that some corrosive attack to both the CrN and TiN coatings occurred and some risk of attack to the cobalt alloy substrate existed due to coating defects or when damage to the coating occurred. TiN coatings were highly effective in preventing corrosion provided they were thick enough to produce complete coverage. Thin TiN coatings displayed some tendency to encourage localized attack of the cobalt alloy at coating defects or where the coating suffered mechanical damage. CrN coatings underwent transpassive breakdown more easily and some degree of pitting at defects within the coating was observed, especially when the CrN coating was polished before the test. No corrosive attack of the cobalt alloy substrate was observed when the CrN coating was mechanically damaged by indentation. DLC coatings produced were much thinner than either of the other two coatings and proved to be rather fragile. They were less effective in preventing apparently high corrosion currents and possibly high rates of corrosion.

Journal Article↗
PubMed2002

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) up-regulates death receptor 5 (DR5) mediated by NFkappaB activation in epithelial derived cell lines.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL/APO-2L) activates nuclear factor kappaB (NFkappaB). This activation is regulated by the recruitment of an adaptor protein Fas associating death domain (FADD) to TRAIL death receptors, death receptor 4 (DR4, TRAIL-R1) and death receptor 5 (DR5 TRAIL-R2). This leads to recruitment of caspase 8 and receptor interacting protein (RIP) to the receptor complex. Upon recruitment of caspase 8 and RIP, NFkappaB inducing kinase (NIK) becomes activated causing NFkappaB activation. The role of TRAIL induced NFkappaB activation in epithelial cells is unknown. Herein we demonstrate that TRAIL increases expression of DR5 in human embryonic kidney (HEK) 293, MCF-7 and MDA MB 231 epithelial cell lines while DR4 expression remains unchanged. Blockage of NFkappaB activation either by expression of dominant negative IkappaB or treatment with proteasome inhibitor lactacystin eliminates TRAIL induced DR5 expression. Expression of FADD dominant negative in HEK 293 cells that prevents the recruitment of caspase 8 and RIP to TRAIL death receptors also eliminates this increase. By over expression of the p65 subunit of NFkappaB that increases NFkappaB transcriptional activity, DR5 expression was increased compared to vector alone expressing cells. By blocking TRAIL induced NFkappaB activation, the sensitivity of cells to undergo TRAIL induced apoptosis was significantly decreased. Conversely, the amount of TRAIL induced apoptosis was increased in HEK 293 cells over expressing p65 subunit of NFkappaB. Finally blockage of NFkappaB activation eliminates the synergistic apoptotic response of TRAIL and etoposide. Thus, TRAIL mediated NFkappaB activation increases DR5 expression thereby amplifying the apoptotic response of TRAIL in epithelial derived cells.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro.

PTPases are key signaling molecules and targets for developing novel therapeutics. We have studied the in vitro biological activity of PTPase inhibitor sodium stibogluconate (SS) on differentiation and proliferation of myeloid leukemia cell lines (NB4, HL-60 and U937). SS (250 microg/ml, 6 days) induced 87% of NB4 cells to reduce nitroblue tetrazolium (NBT), in comparison to the 90% induced by ATRA (1 microM, 6 days). SS treatment of NB4 cells resulted in an increase of CD11b expression and of a morphologically more mature population, coincident with growth arrest at S phase and increased cell death. The effect of SS on NB4 differentiation was irreversible and required continuous drug exposure. SS (400 microg/ml, 6 days) induced 60% and 55% of NBT-positive cells in HL-60 and U937 cell lines, which were augmented in the presence of GM-CSF (25 ng/ml) to levels (85% and 81%, respectively) comparable to those induced by ATRA. SS induced increased tyrosine phosphorylation of cellular proteins in the AML cell lines and inactivated SHP-1 PTPase in NB4 cells, consistent with SS functioning as a PTPase inhibitor in the leukemia cells. These results provide the first evidence of an anti-leukemia activity of SS as a PTPase inhibitor.

Acute Disease↗
PubMed2002

The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres.

Several case-control association studies have raised the possibility that the A allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar chi(2) = 0.29, df = 1, P = 0.59). Also, the haplotype-based haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre (chi(2) < 2.15, df = 1, P > 0.14) and in the total sample (chi(2) = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples (chi(2) = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT(2A) gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size).

Adolescent↗
PubMed2002

Wear of three dental composites under different testing conditions.

Although a great effort has been made to date with research on in vitro wear simulation testing, it is difficult to identify the relationship between the results of in vitro testing and in vivo observations. An intensive study into wear mechanisms is necessary for wear testing simulation. The objective of this research was to study the wear behaviour of three selected dental composites under different wear conditions to provide a more rational explanation for their wear mechanisms. Two typical wear conditions, two- and three-body wear, were conducted on the composites. The results showed that the wear losses had different rankings between two wear conditions. It is therefore unreliable to predict the clinical performance merely by wear loss ranking from in vitro wear testing. Further analysis on the wear surfaces indicated that three dental composites experienced different wear mechanisms under different wear conditions. It is concluded that in vitro analysis of wear mechanisms may lead to a better understanding of in vivo failure patterns. Similar wear mechanisms should be the premise for any correlation between the results of in vitro and in vivo studies.

Analysis of Variance↗
PubMed2002

Attenuation of cell migration and induction of cell death by aged garlic extract in rat sarcoma cells.

Previous studies have shown that aged garlic extract suppresses cancer growth and enhances immune system against cancer, and yet little is known about inhibition of the cancer cell migration. In this study we investigated whether the aged garlic extract inhibits growth and migration of rat sarcoma tumor cells. The suppression of tumor cell growth was demonstrated by counting the cell number in three groups (control, cultured with 10 mg/ml, 20 mg/ml of aged garlic extracts) after culturing for 3 days and 5 days. The results showed that aged garlic extract inhibited the growth of rat sarcoma cancer cells in a dose-dependent manner, compared to the numbers of the cells grown in control group. The inhibition of tumor cell migration was examined by measuring the distance of trails left behind by the tumor cells when they passed through the polybeads overnight in four groups (control, 5 mg/ml, 10 mg/ml, 20 mg/ml aged garlic extracts). The average distance of trails in control group was 7.44 mm, whereas the average distance of cell movement is only 2.48 mm when treated with the highest concentration (20 mg/ml) of the aged garlic extract. The results also showed that the inhibitory effect of aged garlic extracts on tumor cell migration was dose-dependent. This is the first report to show that the aged garlic extract inhibits rat sarcoma cell migration, a critical feature of tumor cell metastasis. It can be thus envisioned that if tumor cell metastasis could be attenuated if not completely stopped, it would be possible to stabilize the tumor in the local area for surgical removal. The results suggest that garlic, as a natural plant, unlike other cancer treatment methods, may play a role in fighting cancer without significant side effects.

Animals↗
PubMed2001

Paired chimpanzee hepatitis B virus (ChHBV) and mtDNA sequences suggest different ChHBV genetic variants are found in geographically distinct chimpanzee subspecies.

The surface antigen gene region from five chronic hepatitis B virus (HBV) infected chimpanzees was amplified by PCR and the sequence determined. Sequence comparison confirmed that all of the sequences were chimpanzee hepatitis B virus (chHBV) and they appeared to represent three distinct clusters or branches. To address the question of whether the three branches represented recently identified subspecies of chimpanzees, we determined the sequence of the mitochondrial DNA hypervariable D loop from hair samples obtained from these five chimpanzees. The results indicated that the three chHBV branches reflected three distinct subspecies of chimpanzees that are from different geographic regions in West Africa. The complete HBV sequence from members of the Pan troglodytes troglodytes cluster and the Pan troglodytes verus cluster are in the published literature; we determined the complete genome sequence for the third branch of HBV present in Pan troglodytes vellerosus.

Animals↗
PubMed2001

Differential effects of transforming growth factor on cell cycle regulatory molecules in human myeloid leukemia cells.

In this report we have studied the mechanism by which Transforming Growth Factor beta (TGF beta) inhibits growth of human myeloid leukemia cell lines. TGF beta 1 arrested cells in G1 phase and significantly downregulated the expression of cyclin D2, cyclin D3, cdk4, cyclin A, and cdk2. The downregulation of the molecules resulted in approximately 50-90% decrease of the molecule-dependent kinase activity, varying with each molecule. Although treatment of cells with TGF beta 1 up-regulated accumulation of p27(kip1) in both nucleus and cytoplasm, the association of the p27(kip1) with cdk2, cyclin A, cyclin D2, cyclin D3, and cdk4 was markedly down-regulated, suggesting that p27(kip1) is not responsible for the downregulation of the kinase activity. In contrast, TGF beta 1 upregulated cyclin E-associated p27(kip1) with no effect on the expression of cyclin E. p27(kip1)-immunodepletion upregulated cyclin E-dependent kinase activity by more than 10-fold in TGF beta 1-treated cells but not in proliferating cells; whereas immunodepletion of p27(kip1) from cdk2-immunoprecipitates markedly downregulated cdk2 kinase activity in the lysates extracted from both proliferating and TGF beta-treated cells. Consistent with this observation, TGF beta 1 and p27(kip1) antisense cDNA had a synergistic or additive inhibitory effect on cdk2 but not cyclin E-dependent kinase activity. Our data suggest that (1) TGF beta 1-mediated growth inhibition is accomplished through multiple pathways and (2) p27(kip1) has opposing effects on cdk2 and cyclin E activity in response to TGF beta 1.

CDC2-CDC28 Kinases↗
PubMed2001

Sequence analysis of the Spodoptera litura multicapsid nucleopolyhedrovirus genome.

The complete Spodoptera litura multicapsid nucleopolyhedrovirus (SpltMNPV) genome contained 139,342 bp with a G+C content of 42.7%, and 141 putative open reading frames (ORFs) or genes of 150 nucleotides or greater that showed minimal overlap. Ninety-six ORFs had homologues in Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), 16 had homologues in other baculoviruses, and 29 were unique to SpltMNPV. The homologues of ubiquitin and gp37 are fused in SpltMNPV. The genome lacked a homologue of the major budded virus glycoprotein gene gp64, but it contained a homologue of ORF130 of Lymantria dispar multicapsid nucleopolyhedrovirus (LdMNPV). There were two homologues of AcMNPV ORF2 (bro gene), and a DnaJ protein gene (SpltORF39) in which the N-terminus showed homologies with the J domain of DnaJ family proteins. Seventeen homologous regions (hrs) were identified, each containing 2-29 palindromic repeats, with an average length of 534 bp and base content (G+C%) of 33.0.

Amino Acid Sequence↗
PubMed2001

An IkappaBalpha inhibitor causes leukemia cell death through a p38 MAP kinase-dependent, NF-kappaB-independent mechanism.

Treatment of U937 cells with an IkappaBalpha phosphorylation inhibitor, Bay 11-7085, induced a rapid phosphorylation of p38 mitogen-activated protein (MAP) kinase, significant apoptosis, extensive necrosis, and a weak phosphorylation of MAP kinase kinase. Bay 11-7085 had no effect on the basal levels of phosphorylated IkappaBalpha but completely inhibited phorbol 12-myristate 13-acetate-induced phosphorylation of IkappaBalpha. Although Bay 11-7085 prevented phorbol 12-myristate 13-acetate-induced NF-kappaB nuclear translocation, SN50, a specific inhibitor of nuclear translocation and function of NF-kappaB, did not induce any significant nuclear/DNA fragmentation, caspase 3 activation, or cell death. The p38 MAP kinase-specific inhibitor, SB203580, completely inhibited the phosphorylation of p38 MAP kinase and significantly decreased Bay 11-7085-induced apoptosis. In contrast, the MAP kinase kinase-specific inhibitor PD98059 had no effect on Bay 11-7085-induced apoptosis. Caspase-specific inhibitor, z-Val-Ala-Asp-fluoromethyl ketone prevented Bay 11-7085-induced activation of caspase 3 but was not able to block Bay 11-7085-induced phosphorylation of p38 MAP kinase. These data suggest that Bay 11-7085 induces apoptosis through a p38 MAP kinase-dependent, NF-kappaB-independent mechanism.

Activating Transcription Factor 2↗
PubMed2001

Bicritical and tetracritical phenomena and scaling properties of the SO(5) theory.

By Monte Carlo simulations on a 3D SO(5) rotator model it is shown that, in contrast to the epsilon expansions of the renormalization group, the bicritical point is stable to biquadratic perturbations of AF-SC (antiferromagnetism-superconductivity) repulsions, which are produced by quantum fluctuations originated from the Gutzwiller projection. Therefore, the present work completes the link from a physical projected SO(5) starting point to an asymptotic SO(5) symmetry point. The tetracritical point is stable for attractive AF-SC interactions. Critical exponents and ratios are evaluated by scaling analysis. Bicritical and tetracritical scaling functions are derived for the first time. Suggestions on experiments are given.

Journal Article↗
PubMed2001

Effects of point defects on the phase diagram of vortex states in high- T(c) superconductors in the B parallel to c axis.

The phase diagram for the vortex states of high- T(c) superconductors with point defects in the B--> parallel to c axis is drawn by large-scale Monte Carlo simulations. The vortex slush (VS) phase is found between the vortex glass (VG) and vortex liquid (VL) phases. The first-order transition between this novel normal phase and the VL phase is characterized by a sharp jump of the density of dislocations. The first-order transition between the Bragg glass (BG) and VG or VS phases is also clarified. These two transitions are compared with the melting transition between the BG and VL phases.

Journal Article↗
PubMed2001

Affected sibling pair linkage analysis of qualitative and quantitative traits for schizophrenia on chromosome 22 in a Chinese population.

We performed nonparametric linkage analysis on 136 families with two or more siblings with schizophrenia from Sichuan, southwestern China. In addition to categorical diagnosis, we used quantitative trait information from the Positive and Negative Symptom Scale and the modified Overt Aggression Scale. Categorical analysis using the diagnosis of schizophrenia and a maximum likelihood identity-by-descent method produced scores of close to 0 throughout the whole region tested. Multipoint analysis allowed exclusion of most markers with a relative risk of > 2, but did not exclude the possibility of a relative risk of < 1.5 for four of the markers. Our results provide no significant evidence for a locus for schizophrenia on chromosome 22. Quantitative linkage analysis using the PANSS-G scale score produced a maximum LOD score of approximately 1.2 with the marker D22S310, using either the Haseman-Elston method or maximum likelihood variance estimation with or without dominance. PANSS-N produced a maximum LOD score of 1.2 at the D22S283 locus. LOD score of about 1 are easily produced by chance. Thus, we conclude that under quantitative trait we also find no evidence of linkage between schizophrenia and markers on chromosome 22 in our Chinese sibling pair sample.

Adolescent↗
PubMed2001

HPV16 E6 gene variations in invasive cervical squamous cell carcinoma and cancer in situ from Russian patients.

HPV16 is frequently seen in invasive cervical cancer (ICC) and cervical intraepithelial neoplasia (CIN). Its E6 gene has frequent sequence variations. Although some E6 variants have been reported to have different biochemical or biological properties, they do not show geographical identity. Moreover, the definition of 'variant' has been a source of confusion because it has been based on all departures from the 'prototype' once isolated randomly from an ICC case. We amplified the HPV16 E6 gene by PCR from fresh-frozen tissue of 104 cases of ICC and CIN from Russian patients and sequenced it in positive cases. We found that 32 of 55 (58.2%) ICC cases and 18 of 49 (36.7%) CIN cases were HPV 16-positive and we could identify 3 groups of E6 variants: group A was characterized by G at nt 350 where group B had T, and group M was a heterogeneous mixture of unique E6 variants; no significant difference existed in the distribution of the different groups between ICC and CIN; the clinically malignant (as defined by FIGO stage) order between the groups was M > A > B in ICC; in the cases with a single HPV16 E6 sequence, coexisting ICC, CIN and normal epithelium in the same patient shared the E6 variant; and 4 cases of ICC had double/multiple E6 variants. The results did not show any importance of E6 variants for ICC progression in Russian women. The results also indicated that the original HPV16 variant persisted during ICC progression, and that at a low frequency, double infections and/or mutation of variants might occur.

Adult↗
PubMed2001

Ligand-dependent formation of retinoid receptors, receptor-interacting protein 140 (RIP140), and histone deacetylase complex is mediated by a novel receptor-interacting motif of RIP140.

Receptor-interacting protein 140 (RIP140) interacts with retinoic acid receptor and retinoid X receptor in a ligand-dependent manner and suppresses retinoic acid (RA) induction of its target genes. The receptor-interacting motif is mapped to a C-terminal peptide sequence (LTKTNPILYYMLQK) of RIP140. The functional role of this motif in mediating the suppressive effects of RIP140 on RA induction is demonstrated in mutation studies. RA induces coimmunoprecipitation of histone deacetylase 3 with retinoic acid receptor/retinoid X receptor in the presence of wild type RIP140, but not in the presence of the C-terminal motif-deleted RIP140. A decrease in histone acetylation on the promoter region that carries a RA response element is associated with the expression of wild type RIP140, but not with expression of the mutant RIP140, in a dose-dependent manner. These data provide a molecular explanation for RIP140 acting as a novel ligand-dependent, negative modulator of RA-regulated gene expression.

Acetylation↗
PubMed2001

Regulation of mouse kappa opioid receptor gene expression by retinoids.

The effect of retinoids on the expression of kappa opioid receptor (KOR) gene was examined in normal and transgenic animals. KOR-lacZ transgene expression was specifically elevated in KOR-positive areas of the developing CNS by depleting vitamin A from animal diets. The endogenous KOR mRNA species, including all three isoforms, were also upregulated by depleting vitamin A in developing animals. Change in the expression of isoforms a and b is similar in prenatal stages but differs during postnatal development. Interestingly, upregulation of isoform c is most significant postnatally. The regulation of KOR gene by vitamin A was substantiated in a mouse embryonal carcinoma P19 culture system in which retinoic acid (RA), the most potent ingredient of vitamin A, was able to suppress the expression of all the three KOR isoforms and KOR protein. The RA-mediated suppression was blocked by an RA receptor antagonist and a histone deacetylase (HDAC) inhibitor. By using a reporter transfection assay in P19 cells, the potential genetic element responsible for RA-mediated suppression of KOR gene expression was located to intron 1 of the mouse KOR gene, which could also be blocked by HDAC inhibitor. Furthermore, suppression of KOR gene expression by RA in P19 cells appeared to be an indirect event and required protein synthesis. A role of RA in KOR gene regulation during developmental stages was discussed.

Animals↗