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Biomedical subjects

G Xiao

Publications and source records attributed to G Xiao.

At least 19 recordsLinked to original sources
PubMed2002

Coherent magnetization rotation and phase control by ultrashort optical pulses in CrO(2) thin films.

We have applied photoexcitation by ultrashort laser pulses to single crystal thin CrO(2) films to trigger coherent transient magnetization rotation on a subnanosecond time scale, in macroscale single domains. Moreover, by applying the photoexcitation by pairs of temporally separated pump pulses, the transient precession of the magnetization can be phase controlled, depending on the time separation between the pulses. The mechanism behind the photoexcitation originates from the modulation of the magnetocrystalline anisotropy by nonthermal hot electron spins.

Journal Article↗
PubMed2001

Inducible activation of c-Myc in adult myocardium in vivo provokes cardiac myocyte hypertrophy and reactivation of DNA synthesis.

c-Myc, a protooncogene, mediates both proliferative and cellular growth in many cell types. Although not expressed in the adult heart under normal physiological conditions, Myc expression is rapidly upregulated in response to hypertrophic stimuli. Although Myc is capable of sustaining hyperplastic growth in fetal myocytes, the effects of its re-expression in adult postmitotic myocardium and its role in mediating cardiac hypertrophy are unknown. To determine the effects of de novo Myc activity in adult postmitotic myocardium in vivo, we created a novel transgenic model in which Myc is expressed and inducibly activated specifically in cardiac myocytes. Activation of Myc in adult myocardium was sufficient to reproduce the characteristic changes in myocyte size, protein synthesis, and cardiac-specific gene expression seen in cardiac hypertrophy. Despite the increased cardiac mass, left ventricular function remained normal. Activation of Myc also provoked cell cycle reentry in postmitotic myocytes, which led to increased nuclei per myocyte and DNA content per nuclei.

Animals↗
PubMed2001

Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha.

IkappaB kinase (IKK) is a key mediator of NF-kappaB activation induced by various immunological signals. In T cells and most other cell types, the primary target of IKK is a labile inhibitor of NF-kappaB, IkappaBalpha, which is responsible for the canonical NF-kappaB activation. Here, we show that in T cells infected with the human T-cell leukemia virus (HTLV), IKKalpha is targeted to a novel signaling pathway that mediates processing of the nfkappab2 precursor protein p100, resulting in active production of the NF-kappaB subunit, p52. This pathogenic action is mediated by the HTLV-encoded oncoprotein Tax, which appears to act by physically recruiting IKKalpha to p100, triggering phosphorylation-dependent ubiquitylation and processing of p100. These findings suggest a novel mechanism by which Tax modulates the NF-kappaB signaling pathway.

Amino Acid Sequence↗
PubMed2001

NF-kappaB signaling pathway governs TRAIL gene expression and human T-cell leukemia virus-I Tax-induced T-cell death.

The Tax oncoprotein encoded by human T-cell leukemia virus induces both T-cell activation and apoptosis. The mechanism by which Tax induces apoptosis has remained unclear. Using genetically manipulated T-cell lines, we demonstrate that Tax-induced T-cell death is dependent on NF-kappaB signaling. Tax fails to induce apoptosis in T cells lacking IkappaB kinase gamma (IKKgamma), an essential component of the NF-kappaB signaling pathway. This defect was rescued when the mutant cells were reconstituted with exogenous IKKgamma. We further demonstrate that the Tax-induced T-cell death is mediated by TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL), because this event can be effectively inhibited by a TRAIL-blocking antibody. Consistent with this functional aspect, Tax stimulates the expression of TRAIL mRNA. Finally, we provide genetic evidence demonstrating that the NF-kappaB signaling pathway is essential for TRAIL gene induction by both Tax and T-cell activation signals. These studies reveal a novel function of the NF-kappaB signaling pathway and suggest a key mechanism by which Tax induces T-cell death.

Apoptosis↗
PubMed2001

Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.

In mammals, the canonical nuclear factor kappaB (NF-kappaB) signaling pathway activated in response to infections is based on degradation of IkappaB inhibitors. This pathway depends on the IkappaB kinase (IKK), which contains two catalytic subunits, IKKalpha and IKKbeta. IKKbeta is essential for inducible IkappaB phosphorylation and degradation, whereas IKKalpha is not. Here we show that IKKalpha is required for B cell maturation, formation of secondary lymphoid organs, increased expression of certain NF-kappaB target genes, and processing of the NF-kappaB2 (p100) precursor. IKKalpha preferentially phosphorylates NF-kappaB2, and this activity requires its phosphorylation by upstream kinases, one of which may be NF-kappaB-inducing kinase (NIK). IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation.

Animals↗
PubMed2001

Synthesis of substituted 5[H]phenanthridin-6-ones as potent poly(ADP-ribose)polymerase-1 (PARP1) inhibitors.

1-, 2-, 3-, 4-, 8-, or 10-Substituted 5(H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared, some showed not only low IC(50) values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5(H)phenanthridin-6-one ring.

Enzyme Inhibitors↗
PubMed2001

Engineering new bone tissue in vitro on highly porous poly(alpha-hydroxyl acids)/hydroxyapatite composite scaffolds.

Engineering new bone tissue with cells and a synthetic extracellular matrix (scaffolding) represents a new approach for the regeneration of mineralized tissues compared with the transplantation of bone (autografts or allografts). In the present work, highly porous poly(L-lactic acid) (PLLA) and PLLA/hydroxyapatite (HAP) composite scaffolds were prepared with a thermally induced phase separation technique. The scaffolds were seeded with osteoblastic cells and cultured in vitro. In the pure PLLA scaffolds, the osteoblasts attached primarily on the outer surface of the polymer. In contrast, the osteoblasts penetrated deep into the PLLA/HAP scaffolds and were uniformly distributed. The osteoblast survival percentage in the PLLA/HAP scaffolds was superior to that in the PLLA scaffolds. The osteoblasts proliferated in both types of the scaffolds, but the cell number was always higher in the PLLA/HAP composite scaffolds during 6 weeks of in vitro cultivation. Bone-specific markers (mRNAs encoding bone sialoprotein and osteocalcin) were expressed more abundantly in the PLLA/HAP composite scaffolds than in the PLLA scaffolds. The new tissue increased continuously in the PLLA/HAP composite scaffolds, whereas new tissue formed only near the surface of pure PLLA scaffolds. These results demonstrate that HAP imparts osteoconductivity and the highly porous PLLA/HAP composite scaffolds are superior to pure PLLA scaffolds for bone tissue engineering.

3T3 Cells↗
PubMed2001

Inhibition of the HIV-1 rev-RRE complex formation by unfused aromatic cations.

RNA viruses cause a wide range of human diseases. Development of new agents to target such viruses is an active area of research. Towards this goal, a series of diphenylfuran cations as potential inhibitors of the Rev-RRE complex have been designed and synthesized. Analysis of the interaction of the diphenylfurans with RRE and TAR RNA model systems by gel shift assays indicates that they exhibit both sequence and structure-dependent binding modes. Our results show a strong interaction between the diphenylfuran ring system and RRE bases, while the TAR interactions are much weaker with the compounds that are the best inhibitors of Rev-RRE.

Aminoglycosides↗
PubMed2001

NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100.

Processing of the nf(kappa)b2 gene product p100 to generate p52 is an important step in NF-kappaB regulation. We show that this step is negatively regulated by a processing-inhibitory domain (PID) within p100 and positively regulated by the NF-kappaB-inducing kinase (NIK). While the PID suppresses the constitutive processing of p100, NIK induces p100 processing by stimulating site-specific phosphorylation and ubiquitination of this precursor protein. Further, a natural mutation of the gene encoding NIK in alymphoplasia (aly) mice cripples the function of NIK in p100 processing, causing a severe defect in p52 production. These data suggest that NIK is a specific kinase regulating p100 processing and explain why the aly and nf(kappa)b2 knockout mice exhibit similar immune deficiencies.

Animals↗
PubMed2001

A novel proton-dependent nucleoside transporter, CeCNT3, from Caenorhabditis elegans.

In this study, we describe the cloning and characterization of a proton-dependent, broadly selective nucleoside transporter from Caenorhabditis elegans. Recently, we constructed a broadly selective nucleoside transporter which accepts both purine and pyrimidine nucleosides. Based on these studies, we hypothesized that CNTs with novel substrate selectivities exist in nature and that a CNT homolog in the C. elegans genomic database may function as a broadly selective nucleoside transporter. We cloned the cDNA for this transporter, termed CeCNT3 because of its broad selectivity, using polymerase chain reaction-based methods. CeCNT3 is predicted to have 575 amino acid residues (63.4 kDa) with 11 to 14 putative transmembrane domains and exhibits approximately 30% identity to members of the mammalian CNT family. This transporter exhibits a novel substrate selectivity, transporting a wide range of purine and pyrimidine nucleosides (inosine, guanosine, adenosine, uridine, and thymidine) but not cytidine. The apparent Km values for inosine and thymidine are 15.2 +/- 5.3 microM and 11.0 +/- 2.4 microM, respectively. Kinetic studies demonstrate that purine and pyrimidine nucleosides share a common recognition site in the transporter. In contrast to all known members of the mammalian CNT family, CeCNT3-mediated transport of nucleosides is proton-, but not sodium-, dependent. Mutation of tyrosine 332 in CeCNT3 decreased both the maximum uptake rate and apparent Km of thymidine, suggesting that this residue is in the domain of nucleoside recognition and translocation. The broad nucleoside specificity of CeCNT3 may be explained by this and other residues that restrict purine and pyrimidine nucleoside uptake and that discriminate among pyrimidine nucleosides.

Amino Acid Sequence↗
PubMed2001

Visualizing pneumococcal infections in the lungs of live mice using bioluminescent Streptococcus pneumoniae transformed with a novel gram-positive lux transposon.

Animal studies with Streptococcus pneumoniae have provided valuable models for drug development. In order to monitor long-term pneumococcal infections noninvasively in living mice, a novel gram-positive lux transposon cassette, Tn4001 luxABCDE Km(r), that allows random integration of lux genes onto the bacterial chromosome was constructed. The cassette was designed so that the luxABCDE and kanamycin resistance genes were linked to form a single promoterless operon. Bioluminescence and kanamycin resistance only occur in a bacterial cell if this operon has transposed downstream of a promoter on the bacterium's chromosome. S. pneumoniae D39 was transformed with plasmid pAUL-A Tn4001 luxABCDE Km(r), and a number of highly bioluminescent colonies were recovered. Genomic DNA from the brightest D39 strain was used to transform a number of clinical S. pneumoniae isolates, and several of these strains were tested in animal models, including a pneumococcal lung infection model. Strong bioluminescent signals were seen in the lungs of the animals containing these pneumococci, allowing the course and antibiotic treatment of the infections to be readily monitored in real time in the living animals. Recovery of the bacteria from the animals showed that the bioluminescent signal corresponded to the number of CFU and that the lux construct was highly stable even after several days in vivo. We believe that this lux transposon will greatly expand the ability to evaluate drug efficacy against gram-positive bacteria in living animals using bioluminescence.

Amoxicillin↗
PubMed2001

Effect of benzene, toluene, xylene on the semen quality and the function of accessory gonad of exposed workers.

The effects on semen and the function of accessory gonad of workers after short and long term exposure to benzene, toluene, and xylene were examined. The semen and blood of 24 married workers exposed to benzene, toluene, and xylene were collected. Routine sperm characteristic, acrosin activity, and Lactate dehydrogenase C4 (LDH-C4) relative activity were detected. The results showed that benzene, toluene, and xylene were found in the blood and semen of some ex-workers at workplaces where the air concentration of benzene, toluene, and xylene exceeded the maximum allowable concentration (MAC). No such solvents were detected in the blood and semen of workers of the control group. The sperm vitality and sperm motility decreased in the exposed workers. The mean acrosin activity, gamma-GT activity and LDH-C4 relative activity in the exposed workers were lower, and fructose concentration was higher than those in the control. There were negative correlations between sperm vitality, sperm activity, acrosin activity, or LDH-C4 relative activity and working history. These results suggest that the mixture of these solvents could affect the sperm and the function of accessory gonad. This might be one reason of the abnormal pregnancy outcome among the wives of workers exposed to benzene, toluene, and xylene.

Acrosin↗
PubMed2001

[Study of noninvasive intracranial pressure monitoring by bioelectric impedance method].

The changes of intracranial components and corresponding brain impedance were analyzed while intracranial pressure was increasing, and the relation of intracranial pressure pulse wave and brain impedance pulse wave were discussed. A theory of noninvasive intracranial pressure monitoring by bioelectric impedance was put forward. The result of primary experiment suggested that the theory be feasible.

Animals↗
PubMed2001

[Effects of quinacrine on gut-origin bacteria/endotoxin translocation in rats with gut ischemia/reperfusion injury].

OBJECTIVE: To explore the influence of quinacrine, which is an inhibitor of phospholipase A2, on gut-origin bacteria/endotoxin translocation in rats with gut ischemia/reperfusion injury. METHODS: Forty-two Wistar rats were randomly divided into normal control (C, n = 6), gut ischemia/reperfusion injury control (IC, n = 12), quinacrine use at 3 hours after the injury(3 h, n = 12), and quinacrine use at 12 hours after the injury (12 h, n = 12) groups. The contents of blood endotoxin and TNF alpha in venae cavae and portal vein were measured in all groups. At the same time, tissue samples from mesenteric lymph nodes, liver, lungs and kidneys were harvested for bacterial culture. RESULTS: Plasma contents of endotoxin and TNF alpha were lowered in both quinacrine treatment groups (P < 0.01). The incidence of bacterial/endotoxin translocation was decreased by quinacrine use in mesenteric lymph nodes, lungs, liver and kidneys after the injury (P < 0.05 approximately 0.01). CONCLUSION: Early application of quinacrine in Wistar rats inflicted by gut ischemia reperfusion injury could obviously lower bacterial/endotoxin translocation and ameliorate the release of pro-inflammatory mediators and cytokines, thus attenuating injury to remote organs.

Animals↗
PubMed2001

[Prognostic influence of parapharyngeal space involvement in nasopharyngeal carcinoma].

OBJECTIVE: To explore the prognostic influence of parapharyngeal space involvement in nasopharyngeal carcinoma (NPC). METHODS: From Jan. 1987 to Dec. 1994, 197 previously untreated NPC patients were examined by CT scan. The prognostic factors ware evaluated by univariate and multivariate analyses on SPSS 8.0 software. RESULTS: The actual survival rate, disease-free survival rate and local failure-free rate were negatively affected by the presence of parapharyngeal space involvement (P = 0.0115, P = 0.0035, P = 0.0367). The 5-year actual survival rate, disease-free survival rate and local failure-free rate in patients without tumor invasion to parapharyngeal space was 87.9%, 88.0% and 96.9%, respectively. The survival rate in patients with tumor invasion to prestyloid space was 75.0%, 71.2% and 93.7%, respectively. That in patients with tumor invasion to poststyloid space was 60.5%, 57.7% and 86.8%, respectively. The 5-year distant metastasis-free survival rate was 88.1% in patients without poststyloid involvement as compared to 73.8% in those with poststyloid involvement. CONCLUSION: The survival and local tumor control are affected by parapharyngeal space involvement. Distant metastasis is more likely to occur when the tumor growth involves poststyloid space.

Adolescent↗
PubMed2001

[Realization of a new segmental bioelectrical impedance method for assessing body composition: correlation analysis of human body parameters].

The method of segmental bioelectrical impedance analysis for assessing body composition requires measurement of segmental lengths and cross-sectional areas; thus its complexity is increased. This paper reports the correlation analysis of human body parameters and the linear regressions for predicting segmental parameters by use of gender, height and weight. Accordingly, segmental impedance analysis is simplified.

Adolescent↗