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Biomedical subjects

X Li

Publications and source records attributed to X Li.

At least 253 records · Page 14Linked to original sources
PubMed2001

Dedifferentiation of epidermal cells to stem cells in vivo.

The effects of growth factors on wound healing have been studied extensively; however epidermal regeneration is not fully understood. We treated eight patients with leg ulcers with recombinant human epidermal growth factor (rhEGF) and compared biopsies of regenerating epidermis with those of controls who did not receive rhEGF. We used immunohistochemistry to identify cells expressing keratin 19 and beta1 integrin in regenerated epidermis from patients and controls. Patients treated with rhEGF had stem cells in the spinous and granular layers of regenerated epidermis. Histological analysis showed that these stem cells had reverted from differentiated to undifferentiated stem cells. Our findings provide evidence for epidermal cell reversion.

Adult↗
PubMed2001

Identification of DNA sequences from a second pathogenicity island of uropathogenic Escherichia coli CFT073: probes specific for uropathogenic populations.

Uropathogenic Escherichia coli is the leading cause of urinary tract infection and hospital visits in North America. Cystitis and acute pyelonephritis, infection of the bladder and kidney, respectively, are the two most common syndromes encountered in patients with urinary tract infection. We sequenced and annotated 71,684 bases of a previously unidentified pathogenicity-associated island (PAI) from E. coli strain CFT073. This PAI contained 89 open-reading frames encoding a pap operon, iron-regulated genes, mobile genetic elements, and a large proportion of unknown or unidentified open-reading frames. Dot blot analysis with 11 DNA sequences from this PAI demonstrated that 7 sequences were more prevalent among uropathogens: 2 probes were more prevalent among cystitis and pyelonephritis isolates, 2 among pyelonephritis isolates only, and 3 among cystitis isolates only than among fecal isolates. These data suggest that groups of uropathogens have genetic differences that may be responsible for the different clinical outcomes.

Bacterial Proteins↗
PubMed2001

Lung tumor KRAS and TP53 mutations in nonsmokers reflect exposure to PAH-rich coal combustion emissions.

We determined the TP53 and codon 12 KRAS mutations in lung tumors from 24 nonsmokers whose tumors were associated with exposure to smoky coal. Among any tumors studied previously, these showed the highest percentage of mutations that (a) were G --> T transversions at either KRAS (86%) or TP53 (76%), (b) clustered at the G-rich codons 153-158 of TP53 (33%), and (c) had 100% of the guanines of the G --> T transversions on the nontranscribed strand. This mutation spectrum is consistent with an exposure to polycyclic aromatic hydrocarbons, which are the primary component of the smoky coal emissions. These results show that mutations in the TP53 and KRAS genes can reflect a specific environmental exposure.

Air Pollution, Indoor↗
PubMed2001

Catalytic amplification of the soft lithographic patterning of Si. Nonelectrochemical orthogonal fabrication of photoluminescent porous Si pixel arrays.

Photoluminescent, porous silicon pixel arrays were fabricated via a Pt-promoted wet etching of p-type Si(100) using a 1:1:1 EtOH/HF/H2O2 solution. The pixels were fabricated with micrometer-scale design rules on a silicon substrate that had been modified with an octadecyltrichlorosilane (OTS) monolayer patterned using microcontact printing. The printed OTS layer serves as an orthogonal resist template for the deposition of a Pt(0) complex, which preferentially deposits metal species in areas not covered with OTS. The Pt centers generate a localized oxidative dissolution process that pits the Si in the Pt-coated regions, resulting in the formation of a porous silicon microstructure that luminesces around 580 nm upon illumination with a UV source. Scanning electron microscopy and fluorescence microscopy images of the fabricated porous silicon structures showed that features in the size range of approximately 10-150 microm, and possibly smaller, can be generated by this catalytically amplified soft lithographic patterning method. Importantly, the OTS acts as an etch mask, so that, even with significant hole transport, etching is confined to areas coated with the Pt(0) complex.

Journal Article↗
PubMed2001

On the aromaticity of square planar Ga4(2-) and In4(2-) in gaseous NaGa4- and NaIn4- clusters.

We investigated the electronic structure and chemical bonding of two bimetallic clusters NaGa4- and NaIn4-. Photoelectron spectra of the anions were obtained and compared with ab initio calculations. We found that the ground state of the two anions contains a square planar dianion interacting with a Na+ cation. The Ga4(2-) and In4(2-) dianions both possess two delocalized pi electrons and are considered to be aromatic, similar to that recently found in Al4(2-). Using calculations for a model compound, we showed that a recently synthesized Ga4-organometallic compound also contains an aromatic -Ga4(2-)- unit, analogous to the gaseous clusters.

Journal Article↗
PubMed2001

Investigation of the influence of mean HPMC particle size and number of polymer particles on the release of aspirin from swellable hydrophilic matrix tablets.

The effects of hydroxypropyl methylcellulose (HPMC) of different particle size ranges, size distributions and concentrations on the release behaviour of aspirin from a swellable matrix tablet system were studied. A mean HPMC (Methocel K15M Premium) particle size of 113 microm was identified as a critical threshold in this study. Drug release rate increased markedly when polymer particle size was increased above 113 microm. Release rate was much less sensitive to changes in particle size below 113 microm. Aspirin release mechanism followed first order kinetics where mean HPMC particle size was below 113 microm. Release mechanism deviated from first order kinetics when the mean particle size was above 113 microm. Polymer fractions with similar mean particle size but differing size distribution were also observed to influence drug release rate but not release mechanism. First order release constant K(1) was found to be quantitatively related to the reciprocal of the cube root of both mean polymer particle size and number of polymer particles in the matrix.

Aspirin↗
PubMed2001

Rabi oscillations of excitons in single quantum dots.

Transient nonlinear optical spectroscopy, performed on excitons confined to single GaAs quantum dots, shows oscillations that are analogous to Rabi oscillations in two-level atomic systems. This demonstration corresponds to a one-qubit rotation in a single quantum dot which is important for proposals using quantum dot excitons for quantum computing. The dipole moment inferred from the data is consistent with that directly obtained from linear absorption studies. The measurement extends the artificial atom model of quantum dot excitonic transitions into the strong-field limit, and makes possible full coherent optical control of the quantum state of single excitons using optical pi pulses.

Journal Article↗
PubMed2001

Tetrakis(mu-2,3-dimethoxybenzoato)bis[(2,2'-bipyridine)(2,3-dimethoxybenzoato)lanthanum(III)].

The title compound, tetrakis(mu-2,3-dimethoxybenzoato)-kappa(4)O:O';kappa(6)O,O':O'-bis[(2,2'-bipyridine-N,N')(2,3-dimethoxybenzoato-O,O')lanthanum(III)], [La(2)(2,3-DMOBA)(6)(2,2'-bpy)(2)], where 2,3-DMOBA is 2,3-dimethoxybenzoate (C(9)H(9)O(4)) and 2,2'-bpy is 2,2'-bipyridine (C(10)H(8)N(2)), is a dimer with a centre of inversion between the La atoms bridged by four carboxylate ligands. The central La atom is ennea-coordinated and has a distorted monocapped square-antiprism geometry.

Journal Article↗
PubMed2001

Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20.

Nonsense-mediated decay (NMD) eliminates mRNAs that prematurely terminate translation. We used antibody to the nuclear cap binding protein CBP80 or its cytoplasmic counterpart eIF4E to immunopurify RNP containing nonsense-free or nonsense-containing transcripts. Data indicate that NMD takes place in association with CBP80. We defined other components of NMD-susceptible mRNP as CBP20, PABP2, eIF4G, and the NMD factors Upf2 and Upf3. Consistent with the dependence of NMD on translation, the NMD of CBP80-bound mRNA is blocked by cycloheximide or suppressor tRNA. These findings provide evidence that translation can take place in association with CBP80. They also indicate that CBP80-bound mRNA undergoes a "pioneer" round of translation, before CBP80-CBP20 are replaced by eIF4E, and Upf2 and Upf3 proteins dissociate from upstream of exon-exon junctions.

3T3 Cells↗
PubMed2001

Use of the probasin promoter ARR2PB to express Bax in androgen receptor-positive prostate cancer cells.

BACKGROUND: Adenovirus-mediated overexpression of the apoptosis-inducing protein Bax can induce apoptosis in prostate cancer cell lines. Constitutive overexpression of Bax could result in unwanted apoptosis in every site of accidental Bax accumulation in vivo. Therefore, we developed an adenoviral construct (Av-ARR2PB-Bax) in which the probasin promoter, modified to contain two androgen response elements, drives Bax expression. This promoter would be expected to limit expression of Bax to cells expressing the androgen receptor. METHODS: A variety of androgen receptor (AR)-positive and -negative cell lines of prostatic or nonprostatic origin were infected with Av-ARR2PB-Bax or a control virus, Av-ARR2PB-CAT, in which the same promoter drives expression of the chloramphenicol acetyl transferase-reporter gene. Bax expression and apoptosis in vitro were assessed by western blot analysis. Tumor size and apoptosis in vivo were assessed after four weekly injections of Av-ARR2PB-Bax or Av-ARR2PB-CAT into subcutaneous LNCaP xenografts growing in uncastrated male mice. All statistical tests were two-sided. RESULTS: Bax was overexpressed in an androgen-dependent way in AR-positive cell lines of prostatic origin but not in AR-positive cells of nonprostatic origin or in AR-negative cell lines of either prostatic or nonprostatic origin. The androgen dihydrotestosterone activated apoptosis in LNCaP cells infected with Av-ARR2PB-Bax but not in those infected with Av-ARR2PB-CAT. Av-ARR2PB-Bax-injected LNCaP xenograft tumors decreased in tumor size from 34.1 mm3 (95% confidence interval [CI] = 25.1 mm3 to 43.1 mm3) to 24.6 mm3 (95% CI = -2.5 mm3 to 51.7 mm3), but the difference was not statistically significant (P =.5). Tumors injected with Av-ARR2PB-CAT increased in size, from 28.9 mm3 (95% CI = 12.7 mm3 to 45.1 mm3) to 206 mm3 (95% CI = 122 mm3 to 290 mm3) (P =.002) and contained statistically significant more apoptotic cells (23.3% [95% CI = 21.1% to 25.6%] versus 9.5% [95% CI = 8.0% to 11.1]) (P<.001). CONCLUSIONS: Av-ARR2PB-Bax induces androgen-dependent therapeutic apoptosis in vitro and in vivo by activating apoptosis in AR-positive cells derived specifically from prostatic epithelium and does not affect nonprostatic cells.

Adenoviridae↗
PubMed2001

N-hydroxyl derivatives of guanidine based drugs as enzymatic NO donors.

Recent research suggests that NO may play a role in the physiological effects of some guanidine-containing drugs. In this report, three guanidine-containing drugs (guanadrel, guanoxan, and guanethidine) together with their N-hydroxyl derivatives were synthesized and their NO-releasing abilities catalyzed by nitric oxide synthases (NOSs) and horseradish peroxidase were evaluated. The guanidine containing compounds could not release NO in the presence of NOS or peroxidase. The corresponding N-hydroxyl compounds exhibited weak NO-releasing ability under the catalyzed of NOS and good NO-releasing ability under the oxidation by horseradish peroxidase in the presence of H(2)O(2). These compounds also displayed vasodilatory activity.

Animals↗
PubMed2001

Repression of bacterial motility by a novel fimbrial gene product.

Proteus mirabilis is a common uropathogen in patients with long-term catheterization or with structural or functional abnormalities in the urinary tract. The mannose-resistant, Proteus-like (MR/P) fimbriae and flagellum are among virulence factors of P.mirabilis that contribute to its colonization in a murine model of ascending urinary tract infection. mrpJ, the last of nine genes of the mrp operon, encodes a 107 amino acid protein that contains a putative helix-turn-helix domain. Using transcriptional lacZ fusions integrated into the chromosome and mutagenesis studies, we demonstrate that MrpJ represses transcription of the flagellar regulon and thus reduces flagella synthesis when MR/P fimbriae are produced. The repression of flagella synthesis by MrpJ is confirmed by electron microscopy. However, a gel mobility shift assay indicates that MrpJ does not bind directly to the regulatory region of the flhDC operon. The isogenic mrpJ null mutant of wild-type P.mirabilis strain HI4320 is attenuated in the murine model. Our data also indicate that PapX encoded by a pap (pyelonephritis- associated pilus) operon of uropathogenic Escherichia coli is a functional homolog of MrpJ.

Animals↗
PubMed2001

The role of bile acids in carcinogenesis.

Bile acids play a role in colorectal carcinogenesis as evidenced by epidemiological and experimental studies. Some bile acids stimulate growth of normal colonic and adenoma cells, but not of colorectal cancer cells. Moreover, bile acids stimulate invasion of colorectal cancer cells, at least in vitro. One possible mechanism of action is bile acid-induced DNA binding and transactivation of the activator protein-1 (AP-1) by co-operate activation of extracellular signal-regulated kinases (ERKs) and PKC signaling. In the present paper, we review the mechanisms by which bile acids influence carcinogenesis.

Animals↗
PubMed2001

Hiv-1 Tat can substantially enhance the capacity of NIK to induce IkappaB degradation.

The human immunodeficiency virus type 1 (HIV-1) Tat is a virally encoded protein that dramatically up-regulates viral replication through interactions with the HIV-1 5' long terminal repeat (LTR) and cellular transcription factors. The HIV-1 LTR is divided into three major regions: modulatory, core and TAR. The modulatory region contains numerous cis-acting sequences for the binding of transcription factors including NF-kappaB, NF-AT, and AP-1. In several reports, Tat has been found to induce NF-kappaB activation of the HIV-1 LTR, while in other studies Tat has been reported to have no effect on activation of NF-kappaB. These discrepancies may arise from differences in experimental conditions such as the source of Tat (exogenous versus endogenous), the detection methods for NF-kappaB activation (DNA binding capability versus IkappaB degradation), and the types of reporters used (HIV-1 versus non-HIV-1 derived). To reconcile these differences we examined the effect of endogenous Tat on NF-kappaB activation, on IkappaB degradation and its interaction with upstream MAP3Ks. We demonstrate that although an 80% reduction in Tat-induced HIV-1 LTR activity can be detected if the kappaB binding sites are mutated, surprisingly endogenous Tat (expressed intracellularly by transfection) lacks direct effect on IkappaB degradation. Further analysis demonstrates that although Tat alone lacks direct effect on IkappaBalpha degradation or dissociation from NF-kappaB, Tat can substantially enhance the capacity of NF-kappaB-inducing kinase (NIK), but not MEKK1, to accelerate degradation of IkappaB. We propose a model to explain these collective experimental findings.

Cysteine Endopeptidases↗
PubMed2001

Detection of rare DNA targets by isothermal ramification amplification.

We described previously a novel DNA amplification technique, termed ramification amplification (RAM) (Zhang et al., Gene 211 (1998) 277). This method was designed to utilize a circular probe (C-probe) that is covalently linked by a DNA ligase when it hybridizes to a target. Then, a DNA polymerase extends the bound forward primer along the C-probe and continuously displaces a downstream strand, generating a multimeric single-stranded DNA (ssDNA), analogous to in vivo 'rolling circle' replication of bacteriophage. This multimeric ssDNA then serves as a template for multiple reverse primers to hybridize, extend, and displace downstream DNA, generating a large ramified (branching) DNA complex, and resulting in an exponential amplification. Previously, we were able to achieve a significant amplification using phi29 DNA polymerase that has a high processivity and strong displacement activity. However, due to the intrinsic limitations of the polymerase, we only achieved a sensitivity of 10,000 target molecules, which is insufficient for most practical uses. Therefore, we tested several DNA polymerases and found that exo(-) Bst DNA polymerase meets the requirement for high sensitivity. By further improving the assay condition and format, we are able to detect fewer than ten targets in 1 h and to apply successfully this method for detection of Epstein-Barr virus in human lymphoma specimens.

Blotting, Southern↗
PubMed2001

IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFkappa B.

The interleukin-1 (IL-1) receptor-associated kinase (IRAK) is required for the IL-1-induced activation of nuclear factor kappaB and c-Jun N-terminal kinase. The goal of this study was to understand how IRAK activates the intermediate proteins TRAF6, TAK1, TAB1, and TAB2. When IRAK is phosphorylated in response to IL-1, it binds to the membrane where it forms a complex with TRAF6; TRAF6 then dissociates and translocates to the cytosol. The membrane-bound IRAK similarly mediates the IL-1-induced translocation of TAB2 from the membrane to the cytosol. Different regions of IRAK are required for the translocation of TAB2 and TRAF6, suggesting that IRAK mediates the translocation of each protein separately. The translocation of TAB2 and TRAF6 is needed to form a TRAF6-TAK1-TAB1-TAB2 complex in the cytosol and thus activate TAK1. Our results show that IRAK is required for the IL-1-induced phosphorylation of TAK1, TAB1, and TAB2. The phosphorylation of these three proteins correlates strongly with the activation of nuclear factor kappaB but is not necessary to activate c-Jun N-terminal kinase.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Short-term exposure to a neuroactive steroid increases alpha4 GABA(A) receptor subunit levels in association with increased anxiety in the female rat.

Previous work from this laboratory has demonstrated that withdrawal from the neuroactive steroid 3alpha,5alpha-THP (3alpha-hydroxy-5alpha-pregnan-20-one) after 3-week exposure to its parent compound, progesterone (P), increases anxiety and produces benzodiazepine (BDZ) insensitivity in female rats. These events were linked to upregulation of the alpha4 subunit of the GABA(A) receptor (GABAR) in the hippocampus [Brain Res. 507 (1998) 91; Nature 392 (1998) 926; J. Neurosci. 18 (1998) 5275]. The present study investigates the role of shorter term hormone treatment on alpha4 subunit levels as well as relevant behavioral and pharmacological end-points related to GABAR function. After 2-3 days of P exposure, two- to threefold increases in alpha4 protein levels were observed, which declined to control values after 5-6 days of hormone exposure. This effect was due to the GABA-modulatory metabolite of P, 3alpha,5alpha-THP. alpha4 upregulation was inversely correlated with BDZ potentiation of GABA-gated current, assessed using whole cell patch clamp techniques on acutely isolated hippocampal pyramidal cells. A near total BDZ insensitivity was observed by 2-3 days of hormone exposure in association with the maximal increase in alpha4 levels. Up-regulation of the alpha4 GABAR subunit was also reflected by an increase in anxiety in the elevated plus maze. A significant decrease in open arm entries was observed after 72-h exposure to P, an effect which recovered by 6 days of P treatment. As demonstrated in vitro, alpha4 upregulation also resulted in a relative insensitivity to the anxiolytic actions of BDZ. These results suggest that short-term exposure to 3alpha,5alpha-THP produces changes in GABAR subunit composition similar to those that occur after chronic exposure and withdrawal from the steroid.

Animals↗