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Biomedical subjects

Wei Liu

Publications and source records attributed to Wei Liu.

At least 217 records · Page 12Linked to original sources

Molecular epidemiology of HIV-1 subtypes in southern China.

The driving forces of the HIV-1 epidemic in Guangxi, China were assessed by investigating virologic and epidemiologic data from a cohort of longitudinally followed injection drug users (IDUs) in Binyang and Pingxiang, major urban areas along 2 separate drug routes in the province. Sera and interview data were obtained in September and October of 2000. Sequence analysis of HIV-1 was performed on the gag-pol region (HXB2 nt 1850-3005) and C2 to V4 env (HXB2 nt 6704-7626). Sequence data demonstrated that 88% of the infections in Pingxiang were CRF01_AE, whereas 96% in Bin-yang were CRF08_BC. Three recently infected subjects in Pingxiang were infected with CRF08_BC, and 1 chronically infected subject had evidence of a recombinant virus. Intersubject distances were statistically greater for CRF01_AE-infected subjects than CRF08_BC-infected subjects for all regions except V4. The epidemic in Binyang is similar to previously described IDU-based epidemics, with a strong founder effect with little variation in V3. The epidemic in Pingxiang may have had multiple introductions of the CRF01_AE epidemic into the city and greater spread through sexual transmission, resulting in greater variation in V3 than typically seen in purely parenterally based epidemics.

Adult↗

Synthesis and cellular studies of nonaggregated water-soluble phthalocyanines.

Water-soluble phthalocyanines are promising photosensitizers for application in cancer therapy and in the photoinactivation of viruses. The water-soluble zinc(II) phthalocyanines 5 and 6 were synthesized by converting the corresponding ester derivative 4 into the sodium carboxylate and carboxylic acid species. Compound 5 can be solubilized in water as a monomeric species, as demonstrated by UV/vis and fluorescence spectroscopy. These compounds were characterized by analytical and spectroscopic methods and, in the case of 4, by X-ray crystallography. The water-soluble phthalocyanines were found to have low dark cytotoxicity toward V79 hamster fibroblasts and human HEp2 cells, to be phototoxic at low light and drug doses, to be taken up by cells in culture, and to localize intracellularly, mainly in the cell lysosomes. Conjugation of the anionic phthalocyanines with positively charged LipoGen liposomes resulted in effective delivery of these compounds into the nuclei of cells. It is concluded that these highly water-soluble phthalocyanines are promising sensitizers for the photodynamic therapy of tumors.

Animals↗

Biological activities of conjugated fatty acids: conjugated eicosadienoic (conj. 20:2delta(c11,t13/t12,c14)), eicosatrienoic (conj. 20:3delta(c8,t12,c14)), and heneicosadienoic (conj. 21:2delta(c12,t14/c13,t15)) acids and other metabolites of conjugated linoleic acid.

The elongated form of conjugated linoleic acid (CLA), conjugated eicosadienoic acid (CEA, conj. 20:2delta(c11,t13/t12,c14)), was generated from CLA by liver microsomal fractions. Subsequent testing showed that dietary CEA significantly reduced body fat, and increased lean mass similar to CLA when compared to controls. CEA also decreased lipoprotein lipase activity and triacylglyceride, and increased glycerol release in 3T3-L1 adipocytes, correlated with the trans-12,cis-14 isomer, but CEA required a longer incubation period than cells treated with CLA. Based on the fact that CEA fed animals had CLA in tissue, we suggest that the effect of CEA is due to the CLA converted from CEA in the system. The delta-6 desaturated and elongated form of trans-10,cis-12 CLA (conjugated eicosatrienoic acid, CETA, conj. 20:3delta(c8,t12,c14)) inhibited LPL activity and increased glycerol release but was less active than trans-10,cis-12 CLA or CEA. The 21-carbon conjugated fatty acid, conjugated heneicosadienoic acid (CHDA, conj. 21:2delta(c12,t14/c13,t15)), was not active on LPL inhibition, triacylglyceride, or glycerol release in 3T3-L1 adipocytes. We also provide evidence that CLA was metabolized to conjugated dodecadienoic acid (conj. 12:2delta(c3,t5/t4,c6)). In addition, there were indications of the presence of conjugated tetradecadienoic acid (conj. 14:2delta(c5,t7/t6,c8)), suggesting that CLA can be metabolized through fatty acid beta-oxidation. This is the first work to report the presence of conjugated 12 and 14 carbon fatty acids, originated from CLA, and the biological activities of CEA, CETA and CHDA.

Animals↗

Distinct functions for Bmp signaling in lip and palate fusion in mice.

Previous work suggested that cleft lip with or without cleft palate (CL/P) is genetically distinct from isolated cleft secondary palate (CP). Mutations in the Bmp target gene Msx1 in families with both forms of orofacial clefting has implicated Bmp signaling in both pathways. To dissect the function of Bmp signaling in orofacial clefting, we conditionally inactivated the type 1 Bmp receptor Bmpr1a in the facial primordia, using the Nestin cre transgenic line. Nestin cre; Bmpr1a mutants had completely penetrant, bilateral CL/P with arrested tooth formation. The cleft secondary palate of Nestin cre; Bmpr1a mutant embryos was associated with diminished cell proliferation in maxillary process mesenchyme and defective anterior posterior patterning. By contrast, we observed elevated apoptosis in the fusing region of the Nestin cre; Bmpr1a mutant medial nasal process. Moreover, conditional inactivation of the Bmp4 gene using the Nestin cre transgenic line resulted in isolated cleft lip. Our data uncover a Bmp4-Bmpr1a genetic pathway that functions in lip fusion, and reveal that Bmp signaling has distinct roles in lip and palate fusion.

Animals↗

Quantitative predictions to conditions of zwitterionic stacking by transient moving chemical reaction boundary created with weak electrolyte buffers in capillary electrophoresis.

This paper develops a novel procedure of quantitative predictions for the on-column stacking conditions of a zwitterionic analyte by a moving chemical reaction boundary (MCRB) in capillary electrophoresis (CE). The procedure concerns the choice of the weak acidic running and alkaline sample buffers and the velocity design of MCRB created with the two buffers. Based on the theory of MCRB, the theoretical computations are performed. From the computations, the following two predictions are refined for the stacking conditions of zwitterion. (1) The zwitterion velocity in the acidic buffer should be greater than that of MCRB moving toward the cathode, or the zwitterion cannot be well stacked by the MCRB. (2) The gap between pH values of the acidic and alkaline sample buffers ought to comprise the isoelectric point (pI) of zwitterion to be stacked; namely, there exists the relation of pH (acidic buffer) < pI < pH (sample). The predictions are quantitatively proved by the experiments of zwitterionic stacking with two kinds of MCRBs. In addition, the experiments also show the tightly stacked peak of zwitterion existing in the process of MCRB, but not after the MCRB. The theoretical and experimental results hold obvious significances to other zwitterion (such as peptide and protein) on-column stacking in CE.

Buffers↗

Pharmacogenetics of outcome in children with acute lymphoblastic leukemia.

Acquired genetic characteristics of acute lymphoblastic leukemia (ALL) cells are used to individualize therapy, whereas germ line genetic characteristics generally are not. We determined whether ALL outcome was related to 16 genetic polymorphisms affecting the pharmacodynamics of antileukemic agents. Of 246 children, 116 were treated on the lower-risk (LR) and 130 on the higher-risk (HR) arms of a St Jude protocol. Patients in the HR group with the glutathione S-transferase (GSTM1) non-null genotype had greater risk of hematologic relapse (P = .03), which was further increased by the thymidylate synthetase (TYMS) 3/3 genotype (P = .03). These genotypes remained predictive in multivariate analyses (P < .001 and .003, respectively). No genotypes were predictive in the LR arm. Expression of these 2 genes in ALL blasts was lower in those with low-activity genotypes. For central nervous system relapse, among the HR group, the vitamin D receptor start site (P = .02) and intron 8 genotypes (P = .04) predisposed, whereas for LR patients the TYMS 3/3 genotype predisposed (P = .04). The GSTM1 non-null and TYMS 3/3 genotypes are plausibly linked to drug resistance. Polymorphisms interact to influence antileukemic outcome and represent determinants of response that can be used to optimize therapy.

Alleles↗

Correlates of HIV status among injection drug users in a border region of southern China and northern Vietnam.

This article presents an analysis of the correlates of HIV status among samples of injection drug users (IDUs) in Lang Son Province, Vietnam (n=348), and Ning Ming County, Guangxi Province, China (n=294), who were interviewed and tested for HIV antibody just before the start of a peer-based HIV prevention intervention in this border region. Participants were largely male, in their 20s, and single. Logistic regression analysis suggests that among Chinese IDUs, border-related factors (eg, living closer to the border, buying drugs across the border more frequently) and younger age are the best predictors of HIV positivity. In Vietnam, HIV status seems to drive behavior (eg, some risk reduction practices are predictive of HIV positivity). These differing patterns may reflect the fact that the intertwined epidemics of heroin injection and HIV began earlier and HIV prevalence has reached significantly higher levels in Lang Son than across the border in Ning Ming. Although border-related factors emerge as predictors in Ning Ming, more IDUs in Lang Son are HIV-positive and may be reacting behaviorally to that status. Their greater likelihood of engaging in risk reduction measures may reflect some combination of a belief that risk reduction can slow disease progression and an altruistic desire to avoid infecting others.

Adult↗

Structural requirements of the extracellular to transmembrane domain junction for erythropoietin receptor function.

The erythropoietin receptor (EpoR) is crucial for erythrocyte formation. The x-ray crystal structures of the EpoR extracellular domain lack the juxtamembrane (JM) region and the junction to the transmembrane (TM) domain. Yet the JM-TM regions are important for transmitting the conformational change imposed on the receptor dimer by Epo binding. Cysteine-scanning mutagenesis of the JM-TM regions identified three novel constitutively active mutants, demonstrating close disulfide-bonded juxtapositioning of these residues in the JM (L223C) and N-terminal TM domain (L226C, I227C). Chemical cross-linking defined the interface of the active helical TM dimer and revealed that the JM-TM segment encompassing Leu(226)-Leu(230) is non-helical. Molecular dynamics and NMR studies indicated that the TM-JM junction forms an N-terminal helix cap. This structure is important for EpoR function because replacement of this motif by consecutive leucines rendered the receptor constitutively active.

Amino Acid Motifs↗

Structural mechanism governing the quaternary organization of monocot mannose-binding lectin revealed by the novel monomeric structure of an orchid lectin.

Two isoforms of an antifungal protein, gastrodianin, were isolated from two subspecies of the orchid Gastrodia elata, belonging to the protein superfamily of monocot mannose-specific lectins. In the context that all available structures in this superfamily are oligomers so far, the crystal structures of the orchid lectins, both at 2.0 A, revealed a novel monomeric structure. It resulted from the rearrangement of the C-terminal peptide inclusive of the 12th beta-strand, which changes from the "C-terminal exchange" into a "C-terminal self-assembly" mode. Thus, the overall tertiary scaffold is stabilized with an intramolecular beta-sheet instead of the hybrid observed on subunit/subunit interface in all known homologous dimeric or tetrameric lectins. In contrast to the constrained extended conformation with a cis peptide bond between residues 98 and 99 commonly occurring in oligomers, a beta-hairpin forms from position 97 to 101 with a normal trans peptide bond at the corresponding site in gastrodianin, which determines the topology of the C-terminal peptide and thereby its unique fold pattern. Sequence and structure comparison shows that residue replacement and insertion at the position where the beta-hairpin occurs in association with cis-trans inter-conversion of the specific peptide bond (97-98) are possibly responsible for such a radical structure switch between monomers and oligomers. Moreover, this seems to be a common melody controlling the quaternary states among bulb lectins through studies on sequence alignment. The observations revealed a structural mechanism by which the quaternary organization of monocot mannose binding lectins could be governed. The mutation experiment performed on maltose-binding protein-gastrodianin fusion protein followed by a few biochemical detections provides direct evidence to support this conclusion. Potential carbohydrate recognition sites and biological implications of the orchid lectin based on its monomeric state are also discussed in this paper.

Amino Acid Sequence↗

Transforming growth factor-beta1 signaling participates in the physiological and pathological regulation of mouse inner ear development by all-trans retinoic acid.

BACKGROUND: Retinoic acid (RA) is a vitamin A derivative that participates in patterning and regulation of inner ear development. Either excess RA or RA deficiency during a critical stage of inner ear development can produce teratogenic effects. Previous studies have shown that in utero exposure of the developing mouse inner ear to a high dose of all-trans RA (atRA) results in severe malformations of the inner ear that are associated with diminished levels of endogenous transforming growth factor-beta1 (TGF-beta(1)) protein. METHODS: In this study, the effects of a teratogenic level of atRA on levels and patterns of expression of TGFbeta receptor II (TGFbetaRII) and Smad2, a downstream component of the TGFbeta signal transduction pathway, are investigated in the developing mouse inner ear. The expression pattern of endogenous RA receptor alpha (RARalpha) and the ability of an RARalpha(1)-specific antisense oligonucleotide (AS) to modulate otic capsule chondrogenesis are demonstrated in the inner ear and in culture. RESULTS: Endogenous TGFbetaRII and Smad2 are downregulated in the inner ear following in utero atRA treatment. In addition, a reduction in endogenous TGFbeta(1) and a marked suppression of chondrogenesis occur in RARalpha(1) AS-treated cultures in comparison to untreated or oligonucleotide-treated control cultures. This chondrogenic suppression can be partially overcome by supplementation of RARalpha(1) AS-treated cultures with exogenous TGFbeta(1) protein. CONCLUSIONS: Our findings support a role for TGFbeta in the physiological and pathological effects of RA on inner ear development.

Abnormalities, Drug-Induced↗

Quantitative study on selective stacking of zwitterions in large-volume sample matrix by moving reaction boundary in capillary electrophoresis.

The paper advanced the theoretical procedures for quantitative design on selective stacking of zwitterions in full capillary sample matrix by a cathodic-direction moving reaction boundary (MRB) in capillary electrophoresis (CE) under control of electroosmotic flow (EOF). With the procedures, we conducted the theoretical computations on the selective stacking of two test analytes of L-histidine (His) and L-tryptophan (Trp) by the MRB created with 30 mM pH 3.0 formic acid-NaOH buffer and 2-80 mM sodium formate. The results revealed the following three predictions. At first, the MRB cannot stack His and Trp plugs if less than 12.5 mM sodium formate is used to form the MRB and prepare the sample matrix. Second, the MRB can stack His and/or Trp sample plugs completely if higher than 50 mM sodium formate is chosen to form the MRB. Third, the MRB can only focus His plug completely, but stack Trp plug partially if 20-50 mM sodium formate is used; this implied the complete MRB-induced selective stacking to His rather than Trp. All the three predictions were quantitatively proved by the experiments. With great dilution of sample matrix and control of EOF, controllable, simultaneous and MRB-induced selective stacking and separation of zwitterions were achieved. The theoretical results hold evident significances to the quantitative design of selective stacking conditions and the increase of detection sensitivity of zwitterions in CE. In addition, the control of EOF by cetyltrimethylammonium bromide (CTAB) can evidently improve the stacking efficiency to both His and Trp.

Cetrimonium↗

Controlling acrylamide in French fry and potato chip models and a mathematical model of acrylamide formation: acrylamide: acidulants, phytate and calcium.

We previously reported that in potato chip and French fry models, the formation of acrylamide can be reduced by controlling pH during processing steps, either by organic (acidulants) or inorganic acids. Use of phytate, a naturally occurring chelator, with or without Ca++ (or divalent ions), can reduce acrylamide formation in both models. However, since phytate itself is acidic, the question remains as to whether the effect of phytate is due to pH alone or to additional effects. In the French fry model, the effects on acrylamide formation of pH, phytate, and/or Ca++ in various combinations were tested in either blanching or soaking (after blanching) steps. All treatments significantly reduced acrylamide levels compared to control. Among variables tested, pH may be the single most important factor for reducing acrylamide levels, while there were independent effects of phytate and/or Ca++ in this French fry model. We also developed a mathematical formula to estimate the final concentration of acrylamide in a potato chip model, using variables that can affect acrylamide formation: glucose and asparagine concentrations, cut potato surface area and shape, cooking temperature and time, and other processing conditions.

Acids↗

Dynamic observation of liver fibrosis in mice infected with Schistosoma japonica.

The expression of TNF-alpha in the liver at different periods post Schistosoma japonica infection and the effect on liver fibrosis after supplementary injection of these cytokines were investigated. The mice infected with schistosome cercariae were divided into 3 groups: normal control group, TNF-alpha-untreated infection group and TNF-alpha-treated infection group. ABC immunohistochemistry and pathologic image multimedia quantification system were applied to dynamically detect the activity of TNF-alpha. The results showed that the levels of TNF-alpha in the liver in TNF-alpha-untreated infection group were slowly decreased with prolongation of infection time (from 8th, 11th, 14th to 18th week), while in the TNF-alpha-treated infection group, those were increased significantly after intraperitoneal injection of TNF-alpha at 6th week after infection. At first to 8th week after the final injection of TNF-alpha, the intrahepatic TNF-alpha levels in the TNF-alpha-treated infection group were significantly higher than in the other two groups (P < 0.01), and the granulomatous inflammation and fibrosis in the liver were also milder in the normal control group. It was concluded that at the early stage of Schistosoma japonica infection mouse liver mainly released Th1 cytokine and TNF-alpha from Th1 activated macrophages. Six weeks after infection (post egg deposition), exogenous supplement with intraperitoneal injection of TNF-alpha could induce the enhanced expression of Th1 cytokines and alleviate the liver granulomatous inflammation and fibrosis.

Animals↗

Preparation and characterization of a truncated caricain lacking 41 residues from the N-terminal.

We purified an 18.8 kD protease from caricain solution. This protease was derived from caricain. It does not have the first 41 residues of the N-terminal sequence of caricain, and its N-terminal residue is Thr. Also, one of the disulfide bonds of caricain (cys22-cys63) was opened during the formation of the protease. We named this 18.8 kD protease caricain II. Caricain II has a wide pH range, and it is more sensitive to temperature changes than caricain. The proteolytic activity of caricain II is twice as much as that of caricain using casein as a substrate. However, caricain II has a low hydrolytic activity with N-benzoyl-L-arginine ethyl ester (BAEE) that is one of the special substrates of caricain. Our results indicate that caricain II is remarkably different from caricain and it can provide an improvement over caricain on the proteolytic activity.

Amino Acid Sequence↗

Microbiological characteristics of medically important Trichosporon species.

Trichosporon species are opportunistic pathogens associated with a high mortality rate in immunocompromised patients. Disseminated trichosporonosis is uncommon but reports are increasing. In this study, using 16 stock clinical isolates of suspected Trichosporon species and 4 known Trichosporon strains, we investigated the morphology, physio-biochemistry, molecular biology and antifungal susceptibility characteristics of these Trichosporon spp. and discovered that ITS sequence-based identification is a rapid and accurate identification alternative to most phenotypic or physio- biochemical methods. In vitro antifungal susceptibility tests showed high amphotericin B, itraconazole and terbinafine MIC value in these Trichosporon strains.

Antifungal Agents↗

Identification and characterization of purine nucleoside transporters from Crithidia fasciculata.

To initiate a molecular dissection into the mechanism by which purine transport is up-regulated in Crithidia, genes encoding nucleoside transporters from Crithidia fasciculata were cloned and functionally characterized. Sequence analysis revealed CfNT1 and CfNT2 to be members of the equilibrative nucleoside transporter family, and the genes isolated encompassed polypeptides of 497 and 502 amino acids, respectively, each with 11 predicted membrane-spanning domains. Heterologous expression of CfNT1 cRNA in Xenopus laevis oocytes or CfNT2 in nucleoside transport-deficient Leishmania donovani demonstrated that CfNT1 is a novel high affinity adenosine transporter that also recognizes inosine, hypoxanthine, and pyrimidine nucleosides, while CfNT2 is a high affinity permease specific for inosine and guanosine. Southern blot analysis revealed that CfNT2 is present as a single copy within the C. fasciculata genome. Starvation of parasites for purines increased CfNT2 transport activity by an order of magnitude, although Northern blot analysis indicated CfNT2 transcript levels increased by <2-fold. These data imply that this metabolic adaptation can mainly be ascribed to post-transcriptional events. Conversely, Southern analysis of CfNT1 suggests that it is a member of a highly homologous multi-copy gene family, indicating that adenosine transport by C. fasciculata is more complex than previously thought.

Adenosine↗

Kinetics of cyanogen chloride destruction by chemical reduction methods.

In this study, membrane introduction mass spectrometry (MIMS) was applied to evaluate the kinetics of cyanogen chloride (ClCN) destruction by chemical reduction methods, using thiosulfate, sulfite, metabisulfite, ferrous ions and zero-valent iron at various concentrations and pH. The ClCN destruction followed second-order reaction kinetics in all cases of using sulfur compounds, though the second-order rate constants varied substantially from approximately 0.3-25.7 M(-1)s(-1) under different experimental conditions. The destruction of ClCN was primarily attributable to the chemical reduction pathway. Hydroxide-assisted ClCN hydrolysis was only significant at pH 9 and also when the observed reduction rate was relatively slow. The second-order rate constants achieved by sulfur(IV) compounds in the form of sulfite were found to be higher than those obtained with thiosulfate and S(IV) compounds in the form of bisulfite. Ferrous ions and zero-valent iron demonstrated slow or no ClCN reduction up to dosages of 1000 mgL(-1) and 100 gL(-1), respectively. These findings suggest that applying moderately high dosages of S(IV) compounds under neutral or alkali conditions with sufficient contact time is required for wastewater ClCN destruction. In addition, ClCN losses during long-term preservation with excess reducing sulfur compounds prior to analysis can be substantial and should be avoided.

Cyanides↗