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L Qi

Publications and source records attributed to L Qi.

At least 37 records · Page 2Linked to original sources

Housekeeping genes commanded to commit suicide in CpG-cleavage commitment upstream of Bcl-2 inhibition in caspase-dependent and -independent pathways.

A CpG-specific commitment common to both caspase-dependent and -independent cell deaths implies critical gene activity from epigenetic modulation. Using a focused microarray (genechip) of 22 housekeeping genes, which have canonical CpG islands at 5'-promoter regions, here we show critical regulation of vital intermediary metabolism and cell structure that are common to both caspase-dependent fasL-mediated and caspase-independent etoposide-mediated cell deaths. Gene activity of at least twofold under or over control levels and common to both cell death pathways was considered to be significantly regulated in common. Seven genes controlling energy production in glycolysis, tricarboxylic acid cycle, and the respiratory electron transport chain were significantly downregulated in common. Energy depletion is lethal. Downregulated pyruvate dehydrogenase E1 gene, in addition, suggested primary metabolic acidification. Cell acidification is also lethal. Critical derangement of the cell structure was suggested by common downregulation of the basal histone gene H2A.X which is required for nucleosome assembly. Common upregulation of the alpha-tubulin gene suggested perturbation of vital microtubular dynamics. Gene-commanded cell suicide was suggested. We further show that a Bcl-2 overexpression of three- to fourfold above normal levels could not prevent the CpG-specific megabase DNA cleavages in the two cell death pathways, but abolished their low-molecular-weight 200-bp ladder cleavages. Together with incomplete suppression of the other apoptotic expressions, the Bcl-2 inhibition point appeared downstream from the CpG-cleavage commitment point.

Annexin A5↗

Suicidal differential housekeeping gene activity in apoptosis induced by DCNP.

Previous suggestions of CpG-specific apoptotic commitment implied critical epigenetic modulation of housekeeping genes which have canonical CpG islands at 5' promoter regions. Differential housekeeping gene activity however has not been shown. Using a focussed microarray (genechip) of 22 housekeeping genes we show this in apoptosis induced in human Chang liver cells by DCNP (2,6-dichloro-4-nitrophenol), a non-genotoxic inhibitor of sulfate detoxification. 3-7 folds downregulation of 9 genes in glycolysis, tricarboxylic acid cycle and the respiratory electron transport chain suggested gene-directed energy depletion which was correlated with observed ATP depletion. 4 folds downregulation of the pyruvate dehydrogenease gene suggested gene-directed metabolic acidosis which was correlated with observed cell acidification. Other differential housekeeping gene activity, including 4 folds upregulation of microtubular alpha-tubulin gene, and 2 folds upregulation of ubiquitin, also had a bearing on apoptosis. Broadspectrum zVAD-fmk caspase inhibition abolished 200 bp DNA ladder fragmentations but not the CpG-specific megabase fragmentations and other hallmarks of cell destruction, suggesting a caspase-independent cell death. Death appeared committed at gene-level.

Adenosine Triphosphate↗

Meiotic metaphase I pairing behavior of a 5BL recombinant isochromosome in wheat.

A recombinant isochromosome i5BLrec of wheat was developed with one arm and the proximal 36% of the other arm of Chinese Spring (CS) origin and the distal 64% of the recombined arm of Triticum turgiduM subsp. dicoccoides origin. The i5BLrec provides an unusual opportunity to analyze the role of the centromere or arm heterozygosity in chromosome prealignment and synapsis during meiosis. In monosomic condition, the i5BLrec formed a ring univalent in 86.8% of the pollen mother cells (PMCs) at meiotic metaphase I. In the disomic condition, the two i5BLrec preferentially paired as a normal bivalent in 74.8% of the PMCs, which differed significantly (p <0.01) from the normal bivalent pairing of 51% observed in diisosomic 5BL chromosomes of the CS (Di5BL(CS)) control plants. In plants with one i5BLrec and a normal 5B(CS), the long arm of 5B(CS) paired with the homologous arm of i5BLrec in 54.4% of the PMCs, and 40.4% of the PMCs had a 5B(CS) univalent and a i5BLrec ring univalent. The implications of the i5BLrec pairing data on the mechanism of Ph1 gene action are discussed.

Chromosome Banding↗

MHC class II presentation of endogenous tumor antigen by cellular vaccines depends on the endocytic pathway but not H2-M.

We have developed cell-based cancer vaccines that activate anti-tumor immunity by directly presenting endogenously synthesized tumor antigens to CD4+ T helper lymphocytes via MHC class II molecules. The vaccines are non-conventional antigen-presenting cells because they express MHC class II, do not express invariant chain or H-2M, and preferentially present endogenous antigen. To further improve therapeutic efficacy we have studied the intracellular trafficking pathway of MHC class II molecules in the vaccines using endoplasmic reticulumlocalized lysozyme as a model antigen. Experiments using endocytic and cytosolic pathway inhibitors (chloroquine, primaquine, and brefeldin A) and protease inhibitors (lactacystin, LLnL, E64, and leupeptin) indicate antigen presentation depends on the endocytic pathway, although antigen degradation is not mediated by endosomal or proteasomal proteases. Because H2-M facilitates presentation of exogenous antigen via the endocytic pathway, we investigated whether transfection of vaccine cells with H-2M could potentiate endogenous antigen presentation. In contrast to its role in conventional antigen presentation, H-2M had no effect on endogenous antigen presentation by vaccine cells or on vaccine efficacy. These results suggest that antigen/MHC class II complexes in the vaccines may follow a novel route for processing and presentation and may produce a repertoire of class II-restricted peptides different from those presented by professional APC. The therapeutic efficacy of the vaccines, therefore, may reside in their ability to present novel tumor peptides, consequently activating tumor-specific CD4+ T cells that would not otherwise be activated.

Acetylcysteine↗

Cell-based vaccines for the stimulation of immunity to metastatic cancers.

We are developing vaccines for inducing immunity to metastatic cancers. Although primary tumors are frequently cured by surgery, chemotherapy, or radiation therapy, metastatic lesions often do not respond to these treatments or proliferate after conventional therapy is terminated. Vaccine therapy for established metastases as well as prophylactic vaccine treatment to prevent outgrowth of latent metastatic tumor cells would therefore be beneficial. Our goal is to activate CD4+ and CD8+ T lymphocytes; however, we have focused on activating tumor-specific CD4+ T-helper lymphocytes because of their pivotal role as regulatory cells and in the generation of long-term immunological memory. The vaccines are based on the premise that tumor cells express potentially immunogenic antigens that could be targeted for T-cell activation, and that if appropriately genetically modified, tumor cells could be antigen presenting cells for these antigens. To facilitate direct antigen presentation to CD4+ T cells, tumor cells have been transfected with syngeneic major histocompatibility complex class II, co-stimulatory molecule, and/or superantigen genes. In vivo studies in three mouse tumor models demonstrate that vaccination protects against future challenge with wild-type tumor, cures some solid primary tumors, reduces established metastatic disease, and extends mean survival time. Antigen presentation studies demonstrate that in vivo vaccine efficacy is directly related to in vitro antigen presentation activity. The relevance of antigen presentation activity of the vaccines is further confirmed by in vivo studies demonstrating that during the immunization process, the vaccines directly present tumor-encoded antigens to CD4+ T lymphocytes. Adaptation of these vaccines for the treatment of human metastatic cancers is discussed.

Animals↗

Endothelial nitric oxide synthase as a potential susceptibility gene in the pathogenesis of emphysema in alpha1-antitrypsin deficiency.

A role for endothelial nitric oxide synthase (NOS3) in the susceptibility of individuals with alpha1-antitrypsin (alpha1AT) deficiency to destructive lung disease was evaluated. Six polymorphic sites were identified within the NOS3 gene (i.e., -924A/G, -788C/T, -691C/T, 774C/T, 894G/T, and 1998C/G). The genotype distribution was determined in 339 patients and 94 control individuals. Frequency of the 774T allele in severely affected individuals was 0.417 versus 0.269 in control subjects (P = 0.018), whereas the 894T allele frequency was 0.427 versus 0.280 in control subjects (P = 0.024). Patients with less severe lung disease had the 774T and 894T allele frequencies of 0.289 and 0.344, respectively, similar to frequencies in a control group (P > 0.3). No direct correlation between pulmonary function and five other NOS3 polymorphisms was observed. Thus, functional allelic variants that are in linkage disequilibrium with the 774C/T and 894G/T may be present in the specified genomic area. These data are consistent with a modulatory role for NOS3 in destructive lung disease associated with alpha1AT deficiency.

Adult↗

[A follow-up study of anterior deciduous cross-bite].

OBJECTIVE: To determine the relationship between anterior deciduous crossbite and anterior permanent crossbite, Angle classification of malocclusion and class III jaw relationship through a follow-up study in community children. METHODS: A follow-up study was done six years later in 102 children who were out of 120 children having anterior deciduous crossbite detected in a survey of six years before. Other 102 children with normal occlusion of deciduous and permanent teeth were treated as the control group. RESULTS: There were 51 out of 102 cases developed anterior permanent crossbite. In comparison with the group with 1-2 anterior deciduous crossbite, the group with more than two neighboring anterior deciduous crossbite had more significant probability to turn into anterior permanent crossbite, OR = 6.8 (95% CI: 2.7-17.6). The patients with more than 2 neighboring anterior deciduous teeth crossbite had significantly more chance of developing Angle III malocclusion and class III jaw relationship than those in the control group and those with 1-2 anterior deciduous teeth crossbite. CONCLUSION: Clinical orthodontists should pay more attention to the patients with more than 2 neighboring anterior deciduous crossbite.

Adolescent↗

[Immunocytochemical localization of two facilitated glucose transporters of Schistosoma mansoni in the tegument of Schistosoma japonicum].

AIM: To observe the distribution of Schistosoma mansoni glucose transport proteins, SGTP1 and SGTP4, in the tegument of Schistosoma japonicum. METHODS: The rapidly frozen fixation technique and ultracryomicrotomy were adopted for preparing ultrathin cryosections of S. japonicum. Anti-SGTP1 and anti-SGTP4 antibodies were used to localize the corresponding antigens in the tegument of adult S. japonicum by immunocytochemical technique. RESULTS: SGTP1 was localized on the basal membrane of the tegument and its infoldings, SGTP4 was localized on the apical membrane of the tegument and its invaginations of S. japonicum. CONCLUSION: The same localization for SGTP 1 and SGTP4 in the tegument of S. japonicum and S. mansoni exhibited apparent homology between SGTPs of the two schistosomes.

Animals↗

[The substituent structures and characteristic infrared spectra of alpha-furan esters].

The characteristic infrared bands of the alpha-furoic esters, alpha-furancarbinol esters and alpha-furanacrylic esters were assigned, and the changing rules of the IR absorption frequency of the alpha-furan esters with alpha-substituent structure were discussed. The results indicated there are three characteristic bands in alpha-furan ring. The strong absorption at 1641 cm(-1) is assigned to the C=C double bond stretching mode in the alpha-furanacrylic esters, while the absorption at 973 cm(-1) is the out-of-plane =C-H bending mode for a trans di-substituted alkene, the strong absorption at about 1713 cm(-1) is assigned to a C=O stretch, and the three strong absorptions near 1305, 1260 and 1165 cm(-1) are due to the symmetric and assymmetric stretching vibrations of C-O-C bond in the ester groups.

Esters↗

[Induction of NAD(P)H: quinone reductase by anticarcinogenic ingredients of tea].

By assaying the activity of NAD(P)H: quinone reductase (QR) in Hep G2 cells exposed to inducing agents, a variety of ingredients in tea, we compared their abilities on inducing QR and preventing cancer. The results showed that tea polyphenols, tea pigments and mixed tea were all able to induce the activity of QR significantly. The single-component ingredients of tea polyphenols and tea pigments, including thearubigens, EGCG and ECG, also enhanced the activity of QR. But EGC, EC, theaflavins, tea polysaccharide and tea caffeine, showed no apparent induction of QR. We found that among those tea ingredients studied, the multi-component ingredients were more effective than the single-component ones. So we thought that the abilities of antioxidation and cancer prevention of tea depended on the combined effects of several kinds of active ingredients, which mainly include tea polyphenols and tea pigments.

Animals↗

Catalytic contribution of phenylalanine-101 of 3-oxo-Delta 5-steroid isomerase.

3-Oxo-delta 5-steroid isomerase (KSI, EC 5.3.3.1) from Pseudomonas testosteroni catalyzes the isomerization of a variety of 3-oxo-delta 5-steroids to their conjugated Delta4-isomers through the formation of an intermediate dienolate ion. It has previously been found in our laboratory that the aromatic ring of Phe-101 is important for catalysis. The present work extends these studies. Two double-mutant KSIs (D38E/F101L and D38E/F101A) were prepared to compare the free energy profiles for the reactions catalyzed by these mutants and by D38E. Both double-mutant KSIs show reduced values of kcat at pH 7 compared to D38E ( approximately 25-fold for D38E/F101L and approximately 200-fold for D38E/F101A), similar to the reduced values for F101L and F101A relative to KSI ( approximately 30-fold for F101L and approximately 270-fold for F101A). Free energy profiles for the reactions catalyzed by D38E/F101L and D38E/F101A indicate that the bound transition state(s) and bound intermediate are destabilized when the large aromatic residue Phe-101 in D38E KSI is replaced by the smaller residues Leu or Ala. The pH-rate profiles for D38E, D38E/F101L, and D38E/F101A in the pH range 3.9-8.7 show that the pKa of the catalytic base (Glu-38) is perturbed. In addition, these mutants have significant catalytic activity in the low-pH region.

Alanine↗

Toroidal coil counter-current chromatography study of the mass transfer rate of proteins in aqueous-aqueous polymer phase system.

The cause of excessive band broadening of protein samples in polymer phase partitioning by counter-current chromatography (CCC) was investigated. A simple rotary device was constructed to measure the mass transfer rates of five samples including potassium dichromate, methylene blue, lysozyme, ovalbumin and human serum albumin. The results indicated that the mass transfer rates of these samples are closely correlated with their molecular masses: the higher the molecular mass, the lower the mass transfer rate. These findings are also consistent with the partition efficiencies of these samples in the same solvent system by CCC. The beneficial effect of the Coriolis force demonstrated in protein separations by the toroidal coil centrifuge may be reasonably explained on the basis of the mass transfer resistance of protein molecules through the interface: we speculate that when the Coriolis force acts parallel to the effective coil segment it can produce large interfacial areas by dispersing the mobile phase into the stationary phase, thus accelerating the mass transfer rate of protein samples.

Chromatography, Liquid↗

Investigation of the Microenvironment in Nonionic Reverse Micelles Using Methyl Orange and Methylene Blue as Absorption Probes

The microenvironment in nonionic reverse micelles of Triton X-100, n-hexanol, and water in cyclohexane is investigated by using methyl orange (MO) and methylene blue (MB) as absorption probes. Information about the states of water in the polar core of the reverse micelles is obtained through the solvatochromic behavior of MO and the sensitivity of the complex formation between MB and Triton X-100 in reverse micelles to the state of water in the polar core. The results obtained from the spectra of MO and MB in the TX-100 reverse micelles with different amounts of water are compatible with the proposal that there are three types of water present in the polar core: the primary bound water, which interacts directly with the ethylene oxide (EO) groups of the surfactant to form a primary hydration shell, the second bound water, which is next to the primary hydration shell of the EO groups and bound less tightly, and the free water, which is present in the water pool and resembles the bulk water. It is found that there is an equilibrium between two states of MB in the reverse micelles: the bound MB and the free MB, and the presence of secondary bound water and free water will lead to the equilibrium shift from bound MB to free MB. In the Triton X-100 reverse micellar system studied, the secondary bound water is present at about W = 1.8 and water pools begin to form when the water content reaches W = 5.3. The strong interaction between MB and nonionic surfactants, which results in the complex formation, and its sensitivity to the state of water in the polar core are found to be also present in the reverse micelles of either Triton X-114 or C12E4 in cyclohexane. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

Euchromatin megabase cleavages and conjoint apoptotic-autophagic death expression with nucleolar ball-and-socket joint dislocations in human Chang liver cells arrested in S-phase by etoposide.

Etoposide induced a megabase (Mb) fragmentation pattern identical with that from genomic digestion by NotI restriction endonuclease which specifically cleaves CpG islands in euchromatin domains. Redigestion by NotI produced no change, suggesting cleavage in the same or closely related sites in euchromatin domains. Preferential euchromatin cleavage was further suggested by harvested metaphase chromosomes showing self-inflicted resolution of light G-bandings (R-bandings), the euchromatin domains. Autodegeneration following Mb euchromatin fragmentations was shown by their degradation into 200 bp ladders, and expressions of apoptotic and "non-apoptotic" active death morphologies that were also seen conjointly in the same cell. The endstage further showed heterochromatin masses anchored to the nucleolus by novel ball-and-socket joints where dislocations occurred with nuclear leakage.

Apoptosis↗

Speciation and absolute bioavailability: risk assessment of arsenic-contaminated sites in a residential suburb in Canberra.

Watson is a fully developed suburb of some 30 years in Canberra (the capital city of Australia). A plunge dip using arsenical pesticides for tick control was operated there between 1946 and 1960. Chemical investigations revealed that many soil samples obtained from the study area contained levels of arsenic exceeding the current health-based investigation levels of 100 mg kg-1 set by the National Healthy and Medical Research Council in Australia. For the speciation study, nine composite samples of surface and sub-surface soils and a composite samples of rocks were selected. ICP-MS analysis showed that arsenic levels in these samples ranged from 32 to 1597 mg kg-1. Chemical speciation of arsenic showed that the arsenite (trivalent) components were 0.32-56% in the soil and 44.8% in the rock composite samples. Using a rat model, the absolute bioavailability of these contaminated soils relative to As3+ or As5+ ranged from 1.02 to 9.87% and 0.26 to 2.98%, respectively. An attempt was made to develop a suitable leachate test as an index of bioavailability. However, the results indicated that there was no significant correlation between the bioavailability and leachates using neutral pH water or 1M HC1. Our results indicate that speciation is highly significant for the interpretation of bioavailability and risk assessment data; the bioavailability fractions of arsenic in soils from Watson are small and therefore the healthy impact upon the environment and humans due to this element is limited.

Animals↗

[The antioxidative mechanisms of tea polyphenols in inhibiting tumor promotion by TPA].

In the mouse study, topical application of green tea polyphenols (GTP) significantly inhibited TPA-induced increasing of epidermal ornithine decarboxylase (ODC) and increased the activities of several antioxidant enzymes (CAT, GR and GST). In another in vitro study, when GTP was incubated with TPA and mice polymorphonuclear leukocytes (PMNs), TPA induced hydrogen peroxide formation was markedly suppressed with a dose-dependent relationship. The results suggest that the antioxidative effect of GTP may play an important role in inhibiting tumor promotion.

Animals↗

[Design and study of carbon fiber tracheal prosthesis].

32 healty adult dogs were selected for this experiment. 10 of them were subjected to the tracheal biomechanics test using indices including the relation between stretcher ratio (lambda) and stress (T), the squeeze stress (delta jy) of medical silk thread on trachea, the side stress (Ts) inducing the tracheal collapse, the functional maximum angle (psi max) of tracheal, and the sever area torsion angle (theta max) of tracheal functional maximum curved. According to the indices measured, two types of tracheal prosthesis were designed, and were made of carbon fiber and silicon. They were the straight tube type tracheal prosthesis and the bifurcate type tracheal prosthesis. The straight tube type tracheal prosthesis was studied with a design of two groups comprising a total of 11 dogs. In the experiment group (n = 6), the outer surface of the tube was not coated with silicon, the average survival period was 379.8 days. In the control group (n = 5), the outer surface of the tube was coated with silicon, the average survival period was 90.4 days. The bifurcate type tracheal prosthesis was studied in 11 dogs, the average survival period was 4.32 days. The main causes of death in the experiment were infection and anastomotic dehiscent.

Animals↗