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Biomedical subjects

Q Zhou

Publications and source records attributed to Q Zhou.

At least 343 records · Page 19Linked to original sources
PubMed1994

Repeated polyketide synthase modules involved in the biosynthesis of a heptaene macrolide by Streptomyces sp. FR-008.

Genes for biosynthesis of a Streptomyces sp. FR-008 heptaene macrolide antibiotic with antifungal and mosquito larvicidal activity were cloned in Escherichia coli using heterologous DNA probes. The cloned genes were implicated in heptaene biosynthesis by gene replacement. The FR-008 antibiotic contains a 38-membered, polyketide-derived macrolide ring. Southern hybridization using probes encoding domains of the type I modular erythromycin polyketide synthase (PKS) showed that the Streptomyces sp. FR-008 PKS gene cluster contains repeated sequences spanning c. 105kb of contiguous DNA; assuming c. 5 kb for each PKS module, this is in striking agreement with the expectation for the 21-step condensation process required for synthesis of the FR-008 carbon chain. The methods developed for transformation and gene replacement in Streptomyces sp. FR-008 make it possible to genetically manipulate polyene macrolide production, and may later lead to the biosynthesis of novel polyene macrolides.

Anti-Bacterial Agents↗
PubMed1994

Possible involvement of NMDA receptor-mediated transmission in barbiturate physical dependence.

1. The competitive antagonists at the N-methyl-D-aspartate (NMDA) receptor, CGP39551 and CGP37849, protected against the barbiturate withdrawal syndrome in mice, as measured by ratings of convulsive behaviour on handling. 2. The effective doses of these compounds were lower than those required to prevent seizures due to NMDA in naive animals; these were in turn lower than those needed to prevent the convulsive effects of the alpha-aminobutyric acid (GABA) antagonist, bicuculline. 3. The NMDA-receptor antagonists did not alter the increase in the incidence of convulsions due to the GABAA antagonist, bicuculline, that is seen during barbiturate withdrawal, although the latencies to these convulsions during barbital withdrawal were significantly increased after CGP39551. 4. Barbiturate withdrawal did not affect the convulsive actions of NMDA, whether measured by the incidence of convulsions or by intravenous infusion. 5. The Bmax for [3H]-dizocilpine ([3H]-MK801) binding was significantly increased by chronic barbital treatment in cerebrocortical but not in hippocampal tissues, while the Kd remained unaltered in either case. 6. At 1 h and 24 h after administration of a single dose of barbitone, the Bmax for [3H]-dizocilpine binding was unaltered in cerebrocortical tissue. Acute addition of barbitone in vitro did not alter [3H]-dizocilpine binding or the displacement of binding of thienylcyclohexylpyridine.

2-Amino-5-phosphonovalerate↗
PubMed1994

Development of a gene cloning system for Streptomyces hygroscopicus subsp. yingchengensis, a producer of three useful antifungal compounds, by elimination of three barriers to DNA transfer.

Streptomyces hygroscopicus 10-22 could not be transformed with any of the commonly used Streptomyces plasmid vectors and was resistant to plaque formation by the Streptomyces phages phi C31 and R4. Repeated selection resulted in the isolation of derivatives of S. hygroscopicus 10-22 that could be transformed with pIJ101- and pJV1-derived cloning vectors and of restriction-deficient derivatives that could accept DNA propagated in Streptomyces lividans 66. These new strains, which include three that still produce the original antibiotics, can be used as hosts for gene cloning. Insertion of nonreplicating vectors by homologous recombination and transposition of Tn4560 were demonstrated in S. hygroscopicus 10-22.

Antifungal Agents↗
PubMed1994

The influence of 25-hydroxycholesterol on phosphatidylinositol content in cultured smooth muscle cells.

The effect of 25-hydroxycholesterol on phosphatidylinositol content was studied in subconfluent human arterial smooth muscle cells exposed to myo-[2-3H]inositol for 90 min and then to 25-hydroxycholesterol at different concentrations or for different incubating periods. Ethanol at a concentration of 0.05% in culture medium was used as control. The results demonstrate that an increased incubation time or an increase in the concentration of 25-hydroxycholesterol produced an increase in phosphatidylinositol and its degraded products. The ratio of precursor to product at each stage of phosphatidylinositol turnover in 25-hydroxycholesterol-treated cells, however, was not different from that in control cells. The data indicate that the presence of 25-hydroxycholesterol in the media induced general activation of phosphatidylinositol synthesis and turnover.

Cells, Cultured↗
PubMed1994

[Detection of P-glycoprotein expression in patients with acute leukaemia and clinical significance].

Anti-P-glycoprotein monoclonal antibody JSB-1 and alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunocytochemical staining technique were used to study the relation between P-glycoprotein expression and clinical multidrug resistance (MDR) in 42 patients with acute leukaemia (23 ALL and 19 ANLL). 10 of 17 patients who were diagnosed as refractory or relapsed acute leukaemia were positive with P-glycoprotein expression, while only 3 of 14 newly diagnosed and 1 of 11 who were in complete remission were positive. The preliminary results indicated that there was a close association between the P-glycoprotein expression and the clinical resistance to chemotherapy in some patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Cholesterol oxides in plasma and lipoproteins of magnesium-deficient rabbits and effects of their lipoproteins on endothelial barrier function.

The cholesterol oxide (ChO) levels in the plasma and low density lipoproteins (LDL and VLDL) in four groups of rabbits fed for seven weeks either normal (NC) or high cholesterol (HC) with low or normal magnesium (Mg) diets were determined and compared with the NC group fed a standard rabbit diet. The plasma from the NC group contained low levels of different cholesterol oxides. These cholesterol oxides were significantly elevated in the plasma of rabbits fed a HC-normal magnesium or a HC-low magnesium diet. In the NC-low Mg group, 7 alpha-hydroxycholesterol, 7 beta-hydroxycholesterol and 7-ketocholesterol were elevated while the other cholesterol oxides remained within the normal range of the NC group. When the cholesterol oxides were assayed in the LDL and VLDL fractions as micrograms/mg protein, the fractions obtained from the groups fed NC-low Mg, HC-normal Mg or HC-low Mg diets showed higher levels of cholesterol oxides than the fractions obtained from the NC group. When LDL and VLDL fractions from the different groups were incubated at equal protein concentration with confluent endothelial cell monolayers, transendothelial albumin transfer was significantly increased by the lipoproteins from the experimental groups as compared to the control group. These results suggest that elevation of cholesterol oxides in magnesium deficiency or hypercholesterolaemia may be related to their atherogenic effects through decreasing the endothelial barrier function which could enhance the deposition of cholesterol rich lipoproteins into the arterial wall.

Animal Feed↗
PubMed1994

[Experimental study of kangli san in treating viral hyperpyrexia].

The hypothermic effect of Kangli San (KLS) on the model of rabbit viral hyperpyrexia caused by rabbit hemorrhagic fever virus was studied. Intraperitoneal injection of 200% KLS (4g/kg) could inhibit the pyrogenic action of the virus efficiently. The results showed that KLS could decrease the function of pyrogenic transmitters such as PGE2 and cAMP etc. in cerebrospinal fluid.

Animals↗
PubMed1994

Defibrotide stimulates expression of thrombomodulin in human endothelial cells.

Cultured human umbilical vein endothelial cells were incubated with defibrotide at concentrations of 0, 5, 50 and 500 micrograms/ml for 4 and 24 h respectively. Thrombomodulin activity and molecules on the surface of the cells were determined by chromogenic assay and radioimmunoassay, thrombomodulin antigen in endothelial cells and in conditioned medium of the cells was measured by immunoradioassay. Thrombomodulin mRNA within the cells was analysed by slot blot. After 24 h of incubation, the activity and molecules of thrombomodulin on the surface of endothelial cells, as well as the antigen and mRNA of thrombomodulin in the cells were significantly increased in a dose dependent manner. However, the level of thrombomodulin antigen in conditioned medium was about equal to that of the control. Our data indicate that defibrotide stimulates expression of thrombomodulin in human endothelial cells. These beneficial effects may play a role in antithrombotic activity of defibrotide.

Cells, Cultured↗
PubMed1994

Effect of dietary magnesium deficiency with/without cholesterol supplementation on phospholipid content in liver, plasma and erythrocytes of rabbits.

The effect of magnesium deficiency with/without supplementary cholesterol on phospholipid content in liver, plasma and erythrocytes was investigated in New Zealand White male rabbits. After the rabbits had been fed a low magnesium and/or high cholesterol diet for seven weeks, the phospholipid content in liver, plasma and erythrocytes was measured. Dietary magnesium deficiency produced a marked elevation of total phospholipid and certain individual phospholipids in the rabbit liver. The elevation was accentuated by cholesterol supplementation. In the plasma, a low magnesium intake enhanced plasma phosphatidylcholine, phosphatidic acid, phosphatidylinositol, and sphingomyelin, but an activated conversion from phosphatidylethanolamine to phosphatidylcholine made the increase in phospholipid insignificant. On the other hand, a low magnesium intake restricted the increase in magnitude of phospholipid caused by cholesterol supplementation. In the erythrocytes, total phospholipid, phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine were decreased by a low magnesium and/or a high cholesterol intake. We suggest that the increased contents of total phospholipid and/or certain individual phospholipids in the livers and plasma resulted from the enhanced synthesis of phospholipid in the liver by low magnesium intake. A decreased utilization of food by low magnesium diet limited the magnitude of plasma phospholipid increase produced by cholesterol supplementation.

Animals↗
PubMed1994

Alterations of Ca++ uptake and lipid content in cultured human arterial smooth muscle cells treated with 26-hydroxycholesterol.

The effects of 26-hydroxycholesterol on 45Ca++ uptake, [14C]cholesterol uptake, [14C] acetate incorporation and the concentrations of 26-hydroxycholesterol and cholesterol in the plasma membrane were studied in cultured human smooth muscle cells isolated from umbilical arteries. The results showed that: (1) 26-hydroxycholesterol enhanced markedly 45Ca++ uptake and the enhancement was not diminished by nifedipine; (2) 26-hydroxycholesterol decreased cholesterol content in plasma membrane by inhibiting cholesterol uptake and synthesis, and [14C]cholesterol uptake was not LDL-receptor dependent; (3) 26-hydroxycholesterol induced a shift of [14C] acetate from cholesterol into phospholipid synthesis, but the radioactive incorporation into triglyceride and cholesterol ester was inhibited by 26-hydroxycholesterol; and (4) 26-hydroxycholesterol inserted itself into the plasma membrane. We suggested that 26-hydroxycholesterol changes the composition of membrane lipids with a consequential alteration of membrane permeability to Ca++.

Biological Transport↗
PubMed1993

Association between proto-oncoprotein Rel and TATA-binding protein mediates transcriptional activation by NF-kappa B.

The c-Rel protein is able to associate in vitro and in vivo with the TATA-binding protein (TBP) of the TFIID complex. Coexpression of TBP with c-Rel augments transactivation from the kappa B site in Drosophila Schneider cells. DNA-binding mutants of TBP not only fail to cooperate, but they repress transactivation by c-Rel. There may be a direct communication between kappa B enhancer binding proteins and basal transcription factors which leads to enhanced transcription.

Animals↗
PubMed1993

Conversion of a dorsal-dependent silencer into an enhancer: evidence for dorsal corepressors.

In Drosophila, the dorsal (dl) morphogen gradient initiates the differentiation of the embryonic mesoderm and neuroectoderm by activating the expression of regulatory genes (e.g. twist and snail) in a concentration-dependent manner. dl also functions as a repressor that establishes the dorsal epidermis and amnioserosa by restricting regulatory genes such as dpp and zen to dorsal regions of the embryo. The ability of dl to function as both an activator and repressor distinguishes it from the bicoid morphogen, which appears to function solely as an activator. In an effort to determine how dl functions as a repressor we have performed a detailed characterization of a zen silencer element, called the VRE, which mediates ventral repression in response to the dl gradient. A minimal 110 bp VRE sequence is identified, which is able to silence the ventral expression of a heterologous promoter. This sequence contains two dl binding sites as well as binding sites for additional nuclear factors present in early embryos. Mutations in the latter binding sites convert the minimal VRE into an enhancer, which mediates transcriptional activation in ventral regions in response to dl. These results suggest that dl is intrinsically an activator, but is converted into a potent silencer when it interacts with neighboring corepressors.

Animals↗
PubMed1993

L-14 lectin recognition of laminin and its promotion of in vitro cell adhesion.

The S-type lactose-binding lectins are found in a variety of animal tissues and their primary sequences are highly conserved between species. Little is known, however, about their functions and endogenous ligands. We report here our studies on the carbohydrate binding specificity of one S-type lectin designated L-14, using glycopeptides and glycoproteins from Chinese hamster ovary cells and mouse teratocarcinoma F9 cells. Our studies demonstrate that L-14 binds with high affinity to oligosaccharides containing multiple repeating units (approximately 4) of the disaccharide [3Gal beta 1-4GlcNAc beta 1]n or poly-N-acetyllactosamine (PL) sequence. Interestingly, terminal beta-galactosyl residues are not necessary for high affinity binding of long PL-containing oligosaccharides to L-14. To characterize the glycoprotein ligands for L-14, we applied total [3H]galactose-labeled glycoproteins from differentiated F9 cells to L-14-Sepharose. Laminin was one of the major glycoproteins in both the cells and the media bound by the lectin. The possible functional significance of this interaction is suggested by the fact that in the absence of Ca2+ L-14 can mediate the binding in vitro of both CHO and F9 cells to immobilized laminin. Taken together, these studies demonstrate that L-14 binds with high affinity to laminin and to relatively long PL chains and indicate that L-14 can promote cell adhesion to laminin.

Animals↗
PubMed1993

Pharmacologic properties of KT2-962 (6-isopropyl-3-[4-(p- chlorobenzenesulfonylamino)-butyl]-azulene-1-sulfonic acid sodium salt); a new TXA2/prostaglandin endoperoxide receptor antagonist.

Pharmacologic properties of KT2-962 (6-isopropyl-3-[4-(p-chlorobenzenesulfonylamino)butyl]-azulene+ ++-1-sulfonic acid sodium salt, KT) were studied in isolated rat aorta, rat tail artery, rabbit aorta, rabbit renal artery, and pig coronary artery. KT competitively inhibited the contractions induced by thromboxane A2 (TXA2) mimetic, U46619 (pA2 values 9.95, 8.85, 7.87, 8.49, and 9.12, respectively). KT also inhibited the contraction of rabbit aorta induced by prostaglandin2 alpha (PGF2 alpha, pA2 value 7.85) and the contraction of guinea pig ileum induced by LTD4 (pA2 value 5.48) but did not alter the contractions induced by norepinephrine (NE), Ca2+, serotonin, and histamine. KT did not alter the contractions of guinea pig ileum, which did not contract with U46619, induced by PGE2 and PGF2 alpha. KT inhibited the aggregations of rabbit platelets induced by U46619, arachidonic acid, and collagen (IC50 values 7.9, 140, and 16 microM, respectively) but not those induced by ADP. It also inhibited the specific binding of TXA2/PGH2 receptor antagonist, [3H]SQ29,548, to rabbit gel-filtered platelets with an IC50 value of 1.5 x 10(-8) M. In in vivo experiments with mice, oral administration of KT protected the U46619-induced sudden death with the minimum effective dose of 0.3 mg/kg and provided such protection for > 8 h at 1.0 mg/kg. These results indicate that KT is a new nonprostanoid type TXA2/PGH2 receptor antagonist that is orally effective and long acting.

Animals↗
PubMed1993

Factors (TAFs) required for activated transcription interact with TATA box-binding protein conserved core domain.

TFIID is a multisubunit protein containing the TATA box-binding polypeptide (TBP) and associated factors (TFIID-TAFs) required for activated transcription by RNA polymerase II. TBPs from different eukaryotes contain a highly conserved carboxy-terminal domain and very divergent amino-terminal domains. Earlier studies proposed that the amino-terminal domains of metazoan TBPs are required for activated transcription. However, we report that a human TFIID complex containing an amino-terminal truncated TBP contains all the major TFIID-TAFs and supports in vitro transcriptional stimulation by different classes of activation domains and from a TATA-less promoter. Protein blotting experiments revealed direct interactions between the conserved domain of TBP and the two largest TAFs. The results suggest a model for the interaction of TFIID-TAFs with TBP.

Amino Acid Sequence↗
PubMed1993

Cytotoxicity of oxysterols on cultured smooth muscle cells from human umbilical arteries.

The lethal effect of 25- and 26-hydroxycholesterol on smooth muscle cells derived from human umbilical arteries was investigated. The extent of cellular death corresponded with increasing oxysterol concentrations and incubation times. Incubation of the cells with 0.5, 2.5, or 10 micrograms/ml of 25- or 26-hydroxycholesterol revealed a proportionality between the degree of cellular death and oxysterol concentration over the 5 days of the experiment. Correlation coefficients among the degree of cellular death, the exposing period, and oxysterol concentration were significantly different (P < 0.05). However, none of these changes were noted in the smooth muscle cells cultured for 5 days in a medium containing the same concentration of cholesterol or 0.5% ethanol. An increase in the concentration of either serum or cholesterol in the culture medium did not significantly reduce the cytotoxicity of 2.5 micrograms/ml of 26-hydroxycholesterol. The results of this study suggest that oxysterols have an injurious effect on arterial cells, and that the injurious effect could not be altered by cholesterol, which was present at a serum concentration 12 times higher than that of oxysterols.

Cell Death↗