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Biomedical subjects

R Liu

Publications and source records attributed to R Liu.

At least 199 records · Page 11Linked to original sources
PubMed1998

Risk factors for glioma in adults: a case-control study in northeast China.

A case-control study of risk factors for glioma in adults was carried out in Heilongjiang province in northeast China. Between September 1989 and May 1995, 218 histologically confirmed cases of glioma requiring surgery for tumor removal (139 astrocytoma glioma and 79 other glioma) and 436 controls with non-neoplastic and non-neurological disease were recruited and personally interviewed in the wards of six major hospitals. Controls were matched by sex, age, and area of residence. Occupational, lifestyle, and medical information was obtained through a standardized questionnaire. Use of liquor was associated with cancer risk. Compared with males who never drank liquor, males with total lifetime liquor consumption of less than 1000 liters had an adjusted odds ratio (OR) of 1.60 (95% CI: 0.89-2.88) and for more than 1000 liters, 2.73 (95% CI: 1.06-7.08). Statistically significant associations were also found for diseases related to the brain (OR: 5.75; 95% CI: 1.08-30.47) and trauma to the head requiring medical attention (OR: 4.09; 95% CI: 2.51-10.31). Increased consumption of vegetables and of fruit were each associated with decreased glioma risk. Compared with lowest quartile intake, adjusted risks associated with highest quartile intake were 0.51 (95% CI: 0.29-0.89) for total vegetables and 0.28 (95% CI: 0.16-0.51) for total fruit.

Adult↗
PubMed1998

Propofol-induced relaxation of rat mesenteric arteries: evidence for a cyclic GMP-mediated mechanism.

Experiments were designed to evaluate whether guanosine 3',5'-cyclic monophosphate (cGMP)-mediated mechanisms contribute to vasodilation via propofol in rat mesenteric resistance arteries. Ring segments were suspended in the myograph system for isometric tension recording, and responses to propofol were tested in the presence and absence of methylene blue (MB), an inhibitor of guanylate cyclase. At concentrations > or = 1 microM, propofol caused concentration-dependent relaxation of vessel rings precontracted with U46619 (a thromboxane analog). The effect was not affected by N-monomethyl-L-arginine (L-NMMA; 50 microM). MB (5 microM) reversed propofol-induced vasodilation by 30% (p < 0.001). In contrast, MB has no effect on nifedipine-inhibited vasocontraction. The propofol-induced relaxation was further tested in rings incubated in Ca2+-free solution. U46619-induced contractions were significantly reduced by propofol (40 microM) but not by nifedipine (1 microM). Propofol reduced to a similar degree the contractions obtained to exogenously added calcium chloride in the absence and the presence of MB. Furthermore, propofol (10-100 microM) increased cGMP content in cultured bovine vascular smooth-muscle cells. Soluble guanylate cyclase inhibitors, such as MB and LY83583, attenuated this effect. This investigation suggests that propofol-induced relaxations in small arteries, in addition to inhibition of calcium influx, are mediated by increases of cGMP in the smooth muscle cells.

Animals↗
PubMed1998

Definition of the role of tyrosine residues of the common beta subunit regulating multiple signaling pathways of granulocyte-macrophage colony-stimulating factor receptor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces various functions, including the proliferation and differentiation of a broad range of hematopoietic cells. We previously reported that at least two distinct pathways are involved in human GM-CSF receptor signaling; both require the box 1 region of the common beta subunit (beta c). This region is essential for the activation of JAK2, which is necessary for all the biological functions of GM-CSF. The activation of JAK2 by GM-CSF leads to rapid tyrosine phosphorylation of cellular proteins, including the beta c. However, the significance of beta c phosphorylation with regard to the regulation of signaling molecules and the expression of GM-CSF functions is less well understood. Here we investigated the role of the cytoplasmic tyrosine residues of the beta c by using a series of beta c mutants expressed in murine BA/F3 cells. A mutant beta c with all eight cytoplasmic tyrosines converted to phenylalanine (Fall) activated JAK2 but not SHP-2, MAPK cascades, STAT5, or the c-fos promoter in BA/F3 cells, and it did not effectively induce proliferation. Adding back each tyrosine to Fall revealed that Tyr577, Tyr612, and Tyr695 are involved in the activation of SHP-2, MAPK cascades, and c-fos transcription, while every tyrosine, particularly Tyr612, Tyr695, Tyr750, and Tyr806, facilitated STAT5 activation. Impaired growth was also restored, at least partly, by any of the tyrosines. These results provide evidence that beta c tyrosines possess distinct yet overlapping functions in activating multiple signaling pathways induced by GM-CSF.

Animals↗
PubMed1998

Molecular determinants of AHPN (CD437)-induced growth arrest and apoptosis in human lung cancer cell lines.

6-[3-(1-Adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN or CD437), originally identified as a retinoic acid receptor gamma-selective retinoid, was previously shown to induce growth inhibition and apoptosis in human breast cancer cells. In this study, we investigated the role of AHPN/CD437 and its mechanism of action in human lung cancer cell lines. Our results demonstrated that AHPN/CD437 effectively inhibited lung cancer cell growth by inducing G0/G1 arrest and apoptosis, a process that is accompanied by rapid induction of c-Jun, nur77, and p21(WAF1/CIP1). In addition, we found that expression of p53 and Bcl-2 was differentially regulated by AHPN/CD437 in different lung cancer cell lines and may play a role in regulating AHPN/CD437-induced apoptotic process. On constitutive expression of the c-JunAla(63,73) protein, a dominant-negative inhibitor of c-Jun, in A549 cells, nur77 expression and apoptosis induction by AHPN/CD437 were impaired, whereas p21(WAF1/CIP1) induction and G0/G1 arrest were not affected. Furthermore, overexpression of antisense nur77 RNA in A549 and H460 lung cancer cell lines largely inhibited AHPN/CD437-induced apoptosis. Thus, expression of c-Jun and nur77 plays a critical role in AHPN/CD437-induced apoptosis. Together, our results reveal a novel pathway for retinoid-induced apoptosis and suggest that AHPN/CD437 or analogs may have a better therapeutic efficacy against lung cancer.

Apoptosis↗
PubMed1998

Spectroscopic and biophysical approaches for studying the structure and function of the P-glycoprotein multidrug transporter.

Multidrug resistance is a serious obstacle to the successful chemotherapeutic treatment of many human cancers. A major cause of multidrug resistance is the overexpression of a 170-kDa plasma membrane protein, known as P-glycoprotein, which appears to function as an ATP-driven efflux pump with a very broad specificity for hydrophobic drugs, peptides, and natural products. P-Glycoprotein is a member of the ABC superfamily and is proposed to consist of two homologous halves, each comprising six membrane-spanning segments and a cytosolic nucleotide binding domain. In recent years, P-glycoprotein has been purified and functionally reconstituted into lipid bilayers, where it retains both ATPase and drug transport activity. The availability of purified active protein has led to substantial advances in our understanding of the molecular structure and mechanism of action of this unique transporter. This review will focus on the recent application of fluorescence spectroscopy, infra-red spectroscopy, circular dichroism spectroscopy, electron microscopy, and other biophysical techniques to the study of P-glycoprotein structure and function.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1998

Combinatorial libraries: studies in molecular recognition.

In recent years, combinatorial libraries have become a major tool for drug discovery and drug development. Along the way, one potential use of combinatorial chemistry libraries almost been neglected: the basic study of intermolecular interactions. Especially "one-bead-one-structure" libraries can be a powerful means for the discovery of ligands to synthetic receptors and vice versa. Encoded combinatorial libraries have been used to disclose ligands for well designed macrocyclic host molecules and to elucidate their specificities for peptide sequences. These studies led via receptors with more flexibility to simple host molecules without elaborate design that are accessible to combinatorial synthesis. These findings open a realm of possibilities and applications. An intriguing one is the development of chemical sensors for analytes that are otherwise hard or only unspecifically detected. Furthermore, such libraries and the techniques that were developed to handle them have been used to find new catalysts and enzyme mimics. In this review we put the emphasis on studies involving "one-bead-one-structure" libraries. We will review the techniques to generate them, to encode and analyze them, and to assay them. We will describe their past usage and the intriguing results of these studies and point out interesting new applications of such libraries for the study of non-covalent intermolecular interactions.

Chemistry↗
PubMed1998

[Cloning and orientation of cefoperazone resistance gene on plasmid pFC in E. coli HX88108].

Cefoperazone resistance gene (CPZr) has been cloned from plasmid pFC of E. coli HX88108 using the vector pMB9 (TCr, 5.3 kb). The plasmid pFC DNA was partially digested with Sau3A I, and its 1-2 kb fragments were ligated into BamH I site of vector plasmid pMB9. The recombinant DNA was then transformed into E. coli DH5 prepared using calcium chloride. CPZ resistant bacterial colonies were selected on the agar SOB plates containing CPZ (40 micrograms/ml). The resistance to CPZ could be stably reserved in generation after generation. The recombinant plasmids which encoded CPZ resistance were designated pFL11, pFL25, pFL33, pFL82, pFL86 and pFL102. Rapid small-scale preparation of plasmid and DNA restrication enzyme analysis were used for identification of bacterial colonies. Five plasmids DNA physical maps have been established. Comparison of recombinant plasmids maps with pFC map confirmed that the CPZr gene was oriented between nucleotide no. 3200 bp and no. 4800 + 40 bp of plasmid pFC total sequence. Its molecular weight was about 1.6 kb. There were EcoR I, Sma I and Pvu II sites within CPZr gene.

Cefoperazone↗
PubMed1998

[Significance and correlation of T lymphocyte subgroup, erythrocyte immune function and argyrophilic protein in nucleolar organizer regions in tuberculosis patients].

OBJECTIVE: To study the significance and relationship of T lymphocyte subgroups, erythrocyte immune functions and argyrophilic protein in nucleolar organizer regions (AgNORs) in tuberculosis patients. METHOD: CD3+, CD4+, CD3+/CD4+ were determined using alkaline phosphatase-antialkaline phosphatase (APAAP) method, E-C3bRR and E-ICR were assayed by observing receptor rate. Granules area of AgNORs (GA) and nuclear area (NA) were studied by image analysis system. RESULT: CD3+, CD4+, CD4+/CD8+, E-C3bRR, GA/NA in tuberculosis patients were significantly lower than those in the healthy group (P < 0.001). However, the values of E-ICR, CD8+ were significantly higher than those of control group (P < 0.001). CONCLUSION: The results of T lymphocyte subgroup, erythrocyte functions and AgNORs are in accord, and might be usefull in assessing diagnosis and prognosis of tuberculosis.

Adult↗
PubMed1998

[Chemotactic response of polymorphonuclear neutrophil to FMLP and IL-8 in rapidly progressive periodontitis patients].

OBJECTIVE: It has been reported that 48%-85% of rapidly progressive periodontitis (RPP) are associated with a defect in polymorphonuclear neutrophil (PMN) chemotactic function. However, some reports failed to detect any defect in PMN chemotaxis in RPP patients. Further, the influence of race on neutrophil function has been suggested. The purpose of the present study was to determine the PMN chemotactic function in Chinese RPP patients. METHODS: Neutrophils were obtained from heparinized peripheral blood of 16 RPP and 14 periodontally healthy control subjects matched for age and sex. Cells were isolated by Percoll discontinuous density gradient centrifugation. Chemotaxis was evaluated using modified Boyden chamber. (N-formyl-methionyl-leucyl-phenylalanine, FMLP) (10(-8) mol/L) and IL-8 (100 micrograms/L) which is a more specific neutrophil chemokines were used in this study. The results were determined by staining the filters followed by visual counting under microscopy at 600 x. Data was analyzed using the Students' t test and the value of RPP was compared with that of control subjects(> mean +/- 2s or < mean +/- 2s). RESULTS AND CONCLUSION: The results showed all RPP patients had normal PMN chemotactic behavior.

Adult↗
PubMed1998

[Effect of calmodulin inhibitor on spinal cord injury].

OBJECTIVE: To evaluate the effect of a special calmodulin (CaM) inhibitor-trifluoperizine (TFP) on spinal cord injury (SCI) and the role of CaM in SCI. METHOD: We observed the effect of TFP on spinal cord blood flow (SCBF), motor evoked potentials (MEP) and motor function in SCI by using hydrogen clearance, inclined plane and electro physiological technique. RESULT: There was significant improvement of SCBF, MEP and motor function with TFP, when adrenaline maintained the system arterial pressure in SCI. CONCLUSION: Prevention by TFP of spinal cord function in SCI suggested that CaM plays a role in the pathogenesis of SCI.

Animals↗
PubMed1998

[Synthesis and structure-activity relationships of novel 14 beta-side chain taxol derivatives].

In order to develop new generation of taxol-like anticancer agents with fewer side effects, improved activity, superior pharmacological properties and broad antitumor spectrum, along with structure-activity relationship study, a series of new taxol derivatives are to be synthesized starting from sinenxan A--a biosynthetic taxane. Eight new 14 beta-side chain taxol derivatives with 4-OH and 4-Ac were synthesized in 5 and 6 steps from semisynthetic taxoid intermediate 7, respectively. These included taxol derivatives modified at C-2 position with benzoate, m-Cl benzoate, valerate and phenylacetate. All target compounds together with two other 14 beta-side chain taxol derivatives were tested in a microtubule assembly assay, and in an in vitro cytotoxicity assay (KB, A2780, HCT-8 cell line). All compounds had no effect in the microtubule assembly assay at 10 mumol.L-1. Most of them showed marginal activity in the in vitro cytotoxicity. The structure-activity relationship was different from taxol derivatives. 2-Aliphatic ester displayed similar activity to 2-aromatic ester, which indicated that the aromatic group at C-2 position was not important for cytotoxicity. Comparing among themselves, 4-OH derivatives possessed stronger activity than 4-Ac.

Antineoplastic Agents, Phytogenic↗
PubMed1998

[Study on the interaction of Et2SnCl2(phen) with DNA].

The absorbance, fluorescence and cyclic voltammetric methods as well as agarose gel electrophoresis were used to study the interaction of the antitumor compound Et2SnCl2(phen) with DNA. The results indicate that Et2SnCl2 (phen) mainly reacts electrostatically with the phosphate backbone of DNA. There also exists an intercalation into the double-helix of DNA through the phenanthroline group of Et2SnCl2(phen). At high concentration Et2SnCl2(phen) can cause unwinding of DNA. The molecular action mechanism of Et2SnCl2(phen) with DNA was first proposed.

Animals↗
PubMed1998

[Synthesis and antiulcer activity of 3,4-dihydro-hainanensine analogs].

In order to search for new compounds with new mode of action, high antiulcer activity and lower toxicity, 26(13 pairs of diastereoisomer A and B) 3,4-dihydro-hananensine analogs were synthesized. All compounds were tested in M1 receptor combined assay and gastric ulcer induced by cold-immersion stress in rats. Most compounds showed antiulcer activity, among them IX3A, IX7A, IX8A, IX12A, IX12B and IX13A exhibited more potent antiulcer activity than the control compound cimetidine. Meanwhile, the relationship between their structures and activity was discussed.

Animals↗
PubMed1998

[Establishment of a method for detecting transforming growth factor beta 1 mRNA].

AIM: To establish a method to measure the TGF-beta 1 mRNA level for studying the mechanism of fibrogenesis caused by schistosomiasis japonica. METHODS: Reverse-transcription polymerase chain reaction and dot blot analysis were used. A plasmid of TGF-beta 1 was constructed for standardization, and beta-actin was used as control. Eight different concentrations of the plasmid and 11 double-tube of TGF-beta 1 mRNA in the peripheral blood mononuclear cell (PBMC) of different persons were measured. RESULTS: Quantitative results of 8 different dilutions of TGF-beta 1 plasmid had positive with the logarithm of the original concentration. The results of the 11 double-tube were 1.71 +/- 0.90 and 1.54 +/- 0.88. CONCLUSION: The duplicability and stability of the method showed it can be used to analyse the TGF-beta 1 mRNA level of the peripheral blood mononuclear cells.

Humans↗
PubMed1998

Effects of endothelial nitric oxide synthase gene expression on the tumor biology of human oral carcinoma SCC-25 cells.

Stable transfection of endothelial nitric oxide synthase (eNOS) cDNA in human oral carcinoma SCC-25 cells was performed. Two eNOS-expressing clones were isolated, and both were shown to have increased eNOS expression as assayed by Northern and Western analyses. Furthermore, a nitrite assay indicated that nitric oxide production in eNOS-transfected cells was increased. The growth rate and plating efficiency of eNOS-transfected cells in vitro were lower than that of the wild-type parental or vector control-transfected cells as assayed by growth curves, [3H]thymidine incorporation, and standard plating efficiency assays in L-arginine-rich medium. However, when these cancer cells were inoculated into nude mice, tumor size of eNOS-transfected cells was smaller during the first 25 days but increased later as compared to tumor size of parental and vector control-transfected cells. It is not clear whether the later increase in tumor size was due to an increase in SCC-25 cancer cell proliferation, normal stromal cell proliferation, or both. These results show significant effects of overexpression of eNOS on tumor growth in vitro and in vivo.

Animals↗
PubMed1997

A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups.

Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3. We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the approximately 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (approximately 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that some of these mutations arose before the affected Middle Eastern populations diverged from one another.

Alleles↗
PubMed1997

Oxidative acylation using thioacids.

Several important prebiotic reactions, including the coupling of amino acids into polypeptides by the formation of amide linkages, involve acylation. Theae reactions present a challenge to the understanding of prebiotic synthesis. Condensation reactions relying on dehydrating agents are either inefficient in aqueous solution or require strongly acidic conditions and high temperatures. Activated amino acids such as thioester derivatives have therefore been suggested as likely substrates for prebiotic peptide synthesis. Here we propose a closely related route to amide bond formation involving oxidative acylation by thioacids. We find that phenylalanine, leucine and phenylphosphate are acylated efficiently in aqueous solution by thioacetic acid and an oxidizing agent. From a prebiotic point of view, oxidative acylation has the advantage of proceeding efficiently in solution and under mild conditions. We anticipate that oxidative acylation should prove to be a general method for activating carboxylic acids, including amino acids.

Acylation↗