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L Liu

Publications and source records attributed to L Liu.

At least 1,225 records · Page 68Linked to original sources

Characterization of activation and deactivation pathways of 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) in rat hepatocytes.

We have characterized the metabolism of 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) in cultured rat hepatocytes and have established the relationship between various metabolic pathways and single-strand breaks (SSB) in DNA. Metabolism of [5-3H]-NNK by carbonyl reduction, alpha-carbon hydroxylation and pyridine N-oxidation was linear from 0.5 to 6 h with 0.25-2 x 10(6) hepatocytes. Using an alkaline elution assay, we observed that NNK induces SSB in DNA in a dose- and time-dependent manner. SSB induced by NNK were rejoined partially within 2 h and totally by 12 h after exposure. NNK-N-oxide produced a smaller number of SSB than NNK, suggesting that pyridine N-oxidation of NNK is a deactivation pathway. Carbonyl reduction of NNK led to 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butan-1-ol (NNAl). Reaction of NNK with methyl magnesium iodide gave 4-(N-nitrosomethylamino)-1-(methyl)-1-(3- pyridyl)butanol-1-ol (1-MeNNAl) 82% yield. NNAl, but not 1-MeNNA1, can be reoxidized to NNK. Doses of 5 mM NNAl and 1-MeNNAl both induced SSB, indicating that NNAl does not require reconversion to NNK to be activated to DNA damaging intermediates. alpha-Methylene hydroxylation resulted in the formation of 4-oxo-4-(3- pyridyl)butanal. At equimolar concentration (5 mM), the aldehyde was more damaging than NNK to hepatocyte DNA. The results of this study demonstrate that NNK is activated by rat hepatocytes and that metabolites formed by alpha-carbon hydroxylation induce SSB.

Animals↗

Clinical and experimental observations on treatment of peptic ulcer with wei yang an (easing peptic-ulcer) capsule.

The therapeutic effects of peptic ulcer treated with cimetidine and Wei Yang An were compared clinically and experimentally by the double blind method. Results showed that the effects of the two are similar, but the long-term effect of Wei Yang An was better. Wei Yang An was also good for most cimetidine resistant ulcers, with few side effect. Animal experiment showed that Wei Yang An inhibited the ulcers.

Adult↗

[Disposition of 3-(N-piperidinomethylarino)methyl-rifamycin SV (FCE 22250) in rats].

After rats being given ig FCE 22250 5, 10 and 25 mg.kg-1, the plasma peak times (Tmax) were 12-14 h, the max plasma concentrations (Cmax) were 3.0, 5.6 and 12 micrograms.ml-1 respectively, and the half-lives of elimination (T1/2) were 24-26 h. The apparent volumes of distribution of the three doses were about 1 L.kg-1, suggesting that FCE 22250 in blood and in tissue was balanced. Total body clearance rate of each of the three doses was 29 ml.kg-1.h-1. The ig absolute bioavailability ranged from 69-84%. Its distribution in rats was as follows: the highest in liver, next in lung and then in fat, kidney, intestine, spleen, lymphaticode, heart, muscle, testis, the lowest in brain. It was eliminated mainly via the bile with feces. The human serum protein binding rate of FCE 22250 was 96.2%. It was shown that the rate was not correlated with drug concentration in serum under our experimental conditions.

Animals↗

Calcium protects pituitary basic fibroblast growth factors from limited proteolysis by co-purifying proteases.

Extracts from bovine pituitaries and other tissues contained basic fibroblast growth factor-like peptides of 22-26 kda, co-fractionating with smaller, 16-20 kda bFGFs. Heparin-bound, 22-26 kda bFGFs were converted to smaller, heparin-binding forms by tryptic proteolysis. In solution, 22-26 kda bFGFs were converted to smaller, heparin-binding forms by an activity present in pituitary extracts. Calcium protected higher molecular weight pituitary bFGFs from truncation by the endogenous activity, which was not acid-activated, co-purified with bFGF during heparin-sepharose chromatography, remained operant at high salt concentrations and was inhibited by phenylmethan-sulfonyl fluoride.

Animals↗

Target areas of presumed auditory projections from lateral and dorsolateral pontine nuclei to posterior cerebellar vermis in rat.

Small injections of the retrograde tracer horseradish peroxidase were made into lobules V through X in the posterior cerebellar vermis of the rat. Labeled cells were counted in the auditory subdivisions of the pontine nuclei, the lateral and dorsolateral pontine nuclei. The results suggest that, within the posterior vermis, lobules VI, VII, and VIII together receive over 90% of projections from the lateral and dorsolateral pontine nuclei.

Animals↗

Blockade of morphine analgesia by both pertussis and cholera toxins in the periaqueductal gray and locus coeruleus.

Rats demonstrating analgesia following microinjection of morphine into the periaqueductal gray (PAG) or locus coeruleus (LC) were injected with either pertussis toxin, cholera toxin or saline into the same brain region. Both pertussis and cholera toxin blocked the analgesic effect of morphine at both injection sites for up to 7 days after toxin treatment. These results indicate that morphine analgesia is a complex response involving systems dependent upon Gs as well as Gi or Go proteins.

Analgesia↗

A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation.

A synthetic peptidemimetic substrate of the human immunodeficiency virus 1 (HIV-1) protease with a nonhydrolyzable pseudodipeptidyl insert at the protease cleavage site was prepared. The peptide U-81749 inhibited recombinant HIV-1 protease in vitro (inhibition constant Ki of 70 nanomolar) and HIV-1 replication in human peripheral blood lymphocytes (inhibitory concentration IC50 of 0.1 to 1 micromolar). Moreover, 10 micromolar concentrations of U-81749 significantly inhibited proteolysis of the HIV-1 gag polyprotein (p55) to the mature viral structural proteins p24 and p17 in cells infected with a recombinant vaccinia virus expressing the HIV-1 gag-pol genes. The HIV-1 like particles released from inhibitor-treated cells contained almost exclusively p55 and other gag precursors, but not p24. Incubation of HIV-like particles recovered from drug-treated cultures in drug-free medium indicated that inhibition of p55 proteolysis was at least partially reversible, suggesting that U-81749 was present within the particles.

Amino Acid Sequence↗

In vitro prostaglandin H synthase- and monooxygenase-mediated binding of aflatoxin B1 to DNA in guinea-pig tissue microsomes.

In order to study the mechanism of cancer production by aflatoxin B1 (AFB1) in extrahepatic tissues which have relatively low cytochrome P450 monooxygenase (P450) activity, we have examined prostaglandin H synthase (PHS)-mediated AFB1 activation [( 3H]AFB1-DNA binding). [3H]AFB1 was activated by both purified PHS and microsomal PHS from guinea-pig kidney and liver, as well as by P450 in lung, kidney and liver microsomes, though P450-mediated [3H]AFB1-DNA binding in lung and liver was much higher than that catalyzed by PHS. Arachidonic acid (AA)-dependent [3H]AFB1-DNA binding could be inhibited by the PHS inhibitor indomethacin (0.1 mM), but was enhanced by the P450 inhibitor SKF-525A (3 mM), confirming that the reaction was independent of P450. Pulmonary PHS-mediated [3H]AFB1--DNA binding was less than 0.1 pmol [3H]AFB1/mg protein/min. HPLC analysis showed only minimal formation of [3H]AFM1 and [3H]AFQ1 by PHS, confirming that the low rate of PHS-dependent [3H]AFB1-DNA adduct formation was not due to conversion of AFB1 to other metabolites by PHS. The omission of AA did not diminish [3H]AFB1-DNA binding. In AA-free incubates, indomethacin inhibited, and SKF-525A enhanced, [3H]AFB1-DNA binding to a similar degree as in complete incubates, indicating that DNA binding in AA-free incubates was catalyzed by PHS. This reaction was also inhibited by 4-bromophenacyl bromide, a phospholipase A2 inhibitor, by 92%. These data are consistent with previous reports indicating the ability of AFB1 to stimulate the release of endogenous AA from membranes, presumably by stimulating phospholipase A2 activity, which may lead to enhanced bioactivation of AFB1 by PHS in vivo.

Aflatoxin B1↗

Biotransformation of aflatoxin B1 in rabbit lung and liver microsomes.

Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin that requires bioactivation to AFB1-2,3-oxide for activity. In addition to epoxidation, microsomal monooxygenases biotransform AFB1 to the less toxic metabolites, aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1). The lung is at risk from AFB1 both via inhalation and via the circulation. In the present study, we have characterized rabbit lung and liver microsomal AFB1-DNA binding (an index of AFB1-2,3-oxide formation), AFM1 formation and AFQ1 formation. Vmax values for AFB1-DNA binding were not different between lung and liver when expressed per mg microsomal protein (1.06 +/- 0.13 and 2.12 +/- 1.30 nmol/mg/h for lung and liver respectively), but lung values were greater than liver when expressed per nmol cytochrome P450 (3.64 +/- 0.31 and 1.29 +/- 0.70 nmol/nmol P450/h for lung and liver respectively). Km values for this reaction were not different between lung and liver. Vmax values for AFM1 formation in liver microsomes were greater than in lung when expressed per mg protein, but not when expressed per nmol P450. No differences were detected for the Km for AFM1 formation between lung and liver microsomes. For AFQ1 formation, no differences were detected between Vmax values of lung and liver, regardless of whether results were expressed per mg protein or per nmol P450, while the Km for AFQ1 formation was lower in liver. SKF-525A inhibited these reactions by 63-74% in lung microsomes and 90-96% in liver microsomes. These results indicate that the lung is capable of activating AFB1, and that rabbit lung microsomes contain high activity for this reaction. Furthermore, little AFM1 and AFQ1 are formed in lung microsomes, leading to minimal shunting of AFB1 from the activation pathway.

Aflatoxin B1↗

Mutagenesis of dimeric plasmids by the transposon gamma delta (Tn1000).

The Escherichia coli F factor mediates conjugal transfer of a plasmid such as pBR322 primarily by replicative transposition of transposon gamma delta (Tn1000) from F to that plasmid to form a cointegrate intermediate. Although resolution of this cointegrate always yields a plasmid containing a single gamma delta insertion, the occasional recovery of transposon-free plasmids after conjugal transfer has led to alternative hypotheses for F mobilization. We show here that gamma delta-free plasmids are found after F-mediated conjugal transfer only when the donor plasmid is a dimer and the recipient is Rec+.

Conjugation, Genetic↗

An abnormality of the gene that encodes neutrophil Fc receptor III in a patient with systemic lupus erythematosus.

In the course of examining the structure and function of Fc receptors on peripheral blood cells of patients with systemic lupus erythematosus, we identified a patient whose neutrophils did not react with either monoclonal or polyclonal antibodies to Fc receptor III. However, neutrophils from the patient were comparable to neutrophils from healthy controls with respect to their expression of Fc receptor II, complement receptor 1, complement receptor 3, and the phosphatidylinositol-linked, complement regulatory protein, decay-accelerating factor. The abnormality of expression of Fc receptor III was limited to the patient's neutrophils (her natural killer cells reacted normally with anti-Fc receptor III antibodies), and was associated with abnormal recognition and binding of IgG-coated erythrocytes. Analysis of genomic DNA revealed evidence that failure of the patient's neutrophils to express Fc receptor III was most likely due to an abnormality of the gene that encodes this receptor.

Adult↗

Characterization of two preparations of antibodies to basic fibroblast growth factor which exhibit distinct patterns of immunolocalization.

Immunoglobulins reactive against basic fibroblast growth factor (bFGF) were obtained from the serum of a single rabbit immunized against residues [1-24] of bFGF conjugated to keyhole limpet hemocyanin (KLH). Pure immunoglobulin preparations no. 1 and no. 2 were prepared using different affinity chromatography columns and preabsorption to KLH-coupled Sepharose for preparation no. 1. Both preparations no. 1 and no. 2 were specific for bFGF in in vitro assays. Competition with synthetic peptides suggests that preparations no. 1 and no. 2 recognize predominantly epitope(s) within residues [16-24]bFGF or residues [1-10]bFGF, respectively, in situ. Furthermore, no. 2 (but not no. 1) antibodies can react with tissue-(heparin-)-bound antigen. When used in indirect immunofluorescence for bFGF in frozen heart sections, preparation no. 1 stained predominantly muscle intercalated discs (IcDs); muscle nuclei were also stained, in an overall punctate fashion. Preparation no. 2 stained muscle nuclei strongly, in association with the nuclear envelope; it also stained basement-membrane associated bFGF. Differences in immunostaining were also observed in uterine smooth muscle and kidney sections but not in skeletal muscle. It is plausible that accessibility of various epitopes within the amino-terminal region depends strongly on the local interactions of bFGF. Our data illustrate the importance of using several different antibodies to localize bFGF in a tissue.

Absorption↗

Immune enhancement of a polysaccharides peptides isolated from Coriolus versicolor.

A protein-bound polysaccharides (PSP) isolated from Coriolus versicolor in Shanghai, at the concentrations of 100-800 micrograms/ml promoted lymphocyte proliferation. PSP 25 mg/kg ip into mice for 5 d antagonized the inhibition of IL-2 production by cyclophosphamide from activated T lymphocytes and restored the suppressed T-cell-mediated delayed, type hypersensitivity response to normal. PSP 10-1000 micrograms/ml induced interferon alpha and gamma production from human peripheral leukocytes 4 and 8 times respectively higher than that of the control groups. Moreover, PSP also increased phagocytic functions of host reticulo-endothelial system. The results suggest that the anti-tumor effects of PSP may be related to its potentiation of host immunological responses.

Animals↗

[Chemical evaluation of vinegar-processing method for fresh rhizoma Corydalis].

Qualitative and quantitative analysis were carried out on the samples of Rhizoma Corydalis in both the locally vinegar-processed (fresh) and traditionally vinegar-processed forms. No difference was found in the main chemical constituents. However, both the total alkaloids and the corydalis B content of the former are higher than those of the latter.

Acetates↗