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D K Liu

Publications and source records attributed to D K Liu.

At least 19 recordsLinked to original sources
PubMed2000

Time of day determines modulation of synaptic transmission by adenosine in the rat hippocampal slices.

Adenosine, an endogenous modulator of synaptic transmission, has been implicated in regulation of sleep and arousal. The effect of adenosine on neuronal excitability depends on its concentration in the extracellular space. The present study shows that the state of activity of laboratory rats determines the level of tonic inhibition by adenosine in hippocampal slices prepared from these animals. Thus, slices taken at the end of the active period showed significantly more inhibition by adenosine, as determined by the effects of the A1 receptor blocker 8-CPT, in comparison to slices taken in the inactive state. The results support the proposed role of adenosine in regulation of sleep and arousal and point to the importance of the time of day at which slices for electrophysiological experiments are prepared.

Adenosine↗
PubMed1999

Efficacy of the topical skin protectant in advanced development.

A topical skin protectant (TSP) (ICD 2289) is being developed to protect service members from exposure to chemical warfare agents (CWA). The TSP is designed for use on the skin at the overgarment closures and other vulnerable areas to enhance protection. The TSP, which is in phase II clinical studies, is a cream containing two chemically inert substances: perfluoroalkylpolyether and polytetrafluoroethylene. Animal data showed that the TSP was effective against percutaneous penetration of a blister agent, sulfur mustard (HD), by reducing the size of skin lesions and against T-2 mycotoxin by preventing the development of erythema and edema. The insect repellent N,N-diethyl-m-toluamide (DEET) reduced the TSP protection against HD regardless of the order of application on rabbit skin prior to dosing of HD. The protection was sustained when DEET was removed with a dry gauze prior to TSP application. The TSP was also effective against percutaneous exposure of nerve agents-thickened (with 5% methyl methacrylamide) soman (TGD) and VX (O-ethyl-S-[2-(diisopropylamino)ethyl]methylphosphonothioate )-by reducing the mortality rate and protecting the red blood cell acetylcholinesterase activity. The TSP was effective against VX when DEET was applied prior to TSP application. Because human efficacy studies using CWA cannot be conducted, the efficacy will be demonstrated by the level of protection against poison ivy (urushiol) contact dermatitis in humans.

Acetylcholinesterase↗
PubMed1992

[Chemistry and antitumor activity of hainanensine analogues].

A synthetic analogue of hainanensine 2a was further modified in order to improve its antitumor activity. Six compounds 3-8, were obtained, and among these compounds 8 showed significant activity. The diastereomer (+/-)8B was resolved by (+) tartaric acid and (-)benzoyl-tartaric acid to the corresponding enantiomers (-)8B and (+)8B, respectively and their optical purities were determined by isotope dilution method as 93% and 96%. The antitumor activity of the newly obtained compounds were tested in vitro, and (-)8B was found to have an IC50 of 1.9 mol/L, eighteen times higher than the original compound 2a.

Animals↗
PubMed1992

[Determination of m-nifedipine and its pharmacokinetic study in rabbits by high-pressure liquid chromatography].

A high-pressure liquid chromatographic method was developed for determination of m-nifedipine in plasma using a chemical bonded C-18 phase column (YWG-C18 10 microns, made in China) with nitrendipine as internal standard. To increase life of the YWG-C18 column a mixture of methanol and 5 mmol.L-1 phosphate buffer (70:30 vol/vol) was selected as mobile phase with a flow rate of 0.8 ml.min-1. The method was sensitive to m-nifedipine 3 ng.ml-1 plasma and the standard curve was linear from 10 to 1000 ng.ml-1 with correlation coefficient of 0.99. The within-day and day-to-day precisions (CV) of this method were 4.5% and 7.0%, respectively, with recoveries of 95-102% (10-1000 ng.ml-1). There was no interference with nifedipine, amiodarone, propranol, and verapamil. A pharmacokinetic study on m-nifedipine was carried out in 8 rabbits. A better computer fitted to a two-compartment model was observed using 3P87 program. The parameters obtained were as follow: Vc 6.3 L.kg-1, Cl 0.021 L.kg-1.min-1, T1/2 alpha 30 min, T1/2 beta 230 min, AUC 102 micrograms.min.ml-1.

Animals↗
PubMed1991

Fractionation and characterization of 2',5'-oligoadenylates by polyacrylamide gel electrophoresis: an alternative method for assaying 2',5'-oligoadenylate synthetase.

2',5'-Linked oligoadenylates of varying chain lengths (2,5As) are formed from ATP by an interferon (IFN)-induced enzyme, 2',5'-oligoadenylate synthetase (2-5A synthetase). To identify these multiple forms, a method was devised utilizing electrophoretic separation of 32P-labeled 2,5As in a thin 20% polyacrylamide gel containing 7 M urea. A mixture of 2,5As synthesized from rat liver nuclear suspension was fractionated by this method. Each species was eluted from the gel for characterization by specific nucleotidylic enzymes. All major species in the gel were identified, including dimeric, trimeric, and tetrameric forms with either 5' tri- or diphosphates, as well as dephosphorylated species. Thus, in a single step, this method produced a more complete assessment of newly synthesized 2,5As and their degradative products than conventional, multistep DEAE-cellulose chromatography. It also allowed more rapid screening of multiple samples than high-pressure liquid chromatography (HPLC). This method, used to assay 2-5A synthetase induction by IFN-alpha in human T-cell H9 and CEM-CM3 lines, should be applicable for routine analysis of clinical specimens.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

[The concentration of homovanillic acid and leucine-enkephalin in the lumbar CSF of patients with Parkinson's disease before and after madopar treatment].

For comparison, the concentrations of homovanillic acid (HVA) and leucine-enkephalin (LEK) in the lumbar cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) before and after treatment with madopar were determined 19 patients, suffering from common surgical diseases, who had CSF withdrawn by lumbar punctures for spinal anesthesia, served as controls. HVA was estimated by fluorescence scanning after polyamide thin-layer chromatography. LEK was measured with radio-immuno-assay. The mean concentration of HVA from 22 patients before madopar treatment (0.085 +/- 0.011 mg/L, means +/- S means) was significantly lower than the control mean value (0.264 +/- 0.022 mg/L) (P less than 0.001); while that of LEK from 25 patients before treatment (197.01 +/- 12.96mg/L, means +/- S means) was significantly higher than the control mean value (88.79 +/- 8.66mg/L) (P less than 0.001). Treatment with madopar increased the concentration of HVA (0.222 +/- 0.032mg/L) (P less than 0.001) but exhibited no significant effect on the levels of LEK. It is confirmed that there is a reduction of HVA in CSF in Parkinsonian patients. The results suggest that an increase of enkephalin in the brain seems to play some role in the pathogenesis of PD, but why madopar could not significantly alter the LEK level in CSF awaits further studies.

Adult↗
PubMed1987

Inhibition of viral reverse transcriptase by 2',5'-oligoadenylates.

Viral reverse transcriptase activity was inhibited in a concentration dependent manner by 2',5'-oligoadenylate. Kinetically this inhibition was of a mixed type where 2',5'-oligoadenylate was not strictly competitive with dTTP. The potency of inhibition was more marked in the absence than in the presence of sulfhydryl agents. 2',5'-oligoadenylate had no effect on DNA-dependent E. coli DNA polymerase and was much less active against mammalian DNA polymerases. This is the first report of reverse transcriptase inhibition by an inducible constitutive natural ligand.

Adenine Nucleotides↗
PubMed1987

An endogenous protein inhibitor of DNA polymerase alpha in normal and neoplastic rat mammary tissues.

Extracts of whole tissue or isolated nuclei from lactating rat mammary gland that has diminished cell replication capacity were more active than the corresponding extracts of pregnant rat mammary gland that contains actively replicating cells in causing a dose-dependent inhibition of DNA polymerase alpha in vitro. Purification of the inhibitor from both tissue and nuclear extracts using a sequence of Sephacryl S200, DEAE-cellulose and CM52 columns confirmed the above assay results. Using the same assay and purification procedures, both tissue and nuclear extracts from the rapidly growing transplanted R3220AC mammary tumors exhibited very little or no inhibitor activity. The partially purified mammary inhibitor (mol. wt of 155kD, high A280 nm/A260 nm ratio, heat labile) was equally inhibitory to the purified DNA polymerase alpha from either R3230AC tumor or calf thymus, and to the nuclear matrix bound DNA polymerase alpha of R3230AC tumor.

Animals↗
PubMed1987

Methylxanthine treatment of rats reduces 2,5-oligoadenylate synthesis in liver nuclei.

The in vivo effects of methylxanthines on 2',5'-oligoadenylate (2,5An) synthetase activity, an interferon-inducible enzyme, were investigated in rat liver nuclei. Caffeine given at 50 mg/kg ip or theobromine given at 80 mg/kg sc twice daily for 5 d resulted in a 60% reduction (p less than 0.01 and p less than 0.05, respectively) of 2,5An synthetase activity in liver nuclei. Theophylline given at 80 mg/kg sc by the same regimen reduced the enzyme activity by 42% (p less than 0.05). Nuclear 2'-phosphodiesterase activity, which catalyzes the degradation of 2,5An, remained low and unchanged following the drug treatments. When animals receiving caffeine were also given the interferon inducer poly(I)poly(C) at 500 micrograms/kg ip once daily for the last 2 d of caffeine treatment, it resulted in the same fourfold increase in 2,5An synthetase activity as shown with poly(I)poly(C) alone. These results suggest that methylxanthines may interact with interferon-mediated actions. The reason for the inhibitory effect of methylxanthines on the basal but not on the induced 2,5An synthetase remains to be investigated.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Milk-specific RNase as a marker of differentiation of rat mammary tumors.

Various rat mammary tumors were analyzed for the presence of a milk-specific Ca2+-stimulated RNase (Ca2+-RNase). When crude extracts of some differentiated tumors--adenocarcinomas of MT/W9, MT/W9a, R3230AC, DMBA-1, DMBA-8, and DMBA-14 and 3MN squamous cell carcinoma--were assayed for RNase activity under various ionic conditions, it was always highest in the presence of Ca2+/EDTA than under any other ionic condition. The opposite was true in invasive MT/W449a and 13762 adenocarcinomas, poorly differentiated SMT/2A carcinomas, MAMF2/TC fibrosarcoma, and MT/A fibroadenoma. Sephacryl S-200 chromatography separation of tumor extracts confirmed the presence of Ca2+-RNase in those differentiated tumors and absence of the enzyme from other tumors. Expressing the activity as a ratio of Ca2+/EDTA to either Mg2+/EDTA or EDTA alone to more clearly represent the relative level of Ca2+-RNase activity further illustrates the distinct differences between tumor classes. Thus Ca2+-RNase is a sensitive marker for use in the characterization of rat tumors with respect to differentiated mammary functions.

Adenocarcinoma↗
PubMed1986

Intranuclear dynamics of DNA polymerase alpha differs between the transplanted R3230AC mammary adenocarcinomas and the host mammary gland depending on lactation cycle.

DNA polymerase alpha activity was markedly higher in all nuclear subfractions, including nuclear matrix, from transplanted R3230AC mammary adenocarcinomas than in the analogous fractions from mammary gland of same tumor-bearing pregnant or lactating rats. Changes in host lactational status had no significant effect on subnuclear distribution of tumor DNA polymerase alpha activity, with the majority (60-75%) localized in soluble nucleoplasm and a significant amount (13-20%) retained in the nuclear matrix. In the host mammary gland, nuclear matrix-bound DNA polymerase alpha was highest, accounting for 48% of total nuclear activity, during late pregnancy when mammary cells undergo rapid raplication. During lactation, when cells in mammary gland cease to divide, only 8% of enzyme activity was in the nuclear matrix, while the majority (60-80%) of DNA polymerase alpha activity was localized in nucleoplasm. In both R3230AC tumor and mammary gland regardless of host's lactational status, the majority (60-80%) of DNA polymerase beta activity was localized in the high salt-soluble chromatin. These present data thus suggest that, regardless of host lactational status, R3230AC tumor has many cycling cells, each with a large pool of DNA polymerase alpha molecules maintaining maximal and constant replicative activity, while normal mammary gland cells have a smaller pool of DNA polymerase alpha which become primarily matrix-bound only during active cell replication during late pregnancy. A constant localization of nuclear DNA polymerase beta in chromatin in both mammary gland and the tumor suggest it is not important in mammary cell proliferation.

Adenocarcinoma↗
PubMed1986

Quantitative autoradiography of 125I-[Sar1, Ile8]-angiotensin II binding in the brain of spontaneously hypertensive rats.

The brain contains its own angiotensin II (AII) system. To better understand the role of central AII in cardiovascular regulation, we used 125I-[Sar1, Ile8]-AII (125I-SI-AII), radioactive AII antagonist, to autoradiographically localize putative AII receptor binding in many parts of the central nervous system of the spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. With 125I-SI-AII binding on brain membrane preparations. Scatchard analysis indicated that Kd values were from 0.10 +/- 0.04 nM to 0.13 +/- 0.05 nM, whereas Bmax values (femtomol/mg protein) were found to be from 6.95 +/- 1.60 to 15.52 +/- 4.99 among brain regions studied. Various SI-AII receptor binding activities among brain regions revealed in this study were therefore most likely due to differences in AII receptor density with high affinity binding of 125I-AII. Using 125I-SI-AII, specific binding for SI-AII was found in the nucleus tractus solitarius (NTS), paraventricular hypothalamic nucleus (PVN), subfornical organ (SFO), suprachiasmatic nucleus (SCN), area postrema, the dorsal motor nucleus of the vagus (DMX), and the nucleus of spinal tract of the trigeminal system (NSV). With quantitative receptor autoradiography in conjunction with radioactive standards, we have observed that the NTS possesses the highest SI-AII binding, followed by the PVN, SFO, NTS, DMX, and NSV. No significant differences were observed between the SHR and WKY rats in the SI-AII binding within the SFO, PVN and NTS. However, SHR at early hypertensive (7 weeks) and established hypertensive (16 weeks) stages contained significantly higher SI-AII bindings in the NSV, as compared to age-matched WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

2',5'-oligoadenylate synthetase activity in human mammary tumors and its potential correlation with tumor growth or hormonal responsiveness.

Since interferon inducible 2',5'-oligoadenylate (2,5An) synthetase activity is present in a wide variety of cells and is affected by various hormonal conditions, primary human mammary tumor extracts were examined for the constitutive presence of this enzyme and its possible relationship with the various hormonal receptor levels in these tissues. Further, since 2,5An synthetase has been implicated as a possible factor controlling cell replication, we assayed DNA polymerases in these same tumor extracts to determine any correlation between 2,5An synthetase activity and growth potential. A survey of the soluble extracts from 24 different surgically removed human mammary tumor specimens for 2,5An synthetase activity indicated that this enzyme was indeed present in all extracts but in widely varying amounts of activity (31-2,666 nmol adenosine 5'-phosphate incorporated/mg protein). The 2,5An synthesized in the enzymic reactions ranged in size from di- to hexamers, with trimers being the abundant 2,5An in the majority of tumors. A comparison of the assay results for estrogen and progestin receptors with 2,5An synthesis indicated that high 2,5An synthetase activity was found in both estrogen or progestin positive and negative tumors. Thus, 2,5An synthetase activity was unrelated (r = 0.329 and 0.077, respectively, for estrogen and progestin receptors) to the hormonal receptor content of these tumors. A similar comparison was made between 2,5An synthesis and assay results for the activities of DNA polymerase alpha, regarded as the principal DNA replicating enzyme, and DNA polymerase beta, regarded as the DNA repair enzyme. Although the activity of the polymerases were also quite varied, the majority of tumor extracts demonstrated higher alpha polymerase activity with no parallel difference between the alpha and beta enzymes. There was, however, a weak correlation (r = 0.751) between 2,5An synthetase activity and DNA polymerase alpha activity among the tumors examined. Less of a correlation existed with DNA polymerase beta activity (r = 0.600). These results suggested that the potential of the tumors to synthesize 2,5An was unrelated to their hormonal responsiveness and only weakly related to their growth potential reflected by DNA polymerase alpha activity.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Heterogeneous localization of adenylate and guanylate cyclases in R3230AC rat mammary adenocarcinoma cells.

Adenylate and guanylate cyclase activities were demonstrated in R3230AC rat mammary adenocarcinomas by electron microscopic cytochemistry. Adenylate (AC) and guanylate (GC) cyclases were detected on plasma membrane of tumor epithelial cells, but not on fibroblasts and endothelial cells in the perivascular space. Both AC and GC activities were enriched in tumor epithelial cells at the periphery of the tumor lobular parenchyma rather than in cells in central core of the lobular parenchyma. Furthermore, the tumor cell plasma membranes facing the connective tissue stroma were in paucity or devoid of either enzyme activity. These heterogeneous distributions of both AC and GC among tumor epithelia suggest that R3230AC epithelial cells in different parts of the tumor mass may vary significantly in their regulation of cellular physiology.

Adenocarcinoma↗
PubMed1985

Inhibition of DNA polymerase alpha activity by proteins from rat liver.

We determined that there is a protein in rat liver capable of inhibiting DNA polymerase alpha. To assay for this inhibitor, DNA polymerase alpha was purified from R3230AC rat mammary tumor, a rich source of this enzyme. Protein fractions from Sephacryl S200 gel filtration of total soluble liver extract showing inhibition of DNA polymerase alpha were further chromatographed on DEAE-cellulose. This step revealed two inhibitor protein populations with the major form corresponding to a molecular weight of 143,000 dalton. Soluble extract from isolated rat liver nuclei also showed the presence of at least two inhibitors; the major form was 200,000+ dalton in molecular weight. Both the 143,000 and 200,000+ dalton inhibitor proteins were capable of inhibiting the R3230AC tumor DNA polymerase alpha in a dose-dependent manner. These inhibitors exhibited similar inhibition of nuclear matrix-associated DNA polymerase alpha from either the R3230AC tumor or from regenerating rat liver.

Animals↗