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PROPERTIES Of THE ATPASE ACTIVITY ASSOCIATED WITH PEROXISOME-ENRICHED fRACTIONS fROM RAT-LIVER - COMPARISON WITH MITOCHONDRIAL f1f0-ATPASE

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BIOCHIMICA ET BIOPHYSICA ACTA 1990年第1期1035卷 6-11页

作者： WOLVETANG, EJ WANDERS, RJA SCHUTGENS, RBH BERDEN, JA TAGER, JM UNIV AMSTERDAM ACAD MED CTR EC SLATER INST BIOCHEM RES 1105 AZ AMSTERDAM NETHERLANDS

Highly purified peroxisomal fractions from rat liver contain ATPase activity (18.8 .+-. 0.1 nmol/min per mg, n = 6). This activity is about 2% of that found in purified mitochondrial fractions. Measurement of marker enzyme activities and immunoblotting of the peroxisomal fraction with an antiserum raised against the .beta.-subunit of mitochondrial ATPase indicates that the ATPase activity in the peroxisomal fractions can not be ascribed to contamination with mitochondria or other subcellular organelles. from the sensitivity of the ATPase present in the peroxisomal fraction towards a variety of ATPase inhibitors, we conclude that it displays both V-type and f-type features and is distinguishable from both the mitochondrial f1f0-ATPase and the lysosomal V-type ATPase.

关键词： ATPase ATPase, f 1 f 0 - permeability peroxisome

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HYPOTENSIVE EffECT INDUCED BY A CYCLIC DOPAMINE ANALOG, TRANS-4-METHYL-7,8-DIHYDROXY-1,2,3,4,4A,5,6,10B-OCTAHYDROBENZO[f]QUINOLINE

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JOURNAL Of PHARMACEUTICAL SCIENCES 1978年第11期67卷 1639-1641页

作者： SHARABI, fM LONG, JP CANNON, JG UNIV IOWA COLL MED DEPT PHARMACOL IOWA CITY IA 52242 USA UNIV IOWA COLL PHARM DIV MED CHEM & NAT PROD IOWA CITY IA 52242 USA

The antihypertensive effects of trans-4-methyl-7,8-dihydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinoline, a dopamine agonist, were investigated in dogs and spontaneous hypertensive rats. I.v. administration of low doses of this cyclic analog of dopamine (0.25-1.00 .mu.g/kg) consistently reduced blood pressure and heart rate, concurrently recorded in the dog. This effect was antagonized by haloperidol, a specific dopamine antagonist. The dopamine analog also reduced systolic blood pressure of spontaneous hypertensive rats. The possibility that the decrease in blood pressure and heart rate elicited by the dopamine analog is attributable to an effect on specific dopaminergic receptors is confirmed.

关键词： trans -4-Methyl-7,8-dihydroxy-1,2,3,4,4a,5,6,1 Ob-octa- hydrobenzo[ f ]quinoline—hypotensive activity evaluated in dogs and spontaneous hypertensive rats Benzo[ f ]quinoline, substituted— hypotensive activity evaluated in dogs and spontaneous hypertensive rats Hypotensive activity—substituted benzo[ f ]quinoline evaluated in dogs and spontaneous hypertensive rats Dopamine analogs, cyclic—hypotensive activity evaluated in dogs and spontaneous hypertensive rats

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ESCHERICHIA-COLI f1-ATPASE - SITE-DIRECTED MUTAGENESIS Of THE BETA-SUBUNIT

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fEBS LETTERS 1988年第1期232卷 111-114页

作者： PARSONAGE, D WILKEMOUNTS, S SENIOR, AE Dept of Biochemistry Box 607 University of Rochester Medical Center Rochester NY 14642 USA

Residues βGlu-181 and βGlu-192 of E. coli f 1 -ATPase (the DCCD-reactive residues) were mutated to Gln. Purified βGln-181 f 1 showed 7-fold impairment of ‘unisite’ P i formation from ATP and a large decrease in affinity for ATP. Thus the β-181 carboxyl group in normal f 1 significantly contributes to catalytic site properties. Also, positive catalytic site cooperativity was attenuated from 5 × 10 4 - to 548-fold in βGln-181 f 1 . In contrast, purified βGln-192 f 1 showed only 6-fold reduction in ‘multisite’ ATPase activity. Residues βGly-149 and βGly-154 were mutated to Ile singly and in combination. These mutations, affecting residues which are strongly conserved in nucleotide-binding proteins, were chosen to hinder conformational motion in a putative ‘flexible loop’ in β-subunit. Impairment of purified f 1 -ATPase ranged from 5 to 61%, with the double mutant f 1 less impaired than either single mutant. f 1 preparations containing βIle-154 showed 2-fold activation after release from membranes, suggesting association with f 0 restrained turnover on f 1 in these mutants.

关键词： f 1 -ATPase Mutagenesis DCCD-reactive glutamate Conserved glycine residue DCCD, dicyclohexylcarbodiimide residue numbers are rationalized to the E. coli β-subunit sequence throughout

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ANAEROBIC METABOLISM Of 2-AMINO-3-METHYL-3H-IMIDAZO[4,5-f]QUINOLINE (IQ) BY HUMAN fECAL fLORA

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MUTATION RESEARCH 1987年第3期190卷 187-190页

作者： BASHIR, M KINGSTON, DGI CARMAN, RJ VANTASSELL, RL WILKINS, TD VIRGINIA POLYTECH INST & STATE UNIV DEPT ANAEROB MICROBIOL BLACKSBURG VA 24061 USA

Incubation of the heterocyclic cooked food mutagen IQ with mixed human fecal microflora under anaerobic conditions yielded 2-amino-3,6-dihydro-3-methyl-7H-imidazo[4,5-f]quinoline-7-one (2) as the major detectable meta... 详细信息

关键词： 2-Amino-3-methyl-3 H -imidazo[4,5- f ]quinoline IQ (Human fecal microflora) Cooked food mutagen IQ, 2-amino-3 H -imidazo[4,5- f ]quinoline, 76180-96-6 N 6 -methyl-5,6-quinolinediamine, 14204-98-4 PTLC, preparative thin-layer chromatography BHI, brain heart infusion DMSO, dimethyl sulfoxide EI, electron impact

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IMIDAZO[4, 5-f]QUINOLINES .3. ANTIBACTERIAL 7-METHYL-9-(SUBSTITUTED ARYLAMINO)IMIDAZO[4, 5-f]QUINOLINES

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JOURNAL Of PHARMACEUTICAL SCIENCES 1977年第8期66卷 1204-1206页

作者： SNYDER, HR SPENCER, Cf fREEDMAN, R NORWICH PHARM CO DEPT RES & DEV NORWICH NY 13815 USA

A series of 7-methyl-9-(substituted arylamino)imidazo-[4,5-f]quinolines were prepared and screened against 4 varieties of bacteria [Staphylococcus aureus, Escherichia coli, Corynebacterium liquefaciens and Haemophilus... 详细信息

关键词： Imidazo[4,5- f ]quinolines, substituted—synthesized, screened for antibacterial activity Antibacterial activity—various substituted imidazo[4,5- f ]quinolines screened Structure-activity relationships—various substituted imidazo[4,5- f ]quinolines screened for antibacterial activity

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Application of Kirchhoff's Laws to pharmacologic and pharmacokinetic analyses

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PHARMACOLOGICAL REVIEWS 2025年第3期77卷 100050页

作者： Benet, Leslie Z. Sodhi, Jasleen K. Tiitto, Markus Ville Xiang, Yue Univ Calif San Francisco Sch Med Dept Bioengn & Therapeut Sci 513 Parnassus Ave Room S-822 San Francisco CA 94143 USA Septerna Dept Drug Metab & Pharmacokinet South San Francisco CA USA Food & Drug Adm Ctr Drug Evaluat & Sci Off Clin Pharmacol Silver Spring MD USA

Recently, we introduced a straightforward approach to derive clearance and rate constant equations, without relying on differential equations, utilizing Kirchhoff's Laws, a well known physics methodology used to describe rate-defining processes either in series or parallel. Manuscripts from our laboratory have re-examined published experimental data, demonstrating that the Kirchhoff's Laws methodology can explain data previously considered anomalous, such as the following: specialIntscript all experimental perfused liver clearance data conforming to the equation once thought to represent the unphysiological well stirred model, specialIntscript instances where linear pharmacokinetic systemic bioavailability determinations exceed unity, specialIntscript renal clearance being influenced by drug input processes, specialIntscript statistically significant differences in bioavailability measures between urinary excretion and systemic concentration mea- surements, and specialIntscript how the long-accepted steady-state clearance approach used in pharmacokinetics for the past half-century leads to unrealistic conclusions about the relationship between liver-to-blood Kp uu and hepatic availability f H . These findings demonstrate the potential for errors in pharmacokinetic evaluations that rely on differential equations. The Kirchhoff's Laws approach is applicable to all pharmacokinetic analyses of quality experimental data, both those that align with present pharma- cokinetic theory, and those that do not. Although 3 publications have attempted to rebut our position, they fail to address unexplained experimental data, and we detail here why these analyses are invalid. Our discoveries are ongoing. Additionally, we briefly discuss the application of Kirchoff's Laws to saturable nonlinear kinetics, explaining increased pharmacodynamic response for extended vs im- mediate release dosage forms, as well as the advantages of successfully formulating high hepatic extraction drugs.

关键词： [ S ] substrate concentration A absorp site amount of drug at the absorption site A body amount of drug in the body AUC area under the curve AUMC area under the moment curve C avg,u,DM average liver unbound concentration for the dispersion model C Blood steady-state concentration of total drug in the blood C H,u average concentration of unbound drug within the liver C in blood concentration of total drug (unbound plus bound) entering the liver C in,u concentration of unbound drug in blood entering the liver CL clearance CL entering entering clearance CL filtration renal filtration clearance CL gut clearance from the gastrointestinal tract CL H hepatic clearance CL H,u hepatic clearance of unbound drug CL int intrinsic clearance CL leaving leaving clearance CL R renal clearance CL R,diff eq renal clearance derived by differential equations C out blood concentration of total drug (unbound plus bound) exiting the liver C out,u unbound drug concentration in the liver exiting blood DM dispersion model ECM extended clearance model ER extended-release f driving force or impetus causing flux f H first pass fractional hepatic bioavailability f u Tub fraction unbound in the renal tubule f uB fraction unbound in the blood GfR glomerular filtration rate IPRL isolated perfused rat liver IR immediate release IVIVE in vitro-in vivo extrapolation J driving flux K coefficient of proportionality k a first-order absorption rate constant k d first-order elimination rate constant K M concentration of substrate at the half-maximal rate of elimination k M first-order rate constant for elimination of a metabolite K puu ratio at steady-state of unbound drug concentration in the liver to the unbound drug concentration in the systemic circulation MAT mean absorption time MRT mean residence time P int,reab intrinsic passive renal reabsorption PTM parallel tube model Q H hepatic blood flow Q R renal blood flow SubQ subcutaneous t time V gut volume of distribution in the gastrointestinal tract V max maximum rate of substrate elimination when

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ANALYSIS Of MUTAGENIC IMIDAZO[4,5-f]QUINOLINES AND IMIDAZO[4,5-f]QUINOXALINES (IQ COMPOUNDS) - COMPARISON Of ELECTROCHEMICAL AND ULTRAVIOLET DETECTION

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MUTATION RESEARCH 1985年第1-2期142卷 5-8页

作者： GRIVAS, S NYHAMMAR, T Department of Chemistry and Molecular Biology Swedish University of Agricultural Sciences S-75007 Uppsala (Sweden)

Two synthetic imidazoquinolin-2-amines (IQ and MeIQ) and two imidazoquinoxalin-2-amines (MeIQx and 4,8-DiMeIQx), all known potent mutagens, have been separated by reversed-phase HPLC and detected by two methods — UV detection and electrochemical (EC) detection. The limits of detection were found to be 2.5 pmoles for UV detection and 0.5–1.5 pmoles for electrochemical detection.

关键词： IQ 3-methyl-3 H -imidazo[4,5- f ]quinolin-2-amine, 76180-96-6 MeIQ 3,4-dimethyl-3 H -imidazo[4,5- f ]-quinolin-2-amine, 77094-11-2 MeIQx 3,8-dimethyl-3 H -imidazo[4,5- f ]quinoxalin-2-amine, 77500-04-0 4,8-DiMeIQx 3,4,8-trimethyl-3 H -imidazo[4,5- f ]quinoxalin-2-amine HPLC high-performance liquid chromatography

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THE BEST APPROXIMATION CONSTANT fOR THE JACKSON'S TYPE OPERATOR J_(n,3) (f;x)

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Analysis in Theory and Applications 1992年第2期8卷 35-45页

作者：王冠闽 Zhangzhou Teacher's College China

In this paper we obtain the best approximation constant of function f(x)(∈C_(2π))by the Jackson's type operator J_(π3)(f;x),i.e. ‖J_(n,3)(f,x)-f(x)‖_c≤(4-6/π)ω(f,1/n), ‖J_(n,3)(f,x)-f(x)‖_c≤(8-17/π)ω_... 详细信息

关键词：兀一 THE BEST APPROXIMATION CONSTANT fOR THE JACKSON’S TYPE OPERATOR J f x n,3

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ETA, DISCO, ODISCO, AND f

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PSYCHOMETRIKA 1988年第3期53卷 393-405页

作者： GUTTMAN, L HEBREW UNIV JERUSALEM JERUSALEMISRAEL ISRAEL INST APPL SOCIAL RES JERUSALEMISRAEL

Two coefficients are proposed for measuring the extent of overlap in distributions as a direct function of the variance between the arithmetic means (“disco” and “odisco”). They are designed to answer such questions as: “Given the value of a numerical variablex, to which population should an individual be assigned so that minimum error would be incurred?” This is just the reverse of the question addressed by ANOVA. These coefficients are shown to be analytic inx and they are related to Pearson's eta and fisher'sf. Extensions of these coefficients (designed for univariate, one-way discrimination) tok-way and multivariate discriminant analysis and measurement of “interaction” are suggested.

关键词： discriminant analysis discriminant coefficients f eta monotonicity coefficients consistent statistics cumulative science ANOVA size of effect interaction

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AN IMPROVING STRICT CONSECUTIVE-k-OUT-Of-n: f SYSTEM

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Chinese Science Bulletin 1992年第19期37卷 1665-1668页

作者：金石川孙惠中 Space Science and Application Research Center Academia Sinica Beijing 100080 PRC

In 1985, Bollinger firstly introduced a repairable system model——a strict consecutive-k-out-of-n: f systems(abbreviated to Bollinger model) in terms ofa nonrepairable system 'consecutive-k-out-of-n: f systems'. However, some conditions in Bollinger modal were assumed too ideally to be used in engineering. for instance, some states (e.g. fGfffffff, n=9, k=2) have already made the system dislocated, but by the assumptions in

关键词： consecutive-kout-of-n: f system system unreliability

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