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PATENT ABSTRACTS 165 iuciferase. A fusion protein encoded by a luxAB fusion gene is a single active protein and is par- ticularly useful as a reporter protein having luciferase activity. An advantage of such a repor- ter system to assay gene expression in many cells which contain FMNH2, such as bacterial and yeast cells, is that an immediate and quantitative assessment of gene expression may be made from real-time light measurements using intact cells. 5196568 COMPOUNDS USEFUL IN ENZYMATIC RESOLUTION SYSTEMS AND THEIR PREPARATION Charles M Zcpp, Stephen A Wald, David R Dodds, Tokyo, assignedto Sepracor Inc This invention relates to novel compositions of matter which are esters with enhanced water solubility, for use in aqueous enzymatic resolu- tion reactions of racemic mixtures of these esters for producing the separate chiral isomers of the racemic mixture. The-invention also relates to novel methods for preparing these esters. The importance of the production of the separate chiral isomers of the racemic mixtures resides in the isolation of the isomers which frequently have different biological activities. Of particular significance regarding the water soluble esters of this invention is that they are derivatized with groups which enhance their aqueous solubility and their reactivity with enzymatic resolving methods which are mediated in an aqueous en- vironment. In addition, the importance of these compounds resides in their being useful in novel methods for facilitating the enzymatic resolution reactions of racemic mixtures o festers, which are derivatized with groups which enhance the esters' aqueous solubility, in 1) a homogeneous aqueous reaction system where an extractive phase is not present, 2) a multiphase dispersion extractive reaction where an extractive phase is present, and 3) an extractive membrane reactor where the enzyme is placed alternatively either (a) in the aqueous phase, (b) in association with the membrane, or (c) in the aqueous phase and in association with the membrane, wherein the aqueous ester phase is contacted with one side of the membrane, and where an organic extractive phase is contacted with the other side of the membrane, wherein the extractive phase serves to remove the resolving reaction product. 5197017 POTENTIOPHOTOMETRIC FIBRINOGEN DETERMINATION Wallace E Carroll, R Davi Jackson, Tokyo, The fibrinogen concentration of a blood plasma sample is measured and simultaneously the pro- thrombin time is determined. Poten- tiophotometric apparatus is used in which the output signal is applied to an analog/digital con- verter and digital recorder. Digital voltage values are developed and then printed in an ar- ray. A computer records digital voltage values produced by the apparatus with a plasma sample in the test tube before injection of throm- boplastin. The time of the injection is identified by a substantial change in the recorded voltage values. After a short time delay the digital vol- tage value is noted and thereafter this voltage value is compared with a second voltage value. A difference of three or more identifies the begin- ning of clotting. The first of the two voltage numbers is identified x and is compared with the voltage value 60 seconds later, which is identified y. The delta voltage value is y-x. The delta vol- tage values for two samples of known but dif- ferent fibrinogen concentrations, one high and one low, are plotted on a linear calibration curve drawn, which is used to determine the fibrinogen concentration values of plasma samples having unknown fibrinogen concentration. 5198336 BIOASSAY FOR CHEMICALS WHICH GENERATE PROOXIDANT STATES Lynda M Knobeloch, George A Blondin, John M Harkin, Tokyo, assigned to Wisconsin Alumni Research Foundation A bioassay making use of submitochondrial par- ticles to test for the presence of toxic substances which induce prooxidant states in vivo. The as- say uses complex I of the electron transport en- zymes on the submitochondrial particles which are capable of donating electrons to the toxicant in solution. The presence of any activated oxy- gen species in the assay solution is detected spectrophotometrically by the adrenochrome reaction.

5198336 Bioassay for chemicals which generate prooxidant states

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PATENT ABSTRACTS 165

iuciferase. A fusion protein encoded by a luxAB fusion gene is a single active protein and is par- ticularly useful as a reporter protein having luciferase activity. An advantage of such a repor- ter system to assay gene expression in many cells which contain FMNH2, such as bacterial and yeast cells, is that an immediate and quantitative assessment of gene expression may be made from real-time light measurements using intact cells.

5196568

C O M P O U N D S U S E F U L I N E N Z Y M A T I C R E S O L U T I O N

S Y S T E M S A N D T H E I R P R E P A R A T I O N

Charles M Zcpp, Stephen A Wald, David R Dodds, Tokyo, assigned to Sepracor Inc

This invention relates to novel compositions of matter which are esters with enhanced water solubility, for use in aqueous enzymatic resolu- tion reactions of racemic mixtures of these esters for producing the separate chiral isomers of the racemic mixture. The-invention also relates to novel methods for preparing these esters. The importance of the production of the separate chiral isomers of the racemic mixtures resides in the isolation of the isomers which frequently have different biological activities. Of particular significance regarding the water soluble esters of this invention is that they are derivatized with groups which enhance their aqueous solubility and their reactivity with enzymatic resolving methods which are mediated in an aqueous en- vironment. In addition, the importance of these compounds resides in their being useful in novel methods for facilitating the enzymatic resolution reactions of racemic mixtures o festers, which are derivatized with groups which enhance the esters' aqueous solubility, in 1) a homogeneous aqueous reaction system where an extractive phase is not present, 2) a multiphase dispersion extractive reaction where an extractive phase is present, and 3) an extractive membrane reactor where the enzyme is placed alternatively either (a) in the aqueous phase, (b) in association with the membrane, or (c) in the aqueous phase and in association with the membrane, wherein the aqueous ester phase is contacted with one side of the membrane, and where an organic extractive phase is contacted with the other side of the membrane, wherein the extractive phase serves to remove the resolving reaction product.

5197017

P O T E N T I O P H O T O M E T R I C F I B R I N O G E N D E T E R M I N A T I O N

Wallace E Carroll, R Davi Jackson, Tokyo,

The fibrinogen concentration of a blood plasma sample is measured and simultaneously the pro- thrombin time is determined. Poten- tiophotometric apparatus is used in which the output signal is applied to an analog/digital con- verter and digital recorder. Digital voltage values are developed and then printed in an ar- ray. A computer records digital voltage values produced by the apparatus with a plasma sample in the test tube before injection of throm- boplastin. The time of the injection is identified by a substantial change in the recorded voltage values. After a short time delay the digital vol- tage value is noted and thereafter this voltage value is compared with a second voltage value. A difference of three or more identifies the begin- ning of clotting. The first of the two voltage numbers is identified x and is compared with the voltage value 60 seconds later, which is identified y. The delta voltage value is y-x. The delta vol- tage values for two samples of known but dif- ferent fibrinogen concentrations, one high and one low, are plotted on a linear calibration curve drawn, which is used to determine the fibrinogen concentration values of plasma samples having unknown fibrinogen concentration.

5198336

B I O A S S A Y F O R C H E M I C A L S W H I C H G E N E R A T E

P R O O X I D A N T S T A T E S

Lynda M Knobeloch, George A Blondin, John M Harkin, Tokyo, assigned to Wisconsin Alumni Research Foundation

A bioassay making use of submitochondrial par- ticles to test for the presence of toxic substances which induce prooxidant states in vivo. The as- say uses complex I of the electron transport en- zymes on the submitochondrial particles which are capable of donating electrons to the toxicant in solution. The presence of any activated oxy- gen species in the assay solution is detected spectrophotometrically by the adrenochrome reaction.