Kalow W


Full name : Kalow Werner

First name : Werner

Mail : Department of Pharmacology, University of Toronto, Toronto, Canada

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Country : Canada

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Website : \/\/journals.lww.com\/jpharmacogenetics\/Citation\/2008\/10000\/In_memoriam__Werner_Kalow,_MD__1917_2008_.1.aspx

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References (28)

Title : The relation of plasma cholinesterases to response to clinical doses of succinylcholine -
Author(s) : Kalow W
Ref : Canadian Journal of Anaesthesia , 55 :860 , 2008
PubMedID: 19050090

Title : Human pharmacogenomics: the development of a science - Kalow_2004_Hum.Genomics_1_375
Author(s) : Kalow W
Ref : Hum Genomics , 1 :375 , 2004
Abstract : Until about 50 years ago, the altering of a normal drug effect by a genetic deficiency was only rarely observed. Here, my discovery of the genetic variant of butyrylcholinesterase affecting succinylcholine action is described in some detail. Such discoveries led to the combination of the two older sciences, genetics and pharmacology, thereby forming pharmacogenetics. After the discovery of similar examples in the years that followed, pharmacogenetics expanded on the basis of two discoveries. First, the common occurrence of interethnic differences in drug response and, secondly, the fact that most pharmacological differences were multigenic. New methodologies brought a transition to pharmacogenomics; this included detection of clinically important genetic variants and has uncovered potentially new drug targets. The arrival of personalised medicine--where a patient's genes determine the choice of drug to be administered--can be hoped to gradually improve drug safety and efficacy. Efforts to reach this level of perfection are, however, dogged by uncertainties.
ESTHER : Kalow_2004_Hum.Genomics_1_375
PubMedSearch : Kalow_2004_Hum.Genomics_1_375
PubMedID: 15588498

Title : Atypical plasma cholinesterase. A personal discovery story: a tale of three cities -
Author(s) : Kalow W
Ref : Canadian Journal of Anaesthesia , 51 :206 , 2004
PubMedID: 15010399

Title : Variable activation of lovastatin by hydrolytic enzymes in human plasma and liver. 4 - Tang_1995_Eur.J.Clin.Pharmacol_47_449
Author(s) : Tang BK , Kalow W
Ref : European Journal of Clinical Pharmacology , 47 :449 , 1995
Abstract : Lovastatin, widely used to lower cholesterol, is a pro-drug that requires metabolic activation through hydrolysis by carboxyesterases. There appear to be at least three distinct esterases in humans capable of catalysing this reaction, one in plasma and two in the liver. The rate of lovastatin hydroxy acid formation was measured as 15.8 pmol.ml-1.min-1 in plasma, 2.13 pmol.mg-1 protein.min-1 in hepatic microsomes and 0.92 pmol.mg-1 protein.min-1 in cytosol. The data suggest that on average the three esterases together are capable of activating about 220 nmol (90 micrograms) lovastatin per minute per person, to which the esterases of plasma, liver microsomes and liver cytosol contribute approximately 18, 15 and 67%, respectively. All three esterases showed evidence of inter-individual variability. In one of 17 livers, both cytosolic and microsomal esterase activity was completely missing, while two other liver specimens lacked one esterase. Such variability must be expected to influence the therapeutic efficacy of the drug, and they might be related to its occasional toxicity.
ESTHER : Tang_1995_Eur.J.Clin.Pharmacol_47_449
PubMedSearch : Tang_1995_Eur.J.Clin.Pharmacol_47_449
PubMedID: 7720768

Title : The Pennsylvania State University College of Medicine 1990 Bernard B. Brodie Lecture. Pharmacogenetics: past and future -
Author(s) : Kalow W
Ref : Life Sciences , 47 :1385 , 1990
PubMedID: 2250557

Title : Ethnic differences in drug metabolism. - Kalow_1982_Clin.Pharmacokinet_7_373
Author(s) : Kalow W
Ref : Clinical Pharmacokinetics , 7 :373 , 1982
Abstract : Interethnic differences in drug-metabolising capacity may be substantial, and they are sufficiently frequent to warrant attention. Such differences may consist of different mean values of quantitative traits in separate populations, or of different frequency distributions as produced by the occurrence of genetic enzyme variants. The collection of population data requires the investigation of substantial numbers of subjects. This may be no problem if drug-metabolising enzymes occur in blood or are sufficiently stable in their tissues to allow investigation in vitro. However, if investigations require the use of probe drugs, new efforts are needed to adapt pharmacokinetic methods to make them suitable for population studies. This development of methods is further called for because genetic variants seem to be more easily detected through the assessment of particular metabolites than through the determination of pharmacokinetic parameters of the parent drug. Many studies with probe drugs comparing different populations have given results that are equivocal in terms of the nature-nurture interplay. However, a set of data with antipyrine has pointed to environmental factors as the principal determinant of differences in metabolising capacity, while data with debrisoquine have indicated monogenically controlled variation of one facet of the cytochrome P-450 system. In several instances, statistically significant differences between population means have been established by testing small numbers of subjects, numbers insufficient to establish distribution patterns that would allow the recognition of genetic polymorphism. The populations studied range from Greenlanders to South African Blacks, but most comparisons pertain to Caucasians and Orientals.
ESTHER : Kalow_1982_Clin.Pharmacokinet_7_373
PubMedSearch : Kalow_1982_Clin.Pharmacokinet_7_373
PubMedID: 6754206

Title : The plasma cholinesteerases: a new perspective. -
Author(s) : Brown SS , Kalow W , Pilz W , Whittaker M , Woronick CL
Ref : Advances in Clinical Chemistry , 22 :1 , 1981
PubMedID: 7027759

Title : Cocaine metabolism: cocaine and norcocaine hydrolysis by liver and serum esterases - Stewart_1979_Clin.Pharmacol.Ther_25_464
Author(s) : Stewart DJ , Inaba T , Lucassen M , Kalow W
Ref : Clinical Pharmacology & Therapeutics , 25 :464 , 1979
Abstract : The hydrolysis of cocaine and its N-demethylated product, norcocaine, by esterases was examined in liver and serum. Both liver and serum enzymatically formed ecgonine methyl ester from cocaine. The liver enzyme had a much lower affinity for cocaine than that of serum, indicating that a different form of esterase was present in liver. The liver enzyme had a similar affinity for both norcocaine and cocaine. Likewise, the serum enzyme showed similar affinities for both substrates. The Vmax estimates, however, were consistently higher for norcocaine than cocaine in both liver and serum. Benzoyl ecgonine, a major metabolite of cocaine formed by hydrolysis, was not produced enzymatically in either serum or liver; the rate of spontaneous formation at physiological pH suggests that this metabolite may arise nonenzymatically in the body.
ESTHER : Stewart_1979_Clin.Pharmacol.Ther_25_464
PubMedSearch : Stewart_1979_Clin.Pharmacol.Ther_25_464
PubMedID: 428191

Title : Metabolism of cocaine in man - Inaba_1978_Clin.Pharmacol.Ther_23_547
Author(s) : Inaba T , Stewart DJ , Kalow W
Ref : Clinical Pharmacology & Therapeutics , 23 :547 , 1978
Abstract : Following ingestion of [N-14CH3]cocaine (10 mg, 2.3 muCi) by 2 healthy subjects, breath, saliva, serum, and urine samples were collected serially. Labeled CO2 production was monitored as a measure of N-demethylation of cocaine. The cumulative excretion of 14CO2 in 5 hr was 2.4% and 6.2% of the administered dose with half-lives of 2.3 and 1.4 hr, respectively. The greater N-demethylation was found in a subject with lower plasma cholinesterase activity. Radioactivity excreted in 0 to 28 hr urine reached 65% to 75% of the dose. Ecgonine methyl ester, a product of cocaine hydrolysis by plasma cholinesterase, was identified as a major metabolite in the urine of both subjects and accounted for 32% to 49% of the urinary metabolites.
ESTHER : Inaba_1978_Clin.Pharmacol.Ther_23_547
PubMedSearch : Inaba_1978_Clin.Pharmacol.Ther_23_547
PubMedID: 639429

Title : Hydrolysis of cocaine in human plasma by cholinesterase -
Author(s) : Stewart DJ , Inaba T , Tang BK , Kalow W
Ref : Life Sciences , 20 :1557 , 1977
PubMedID: 17804

Title : Genetic factors in adverse drug reactions -
Author(s) : Kalow W
Ref : Internationale Zeitschrift fur Klinische Pharmakologie, Therapie und Toxikologie , 5 :38 , 1971
PubMedID: 5570061

Title : Soluble esterases of human lung -
Author(s) : Brebner J , Kalow W
Ref : Canadian Journal of Biochemistry , 48 :970 , 1970
PubMedID: 5475473

Title : Pharmacology and biological variation -
Author(s) : Simpson NE , Kalow W
Ref : Annals of the New York Academy of Sciences , 134 :864 , 1966

Title : [Pharmacogenetic problems in anesthesia]. -
Author(s) : Kalow W
Ref : Anaesthesist , 15 :13 , 1966
PubMedID: 4861645

Title : Poisoning with organophosphorus insecticides - Taylor_1965_Can.Med.Assoc.J_93_966
Author(s) : Taylor WJ , Kalow W , Sellers EA
Ref : Canadian Medical Association Journal , 93 :966 , 1965
Abstract : Because of an increasing incidence of poisoning with the newer organophosphorus anticholinesterase insecticides, these compounds have been reviewed in terms of their history and pharmacology, relationship with other drugs, factors affecting toxicity, mechanism of action, toxic signs and treatment. The modern organophosphorus pesticide requires metabolic conversion before toxicity develops. Insects have a greater propensity for this conversion than humans. Nevertheless, this conversion does occur in humans and can be potentiated by other drugs. Toxicity also varies with age, sex, route and frequency of administration, and previous exposure. The mechanism of toxicity is inhibition of acetylcholinesterase, causing an intoxicating build-up of acetylcholine. Signs and symptoms consist of the clinical manifestations of unopposed parasympathetic and central activity. Treatment must be initiated early. Respiration must be maintained and the effects of acetylcholine must be counteracted by massive doses of atropine. Metaraminol enhances the antagonistic action of atropine against acetylcholine and may also be given. Once acetylcholinesterase is inactivated, restoration is slow. Recovery can be accelerated by enzyme reactivators like the oxime compounds. Pyridine aldoxime (Pralidoxime, Protopam, P(2)S and 2-PAM) can be given in combination with atropine and metaraminol (AMP therapy) and may be the treatment of choice.
ESTHER : Taylor_1965_Can.Med.Assoc.J_93_966
PubMedSearch : Taylor_1965_Can.Med.Assoc.J_93_966
PubMedID: 66011071

Title : Contribution of hereditary factors to the response to drugs -
Author(s) : Kalow W
Ref : Federation Proceedings , 24 :1259 , 1965
PubMedID: 5853146

Title : The effects of sialidase on pseudocholinesterase types -
Author(s) : Ecobichon DJ , Kalow W
Ref : Canadian Journal of Biochemistry & Pharmacology , 41 :969 , 1963

Title : Some properties of the soluble esterases of liver -
Author(s) : Kalow W
Ref : Canadian Journal of Biochemistry & Pharmacology , 39 :1329 , 1961

Title : The action of normal and atypical cholinesterase of human serum upon a series of esters of choline -
Author(s) : Davies RO , Marton AV , Kalow W
Ref : Canadian Journal of Biochemistry & Pharmacology , 38 :545 , 1960
PubMedID: 13814417

Title : Some statistical data on atypical cholinesterase of human serum -
Author(s) : Kalow W , Gunn DR
Ref : Annals of Human Genetics , 23 :239 , 1959
PubMedID: 14404182

Title : The activity of various esterase inhibitors towards atypical human serum cholinesterase -
Author(s) : Kalow W , Davies R0
Ref : Biochemical Pharmacology , 1 :183 , 1958

Title : The relation between dose of succinylcholine and duration of apnea in man -
Author(s) : Kalow W , Gunn DR
Ref : Journal of Pharmacology & Experimental Therapeutics , 120 :203 , 1957
PubMedID: 13463742

Title : A method for the detection of atypical forms of human serum cholinesterases. Determination of dibucaine numbers -
Author(s) : Kalow W , Genest K
Ref : Canadian Journal of Biochemistry , 35 :339 , 1957
PubMedID: 13437188

Title : On distribution and inheritance of atypical forms of human serum cholinesterase, as indicated by dibucaine numbers -
Author(s) : Kalow W , Staron N
Ref : Canadian Journal of Biochemistry , 35 :1305 , 1957
PubMedID: 13479831

Title : Kinetic studies on the hydrolyses of benzoylcholine by human serum cholinesterase -
Author(s) : Kalow W , Genest K , Staron N
Ref : Canadian Journal of Biochemistry , 34 :637 , 1956

Title : Abnormal behavior of human serum cholinesterase -
Author(s) : Kalow W , Lindsay HA
Ref : Journal of Pharmacology & Experimental Therapeutics , 116 :34 , 1956

Title : The interaction between cholinesterases and a series of local anesthetics -
Author(s) : Kalow W , Maykut MO
Ref : Journal of Pharmacology & Experimental Therapeutics , 116 :418 , 1956
PubMedID: 13320285

Title : A comparison of optical and manometric methods for the assay of human serum cholinesterase -
Author(s) : Kalow W , Lindsay HA
Ref : Canadian Journal of Biochemistry & Physiology , 33 :568 , 1955