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Biomedical subjects

A L Kerremans

Publications and source records attributed to A L Kerremans.

6 recordsLinked to original sources
PubMed1992

[Ischemic hepatitis].

Triggered by a case of ischaemic hepatitis (shock liver) in a patient with severe respiratory insufficiency, we tried to gather information about clinical characteristics and incidence. To our surprise, this information could be found neither in major critical care, medical or gastroenterology textbooks nor in textbook indices or works on differential diagnosis. From Sept. 1989 to May 1990 we studied all possible cases of ischaemic hepatitis in a 390 bed general hospital, to establish incidence. Using computerised data from the clinical chemistry laboratory, all patients with grossly abnormal liver function tests were identified. In this nine-month period 27 adult patients had a peak ALAT level of > 500 U/l: 8 of these suffered from ischaemic hepatitis, using the criteria described by Gibson et al. In another 5 this diagnosis was suspected but could not be ascertained before death (30% and 18% of all cases). In all these cases ASAT, ALAT, LDH levels were 8-100 times normal, but bilirubin, alkaline phosphatase, gamma-glutamyl transferase and prothrombin time were only slightly abnormal. With correction of the underlying disorder enzyme levels returned to normal very rapidly, in 5-10 days. Ischaemic hepatitis could easily be distinguished from other causes such as alcoholic, viral or drug-induced hepatitis. Ischaemic hepatitis was the most frequent cause of severely elevated ASAT, ALAT and LDH in hospitalised patients. The diagnosis can easily be made on clinical characteristics and the typical biochemical pattern. An elaborate work-up or invasive procedure is redundant. Prognosis per se is excellent but depends on the underlying disorder.

Aged↗
PubMed1985

Cephalosporin-induced hypoprothrombinemia: possible role for thiol methylation of 1-methyltetrazole-5-thiol and 2-methyl-1,3,4-thiadiazole-5-thiol.

Heterocyclic thiol metabolites of cephalosporin antibiotics may play an important role in the pathophysiology of hypoprothrombinemia and hemorrhage in patients treated with these drugs. A heterocyclic thiol metabolite of moxalactam, 1-methyltetrazole-5-thiol (MTT), inhibits the gamma carboxylation of glutamic acid that is required for the formation of active clotting factors. One possible pathway for the biotransformation of thiol compounds such as MTT is S-methylation catalyzed by either thiopurine methyltransferase (TPMT), a soluble enzyme, or by thiol methyltransferase, a microsomal enzyme. Therefore, MTT and 2-methyl-1,3,4-thiadiazole-5-thiol (MTD), a thiol "leaving group" structurally related to MTT that is present in cefazolin, were tested as possible substrates for S-methylation catalyzed by purified human kidney TPMT or by human liver microsomes, a source of thiol methyltransferase. MTT and MTD were methylated by both human kidney TPMT and human liver microsomes. The products of these reactions were shown by high-performance liquid chromatography to be S-methyl MTT and S-methyl MTD. Apparent Km constants for the methylation of MTT and MTD by TPMT were 0.26 and 0.068 mM, respectively. Apparent Km constants for the methylation of MTT and MTD by human liver microsomes were 0.60 and 0.20 mM, respectively. Maximal velocity (Vmax) values for the S-methylation of MTD catalyzed by TPMT and by human liver microsomes were 3.58- and 678-fold greater than were those for the thiol methylation of MTT. Finally, S-methyl derivatives of MTT and MTD were one to two orders of magnitude less potent as inhibitors of the in vitro gamma carboxylation of glutamic acid than were MTT and MTD themselves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Human hepatic microsomal thiol methyltransferase. Assay conditions, biochemical properties, and correlation studies.

Thiol methyltransferase (TMT) catalyzes the S-methylation of aliphatic sulfhydryl drugs and xenobiotic compounds. As a first step in the determination of whether genetic control of TMT activity in an easily accessible human cell, the red blood cell (RBC), might reflect the regulation of TMT in the human liver, we determined optimal conditions for the assay of human hepatic microsomal TMT activity. We then used those assay conditions to study the biochemical properties and regulation of TMT in the human liver for comparison with the properties of TMT in the human RBC. Substrate kinetic studies of hepatic microsomes performed with 2-mercaptoethanol (2-ME) revealed biphasic kinetics similar to those found in the human RBC, with apparent "high-" and "low"-affinity forms of TMT activity. The high-affinity form had an optimal pH of 7.2-7.6 and apparent KM values of 9.0 microM for 2-ME and 7.5 microM for S-adenosyl-L-methionine. The low-affinity form had an optimal pH of 8.8 and apparent KM values of 20 mM for 2-ME and 44 microM for S-adenosyl-L-methionine. Both forms were inhibited by compounds that also inhibited human RBC membrane TMT. The two kinetic forms of hepatic microsomal TMT activity were inactivated approximately 50% by heating for 15 min at 53 degrees C and, as was found with RBC TMT, had very similar thermal stability profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme Activation↗
PubMedDate not supplied

S-Methylation of D- and L-penicillamine by human erythrocyte membrane thiol methyltransferase.

Human red blood cell (RBC) membranes contain a thiol methyltransferase activity that catalyzes the S-methylation of 2-mercaptoethanol (2-ME). These experiments were performed to determine whether human RBC membranes contain enzymes that can catalyze the S-methylation of D- and L-penicillamine, to determine whether those enzymes are similar to the RBC membrane thiol methyltransferase that catalyzes the S-methylation of 2-ME, and to determine whether lipophilic conjugates of the S-methyl metabolites of D- and L-penicillamine are formed by RBC membranes. Human RBC membranes were able to catalyze the S-methylation of D- and L-penicillamine. The apparent Michaelis (Km) constants for D- and L-penicillamine were 7.53 and 7.27 mM, respectively. However, the Vmax value for L-penicillamine was more than 2.5 times greater than the Vmax value for D-penicillamine. D- and L-Penicillamine methyltransferases and 2-ME thiol methyltransferase were similar with respect to their subcellular distributions, inhibitor sensitivities, and thermal stabilities. In addition, when methyltransferase activities for 2-ME and for D- and L-penicillamine were measured in RBC membranes from 19 individual subjects, there were highly significant correlations among all three activities (r greater than 0.98, p less than 0.001 for all three comparisons). These observations suggest either that a single enzyme in the human RBC membrane catalyzes the S-methylation of all three compounds, or, less likely, that these reactions are catalyzed by three separate enzymes that are regulated in parallel and have similar properties. Experiments were then performed to identify the products of the penicillamine methylation reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Mouse liver thiol methyltransferase. Assay conditions, biochemical properties, and strain variation.

Thiol methyltransferase (TMT) catalyzes the S-methylation of aliphatic sulfhydryl drugs and xenobiotic compounds. It would be useful if there were an experimental animal model in which the regulation and function of TMT could be studied. Therefore, TMT activity was measured in hepatic microsomes from A/J mice. Substrate kinetics for mouse liver microsomal TMT, like those for the enzyme in human red blood cell membranes and human kidney microsomes, were biphasic, with apparent "high" and "low" affinity forms of TMT with 2-mercaptoethanol as the methyl acceptor substrate. Apparent Michaelis (Km) constants of the high and low affinity activities for 2-mercaptoethanol were 30 microM and 12 mM, respectively. Apparent Km values of the high and low affinity activities for S-adenosyl-L-methionine, the methyl donor for the reaction, were 47 microM and 61 microM, respectively. The optimal pH for the high affinity activity was between 7.2 and 8.1, whereas the optimal pH for the low affinity activity was approximately 9.2. Differential centrifugation showed that more than 85% of both activities was associated with membrane fractions. SKF 525A, a potent inhibitor of TMT in human tissues, inhibited mouse liver high and low affinity TMT activities by 88% and 46%, respectively, at a concentration of 0.5 mM. TMT activities were then measured in hepatic microsomes from nine additional inbred strains of mice. High affinity TMT activities varied 1.7-fold, whereas low affinity activities varied 2.1-fold among these strains. Since the properties of TMT in mouse liver are similar to those of the enzyme in human tissue, the inbred mouse will be a useful experimental animal model in which to study the regulation and function of TMT.

Animals↗