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Biomedical subjects

J Meier

Publications and source records attributed to J Meier.

At least 19 recordsLinked to original sources
PubMed1992

Purification and characterization of an antithrombin III inactivating enzyme from the venom of the African night adder (Causus rhombeatus).

A serine proteinase was isolated from the venom of the night adder (Causus rhombeatus) by fast protein liquid chromatography (anion-exchange, gel filtration and hydrophobic interaction). The protein (termed CR-serpinase) had an estimated mol. wt of 45,500 as determined by SDS-PAGE, pI of 4.7 and a carbohydrate content of 18.9%. Incubation of CR-serpinase with purified human antithrombin III at a molar ratio of 1:66 resulted in a loss of more than 90% of the initial AT III activity within 10 min. The reaction was dependent on heparin. In SDS-PAGE inactivation of human antithrombin III was correlated with the occurrence of two cleavage products. The cleavage site in the antithrombin III molecule was determined to be Arg 393-Ser 394 by amino-terminal sequencing. CR-Serpinase had no thrombin-like activity since no fibrinogen conversion was induced and had no procoagulant activity. CR-Serpinase activity was not inhibited by antithrombin III-heparin and was not decreased by a 10-min preincubation in normal human plasma. Inactivation of antithrombin III by CR-serpinase appeared to be very specific.

Amino Acid Sequence↗
PubMed1979

Mutagenicity and metabolism of dimethylnitrosamine and benzo[alpha]pyrene in tissue homogenates from inbred Syrian hamsters treated with phenobarbital, 3-methylcholanthrene or polychlorinated biphenyls.

There are significant differences between mice and hamsters in polycyclic hydrocarbon and nitrosamine metabolism. Homogenates of liver, lung and intestinal mucosa from 6 strains of Syrian golden hamster were compared for their ability to metabolize benzo[alpha]pyrene (BP) and dimethylnitrosamine (DMN) to mutagens. Females of strains MHA/SSLak, LSH/SlLak, CB/SsLak, PD4/Lak LHC/Lak and Lak:LVG (SYR) were either untreated or received phenobarbital (PB), 3-methylcholanthrene (MC) or polychlorinated biphenyls (AR) to induce drug-metabolizing enzymes. Salmonella typhimurium TA92 and TA98 were used as indicators of the formation of mutagans. Dimethylnitrosamine demethylase (DMND) was assayed using 1 mM DMN as substrate. Aryl hydrocarbon hydroxylase (AHH) was measured using benzo[alpha]pyrene as substrate. MC does not induced AHH activity in hamster liver, but is an excellent inducer of enzymes converting BP to mutagens. This lack of correlation between increased AHH activity and increased metabolism of BP to mutagen in liver is in marked contrast to correlations seen in mice. MC induces AHH in hamster lung and intestinal mucosa. AR induces AHH in liver, lung and intestinal mucosa. Activity of DMND in liver is not affected by treatment of hamsters with BP or AR, but is repressed approx. 30% by treatment with MC. Activity of DMND and conversion of DMN to mutagen are correlated (r = 0.59) in hamster liver. Microsomes of hamster liver are more effective than those from mouse in converting DMN to mutagen, despite similar DMND activities in livers from the two species.

Animals↗
PubMed1979

Comparison of the in vitro mutagenicity and metabolism of dimethylnitrosamine and benzo[a]pyrene in tissues from inbred mice treated with phenobarbital, 3-methylcholanthrene or polychlorinated biphenyls.

Homogenates of liver, lung, kidney, stomach, small intestine and colon from 8 strains of mice were compared for their ability to metabolize benzo[a]pyrene (BP) and dimethylnitrosamine (DMN) to mutagens. Females of strains CF1, AKR/J, AU/SsJ, DBA/2J, SWR/J, A/J, C3H/HeJ, and C57BL/6J were either untreated or received phenobarbital (PB), 3-methylcholanthrene (MC) or polychlorinated biphenyls (AR) to induce drug-metabolizing enzymes. The effects of these drugs on organ weight and on the amounts of DNA, S-10 protein, and microsomal protein per unit weight of tissue are reported. Salmonella typhimurium TA92 and TA98 were used as indicators of the formation of mutagens. For each organ there was an optimal balance between amount of tissue homogenate and concentration of test compound for maximal yield of revertants. A sensitive radiometric assay of DMN demethylase (DMND) is described which permits measurement of the enzyme in liver, lung and kidney. DMN at 1 mM is used as substrate. Aryl hydrocarbon hydroxylase (AHH) was measured in all tissue using BP as substrate. AR and MC are very good inducers of AHH activity in livers of mice classified as aromatic hydrocarbon responsive, but not in those classified as hydrocarbon nonresponsive. Responsiveness is strain-specific and genetically regulated. Metabolism of BP to mutagens by liver homogenates was correlated with extent of AHH induction. This dimorphism of response of AHH to inducers was present, but less pronounced, in non-hepatic tissues. Basal activities of AHH and DMND were correlated in livers and lungs from untreated mice. DMND activities were increased less than 2-fold by PB, MC or AR treatments. Metabolism of DMN to mutagens was not closely correlated with DMND activities. Strain of mouse, type of tissue and test substance are important variables in assessing the potential effect of microsomal enzyme-inducing agents on the metabolism of mutagenic substances.

Animals↗
PubMed1979

Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide.

1. The metabolism and plasma kinetics of chlordiazepoxide have been determined in a group of volunteers and in a group of patients with acute alcohol intoxication. 2. Using the SAAM 26 non-linear least squares fitting programme, all chlordiazepoxide plasma concentration v time data following oral administration could be analysed in terms of a one-compartment open model with metabolic conversion of chlordiazepoxide to desmethylchlordiazepoxide. 3. Acutely intoxicated patients showed a prolonged elimination of chlordiazepoxide and a reduced clearance when compared with alcohol-free volunteers. The elimination of desmethylchlordiazepoxide, on the other hand, appeared to be faster in the alcoholics. 4. Alcohol exerts significant effects on the metabolism of chlordiazepoxide in acutely intoxicated patients.

Adult↗
PubMed1978

[Permeability of hydrogel plastics (PHEMA) to different substances of corneal metabolism (author's transl)].

With a new two-chamber apparatus for diffusion measurements, the permeability of Poly (2-hydroxy-ethyl-methacrylate) (PHEMA) is determined for metabolites of the corneal metabolism. Except for ATP, all substances tested, including several amino acids, penetrated the PHEMA material. Compared to the corneal stroma, the permeability of PHEMA is relatively low. Therefore, intracorneal implants of this hydrogel should be as thin as possible.

Acrylates↗
PubMed1978

The application of HPLC to the determination of some 1,4 benzodiazepines and their metabolites in plasma.

1 A high pressure liquid chromatographic (HPLC) assay has been developed for the measurement of chlordiazepoxide and its metabolites, N-desmethylchlordiazepoxide and demoxepam in microgram concentrations in human plasma. 2 Another metabolite was detected in appreciable amounts in the plasma from patients receiving high doses of chlordiazepoxide after the first 3 days of treatment. 3 Preliminary studies would indicate that this metabolite is N-desmethyldiazepam. 4 A modified HPLC system, using a microparticulate column was developed to separate N-desmethyldiazepam from chlordiazepoxide and its other metabolites in plasma.

Benzodiazepines↗
PubMed1978

The distribution of proquazone and three of its metabolites in serum and synovial fluid.

In 13 patients with hydrarthrosis of the knee, samples of synovial fluid and blood were drawn at regular intervals, following a single oral dose of 600 mg proquazone. The concentrations of the unchanged drug were measured fluorimetrically and those of its three principal, active metabolites by high pressure liquid chromatography. The absorption and distribution of proquazone and its metabolites were rapid. Measurable--in some cases considerable--concentrations were to be found in both the synovial fluid and serum as early as 30 minutes after intake. High concentrations were still present up to 7 hours after intake. Considerable variations were observed, both between patients and over time for each patient, so that only qualitative rather than quantitative kinetic conclusions could be drawn from the results. The concentrations were generally lower in the synovial fluid than in the serum, which may be ascribed to the drug's high protein binding.

Administration, Oral↗
PubMed1977

Mental, motor, and social behavior of infants with cleft lip and/or cleft palate.

This is a report of analyses of cross-sectional and longitudinal samples of the mental, motor, and social behavior of children with cleft lip and/or palate as measured by the Bayley Scales for Infant Development. Seventy-five patients of the Lancaster Cleft Palate Clinic were the subjects for the sample. The longitudinal sample consisted of 28 of these Ss for whom there were complete data at 6, 12, 18, and 24 months. The results indicated that there were no significant differences in mental and motor functioning. In both analyses, the social behavior of patients with oral-facial clefts was more passive than the Bayley normative sample. The implications of these findings for future research are discussed.

Child Behavior↗
PubMed1976

[Comparative study on the elimination of pindolol (visken) and antipyrin in patients with liver diseases].

25 patients suffering from different hepatic diseases were studied in order to investigate the elimination of the beta-receptor blocking drug pindolol in hepatic disease. Following an overnight fasting period the patients received simultaneously 3 mg pindolol intravenously and 1000 mg antipyrine orally. Plasma samples were taken at certain time intervals for 24 hs and urine was collected for 72 hs for the measurements of drug concentrations in plasma and urine. From these measurements different pharmacokinetic parameters were calculated for both drugs used in the present study according to a one-compartment open model. The total body clearance of antipyrine was selected as a parameter of the metabolic capacity of the liver microsomal enzyme system and was compared with the pharmacokinetic parameters calculated for pindolol by means of linear regression. There was no significant correlation between the total body clearance of antipyrine and the kinetic parameters of pindolol in any of the 25 patients irrespective of the differences in liver disease. On the other hand, 14 patients suffering from cirrhosis of the liver showed a significant correlation between the total body clearance of antipyrine and the overall elimination rate constant or metabolic clearance of pindolol. No correlation was found between antipyrine clearance and total body clearance of pindolol, as some patients with intact renal function excreted a higher proportion of pindolol in the urine as liver function decompensated. The mechanism of such compensatory elimination is unknown. In conclusion, the total body clearance of antipyrine known to represent metabolic liver function showed a significant correlation with the metabolic clearance of pindolol in patients with cirrhosis of the liver. For the other liver diseases investigated, too few patients were studied to calculate an adequate correlation.

Antipyrine↗
PubMed1976

Adenosine deaminase activity in peripheral blood cells of patients with haematological malignancies.

Adenosine deaminase (EC 3.5.4.4, ADA) has been assayed in lymphocytes, granulocytes and erythrocytes from 45 patients with haematological malignancies. Activities were uniformly low in lymphocytes from patients with chronic lymphocytic leukaemia. Variable, but abnormal activities were frequently found in multiple myeloma, untreated lymphoma and leukaemic reticuloendotheliosis. High values were observed in lymphocytes from patients with lymphoma during intensive combination chemotherapy. ADA levels in lymphocytes were not correlated with levels in granulocytes or erythrocytes. ADA was elevated in blasts of patients with acute lymphocytic and myelogenous leukaemias but the ranges of activities per cell were so similar that ADA assay is unlikely to be of major help in distinguishing the two diseases.

Adenosine Deaminase↗