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Biomedical subjects

K Olek

Publications and source records attributed to K Olek.

108 records · Page 6Linked to original sources

[Possibilities and limits of temporary liver substitution by hemoperfusion with biological material].

For temporary hepatic assistance we used 200 g porcine liver pieces (5 X 5 X 5 mm3) which were perfused for 6 h with 11 swine blood. ATP and energy reserve values reached their maxima 30 min after starting perfusion, remained unchanged for 120 min, and decreased thereafter. Following 30 min of perfusion energy charge values increased from 0.260 +/- 0.110 mumol/g to 0.560 +/- 0.093 mumol/g (normal value; 0.854 +/- 0.022 mumol/g) and thereafter remained unchanged for 6 h. These results suggest that good energy regulation was maintained in the liver pieces. The small liver cubes showed excellent ammonia and phenol detoxication. However, the liver pieces were not found to be able to conjugate serum bilirubin, which might have been caused by a lack of this anatomic pathway in our model. Levels of hepatic and lytic enzymes in the perfusate increased with the time of perfusion, though they were relatively low as compared to levels in patients with acute hepatic failure. The concentration of free fatty acids in the perfusate, which are known to potentiate hepatic coma, increased slightly. However, methyl mercaptane remained constant during perfusion. Concentrations of nearly all amino acids rose during 6-h perfusion due to damage of hepatic tissues, but the molar ratio of the branched chain amino acid to aromatic amino acid was not changed. These results suggest that liberated substances from the damaged liver would not potentiate hepatic encephalopathy. We feel that hemoperfusion over small liver pieces could be a useful method for hepatic assistance.

Adenine Nucleotides↗

Comparison of a charcoal sorbent fiber with commercial charcoals for hemoperfusion.

A charcoal sorbent fiber (Enka, F.R.G.), was assessed for impurities, surface area, and adsorptive properties of its native charcoal, and compared with other uncoated activated charcoals. In vivo and in vitro hemocompatibility of the fiber were assessed as well as the adsorptive properties for endogenous toxins. The charcoal of the fiber had few impurities and a high surface area of 1,200 m2/g charcoal. For measuring the adsorptive speeds, 2 g of the uncoated charcoals were milled and screened to a particle size of 150-250 microns (Enka; 30-40 microns) and then mixed with the solutions of the individual solutes. The charcoal types of Enka, used in the charcoal sorbent fiber, and of Sutcliffe Speakman, used in the acrylic hydrogel coated charcoal, exhibited the highest adsorptive rates for bromthalein (middle molecular weight marker) and inulin (high molecular weight marker). No hematological differences among the various charcoals were found during the in vivo hemoperfusions. In the in vitro hemoperfusions with heparinized fresh blood, the fibers showed the lowest loss of leucocytes and thrombocytes. In the in vitro evaluation of the absorbents for hepatic support, the charcoal fiber and the petroleum pitch charcoal of Asahi had the best adsorptive properties for substances in the low molecular weight range.

Adsorption↗

Amino acid metabolism during hemoperfusion over biological materials.

We investigated the possibilities of liberation of toxic coma potentiating substances from the damaged hepatic tissues during the hemoperfusion over small liver pieces. Concentrations of nearly all amino acids rose during the perfusion due to the damage of hepatic tissues, but the molar ratio of BCAA to AAA was not changed. Free fatty acid levels in the perfusates increased slightly, however, methylmercaptan level remained constant. These results suggest that liberated substances from the damaged liver would not potentiate hepatic encephalopathy. Therefore, hemoperfusion over small liver pieces should be an useful method for hepatic assist because of excellent detoxification effects.

Amino Acids↗

[Excretion of transamination products in hyperphenylalaninemia (author's transl)].

A low-phenylalanine diet was given for a period of three weeks to four untreated adult phenylketonurics with mental deficiency. One week before the diet was started, in the course of the diet and one week after its termination, some transamination products of phenylalanine, tryptophan and histidine were determined quantitatively. Each of the transamination products showed a positive correlation to the serum phenylalanine levels of the patients, probably due to the large affinity of 4-hydroxyphenylpyruvic acid and phenylpyruvic acid for the amino groups of the aromatic amino acids. This may also explain the low levels of epinephrine, norepinephrine and serotonine which has been observed by other authors in untreated phenylketonurics. Accordingly, treated phenylketonurics should suffer from a chronic deficiency of biogenic amines after termination of the low-phenylalanine diet.

Adult↗

Dihydropteridine reductase variation in man and the characid fish "Cheirodon axelrodi": evidence for a dimeric enzyme structure.

Genetic evidence for a dimeric structure of dihydropteridine reductase in man and in the fish species "Cheirodon axelrodi" and "Salmo irideus" is presented. A single locus in man and two loci in the fishes examined encode this enzyme. Zymograms revealed two alleles for the locus in man and two alleles for each locus in the fish "Cheirodon axelrodi". The liver homogenate of a patient with dihydropteridine reductase deficiency showed no detectable activity in the gel, while his parents showed the normal electrophoretic phenotype.

Alleles↗

[Quantitative determination of the o-phthaldialdehyde derivatives of noradrenaline, dopamine and normetadrenaline in urine with an amino acid analyzer (author's transl)].

Noradrenaline, dopamine and normetadrenaline in urine are separated by a cation-exchange resin (DC 6A, Durrum) and a commercially available amino acid analyzer. After separation, the o-phthalaldehyde derivatives of the compounds are formed by the usual pumping system and are quantified with a fluorimeter. Pre-packed ion-exchange columns (Bio-Rad, Munich) are used for purification and fractionation of the urine samples.

Autoanalysis↗

Assignment of a gene for human quinoid-dihydropteridine reductase (QDPR, EC 1.6.5.1) to chromosome 4.

An acrylamide gel electrophoretic procedure is described which allows the separation of human quinoid-dihydropteridine reductase (QDPR), EC 1.6.5.1) from the homologous enzyme expressed in established rodent cell lines. The human enzyme marker segregates exclusively with chromosome 4 in a series of well characterized man-mouse somatic cell hybrid clones from our clone bank. This observation supports the assignment of a structural gene for QDPR to human chromosome 4.

Animals↗

[Influence of storing conditions on the amino acid concentration in human serum (author's transl)].

Whole blood, serum and deproteinized serum were stored at room temperature up to 24 h and at - 30 degrees C up to one month. The amino acid content was then determined with an automatic amino acid analyser. When whole blood is left at room temperature the concentration of citrulline, alpha-aminobutyric acid, cysteine and tryptophan remains unchanged, whereas the other amino acids show a remarkable increase or decrease. In serum stored for 24 h at room temperature, only the concentrations of aspartic and glutamic acid, serine, cysteine and phenylalanine were altered. With the exception of aspartic and glutamic acid it was possible to leave deproteinized serum up to 24 h at room temperature and up to one month at - 30 degrees C without observing a change in the concentration of the other amino acids. No change occurred, when serum was stored at - 30 degrees C for 24 h.

Amino Acids↗

Influence of the phenylalanine dose on the aromatic acid excretion in phenylketonuric heterozygotes and controls after oral loading.

Heterozygotes for phenylketonuria and controls were given oral loads of 100 mg and 200 mg L-phenylalanine per kilogram body weight. The concentrations of urinary aromatic acids were determined by gas-chromatography after isolation by ion-exchange chromatography and ethylacetate extraction. On an intake of 100 mg L-phenylalanine per kilogram, controls and carriers of classical phenylketonuria excreted nearly the same amounts of aromatic acids (P greater than 0.05). However on an intake of 200 mg per kilogram L-phenylalanine they could be distinguished from one another (P less than 0.001).

Genetic Carrier Screening↗

[Gas chromatographic estimation of acidic urinary metabolites after separation on prepacked silica gel columns (author's transl)].

The acidic ethylacetate extracts of 24-h urine specimens are evaporated and redissolved in chloroform--methanol--acetic acid. The resulting solution is transferred to a prepacked silica gel column. Elution takes 160 min using a specially designed chloroform--methanol--acetic acid gradient. The eluate is divided into fractions (16 min each) which are evaporated to dryness. The residues are silvlated and determined quantitatively by gas chromatography. The capacity of the silica gel column allows analysis of 30% of a 24-h urine specimen. In consequence, metabolites can be quantitated at concentrations less than 1 mg per 24 h. The method is suitable to obtain more detailed metabolic profiles of the carboxylic acids in urine.

Benzoates↗

[Short programs for the determination of amino acids in physiological fluids (author's transl)].

Short programs for the determination of a few amino acids are described. The studies were performed with two commercially available ion exchange resins (Durrum DC6A, Phoenix XX 907 OPKU). All the programs are constructed so that they are suitable for urine analysis with unfavourable concentration ratios. The economic aspects and the areas of application of these methods are discussed.

Amino Acids↗

[Quantitative determination of aromatic carboxylic acids with glass-capillary-columns (author's transl)].

With a glass-capillary column 20 aromatic acids, probably present in urine, were analysed quantitatively. In comparison with a packed column the capillary column offers several advantages: a higher resolution; a greatly reduced analysis time, an increased sensitivity. Though a split system is used, repeatability and linearity are suitable for quantitative analysis. The advantages are best recognized by the analysis of urine specimens of patients with a metabolic disorder (phenylketonuria).

Benzoates↗

Cystinuric heterozygotes and cystine-loading.

During routine screening procedures for amino acid disorders by thin layer chromatography, performed in a children's psychiatric hospital, we detected 6 children who excreted excessive amounts of dibasic amino acids. The probands, their siblings and parents and 11 controls (29 subjects in all) were loaded with cystine. On the basis of the urinary excretion after the loading we distinguished normal subjects from cystinuric heterozygotes, which we further subdivided in heterozygotes type II and III by the corresponding serum response.

Cystine↗

Statistical evaluation of a new method to detect carriers of phenylketonuria.

40 positive heterozygotes and 43 controls were loaded with 200 mg phenylalanine per kilogram body weight. The aromatic acids excreted 2 hrs after the loading were quantified by gaschromatography. The amounts of mandelic acid (MA), 2-hydroxyphenylacetic acid (2HOPAA) and phenylpyruvic acid (PPA) were used for a discriminatory analysis. The MA concentration alone gives a better discrimination than the statistical analysis.

Evaluation Studies as Topic↗

Phenylketonuria in a patient with cystinuria.

During routine screening procedures for amino-acid disorders by thin-layer chromatography, a 16-year-old boy was found to have phenylketonuria and cystinuria. A phenylalanine and a cystine loading were carried out. The patient was found to be homozygous for phenylketonuria and heterozygous for cystinuria type II. His father was heterozygous for phenylketonuria and cystinuria, while his mother proved to be heterozygous only for phenylketonuria.

Adolescent↗

Hypersarcosinemia with craniostenosis-syndactylism syndrome.

Hypersarcosinemia with craniostenosis-syndactylism syndrome. After a sarcosine loading the sarcosine-glycine ratios seem to be a more reliable criterion to distinguish different genotypes than the sarcosine tolerance curves.

Amino Acid Metabolism, Inborn Errors↗