PubMed Health⌕ Search

Biomedical subjects

K O Raivio

Publications and source records attributed to K O Raivio.

At least 19 recordsLinked to original sources
PubMed1992

[3H]-adenine metabolism and radiation damage during in vitro development of the kidney.

We followed the early post-induction changes in nucleic acid synthesis of the metanephric kidney anlage in vitro. Enhanced incorporation of [3H]-thymidine and [3H]-adenine was detected, but several factors were shown to influence the interpretation of such in vitro experiments. The incorporation is dependent not only on the stage of development of the target organ but also on its transfer to organ culture, as early rudiments require an "adaptive" pre-cultivation to stabilize their metabolism; at more advanced stages growth and DNA synthesis proceed without delay. Another potential artifact is radiation damage which is caused by the incorporated radioisotope and can be detected in prolonged cultures. A [3H]-adenine pulse of more than 1 microCi/ml for 2 hr leads to definite growth retardation, and a 10-microCi/ml pulse causes extensive cell death and atrophy on a 4- to 6-day subculture. The radiation damage is dose-dependent and of variable severity in the different cell lineages within the organ. Since the radioisotope doses were in the range of those commonly used for monitoring cell proliferation and metabolism, we stress the risk of obtaining artifactual results, especially in prolonged cultures after pulse-labeling.

Adenine↗
PubMed1992

Differential sensitivity of human fibroblasts and endothelial cells to reactive oxygen metabolites.

Reactive oxygen metabolites are implicated in tissue damage, which is often followed by fibrosis. Our aim was to evaluate the sensitivity of human fibroblasts, in comparison with umbilical vein endothelial cells, to two common reactive oxygen metabolites, to superoxide produced by hypoxanthine and xanthine oxidase, and to reagent hydrogen peroxide. Depletion of the prelabeled adenine nucleotide pool, which is a sensitive index of cell damage, was used as the basis for comparison. In the presence of hypoxanthine, xanthine oxidase caused a dose-dependent nucleotide depletion, which was more pronounced in endothelial cells. After 4 h of exposure to 100 microM hypoxanthine and 80 mU/mL xanthine oxidase, fibroblasts retained 73 +/- 2% of their adenine nucleotides but endothelial cells retained only 11 +/- 2%. Hydrogen peroxide also had a larger effect on endothelial cells; after exposure to 100 microM for 30 min, adenine nucleotides retained 36 +/- 26% of their initial radioactivity in endothelial cells but 76 +/- 8% in fibroblasts. We conclude that umbilical vein endothelial cells are inherently more sensitive to the harmful effects of reactive oxygen metabolites than are fetal skin fibroblasts.

Adenine Nucleotides↗
PubMed1990

Postnatal changes in serum immunoreactive erythropoietin in relation to hypoxia before and after birth.

To assess the immediate postnatal changes of serum immunoreactive erythropoietin (EP) in infants born after acute or chronic fetal hypoxia, and to estimate the rate of EP disappearance, we studied EP concentration, measured by double-antibody radioimmunoassay, in cord venous plasma and in serum at a mean age of 8 hours in a control group (n = 9) and in three patient groups: (1) infants with polycythemia (n = 10), (2) infants born to mothers with preeclampsia of pregnancy, without (n = 22) or with (n = 11) acidosis at birth, and (3) infants with acute birth asphyxia (n = 19), seven of whom had postnatal hypoxia. In all patient groups, cord venous EP was elevated in comparison with values in control infants. No change was found in EP level between birth and 8 hours in control infants (geometric mean in cord and 8-hour sample: 20 and 16 mU/ml, not significant) or in acutely asphyxiated infants with postnatal hypoxia (122 and 72 mU/ml, not significant), whereas the EP level decreased in all other groups: infants with polycythemia (123 to 24 mU/ml, p less than 0.001), nonacidotic infants (78 to 26 mU/ml, p less than 0.001) and acidotic infants (176 to 38 mU/ml, p less than 0.001) of the preeclampsia group, and acutely asphyxiated infants without postnatal hypoxia (58 to 30 mU/ml, p less than 0.001). The mean (+/- SD) half-time of EP disappearance was 2.6 +/- 0.5 hours in infants with polycythemia and 3.7 +/- 0.9 hours in infants of the preeclampsia group.

Acidosis↗
PubMed1990

Adenine nucleotide depletion from endothelial cells exposed to xanthine oxidase.

Hypoxia causes breakdown of cellular nucleotides, accumulation of hypoxanthine (HX), and conversion of xanthine dehydrogenase into xanthine oxidase (XO). Upon reoxygenation, the HX-XO reaction generates free radicals, one potential mechanism of tissue damage. Because endothelial cells contain XO and are exposed to circulating HX, they are a likely target for damage. We studied the effect of XO and/or HX at physiologically relevant concentrations on nucleotide metabolism of cultured endothelial cells from human umbilical veins. Cells were labeled with [14C]adenine and incubated for up to 6 h with HX, XO, or both, in the absence or presence of serum. Adenine nucleotides from cell extracts and nucleotide breakdown products (HX, xanthine, and urate) from the medium were separated and counted. HX alone had no effect. XO (80 mU/ml) alone caused a 70% (no serum) or 40% (with serum) fall in adenine nucleotides and an equivalent increase of xanthine and urate. The combination of HX and XO caused a 90% (no serum) or 70% (with serum) decrease in nucleotides, decrease in energy charge, and detachment of cells from the culture plate. Nucleotide depletion was not accounted for by proteolytic activity in the XO preparation. Albumin was only half as effective as serum in preventing nucleotide loss. Thus exogenous XO, in the presence of endogenous HX, triggers adenine nucleotide catabolism, but endogenous XO activity is too low to influence nucleotide levels even at high exogenous HX concentrations. Serum limits the catabolic effect of XO and thus protects cells from free radical damage.

Adenine↗
PubMed1990

Key enzymes of purine degradation and reutilization in human fetal liver and brain.

The activities and kinetic parameters of 5'-nucleotidase, adenosine monophosphate (AMP) deaminase, and hypoxanthine/guanine phosphoribosyltransferase (HGPRT) were assayed in human fetal brain and liver. The apparent activity of 5'-nucleotidase decreases in the liver and increases in the brain with gestation. Its apparent Km is about 27 microM for AMP in the brain at term and liver throughout gestation but about 60 microM in the premature brain. The activity of (AMP) deaminase in the liver increases, while that in the brain does not significantly change with gestation. Its apparent Km for AMP is about 5 mM in the tissues studied. The activity of HGPRT increases with gestation in both the fetal brain and liver, and is altogether high in the fetal brain. Its apparent Km for hypoxanthine appears to be high, about 59 microM, in the tissues studied. The activities measured reflect the maximal capacities of the enzymes. Conclusions concerning their in vivo activities cannot, however, be based on studies employing disrupted cells.

5'-Nucleotidase↗
PubMed1990

Xanthine oxidase during human fetal development.

Through oxygen free-radical production, xanthine oxidase (XOD, E.C.1.2.3.2) has been implicated in the pathogenesis of postischemic and hyperoxic tissue injuries among newborn. We measured the activity and evaluated the kinetic characteristics of XOD in human fetal liver, intestine, brain, and myocardium. Both the fetal liver and intestine contain a high XOD activity through gestation. The activity increases in the liver and decreases in the intestine with advancing gestation. The apparent Km for hypoxanthine is 4.8-5.5 microM in the intestine throughout gestation and in the liver at term but higher than 30 microM in the liver during the first half of pregnancy. The activity is undetectable both in the fetal brain and myocardium throughout gestation. Thus, XOD activity is present at least in the liver and intestine to account for the oxidation of hypoxanthine and xanthine. However, direct evidence for adenine nucleotide catabolism, followed by oxidation of the accumulated hypoxanthine during tissue reoxygenation in the human liver or intestine is not available.

Brain↗
PubMed1979

Increased urinary excretion of free N-acetylneuraminic acid in thirteen patients with Salla disease.

Thirteen severely retarded patients with Salla disease, a new type of lysosomal storage disorder, have been studied biochemically. All patients excreted approximately ten times more free sialic acid than normal individuals. The isolated sialic acid was characterized by paper chromatography, thin-layer chromatography, optical rotation, 13C and 1H nuclear magnetic resonance spectroscopy, and mass spectrometry of its permethylated derivative. The results clearly indicated that the excreted sialic acid was identical to N-acetylneuraminic acid. The main sialylated trisaccharide present in the urine of the patients was identified as 3'-sialyllactose by sugar and methylation analysis. The excreted amounts were found to be within normal range.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1979

Adenine nucleotide degradation during energy depletion in human lymphoblasts. Adenosine accumulation and adenylate energy charge correlation.

Adenine nucleotide breakdown to nucleosides and purine bases was measured in cultures of human lymphoblastoid cells following: 1) the inhibition of oxidative phosphorylation in the absence of glucose or 2) the addition of 2-deoxyglucose. A mutant cell line, deficient in adenosine kinase, in the presence of an adenosine deaminase inhibitor was used to measure utilization of the two pathways of AMP catabolism involving initial action of either purine 5'-nucleotidase or AMP deaminase. In such a system the appearance of adenosine induced by the oxidative phosphorylation inhibitor, rotenone, implies that approximately 70% of AMP breakdown occurs via dephosphorylation. By the same method, deamination accounts for 82% of AMP breakdown when 2-deoxyglucose is added. The occurrence of AMP dephosphorylation is not correlated with elevated concentrations of substrate or with decreased concentrations of the inhibitors of 5'-nucleotidase, ATP and ADP. Dephosphorylation occurs if, and only if, the adenylate energy charge decreases to about 0.6 in these experiments. In cultures deprived of glucose and oxygen, adenine nucleotide degradation via dephosphorylation results in recovery of normal energy charge values.

Adenine Nucleotides↗
PubMed1979

"Salla disease": a new lysosomal storage disorder.

Severe mental retardation, coarse facial features, clumsiness, and speech failure were common findings in three brothers and one female third-cousin of a family from northern Finland. All the patients had vacuolated lymphocytes in peripheral blood smears, and electron microscopy of fresh skin biopsy specimens showed abundant cytoplasmic inclusions in various types of cells of the skin. Eight lysosomal hydrolases were assayed in peripheral blood lymphocytes and cultured skin fibroblasts, but no enzyme deficiency was detected. Urinary excretion of mucopolysaccharides, amino acids, glycoasparagines, and oligosaccharides was normal. Clinical findings, course of the disease, and the presence of cytoplasmic inclusions, indicating lysosomal storage phenomenon, suggest that the patients suffer from a genetic lysosomal storage disorder not described earlier. The eponym "Salla disease" was introduced, referring to the geographically restricted area where the family resides.

Adult↗