[Old brain injuries and driver's licence].
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Biomedical subjects
Publications and source records attributed to K Karkola.
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Narrowings of the coronary arteries were measured in 94 infants aged less than 1 year who died in hospital and 102 1- to 16-year-old children who died accidentally. The arteries were transformed mathematically to circles. The degree of narrowing caused by intimal thickening was determined as the ratio of intimal area to the original luminal area. This ratio was further transformed to percentage. The degree of narrowing varied between 0 and 58% (mean 20%). The mean degree of narrowing in the left coronary artery during the first year of life was 17% and, between 12 and 15 years, 34%. Narrowing was greater in males (P = 0.02), when all the 333 coronary samples were included in the analysis. The birthplaces of the subjects' grandparents were traced from population registers and it was found that narrowing in the left coronary artery of infants was greater in those descended from grandparents from eastern Finland, an area of high mortality from coronary heart disease (CHD). Intimal thickening in infants and children seems to be a morphological manifestation of hereditary predisposition to CHD.
Spermidine synthase was purified to apparent homogeneity from human spleens (8700-fold) by affinity chromatography. The native enzyme was composed of two subunits of identical Mr (35,000) and showed an apparent Mr of 62,000 in pore-gradient gel electrophoresis. Its pI was 5.1, Spermine synthase was purified to apparent homogeneity from placenta (5300-fold) and from kidney (4600-fold). The native enzyme was composed of two subunits of identical Mr (45,000) and showed an apparent Mr of 78,000 in pore-gradient gel electrophoresis. In isoelectric focusing it revealed two bands, with pI values of 4.9 and 5.0. Both synthases were present in all human tissues studied, but revealed a clear tissue-specific pattern. Mouse antisera against spermidine synthase revealed only one band, of Mr 35,000, in all purified enzyme preparations and in crude human tissue extracts in immunoblotting. Antisera against spermine synthase showed an immunoreactive band corresponding to the Mr of the subunit of spermine synthase. These antisera did not indicate any cross-reactivity in immunoblotting. Thus spermine synthase and spermidine synthase do not share homologous antigenic sites and are totally different proteins.
The distribution of tryptase in various human tissue high-salt extracts (skin, lung, pancreas, liver, kidney, and spleen) was studied. Tryptase activity was compared with tissue histamine concentration, chymase activity, and cathepsin D, and histamine-N-methyltransferase (HMT) activities. Tryptase activity, found biochemically in tissue extracts, was localized in tissue sections by an enzyme-histochemical method using peptide 4-methoxy-2-naphthylamide substrates and Fast Garnet GBC as the chromogen. The highest levels of tryptase activity were found in lung and skin extracts. Liver, kidney, and spleen extracts displayed only a little activity. The distribution of histamine was similar to that of tryptase, whereas distributions of cathepsin D and HMT were quite different from that of tryptase. High-salt extracts of lung contained no detectable chymase activity, but in skin extracts this activity was high. Using an enzyme-histochemical method, the tryptase activity in tissue sections seemed solely to be confined to cells, which were granular and Giemsa positive after the red azo dye had been removed with Tween 20. Skin and lung sections contained the highest number of positively stained cells. The inhibition properties of tryptase, found in both tissue extracts and sections, and the substrate profile in tissue sections were identical. Human leukocyte preparation was negative for tryptase when stained enzyme-histochemically. The present results suggest that tryptase in human tissues is found only in the mast cells. The enzyme seems to be identical in the various human tissues studied because the different high-salt extracts were immunologically cross-reactive when tested with a rabbit polyclonal antibody against skin tryptase.
Men in Eastern Finland show a substantially higher rate of coronary heart disease (CHD) than men in the Western part of the country. To study possible differences in the biochemical composition and atherosclerotic involvement of coronary arteries between these two populations, we analyzed major lipid and non-lipid components of coronary arteries from 15- to 60-year-old Finnish men after accidental death. The material consisted of 59 age-matched pairs from East and West Finland, respectively, collected at successive autopsies during 1979-1983. The coronary arteries from East Finland contained significantly more esterified cholesterol and a higher percentage of oleate in cholesteryl esters. The findings were most conspicuous under the age of 40 years, and imply a higher degree of atherosclerosis together with an increased rate of intracellular cholesterol esterification in coronary arteries in Eastern as compared with Western Finland. The vessels from East Finland also tended to contain more free cholesterol and raised lesions, but the differences were not statistically significant. No major regional differences were seen in total phospholipids, phospholipid subfractions, DNA, calcium, collagen, total protein, or glycosaminoglycans.
Three methods of expressing the results of biochemical analyses of normal and atherosclerotic human coronary intima-medias were compared by calculating the results per unit area of vessel surface to obtain the content, per unit weight of dry defatted tissue (d.t.) to obtain the concentration, and per unit weight of organic d.t. to obtain the inorganic salt-corrected concentration. The content reflects the amount of a substance in an anatomically defined portion of the arterial wall, whereas the concentration gives the amount of the substance relative to a defined mass of arterial tissue. Since calcium salts form a sizable portion of fibrous plaques, concentrations become overcorrected in the oldest age groups. For example, there was an unexpected age-related decrease of collagen concentration in fibrous plaques-containing coronary arteries while its content and inorganic salt-corrected concentration increased. In studies involving arterial biochemical analyses it is appropriate to calculate the results in terms of both the content and the concentration. If severely affected specimens are studied, it is recommendable also to use the inorganic salt-corrected concentration, especially when different age groups are compared with one another.
Glycosaminoglycans (GAGs) were studied in normal and atherosclerotic coronary arteries of 15- to 60-year-old Finnish men who had died accidentally. The GAGs were fractionated and quantified with electrophoretic techniques. The contents of sulfated GAGs (micrograms/cm2 vessel surface area) increased continuously until 20 to 30% of the vessel surface area was covered with fibrous plaques, after which they started to decrease. The largest increases were seen in chondroitin sulfates A and C and dermatan sulfate, the former of which rose earlier with lesion development. In normal coronary arteries the contents of dermatan sulfate and chondroitin sulfates A and C increased significantly with age, but the rises were much smaller than those found in affected vessels. The age-related changes in the percentage composition of GAGs in normal coronaries were qualitatively similar to those found in affected coronaries during lesion development. The alterations in arterial GAGs, therefore, seem to be related to two processes, both of which involve increased formation of connective tissue components by arterial smooth muscle cells: the normal growth and maturation of the vessels with a slow development of diffuse intimal thickening, and atherogenesis, which greatly increases the contents of sulfated GAGs in affected arteries.
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