The costs of diseases and violence in Finland in 1972.
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Biomedical subjects
Publications and source records attributed to K Hemminki.
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Styrene and styrene oxide were injected into the air space of fertilized chicken eggs at different times during an incubation period of 14 days. The toxicity of styrene and styrene oxide when injected on the fourth day of incubation revealed an LD50 of 40 mumol/egg and 1.5 mumol/egg, respectively. Malformations were found in 0-20% of the embryos, but never in the controls. The results obtained point to a need for further experimental, and possibly epidemiologic, studies on the consequences of styrene exposure.
The concentration of free phosphate groups is measured in rat liver chromatin after DNase II digestion using polylysine titration. The unsheared chromatin completely precipitates at lysine/DNA phosphate ratios of 0.5 to 0.6. Digestion of the chromatin reduces the lysine/DNA phosphate ratio of complete precipitation by about 0.2 units suggesting the removal of free phosphate groups. The two chromatin fractions: MgC12 insoluble (template-inactive) and Mg12 soluble (template-active) chromatins precipitate at about the same lysine/DNA phosphate ratio. Some 15% of the MgC12 soluble chromatin remains in solution at any polylysine concentration. The removal of histone H 1 FROM THE MgC12 insoluble chromatin increases the lysine/DNA phosphate ratio by about 0.2 units suggesting that 20% of the DNA phosphate groups in nucleosomes are masked by histone H 1.
Rat lung tissue is labelled in vitro with [3H]leucine and nuclei are prepared. They are digested with deoxyribonuclease II and four subfractions are isolated after differential centrifugation: MgCl2-soluble (active) and MgCl2-insoluble (inactive) chromatin, nuclear matrix sediment and matrix extract using 2M NaCl. The matrix extract fraction is found to be enriched in radioactive DNA after a short pulse of [3H]thymidine. The labelling kinetics of histones are similar in each subfraction, suggesting that histones are not preferentially incorporated onto nascent DNA. Nonhistones isolated from the subfractions, except for the matrix sediment fraction, also follow closely similar incorporation kinetics with [3H]-leucine. The matrix sedimnent fraction is three times more actively labelled than nonhistones of the other fractions and displaying a unique protein composition, suggesting distinct functional properties.
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The effect of secondary stimulation with estrogen on synthesis of nuclear and nucleolar proteins is studied in chick oviduct. Isolated nuclei and nucleoli have a protein/DNA ratio of 5.2 and 5.6, respectively. 35% of nuclear and nucleolar protein is recovered in the histone fraction after hydroxylapatite chromatography. Gel electrophoretic separations of nuclear and nucleolar nonhistones are largely similar as to visible bands and distribution of radioactivity. Nucleoli bind 1.4 times more [3H] estradiol as compared to whole nuclei. Nucleolar histones are labelled slightly more actively with [3H] leucine than nuclear histones; nucleolar nonhistones are labelled about 3 times more actively than nuclear nonhistones. An 18 hour secondary stimulation with estrogen increases the radioactivity of histones by 6-fold and that of nonhistones by 2.5-fold in whole nuclei as well as in nucleoli. Stimulation appears to increase preferentially radioactivity of nonhistones at 50 000 daltons. As this change is observed in whole nuclei and nucleoli and is not reduced with hydroxyurea, it is suggested that this may be related to a gross structural reorganisation of chromatin induced by the hormone.
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Hen oviduct chromatin was digested with DNase II and separated into two fractions. The MgCl2 insoluble chromatin fraction (43% of the total DNA) was enriched in nucleosome-like particles, which sedimented at 11 S and contained 185 base pairs of DNA. The MgCl2 soluble chromatin fraction (5% of the total DNA) was characterized by 5 S and 14 S peaks in sucrose gradients; Estrogen receptors in the chromatin fractions were labelled with [3H] estradiol using the steroid exchange assay. The concentration of receptors in the MgCl2 soluble chromatin was 4;5 times higher than that in the MgCl2 insoluble chromatinmin sucrose gradient analysis the 11 S particles displayed a negligible specific radioactivity suggesting that estrogen receptors mainly bind to extranucleosomal chromatin.
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The theory of competing risks of death has been applied in this study for the construction of two indices: (1) increase in the expectation of life as a function of age, and (2) increase in the average number of years to be lived by a newborn up to various ages, when selected causes of death are eliminated. The indices have been applied to the 1970 mortality in Finland. Vascular diseases comprise the most important cause of death in both sexes, when the first index is applied. According to the second index, considering ages up to 65 years, violent deaths emerge as the most important cause of death among men and neoplasms appear equally important as vascular diseases among women. The magnitude of a health problem was found to be dependent on the index selected, which should be considered in health planning.
Cytoplasmic and nuclear RNA is prepared from chick embryo skin, muscle and brain at 13 days of incubation. The concentration and labelling of RNA is measured after oligo(dT) chromatography. Skin, muscle and brain contain respectively 4.8, 3.6 and 5.6% cytoplasmic RNA with a poly(A) segment. The corresponding figures for nuclear poly(A)-containing RNA are 13, 16 and 9.4%. In skin, incorporation of [3H]uridine in RNA lacking poly(A) exceeds the rate of incorporation into muscle and brain RNA by about 2.5- and 5-fold, respectively. By contrast, no such large differences in rates of incorporation between the tissues are observed with poly(A)-containing RNA.
The amount and the labelling of RNA were studied in chick oviduct after secondary stimulation of pre-treated chicks with oestrogen. The weight of the oviduct increases over 2 fold in 20 h of oestrogen action using a dose of 1 mg. During the hormonal treatment the amount of cytoplasmic and nuclear RNA increases about 3 and 1.5 fold, respectively. The amount of poly(A) containing RNA increases somewhat less than that of RNA lacking poly(A). The proportion of poly(A) containing species of the total cytoplasmic and nuclear RNA decreases from 5.8% to 4.4% and from 7.8% to 6.3%, respectively. Hydroxyurea largely prevents the effect of oestrogen in increasing the amount of RNA. Incorporation of [3H]uridine in RNA in vitro is stimulated about 2.5 fold in cytoplasmic RNA lacking poly(A) and only 1.2 fold in RNA containing poly(A) in 20 h of oestrogen action. In nuclear RNA the labelling of the two species is stimulated about 1.7 fold. Hydroxyurea fails to interfere with the oestrogen-induced stimulation in the labelling of RNA. Cytoplasmic and nuclear RNA containing poly(A) is distributed in a peak of about 20 S in agarose-acrylamide gels.
Kinetics of incorporation of (3H) uridine into cytoplasmic RNA fractions of rat liver is investigated. The fractions include free and membrane bound polysomes, rough membranes sedimenting with mitochondria and free cytoplasmic RNA particles. (1) Poly(A) containing RNA, isolated by oligo-dT cellulose, amounts to 0.4% of the total RNA in the homogenate, 0.5% in bound polysomes, 3.4% in free polysomes and 16% in free cytoplasmic RNA particles. (2) The rate of (3H) uridine incorporation into RNA lacking poly(A) proceeds uniformly in all subcellular fractions except for free cytoplasmic RNA particles, which accumulate negligible amounts of radioactivity. (3) The initial labelling of RNA containing poly(A) is most active in free cytoplasmic RNA particles supporting their identity as mRNA en route to polysomes. The initial specific radioactivities decrease in the following order: homogenate, bound polysomes, rough membranes sedimenting with mitochondria, free polysomes. The data suggest that mRNA is supplied to free and membrane-bound polysomes via different routes. The kinetic analysis indicates that free cytoplasmic RNA particles may be a precursor of mRNA of free polysomes rather than that of bound polysomes. (4) The kinetic differences of free and membrane bound polysomes are also demonstrated by comparing the radioactivity of RNA containing poly(A) to the total radioactivity at various incorporation times. In bound polysomes this decreases from 31% at 1 h to 10% at 25 h, whereas in free polysomes the corresponding ratio increases from 10 to 13%. RNA containing poly(A) of free cytoplasmic RNA particles represents 64% of the total radioactivity throughout the experiment.
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Synthesis of nuclear histones and nonhistones was studied in chick oviduct during stimulation with estrogen and progesterone. In estrogen primed chicks, as compared to progesterone primed chicks, oviduct nonhistones are enriched in polypeptides of 50,000 daltons and larger. A secondary stimulation with the steroids increases the amino acid incorporation into histones and nonhistones two to six fold. Injection with estrogen induces preferential labelling of nonhistone polypeptides at 50,000 to 60,000 daltons independent of the kind of primary stimulation. A secondary injection with progesterone increases the amounts of highly labelled polypeptides with a molecular weight of over 70,000 daltons.