Superman and the Malboro woman. The lungs of Lois Lane.
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Biomedical subjects
P Magnus
Publications and source records attributed to P Magnus.
Factor VIII and factor IX in a twin population. Evidence for a major effect of ABO locus on factor VIII level.
In order to establish the relative importance of genetic factors on the variation in plasma concentration of coagulation factors VIII and IX, these parameters were determined in 74 monozygotic and 84 like-sexed dizygotic twin pairs. The twins belonged to two age groups: 33-39 years and 57-62 years. Factor VIII was determined as factor VIII coagulant antigen (VIIICAg) and as factor VIII-related antigen (VIIIRAg). Factor IX was determined as factor IX antigen (IXAg). A higher value for each coagulation factor was found in the older-age group compared to the younger group, whereas no difference was found between the sexes. A significant correlation was found between values for VIIIRAg and VIIICAg (r = .56). For VIIICAg, it could be demonstrated that the age effect was secondary to the age effect on VIIIRAg. The concentration of VIIICAg and VIIIRAg varied among ABO blood types, being lowest in type O individuals, higher in A2 individuals, and highest in A1 and B individuals. The effect of the ABO locus on VIIICAg was secondary to an effect on VIIIRAg. Analysis of variance revealed a significant genetic influence on the variance of VIIICAg and VIIIRAg with a heritability estimate of .57 for VIIICAg and .66 for VIIIRAg. This is in agreement with a previous hypothesis of an effect of several autosomal genes on factor VIII concentration. Thirty percent of the genetic variance of VIIIRAg was due to the effect of ABO blood type. The ABO locus is therefore a major locus for the determination of factor VIII concentration. No significant genetic effect on the variation in plasma concentration of IXAg could be detected.
ABO Blood-Group System↗
New information on the effect of genes on the variation in birth weight.
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Birth Weight↗
Increase in the ratio of serum levels of apolipoproteins A-I and A-II during prolonged physical strain and calorie deficiency.
Effects of four days of intense physical activity on serum concentrations of total triglycerides, total cholesterol and apolipoproteins A-I, A-II, and B were studied in 35 well-trained young men. Serum total triglyceride levels decreased to 70% of baseline levels after 24 h, and fell further to 50% of baseline levels after 4 days. Serum levels of total cholesterol fell steadily to about 80% of baseline levels on the 4th day. Apo-B levels fell to 85% of baseline levels after 24 h, and remained at that level. Apo A-I fell to about 90%, and apo A-II to about 80% of baseline levels, causing a significant increase in the ratio of apo A-I to apo A-II. The intraindividual changes in apo B were positively correlated to changes in cholesterol during the first day (r = 0.60). The changes in apo A-I and apo A-II had no significant correlation with changes in total cholesterol or triglycerides, or with one another, suggesting that apo A-I and apo A-II are metabolized independently during conditions of hard physical exercise.
Adult↗
Distinguishing fetal and maternal genetic effects on variation in birth weight.
In an attempt to uncover the causes of variation in birth weight for 13,970 offspring of MZ and DZ twins, several models were tested. Mean squares from nested analysis of variance were analysed with respect to fetal and maternal effects on variation in birth weight. The major part of the total variation in birth weight was found to be due to effects of genes. The contribution of fetal genes was larger than the contribution of maternal genes. About 11% of the variation could be attributed to effects of interactions between fetal and maternal genes. However, in this data set, the interaction variance could not be distinguished from variance due to fetal dominance or to effects of common environment of sibs.
Analysis of Variance↗
Causes of variation in birth weight: a study of offspring of twins.
In an effort to explain the causes of variation in birth weight within and between families, birth weights of 13,970 sons and daughters of monozygotic (MZ) and dizygotic (DZ) twins were analysed. The sample included birth weights of halfsibs and cousins related either through females or males, permitting the distinction between maternal and fetal genetic effects. Models of genetic and environmental variances were fitted to mean squares from analysis of variance. The results indicate that more than 50% of the total variation in birth weight is caused by variation in fetal genes, and that less than 20% is caused by variation in maternal genes. The remaining variance (20-30%) could be explained by random environmental effects. No certain effects were found of family-specific environment or of interactions between fetal and maternal genes.
Birth Weight↗
Further evidence for a significant effect of fetal genes on variation in birth weight.
The contribution of fetal and maternal genes to the variation in birth weight was estimated in a sample of 5,625 grandchildren of monozygotic and dizygotic twins. Fetal and maternal genetic effects were separated by comparing the covariance structure for offspring of daughters of twins with that for offspring of sons of twins. Only insignificant amounts (3.0%) of the total variance in birth weight could be accounted for by maternal genes, while fetal genes seemed to account for the major part (69.4%) of the variation. Environmental factors common to sibs could explain 8.6% and random environmental factors 19.0% of the total variance. The findings are consistent with the results of an earlier study of birth weight in the same population but differ from findings in other populations.
Analysis of Variance↗
Parental determinants of birth weight.
As part of a study on causes of variation in birth weight, questionnaire data on parental measures were related to offspring birth weights recorded in the Medical Birth Registry of Norway. A genetic analysis of parent-offspring covariances in birth weight indicated that about 60% of the variance in birth weight could be explained by effects of fetal genes, while no effects of maternal genes were detectable. Multiple regression analysis showed that height and weight of both parents and maternal smoking status were associated with variation in birth weight. Socioeconomic status, educational attainment and paternal smoking habit had no independent effects. The adult, parental variables could only explain 10% of the variation in mean offspring birth weight.
Birth Weight↗
Multiple risk factor intervention in cardiovascular disease.
This paper describes multiple risk factor intervention, its rationale and the form it takes, referring to recent intervention trials and the issues arising from their approaches and outcomes. Some questions relevant to intervention are raised and some guesses made as to future directions and opportunities.
Coronary Disease↗
Evidence for genetic effects on variation in plasma unsaturated transcobalamin II and cobalamin (vitamin B12).
Unsaturated plasma transcobalamin II (UTC II) and cobalamin were measured in two selected age-groups of like-sexed mono- and dizygotic twins. For UTC II, a higher mean level was found in women than in men, and in the older (57 to 61 years) than in the younger (33 to 39 years) age group. Testing of genetic-environmental models revealed that variation in plasma levels of UTC II is almost exclusively genetically determined. More than 50% of the variation in cobalamin levels was accounted for by genes, the remainder being due to person-specific environmental factors (for older males no model gave a good fit). A negative correlation was noted between UTC II and cobalamin levels. The correlation coefficient was low, and the variation in UTC II accounted for only about 4% of the variation in the cobalamin level. This finding suggests that a pathologically high value of one of the variables may have clinical significance, regardless of the value of the other variable. For 22 patients studied longitudinally, a clear tendency to maintain plasma levels at constant levels over long periods of time was found, suggesting that certain degrees of deviation from these levels may have clinical relevance.
Adult↗
A comparison of populations self-selected and randomly selected for coronary risk factor screening.
Levels of coronary risk factors in 3,090 adults who sought screening over a 2-year period in Perth, Western Australia, were compared with those in 722 subjects who were selected at random to attend the screening center. Self-referred (SR) subjects were less likely than random-sample (RS) subjects to have suffered from, or be on treatment for, heart disease, hypertension, gout, or diabetes but were more likely to have a family history of premature heart disease. They were less likely to be current smokers and overweight (women only) but more likely to be sedentary at work and have higher mean serum cholesterol levels. SR also had more knowledge about coronary heart disease (CHD) and its causes and were more likely to believe that this knowledge had influenced their behavior, but were less likely than RS to be satisfied with their knowledge level. Smokers among SR were more likely to express a wish to give up smoking than smokers in the RS. These findings are consistent with previous observations. The differences, although statistically significant, were generally small and did not clearly favor one group with respect to total risk of CHD. Therefore the effectiveness of risk factor modification following screening should not be greatly affected by self-selection for screening. Effectiveness may be greater in self-selected subjects because of their apparently greater motivation toward risk factor change.
Adult↗
Predicting zygosity in Norwegian twin pairs born 1915-1960.
Present addresses of 12,752 like-sexed twin pairs born in the period 1915-1960 were identified. A questionnaire, concerning the similarity of pair members, was sent to all individuals. Responses were obtained from 83.7% of the subjects. The zygosity of 207 pairs was established by examination of genetic markers. By using discriminant analysis on the responses from this subgroup, functions were obtained for prediction of zygosity from questionnaire data. It was estimated that 2.4% of the pairs would be misclassified if the questionnaire responses from both pair members were used, and 3.9% if only the response from one of the twins was used. Accordingly, zygosity could be predicted with satisfactory reliability also for twin pairs where only one of the twins had responded. The predicted percentage of monozygotic (MZ) pairs among pairs where one or both twins had responded, was 39.4 (4,402/11,175). The percentage of MZ pairs was significantly lower (34.5) in death-discordant pairs than in pairs in which both twins were alive (39.6). The zygosity questionnaire data are sufficient to adequately score twin pairs for zygosity in the great majority of cases.
Adult↗
Distribution of common eye diseases in the families of Norwegian twins.
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Adult↗
Apparent phase-shifts of circadian rhythms (masking effects) during rapid shift rotation.
Six subjects worked an experimental 8 h rapidly rotating shift system in which 6 shifts were compressed into 5 d (work two mornings - 8 h interval - work two nights - 8 h interval - work two afternoons). Rectal temperature was continuously recorded and urinary excretion rates of adrenaline, noradrenaline, K+, Na+ and Hg+ were assessed in samples collected at 4 h intervals. Higher rectal temperatures and higher excretion rates of the two each catecholamines than those expected from the normal circadian rhythms were observed during night work, while lower than expected values were recorded forenoon sleep. In these three rhythms, immediate, significant 3-4 h delay phase-shifts occurred in the two days following night shifts. The acrophases reverted suddenly to their initial positions when the subjects returned to their normal sleep/wake schedule. The circadian rhythms of the excretion of electrolytes were not perceptibly disturbed. It is concluded that the apparent phase-shifts were due to a direct influence (masking effect) of the changes in body functions during sleep and wakefulness on the measured parameters, and that no true phase-shifts (entrainment) occurred in the endogenous circadian regulation. The evidence of such an immediate, partial adaptation to unconventional sleep/wake patterns supports the adoption of rapidly rotating shift systems which would not greatly interfere with the endogenous oscillators.
Adult↗
A twin study of aryl hydrocarbon hydroxylase (AHH) inducibility in cultured lymphocytes.
Aryl hydrocarbon hydroxylase (AHH) inducibility was studied in cultured lymphocytes from 28 monozygotic (MZ) and 19 dizygotic (DZ) twin pairs. The results indicate that the induced level of AHH activity as well as inducibility (expressed as the ratio between levels in induced and non-induced cells) are inherited. The best (h2) estimate of heritability is 0.7. There was no suggestion that non-induced AHH activity level is an inherited trait. Inducibility of AHH was not normally distributed and the distribution observed in this limited series might even be trimodal. The results of the study appear to confirm previous reports that AHH inducibility is an inherited trait, and do not exclude the possibility that the major part of the variation is controlled by one locus.
Adult↗
Low density lipoprotein receptor activity in cultured fibroblasts from subjects with or without ischemic heart disease (in the absence of familial hypercholesterolemia).
Fibroblast strains from six subjects with ischemic heart disease (IHDs) were compared to strains from 43 subjects without a history of IHD (non-IHDs), with respect to association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated LDL (125I-LDL). The subjects (25 females and 24 males) were selected on the criteria that they were twins (one from each pair), 58-61 years old, and living within 200 km of Oslo. None of them suffered from autosomal, dominant hypercholesterolemia, which is associated with reduced cell surface LDL receptor activity and increased susceptibility to IHD. There was a trend towards lower 125I-LDL association values in strains from IHDs than in strains from non-IHDs (P=0.009). There was a significant negative correlation between, on one hand, serum total cholesterol level and on the other fibroblast association (P=0.03) or degradation (P=0.04) of 125I-LDL. We have previously presented data indicating that fibroblast association of LDL may be determined by alternate genes at one single locus. Together with the present limited data, this raises the possibility that normal genes at the LDL receptor locus may render subjects more or less susceptible to ischemic heart disease.
Apolipoproteins↗
Effects of age, sex and genes on sister chromatid exchange.
Sister chromatid exchange (SCE) was studied in cultured lymphocytes from a limited series of 21 like-sexed twin pairs; 11 monozygotic (MZ) and 10 dizygotic (DZ) pairs. The 18 subjects, who were between 57 and 61 years old, had an SCE mean value (mean) of 8.0 whereas the 24 subjects between 33 and 39 years of age had a mean of 6.8. The difference was statistically significant (P less than 0.001). The effect of age appeared to be present in both sexes. No significant difference was found between females (mean = 7.3) and males (mean = 7.5), nor between smokers (mean = 7.3) and non-smokers (mean = 7.4). Drug users had a slightly higher mean (mean = 7.9) than non-users (mean = 7.0) (P less than 0.05). This trend was found in each age group. The within-pair variance was slightly higher in DZ than in MZ pairs. The difference was not significant. We conclude that genetic factors are probably not a major source of subject variation in SCE mean value.
Adult↗
Genetics of the low density lipoprotein receptor: II. Genetic control of variation in cell membrane low density lipoprotein receptor activity in cultured fibroblasts.
Fibroblast low density lipoprotein (LDL) plasma membrane receptor activity, measured as 125I-LDL association (plasma membrane binding plus intracellular accumulation) and degradation was determined in cell strains from 14 monozygotic (MZ) and 21 like-sexed dizygotic (DZ) normolipidemic twin pairs. The twins were between 57 and 62 years old and had liver apart for an average of 38 years (range 0-60). The intrapair differences were significantly smaller in MZ than in DZ twin pairs in fibroblast 125I-LDL association as well as degradation assays (P less than 0.05). These findings suggest a genetic influence on normal variation in LDL receptor activity in vitro. In two MZ pairs discordant for psoriasis, the psoriatic twin had markedly lower LDL receptor activity than the cotwin.
Cell Membrane↗