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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 307 records · Page 17Linked to original sources
PubMed1989

Possible effect of secretor locus on plasma concentration of factor VIII and von Willebrand factor.

A significant fraction (30%) of the genetically determined variance in plasma concentration of the von Willebrand factor antigen (vWf:Ag) has been shown to be related to ABH determinants. Individuals with blood group O, who have the highest amounts of blood group H substance, have the lowest concentration of vWf:Ag. The Lewis substances, Le(a) and Le(b), are biochemically closely related to the ABH substances as both can be produced from the same precursor substance. We studied the effect of the presence of the Lewis antigens on the plasma concentration of vWf:Ag and factor VIII antigen (VIII:Ag) in 323 individuals of different ABO groups from a series of twins and in 58 blood donors of blood group O. Among persons belonging to blood group O, those with the Le(a) antigen had a higher concentration of both vWf:Ag and VIII:Ag than individuals lacking Le(a). Le(a+b-) people are nonsecretors and Le(a-b+) people are secretors of ABH substance. Thus, the lowest concentration of vWf:Ag and VIII:Ag was found in group O secretors. The effect is most likely due to an effect of the secretor locus. This finding may be of importance for the detection of carriers of hemophilia A and for the diagnosis of type I von Willebrand disease.

ABO Blood-Group System↗
PubMed1989

Impact of medical genetics on research and practices in the area of cardiovascular disease.

The evidence that genetic factors are of importance in the etiology of coronary heart disease (CHD) originates from several areas. Cases of premature CHD cluster in families in a way which indicates the importance of genetic factors, and having a first-degree relative who contracted CHD before the age of 50-55 is by itself a significant risk factor. Genes are of importance in determining the level of several established risk or "anti-risk" factors, and association between risk factor level and random genetic markers has been known for several years. The "candidate gene" approach was first applied in the 1970s, when a strong association between genetically determined Lp(a) lipoprotein and premature CHD was found, and associations between Ag allotypes and lipid levels were uncovered. The new DNA technology has greatly increased the potential of the "candidate gene" approach. Genes are of importance not only for the absolute risk factor level but also with respect to the amount of variation in risk factor level that any one person can have. Thus, in addition to traditional "level genes", new "variability genes" are being identified. Knowledge of genetic factors in the etiology of coronary heart disease has not so far been adequately utilized in attempts to combat premature CHD. The time has now come to utilize genetic information in a setting of family-oriented preventive medicine. This approach would greatly improve the efficiency of preventive efforts, utilizing predictive genetic testing and targeting counseling on those who need it most.

Cholesterol↗
PubMed1989

Effect of reduced training volume on cardiac function, VO2 max, and running performance.

This study examined the physiological effects of reducing training mileage in a veteran long distance runner while increasing exercise intensity. Variables measured included stroke volume, cardiac output, maximum oxygen uptake, ventilation threshold and performance time in a 10,000 m run. For 8 weeks, training mileage was reduced from 75.8 miles per week to 42.5 miles per week including interval training twice weekly. Following the specialized training, performance time was 10 seconds faster although VO2max and heart contractility had decreased. It was concluded that distance running performance can be maintained while considerably reducing training mileage and increasing exercise intensity twice a week.

Adult↗
PubMed1988

Distribution of orthogonal arrays of particles in the Müller cell membrane of the mouse retina.

In the present study we investigated the Müller cell membrane of the mouse retina by freeze-fracturing. The mouse retina is vascularized and the vessels running outside the nerve fiber layer are completely encased by Müller cell endfeet. Orthogonal arrays of particles (OAP) reside in all membrane areas of the Müller cells. The paravitreous as well as the pericapillary endfeet reveal a considerably higher density of OAP than the nonendfoot membranes including the perikaryal ones. This is in contrast to the Müller cell membrane of the rabbit retina studied previously (Wolburg and Berg: Neurosci, Lett., 82:273-277, 1987). There we found a completely different distribution of OAP; practically all OAP reside in the endfoot membrane facing the vitreous body. The nonendfoot and perikaryal membranes were devoid of OAP. The OAP distribution in both species corresponds roughly to the distribution of the K+ conductances measured by Newman (J. Neurosci., 7:2423-2432, 1987). The putative relationship between OAP and K+ channels, including functional aspects, is discussed.

Animals↗
PubMed1988

Prenatal diagnosis in a female carrying a deletion close to the Duchenne locus.

Family studies including the proband are usually needed before a prenatal diagnosis may be performed for Duchenne muscular dystrophy. We report here on prenatal diagnosis in a family where the solitary index case was dead, and where the consultand and her mother were assumed to be carriers by independent evidence. DNA analysis revealed that both the consultand and her mother had an X chromosome deleted for DNA material in the Xp21 region. The female fetus also carried the deleted X chromosome.

Chromosome Deletion↗
PubMed1988

Linkage disequilibrium analyses and restriction mapping of four RFLPs at the pro alpha 2(I) collagen locus: lack of correlation between linkage disequilibrium and physical distance.

Restriction fragment length polymorphisms (RRLPs) located at short distances may demonstrate linkage disequilibrium. Under the assumption that the distances between the loci of the RFLPs are inversely related to the linkage disequilibria, gene order may be deduced. However, if the assumption is invalid, the results may be incorrect. We have studied four different DNA polymorphisms at the COLIA2 locus in 180 unrelated Norwegian individuals. Observed frequencies (presence/absence) for the different polymorphic sites were as follows: site A (EcoRI) 0.30/0.70, site B (MspI) 0.83/0.16, site C (StuI) 0.86/0.14, and site D (RsaI) 0.66/0.34. Of 16 possible haplotypes 12 were demonstrated, and 2 additional were deduced to be present. Restriction mapping of the four polymorphic sites gave the following order of the sites from the 5' to the 3' of the gene: A-D-B-C. Linkage disequilibrium was not found between the sites A and D; strong disequilibrium was found between sites A and C, and B and C; and less strong, between A and B, B and D, and C and D. Analysis of linkage disequilibrium coefficients between all pairs of loci demonstrated that there is no consistent relationship between linkage disequilibrium and physical distance (tau = -0.07). These results suggest that for a small region of the genome, factors such as deviating mutation rate and gene conversion may add significantly to rearrangements by recombination. Thus, a deduced gene order from linkage disequilibrium data has to be regarded with great caution.

Chromosome Mapping↗
PubMed1988

Hodgkin cells in freeze-fracture replicas.

Lymph nodes from six patients with Hodgkin's disease (three with the nodular sclerosing subtype, one with mixed cellularity and two with the lymphocyte-predominant subtype) were analysed by electron microscopy in freeze-fracture replicas and thin sections. Two main variants of Hodgkin cell could be identified in the nodular sclerosing and mixed cellularity subtypes. (1) Hodgkin cells with wide cytoplasm and short, smooth- and rough-surfaced tubular profiles of endoplasmic reticulum (ER) unevenly scattered in the cytoplasm. (2) Hodgkin cells with well developed rough ER. In freeze-fracture replicas the ER was seen to consist of both short and long tubules, some of the latter forming anastomoses with each other. Both cell types possessed branching cytoplasmic processes. A P-face rich in intramembrane particles (IMP) and an E-face with few IMP were common to both Hodgkin cell types. These cells do not, therefore, possess the membrane features characteristic of interdigitating reticulum cells, thus refuting the previously held belief that Hodgkin cells, in particular lacunar cells, are related to interdigitating reticulum cells. The cytoplasmic structures and membrane characteristics of Hodgkin cells in the lymphocyte-predominant subtype (L & H cells) are similar to other Hodgkin cells in that they may show a high content of rER, and the P-face of these cells contains more IMP than the E-face. Both characteristics support the theory put forward in the literature (based on immunohistochemical findings) that these are lymphoid cells (immunoblasts or immature plasma cells).

Freeze Fracturing↗
PubMed1988

Factor analysis of plasma lipoprotein components.

Serum phospholipids were analyzed for their content of long-chained fatty acids together with other components of lipoproteins (total- and HDL-cholesterol, apolipoproteins A-I and B, triglycerides), in 60 coronary heart disease patients and 30 control individuals. Some of the individual variations in content of the various components showed co-variation with each other. This formed the basis for the extraction of 7 'factors' by the statistical procedure 'factor analysis'. Analysis of variance was performed with the 'factor scores' for subgroups of high and low age and high and low total serum cholesterol. The analysis revealed two unexpected factors which discriminated with statistical significance between young, hypercholesterolaemic patients and controls. One factor was a positive risk factor and the other a negative one. They could possibly be dependent on the existence of two at present uncharacterized subgroups of lipoproteins. These lipoproteins contained, according to the analysis, large amounts of certain fatty acids. It is suggested that fatty acid analysis might be useful in the characterization of lipoproteins that are involved in the development of atherosclerosis.

Aged↗
PubMed1988

Effects of lovastatin alone and in combination with cholestyramine on serum lipids and apolipoproteins in heterozygotes for familial hypercholesterolemia.

We have studied the effect of lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase), alone and in combination with the bile acid sequestrant cholestyramine on lipid parameters in 30 heterozygous patients with familial hypercholesterolemia (FH) during a 20-week open trial. Lovastatin 40 mg bid (twice daily) decreased significantly total serum cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides and apolipoprotein B by 36%, 45%, 29% and 11%, respectively, while high density lipoprotein (HDL)-cholesterol and apolipoprotein A-I were increased significantly by 16% and 37%, respectively. These data are consistent with a reduction in both the number of LDL particles and in their cholesterol content. Addition of cholestyramine 4 g bid caused a significant further decrease in total serum cholesterol and LDL-cholesterol to a total of 43% and 61%, respectively. The addition of 4 g bid or 8 g bid of cholestyramine caused only minor changes in the other lipid parameters. No effect was found by these drugs on Lp(a) lipoprotein level. We conclude that lovastatin alone or in combination with a small dose of cholestyramine normalizes the lipid profile in most FH heterozygotes.

Adult↗
PubMed1988

Isolated rat liver perfusion studies with cyclic heptapeptide toxins of Microcystis and Oscillatoria (freshwater cyanobacteria).

Isolated perfused rat livers were used to study the dose-dependent effects of three cyclic heptapeptide toxins isolated from Norwegian freshwater bloom samples containing Microcystis aeruginosa, Oscillatoria agardhii var. and Oscillatoria agardhii var. isothrix. The high pressure liquid chromatography (HPLC) purified toxins had an i.p. LD50 in the rat and mouse of approximately 50, 500 and 1000 micrograms/kg, respectively. Hepatic insult of the toxins at concentrations of 0.5-4.0 times the rat i.p. lethal dose were assessed by monitoring bile flow, accumulation of total protein in the perfusate, release of intracellular enzymes and histopathologic examination of perfused liver tissue. One hundred micrograms of Microcystis toxin produced cessation of bile flow during a 1 hr perfusion period, while the two Oscillatoria toxins required 1000 and 2000 micrograms of toxin, consistent with their lower LD50 values. Hepatic cell membranes remained intact during the perfusion since release of enzymes and proteins into the perfusate was similar for toxin treated and control livers, and histopathologic examination of Trypan Blue infused livers revealed exclusion of the dye from the intracellular compartment of the parenchyma. Histopathologic findings for all three toxins showed hepatocellular disassociation that increased with toxin concentration. At the ultrastructural level, all three toxins caused dose-dependent vesiculation of rough endoplasmic reticulum, formation of concentric whorls composed of rough-ER, mitochondrial swelling, large cytoplasmic vacuoles and altered bile canaliculi. These changes were similar to those found for previous in vivo studies using Microcystis cyclic heptapeptides from Scotland and Australia. The Oscillatoria toxins required five to ten times more toxin to produce similar effects as the Microcystis toxin. At the higher concentrations, the Oscillatoria toxins also caused a proliferation of smooth-ER. The isolated perfused rat liver was found to be a good model for studying the hepatocellular effects of different cyclic peptide toxins from cyanobacteria.

Animals↗
PubMed1988

Familial aggregation of congenital dislocation of the hip in a Norwegian population.

Previous studies of congenital dislocation of the hip have not used adequate control groups in estimating the level of genetic influence on that trait. Furthermore, it could not be demonstrated that alleged maternal effects were not an artifact of reporting bias. To that end, information was obtained on the presence of the anomaly in the families of adult twins and their spouses participating in the Norwegian Twin Registry. The prevalence odds ratio for having that disorder in first degree relatives was 10.0. Stratifying by class of relatives, the prevalence odds ratio was 8.1 for fathers, 35.8 for mothers, 12.7 for siblings, and 3.3 for offspring. The increased prevalence odds ratio for mothers over that of fathers suggests a maternal effect. Since both males and females reported on the anomaly for each parental type, it is unlikely that the difference in prevalence odds ratios is due to general reporting bias.

Diseases in Twins↗
PubMed1988

Photodynamic effects of Photofrin II on cell division in human NHIK 3025 cells.

Human cervix carcinoma cells of the line NHIK 3025 were exposed to light after 18 h incubation with Photofrin II. After this photodynamic treatment cells in the interphase were retarded with respect to entry into mitosis for a period which increased with increasing light dose. Following the prolonged interphase, an increase in the mitotic index was observed, giving rise to a 3-fold higher level of mitotic cells compared to the control level. Staining of methanol-fixed cells with the DNA-specific dye mithramycin indicated that the increase in mitotic index was due to a prolongation of the metaphase. For all the light doses studied most of the metaphase cells could be characterized as three-group metaphases or c-metaphase-like structures for the first 8 h after treatment. An approximately 10-fold increase above the control level in the number of tripolar mitoses was also observed. A 2h incubation in a Photofrin II-free medium after the 18 h incubation with Photofrin II and before light exposure reduced the fluorescence of the cells by 30 per cent. However, this wash-out period had no effect on the increase in mitotic index after light exposure. A light dose corresponding to 80 per cent survival (as assayed on asynchronous cells) was given to cells in mitosis after Photofrin II incubation. This treatment delayed more than 90 per cent of the metaphase cells from entering the anaphase for at least 1 h. Cells photodynamically treated in the anaphase and telophase entered the interphase at a similar rate as control cells. These observations indicate a temporary block in the initiation of the anaphase and a prolongation of the metaphase. A microscopic study of cells immunologically stained for beta-tubulin 1 h after photodynamic treatment indicated that the organization of the spindle apparatus was disturbed by the photodynamic treatment. Such perturbations are suggested to be the cause of the observed accumulation of cells in mitosis.

Cell Division↗
PubMed1988

Normal DNA polymorphism at the low density lipoprotein receptor (LDLR) locus associated with serum cholesterol level.

A restriction fragment length polymorphism (RFLP) at the low density lipoprotein receptor (LDLR) locus detectable with the restriction enzyme PvuII exhibits association with total serum cholesterol level. People who are homozygous for absence of the PvuII restriction site have a significantly higher total cholesterol level than heterozygotes (the number of homozygotes for presence of the restriction site was too small to permit meaningful comparison). This difference is significant at the 2% level. Thus, this study of sex- and age-adjusted cholesterol levels in a sample of healthy people yields additional evidence and sustains our previous proposal that normal alleles at the LDLR locus contribute to the population variation in total cholesterol levels. Absence of the PvuII site appears to confer an odds ratio of approximately 2.7 for having a cholesterol level in the top quartile of the population distribution.

Adult↗
PubMed1988

Further evidence for an association between the XbaI polymorphism at the apolipoprotein B locus and lipoprotein level.

Subjects with non-familial hypercholesterolemia who were homozygous for absence of an XbaI restriction site in the apolipoprotein B gene (genotype X2X2) had significantly lower values of apolipoprotein B than those possessing the site. Our data are in agreement with those of Berg (1986) and Law et al. (1986) indicating that X2X2 homozygotes have lower levels of apolipoprotein B, total serum cholesterol, triglycerides and LDL cholesterol. The mechanism underlying this effect is unknown, but could reflect different LDL metabolism between subjects with different genotypes.

Apolipoproteins B↗
PubMed1988

Variability gene effect on cholesterol at the Kidd blood group locus.

The within-pair difference in lipid levels was examined in 142 monozygotic (MZ) twin pairs drawn from the population-based Norwegian Twin Panel. Mean within-pair difference in serum total cholesterol was lower in MZ pairs who were heterozygous for blood group Kidd genes or homozygous for the Jkb gene than in pairs who were homozygous for the Jka gene. The difference between the two categories of homozygotes was significant at the 2% level. The analyses suggest that the main reason for the difference observed is a restrictive effect of the Jkb gene on total cholesterol variability. No effect on triglycerides or HDL cholesterol variability was detected and there was no association between Kidd blood groups and sex and age-adjusted levels of cholesterol, triglycerides or HDL cholesterol. The present data confirm findings we reported when we introduced the study of within-pair variability in MZ twins as a method to analyze gene-environment interactions and validate the "variability gene" concept. A person's net risk for coronary heart disease may depend on his or her combination of "level genes" and "variability genes" as well as on environmental or life-style factors.

Blood Group Antigens↗
PubMed1988

Mutagenicity testing of amniotic fluid from diabetic women, with special reference to their smoking habits.

Amniotic fluid from 16 diabetic and 78 healthy women at term was tested for capacity to cause mutations in Salmonella typhimurium bacterial tester strain TA98 (Ames test). Diabetes as well as heavy smoking increased the mutagenic activity of amniotic fluid. The difference between groups of diabetics and controls was significant in both nonsmokers and women who had smoked more than 5 cigarettes the last 48 h before delivery. It seems plausible that metabolic disturbances, perhaps enhanced by a lowered oxygenation, in some instances could produce mutagenic compounds. Mutagenic activity in amniotic fluid may be one of the factors underlying the increased incidence of congenital malformations in the offspring of diabetic women. Early mutations could cause such developmental errors in the embryos, and possibly also in future generations by damage to germ cells. Heavy smoking alone also caused an increase in mutagenic activity in term amniotic fluid. Our findings reflected an enhancing effect of smoking in diabetes. A pregnant diabetic woman who smoked would thus further endanger her already jeopardized pregnancy.

Amniotic Fluid↗
PubMed1988

Studies of serum lipids in hypercholesterolaemic rabbits treated with doxazosin.

Serum lipids were studied in hypercholesterolaemic rabbits treated with the selective alpha 1-adrenoreceptor antagonist doxazosin. Hypercholesterolaemia had been induced by cholesterol feeding which raised mean (+/- SEM) total serum cholesterol from 1.4 (+/- 0.1) mmol/l to 84.1 (+/- 3.6) mmol/l. A cross-over design was used to compare the effect of doxazosin with placebo in 20 rabbits of which 16 completed the study. Doxazosin (2 mg/kg) or placebo vehicle was administered subcutaneously once daily for three weeks. Compared with placebo, doxazosin produced an 8.6% greater reduction in total serum cholesterol. This difference did not, however, reach statistical significance.

Adrenergic alpha-Antagonists↗