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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 397 records · Page 22Linked to original sources

Twin studies of coronary heart disease and its risk factors.

The ongoing comprehensive study of the updated population-based Norwegian Twin Panel (like-sexed twin pairs born since 1915) has already given results of interest to the research on coronary heart disease and its risk factors. Significantly more dizygotic (DZ) than monozygotic (MZ) pairs are discordant for death between 40 and 60 years of age. Presumably, several of the cases must have been coronary heart disease deaths. In pairs where both members are alive, concordance rate for coronary heart disease before the age of 60 years is significantly higher in MZ than in DZ pairs. Concordance rate for reported hypertension is significantly higher in MZ than in DZ pairs. These findings are compatible with a significant genetic effect on premature death, coronary heart disease and hypertension. There is a strong genetic effect on serum level of apoB, apoA-I and apoA-II, a weaker effect on cholesterol level and a doubtful effect on triglyceride level. Genes belonging to several normal genetic polymorphisms may participate in the control of environmentally/dietary caused variability in lipid and lipoprotein parameters. The study of MZ twins that was conducted to detect these effects holds considerable promise for the detection of gene control of many kinds of quantitative parameters. Further work with this twin panel may provide more definite answers to several questions raised during the present investigation. Application of more sophisticated models for twin family analysis on several normal and pathological traits may be very informative. Also, this updated Norwegian Twin Panel should in the long run make it possible to estimate the predictive value for the second member of a twin pair of having a twin contracting coronary heart disease (or any other reasonably frequent disease) by a given age. Finally, the subsample that is subjected to extensive laboratory analyses will provide useful data for genetic linkage analyses since in many cases, offspring of two members of a MZ pair can effectively be considered as one single (more informative) sibship.

Adult↗

Identification, production, and characterization of murine monoclonal antibody (LO-22) recognizing 12 native species of human alpha interferon.

The present study describes the development of a murine monoclonal antibody (LO-22) directed against 12 native species of HuIFN-alpha. Mice were immunized with purified HuIFN-alpha preparations containing all native species of HuIFN-alpha and spleen cells from immunized mice were fused with P3X63MS1 mouse myeloma cells. Positive hybridoma clones secreting antibodies to HuIFN-alpha were identified by means of a new, extremely sensitive biological semisolid binding assay which was able to disclose positive hybridoma clones consisting of less than 30 hybridoma cells. Antibody affinity columns, made by the LO-22 IgG and monospecific, but polyclonal rabbit IgG, showed identical binding abilities as demonstrated by comparative affinity chromatographies in that the same number of IFN species (12 in total) were found in eluates from parallel experiments. Since LO-22 IgG also recognizes porcine leucocyte interferon, it is suggested that the LO-22 is directed against a common epitope which has been very well conserved in the HuIFN-alpha system, per se. It is suggested that the LO-22 IgG can be used for purification of all HuIFN-alpha proteins--be they recombinantly derived or native--but exerting the common determinant. Preliminary experiments have shown that the LO-22 IgG is highly suitable for ELISA tests.

Animals↗

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↗

Low density lipoprotein receptors in cultured skin fibroblasts from psoriasis patients.

Low density lipoprotein (LDL) receptor activity, measured as 125I-LDL association and degradation at 37 degrees C, was determined in cultured fibroblasts from involved as well as uninvolved skin obtained from 20 psoriasis patients. The same analyses were conducted in fibroblasts from two reference groups consisting of 19 heterozygotes for familial hypercholesterolemia and 16 normal subjects, respectively. Psoriasis patients had significantly lower LDL receptor activity than normals, and it was comparable to that of the heterozygotes for familial hypercholesterolemia. The reduced LDL receptor activity was not accompanied by an increase in total serum cholesterol. The psoriasis patients had a significant reduction in apo-B concentration, but did not differ from the normals in the other serum lipid or lipoprotein parameters. There was no difference in LDL receptor activity between involved and uninvolved skin from psoriasis patients. These results suggest that there is an abnormal cell membrane in dermal fibroblasts from psoriasis patients. Since their total serum cholesterol is normal, their low LDL receptor activity may be confined to dermal cells, leaving the hepatic lipid metabolism normal. The pathogenetic significance of this finding is unknown.

Apolipoprotein A-I↗

Ankylosing spondylitis is part of a multifactorial syndrome: hereditary multifocal relapsing inflammation (HEMRI).

Complex associations between the different subgroups of seronegative arthritis, acute anterior uveitis, psoriasis and inflammatory bowel disease were found in a series of patients and relatives. Different HLA-B antigens were associated with different clinical signs. The results indicated the existence of a multigenic syndrome whose main clinical manifestations are relapsing innflammations at various sites. The genetic factors appeared to be 1) HLA-B27 associated disease susceptibility, 2) predisposition to psoriatic arthropathy, 3) predisposition to early onset familial psoriasis and, 4) a probable predisposition to inflammatory bowel disease and its associated arthropathy. The results indicated that the different genetic factors may interact and influence each other's penetrance and expression.

Arthritis↗

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↗

Family studies in Bechterew's syndrome (ankylosing spondylitis). I. Prevalences of symptoms and signs in relatives of HLAB27 positive probands.

All available adult first-degree relatives of 66 patients with HLAB27 positive ankylosing spondylitis were examined clinically and radiographically and their white blood cells were HLA typed. Ten per cent of all relatives and 20% of HLAB27 positive relatives had Bechterew's syndrome. An additional 10% had minimal radiographical changes in the sacro-iliac joints, or peripheral arthropathy. Sixteen out of 19 persons who had minimal radiographical changes in the sacro-iliac joints were HLAB27 positive. Backache was common (25% or more) in any group of relatives, and did not discriminate well between relatives with or without Bechterew's syndrome. Spine or chest stiffness should prompt examination for Bechterew's syndrome, but is an inadequate diagnostic criterion for the syndrome. Typing for HLAB27 is probably the best prognostic test, although most HLAB27 positive persons did not exhibit any objective sign of disease. Repeated radiographical examination of HLAB27 negative persons should be avoided.

Adult↗

Family studies in Bechterew's syndrome (ankylosing spondylitis). II. Prevalences of symptoms and signs in relatives of HLAB27 negative probands.

All available adult first-degree relatives of 9 probands with HLAB27 negative ankylosing spondylitis were examined. Completion rate was 90%. Prevalences of symptoms and signs and distributions of chest and spinal mobility are presented. No secondary case of Bechterew's syndrome was found among the relatives, compared with 10% among the relatives of HLAB27 positive probands (p = 0.05). We conclude from this study and that of relatives of HLAB27 positive probands, that a HLAB27 negative relative runs a low risk of contracting Bechterew's syndrome, irrespective of the HLAB27 status of the proband.

Adult↗

The gene for apolipoprotein C-II is closely linked to the gene for apolipo-protein E on chromosome 19.

We have used a common TaqI restriction fragment length polymorphism (RFLP) near the human apolipoprotein C-II (apoC-II) gene to study linkage with apolipoprotein E (apoE). The inheritance of the apoC-II RFLP was followed in seven families that were segregating for apoE protein variants. No recombinants were observed in 20 informative meioses, giving an overall lod score of greater than 4.0 at recombination fraction 0. We have also observed apparent linkage disequilibrium between apoE and the apoC-II RFLP. Taken together these results demonstrate that these two apolipoprotein genes are closely linked and confirm that the gene for apoC-II is on human chromosome 19.

Apolipoprotein C-II↗

Molecular heterogeneity in the mild autosomal dominant forms of osteogenesis imperfecta.

Mild osteogenesis imperfecta (OI type I and OI type IV) is characterized by postnatal onset of fractures, absence of skeletal deformity, presenile hearing loss with or without blue sclerae, and dentinogenesis imperfecta. Using one common DNA polymorphism associated with the pro alpha 2(I) human collagen gene, we found genetic heterogeneity in this disorder. In three families, the OI phenotype segregated independently of the DNA polymorphism, whereas in one family, the OI phenotype cosegregated with a DNA polymorphism in a manner suggesting linkage. Use of DNA polymorphisms associated with both type I procollagen genes should provide a tool to unravel the molecular heterogeneity of various heritable disorders of the connective tissue.

DNA Restriction Enzymes↗

Physiological characteristics of high-ability prepubescent wrestlers.

The present study compared the physiological responses to exercise, the anaerobic fitness, and the body composition of high-ability prepubescent wrestlers and normally active boys. The wrestlers (N = 15, mean age +/- S.D. = 11.3 +/- 0.30 yr) were recruited to participate in a summer wrestling camp. Their wrestling experience averaged 3.0 +/- 1.63 yr, during which time they won 78 +/- 10.5% of the matches. The comparison boys (N = 13, 10.7 +/- 0.36 yr) were volunteers from a local Boy's Club. Each subject performed a graded treadmill exercise test (Bruce protocol) and an anaerobic cycle ergometer test. Additionally, body composition was assessed using densitometry and skinfolds. There were no differences (P greater than 0.05) between the wrestlers and the comparison subjects for age or height. The wrestlers exercised for 1.5 min longer on the treadmill and obtained a higher VO2max (54.0 +/- 1.15 ml X min-1 X kg-1, P less than 0.05) than the comparison subjects (45.6 +/- 2.10 ml X min-1 X kg-1). Also, the wrestlers had higher anaerobic test scores, greater body densities, and lower subcutaneous fat totals at all sites than the normally active boys. These data indicate that the favorable fitness and body composition scores found previously for more mature wrestlers are already present in prepubescent wrestlers.

Adipose Tissue↗

13 native human interferon-alpha species assessed for immunoregulatory properties.

Human leukocytes treated with Sendai virus yield interferon predominantly of the alpha-type (HuIFN-alpha). Successful attempts to purify these "native" species have been performed and the final analysis, which included an SDS-PAGE disclosed 13 stained and separated IFN-proteins in the molecular weight-range of 16.6-23.5 kD. These stained IFN proteins were eluted individually from the gel slices and assessed for antiviral activity in human, monkey, and bovine cells, as well as for immunomodulatory effects (in vitro) on human lymphocytes. Based on equal amounts of (human) IFN units, as determined by IFN titration on human cells, the "immunological efficacies" of the 13 different HuIFN-alpha species were determined in three different immunological systems with the following results: (1) Augmentation of the NK function was a property of all species, although the two lower species (16.6 kD, 16.9 kD) were clearly less efficient with "titers" in the NK system reduced 25-fold. (2) Enhanced expression of HLA on lymphocyte membranes was induced by all the HuIFN-alpha species to the same extent. (3) Addition of IFN to mixed lymphocyte reaction (MLR) augmented the CML outcome of the cultures. In this system all 13 species exerted their effect equally well; no clear inferiority or superiority of individual species were seen. It is concluded that the fractionation of the IFN-alpha into 13 species does not give rise to IFN species which are specific only for some functions and not for others. All species exert all functions, although the relatively "immunological" titers in the NK system varied within the species.

Antiviral Agents↗

Seronegative arthropathy and associated diseases--a multigenic syndrome?

Patients hospitalized for psoriasis, acute anterior uveitis, ankylosing spondylitis or with chronic prostatis were examined. From previous reports and our own results we formulated hypotheses of the genetic mechanisms involved. We then examined all available adult relatives of 75 patients with ankylosing spondylitis. Our previously established genetic hypotheses were tested by segregation analyses in these families. All our results point to the existence of a syndrome of distinct but interacting genetic factors. The main factor is the HLA-B27 associated disease predisposition. Manifestation of this predisposition seems to be influenced by sex and by presence of factors coding for psoriasis and/or psoriatic arthropathy. Our results concerning psoriasis and psoriatic arthropathy supported the previous suggestions that these diseases exhibit genetic heterogeneity. It is known that disease signs may be triggered by infection in genetically predisposed persons. The syndrome therefore has a multifactorial aetiology. Seronegative arthropathy is a term that includes all arthritic components of the syndrome. There is a need for a term that encompasses all clinical signs of the genetic factors involved. We propose 'Hereditary multifocal relapsing inflammation' (HEMRI) as a descriptive term for this syndrome. The disease entities included may be regarded as subtypes of the syndrome.

Adult↗

Family studies in Bechterew's syndrome (ankylosing spondylitis) III. Genetics.

The results of segregation analyses in 75 families where the proband had ankylosing spondylitis, are presented. Of the 278 adult, living first degree relatives, approximately 85% cooperated in the study. Clinical and radiographical examinations were performed and HLA typing was conducted. The results were in agreement with our hypothesis that ankylosing spondylitis is part of a syndrome where different genetic factors interact. Such known factors are HLA B27 associated disease susceptibility, susceptibility to psoriatic arthropathy and susceptibility to entero-arthropathy. Radiographical sacro-iliitis was restricted to HLA B27 positive relatives, and was more frequently found in relatives to probands with psoriasis than in relatives to probands without psoriasis. Environmental factors (intestinal bacteria) are known to trigger the disease at least in some persons, and we have postulated that all or most of them have the predisposition to develop disease. Thus, the syndrome has a multifactorial etiology. The phenotypic expressions of the different genetic predispositions involved, include sacro-iliitis, psoriasis, acute anterior uveitis, peripheral arthropathy and inflammatory bowel disease. We suggest the descriptive name HEREDITARY MULTIFOCAL RELAPSING INFLAMMATION (HEMRI) for this syndrome. Ankylosing spondylitis, psoriatic arthropathy and entero-arthropathy may be regarded as clinical sub-types of the syndrome.

Adult↗