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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 433 records · Page 24Linked to original sources

HLA phenotypes and joint affection in psoriasis, acute anterior uveitis and chronic prostatitis.

In a prospective study, 50 patients hospitalized for psoriasis, 34 patients hospitalized for acute anterior uveitis (AAU) and 29 patients hospitalized for chronic prostatitis, were examined. The expected increased frequencies of HLA B13 and HLA B17 in psoriasis and of HLA B27 in AAU over healthy people were found. No unsuspected association between HLA antigens was observed. Psoriatic patients with peripheral joint affection frequently had affected sacro-iliac joints and were HLA B27 negative. Joint affection was frequently seen in HLA B27 positive patients with psoriasis or AAU. In the patients with AAU, 12 out of 22 patients positive for HLA B27 exhibited radiographical sacro-iliitis. This high prevalence of sacro-iliitis suggests an interaction between genes predisposing for AAU and sacro-iliitis. Asymptomatic sacro-iliitis was found in both HLA B27 positive and negative patients. The low frequency of clinical symptoms in psoriatic sacro-iliitis could not be explained by the absence of HLA B27.

Female↗

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↗

Lp(a) lipoprotein enters cultured fibroblasts independently of the plasma membrane low density lipoprotein receptor.

Lp(a) lipoprotein shares the apoB antigen with low density lipoprotein (LDL). The Lp(a) antigen is unique for Lp(a) lipoprotein. Fibroblast association (i.e. plasma membrane binding plus intracellular accumulation), plasma membrane binding, intracellular accumulation and degradation of 125I-Lp(a) lipoprotein were studied in strains from subjects with or without autosomal dominant hypercholesterolemia (HC). Subjects without HC (non-HCs) have cell surface receptors for low density lipoprotein (LDL receptors). On the average, HC heterozygotes have half-normal LDL receptor activity and "receptor-negative" HC homozygous cell strains lack functional receptors. Fibroblast processing of 125I-Lp(a) lipoprotein was compared to fibroblast processing of 125I-LDL. LDL receptor-dependent processing of 125I-LDL was saturated at about 50 microgram apo 125I-LDL.ml-1 in non-HC fibroblasts. 125I-Lp(a) lipoprotein was, however, largely processed independently of receptor mechanisms by non-HC cells (highest concentration examined 150 microgram apo 125I-Lp(a) lipoprotein . ml-1). Lp(a) lipoprotein did not interfere with 125I-LDL for fibroblast association, but inhibited 125I-LDL degradation. The interference with 125I-LDL degradation was time dependent. Only slightly higher 125I-Lp(a) lipoprotein processing values were found in non-HC and HC heterozygous strains than in "receptor-negative" HC homozygous strains. However, non-HC cells had more than tenfold higher 125I-LDL processing values than "receptor-negative" HC homozygous cells.

Adolescent↗

The apoE polymorphism studied by two-dimensional, high-resolution gel electrophoresis of serum.

The apoE polymorphism of human very low density lipoprotein (VLDL) was studied by the two-dimensional high-resolution gel electrophoresis technique of O'Farrell, which combines isoelectric focusing and SDA-polyacrylamide gel electrophoresis. With whole serum, six major patterns and two "sub-variants" of apoE were observed. A series of twin pairs (21 monozygotic (MZ) and 13 dizygotic (DZ) pairs) as well as unrelated people were analyzed. both members of MZ pairs always exhibited the same pattern, whereas DZ twins were often discordant. The patterns observed would be consistent with the hypothesis that three apoE isopeptides are coded for by three different alleles at one single locus. In this small series, all three postulated homozygous patterns, namely apoE-II, apoE-III and apoE-IV as well as the three heterozygous patterns apoE-II,III; apoE-III,IV and apoE-II,IV were seen.

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↗

Interferon enhances the antibody-dependent cellular cytotoxicity (ADCC) of human polymorphonuclear leukocytes.

Polymorphonuclear leukocytes (PMN) from healthy volunteers were tested for ADCC activity against both erythrocyte and tumor targets with and without the addition of human leukocyte interferon (IFN). It was demonstrated that IFN within 30 to 60 min enhanced the reaction in a dose-dependent manner with minimal IFN doses ranging from 1 to 100 units. Formal proof that the augmenting agent was IFN was obtained by using pure IFN proteins in combination with both mock-IFN preparations, which showed no enhancing activity, and anti-IFN antisera, which inhibited the action of the completely purified IFN proteins. In the light of data demonstrating that the IFN effect was most pronounced when the IgG antibodies in the ADCC reaction were present in suboptimal amounts, it is hypothesized that IFN may play a special role in the early nonspecific immune response against non-self antigens.

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↗

Genetics of the low density lipoprotein receptor: III. Evidence for multiple normal alleles at the low density lipoprotein receptor locus.

Fibroblast association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated low density lipoprotein (125I-LDL) index plasma membrane LDL receptor activity. Cultured fibroblasts from 23 subjects affected with familial hypercholesterolemia (HC) and from 95 subjects without HC (non-HCs) were tested for 125I-LDL association and degradation. Both LDL receptor activity indices were twice as high in non-HC and HC heterozygous cell strains. This is compatible with a major gene effect on LDL receptor activity. However, a considerable overlap between non-HC and HC heterozygous values was found in the 125I-LDL association assay [median (range) 970 (330-2500), and 450 (250-490), respectively] and in the degradation assay [median (range) 810 (280-2020), and 470 (160-790), respectively]. The values are expressed as ng 125I-LDL X mg cell protein-1 X 4.5 h-1. These great overlaps in the LDL receptor activity indices support the view that the influence of LDL receptor activity on the HC phenotype may be smaller than believed previously. Furthermore, for the diagnosis of HC, these LDL receptor activity assays are far more expensive and have less sensitivity and specificity than simple serum cholesterol determination. The LDL receptor-dependent 125I-LDL association values for the HC heterozygous individuals clustered into four groups. Family data supported the hypothesis that this variation could be due to four different LDL receptor variants, each coded for by different alleles at the LDL receptor locus. If confirmed, this finding may have implications for the understanding of the variable expression of HC and also of the genetic impact on lipoprotein metabolism and susceptibility to atherosclerosis in non-HCs.

Adolescent↗

Serum reserve cholesterol binding capacity (SRCBC): the relative importance of different lipoprotein classes.

Findings by several authors have motivated studies in our laboratory on the relationship between HDL and "serum reserve cholesterol binding capacity" (SRCBC). We found that incubation for 25 hours at 37 degrees C provided optimal conditions for uptake and saturation when 14 mg sonicated and pulverized cholesterol was added to 1 ml serum. Upon separation of serum to which 14C labelled cholesterol had been added, into lipoprotein classes, a higher cpm:protein ratio than expected (from the free cholesterol:protein ratio, assuming isotope exchange exclusively) was found in LDL and the HDL fraction. In a second series of experiments, the different lipoprotein classes were separated prior to addition of 14C-cholesterol. The highest capacity for uptake of labelled cholesterol was found in the HDL fraction. The major part of the 14C-cholesterol appeared in the LDL density area when this HDL fraction was subjected to repeated ultracentrifugation. This suggested that the uptake of added cholesterol by HDL had led to the formation of an altered particle with density characteristics similar to those of LDL particles. This was confirmed by the demonstration of a "new" particle which contained apoA-I, apoA-II, and apoE, but no apoB or Lp(a) antigen. Its electrophoretic mobility was similar to that of HDL. Electron microscopy revealed that this particle is larger than normal HDL. The findings suggest that a sub-population of HDL molecules may be responsible for serum binding of added excess cholesterol.

Apolipoprotein A-I↗

The effect of Gemfibrozil on human serum apolipoproteins and on serum reserve cholesterol binding capacity (SRCBC).

The lipid lowering drug Gemfibrozil significantly increased the levels of HDL-apoproteins, apoA-I and apoA-II in a group of 20 Swedish hyperlipemic males who were given 1200 mg daily of the drug for 8 weeks and thereafter submitted to a 4 weeks placebo period. It strikingly increased serum reserve cholesterol in binding capacity (SRCBC). No change was observed in "free" apoA-I or inthe level of Lp(a) lipoprotein. The results suggest that the effect of Gemfibrozil on HDL, may be particularly striking on a subclass (or on subclasses) of HDL responsible for most of SRCBC. The findings suggest that Gemfibrozil may become a useful drug for hyperlipidemic people, if its safety in pharmacological doses can be established.

Apolipoproteins↗

SDS-polyacrylamide gel electrophoresis of purified human leucocyte interferon and the antiviral and anticellular activities of the different interferon species.

Human leucocyte interferon (HuLeIF) was purified by a series of techniques involving precipitation, gel filtration, Cu-chelate-, blue dextran- and antibody-affinity chromatography. The two major species of HuLeIF were identified in SDS-PAGE as two clearly separable and stainable proteins representing 85% of the biological activity. Three more species of HuLeIF representing 15% of the biological activity were also demonstrated. The specific activity of pure interferon proteins was approx. 10(9) IFU/mg protein. Recovery was about 50% and the purification factor exceeded 350000. All five species of HuLeIF had definite anticellular activities when tested with Daudi cells (inhibition of thymidine uptake).

Cell Division↗

The complete purification of human leucocyte interferon.

Human leucocyte interferon (HuLeIF) has now for the first time been purified by a series of techniques involving precipitation, gel filtration, and affinity chromatography with Cu-chelate, blue dextran, and antibody. The two major species of HuLeIF were identified as two clearly separable and stainable proteins representing 85% of the biological activity with molecular weights of 18,400 and 20,180 daltons. Three more subspecies of HuLeIF were demonstrated with molecular weights of 19,500, 20,900 and 22,130 daltons, representing 15% of the biological activity. Specific activity of pure interferon is 2 x 10(9) interferon units/mg protein. Recovery was about 50%, and the purification factor exceeded 350,000.

Antibody Affinity↗