Search PubMed⌕ Search

Biomedical subjects

L Berglund

Publications and source records attributed to L Berglund.

At least 91 records · Page 5Linked to original sources
PubMed1998

Assignment of disulfide bridges in bovine CD36.

The multifunctional membrane protein CD36 is expressed on platelets, mature monocytes and macrophages, microvascular endothelial cells and mammary epithelial cells. The exact physiological function of this glycoprotein is unclear. In order to determine the number and pattern of disulfide bridges, CD36 was purified from bovine milk fat globule membranes. The purification procedure involved Triton X-114 extraction, DEAE-Sepharose ion-exchange chromatography and reverse-phase chromatography on a Resource RPC column. The CD36 preparation was used for characterization of the disulfide bridge pattern, which was determined by peptide mapping, amino acid sequence analysis, and matrix-assisted laser-desorption ionization/time of flight mass spectrometry. We have found that there are no free cysteines in CD36 and that the six centrally clustered cysteines are linked by disulfide bonds, Cys242-Cys310, Cys271-Cys332 and Cys312-Cys321, resulting in a 1-3, 2-6 and 4-5 arrangement of the disulfide bridges. These data are in agreement with a model where the protein is oriented so that it has two short intracellular segments (residues 1-6 and 461-471) and two transmembrane domains (residues 7-28 and 439-460), and with four cysteines expected to be acylated placed near the intracellular side of the membrane. The remaining part of CD36 is extracellular, comprising eight glycosylations and three disulfide bridges. In the CD36 family of membrane proteins, it is likely that a similar pattern of disulfide bridges can be found in the sensory neuron membrane protein-1 from the silk moth Antheraea polyphemus and the mammalian scavenger receptor class B type I, whereas lysosome membrane protein II, and epithelial membrane protein from Drosophila melanogaster are both lacking one cysteine in the area of interest.

Amino Acid Sequence↗
PubMed1998

A refined kinetic analysis of plasminogen activation by recombinant bovine tissue-type plasminogen activator indicates two interconvertible activator forms.

Bovine tissue-type plasminogen activator (tPA) was heterologously expressed in the methylotrophic yeast Pichia pastoris and characterized structurally and kinetically. The bovine single-chain tPA-mediated activation of bovine plasminogen was studied in the presence and absence of fibrinogen fragments. We have proposed a refined new method of kinetic analysis which allows examination of both stationary and prestationary phases of this process. The investigation revealed the presence of two interconvertible forms of the recombinant bovine tPA being in equilibrium at a 1 to 50 ratio. Only the minor form was able to bind and activate plasminogen. Saturation of the whole pool of tPA required high plasminogen concentration (Km >/= 5 microM) in order to reverse the equilibrium between the two forms. Fibrinogen fragments activated the single-chain tPA due to preferential binding and stabilization of the minor "active" form of the enzyme until all the molecules of tPA were converted. The same mechanism could be applied to human tPA as well. The Km values, obtained for recombinant bovine and human tPA in the presence of fibrinogen fragments, were found to be similar (Km = 0.1 microM) while kcat of human tPA was 5-10 times higher.

Animals↗
PubMed1998

Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29.

OBJECTIVE: To establish whether fetal growth rate (as distinct from size at birth) is associated with mortality from ischaemic heart disease. DESIGN: Cohort study based on uniquely detailed obstetric records with 97% follow up over the entire life course and linkage to census data in adult life. SUBJECTS: All 14 611 babies delivered at the Uppsala Academic Hospital, Sweden, during 1915-29 followed up to end of 1995. MAIN OUTCOME MEASURES: Mortality from ischaemic heart disease and other causes. RESULTS: Cardiovascular disease showed an inverse association with birth weight for both men and women, although this was significant only for men. In men a 1000 g increase in birth weight was associated with a proportional reduction in the rate of ischaemic heart disease of 0.77 (95% confidence interval 0.67 to 0.90). Adjustment for socioeconomic circumstances at birth and in adult life led to slight attenuation of this effect. Relative to the lowest fourth of birth weight for gestational age, mortality from ischaemic heart disease in men in the second, third, and fourth fourths was 0.81 (0.66 to 0.98), 0.63 (0.50 to 0.78), and 0.67 (0.54 to 0.82), respectively. The inclusion of birth weight per se and birth weight for gestational age in the same model strengthened the association with birth weight for gestational age but removed the association with birth weight. CONCLUSION: This study provides by far the most persuasive evidence of a real association between size at birth and mortality from ischaemic heart disease in men, which cannot be explained by methodological artefact or socioeconomic confounding. It strongly suggests that it is variation in fetal growth rate rather than size at birth that is aetiologically important.

Adolescent↗
PubMed1998

Plasma levels on nociceptin in female fibromyalgia syndrome patients.

Fibromyalgia syndrome (FMS) is a frequent pain disorder in women. The pathophysiologic mechanism behind this disorder is still unexplained; however, alterations in both monoamines, neuropeptides and in the stress axis have been found. This study was designed to determine the levels of the newly discovered neuropeptide nociceptin in hormonally different FMS patients and corresponding controls. The results showed that the nociceptin concentrations of the patients were lower than in controls. It also showed decreased levels with significant differences between the cyclic patients in the luteal phase of the menstrual cycle, compared to the corresponding controls. Our results suggest that the perturbed nociceptin concentrations of the FMS patients may be linked to both the sex hormones and to the stress system and that these changes might be one of several possible pathophysiologic mechanisms involved in the FMS.

Adult↗
PubMed1998

Hepatic cholesterol metabolism in experimental nephrotic syndrome.

Hypercholesterolemia is a consistent feature of the nephrotic syndrome. However, the mechanisms underlying this perturbation are unclear. In the present work, we have investigated different factors that influence hepatic cholesterol metabolism using the nephrotic rat as a model. The induction of nephrosis resulted in a severe and sustained hypercholesterolemia. However, no effect on the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl CoA reductase, could be detected. Further, plasma lathosterol/cholesterol ratio, a measure of cholesterol synthesis, was not altered. Also, plasma levels of mevalonate, both a substrate for cholesterogenesis beyond the rate-limiting step and a marker for cholesterol synthesis, did not differ between control rats and those with established hypercholesterolemia. There was no detectable change in the expression of low density lipoprotein (LDL) receptor between the two experimental groups. We conclude that the early increase in cholesterol synthesis reported after the induction of nephrosis is not necessary for the maintenance of hypercholesterolemia. Established hypercholesterolemia of the nephrotic syndrome seems to represent a steady state in which neither enhanced hepatic cholesterol synthesis nor retarded LDL cholesterol clearance is of major importance.

Animals↗
PubMed1998

Lipid and lipoprotein levels remain stable in acute ischemic stroke: the Northern Manhattan Stroke Study.

Serum lipoproteins including lipoprotein(a), Lp(a), are emerging as possible biological markers for cerebrovascular disease. Existing data on Lp(a) and serum lipids levels following acute ischemic stroke (AIS) are however equivocal. To determine whether serum Lp(a) and other lipid levels obtained within 24 h of acute ischemic stroke onset changed over the ensuing 4 weeks and whether these levels are related to an acute phase response, acquired nutritional deficiency, and neurovascular data, we conducted repeated measurement analyses among 19 subjects (mean age 65.0 +/- 12.1 years; 32% women) presenting with AIS (evaluated within 9.7 +/- 12.7 h). Eleven of the subjects had a moderate-to-severe stroke, defined by NIH stroke severity scale, and seven patients had a large cerebral infarction. Seven serial measurements of Lp(a), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and other lipoproteins, major acute phase reactants and albumin levels were collected for each subject over 4 weeks. The mean initial levels, (mg/dl), of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Lp(a), apolipoproteins A-I and B were: 225 +/- 57.6, 154 +/- 56.0, 40 +/- 10.4, 181 +/- 93.7, 52 +/- 28.6, 130 +/- 24.6, and 141 +/- 46.1, respectively. There were no significant changes in mean serum lipid, apolipoprotein or Lp(a) levels over the 4-week study period, analyzed by a random effects model to test for time trend. In addition, there were no significant changes in established acute phase or nutritional markers (C-reactive protein, alpha 1-glycoprotein, haptoglobin or serum albumin). Our findings suggest that serum lipid, apolipoprotein and Lp(a) levels remain stable following AIS, consistent with the absence of acute phase response or nutritional deficiency.

Acute Disease↗
PubMed1998

Apo(a)-isoform size, nutritional status and inflammatory markers in chronic renal failure.

Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. Levels of lipoprotein (a) [Lp(a)], an established cardiovascular risk factor, are elevated in uremic patients. Moreover, low serum albumin levels indicating malnutrition have been associated with elevated plasma Lp(a) levels in dialysis patients. However, serum albumin levels are also influenced by an inflammatory reaction. The present study was undertaken to further investigate the relationship between Lp(a), inflammation and malnutrition in patients with chronic renal failure (CRF) prior to the initiation of renal replacement therapy, and to investigate the potential relation between these factors and apo(a)-isoform size, an important determinant of plasma Lp(a) levels. A total of 83 patients (mean age 52 +/- 1 year) with terminal (creatinine clearance 9 +/- 1 ml/min) CRF were cross sectionally investigated. In addition to lipid parameters and apo(a)-isoform size, C-reactive protein (CRP), nutritional parameters including serum levels of albumin and body composition (dual energy x-ray absorptiometry), as well as a subjective global assessment (SGA) and the prevalence of cardiovascular disease (CVD) were evaluated. Malnourished patients (N = 39) had a significantly (P < 0.05) higher median plasma Lp(a) level (19.5 mg/dl) as compared to 44 well-nourished patients, (11.7 mg/dl). No difference was found for other lipid or lipoprotein parameters. A significant relationship was found between CRP and plasma Lp(a), whereas no significant relation was observed between plasma Lp(a) and serum albumin levels. The apo(a)-isoform distribution was similar among malnourished and well-nourished patients. There was no difference in nutritional parameters when comparing patients with small- and large-size apo(a) isoforms. However, a subgroup of patients (12%) with no detectable apo(a)-bands and low Lp(a) levels had significantly higher lean body mass. The present study demonstrates elevated plasma Lp(a) levels in CRF patients with signs of malnutrition, even though no direct relationships between plasma Lp(a) levels and various nutritional parameters were observed. The observed relationship between Lp(a) and CRP suggests that inflammatory factors, more prevalent in patients with malnutrition, may contribute to the Lp(a) increase in malnourished CRF.

Adult↗
PubMed1998

Validation of an oscillometric blood pressure measuring device: a substudy of the HOT Study. Hypertension Optimal Treatment.

The accuracy of a semi-automated oscillometric blood pressure measuring device (Visomat OZ D2 International) was studied by simultaneous comparison with a standard sphygmomanometer in 407 normotensive subjects and hypertensive patients. Four pairs of measurements, at least 1 min apart, were obtained from all patients. The oscillometric device tended to give lower measurements than the standard device; the mean difference was -0.9 mmHg for diastolic blood pressure and -6.4 mmHg for systolic blood pressure. The size of this difference was not dependent on the mean blood pressure. Intra-individual standard deviations were similar with the two techniques. The oscillometric device tended to produce higher readings on the first measurement than on the subsequent three, whereas the reverse was true of the standard sphygmomanometer. It is concluded that the oscillometric device used in the HOT Study provides reliable measurements of blood pressure. The slight difference in mean readings between the two methods is unlikely to be of importance for the comparison of differences in treatment blood pressure values in the HOT Study.

Automation↗
PubMed1998

Plasminogen activator inhibitor-1 activity is independently related to both insulin sensitivity and serum triglycerides in 70-year-old men.

Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been discussed as a part of the insulin resistance syndrome. However, it is not clear whether the relationship between PAI-1 and insulin resistance is independent of or mediated by increased triglycerides levels. The aim of this study was to investigate whether PAI-1 activity is associated with insulin sensitivity independently of serum triglycerides (sTG) and of other potential confounders. Seventy-year-old men (n=871), participating in a cohort study undergoing extensive metabolic investigations, had blood samples taken for determination of PAI-1 activity. Insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp. In multivariate correlation and regression analyses, insulin sensitivity was a statistically significant determinant of PAI-1 activity (partial r=-.12; P<.001), independent of sTG, body mass index, waist-hip ratio, and other potential confounders. The levels of sTG were also independently related to PAI-1 activity (partial r=.18; P<.001). The relationships between PAI-1 and insulin sensitivity and sTG were independent of fasting glucose levels. Aggregation of risk factors of the insulin resistance syndrome was associated with increased activity of PAI-1 in men with normal glucose tolerance. We conclude that PAI-1 activity is related to insulin sensitivity and sTG, independently of each other and of other potential confounders, and that increased levels of PAI-1 should be regarded as a component of the insulin resistance syndrome.

Aged↗
PubMed1998

Doping among high school students in Uppsala, Sweden: A presentation of the attitudes, distribution, side effects, and extent of use.

The aim of this study was to determine the extent of doping drug use among adolescents in Uppsala, Sweden, and to analyse the main reasons for the use. An anonymous multiple-choice questionnaire was distributed among pupils in the first and the third grades at high school; 2,742 pupils participated in the study. The results showed that 2.7% of the male and 0.4% of the female adolescents had used doping drugs at some time in their life. However, knowledge of how to get doping drugs far exceeded use. The main reasons for using doping drugs were to improve appearance and to enhance performance in sports. Some boys self-reported side effects of AAS. Despite the still predominantly negative attitude toward doping prevention programs have to be taken.

Adolescent↗
PubMed1998

Three-fold effect of lovastatin treatment on low density lipoprotein metabolism in subjects with hyperlipidemia: increase in receptor activity, decrease in apoB production, and decrease in particle affinity for the receptor. Results from a novel triple-tracer approach.

To differentiate effects of lovastatin on low density lipoprotein (LDL) receptor activity from effects on LDL metabolic properties, LDL apolipoprotein B (apoB) turnover was studied in eight hyperlipidemic subjects during baseline and lovastatin treatment, in the latter case with LDL tracers isolated during both baseline (CLDL) and drug treatment (Rx-LDL) conditions. Lovastatin (40 mg/day) significantly lowered total plasma and LDL cholesterol levels (27% and 25%, respectively) as well as plasma triglyceride levels (30%). Using contemporaneous tracers (C-LDL before and Rx-LDL during treatment), lovastatin caused a modest increase in LDL fractional catabolic rate (FCR) (0.410+/-0.113 vs. 0.339+/-0.108 pools/day, P < 0.04 by paired t). The increase in LDL tracer FCR was higher when C-LDL tracer isolated during the untreated period was injected during lovastatin treatment (0.496+/-0.177 vs. 0.339+/-0.108 pools/day, P < 0.02). These in vivo studies in humans were confirmed by injecting LDL tracers from two patients into five guinea pigs. The C-LDL tracer was cleared consistently faster than the Rx-LDL tracer (0.082+/-0.018 vs. 0.057+/-0.015 pools/h, P< 0.001). The results demonstrate three important outcomes of lovastatin treatment in these subjects: LDL receptor activity increased by 49% (P < 0.02); LDL apoB production rate decreased by 17% (P < 0.03), and LDL particle in vivo affinity for the LDL receptor decreased by 15% (P < 0.01). The decrease in LDL particle affinity partially negated the expected effect of increased LDL receptors on LDL clearance. The present study provides an explanation for earlier observations by several investigators using contemporaneous tracers that treatment with HMG-CoA reductase inhibitors resulted in only modest increases in low density lipoprotein functional catabolic rate.

Adult↗
PubMed1997

Cloning of the murine tetranectin gene and 5'-flanking region.

The gene encoding murine tetranectin (Tna) and its 5'-flanking region was isolated and cloned from a EMBL3 SP6/T7 genomic library. The compiled nucleotide sequence was determined by sequencing, revealing a conserved Tna structure in man and mouse. Mapping of the transcription start point (tsp) suggests that murine Tna has more than one of these. In addition, no consensus TATA-box was found uptream for the putative tsp(s) in the 5'-flanking region of the gene, indicating that the murine Tna promoter belongs to the TATA-less class of genes. The cloned murine Tna was mapped to region F1-F3 on mouse chromosome 9 by fluorescence in situ hybridization (FISH).

Animals↗
PubMed1997

Subendothelial retention of lipoprotein (a). Evidence that reduced heparan sulfate promotes lipoprotein binding to subendothelial matrix.

Vessel wall subendothelial extracellular matrix, a dense mesh formed of collagens, fibronectin, laminin, and proteoglycans, has important roles in lipid and lipoprotein retention and cell adhesion. In atherosclerosis, vessel wall heparan sulfate proteoglycans (HSPG) are decreased and we therefore tested whether selective loss of HSPG affects lipoprotein retention. A matrix synthesized by aortic endothelial cells and a commercially available matrix (Matrigel; , Rutherford, NJ) were used. Treatment of matrix with heparinase/heparitinase (1 U/ml each) increased LDL binding by approximately 1.5-fold. Binding of lipoprotein (a) [Lp(a)] to both subendothelial matrix and Matrigel(R) increased 2-10-fold when the HSPG were removed by heparinase treatment. Incubation of endothelial cells with oxidized LDL (OxLDL) or lysolecithin resulted in decreased matrix proteoglycans and increased Lp(a) retention by matrix. The effect of OxLDL or lysolecithin on endothelial PG was abolished in the presence of HDL. The decrease in matrix HSPG was associated with production of a heparanase-like activity by OxLDL-stimulated endothelial cells. To test whether removal of HSPG exposes fibronectin, a candidate Lp(a) binding protein in the matrix, antifibronectin antibodies were used. The increased Lp(a) binding after HSPG removal was inhibited 60% by antifibronectin antibodies. Similarly, the increased Lp(a) binding to matrix from OxLDL-treated endothelial cells was inhibited by antifibronectin antibodies. We hypothesize that atherogenic lipoproteins stimulate endothelial cell production of heparanase. This enzyme reduces HSPG which in turn promotes Lp(a) retention.

Animals↗
PubMed1997

Bovine PAS-6/7 binds alpha v beta 5 integrins and anionic phospholipids through two domains.

Bovine milk fat globule membranes are a rich source of glycoproteins PAS-6 (52 kDa) and PAS-7 (47 kDa). They are glycosylation variants sharing a common polypeptide core. The PAS-6/7 protein consists of two EGF-like domains and a tandem repeated structure with a high degree of similarity to the C1 and C2 domains found in blood-clotting factors V and VIII. The second EGF-like domain contains an RGD cell adhesion sequence with the possibility of binding integrins, while the C-terminal end of the C2-like domain contains a probable amphipathic alpha-helix. Using a PAS-6/7 column, bovine alpha v beta 5 integrin was purified from mammary gland tissue by affinity chromatography and characterized by Western blotting and N-terminal sequencing. The interaction between PAS-6/7 and the alpha v beta 5 integrin was shown to be RGD dependent. Lipid binding assays showed that PAS-6/7 binds to surfaces of phosphatidylserine, -inositol, and -glycerol, and their precursor, phosphatidic acid, but not phosphatidylcholine. Furthermore, PAS-6/7 displayed the highest affinity toward a total lipid fraction derived from the milk fat globule membrane as compared to pure phospholipids. Using Western blotting technique, PAS-6/7 was shown to be widely expressed in a number of tissues. These results show that PAS-6/7 is a common protein which can bind to membranes by two distinct mechanisms, one through affinity to integrin alpha v beta 5 and another by direct binding to phospholipids.

Amino Acid Sequence↗