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Biomedical subjects

L Berglund

Publications and source records attributed to L Berglund.

At least 19 recordsLinked to original sources
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↗
PubMed1997

Primary structure of EPV20, a secretory glycoprotein containing a previously uncharacterized type of domain.

A 20-kDa glycoprotein, EPV20, was isolated from bovine milk and characterized. The primary structure was determined by cDNA and protein sequencing combined with mass spectrometry. EPV20 is a 130-residue polypeptide synthesized with a 19-residue signal peptide. The function of EPV20 is unknown, but it displays 79% sequence similarity to a putative protein deduced from a human testis cDNA sequence designated HE1 (human epididymis clone 1) (Kirchhoff, C., 1992. EMBL/GeneBank/DDBJ Databases, accession number X67698). Northern blot analysis showed the bovine EPV20 to be expressed in kidney, spleen, liver and mammary gland, but remarkably not in bovine testis. The six Cys residues of EPV20 were found to be disulfide-linked in a 1-6, 2-3 and 4 5 pattern. This disulfide arrangement has been observed in other proteins, e.g. in human prostatic acid phosphatase, but the spacing between the cystines differs. Therefore, EPV20 represents a new structure among the large group of proteins containing domains with three disulfide bonds.

Amino Acid Sequence↗
PubMed1997

Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM.

Mutations in the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene cause the type 1 form of maturity onset diabetes of the young (MODY1). To address the question of whether genetic variability of HNF-4alpha is associated with late onset non-insulin-dependent diabetes mellitus (NIDDM) we have sequenced the coding region and intron/exon boundaries of the gene in 36 randomly recruited Danish NIDDM patients. Two nucleotide substitutions that changed the sequence of HNF-4alpha were identified: Thr/Ile130, which has been reported previously and a novel Val/Met255. The Val/Met 255 mutation was found in 4 of 477 Danish NIDDM patients and in none of 217 glucose tolerant control subjects; thus it cannot be excluded that this mutation may have an impact on NIDDM susceptibility. Among 509 NIDDM patients the allelic frequency of the Thr/Ile130 variant was 4.7% (95% confidence interval: 3.4-6.0%) compared to 1.9% (0.7-3.1%) among 239 control subjects (p = 0.008). However, in a population sample of 942 Swedish men with an average age of 70 years the allelic frequency of the variant was similar in 246 men with either impaired glucose tolerance (5.6% [2.6-8.6%]) or NIDDM (5.4% [2.7-8.1%]) as compared to 666 glucose tolerant men (5.1% [3.9-6.3%]). Also in a population sample of 369 young healthy Danes the prevalence of the codon 130 variant (4.7% [3.2-6.2%]) was similar to what was found in Swedish Caucasians. Thus, the allelic frequency of the Thr/Ile130 variant among the control subjects in the Danish case-control study deviates from the prevalence in the two other studies which is why we consider the significant association between the codon 130 variant and NIDDM an incidental finding. In glucose tolerant subjects the codon 130 variant in its heterozygous form had no major effect on glucose-induced insulin and C-peptide release although a tendency to a lower insulin secretion during an oral glucose tolerance test was seen in middle-aged subjects. In conclusion, variability in the coding region of the HNF-4alpha gene is not a common cause of NIDDM among whites of Danish ancestry. However, a Val/Met255 mutation was found exclusively in NIDDM patients (0.8% of cases) and functional as well as family segregation studies are needed to determine whether this HNF-4alpha variant is a NIDDM causing mutation.

Aged↗
PubMed1997

On the interrelationship between hepatic carnitine, fatty acid oxidation, and triglyceride biosynthesis in nephrosis.

The nephrotic syndrome is associated with disturbances in plasma lipid pattern and metabolism. However, the reason for these perturbations is poorly understood. In the present study, we have investigated hepatic triglyceride metabolism in puromycin aminonucleoside-induced nephrotic syndrome in rats. Nephrotic rats displayed a 70% increase in hepatic triglyceride levels compared to controls (16.9 +/- 1.6 vs. 9.8 +/- 0.6 mumol/g liver; means +/- SEM, P < 0.01). The capacity for hepatic mitochondrial beta-oxidation of fatty acids was substantially elevated (80%). This was associated with a rise in the liver content of the fatty acid carrier carnitine (1.24 +/- 0.06 vs. 0.85 +/- 0.07 mumol/g dry weight, P < 0.05). A positive correlation between the levels of acetylcarnitine and acetyl-CoA was found in normal as well as in nephrotic rats, implying that carnitine plays an important role as an acetyl group acceptor in the liver under normo- and hyperlipidemic conditions. Changes in carnitine levels seem to be tightly coupled to the rate of fatty acid oxidation. There was a significant elevation in the activity of phosphatidate phosphohydrolase (E.C. 3.1.3.4) in liver microsomes from nephrotic rats (1.07 +/- 0.09 vs. 0.81 +/- 0.04 nmol/min.mg protein, P < 0.02). Hepatic very low density lipoprotein (VLDL)-triglyceride secretion rate was 18% higher in nephrotic rats than in controls. The results demonstrate a deranged hepatic triglyceride metabolism in nephrosis, with an increased hepatic triglyceride biosynthesis, a sizable accumulation of hepatic triglycerides, and only a modest increase in VLDL triglyceride secretion. In addition, mitochondrial beta-oxidation of fatty acids was enhanced, associated with an increased availability of carnitine.

Acetyl Coenzyme A↗
PubMed1997

Bone loss in elderly women prevented by ultralow doses of parenteral 17beta-estradiol.

OBJECTIVES: Our purpose was to assess whether an ultralow dose of parental estradiol, aimed for treatment of vaginal atrophy, affects bone metabolism and bone density. STUDY DESIGN: Thirty healthy women > or = 60 years old were randomly assigned to a 6-month treatment with either an ultralow dose of parenteral estradiol (7.5 microg/24 hours) delivered by vaginal rings or no treatment in the proportion 2:1. RESULTS: Forearm bone density increased in estradiol users by 2.1% (95% confidence interval 0.4 to 3.8, p = 0.008), contrasting to a decrease in nonusers of -2.7% (95% confidence interval -5.9 to 0.4, p = 0.077). In analysis of variance the changes in the two study groups differed significantly (p = 0.0004). Consistently, serum alkaline phosphatases, bone-specific alkaline phosphatases, and osteocalcin concentrations decreased in the treatment group (8%, p = 0.019; 14%, p = 0.0006; and 9%, p = 0.02, respectively), suggesting reduced bone turnover. No significant changes were found in nonusers. CONCLUSION: Ultralow doses of estradiol may potentially prevent bone loss in women > or = 60 years old.

Administration, Intravaginal↗
PubMed1997

Serum calcium: a new, independent, prospective risk factor for myocardial infarction in middle-aged men followed for 18 years.

BACKGROUND: Primary hyperparathyroidism (HPT) is a disease characterized by hypercalcemia, and associated with an increased mortality in cardiovascular diseases. However, serum calcium levels within the normal range have not been evaluated as a prospective cardiovascular risk factor. METHODS: A cohort of males aged 50 (n = 2183) were investigated in 1970-1973 for serum calcium and known cardiovascular risk factors. They were then followed up over the next 18 years. RESULTS: During the follow-up period, 180 subjects experienced a myocardial infarction (MI). The serum calcium levels were significantly elevated at the baseline (2.37 +/- 0.09 SD versus 2.35 +/- 0.09 mmol/l, p < 0.03) in the subjects who developed a MI when compared with the rest of the cohort. Also blood pressure, body mass index (BMI), fasting insulin, serum cholesterol, serum triglycerides, and the atherogenic index were significantly elevated in the MI group (p < 0.01), while HDL-cholesterol was lower at the baseline investigation (p < 0.01). Cox's proportional hazard analysis showed that only serum calcium (p < 0.01), BMI (p < 0.0003), diastolic blood pressure (p < 0.0009), and the atherogenic index (p < 0.002) were significantly independent risk factors for MI. The range of serum calcium levels from the mean value, -2 SDs to the mean value +2 SDs corresponds to a variation in estimated risk for MI ranging from 0.06 to 0.15. CONCLUSIONS: Serum calcium was found to be an independent, prospective risk factor for MI in middle-aged males suggesting a role for extracellular calcium levels in the atherosclerotic process.

Calcium↗
PubMed1997

The alterations in insulin sensitivity during angiotensin converting enzyme inhibitor treatment are related to changes in the calcium/magnesium balance.

The present analysis was undertaken to investigate the relations between alterations in mineral factors, especially the balance between serum calcium and magnesium concentrations (S-Ca and S-Mg, respectively), and variables reflecting glucose and lipid metabolism during angiotensin converting enzyme (ACE) inhibitor treatment. A total of 96 patients with essential hypertension, participating in four double-blind studies with four different ACE inhibitors and similar protocols, were included. At the end of the initial placebo period and at the end of the period of active drug treatment, a hyperinsulinemic euglycemic clamp test was carried out, lipoprotein status was assessed, and the concentrations of serum electrolytes were measured. The serum ACE activity was determined in the group treated with fosinopril. Changes in insulin sensitivity index (M/I) were directly correlated to alterations in S-Mg (r = 0.24, P < .02), and inversely correlated to changes in S-Ca (r = -0.19, P = .07) and the ratio between serum calcium and magnesium concentrations (Ca/Mg) (r = -0.27, P < .008). The change in total serum triglycerides (S-Tg) was inversely correlated to the change in S-Mg (r = -0.35, P < .0005), and directly correlated to the change in Ca/Mg ratio (r = 0.36, P < .0004). The reduction in serum ACE activity correlated to a more pronounced increase in S-Mg r = -0.62, P < .002), and decrease in the Ca/Mg ratio (r = 0.73, P = .0002). We conclude that the changes in the studied metabolic variables and serum ACE activity during ACE inhibitor treatment are related to alterations in mineral status and the balance between calcium and magnesium concentrations in serum.

Adolescent↗
PubMed1997

Low-density lipoprotein metabolism and its association to plasma lipoprotein(a) in the nephrotic syndrome.

Patients with nephrotic syndrome have multiple abnormalities of lipoprotein metabolism, but the cause and exact nature of these abnormalities have not been established. In the present study we have determined the kinetics of plasma low-density lipoprotein (LDL) apoB in seven nephrotic patients demonstrating an elevated LDL apoB production rate (25.7 +/- 6.4 vs. 13.1 +/- 0.3 mgkg-1 day-1; P < 0.001) but a normal LDL apoB fractional catabolic rate (FCR) (0.31 +/- 0.04 vs. 0.33 +/- 0.008 pools day-1; NS) compared with 41 healthy control subjects. However, two out of the seven patients had a markedly low LDL apoB-FCR. Serum albumin was inversely correlated with the LDL apoB production rate (R = -0.82; P < 0.05). Plasma lipoprotein (a) [Lp(a)] levels were significantly (P < 0.001) increased in the nephrotic patients compared with control subjects. Significant correlations were observed between log Lp(a) and LDL apoB production rate (R = 0.90; P < 0.01), VLDL-cholesterol (R = 0.95; P < 0.001) and VLDL-triglycerides (R = 0.80; P < 0.05) respectively. In summary, the present study suggests that nephrotic hyperlipidaemia may be caused by at least two independent mechanisms. The elevated LDL apoB production rate is highly correlated with the prevailing levels of serum albumin, whereas some nephrotic patients seem to have a decreased LDL apoB clearance, suggesting impaired LDL receptor-mediated clearance. The present results also suggest that the elevated plasma Lp(a) levels in nephrosis are related to an increased hepatic synthesis rather than a decreased catabolism of lipoproteins.

Adolescent↗
PubMed1997

Influence of variation at the apolipoprotein E locus on lipid and lipoprotein levels in CAPD patients.

BACKGROUND: Variation at the apolipoprotein E (apo E) locus influence lipid and lipoprotein levels in the normal population, and is associated with premature coronary artery disease. Patients with end-stage kidney disease or undergoing dialysis treatment are particularly prone to develop accelerated atherosclerosis. METHODS: To evaluate the influence of genetic variation at the apo E locus, apo E genotypes and serum lipid and lipoprotein levels were measured in 51 subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). RESULTS: The distribution of apo E phenotypes and apo E allelic frequency among the CAPD subjects (epsilon 2 0.049; epsilon 3 0.745: epsilon 4 0.206) corresponded to the healthy Swedish population. In the CAPD subjects, total serum and LDL cholesterol levels were high (6.7 +/- 1.5 mmol/l and 4.2 +/- 1.3 mmol/l respectively) and HDL cholesterol levels were low (1.2 +/- 0.5 mmol/l). When directly comparing the two major apo E groups. E 3/3 subjects (n = 30) and E4/3 and 4/4 subjects, epsilon 4-carriers, (n = 16), LDL cholesterol levels were significantly higher among epsilon 4-carriers (4.8 +/- 1.1 vs 4.0 +/- 1.2 mmol/l, P < 0.03), but total serum cholesterol levels was not higher among the epsilon 4-carriers (7.3 +/- 1.3 vs 6.5 +/- 1.5 mmol/l, P < 0.08). Serum triglycerides or HDL cholesterol levels did not differ significantly between epsilon 3-homozygotes and epsilon 4-carriers. CONCLUSIONS: The results demonstrate a strong effect of variation of the apo E locus on LDL cholesterol levels in CAPD subjects, suggesting that epsilon 4-carriers may be more susceptible to accelerated development of atherosclerosis in this condition.

Adult↗
PubMed1997

Detection of Francisella tularensis in ulcers of patients with tularemia by PCR.

The diagnosis of human cases of tularemia is usually confirmed by the demonstration of an antibody response to Francisella tularensis, which occurs about 2 weeks after the onset of disease. Due to a high risk of infection in the laboratory, cultivation of the causative agent tends to be avoided. During an outbreak in Sweden, the use of PCR for diagnosing the ulceroglandular form of tularemia was evaluated. Extraction and preparation of F. tularensis DNA from swab samples from the wounds of patients with tularemia involved the use of the nuclease inhibitor guanidine thiocyanate. The DNA was detected by multiplex PCR targeting the 16S rRNA gene and a 17-kDa lipoprotein gene of F. tularensis. In 29 of 40 (73%) patients with serologically confirmed tularemia, F. tularensis DNA was successfully amplified. Considering the limitations of current diagnostic procedures, PCR may become useful for the early diagnosis of tularemia.

Adolescent↗
PubMed1997

Race-ethnicity and determinants of carotid atherosclerosis in a multiethnic population. The Northern Manhattan Stroke Study.

BACKGROUND AND PURPOSE: Risk factors for carotid atherosclerosis have been studied in white populations but infrequently in multiethnic cohorts. The aim of this study was to determine the importance of race-ethnicity and other factors associated with carotid atherosclerosis in a mixed population of Hispanics, blacks, and whites. METHODS: As part of the Northern Manhattan Stroke Study, 526 stroke-free community residents (aged > or = 40 years; 41% men, 59% women; 46% Hispanic, 31% black, 23% white) were recruited through random-digit dialing and had vascular risk factor evaluations. Maximum internal carotid artery plaque thickness (MICPT) was measured with B-mode ultrasound. The frequency distribution of MICPT was examined in the three race-ethnic groups, and multivariate regression was performed to identify factors that were independently associated with MICPT. RESULTS: Mean MICPT in the entire sample was 1.5 +/- 1.4 mm, increased directly with age, and was greater in whites and blacks than Hispanics. Other independent determinants of MICPT included smoking, glucose, LDL cholesterol, and hypertension. After we controlled for these covariates, Hispanic (versus non-Hispanic) race-ethnicity was still an independent determinant of less carotid plaque. There was a significant interaction between race-ethnicity and LDL cholesterol, with a greater effect of increasing LDL cholesterol among Hispanics. CONCLUSIONS: Atherosclerotic risk factors were predictive of MICPT in this mixed-ethnic cohort. Hispanics had significantly less carotid plaque after adjustment for other known risk factors, but they also had a greater impact of increasing LDL cholesterol.

Adult↗
PubMed1997

Size at birth and hypertension in longitudinally followed 50-70-year-old men.

We investigated the relationship between weight at birth and the prevalence of hypertension (defined as treatment and/or systolic blood pressure > 160 mmHg) at ages 50, 60 and 70 years in a cohort of Swedish men followed longitudinally, in which we had previously found a strong inverse association of birthweight with blood pressure at age 50. In men of above median adult height (> 176 cm), a 1000 g decrease in birthweight was associated with an odds ratio for hypertension of 2.53 (95% CI 1.10, 5.85) at age 50, 1.63 (95% CI 0.97, 2.72) at 60 and 1.72 (95% CI 1.10, 2.69) at 70. As the overall prevalence of hypertension increased steeply with age, the absolute difference in the risk of hypertension between those of low and high birthweight increased with age. In men of below median height, birthweight was not significantly associated with blood pressure at any age. Small size at birth is associated with hypertension at 50, 60 and 70 years in men of a high growth potential. The strength of the relationship between birthweight and hypertension does not increase from 50 to 70 years, although the risk of hypertension attributable to low birthweight does increase with age.

Age Factors↗
PubMed1996

The serum cholesterol ester fatty acid composition but not the serum concentration of alpha tocopherol predicts the development of myocardial infarction in 50-year-old men: 19 years follow-up.

A low serum tocopherol concentration and a low proportion of linoleic acid in plasma cholesterol esters have been reported to be associated with coronary heart disease. This study was undertaken to evaluate the predictive importance of the serum cholesterol ester fatty acid composition and serum tocopherol concentration in addition to established risk factors for myocardial infarction. The study comprised 2322 fifty-year-old men who participated in a health survey in 1970-1973 regarding risk factors for coronary heart disease. The proportions of myristic, palmitic, palmitoleic, and dihomogammalinolenic acid were significantly higher in 1970-1973 in subjects who suffered myocardial infarction during the following 19 years, while the proportion of linoleic acid was lower, than in those who remained healthy. Serum tocopherol did not differ significantly between the groups. LDL/HDL ratio, systolic blood pressure, and arachidonic acid/dihomogammalinolenic acid ratio were significant independent discriminators between cases and controls in a stepwise logistic regression analysis. This study suggests that middle-aged men who later develop a myocardial infarction are characterized not only by conventional risk factors but also by an altered fatty acid composition of serum cholesterol esters, with a low arachidonic to dihomogammalinolenic acid ratio, indicating reduced delta 5 desaturase activity. This may imply that changes in the quality of dietary fat intake, or an altered capacity to metabolize fatty acids in the body, could precede the development of coronary heart disease.

Biomarkers↗
PubMed1996

Structural characterization of bovine CD36 from the milk fat globule membrane.

Bovine CD36 from milk fat globule membranes was characterized and a full-length CD36 cDNA of 2772 nucleotides was isolated from a bovine mammary gland cDNA library. The deduced protein sequence contains 472 amino acid residues with 82-84% identity to the amino acid sequences of CD36 from other species. Peptides corresponding to 43% of the protein were sequenced. All eight potential N-glycosylation sites were glycosylated and the carbohydrate compositions of the individual sites were determined.

Amino Acid Sequence↗
PubMed1996

Characterization of glycoprotein PAS-6/7 from membranes of bovine milk fat globules.

Glycoprotein components PAS-6 and PAS-7 were purified from bovine milk-fat-globule membranes and the amino acid sequence of their common polypeptide core, PAS-6/7, was determined by peptide and cDNA sequencing. The cDNA encoded a signal peptide of 18 amino acid residues and a mature PAS-6/ 7 protein of 409 amino acid residues. A cDNA splice variant was identified by reverse transcription/ PCR. Results obtained by amino acid analyses, amino-acid-sequence analyses, carbohydrate-composition determinations, and MS analyses of glycopeptides revealed that both proteins were glycosylated with a carbohydrate structure that contained galactose, N-acetylgalactosamine and fucose, and which was O-linked to Ser9 in PAS-6 and to Thr16 in PAS-7. In addition, PAS-6 and PAS-7 were N-glycosylated at Asn41 with a hybrid-type-carbohydrate structure. A high-mannose glycan was N-linked to Asn209 of PAS-6. The sequence of PAS-6/7 contained two epidermal growth factor (EGF)-like domains in the N-terminal region, the second of which contained an RGD cell-adhesion sequence in an extended loop. The EGF-like domains were followed by a C-terminal tandem repeat, which showed 60-63% similarity to the C1-C2 domain of blood-clotting factors V and VIII. The disulfide bonds within the C1-C2 domain were identified.

Alternative Splicing↗
PubMed1996

The bovine PP3 gene is homologous to the murine GlyCAM 1 gene.

Proteose peptone component 3 (PP3) is a protein synthesized in the bovine mammary gland. A genomic 4.5-kb clone has been sequenced comprising a 2.9-kb PP3 transcriptional unit plus 1 kb of 5' and 0.6 kb of 3' flanking sequence. Bovine retroposons of the short interspersed nuclear element sequence class (SINES) and one microsatellite were localized in the PP3 gene. PP3 is homologous with the murine glycosylation-dependent cell-adhesion molecule 1 (GlyCAM 1) and this homology also extends to the exon/intron organization of the genes.

Adenosine Triphosphatases↗