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Biomedical subjects

L Berglund

Publications and source records attributed to L Berglund.

At least 127 records · Page 7Linked to original sources

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↗

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↗

Failure to realise growth potential in utero and adult obesity in relation to blood pressure in 50 year old Swedish men.

OBJECTIVES: To clarify the type of fetal growth impairment associated with increased blood pressure in adult life, and to establish whether this association is influenced by obesity and is mediated through impairment of insulin action. DESIGN: Cross sectional survey with retrospective ascertainment of size at birth from obstetric archives. SUBJECTS: 1333 men resident in Uppsala, Sweden, who took part in a 1970 study of coronary risk factors at age 50 and for whom birth weight was traced. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure at age 50. RESULTS: In the full study population for a 1000g increase in birth weight there was a small change in systolic blood pressure of -2.2mmHg (95% confidence interval -4.2 to - 0.3mmHg) and in diastolic blood pressure of -1.0mmHg (-2.2 to 0.1mmHg). Much stronger effects were observed among men who were born at term and were in the top third of body mass index at age 50, for whom a 1000g increase in birth weight was associated with a change of -9.1mmHg (-16.4 to-1.9mmHg) systolic and -4.2mmHg (-8.3 to -0.1mmHg) diastolic blood pressure. Men who were light at birth (<3250g) but were above median adult height had particularly high blood pressure. Adjustment for insulin concentrations reduced the associations of birth weight with systolic and diastolic blood pressure. CONCLUSIONS: A failure to realise growth potential in utero (as indicated by being light at birth but tall as an adult) is associated with raised adult blood pressure. Impaired fetal growth may lead to substantial increases in adult blood pressure among only those who become obese. Metabolic disturbances, possibly related to insulin resistance, may provide a pathway through which fetal growth affects blood pressure.

Birth Weight↗

Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years.

OBJECTIVE: To establish whether the relation between size at birth and non-insulin dependent diabetes is mediated through impaired beta cell function or insulin resistance. DESIGN: Cohort study. SETTING: Uppsala, Sweden. SUBJECTS: 1333 men whose birth records were traced from a cohort of 2322 men born during 1920-4 and resident in Uppsala in 1970. MAIN OUTCOME MEASURES: Intravenous glucose tolerance test at age 50 years and non-insulin dependent diabetes at age 60 years. RESULTS: There was a weak inverse correlation (r=-0.07, P=0.03) between ponderal index at birth and 60 minute insulin concentrations in the intravenous glucose tolerance test at age 50 years. This association was stronger (r=-0.19, P=0.001) in the highest third of the distribution of body mass index than in the other two thirds (P=0.01 for the interaction between ponderal index and the body mass index). Prevalence of diabetes at age 60 years was 8% in men whose birth weight was less than 3250 g compared with 5% in men with birth weight 3250 g or more (P=0.08; 95% confidence interval for difference -0.3% to 6.8%). There was a stronger association between diabetes and ponderal index: prevalence of diabetes was 12% in the lowest fifth of ponderal index compared with 4% in the other four fifths (P=0.001; 3.0% to 12.6%). CONCLUSION: These results confirm that reduced fetal growth is associated with increased risk of diabetes and suggest a specific association with thinness at birth. This relation seems to be mediated through insulin resistance rather than through impaired beta cell function and to depend on an interaction with obesity in adult life.

B-Lymphocytes↗

Influence of a diet regimen on glucose homeostasis and serum lipid levels of male elite athletes.

Physical training affects carbohydrate metabolism and results in an increased insulin-stimulated glucose disposal. To investigate if carbohydrate and lipid metabolism would be affected by nutritional factors in optimally trained elite athletes, during a 1-year period we studies elite ice-hockey players on two Swedish top-performance teams. Players on one team were subjected to extensive dietary monitoring and intervention, whereas players on the second team continued their ordinary diet. Blood levels of insulin, C-peptide, glucose, hemoglobin A1C (HbA1c), lipids, and lipoproteins were measured repeatedly. Basal insulin levels and insulin resistance (IR) were significantly lower among athletes on both teams compared with a sedentary group, and muscle weight and body mass index were significantly higher. During the course of the study in the intervention group, insulin levels decreased (3.6 +/- 0.3 v 6.2 +/- 0.6 [mean +/- SEM], P <.05) in conjunction with a decreased relative fat energy content, but returned toward baseline levels when relative fat energy content increased. IR decreased in parallel (0.59 +/- 0.05 v l.12 +/- 0.12, P <.05) and followed a similar pattern, reverting toward baseline levels. Also, levels of HbA1c changed during dietary manipulation. No changes in these parameters were observed among the elite players from the team not participating in the diet regimen. In contrast to the parameters for glucose homeostasis, no significant changes were found in serum lipid or lipoprotein levels in either team during the course of the study. The results verify the presence of an improved carbohydrate metabolism in elite athletes. The observed changes in glycemic control and glucose homeostasis as a consequence of dietary modification demonstrate further that nutritional factors may affect carbohydrate metabolism also in well-trained athletes.

Adult↗

Orthodontic pre-treatment prior to autotransplantation of palatally impacted maxillary canines: case reports on a new approach.

Impacted maxillary canines in oblique horizontal positions may make orthodontic appliance treatment hazardous or impossible. Autotransplantation may be considered but the removal of the canine is often difficult and since atraumatic removal of the transplant is essential, autotransplantation is then impossible. A new possibility is orthodontic pre-treatment with distal and vertical traction of the impacted maxillary canine to bring the maxillary canine to a more favourable position and facilitate surgical removal and autotransplantation. Eight canines were surgically exposed and pre-treated prior to autotransplantation. Of 21 autotransplantations of maxillary canines, 20 were successful, among them all eight pre-treated cases. The orthodontic and surgical technique is described and illustrated in two case reports.

Adolescent↗

Irrigating fluid absorption from the intact uterus.

OBJECTIVE: Absorption of irrigating fluid may occur through severed blood vessels during endometrial resection. We studied whether irrigating fluid can also be absorbed through the undamaged uterus. PARTICIPANTS: We studied 25 women, aged 28-46 years (mean 38 years), who underwent elective laparoscopic sterilisation under general anaesthesia. INTERVENTIONS: In 15 women blue-stained irrigating fluid containing glycine 1.5% and ethanol 1% was applied to the uterine cavity under increasing pressure. Laparoscopy was employed to see when fluid emerged from the Fallopian tubes. Another 10 women had their Fallopian tubes clamped before the fluid pressure was raised, and systemic absorption was detected by measuring the serum glycine concentration. RESULTS: Passage of fluid through the Fallopian tubes occurred in 14 of the 15 patients at a uteroabdominal pressure gradient of 40 mmHg (n = 4), 80 mmHg (n = 4), 120 mmHg (n = 3), and 160 mmHg (n = 3), respectively. The fluid passage rate ranged between 0.5 and 13 (mean 6.4) ml min-1. Of the women with clamped Fallopian tubes, 8 of 10 showed an increase in the serum glycine level of 60% at a pressure gradient of 160 mmHg, and of 120% at 200 mmHg. CONCLUSIONS: Uterotubal and transendometrial passage of small to moderate amounts of irrigating solution occurred frequently at the intrauterine fluid pressures normally used during endometrial resection.

Absorption↗

Increased plasma lipoprotein(a) in continuous ambulatory peritoneal dialysis is related to peritoneal transport of proteins and glucose.

Markedly increased plasma lipoprotein(a) [Lp(a)] levels have recently been reported in continuous ambulatory peritoneal dialysis (CAPD) patients but the genesis is obscure. Lp(a) levels in CAPD are in general higher than in hemodialysis (HD) patients, suggesting that the dialysis procedure might be of importance. In the present study, we investigated relationships between Lp(a) and parameters related to the dialysis procedure per se (dialysis dose, peritoneal glucose absorption, protein losses and protein clearances) in 32 adult CAPD patients. Uremic patients treated with HD (n = 73) as well as a group of 43 healthy subjects served as control groups. The plasma level of Lp(a) was significantly higher in the CAPD patients (median 28.2 mg/dl) than in the HD patients (median 9.2 mg/dl) and the healthy controls (median 7.0 mg/dl), whereas Lp(a) levels in the HD patients did not differ from the healthy controls. In the CAPD patients, significant correlations were found between Lp(a) and 24-hour peritoneal and total clearance for albumin (r = 0.472 and r = 0.368, p < 0.01 and p < 0.05, respectively), and between Lp(a) and 24-hour peritoneal clearance for beta(2)-microglobulin (r = 0.421; p < 0.05). Similar correlations were found between Lp(a) and 24-hour peritoneal albumin excretion, total albumin excretion and peritoneal beta(2)-microglobulin excretion. Furthermore, a significant correlation was found between Lp(a) and peritoneal glucose absorption (r = 0.352; p < 0.05). Serum cholesterol showed significant correlations with 24-hour .peritoneal albumin loss and 24-hour peritoneal beta(2)-microglobulin clearance, whereas LDL cholesterol showed a significant correlation with 24-hour peritoneal beta(2)-microglobulin clearance. In a longitudinal study of 12 CAPD patients, Lp(a) levels increased significantly between the start of CAPD and at follow-up 3-5 months later. The correlation of the markedly increased levels of Lp(a) with peritoneal albumin and beta(2)-microglobulin clearance suggests that the mechanism behind the increased Lp(a) levels may be related to the large protein losses in CAPD, perhaps via an increased synthesis rate of apolipoprotein (a) in the liver or via decreased Lp(a) catabolism in CAPD patients. Finally, the correlation between Lp(a) and peritoneal glucose absorption also indicates that the increased plasma Lp(a) levels in CAPD are related to the dialysis procedure, in particular peritoneal transport of proteins and glucose.

Adult↗

Early detection of 'endometrial resection syndrome'.

We report a patient who developed symptoms of fluid overload after having absorbed 3 litres of irrigating fluid during transcervical resection of the endometrium. Four methods were used to measure the absorption at 10-min intervals throughout the operation. There were strong intercorrelations between the results of these monitoring methods, which consisted in breath ethanol analyses and measurements of the serum sodium and glycine concentrations and of the volumetric fluid balance. However, the ethanol method was easiest to perform and provided immediate results. This monitoring gave the operating team as much as 45 min to prevent further absorption before it became large enough to elicit a transcervical endometrial resection syndrome.

Absorption↗

Hormonal regulation of serum lipoprotein (a) levels: effects of parenteral administration of estrogen or testosterone in males.

When given orally, estrogens, as well as androgens, lower serum lipoprotein (a)[Lp(a)]levels. To determine whether these effects occur also after parenteral administration of steroids, Lp(a) levels were determined in two groups of elderly males suffering from prostatic carcinoma, who were randomized to treatment with parenteral estrogen (n = 8) or orchidectomy (n = 6). One group of healthy male volunteers (n = 9) was studied after parenteral administration of testosterone. Estrogen was given as im polyestradiol phosphate, 240 mg twice monthly, and testosterone was given as im injections, 250 mg/week. In the orchidectomized subjects, Lp(a) levels increased by 20% by month 3 after treatment (P < 0.05). In spite of drastic changes in serum hormone levels, no change in Lp(a) levels was observed in the estrogen-treated subjects. Concomitantly, low-density lipoprotein cholesterol levels were lowered by 15% and high-density lipoprotein cholesterol levels increased by 20%. Testosterone administration lowered Lp(a) levels by 20% (P < 0.05). No significant changes in serum lipid levels were observed in the testosterone-treated subjects or in the orchidectomy group. Thus, during parenteral administration of estrogens or androgens, diverging effects on Lp(a) and serum lipoproteins were observed. In particular, the mode of administration of estrogen influenced the response in Lp(a) levels. This suggests that the regulatory role of sex hormones on serum Lp(a) levels may depend on their capability to influence hepatic metabolic pathways of Lp(a).

Adult↗

Prediction models for insulin resistance.

A prediction model for estimating insulin resistance in hypertensive patients is presented. Body-mass index, serum triglyceride concentrations and liver enzyme activity in plasma correlate to insulin resistance determined with the euglycaemic, hyperinsulinaemic clamp technique. Prediction models using body-mass index and either triglycerides or serum alanine-amino transferase were equally good in predicting insulin resistance and gave results that were as reliable as those obtained in a model using fasting-insulin concentrations. The hyperinsulinaemic clamp had a reproducibility error of 14%, and body-mass index and serum triglycerides had a multiple correlation of 0.57 to the insulin-sensitivity results. The model predicts insulin resistance with acceptable statistical power, whereas the power to predict high values of insulin sensitivity is less good.

Aged↗

Purification of the bovine xanthine oxidoreductase from milk fat globule membranes and cloning of complementary deoxyribonucleic acid.

The amino acid sequence of the bovine xanthine oxidoreductase was determined by cloning and sequencing cDNA clones encoding the enzyme. Partial amino acid sequence corresponding to 54% of the total sequence were also determined from purified bovine milk xanthine oxidoreductase, showing identity with the translated cDNA sequence. The cDNA of 4719 nucleotides included a 5' untranslated region of 96 nucleotides, an open reading frame encoding a xanthine oxidoreductase of 1332 amino acid residues, and a 3' untranslated region of 624 nucleotides including two polyadenylation signals and a poly (A) tail of 74 nucleotides. The identity between the amino acid sequence of the bovine xanthine oxidoreductase and xanthine oxidoreductase from mammalian species was 86 to 90%.

Amino Acid Sequence↗

Increased prevalence of atherosclerotic wall changes in patients with hyperlipidaemia after renal transplantation.

OBJECTIVES: The initial aim of this study was to evaluate the possibility of influencing atherosclerosis in hyperlipidaemic renal transplant patients by lowering blood lipids with gemfibrozil treatment. DESIGN: Although this double-blind, randomized trial was stopped after 6 months owing to the suspicion of drug interference, we report here on the results of baseline ultrasonographic examinations. SETTING: The outpatient clinic at the Department of Transplantation Surgery, Huddinge University Hospital, Huddinge, Sweden. SUBJECTS AND METHODS: The carotid arteries were examined in 16 out of the 19 kidney transplant patients included in the study using an ultrasonographic duplex scanner. MAIN OUTCOME MEASURES: Plaque occurrence and the common carotid intima-media thickness of the renal transplant recipients were compared to the same parameters in a normotensive control group of approximately the same age from a previous study. RESULTS: An increased prevalence of plaque (75% of the patients having plaque on one or both sides) was seen in the hyperlipidaemic renal transplant patients in comparison with the control group (16%; P < 0.001). The common carotid intima-media complex was thicker (P < 0.05), and the lumen diameter and the calculated cross-sectional intima-media area were greater (P < 0.01-0.001) in the transplant recipients. CONCLUSIONS: Markedly increased atherosclerotic wall changes are seen in the carotid arteries of patients with hyperlipidaemia after renal transplantation.

Adult↗

Lipoprotein(a) in chronic renal disease.

Atherosclerotic vascular disease is a major cause of morbidity and mortality in patients with chronic renal disease and in renal transplant recipients. Epidemiological studies have shown that a high lipoprotein(a) [Lp(a)] concentration in the general population is an independent risk factor for the development of atherosclerotic complications, such as coronary heart disease. Interestingly, plasma levels of Lp(a) have often been reported to be elevated in chronic renal disease. Recent studies have found no difference in the isoform distribution of apo(a) between healthy subjects and patients with renal disease, suggesting that factors other than genetic differences are involved in the high levels of Lp(a) reported in chronic renal disease. In particular, patients with major losses of protein in urine and/or dialysate, such as nephrotic patients and those treated with continuous ambulatory peritoneal dialysis, have been reported to have elevated plasma Lp(a) levels. The results regarding plasma Lp(a) levels in hemodialysis patients are conflicting, although recent evidence suggests that serum albumin levels are of importance for the prevailing Lp(a) levels. In renal transplant recipients conflicting data regarding plasma Lp(a) levels have also been reported, a finding that may be attributable to posttransplant urinary protein losses and/or different immunosuppressive regimens. The importance of Lp(a) as a risk factor for atherosclerotic disease in patients with chronic renal failure remains to established, and prospective evaluations of the role of Lp(a) are necessary.

Arteriosclerosis↗

Characterization of three types of human alpha s1-casein mRNA transcripts.

Here we report the molecular cloning and sequencing of three types of human alpha s1-casein transcripts and present evidence indicating that exon skipping is responsible for deleted mRNA transcripts. The largest transcript comprised 981 bp encoding a signal peptide of 15 amino acids followed by the mature alpha s1-casein sequence of 170 amino acids. Human alpha s1-casein has been reported to exist naturally as a multimer in complex with kappa-casein in mature human milk, thereby being unique among alpha s1-caseins [Rasmussen, Due and Petersen (1995) Comp. Biochem. Physiol., in the press]. The present demonstration of three cysteines in the mature protein provides a molecular explanation of the interactions in this complex. Tissue-specific expression of human alpha s1-casein was indicated by Northern-blot analysis. In addition, two cryptic exons were localized in the bovine alpha s1-casein gene.

Alternative Splicing↗

Hepatic fatty acid metabolism as a determinant of plasma and liver triacylglycerol levels. Studies on tetradecylthioacetic and tetradecylthiopropionic acids.

To investigate the importance of factors influencing substrate availability for triacylglycerol biosynthesis on lipoprotein metabolism, the effects of two opposite-acting sulphur-substituted fatty acid analogues, tetradecylthioacetic acid and tetradecylthiopropionic acid were studied. Administration of tetradecylthioacetic acid to rats resulted in a reduction of plasma levels of triacylglycerols (44%) and cholesterol (26%). This was accompanied by a reduction in very-low-density lipoprotein (VLDL) triacylglycerols (48%), VLDL cholesterol (36%), low-density lipoprotein (LDL) cholesterol (36%) and high-density lipoprotein (HDL) triacylglycerols (50%), whereas HDL cholesterol levels did not change. Subsequently, the HDL/LDL-cholesterol ratio increased by 40%. The cholesterol-lowering effect was accompanied by a reduction in hydroxymethylglutaryl CoA (HMG-CoA) reductase activity (37%). Both mitochondrial and peroxisomal fatty acid oxidation increased (1.7-fold and 5.3-fold, respectively). Furthermore, there was a significant negative correlation between plasma triacylglycerols and mitochondrial fatty acid oxidation. Hepatic triacylglycerol synthesis was retarded, as indicated by a decrease in VLDL triacylglycerol secretion (40%), and by a reduced liver triacylglycerol content (29%). The activities of lipoprotein lipase and hepatic lipase in post-heparin plasma were not affected. Microsomal and cytosolic phosphatidate phosphohydrolase activities were inhibited (28% and 70%, respectively). Hepatic malonyl-CoA levels decreased by 29% and the total activity of acetyl-CoA carboxylase was reduced (23%). In hepatocytes treated with tetradecylthioacetic acid, mitochondrial fatty acid oxidation increased markedly (100%) and triacylglycerol secretion was reduced (40%). In tetradecylthiopropionic-acid-treated rats, a significant increase in both plasma and VLDL triacylglycerols was found (46% and 72%, respectively) but VLDL triacylglycerol secretion was unaffected. However, no effect on either plasma or lipoprotein cholesterol levels was seen. Mitochondrial fatty acid oxidation was decreased by 50% and hepatic triacylglycerol levels increased by 33%. In hepatocytes exposed to tetradecylthiopropionic acid, triacylglycerol synthesis increased (100%) while triacylglycerol secretion and fatty acid oxidation remained unaltered. The results illustrate that lipoprotein triacylglycerol levels can be modulated by changes in the availability of fatty acid substrate for triacylglycerol biosynthesis, mainly by affecting mitochondrial fatty acid oxidation. In addition, we demonstrate that suppression of rat hepatic HMG-CoA reductase activity during treatment with tetradecylthioacetic acid may contribute to a cholesterol-lowering effect.

Animals↗

Cloning of a cDNA encoding murine tetranectin.

A full-length cDNA encoding murine tetranectin (TN) was isolated and cloned from a murine lung lambda ZAPII cDNA library. The complete nucleotide sequence was determined revealing an open reading frame encoding 202 amino acids (aa) including a signal peptide of 21 aa. An overall aa identity of 79% exists between the deduced aa sequences of human and murine TN, revealing a high evolutionary conservation of the protein. The highest expression of mouse TN was found in lung and skeletal muscle.

Amino Acid Sequence↗