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Biomedical subjects

L Berglund

Publications and source records attributed to L Berglund.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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