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Biomedical subjects

R Jacobsen

Publications and source records attributed to R Jacobsen.

At least 19 recordsLinked to original sources
PubMed2006

Subnormal energy expenditure: a putative causal factor in the weight gain induced by treatment of hyperthyroidism.

AIMS: To examine the causes of weight gain occurring as an adverse effect of treatment of hyperthyroidism. METHODS: We measured 24-h energy expenditure (EE), body composition and spontaneous physical activity (SPA) in eight patients before and 1 year after treatment of hyperthyroidism was initiated, and eight controls. RESULTS: One year after initiation of treatment thyrotropin was normalized, thyroid hormones had fallen to the lower end of the reference range and fat mass had increased by 3.5 kg (p < 0.001). Twenty-four hour EE adjusted for fat-free mass (FFM) was 15% higher in hyperthyroid patients before treatment than in controls (p = 0.003), and treatment decreased 24-h EE by 1.9 MJ/day (p = 0.001). After treatment, 24-h EE, adjusted for FFM, was similar to the controls. Multiple regression analyses showed that the suppressed EE could partly be attributed to an iatrogenic suppression of thyroid hormones, resulting in lower sleeping EE. Twenty-four hour SPA was normal in the hyperthyroid state, but decreased after treatment by 21% (p = 0.045), to a level not significantly different, but still below that of the controls. CONCLUSIONS: The study suggests that weight gain during treatment of hyperthyroidism might be due to subnormal levels of EE and SPA caused by a suppression of the thyroid hormone to a level in the lower end of the normal range.

Body Composition↗
PubMed2005

Effects of soy supplementation on blood lipids and arterial function in hypercholesterolaemic subjects.

BACKGROUND: Studies on soy supplementation suggest a cardioprotective potential. OBJECTIVE: To examine the effects on LDL cholesterol and arterial function as a result of dietary enrichment with soy supplementation. DESIGN: A Randomized, double blind, parallel intervention trial. SETTING: Department of Endocrinology and Metabolism C, Aarhus University Hospital, and Department of Human Nutrition, The Royal Veterinary and Agricultural University, Denmark. SUBJECTS: In all, 100 hypercholesterolaemic but otherwise healthy subjects were included in the study of which 89 completed it. INTERVENTIONS: Subjects were randomly assigned to 24 weeks of daily intake of either a soy supplement, Abalon (30 g soy protein, 9 g cotyledon fibre and 100 mg isoflavones) or placebo (30 g of casein). The soy supplement and placebo were provided in two sachets daily that were stirred in water. Fasting plasma lipids, TNF-alpha, homocysteine, insulin sensitivity, homeostasis model assessment (HOMA-IR), serum insulin, serum glucose, blood pressure as well as Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and plasma lipids to a fat-rich meal were recorded before and after the intervention. In a sub study in 32 subjects, arterial dilatory capacity, compliance, and distensibility were recorded before and after the intervention. RESULTS: In the main study, no difference in fasting plasma lipid levels or insulin sensitivity was found between soy-based supplement and placebo. A significant postprandial increase in GIP to the meal test was observed in the soy group (P < 0.05). In a substudy, no difference between the groups in changes in flow-mediated vasodilatation (P = 0.84) was detected, while the soy supplementation caused a reduction in LDL and total cholesterol. CONCLUSIONS: No significant effects on blood lipids were observed in the main study to a soy supplementation in hypercholesterolaemic subjects after 24 weeks. In the substudy, the soy supplementation, however, reduced LDL and total cholesterol but did not influence markers of arterial function.

Anticholesteremic Agents↗
PubMed2005

Effect of short-term high dietary calcium intake on 24-h energy expenditure, fat oxidation, and fecal fat excretion.

BACKGROUND: Observational studies have shown an inverse association between dietary calcium intake and body weight, and a causal relation is likely. However, the underlying mechanisms are not understood. OBJECTIVE: We examined whether high and low calcium intakes from mainly low-fat dairy products, in diets high or normal in protein content, have effects on 24-h energy expenditure (EE) and substrate oxidation, fecal energy and fat excretion, and concentrations of substrates and hormones involved in energy metabolism and appetite. DESIGN: In all, 10 subjects participated in a randomized crossover study of three isocaloric 1-week diets with: low calcium and normal protein (LC/NP: 500 mg calcium, 15% of energy (E%) from protein), high calcium and normal protein (HC/NP: 1800 mg calcium, 15E% protein), and high calcium and high protein (HC/HP: 1800 mg calcium, 23E% protein). RESULTS: The calcium intake had no effect on 24-h EE or fat oxidation, but fecal fat excretion increased approximately 2.5-fold during the HC/NP diet compared with the LC/NP and the HC/HP diets (14.2 vs 6.0 and 5.9 g/day; P < 0.05). The HC/NP diet also increased fecal energy excretion as compared with the LC/NP and the HC/HP diets (1045 vs 684 and 668 kJ/day; P < 0.05). There were no effects on blood cholesterol, free fatty acids, triacylglycerol, insulin, leptin, or thyroid hormones. CONCLUSIONS: A short-term increase in dietary calcium intake, together with a normal protein intake, increased fecal fat and energy excretion by approximately 350 kJ/day. This observation may contribute to explain why a high-calcium diet produces weight loss, and it suggests that an interaction with dietary protein level may be important.

Adolescent↗
PubMed2002

Long term mortality trends behind low life expectancy of Danish women.

STUDY OBJECTIVE: To examine the long time mortality trends of women in Denmark. DESIGN: Age-period-cohort analysis. SETTING: To search for possible causes we analysed mortality rates for all Danish women and men aged 40-84 during 1960-1999. Age-period-cohort modelling was used, handling the well known indeterminacy in a sensitivity analysis. MAIN RESULTS: The results indicate that the high risk of dying among Danish women is associated with being born between the two world wars. A similar pattern was not seen for men. CONCLUSION: The rather simple descriptive exploration in the framework of age-period-cohort modelling used, revealed a pattern not reflected by the commonly used life expectancy calculation. It is suggested that future studies on the low life expectancy of Danish women focus on the "between wars" generations identified with a high risk of dying in this study.

Adult↗
PubMed2001

Solution conformation of alpha-conotoxin EI, a neuromuscular toxin specific for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor.

A high resolution structure of alpha-conotoxin EI has been determined by (1)H NMR spectroscopy and molecular modeling. alpha-Conotoxin EI has the same disulfide framework as alpha 4/7 conotoxins targeting neuronal nicotinic acetylcholine receptors but antagonizes the neuromuscular receptor as do the alpha 3/5 and alpha A conotoxins. The unique binding preference of alpha-conotoxin EI to the alpha(1)/delta subunit interface of Torpedo neuromuscular receptor makes it a valuable structural template for superposition of various alpha-conotoxins possessing distinct receptor subtype specificities. Structural comparison of alpha-conotoxin EI with the gamma-subunit favoring alpha-conotoxin GI suggests that the Torpedo delta-subunit preference of the former originates from its second loop. Superposition of three-dimensional structures of seven alpha-conotoxins reveals that the estimated size of the toxin-binding pocket in nicotinic acetylcholine receptor is approximately 20 A (height) x 20 A (width) x 15 A (thickness).

Amino Acid Sequence↗
PubMed2000

Risk of testicular cancer in men with abnormal semen characteristics: cohort study.

OBJECTIVE: To explore the associations between semen characteristics and subsequent risk of testicular cancer. DESIGN: Cohort study. PARTICIPANTS: 32 442 men who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen during 1963-95. MAIN OUTCOME MEASURE: Standardised incidence ratios of testicular cancer compared with total population of Danish men. RESULTS: Men in couples with fertility problems were more likely to develop testicular cancer than other men (89 cases, standardised incidence ratio 1.6; 95% confidence interval 1.3 to 1.9). The risk was relatively constant with increasing time between semen analysis and cancer diagnosis. Analysis according to specific semen characteristics showed that low semen concentration (standardised incidence ratio 2.3), poor motility of the spermatozoa (2.5), and high proportion of morphologically abnormal spermatozoa (3.0) were all associated with an increased risk of testicular cancer. The only other cancer group that showed increased incidence was "peritoneum and other digestive organs" (six cases; 3.7, 1.3 to 8.0). Of these, two cases were probably and two cases were possibly extragonadal germ cell tumours. CONCLUSIONS: The results point towards the existence of common aetiological factors for low semen quality and testicular cancer. Low semen quality may also be associated with increased incidence of extragonadal germ cell tumours.

Adult↗
PubMed2000

Offspring sex ratio of subfertile men and men with abnormal sperm characteristics.

Previous work has suggested an association between male subfertility and a female-biased offspring sex ratio. This study of the reproduction of men who had a semen analysis at the Sperm Analysis Laboratory in Copenhagen in the period 1963-1993 showed that the subfertile men had an offspring sex ratio as expected (51.0% boys versus 51.3%, P: = 0.56), and within the cohort, the offspring sex ratio had no material association with particular semen characteristics. Our results thus suggest that no important association exists between general male subfertility and a female-biased offspring sex ratio.

Cohort Studies↗
PubMed2000

Fertility and offspring sex ratio of men who develop testicular cancer: a record linkage study.

Analysis of associations between testicular cancer, subfertility and offspring sex ratio (proportion of males born among newborns) was performed on 3530 Danish men, born 1945-1980, who developed testicular cancer in the period 1960-1993. As the basis of comparison we used the total population of Danish men born in the period 1945-1980 (n = 1 488 957) and their biological children (n = 1 250 989). Men who developed testicular cancer had, prior to the cancer diagnosis, a reduced fertility (standardized fertility rate ratio: 0.93, 95% confidence interval: 0.89-0.97) and a significantly lower proportion of boys (48.9%, P: = 0.02) compared with the general population (51.3%). The reduction in fertility was more pronounced in men with non-seminoma but the reduction in offspring sex ratio was independent of histological type. This confirms earlier results from less conclusive studies and indicates that testicular cancer, male subfertility and a female-biased sex ratio among new-born infants are characteristics of male reproduction that are linked by biological mechanisms.

Adult↗
PubMed1999

Natural variation in the human sex ratio.

Analysis of the effect of multiple birth, birth order, age of parents and the sexes of preceding siblings on the secondary sex ratio was performed for 815 891 children, born in Denmark, 1980-1993. The proportion of males was analysed as a function of multiple birth, birth order, age of parents and the sexes of preceding siblings, using contingency tables, chi(2) tests and logistic regression analysis. The secondary sex ratio decreased with increased number of children per plural birth and with paternal age, whereas no independent effect was observed for maternal age, birth order, the sex of the preceding child, or the combination of sexes of previously born children in the family.

Adult↗
PubMed1999

Fertility rates in Denmark in relation to the sexes of preceding children in the family.

Analysis of the effect of sex combination of previously born children in the family on fertility rates was performed for 363,373 Danish families comprising a total of 613,900 children, to address the questions of sex preference and combination preference. The fertility rates were stratified by parental age, period and latency time to the next child, and fertility rate ratios were estimated using multiplicative Poisson regression models. Our results demonstrate a strong preference for a balanced composition of sexes in Danish families. In families with two or three children the highest fertility rates were seen in families who had same-sexed children. The lowest fertility rates were in families with two children of identical sex followed by a child of the opposite sex. A moderate sex preference for girls was indicated by higher fertility rates in two-boy families than in two-girl families.

Birth Rate↗
PubMed1998

Inactivation of a serotonin-gated ion channel by a polypeptide toxin from marine snails.

The venom of predatory marine snails is a rich source of natural products that act on specific receptors and ion channels within the mammalian nervous system. A 41-amino acid peptide, final sigma-conotoxin GVIIIA, was purified on the basis of its ability to inactivate the 5-HT3 receptor, an excitatory serotonin-gated ion channel. final sigma-Conotoxin contains a brominated tryptophan residue, which may be important for peptide activity because the endogenous ligand for the 5-HT3 receptor is a hydroxylated derivative of tryptophan. final sigma-Conotoxin inactivates the 5-HT3 receptor through competitive antagonism and is a highly selective inhibitor of this receptor. Serotonin receptors can now be included among the molecular targets of natural polypeptide neurotoxins.

Amino Acid Sequence↗
PubMed1998

kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel.

kappa-Conotoxin PVIIA (kappa-PVIIA), a 27-amino acid toxin from Conus purpurascens venom that inhibits the Shaker potassium channel, was chemically synthesized in a biologically active form. The disulfide connectivity of the peptide was determined. kappa-Conotoxin PVIIA has the following structure. This is the first Conus peptide known to target K+ channels. [structure: see text] Although the Shaker K+ channel is sensitive to kappa-PVIIA, the rat brain Kv1.1 subtype is resistant. Chimeras between Shaker and the Kv1.1 K+ channels were constructed and expressed in Xenopus oocytes. Only channels containing the putative pore-forming region between the fifth and sixth transmembrane domains of Shaker retained toxin sensitivity, indicating that the toxin target site is in this region of the channel. Evidence is presented that kappa-PVIIA interacts with the external tetraethyl-ammonium binding site on the Shaker channel. Although both kappa-PVIIA and charybdotoxin inhibit the Shaker channel, they must interact differently. The F425G Shaker mutation increases charybdotoxin affinity by 3 orders of magnitude but abolishes kappa-PVIIA sensitivity. The precursor sequence of kappa-PVIIA was deduced from a cDNA clone, revealing a prepropeptide comprising 72 amino acids. The N-terminal region of the kappa-PVIIA prepropeptide exhibits striking homology to the omega-, muO-, and delta-conotoxins. Thus, at least four pharmacologically distinct superfamilies of Conus peptides belong to the same "O" superfamily, with the omega- and kappa-conotoxins forming one branch, and the delta- and muO-conotoxins forming a second major branch.

Amino Acid Sequence↗
PubMed1998

Coexpression of G-CSF with an unglycosylated G-CSF receptor mutant results in secretion of a stable complex.

Previously, we have shown that the entire extracellular domain of the granulocyte-colony stimulating factor receptor (sG-CSFr) produced in Chinese hamster ovary (CHO) cells forms a stable complex with its ligand G-CSF, at a stoichiometry of 2:2. A truncated receptor molecule consisting of the cytokine receptor homology domain and N-terminus Ig-like domain (Ig CRH) behaves quite similarly. Both of these forms of the receptor are highly glycosylated. To address the importance of glycosylation toward receptor activity and stability, and possibly obtain nonglycosylated receptor for crystallization, mutations were made to replace four Asn residues which are N-glycosylated in the truncated receptor. Virtually no receptor was recovered from conditioned media of CHO cells transfected with this mutant construct, although a high-level of mRNA coding for receptor was detected; this mRNA was translated as determined by Western blots of cell lysates. These results indicate that the translated product is apparently not secreted from these cells. Cells transfected with mutant receptor cDNA were cotransfected with a cDNA construct expressing G-CSF in which the single O-glycosylation site was eliminated by mutation. Upon fermentation of the cotransfectants, we observed a large amount of receptor-ligand complex in the conditioned media. The purified unglycosylated complex appeared to be of the same binding stoichiometry and approximate binding affinity as that of complex formed by addition of purified ligand and unmutated receptor. These results show that while glycosylation of sG-CSFr is not necessary for ligand binding, it appears to be crucial in folding and export from the cell.

Animals↗
PubMed1998

The contryphans, a D-tryptophan-containing family of Conus peptides: interconversion between conformers.

We previously characterized contryphan-R, a D-tryptophan-containing octapeptide from the venom of Conus radiatus. In this study, we present evidence that the contryphan family of peptides is widely distributed in venoms of the fish-hunting cone snails. We purified, synthesized and characterized contryphan-Sm from Conus stercusmuscarum venom, and obtained molecular evidence for the existence of a third peptide, contryphan-P from Conus purpurascens venom ducts. The sequences of these three contryphans showed identity in seven of eight amino acids and a conserved pattern of post-translational modification. We also demonstrate that contryphan-Sm equilibrates between two distinct conformational states.

Amino Acid Sequence↗