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Study objectiveThe aim was to estimate health and economic consequences of interventions aimed at reducing the daily intake of salt (sodium chloride) by 6 g per person in the Norwegian population. Health promotion (information campaigns), development of new industry food recipes, declaration of salt content in food and taxes on salty food/subsidies of products with less salt, were possible interventions.DesignThe study was a simulation model based on present age and sex specific mortality in Norway and estimated impact of blood pressure reductions on the risks of myocardial infarction and stroke as observed in Norwegian follow up studies. A reduction of 2 mm Hg systolic blood pressure (range 1-4) was assumed through the actual interventions. The cost of the interventions in themselves, welfare losses from taxation of salty food/subsidising of food products with little salt, cost of avoided myocardial infarction and stroke treatment, cost of avoided antihypertensive treatment, hospital costs in additional life years and productivity gains from reduced morbidity and mortality were included.ResultsThe estimated increase in life expectancy was 1.8 months in men and 1.4 in women. The net discounted (5%) cost of the interventions was minus $118 millions (that is, cost saving) in the base case. Sensitivity analyses indicate that the interventions would be cost saving unless the systolic blood pressure reduction were less than 2 mm Hg, productivity gains were disregarded or the welfare losses from price interventions were high.ConclusionPopulation interventions to reduce the intake of salt are likely to improve the population's health and save costs to society.

Abstract.: Cardiac sarcoplasmic reticulum (SR) contains an endogenous phosphorylation system that under specific conditions phosphorylates two proteins with apparent molecular masses of 150 and 130 kDa. The conditions for their phosphorylation are as for the skeletal muscle sarcalumenin and the histidine-rich Ca2+ binding protein (HCP) with respect to: (i) Ca2+ and high concentrations of NaF are required; (ii) phosphorylation is obtained with no added Mg2+ and shows a similar time course and ATP concentration dependence; (iii) inhibition by similar concentrations of La3+; (iv) phosphorylation is obtained with [γ-32P]GTP; (v) ryanodine binding is inhibited parallel to the phosphorylation of the two proteins. The endogenous kinase is identified as casein kinase II (CK II) based on its ability to use GTP as effectively as ATP, and its inhibition by La3+. The association of CK II with the cardiac SR, even after EGTA extraction at alkaline pH, is demonstrated using antibodies against CK II. The cardiac 130 kDa protein is identified as sarcalumenin based on its partial amino acid sequence and its blue staining with Stains-All. Cardiac sarcalumenin is different from the skeletal muscle protein based on electrophoretic mobilities, immunological analysis, peptide and phosphopeptide maps, as well as amino acid sequencing. Preincubation of SR with NaF and ATP, but not with NaF and AMP-PNP caused strong inhibition of ryanodine binding. This is due to decrease in Ca2+- and ryanodine-binding affinities of the ryanodine receptor (RyR) by about 6.6 and 18-fold, respectively. These results suggest that cardiac sarcalumenin is an isoform of the skeletal muscle protein. An endogenous CK II can phosphorylate sarcalumenin, and in parallel to its phosphorylation the properties of the ryanodine receptor are modified.

ObjectiveMental distress may entail increased risk of hip fracture, but it is uncertain whether the effect consists solely of an indirect effect through use of medication, or whether it is also mediated through other mechanism. The purpose of this study was to examine the association between mental distress and risk of hip fracture in women, adjusted for medication (that is, use of tranquillisers/sedatives or hypnotics).DesignA three year follow up of hip fracture was conducted on 18 612 women, consisting of 92.5% of all women aged 50 years or older in a Norwegian county. Three hundred and twenty nine suffered a hip fracture. A mental distress index was based on questions about life dissatisfaction, nervousness, loneliness, sleep disorders, troubled and uneasy feelings, depression and impairment attributable to psychological complaints. Relative risk with 95% confidence intervals (CI) of hip fracture with respect to mental distress were controlled for medication, age, body mass index (BMI), smoking, physical inactivity, and physical illness by means of Cox regression.ResultsThe 10% of women with the highest mental distress had more than twofold increased risk of hip fracture compared with the 10% of women with the lowest mental distress, after adjustment for age and medication. The relative risk was 1.95 (95% CI 1.2, 3.3) after additional control for BMI, smoking, physical inactivity, and physical illness. The relative risk of hip fracture for daily users of medication compared with never users was 2.1 (95% CI 1.6, 2.9). After adjusting for mental distress it was 1.5 (95% CI 1.0, 2.2).ConclusionsRisk of hip fracture was positively related to mental distress, also after adjustment for medication use. The effect of tranquillisers/sedatives or hypnotics on hip fracture risk may be overestimated in studies with no adjustments for mental distress.

Tau protein can be transformed into an Alzheimer‐like state by phosphorylation with a kinase activity from brain [Biernat et al. (1992) EMBO J. 11, 1593–1597]. Here we show that the phosphorylation at Ser‐Pro motifs strongly decreases tau's affinity for Microtubules. The major reduction occurs during the first of the three main stages of phosphorylation. The data explain the lower Stability of microtubules resulting from the pathological tau phosphorylation.

To obtain access to novel proteins of the neuronal synapse, we have raised antisera against proteins of synaptic plasma membranes and used them for immunoscreening brain cDNA expression libraries. One of the newly isolated cDNAs encodes an acidic protein of 75 kDa with a distinct architecture of structural domains and multiple potential phosphorylation sites. Light and electron microscopy employing monospecific antisera raised against the expression product indicate a synapse‐specific, presynaptic localization of this protein in many synapses of the chicken and rat nervous system. Its overall distribution in brain is very similar to that of synaptophysin, a ubiquitous protein of synaptic vesicles. In addition to brain, the protein or its mRNA is expressed in adrenal gland and anterior and posterior pituitary, but was not detected in a variety of other tissues. In controlled pore glass chromatography the native protein copurifies with synaptic vesicles and largely remains associated with them under various washing conditions. However, its amino acid sequence is very hydrophilic and it segregates into the aqueous phase in detergent phase partition. An earlier step of synaptic vesicle purification, sucrose cushion centrifugation, separates a vesicle‐bound fraction of this protein from an unbound fraction. This seems to be a new, perhaps peripheral, protein of synaptic vesicles for which we propose the name, amphiphysin.

Background: Polypeptides in Hevea latex are known as the major cause of latex type I sensitivities. So far, only a few of them have been characterized. Methods: Proteins with a molecular weight lower than 10 kd in fresh Hevea latex were separated by ultrafiltration and further characterized by liquid chromatography on-line-coupled electrospray mass spectrometry. Hevein in this fraction was then purified by preparative reverse-phase high-performance liquid chromatography and characterized by matrix-assisted laser desorption ionization mass spectrometry and protein sequencing. Skin prick tests, enzyme-linked allergosorbent tests, and inhibition immunoblotting were performed to show the allergenicity of the purified hevein. Results: Hevein, a 4.7 kd polypeptide, is the predominant component in the fraction with latex proteins of smaller than 10 kd. Specific IgE antibodies to hevein were detected by enzyme-linked allergosorbent test in 48 of 64 (75%) sera from health care workers allergic to latex and in three of 11 (27%) sera from patients with spina bifida and hypersensitivity reactions to latex. Inhibition immunoblotting demonstrated that the preincubation of 14 sera and a serum pool from patients allergic to latex with purified hevein completely inhibited IgE binding to the 20 kd protein, which has been recently reported to be a major allergen in latex (prohevein). Skin prick testing showed a positive reaction to hevein in 17 of 21 (81%) patients with latex allergy. Conclusions: The results clearly demonstrate that hevein is an important latex allergen, and the IgE-binding capacity of prohevein in latex is mostly attributed to hevein, the N-terminal domain of prohevein. ( J Allergy Clin Immunol 1997;99:402-9.)

In the present study, the purification and sequence analysis of a peptide extracted from human plasma is described. After three chromatographic steps in one of the plasma fractions, a molecular mass of 920 Da was determined with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis. Further analysis with post-source-decay (PSD)-MALDI-MS revealed an amino acid sequence arg-pro(pro-gly+16)-phe-ser-pro-phe. With the data given from the spectrum, it was impossible to clarify the partial sequence (pro-gly+16). A comparison with a data base suggested that the sequence is very similar to des-arg9bradykinin (arg-pro-pro-gly-phe-ser-pro-phe). But many fragment masses, including the mass of the parent ion of the unknown peptide, are 16 Da larger than the corresponding fragment masses of des-arg9-bradykinin. The interpretation of the fragment pattern does not allow determination of the position of the amino acid that is 16 Da larger. With automated Edman sequence analysis of the fraction of interest, three more major component peptides in this fraction were observed, which were not detected with MALDI-MS. Nevertheless, with the help of the Edman sequence data it was possible to identify the unknown amino acid in the PSD-MALDI-MS sequence as hydroxyproline at the third position. In conclusion, the existence of des-arg9[hyp3]-bradykinin (arg-pro-hyp-gly-phe-ser-pro-phe) in human plasma is described. Furthermore, the study demonstrates that PSD-MALDI-MS and automated Edman sequence analysis complement each other if single unknown peptides from mixtures are to be sequenced.

Lantibiotics are antibiotic peptides produced via ribosomal synthesis of precursor proteins by gram-positive bacteria. They contain various unusual post-translational modifications, which include the formation of sulfide rings by lanthionine or β-methyllanthionine, and 2,3-didehydroamino acids. The N-terminus may be blocked by a 2-oxobutyryl group and the C-terminus may be inaccessible in some of the lantibiotics. Due to these modifications the analysis of such peptides is very tedious. Chemical modifications using an ethanethiol-containing reaction mixture and/or trifluoroperacetic acid treatment were used to solve these analytical problems. Investigating the tetracyclic 22-peptide gallidermin and the N-terminally blocked tricyclic 34-peptide Pep5 as examples, a novel access to the primary structure of lantibiotics is demonstrated.

Complementary DNAs for the γ subunit of the calcium channel of rabbit skeletal muscle were isolated on the basis of peptide sequences derived from the purified protein. The deduced primary structure is without homology to other known protein sequences and is consistent with the γ subunit being an integral membrane protein.