Prevalence and correlates of insufficient calcium intake in a Swedish population

OBJECTIVE: To examine associations between calcium intake in the diet, lifestyle factors, and forearm bone mineral density (BMD) in order to identify population subgroups for targeting by screening programs. METHODS: A questionnaire was sent to a random sample of 15% of the inhabitants aged 20-79 years from 2 Swedish municipalities, and the subsample from one of the municipalities was invited to measurement of BMD. The survey response rate was 74% (n = 1,112/1,510) and participation in BMD measurements was 68% (n = 448/659). RESULTS: Only a tendency ( p = .085) toward direct association between calcium intake and forearm BMD was found, and the best multiple regression model was retained to explain BMD excluded calcium intake. Low calcium intake was, instead, in complementary analyses, found to be correlated with the factors old age, female sex, and urban residence in the best multiple regression model. CONCLUSIONS: Population subgroups whose calcium intake is in a range that justifies preventive action could be identified. Screening programs staffed by public health nurses can thereby be informed regarding the subgroups of the population that are at the highest risk of insufficient calcium intake.     

T cell activation enhancement by endogenous pMHC acts for both weak and strong agonists but varies with differentiation state

T cells are extremely sensitive in their ability to find minute amounts of antigenic peptide in the midst of many endogenous peptides presented on an antigen-presenting cell. The role of endogenous peptides in the recognition of foreign peptide and hence in T cell activation has remained controversial for CD8⁺ T cell activation. We showed previously that in a CD8⁺ T cell hybridoma, nonstimulatory endogenous peptides enhance T cell sensitivity to antigen by increasing the coreceptor function of CD8. However, others were not able to detect such enhancement in naive and activated CD8⁺ T cells. Here, we show that endogenous peptides substantially enhance the ability of T cells to detect antigen, an effect measurable by up-regulation of activation or maturation markers and by increased effector function. This enhancement is most pronounced in thymocytes, moderate in naive T cells, and mild in effector T cells. The importance of endogenous peptides is inversely proportional to the agonist activity of the stimulatory peptide presented. Unlike for CD4⁺ T cells, the T cell receptor of CD8⁺ T cells does not distinguish between endogenous peptides for their ability to enhance antigen recognition.     

Progressive neurodegeneration and motor disabilities induced by chronic expression of IL-1beta in the substantia nigra

The functional role of the long-lasting inflammation found in the substantia nigra (SN) of Parkinson's disease (PD) patients and animal models is unclear. Proinflammatory cytokines such as interleukin-1beta (IL-1beta) could be involved in mediating neuronal demise. However, it is unknown whether the chronic expression of cytokines such as IL-1beta in the SN can alter neuronal vitality. The aim of this study was to investigate the effects of the chronic expression of IL-1beta in the adult rat SN using a recombinant adenovirus expressing IL-1beta. The chronic expression of IL-1beta for 60 days induced dopaminergic cell death in the SN and unilateral akinesia starting only at 21 days post-injection. Microglial cell activation and inflammatory cell infiltrate were associated with dopaminergic cell death and motor disabilities. Astrocytic activation was delayed and associated with scar formation. The chronic expression of a single proinflammatory cytokine as IL-1beta in the SN elicited most of the characteristics of PD, including progressive dopaminergic cell death, akinesia and glial activation. Our data suggest that IL-1beta per se is able to mediate inflammatory-mediated toxic effects in the SN if its expression is sustained. This model will be helpful to identify possible therapeutic targets related to inflammation-derived neurodegeneration in the SN.     

Gene expression profilers and conventional clinical markers to predict distant recurrences for premenopausal breast cancer patients after adjuvant chemotherapy

A large proportion of breast cancer patients are treated with adjuvant chemotherapy after the primary operation, but some will recur in spite of this treatment. In order to achieve an improved and more individualised therapy, our knowledge in mechanisms for drug resistance needs to be increased. We have investigated to what extent cDNA microarray measurements could distinguish the likelihood of recurrences after adjuvant CMF (cyclophosphamide, methotrexate and 5-fluorouracil) treatment of premenopausal, lymph node positive breast cancer patients, and have also compared this with the corresponding performance when using conventional clinical variables. We tried several gene selection strategies, and built classifiers using the resulting gene lists. The best performing classifier with odds ratio (OR)=6.5 (95% confidence interval (CI)=1.4-62) did not outperform corresponding classifiers based on clinical variables. For the clinical variables, calibrated on the samples, either using all the clinical parameters or the Nottingham Prognostic Index (NPI) parameters, the areas under the receiver operating characteristics (ROC) curve were 0.78 and 0.79, respectively. The ORs at 90% sensitivity were 15 (95% CI=3.1-140) and 10 (95% CI=2.1-97), respectively. Our data have provided evidence for a comparable prediction of clinical outcome in CMF-treated breast cancer patients using conventional clinical variables and gene expression based markers.     

Protein-tyrosine phosphatases and cancer

Tyrosine phosphorylation is an important signalling mechanism in eukaryotic cells. In cancer, oncogenic activation of tyrosine kinases is a common feature, and novel anticancer drugs have been introduced that target these enzymes. Tyrosine phosphorylation is also controlled by protein-tyrosine phosphatases (PTPs). Recent evidence has shown that PTPs can function as tumour suppressors. In addition, some PTPs, including SHP2, positively regulate the signalling of growth-factor receptors, and can be oncogenic. An improved understanding of how these enzymes function and how they are regulated might aid the development of new anticancer agents.