No abstract

No abstract

Pulmonary alveolar proteinosis (PAP) is a potentially fatal complication of lysinuric protein intolerance (LPI), an inherited disorder of cationic amino acid transport. The patients often present with mild respiratory symptoms, which may rapidly progress to acute respiratory failure responding poorly to conventional treatment with steroids and bronchoalveolar lavations (BALs). The pathogenesis of PAP in LPI is still largely unclear. In previous studies, we have shown disturbances in the function and activity of alveolar macrophages of these patients, suggesting that increasing the activity and the number of macrophages by recombinant human GM-CSF (rhuGM-CSF) might be beneficial in this patient group.Two LPI patients with complicated PAP were treated with experimental inhaled rhuGM-CSF (sargramostim) after poor response to maximal conventional therapy.

Abstract. Lysinuric protein intolerance (LPI) is an inherited aminoaciduria caused by recessive mutations in the SLC7A7 gene encoding y + L amino acid transporter 1 (y + LAT1), which combines with 4F2hc to generate an active transporter responsible for the system y + L amino acid transport. We have previously shown that the y + LAT1 proteins with point mutations are expressed in the plasma membrane, while those with frame shift mutations are retained in the cytoplasm. This finding has prompted us to study whether the difference in localization is due to the inability of the structurally altered mutant y + LAT1 proteins to heteromerize with 4F2hc. For this purpose, we utilized FACS technique to reveal fluorescence resonance energy transfer (FRET) in cells expressing wild type or LPI-mutant CFP-tagged y + LAT1 and YFP-tagged 4F2hc. The heteromerization of y + LAT1 and 4F2hc within the cell is not disrupted by any of the tested LPI mutations. In addition, the expression rate of the LPI mutant y + LAT1 proteins was significantly lower and cellular mortality was markedly increased than that of the wild type y + LAT1 in transfected samples. Our results indicate that the FACS-FRET method provides an alternative approach for screening of potential protein associations.

<b><i>Objective:</i></b> The aim of this study was to gain insight into the understanding of genetics and perceptions on the ethical issues related to genotype disclosure of the participants in a nutrigenetic study. <b><i>Methods:</i></b> A close-ended questionnaire was developed based on literature and discussions among the research group members. The questionnaire contained a ­total of 33 questions, which were divided into 4 categories – demographics, knowledge assessment, concerns related to participation, and opinions on disclosure of information. Majority of the participants (250 out of 281) of a nutrigenetic study, in which effect of disclosing <i>APOE</i> allele status on lifestyle changes was studied, completed the questionnaire online following the informed consent process. The responses from the knowledge assessment and the concern categories were transformed into knowledge and concern scales, respectively, and analysed by descriptive statistical methods. The statistical associations between the categorical variables were determined using χ² test of independence. The relationship between the continuous variables was assessed using Pearson product-moment correlation coefficient and internal consistency of questions by Cronbach’s alpha. <b><i>Results:</i></b> No correlation was observed between the level of education and knowledge scores. About 10% of the participants thought that the genetic predisposition would be stressful to them and their family members. <b><i>Conclusions:</i></b> Careful distribution of information before a nutrigenetic study supports understanding and reduces concerns of genetic susceptibility. In Finland, strong basic education is likely to have strengthened the trust in research process.