Ribose-enhanced synthesis of UTP, CTP, and GTP from parent nucleosides in cardiac myocytes

1. Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs. 2. We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR-SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3'-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively. 3. Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17-18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer. 4. The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping.     

Pulmonary vein stenosis after catheter ablation of atrial fibrillation

BACKGROUND: This report describes the complication of pulmonary vein stenosis with resultant severe pulmonary hypertension that developed in 2 patients after successful catheter ablation of chronic atrial fibrillation. METHODS AND RESULTS: Three months after successful catheter ablation of atrial fibrillation, both patients developed progressive dyspnea and pulmonary hypertension. Both were found to have severe stenosis of all 4 pulmonary veins near the junction with the left atrium. Balloon dilation of the stenotic pulmonary veins was performed in these patients, with improvement in dyspnea and pulmonary hypertension. CONCLUSIONS: The complication of pulmonary vein stenosis is potentially life-threatening, and the application of radiofrequency current within the pulmonary veins with standard catheter technology should be avoided. This complication can be treated with balloon dilation, although the long-term course is unknown.     

A primate model for enteral nutrition by tube

To establish an animal model for the controlled study of enteral nutrition by tube, five adult chair-adapted primates (Macaca fasicularis) had gastrostomy and jejunostomy tubes placed for the delivery of a modified protein isolate diet. Following 7 days of postoperative depletion with a hypocaloric infusion of dextrose (20 kcal, 0 g N/kg/day), the animals were repleted for 10 days with tube feedings (124 kcal, 0.73 g N/kg/day). There was no operative mortality or morbidity and each animal demonstrated conversion to anabolism by significant weight gain, positive nitrogen balance, and net protein synthesis as determined by [15N]glycine protein turnover rates. Significant correlation was found between caloric intake and nitrogen balance at the level of nitrogen provided in this diet (r = 0.88, p less than 0.05). This model was found to be well suited for the surgical and nutritional techniques required for the long-term study of enteral nutrition by tube.     

Comparison of urinary excretion of UV-absorbing constituents in healthy subjects and patients with rheumatoid arthritis using analytical isotachophoresis

Analytical isotachophoresis has been applied to the separation of urinary constituents in healthy controls and patients with rheumatoid and osteoarthritis. Various methods of comparing isotachograms have been investigated. Significant differences have been demonstrated between the pattern of UV-absorbing components in patients with rheumatoid arthritis and healthy subjects.     

Action research in user-centred product development

Technological development and increased international competition have imposed a significant burden on the product development function of many companies. The growing complexity of products demands a larger product development team with people having various competencies. Simultaneously the importance of good quality, usability and customisation of products is growing, and many companies want to involve customers and users directly in the development work. Both the complexity and quality demand new ways of working that support collaboration between people with various competencies, interests and responsibilities both inside and outside the company. This paper reports experiences from using action research to introduce new user-centred work practices in two commercial product development projects. The interventions varied. In the first project it was found rewarding to engage customers and users in workshops based on participatory inquiry and collaborative design. The design process was iterative and the workshops took place several times involving concept through detailed design. In the second project, new design representations are introduced. The experiences highlight the importance of creating and reifying insights in design representations and using these to both support collaboration, and create continuity in the project. The paper ends with a discussion of scientific rigor in action research and what the new work practices imply for the development team.     

Phase equilibrium and growth of homogeneous crystals in the γLa2S3  γNd2S3 system

T-x diagram of the γLa₂S₃  γNd₂S₃ system was plotted for the temperature interval 1400–2100°C. γLa₂S₃ and γNd₂S₃ form unlimited solid solutions of the substitution type. Basing on this phase diagram the theoretical distribution curves of Nd₂S₃ along the ingot of length were calculated. The experimental distribution curves were determined by chemical and electron microprobe measurements of La and Nd content in γ(La,Nd)₂S₃ ingots directionally solidified from the melt of different composition. Character of the component distribution in the ingots shows that diffusion of neodymium and lanthanum is exeptionally fast at 1700–2000°C. This phenomenon is explained by vacancy diffusion mechanism in γLa₂S₃  γNd₂S₃ solid solutions. Crystal structure of these solid solutions belongs to Th₃P₄ type with high concentration of randomly distributed cation vacancies.     

Analysis and synthesis of modally balanced systems

We study a special kind of linear dynamical systems, namely modally balanced systems, in which the transition function’s poles are proportional to Hankel singular values. We analyze existence conditions and properties of such systems and develop algorithms for their synthesis. Our results include algebraic modal balance criteria.