Quality assurance of the donation process.

The quality of the organs harvested from a deceased donor is of critical importance for the outcome of the transplantations. During 2005, a quality assurance project was initiated to evaluate the donor management, harvest operation, and flow of information during the donation process. Three kinds of questionnaires were used in each donation. They were completed by the transplant coordinator, the harvesting surgeon, and the surgeons performing the liver and kidney transplantations. Feedback is given to the harvesting teams within 2 weeks after the procedures. The most important findings related to missed information concerning organ abnormalities or organ damage from the procurement operation. Procurement of organs from a deceased donor involves a complex chain of events. Based on our experiences in this 1-year project, we believe that standardized registration of the various parts of the process and structured feedback to the staff give possibilities to improve performance. After minor modifications, this method for quality assurance has been introduced as a permanent part of our donation procedure. We believe that this strategy can help to detect weaknesses and improve transplant outcomes.

Changing donation pattern in central Sweden.

Since 1990, the Organisation for Organ donation in Central Sweden has registered the numbers of donations at the various hospitals in the area. During this period, a significant decrease in donation rate was observed in the large hospitals, while there was an increase in donation rate in the smaller hospitals. Taken together, the small hospitals are now at least as important as the large hospitals. Possible reasons for the observed change in donation pattern are discussed.

Monitoring patients in complete cytogenetic remission after treatment of CML in chronic phase with imatinib: patterns of residual leukaemia and prognostic factors for cytogenetic relapse.

We monitored BCR-ABL transcript levels by quantitative real-time PCR in 103 patients treated with imatinib for chronic myeloid leukaemia in chronic phase for a median of 30.3 months (range 5.5-49.9) after they achieved complete cytogenetic remission (CCyR). The patients could be divided into three groups: (1) in 32 patients transcript levels continued to decline during the period of observation (nadir BCR-ABL/ABL ratio 0.015%); in five of these patients BCR-ABL transcripts became undetectable on repeated testing, (2) in 42 patients the transcript levels reached a plateau and (3) in 26 patients transcript numbers increased and the initial CCyR was lost. Three patients were not evaluable. Patients who remained in CCyR for at least 24 months appeared to have a low risk of subsequent cytogenetic relapse. We conclude that the pattern of 'residual' disease after achieving CCyR on imatinib is variable: some patients in CCyR show a progressive reduction in the level of residual disease, some reach a plateau where transcript numbers are relatively stable and others relapse with Ph-positive metaphases.

Suppressors of ssy1 and ptr3 null mutations define novel amino acid sensor-independent genes in Saccharomyces cerevisiae.

Ssy1p and Ptr3p are components of the yeast plasma membrane SPS amino acid sensor. In response to extracellular amino acids this sensor initiates metabolic signals that ultimately regulate the functional expression of several amino acid-metabolizing enzymes and amino acid permeases (AAPs). As a result of diminished leucine uptake capabilities, ssy1Delta leu2 and ptr3Delta leu2 mutant strains are unable to grow on synthetic complete medium (SC). Genes affecting the functional expression of AAPs were identified by selecting spontaneous suppressing mutations in amino acid sensor-independent (ASI) genes that restore growth on SC. The suppressors define 11 recessive (asi) complementation groups and 5 dominant (ASI) linkage groups. Strains with mutations in genes assigned to these 16 groups fall into two phenotypic classes. Mutations in the class I genes (ASI1, ASI2, ASI3, TUP1, SSN6, ASI13) derepress the transcription of AAP genes. ASI1, ASI2, and ASI3 encode novel membrane proteins, and Asi1p and Asi3p are homologous proteins that have conserved ubiquitin ligase-like RING domains at their extreme C termini. Several of the class II genes (DOA4, UBA1, BRO1, BUL1, RSP5, VPS20, VPS36) encode proteins implicated in controlling aspects of post-Golgi endosomal-vacuolar protein sorting. The results from genetic and phenotypic analysis indicate that SPS sensor-initiated signals function positively to facilitate amino acid uptake and that two independent ubiquitin-mediated processes negatively modulate amino acid uptake.