ABSTRACT
The central role for PrP in the pathogenesis of the transmissible spongiform encephalopathies (TSEs) is illustrated by the resistance of Prnp(0/0) mice to disease and by the inverse association of Prnp gene dosage with incubation period. Understanding the role of PrP(C) in TSEs necessitates knowledge of expression levels of the Prnp gene during the development of disease. SSBP/1 scrapie shows a defined pattern of disease progression and here we show that Prnp and shadow of PrP (Sprn) are differentially expressed in different brain areas and lymphoid tissues. Counter-intuitively we found that there is no positive correlation between expression of Prnp or Sprn and patterns of disease progression. Prnp and Sprn expression levels are both influenced by Prnp genotype; although the scrapie-sensitive VRQ/VRQ sheep did not express the highest level of either. In addition, infection with SSBP/1 scrapie seems to have little effect on either PrP or Shadoo expression levels.
Subject(s)
Gene Expression , Nerve Tissue Proteins/genetics , PrPC Proteins/genetics , Scrapie/genetics , Sheep, Domestic/genetics , Animals , Brain/metabolism , Genotype , Lymphoid Tissue/metabolism , Phenotype , Transcription, GeneticABSTRACT
The Potassium Adherence Clinical Trial (PACT) incorporates one randomized clinical trial within another. A randomized trial of interventions to increase adherence to medication is nested within a second randomized clinical trial testing hypotensive effect of supplemental oral potassium. The trial aims principally to compare the effects of three intervention strategies: two sessions of individual patient counseling, two telephone contacts, or standard care. The trial aims secondarily to evaluate the effect of 60 mEq supplemental oral potassium daily on sitting systolic and diastolic blood pressure in hypertensive patients on established drug therapy. Therefore, it organizes the patients given potassium into three study groups for adherence interventions, and the patients assigned to placebo into a further three. We evaluate adherence primarily by means of the Medication Event Monitoring System (MEMS), an electronic system that records the date and time that the container of study medication is opened. Additional measurements, such as assessments of change in levels of urinary potassium, pill counts, appointment records, self-reporting by patients, and estimates by physician of adherence, are used and correlated with MEMS data. At a single center, the trial enrolled 107 participants between the ages of 26 and 80. This paper describes the background to this trial within a trial, details its design, documents the baseline characteristics of participants enrolled, and describes issues experienced during implementation of the trial.
Subject(s)
Hypertension/drug therapy , Patient Compliance , Potassium/therapeutic use , Randomized Controlled Trials as Topic/methods , Adult , Aged , Aged, 80 and over , Dietary Supplements , Female , Humans , Male , Middle Aged , Patient Education as Topic , Reminder Systems , Research Design , TelephoneABSTRACT
An unknown sequence that may encode a fragment of the Ser/Thr protein phosphatase (designated PP6Zm) related to PPT/rdgC phosphatases was identified using PCR on maize genomic DNA. A dbEST search using a partial amino acid sequence of PP6Zm revealed a putative homolog of PP6Zm expressed in Arabidopsis thaliana (EMBL AT6726). A search of the SwissProt database indicated that the partial amino acid sequence of AT6726 has the highest identity (54.3%) to the rdgC phosphatase from Drosophila melanogaster. The maize phosphatase PP1Zm6, described previously as a PP1 isoform (EMBO J., 1993, vol. 12, p. 3497), was found by us to be plant homolog of mammalian PPT. In addition, six fragments of new (pseudo) genes homologous to the phosphatase genes encoding PP1, PP2A, and PPX isoforms were detected in the maize genome. The existence in maize of a multigene PP2A family, reported only for dicotyledons, and of a PP1 multigene family, found earlier in both di- and monocotyledons, was shown.
