MHC class II association with lipid rafts on the antigen presenting cell surface.

MHC class II (MHC-II) molecules function by binding peptides derived from either self or foreign proteins and expressing these peptides on the surface of antigen presenting cells (APCs) for recognition by CD4 T cells. MHC-II is known to exist on clusters on the surface of APCs, and a variety of biochemical and functional studies have suggested that these clusters represent lipid raft microdomain-associated MHC-II. This review will summarize data exploring the biosynthesis of raft-associated MHC-II and the role that lipid raft association plays in regulating T cell activation by APCs. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.

Evaluation of butyrate-induced production of a mannose-6-phosphorylated therapeutic enzyme using parallel bioreactors.

Bioreactor process changes can have a profound effect on the yield and quality of biotechnology products. Mannose-6-phosphate (M6P) glycan content and the enzymatic catalytic kinetic parameters are critical quality attributes (CQAs) of many therapeutic enzymes used to treat lysosomal storage diseases (LSDs). Here, we have evaluated the effect of adding butyrate to bioreactor production cultures of human recombinant ß-glucuronidase produced from CHO-K1 cells, with an emphasis on CQAs. The ß-glucuronidase produced in parallel bioreactors was quantified by capillary electrophoresis, the catalytic kinetic parameters were measured using steady-state analysis, and mannose-6-phosphorylation status was assessed using an M6P-specific single-chain antibody fragment. Using this approach, we found that butyrate treatment increased ß-glucuronidase production up to approximately threefold without significantly affecting the catalytic properties of the enzyme. However, M6P content in ß-glucuronidase was inversely correlated with the increased enzyme production induced by butyrate treatment. This assessment demonstrated that although butyrate dramatically increased ß-glucuronidase production in bioreactors, it adversely impacted the mannose-6-phosphorylation of this LSD therapeutic enzyme. This strategy may have utility in evaluating manufacturing process changes to improve therapeutic enzyme yields and CQAs.

Differences in medication errors between central and remote site telepharmacies.

OBJECTIVE: To examine differences in dispensing errors within community telepharmacy practices by comparing error rates across central sites (community telepharmacy sites with pharmacists present) and the corresponding remote sites, which are staffed by registered technicians and overseen by the central site pharmacist. DESIGN: Cross-sectional pilot study with a test group (remote sites) and comparison group (central sites). SETTING: 24 rural community telepharmacies (14 remote sites and 10 central sites). PARTICIPANTS: Pharmacy staff. INTERVENTION: The Pharmacy Quality Commitment (PQC) reporting system was integrated into the North Dakota Telepharmacy Project and used to track dispensing errors over a 45-month period. Both pharmacists and pharmacy technicians were trained on the use of the PQC system. The PQC system focused on two quality-related events (QREs): a "near miss" (i.e., a mistake discovered by the pharmacy staff before a medication reaches the patient) and an "error" (i.e., a mistake discovered after the patient leaves the pharmacy with the medication). MAIN OUTCOME MEASURES: The distribution of QREs across central and remote sites. RESULTS: The remote (central) telepharmacy group reported 47,078 (62,480) prescriptions and a QRE rate of 1.34% (1.43%). QREs at the remote sites were more likely than at the central sites to be caught at the final pharmacist check (58.2% vs. 40.8%, P < 0.01) and less likely to be caught by the patient (0.17% vs. 0.28%, P < 0.01). Remote sites were more likely to include incorrect directions (18.9% vs. 13.4%, P = 0.01) in the medication entry process. CONCLUSION: QRE rates for remote site and central site telepharmacies were consistent with each other and with national estimates in traditional community pharmacies. However, significant differences between central and remote sites existed based on how QREs arose and how they were caught. Pharmacists must recognize this fact and use diligence when working in a telepharmacy setting.

Do remote community telepharmacies have higher medication error rates than traditional community pharmacies? Evidence from the North Dakota Telepharmacy Project.

OBJECTIVE: To evaluate the differences in medication dispensing errors between remote telepharmacy sites (pharmacist not physically present) and standard community pharmacy sites (pharmacist physically present and no telepharmacy technology; comparison group). DESIGN: Pilot, cross-sectional, comparison study. SETTING: North Dakota from January 2005 to September 2008. PARTICIPANTS: Pharmacy staff at 14 remote telepharmacy sites and 8 comparison community pharmacies. INTERVENTION: The Pharmacy Quality Commitment (PQC) reporting system was incorporated into the North Dakota Telepharmacy Project. A session was conducted to train pharmacists and technicians on use of the PQC system. A quality-related event (QRE) was defined as either a near miss (i.e., mistake caught before reaching patient; pharmacy discovery), or an error (i.e., mistake discovered after patient received medication; patient discovery). MAIN OUTCOME MEASURE: QREs for prescriptions. RESULTS: During a 45-month period, the remote telepharmacy group reported 47,078 prescriptions and 631 QREs compared with 123,346 prescriptions and 1,002 QREs in the standard pharmacy group. Results for near misses (pharmacy discovery) and errors (patient discovery) for the remote and comparison sites were 553 and 887 and 78 and 125, respectively. Percentage of "where the mistake was caught" (i.e., pharmacist check) for the remote and comparison sites were 58% and 69%, respectively. CONCLUSION: This study reported a lower overall rate (1.0%) and a slight difference in medication dispensing error rates between remote telepharmacy sites (1.3%) and comparison sites (0.8%). Both rates are comparable with nationally reported levels (1.7% error rate for 50 pharmacies).

Scheduled napping as a countermeasure to sleepiness in air traffic controllers.

The aims of this study were to measure sleep during a planned nap on the night shift; and to use objective measures of performance and alertness to compare the effects of the nap opportunity versus staying awake. Twenty-eight air traffic controllers (mean age 36 years, nine women) completed four night shifts (two with early starts and two with late starts). Each type of night shift (early/late start) included a 40-min planned nap opportunity on one occasion and no nap on the other. Polysomnographic data were used to measure sleep and waking alertness [spectral power in the electroencephalogram (EEG) during the last hour of the night shift and the occurrence of slow rolling eye movements (SEMs) subsequent to the nap]. Psychomotor performance task [Psychomotor Vigilance Task (PVT)] was completed at the beginning and end of the shift, and after the nap (or an equivalent time if no nap was taken). Nap sleep latencies were relatively long (mean = 19 min) and total sleep time short (mean = 18 min), with minimal slow wave sleep (SWS, mean = 0%), and no rapid eye movement sleep. Nap sleep resulted in improved PVT performance (mean and slowest 10% of reaction time events), decreased spectral power in the EEG and reduced the likelihood of SEMs. The occurrence of SWS in the nap decreased spectral power in the EEG. This study indicates that although sleep taken at work is likely to be short and of poor quality it still results in an improvement in objective measures of alertness and performance.

Natural anticoagulant proteins in the regulation of autoimmunity: potential role of protein S.

Autoimmunity results when the immune system fails to distinguish between self and non-self factors in the body. The cellular and biochemical mechanisms that underlie development of autoimmunity are only partly understood. One current theory is that autoimmunity can result when there is a failure to clear dying cells from a tissue before they undergo lysis of the plasma membrane. That is, cells that die by apoptosis are thought to be cleared from a tissue by neighboring phagocytic cells, such as macrophages, before the cells have lost their plasma membrane integrity. This rapid removal of early apoptotic cells is thought to prevent induction of an inflammatory response to intracellular macromolecules, thereby allowing for an immunologically silent removal of the dying cells. Hence, any factor or condition that inhibits phagocytosis of early apoptotic cells may trigger or promote an autoimmune response to intracellular components. Depletion of factors required for the efficient phagocytosis of dying cells would have a similar outcome. The recent discovery that the natural anticoagulant protein S is required for efficient uptake of apoptotic cells (Anderson, H.A., Maylock, C.A., Williams, J.A., Paweletz, C.P., Shu, H., and Shacter, E. (2003) Nature Immunology 4, 87-91) reveals a potential new linkage between autoimmunity and coagulation systems. This article will review the dual roles of protein S as an anticoagulant and in regulating phagocytosis of apoptotic cells, with emphasis on exposing a possible novel role in regulating autoimmunity.