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B lymphocyte memory generates antibody-secreting cells (ASCs) that represent a source of protective antibodies that may be exploited for therapeutics. Here we vaccinated four donors with Pneumovax®23 and produced human monoclonal antibodies (hmAbs) from ASCs. We have cloned 137 hmAbs and the specificities of these antibodies encompass 19 of the 23 serotypes in the vaccine, as well as cell wall polysaccharide (CWPS). Although the majority of the antibodies are serotype specific, 12% cross-react with two serotypes. The Pneumovax®23 ASC antibody sequences are highly mutated and clonal, indicating an anamnestic response, even though this was a primary vaccination. Hmabs from 64% of the clonal families facilitate opsonophagocytosis. Although 9% of the total antibodies bind to CWPS impurity in the vaccine, none of these clonal families showed opsonophagocytic activity. Overall, these studies have allowed us to address unanswered questions in the field of human immune responses to polysaccharide vaccines, including the cross-reactivity of individual antibodies between serotypes and the percentage of antibodies that are protective after vaccination with Pneumovax®23., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Presence of guanine nucleotide within the matrix of mitochondria is uncontested; the mechanism by which GTP takes up residence in the matrix is unknown. In this report, we demonstrate for the first time that direct transport of guanine nucleotide across the inner membrane of heart mitochondria is possible. Transport of guanine nucleotides from the medium to the matrix was suggested by inhibition of translation in isolated rat heart mitochondria when GTP-gamma-S was added to the medium. This result suggested that GTP was one source of matrix GTP. Other sources were investigated by measuring matrix uptake and conversion to GTP of several purines, purine nucleosides, and purine nucleotides. Results demonstrated that [14C]-guanine and [3H]-guanosine were not taken up by isolated mitochondria and were not converted to any other compound. While [14C]-ATP and [3H]-AMP were taken up readily into the matrix, radioactivity was never associated with a guanine compound. [3H]-IMP was not taken up into the matrix and was never converted to another compound. Our data showed that label added as [3H]-GTP, [3H]-GDP, or [3H]-GMP was readily taken up and concentrated in the matrix of isolated mitochondria., (Copyright 1999 Academic Press.)

Experience with Staphylococcus aureus infections in a hemodialysis unit in which arteriovenous fistulas were used routinely for dialysis is reviewed, including an epidemic involving multiple bacteriophage types. Most infections involved the fistula site and were associated with bacteremia, although bacteremia without an obvious fistula infection did occur. Despite recurrent bacteremia, endocarditis was not documented, and patients did not develop teichoic acid antibodies as measured by an immunodiffusion technique. Patients with fistula infections responded to antibiotic therapy and did not require removal of the fistula except in two patients whose fistulas ruptured. Patients with shunt infections had to have their shunts removed to control infection. The epidemic developed after the hemodialysis unit was moved into a larger area to facilitate an increasing number of patients and after diabetic patients were admitted to the dialysis program. Both autoinfection and cross-infection contributed to the epidemic, which resolved with improvements in aseptic techniques. A culture survey indicated that the nasal carriage of staphylococci was not unusually high during the epidemic. This report emphasizes that staphylococcal infections remain a problem in continually changing hospital environments.