Mimotope/anti-mimotope probing of structural relationships in platelet glycoprotein Ib alpha.

A bacteriophage library displaying random decapeptides was used to characterize the binding preference of C-34, a monoclonal antibody originally raised against platelet-type von Willebrand disease platelets heterozygous for the mutation 23OWKQ (G --> V)233V234 in the alpha chain of glycoprotein Ib (GPIb alpha). Three rounds of biopanning C-34 against the library resulted in striking convergence upon the sequence WNWRYREYV. Since no portion of this sequence corresponds to a recognizable peptide sequence within human platelet GPIb alpha, it may be considered a "mimotope" of the naturally occurring C-34 epitope, presumably bearing similarity to it in three-dimensional structure. Synthetic AWNWRYREYV peptide preincubated with C-34 fully neutralized the ability of C-34 to inhibit platelet aggregation, with an IC50 of approximately 6 microg/ml. When biotinylated AWNWRYREYV was subsequently bioparmed against the original decapeptide library, the sole clone demonstrating inhibitory activity above background level in a functional platelet assay displayed the sequence RHVAWWRQGV, and chemically synthesized peptide fully inhibited ristocetin-induced aggregation, with an IC50 of 200-400 microg/ml. Synthesized RHVAWWKQGV peptide exerted only slight inhibition, whereas RHVAWWKQVV peptide showed potent inhibitory activity. Moreover, whereas synthesized wild-type 228YVWKQGVDVK237 GPIb alpha peptide was virtually without inhibitory activity, the 228YVWKQ(G -->V) 233VDVK237 peptide fully inhibited ristocetin-induced aggregation, with an IC50 of approximately 400 microg/ml. These studies raise the possibility of an intramolecular association of peptide regions within GPIb alpha that may play a role in the regulation of von Willebrand factor-dependent platelet aggregation.     

Factors Driving the HIV Epidemic in Southern Africa

The HIV pandemic has disproportionately impacted sub-Saharan Africa and Southern Africa in particular. The concurrent presence of overlapping epidemic drivers likely underpins how and why the HIV epidemic is so explosive in this region, with implications for understanding approaches to reduce transmission. In this review, we discuss the relative contribution and interaction between epidemic drivers in the Southern African context, including factors both distally and proximally associated with the likelihood and degree of exposure to HIV and factors that increase the probability of transmission when exposure occurs. In particular, we focus on young women as a key population in need of HIV prevention and highlight factors that increase their risk on several levels.     

Editorial

Z-Score neurofeedback has expanded to include 19-channel models (19ZNF) such that clinicians now have the option to use from 1 to 19 electrodes in a z-score neurofeedback protocol. Benefits and limitations of this new model are discussed from the clinical perspective of an early adopter of 19ZNF who has more than 4 years of experience with this modality after having several years of experience with QEEG-guided NF (QNF). Comparisons between QNF and 19ZNF are discussed. It has been suggested that 19ZNF can bring about positive clinical outcomes in fewer sessions than traditional NF, which matches the author's experience (average of 38 with QNF vs. an average of 11 with 19ZNF). Unique implications of 19ZNF that have not yet been discussed in the literature, such as the advantage of once-per-week sessions, or questions about whether there could be times when change can occur too fast, are introduced. Directions for future research to further evaluate 19ZNF are suggested.     

Major Hepatectomy Induces Phenotypic Changes in Circulating Dendritic Cells and Monocytes

Introduction  Patients undergoing major hepatectomy are at increased risk for post-operative morbidity and mortality, and changes in the phenotype of effector cells may predispose these patients to infectious sequelae. Methods  To better understand post-hepatectomy immune responses, peripheral blood from 15 hepatectomy patients was drawn immediately before and after liver resection and on post-operative days 1, 3, and 5. Circulating monocytes and dendritic cells were analyzed by flow cytometry for quantity, phenotype, activation status, human leukocyte antigen DR (HLA-DR) expression, and toll-like receptor-2 and -4 expression. Results  Major hepatectomy increased the numbers of activated CD16^bright blood monocytes and the percentage of activated dendritic cells, although monocyte HLA-DR expression was reduced. These results may represent both dysfunctional antigen presentation and pending anergy, as well as cellular priming of immune effector cells. Better understanding of the alterations in innate immunity induced by hepatectomy may identify strategies to reduce infectious outcomes.