Signaling in B cells via Toll-like receptors

Toll-like receptors (TLRs) and their ligands have emerged as important regulators of immunity, relevant to a wide range of effector responses from vaccination to autoimmunity. The most well-studied ligands of TLRs expressed on B cells include the lipopolysaccharides (for TLR4) and CpG-containing DNAs (for TLR9), which induce and/or co-stimulate B cells to undergo proliferation, class switching and differentiation into antibody-secreting cells. Recent developments in this area include advancements into our understanding of the role of these receptor pathways in B cells, and in particular the relevance of TLR9, which has received substantial attention as both a Th1-like inflammatory immunomodulator and a pathogenic co-stimulator of autoreactive B cell responses.     

CD8 T lymphocytes do not express cytotoxic proteins in coronary artery aneurysms in acute Kawasaki disease

Coronary arterial inflammation in acute Kawasaki disease (KD) is characterized by transmural infiltration of CD8 T lymphocytes, suggesting that CD8 T lymphocyte cytotoxic activity may be important in the pathogenesis of coronary arterial damage in acute KD. We performed immunohistochemistry for the cytotoxic proteins perforin and granzyme B on paraffin-embedded, formalin-fixed coronary artery aneurysm tissue from 6 children who died in the acute stage of KD. Neither perforin nor granzyme B was detected in the KD coronary aneurysm wall. We speculate that the etiologic agent of KD interferes with expression of these cytotoxic proteins by CD8 T lymphocytes, prolonging inflammation in the arterial wall and leading to coronary artery aneurysm formation.     

Subcortical loops through the basal ganglia

Parallel, largely segregated, closed-loop projections are an important component of cortical-basal ganglia-cortical connectional architecture. Here, we present the hypothesis that such loops involving the neocortex are neither novel nor the first evolutionary example of closed-loop architecture involving the basal ganglia. Specifically, we propose that a phylogenetically older, closed-loop series of subcortical connections exists between the basal ganglia and brainstem sensorimotor structures, a good example of which is the midbrain superior colliculus. Insofar as this organization represents a general feature of brain architecture, cortical and subcortical inputs to the basal ganglia might act independently, co-operatively or competitively to influence the mechanisms of action selection.     

Electrophysiological substrates of impulsiveness: potential effects on aggressive behavior

Previous investigations attempting to examine impulsiveness as a personality construct are likely confounded with a high incidence of aggressive and antisocial behavior. The present study assessed electroencephalographic activity at rest and during photic stimulation in two groups: (1) an impulsive group (n=10) scoring high on the Barratt Impulsiveness Scale (BIS-11) and reporting no indication of impulsive aggressive behavior; and (2) a non-aggressive control group (n=14) scoring within the normal range on the BIS-11. All subjects completed a brief battery of personality measures related to impulsivity and aggression. Resting EEG was recorded at 9 electrode sites. Photic stimulation was administered at three frequency levels. The primary findings were consistently lower frontal delta and theta activity in the impulsive group as well as a different topographical pattern of beta activity between the groups. These differences appeared to be independent of photic stimulation. Personality analyses indicated significantly greater hostility and lifetime history of aggression in the impulsive group. Taken together, the personality and EEG results suggest some similarity between the present impulsive group and research on groups regularly exhibiting premeditated aggression. These results provide unique insight into the construct of impulsivity and its role in the expression of specific subtypes of aggressive behavior.     

Reduction in pediatric hospitalizations for varicella-related invasive group A streptococcal infections in the varicella vaccine era

OBJECTIVES: To assess changes in hospitalization rates for invasive group A streptococcal (IGAS) and varicella-associated IGAS (VA-IGAS) infections at a pediatric hospital over a period of 9 years, to characterize clinical features of patients with IGAS infections, and to assess frequency of macrolide-resistant IGAS isolates.Study design Medical records of all hospitalized patients with group A streptococcus isolated from a normally sterile site from 1993 to 2001 were reviewed. Data collected included demographics, clinical course, microbiologic features, outcome, and presence of streptococcal toxic shock syndrome (STSS) or necrotizing fasciitis (NF). Annual hospitalization rates for IGAS were determined. RESULTS: There were 144 patients with IGAS infections, including 11 (8%) with STSS or NF. Overall mortality rate was 2% (3/144) but 18% (2/11) among patients with STSS or NF. Preexisting varicella was present in 16% (23/144); 4 of 23 VA-IGAS cases had STSS or NF. Although there was no change in annual hospitalization rates for IGAS infections during the study period, the percentage of VA-IGAS hospitalizations decreased from 27% in the prevaccine era (1993 to 1995), to 16% during vaccine implementation (1996 to 1998) and 2% during widespread vaccine use (1999 to 2001) (linear-by-linear association, P=.001). Macrolide resistance was low in 1993 to 1995 (5%, 1/19) and 1996 to 1998 (0%, 0/42) among tested IGAS isolates and increased significantly in 1999 to 2001 (13%, 5/38) (Fisher exact, P=.035). CONCLUSIONS: A decline in pediatric varicella-related IGAS hospitalizations was temporally associated with utilization of varicella vaccine. These data reinforce the importance of universal varicella vaccination for children. Increasing macrolide resistance among IGAS isolates indicates a need for continued surveillance.