Treatment with an anti-CD18 monoclonal antibody in rabbits inhibits pneumococcal-induced leukocyte recruitment in the skin,but not in the meninges

Inflammatory recruitment of leukocytes into the cerebrospinal fluid (CSF) during bacterial meningitis has been shown to contribute to the neurological damage commonly associated with this disease. In this study we tested whether inhibition of firm leukocyte adhesion to vascular endothelium could reduce leukocyte recruitment into the subarachnoid space (SAS) and into the skin in rabbits challenged with pneumococcal cell wall (PCW) antigen. PCW was given either as an intracisternal or an intradermal (i.d.) injection. Intravenous (i.v.) treatment with a monoclonal antibody (mAb), IB4, against the leukocytic adhesion molecule CD18 has previously been documented to attenuate leukocyte CSF accumulation in experimental bacterial meningitis. In the present study, i.v. treatment with anti-CD18 mAbs (IB4) only tended to inhibit CSF leukocyte influx in animals with PCW-induced meningitis. However, if the antigen was injected i.d., treatment i.v. with the same mAb (IB4) dramatically reduced leukocyte accumulation in the skin. Our findings indicate that the mechanisms responsible for PCW-induced inflammatory accumulation of leukocytes in skin and meninges are different.     

An intravital microscopic model for mast cell-dependent inflammation in the hamster cheek pouch

Topical antigen challenge in cheek pouches of immunized hamsters led to an acute inflammatory reaction which was characterized by intravital microscopy. The response consisted of short-lasting arteriolar spasm, followed by leakage of plasma, vasodilation, and accumulation of leucocytes. Several observations indicated that the reaction was due to mast cell activation. Thus, a very similar inflammatory response was seen after challenge with compound 48/80, and both antigen and compound 48/80 degranulated the numerous mast cells present in the cheek pouch. In addition, fluorescein-labelled antigen bound specifically to mast cells in cheek pouches of immunized animals, also suggesting the presence of mast cell-fixed antigen-specific antibodies, possibly immunoglobulin E. However, although antigen and compound 48/80 caused similar microvascular responses, cross-desensitization experiments indicated that the two stimuli activated mast cells via different mechanisms. The histamine antagonist mepyramine, which abolished plasma leakage induced by exogenous histamine, substantially inhibited the increase of microvascular permeability evoked by antigen or compound 48/80, but did not appear to affect the vasospasm and leucocyte accumulation. It is concluded that the hamster cheek pouch may be a most useful tool for investigation of dynamic microvascular events during allergic mast cell-dependent inflammation.     

Clinical, morphologic, immunophenotypic, and molecular cytogenetic assessment of CD4-/CD8-γδ T-cell large granular lymphocytic leukemia

γδ T-cell large granular lymphocytic (T-LGL) leukemia of the CD4-/CD8- subtype is rare, and data are limited in the literature. This study evaluated the clinical, morphologic, immunophenotypic, and molecular cytogenetic features of 7 cases of CD4-/CD8- γδ T-LGL leukemia. Although this variant shares several clinical and morphologic features with the more common T-LGL leukemias, the incidences of autoimmune hemolytic anemia and pure red cell aplasia are higher. Another striking feature observed in our study was the lack of increased large granular lymphocytes in the peripheral blood in the majority of cases despite prominent bone marrow or splenic involvement. CD4-/CD8- γδ T-LGL leukemia also displays an immunophenotype and pattern of splenic involvement overlapping with hepatosplenic T-cell lymphoma. Clinically, this variant of T-LGL leukemia shows an overall indolent course, but treatment is often required in the initial stages of the disease. Awareness of these features is important for early recognition and accurate diagnosis of patients with CD4-/CD8- γδ T-LGL leukemia.     

A Tutorial Review on Multi-subject Decomposition of EEG

Over the last years we saw a steady increase in the relevance of big neuroscience data sets, and with it grew the need for analysis tools capable of handling such large data sets while simultaneously extracting properties of brain activity that generalize across subjects. For functional magnetic resonance imaging, multi-subject or group-level independent component analysis provided a data-driven approach to extract intrinsic functional networks, such as the default mode network. Meanwhile, this methodological framework has been adapted for the analysis of electroencephalography (EEG) data. Here, we provide an overview of the currently available approaches for multi-subject data decomposition as applied to EEG, and highlight the characteristics of EEG that warrant special consideration. We further illustrate the importance of matching one’s choice of method to the data characteristics at hand by guiding the reader through a set of simulations. In sum, algorithms for group-level decomposition of EEG provide an innovative and powerful tool to study the richness of functional brain networks in multi-subject EEG data sets.