Copolymer effects on microglia and T cells in the central nervous system of humanized mice

The random amino acid copolymers FYAK and VWAK ameliorate EAE in a humanized mouse model expressing both a human transgenic myelin basic protein (MBP)85-99-specific T cell receptor and HLA-DR2. Here we show that microglia isolated from the central nervous system (CNS) of humanized mice with EAE induced by MBP85-99 and treated with these copolymers had reduced expression of HLA-DR, and thus reduced capacity to present MBP85-99 and activate transgenic T cells. In vitro microglia up-regulated empty HLA-DR2 upon activation with GM-CSF with or without LPS or IFN-gamma, but not with IL-4 or IL-10. Correspondingly, gene chip arrays showed that the CNS of untreated and YFAK-treated mice differentially expressed pro- and anti-inflammatory molecules during MBP85-99-induced EAE. Interestingly, microglia expressed the full-length gammabeta and alphabeta subunits of the tetrameric adaptor protein complexes AP-1 and AP-2 respectively, but after treatment with GM-CSF these complexes were cleaved, as had been found in immature dendritic cells derived from bone marrow. Strikingly, in vivo the perivascular lymphocyte infiltration seen in untreated mice immunized with MBP85-99 was composed of equal numbers of hVbeta2+ MPB85-99-specific transgenic and hVbeta2- endogenous T cells, while the much smaller infiltration seen after treatment with YFAK was composed predominantly of hVbeta2- endogenous T cells.     

Rubinstein-Taybi syndrome medical guidelines

Children and adults with Rubinstein-Taybi Syndrome have specific medical conditions that occur with greater frequency than the general population. Based on the available information from the literature and clinical experience, recommendations for specific surveillance and interventions are made to guide those clinicians caring for individuals with Rubinstein-Taybi Syndrome. This is a first attempt at medical guidelines for individuals with RTS in the United States. On-going research is needed in many areas to guide decisions in medical care and allow for refinement of these medical guidelines.     

Chitinases and chitinase-like proteins in T(H)2 inflammation and asthma

Chitin is the second most abundant biopolymer in nature, where it protects crustaceans, parasites, fungi, and other pathogens from the adverse effects of their environments, hosts, or both. Because chitin does not exist in mammals, it had been assumed that the chitinases that degrade it are also restricted to lower life forms. However, chitinases and chitinase-like proteins have recently been noted in mice and human subjects. The prototypic chitinase, acidic mammalian chitinase, was also noted to be induced during T(H)2 inflammation through an IL-13-dependent mechanism. It was also shown to play an important role in the pathogenesis of T(H)2 inflammation and IL-13 effector pathway activation and demonstrated to be expressed in an exaggerated fashion in human asthmatic tissues. The finding that chitinases contribute to host anti-parasite responses and asthmatic T(H)2 inflammation support the concept that asthma might be a parasite-independent anti-parasite response.     

Langerhans cell histiocytosis immunohistochemical expression of fascin,a dendritic cell marker

Langerhans cell histiocytosis (LCH) is a clonal disorder believed to be derivedfrom cells of the dendritic system. Fascin, a 55-kd actin-bundling protein, represents a highly selective marker for dendritic cells of lymphoid tissues and peripheral blood and is involved in the formation of dendritic processes in maturing epidermal Langerhans cells. Since lesional cells of LCH may represent Langerhans cells arrested at an early stage of activation, immunohistochemical expression offascin in epidermal Langerhans cells and in the lesional cells of 34 cases of LCH was evaluated in paraffin sections using an immunoalkaline phosphatase technique. Though epidermal Langerhans cells were nonreactive for fascin, lesional cells in all LCH cases exhibited immunoreactivityforfascin, CD1a, and S-100 protein. Variation in staining intensity was observed in some cases, possibly reflecting differences in cell maturation or activation. Involved tissues included bone, soft tissue, lymph node, thyroid, orbit, and extradural cranial tissue. Immunoreactivity of lesional cells of LCH for fascin supports their derivation from cells of the dendritic system and represents another alteration in the phenotype of Langerhans cells that is associated with maturation, migration, culture, or clonal expansion.     

Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists

Background  

Cytokine production is critical in ischemia/reperfusion (IR) injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury.     

Nodal and paranodal structural changes in frog optic nerve during early Wallerian degeneration

Summary Ultrastructural changes in the nodal and paranodal regions of myelinated nerve fibres of frog optic nerves were studied during early stages of Wallerian degeneration. The earliest changes seen include retraction of paranodal loops of myelin from the axolemma and disconnection of paranodal myelin loops from myelin lamellae. These paranodal changes are asymmetric around the node and may be more advanced on either the proximal or distal side. Axoplasmic changes, including segregation of microtubules from neurofilaments, disorientation of microtubules and accumulation of abnormal organelles at nodes, appear shortly. In some axons the undercoating along the widened nodal surfaces becomes patchy, and blebs appear in the nodal axolemma. In freeze-fracture replicas a mixture of particle clusters and particle-free areas appears in both E- and P-faces of the nodal axolemma. Blebs remain particle free. Initially, E-face particles remain segregated to the node and are present only at much lower concentrations in the demyelinated paranodal axolemma, suggesting that they are not freely mobile at this stage. Nodal E-face particles begin to decrease on day 5 associated with an increase in particles at the adjacent demyelinated paranode, and by day 11 the particle distribution is uniformly low over the entire extent of the nodal and demyelinated paranodal axolemma. If nodal E-face particles represent sodium channels, as has been proposed, the sequence of changes in Wallerian degeneration would be compatible with a gradual redistribution of nodal sodium channels into the demyelinated paranode.     

Pathogenesis of Herpetic Neuritis and Ganglionitis in Mice: Evidence for Intra-Axonal Transport of Infection

The pathogenesis of acute herpetic infection in the nervous system has been studied following rear footpad inoculation of mice. Viral assays performed on appropriate tissues at various time intervals indicated that the infection progressed sequentially from peripheral to the central nervous system, with infectious virus reaching the sacrosciatic spinal ganglia in 20 to 24 hr. The infection also progressed to ganglia in mice given high levels of anti-viral antibody. Immunofluorescent techniques demonstrated that both neurons and supporting cells produced virus-specific antigens. By electron microscopy, neurons were found to produce morphologically complete virions, but supporting cells replicated principally nucleocapsids. These results are discussed in the context of possible mechanisms by which herpes simplex virus might travel in nerve trunks. They are considered to offer strong support for centripetal transport in axons.     

Heart rate reactivity and heart period variability throughout the first year after heart transplantation

Heart rate reactivity to mental stress is substantially blunted early after heart transplantation, suggesting that the loss of neural modulation limits the cardiovascular response to mental stress. We tested whether reactivity to mental stress recovers during the first year after heart transplantation. Hemodynamic and respiratory responses to mental arithmetic challenge were studied in 20 heart transplant recipients 3, 6, and 12 months after surgery. A normal comparison group was studied at equivalent intervals. Heart rate reactivity to mental arithmetic was significantly reduced in the cardiac transplant group compared to the normal subjects. This effect persisted up to 1 year after transplantation. Heart period variability in the heart transplant recipients was minimal in all three-test sessions. The findings suggest that no functional reinnervation or other compensatory adaptation occurs up to 1 year after heart transplantation.     

Are Compulsive Checkers Impaired in Memory? A Meta‐Analytic Review

Researchers have hypothesized that compulsive checkers suffer from impairment in explicit memory (e.g., Sher, Frost, & Otto, 1983 ), low confidence in explicit memory (e.g., McNally & Kohlbeck, 1993 ), or both. However, empirical findings have been equivocal, possibly due to variability in effect sizes produced by small samples. Combining data across studies may yield more meaningful conclusions than can be surmised from a narrative review. Following a brief review of the literature on checking and memory, we present meta-analytic results suggesting that checkers are impaired on many types of memory tasks (e.g., verbal free recall, verbal cued recall, and recall of actions) and are less confident in recognition than noncheckers. We discuss implications of these findings, suggestions for future research, and limitations of this analysis.