Imaging in neurooncology.

Imaging in patients with brain tumors aims toward the determination of the localization, extend, type, and malignancy of the tumor. Imaging is being used for primary diagnosis, planning of treatment including placement of stereotaxic biopsy, resection, radiation, guided application of experimental therapeutics, and delineation of tumor from functionally important neuronal tissue. After treatment, imaging is being used to quantify the treatment response and the extent of residual tumor.

Neuroimaging-guided rTMS of the left inferior frontal gyrus interferes with repetition priming.

Neuroimaging studies of right-handed normal volunteers under semantic word generation tasks have consistently reported left lateralized activation of the anterior inferior frontal gyrus (ifg) which decreased during task repetition. This repetition-related activation decrease has been interpreted as the neurophysiological correlate of repetition priming, a mechanism of implicit memory for initial semantic processing. We interfered with left lateralized ifg activation, as identified by O-15-water PET activation, using repetitive transcranial magnetic stimulation (rTMS) in five right-handed male normal subjects, once using new (unprimed) nouns and once using known (primed) nouns for the procedure.

HLA-B27-restricted CD8+ T cell response to cartilage-derived self peptides in ankylosing spondylitis.

Objective: Several hypotheses have been proposed to explain the strong association between HLA-B27 and ankylosing spondylitis (AS). Among these, the arthritogenic peptide theory proposes that certain B27 subtype alleles bind specific arthritogenic peptide(s) due to their unique amino acid anchor residues. Cartilage antigens have been discussed as candidate targets for the immune response in AS.

Essential language function of the right hemisphere in brain tumor patients.

Neuroimaging studies of language networks in patients with brain lesions of the left language-dominant hemisphere have shown activation in the right inferior frontal gyrus (IFG). We tested the functional relevance of right IFG activation using neuroimaging-guided repetitive transcranial magnetic stimulation (rTMS) to disturb language function over bilateral IFG in right-handed patients with brain tumors and controls. All subjects were susceptible to TMS over the left IFG.

Analysis of the CD8+ T cell response to the G1 domain of aggrecan in ankylosing spondylitis.

Background: CD4+ T cell responses to the G1 domain of aggrecan in patients with ankylosing spondylitis (AS) were recently reported. Whether such an immune response can be seen in the CD8+ subpopulation has not yet been determined.

Objective: To determine if HLA-B27 restricted G1-specific CD8+ T cells are present in AS and to analyse immunodominant CD8+ T cell epitopes.

Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis.

Reports of the use of HLA-B27/peptide tetrameric complexes to study peptide-specific CD8+ T cells in HLA-B27+-related diseases are rare. To establish HLA-B27 tetramers we first compared the function of HLA-B27 tetramers with HLA-A2 tetramers by using viral epitopes. HLA-B27 and HLA-A2 tetramers loaded with immunodominant peptides from Epstein-Barr virus were generated with comparable yields and both molecules detected antigen-specific CD8+ T cells.

Which time-to-peak threshold best identifies penumbral flow? A comparison of perfusion-weighted magnetic resonance imaging and positron emission tomography in acute ischemic stroke.

Background And Purpose: In acute ischemic stroke, the hypoperfused but viable tissue is the main therapeutic target. In clinical routine, time-to-peak (TTP) maps are frequently used to estimate the hemodynamic compromise and to calculate the mismatch volume. We evaluated the accuracy of TTP maps to identify penumbral flow by comparison with positron emission tomography (PET).

Cell therapy for autoimmune diseases: does it have a future?

Almost all current therapeutic concepts in autoimmune diseases are based on the systemic suppression of immune functions and are not curative. The recent introduction of biologicals such as tumour necrosis factor blocking antibodies or receptors has added greater specificity to efficient management of disease by targeted suppression of rheumatic inflammation. It is evident, however, that only the elimination of the cells secreting inflammatory mediators, rather than the blockade of secreted molecules, will offer real specific therapeutic advantages in the future.

Stem cell transplantation for autoimmune disorders. Immune reconstitution.

Lymphocyte recovery is delayed following autologous haematopoietic stem cell transplantation (HSCT). B-cells recover before T-cells and CD8+ before CD4+ T-cells. The initial phase of T-cell recovery is dependent upon the expansion of mature host T-cells that have survived conditioning or are transferred back with the graft.

The IkappaB kinase complex and NF-kappaB act as master regulators of lipopolysaccharide-induced gene expression and control subordinate activation of AP-1.

Toll-like receptors (TLRs) recognize conserved products of microbial pathogens to initiate the innate immune response. TLR4 signaling is triggered upon binding of lipopolysaccharides (LPS) from gram-negative bacteria. Using comparative gene expression profiling, we demonstrate a master regulatory role of IkappaB kinase (IKK)/NF-kappaB signaling for immediate-early gene induction after LPS engagement in precursor B cells.

Probability of cortical infarction predicted by flumazenil binding and diffusion-weighted imaging signal intensity: a comparative positron emission tomography/magnetic resonance imaging study in early ischemic stroke.

Background And Purpose: The differentiation of reversible from irreversible ischemic damage is essential for identifying patients with acute ischemic deficits who may benefit from therapeutic interventions. Diffusion-weighted imaging (DWI) has become the method of choice to detect ischemic lesions. Positron emission tomography (PET) of the central benzodiazepine receptor ligand 11C flumazenil (FMZ) has been shown to be a reliable marker of neuronal integrity.

The small subset of CD56brightCD16- natural killer cells is selectively responsible for both cell proliferation and interferon-gamma production upon interaction with dendritic cells.

The encounter of NK cells with dendritic cells (DC) undergoing maturation may result in the induction of NK cell proliferation. Whether such proliferation involves most NK cells or just a subset has yet to be determined. In the present study we analyzed the nature of such proliferating NK cells by combining carboxyfluorescein succinimidyl ester staining and double-fluorescence cytofluorimetric analysis.

Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex.

The crystal structure of the human electron transferring flavoprotein (ETF).medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of protein-protein interaction, imparting both specificity and promiscuity in the interaction of ETF with a range of structurally distinct primary dehydrogenases. ETF partitions the functions of partner binding and electron transfer between (i) the recognition loop, which acts as a static anchor at the ETF.

Antigen-specific cytometry--new tools arrived!

Until recently, immunofluorescence-based cytometry and cell sorting, which have now found their place in the repertoire of state-of-the-art technologies, have mostly served to identify and assess subsets of leukocytes and thereby to evaluate rather systemic changes of the immune system. A more detailed defined evaluation of immune responses was not possible for a long time. In particular, a focus of the cytometric analysis on those lymphocytes specifically recognizing a defined antigen was hampered due to technical limitations.

Plasma cell-like morphology of Th1-cytokine-producing cells associated with the loss of CD3 expression.

Here we clarified the morphology and phenotype of interleukin (IL)-17- and interferon (IFN)-gamma-producing cells in both in vitro and in vivo situations. Oligoclonal activation of normal peripheral blood mononuclear cells with the superantigen Staphylococcus aureus enterotoxin B and polyclonal activation with phorbol myristate acetate/phytohemagglutinin were used as in vitro models. This study was extended to various in vivo situations such as rheumatoid arthritis, dermatomyositis, and normal activated lymph nodes.

Activation of basal ganglia loops in idiopathic Parkinson's disease: a PET study.

Patients with idiopathic Parkinson's syndrome (IPS) show dysexecutive deficits which are not related to dementia. We investigated whether these deficits may be caused by a disturbed interaction of prefrontal cortex and selective basal ganglia loops. 5 healthy right-handed volunteers and 5 non demented IPS patients were studied with FDG PET while performing a gambling task paradigm.

Disturbance and recovery of language function: correlates in PET activation studies.

Disturbance of neurologic function in disorders of the central nervous system is expressed as an altered activation pattern in functional networks employed by specific tasks and can be studied by functional imaging modalities, e.g., positron emission tomography.

Substitution in position 3 of cyclosporin A abolishes the cyclophilin-mediated gain-of-function mechanism but not immunosuppression.

Binary complex formation between the immunosuppressive drug cyclosporin A (CsA) and cyclophilin 18 is the prerequisite for the ability of CsA to inhibit the protein phosphatase activity of calcineurin, a central mediator of antigen-receptor signaling. We show here that several CsA derivatives substituted in position 3 can inhibit calcineurin without prior formation of a complex with cyclophilin 18. [Methylsarcosine(3)]CsA was shown to inhibit calcineurin, either in its free form with an IC(50) value of 10 microm, or in its complex form with cyclophilin 18 with an IC(50) of 500 nm.

Insights into catalysis by a knotted TrmD tRNA methyltransferase.

The crystal structure of Escherichia coli tRNA (guanosine-1) methyltransferase (TrmD) complexed with S-adenosyl homocysteine (AdoHcy) has been determined at 2.5A resolution. TrmD, which methylates G37 of tRNAs containing the sequence G36pG37, is a homo-dimer.

Acetylsalicylic acid pretreatment, concomitant heparin therapy and the risk of early intracranial hemorrhage following systemic thrombolysis for acute ischemic stroke.

Background: The risk of intracerebral hemorrhage in systemic thrombolysis for acute ischemic stroke after acetylsalicylic acid (ASA) pretreatment or with subsequent heparin is controversially discussed.

Methods: 300 consecutive stroke patients were treated with recombinant tissue-type plasminogen activator (rt-PA) in a prospective open study (92 pretreated with ASA, 202 ASA nonusers) with 3 months of follow-up. After thrombolysis, 122 patients received low-dose, 153 patients high-dose heparin.

Aquaporin gene expression and regulation in the ovine fetal lung.

Fetal lung development is dependent upon secretion of liquid into the future airways which must be cleared at birth to establish air-breathing. Aquaporins (AQP) 1, 3, 4 and 5 are membranous water channel proteins that are present in the lung after birth in rodents, with little expression before birth. Our aim was to describe the changes in AQP1, 3, 4 and 5 expression and protein levels in the fetal lung of a long-gestation species (sheep) and in response to physiological factors known to alter fetal lung liquid dynamics.

Functional imaging in the assessment of capability for recovery after stroke.

After an ischaemic lesion preserved components of a functional network are utilized for recovery from neurological defects. The hierarchy of the individual parts within the damaged network, however, determines the quality of the outcome. This could be clearly demonstrated for the complex network of language ability, for which the left temporal region plays an integrative role: only if the left temporal regions are morphologically preserved and can be reactivated in imaging studies of speech performance was the outcome of poststroke aphasia satisfying.

Up regulation of the production of tumour necrosis factor alpha and interferon gamma by T cells in ankylosing spondylitis during treatment with etanercept.

Background: Treatment of active ankylosing spondylitis (AS) with the recombinant, soluble tumour necrosis factor alpha (TNFalpha) receptor molecule etanercept has been shown to be clinically highly effective. The precise mechanism of action, however, is not known.

Objective: To assess the change in the cytokine secreting ability of CD4+ and CD8+ T cells and macrophages during etanercept treatment.

Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis.

Objectives: Based on their HLA association, both ankylosing spondylitis (AS) and rheumatoid arthritis (RA) seem to be T-cell-driven diseases in which the autoantigens remain to be defined. One possible autoantigen is the G1 domain of aggrecan, the major cartilage proteoglycan. In BALB/c mice immunized with this protein, spondylitis and erosive polyarthritis have been reported.

Down-regulation of the nonspecific and antigen-specific T cell cytokine response in ankylosing spondylitis during treatment with infliximab.

Objective: Treatment of active ankylosing spondylitis (AS) with the monoclonal tumor necrosis factor alpha (TNF alpha) antibody infliximab is highly clinically effective. This study was undertaken to investigate the precise mechanism of action of anti-TNF alpha treatment in AS.

Methods: Cytokine expression of CD4+ and CD8+ T cells was investigated before and 6 and 12 weeks after the start of treatment in 10 patients treated with infliximab, and before and after 6 weeks of treatment and 6 weeks after placebo was switched to infliximab in 10 patients treated initially with placebo.