Macrophage clustering as a diagnostic marker in sural nerve biopsies of patients with CIDP.

Background: In adult patients with a slowly progressive demyelinating neuropathy, it may be difficult to distinguish between a hereditary neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP). The authors previously observed clustering of macrophages around endoneurial blood vessels in sural nerve biopsies from patients with CIDP.

Objectives: To quantitate macrophage clustering around endoneurial blood vessels in CIDP vs hereditary neuropathies.

Cytokine profile of iron-laden macrophages: implications for cellular magnetic resonance imaging.

Superparamagnetic iron oxide (SPIO/USPIO) particles are a promising new tool to label cells for in vivo monitoring of their migration into the nervous system by magnetic resonance imaging (MRI). Upon systemic application, SPIO/USPIO particles are preferentially internalized by macrophages. It is unclear whether this affects their immunological profile.

Assessment of lesion evolution in experimental autoimmune neuritis by gadofluorine M-enhanced MR neurography.

Experimental autoimmune neuritis (EAN) represents an animal model of acute inflammatory nerve injury mirroring pathophysiological aspects of the human Guillain-Barré syndrome. In the present study, we for the first time visualized the spatiotemporal evolution of autoimmune nerve injury and recovery by magnetic resonance imaging (MRI) by use of the novel micellar magnetic resonance (MR) contrast agent gadofluorine M (Gf). EAN was induced in Lewis rats by T-cell transfer (AT-EAN) leading to severe axonal damage, and Gf was applied intravenously at various disease stages mostly 24 h before MRI.

Iron particles enhance visualization of experimental gliomas with high-resolution sonography.

Background And Purpose: Intraoperative MR imaging and sonography are used for navigation during neurosurgical procedures. The purpose of this experimental study was to evaluate the potential of high-resolution sonography using superparamagnetic iron oxide (SPIO) particles as a contrast medium to delineate brain tumors and to relate these findings with those of MR imaging.

Methods: C6 gliomas were implanted in 36 rats.

In vivo detection of developing vessel occlusion in photothrombotic ischemic brain lesions in the rat by iron particle enhanced MRI.

The aim of our study was to visualize developing vessel occlusion in focal cerebral ischemia in vivo. Cortical photothrombosis (PT) was induced in rats, which in addition received superparamagnetic iron oxide (SPIO) particles intravenously. When SPIO particles were applied simultaneously during illumination of the brain for induction of PT, animals showed a markedly hypointense cortical lesion on T2-weighted (T2-w) magnetic-resonance images (MRI).

Contralateral cytokine gene induction after peripheral nerve lesions: dependence on the mode of injury and NMDA receptor signaling.

There is increasing evidence that unilateral nerve injury evokes contralateral responses, but the underlying mechanisms are largely unknown. In the present investigation, we analyzed cytokine and chemokine gene induction in contralateral, non-lesioned nerves after sciatic nerve crush and chronic constriction injury (CCI) by quantitative reverse transcriptase polymerase chain reaction in mice. After sciatic nerve crush, contralateral changes in cytokine gene expression were restricted to interleukin (IL)-1beta, which showed a monophasic peak at the first postoperative day.

Assessment of nerve degeneration by gadofluorine M-enhanced magnetic resonance imaging.

Nerve injury represents a major cause of disability. In the peripheral nervous system, nerves have the capacity to regrow but within weeks after injury, it is impossible to clarify whether proper regeneration is under way or is failing. In this experimental study, we report on a novel tool to assess nerve outgrowth in vivo.

Osteopontin, a macrophage-derived matricellular glycoprotein, inhibits axon outgrowth.

Transected axons can regenerate beyond the site of injury in the peripheral but not in the central nervous system (CNS). Increasing evidence implicates inflammatory processes as modulators of axon regeneration after injury. In this study, we addressed a possible role of the matricellular glycoprotein osteopontin (OPN) using crush lesions of the optic and sciatic nerve as models of central and peripheral axotomy, respectively.

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies.

Induction of granulocyte colony-stimulating factor mRNA by focal cerebral ischemia and cortical spreading depression.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with neuroprotective and antiinflammatory properties. By real-time polymerase chain reaction we show that G-CSF transcripts are induced 485-fold at 4 h and 65-fold at 16 h in ischemic lesions after middle cerebral artery occlusion compared to control brains. Further analysis in photochemically induced focal ischemia revealed that G-CSF induction involved both the infarct area and remote nonischemic brain regions.

Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d(CpG) steps.

We describe herein a computationally intensive project aimed at carrying out molecular dynamics (MD) simulations including water and counterions on B-DNA oligomers containing all 136 unique tetranucleotide base sequences. This initiative was undertaken by an international collaborative effort involving nine research groups, the "Ascona B-DNA Consortium" (ABC). Calculations were carried out on the 136 cases imbedded in 39 DNA oligomers with repeating tetranucleotide sequences, capped on both ends by GC pairs and each having a total length of 15 nucleotide pairs.

Wallerian degeneration after crush or chronic constriction injury of rodent sciatic nerve is associated with a depletion of endoneurial interleukin-10 protein.

We used enzyme-linked immunoassay (ELISA), immunohistochemistry (IHC), and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to determine whether interleukin (IL)-10 protein is changed after unilateral crush or chronic constriction injury (CCI) of mouse or rat sciatic nerve and whether IL-10 protein and mRNA are differentially regulated. In the mouse sciatic nerve, IL-10 protein declined rapidly to 10-20% of baseline early after crush or CCI, while the IL10 mRNA was up-regulated with a maximum on Days 1 and 3. In the rat sciatic nerve, IL-10 protein was significantly reduced on Day 3 after CCI, and IL-10 mRNA was up-regulated in both models.

Multifocal motor neuropathy presenting as chronic progressive proximal leg weakness.

We report on a 47-year-old man with a 12-year history of progressive and ultimately severe proximal weakness of his right lower limb. Motor conduction block at the unaffected tibial nerve and positive IgM antibodies against GM1 gangliosides lead us to suggest a diagnosis of oligosymptomatic multifocal motor neuropathy. He rapidly responded to intravenous immunoglobulins, with complete remission lasting 4 weeks, and had a repeated treatment response to intravenous immunoglobulins during subsequent exacerbations.

In vivo monitoring of macrophage infiltration in experimental autoimmune neuritis by magnetic resonance imaging.

We report on the in vivo assessment of macrophage infiltration in adoptive transfer experimental autoimmune neuritis (AT-EAN), a prototypic Th-1-mediated autoimmune disorder of the peripheral nervous system (PNS). Lewis rats received systemic injections of superparamagnetic iron oxide (SPIO) particles at days 2, 3, 4, 5, or 9 after adoptive transfer of P2-specific T-cells and were scanned by standard 1.5 T magnetic resonance imaging (MRI) always 24 h later.

The extent of cytokine induction in peripheral nerve lesions depends on the mode of injury and NMDA receptor signaling.

We compared cytokine and chemokine induction in mice after sciatic nerve crush and chronic constriction injury (CCI) by quantitative reverse transcriptase polymerase chain reaction. In both nerve lesion paradigms, transcripts for tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-10, and monocyte chemoattractant protein-1 (MCP-1) were significantly increased in degenerating nerve stumps already at day 1, with a greater magnitude and longer duration in CCI. NMDA receptor blockade significantly reduced cytokine expression after CCI on the mRNA and protein level.

Lesion-associated expression of transforming growth factor-beta-2 in the rat nervous system: evidence for down-regulating the phagocytic activity of microglia and macrophages.

The mechanisms that control the phagocytic activities of microglia and macrophages during disorders of the nervous system are largely unknown. In the present investigation, we assessed the functional role of transforming growth factor (TGF)beta2 in vitro and studied TGFbeta-2mRNA and protein expression in two CNS lesion paradigms in vivo characterized by fundamental differences in microglia/macrophage behaviour: optic nerve crush exhibiting slow, and focal cerebral ischemia exhibiting rapid phagocytic transformation. Furthermore, we used sciatic nerve crush injury as a PNS lesion paradigm comparable to brain ischemia in its rapid phagocyte response.

Influence of postoperative complementary treatment with lectin-standardized mistletoe extract on breast cancer patients. A controlled epidemiological multicentric retrolective cohort study.

This epidemiological study was performed to evaluate the influence of postoperative complementary treatment with lectin-standardized mistletoe extract (sME) on breast cancer patients. The design (retrolective cohort analysis with parallel groups) and conduct of the study were in agreement with current standards for prospectively randomized clinical trials. A cohort of 1,248 breast cancer patients on postoperative chemo-, radio-, hormone-therapy were studied in 27 randomized centers.

Caught in the act: in vivo mapping of macrophage infiltration in nerve injury by magnetic resonance imaging.

In vivo tracking of hematogenous macrophages has been a major challenge because these cells are key players in nerve injury and repair. We visualized the spatiotemporal course of macrophage infiltration after acute peripheral nerve injury in living rats by using superparamagnetic iron oxide (SPIO) particles and magnetic resonance imaging (MRI). A signal loss on MR images indicating iron accumulation was present in degenerating sciatic nerves between days 1 and 8 after a crush lesion, ceased thereafter, and corresponded to the transient presence of iron-labeled ED1-positive macrophages in tissue sections.

In vivo monitoring of macrophage infiltration in experimental ischemic brain lesions by magnetic resonance imaging.

Although macrophages represent the major inflammatory cells in cerebral ischemia, the kinetics of macrophage infiltration are largely unknown. To address this issue, we injected superparamagnetic iron oxide (SPIO) particles into the circulation of rats at different time points after focal photothrombotic cerebral infarction and performed magnetic resonance imaging (MRI) 24 hours later. Infarcts appeared as hyperintense lesions on T2-w and CISS MR images during all stages.

Botulism type B presenting as pure autonomic dysfunction.

Botulism nowadays is a rare mostly food-borne disease caused by the toxin of Clostridium botulinum. On the other hand, botulinum toxin blocking cholinergic transmission has become a most powerful treatment option for many focal movement disorders and is increasingly used to treat autonomic disorders [2, 7, 8]. Although muscle weakness is the hallmark of botulism, autonomic dysfunction may be the leading clinical symptom in rare cases and should be included in the differential diagnosis of pure dysautonomia.

CD8+ phagocyte recruitment in rat experimental autoimmune encephalomyelitis: association with inflammatory tissue destruction.

Increasing evidence suggests an important role of CD8(+) cells in the pathogenesis of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). In our present study we analyzed the spatiotemporal expression pattern of the CD8 antigen in various rat EAE models characterized by a different extent of inflammation, demyelination, and axonal injury. Unexpectedly, in chronic demyelinating EAE induced by immunization against myelin oligodendrocyte glycoprotein (MOG) the majority of CD8 immunoreactivity was expressed on ED1(+) microglia/macrophages whereas only limited CD8(+) T-cell infiltration was present.

Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus.

We report the clinical and bioptic findings for a 57-year-old woman with severe chloroquine-induced myopathy. Since 1989, she had been suffering from systemic lupus erythematosus (SLE) with renal involvement and undergone periods of treatment with azathioprine and cyclophosphamide. Additional therapy with chloroquine (CQ) was started because of arthralgia.

Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system.

Lesions in the nervous system induce rapid activation of glial cells and under certain conditions additional recruitment of granulocytes, T-cells and monocytes/macrophages from the blood stream triggered by upregulation of cell adhesion molecules, chemokines and cytokines. Hematogenous cell infiltration is not restricted to infectious or autoimmune disorders of the nervous system, but also occurs in response to cerebral ischemia and traumatic lesions. Neuroinflammation can cause neuronal damage, but also confers neuroprotection.