Extensive myelitis associated with anti-NMDA receptor antibodies

Background

Encephalitis with anti-N-methyl-D-aspartate receptor antibodies (anti-NMDAR-Ab) is a rapid-onset encephalitis including psychosis, seizures, various movement disorders and autonomic system disturbances.

Case presentation

We report a very unusual case of extensive myelitis associated with anti-NMDAR-Ab. MRI also revealed a hyperintense T2 lesion, non-suggestive of MS, which progressively extended, associated with periventricular gadolinium enhancement visualized on brain MRI. Ophthalmological evaluation showed subclinical right optic neuritis. The absence of anti-AQP4 antibody argued against neuromyelitis optica spectrum disorder. A slight psychomotor slowing prompted us to search for various causes of autoimmune encephalitis. Anti-NMDAR-Ab was found in cerebrospinal fluid.

Conclusion

In patients with extensive myelitis who are seronegative for anti-AQP4 antibodies, and after other classical causes have been excluded, the hypothesis of atypical anti-NMDAR-Ab encephalitis should also be considered.

     

Prevalence of tick-borne encephalitis virus antibodies in dogs from Denmark

Background  

Large regions of central and eastern Europe are recognized as areas where tick-borne encephalitis virus (TBEV) is endemic, including countries neighbouring Denmark. It is therefore timely and relevant to determine if TBEV infections occur in Denmark. This study investigates the presence of antibodies against TBEV in a cross-section of the Danish canine population to assess the level of exposure to TBEV and possibly identify TBEV microfoci in Denmark.     

Identification and properties of proteases from an Acanthamoeba isolate capable of producing granulomatous encephalitis

Background  

Granulomatous amoebic encephalitis due to Acanthamoeba is often a fatal human disease. However, the pathogenesis and pathophysiology of Acanthamoeba encephalitis remain unclear. In this study, the role of extracellular Acanthamoeba proteases in central nervous system pathogenesis and pathophysiology was examined.     

Inhibition of apoptosis prevents West Nile virus induced cell death

Background  

West Nile virus (WNV) infection can cause severe meningitis and encephalitis in humans. Apoptosis was recently shown to contribute to the pathogenesis of WNV encephalitis. Here, we used WNV-infected glioma cells to study WNV-replication and WNV-induced apoptosis in human brain-derived cells.     

Gamma-aminobutyric acid-B limbic encephalitis and asystolic cardiac arrest: a case report

Background

Gamma-aminobutyric acid-B receptor autoantibodies are becoming an increasingly recognized contributor to the spectrum of autoimmune limbic encephalitis. They are classically associated with seizures and behavioral disturbance, and may coexist with other autoantibodies. Many are paraneoplastic, most commonly associated with small cell lung cancer. Until now there have been no reports of cardiac dysrhythmias in these patients.

Case presentation

A 65-year-old Caucasian man presented with multiple seizures, dysarthria and behavioral disturbance of unclear etiology, with associated asystolic cardiac arrest. Antibody testing showed anti-Gamma-aminobutyric acid-B receptor and anti-Hu antibodies in serum and Gamma-aminobutyric acid-B receptor autoantibodies in cerebrospinal fluid. The diagnosis of small cell lung cancer was subsequently made after lung biopsy, and the patient showed improvement with chemotherapy and intravenous immunoglobulin.

Conclusions

We present the case of a patient with Gamma-aminobutyric acid-B receptor limbic encephalitis associated with asystolic cardiac arrest, an association not previously described. This case illustrates how difficult it is to make the diagnosis on clinical grounds alone. We therefore propose more routine antibody testing in patients with similar symptomatology who remain undifferentiated after initial workup. We also recommend that in the acute setting, patients with Gamma-aminobutyric acid-B receptor encephalitis should receive cardiac monitoring, as further research is required to clarify its possible link with cardiac dysrhythmias.

     

Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV)

Background  

Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV.     

<Emphasis Type="Italic">Acanthamoeba</Emphasis> produces disseminated infection in locusts and traverses the locust blood-brain barrier to invade the central nervous system

Background  

Many aspects of Acanthamoeba granulomatous encephalitis remain poorly understood, including host susceptibility and chronic colonization which represent important features of the spectrum of host-pathogen interactions. Previous studies have suggested locusts as a tractable model in which to study Acanthamoeba pathogenesis. Here we determined the mode of parasite invasion of the central nervous system (CNS).     

Detection of <Emphasis Type="Italic">Balamuthia mandrillaris</Emphasis> DNA by real-time PCR targeting the RNase P gene

Background  

The free-living amoeba Balamuthia mandrillaris may cause fatal encephalitis both in immunocompromised and in - apparently - immunocompetent humans and other mammalian species. Rapid, specific, sensitive, and reliable detection requiring little pathogen-specific expertise is an absolute prerequisite for a successful therapy and a welcome tool for both experimental and epidemiological research.     

Isolation of anti-toxin single domain antibodies from a semi-synthetic spiny dogfish shark display library

Background  

Shark heavy chain antibody, also called new antigen receptor (NAR), consists of one single Variable domain (V_H), containing only two complementarity-determining regions (CDRs). The antigen binding affinity and specificity are mainly determined by these two CDRs. The good solubility, excellent thermal stability and complex sequence variation of small single domain antibodies (sdAbs) make them attractive alternatives to conventional antibodies. In this report, we construct and characterize a diversity enhanced semi-synthetic NAR V display library based on naturally occurring NAR V sequences.     

Antibodies against prM protein distinguish between previous infection with dengue and Japanese encephalitis viruses.

Background

In Southeast Asia, dengue viruses often co-circulate with other flaviviruses such as Japanese encephalitis virus, and due to the presence of shared antigenic epitopes it is often difficult to use serological methods to distinguish between previous infections by these flaviviruses.

Results

Convalescent sera from 69 individuals who were known to have had dengue or Japanese encephalitis virus infection were tested by western blotting against dengue, Japanese encephalitis and West Nile virus antigens. We determined that individuals who had been infected with dengue viruses had IgG responses against the premembrane protein of dengue viruses but not Japanese encephalitis, whereas individuals who had been infected with Japanese encephalitis had IgG specific for the premembrane protein of Japanese encephalitis virus but not the dengue viruses. None reacted with the premembrane protein of West Nile virus. Using the Pearson Chi Square test, it was determined that the difference between the two groups was highly significant with a p value of <0.001.

Conclusion

The use of flavivirus premembrane protein in seroepidemiological studies will be useful in determining what flaviviruses have circulated in a community.     

Aldosterone-producing adenoma and other surgically correctable forms of primary aldosteronism

Background

A severe encephalitis that associates with auto-antibodies to the NR1 subunit of the NMDA receptor (NMDA-R) was recently reported. Patients' antibodies cause a decrease of the density of NMDA-R and synaptic mediated currents, but the in vivo effects on the extracellular glutamate and glutamatergic transmission are unknown.

Methods

We investigated the acute metabolic effects of patients' CSF and purified IgG injected in vivo. Injections were performed in CA1 area of Ammon's horn and in premotor cortex in rats.

Results

Patient's CSF increased the concentrations of glutamate in the extracellular space. The increase was dose-dependent and was dramatic with purified IgG. Patients' CSF impaired both the NMDA- and the AMPA-mediated synaptic regulation of glutamate, and did not affect the glial transport of glutamate. Blockade of GABA-A receptors was associated with a marked elevation of extra-cellular levels of glutamate following a pretreatment with patients' CSF.

Conclusion

These results support a direct role of NMDA-R antibodies upon altering glutamatergic transmission. Furthermore, we provide additional evidence in vivo that NMDA-R antibodies deregulate the glutamatergic pathways and that the encephalitis associated with these antibodies is an auto-immune synaptic disorder.     

Issues associated with the use of phosphospecific antibodies to localise active and inactive pools of GSK-3 in cells

Abstract  

     

Application of methods of identifying receptor binding models and analysis of parameters

Background  

Possible methods for distinguishing receptor binding models and analysing their parameters are considered.     

Biochemical characterization of a recombinant Japanese encephalitis virus RNA-dependent RNA polymerase

Background  

Japanese encephalitis virus (JEV) NS5 is a viral nonstructural protein that carries both methyltransferase and RNA-dependent RNA polymerase (RdRp) domains. It is a key component of the viral RNA replicase complex that presumably includes other viral nonstructural and cellular proteins. The biochemical properties of JEV NS5 have not been characterized due to the lack of a robust in vitro RdRp assay system, and the molecular mechanisms for the initiation of RNA synthesis by JEV NS5 remain to be elucidated.     

Immunoexpression of the relaxin receptor LGR7 in breast and uterine tissues of humans and primates

Background  

The receptor for the peptide hormone relaxin has recently been identified as the heptahelical G-protein coupled receptor, LGR7. In order to generate molecular tools with which to characterize both in vivo and in vitro expression of this receptor in human and primate tissues, specific monotypic antibodies have been generated and applied to a preliminary analysis of human and primate female reproductive tissues.     

Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay

Background  

We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF).     

Up-regulation of uPARAP/Endo180 during culture activation of rat hepatic stellate cells and its presence in hepatic stellate cell lines from different species

Background  

The urokinase plasminogen activator receptor associated protein (uPARAP)/Endo180 is a novel endocytic receptor that mediates collagen uptake and is implicated to play a role in physiological and pathological tissue-remodelling processes by mediating intracellular collagen degradation.     

A receptor fusion protein for the inhibition of murine oncostatin M

Background  

Most cytokines signal through heteromeric receptor complexes consisting of two or more different receptor subunits. Fusion proteins of the extracellular parts of receptor subunits turned out to be promising cytokine inhibitors useful in anti-cytokine therapy and cytokine research.     

Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors

Background  

The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) evolved from a common ancestor. Still not completely understood is how specificity for glucocorticoids (e.g. cortisol) and mineralocorticoids (e.g. aldosterone) evolved in these receptors.     

Effect of buspirone on thermal sensory and pain thresholds in human volunteers

Background  

Buspirone is a partial 5-HT_1A receptor agonist. Animal studies have shown that modulation of serotoninergic transmission at the 5-HT_1A receptor can induce analgesia in acute pain models. However, no studies have been published so far on the effects of serotonin receptor agonists on pain perception in humans.