Pathogenic T cell responses against aquaporin 4

Inflammatory lesions in the central nervous system of patients with neuromyelitis optica are characterized by infiltration of T cells and deposition of aquaporin-4-specific antibodies and complement on astrocytes at the glia limitans. Although the contribution of aquaporin-4-specific autoantibodies to the disease process has been recently elucidated, a potential role of aquaporin-4-specific T cells in lesion formation is unresolved. To address this issue, we raised aquaporin-4-specific T cell lines in Lewis rats and characterized their pathogenic potential in the presence and absence of aquaporin-4-specific autoantibodies of neuromyelitis optica patients. We show that aquaporin-4-specific T cells induce brain inflammation with particular targeting of the astrocytic glia limitans and permit the entry of pathogenic anti-aquaporin-4-specific antibodies to induce NMO-like lesions in spinal cord and brain. In addition, transfer of aquaporin-4-specific T cells provoked mild (subclinical) myositis and interstitial nephritis. We further show that the expression of the conformational epitope, recognized by NMO patient-derived aquaporin-4-specific antibodies is induced in kidney cells by the pro-inflammatory cytokine gamma-interferon. Our data provide further support for the view that NMO lesions may be induced by a complex interplay of T cell mediated and humoral immune responses against aquaporin-4

O brendiranju žigova i pečata

MBP staining of murine organotypic brain slices shows myelin health status of all MOG-positive samples (MOG 1-10) and MOG-negative control (Ctrl 1) as well as healthy control sample (HC 1) in combination with human complement. (DOCX 6029 kb

Über eine Klasse polynomialer Scharen selbstadjungierter Operatoren im Hilbertraum

HEK293A cells expressing either mouse MOG (mMOG) or rat MOG (rMOG) C terminally tagged with EGFP. (DOCX 2792 kb

Patterns of Substance Abuse in Offenders With Schizophrenia— Illness-Related or Criminal Life-Style?

Objective: The impact of substance abuse on violent behavior in patients suffering from schizophrenia is well-known. However, the association between the pattern of substance abuse and certain aspects of criminal behavior like the severity of offense, the previous history of violence and the age at onset of the criminal career is still unclear. Method: To assess the relationship between substance abuse, schizophrenia and violent behavior we examined healthy non-offenders; healthy offenders; non-offenders suffering from schizophrenia; and offenders suffering from schizophrenia, with respect to different patterns of substance abuse (none, alcohol only, illicit drugs only, and multiple substances). Results: Healthy offenders as well as offenders and non-offenders suffering from schizophrenia are characterized by increased rates of alcohol and illicit drug abuse. Especially multiple substance abuse appears to lower the threshold of aggression and illegal behavior. This effect is more pronounced in subjects suffering from schizophrenia. In both offender groups the abuse of psychoactive substances is associated with an earlier onset of the criminal career, but has no impact on the severity of the offenses. Conclusion: Our results point to the need for a differentiated view on the contribution of substance abuse to the criminality of subjects suffering from schizophrenia.(VLID)470755

Patterns of Substance Abuse in Offenders With Schizophrenia— Illness-Related or Criminal Life-Style?

Objective: The impact of substance abuse on violent behavior in patients suffering from schizophrenia is well-known. However, the association between the pattern of substance abuse and certain aspects of criminal behavior like the severity of offense, the previous history of violence and the age at onset of the criminal career is still unclear.Method: To assess the relationship between substance abuse, schizophrenia and violent behavior we examined healthy non-offenders; healthy offenders; non-offenders suffering from schizophrenia; and offenders suffering from schizophrenia, with respect to different patterns of substance abuse (none, alcohol only, illicit drugs only, and multiple substances).Results: Healthy offenders as well as offenders and non-offenders suffering from schizophrenia are characterized by increased rates of alcohol and illicit drug abuse. Especially multiple substance abuse appears to lower the threshold of aggression and illegal behavior. This effect is more pronounced in subjects suffering from schizophrenia. In both offender groups the abuse of psychoactive substances is associated with an earlier onset of the criminal career, but has no impact on the severity of the offenses.Conclusion: Our results point to the need for a differentiated view on the contribution of substance abuse to the criminality of subjects suffering from schizophrenia

The treating psychiatrist as expert in the courts: is it necessary or possible to separate the roles of physician and expert?

Background Certified medical specialists, including forensic psychiatrists, from the 27 member states of the European Union (EU) may practise in each other's countries, but there are professional and legal differences between them. One may lie in whether a patient's treating doctor/clinician may give expert evidence about that person in court. Aims To examine similarities and differences between EU jurisdictions in law and practice in combining or separating such roles and to review the evidence in support of either position. Methods A psychiatrist with court experience was contacted in each EU country about law, practice and guidance on division of clinician–expert roles. Published literature was searched for an evidence base for practice in the field. Additional material is from discussion at a residential meeting of practising forensic psychiatrists from Austria, Belgium, Denmark, Germany, Hungary, the Netherlands, Switzerland and the UK. Results All acknowledge that a treating clinician can never be an independent expert in that case, but the 22 (of 27) EU countries responding vary in law and practice on whether the dual role may be assumed. There has been almost no research interest in factors relevant to separation of roles. International discussion revealed that ethical and practice issues are not straightforward. Conclusions On current evidence, either separation or combination of clinical and expert roles in a particular case may be acceptable. Insofar as there are national legal or professional guidelines on this issue, anyone practising in that country must follow them and may safely do so, regardless of practice in their native country. The most important ethical issue lies in clarity for all parties on the nature and extent of roles in the case. This paper has additional material online. Copyright © 2012 John Wiley & Sons, Ltd

Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD.

Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease of the central nervous system (CNS). In the majority of patients, it is associated with the presence of pathogenic serum autoantibodies (the so-called NMO-IgGs) directed against the water channel aquaporin 4 (AQP4), and with the formation of large, astrocyte-destructive lesions in spinal cord and optic nerves. A large number of recent studies using optical coherence tomography (OCT) demonstrated that damage to optic nerves in NMO/SD is also associated with retinal injury, as evidenced by retinal nerve fiber layer (RNFL) thinning and microcystic inner nuclear layer abnormalities. These studies concluded that retinal injury in NMO/SD patients results from secondary neurodegeneration triggered by optic neuritis.However, the eye also contains cells expressing AQP4, i.e., Müller cells and astrocytes in the retina, epithelial cells of the ciliary body, and epithelial cells of the iris, which raised the question whether the eye can also be a primary target in NMO/SD. Here, we addressed this point in experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285-specific T cells and NMO-IgG.We show that these animals show retinitis and subsequent dysfunction/damage of retinal axons and neurons, and that this pathology occurs independently of the action of NMO-IgG. We further show that in the retinae of ENMO animals Müller cell side branches lose AQP4 reactivity, while retinal astrocytes and Müller cell processes in the RNFL/ganglionic cell layers are spared. These changes only occur in the presence of both AQP4268-285-specific T cells and NMO-IgG.Cumulatively, our data show that damage to retinal cells can be a primary event in NMO/SD