Interleukin-10 containing normal human serum inhibits granzyme B release but not perforin release from alloreactive and EBV-specific T cell clones

Interleukin-10 (IL-10), also known as cytokine synthesis inhibitory factor, has pleiotropic effects in immunoregulation and inflammation. It is capable of inhibiting synthesis of pro-inflammatory cytokines like interferon γ (IFNγ), IL-2, IL-3, tumor necrosis factor α(TNFα) and granulocyte macrophage colony stimulating factor (GM-CSF) made by cells such as macrophages and T helper Type 1 cells. We observed that normal human serum, derived from a healthy individual but containing large amounts of IL-10 (arbitrarily designated as "IL-10 serum"), inhibited cytotoxic activity and interfered with granzyme B release from alloreactive cytotoxic T cell (CTL) clones _in vitro_, but did not affect perforin release. The addition of normal human serum containing high levels of anti-IL-10 IgG (arbitrarily designated as "anti-IL-10 IgG serum") neutralized the inhibitory effects of IL-10 serum. Moreover, we have identified that cytotoxic activity and granzyme B release from an Epstein-Barr virus (EBV)-specific CTL clone was similarly inhibited in the presence of IL-10 serum, while perforin release was unaffected. Anti-IL-10 IgG serum also appeared to neutralize the inhibitory effect of IL-10 serum on an EBV-specific CTL clone

Fluvoxamine may prevent onset of psychosis: a case report of a patient at ultra-high risk of psychotic disorder

<p>Abstract</p> <p>Background</p> <p>There is emerging evidence that antidepressants may be effective in preventing patients with non-specific and psychotic-like prodromal symptoms, defined as patients at ultra-high risk (UHR) of psychotic disorder, from transitioning to psychosis. However, the mechanism of such an effect is still unknown.</p> <p>Methods</p> <p>We report the case of a 19-year-old Japanese man determined to be at UHR of psychotic disorder in whom fluvoxamine (one of the antidepressants with sigma-1 receptor agonism) showed preventive effects on psychotic-like prodromal symptoms.</p> <p>Results</p> <p>Our patient's depressive symptoms were reduced and maintained below remission as a result of treatment with 100 mg/day of fluvoxamine. In addition, it is likely that an additional dose of fluvoxamine (50 mg/day) improved his psychotic-like prodromal symptoms directly, independent of its antidepressive effects.</p> <p>Conclusion</p> <p>Fluvoxamine, a sigma-1 receptor agonist, may be effective in preventing patients at UHR of psychotic disorder from onset of psychosis via its neuroprotective/neurotropic actions, independent of its antidepressive effects.</p

Behavioural disorder in people with an intellectual disability and epilepsy: a report of the Intellectual Disability Task Force of the Neuropsychiatric Commission of ILAE

The management and needs of people with intellectual disability (ID) and epilepsy are well evidenced; less so, the comorbidity of behavioural disorder in this population. ‘Behavioural disorder’ is defined as behaviours that are difficult or disruptive, including stereotypes, difficult or disruptive behaviour, aggressive behaviour toward other people, behaviours that lead to injury to self or others, and destruction of property. These have an important link to emotional disturbance. This report, produced by the Intellectual Disability Task Force of the Neuropsychiatric Commission of the ILAE, aims to provide a brief review of some key areas of concern regarding behavioural disorder among this population, and proposes a range of research and clinical practice recommendations generated by Task Force members. The areas covered in this report were identified by experts in the field as being of specific relevance to the broad epilepsy community when considering behavioural disorder in persons with epilepsy and ID; they are not intended to be exhaustive. The practice recommendations are based on the authors’ review of the limited research in this field combined with their experience supporting this population. These points are not graded but can be seen as expert opinion guiding future research and clinical practice

Comparative evaluation of 11 commercialized rapid diagnostic tests for detecting Trypanosoma cruzi antibodies in serum banks in areas of endemicity and nonendemicity

Chagas disease is one of the main public health issues in Latin America. Increasingly during the past few decades, Trypanosoma cruzi infection has been detected in North America, Europe, and the Western Pacific, mainly as a result of population movement. The limited availability of rapid serological diagnostic tests hinders rapid diagnosis and early treatment in areas of endemicity and nonendemicity. In collaboration with 11 national reference laboratories (NRLs) from different geographical areas, we evaluated the performances of commercialized serological rapid diagnostic tests (RDT) for T. cruzi infection. Eleven commercialized T. cruzi infection RDTs were evaluated on a total of 474 samples extensively tested with at least three different techniques for Chagas disease, maintained at controlled low temperatures, and stored in the serum banks of the 11 NRLs. We measured the sensitivity, specificity, and concordance of each RDT and provided an additional questionnaire to evaluate its ease of use. The selected RDTs in this study were performed under controlled laboratory conditions. Out of the 11 RDTs, we found 8 of them to be useful, with the cassette format favored over the strip. We did not observe significant differences in RDT performances in the different regions. Overall, the performance results were lower than those disclosed by the manufacturers. The results of this evaluation validate the possibility of using RDTs to diagnose Chagas disease, thereby decreasing the time to treatment at a primary health care facility for patients who are willing to be treated. Further studies should be conducted in the laboratory and in the field to confirm these data, expressly to evaluate reproducibility in resource-limited settings, or using whole blood in clinical settings in areas of endemicity and nonendemicity

地震発生帯における深部掘削孔を用いた長期計測

Large earthquakes occur frequently in subduction zones. Most earthquakes are generated in the seismogenic zone, a fairly limited area confined to the shallower regions of the subduction plate boundary. To understand the processes of earthquake generation, it is essential to monitor the physical and mechanical properties of the seismogenic zone over long periods. At present, there are no deep borehole observations of the seismogenic zone more than 3km below seafloor, because it has, until now, been impossible to penetrate to such depths below the sea floor. The Integrated Ocean Drilling Program (IODP), scheduled to begin in 2003, plans to drill boreholes beneath the ocean floor using a multiple-drilling platform operation. The IODP riser-quipped drilling ship (Chikyu) enables the emplacement of boreholes up to 0km beneath the ocean floor, and will provide opportunities to conduct long-term deep borehole observations in the seismogenic zone. Long-term borehole observations in the seismogenic zone are expected to require the development of advanced sampling, monitoring, and recording technology. Here, we discuss the scientific objectives, engineering and technical challenges, and experimental design for a deep borehole, long-term deepborehole monitoring system aimed at understanding the processes of earthquake generation in the seismogenic zone of subduction plate boundaries. We focus specifically on the relationships between environmental conditions in the deep subsurface, details of monitoring and recording, and design and implementation of scientific tools and programs

Affinity Association Between Polynucleotide, Glycoprotein, or Sulfated Polysaccharides and Disease-Associated Prion Protein

Proteinase-K resistant prion protein (PrPres) has the property to aggregate in TSE-injured animal tissues. We have developed a test method to discriminate scrapie-infected and mock-infected hamsters by detecting the PrPres in plasma. It seemed that aggregation of the PrPres with some heterogeneous molecule(s) enabled successful detection by this method. In order to investigate which molecule became the partner in the PrPres aggregates; we examined some molecules that could presumably have this ability. As a result, we found synthetic Poly-A RNA, especially in its denatured form, to be the most effective entity although glycoprotein, sulfated polysaccharide showed less effectiveness. DNA in the denatured form also has a high affinity, although in the presence of protein the effectiveness unsuccessful. On the basis of this result, it is possible that the PrPres aggregate in scrapie-infected hamster plasma is composed of PrPres and RNA