Autoantibodies in Silicosis Patients: Silica-Induced Dysregulation of Autoimmunity

Silica particles cause silicosis (SIL) and represent one of the most typical environmental and occupational substances that induce autoimmune disorders among the exposed population. Anti-nuclear antibody (ANA), anti-Sjögren’s-syndrome-related antigen A (SS-A), anti-centromere protein B (CENP)-B, and anti-scleroderma (Scl)-70 autoantibodies were examined in SIL and compared with those in healthy volunteers (HV) and patients with systemic sclerosis (SSc). Individuals with SIL were prone to autoimmune diseases and some autoantibodies seemed to be important as an estimation of this condition. Anti-Fas autoantibody found in SIL was functionally capable of inducing apoptosis in Fas-expressing cells, and this may cause a decrease of regulatory T cells (Tregs) expressing Fas in SIL. Moreover, responder T cells (Tresps) in SIL seemed to be activated chronically and protected from Fas-mediated apoptosis. Thus, an imbalance of Tresps (dominant) and Tregs (less) occurred in SIL. All of these causes of SIL are ready to further develop autoimmune diseases

Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect

AbstractWe identified a novel mutation Ala178fs/105 missing S3–S6 and C-terminus portions of KCNQ1 channel. Ala178fs/105-KCNQ1 expressed in COS-7 cells demonstrated no current expression. Co-expression with wild-type (WT) revealed a dominant-negative effect, which suggests the formation of hetero-multimer by mutant and WT. Confocal laser microscopy displayed intracellular retention of Ala178fs/105-KCNQ1 protein. Co-expression of the mutant and WT also increased intracellular retention of channel protein compared to WT alone. Our findings suggest a novel mechanism for LQT1 that the truncated S1–S2 KCNQ1 mutant forms hetero-multimer and cause a dominant-negative effect due to trafficking defect

Analysis of negative historical control group data from the in vitro micronucleus assay using TK6 cells.

The recent revisions of the Organisation for Economic Co-operation and Development (OECD) genetic toxicology test guidelines emphasize the importance of historical negative controls both for data quality and interpretation. The goal of a HESI Genetic Toxicology Technical Committee (GTTC) workgroup was to collect data from participating laboratories and to conduct a statistical analysis to understand and publish the range of values that are normally seen in experienced laboratories using TK6 cells to conduct the in vitro micronucleus assay. Data from negative control samples from in vitro micronucleus assays using TK6 cells from 13 laboratories were collected using a standard collection form. Although in some cases statistically significant differences can be seen within laboratories for different test conditions, they were very small. The mean incidence of micronucleated cells/1000 cells ranged from 3.2/1000 to 13.8/1000. These almost four-fold differences in micronucleus levels cannot be explained by differences in scoring method, presence or absence of exogenous metabolic activation (S9), length of treatment, presence or absence of cytochalasin B or different solvents used as vehicles. The range of means from the four laboratories using flow cytometry methods (3.7-fold: 3.5-12.9 micronucleated cells/1000 cells) was similar to that from the nine laboratories using other scoring methods (4.3-fold: 3.2-13.8 micronucleated cells/1000 cells). No laboratory could be identified as an outlier or as showing unacceptably high variability. Quality Control (QC) methods applied to analyse the intra-laboratory variability showed that there was evidence of inter-experimental variability greater than would be expected by chance (i.e. over-dispersion). However, in general, this was low. This study demonstrates the value of QC methods in helping to analyse the reproducibility of results, building up a 'normal' range of values, and as an aid to identify variability within a laboratory in order to implement processes to maintain and improve uniformity

Laughter and humor as complementary and alternative medicines for dementia patients

<p>Abstract</p> <p>Background</p> <p>The number of dementia patients has increased worldwide, with an estimated 13.7 million dementia patients in the Asia Pacific region alone. This number is expected to increase to 64.6 million by the year 2050.</p> <p>Discussion</p> <p>As a result of advances in research, there several pharmacological therapies available for the treatment of dementia patients. However, current treatments do not suppress the disease process and cannot prevent dementia, and it will be some time before these goals are realized. In the meantime, complementary and alternative medicine (CAM) is an important aspect in the treatment of dementia patients to improve their quality of life throughout the long course of the disease. Considering the individuality of dementia patients, applicability of laughter and humor therapy is discussed. Even though there are many things that need to be elucidated regarding the mechanisms underlying the beneficial effects of laughter and humor, both may be good CAM for dementia patients if they are applied carefully and properly.</p> <p>Summary</p> <p>In this debate article, the physiological basis and actual application of laughter and humor in the treatment of dementia patients are presented for discussion on the applicability to dementia patients.</p