The authors identified eight patients with Ullrich disease in whom collagen VI was present in the interstitium but was absent from the sarcolemma. By electron microscopy, collagen VI in the interstitium was never linked to the basal lamina. These findings suggest that in these patients it is not the total absence of collagen VI from the muscle but the failure of collagen VI to anchor the basal lamina to the interstitium that is the cause of Ullrich disease. Only one of the patients had a mutation in the collagen VI gene, suggesting that the primary abnormality in most of the patients involved some other molecules.
Peroxiredoxin-ll (Prxll) and glutathione peroxidase-l (GPxl) are regulators of the redox system that is one of the most crucial supporting systems in neurons. This system is an antioxidant enzyme defense system and is synchronously linked to other important cell supporting systems. To clarify the common self-survival mechanism of the residual motor neurons affected by amyotrophic lateral sclerosis (ALS), we examined motor neurons from 40 patients with sporadic ALS (SALS) and 5 patients with superoxide dismutase 1 (SOD1)-mutated familial ALS (FALS) from two different families (frame-shift 126 mutation and A4 V) as well as four different strains of the SOD1-mutated ALS models (H46R/G93A rats and G1H/G1L-G93A mice). We investigated the immunohistochemical expression of Prxll/GPxl in motor neurons from the viewpoint of the redox system. In normal subjects, Prxll/GPxl immunoreactivity in the anterior horns of the normal spinal cords of humans, rats and mice was primarily identified in the neurons: cytoplasmic staining was observed in almost all of the motor neurons. Histologically, the number of spinal motor neurons in ALS decreased with disease progression. Immunohistochemically, the number of neurons negative for Prxll/GPxl increased with ALS disease progression. Some residual motor neurons coexpressing Prxll/GPxl were, however, observed throughout the clinical courses in some cases of SALS patients, SOD1-mutated FALS patients, and ALS animal models. In particular, motor neurons overexpressing Prxll/GPxl, i.e., neurons showing redox system up-regulation, were commonly evident during the clinical courses in ALS. For patients with SALS, motor neurons overexpressing Prxll/GPxl were present mainly within approximately 3 years after disease onset, and these overexpressing neurons thereafter decreased in number dramatically as the disease progressed. For SOD1-mutated FALS patients, like in SALS patients, certain residual motor neurons without inclusions also overexpressed Prxll/GPxl in the short-term-surviving FALS patients. In the ALS animal models, as in the human diseases, certain residual motor neurons showed overexpression of Prxll/GPxl during their clinical courses. At the terminal stage of ALS, however, a disruption of this common Prxll/GPxl-overexpression mechanism in neurons was observed. These findings lead us to the conclusion that the residual ALS neurons showing redox system up-regulation would be less susceptible to ALS stress and protect themselves from ALS neuronal death, whereas the breakdown of this redox system at the advanced disease stage accelerates neuronal degeneration and/or the process of neuronal death.
Objective: Kawasaki disease (KD), an acute febrile disease that induces systemic vasculitis in infants, has been proposed by Awaya and Sahashi in 2003 to be epidemiologically linked with pollen exposure. In this report, seasonal variation patterns of the monthly development of KD in 5,917 patients (Pt.) in Kanagawa, Japan were compared with the monthly pollen release numbers (Nos.) from 1991 to 2002. Methodology: A correlation coefficient (c.c.) matrix was generated using regression analyses of the correlation of KD onset and pollen exposure in each month. The percent of Japanese cedar pollen Nos. was calculated from the pollen numbers (Po.Nos.) of all the species surveyed in March and April throughout the years. Results: Significant c.c. associations were revealed between Po.Nos. from all species in March and KD Pt.Nos. in August (0.88), November (0.72), May (0.68), and April (0.66). Significant c.c. associations were also found between Po.Nos. from all species in April and KD Pt.Nos. in August (0.70), and between Po.Nos from all species in February and KD Pt.Nos. in July (0.62). Mean c.c. values of 0.60 in March, 0.47 in October, 0.45 in July, 0.35 in April, and 0.31 in February between Po.Nos. and KD Pt.Nos. were shown. February, March and April contributed 4.7%, 40.6% and 38.8% of the annual Po.Nos., respectively, of which 93.8%, 84.3% and 10.9% were from cedar pollen, respectively. Conclusions: A positive association was demonstrated between the Po.Nos. from all species, particularly cedar Po.Nos. in March, and the KD Pt.Nos. in the following several months.
SUMMARYBleomycin (BLM), an antitumour drug, is known to cause interstitial pneumonia followed by pulmonary fibrosis, and has often been used to produce an animal model of pulmonary fibrosis. In the present study, we examined the effect of a nonapeptide thymic hormone, facteur thymique serique (FTS), on the murine lung fibrosis induced by intratracheal instillation of BLM. Treatment with FTS ameliorated BLM-induced fibrotic changes in a dose-dependent manner, as indicated by the reduced accumulation of hydroxyproline (HP). In addition, FTS suppressed BLM-induced cellular inflammatory response in the lungs, as evidenced by inhibition of increased lung weight, reduced accumulation of inflammatory leucocytes, including lymphocytes and neutrophils, but not macrophages, and less pronounced histopathological changes. Finally, BLM challenge increased the local synthesis of proinflammatory cytokines, TNF-a and IL-1b and chemokines, MCP-1, MIP-1a RANTES, MIP-2 and KC, while administration of FTS suppressed the production of these cytokines, except for MCP-1. These effects of FTS were observed only when mice received intratracheal instillation with BLM. Considered collectively, our results indicated that FTS treatment ameliorated the cellular inflammatory responses and fibrotic changes in the lungs caused by BLM and such inhibition was well correlated with reduced synthesis of several fibrosis-related cytokines, and suggested that FTS may be potentially useful for the treatment of pulmonary fibrosis.
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