Search

Objective: GNE myopathy is a rare autosomal recessive adult-onset distal myopathy caused by biallelic pathogenic variants in GNE. Although some extra-muscular manifestations associated with GNE myopathy have been reported, little is known about whether they are disease-specific and how often they present. This study aimed to characterize extra-muscular manifestations of GNE myopathy., Methods: We conducted a questionnaire survey of GNE myopathy patients registered in a national registry in Japan. The questionnaire requested information regarding idiopathic thrombocytopenia, cardiac involvement, respiratory involvement, sleep apnea syndrome (SAS), and psychiatric diseases., Results: The response rate was 62.4% (126/198), yielding a total of 51 male and 75 female participants. Of the participants, 4.1% (5/123) had a diagnosis of idiopathic thrombocytopenia, and 16.3% (8/49) of males and 6.6% of females (5/76) had a diagnosis of SAS. In total, 0.8% (1/126) of participants had pervasive developmental disabilities and 14.7% (16/109) had a psychiatric disease., Conclusion: The frequencies of idiopathic thrombocytopenia and SAS among Japanese GNE myopathy patients were higher than those observed in the general Japanese population. Routine blood tests and evaluation of sleep-disordered breathing should be considered in order to better manage GNE myopathy patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In a Japanese chemical factory, a lung disease like pneumoconiosis appeared at a high rate among workers handling cross-linked water-soluble acrylic acid polymer (CWAAP). To our knowledge, no such case was known in the world until very recently. The present study was designed to elucidate the effect of single intratracheal CWAAP instillation on the lung of rats. The CWAAP group had a significant increase in relative lung weight accompanied by a significant elevation in the number of total cells, total protein concentrations, and myeloperoxidase concentrations in bronchoalveolar lavage fluid when compared to the control group. The histopathological study revealed acute lung inflammation with the destruction of alveoli. The factors promoting fibrosis, macrophages, TGF-β1, collagen and fibronectin vs. the factors suppressing fibrosis, matrix metalloproteinases were more powerfully driven in the CWAAP group, resultantly leading to fibrotic formation. In turn, we examined if acute lung inflammation and the subsequent fibrotic formation seen in the CWAAP group appeared in the other water-soluble polymer groups. Their histopathological findings were observed only in the polyacrylic acid sodium (PAAS), a monomer of CWAAP, group. The degree of inflammation and fibrogenesis was stronger in the CWAAP group than in the PAAS group. In conclusion, the present study demonstrated the induction of acute lung inflammation and the subsequent fibrotic formation by single intratracheal CWAAP instillation. The structural features of CWAAP that contains many carboxyl groups and cross-linked chains may be responsible for enhanced inflammation and fibrogenesis in the lung., (Copyright © 2020. Published by Elsevier B.V.)

In the developing mammalian brain, neural network formation is regulated by complex signaling cascades. In utero and lactational dioxin exposure is known to induce higher brain function abnormalities and dendritic growth disruption in rodents. However, it is unclear whether perinatal dioxin exposure affects the expression of genes involved in neural network formation. Therefore, we investigated changes in gene expression in the brain regions of developing mice born to dams administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dose: 0, 0.6, or 3.0 μg/kg) on gestational day 12.5. Quantitative RT-PCR showed that TCDD exposure induced Ahrr expression in the cerebral cortex, hippocampus, and olfactory bulb of 3-day-old mice. Gene microarray analysis indicated that the mRNA expression levels of Sema3b and Sema3g, which encode proteins that are known to control axonal projections, were elevated in the olfactory bulb of TCDD-exposed mice, and the induction of these genes was observed during a 2-week postnatal period. Increased Sema3g expression was also observed in the brain but not in the kidney, liver, lung, and spleen of TCDD-exposed neonatal mice. These results indicate that the Sema3b and Sema3g genes are sensitive to brain-specific induction by dioxin exposure, which may disrupt neural network formation in the mammalian nervous system, thereby leading to abnormal higher brain function in adulthood., (Copyright © 2016 Elsevier Inc. All rights reserved.)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1 mRNA expression, and co-treatment with the protein synthesis inhibitor, cycloheximide (CHX) magnifies its expression severalfold further. Although this phenomenon has been reported as superinduction, its molecular mechanism is still obscure. In the present study, we analyzed the influence of the CYP1A1 internal genomic sequence on CHX-mediated superinduction. Partial sequences of the human CYP1A1 were inserted at the 5' end of the internal ribosomal entry site (IRES) connected to luciferase cDNA, and generated constructs were transiently transfected into CHO or HepG2 cells. Intron-1 deletion constructs showed higher inductivity than intron-1 intact constructs by TCDD. Quantitative RT-PCR analyses revealed that the superinduced levels by CHX of the intron-1 intact constructs were greater than those of the intron-1 deletion constructs. The present results indicate that internal genomic sequences of the human CYP1A1 gene, especially the internal sequence of intron-1, are involved in superinduction of the CYP1A1 gene by CHX.

The purpose of this study was to evaluate the sealing ability of a dentinal apical plug treated with a bonding agent. Ninety human lower premolars were used. The teeth were divided into three groups. in groups 1 and 2, to prepare an apical isthmus of 1 mm in length, the first apical seat was prepared with a #45 K file 1 mm short of the anatomical apex and with a #60 K file 2 mm short for the second apical seat. Dry dentin fillings were packed in the apical isthmus with a #60 K file. In group 1, the root canal was obturated with gutta-percha and Canals root canal sealer by the lateral condensation method. In group 2, following an application of the bonding agent to the plug, the root canal was obturated in the same way. In group 3 (control), a single apical seat was prepared with a #60 K file 1 mm short of the apex and the root canal was obturated similarly. The teeth of three groups were immersed in a 1% methylene blue solution for 1, 2, and 4 wk. Dye penetration depth from the apical foramen was determined. Group 2 showed no leakage after 4 wk. Groups 1 and 3 showed dye penetration into the root canal, and in these two groups dye penetration increased with time.