The Action of Antihistamines on the Lymph Formation and Its Effect on the Action of Some Lymphagogues

Increase of capillary permeability is the chief symptomatic reaction of various pathologic states, especially that of localized inflammation, and this is the characteristic pharmacological properties of histamine at a far smaller concentration than that of any other chemical substances (Lewis, 1927; Crammer and Hele, 1944). There are numerous observations as to the diminishing effect of antihistamines on the flare and wheal caused by histamine and the inhibition by antihistamines of localized accumulation of intravenously injected dyes, such as trypan blue, referable to intradermal injection of histamine (for refs. cf. Loew, 1947; Fe£nberg et al., 1950). As for the inhibition of capillary permeability by antihistamines, some maintain that this action is limited to the case where such permeability has been increased by histamine (Wells, Morris and Dragstedt, 1946; Netter, 1947; Rigdon, 1949), but no single and decisive conclusion can yet be given.</p

The Exon Junction Complex Controls the Efficient and Faithful Splicing of a Subset of Transcripts Involved in Mitotic Cell-Cycle Progression

The exon junction complex (EJC) that is deposited onto spliced mRNAs upstream of exon–exon junctions plays important roles in multiple post-splicing gene expression events, such as mRNA export, surveillance, localization, and translation. However, a direct role for the human EJC in pre-mRNA splicing has not been fully understood. Using HeLa cells, we depleted one of the EJC core components, Y14, and the resulting transcriptome was analyzed by deep sequencing (RNA-Seq) and confirmed by RT–PCR. We found that Y14 is required for efficient and faithful splicing of a group of transcripts that is enriched in short intron-containing genes involved in mitotic cell-cycle progression. Tethering of EJC core components (Y14, eIF4AIII or MAGOH) to a model reporter pre-mRNA harboring a short intron showed that these core components are prerequisites for the splicing activation. Taken together, we conclude that the EJC core assembled on pre-mRNA is critical for efficient and faithful splicing of a specific subset of short introns in mitotic cell cycle-related genes

Targeted skipping of a single exon harboring a premature termination codon mutation: Implications and potential for gene correction therapy for selective dystrophic epidermolysis bullosa patients

This study examined the feasibility of antisense oligoribonucleotide (AON) therapy for dystrophic epidermolysis bullosa (DEB). AON was designed to induce skipping of a targeted exon containing a premature termination codon mutation, resulting in restoration of the open reading frame. We targeted exon 70 of COL7A1, as a recurrent mutation 5818delC in Japanese DEB patients was localized to exon 70. We found that one AON induced effective skipping of normal exon 70 containing 16 amino acids. Attachment and migration analyses showed that recombinant collagen without contribution of exon 70 was similar in effect to normal type VII collagen. Next, we synthesized mutation-specific AON by deleting cytosine at 5818. Introduction of this AON into DEB keratinocytes harboring 5818delC showed that the AON induced skipping of exon 70 in the abnormal 5818delC allele. Furthermore, 6.2% of DEB keratinocytes started to express type VII collagen in vitro after application of the mutation-specific AON. Injection of the AON into rat model grafted with DEB keratinocytes and fibroblasts induced a low amount of type VII collagen expression. We conclude that skipping of targeted exons using mutation-specific AON may show potential for future gene therapy for DEB patients