No abstract

For the last 20 years, a great amount of evidence has accumulated through epidemiological studies that most of the dry eye disease encountered in daily life, especially in video display terminal (VDT) workers, involves short tear film breakup time (TFBUT) type dry eye, a category characterized by severe symptoms but minimal clinical signs other than short TFBUT. An unstable tear film also affects the visual function, possibly due to the increase of higher order aberrations. Based on the change in the understanding of the types, symptoms, and signs of dry eye disease, the Asia Dry Eye Society agreed to the following definition of dry eye: "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The definition stresses instability of the tear film as well as the importance of visual impairment, highlighting an essential role for TFBUT assessment. This paper discusses the concept of Tear Film Oriented Therapy (TFOT), which evolved from the definition of dry eye, emphasizing the importance of a stable tear film.

A clinical isolate of Serratia marcescens (TN9106) produced a metallo 13-lactamase (IMP-1) which conferred resistance to imipenem and broad-spectrum 13-lactams. The consensus amino acid residues, His-95, His-97, Cys-176, and His-215, which form putative zinc ligands, were conserved in the deduced amino acid sequence of IMP-1. By determination of the amino acid sequence at the N terminus of purified mature IMP-1, 18 amino acid residues were found to be processed from the N terminus of the premature enzyme as a signal peptide. These results clearly show that IMP-1 is an enterobacterial metallo 13-lactamase, of which the primary structure has been completely determined, that confers resistance to carbapenems and other broad-spectrum 13-lactams.Many extended-spectrum 13-lactamases conferring high levels of resistance to broad-spectrum P-lactam antibiotics have been found worldwide with the increasing use of newly developed broad-spectrum P-lactam antibiotics (10, 11).They are mostly R plasmid-mediated TEM-or SHV-related class A enzymes (4,12,18,22,29,32). However, plasmidmediated AmpC-type ,-lactamases that belong to class C have recently been reported (9, 21). These plasmid-mediated extended-spectrum ,B-lactamases have a serine residue at the active center of the enzyme, and they effectively hydrolyze broad-spectrum ,-lactams, except carbapenems. Although it was reported by genetic analyses that bacteria belonging to the family Enterobacteriaceae, except Klebsiella spp. (1, 2) and Pseudomonas spp., have chromosomally encoded inducible AmpC 3-lactamases (8,14,16,20,26,34) times show resistance to imipenem and broad-spectrum P-lactams (7,17,37). The imipenem resistances of these bacteria are mainly due to the production of metallo 3-lactamases that belong to class B. The class B enzymes require zinc ions for enzyme activity and demonstrate a primary structure quite different from those of the class A and class C enzymes belonging to the group of serine P-lactamases.Recently, several strains of Serratia marcescens were reported to show resistance to carbapenems as well (35). In this study, we clearly show that a clinically isolated strain of S. marcescens (TN9106) showing resistance to imipenem has a chromosomally encoded metallo 3-lactamase gene.

Ethylene-responsive element binding factors (ERFs) are members of a novel family of transcription factors that are specific to plants. A highly conserved DNA binding domain known as the ERF domain is the unique feature of this protein family. To characterize in detail this family of transcription factors, we isolated Arabidopsis cDNAs encoding five different ERF proteins (AtERF1 to AtERF5) and analyzed their structure, DNA binding preference, transactivation ability, and mRNA expression profiles. The isolated AtERFs were placed into three classes based on amino acid identity within the ERF domain, although all five displayed GCC box-specific binding activity. AtERF1, AtERF2, and AtERF5 functioned as activators of GCC box-dependent transcription in Arabidopsis leaves. By contrast, AtERF3 and AtERF4 acted as repressors that downregulated not only basal transcription levels of a reporter gene but also the transactivation activity of other transcription factors. The AtERF genes were differentially regulated by ethylene and by abiotic stress conditions, such as wounding, cold, high salinity, or drought, via ETHYLENE-INSENSITIVE2 (EIN2)-dependent or -independent pathways. Cycloheximide, a protein synthesis inhibitor, also induced marked accumulation of AtERF mRNAs. Thus, we conclude that AtERFs are factors that respond to extracellular signals to modulate GCC box-mediated gene expression positively or negatively.