Increased anti-oxidative action compensates for collagen tissue degeneration in vitiligo dermis

Vitiligo is a common depigmentation disorder characterized by the selective loss of melanocytes. In our daily clinic experience, we noticed that the skin tightness of hypopigmented lesions would be more evident in comparison to that of uninvolved perilesional skin in vitiligo patients. Therefore, we hypothesized that collagen homeostasis might be maintained in vitiligo lesions, irrespective of the substantial excessive oxidative stress that occurs in association with the disease. We found that the expression levels of collagen-related genes and anti-oxidative enzymes were upregulated in vitiligo-derived fibroblasts. Abundant collagenous fibers were observed in the papillary dermis of vitiligo lesions in comparison to uninvolved perilesional skin by electron microscopy. The production of matrix metalloproteinases that degraded collagen fibers was suppressed. The deposition of acrolein adduct protein, which is a product of oxidative stress, was significantly reduced in vitiligo dermis and fibroblasts. As part of the mechanism, we found upregulation of the NRF2 signaling pathway activity, which is an important defense system against oxidative stress. Taken together, we demonstrated that the anti-oxidative action and collagen production were upregulated and that the collagen degeneration was attenuated in vitiligo dermis. These new findings may provide important clues for the maintenance of antioxidant ability in vitiligo lesions.     

New fluorogenic substrates for horseradish peroxidase: Rapid and sensitive assays for hydrogen peroxide and the peroxidase

p-Hydroxyphenyl compounds [3-(p-hydroxyphenyl)propionic acid, p-hydroxyphenethyl alcohol, hordenine, p-ethylphenol, 3-(p-hydroxyphenyl)-1-propanol, p-n-propylphenol, and p-hydroxyphenyllactic acid] were recently found to be excellent fluorogenic substrates for the horseradish peroxidase-mediated reaction with hydrogen peroxide. A very rapid and sensitive method for the fluorometric assays of hydrogen peroxide and the peroxidase was established by using 3-(p-hydroxyphenyl)propionic acid as the best of these substrates; hydrogen peroxide can be assayed precisely in amounts as small as 0.1 nmol, with peroxidase activity as low as 7.8 μU.     

Genetic polymorphisms of blood proteins in the troops of Japanese macaques,Macaca fuscata: V. Erythrocyte phosphohexose isomerase polymorphism

The electrophoretic variations of erythrocyte phosphohexose isomerase (PHI) were examined in 1433 blood samples from 37 troops of Japanese macaques in order to clarify the gene dynamics of this species. The genetic polymorphisms were observed in several troops. The troops showing the variation of PHI were Fukushima, Shiga A, Shiga C, Ryozenyama, Mikata I and II, Kawara, Takasakiyama A, B, and C, Itsuki, Koshima and Kushima. The variant alleles found in these troops were PHI ₂ ^mac , PHI ₇ ^mac , PHI ₈ ^mac , and PHI ₁₀ ^mac alleles, and the PHI ₁₀ ^mac allele was newly found in the present work.     

Fast atom bombardment tandem mass spectrometric analysis of N-carbamoylamino acids.

Using fast atom bombardment (FAB) and tandem mass spectrometry (MS/MS), we examined 12 synthetic N-carbamoylamino acids (CAA) as tert-butyldimethylsilyl (TBDMS) derivatives. In FAB mass spectrometry and FAB MS/MS, spectra of protonated molecules for CAA provide specific cleavages involving the TBDMS carbamoyl moiety. The daughter scan spectrum of the parent ion indicated that it was useful for structural elucidation and differentiation of structural isomers of CAA. We have also identified each CAA separately in a mixture using a neutral loss scan for characteristic ions. In addition, we demonstrated that CAA in urine samples from patients with ornithine carbamoyl transferase deficiency gave collision-induced dissociation (CID) spectra which correspond well with CID spectra obtained using synthetically prepared CAA.     

Genetic polymorphisms of blood proteins in the troops of Japanese macaques,Macaca fuscata: IV. Erythrocyte esterase polymorphism inMacaca fuscata

Genetic variation at the locus controlling A₁ band of erythrocyte esterase was found in the Japanese macaque,Macaca fuscata. Existence of four alleles,Es-A ₁ ¹ ,Es-A ₁ ² ,Es-A ₁ ³ , andEs-A ₁ ⁴ , controlling the mobility of the band and codominance relation between them were postulated. A majority of the troops examined were monomorphic inEs-A ₁ 1-1 phenotype, and the variant phenotypes were observed to occur only in Yugawara-Ihama, Arashiyama, and Koshima areas.     

Genetic polymorphisms of blood proteins in the troops of Japanese macaques,Macaca fuscata: III. Erythrocyte carbonic anhydrase polymorphism inMacaca fuscata

In order to clarify the genetic relationships between troops of Japanese macaques, the authors have been looking for the genetic variation of blood proteins by electrophoretical technique. In this work the genetic variants of erythrocyte carbonic anhydrase isozymes of 1273 blood samples from 34 troops of this species were examined. The genetic polymorphisms were observed in several troops. The variable troops of CA I were Fukushima, Takasakiyama, Kohchi, Shimane, Shodoshima I, K, and T, Kashima, Kawara, Takasakiyama A, B, and C, and Tomogashima. The variant allele found in these troops is onlyd ₂ allele, which was probably identical with that reported byTashian et al. (1971). The frequencies ofd ₂ allele in the Shodoshima and Kashima troops were very high, and this phenomenon was interpreted as being a result of the founder effect and the random fluctuation of gene frequencies in these troops.     

SCF-Fbxo42 promotes synaptonemal complex assembly by downregulating PP2A-B56

Meiosis creates genetic diversity by recombination and segregation of chromosomes. The synaptonemal complex assembles during meiotic prophase I and assists faithful exchanges between homologous chromosomes, but how its assembly/disassembly is regulated remains to be understood. Here, we report how two major posttranslational modifications, phosphorylation and ubiquitination, cooperate to promote synaptonemal complex assembly. We found that the ubiquitin ligase complex SCF is important for assembly and maintenance of the synaptonemal complex in Drosophila female meiosis. This function of SCF is mediated by two substrate-recognizing F-box proteins, Slmb/βTrcp and Fbxo42. SCF-Fbxo42 down-regulates the phosphatase subunit PP2A-B56, which is important for synaptonemal complex assembly and maintenance.     

Acid-Catalyzed Photosubstitution of 5-Fluoro-1,3-Dimethyluracil with Substituted Benzenes

Abstract

The substantial photosubstitution of 5-fluoro-1,3-dimethyluracil with substituted benzenes is first achieved by the addition of trifluoroacetic acid to the reaction mixture. The presence of protons is essential for the formation of 5-aryl-1,3-dimethyluracils.     

Synthesis of Iodoaminoimidazole Arabinoside (IAIA): A Potential Reductive Metabolite of the Spect Imaging Agent,Iodoazomycin Arabinoside (IAZA)

Abstract

The stereospecific synthesis of 1-(5-deoxy-5-iodo-α-D-arabino-furanosyl)-2-aminoimidazole (iodoaminoimidazole arabinoside: IAIA, 2) is described. The reaction of the protected sugar bromide (8) and trifluoroacetamidoimidazole (10B) gave the coupled product (11B), which gave the free nucleoside (4) on deblocking. It was identical with AIA obtained by reduction of AZA (azomycin arabinoside), whose anomeric configuration was found to be a by the X-ray crystallography.     

Novel Twin Streptolysin S-Like Peptides Encoded in the sag Operon Homologue of Beta-Hemolytic Streptococcus anginosus

Streptococcus anginosus is a member of the anginosus group streptococci, which form part of the normal human oral flora. In contrast to the pyogenic group streptococci, our knowledge of the virulence factors of the anginosus group streptococci, including S. anginosus, is not sufficient to allow a clear understanding of the basis of their pathogenicity. Generally, hemolysins are thought to be important virulence factors in streptococcal infections. In the present study, a sag operon homologue was shown to be responsible for beta-hemolysis in S. anginosus strains by random gene knockout. Interestingly, contrary to pyogenic group streptococci, beta-hemolytic S. anginosus was shown to have two tandem sagA homologues, encoding streptolysin S (SLS)-like peptides, in the sag operon homologue. Gene deletion and complementation experiments revealed that both genes were functional, and these SLS-like peptides were essential for beta-hemolysis in beta-hemolytic S. anginosus. Furthermore, the amino acid sequence of these SLS-like peptides differed from that of the typical SLS of S. pyogenes, especially in their propeptide domain, and an amino acid residue indicated to be important for the cytolytic activity of SLS in S. pyogenes was deleted in both S. anginosus homologues. These data suggest that SLS-like peptides encoded by two sagA homologues in beta-hemolytic S. anginosus may be potential virulence factors with a different structure essential for hemolytic activity and/or the maturation process compared to the typical SLS present in pyogenic group streptococci.