Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer

Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.     

Preparation of Mn2+-Cu+ co-doped P2O5–ZnO–Al2O3 glasses and their red fluorescence properties

To make a Mn²⁺-doped red glass phosphor that can be excited with ultraviolet (UV) light of light-emitting diodes (LEDs), 60P₂O₅-35ZnO-5Al₂O₃-8MnO-xCu₂O glasses (x = 0-1.00) were prepared by a melt-quenching method at 1200-1400°C for 30-180 minutes in atmospheric air, and the redox of Mn and Cu as well as fluorescence properties were investigated. The Mn²⁺ ion was not reduced and oxidized in the melting, quenching, and annealing processes. The valence of Cu in the glasses changed in the order of 0, 1+, and 2+ with the increase in the amount of Cu₂O and in the melting temperature and time. In this study, a 60P₂O₅-35ZnO-5Al₂O₃-8MnO-0.10Cu₂O glass melted at 1250°C for 90 minutes, having the highest Cu⁺ concentration, showed the strongest Mn²⁺ red fluorescence under the UV light at 275 nm. This strong Mn²⁺ red fluorescence has been caused by the energy transfer from excited Cu⁺ ions to Mn²⁺ ions.     

Piperacillin/tazobactam‐induced neurotoxicity in a hemodialysis patient: A case report

Antibiotics are potentially a cause of neurotoxicity in dialysis patients, the most common are the beta‐lactams as ceftazidime and cefepime, and few cases have been reported after piperacillin/tazobactam use. This report presents a case of a hypertensive and diabetic 67‐year‐old woman in regular hemodialysis, which previously had a stroke. She was hospitalized presenting pneumonia, which was initially treated with cefepime. Two days after treatment, she presented dysarthria, left hemiparesis, ataxia, and IX and X cranial nerves paresis. Computed tomography showed no acute lesions and cefepime neurotoxicity was hypothesized, and the antibiotic was replaced by piperacillin/tazobactam. The neurologic signs disappeared; however, 4 days after with piperacillin/tazobactam treatment, the neurological manifestations returned. A new computed tomography showed no new lesions, and the second antibiotic regimen withdrawn. After two hemodialysis sessions, the patient completely recovered from neurological manifestations. The patient presented sequentially neurotoxicity caused by two beta‐lactams antibiotics. This report meant to alert clinicians that these antibiotics have dangerous neurological effects in chronic kidney disease patients.     

Oxidation of doped europium in BaMgAl10O17 by annealing studied by x‐ray‐absorption fine‐structure measurements

Abstract— We studied the influence of annealing in air on doped europium in BaMgAl₁₀O₁₇ by performing x‐ray absorption fine‐structure measurements. We determined the oxidation of doped divalent europium by annealing in air at over 500°C. The interatomic distance between the europium and the surrounding oxygen atoms was compressed by oxidation. It also appears that the oxidation process of europium is determined by the diffusion of oxygen into BaMgAl₁₀O₁₇.     

Influence of doping on the electronic structure of (La,Sr)2CuO4

High-statistics (>4 × 10⁸ counts), room-temperature measurements of the electron-positron momentum density of La_2?x Sr _x CuO₄ have been performed for samples with Sr concentrations of x=0.0, 0.1, 0.13, and 0.2. These spectra have been analyzed in conjunction with theoretical calculations of the electron-positron momentum density. The metallic samples show features consistent with the presence of a Fermi surface, but its evolution with increasing Sr concentration does not follow the predictions of band theory. These results may indicate the effects of electron-electron correlation on the electron momentum distribution in the Cu-O plane.     

Solution structure of bromelain inhibitor IV from pineapple stem: structural similarity with Bowman-Birk trypsin/chymotrypsin inhibitor from soybean

Bromelain inhibitor VI from pineapple stem (BI-VI) is a unique double-chain inhibitor with an 11-residue light chain and a 41-residue heavy chain by disulfide bonds and inhibits the cysteine proteinase bromelain competitively. The structure of BI-VI in aqueous solution was determined using nuclear magnetic resonance spectroscopy and simulated annealing-based calculations. Its three-dimensional structure was shown to be composed of two distinct domains, each of which is formed by a three-stranded antiparallel beta-sheet. Unexpectedly, BI-VI was found to share a similar folding and disulfide bond connectivities not with cystatin superfamily inhibitors which inhibit the same cysteine proteinases but with the Bowman-Birk trypsin/chymotrypsin inhibitor from soybean (BBI-I). BBI-I is a 71-residue inhibitor which has two independent inhibitory sites toward the serine proteinases trypsin and chymotrypsin. These structural similarities with BBI-I suggest that they have evolved from a common ancestor and differentiated in function during a course of molecular evolution.     

Molecular basis of a hereditary type I protein S deficiency caused by a substitution of Cys for Arg474

The molecular basis for a hereditary type I protein S (PS) deficiency was investigated. DNA sequence analysis in the proband showed a novel missense mutation substituting Cys (TGT) for Arg474 (CGT) that is a highly conserved amino acid residue among the related proteins. This missense mutation cosegregated with the type I PS deficiency in this family. Transient expression studies showed that the secretion of the recombinant Cys-mutant PS was markedly decreased compared with that of the recombinant wild-type PS, reproducing the observed phenotype of type I deficiency. Stable expression and pulse-chase experiments demonstrated an intracellular degradation and an impaired secretion of the recombinant Cys-mutant PS. Furthermore, the substitution of Arg474 by Ala or Glu, but not by Lys, markedly reduced the secretion of the recombinant PS mutants in transient expression studies, suggesting that a positively charged basic amino acid might be needed at residue 474 and might play a key role in the protein structure and conformation of the sex hormone binding globulin-homology domain of the PS molecule. We postulate that the loss of the highly conserved Arg474 might be responsible for the type I PS deficiency inherited in this family.