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.     

Detection of Multiple Blockages in Parallelized Microreactors

In a plant consisting of parallelized microreactors (MRs), the product quality is lowered because of a lack of flow uniformity among them when blockage occurs. It is not practical to install sensors in every MR from the viewpoint of cost when detecting the blocked MRs. In the previous study, the multiple blockage detection (MBD) method using a small number of sensors was proposed, but its performance became low when the number of sensors decreased. Here, the conventional algorithm for MBD is improved by considering the process behavior on blockage occurrence, and the effectiveness of the improved algorithm is demonstrated through a numerical case study. The effects of flow distributor types and sensor types on the MBD performance are numerically investigated.     

A comparative study of DPSK and OOK WDM transmission over transoceanic distances and their performance degradations due to nonlinear phase noise

We have compared experimentally the transmission performance of return-to-zero differential phase-shift keying (RZ-DPSK) with RZ-ON-OFF keying (OOK), nonreturn-to-zero differential phase-shift keying (NRZ-DPSK), and NRZ-OOK for 100/spl times/10-Gb/s transmission with a spectral efficiency of 0.22 b/s/Hz over transoceanic distances. The Q degradation of the RZ-DPSK after transmission over 9180 km was 3 dB greater than that of RZ-OOK. The experimental results clearly showed the major cause of degradation for DPSK is not cross-phase modulation but self-phase modulation. The calculated nonlinear phase noise, i.e., the Gordon-Mollenauer effect, agreed with the experimental results. A distributed-Raman-amplifier assisted erbium-doped-fiber-amplified transmission line acted well in reducing the nonlinear phase noise.     

Phase fluctuations of cross-polarized signals at 4 GHz in fine weather on earth-space paths

On an earthspace propagation path with the low elevation angle of 10 deg, the phase between co- and crosspolar signals occasionally showed rapid and irregular fluctuations during fine weather. These fluctuations were generally significant during the daytime, and were strongly in phase with the occurrence of the copolar amplitude scintillations. This could be attributed to the combined effects of the crosspolar phase pattern of the receiving antenna and small fluctuations of the angle of arrival of the radiowaves.     

Efficiency of repeated batch penicillin fermentation using two fermentors. Computer simulation and optimisation

Repeated batch operation using two fermentors (RBTF) to penicillin fermentation was demonstrated by computer simulation to improve productivity. Three operation modes were compared: chemostat, repeated batch operation using a single fermentor (RBSF) and RBTF; in each case account was made of the lag period before growth. The simulated fermentor performances were assessed on the basis of the penicillin productivity and concentration; the simulation was based on published batch fermentation data. It was shown that RBTF was superior to RBSF and chemostat. The advantage of RBTF increased as the lag period became greater.     

Application of gene gun for local-regional cancer

We studied the in vivo gene transfusion using a gene gun, formerly used in plants and culture cells. The hand-held type gene gun (Helios Gene Gun System) is simple and convenient for effective gene transfection in living animals. This method has some advantages in that there is no need for use of viral vector, independence on the cell cycle and local inducement of plural genes. There is a great possibility for application to local-regional cancer.     

Age-related changes in innervation in hypertrophic pyloric stenosis

BACKGROUND/PURPOSE: Recent reports have identified abnormal innervation of the circular muscle layer involving the fine intramuscular nerve fibers in hypertrophic pyloric stenous (HPS). HPS presenting after 3 months of age is rare. The aim of this study was to determine the distribution pattern of nerve fibers in the smooth muscle layers in HPS and correlate this with age at presentation. METHODS: Full-thickness pyloric muscle biopsy specimens were obtained from eight patients with HPS (five age 3 to 5 weeks, two age 3 months, and one age 7 months) and five controls with normal pylorus (age 5 days to 3 years). All specimens were stained with monoclonal antibody to the neural cell adhesion molecule (NCAM) using immunohistochemistry. RESULTS: There were many NCAM-positive nerve fibers in the circular and longitudinal muscle layers in the controls. No NCAM positive nerve fibers were seen in the circular or longitudinal muscle layers in the five cases of HPS in which the patients were less than 5 weeks old. In the two cases in which the patients were 3 months old, occasional NCAM-positive nerve fibers were seen in the circular layer, and moderate numbers of NCAM positive fibers were seen in the longitudinal muscle layers. Moderate numbers of NCAM-positive nerve fibers in the circular muscle layer and many NCAM positive nerve fibers in the longitudinal muscle layers were identified in the 7-month-old HPS patient. CONCLUSIONS: The data suggest that the pyloric muscle lacks innervation in the young HPS infant. Whereas, at 3 months of age the hypertrophied pyloric muscle is partially innervated, and at 7 months of age the pyloric muscle has practically normal innervation.     

The molecular interaction of Fas and FAP-1. A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis

Fas (APO-1/CD95), which is a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. A protein tyrosine phosphatase, Fas-associated phosphatase-1 (FAP-1), that was previously identified as a Fas binding protein interacts with the C-terminal 15 amino acids of the regulatory domain of the Fas receptor. To identify the minimal region of the Fas C-terminal necessary for binding to FAP-1, we employed an in vitro inhibition assay of Fas/FAP-1 binding using a series of synthetic peptides as well as a screen of random peptide libraries by the yeast two-hybrid system. The results showed that the C-terminal three amino acids (SLV) of human Fas were necessary and sufficient for its interaction with the third PDZ (GLGF) domain of FAP-1. Furthermore, the direct cytoplasmic microinjection of this tripeptide (Ac-SLV) resulted in the induction of Fas-mediated apoptosis in a colon cancer cell line that expresses both Fas and FAP-1. Since t(S/T)X(V/L/I) motifs in the C termini of several other receptors have been shown to interact with PDZ domain in signal transducing molecules, this may represent a general motif for protein-protein interactions with important biological functions.