Transforming growth factor-beta inhibits interferon-gamma secretion by lymphokine-activated killer cells stimulated with tumor cells

The effect of transforming growth factor-beta (TGF-beta) secreted by glioblastoma (T98G) cells on the secretion of interferon-gamma (IFN-gamma) by lymphokine-activated killer (LAK) cells stimulated with tumor cells was investigated in cocultures of LAK and Daudi cells supplemented with T98G culture supernatant, T98G culture supernatant preincubated with anti-TGF-beta 1 and anti-TGF-beta 2 neutralizing antibodies, anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, or natural human TGF-beta 1 or recombinant human TGF-beta 2. LAK cells were incubated with anti-TGF-beta 1 and anti-TGF-beta 2 antibodies, and with T98G cells of which the supernatant contained both active and latent forms of TGF-beta 1 and TGF-beta 2, with or without neutralizing antibodies. Addition of the supernatant from T98G cells to LAK/Daudi culture caused inhibition of IFN-gamma secretion by LAK cells. The inhibition was abolished by pretreatment of the supernatants with anti-TGF-beta antibodies. Addition of TGF-beta 1 and TGF-beta 2 to the LAK/Daudi culture inhibited IFN-gamma secretion by LAK cells in a dose-dependent manner. Addition of anti-TGF-beta antibodies to the LAK culture resulted in increased IFN-gamma secretion. T98G cells failed to stimulate LAK cells to secrete more IFN-gamma. Addition of anti-TGF-beta antibodies to the LAK-T98G culture resulted in increased IFN-gamma secretion by LAK cells. These results suggest that most malignant glioma cells which secrete high levels of TGF-beta can inhibit IFN-gamma secretion by LAK cells even after tumor cell stimulation.     

The elevated mRNA content as a potential indicator of precancerous states of the gallbladder mucosa in patients with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) patients have a high incidence of cancer in the gallbladder. In the present study, we showed that precancerous lesions in the gallbladder of PBM such as hyperplasia or metaplasia, indicated high concentration of the amount of total mRNA. The mRNA content could be easily measured by our new technique utilizing a GenePlate, which is a poly (dT) oligonucleotide immobilized plastic plate, and Yoyo-1, a fluorescent DNA intercalator. To standardize the mRNA contents, we utilized which was defined as the ratio of total mRNA contents to total nucleic acids in a same sample. The mRNA index of the proliferating cells was significantly higher than that of the resting cells, and the mRNA index of cancer cells, such as gastric cancer, colon cancer, bile duct cancer, and gallbladder cancer also showed significantly higher concentration than that of normal mucosa. In the study of precancerous lesion, PBM, the mRNA index was significantly higher than that of mild cholecystitis but less than that of gallbladder cancer, suggesting that in the gallbladder mucosa of PBM, a precancerous state was able to be diagnosed by the mRNA index.     

A gene cluster for 6-deoxy-L-talan synthesis in Actinobacillus actinomycetemcomitans

The serotype c antigen of Actinobacillus actinomycetemcomitans consists of 6-deoxy-l-talose. A gene cluster involved in the synthesis of serotype-specific polysaccharide antigen was cloned from the chromosomal DNA of A. actinomycetemcomitans NCTC 9710 (serotype c). This cluster consisted of 17 open reading frames. Escherichia coli produced the polysaccharide that reacts with the serotype c-specific antibody when transformed with a plasmid containing the cluster. Comparing the structure of the gene cluster with a similar cluster from A. actinomycetemcomitans Y4 (serotype b), which produces a polysaccharide consisting of l-rhamnose and d-fucose, revealed that a 5.7 kb region containing seven genes in the cluster from strain Y4 was replaced by a 3.8 kb region containing three genes in strain NCTC 9710. The results suggest that these region, as well as dTDP-6-deoxy-l-talose-forming dTDP-4-keto-l-rhamnose reductase, is essential to the production of extracellular polysaccharide specific to serotype c.     

Reflected infrared spectrum of a massive protostar in Orion

The infrared source IRc2 in the star-forming region Orion-KL is generally believed to contain a massive and very young star. Its nature and evolutionary status, however, are difficult to determine because it is hidden from direct view by a dense disklike envelope of gas and dust. Here we report observations of infrared radiation (at a wavelength of about 2 microm) that has escaped the surrounding dust in the polar direction, perpendicular to the plane of the disk, and then been reflected towards us by dust farther away from the star. The reflected spectrum contains absorption lines of neutral metallic atoms and carbon monoxide, which we interpret as indicating a source temperature of about 4,500 K. But, given the luminosity of the source, its radius must be at least 300 solar radii-too large to be attained with the modest gas-accretion rates in existing theories of massive-star formation. Whether the infrared radiation is coming from the protostar itself or the self-luminous accretion disk around it, the accretion rate must be around (5-15) x 10(-3) solar masses per year, at least two orders of magnitude greater than is commonly assumed in models of star formation.     

Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway

Activation of Ras leads to the constitutive activation of a downstream phosphorylation cascade comprised of Raf-1, mitogen-activated protein kinase (MAPK) kinase, and MAPK. We have developed a yeast-based assay in which the Saccharomyces cerevisiae mating pheromone-induced MAPK pathway relied on co-expression of K-Ras and Raf-1. Radicicol, an antifungal antibiotic, was found to inhibit the K-ras signaling pathway reconstituted in yeast. In K-ras-transformed, rat epithelial, and K-ras-activated, human pancreatic carcinoma cell lines, radicicol inhibited K-Ras-induced hyperphosphorylation of Erk2. In addition, the level of Raf kinase was significantly decreased in radicicol-treated cells, whereas the levels of K-Ras and MAPK remained unchanged. These results suggest that radicicol disrupts the K-Ras-activated signaling pathway by selectively depleting Raf kinase and raises the possibility that pharmacological destabilization of Raf kinase could be a new and powerful approach for the treatment of K-ras-activated human cancers.     

Research and development related to PFM for aged nuclear components

At the Japan Atomic Energy Research Institute (JAERI), research activities related to probabilistic fracture mechanics (PFM) have been conducted as a part of the research program on aging and structural integrity of LWR components. This paper describes the outline of two activities related to PFM, i.e. the development of a PFM code and a contract research on ‘Application of PFM Methodology to Reliability Assessment of Nuclear Components’ implemented by the Japan Welding Engineering Society (JWES). In the former research, a new PFM code PASCAL (PFM Analysis of Structural Components in Aging LWR) was developed. This code has some new functions in models of semi-elliptical crack extension, elastic–plastic fracture analysis based on R6 method and options for the evaluation of overlay cladding and warm pre-stress (WPS) effect. Besides, the code has the function to evaluate the effect of irradiation embrittlement recovery by thermal annealing of a reactor pressure vessel and re-irradiation embrittlement. Based on the analyses on benchmark problem conducted by USNRC/EPRI, performance and functions introduced in the code were examined. Some case studies were also carried out to investigate the influence of various parameters. On the other hand, JAERI has been sponsoring the PFM related activities in relation to the structural integrity of LWR components. These activities have been conducted at JSME and JWES. The objective of this activity has been to provide for the future need of PFM methodology.     

Problems in pharmacological evaluation of patients with paroxysmal atrial fibrillation: clinical analysis of more than 100 consecutive patients

To address the problems of pharmacological evaluation in paroxysmal atrial fibrillation (PAf), we interviewed 108 consecutive patients with documented PAf regarding symptoms, frequency and trigger factors of PAf and analyzed the 24-hour ambulatory electrocardiographic monitoring (Holter monitoring) records in relation to symptoms. Twenty-nine patients were totally asymptomatic, while 79 patients were symptomatic of which 49 patients had obvious trigger factors. PAf was documented by Holter monitoring in 22 of 79 symptomatic patients. On analysis of PAf-documented 25 Holter monitoring records, the patients checked event marks as PAf in only 20 of 155 PAf episodes. Six episodes of 26 event marks that patients thought to be PAf proved to be premature atrial or ventricular contractions. Nine patients in whom PAf persisted for more than 24 hours became asymptomatic. Patients suitable for pharmacological evaluation constituted about one-fifth of the PAf patients in our consecutive study. Even with the selection of these patients, pharmacological evaluation based on symptoms is difficult because disappearance of PAf may be associated with persistent atrial fibrillation.     

Fully digital LCoS device for consumer applications

Abstract— This paper presents a new display device, which combines a digital backplane and a vertically aligned nematic liquid‐crystal layer. The device has 1280 × 720 pixels in a 0.7‐in.‐diagonal display area. In this paper, we present the concept of the new device and overview the performance of the device for a rear‐projection television application.     

Human chymase, an enzyme forming novel bioactive 31-amino acid length endothelins

We report the novel role of human chymase in the production of bioactive 31-amino acid length endothelins (ETs), which may play a role in allergies and vascular diseases. In the bronchi of asthmatic patients, the vascular tissue in atherosclerosis, and the heart muscle in cardiac hypertrophy, both ET-like immunoreactivity and the accumulation of mast cells significantly increase. Chymase from human mast cells selectively cleaves big ET-1, -2 and -3 at their Tyr31-Gly32 bonds, and produces novel bioactive 31-amino acid length ETs, ETs(1-31), without any further degradation products. However, chymases from other species, human cathepsin G, and porcine alpha-chymotrypsin, degrade big ETs. ETs(1-31) at concentrations between 10(-9) M and 10(-7) M exhibited various contractile potencies in rat tracheae and porcine coronary arteries in a dose-dependent manner. Furthermore, ET-1(1-31) at concentrations between 10(-14) M and 10(-10) M caused a significant increase in the intracellular free Ca2+ concentration. The contractile activity of ETs(1-31) may not be the consequence of conversion to the corresponding ETs(1-21) by phosphoramidon-sensitive ET converting enzyme(s) or other chymotrypsin-type proteases and metallo-endopeptidases, because the contractile activity was not significantly inhibited on treatment with inhibitors of these proteases prior to the addition of ET-1(1-31).