Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer

This study was performed to clarify the different effects of each mutant exon of p53 as indicators of a poor prognosis in patients with non-small cell lung cancer (NSCLC). Tumor tissues of 204 patients with NSCLC were analysed; 96 tumors were stage I, 22 stage II, and 86 stage III. DNA was extracted from frozen specimens and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to investigate mutations of p53 from exon 5 to exon 8. Seventy-five patients with NSCLC (36.8%) had mutations in p53 which included 72 cases of missense mutations and three cases of non-missense mutations. The overall survival rate of patients with mutant p53 adenocarcinomas was strikingly worse than that of patients whose tumors had wild-type p53 (35.7% vs 53.8%; P=0.041), but no significant difference in survival was found in the patients with NSCLC and squamous cell carcinoma. Mutations in exon 5 of p53 occurred in 33 cases (16.2%), mutation in exon 6 was detected in only one case (0.5%), mutations in exon 7 in 20 cases (9.8%), and mutations in exon 8 in 18 cases (8.8%). The overall survival rate of patients with mutations in exon 7 was worse than that of patients with wild-type p53 in NSCLCs and adenocarcinomas (42.9% vs 56.0%; P=0.025 and 33.3% vs 53.8%; P=0.048, respectively), whereas the overall survival of patients with mutations in exon 5 was almost the same as that of patients with wild-type p53. In addition, the overall survival rate of patients with mutations in exon 8 was strikingly worse than that of patients with wild-type p53 in NSCLCs, adenocarcinomas and squamous cell carcinomas (22.9% vs 56.0%; P<0.001, 19.0% vs 53.8%; P=0.004 and 33.3% vs 62.5%; P=0.042, respectively). Multivariate analysis with the Cox regression model of patients with NSCLC, adenocarcinoma and squamous cell carcinoma indicated that mutations in exon 8 were best correlated with the overall survival rate, followed by lymph node status (P<0.001, P=0.015 and P=0.006, respectively), and mutations in exon 7 of NSCLC were also revealed to have good correlation, followed by lymph node status and mutations in exon 8 (P=0.031). Mutation of p53 was a poor prognostic factor for adenocarcinoma as described previously. Moreover, mutations in exon 8 were more useful indicators of prognosis not only for adenocarcinoma but also for NSCLC. Worse overall survival of the patients with mutations in exon 8 of p53 was suggested to be associated with codon 273 mutations as well as mutations between codon 280 and 285 included into the H2 alpha helix corresponding to residues 278-286. These results suggested that abnormal conformation of H2 alpha helix might play an important role not only in the loss of normal function but also in the acquisition of tumorigenesis. Investigation of mutations in exon 8, especially codon 273 mutation and mutant H2 alpha helix was considered to be a clinically useful approach for determining the prognosis of patients with NSCLC.     

The use of epoxy patch grafts for the repair of experimentally-created diaphragmatic defects in dogs

Canine pericardium which had been treated with polyepoxy compounds (Denacol EX-313) was used as a patch graft for the correction of experimentally-created diaphragmatic defects in five dogs belonging to the same litter. Clinical, macroscopic and histological examinations were conducted every month up to five months after suturing of the patch graft. Clinical examination of the patch graft showed no apparent abnormalities. Macroscopic examination conducted during autopsy showed that the patch graft maintained adequate elasticity for five months after suturing, the surface of the patch graft was covered with a thin membrane and neovascularization was observed. Histological examination showed that the surface of the patch graft was covered with a thin membrane. Inflammatory tissue reactions were observed at one month, but gradually decreased from the second month onwards. In addition, the patch graft had excellent tissue affinity.     

Disappearance of aromatic hydrocarbons and organic sulfur compounds from fish flesh reared in crude oil suspension

Eels (Anguilla Japonica Temminck et Schlegel) were reared in sea water containing a crude oil suspension (50 ppm for 10 days for aromatic hydrocarbons, 2500 ppm for 3 days for organic sulfur compounds), then transferred to clean sea water. The disappearance of aromatic hydrocarbons and organic sulfur compounds from eel flesh was examined. The concentration ratio (concentration of eel flesh/concentration of water) of benzene, toluene, m- or p-xylene and o-xylene at 10 days was 3.5, 13.2, 23.6 and 21.4 respectively.Benzene, toluene, m- or p-xylene and o-xylene disappeared after the transfer to clean sea water, and the half-life period was 0.5, 1.4, 2.6 and 2.0 days respectively in the first phase which lasted 0–5 days.Organic sulfur compounds in cel flesh decreased as the time spent in clean sea water increased, but were still present after 30 days.The results suggest that aromatic hydrocarbons and organic sulfur compounds could serve as markers of oil pollution in fish.     

Morphologic analysis of the facet joint in the immature lumbosacral spine with special reference to spondylolysis

STUDY DESIGN: Morphological analysis was performed of the facet joint of the normal and spondylolytic lumbosacral spine in children and adolescents. OBJECTIVES: This study was performed to estimate the influence of spondylolysis on growth of the neural arch of the lumbosacral spine. SUMMARY OF BACKGROUND DATA: The development of the facet joint and its relation to spondylolysis have not been documented in the literature. METHODS: The dimension and orientation of the facet joint at L5/S were measured on radiographs and computed tomography scans from 144 boys without pars defects and 104 boys with pars defects. The latter group was further investigated according to the stage of pars defects. Patients in both groups were between 9 and 18 years of age. RESULTS: Growth of the facet joint in the sagittal and transverse directions and the increase of the transverse angle were remarkable up to approximately 13 years of age. Concavity of the facet joints also progressed in children of the same age. The growth of the facet joint in patients with spondylolysis was significantly retarded as the pars defects advanced from the progressive to the terminal stage. The joint surface was more coronal in orientation and flatter in shape compared with controls. CONCLUSIONS: The present results suggest that pars defects occurring in children disturb or retard the growth of the facet joint and that the morphological characteristics of the joint surfaces in patients with spondylolysis are the consequence of these defects.     

Neocognitron: A new algorithm for pattern recognition tolerant of deformations and shifts in position

Suggested by the structure of the visual nervous system, a new algorithm is proposed for pattern recognition. This algorithm can be realized with a multilayered network consisting of neuron-like cells. The network, “neocognitron”, is self-organized by unsupervised learning, and acquires the ability to recognize stimulus patterns according to the differences in their shapes: Any patterns which we human beings judge to be alike are also judged to be of the same category by the neocognitron. The neocognitron recognizes stimulus patterns correctly without being affected by shifts in position or even by considerable distortions in shape of the stimulus patterns.     

Development of a non-contact micro-liquid mixing method and application to chemical auto-analyzers

A new mixing method, which can mix some hundred microliters of liquid in a vessel without any physical contact, was developed. This mixing method used free surface waves in a vessel generated by ultrasound irradiation from outside the vessel. First, feasibility of circulation flow induced by waves was discussed with a numerical simulation. The mixing mechanism was then experimentally verified by flow visualization using a dye. Next, the method was applied to mixing serums and reagents. The serum-reagent mixture was visualized by using the Schlieren method, and the mixing performance was quantified from the visualized images. The experimental results show that the new mixing method is suitable for volumes of serum-reagent mixtures ranging up to . Finally, by implementing the new mixing method in a standard chemical auto-analyzer, a new kind of chemical auto-analyzer that does not suffer cross-contamination between samples was produced.     

Permeation, diffusion and dissolution of hydrogen isotopes, methane and inert gases through/in a tetrafluoroethylene film

Tetrafluoroethylene (TFE) is widely used for conventional tritium handling systems such as vacuum seals, tubing and so on. We measured the permeation of the three hydrogen isotopes, methane and the inert gases through a TFE film at room temperature by means of the time-lag method in order to establish the physicochemical properties which determine the solubility and diffusivity of those gases. It was found that the diffusion constant of the inert gases changed exponentially with the heat of vaporization and the solubility was an exponential function of the Lennard-Jones force constant of the gases. On the other hand, hydrogen isotopes and methane deviated from these relations. It is concluded that chemical interactions between the solute and the solvent play an important role for the dissolution and the diffusion of these gases in TFE.     

Distribution of radioactivity from 14C-formaldehyde in pregnant mice and their fetuses

Fine structure, location and size of the core of 12 calcium oxalate monohydrate (COM) papillar calculi from different 'idiopathic' stone-formers were studied by an optical and scanning electron microscope equipped with the EDAX analytical device. Each individual core exhibited a unique overall structure composed of loosely arranged twined and intergrown crystals of plate-like and/or columnar shape and particles of 'rosette' structure with considerable void space among crystals in some cases or compact structure in others. Crystals were covered by a thin layer or organic material mostly invisible to the microscope. Sometimes debris of organic origin in a core was observed. A substantial amount of organic matrix appeared at the core boundary, often in the form of amorphous plates. The outer striated layer of COM stone consisting of tightly packed columnar crystals originated on this matrix. The stone core was located near the stone surface that was attached to the kidney wall and contained foreign particles that act as heterogeneous nucleants of calcium oxalate crystals.     

A very small dielectric planar filter for portable telephones

A high performance, high-dielectric stripline filter with the size of 4.5 mm×3.2 mm×2.0 mm has been developed. The filter consists of planar resonators and its structure is made of high permittivity multilayer ceramic in the Bi-Ca-Nb-O system. The performance is distinctive with its attenuation pole. An equivalent lumped circuit is derived to explain the behavior of the attenuation pole quantitatively. A precise design procedure is also described     

Hemophagocytic syndrome in five patients with Epstein-Barr virus negative B-cell lymphoma

BACKGROUND: The recent recognition of the association of Epstein-Barr virus (EBV) with T-cell/natural killer cell (T/NK-cell) lymphoma has documented that particular types of EBV-containing T/NK-cell lymphoma are frequently complicated by hemophagocytic syndrome (HPS). This observation suggests that both EBV and proliferating T/NK-lymphoma cells play significant roles in the development of HPS. Cytokines released from neoplastic T cells are presumed to account for the activation of macrophages, which is followed by a complex cascade of cytokine production, resulting in full-blown HPS. Five patients with B-cell lymphoma complicated by HPS were studied for elevated serum cytokines, the association of EBV, and CD25 expression of lymphoma cells; the aim of this study was to verify whether the mechanisms of HPS development hypothesized for T/NK-cell lymphoma also operate in B-cell lymphoma. METHODS: Sera were analyzed for the presence of inflammatory and immunoregulatory cytokines. Flow cytometry, immunohistology (IH), in situ hybridization (ISH), polymerase chain reaction (PCR), and Southern blot analysis were performed using bone marrow aspirates, biopsy specimens, and autopsy specimens. RESULTS: Immunophenotypic and Southern blot studies verified that the lymphoma cells of all five patients were of B-cell lineage. Bone marrow aspirates demonstrated histiocytosis with extensive hemophagocytic activity. Marked elevation of serum cytokines and expression of CD25 were observed in all five patients. However, the results of PCR, ISH using EBER1 probe, and IH for latent membrane protein indicated that these lymphoma cells were free of EBV infection. CONCLUSIONS: In patients with B-cell lymphoma, EBV infection is not necessarily required for the initiation of HPS. In this article, the pathogenesis of HPS assumed to be operative in B-cell lymphoma is discussed with reference to T/NK-cell lymphoma complicated by HPS.