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Molecular subtyping in gastrointestinal stromal tumours is a useful method for predicting the efficacy of treatment using tyrosine kinase inhibitors in humans. However, owing to the paucity of reports on mutational analyses, the association between genetic mutations and the therapeutic response to tyrosine kinase inhibitors remains unclear in feline gastrointestinal stromal tumours. In this report, we describe the case of a cat with a gastrointestinal stromal tumour which was unresponsive to tyrosine kinase inhibitors. A mutational analysis revealed that the cat lacked mutations in both the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. Our findings are consistent with the fact that KIT/PDGFRA wild-type gastrointestinal stromal tumours are less responsive to tyrosine kinase inhibitors in humans. This signifies the need for further evaluation and possibly individualised treatment for gastrointestinal stromal tumours in cats on the basis of mutational analyses.

Aim Many studies support the role of carcinoembryonic antigen (CEA) as a strong indicator of the status of colorectal cancer patients, but evidence for carbohydrate antigen 19-9 (CA19-9) is poor. For this reason the study aimed to evaluate the prognostic value of preoperative serum CA19-9 levels in colorectal cancer patients. Method In all, 1190 colorectal cancer patients were included in this study, of whom 955 underwent a potentially curative resection. These were analysed for recurrence and survival. The 255 patients with Stage IV disease were analysed for metastatic status. Results Patients with an elevated preoperative CEA with Stage II and III disease showed a significantly poorer survival than those with normal levels. In contrast patients with elevated preoperative CA19-9 levels were associated with a significantly poorer survival irrespective of disease stage. Of the 255 patients with Stage IV disease, 92 (39.1%) had peritoneal dissemination at laparotomy observed more frequently in patients with an elevated CA19-9 (47.9%). Of the 955 patients having a curative resection, 18 (1.9%) developed peritoneal dissemination. In multivariate analysis, an elevated preoperative CA19-9 level was a significant risk factor for postoperative peritoneal recurrence. Conclusion After curative surgery for colorectal cancer the preoperative CA19-9 level is a strong prognostic indicator of higher risk of peritoneal dissemination.

Summary Background Tumour necrosis factor alpha is the key inflammatory cytokine involved in the pathogenesis of Crohn’s disease. Infliximab, a chimaeric monoclonal antibody of tumour necrosis factor-α is successfully used for the treatment of Crohn’s disease, although the response to infliximab therapy differs among patients. The genetic background of the individual may partially explain the differences of the responsiveness. Aim To investigate whether the polymorphisms in these genes are associated with the response to infliximab treatment as tumour necrosis factor-α exerts its biological activity through TNF receptor superfamily 1A and 1B. Methods Eighty Crohn’s disease patients were enrolled in the study and classified into responder and nonresponder according to the efficacy of infliximab treatment. Single nucleotide polymorphisms of TNF receptor superfamily 1A (rs767455 and rs4149570) and TNF receptor superfamily 1B (rs1061622, rs1061624 and rs3397) were determined. Results The minor allele carrier of rs767455 showed a significant association with a lack of efficacy compared to the major genotype (OR = 0.26; 95% CI: 0.08–0.91). A TNF receptor superfamily 1B haplotype inferred by rs1061624 and rs3397 also showed significant differences in the distribution between responder and nonresponder (P = 0.01). Conclusion These results suggest that tumour necrosis factor receptor genotypes may be involved in the different responses to infliximab in Japanese patients with Crohn’s disease.

We have successfully fabricated high-power AlGaInN laser diodes with long lifetime, high kink level, wide beam divergence angle parallel to the junction plane (θ || ), and low relative intensity noise (RIN). We have also adopted a 3Φ sapphire substrate to improve productivity and have achieved uniform fabrication using a carefully designed quartz reactor and heating system. The introduction of a new laser structure successfully provided a dramatic improvement in device properties. In particular, the characteristic temperature (To) was improved to 235 K, which is the highest ever reported. In addition, we fabricated a super high power (SHP) AlGaInN blue-violet laser diode array, achieving a maximum light output power of 4.2 W under cw-operation at 25 °C with a lifetime under 1 W cw-operation at 25 °C of more than 1000 h.

The relationships between ORP (oxidation-reduction potential) and pH were measured using samples of blood plasma, amniotic fluid, saliva, urine, vegetables, fruits, livestock products, fishery products, and various kinds of commercial beverages. It was found that these samples were in the reduction system region with respect to the equilibrium ORP level, which signifies that plants and animals, including human beings, have a reductive characteristic in terms of ORP. Here we propose that a conceptual kind of water having a reductive characteristic in terms of ORP and a pH value ranging from weak acidity to weak alkalinity can be categorized as “Vital Water”, which is analogous to human body fluid.

Background: Helicobacter pylori eradication triple therapy with a combination of lansoprazole, amoxicillin and clarithromycin was approved in Japan in September 2000. Aim: To compare the cost-effectiveness of this eradication therapy with conventional histamine-2 receptor antagonist therapy in Japan. Methods: We established two Markov models for gastric and duodenal ulcers. The model design was based on the Japanese H. pylori eradication guideline and a specialist’s opinions, and the model inputs were obtained from a literature review. The models predict the direct medical costs, number of disease-free days and cost per disease-free day for 5 years. Results: In the gastric ulcer model, the expected total costs of eradication and conventional therapies per patient were ¥169 719 and ¥390 921, respectively; the expected numbers of disease-free days were 1454 days and 1313 days, respectively. In the duodenal ulcer model, the expected total costs were ¥134 786 and ¥324 689, respectively; the expected numbers of disease-free days were 1503 days and 1387 days, respectively. The sensitivity analyses showed that the results of the base case analysis were robust. Conclusions: This eradication therapy is less costly and more effective than conventional therapy for the treatment of gastric and duodenal ulcers in a Japanese medical setting.

Two promoter polymorphisms of the high-affinity IgE receptor alpha-subunit (FcepsilonRIalpha) gene (FCER1A), -66T>C (rs2251746) and -315C>T (rs2427827), were analysed in Japanese atopic dermatitis subjects. Patients with the -315CT/TT genotype tended to have higher total serum IgE levels, while the proportion of -315CT/TT genotype or the -315T allele was significantly higher in those with highly elevated total serum IgE concentrations.

Eight polymorphic microsatellite markers were developed in Dryobalanops aromatica, an emergent tree in tropical rain forests in Southeast Asia, using an enriched library method. For the assessment of microsatellite variation, 36 individuals from a natural population were analysed. The number of alleles per locus ranged from three to 16, with observed heterozygosity of 0.056–0.833 and expected heterozygosity of 0.054–0.882. These microsatellite markers will be useful for studies of population genetics, reproductive ecology and regeneration dynamics of D. aromatica.

A main purpose of this paper is to present a density matrix treatment of the magnetic quenching of molecular luminescence. Unlike the previous theories, which only consider the magnetic effect on the nonradiative rate constant, the present theory describes the time-evolution of the system under the action of a magnetic field. Our theory can treat both the steady state and transient molecular luminescence affected by a magnetic field.

Adult T-cell leukemia/lymphoma (ATL) usually develops after age 40 in Japan, suggesting a long latency since HTLV-I is considered to be transmitted mainly from mothers to babies via breast milk. Our previous studies had suggested that HTLV-I carriers who have a monoclonal integration of HTLV-I proviral DNA in the peripheral blood cells, designated pre-ATL, account for about 2% of healthy carriers and are at high risk of developing ATL. Their ages ranged from 32 to 80 (median 57). Nevertheless, many cases of pre-ATL showed a long-lasting carrier state (10-year probability around 90%). In the present investigation we conducted a large-scale molecular detection of monoclonal integration in a population (481 cases) of healthy carriers with ages ranging from 16 to 82 (median 49) for the purpose of clarifying the earliest onset of this pre-ATL state. Southern-blot analysis of DNA extracted from peripheral blood mononuclear cells revealed 6 cases (1.2%) with a monoclonal band. All of these 6 were older than 40; no single positive case was found in 220 carriers under age 40. These results indicate that the molecularly detectable pre-ATL state also develops after a long latency. Thus the pre-ATL state seems to be a subtype of ATL showing an extremely indolent course of disease development, but not merely an early phase of all subtypes of ATL. We propose that, in order to reveal a promoter(s) responsible for the development of ATL from the pre-ATL state, intensive epidemiological investigation of life style, eating habits, occupation and exposure to carcinogens must be conducted on this unique group prone to ATL. It is also important to perform such an epidemiological study on the general population of carriers by paying special attention to the first 3-4 decades of each carrier's life in Japan and by comparing the data with those from carriers in different geographical areas of the world.

The electrical potential difference between the interface and the bulk in TiO2 is obtained as a function of temperature, oxygen pressure, and acceptor or donor doping from a space charge model that explicitly includes the high-temperature lattice defect chemistry. Using defect equilibrium constants for TiO2 from previous literature studies, it is shown that for a space charge determined by ionic defect equilibration with the interface, the potential is negative in undoped and acceptor-doped TiO2 and positive at high donor concentrations. The isoelectric point lies in the donor-doped regime at high temperatures due to the contribution of defects from reduction, even for fairly oxidizing ambients.

A quantitative study of space charge solute segregation at grain boundaries in TiO[sub 2] is conducted, using a new STEM method for the measurement of aliovalent solute accumulation. It is shown that the electrostatic potential at grain boundaries can be varied in sign and magnitude with doping, oxygen pressure, and temperature, and that the isoelectric point lies in slightly donor-doped compositions for samples annealed in air. The experimental results closely fit the space charge model in Part 1. Space charge solute segregation is found even in defect regimes of high electron concentration. Approximately one in ten grain boundaries are special in exhibiting no detectable segregation; in one such instance a twin boundary is identified. Among boundaries with significant amounts of segregation, clear differences in potential also exist. From the potential determined in acceptor- and donor-doped composition, the Frenkel energy (assumed to be lower than the Schottky energy in TiO[sub 2]) can be separated into its individual terms. An average value for the titanium vacancy formation energy of g[sub v[sub Ti]] = 2.4 eV and an upper limit to the titanium interstitial formation energy of g[sub Ti[sub i]] = 2.6 eV are obtained.

Summary A serine protease from mite faecal extract, Dermatophagoides farinae, was purified using DEAE-Sephacel anion exchange chromatography and Supcrdex 75 pg gel chromato-graphy. The molecular weight of this protease was 34 kD on SDS-PAGE under reducing conditions. The optimal pH and temperature of the protease were 8-0 and 47 C, respectively. In addition, this protease cleaved arginyl or lysyl residue containing substrates selectively and was only inhibited by aprotinin, PUT-175, tind soy bean trypsin inhibitor and not by chymostatin, E-64 and iodoacetic acid. These results show that our purified serine protease belongs to the trypsin-type. Purified trypsin-like protease was shown to be allergenic by enzyme-linked immunosorbent assay. Antigeni-city of trypsin-like protease was completely different from those of Der f I and Der f II. Both, 20 N-terminal amino acid sequence and amino acid compositions of the purified protease were very similar to those of Der f III. Good similarities were found between trypsin-like protease and Der f III concerning physicochemical properties such as molecular weight on SDS-PAGE and ammonium sulphate solubility. Summarizing the above data, it can be concluded that a trypsin-like protease from mite faecal extract is actually the Der f III allergen and that it may be involved in the digestive process of the mite as it was found not in mite body but in mite faeces.

A chemically synthesized lipid A subunit analogue, GLA-60 (2-deoxy-4–0-phosphono-2-[(3R)-3-hydroxytetradecanamido] - 3 - 0- [(3R) - 3 -tetradecanoyloxytetradecanoyl]-D-glucose), has many of the activities of endotoxins but little, if any, toxicity. We investigated the protective activity of GLA-60 against murine cytomegalovirus (MCMV) infection in NMRI mice. Intraperitoneal administration of GLA-60 at 1 day before MCMV infection at doses of 1, 10, or 100 μg per mouse significantly reduced mortality. GLA-60 stimulated peritoneal natural killer (NK) cell and macrophage activities, and these activities were abolished by in vitro treatment with anti-asialo GM1 antibody and anti-Mac1 antibody, respectively. GLA-60 proved also protective against MCMV infection in mice in which either NK cells or macrophages were depleted by in vivo treatment with anti-asialo GM1 or anti-Mac1 antibody. The anti-MCMV activity of GLA-60 can at least be partially attributed to activation of NK cells and macrophages. © 1993 Wiley-Liss, Inc.

During the oxidation of redued single crystals of Al-doped rutile, unusual anisotropies in color-boundary migration have been observed that are opposite to those predicted from published diffusion data. Analysis of the redox kinetics and of surface segregation (using ESCA and AES) shows that rapid transport of minority Al interstitials in the c-axis direction occurs under an oxidation potential, resulting in a surface segregation layer inhibiting further reoxidation. This surface segregation is nonequilibrium in nature, is driven by oxidation, and bears similarities to the phenomena of kinetic demixing in ionic systems. The results show that minority defects can play critical roles in demixing at the local scale; in their absence this system would not be expected to demix. This thus appears to be an additional mechanism for nonequilibrium interfacial segregation in ionic systems.

To investigate the effect of the overexpression of beta-amyloid precursor protein (APP) on the production of two major amyloid beta protein (Abeta) species, Abeta40 and Abeta42(43), we measured amounts of Abeta1-40 and Abeta1-42(43) in the plasma from 44 patients with Down's syndrome (DS) (age, 19-61 years) and 66 age-matched normal controls using enzyme-linked immunosorbent assays. Plasma concentrations of both Abeta1-40 and Abeta1-42(43) were increased about 3-fold and 2-fold, respectively, in DS patients compared with normal controls. Especially, the increases in plasma Abeta1-40 in DS patients were statistically higher than the 1.5-fold increase one might predict based on the gene dose of APP in DS. These findings showed that both Abeta1-40 and Abeta1-42(43) are increased in plasma in DS patients, the former more than the latter, suggesting that overexpression of APP and/or other genes may have different effects on the production of these two Abeta species in DS.

The butanol, methanol, water and chloroform extracts of the roots of Eurycoma longifolia Jack were studied using various tests of potency of treated male rats. The results showed that E. longifolia produced a dose-dependent, recurrent and significant increase in the episodes of penile reflexes as evidenced by increases in quick flips, long flips and erections of the treated male rats during the 30 min observation period. These results provide further evidence that E. longifolia increases the aphrodisiac potency activity in treated animals.

Some structural considerations are made on the Finslerian gravitational field: A Finslerian metrical structure such as gλχ(x, y) = γλχ(x) + hλχ(x, y) is proposed, where γλχ denotes the Riemann metric of Einstein's gravitational field, while hλχ the Finsler metric induced by the Riemann metric hij(y) of the internal field; The intrinsic behaviour of the internal variable y, which is expressed as ȳi = K(x, y) yj in the internal field, is grasped by the Finslerian parallelism δyi (=0), which is reflected in the spatial structure of the external gravitational field by the mapping relation δyχ = e(x) δyi. The whole metrical Finsler connection D for gλχ(i.e., Dgλχ = 0) is determined by taking account of the intrinsic behaviour δyχ. Zur Theorie des Gravitationsfeldes in Finslerschen Raumen Einige Strukturbetrachtungen zum Finslerschen Gravitationsfeld werden gemacht: Eine Finslersche metrische Struktur der Art gλχ(x, y) = γλχ(x) + hλχ(x, y) wird vorgeschlagen, wobei γλχ die Riemannmetrik des Einsteinschen Gravitationsfeldes bezeichnet, hλχ ist die durch die Riemannsche Metrik hij(y) des inneren Feldes hervorgerufene Finslersche Metrik. Das charakteristische Verhalten der inneren Variable y, ausgedruckt durch ȳi = K(x, y) yi im inneren Feld, wird durch den Finslerschen Parallelismus δyi (=0) festgelegt, welcher in der Raumstruktur des externen Gravitationsfeldes uber die Abbildungsralation δyχ = e(x) δyi zum Ausdruck kommt. Die ganze Finslersche metrische Verbindung D fur gλχ (d. h. Dgλχ = 0) wird unter Berucksichtigung des charakteristischen Verhaltens von δyχ bestimmt.

We investigated antibodies against pX gene product, p40tax, by ELISA using recombinant p40tax protein in HTLV-I seropositive carriers as well as patients with adult T cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). Seventy (49.0%) out of 143 HTLV-I healthy carriers were found to be positive for antibody against p40tax antigen and the follow-up samples at two-year intervals revealed constant reactivity by ELISA in each carrier. The onset of antibody production was delayed 4 to 12 weeks as compared with anti-HTLV-I in primary infection cases. The anti-p40tax-positive rate (90%) in HAM patients was significantly higher than that of healthy carriers, acute and chronic ATL patients and their family members. Furthermore, HAM patients and a few healthy carriers showed high reactivities by ELISA. Children from mothers with anti-p40tax showed a higher anti-HTLV-I-positive rate than that of children from mothers without anti-p40tax (54.5% versus 12.5%). Two men without anti-p40tax and one female with low anti-p40tax developed ATL during follow-up studies. These results suggest that HTLV-I carriers could be divided into 2 or 3 sub-populations according to antibody response to p40tax. A smaller population with anti-p40tax, especially a high antibody reactivity, could have a high risk of developing HAM and of transmission from mother to child. In addition, ATL may occur in a population with low or absent anti-p40tax.

The mechanism of voltage contrast of passivated devices is investigated. Previous works on the voltage contrast over the passivation are reviewed, and experimental results on glass cover slips with a carbon-coated surface are described. The voltage contrast is observed over the carbon-coated equipotential surface. This result cannot be explained by the surface potential model of voltage contrast. An interpretation of the result using a contrast model previously introduced by the authors is provided.

Die Diffusion von Schwefelsaure in Nylon 6 wurde mit S-35 als Tracer mittels der Membran-Roll-Methode untersucht. Das Diffusionsprofil in Nylon zeigt, das der Diffusionskoeffizient der Schwefelsaure konzentrationsabhangig ist. Die Aktivierungsenergie der Diffusion verandert sich bei 30°C. Man kann diese Temperatur der Glasumwandlung zuschreiben. Die Konzentrationsabhangigkeit des Diffusionskoeffizienten stimmt viel besser mit dem chemischen Potential-Modell als mit dem Aktivitatsgradienten-Modell uberein. Der Selbstdiffusionskoeffizient bei bestimmtem Sattigungsgrad war konstant. The diffusion of sulphonic acid in nylon 6 was investigated using S-35 as tracer by means of film roll method. The concentration profile of sulphonic acid in nylon shows that the diffusion coefficient is dependent on the concentration in the polymer substrate. The activation energy of diffusion changed at 30°C. The temperature was assigned as glass transition. The concentration dependence of the diffusion coefficient was better described by the chemical potential gradient model than the activity gradient model. The selfdiffusion coefficient at a definite saturation value of amino end group site was constant.