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Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma.

Background and Purpose Mast cell hyperplasia has been observed in the lungs of mice with experimental asthma, but few reports have studied basophils. Here, we attempted to discriminate and quantify mast cells and basophils in the lungs in a murine asthma model, determine if both cells were increased by multiple antigen challenges and assess the roles of those cells in asthmatic responses. Experimental Approach Sensitized Balb/c mice were intratracheally challenged with ovalbumin four times. Mast cells and basophils in enzymatically digested lung tissue were detected by flow cytometry. An anti-FceRI monoclonal antibody, MAR-1, was i.p. administered during the multiple challenges. Key Results The numbers of both mast cells (IgE+ C-kit+) and basophils (IgE+ C-kit− CD49b+) increased in the lungs after three challenges. Treatment with MAR-1 completely abolished the increases; however, a late-phase increase in specific airway resistance (sRaw), and airway eosinophilia and neutrophilia were not affected by the treatment, although the early-phase increase in sRaw was suppressed. MAR-1 reduced antigen-induced airway IL-4 production. Basophils infiltrating the lung clearly produced IL-4 after antigen stimulation in vitro; however, histamine and murine mast cell protease 1 were not increased in the serum after the challenge, indicating that mast cell activation was not evoked. Conclusion and Implications Both mast cells and basophils infiltrated the lungs by multiple intratracheal antigen challenges in sensitized mice. Neither mast cells nor basophils were involved in late-phase airway obstruction, although early-phase obstruction was mediated by basophils. Targeting basophils in asthma therapy may be useful for an early asthmatic response.

SummaryBackground Although an abnormality in arachidonic acid metabolism may be responsible for aspirin-intolerant asthma (AIA), there is little knowledge about the concentrations of urinary lipoxin A4 (LXA4) and the 15-epimer of LXA4 (15-epi-LXA4) in relation to asthma severity in AIA subjects. Objective The purpose of this study is to estimate urinary LXA4 and the 15-epimer concentrations to investigate lipoxins in AIA. Methods In this study, we examined AIA, aspirin-tolerant asthma (ATA) and healthy control groups. The AIA and ATA groups were subdivided into the severe asthma and non-severe asthma subgroups. Urinary LXA4, 15-epi-LXA4 and leukotriene E4 (LTE4) were quantified using enzyme immunoassay after separating these compounds using high-performance liquid chromatography. Results The urinary LXA4 concentration was significantly lower than the 15-epi-LXA4 concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15-epi-LXA4 (P

We have proposed a numerical methodology called the pixel mapping (PM) method which is based on crystallography. The PM method can characterize various types of defects in 24 prototype crystals listed in the Strukturbericht database. It identifies point defects, linear defects, planar defects (including antiphase domains in compound crystals), and also structure change (including amorphization). The long-range order (LRO) parameter has been defined as a set of LRO components for each prototype. A further advantage of the PM method results from its coarse-grained viewpoint. This allows us to specify the Miller index of a planar defect with the areal density or crystallographic direction of a linear defect. Using PM we found a tetrahedral antisite cluster, (CSi(SiC)4), in 3C-SiC due to ion irradiation. The bonding directions from the central to the surrounding atoms were all in the direction. We examined the reason why such a cluster was formed. Whenever this type of cluster was formed, collapse of LRO preceded, where large numbers of complexes of antisites–vacancy pairs emerged. © 2011 Wiley Periodicals, Inc. Electr Eng Jpn, 177(3): 54–61, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21151

Takeuchi, Y., Fujino, Y., Fukushima, K., Watanabe, M., Nakagawa, T., Ohno, K., Sasaki, N., Sugano, S., Tsujimoto, H. Biological effect of tyrosine kinase inhibitors on three canine mast cell tumor cell lines with various KIT statuses. J. vet. Pharmacol. Therap. 35, 97–104. Tyrosine kinase inhibitors (TKIs) can be important in the treatment of canine mast cell tumor (cMCT). Meanwhile, some TKIs have been identified as substrates for ABCB1. The inhibitory effect of four TKIs (axitinib, imatinib, masitinib, and vatalanib) for proliferation and phosphorylation of c-Kit receptor as well as the expression and function of ABCB1 were investigated in three cMCT cell lines (HRMC, VIMC1, and CMMC1). The IC50 values of the TKIs in HRMC, the only cell line with wild-type KIT, were clearly higher than those in CMMC1 and VIMC1. In HRMC and CMMC1, both the growth and phosphorylation of c-Kit receptor were suppressed proportionally by the TKIs. VIMC1 required higher concentrations for the inhibition of c-Kit receptor phosphorylation than those in cell growth. The treatment with cyclosporine increased the effects of the TKIs on VIMC1 since ABCB1 was expressed in VIMC1. The results indicated that cMCT cell lines harboring wild-type KIT had lower sensitivity to TKIs. The growth of VIMC1 was seemingly reduced by TKIs through the inhibition of other tyrosine kinases than c-Kit receptor. There was little influence of ABCB1 on TKI effects to the proliferation of VIMC1. These results will be helpful to understand the different sensitivity to TKIs in cMCT patients.

Brain-derived neurotrophic factor (BDNF) has been implicated in learning, depression and energy metabolism. However, the neuronal mechanisms underlying the effects of BDNF on energy metabolism remain unclear. The present study aimed to elucidate the neuronal pathways by which BDNF controls feeding behaviour and energy balance. Using an osmotic mini-pump, BDNF or control artificial cerebrospinal fluid was infused i.c.v. at the lateral ventricle or into the paraventricular nucleus of the hypothalamus (PVN) for 12 days. Intracerebroventricular BDNF up-regulated mRNA expression of corticotrophin-releasing hormone (CRH) and urocortin in the PVN. TrkB, the receptor for BDNF, was expressed in the PVN neurones, including those containing CRH. Both i.c.v. and intra-PVN-administered BDNF decreased food intake and body weight. These effects of BDNF on food intake and body weight were counteracted by the co-administration of alpha-helical-CRH, an antagonist for the CRH and urocortin receptors CRH-R1/R2, and partly attenuated by a selective antagonist for CRH-R2 but not CRH-R1. Intracerebroventricular BDNF also decreased the subcutaneous and visceral fat mass, adipocyte size and serum triglyceride levels, which were all attenuated by alpha-helical-CRH. Furthermore, BDNF decreased the respiratory quotient and raised rectal temperature, which were counteracted by alpha-helical-CRH. These results indicate that the CRH-urocortin-CRH-R2 pathway in the PVN and connected areas mediates the long-term effects of BDNF to depress feeding and promote lipolysis.

Aims The F1S and A genetic variants of α1-acid glycoprotein (AAG) change under various physiological and pathological conditions. They also vary in their drug binding abilities. We have studied the stereoselective binding ability of each of the AAG variants using enantiomers of disopyramide (DP) and warfarin (WR). Methods The AAG variants were separated by hydroxyapatite chromatography. Binding of drug enantiomers to the AAG variants was studied by the Hummel–Dreyer method. The characteristics of the binding activities were examined by Scatchard plot analysis. The first five amino-terminal amino acids (residues 112–116) of the cyanogen bromide (CNBr) fragment (residues 112–181) of each of the separated AAG fractions were elucidated by Edman degradation. Results Commercial AAG was separated into two main fractions. Residues 112–116 of fraction 2 were identical to the amino acid sequences predicted from the AAG A gene, LAFDV, and encode the F1S variant. In fraction 3, the deduced amino acid sequence of the AAG B gene, FGSYL, was established, and encodes the A variant. The binding affinities of both DP enantiomers in fraction 3 were significantly higher than those in fraction 2. The differences between dissociation constants (Kd) in fractions 2 and 3 were 5.2-fold for (S)-DP (P

When titanium (Ti) metal absorbs a lot of hydrogen, the XPS spectrum shows a remarkable change in the valence band. Making use of molecular orbital (MO) calculations, we ascribed the peak shift to the formation of a hydrogen-induced state of Ti. The trapped site of hydrogen in Ti may be at the lattice point in titanium hydride (TiH2), which forms a polycrystal with the small Ti crystals. Copyright © 2003 John Wiley & Sons, Ltd.

We considered that elucidation of the movements of perioral soft tissues during mastication would be useful in evaluating masticatory movements. However, evaluation of movements specific to soft tissues is difficult because movements of the surface of the lower face during mastication include movements of the muscles of facial expression and mandibular movements. The aims of this study were to elucidate the influence of mandibular movements on perioral soft tissue movements during mastication using principal component analysis (PCA) and to abstract the component of movement specific to soft tissues in order to evaluate masticatory movements from the movements of perioral soft tissues. The subjects were 10 healthy persons with complete natural dentition. The experimental food used in this study was sufficiently softened chewing gum. The results of this study showed that the movements of mandibular and perioral soft tissue were closely related in the first and third PCs; in other words, the second PC was the component of movement specific to soft tissues. Thus, elucidation of the second PC is useful for evaluation of masticatory movements from movements of perioral soft tissues.

Arginine-specific gingipain (HRgpA) and lysine-specific gingipain (Kgp), enzymes produced by Porphyromonas gingivalis, may be candidates for an anti-P. gingivalis vaccine. The purpose of our study was to determine whether HRgpA and Kgp have opsonic target sites and whether these sites are available and accessible on intact P. gingivalis cells. Rabbits were used to generate polyclonal antibodies to both proteins. Animals were immunized and immunoglobulin G (IgG) fractions were isolated from preimmune and immune sera. Functional characteristics of the antibodies were assessed by determining antibody titers by enzyme-linked immunosorbent assay (ELISA), generating Western immunoblots, and measuring antibody enhancement of P. gingivalis opsonization, phagocytosis and killing by polymorphonuclear leukocytes (PMN) of intact cells of strains of P. gingivalis representative of the four serotypes. Strains studied included 33277 (serotype A), A7A1-28 (serotype B), W50 (serotype C) and 381 (serotype D). Both HRgpA and Kgp induced high titers of IgG antibody. Anti-HRgpA and anti-Kgp bound to both HRgpA and Kgp demonstrating a large proportion of shared antigenic epitopes. The two antibodies bound equally well to all four P. gingivalis serotypes with titers ranging from 77 to 205 ELISA units when compared to preimmune IgG set at 1 ELISA unit. The immunoblot patterns of binding of the two antibodies to HRgpA and Kgp and to sonicates of the four P. gingivalis serotypes were virtually identical. Both antibodies detected components in HRgpA at 27, 35 and 45 kDa and in Kgp at 27, 32, 35, 40 and 55 kDa. The antibodies also detected components at or near these same positions in addition to multiple high molecular mass components in the cell sonicates of P. gingivalis. Both proteins induced antibodies that significantly enhanced opsonization as assessed by chemiluminescence, with values ranging from 130 mV to 375 mV for anti-HRgpA IgG and from 240 mV to 475 mV for anti-Kgp IgG. Both antibodies significantly enhanced PMN-mediated bacterial killing of the four P. gingivalis serotypes, although the percentage of killing varied among the serotypes (24-81% for anti-HRgpA and 37-89% for anti-Kgp). Thus, both HRgpA and Kgp express opsonic target sites and induce high titers of antibodies that opsonize and enhance killing of all four serotypes of P. gingivalis. These two proteins appear to be potential candidate antigens for an anti-P. gingivalis vaccine.

SUMMARY We considered that elucidation of the movements of perioral soft tissue during mastication would be useful in evaluating masticatory movements. However, the evaluation of these movements is difficult because multivariable analysis is needed. In this study, we considered whether principal component analysis (PCA), a form of the multivariate analysis, can reduce the number of degrees of freedom (d.f.) of perioral skin movements (i.e. the time-series data with 45 d.f.). The subjects were 15 healthy persons with complete natural dentition. The chosen experimental food for this study was sufficiently softened chewing gum. Over 95% of the perioral soft tissue movements of healthy subjects with complete natural dentition during mastication could be expressed by PCA using the first three principal components (PCs). Therefore, perioral soft tissue movements in these subjects during mastication were considered to be spatially smooth. Moreover, time analysis of these movements was made possible by the application of proportion diagrams. The results of this study showed that the spatiostructural and temporal analyses of the movements of perioral soft tissue during mastication made possible by the application of PCA.

The goal of our research program is to develop a Porphyromonas gingivalis vaccine. Vaccine development requires identification of antigenic components shared by the many clonal types of P. gingivalis. The purpose of the present study was to evaluate the extent and nature of antigenic cross-reactivity among serotypes of P. gingivalis and to identify shared antigenic components. Strains selected to represent serotypes A-D were 33277, A7A1-28 W50 and 381, respectively. Using intact cells, antibodies were raised in rabbits. Titers were assessed by enzyme-linked immunosorbent assay (ELISA) using intact cells as antigen, Western blots were prepared and biologic activity was measured as opsonization (chemiluminescence expressed as mV) and enhancement of phagocytosis and killing by polymorphonuclear leukocytes. Extensive cross-reactivity that varied greatly among serotypes was observed by ELISA. The Western blots showed an even greater extent of cross-reactivity, with shared protein components at approximately 140, 130, 37, 32 and 28 kDa and a shared variable molecular mass smear considered to be lipopolysaccharide and other carbohydrate. Additional protein components at 110, 85, 35 and 20 kDa appeared to be shared by some but not all serotypes. In the functional assays, strains 33277 and 381 were equally well opsonized by anti-33277 and anti-381 (500-650 mV) but opsonized to a much lesser extent by anti-A7A1-28 and anti-W50 (roughly 125 mV and 350 mV respectively). A7A1-28 and W50 were opsonized by all four immune sera almost equally but to a much lower extent (roughly 400 mV and 250 mV respectively). Enhancement of phagocytosis and killing in the presence of active complement mirrored opsonization with the exception that 381 was reasonably well opsonized by anti-A7A1-28 (400 mV) and anti-W50 (350 mV), but poorly killed. The protein components at 140, 130, 37 and 28 kDa shared by all of the four serotypes appear to have potential as vaccine candidate antigens.

The efficiency of L-cysteine (cysteine) and sodium sulfite as antioxidants was examined in the browning of an aqueous solution of 100 mM dehydroascorbic acid (DHA). The browning was suppressed at 100 mM cysteine and at 40 mM and higher concentrations of sodium sulfite, but it increased in the presence of 10 mM of those agents. These agents did not allow the reduction of DHA to L-ascorbic acid (AA). These results suggest that the suppression or acceleration of browning is likely to be related to some degraded intermediates of DHA. The two colorless intermediates, which during DHA breakdown eventually transform into browning pigments, were discussed with regard to the browning regulation mechanism.

We analyzed immunoreactive hCG/hCG β (IR-β) in the sera and urine of patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme immunoassays (EIAs) specific for intact hCG, free hCG β, and β-core fragment of hCG (β-CF). In trophoblastic diseases, while intact hCG and free hCG β were contained in both serum and urine, the β-CF could be detected only in the urine of the patients. The relative contribution of the β-CF to the total urinary IR-β accounted for about 30-50% in normal early pregnancy and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that intact hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic dieseases, and suggested that the ratios of intact hCG, free hCG β, and β-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-β was also investigated in the sera and urine of the patients with cervical, endometrial, ovarian, lung, and bladder carcinomas. We found that even when IR-β could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-β. The chromatographic study indicated that these urinary IR-β were essentially attributed to β-CF, leading to the evaluation of urinary β-CF as a tumor marker. The positive rated of urinary β-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG β by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when β-CF is measured in urine of the patients.

In order to examine the dependence of the electronic stopping power (dE/dx) on the impact parameter p, the energy dissipation of axially channeled ions with curved trajectories is studied theoretically by means of a cluster model. dE/dx is accounted in the framework of nonlinear molecular dynamics (MD) coupled with the local density approach (LDA) based on the Lindhard-Winther (LW) theory. A correction factor of 2 is introduced to compensate the lower dE/dx, especially for low-energy ions. B ions are implanted into Si 〈100〉 and 〈110〉 at incident energy in the region 10 keV ≦ E0 ≦ 10 MeV. Results are the following. Firstly two kinds of solid-state effects on the p-dependence of dE/dx are found at high and low E0, respectively. At high E0 (> 100 keV) the core electrons reveal quite different profiles of dE/dx versus p than valence ones, and at low E0 (< 100 keV) the topological difference in the electron distribution among axial channels appears in those profiles, which cannot be explained by means of collisions with single atom. Secondly, the p-dependence of dE/dx is intended to adapt the simple form dE(p)/dx = A exp (-sp/a). The factor s due to core electrons increases distinctly with E0, while that due to valence electrons is almost invariant, smaller than 0.3.

Recently, acid precipitation problems have become serious in many regions of the world. The adverse effects of acid precipitation on soils are also feared. In this study, our objective was to determine the effect of inflowing solution pH on saturated hydraulic conductivity (K). The K values were determined at a constant hydraulic gradient in columns packed at a dry bulk density of 0.51 Mg m -3 . Influent solutions with the same electrolyte level (1 mol c m -3 ) were prepared at pH 3, 4.2, 5.7, 10, and 11, respectively. The K values decreased when the influent solutions were pH 3 and 11. The K values at 38 pore volumes of an efluent decreased to ≃0.067 of the initial K 0 at pH 3, and ≃0.25 of the initial K 0 at pH 11, respectively (.)

Summary Skin tests with histamine, the histamine-liberator, codeine, and various allergens as well as blood basophil degranulation by anti-IgE or anti-IgG4 and total serum IgE levels have been studied in two female populations of different ages (average 23-1 and 73-9 years). All thirty-one patients selected for this study were clinically non-allergic. We observed a trend towards reduced skin reactions to histamine and codeine in the higher age-group; on the other hand, we could not find any decrease of basophil degranulation as a sign of basophil impairment with age. Likewise no difference in total serum IgE levels have been noticed. No correlation between skin tests and basophil degranulation was observed; yet patients with isolated, positive skin tests to house dust and/or Candida albicans showed a statistically significant reduced blood basophil degranulation by anti-IgE or anti-IgG4.

The fatigue phenomenon of mild steel is characterized by the existence of a fatigue limit and coaxing effects. Although many studies have been made on strain ageing due to interstitial solute atoms of carbon and nitrogen, the effect of strain ageing on the fatigue limit is not yet fully understood. The objective of this work is to clarify the effect of strain ageing on the fatigue limit. Experiments were undertaken from the view point that fatigue is a competitive process of two mechanisms of damage and strengthening of the material. Two techniques were applied for this purpose. One was the measurement of the change in solute contents of C and N atoms, and the other the reversion of the Cottrell atmosphere. The experimental results recognized that strain ageing occurred in the fatigue process and that by removing the strain ageing effect, specimens could fail below the fatigue limit. The fatigue limit could be increased above the original value by suppressing dislocation multiplication during fatigue. It was also observed that, as the time for strain ageing increased at higher temperatures, the knee of the S–N curve shifted to smaller number of cycles.

The effect of N,N-dialkyl dithiocarbamate substitution on the radiation stability of poly(vinyl chloride) (PVC) film was studied. PVC containing 6.5-15.7 mole-percent N,N-dimethyl dithiocarbamate (PDE) was irradiated with ..gamma..-rays from a /sup 60/Co source at room temperature under vacuum. The evolved gaseous products were measured and analyzed with a mass spectrometer. The apparent G values for gas evolution of PDM and PDE decreased remarkably. The external protection was studied using polymer-blended films of PVC and PDE or PDM. The stabilization coefficients for internal protection and external protection in polymer blends were calculated. Although the ESR spectrum of the irradiated PDM, PDE, and PVDE which is synthesized by polymerization of S-vinyl-N,N-diethyl dithiocarbamate (VDE) showed the same sulfur radicals, they were different from those of the irradiated cysteamine hydrochloride and PVC containing N-methyl dithiocarbamate (PMD). From these results, the protection of a polymer by a covalently bound dithiocarbamate was discussed.

The reaction of poly(vinyl chloride) containing N-methyl dithiocarbamate (PMD) with metal ions in a heterogeneous system and the effect of ..gamma..-irradiation on the reactivity were studied. PMD powder suspended in aqueous solutions did not show any reactivity toward metal ions. However, the PMD powder suspended in a methyl alcohol solution formed a chelate with various metal ions. The effects of the reaction time, pH, and the initial concentration of the metal ion were examined. PMD irradiated in methyl alcohol with ..gamma..-irradiation doses up to 28 Mrad was compared with the original PMD. The reactivity of the irradiated PMD toward the metal ions did not show any apparent decrease.

Thermal reaction of coumalic acid with 1,3-butadienes gave after diazomethane treatment dimethyl tricyclo[3.2.1.02,7]oct-3-ene-2,4-dicarboxylate via double Diels-Alder reaction. This represents the simplest synthesis of such a tricyclic system. The reaction with cyclopentadiene was also studied.

The reaction of furfuryl alcohols with maleic anhydride leads to tricyclic lactone-carboxylic acids through the sequence of esterification and intramolecular Diels–Alder reaction. Anodic oxidative decarboxylation of the hydrogenated products in MeOH affords 1,2,3-trisubstituted cyclopentane derivatives, viz. 1-hydroxymethyl-3-methoxy-2-oxabicyclo[2.2.1]heptane-7-syn-carboxylic lactones, potential intermediates for synthesis of iridoids.