Effect of the Electrodeposition Temperature on the Cyclic-Oxidation Resistance of Ni Aluminide Containing Zr Formed by Molten-Salt Electrodeposition

The effect of the Al electrodeposition temperature on the cyclic oxidation resistance of Ni aluminide containing Zr formed by molten salt electrodeposition was investigated. Zr and Al were deposited by molten salt electrolysis. For the sample treated with the Al deposition at 1073 K, a layer consisting of Ni 2 Al 3 was uniformly formed. On the other hand, for the sample treated by Zr deposition, followed by Al deposition at 1073 K, a layer consisting of Ni 2 Al 3 and a Ni aluminide layer containing Zr on the Ni 2 Al 3 layer were formed. Furthermore, when the Al electrodeposition temperature was changed, the concentration of Zr in the Ni aluminide layer containing Zr changed. When the Al electrodeposition was carried out at 1153 and 1173 K, the Zr was scarcely observed in the surface region of the Ni aluminide layer. The cyclic oxidation test showed that for the sample treated with only the Al deposition and the sample treated with the Zr deposition, followed by Al deposition at 1073 K, a mass reduction due to scale exfoliation took place, whereas for the samples treated with the Zr deposition, followed by Al deposition at 1153 and 1173 K, no mass reduction was observed. For these samples, after the cyclic oxidation test, a scale consisting of -Al 2 O 3 adhering to the substrate was formed. Consequently, it was found that the cyclic oxidation resistance of Ni was improved by Zr deposition, followed by Al deposition at 1153 and 1173 K

Suppression Effects of Human Recombinant Tissue Inhibitor of Metalloproteinases-1(TIMP-1) on Tumor Proliferation Using in Vivo Treatment Model of Well-differentiated Colon Cancer Cell Line, HT29

To investigate the suppressive effect of human recombinant TIMP-1 (rh-TIMP-1) on tumor proliferation using an in vivo xenograft system, HT29 was suspended in 0.1 ml phosphate buffered saline (PBS) and then subcutaneously injected in the back of female mice (BALB/C nu/nu). The mice were divided into 2 groups an and the tumor diameter was measured after rh-TIMP-1 (2 mg/kg) (rh-TIMP-1 group) or PBS (control group) was administered injections according to the following schedules. Schedule 1 : Beginning 2 weeks after the subcutaneous injection of HT29, an intraperitoneal injection of rh-TIMP-1 or PBS were performed twice a day (every 12 h) for 14 consecutive days. Schedule 2 : Beginning 1 week after the subcutaneous injection of HT29, an intraperitoneal injection was performed twice a day for 14 consecutive days. Schedule 3 : Intraperitoneal injections were started simultaneously with the subcutaneous injection of HT29, and then performed twice a day for 21 consecutive days. The mice were sacrificed and the tumors extirpated for immunohistochemical investigation. In addition, gelatin zymography and a cell proliferation assay were performed. With Schedule 1, the changes in the tumor diameter in the rh-TIMP-1 group followed the same course as those in the control group, and no suppressive effect on tumor proliferation was observed. However, with Schedule 3, a remarkable suppressive effect was observed throughout the treatment period. In immunostaining, more cases negative for MMP-9 were observed in the rh-TIMP-1 group than in the control group. Cases negative for CD34 were significantly more observed in the rh-TIMP-1 group than in the control group with Schedule 3. All of the results were obtained through the suppressive effect of rh-TIMP-1 on angiogenesis

A portable dermatoscope for easy, rapid examination of periungual nailfold capillary changes in patients with systemic sclerosis.

Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenic role. The presence of nailfold capillary abnormalities is useful in diagnosing SSc. Capillaroscopy, however, usually requires special equipment and may be time consuming. Dermatoscope has been presented as a new diagnostic tool for quick and efficient examination of nailfold capillaries for circumstances when standard microscope equipment is not available. To assess the practical utility of dermatoscope for assessment of capillary morphology in patients with SSc, 83 Japanese patients with SSc (68 women, 15 men) and 68 healthy controls were examined in the study. Twenty-one patients (16 women, 5 men) had diffuse cutaneous SSc and 62 (52 women, 10 men) had limited cutaneous SSc. Enlarged capillaries and hemorrhages were evaluated in all 10 fingers with either naked eyes or DermLite((R)) DL100 dermatoscope. Enlarged capillaries and hemorrhages were significantly more frequently detected with dermatoscope than without it. These findings were observed most frequently in the fourth finger. The presence of two or more enlarged capillaries in one or more fingers showed 83.1% sensitivity and 100% specificity for SSc. Among patients with SSc with anti-topoisomerase I antibody, the disease duration correlated negatively with the dermatoscopic number of enlarged capillaries and hemorrhages. Dermatoscope allows the easy and rapid identification of capillary nailfold morphological changes in SSc and should be routinely used for diagnosing SSc.The original publication is available at www.springerlink.co

RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels.

International audienceThe molecular organization of presynaptic active zones is important for the neurotransmitter release that is triggered by depolarization-induced Ca2+ influx. Here, we demonstrate a previously unknown interaction between two components of the presynaptic active zone, RIM1 and voltage-dependent Ca2+ channels (VDCCs), that controls neurotransmitter release in mammalian neurons. RIM1 associated with VDCC beta-subunits via its C terminus to markedly suppress voltage-dependent inactivation among different neuronal VDCCs. Consistently, in pheochromocytoma neuroendocrine PC12 cells, acetylcholine release was significantly potentiated by the full-length and C-terminal RIM1 constructs, but membrane docking of vesicles was enhanced only by the full-length RIM1. The beta construct beta-AID dominant negative, which disrupts the RIM1-beta association, accelerated the inactivation of native VDCC currents, suppressed vesicle docking and acetylcholine release in PC12 cells, and inhibited glutamate release in cultured cerebellar neurons. Thus, RIM1 association with beta in the presynaptic active zone supports release via two distinct mechanisms: sustaining Ca2+ influx through inhibition of channel inactivation, and anchoring neurotransmitter-containing vesicles in the vicinity of VDCCs

Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide.

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury, for which the involvement of nitric oxide (NO) and carbon monoxide (CO) has been suggested. NO is induced by NO synthase (NOS) and CO is generated by haeme oxygenase (HO). Among HO isoenzymes, HO-1 is an induced type. To assess the role of NO and CO in the pathogenic process, the cutaneous reverse passive Arthus reaction was examined using NOS inhibitor, HO-1 stimulator and HO-1 inhibitor. To evaluate the reaction we considered oedema, tumour necrosis factor-alpha, interleukin-6, and neutrophil number. The values of these four parameters were significantly reduced in mice treated with HO-1 stimulator as compared with the positive control mice. Quite the reverse was observed in mice treated with HO-1 inhibitor. These results suggest that the HO-1/CO signalling pathway is a therapeutic target for human IC-mediated disease

Decreased levels of autoantibody against histone deacetylase 3 in patients with systemic sclerosis.

Systemic sclerosis (SSc) is characterized by immunological abnormalities, especially the production of autoantibodies against various cellular components. Treatment with histone deacetylase (HDAC) inhibitors prevents collagen accumulation in a mouse SSc model. Additionally, autoantibody against HDAC-3 is produced in colon cancer patients, while HDAC-1 and HDAC-2 do not elicit autoantibody response. To determine the presence and levels of antibodies (Abs) against HDAC-3 in SSc. Anti-HDAC-3 Ab was examined by enzyme-linked immunosorbent assay (ELISA) and immunoblotting using human recombinant HDAC-3. The HDAC-3 activity was evaluated by ELISA using the fluorimetric HDAC lysyl substrate that comprises an acetylated lysine side chain. Contrary to our hypothesis that autoimmune background in SSc induced the production of autoantibody against HDACs, IgG and IgM anti-HDAC-3 Ab levels in SSc patients were significantly lower than in normal controls (p < 0.0005 and 0.001, respectively). Furthermore, decreased levels of IgG anti-HDAC-3 Ab were specific to SSc, since IgG anti-HDAC-3 Ab levels in patients with dermatomyositis (DM) and those with systemic lupus erythematosus (SLE) were similar and slightly increased relative to normal controls, respectively. Immunoblotting analysis showed that anti-HDAC-3 Ab was detected in normal controls and patients with DM or SLE, while it was absent in SSc patients. The HDAC-3 activity was significantly inhibited by IgG isolated from sera of normal controls, whereas such inhibitory effect was not observed by IgG isolated from sera of SSc patients. These results indicate the lack of anti-HDAC-3 autoantibody in SSc patients, which is produced in healthy individuals as well as DM and SLE patients, suggesting that this autoantibody might function as protective Ab.This is an electronic version of an article published in Free Radical Research, 42(11-12), 957-965: 2008 November. Free Radical Research is available online at: http://informahealthcare.com/doi/abs/10.1080/0891693080240630

Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines

BACKGROUND: YM529 is a newly developed nitrogen-containing bisphosphonate (BP) classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC). METHODS: Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157) were measured by MTS assay and calculated inhibition concentration 50 % (IC(50)) values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G(1 )method). We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. RESULTS: We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC(50 )values were 2.1 to 7.9 μM and YM529 induced apoptosis and G(1 )arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819). CONCLUSION: Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC

The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity.

Sensitization and challenge using DNFB induce contact hypersensitivity (CHS) with predominant type 1 helper (Th1) cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. CHS results from inflammatory cell infiltration, a process that is highly regulated by the expression of multiple adhesion molecules. We attempted to determine the role of L-selectin and ICAM-1 in Th1- and Th2-type CHS induced by DNFB or FITC in mice lacking either L-selectin, ICAM-1, or both. Th1-type CHS induced by DNFB was inhibited by L-selectin and/or ICAM-1 deficiency, which was associated with reduced IFN-gamma expression. Similarly, Th2-type CHS induced by FITC was inhibited by L-selectin deficiency. However, Th2-type CHS was increased by ICAM-1 deficiency and accompanied by increased Th2 cytokine expression. Infiltration of in vitro-generated Th1 cells into the FITC-challenged skin decreased in ICAM-1-deficient mice, whereas in vitro-generated Th2 cell infiltration increased, suggesting that ICAM-1 mediates Th1 cell migration and that in the absence of ICAM-1, Th1 cell recruitment decreased, whereas relative Th2 cell migration increased. These results suggest that ICAM-1 mediates Th1 cell recruitment irrespective of DNFB or FITC and that L-selectin recruits Th1 cells in Th1-type CHS, whereas it recruits Th2 cells in Th2-type CHS

P-selectin glycoprotein ligand-1 contributes to wound healing predominantly as a p-selectin ligand and partly as an e-selectin ligand.

Cell adhesion molecules are critical to wound healing through leukocyte recruitment. Although P-selectin glycoprotein ligand-1 (PSGL-1) regulates leukocyte rolling by binding P-selectin, but also binding E- and L-selectins with lower affinity, little is known about a role of PSGL-1 in wound healing. To clarify a role of PSGL-1 and its interaction with E- and P-selectins in wound healing, we investigated cutaneous wound healing in PSGL-1-deficient (PSGL-1(-/-)) mice in comparison with E-selectin(-/-), P-selectin(-/-), and P-selectin(-/-) mice treated with an anti-E-selectin antibody. PSGL-1 deficiency inhibited early wound healing, which was accompanied by decreased inflammatory cell infiltration and growth factor expression. By contrast, E-selectin deficiency did not affect wound healing. In general, the inhibitory effect of PSGL-1 deficiency on wound healing was similar to that of P-selectin deficiency either alone or with E-selectin blockade. However, early granulation tissue formation, late angiogenesis, and early infiltration of neutrophils and macrophages in PSGL-1(-/-) mice were inhibited beyond the inhibition in P-selectin(-/-) mice, but to a similar level of inhibition in P-selectin(-/-) mice with E-selectin blockade. These results suggest that PSGL-1 contributes to wound healing predominantly as a P-selectin ligand and partly as an E-selectin ligand by mediating infiltration of inflammatory cells