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We developed a convenient and reliable procedure for the cell-mediated passive transfer of type II collagen (CII)-induced arthritis (CA). Spleen cells from DBA/I mice with CA were intravenously transferred into syngeneic recipient mice. Arthritis developed only in those recipients which had received whole-body x-irradiation (8 Gy) just before cell transfer and intraperitoneally given soluble CII without adjuvant immediately after transfer. Non-immunized splenocytes could not induce arthritis even in irradiated recipients given soluble CII. Development of arthritis depended on the number of cells transferred; 5 ×107 cells induced severe and long-lasting arthritis in every recipient approximately 10 days after transfer. Severity of this arthritis was clinically and histologically similar to classical CA in donors. Arthritogenic splenocytes were generated in donors no later than 20 days after priming with CII in Freund's complete adjuvant, when arthritis had yet to occur. and were detected for more than 5 weeks. One splenocyte population responsible for transferring arthritis was CD4+ T cells. We then applied this system to show that prophylactic treatment of CII-immunized mice with cyclophosphamide (CY. 7 mg/kg), but not interferon-gamma (IFN-γ. 105 U/mouse), suppressed the arthritogenic ability of their spleen cells, although both treatments inhibited the development of CA. Treatment of recipients with IFN-γ. however, inhibited the development of arthritis upon transfer with CII-immunized splenocytes. These results indicate that CY and IFN-γ act at the induction and effector phases of arthritogenic lymphocytes, respectively. Thus, this system facilitates investigation of pathological mechanisms of CA. and of mechanisms of anti-arthrities. [ABSTRACT FROM AUTHOR]

Eking thyroid peroxidase (TPO), which was purified from the thyroid of patients with Graves' disease, we attempted to determine whether sera from patients with chronic thyroiditis Contained antibodies to the enzyme. When the binding was tested by ELISA. sera from patients with chronic thyroiditis revealed high binding activities to TPO. When TPO was incubated with IgG from sera followed by treatment with protein A-Sepharose and centrifugation. the remaining TPO activities in the supernatant fraction were lower in most of the patients, as compared to normal controls. Moreover. IgG purified by DEAE-cellulose chromatography from sera in patients interfered with the TPO activities, litres of anti-TPO antibodies correlated well with those of anti-microsome antibodies. These results indicate the presence of autoantibodies to TPO in sera of most patients with chronic thyroiditis and that TPO may be one component of microsome antigen complexes recognized by the autoantibodies. Studies on the inhibition of TPO by lgG isolated from sera of patients using guaiacol and iodide assays reseated that at least three epitopes of TPO molecule were recognized by autoantibodies and that the antigenic determinants on TP() molecule recognized by autoantibodies could be heterogeneous in patients. [ABSTRACT FROM AUTHOR]

We established a thyroglobutin (Tg)-specific, thyroiditis-inducing T-cell clone, B12G, from B6C3F1 mice by the immunization of mouse Tg with lipopolysaccharide (LPS) from Klebsiella strain LEN (O3:K1), B12G was Thy-1.2+, CD3+, CD4+, CD18+, and CD8-, and could transfer thyroiditis to recipient mice after in vitro stimulation with mouse or bovine Tg. Histological examination showed severe thyroiditis with predominant infiltrations of polymorphonuclear cells; few mononuclear cells were observed. B12G proliferated in response to bovine, mouse, porcine, and rat Tg in the presence of irradiated spleen cells, but did not respond to chicken or human Tg. H-2b, a low-responder haplotype of experimental autoimmune thyroiditis, governed the response of the clone to Tg. B12G produced interleukin-4 (IL-4) and IL-6, but not IL-2 or interferon-γ (IFN-γ), on stimulation with mouse Tg. These findings were different from characteristics of previously reported Tg-specific T-cell clones from high-responder mice in terms of epitope specificity and cytokine production pattern, raising the possibility that the specificities and functions of T cells involved in the development of autoimmune thyroiditis in low-responder mice differ from those in high responders. [ABSTRACT FROM AUTHOR]

We have investigated the effects of recombinant murine interferon-gamma (rIFN-γ) on type II collagen-induced arthritis (CA) in DBA/l mice. Therapeutic as well as prophylactic treatment with subcutaneous rIFN-γ, at 105 U/mouse six times a week, inhibited the development of CA without any obvious side effects. The accompanying suppression of anti-CII antibody responses may partly explain the inhibition of CA by rIFN-γ. The possible role of the anti-inflammatory effect of systemic IFN-γ in the inhibition of CA is discussed. [ABSTRACT FROM AUTHOR]

The Pulse Shape Processor is a digital signal processing electronics for the microcalorimeter instrument onboard ASTRO-H. Receiving digitized waveform (14 bit, 12.5 kHz sample) from 2×18 channels, two identical units of PSP-A and -B trigger X-ray events, assign five kinds of event grade, and perform optimal filtering to measure energy deposit on the 6×6 microcalorimeter pixels. One unit of PSP is composed of one FPGA board and two CPU boards. This paper describes the event processing algorithm to fulfill requirements for the signal processing, and task sharing between FPGA and CPU. [ABSTRACT FROM AUTHOR]

We report the design and the performance of the engineering model of the digital signal processing system called the Pulse Shape Processor (PSP) for the Soft X-ray Spectrometer (SXS) onboard the ASTRO-H satellite. The SXS employs an X-ray microcalorimeter system, in which X-ray photons are detected as a heat pulse due to photoelectric absorption. The pixelized HgTe absorbers are cooled down to 50 mK. The required energy resolution is 7 eV (FWHM) at 6 keV. Since the data link to the satellite data recorder is limited to 200 kbit s^-1, the onboard digital processor PSP plays a critical role in achieving the required resolution. The PSP is also the rate-limiting factor for other performance of the SXS, such as maximum count rate and energy range. In this paper, we show the design of the PSP, and show the performance based on a series of laboratory tests performed with the engineering models of the detector and the analog readout electronics. We found that (1) the PSP can register energy in the 0.07–18 keV band [energy range], (2) the energy resolution of the engineering model system, including the detector, analog electronics, and the PSP, is 4.8–5.7 eV at 5.9 keV [energy resolution], and (3) the PSP has sufficient processing power to handle a point-like source fainter than 0.3 Crab [maximum count rate]. These results are expected to be quite similar to those with the flight model, thus the results will be useful for the observation planning using the SXS. [ABSTRACT FROM AUTHOR]

Background and purpose:KP-496 is a novel dual antagonist for cysteinyl leukotriene receptor 1 (CysLT1) and thromboxane A2 (TXA2) receptor (TP). The aim of this study was to evaluate the pharmacological profile of inhaled KP-496 and its effects on airway obstruction.Experimental approach:Antagonist activities of inhaled KP-496 were investigated using bronchoconstriction induced in guinea pigs by LTD4 or U46619, a stable TXA2 mimetic. Guinea pigs sensitized with injections of ovalbumin were used to assess the effects of inhaled KP-496 on bronchoconstriction induced by antigen (i.v.). Another set of guinea pigs were sensitized and challenged with ovalbumin by inhalation and the effects of inhaled KP-496 on immediate and late airway responses and airway hyperresponsiveness were investigated.Key results:KP-496 significantly inhibited LTD4- and U46619-induced bronchoconstriction in a dose-dependent manner. The inhibitory effects of KP-496 (1%) were comparable to those of montelukast (a CysLT1 antagonist, p.o., 0.3 mg kg−1) or seratrodast (a TP antagonist, p.o., 3 mg kg−1). KP-496 (1%) and oral co-administration of montelukast (10 mg kg−1) and seratrodast (20 mg kg−1) significantly inhibited antigen-induced bronchoconstriction, whereas administration of montelukast or seratrodast separately did not inhibit antigen-induced bronchoconstriction. KP-496 exhibited dose-dependent and significant inhibitory effects on the immediate and late airway responses and airway hyperresponsiveness following antigen challenge.Conclusions and implications:KP-496 exerts effects in guinea pigs which could be beneficial in asthma. These effects of KP-496 were greater than those of a CysLT1 antagonist or a TP antagonist, in preventing antigen-induced airway obstruction.British Journal of Pharmacology (2008) 153, 669–675; doi:10.1038/sj.bjp.0707602; published online 26 November 2007 [ABSTRACT FROM AUTHOR]