Ischemia with subsequent reperfusion (IR) injury is a significant clinical problem that occurs after physical and surgical trauma, myocardial infarction, and organ transplantation. IR injury of mouse skeletal muscle depends on the presence of both natural IgM and an intact C pathway. Disruption of the skeletal muscle architecture and permeability also requires mast cell (MC) participation, as revealed by the fact that IR injury is markedly reduced in c-kit defective, MC-deficient mouse strains. In this study, we sought to identify the pathobiologic MC products expressed in IR injury using transgenic mouse strains with normal MC development, except for the lack of a particular MC-derived mediator. Histologic analysis of skeletal muscle from BALB/c and C57BL/6 mice revealed a strong positive correlation (R2 = 0.85) between the extent of IR injury and the level of MC degranulation. Linkage between C activation and MC degranulation was demonstrated in mice lacking C4, in which only limited MC degranulation and muscle injury were apparent. No reduction in injury was observed in transgenic mice lacking leukotriene C4 synthase, hemopoietic PGD2 synthase, N-deacetylase/N-sulfotransferase-2 (enzyme involved in heparin biosynthesis), or mouse MC protease (mMCP) 1. In contrast, muscle injury was significantly attenuated in mMCP-5-null mice. The MCs that reside in skeletal muscle contain abundant amounts of mMCP-5 which is the serine protease that is most similar in sequence to human MC chymase. We now report a cytotoxic activity associated with a MC-specific protease and demonstrate that mMCP-5 is critical for irreversible IR injury of skeletal muscle.

Objective To assess cost-effectiveness of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in rheumatoid arthritis. Methods We conducted 3 analyses: a lifetime analysis with a cohort model (study A) and 2 short-term analyses (studies B and C). Study A evaluated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained from costs of standard treatments. Study B evaluated yearly costs per person achieving American College of Rheumatology (ACR) response (ACR20, ACR50, and ACR70), and study C, costs per person achieving previously defined claims-based effectiveness (equivalent to 28-joint Disease Activity Score [DAS28] ≤ 3.2). The proportion of ACR responders to the drugs of interest were determined by mixed treatment comparisons. Studies B and C estimated costs using a claims database. Results In study A, ICERs of all b/tsDMARDs were lower than 5.0 million JPY per QALY. In study B, yearly costs per person with ACR50 response were lower for subcutaneous tocilizumab (1.9 million JPY) and subcutaneous abatacept (2.3 million JPY). In study C, costs per person were lower for subcutaneous tocilizumab (1.3 million JPY) and intravenous tocilizumab (1.6 million JPY) and effectiveness rates were higher for intravenous tocilizumab (45.3%) and infliximab (43.0%). Conclusion The b/tsDMARDs with lower prices showed higher cost-effectiveness.

High-temperature creep resistance in cations co-doped polycrystalline Al 2 O 3 was examined by uniaxial compression creep test at 1250 C. The dopant oxides used in this study were 0.1 mol% of YO 1:5 , ZrO 2 , SrO, MgO and TiO 2 . The creep rate in Al 2 O 3 was significantly changed by cations co-doping. For instance, Zr/Y co-doping suppressed the creep rate in Al 2 O 3 by a factor of about 400. A high-resolution transmission electron microscopy (HREM) and nano-probe energy dispersive X-ray spectroscopy (EDS) analysis revealed that Y and Zr cations segregate along grain boundaries. The grain boundary diffusion in Al 2 O 3 was supposed to be retarded by the segregation of Y and Zr cations. A firstprinciple molecular orbital calculation was made for cations co-doped Al 2 O 3 and cation singly doped Al 2 O 3 model cluster. The creep rate was correlated with the value of net charge in oxygen anion. The net charge of oxygen anion was one of the most important factors to determine the creep resistance in Al 2 O 3 .

ABSTRACT. We evaluated the usefulness of MRI and compared it with CT for diagnosis of mesenteric lymphoma in a dog. The results in the plain CT, dynamic CT and plain MR (T1WI and T2WI) images suggested that the mass was a large single nodular lesion with abundant blood perfusion. On enhanced MRI(T1WI) , the mass was depicted as a tumor with adhesion to the gut wall. Exploratory laparotomy confirmed the mass was consistent with the findings on enhanced MRI. We think that MRI might be a useful imaging tool for diagnosis of canine mesenteric lymphoma. KEY WORDS: canine, magnetic resonance imaging, mesenteric lymphoma.

To identify the characteristics of ulcerative colitis (UC)-associated carcinomas, 8 lesions, high-grade dysplasias and invasive carcinomas, were implanted into severely combined immunodeficient (SCID) mice and/or cultured in vitro. Intramucosal neoplasias consisting of high-grade dysplasia showed extremely slow proliferation after implantation (2/3 cases) and in vitro culture failed (4 cases). However, invasive carcinomas demonstrated rapid growth both after SCID mouse implantation and in vitro (4/4 cases). From two cases of invasive carcinomas, 6 cell lines were established, and these are the first to be described in the literature. In addition to variation in immunohistochemically determined phenotypic expression regarding α α α α-fetoprotein, chromogranin A and estrogen receptors, the established cell lines showed varying differentiation (moderately or poorly n patients with long-standing ulcerative colitis (UC), colorectal dysplasias and carcinomas frequently develop, and a chronic inflammation-carcinoma sequence has been noted. [1][2][3][4][5] UC-associated tumors have several characteristics, including multiplicity and varying gross appearance of flat, depressed or villous intramucosal lesions with no clear border. 4,6) Regarding genetic alterations, although p53 alteration occurs rather often with loss of heterozygosity (LOH), a low prevalence of APC and ras mutations in UC-associated tumors has been described, along with a high LOH frequency of chromosomes 3 and 18 and p16, compared to sporadic colorectal carcinomas.7-10) Establishment of cell lines of UC-associated tumors should facilitate assessment of differences from the adenoma-carcinoma sequence or the de novo cancer pathway. In the present study, UC-associated dysplasias and invasive carcinomas were implanted into severely combined immunodeficient (SCID) mice and cultured in vitro. Genetic and histopathological features of the established cell lines were then compared with those of sporadic colorectal carcinomas, previously generated in our laboratory. Materials and MethodsSource of tumor cells. Neoplastic lesions, including 4 highgrade dysplasias and 4 invasive carcinomas were obtained from surgically resected rectal tissue in 8 cases (21-73 years old; 5 males, 3 females) with UC (Table 1). Total duration of illness was 6 to 18 years. For comparison, cell lines KE-43, KE-43C4 (subclone of KE43) and KE-24, which were established from invasive sporadic carcinoma lesions (ascending and sigmoid colons; 76-year-old male and 54-year-old female, respectively) in our laboratory were used (Table 1). This work was conducted after receiving the standard informed consent from patients and was approved by our Medical School and University Hospital Ethics Committee (No. B01-20). Implantation of tumor cells into SCID mice and in vitro cell culture.After sterilization of surgically obtained tissue with Isogen (Meiji Seika, Tokyo), tumor tissues were cut and used for implantation under the backskin of 6-week-old, female SCID mice (CB-17/ICR-SCID, Nippon Clea, Os...