start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=760 end-page=766 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Mizoribine, tacrolimus, and corticosteroid combination therapy successfully induces remission in patients with lupus nephritis en-subtitle= kn-subtitle= en-abstract= kn-abstract=Conventional cyclophosphamide-based treatment regimens for lupus nephritis (LN) are still not considered to be optimal. The aim of this study was to evaluate the efficacy and safety of mizoribine, tacrolimus, and corticosteroid combination therapy for LN. We retrospectively evaluated a combination treatment of mizoribine and tacrolimus with corticosteroids as induction therapy in eight newly diagnosed systemic lupus erythematosus (SLE) patients with biopsy-proven LN. All patients were women, and their mean [standard deviation (SD)] age was 48.5 (20) years. All patients (100 %) had positive anti-double-stranded DNA (anti-dsDNA) antibody titers, and four (50.0 %) were nephrotic. Mean (SD) serum creatinine and daily proteinuria levels were 0.72 (0.4) mg/dl (range 0.33-1.55 mg/dl) and 4.56 (2.8) g (range 0.77-8.2 g), respectively. By month 2, significant improvements in the anti-dsDNA antibody titers, levels of proteinuria, serum albumin, and C3, and SLE disease activity index score were observed. By month 6, seven patients (87.5 %) were in complete remission, with normalized levels of both proteinuria and serum creatinine. This pilot study suggests that mizoribine and tacrolimus treatment with corticosteroids is well tolerated and may prove to be an optimal alternative remission-inducing regimen for LN. en-copyright= kn-copyright= en-aut-name=KagawaHidetoshi en-aut-sei=Kagawa en-aut-mei=Hidetoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HiromasaTsutomu en-aut-sei=Hiromasa en-aut-mei=Tsutomu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=HaraTakayuki en-aut-sei=Hara en-aut-mei=Takayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TakakiAyako en-aut-sei=Takaki en-aut-mei=Ayako kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamanakaRyutaro en-aut-sei=Yamanaka en-aut-mei=Ryutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SadaKen-ei en-aut-sei=Sada en-aut-mei=Ken-ei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=Himeji Red Cross Hosp, Dept Internal Med affil-num=2 en-affil= kn-affil=Himeji Red Cross Hosp, Dept Internal Med affil-num=3 en-affil= kn-affil=Himeji Red Cross Hosp, Dept Internal Med affil-num=4 en-affil= kn-affil=Himeji Red Cross Hosp, Dept Internal Med affil-num=5 en-affil= kn-affil=Himeji Red Cross Hosp, Dept Internal Med affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci en-keyword=Induction therapy kn-keyword=Induction therapy en-keyword=Lupus nephritis kn-keyword=Lupus nephritis en-keyword=Mizoribine kn-keyword=Mizoribine en-keyword=Multitarget therapy kn-keyword=Multitarget therapy en-keyword=Systemic lupus erythematosus kn-keyword=Systemic lupus erythematosus en-keyword=Tacrolimus kn-keyword=Tacrolimus END start-ver=1.4 cd-journal=joma no-vol=16 cd-vols= no-issue=5 article-no= start-page=739 end-page=748 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201210 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney en-subtitle= kn-subtitle= en-abstract= kn-abstract=Inflammatory process is involved in pathogenesis of diabetic nephropathy, although the activation and phenotypic change of macrophages in diabetic kidney has remained unclear. Sialoadhesin is a macrophage adhesion molecule containing 17 extracellular immunoglobulin-like domains, and is an I-type lectin which binds to sialic acid ligands expressed on hematopoietic cells. The aim of this study is to clarify the activation and phenotypic change of macrophages in the progression of diabetic nephropathy. We examined the expression of surface markers for pan-macrophages, resident macrophages, sialoadhesin, major histocompatibility complex class II and alpha-smooth muscle actin in the glomeruli of diabetic rats using immunohistochemistry at 0, 1, 4, 12, and 24 weeks after induction of diabetes by streptozotocin. Expression of type IV collagen and the change of mesangial matrix area were also measured. The mechanism for up-regulated expression of sialoadhesin on macrophages was evaluated in vitro. The number of macrophages was increased in diabetic glomeruli at 1 month after induction of diabetes and the increased number was maintained until 6 months. On the other hand, sialoadhesin-positive macrophages were increased during the late stage of diabetes concomitantly with the increase of alpha-smooth muscle actin-positive mesangial cells, mesangial matrix area and type IV collagen. Gene expression of sialoadhesin was induced by stimulation with interleukin (IL)-1 beta and tumor necrosis factor-alpha but not with IL-4, transforming growth factor-beta and high glucose in cultured human macrophages. The present findings suggest that sialoadhesin-positive macrophages may contribute to the progression of diabetic nephropathy. en-copyright= kn-copyright= en-aut-name=NagaseRyo en-aut-sei=Nagase en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajitaniNobuo en-aut-sei=Kajitani en-aut-mei=Nobuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShikataKenichi en-aut-sei=Shikata en-aut-mei=Kenichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OgawaDaisuke en-aut-sei=Ogawa en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KoderaRyo en-aut-sei=Kodera en-aut-mei=Ryo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=OkadaShinichi en-aut-sei=Okada en-aut-mei=Shinichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=KidoYuichi en-aut-sei=Kido en-aut-mei=Yuichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=MakinoHirofumi en-aut-sei=Makino en-aut-mei=Hirofumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci END