Effects of FTY720 on rat lymphoid organs.

INTRODUCTION: In this study, we examined the in vivo effect of FTY720 on rat thymus and spleen. MATERIALS AND METHODS: Inbred male Lewis (RT-I(l)) rats, 5-weeks-old, received FTY720 (0.1, 1, or 10 mg/kg) by intramuscular injection into 1 of 4 limbs daily for 7 days. The rats were humanely killed at 1, 3, 5, or 7 days after starting administration of FTY720. The thymus and spleen were obtained for hematoxylin and eosin (HE) as well as immunoperoxidase staining using the antibodies OX8 (CD8), W3/25 (CD4), and OX6 (major histocompatibility complex class II). RESULTS: HE staining revealed marked atrophy in the cortical region of the thymus among rats administered FTY720 at the dose of 10 mg/kg. The atrophy extended to the whole cortex. On day 7 of administration of FTY 720 (10 mg/kg), the medulla of the thymus showed relative expansion due to cells accumulation. Also, the spleens of FTY720-treated rats revealed an obvious reduction in the T-cell-dependent areas around the central artery. In conclusion, the immunosuppressive effect of FTY720 may be due to an inhibitory effect on T-cell emigration from the thymus to the periphery.

Two cases of recurrent IgA nephropathy following kidney transplantation.

Recurrence of immunoglobulin (Ig) A nephropathy following kidney transplantation has been described as occurring in 40% to 60% of cases. Although this type of recurrence was considered a benign condition for a long time, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We present 2 cases of recurrent IgA nephropathy following kidney transplantation. In case 1, renal function remained stable with a creatinine level of 1.2 mg/dL at 5 months after diagnosis and 61 months after transplantation. In case 2, the patient lost his graft and returned to regular hemodialysis at 36 months after diagnosis and 125 months after kidney transplantation.

Phytogrowth-Inhibitory activities of beta-dolabrin and gamma-thujaplicin, hinokitiol-related compounds and constituents of Thujopsis dolabrata Sieb. et Zucc. var hondai Makino.

Beta-dolabrin and gamma-thujaplicin isolated from Thujopsis dolabrata Sieb. et Zucc. var hondai Makino, like hinokitiol, showed strong phytogrowth-inhibitory activities, and their growth-inhibitory activities were as high as that of sodium 2,4-dichlorophenoxyacetate used as a positive control. In particular, the phytogrowth-inhibitory activity of gamma-thujaplicin was strong and it completely inhibited the germination of this seed of Brassica campestris L. subsp. rapa Hook f. et Anders at the concentration of 30 ppm. Both compounds exhibited inhibitory activities on B. campestris L. subsp. rapa Hook f. et Anders and Sesamum indicum Linne, even at the low concentration of 10 ppm. At 7 d after treatment with beta-dolabrin and gamma-thujaplicin, the amount of chlorophyll in the cotyledons of B. campestris L. subsp. rapa Hook f. et Anders treated with both compounds was greatly decreased as compared with the control. The findings indicate that the phytogrowth-inhibitory action might be a common biological activity of hinokitiol-related compounds, suggesting that at least a part of their phytogrowth-inhibitory actions seems to be related to a decrease in chlorophyll content.

Isolation, characterization and gene sequence analysis of a membrane-associated 89 kDa Fe(III) reducing cytochrome c from Geobacter sulfurreducens.

Geobacter sulfurreducens is capable of anaerobic respiration with Fe(III) as a terminal electron acceptor via a membrane-bound Fe(III) reductase activity associated with a large molecular mass cytochrome c. This cytochrome was purified by detergent extraction of the membrane fraction, Q-Sepharose ion-exchange chromatography, preparative electrophoresis, and MonoQ ion-exchange chromatography. Spectrophotometric analysis of the purified cytochrome reveals a c-type haem, with no evidence of haem a, haem b or sirohaem. The cytochrome has an M(r) of 89000 as determined by denaturing PAGE, and has an isoelectric point of 5.2 as determined by analytical isoelectric focusing. Dithionite-reduced cytochrome can donate electrons to Fe(III)-nitrilotriacetic acid and synthetic ferrihydrite, thus demonstrating that the cytochrome has redox and thermodynamic properties required for reduction of Fe(III). Analysis using cyclic voltammetry confirmed that the reduced cytochrome can catalytically transfer electrons to ferrihydrite, further demonstrating its ability to be an electron transport mediator in anaerobic Fe(III) respiration. Sequence analysis of a cloned chromosomal DNA fragment revealed a 2307 bp open reading frame (ferA) encoding a 768 amino acid protein corresponding to the 89 kDa cytochrome. The deduced amino acid sequence (FerA) translated from the open reading frame contained 12 putative haem-binding motifs, as well as a hydrophobic N-terminal membrane anchor sequence, a lipid-attachment site and an ATP/GTP-binding site. FerA displayed 20% or less identity with amino acid sequences of other known cytochromes, although it does share some features with characterized polyhaem cytochromes c.