Anaplastic large cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma characterized by the CD30+ large neoplastic cells and sometimes carries a t(2;5)(p23;q35). Recently, we found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in ALCLs with t(2;5). Subsequent cDNA cloning showed p80 to be a fusion protein of two genes, the novel tyrosine kinase gene and the nucleophosmin gene, in accordance with the sequence of the NPM/ALK gene (Morris et al, Science 263:1281, 1994). Meanwhile, the clinicopathologic features of p80-carrying ALCLs have remained unclear. Paraffin sections of 105 cases of ALCL were immunostained using anti-p80 antibody, and 30 of them were shown to express p80. Clinicopathologic comparison between p80-positive and -negative ALCLs showed that p80-positive cases occurred in a far younger patient age group (16.2 +/- 12.9 years; p80- negative cases, 51.0 +/- 22.3 years; P < .0001) and the patients showed a far better 5-year survival rate (79.8%; p80-negative group, 32.9%; P < .01). These data showed that p80-positive ALCL is a distinct entity both clinically and pathogenetically and should be differentiated from p80-negative ALCL.

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder characterized by circulating serum IgG antibodies against two hemidesmosomal proteins: BP180 and BP230. Fundamentally, immunosuppressive therapies are administered to treat this disease, but plasmapheresis can be added for refractory patients. We experienced the case of a 63-year-old patient with refractory BP for which we administered double filtration plasmapheresis (DFPP). His skin lesions improved along with decreased IgG BP180 antibodies, but factor XIII (FXIII) and fibrinogen were also reduced by DFPP repetition. Reportedly, deficiency of those factors can cause lethal bleeding. Especially, decreased FXIII cannot be detected by prolongation of bleeding or coagulation time. To prevent further reduction of those factors and bleeding complications, DFPP was switched to selective plasma exchange (SePE), a new modality of plasmapheresis that uses a membrane plasma separator with smaller than ordinary pores. SePE further reduced pathogenic IgG BP180 antibodies, but FXIII and fibrinogen recovered. For this case, we measured the mean of reduction ratios in serum IgG and FXIII both before and after plasmapheresis sessions and detected the decreased levels of FXIII and fibrinogen during DFPP. We were able to switch to SePE from DFPP appropriately before any bleeding event occurred. The utility of SePE was demonstrated, especially for the reduction of pathogenic antibodies with retention of FXIII and fibrinogen, which have the longest half-lives among coagulation factors and which take a long time to recover.

Background Tubulointerstitial fibrosis is a hallmark of chronic kidney disease (CKD), and is initiated by tubular epithelial cell (TEC) injury. Hypoxia promotes tubular cell death, fibrosis and CKD progression. Munc18-1-interacting protein 3 (Mint3) is a molecule that activates hypoxia-inducible factors (HIFs) by binding and suppressing factor inhibiting HIF-1 (FIH). However, the role of Mint3 in tubulointerstitial fibrosis remains unknown. Methods We induced fibrosis of the kidney after unilateral ischemia–reperfusion injury (uIRI) in Mint3-knockout and littermate wild-type mice. The duration of ischemia was 23 min and the kidneys were harvested at 24 h and 7 days after ischemia–reperfusion. The function of Mint3 was further investigated by using mouse cortical tubular (MCT) cells, which were treated with Mint3 and/or FIH small interfering RNA and exposed to normoxia or hypoxia. Results Knockout of Mint3 did not affect the acute injury induced by uIRI, but exacerbated the tubulointerstitial fibrosis, accompanied by an increase in TEC apoptosis. Consistently, hypoxia-induced apoptosis of MCT cells was aggravated by Mint3 knockdown. Unexpectedly, the additional knockdown of FIH did not suppress the increase in apoptosis by Mint3 knockdown, demonstrating the irrelevance of the FIH/HIF pathway. Therefore, we next focused on nuclear factor (NF)-κB, which has an anti-apoptotic role. Indeed, not only the expression of the inhibitory NF-κB p50 but also the DNA-binding activity of p50/p50 homodimer was increased by knockdown of Mint3 in the TECs, along with the decreased expressions of the NF-κB-targeted anti-apoptotic genes. An increase in NF-κB p50 was also confirmed in Mint3-knockout kidneys. Conclusions Mint3 in epithelial cells protects the cells from apoptosis by up-regulating anti-apoptotic effects of NF-κB, leading to fibrosis suppression. This new pathophysiology of tubulointerstitial fibrosis could be a target of future therapy for CKD.

We designed a new bio-material using sodium polyphosphate [poly(P)] that can be used for acceleration of periodontal regeneration. The effects of poly(P) on cell calcification and periodontal regeneration, including alveolar bone regeneration, were investigated in vitro and in vivo. Expressions of osteopontin (OPN) and osteocalcin (OC) mRNAs were induced by poly(P) treatment of MC3T3-E1cells. Alkaline phosphatase (ALPase) activity was also enhanced by poly(P), and the cells treated with poly(P) were strongly stained by alizarin red. As an in vivo experiment, artificial periodontal pockets were made in the buccal alveolar bone of mandibular first and second molars of each rat. Poly(P) was injected into the artificial pockets over a period of 1 to 3 weeks, and the regeneration of alveolar bone was evaluated histologically. At 1 week after the start of poly(P) treatment, remarkable regeneration of periodontal tissues, including alveolar bone, was observed in the poly(P)-treated group, whereas little regeneration was observed in the control group. The average area of regeneration in the poly(P)-treated group (after 2-weeks treatment) was more than 2-fold larger than that in the control group, suggesting that poly(P) positively stimulates alveolar bone formation. In addition, inflammation of the defected area was diminished and tissue repair was also accelerated in the poly(P)-treated group. Since poly(P) has antibacterial activity against P. gingivalis and S. mutans and since poly(P) stimulates the growth of fibroblasts by stabilizing fibroblast growth factors (FGFs), poly(P) could be effective for periodontal regeneration.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological condition with diverse neurological manifestations. Many clinical factors are known causes of PRES, but only a few cases of PRES have been reported in patients with chronic kidney disease (CKD) and infectious disease. We describe three cases of PRES in patients with CKD triggered by various infectious diseases. Characteristic hyperintense signals on magnetic resonance imaging (MRI) indicating reversible vasogenic brain oedema in various parts of the brain were observed. To explain the pathophysiology of PRES, the hypertension/hyperperfusion and hypoperfusion/vasoconstriction theories have been proposed. Patients with CKD have many complications including uraemia, hypertension, and immunosuppression. Therefore, physicians should recognize that patients with CKD are at high risk of PRES triggered by infectious diseases and promptly diagnose PRES because immediate treatment of the triggers often leads to complete resolution.