Reiji Fukano

Serum and cerebrospinal fluid cytokine profile of patients with 2009 pandemic H1N1 influenza virus-associated encephalopathy

PURPOSE Since April 2009, the number of patients with 2009 pandemic H1N1 influenza virus infection has been increasing in Japan just as in the rest of the world. Patients with 2009 pandemic H1N1 influenza-associated encephalopathy (pIE) have also been reported. The common clinical symptoms of this condition are seizures and progressive coma with high-grade fever. We previously reported the possible association between seasonal influenza-associated encephalopathy (sIE) and proinflammatory cytokines. However, the pathogenesis of pIE remains to be elucidated. RESULTS In pIE patients with a poor outcome, the serum levels of interleukin (IL)-6, IL-10, and soluble tumor necrosis factor (TNF) receptor (sTNFR1) were significantly higher than those in pIE patients without neurological sequelae. Similarly, the cerebrospinal fluid (CSF) IL-6 levels in pIE patients with a poor outcome were significantly higher than those in pIE patients without neurological sequelae. CONCLUSION Our results suggest that IL-6, TNF-α, and IL-10 play important roles in pIE, and that the serum levels of IL-6, IL-10, and sTNFR1 and the CSF levels of IL-6 are related to neurological complications.

Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan.

Reports of non‐anaplastic peripheral T‐cell lymphoma (PTCL) in pediatric patients are relatively rare.

Functional expression of cysteinyl leukotriene receptors on human platelets.

Normal peripheral blood leukocytes, such as basophils, eosinophils, B lymphocytes and monocytes/macrophages, have a cysteinyl leukotriene 1 (CysLT1) receptor, while the cysteinyl leukotriene 2 (CysLT2) receptor is expressed in cardiac Purkinje cells, endothelium, brain and leukocytes. However, it is unknown whether or not platelets express the CysLT1 or CysLT2 receptor. In this study we identify and characterize the biological function of the CysLT receptor of human platelets. We determined the CysLT1 or CysLT2 receptor mRNA expression in normal human platelets by RT-PCR and determined protein expression by Western blotting and flow cytometry. Moreover, we examined the effect of cysteinyl leukotrienes (CysLTs) in platelets on the induction of RANTES (Regulated on Activation, Normal T Expressed, and presumably Secreted). We also investigated whether the CysLT1 receptor antagonist pranlukast inhibits CysLT-induced RANTES release. In conclusion, we showed the functional expression of CysLT receptors on human platelets and demonstrated that CysLTs induced the release of significant amounts of RANTES, which suggests a novel role for human platelets in CysLT-mediated allergic inflammation.

Intravenous immunoglobulin does not increase FcγRIIB expression levels on monocytes in children with immune thrombocytopenia.

Intravenous immunoglobulin (IVIG) produces a rapid and prolonged increase in the platelet counts of children with immune thrombocytopenia (ITP). The mechanism of IVIG efficacy in a murine model of ITP has been reported to operate through an IVIG‐mediated increase in the expression of the inhibitory Fc receptor FcγRIIB(CD32B) on splenic macrophages. This investigation examined whether IVIG administration results in a similar increase in FcγRIIB expression on peripheral blood CD14+ monocytes in 20 children with ITP. FcγRIIB expression on peripheral blood monocytes was measured by flow cytometry in ITP patients, before and after IVIG therapy, as well as in control subjects. Peripheral blood monocytes were labelled with fluorescent‐specific antibodies. There were no significant differences in the percentages or numbers of CD14+CD32B+ monocytes, or in the percentage of CD14+CD32B+ monocytes present in children with ITP before and after IVIG therapy. We suggest that IVIG does not increase FcγRIIB expression in peripheral blood monocytes in children with ITP.

Amino acids exhibit anti-inflammatory effects in human monocytic leukemia cell line, THP-1 cells

ObjectiveThe elemental diet is one of the effective therapies for inflammatory bowel disease. However, the mechanism remains unclear, and there have never been reports about the inhibitory effects of amino acids in human monocytes/macrophages. We investigated the inhibitory effects of amino acids on cytokine production or expression of adhesion molecules that are involved in inflammatory diseases, in human monocytes/macrophages.MethodsWe examined the inhibitory effects of cysteine, histidine or glycine on the induction of nuclear factor-κB (NF-κB) activation, expression of intracellular adhesion molecule-1 (ICAM-1, CD54) and production of interleukin-8 (IL-8) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs) stimulated with tumor necrosis factor-α (TNF-α).ResultsCysteine, histidine and glycine significantly reduced the activation of NF-κB in THP-1 cells stimulated with TNF-α. In addition, cysteine and histidine significantly inhibited the expression of ICAM-1 and production of IL-8 in THP-1 cells and PBMCs.ConclusionsOur results suggest that cysteine and histidine exhibit anti-inflammatory effects in THP-1 cells, and may be responsible for the efficacy of treatment in inflammatory bowel diseases.

Rhabdomyosarcoma masquerading as acute leukemia

Rhabdomyosarcoma (RMS) masquerading as acute leukemia (AL) is very rare. We describe three cases with RMS without any symptoms of solid tumors. Bone marrow (BM) showed approximately 95% of blast‐like abnormal cells, lacking almost all of the surface antigens of myeloid‐ and lymphoid‐lineage. The immunohistochemistry revealed positive of the cells for actin, desmin and myoglobin. It is important to examine BM samples by immunohistochemistry, when a flow cytometric analysis reveals an unusual presentation. Pediatr Blood Cancer 2009;52:286–287.

Haematopoietic stem cell transplantation for relapsed or refractory anaplastic large cell lymphoma: a study of children and adolescents in Japan

To evaluate haematopoietic stem cell transplantation (HSCT) in children and adolescents, we reviewed the records of 47 patients who were ≤18 years, had relapsed or refractory anaplastic large cell lymphoma, and received HSCT between 1990 and 2010. At HSCT, complete remission (CR) was less common in allogeneic HSCT recipients (n = 24) than in autologous HSCT recipients (n = 23) (P = 0·01). The autologous and allogeneic HSCT groups differed in terms of 5‐year event‐free survival (EFS) (38% vs. 50%, P = 0·63), cumulative incidence of progress or relapse (49% vs. 28%, P = 0·25), and treatment‐related mortality (12% vs. 25%, P = 0·40). However, these differences were not significant. Patients with non‐CR at autologous HSCT had a significantly lower EFS rate (14% vs. 48%, P = 0·03). Conversely, although those with non‐CR at allogeneic HSCT had a lower EFS rate, this was not significant (44% vs. 63%, P = 0·26). Reduced‐intensity conditioning regimens were used for three of the 16 allogeneic HSCTs received by patients with non‐CR. These three patients achieved CR, surviving 32–65 months after HSCT. These results demonstrated that allogeneic HSCT might be a treatment option for patients who do not achieve CR through conventional chemotherapy.

Outcomes of immunological interventions for mixed chimerism following allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia.

For children with juvenile myelomonocytic leukemia (JMML) who undergo stem cell transplantation (SCT), the role of immunological interventions including withdrawal of immunosuppressive therapy (IST) and donor lymphocyte infusion (DLI) for treatment of disease recurrence remains uncertain.

Reconstruction of the proximal humerus by combined use of extracorporeally-irradiated osteochondral graft and free vascularized fibula following resection of Ewing sarcoma

Reconstruction of the proximal humerus following limb-saving resection of malignant bone tumor is extremely challenging. We describe here a novel anatomical reconstruction technique in a young patient. A 6-year-old girl with Ewing sarcoma of the proximal humerus was treated by wide excision of the tumor followed by reconstruction with extracorporeally-irradiated osteoarticular autograft combined with an intramedullary inserted free vascularized fibula graft. Proper alignment of the shoulder joint was maintained with no osteoarthritic changes after 16 months. The resulting limb function was satisfactory. This biological reconstruction method was safe and without serious complication. It is indicated for the reconstruction of non-weight-bearing joints and is ideal for the proximal humerus.

Hematopoietic stem cell transplantation following unsuccessful salvage treatment for relapsed acute lymphoblastic leukemia in children

For children who experience a re‐induction failure or multiple recurrences following the first relapse of acute lymphoblastic leukemia (ALL), it is uncertain whether additional intensive chemotherapy aimed at hematopoietic stem cell transplantation (SCT) in complete remission (CR) or immediate SCT even in non‐CR should be performed. This study aimed to investigate the impact of disease status at SCT on the outcomes of SCT for these children, whose prognosis is considered unquestionably poor even with SCT.