A 9-month-old infant with acquired idiopathic thrombotic thrombocytopenic purpura caused by inhibitory IgG-autoantibody to ADAMTS13.

Although acquired idiopathic thrombotic thrombocytopenic purpura (ai-TTP) is rare in children, the authors present the case of a 9-month-old boy with ai-TTP showing severe deficiency of ADAMTS13 activity by its inhibitory IgG-autoantibody (4.8 Bethesda units/mL). Plasma exchange therapy was clinically effective but transient. Deficient activity of ADAMTS13 with the presence of its inhibitor persisted for 7 months after the initial diagnosis. However, other laboratory findings improved gradually with steroid (pulse) therapy. The hitherto insufficiently characterized clinical settings of ai-TTP during early childhood underscore the importance of measuring ADAMTS13 activity and its inhibitors for differential diagnosis in patients with thrombocytopenia of unknown etiology.

Refractory chronic immune thrombocytopenic purpura in a child with acute lymphoblastic leukemia.

Immune thrombocytopenic purpura (ITP) has been associated with several hematologic malignancies such as Hodgkin and non-Hodgkin lymphomas and chronic lymphocytic leukemia, but it is rare in children with acute lymphoblastic leukemia (ALL). Here, we report a 7-year-old girl with chronic ITP during early intensive phase of chemotherapy for ALL. She underwent splenectomy because thrombocytopenia had persisted even after treatment with intravenous immunoglobulin (IVIG), steroids, vincristine, rituximab, and anti-D antibody. After splenectomy, her platelet count had recovered, and maintenance therapy could be resumed with a support of IVIG. To our knowledge, this is the first child case of chronic ITP during chemotherapy for ALL and splenectomy was effective in this patient.

Effect of aminoguanidine on lipopolysaccharide-induced changes in rat liver transporters and transcription factors.

To determine the role of nitric oxide (NO) in rat liver transporter regulation, we investigated whether NO mediates lipopolysaccharide (LPS)-induced changes in transporters and their transcription factor expression using aminoguanidine (AG), an inhibitor of induced nitric oxide synthase (iNOS). We confirmed that LPS decreased mRNA levels for Ntcp, Oatp1, Oatp2, Oatp4, Oct1, Mrp2, Mdr1a and increased those for Mdr1b at 16 h after administration. AG attenuated these decreases for Ntcp, Oatp1 and Oatp4 (retinoid X receptor (RXR)alpha- and hepatocyte nuclear factor (HNF)4alpha-dependent genes) and increase for Mdr1b (nuclear factor (NF)-kappaB-dependent gene). Concomitantly, it suppressed LPS-induced NF-kappaB-dependent gene transcription, such as those for proinflammatory cytokines (cytokines; tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6) and iNOS, and also suppressed IL-1beta release from Kupffer cells (KCs) at post-translational levels, but had little effect on the LPS-induced decreases in RXRalpha and HNF4alpha transcriptional activities. These findings indicate that hepatocytes were stimulated directly by LPS, which lead to the activation of NF-kappaB and reduction of RXRalpha and HNF4alpha transcriptional activities as early responses, and indirectly by cytokines and NO released from KCs via activation of NF-kappaB by LPS as delayed responses. We conclude that AG, which suppresses LPS-induced NF-kappaB activation in both hepatocytes and KCs and then the release of cytokines and NO from KCs, attenuates LPS-induced changes of Ntcp, Oatp1, Oatp4 and Mdr1b transcription in hepatocytes. The roles of cytokines and NO could not be distinguished, however. Further in vitro study is needed to clarify the role of NO in transporter regulation.

Alteration in the cellular response to retinoic acid of a human acute promyelocytic leukemia cell line, UF-1, carrying a patient-derived mutant PML-RARalpha chimeric gene.

Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-alpha (PML-RARalpha) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARalpha. Although the mutant protein showed a decreased ligand-dependent transcriptional activity and retained a dominant-negative effect on normal RARalpha, UF-1 cells underwent growth inhibition, maturation and apoptosis in response to ATRA at 1 microM, but not < or = 100 nM, after 4 days of treatment with ATRA. Moreover, in the presence of 1 microM ATRA, approximately 50% of UF-1 cells expressing annexin V, an early-apoptotic marker, was negative for CD11b and showed immature morphology. These findings suggest that UF-1 cells, despite expressing mutant PML-RARalpha protein, can be induced by ATRA to undergo differentiation and apoptosis through RA-inducible mechanism(s), in which a proportion of apoptosis may occur independent of terminal differentiation. This unique cell line may be useful for investigating the pathogenesis of ATRA resistance and the mechanism of ATRA-induced apoptosis in APL.

Acute renal failure due to leukemic cell infiltration followed by relapse at multiple extramedullary sites in a child with acute lymphoblastic leukemia.

Acute renal failure due to leukemic infiltration into the kidney is rare in childhood acute lymphoblastic leukemia (ALL). We report here a five year-old boy with ALL who presented acute renal failure caused by leukemic infiltration at onset. Treatment with predonisolone and hemodialysis was effective. However, he showed persistent or repeated relapses at extramedullary sites, such as central nervous system, testis, and pancreas, suggesting that leukemic cells of this patient may have had a high affinity to extramedullary organs. On the basis of previous reports and the experience of this patient, intensive treatment may be needed in ALL children with renal involvement.