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Severe congenital neutropenia (SCN) is characterized by chronic neutropenia with recurrent infections from early infancy and a predisposition to myelodysplastic syndrome/acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with SCN who develop myelodysplastic syndrome/AML. We report an 8-year-old girl with SCN carrying an ELANE mutation that had been refractory to granulocyte colony-stimulating factor. The patient experienced recurrent infections and then developed AML. The counts of leukemic blasts that harbored both CSF3R and RUNX1 mutations spontaneously decreased with antimicrobial therapy, leading to partial remission. After AML recurrence, HSCT was successfully performed using modified chemotherapy and a conditioning regimen. Serial donor lymphocyte infusions against mixed chimerism induced complete donor chimerism over 4 years without any infections or AML relapse. This case suggests the importance of carefully managing neutropenia-related infections, leukemia progression, and HSCT in patients with SCN developing AML. [ABSTRACT FROM AUTHOR]

The present study was conducted to determine the contribution of muscle protein synthesis to the prevention of anesthesia-induced hypothermia by intravenous administration of an amino acid (AA) mixture. We examined the changes of intraperitoneal temperature (Tcore) and the rates of protein synthesis ([K.sub.s]) and the phosphorylation states of translation initiation regulators and their upstream signaling components in skeletal muscle in conscious (Nor) or propofol-anesthetized (Ane) rats after a 3-h intravenous administration of a balanced AA mixture or saline (Sal). Compared with Sal administration, the AA mixture administration markedly attenuated the decrease in Tcore in rats during anesthesia, whereas Tcore in the Nor-AA group became slightly elevated during treatment. Stimulation of muscle protein synthesis resulting from AA administration was observed in each case, although Ks remained lower in the Ane-AA group than in the Nor-Sal group. AA administration during anesthesia significantly increased insulin concentrations to levels ~6-fold greater than in the Nor-AA group and enhanced phosphorylation of eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and ribosomal protein $6 protein kinase relative to all other groups and treatments. The alterations in the Ane-AA group were accompanied by hyperphosphorylation of protein kinase B and the mammalian target of rapamycin (mTOR). These results suggest that administration of an AA mixture during anesthesia stimulates muscle protein synthesis via insulin-roTOR-dependent activation of translation initiation regulators caused by markedly elevated insulin and, thereby, facilitates thermal accumulation in the body. thermogenesis; translation initiation; insulin; hypothermia

Leucine and isoleucine were shown to stimulate insulin-independent glucose uptake in skeletal muscle cells in vitro. In this study, we examined the effects of leucine and isoleucine on blood glucose in food-deprived rats and on glucose metabolism in skeletal muscle in vivo. Furthermore, we investigated the possible involvement of the energy sensor, 5'-AMP-activated protein kinase (AMPK), in the modulation of glucose uptake in skeletal muscle, which is independent of insulin, and also in leucine- or isoleucine-stimulated glucose uptake. Oral administration of isoleucine, but not leucine, significantly decreased the plasma glucose concentration. An i.v. bolus of 2-[1,[2-.sup.3]H]-deoxyglucose (2-[[sup.3]H]DG) was administered to calculate glucose uptake. Glucose uptake in the skeletal muscle did not differ after leucine administration, but glucose uptake in the muscles of rats administered isoleucine was 73% greater than in controls, suggesting that isoleucine increases skeletal muscle glucose uptake in vivo. On the contrary, in the skeletal muscles, administration of leucine but not isoleucine significantly increased [U-[sup.14]C]-glucose incorporation into glycogen compared with controls. AMPK [alpha]1 activity in skeletal muscle was not affected by leucine or isoleucine administration. However, isoleucine, but not leucine, significantly decreased AMPK [alpha]2 activity. The decrease in AMPK [alpha]2 activity was thought to be due to decreases in AMP content and the AMP:ATP ratio, which were related to the isoleucine administration. This is the first report of isoleucine stimulating glucose uptake in rat skeletal muscle in vivo, and these results indicate that there might be a relation between the reduction in blood glucose and the increase in skeletal muscle glucose uptake that occur with isoleucine administration in rats. The alterations in glucose metabolism caused by isoleucine may result in an improvement of the availability of ATP in the absence of increases in AMP-activated protein kinase activity in skeletal muscle. KEY WORDS: * isoleucine * leucine * glucose * muscle * AMP-activated protein kinase

The efficacy of second allogeneic stem cell transplantation (SCT2) using cord blood (CB) for patients with relapsed hematological malignancies after initial allogeneic stem cell transplantation (SCT1) is unknown. We analyzed the results of SCT2 using single-unit unrelated CB in 34 adult patients with relapsed hematological malignancies after SCT1 in our institution. The patients had acute myeloid leukemia (n = 23), acute lymphoblastic leukemia (n = 7), chronic myelogenous leukemia (n = 2), and myelodysplastic syndrome (n = 2). The cumulative incidence of neutrophil and platelet engraftment was 81.6% at 30 days and 68.5% at 100 days, respectively. With a median follow-up of 40 months, the probability of overall survival at 3 years was 29.0%. The cumulative incidence of relapse and transplant-related mortality at 3 years were 60.7% and 27.2%, respectively. The use of CB could offer the opportunity to receive SCT2 for patients who experienced disease relapse after SCT1 without HLA-identical related or unrelated donors. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the effect of ethionine administration to female rats' livers. The study determined the involvement of adenosine monophosphate (AMP)-activated protein kinase (AMPK) to the ethionine-induced depletion of liver adenosine triphosphate (ATP) and the subsequent suppressed mammalian target of rapamycin (mTOR) signaling. Results of the study revealed that ethionine decreased the physiological activities of AMPK.

AbstractIn prospective Japanese studies of pediatric renal tumors, 5-year event-free survival and overall survival (OS) for patients with nephroblastoma ranges from 75–90% and 89–97%, respectively. However, treatments strategies for recurrent nephroblastoma in Japanese patients remain unclear. This retrospective study aimed to inform the development of treatment strategies by analyzing the long-term results and side effects of salvage therapies for recurrent nephroblastoma in Japan. A questionnaire survey involving 41 institutions (74 patients) collected clinical data on recurrent cases reported to the Renal Tumor Committee of the Japan Children’s Cancer Group. Survey forms from 54 cases were evaluated. Median time to recurrence was 9.5 months among 51 patients without underlying disorders. Recurrence occurred at lung-only in 18 patients and at other sites in 33. The 5-year OS for all 51 patients was 70.6%, with recurrent disease causing death in 15 patients and one patient dying from treatment-related complications. Patients with lung-only recurrence had higher 5-year OS rates than those with other-site recurrence. Initial chemotherapy intensity also affected prognosis, with lower intensity associated with higher 5-year OS. In 17 survivors with lung-only recurrence, the most frequent treatment approach combined chemotherapy, surgery and radiotherapy. Conventional chemotherapy included platinum-containing regimens and/or Regimen I-based treatment containing cyclophosphamide and etoposide. Salvage therapies showed remarkable effectiveness for patients with lung-only recurrence or low intensity of the initial chemotherapy, highlighting the need to standardize prospective studies for post-recurrence treatment and identify risks of late complications for long-term survivors. [ABSTRACT FROM AUTHOR]