Biomedical subjects

Norio Asou

Publications and source records attributed to Norio Asou.

23 records · Page 2Linked to original sources

PubMed2003

[Allergic reaction against an emulsifier, HCO-60, contained in multamin and enocitabine].

We report two cases of an allergic reaction to HCO-60, which is used as an emulsifien for Multamin and enocitabine. A 55-year-old woman with M 4 Eo developed a high fever, urticaria and erythema after induction chemotherapy. After stopping the administration of Multamin, her fever and eruptions subsided. A 51-year-old woman with L 2 developed erythema and hypotension 30 minutes after the third administration of Multamin. When the patient was given enocitabine, she developed anaphylactic shock. During chemotherapy in patients with leukemia, it is important to distinguish the allergic reaction against Multamin-containing HCO-60 from infection and allergies to other drugs.

Acute Disease↗

PubMed2003

[Preventive effects of oren-gedoku-to on mucositis caused by anticancer agents in patients with acute leukemia].

Most anticancer agents frequently cause mucositis, such as stomatitis and gastrointestinal mucosal injury, which is closely associated with decrease in quality of life, infections and discontinuation of chemotherapy in patients with malignancy. We retrospectively evaluated the preventive effect of oral administration of oren-gedoku-to on stomatitis and diarrhea induced by cytotoxic drugs in 40 patients with acute leukemia. Incidence of stomatitis was 27.9% in the group given oren-gedoku-to, which was significantly lower compared with 71.6% in those who received a gargle consisting of allopurinol, sodium gualenate, and povidone-iodine. Drug-induced diarrhea was observed in 9.3% of the oren-gedoku-to group compared with 31.7% of the control group. These observations indicate a significant preventive effect of oren-gedoku-to on mucositis caused by anticancer agents.

Acute Disease↗

PubMed2002

Heterozygous PU.1 mutations are associated with acute myeloid leukemia.

The transcription factor PU.1 is required for normal blood cell development. PU.1 regulates the expression of a number of crucial myeloid genes, such as the macrophage colony-stimulating factor (M-CSF) receptor, the granulocyte colony-stimulating factor (G-CSF) receptor, and the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor. Myeloid cells derived from PU.1(-/-) mice are blocked at the earliest stage of myeloid differentiation, similar to the blast cells that are the hallmark of human acute myeloid leukemia (AML). These facts led us to hypothesize that molecular abnormalities involving the PU.1 gene could contribute to the development of AML. We identified 10 mutant alleles of the PU.1 gene in 9 of 126 AML patients. The PU.1 mutations comprised 5 deletions affecting the DNA-binding domain, and 5 point mutations in 1) the DNA-binding domain (2 patients), 2) the PEST domain (2 patients), and 3) the transactivation domain (one patient). DNA binding to and transactivation of the M-CSF receptor promoter, a direct PU.1 target gene, were deficient in the 7 PU.1 mutants that affected the DNA-binding domain. In addition, these mutations decreased the ability of PU.1 to synergize with PU.1-interacting proteins such as AML1 or c-Jun in the activation of PU.1 target genes. This is the first report of mutations in the PU.1 gene in human neoplasia and suggests that disruption of PU.1 function contributes to the block in differentiation found in AML patients.

Acute Disease↗

PubMed2002

In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis.

Familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML) is an autosomal dominant familial platelet disorder characterized by thrombocytopenia and a propensity to develop AML. Mutation analyses of RUNX1 in 3 families with FPD/AML showing linkage to chromosome 21q22.1 revealed 3 novel heterozygous point mutations (K83E, R135fsX177 (IVS4 + 3delA), and Y260X). Functional investigations of the 7 FPD/AML RUNX1 Runt domain point mutations described to date (2 frameshift, 2 nonsense, and 3 missense mutations) were performed. Consistent with the position of the mutations in the Runt domain at the RUNX1-DNA interface, DNA binding of all mutant RUNX1 proteins was absent or significantly decreased. In general, missense and nonsense RUNX1 proteins retained the ability to heterodimerize with PEBP2beta/CBFbeta and inhibited transactivation of a reporter gene by wild-type RUNX1. Colocalization of mutant RUNX1 and PEBP2beta/CBFbeta in the cytoplasm was observed. These results suggest that the sequestration of PEBP2beta/CBFbeta by mutant RUNX1 may cause the inhibitory effects. While haploinsufficiency of RUNX1 causes FPD/AML in some families (deletions and frameshifts), mutant RUNX1 proteins (missense and nonsense) may also inhibit wild-type RUNX1, possibly creating a higher propensity to develop leukemia. This is consistent with the hypothesis that a second mutation has to occur, either in RUNX1 or another gene, to cause leukemia among individuals harboring RUNX1 FPD/AML mutations and that the propensity to acquire these additional mutations is determined, at least partially, by the initial RUNX1 mutation.

Blood Platelet Disorders↗

PubMed2002

The absence of the p15INK4B gene alterations in adult patients with precursor B-cell acute lymphoblastic leukaemia is a favourable prognostic factor.

We examined deletion and methylation of the p15INK4B (p15) and p16INK4A (p16) genes, using Southern blotting and methylation-specific polymerase chain reaction (PCR), in 70 untreated adult patients with precursor B-cell acute lymphoblastic leukaemia (PBC-ALL) and analysed the relationship between their genetic changes and clinical outcome. Methylation and homozygous deletion of the p15 gene were detected in 30 (43%) and 18 (26%) patients, while those of the p16 gene were found in 16 (23%) and 11 (16%) patients respectively. Thirteen out of 17 patients with wild-type p15 gene showed expression of p15 mRNA, whereas 31 out of 39 patients with alteration (deletion and methylation) of the p15 gene showed no p15 mRNA expression by reverse transcription-PCR, suggesting that alterations of the p15 gene are highly associated with loss of p15 mRNA expression. Disease-free survival (DFS) at 4 years in patients with wild-type p15 gene is 33%, compared with 4% of those with p15 gene alterations (P = 0.049). Multivariate analysis showed that the absence of p15 gene alterations was an independent significant favourable prognostic factor for longer DFS (P = 0.0001). These results suggest that alterations in the p15 but not p16 gene can be used as a genetic prognostic indicator in PBC-ALL.

Adolescent↗