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In this report we describe a case of severe chronic infantile neurologic, cutaneous, articular (CINCA) syndrome with a novel G307V cryopyrin mutation and all of the characteristic clinical and laboratory features of this autoinflammatory disease. There was no clear response to standard therapies, including human interleukin-1 (IL-1) receptor antagonist (anakinra) and soluble tumor necrosis factor receptor (etanercept). The patient finally had a partial clinical response (reduction in fever and irritability) and complete laboratory response (improved C-reactive protein and serum amyloid A levels) to humanized anti-IL-6 receptor antibody (MRA), but died from congestive heart failure and interstitial pneumonia 2 months after initiation of therapy. We serially measured the serum cytokine levels and expression of NF-B activation in the patient's peripheral blood mononuclear cells before and during consecutive therapies. Pathologic examination of autopsy specimens was also performed. This case illustrates the continued difficulty in management of patients with CINCA syndrome and the complexity of the inflammatory pathways in this disorder.

A novel human leukemia cell line (Kasumi‐3) was established from the blast cells of a 57‐year‐old man suffering from myeloperoxidase‐negative acute leukemia. The cell line had five distinctive features, as follows. 1) Flow cytometric analyses showed cell surface expression of CD7, CD4, CD13, CD33, CD34, HLA‐DR and c‐Kit. This phenotype is compatible with that of acute myelocytic leukemia cells with the M0 subtype in the French‐American‐British classification. 2) Kasumi‐3 cells carried chromosomal abnormalities of t(3;7)(q27:q22), del(5)(q15), del(9)(q32), and add(12)(pll). The breakpoint of 3q27 was located near the EVI1 gene, and a high level of expression of the EVI1 gene was observed. 4) Kasumi‐3 cells treated with TPA showed maturation to monocytic lineage. 5) Treatment with either interleukin (IL)‐2, IL‐3, IL‐4, granulocyte‐macrophage colony‐stimulating or stem cell factor induced the proliferation of Kasnmi‐3 cells. Thus, the Kasumi‐3 cell line shows the characteristic features of undifferentiated leukemia. It should, therefore, be useful both for studying the biological characteristics of acute myelogenous leukemia M0 subtype and for investigating the role of the EVI1 gene in leukemogenesis.

Many authors have reported the effectiveness of betaine in the therapy of homocystinuria. However, the appropriate dose and interval of betaine adminis-10 tration have not been established. We have developed a high-performance liquid chromatographic (HPLC) method for assaying serum betaine (Sakura et al 1997) and estimated the dose and interval of betaine sufficient to correct increased concentrations of homocysteine in a homocystinuric patient with 5,10-methylenetetrahydrofolate reductase (MTHFR, EC 1.1.1.68) deficiency (McKusick 172460) 15 (Kishi et al 1994).To determine the pharmacokinetics of betaine, betaine loading tests (100 mg/kg) were performed in 3 healthy adult volunteers. Peak serum concentrations were reached at 1 or 2 h after loading and the increase of betaine concentration varied with individuals (148^258 mmol/L). As betaine pharmacokinetics varied between 20 individuals, the administration schedule must be determined on an individual basis.In the patient with MTHFR de¢ciency, the concentration of serum betaine reached a maximum at 2 h, with an increase of 157 mmol/L. The biological half-life was approximately 1 h. From these results, we recommend that betaine be given repeatedly at short intervals to achieve a concentration at which homocysteine is maximally 25 methylated to methionine.The relationship between serum concentrations of betaine and total homocysteine was estimated during therapy with varying doses of oral betaine (20^120 mg/kg) in the patient with MTHFR de¢ciency. Serum concentrations of total homocysteine decreased proportionally as those of betaine increased. However, the total homo-30 cysteine concentrations did not decrease further at betaine concentrations of 400 mmol/L or above, and the concentrations of total homocysteine did not decrease to the normal range (<10 mmol/L), remaining elevated at approximately 60 mmol/L.The serum concentration of betaine needed to reduce the serum concentration of total homocysteine in patients with MTHFR de¢ciency has not previously been 35 determined, but our observations suggest a therapeutic threshold of approximately 400 mmol/L. We reanalysed the data from Allen and his associates (1993) and found that serum concentrations of total homocysteine reached plateau levels at betaine concentrations of 500 mmol/L or greater in patients with cobalamin de¢ciency. This level is similar to that found in our study.

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