Susumu Iizuka

Increase in the glucosylated form of erythrocyte Cu-Zn-superoxide dismutase in diabetes and close association of the nonenzymatic glucosylation with the enzyme activity

Human erythrocytes contain glucosylated and nonglucosylated Cu-Zn-superoxide dismutases which can be separated by boronate affinity chromatography. The percentage of the glucosylated form is significantly increased in the erythrocytes of patients with diabetes as compared to normal erythrocytes. The nonglucosylated form of Cu-Zn-superoxide dismutase, which was washed through the boronate column, was glucosylated in vitro upon exposure to radioactive or non-radioactive D-glucose. Incorporation of D-glucose into the protein was observed, and with the increase in glucosylation, the enzymatic activity decreased, indicating that the glucosylation of the enzyme led to a low active form. This is the first demonstration that superoxide dismutase is glucosylated in erythrocytes and that the glucosylation leads to the inactivation of the enzyme.

Elevated serum manganese superoxide dismutase in acute leukemias

We measured the serum levels of manganese-superoxide dismutase (Mn-SOD) in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Serum Mn-SOD level for normal subjects was 94.1 +/- 23.5 ng/ml (mean +/- S.D.), the levels for AML and ALL patients were 159.6 +/- 77.1 ng/ml and 154.4 +/- 77.0 ng/ml, respectively. The serum Mn-SOD levels were unrelated to individual intracellular Mn-SOD levels, but correlated well with serum lactate dehydrogenase values. Regression of the leukemia was accompanied by decrease in the serum level of Mn-SOD. Serum Mn-SOD may thus serve as a measure of the activity of the disease.

High levels of Mn-superoxide dismutase in serum of patients with neuroblastoma and in human neuroblastoma cell lines

Levels of serum manganese superoxide dismutase (Mn-SOD) in normal children aged from 1 to 14 years and children with various hematological and malignant diseases were determined by enzyme-linked immunosorbent assay (ELISA). In the normal children, the serum Mn-SOD levels gradually increased in proportion to age. By 8 years of age, the Mn-SOD level was nearly at the adult level. The normal values of serum Mn-SOD (mean +/- SD) of children below 4 and above 8 years old were 48 +/- 10.2 ng/ml and 84 +/- 22.5 ng/ml, respectively. Assuming the upper limit of normal Mn-SOD level in serum to be the mean value +/- 2 SD of children at each age, high serum levels of Mn-SOD were found for 8 of 12 patients with neuroblastoma, three of four patients with Wilms tumor, and four of five patients with acute myeloid leukemia. The patients with neuroblastoma exhibited a transient increase in Mn-SOD following chemotherapy, but after 1 week the levels decreased markedly to the control levels. The changes in serum Mn-SOD levels in the patients with neuroblastoma correlated well with the levels of neuron-specific enolase. Mn-SOD was intensely stained in bone marrow cells of patients whose cancer cells had moved into the bone marrow. High levels of Mn-SOD were also found in cultured human neuroblastoma cells. These data indicate that Mn-SOD is expressed in neuroblastoma cells, may serve as one of the diagnostic and prognostic markers for the neuroblastoma, and may be useful to predict the effectiveness of chemotherapy for neuroblastoma and the recurrence of this disease.

Purification of Cu-Zn-superoxide dismutase from human erythrocytes by immunoaffinity chromatography Evidence for the presence of isoelectric heterogeneity

Cu-Zn-superoxide dismutase (SOD) was prepared in highly purified form from human erythrocytes by immunoaffinity chromatography using anti-human Cu-Zn-SOD goat IgG. The purified SOD had a high specific activity and gave a single band on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. On isoelectric focusing and immunoblotting several bands with enzyme activity and antigenicity were discerned.

Refractory sacrococcygeal germ cell tumor in Schinzel-Giedion syndrome.

We describe a boy with Schinzel-Giedion syndrome who developed refractory sacrococcygeal germ cell tumor with elements of embryonal carcinoma and immature teratoma. He developed local recurrence soon after tumor resection. The tumor was highly resistant to platinum-based combination chemotherapy, local irradiation, and salvage chemotherapy. Frequent infections resulted in a delay in treatment, although apparent fragility had not been observed clinically. He died from tumor progression at 32 months of age. Intensification of chemotherapy does not seem to be feasible for tumors in patients with Schinzel-Giedion syndrome.

A case of 45,X/47,XXX mosaic Turner syndrome with limb length discrepancy

Abstract. Patients with Turner syndrome (TS) frequently show short stature and skeletal deformities, such as kyphosis and scoliosis. However, to the best of our knowledge, limb length discrepancy (LLD) has not yet been reported in patients with TS. The case of a 12-yr-old girl with 45,X/47,XXX mosaic TS showing LLD is herein presented. She was on GH therapy for short stature and was noted to have scoliosis in the standing position at a regular examination; however, the scoliosis became less evident in the supine position, which is indicative of LLD. The length of the left leg was 5.0 cm shorter than that of the right leg when measured. She was referred to orthopedics and underwent right distal femoral and right proximal tibial staple epiphysiodesis to shorten the abnormally long limb at 10 yr 6 mo of age. One year after the operation, the LLD decreased from 5.0 to 1.5 cm. During this period, GH was continued. LLD is a rare complication in TS, but when patients with TS show scoliosis in the standing position, re-evaluation for scoliosis in the supine position should be performed and the lengths of both legs should be measured.

Genetic and prenatal findings in two Japanese patients with Schinzel–Giedion syndrome

We report two Japanese patients with Schinzel–Giedion syndrome. When polyhydramnios is observed, additional fetal findings such as overlapping fingers, hydrocephalus, hydronephrosis, and very characteristic facial appearance comprising high, prominent forehead, hypertelorism, and depressed nasal root may suggest Schinzel–Giedion syndrome.

A 25-Year Observation of a Japanese Female Patient with Hb Nottingham who has Two Children with the Same Disorder

We undertook a 25-year observation of a female patient with an unstable variant, Hb Nottingham or β98(FG5)Val→Gly, GTG>GGG. The proband was diagnosed with Hb Nottingham at the age of 9 years. Splenectomy was performed in order to successfully aid her height growth due to chronic anemia at the age of 11, although anemia improvement was transient. She experienced pregnancy/delivery twice, at age 23 and 26, respectively. During both pregnancies, a large number of nucleated red blood cells (NRBCs) appeared in her peripheral blood. No developmental delay of the fetus was noted in either pregnancy, and she gave birth without any maternal complications or perinatal problems. Both babies were diagnosed with Hb Nottingham. To the best of our knowledge, this is the first report of a long-term observation of a proband with Hb Nottingham, including her pregnancy/delivery and the neonatal course of her children with the same disorder.