Katsuo Sugita

High-dose intravenous intact IgG infusion in refractory autoimmune hemolytic anemia (Evans syndrome)

AUTOIMMUNE HEMOLYTIC ANEMIA in childhood has been reported to have two main clinical patterns: acute and chronic. The acute type responds well to corticosteroid therapy and transfusion, but the chronic type requires prolonged corticosteroid therapy, immunosuppressive agents, splenectomy, and plasma exchangeJ -3 Evans syndrome, a combination of AIHA and idiopathic thrombocytopenic purpura, in particular is usually refractory and relapses exclusively in chronic-type AIHA. 4 Recently, high-dose intravenous lgG therapy for the treatment of ITP has been reported, 5-7 but it has not been successful in the management of AIHA. We attempted this therapy in a boy with refractorY Evans syndrome because of the presumed common pathophysiologic characteristics of immune hemolysis and immune thrombocytopenia, and successful control was obtained.

MRI changes and deficits of higher brain functions in preterm diplegia

Goto M, Ota R, Iai M, Sugita K, Tanabe Y. MRI changes and deficits of higher brain functions in preterm diplegia. Acta Pædiatr 1994;83:506–11. Stockholm. ISSN 0803–5253

Increased expression of GRP94 protein is associated with decreased sensitivity to X-rays in cervical cancer cell lines

Purpose: Radiation therapy is one of the standard treatments for cervical cancer. Glucose regulated protein 94 (GRP94) is a molecular chaperone, which increases in amount after X-ray irradiation. This study examined the involvement of GRP94 in radio-resistance in human cervical cancer cells. Materials and methods: Seven human cervical carcinoma cell lines (HeLa, SKG-I, SKG-IIIb, QG-U, Caski, SiHa and C33A) were examined for basal levels of GRP94 protein by western blotting analysis. Sensitivity to X-ray irradiation of these cell lines was determined with a colony survival assay. The suppression of GRP94 expression was performed using specific small-interfering RNA (siRNA) in HeLa and Caski cells. Results: HeLa cells and QG-U cells, with higher basal levels of GRP94, exhibited a low sensitivity to X-ray cell killing. In HeLa cells, the sensitivity increased when protein GRP94 levels were reduced by specific siRNA transfection. However, a reduction in GRP94 protein had little effect on the X-ray sensitivity of Caski cells, which expressed low basal GRP94 protein levels but showed a low sensitivity to X-rays. Conclusions: High basal protein levels of GRP94 were correlated with a modest decrease in sensitivity to X-ray cell death in some cervical cancer cell lines. These results suggest that higher GRP94 protein expression is one of the molecular mechanisms causing resistance to radiation, and therefore GRP94 siRNA might be useful in tumor-specific gene therapy by reversing radio-resistance prior to radiation in cervical cancer.

Antiphospholipid antibody syndrome in childhood strokes

The significance of antiphospholipid antibodies was examined in patients with childhood strokes. Eight patients, aged 2-13 years, who presented with acute hemiplegia were studied. On the basis of magnetic resonance imaging, magnetic resonance angiography, single photon emission computed tomography, and cerebral angiographic findings, 3 children were diagnosed as having infarctions due to moyamoya disease, and the others as having idiopathic infarctions. Serologic studies revealed elevated anticardiolipin antibody (ACA) IgG in 3 of the 5 patients with idiopathic infarction; no such elevation was revealed in patients with moyamoya disease. Values for all other tests, including ACA IgM and lupus anticoagulant, were within normal limits or negative in all patients. ACA IgG, therefore, may be a more important causative agent of childhood strokes than was previously considered.

Moyamoya syndrome in a patient with Down syndrome presenting with chorea

An 11-year-old girl with Down syndrome is reported with moyamoya syndrome; she presented with chorea and mental regression, but had no hemiplegia or convulsions. Magnetic resonance imaging and magnetic resonance angiography were valuable for diagnosis of moyamoya syndrome. It is suggested that moyamoya syndrome be considered as a possible cause of involuntary movements in Down syndrome patients.

Effects of human interferon on cellular response to UV in UV-sensitive human cell strains.

Cells of a human RSa cell line, with high sensitivity to UV killing and low capacity for DNA repair, when pretreated with 1-100 units/ml of human interferon (HuIFN) preparations for more than 12 h before irradiation, acquired an enhancement of UV-induced DNA-repair replication synthesis in association with recovery from inhibition of total cellular DNA synthesis and UV survival. Prompt and transient induction of plasminogen activator activities was also found within 5 min after UV irradiation in the cells pretreated with HuIFN but not in the cells non-pretreated with HuIFN. The enhancement and induction effects of HuIFN were observed, irrespective of the kind of HuIFN preparation used (alpha, beta or gamma, and natural or recombinant) and in other UV-sensitive fibroblast cells which were derived from Cockayne syndrome and xeroderma pigmentosum fibroblasts (XP1KY). However, all of the enhancement of DNA-repair synthesis and the induction of plasminogen activator activities by HuIFN was suppressed by treatment with cycloheximide immediately after UV irradiation.

Neuroradiological findings in children with congenital myotonic dystrophy

We studied seven children with congenital myotonic dystrophy, aged 2.1–8.3 years, and the results of computed tomography and magnetic resonance imaging of the brain were analyzed and neurological development was assessed from the neonatal period. We found that ventricular dilatation that had been seen on the first day of life in two of three infants had not progressed in sequential follow‐up computed tomography scans taken at intervals of one to six years. Also, in T2‐weighted magnetic resonance imagings, areas of periventricular hyperintensity were identified in all children, as well as areas of subcortical hyperintensity in one child. Further, an asphyxial episode had occurred at birth in five patients and the extent of the periventricular hyperintensity was found to correlate significantly with Apgar scores, indicating that the degree of perinatal asphyxia that had occurred was responsible for the abnormalities uncovered by the magnetic resonance imagings. However, there was no correlation between the neurodevelopmental outcome and the extent of the periventricular hyperintensity or ventriculomegaly. Therefore, in patients with congenital myotonic dystrophy, a neonatal episode of asphyxia can be responsible for a finding of periventricular hyperintensity, but it is unlikely that an integral part of the mental retardation is attributable to brain damage due to perinatal asphyxia.

The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care

Purpose:Cockayne syndrome (CS) is a rare, autosomal-recessive disorder characterized by microcephaly, impaired postnatal growth, and premature pathological aging. It has historically been considered a DNA repair disorder; fibroblasts from classic patients often exhibit impaired transcription-coupled nucleotide excision repair. Previous studies have largely been restricted to case reports and small series, and no guidelines for care have been established.Methods:One hundred two study participants were identified through a network of collaborating clinicians and the Amy and Friends CS support groups. Families with a diagnosis of CS could also self-recruit. Comprehensive clinical information for analysis was obtained directly from families and their clinicians.Results and Conclusion:We present the most complete evaluation of Cockayne syndrome to date, including detailed information on the prevalence and onset of clinical features, achievement of neurodevelopmental milestones, and patient management. We confirm that the most valuable prognostic factor in CS is the presence of early cataracts. Using this evidence, we have created simple guidelines for the care of individuals with CS. We aim to assist clinicians in the recognition, diagnosis, and management of this condition and to enable families to understand what problems they may encounter as CS progresses.Genet Med 18 5, 483–493.

Nationwide survey of nevoid basal cell carcinoma syndrome in Japan revealing the low frequency of basal cell carcinoma.

Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by developmental defects and tumorigenesis. The clinical manifestations of NBCCS have been reported in large epidemiological studies from the United States, the United Kingdom, and Australia, but not from an Asian country. We conducted a nationwide survey and identified 311 NBCCS patients in Japan. We investigated the detailed clinical manifestations of 157 patients ranging in age from 9 months to 77 years old (mean: 33.1 years). We then compared the frequency and age of onset for various tumors developed in Japanese NBCCS patients with patients from the three countries listed above in which NBCCS studies were previously conducted. Our most significant finding was the low frequency of basal cell carcinoma (BCC) in Japanese patients. Frequency of BCC in patients over 20 years of age was 51.4%, a much lower rate compared to the United States, Australia, and the United Kingdom (91%, 85%, and 73%, respectively). The mean age of BCC onset was 37.4 years of age, a much older age compared to the above‐mentioned countries. These findings suggest that differences in ethnicity and/or environmental factors affect the incidence of BCC. Because the age of BCC onset is generally higher in Japanese NBCCS patients, careful skin examination over a prolonged period of time is warranted.

Longitudinal MR imaging and proton MR spectroscopy in herpes simplex encephalitis.

Longitudinal MR imaging and proton MR spectroscopy were performed in an 11 year-old female case of herpes simplex encephalitis with a complete recovery. On MR imaging, the white matter lesions, which could be seen in the subacute stage, but not in the acute or chronic stage, might represent edema due to postinfectious neuroallergic phenomena. Proton MR spectroscopy revealed marked reduction of the NAA/Cr ratio in the chronic stage, which increased gradually to within normal range in a year.