Jun-ichi Hirao

Generalized metaphyseal modification with cone-shaped epiphyses following long-term administration of 13-cis-retinoic acid

Abstract We report on a 6-year-old girl with short stature which developed following the administration of 13-cis-retinoic acid (a synthetic derivative of vitamin A or retinoid) for 40 months as adjunct chemotherapy for neuroblastoma. Radiographic examination suggested osteophyte formation in the cervical spine, which is the most common skeletal manifestation of retinoid toxicity [10, 11]. In addition, severe metaphyseal cupping with a cone-shaped epiphysis primarily affecting rapidly growing long bones was found, which represented impaired enchondral ossification. This epi-metaphyseal alteration, though unusually severe, was reminiscent of the premature epiphyseal closure which has been described as an adverse effect of 13-cis-retinoic acid [10–12]. Other minor skeletal changes included posterior scalloping of the vertebral bodies and increased interpediculate distances, which were related to a widened spinal canal found on CT. A literature search disclosed several primary skeletal dysplasias with superficial radiological similarities to those of the present patient. However, these entities showed significant clinical and radiological differences from our patient. Conclusion The precise cause of the generalized skeletal alteration in the present patient remained unknown, but it conceivably resulted from the administration of 13-cis-retinoid acid.

Development of coronary artery lesions in Kawasaki disease patients in relation to plasma interferon‐γ and interleukin‐α levels in the acute phase

Kawasaki disease (KD) is an acute self-limited childhood vasculitis of unknown etiology with the clinical features of fever, rash, lymphadenopathy, oropharyngeal inflammation, conjunctivitis and peripheral desquamation.’ The blood concentrations of interferon (1FN)-y and interleukin (1L)-2, produced by type I helper T cells (ThI),’ are elevated in patients with KD in the acute phase, and high, in particular, in KD patients with coronary artery lesions (CAL).3.4 However, the blood concentrations of cytokines produced by type 2 helper T cells (Th2),’ for example, IL-4, 6, 10, are not fully determined in patients with CAL. The Th I/Th2-like cytokine profile may be closely associated with the disease state of protection from infection and immunologic diseases.’ In the present study, we investigated the cytokine profile in KD by using the plasma of patients with KD in the acute and convalescent phase, and by simultaneously measuring the concentrations of IFN-y, a typical Thl-like cytokine, and of IL-4, a typical Th2-like cytokine, and compared the Th liTh2-like cytokine profile in KD with CAL and without CAL. the onset of disease in each patient. The day of onset of fever was recognized as the first day of illness.The acute phase was considered to be the second to sixth day (4.0 f 1.1 days) before the treatment, and the convalescent phase was the 25th to the 40th day (35.1 f 8.8 days) when the clinical symptoms disappeared and all laboratory test results showed a normal state. Nine healthy children aged 3 months to 5 years (mean 1 year 1 1 months) were selected as control subjects.

Erratum to “An analysis of epilepsy with chromosomal abnormalities” [Brain Dev. 27 (2005) 370–377]

Erratum to “An analysis of epilepsy with chromosomal abnormalities” [Brain Dev. 27 (2005) 370–377] Hideo Yamanouchi*, George Imataka, Eiji Nakagawa, Akihisa Nitta, Naomitsu Suzuki, Jun-ichi Hirao, Hiroshi Suzumura, Hiroshi Watanabe, Osamu Arisaka, Mitsuoki Eguchi Department of Pediatrics and Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan Obstetrics, Dokkyo Univerity School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-0293, Japan

The Effect of Gamma Globulin for Apoptosis of the Kawasaki Disease Patient Neutrophils

(Objective) Intravenous gamma globulin (IVGG) treatment is the most important therapy in the Kawasaki disease (KD), however there are many uncertainties about active mechanism of this treatment. This time, we examined active mechanisms of IVGG treatment affecting on apoptosis of neutrophils. (Patients and controls) Fifteen subjects (4 months ∼ 4 years old) were selected from the KD patients who had been admitted to Dokkyo University Hospital between June, 2000 and May, 2001. Healthy adults were used as controls.(Materials and methods) (1) Neutrophils were separated from heparinized blood by the specific gravity centrifugation. (2) Venoglobulin-I was used as human IgG for this experiment. (3) Apoptosis was determined with microscopic examination and flow cytometry. DNA quantity of the cells stained with PI alone and PI and anexin V was measured in flow cytometry.(Results) (1) Spontaneous apoptosis on KD patient neutrophils was more delayed than that on controls, as the picking illness day was earlier. (2) When healthy adult neutrophils was cultured in the presence of IgG (1mg/ml), apoptosis was promoted, but this effect was not observed under less than 0.1mg/ml IgG. Therefore, IgG was used at the concentration of 1mg/ml in further experiments. (3) The morphological changes unlike control neutrophils were observed on KD patient neutrophils after the culture in the presence of IgG. (4) Based on apoptosis pattern of neutrophils in the presence of IgG, samples were divided into two groups, promoted example and not. The promotion of apoptosis by the IgG addition in vitro was observed in about half of samples from the patients, in which IVGG gave more remarkable effects clinically. (Conclusions) We considered the possibility in which one part of the clinical effects of IVGG treatment had appeared by promoting the apoptotic effects to neutrophils.

Immunosuppressive factors in sera of children with non A, non B, hepatitis

It has been reported that sera of patients with acute phase of hepatitis B or other various diseases contain immunosuppressive factor(s). Today, the research of etiologic virus(es) has been tried about non-A, non B hepatitis. We used sera of six children with nonA, non B hepatitis and studied whether those contained immunosuppressive factor(s). Regarding to those factors, we researched firstly rosette inhibition factor (RIF) that suppressed rosette formation of T lymphocytes and sheep red blood cells, and secondly serum immunosuppressive factor (SIF) that suppressed mitogeninduced activation of lymphocytes. It was accepted that those sera contained both of RIF and SIF at high rates and, both factors disappeared with improvement of liver functions, When those sera were classified by the density ultracentrifugation separation method, RIF was present in the low density lipoprotein fraction (1.01 6 < d < 1.063) and, SIF in the lipoprotein deficient serum (d > 1.25). Therefore, the two factors would be different from each other.