Mizuho Watanabe
Gifu University
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Pediatric Research | 2001
Yukitoshi Takahashi; Kazuko Sukegawa; Minako Aoki; Akiko Ito; Kiyotaka Suzuki; Heima Sakaguchi; Mizuho Watanabe; Kouji Isogai; Shinji Mizuno; Hiroaki Hoshi; Kazuo Kuwata; Shunji Tomatsu; Shunichi Kato; Tsuyoshi Ito; Naomi Kondo; Tadao Orii
In seven patients with mucopolysaccharidoses (1 Hurler, 1 Hurler-Scheie, 4 Hunter, 1 Sly), cranial 1H-magnetic resonance spectroscopy was performed to evaluate the accumulation of mucopolysaccharides and biochemical changes in the CNS in vivo before and after bone marrow transplantation (BMT). In two of seven patients, 1H-magnetic resonance spectroscopy was performed before and after BMT. Nuclear magnetic resonance spectra of dermatan sulfate and chondroitin sulfate-C and magnetic resonance spectroscopy of chondroitin sulfate-C and urine from patients with mucopolysaccharidoses showed resonance higher than the chemical shift of myoinositol in the brain (3.7 ppm). The resonance was considered to contain signals from mucopolysaccharide molecules. The resonance was measured as presumptive mucopolysaccharides (pMPS). In white matter lesions detected by magnetic resonance imaging, pMPS/creatine ratios and choline/creatine ratios were consistently higher than control ratios. In white matter without lesions, choline/creatine ratios were higher than control ratios. Patients with higher developmental quotient or intelligence quotient tended to show higher N-acetylaspartate/creatine ratios and lower pMPS/creatine ratios in basal ganglia. After BMT, the pMPS/creatine ratio in white matter lesions of patient 3, with Hunter syndrome, was slightly decreased, but in none of the patients was the ratio ever below the control ratios, even 7 y after BMT. In white matter without lesions, the pMPS/creatine ratio in patient 3 was decreased to the control ratios after BMT, but although the choline/creatine ratios were gradually decreased, they remained higher than the control ratio, 2 y after BMT. These results suggest that evaluation of pMPS, choline, and N-acetylaspartate by 1H-magnetic resonance spectroscopy is an important technique that may provide useful biochemical information in vivo on the neurologic process and the efficacy of BMT in patients with mucopolysaccharidoses.
Clinical & Experimental Allergy | 2001
H. Shikano; Zenichiro Kato; Hideo Kaneko; Mizuho Watanabe; R. Inoue; Kimiko Kasahara; Masao Takemura; Naomi Kondo
Background Several studies have shown that interleukin (IL)‐4 and interferon‐gamma (IFN‐γ) are important for the regulation of immunoglobulin E (IgE) production and that IL‐18 and IL‐12 induce IFN‐γ.
Clinical & Experimental Allergy | 2001
Naomi Kondo; Eiko Matsui; Hideo Kaneko; Toshiyuki Fukao; Takahide Teramoto; R. Inoue; Mizuho Watanabe; Minako Aoki; Kimiko Kasahara; Naoko Morimoto
Atopy, which is characterized by enhanced IgE responses to environmental antigens, leads to clinical disorders such as asthma, eczema and rhinitis. These atopic disorders develop due to the interactions between genetic and environmental factors. The class switch to IgE and production of IgE in B lymphocytes are regulated by cytokines [1±6]. IL-12 is one of the most important cytokines which down-regulate IgE production. In this paper, the relationship between atopy and aberrant IL-12 signal transduction, particularly mutations in the IL-12 receptor (IL-12R) chain gene is focused upon.
International Archives of Allergy and Immunology | 2001
Naomi Kondo; Eiko Matsui; Hideo Kaneko; Toshiyuki Fukao; Takahide Teramoto; Ryosuke Inoue; Mizuho Watanabe; Kimiko Kasahara; Naoko Morimoto
Background: The atopic patient has a predisposition to selective synthesis of IgE antibodies to common environmental antigens. IgE production is upregulated by interleukin-4 (IL-4) and downregulated by interferon-γ (IFN-γ). IL-12 is a cytokine that induces IFN-γ production. The signal of IL-12 is transduced through the IL-12 receptor (IL-12R) and Stat4. Methods: We examined IFN-γ production in peripheral blood mononuclear cells (PBMCs) following stimulation with IL-12 or phytohemagglutinin (PHA) in healthy controls and atopic patients. Moreover, sequences of the IL-12R β2 chain gene were analyzed. Results: The serum IgE levels were negatively correlated (p < 0.001) with IFN-γ production. In 24 out of 75 atopic patients, IFN-γ production in PBMCs following stimulation with IL-12 was under the detection limit, but PHA stimulation elicited detectable IFN-γ production. Sequence analysis of the cDNA of IL-12R β2 revealed three kinds of distinct genetic mutations (2496 del 91, 1577 A to G and 2799 A to G) in 10 unrelated subjects of the 24 whose IFN-γ production following IL-12 stimulation was under the detection limit. PBMCs cultured with IL-12 and PHA in these 10 subjects showed decreased tyrosine phosphorylation of Stat4. Conclusions: The results of our study indicate that atopic diseases are caused, in part, by impairment of the IL-12 signal cascade, which downregulates IgE production, and that the mutation of the IL-12R β2 chain gene is one of the causative genes for atopy.
European Journal of Pediatrics | 2003
Zenichiro Kato; Mizuho Watanabe; Naomi Kondo
A drug-induced immunoglobulin deficiency has been associated with many drugs, yet carbamazepine (CBZ) associated immunoglobulin deficiency has not been well characterised [9]. We present here a case of immunoglobulin deficiency associated with CBZ therapy that resulted in recurrent enterocolitis and otitis media. A 9-year-old boy was admitted to our hospital because of diarrhoea of 1-week duration. He was not febrile, but he had abdominal pain with watery stools. He was diagnosed as having enterocolitis and treated with continuous drip infusion and antibiotics. He recovered quickly and was discharged after 1 week. A laboratory test showed a white blood count of 2,800 mm (neutrophils 29%, lymphocytes 57%, monocytes 10%) and C-reactive protein level of <0.15 mg/dl. A stool culture did not show any pathologic bacteria, while throat swab culture was positive for Haemophilus influenzae. Hypogammaglobulinaemia was observed for IgG and IgA (IgG, 693 mg/dl; IgA, 15 mg/dl; IgM, 172 mg/dl; Table 1). Family history, particularly with respect to immunological diseases, was unremarkable. The patient had been treated with valproate (VPA) and CBZ for complex partial seizures. Past records of immunoglobulin levels showed a gradual decrease in IgG and IgA after administration of CBZ (300 mg/day) in addition to VPA (600 mg/day) (Table 1). At this admission he was given 600 mg of VPA and 500 mg of CBZ; the serum concentrations were 60.2 lg/ml (therapeutic range: 50–100 lg/ml) and 11.4 lg/ml (therapeutic range: 4–8 lg/ml), respectively. Subsequent immunological examinations revealed a decrease in levels of IgG2 and IgG4 (IgG1, 634 mg/dl; IgG2, 10 mg/dl; IgG3, 23 mg/dl; IgG4, <0.45 mg/dl). The number of circulating IgG+ B cells and IgA+ B cells was low (0%), while the number of circulating IgM+ B cells and IgD+ B cells was slightly elevated (15% and 14%, respectively). The levels of IgG2 against both Haemophilus influenzae and Streptococcus pneumoniae were markedly decreased, i.e. <20 ng/ml and 0.2 lg/ml, respectively. Other immunological examinations including cell marker analysis (CD3+, CD8+, CD4+, CD19+) and mitogen stimulated cell responses (PHA, Con-A, PWM) were normal. CBZ was replaced with zonisamide (ZNS) and the patient had no more episodes of complex partial seizures for 1 year. However, his recurrent enterocolitis and otitis media have not been resolved. The IgG2, IgG4 and IgA levels remain very low (IgG, 680 mg/dl; IgA, 7 mg/ dl; IgM, 92 mg/dl; IgG1, 443 mg/dl; IgG2, <8.0 mg/dl; IgG3, 38 mg/dl; IgG4, <3.0 mg/dl) and the number of circulating IgA+ B cells was low (0%), while IgG+, IgM+ or IgD+ B cells were almost normal. An adverse effect of CBZ on the serum IgG2 level (from 321 mg/dl to 247 mg/dl of mean value in 20 patients) was reported by Gilhus et al. [2]. To our knowledge, only five cases of multiple immunoglobulin deficiency associated with CBZ were reported (Table 2). These patients had urinary tract infection, recurrent respiratory infection, sinusitis, fever with rash, or leishmaniasis. They recovered following antibiotic therapy alone or in combination with granulocyte-colony stimulating factor (G-CSF) therapy for leukopoenia. Our patient showed recurrent symptoms of enterocolitis and otitis media, which were treated with antibiotics, but his disease condition did not require additional therapy such as G-CSF therapy. Total B cell count in 3 of 5 reported cases decreased. In our patient, total B cell count did not decrease, but B cells expressing IgG or IgA did decrease. Withdrawal of CBZ was effective in 2 out of 5 patients in CBZ-associated immunoglobulin deficiency Eur J Pediatr (2003) 162: 209–211 DOI 10.1007/s00431-002-1146-y
Biochemical and Biophysical Research Communications | 1999
Eiko Matsui; Hideo Kaneko; Toshiyuki Fukao; Takahide Teramoto; Ryosuke Inoue; Mizuho Watanabe; Kimiko Kasahara; Naomi Kondo
The Journal of Allergy and Clinical Immunology | 2002
Mizuho Watanabe; Hideo Kaneko; Hiroaki Shikano; Minako Aoki; Heima Sakaguchi; Eiko Matsui; Ryosuke Inoue; Zenichiro Kato; Kimiko Kasahara; Osamu Fukutomi; Tomio Kondo; Naomi Kondo
International Journal of Molecular Medicine | 2003
Minako Aoki; Eiko Matsui; Hideo Kaneko; Ryosuke Inoue; Toshiyuki Fukao; Mizuho Watanabe; Takahide Teramoto; Zenichiro Kato; Kiyotaka Suzuki; Yasuyuki Suzuki; Kimiko Kasahara; Naomi Kondo
European Journal of Pediatrics | 2001
Minako Aoki; Toshiyuki Fukao; Yukiko Fujita; Mizuho Watanabe; Takahide Teramoto; Yoshihiro Kato; Yasuyuki Suzuki; Naomi Kondo
Allergology International | 2003
Hidenori Ohnishi; Zenichiro Kato; Mizuho Watanabe; Osamu Fukutomi; Ryosuke Inoue; Takahide Teramoto; Naomi Kondo