Minako Aoki

Evaluation of accumulated mucopolysaccharides in the brain of patients with mucopolysaccharidoses by 1H-magnetic resonance spectroscopy before and after bone marrow transplantation

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.

Improvement of neurological symptoms by enzyme replacement therapy for Gaucher disease type IIIb.

Enzyme replacement therapy might improve chronic liver dysfunction and contribute to the resolution of basal ganglia lesions in patients with type 3b Gaucher disease.

Atopy and mutations of IL-12 receptor β2 chain gene

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.

RNA editing of interleukin‐12 receptor β2, 2451 C‐to‐U (Ala 604 Val) conversion, associated with atopy

Background The production of IgE in B lymphocytes is down‐regulated by IFN‐γ. IL‐12 induces IFN‐γ production by T lymphocytes and natural killer cells by binding to its specific receptor. RNA editing is a post‐transcriptional modification.

Neuroradiologic findings in Sotos syndrome.

Sotos syndrome is a well-known anomaly syndrome characterized by overgrowth, characteristic facial gestalt, and developmental delay, and haploinsufficiency of the NSD1 gene has been revealed as one of the major genetic causes. However, there have been only a few reports on neuroradiologic findings by computed tomography (CT) or magnetic resonance imaging (MRI), and functional examination of the brain has not been reported. We examined three cases with typical Sotos syndrome, which also were confirmed by genetic analysis with a specific probe for the NSD1 gene. The results of MRI showed the characteristic features that have been reported previously. The findings obtained by using single-photon emission computed tomography and magnetic resonance spectroscopy suggested an association between mental delay and behavioral tendency in Sotos syndrome and immaturity in frontal brain function. (J Child Neurol 2006;21:614—618; DOI 10.2310/7010.2006.00145).

The correlation between ovomucoid-derived peptides, human leucocyte antigen class II molecules and T cell receptor-complementarity determining region 3 compositions in patients with egg-white allergy.

Background Food allergies are more prevalent in children, due to the immature gastrointestinal epithelial membrane barrier allowing more proteins through the barrier and into circulation. Ovomucoid (OM) is one of the major allergens that is found in egg white.

Suppression of IFN-gamma production in atopic group at the acute phase of RSV infection.

Several studies have suggested that respiratory syncytial virus (RSV) bronchiolitis induced the change of cytokine production profile in childhood. We sought to determine whether the RSV‐induced cytokine production was affected by the patients atopic background. We quantified interferon‐gamma (IFN‐gamma) and interleukin (IL)‐4 in the supernatant of peripheral blood mononuclear cells (PBMCs) cultured for 24 h and in the presence of phytohemaglutinin (PHA), IL‐12, or IL‐18, from 14 infants who were divided into two groups, those who are non‐atopic and an atopic group. In RSV‐infected infants with atopic diseases, IFN‐gamma production from IL‐12‐ or especially IL‐18‐stimulated PBMCs was subtotally suppressed in the acute phase, whereas in RSV‐infected infants without atopic diseases IFN‐gamma production was not suppressed on acute phase. The IFN‐gamma suppression observed in the atopic group is not caused by the immaturity of an infants immune system since reduced IFN‐gamma production to RSV is not observed in the infants of non‐atopic group. IFN‐gamma suppression in regard to RSV infection might be caused by some genetic factor involved in the development of atopic disease such as IL‐18 signal cascade.