Hiroaki Miyahara

Elevated umbilical cord serum TARC/CCL17 levels predict the development of atopic dermatitis in infancy

Cite this as: H. Miyahara, N. Okazaki,T. Nagakura, S. Korematsu and T. Izumi,Clinical & Experimental Allergy, 2011 (41) 186–191.

A relapse of systemic type juvenile idiopathic arthritis after a rubella vaccination in a patient during a long-term remission period

An 11-year-old female patient, whose systemic type juvenile idiopathic arthritis (JIA) had maintained in remission for the previous 4 years while taking only a small amounts of ibuprofen, showed an abrupt 2nd relapse with congestive heart failure five days after receiving a live-attenuated rubella vaccine, which was a primary immunization. Her serum levels of anti-rubella IgM and IgG antibodies increased, and her laboratory findings such as a leukocytosis, elevated serum levels of CRP, IL-6 and other inflammatory cytokine profiles were similar to the findings observed during her previous JIA active stage. After being administration of co-therapy with steroid pulse, ibuprofen, methotrexate and phosphodiesterase inhibitor gradually improved her clinical symptoms such as spiky fever, heart failure and arthralgia. Her intermittent fever and increased serum levels of CRP and IL-6, however, have been sustained for more than 2 years, and this prolonged active clinical course therefore differed from her previous JIA active stage.This abrupt relapse only five days after vaccination was suggested not to be directly related with rubella infection, but instead to be related with the molecular mimicry between rubella and JIA.

Theophylline-associated seizures and their clinical characterizations

Background: To elucidate the basic mechanism of theophylline‐associated seizures (TAS), the clinical symptoms, electroencephalogram (EEG) and neuroradiological imaging of eight pediatric patients were all retrospectively evaluated.

Suppressed Expression of Autophagosomal Protein LC3 in Cortical Tubers of Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is characterized by benign tumors and hamartomas, including cortical tubers. Hamartin and tuberin, encoded by the TSC 1 and 2 genes, respectively, constitute a functional complex that negatively regulates the mammalian target of rapamycin (mTOR) signaling pathway, eventually promoting the induction of autophagy. In the present study, we assessed the induction of autophagy in cortical tubers surgically removed from seven patients with TSC in comparison with five controls of cortical tissue taken from non‐TSC patients with epilepsy. Immunoblotting demonstrated a marked reduction of LC3B‐I and LC3B‐II in tubers relative to the controls. In tubers, strong, diffuse and dot‐like immunoreactivity (IR) for LC3B was observed in dysmorphic neurons and balloon cells, but LC3B‐IR in other neurons with normal morphology was significantly weaker than that in neurons in the controls. Immunoelectron microscopy revealed diffuse distribution of LC3B‐IR within the cytoplasm of balloon cells. The dot‐like pattern may correspond to abnormal aggregation bodies involving LC3. In an autopsy patient with TSC, we observed that LC3B‐IR in neurons located outside of the tubers was preserved. Thus, autophagy is suppressed in tubers presumably through the mTOR pathway, and possibly a pathological autophagy reaction occurs in the dysmorphic neurons and balloon cells.

The indication and effectiveness of low-dose erythromycin therapy in pediatric patients with bronchial asthma*

Korematsu S, Yamamoto K, Nagakura T, Miyahara H, Okazaki N, Akiyoshi K, Maeda T, Suenobu S‐i, Izumi T. The indication and effectiveness of low‐dose erythromycin therapy in pediatric patients with bronchial asthma.
Pediatr Allergy Immunol 2010: 21: 489–492.
© 2010 John Wiley & Sons A/S

The characterization of cerebrospinal fluid and serum cytokines in patients with Kawasaki disease.

Background: The central nervous system (CNS) inflammation of Kawasaki disease (KD) has not been sufficiently evaluated in spite of the complications of irritability and CSF pleocytosis. Patients and Methods: Cerebrospinal fluid (CSF) and serum inflammatory cytokine values were simultaneously examined in 10 patients (2.6 ± 2.1 year of age) during the acute phase. They were all irritable and demonstrated mild consciousness disturbance. Results: The CSF IL6 was elevated (>3.0 pg/mL) in 6 patients, and 4 of them showed higher CSF than serum values. The CSF sTNFR1 was elevated (>0.5 μg/mL) in 6 patients, and 1 showed higher CSF than serum values. These CSF cytokine (IL6; 81.4 ± 192.8 pg/mL, sTNFR1; 1.1 ± 0.8 μg/mL) and CSF/serum ratio (IL6; 2.8 ± 5.2, sTNFR1 0.4 ± 0.4) in patients with KD were the same as those of patients with acute encephalitis/acute encephalopathy. Conclusions: The differences in the inflammatory cytokine value between CSF and serum suggest that the degree of systemic vasculitis is different between CSF and the circulating blood, and some patients with KD showed a higher degree of CSF inflammation.

Detection of platelet-binding anti-measles and anti-rubella virus IgG antibodies in infants with vaccine-induced thrombocytopenic purpura.

A 15-month-old infant presented with thrombocytopenic purpura after sequential administration of measles-rubella combined vaccine, varicella vaccine and mumps vaccine every 4 weeks. Her thrombocytopenia persisted for more than 12 months. Both anti-measles and anti-rubella virus IgG antibodies were detected in the patients-isolated platelets on day 154 of illness, which were not detected when there was a reduction of the serum IgG antibody titers on days 298 and 373 of illness, respectively.We also detected the isolated platelet-binding anti-measles and anti-rubella virus IgG antibodies in two other pediatric patients. This is the first report demonstrating direct evidence of vaccine-induced thrombocytopenic purpura.

Overexpression of p53 but not Rb in the cytoplasm of neurons and small vessels in an autopsy of a patient with Cockayne syndrome.

Cockayne syndrome presents senescence‐like changes starting in early infancy; however, the mechanism of premature aging remains unclear. In an autopsy of a 23‐year‐old woman with Cockayne syndrome, we evaluated the correlation between Cockayne pathology and the expression patterns of the senescence‐associated proteins p53 and Rb. Neuropathological findings in this case revealed basal ganglia calcification, tigroid leukodystrophy, bizarre reactive astrocytes, severe cerebellar atrophy with loss of Purkinje cells, and arteriolar/neuronal calcifications in the hypothalamus. Multiple arteriolar calcifications and sclerotic changes were seen in the central nervous system and kidney, but the endothelium of the aorta and coronary arteries remained intact appropriately for the individuals age without any finding of arteriosclerosis. Overexpression of p53 protein was confirmed in the cytoplasm of neurons in the basal ganglia, thalamus, hypothalamus, hippocampus and cerebellum, of arteriolar endothelial cells of the cerebrum and renal glomerular capillaries, and of cutaneous epithelial cells. The distribution of p53 overexpression was coincident with that of pathological alteration, such as neuronal loss, calcification and atrophy. High expression of p53 was localized in the cytoplasm, not in the nucleus. In contrast to p53, Rb was not expressed in any senescence lesion. In terms of senescence, distinct differences are found among organs in a patient with Cockayne syndrome. This segmental progeria differs from natural aging, and implicates p53 overexpression in the etiology of CS.

Elevated serum anti-phosphatidylcholine IgG antibodies in patients with influenza vaccination-associated optic neuritis.

INTRODUCTION Because the optic nerve is mainly comprised from phospholipids such as phosphatidylcholine, the association between optic neuritis, anti-phospholipids antibodies and vaccination was examined. SUBJECTS Two female pediatric patients suddenly presented bilateral optic neuritis after administration of trivalent inactivated influenza vaccine. METHODS These two patients and another 11 patients with central nervous system demyelinating diseases were examined these anti-phospholipids antibodies. And immune histopathology was examined using serum derived from a patient with optic neuritis. RESULTS High serum titer of anti-phosphatidylcholine antibody levels were detected during acute phase in patients with optic neuritis. The patients serum IgG antibodies were found to have stained the capillary endotheliums in the preserved autopsied optic nerve. Patients with optic neuritis had significantly elevated serum levels of anti-phosphatidylcholine antibody in comparison to the other patients without optic neuritis. CONCLUSION Anti-phosphatidylcholine antibodies may be one of the causes of optic neuritis.

Neuronal differentiation associated with Gli3 expression predicts favorable outcome for patients with medulloblastoma

Medulloblastoma (MB) is a malignant cerebellar tumor arising in children, and its ontogenesis is regulated by Sonic Hedgehog (Shh) signaling. No data are available regarding the correlation between expression of Gli3, a protein lying downstream of Shh, and neuronal differentiation of MB cells, or the prognostic significance of these features. We re‐evaluated the histopathological features of surgical specimens of MB taken from 32 patients, and defined 15 of them as MB with neuronal differentiation (ND), three as MB with both glial and neuronal differentiation (GD), and 14 as differentiation‐free (DF) MB. Gli3‐immunoreactivity (IR) was evident as a clear circular stain outlining the nuclei of the tumor cells. The difference in the frequency of IR between the ND+GD (94.4%) and DF (0%) groups was significant (P < 0.001). The tumor cells with ND showed IR for both Gli3 and neuronal nuclei. Ultrastructurally, Gli3‐IR was observed at the nuclear membrane. The overall survival and event‐free survival rates of the patients in the ND group were significantly higher than those in the other groups. The expression profile of Gli3 is of considerable significance, and the association of ND with this feature may be prognostically favorable in patients with MB.