Takahide Teramoto

Reduced IFNγ production in response to IL‐12 stimulation and/or reduced IL‐12 production in atopic patients

Several studies have shown that interleukin (IL)‐4 and interferon‐gamma (IFNγ) are important for the regulation of IgE production and that IL‐12 induces IFNγ.

Clinical improvement of diffuse lymphangiomatosis with pegylated interferon alfa-2b therapy: case report and review of the literature.

Diffuse lymphangiomatosis is a very rare congenital disease, characterized by diffuse or multifocal lymphangioma in the skeletal tissue, spleen, liver, mediastinum, and/or lung. The prognosis is usually poor, especially for children with thoracic lesion, and treatments for the disease are controversial. The authors report a 9-year-old boy with diffuse lymphangiomatosis involving the thorax with pleural effusions, the spleen, and systemic bone. The patient was treated with pegylated interferon alfa-2b, and achieved good clinical and radiological improvement.

Acute cerebellitis in primary human herpesvirus-6 infection

Acute cerebellitis has been described in infections caused by many kinds of pathogens, but as yet has not been described in human herpesvirus-6 (HHV-6) infection [11]. We report here a case of acute cerebellitis during primary HHV-6 infection. A 2.5-year-old girl was admitted to a local hospital because of a 3-day history of high fever and generalised tonic convulsions which occurred four times on the 3rd day. Physical examination showed a normally developed alert infant with truncal ataxia. A cranial CT scan was normal. Her CSF showed normal concentrations of protein and glucose and no pleocytosis. In the evening of the day of admission, she had five episodes of generalised tonic convulsions with high fever and became irritable, but was well oriented. Skin erythema on the face, trunk, and extremities clearly appeared the next morning and she became drowsy; she was then transferred to our hospital. On admission, she was unconscious and showed a withdrawal movement, crying briefly in response to pain (Glasgow coma scale E3V2M4). Both pupils were equal in size and prompt in light reflex and her tendon reflexes were normal. There was no optic oedema. There was a rubella-like erythema on her face, trunk, and extremities without vesicles or petechiae. Laboratory data, including levels of ammonia, lactate and pyruvate, were normal except that of serum CK (1711 IU/l). Analysis of CSF showed 402 leukocytes/mm (segmented 322, mononuclear 80), a glucose level of 68 mg/dl and a protein level of 79 mg/dl. No oligoclonal IgG bands or myelin basic protein were observed. Neuron specific enolase (NSE) in CSF was elevated (130 ng/ml; control mean 13.1 ng/ml). Her EEG showed normal findings. MRI on the 5th day of illness demonstrated a diffuse hyperintensity in the cerebellum based on the diffusion-weighted sequence but not obvious on the T1or T2-weighted images (Fig. 1a). Brain single photon emission CT (SPECT) by ECD on the same day showed a marked hyperperfusion in the bilateral hemispheres of the cerebellum (Fig. 1b,c). With the diagnosis of acute encephalitis, predominantly in the cerebellum, she was treated with mannitol, dexamethasone, and phenobarbital. Acyclovir (10 mg/kg per dose) was used every 8 h for 2 weeks. She did not experience any convulsions after the therapy had started and she recovered her full consciousness within 1 week. After this significant recovery, severe cerebellar dysfunctions such as ataxia and dysmetria were more obvious, but excellent improvement was achieved within 1 month without any sequelae. The hyperintensity on MRI and hyperperfusion on SPECT in the cerebellum disappeared with clinical improvement (Fig. 1d,e,f). In addition to these radiological findings, MRI on admission demonstrated abnormal high intensities at the splenium of the corpus callosum on T2and diffusionweighted images, which disappeared 72 h after the first MRI [6]. Titres of serum immunoglobulins for HHV-6 (fluorescent antibody method) were significantly elevated during the illness (on the 6th day of illness: IgG <1:10, IgM 1:10; on the 25th day of illness: IgG 1:320, IgM 1:20), while those in CSF were not (on the 6th day of illness: IgG <1:10, IgM <1:10; on the 25th day of illness: IgG <1:10, IgM <1:10). The titres against the many other pathogens which can cause erythema or encephalitis including HHV-7, herpes simplex, EpsteinBarr virus, varicella zoster virus, rubella virus, measles virus, parbovirus, enterovirus 71, influenza virus, and Mycoplasma pneumoniae were not significantly elevated. Cultures of CSF did not reveal any viral pathogen. PCR analysis of CSF with specific primers for the U31 gene of HHV-6 (forward primer: 5’-TGCACCACCTCTCTGCTTATAAC-3’, reverse primer: 5’-CTAATTGCCGTAGCGTGAGAAC-3’) and the sequencing of the Eur J Pediatr (2003) 162: 801–803 DOI 10.1007/s00431-003-1287-7

Progressive multifocal leukoencephalopathy in a patient with X-linked agammaglobulinemia.

To our knowledge, this is the first case report describing progressive multifocal leukoencephalopathy (PML) associated with X-linked agammaglobulinemia. The JC virus was confirmed at autopsy and PML was diagnosed. Humoral immunodeficiency with normal cellular immunity could be infected with JCV.

Autonomic regulation after exercise evidenced by spectral analysis of heart rate variability in asthmatic children

BACKGROUND Bronchial asthma is associated with abnormal autonomic nervous function in childhood. Exercise is one of the most common precipitating factors of acute asthmatic crises although the exact mechanism of autonomic regulation in asthmatic children after exercise is unclear. OBJECTIVE The aim of this study was to investigate the features of autonomic regulation after exercise in asthmatic and control children. METHODS Pulmonary function tests and heart rate variability spectral analysis were performed in 15 asthmatic children and 7 control children (age 6 to 15 years) during and after an exercise challenge. RESULTS The maximum % fall of forced expiratory volume in 1 second (FEV1) was significantly greater (P < .01) in asthmatic subjects (9.1 +/- 5.1%) than in normal control subjects (1.0 +/- 2.5%). The high frequency band (HF) amplitude, an index of cardiac vagal tone, 5 minutes after exercise was significantly higher (P < .05) in the asthmatic subjects (14.4 +/- 7.9 msec) than in control subjects (5.9 +/- 2.6 msec). Furthermore, the difference in the HF amplitude between the control group and the exercise-induced asthma group was significant both 5 minutes (P < .01) and 10 minutes (P < .05) after challenge. There was a significant correlation (P = .565, P = .0165) between HF amplitude 5 minutes after exercise and the magnitude of the decrease in FEV1. On the other hand, no significant difference was observed in the low frequency band amplitude between the controls and the asthmatic subjects. The ratio of low frequency to high frequency power, which is suggested to correlate with cardiac sympathetic activity, did not differ between the two groups. CONCLUSION These findings suggest that autonomic nervous activities, particularly vagal response after exercise, in asthmatic children is different from that in control children.

Reduced Expression of the Interferon‐Gamma Messenger RNA in IgG2 Deficiency

The specific defect that causes IgG2 deficiency, which is one of the primary immunodeficiencies, is unknown. Recently, it was shown that interferon‐γ (IFN‐γ) induces synthesis of human germline Cγ2 transcripts. In the authors’ previous study and the present one, peripheral blood lymphocytes (PBLs) of all five tested patients with IgG2 deficiency failed to produce enough IFN‐γ when stimulated with phytohaemagglutinin or concanavalin A although they produced a sufficient amount of interleukin‐2 (IL‐2). The low level of IgG2 production in pokeweed mitogen‐stimulated PBLs of four tested patients was improved by the addition of recombinant IFN‐γ. In this study, the amount of IFN‐γ messenger RNA showed various degrees of reduction in all five tested patients. Sequence analysis of the IFN‐γ coding regions and flanking regions revealed neither a point mutation nor a deletion for any of the patients. Thus the results suggest that the reduced expression of IFN‐γ messenger RNA may play an important role in the IgG2 deficiency of these patients.

Escherichia coli O-157-induced hemolytic uremic syndrome: Usefulness of SCWP score for the prediction of neurological complication

Background:  Hemolytic uremic syndrome (HUS) is commonly caused by hemorrhagic colitis with Shiga toxin‐producing Escherichia coli O‐157. Central nervous system (CNS) involvements, including seizures, encephalopathy and brain infarction, are serious complications, but there are no useful scores for the prediction of CNS complications.

Microsatellite instability in B-cell lymphoma originating from Bloom syndrome.

Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized by lupus‐like erythematous telangiectasias of the face, sun sensitivity, stunted growth infertility and immunodeficiency. In addition, BS patients are highly predisposed to cancers. Although recently the causative gene of BS (BLM) was identified as a DNA helicase homologue, the function of BLM in DNA replication has not been elucidated. In this study, p53 mutation and microsatellite instability in B‐cell lymphomas originating from 2 sibling BS patients were investigated. In the originally developed tumor of both patients, no p53 mutation was detected. In one patient, however, after treatment by ionizing radiation the B‐cell lymphoma recurred, showing a 9‐bp deletion in exon 7. In lymphoma cells and an EB‐virus‐transformed cell line from BS lymphocytes of this patient, microsatellite instability was also detected from the reduced length of microsatellite DNA markers, although in the other patient microsatellite instability was not detected. Thus, 2 B‐cell lymphomas, despite having the same BLM mutation, showed different phenotypes in terms of p53 mutation and microsatellite instability.

Leaky phenotype of X-linked agammaglobulinaemia in a Japanese family

X‐linked agammaglobulinaemia (XLA) is an inherited immunodeficiency that is caused by a block in early B‐cell differentiation. Whereas early B precursors in the bone marrow are present in substantial numbers, XLA‐affected individuals have dramatically reduced numbers of circulating mature B cells, plasma cells and immunoglobulins of all isotypes. We report on a Japanese family with 3 XLA patients, in whom the serum immunoglobulin levels and number of B cells showed a significant difference among them in spite of harbouring the same splice donor site mutation in the BTK gene. We developed concise method for detection of this mutation, which is helpful for discovering the carrier. Patient 2 showed a significant serum immunoglobulin levels of all isotypes, including allergen‐specific IgE. Expression of a normal and truncated size BTK gene was detected in patient 2′s peripheral blood mononuclear cells (PBMCs). Expression of BTK protein was also detected in some B cells. These results suggest that the leaky phenotype in patient 2 was caused in part by the expression of a normal BTK gene transcript. The increased frequency of infection with age expanded the number of B cells with normal BTK gene expression and produced the serum immunoglobulin, including IgE.

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.