Safety and tolerability of IgPro10 in Japanese primary immunodeficiency patients: a registrational study.

Studies investigating the safety of IgPro10 (Privigen, CSL Behring, King of Prussia, PA, USA) in Japanese patients with primary immunodeficiency (PID) are lacking. This study evaluated safety and tolerability of IgPro10 in Japanese patients with PID. In this prospective, open-label, single-arm, registrational study for Japan, IgPro10 was administered intravenously at pre-study doses of 138-556 mg/kg body weight per 3-/4-weekly dosing cycle for up to 4 months.

Pediatric intestinal Behçet disease complicated by myeloid malignancies.

Behçet disease (BD) is rarely seen in children. Its clinical manifestations are believed to differ between pediatric and adult patients. The characteristics of BD complicated by myelodysplastic syndrome (MDS) are well established for adult patients; however, because only a few cases of pediatric-onset BD complicated by MDS have been reported, its clinical characteristics remain unknown.

Cellulitis-Like Rash Associated with Kawasaki Disease.

We present the case of a 5-year-old-boy who developed a fever and cellulitis-like groin rash 5 days before developing conjunctivitis and 6 to 7 days before other typical signs of Kawasaki disease (KD) appeared. The cellulitis failed to respond to antibiotics and no pathogens were isolated. His fever and clinical signs resolved with intravenous immunoglobulin and high-dose aspirin after discontinuation of antibiotics.

Immunity against Mycobacterium tuberculosis and the risk of biologic anti-TNF-α reagents.

A third of the world's population is exposed to Mycobacterium tuberculosis in their lifetime. Over eight million people develop a tuberculosis (TB) illness and 1.3 million people die from the disease every year.

[Immunity against mycobacterium tuberculosis and risk of biological anti-rheumatic agents].

A third of world's population is invaded with Mycobacterium tuberculosis, about 9.0 million people developed tuberculosis (TB) illness and 1.3 million people died from the disease every year.

Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disorder characterized by an inability to produce reactive oxygen species, resulting in recurrent life-threatening infections. Curiously, half of the patients with CGD suffer from aseptic bowel inflammation (CGD colitis) due to dysregulated inflammation induced by TNF-α and IL-1β. Thus, developing therapies that regulate excessive inflammatory responses without interrupting antimicrobial immunity would benefit CGD colitis patients.

Onset of polyarticular juvenile idiopathic arthritis with both anti-cyclic citrullinated peptide antibodies and rheumatoid factor in a 3-year-old girl.

This report describes 3 year old girl with the unusual presentation of polyarticular juvenile idiopathic arthritis (JIA) with anti-cyclic citrullinated peptide (anti-CCP) antibodies and a positive rheumatoid factor (RF). She was initially treated with a nonsteroidal anti-inflammatory drug (NSAID; ibuprofen) followed by methotrexate (MTX, 10 mg/m2/week) and prednisolone (0.25 mg/kg/day), but these treatments were ineffective.

Tumor necrosis factor-α can induce Langhans-type multinucleated giant cell formation derived from myeloid dendritic cells.

The formation of the rich cellular features of MGCs, where the nuclei are arranged circularly at the periphery of the cell (morphologically epithelioid; Langhans-type), is assumed to be associated with any granulomatous disease. The mechanism by which TNF controls the formation of human MGCs in vitro was investigated, focusing on the effect of the TNF-neutralizing antibody. Peripheral blood monocytes were isolated with mAb-coated immunologic magnetic beads and cultured for 10 days in the presence of 20 ng/mL GM-CSF and 10 ng/mL IL-4.

Increased eosinophilic cationic protein in nasal fluid in hospitalized wheezy infants with RSV infection.

Background: Respiratory syncytial virus (RSV) is a major respiratory pathogen which causes bronchiolitis with dyspnea and wheezing in children less than 2 years old. RSV bronchiolitis in infancy severe enough to cause hospitalization might be a risk factor for allergic sensitization and bronchial asthma in future. However, the pathophysiology behind this development has not been clearly characterized.

[Thalidomide as immunomodulatory drug: pharmacological actions and its indications].

Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modulatory drug. It has been administered successfully for the treatment of erythema nodosum leprosum, aphthous ulceration and cachexia in HIV disease, inflammatory bowel diseases, and several malignant diseases. The suppressive effect of thalidomide on the activation of the nuclear transcription factor NF-κB may explain these effects of thalidomide.

The clinical characteristics of vitamin D deficiency in childhood: a systematic literature review of Japanese patients.

To describe the characteristics of children with vitamin D deficiency, we reviewed the reports of vitamin D deficiency among Japanese children that were published between 1989 and 2008. We identified 25 patients with vitamin D deficiency in 9 published studies and evaluated their clinical characteristics together with those of 3 patients we recently treated. The patients were distributed in two distinct age groups at diagnosis: < 1 year old and > or = 1 year old.

Increase of tumor necrosis factor-alpha in the blood induces early activation of matrix metalloproteinase-9 in the brain.

Increases of cytokine in the blood play important roles in the pathogenesis of influenza-associated encephalopathy. TNF-alpha was administered intravenously to wild-type mice, after which blood, CSF and brain tissue were obtained, and changes in BBB permeability, the amounts of MMP-9 and TIMP-1, and the localization of activated MMP were assessed. There was a significant increase in BBB permeability after 6 and 12 hr.

Thalidomide dramatically improves the symptoms of early-onset sarcoidosis/Blau syndrome: its possible action and mechanism.

Objective: Early-onset sarcoidosis (EOS), which occurs in children younger than 5 years of age, is associated with granulomatous lesions and a sporadic genetic mutation of the nucleotide-binding oligomerization domain 2 that causes constitutive NF-kappaB activation. The symptoms of EOS can be uncontrollable, progressive, and associated with profound complications. However, appropriate therapy is still under investigation.

Adult onset X-linked chronic granulomatous disease in a woman patient caused by a de novo mutation in paternal-origin CYBB gene and skewed inactivation of normal maternal X chromosome.

We report a 28-year-old woman patient suffering from refractory subcutaneous abscess. Stimuli-induced microbicidal reactive oxygen metabolites formation test of the patient's neutrophils revealed that only 9.6% of the neutrophils produced H2O2.

Anakinra improves sensory deafness in a Japanese patient with Muckle-Wells syndrome, possibly by inhibiting the cryopyrin inflammasome.

Muckle-Wells syndrome (MWS) is a dominantly inherited autoinflammatory syndrome. Patients with MWS have a mutation in CIAS1, the gene encoding cryopyrin, a component of the inflammasome that regulates the processing of interleukin-1beta (IL-1beta). In this report we describe an 8-year-old Japanese girl with MWS who had symptoms of periodic fever, urticarial rash, conjunctivitis, arthropathy, and sensory deafness.

Recent changes in the trends of seasonal influenza outbreaks in the Nagano Prefectural area of Japan: an oseltamivir effect?

We carried out a study to assess the pharmacological role of oseltamivir in the regulation of influenza epidemics in Japan, examining data for the years 1998 to 2006 from Nagano Prefecture. Oseltamivir is effective for the treatment of influenza, and its use in Japan has increased in the 3 years from 2003 to 2006. We found that, in the Nagano Prefectural area, the peak in the number of influenza infections showed a deviation to later periods after the 2003 season.

Thalidomide for treatment of intestinal involvement of juvenile-onset Behçet disease.

Background: Thalidomide has been identified and its anti-inflammatory and immunomodulatory properties clarified. This report expands our report of 2 entero-Behçet disease children who developed significant steroid toxicity and improved dramatically with thalidomide.

Methods: We studied the effects of thalidomide in 7 juvenile-onset patients with severe, recurrent intestinal involvement of Behçet disease.

Simultaneous onset of type 1 diabetes in monozygotic twins younger than 1 year.

This report describes type 1 insulin deficient diabetes mellitus (IDDM) arising in identical twins aged under one year. One twin presented with symptoms and was diagnosed with type 1 IDDM; the diagnosis of type 1 IDDM was simultaneously made in the second twin without clinical symptoms. Both twins were positive for anti-GAD (glutamic acid decarboxylase) antibody at first, and then positive for islet cell antibodies.

Perfluorocarbon suppresses lipopolysaccharide- and alpha-toxin-induced interleukin-8 release from alveolar epithelial cells.

Background/aims: Human pulmonary alveolar epithelial (A549) cells release interleukin-8 (IL-8) on stimulation by lipopolysaccharide (LPS) and alpha-toxin. We hypothesised that the perfluorocarbons (PFCs), perflubron and FC-84, would block stimulation of A549 cells by these toxins.

Methods: The levels of IL-8 production in A549 cells were measured following exposure to toxins for 24 h with or without PFC.

CD30+ anaplastic large cell lymphoma complicated by pyoderma gangrenosum with increased levels of serum cytokines.

We here present the case of a 5-yr-old girl with pyoderma gangrenosum (PG) in association with underlying CD30+ anaplastic large cell lymphoma with increased serum cytokine levels (interleukin-8, granulocyte colony-stimulating factor). An association between PG and increased cytokine levels was suggested. Even in children, dermatosis of PG should receive prompt careful evaluation for underlying hematological malignancy.

Differential effects of short-acting beta2-agonists on human granulocyte functions.

Background: beta2-Adrenergic agonists play a pivotal role in the management of bronchial asthma. Although the major effect of short-acting beta2-agonists on the airway is relaxation of smooth muscles, they may also have several effects on surrounding immunomodulatory cells.

Methods: We examined whether widely used short-acting beta2-agonists differ in their ability to modulate granulocyte functions, such as superoxide anion (O2-) production and degranulation.

Effective combination therapy using interferon-gamma and interleukin-2 for disseminated Mycobacterium avium complex infection in a pediatric patient with AIDS.

A 5-year-old girl presented with disseminated Mycobacterium avium complex infection during advanced human immunodeficiency virus infection. Interferon-gamma or interleukin-2 monotherapy showed only limited effects. Use of a combination of interferon-gamma and interferon-2 resulted in a remarkable improvement in the patient's condition, accompanied by an increase in circulating CD4+ T cells.

Superoxide dismutase (SOD) as a potential inhibitory mediator of inflammation via neutrophil apoptosis.

Superoxide dismutase (SOD) is supposed to be an effective agent for neutrophil-mediated inflammation in the area of critical medicine. We investigated the involvement of SOD in the regulation of neutrophil apoptosis. Exogenously added SOD effectively induced neutrophil apoptosis, and the fluorescence patterns determined using annexin-V and the 7-AAD were similar to those seen in Fas-mediated neutrophil apoptosis.