Biomedical subjects

T Fukao

Publications and source records attributed to T Fukao.

132 records · Page 8Linked to original sources

PubMedDate not supplied

Reduced interferon-gamma production and mutations of the interleukin-12 receptor beta(2) chain gene in atopic subjects.

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-gamma (IFN-gamma). IL-12 is a cytokine that induces IFN-gamma production. The signal of IL-12 is transduced through the IL-12 receptor (IL-12R) and Stat4. METHODS: We examined IFN-gamma 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 beta(2) chain gene were analyzed. RESULTS: The serum IgE levels were negatively correlated (p < 0.001) with IFN-gamma production. In 24 out of 75 atopic patients, IFN-gamma production in PBMCs following stimulation with IL-12 was under the detection limit, but PHA stimulation elicited detectable IFN-gamma production. Sequence analysis of the cDNA of IL-12R beta(2) 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-gamma 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 beta(2) chain gene is one of the causative genes for atopy.

Cells, Cultured↗

PubMedDate not supplied

Ataxia telangiectasia associated with B-cell lymphoma: the effect of a half-dose of the drugs administered according to the acute lymphoblastic leukemia standard risk protocol.

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by cerebellar ataxia, oculocutaneous telangiectasia, and variable degrees of humoral and cellular immunodeficiency. Affected individuals are known to exhibit a high incidence of lymphoma and leukemia. Because of increased chemosensitivity, the treatment of A-T patients with malignancies requires extremely careful planning and caution with respect to the use of chemotherapy. The authors report on a 12-year-old boy with A-T who developed B-cell lymphoma. He received a half-dose of the drugs administered according to the acute lymphoblastic leukemia (ALL) protocol issued by our children's cancer study group (9104 Standard Risk Protocol, Tokai Pediatric Oncology Study Group). As a result, he continues to be in complete remission and free of treatment complications 32 months after the diagnosis of B-cell lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Time-course study of the levels of urinary leukotriene E4, serum thromboxane B2 and serum eosinophil cationic protein in spontaneous asthma attacks in five children.

Leukotrienes thromboxanes, and eosinophil cationic protein (ECP) are chemical mediators involved in airway inflammation. We investigated time courses of urinary leukotriene E4 (LTE4), serum thromboxane B2 (TXB2) and serum ECP, together with blood eosinophil count during asthmatic attacks in five children. Just after the onset of an asthma attack, urinary LTE4 levels reflected the severity of the attack and decreased during the course of clinical improvement with various therapies; however, they did not change in the course of an attack in one of five patients. The other parameters showed less or no significant relation to clinical severity and improvements. Since LTE4 is a stable product from total cysteinyl leukotrienes, it appears to be one of important mediators in most asthma attacks in children. This study suggests that LTE4 is a useful marker for monitoring severity and improvement of spontaneous attacks of asthma.

Antibody Specificity↗

PubMedDate not supplied

Immunoblot analysis for laboratory diagnosis of ataxia-telangiectasia: use of Epstein-Barr virus-transformed or phytohemagglutinin-stimulated lymphoblasts for detection of ATM protein.

Ataxia-telangiectasia (A-T) is a genetic disorder characterized by a progressive ataxia, immunodeficiency, neurological abnormalities, hypersensitivity to ionizing radiation, and predisposition to cancer. The gene responsible for A-T (ATM) has been cloned and shown to code for a 350 kDa polypeptide containing 3,056 amino acid residues. Detection of ATM mutations for laboratory diagnosis of A-T is laborious and not practical, unless there are common mutations in a population. We describe here immunoblot analysis for the detection of ATM in seven Japanese A-T patients from five families and in controls using ATM3BA antibody. ATM protein was routinely and clearly detected in Epstein-Barr virus (EBV)-transformed or phytohemagglutinin (PHA)-stimulated lymphoblasts from controls. However, it could not be detected consistently in unstimulated peripheral blood mononuclear cells (PBMCs) from controls. We also detected ATM protein in control fibroblasts, but the background was relatively higher than in control lymphoblasts. ATM protein was not detected or dramatically decreased in EBV-transformed lymphoblasts from all seven patients tested and in fibroblasts from one patient. Immunoblot analysis using EBV-transformed or PHA-stimulated lymphoblasts represents a useful approach for laboratory diagnosis for A-T. The latter is especially preferable since it takes only 3 days to obtain sufficient cells for analysis.

Adult↗

PubMedDate not supplied

Inhibition of interferon-gamma production from lymphocytes stimulated with food antigens by a beta 2-agonist, procaterol, in patients with food-sensitive atopic dermatitis.

Procaterol hydrochloride is a relatively new beta 2-selective agonist with a unique carbostyril nucleus. In this study, procaterol dose-dependently inhibited IFN-gamma production of peripheral blood mononuclear cells stimulated with ovalbumin in patients with hen's egg-sensitive atopic dermatitis, without inhibition of proliferative responses of peripheral blood mononuclear cells. Our results suggest that procaterol also has an effect as an immunomodulator, in addition to its effect as a beta 2-selective agonist.

Adrenergic beta-Agonists↗

PubMedDate not supplied

DNase I hypersensitive sites in human I epsilon region of immunoglobulin heavy chain genes abnormally induced by interleukin-4 in B-lymphocytes of atopic patients with high levels of serum IgE.

Interleukin-4 (IL-4) induces germline C epsilon transcripts prior to C epsilon switch recombination in human B-lymphocytes. In chromatin, nucleosome-free regions known as nuclease hypersensitive sites represent the "open windows" that allow enhanced access of crucial resident cis-acting DNA sequences to transacting factors. In this study, lymphoblastoid cell lines (LCLs) were established from surface IgE negative B-cells of healthy children and patients with high levels of serum IgE, using Epstein-Barr virus. The germline C epsilon transcript was amplified from cDNA of the patients' LCLs cultured with low concentrations of recombinant interleukin-4 (rIL-4, 10 IU/ml), while it was not amplified from the cDNA of the healthy LCLs with the low concentration of rIL-4. The germline C epsilon transcript was strongly amplified from cDNA of the patients' LCLs with high concentrations of rIL-4 (100 IU/ml), compared with that of the healthy LCLs with the high concentrations of rIL-4. Moreover, the DNase I hypersensitive site of the I epsilon region was abnormally induced in the patients' LCLs even by a low concentration of rIL-4, compared with that of healthy LCLs. Our results indicate that DNase I hypersensitive sites in the I epsilon region of immunoglobulin-heavy chain genes are abnormally induced by IL-4 in the B-cells of atopic patients with high levels of serum IgE, and, as a result, the germline C epsilon transcript is abnormally expressed.

Asthma↗