The involvement of serotonin in the catecholamine release from the adrenal medulla.
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Adrenal Medulla↗
Biomedical subjects
T Noma
Publications and source records attributed to T Noma.
Inhibition by lecithin-bound iodine (LBI) of inducible allergen-specific T lymphocytes' responses in allergic diseases.
In atopic patients, allergen-sensitized T lymphocytes specifically proliferate in the presence of T cell-growth factor, interleukin 2 (IL-2). Lecithin-bound iodine (LBI), which has been used as a therapeutic modality for patients with bronchial asthma (BA), effectively inhibited Dermatophagoides farinae (Df) mite antigen-induced IL-2 responsiveness in concentrations comparable to LBI concentrations in blood. IL-2-responding T cells were more sensitive to LBI than antigen-presenting cells, whereas LBI suppressed the release of interleukin 1 (IL-1) elicited by Df antigen. In addition, ovalbumin (OVA)-induced IL-2 responsiveness in egg sensitive patients and purified protein-derivative (PPD)-induced IL-2 responsiveness were similarly inhibited by LBI. The IL-2 responsiveness induced by concanavalin A (Con A), however, was not changed. On the basis of these results, LBI may act as a slight immunosuppressant to inhibit the induction of allergen-specific lymphocytes and to improve the clinical status in allergic diseases.
Adult↗
Induction of allergen-specific IL-2 responsiveness of lymphocytes after respiratory syncytial virus infection and prediction of onset of recurrent wheezing and bronchial asthma.
BACKGROUND: In pediatric patients with bronchial asthma and/or atopic dermatitis, peripheral lymphocytes are activated if they are stimulated with the responsible antigen, resulting in induction of responsiveness to IL-2. Because some nursing infants experience recurrent wheezing after respiratory syncytial virus (RSV) infection, attention is being directed to progression of the disease to bronchial asthma. OBJECTIVE: The study was designed to elucidate the mechanism of the onset of allergic diseases after RSV infection. METHODS: We examined allergen-specific IL-2 responsiveness induced in lymphocytes in the peripheral blood of infants after infection by RSV. The relationship between the onset of recurrent wheezing and antigen-specific IL-2 responsiveness was analyzed in 25 pediatric patients who could be followed up for 3 years after RSV infection. RESULTS: Stimulation of lymphocytes with ovalbumin, alpha-casein, and mite (Dermatophagoides farinae) antigens induced significantly higher responsiveness to IL-2 in the RSV-infected infant group than in the healthy infant and disease control groups of the same age. There was no clear correlation between the IgE RAST scores for D. farinae, ovalbumin, and alpha-casein and IL-2 responsiveness. The families of RSV-infected infants had a high incidence of history of allergy (67%), but there was no significant difference in the incidence of patients with positive test results for IL-2 responsiveness between the groups with and without a familial history of allergy. The D. farinae-specific IL-2 responsiveness was significantly increased in the group with the symptom (16 patients) for a value of 1.64 +/- 0.13 (mean +/- SEM) compared with the value of 1.31 +/- 0.21 in the asymptomatic group (9 patients). The incidence of patients with positive test results for IL-2 responsiveness was 68.8% in the symptomatic group and 44.4% in the asymptomatic group. Similarly, the ovalbumin-specific IL-2 responsiveness was significantly increased in the symptomatic group (1.63 +/- 0.17) compared with the asymptomatic group (1.12 +/- 0.26). The incidence of patients with positive test results was 62.5% and 22.2%, respectively. alpha-Casein-specific IL-2 responsiveness was also higher in the symptomatic group than in the asymptomatic group, but the difference was not statistically significant. In the patient groups without RSV infection, on the other hand, the D. farinae-, ovalbumin-, and alpha-casein-specific IL-2 responsiveness in the symptomatic group were all similar to that in the asymptomatic group; no significant increases were detected. CONCLUSION: The results indicated that after RSV infection, lymphocytes acquire specific susceptibility to D. farinae, a mite antigen, and food antigens, particularly ovalbumin. Hence, it is thought that positive IL-2 responsiveness specific for D. farinae and/or ovalbumin, detected several months after RSV infection, can be a prediction factor for the onset of allergic diseases, such as recurrent wheezing and bronchial asthma.
Allergens↗
Role of interleukin-2 and interferon-gamma in inducing production of IgG subclasses in lymphocytes of human newborns.
Unlike lymphocytes from adults, lymphocytes from cord blood of neonates cannot synthesize immunoglobulin G (IgG) in response to pokeweed mitogen (PWM). By using this mitogen in concert with interferon-gamma (IFN-gamma), interleukin-2 (IL-2), or interleukin-6 (IL-6), we studied the induction of IgG subclass molecules in lymphocytes of human neonates. IFN-gamma induced a limited, but substantial, enhancement of IgG2 production by neonatal lymphocytes. IL-2 dose dependently increased the production of each neonatal IgG subclass, whereas IL-6 did not. However, in adult lymphocytes, and under specific conditions, IL-6 or IL-2 each increased the production of all four IgG subclasses. Early in the culture IFN-gamma synergized with IL-2 during the latter or whole culture period to enhance cord blood IgG2 levels. This finding contrasted with the adult IgG2 synthesis synergistically up-regulated by IFN-gamma and IL-6. IL-2 caused a graded increase in immunoglobulin production in neonatal lymphocytes with IgG3 being the highest and IgG2 the lowest, thus corresponding to the differential increase of serum levels of IgG3/IgG1 and IgG4/IgG2 early in childhood. Results suggest that IL-2, but not IL-6, is critical to the development of human IgG subclass production.
Cells, Cultured↗
T cell mediation of abnormally low production of ovalbumin-specific immunoglobulin A in patients allergic to eggs.
Cells producing IgA specific to ovalbumin (OVA) were detected with an assay of plaque-forming cells (PFC). Non-T cells were separated on a polystyrene resin column and were further depleted of B cells that bound sheep erythrocytes (SRBC) by SRBC-rosette sedimentation. The cells were recombined with T cells separated on a polystyrene resin column, stimulated with OVA antigen, and then cultured for 5 d. The number of OVA-specific IgA-PFC from the lymphocytes of infants allergic to hen's eggs (7 +/- 5 per 7 x 10(4) non-T cells, n = 9) was significantly less than that of PFC from lymphocytes of age-matched controls (110 +/- 18 per 7 x 10(4) non-T cells, n = 7) and from those of children with atopic dermatitis who were not allergic to hen's eggs (90 +/- 30 per 7 x 10(4) non-T cells, n = 4). Patients' B cells added to the culture supernatant from OVA-stimulated normal T cells (82 +/- 18 per 7 x 10(4) non-T cells, n = 4) were able to produce the specific IgA to levels comparable to those of normal B cells (92 +/- 9 per 7 x 10(4) non-T cells, n = 6), but the patients' T cells did not cause normal B cells to produce the antibody (8 +/- 2 per 7 x 10(4) non-T cells, n = 4). This indicates that the patients' T cells were less able than were normal T cells to promote the production of OVA-specific IgA-PFC. Until the age of 6 y, the ability of the patients' lymphocytes to produce specific IgA was abnormally low; from that age on, it was normal. At the stage of allergen entry, this transiently low production of OVA-specific IgA may contribute to the onset of allergy to hen's eggs.
Cells, Cultured↗
[Inhibitory effect of Kanpo-medicines: saiboku-to, syouseryu-to, sairei-to on Dermatophagoides farinae antigen-induced IL2 responsiveness in lymphocytes from patients with bronchial asthma and their comparison].
We had previously reported that antigen-induced IL2 responsiveness by lymphocytes can be used to identify etiological allergens and to monitor the clinical activity in atopic diseases. The effect of Kanpo-Medicines; Saiboku-to, Syoseiryu-to, Sairei-to, antiallergic agents, on Dermatophagoides farinae (Df) antigen-induced interleukin 2 (IL2) responsiveness from patients with bronchial asthma was studied and compared among 3 Kanpo-medicines. Allergen-sensitized patient mononuclear cells pretreated with 30-30,000 ng/ml doses of Saiboku-to for 16 hours failed to induce responsiveness to IL2 on stimulation with Df antigen in 8 patients out of 11 (73%). The cells treated with 30 micrograms/ml of Syoseiryu-to also failed to introduce the response in 6 out of 10 (60%) with less frequency compared with Saiboku-to. Sairei-to also suppressed the response on stimulation with a 10 micrograms/ml dose alone in 1 x 10(-3)-1 x 10(-4)ng/ml doses examined in 6 patients out of 17 (35%) with much less frequency and % inhibition. Also Saiboku-to and Sairei-to not Syoseiryu-to inhibited purified protein derivatives (PPD)-induced IL2 responsiveness. However. These agents failed to suppress the Con A-induced IL2 responsiveness. Antigen-presenting adherent cells were more susceptible to any Kanpo-medicines studied rather than IL2-responding T cells except Sairei-to. These results indicated that Kanpo-medicines studied have a weak immuno-suppressive property resulting in inhibiting antigen-induced IL2-responsiveness. Suppressive effects of each Kanpo-medicine seemed to depend on combinations and doses of their elements (Syouyaku). Decreased suppressive effect of higher doses of any Kanpo-medicine was likely to be mitogenic effects of each element on T cells.
Adolescent↗
[Suppressive effect of roxithromycin on the induction of IL-2 responsiveness by DF-stimulated lymphocytes from patients with bronchial asthma].
Roxithromycin (RXM) is a new macrolide antibiotics, with anti-allergic properties, the mechanisms of which action has not been well understood. The effect of RXM-treatment on the induction of interleukin 2 (IL-2) responsiveness by Dermatophagoides farinase (Df)-stimulated lymphocytes was studied in patients with bronchial asthma. RXM alone has almost no effect on lymphocyte activation. Patient's lymphocytes treated with 10 to 400 micrograms/ml doses of RXMs failed to generate Df-induced IL-2 responsiveness in a dose-dependent manner. The target cells for suppressive effect of RXM were antigen-presenting cells such as macrophages and dendritic cells rather than responder T cells. PPD-induced IL-2 responsiveness was also suppressed by the treatment, but the Con A-induced response was not. The results suggest that RXM is a slight immunosuppressant to block the induction of IL-2 responsiveness by Df-stimulated patient's lymphocytes, resulting in the interruption of a cytokine cascade of allergic responses.
Antigen-Presenting Cells↗
[Correlation of interleukin-2 (IL-2) responsiveness by egg white-stimulated lymphocytes with hen egg oral provocation test in atopic children].
One hundred and twenty five cases of atopic children such as atopic dermatitis and bronchial asthma were orally provocated with rare hen egg every 20 minutes one by one upto the whole amount. In one week observation 75 cases showed any symptoms of allergy including eruption and exacerbation of atopic eczema in an immediate, late, and/or delayed responses. Frequency of positive egg white-induce IL-2 responsiveness test in patients with positive oral provocation was 90.7% (68 out of 75 cases; sensitivity). That of negative test in patients with negative provocation was 84.0% (42 out of 50 cases; specificity). In contrast, specificity of IgE RAST for egg white were 88.0% comparable to the value of antigen-specific IL-2 responsiveness (AIR) test, but the specificity was lower value (37.3%) for screening the etiological antigens as compared to that of AIR test. High frequency of positive egg white-induced IL-2 responsiveness test was observed over an immediate, late and delayed responses, while low frequency of positive IgE RAST for hen egg was observed largely in patients showing delayed but not immediate response. The results indicate that IgE RAST in this study reflects IgE-mediated immediate type hypersensitivity, whereas AIR test reflects, in addition to immediate responses, late and delayed type hypersensitivity. The combined results suggest that AIR test in hen egg allergy is a useful method in vitro for both screening and determining etiological allergens, and might be able to substitute for provocation test in vivo for which many times, labours, expenses, and patients' risks are required, and to cover IgE RAST which fails to determine etiological allergens in 62.7% of patients with positive oral provocation.
Adolescent↗
Cytokine production in children outgrowing hen egg allergy.
BACKGROUND: Approximately 40 to 80% of egg-allergic children outgrow egg allergy after 2 to 5 years. OBJECTIVE AND METHODS: To detail the immunologic mechanisms involved in the development of tolerance to egg proteins, the balance between interleukin 4 (IL4) and interferon-gamma (IFN-gamma) synthesis in patients with active atopic dermatitis allergic to hen egg and in those outgrowing hen egg allergy was evaluated. RESULTS: A marked increase in IL4 and a decrease in IFN-gamma synthesis by peripheral blood lymphocytes following ovalbumin (OVA) specific in vitro stimulation was observed in active atopic dermatitis. In contrast, OVA-induced IL4 synthesis in patients in remission was comparable to that in normal individuals. An intriguing finding was higher production of IFN-gamma by lymphocytes from ovalbumin-insensitive patients in remission as compared to normal individuals following antigen stimulation, although cell proliferation in OVA-stimulated lymphocytes was reduced in patients during remission. CONCLUSION: OVA antigen may be capable of inducing a population of Th1-type cells to produce cytokines such as IFN-gamma, resulting in suppression of Th2-type responses, i.e. IL4 secretion. We speculate that the changes in the balance of relevant antigen-induced cytokine synthesis seen in such patients may be causally associated with the improvement in their clinical status.
Antigens↗
Ketotifen inhibits allergen-specific T lymphocytes' responses by suppressing antigen presentation with concomitant decrease of HLA-DQ antigen on macrophages.
Allergen activates T lymphocytes responsive to interleukin 2 (IL-2) in allergic patients but not in normal individuals. This response was suppressed by anti-allergic agent, Ketotifen (4-(1-methyl-4-piperidylidene)-4H-benzo [4, 5] cyclohepta [1, 2-b] thiophen-10 (9H)-one hydrogen (fumarate). Prolonged culture of antigen-presenting adherent cells impaired the ability to present Dermatophagoides farinae (Df) antigen to T cells, whereas stimulation of adherent cells with recombinant interferon-gamma (IFN-gamma) restored the antigen-presenting capability. The maintained antigen presenting ability of adherent cells treated with IFN-gamma was also suppressed by Ketotifen. Fluorescence activated cell sorter (FACS) analysis disclosed that Ketotifen selectively reduced the expression of HLA-DQ antigen, crucial restriction elements in Df antigen-related responses, on macrophages but not on B cells, even in the presence of IFN-gamma. Collectively, Ketotifen prevented macrophages from inducing allergen-activated T lymphocytes' responsiveness to IL-2 at least in part by decreasing the expression of HLA-DQ antigen.
Adolescent↗
NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma.
nm23 was originally identified as an antimetastatic gene, the expression of which was inversely correlated with tumor metastatic potential in rodent model systems. Subsequently, two related human nm23 genes, nm23-H1 and nm23-H2, were identified. The relationship between expression of nm23-H1 and nm23-H2 in hepatocellular carcinoma specimens from 30 patients and metastatic potential was investigated with the use of a quantitative reverse transcription-PCR procedure. The abundance of nm23-H1 and nm23-H2 mRNA was compared with serum alpha-fetoprotein concentration, tumor size (maximum diameter), and histopathological parameters such as portal vein tumor thrombus, intrahepatic metastasis, capsular formation, capsular infiltration, differentiation of tumor cells, and TNM stage. The abundance of nm23-H1 mRNA showed a significant inverse correlation with intrahepatic metastasis and TNM stage. Furthermore, we confirmed that reduced expression of nm23-H1 mRNA was in accordance with a reduced amount of NM23-H1 protein using Western blot analysis. No correlation was apparent between nm23-H2 mRNA abundance and intrahepatic metastasis. These data support the conclusion that nm23-H1 may play a more important role than nm23-H2 in intrahepatic metastasis in hepatocellular carcinoma. Furthermore, nm23-H1 mRNA abundance may be a predictor of intrahepatic metastasis, the most important factor correlated with the metastatic potential of hepatocellular carcinoma.
Age Factors↗
Upregulated IFN-gamma production in hen's egg-induced atopic dermatitis in remission.
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Animals↗
Dual action of IL-4 on mite antigen-induced IgE synthesis in lymphocytes from individuals with bronchial asthma.
Polyclonal IgE synthesis was efficiently induced by Dermatophagoides farinae (Df) antigen in freshly derived peripheral blood lymphocytes from mite-sensitive individuals with bronchial asthma. The in vitro IgE production was significantly correlated with total serum IgE values. The induced IgE synthesis was inhibited in a dose-dependent manner by antibodies to IL-4, indicating a role for endogenous IL-4. Although IL-4 alone increased IgE production, high concentrations (1-100 U/ml) of the cytokine inhibited Df antigen-stimulated production of IgE. However, low concentrations (0.001-0.01 U/ml) of IL-4 significantly enhanced Df antigen-induced IgE production, as did high doses of IL-4 when endogenous IL-4 was neutralized by antibodies to IL-4. Two other cytokines, IL-10 and interferon-gamma (IFN-gamma), showed contrasting actions, as judged from experiments with, exogenous cytokine and anti-cytokine antibodies: IL-10 enhanced and IFN-gamma inhibited Df antigen-induced IgE synthesis. Thus, mite-stimulated IgE production in lymphocytes from individuals with bronchial asthma appears to be regulated by at least three cytokines: IL-4, IL-10, and IFN-gamma.
Adolescent↗
Modulation of mite antigen-induced immune responses by lecithin-bound iodine in peripheral blood lymphocytes from patients with bronchial asthma.
1. Dermatophagoides farinae (Df) mite antigen induced IgE synthesis associated with an imbalance of cytokine production in mite-sensitive patients with bronchial asthma; increased production of interleukin 4 (IL-4), and decreased production of interferon-gamma (IFN-gamma) was specifically induced in these patients' lymphocytes. 2. Lecithin-bound iodine (LBI), with which children with bronchial asthma have been successfully treated in the range of 0.5 to 5 microM, concentrations comparable to LBI blood levels in medicated individuals, modified mite antigen-induced immune responses, thereby decreasing abnormal lymphocyte functions. 3. In Df antigen-driven immune responses, inhibition of IgE generation accompanied by suppression of IL-4 and the recovery of IFN-gamma production was successful when LBI was used in vitro. 4. LBI also acted on normal PBMCs by downregulating the IL-4-induced IgE synthesis, phytohaemagglutin (PHA)- and phorbol myristate acetate (PMA) plus calcium ionophore (CaI)-induced IL-4 secretion, and by upregulating purified protein derivatives (PPD)-induced IFN-gamma production. Therefore, LBI was capable of inhibiting the IgE and IL-4 responses and of enhancing IFN-gamma production both from allergen-stimulated atopic cells and from non-atopic cells appropriately stimulated. 5. The expression of human histocompatibility leukocyte antigen (HLA), class II antigens and intercellular adhesion molecule 1 (ICAM-1) on monocytes, crucial molecules for T cell-monocyte interactions, was not altered by LBI. 6. LBI probably acts as an immunomodulator to ameliorate mite antigen-induced abnormal cell-mediated immune responses in patients with bronchial asthma caused by Df antigen thereby leading to improvement of their clinical status.
Animals↗
Pattern of cytokine production by T cells from adolescents with asthma in remission, after stimulation with Dermatophagoides farinae antigen.
Children with asthma usually become asymptomatic by the time they reach age 20 y. To clarify the immunologic mechanisms responsible for this phenomenon, we studied patients in remission and others who still had frequent asthma attacks. Patients were grouped by clinical status, and three variables were measured: serum levels of IgE, production of IL4 and interferon (IFN)-gamma, and the activation of T cells induced by Dermatophagoides farinae (Df) antigen. Df-induced activation of T cells (as measured by antigen-induced IL2 responsiveness) or IL2 synthesis itself was induced in patients with active asthma but not in normal subjects. These responses were much weaker in patients in remission. When stimulated by Df antigen in vitro, lymphocytes from patients with active asthma produced much more IL4 than did the cells from normal subjects, and cells from patients in remission produced only a small amount. In contrast, under similar conditions lymphocytes from patients with active asthma produced less IFN-gamma than did the cells from normal subjects. Production of IFN-gamma stimulated by Df antigen was high in patients in remission but not in normal subjects. Thus, upregulated IFN-gamma production after exposure to Df antigen might reduce IL4 secretion, which would suppress IgE production and would improve clinical status. Df antigen may suppress Df-induced allergic responses in patients with asthma in remission.
Adolescent↗
[Effect of IL-10 on the mite antigen-induced IFN-gamma production by peripheral blood lymphocytes from individuals with bronchial asthma].
Interferon-gamma (IFN-gamma) production was dose-dependently suppressed by the addition of Dermatophagoides farinae (Df), mite antigen in peripheral blood mononuclear cells from children with bronchial asthma. By contrast, the levels of IFN-gamma did not change on stimulation with Df antigen in the normal lymphocytes from nonallergic individuals not sensitized with mite. Recombinant interleukin 10 (IL-10), when added to the normal lymphocytes, significantly reduced the production of IFN-gamma. Moreover, the decreased synthesis of IFN-gamma in patients' lymphocytes was inversely up-regulated by the treatment with anti-IL-10 antibody. Taken together, results suggest the regulatory role of IL-10 in the secretion of IFN-gamma in Df antigen-driven immune responses.
Adolescent↗
[Molecular diversity of enzymes by transcriptional and translational mechanism].
This article discusses a molecular basis for isozyme production. Molecular diversity of enzymes is often created by genetic mechanisms, especially at the level of transcription and translation. First, transcription from several promoters in the same gene and alternative splicing make several transcripts which vary in length and the context. Isozymes are produced if the translation initiating codons are located in the in-frame position. Additional regions usually have the information of the targeting signal to the cellular compartment and/or the regulatory mechanism of enzyme activity. Second, the regulation of the translational initiation is another important step to make isozymes. Two mechanisms, that is, cap-dependent and internal ribosome binding, are currently recognized for the translational initiation.
Animals↗
[IgE production and gene expression of interleukin-4 and interferon-gamma by peripheral mononuclear cells in asthmatic children].
In asthmatic children without he egg allergy, spontaneous IgE production of PBMC showed 1.27 +/- 0.28 IU/ml (Mean +/- SE) and IgE production of Dermatophagoides farinae (Df) stimulated PBMC after which IFN-gamma decreased to 0.89 +/- 0.23 IU/ml (Mean +/- SE) (p < 0.001). IgE production of Ovalbumin (OVA) stimulated PBMC after which IFN-gamma showed no decrease. In asthmatic children with hen egg allergy, IgE production of OVA stimulated PBMC and IFN-gamma decreased to 1.0 +/- 0.52 IU/ml (Mean +/- SE). In spontaneous IgE production it was 1.61 +/- 0.91 IU/ml. (p < 0.05). IL-4 mRNA was expressed in spontaneous PBMC in asthmatic children, but not in healthy non atopic children. The expression of IL-4 mRNA was suppressed in Df stimulated PBMC followed by IFN-gamma in asthmatic children. In asthmatic children, IFN-gamma mRNA were expressed in Df stimulated PBMC after which IFN-gamma. And simultaneously IgE production in Df stimulated PBMC were suppressed by addition of IFN-gamma.
Adolescent↗