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Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 595 records · Page 33Linked to original sources
PubMedDate not supplied

A protective effect of coenzyme Q10 on isolated rabbit ventricular muscle under hypoxic condition.

Effects of coenzyme Q10 (CoQ10) on transmembrane action potential, isometric tension, and tissue ATP contents of isolated rabbit ventricular muscles were examined under the hypoxic condition and subsequent reoxygenation. CoQ10 (10 mg/kg/day) was administered intravenously to 15 rabbits for 3 days (CoQ10 group), and 15 other rabbits were treated only with a vehicle for CoQ10 (control group). Membrane action potentials, mechanical contraction, and ATP contents of the preparations under aerobic condition were not affected by the CoQ10 or vehicle pretreatment. Hypoxia for 60 min caused a shortening of action potential duration (APD), a decrease in peak developed tension (DT), and an elevation of resting tension (RT), as well as a decrease in ATP contents of the preparations in both groups. However, these changes were significantly less in the CoQ10 group than those in the control group. A better recovery of APD, DT, and RT of the preparations during reoxygenation period was also observed in the CoQ10 group. These results indicate that the prior and repetitive administration of CoQ10 may protect cardiac muscles from functional deterioration induced by hypoxia, suggesting a beneficial effect of this substance on the metabolism of the energy-depleted myocardium.

Action Potentials↗
PubMedDate not supplied

Electrical and mechanical effects of amrinone on isolated guinea pig ventricular muscle.

The electromechanical effects of amrinone on isolated guinea pig papillary muscle were studied at various driving frequencies and under the influence of several antagonists and a low calcium medium. Amrinone (3 X 10(-5)-2 X 10(-3)M) caused a positive inotropic effect on preparations driven at 1.0 Hz in a concentration-dependent manner. When the preparations were driven at a frequency lower than 0.5 Hz, the positive inotropic effect of the drug was markedly attenuated. Amrinone caused a significant prolongation in action potential duration at an early repolarization phase--but not at a late repolarization phase--without affecting any other parameters of action potential. These effects of amrinone were not blocked by a beta-adrenoceptor antagonist or tetrodotoxin, but were inhibited by treatment with verapamil (5 X 10(-6)M) or a low calcium medium (0.1 or 0.3 mM). In papillary muscles depolarized by 30 mM [K+]o, amrinone enhanced the slow action potentials. In voltage clamp experiments using a single sucrose-gap method, amrinone (6 X 10(-4)M) caused a marked increase in the peak amplitude of the slow inward current, while it did not affect the net outward current. The results suggest that the slow calcium inward current may play a predominant role in the positive inotropic effect of amrinone.

Action Potentials↗
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

Eosinophils are neither migrated nor activated in the skin lesions of atopic dermatitis in infants.

Eosinophils and eosinophil cationic protein (ECP) were examined in the skin lesions of 10 infants with atopic dermatitis (aged 4 months to 7 years). In all 10 patients, neutrophils and eosinophils were rarely seen in these lesions. Moreover, in the immunohistochemical study, ECP was scarcely detected in any of them. Our results suggest that eosinophils are neither migrated nor activated in the skin in atopic dermatitis in infants.

Blood Proteins↗
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

Evaluation of theophylline clearance in children with bronchial asthma.

The total body clearance of theophylline was examined in 95 children aged 6 months to 15 years with chronic bronchial asthma. Each patient received sustained-release theophylline preparations and was evaluated at steady state. Blood samples were obtained 1-8 hours after a morning dose, and individual total body clearance was determined with a Bayesian forecasting computer model. Changes in theophylline clearance were evaluated within age groups, with the age determined at the time of blood sampling. Total body clearance tended to increase with age up to 10 years. In children over 10 years old, total body clearance significantly decreased with age. The interpatient variability of theophylline clearance was most noticeable at 2-4 years of age. Changes in volume of distribution were similar to those in clearance. In conclusion, there are pronounced age-dependent differences in theophylline clearance that require individual adjustment of dosage regimens on the basis of serum concentrations and clinical response in children. Individualization of the oral dose based on frequent serum measurements is necessary to maintain theophylline levels in the therapeutic range.

Adolescent↗
PubMedDate not supplied

IgE production by B-cells stimulated with interleukin-4 and Epstein-Barr virus in patients with elevated serum IgE levels.

Epstein-Barr virus (EBV) and recombinant interleukin-4 (rIL-4) induce IgE production by normal B-cells. We demonstrate here the difference in IgE synthesis in patients with elevated IgE levels and normal control subjects. EBV and rIL-4 induced the synthesis of IgE by surface IgE-negative B-cell precursors isolated by cell sorting. IgE synthesis in normal subjects became apparent in the second week with increasing rIL-4 concentrations, whereas in patients with elevated IgE levels, there was a marked elevation in IgE synthesis without rIL-4 stimulation. We did not observe the presence of DNA rearrangement occurring between IgM and IgE switch regions (S mu and S epsilon, respectively) during switching to IgE isotype in patients with elevated IgE levels. We found that with the limited sensitivity of Southern blotting, this method may not be useful for the study of B-cell populations in which only a small percentage of cells have undergone switching.

B-Lymphocytes↗
PubMedDate not supplied

Evaluation of lymphocyte proliferative responses to casein hydrolysate formula in cow's milk-sensitive children: response of peripheral blood mononuclear cells to hydrolysate formula.

The proliferative responses of peripheral blood mononuclear cells (PBMCs) to cow's milk proteins and a casein hydrolysate formula were investigated in 10 cow's milk-sensitive patients. The casein hydrolysate formula reduced the symptoms in seven children but not in three. The proliferative responses of PBMCs to cow's milk proteins and the formula were higher in the three patients whose symptoms were not reduced by casein hydrolysate formula. However, the proliferative responses of PBMCs to hydrolysate formula were lower than those to cow's milk proteins in patients whose symptoms were reduced by casein hydrolysate formula. These results suggest that an elimination diet with casein hydrolysate formula may not be as effective in some patients with cow's milk allergy whose PBMCs proliferate to casein hydrolysate formula.

Caseins↗
PubMedDate not supplied

Responses of lymphocytes to Epstein-Barr virus in patients with primary immunodeficiencies.

Several reports have demonstrated that the responses of B-cells to Epstein-Barr virus (EBV) are variable in common variable immunodeficiency (CVID). In this study in patients with selected primary immunodeficiencies, i.e., Bloom's syndrome, Wiskott-Aldrich syndrome or IgA deficiency, the responses of peripheral blood mononuclear cells (PBMCs) to EBV were investigated. In the two patients with Bloom's syndrome, PBMCs stimulated with EBV showed decreased proliferation and immunoglobulin production, suggesting a mild abnormality of B-cells. In patients with Wiskott-Aldrich syndrome, the responses were variable. In the patient with IgA deficiency, PBMCs responded normally to EBV in proliferation, whereas PBMCs responded poorly to EBV in IgA production, suggesting an abnormality only in the IgA production mechanism.

B-Lymphocytes↗
PubMedDate not supplied

Suppression of IgA production by lymphocytes induced by diphenylhydantoin.

In this study, the mechanisms for suppression of immunoglobulin production by lymphocytes induced by diphenylhydantoin (DPH) were investigated using peripheral blood mononuclear cells from one patient 3 months after discontinuation of DPH, when IgA deficiency was improved. Immunoglobulin production in PBMCs was dose-dependently suppressed by DPH and the suppressive effect of DPH on IgA production tended to be greater than the effect on IgM or IgG production. Moreover, cell separation experiments indicated that DPH suppresses immunoglobulin production by PBMCs through a suppression of B cell, but not T cell, function. The finding that the suppressive effect of DPH on IgA production tended to be greater than the effect on IgM or IgG production might be related to the fact that the alpha-chain gene is located in the 3' end of the gene coding the constant regions of human heavy chains.

B-Lymphocytes↗
PubMedDate not supplied

Effects of the antiallergic drug azelastine hydrochloride on proliferative responses of lymphocytes to food antigens in patients with food-sensitive atopic dermatitis.

We previously reported that the proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA) or bovine serum albumin (BSA) in children with atopic dermatitis (AD) who are sensitive to hen's egg or cow's milk were significantly higher than those of healthy children and hen's egg- or cow's milk-sensitive children with immediate symptoms. Azelastine hydrochloride is an antiallergic drug used in the treatment of rhinitis and asthma. In this study, we have shown that the proliferative responses of PBMCs to OA are concentration-dependently inhibited by azelastine in patients with AD. Moreover, the inhibition resulted from the effects of azelastine on T-cells.

Animals↗
PubMedDate not supplied

Interleukin-2 and interferon-gamma production by peripheral blood lymphocytes of patients with common variable immunodeficiency.

We evaluated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) in peripheral blood lymphocytes (PBLs) from six patients with common variable immunodeficiency (CVID). IL-2 production and IFN-gamma concentrations were not reduced in these patients. As the production of IL-2 and IFN-gamma secreted from TH1 clones was within the normal range in patients with CVID, we concluded that TH1 function was normal in these patients. Our previous report showed B-cell dysfunction in CVID patients. Therefore, we concluded that the immune defect in these patients is caused by B-cell dysfunction rather than T-cell dysfunction.

Adult↗
PubMedDate not supplied

Immunoglobulin-secreting cells in healthy peripheral blood mononuclear cells.

Immunoglobulin-secreting cells were measured in healthy uncultured peripheral blood mononuclear cells (PBMCs) in vitro. The percentage of IgM-, IgG- and IgA-secreting cells in adult PBMCs was 0.053, 0.099 and 0.065%, respectively. The percentage of IgM-, IgG- and IgA-secreting cells was 0.73, 5.2 and 3.8% of surface IgM-, IgG- and IgA-bearing cells, respectively. The numbers of IgM-, IgG- and IgA-secreting cells increased with age in childhood. However, the numbers of all three classes were slightly decreased in adults compared with children aged 9-15 years. These results may explain the difference in immunity in vivo.

Adolescent↗
PubMedDate not supplied

Evaluation of lymphocyte proliferative responses to food antigens with regard to age and food-specific IgE antibodies in food-sensitive atopic dermatitis.

Peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD), selected for sensitivity to hen's egg or cow's milk, showed significant proliferation in response to food antigens, ovalbumin or bovine serum albumin compared with PBMCs from nonatopic control subjects. The proliferative responses of PBMCs to food antigens were evaluated with regard to age and specific IgE antibodies to food antigens in food-sensitive patients with AD. There were no differences in proliferation between each age group, and the proliferation in patients with AD was significantly higher than in age-matched control subjects. There was no relationship between proliferative responses of PBMCs and specific IgE antibodies to food antigens in patients with AD. These results suggest that the responsiveness of lymphocytes to food antigens is independent of age and food-specific IgE antibodies in food-sensitive patients with AD.

Adolescent↗
PubMedDate not supplied

Immunoglobulin-secreting cells in primary immunodeficiency diseases.

To assess immunoglobulin production in vivo, the numbers of immunoglobulin-secreting cells were measured in uncultured peripheral blood mononuclear cells (PBMCs) of patients with primary immunoglobulin deficiency. The numbers of immunoglobulin-secreting cells were found to be variable, and they were well correlated with the serum concentrations of all three major immunoglobulin classes. Our results suggest that measurement of immunoglobulin-secreting cells in PBMCs is useful in the assessment of the ability to produce immunoglobulin in vivo.

Antibody-Producing Cells↗