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Biomedical subjects

T Nagakura

Publications and source records attributed to T Nagakura.

At least 37 records · Page 2Linked to original sources

Interleukin 4 induces CD4+/CD8- to CD8+/CD4- transformation of human neonatal T cells by way of a double positive intermediate.

We have determined that IL-4 induces the generation of CD4+/CD8+ T cells in cultures of neonatal lymphocytes. Sorting, positive, and negative selection experiments indicate that these cells arise from a subpopulation of CD4+/CD8- cells present in the neonate but not in the adult. We have further determined that these IL-4 generated "double positive" cells further differentiate to express only the CD8 marker. Our findings suggest an undescribed and dramatic role for IL-4 in T cell differentiation.

Antigens, CD↗

Chemical mediators in hypersensitivity reactions.

The study of chemical mediators is essential in clarifying the mechanism of hypersensitivity reactions. Recent advances in this field have been made particularly with the arachidonic acid metabolites, several of which strongly contract smooth muscle, attract granulocytes to inflammatory foci and lead to increased vascular permeability. These functions play a crucial role in allergic reactions. Furthermore these mediators might work to modulate the intracellular network which mediates the complicated inflammatory process of hypersensitivity reactions.

Autacoids↗

Treatment of status asthmaticus--hormone changes before and after aminophylline i.v. drip therapy.

The treatment of status asthmaticus is one of the most important factors in controlling the patient with asthma attacks. We have studied hormone changes in status asthmaticus and considered what is the best treatment in the asthma attack condition in children. Antidiuretic hormone (ADH), renin activity, and aldosterone activity are elevated in severe asthma attack conditions, and these high levels are correlated with high levels in Wood's clinical score. It is theoretical that patients with dehydration and respiratory failure show such elevation in hormones, and it is well known that under such conditions beta 2-stimulant enhances renin production. From our study, it is concluded that beta 2-stimulant subcutaneous injection must be considered in status asthmaticus. In children, aminophylline i.v. drip therapy may be one of the best treatments in status asthmaticus.

Adolescent↗

Human cord blood lymphocytes do not simultaneously express CD4 and CD8 cell surface markers.

Several authors have reported finding significant numbers of immature T lymphocytes of the CD4/CD8 'double positive' phenotype in human cord blood. We have studied over 30 cord blood samples using directly conjugated reagents and have failed to detect such cells in any of the samples. Differences in staining methodologies that may account for this discrepancy are discussed.

Antigens, Differentiation, T-Lymphocyte↗

Enhancement of the expression of eosinophil IgE receptor (Fc epsilon R2) and its function by platelet-activating factor.

Eosinophils possess low-affinity Fc immunoglobulin E (IgE) receptors (Fc epsilon R2). We have compared platelet-activating factor (PAF) with lyso-PAF, leukotriene B4 (LTB4) and histamine for their ability to influence the binding of a native myeloma IgE to normal-density human eosinophils, using flow cytometry and a fluorescein-conjugated anti-IgE polyclonal antibody. Preincubation with PAF gave a dose- and time-dependent increase in IgE binding optimal at 10(-7) M (P less than 0.01) and 30 min respectively. A smaller but significant effect was observed with LTB4 and histamine (optimal at 10(-7) M (P less than 0.01) and 10(-5) M (P less than 0.05) respectively). Diluent alone or lyso-PAF had no effect. These results suggest enhanced expression of Fc epsilon R2 by stimulated eosinophils. Further confirmation of enhancement was obtained using two functional assays, i.e., cytotoxicity and mediator (LTC4) generation. IgE-dependent cytotoxicity against schistosomula of Schistosoma mansoni was enhanced by prior incubation of normal eosinophils with PAF (optimal at 10(-7) M), but not lyso-PAF. No LTC4 was detectable following incubation of unstimulated eosinophils with S. mansoni coated with specific IgE. Preincubation of these cells with PAF (10(-7) M) resulted in the generation of 4.4 pmol of LTC4 per 10(6) cells. Our data demonstrate that normal-density eosinophil Fc epsilon R2 expression can be up-regulated in vitro by PAF and LTB4 and that these changes are accompanied by enhanced functional properties.

Animals↗

Exercise-induced anaphylaxis: improvement after removal of amalgam in dental caries.

We present a case of exercise-induced anaphylaxis with improvement following the removal of dental amalgam. Although her symptoms were unresponsive to various kinds of therapy until removal of the amalgam, her symptoms related to exercise improved remarkably after the removal. The increase in plasma histamine levels for exercise provocation test also improved. This suggests that sensitivity to metals might cause exercise-induced asthma in some patients.

Anaphylaxis↗

The effect of platelet-activating factor on IgE binding to, and IgE-dependent biological properties of, human eosinophils.

This study investigated the effect of platelet-activating factor (PAF), leukotriene B4 (LTB4) histamine and formyl-methionyl-leucyl-phenylalanine (FMLP) on immunoglobulin E (IgE) binding and IgE-dependent cytotoxicity of human normal density eosinophils. The binding of a native myeloma IgE to normal human eosinophils was measured by flow cytometry using a fluorescein-conjugated polyclonal anti-IgE antibody. Preincubation with PAF (optimal at 10(-7)M), but not lyso-PAF or FMLP, gave dose-dependent increases in IgE binding. PAF and LTB4 gave significant increases in IgE binding after 5 min preincubation (P less than 0.05); the effect was further enhanced at 30 min (P less than 0.01). This was further confirmed using the rosette assay where PAF and LTB4, but not lyso-PAF or FMLP, gave dose- and time-dependent increases in IgE eosinophil rosettes. Eosinophil cytotoxicity for schistosomula of Schistosoma mansoni, incubated with immune serum, was also significantly enhanced (P less than 0.01) by PAF in a dose-dependent fashion (optimal at 10(-8) M). Schistosomula coated with FPLC-purified IgE fractions were susceptible to killing by normal density eosinophils, and this was enhanced with PAF (10(-8)M), LTB4 (10(-7)M) and histamine (10(-5)M) but not with FMLP (10(-7)M) or lyso-PAF. IgE-dependent cytotoxicity was confirmed by the removal of contaminating IgG from IgE-rich fractions, and by the abolishment of IgE-dependent cytotoxicity after IgE adsorption. These results suggest that PAF (and to a lesser extent LTB4 and histamine) increase IgE binding, IgE-dependent adherence and cytotoxicity of normal human eosinophils. Although IgE receptors have not been identified, the data support current concepts that certain biological properties of eosinophils may be IgE associated.

Cells, Cultured↗

Release of high-molecular-weight neutrophil chemotactic activity from resected human nasal turbinate after antigen challenge.

Eleven patients with allergic rhinitis were studied. All subjects were sensitive to house dust mite documented by skin test, RAST score, and nasal provocation test. The patients needed lower turbinectomy because of chronic hypertrophic rhinitis. Tissues of the lower turbinate were obtained at the time of surgery, fragmented, and subsequently challenged with house dust mite in vitro. Diffusates were collected for measurement of neutrophil chemotactic activity (NCA) and histamine. NCA and histamine were released in a dose-dependent manner, and the time course of release of these mediators was identical. Release of NCA and histamine correlated significantly (p less than 0.001). The prior administration of the antiallergic drugs, disodium cromoglycate or tranilast, significantly blocked the release of NCA and histamine from antigen-challenged tissues. NCA released from nasal tissues eluted as a single peak with estimated molecular size of between 669 kd and 440 kd in three subjects and as two or three peaks in two patients. These results provide evidence that NCA might be involved in the pathogenesis of allergic rhinitis.

Adolescent↗

Release of high molecular weight-neutrophil chemotactic activity from human tissues, cells and secretion.

Release of high molecular weight-neutrophil chemotactic activity from human tissues, cells and secretion was studied in vivo and in vitro. Lung, nasal turbinate, nasal polyps, skin of neurofibromatosis, basophils from chronic myeloid leukemia and cultured basophilic cells from cord blood released this mediator following calcium ionophore, antigen, anti-IgE or homogenization in vitro. Its release was also demonstrated in human nasal secretions from patients with allergic rhinitis following antigen challenge. Regarding mononuclear cells no release of this mediator was observed from normal donors or asthmatic patients having no active attack upon challenge with calcium ionophore, phytohemagglutinin or antigen. Homogenized duodenum released high molecular weight-neutrophil chemotactic activity but less activity in comparison with other tissues or cells mentioned above.

Asthma↗

Flow-cytometric analysis of increased IgE uptake by normal eosinophils following activation with PAF-acether and other inflammatory mediators.

Using flow-cytometric analysis and a fluorescein-conjugated anti-IgE antibody, we have investigated whether normal-density human eosinophils will bind greater amounts of native IgE following activation with platelet-activating factor (PAF), leukotriene B4 (LTB4) and histamine. Incubation with PAF resulted in a large dose- and time-dependent increase in IgE binding, optimal at 10(-7) M and 30 min, respectively. LTB4 and histamine gave lower but significant increases in IgE binding. Enhanced binding of IgE by activated normal-density eosinophils is probably a consequence of enhanced Fc epsilon RII receptor expression, suggesting a functional role for this receptor in allergic inflammation.

Antigens, Differentiation, B-Lymphocyte↗

Determination of 3 beta-hydroxylated bile acids in human serum and liver tissue.

3 beta, 7 alpha-Dihydroxy-5 beta-cholanoic acid (3 beta, 7 alpha-diOH) was detected in serum of 3 patients with intrahepatic cholestasis. 3 beta, 7 beta-dihydroxy-5 beta-cholanoic acid (3 beta, 7 beta-diOH) appeared in serum of those patients after treatment with ursodeoxycholic acid (UDC). These bile acids were also detected in only unconjugated fractions of serum of another 7 patients with chronic liver diseases, but not in liver tissue of them. The liver does not seem to from these bile acids itself because they were absent in liver tissue.

Bile Acids and Salts↗

Effects of human recombinant interleukin 5 and 3 on the differentiation of cord blood-derived eosinophils and basophils.

When mononuclear cells from umbilical-cord blood were cultured for 3 weeks, low concentrations of interleukin 3 supported the preferential growth of basophils, with eosinophils comprising a smaller proportion. These basophils contained 0.15-0.3 microgram histamine per 10(6) cells, and released histamine by the IgE-dependent and -independent stimuli. Interleukin 5 increased the number and proportion of eosinophils in a dose-dependent manner without affecting the proliferation of other cell types in the interleukin 3-supplemented cultures. These cultured eosinophils could be activated by platelet-activating factor.

Basophils↗

How to prevent allergic disease. I. Study of specific IgE, IgG, and IgG4 antibodies in serum of pregnant mothers, cord blood, and infants.

We have investigated methods for decreasing the number of allergic patients and have produced the following data. We compared mothers' total IgE levels and allergen-specific IgG and IgG4 levels in 72 paired cases. In mothers with high total IgE, the cord blood levels of IgG and IgG4 specific for egg, milk, and mite allergens were significantly higher than in mothers with low IgE levels. Mothers who took over 200 ml of milk per day showed a statistically higher level of milk-specific IgG antibody. From our studies of IgE, IgG, and IgG4 antibody levels in atopic dermatitis patients, we conclude that specific IgG and IgG4 levels should be considered when eliminating offending foods. Infants with high egg-specific IgG antibody levels in cord blood were statistically more prone to develop allergic disease.

Eggs↗

Studies on steroids. CCXXXVIII. Determination of bile acids in liver tissue by gas chromatography-mass spectrometry with negative ion chemical ionization detection.

A method for the determination of bile acids in 2-10 mg of human liver tissue by gas chromatography (GC) in combination with negative ion chemical ionization (NICI) mass spectrometry is described. Unconjugated, glycine- and taurine-conjugated bile acids labelled with 18O and 2H were used as internal standards. The preparation of these compounds was attained by the exchange reaction of the carbonyl group with H218O, followed by metal hydride reduction. Bile acids in solubilized liver tissue were extracted with a Sep-Pak C18 cartridge, separated into the unconjugated, glycine- and taurine-conjugated fractions by ion-exchange chromatography on piperidinohydroxypropyl-Sephadex LH-20 and then derivatized to the pentafluorobenzyl ester-dimethylethylsilyl ethers. Subsequent resolution of each fraction into lithocholate, deoxycholate, chenodeoxycholate, ursodeoxycholate and cholate was attained by GC on a cross-linked 5% phenylmethyl silicone fused-silica capillary column where bile acids were monitored with a characteristic carboxylate anion [M - 181]-in the NICI mode using isobutane as a reagent gas. The newly developed method was applied to the quantitation of bile acids in liver tissue with satisfactory sensitivity and reliability.

Bile Acids and Salts↗

Role of chemical mediators after antigen and exercise challenge in children with asthma.

Changes in chemical mediators after antigen challenge and exercise challenge tests were studied in children with asthma. Chemical mediators studied after antigen challenge and exercise challenge included histamine, leukotrienes (LTB4, LTC4, and LTD4), and neutrophil chemotactic factor of anaphylaxis (NCA). The pharmacologic modification of immediate and late-phase reactions was evaluated for procaterol (beta 2-agonist), cromolyn sodium, and prednisolone. Histamine levels were noted to rise in patients who had a dual response of a mild to moderate nature, but did not change in patients who had severe asthma. During exercise challenge cromolyn sodium inhibited both immediate and late-phase reactions but also inhibited plasma generation of NCA. Prednisolone, on the other hand, did not affect immediate reactions, but blocked late-phase reactions to exercise and also decreased NCA generation. Procaterol inhibited the generation of LTD4 and also inhibited NCA when compared with placebo. Exercise challenge did not alter levels of plasma histamine or of LTB4 or LTC4.

Adolescent↗