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Biomedical subjects

R Soda

Publications and source records attributed to R Soda.

At least 55 records · Page 3Linked to original sources

[Studies on IFN-gamma production by peripheral blood mononuclear cells cultured with Candida antigen in asthmatics].

T-cell-derived lymphokine, IFN-gamma, has potent effects on B-cell differentiation and leukotriene C4 production in leukocytes, and inhibits the effect of IL-4 on IgE production. To investigate the role of IFN-gamma in the pathogenesis of bronchial asthma, we examined IFN-gamma production by peripheral blood mononuclear cells cultured with Candida antigen and serum Candida specific IgG1 antibody from 20 asthmatics. The results were as follows: 1) IFN-gamma production in non-atopic severe asthmatics was significantly higher than in healthy subjects, atopic mild and moderate asthmatics, and atopic severe asthmatics (p < 0.05). 2) There was a significant correlation between IFN-gamma production induced by Candida antigen and serum Candida specific IgG1 antibody (r = 0.72, p < 0.01). These results suggest that IFN-gamma may play an important role in the pathogenesis of non-atopic severe bronchial asthma.

Adult↗

[Effects of a specific thromboxane A2 synthetase inhibitor on lymphocyte and neutrophil functions in adult intractable asthmatics].

To clarify whether thromboxane A2 (TXA2) is involved in type III and IV allergy, or so called "cell-mediated allergy", we studied the effect of a specific TXA2 synthetase inhibitor, sodium ozagrel (OKY-046) on peripheral blood mononuclear cells and neutrophils in adult intractable asthmatics. The results revealed, firstly, that lymphocyte blastogenesis and interleukin-2 (IL-2) production from peripheral blood mononuclear cells stimulated by PHA and Candida antigen in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. Secondly, there was a tendency that neutrophil chemotactic factor (NCF) and eosinophil chemotactic factor (ECF) from peripheral blood mononuclear cells stimulated by Candida antigen in intractable asthmatics were suppressed by OKY-046. Thirdly, leukotriene (LTC4) and superoxide (O2-) production from peripheral blood neutrophils in intractable asthmatics was significantly suppressed dose-dependently by OKY-046. That is, OKY-046 has a suppressive effect on type IV allergy caused by lymphocyte activation and on mediator release from neutrophils. These results suggest that TXA2 plays an important role in the development of bronchial asthma and OKY-046 might be a useful drug in the treatment of intractable asthmatics.

Adult↗

[A case of pulmonary infiltration with eosinophilia (PIE) syndrome induced by Saiboku-To (TJ96). Detection of ECF activity in lymphocytes stimulated with TJ96].

A case of PIE syndrome induced by Saiboku-To (TJ96) is reported. A 56-year-old woman had been treated for intractable bronchial asthma since the age of 42 years. She had a history of PIE syndrome induced by disodium cromoglycate 4 years previously (Jpn. J. Thoracic Disease, 27.1.1989). To reduce the dose of prednisolone for her asthma, administration of TJ96 was started in Dec. 1989. After 5 months of TJ96 treatment, she developed dry cough, fever, and chest pain. Physical findings and laboratory examinations revealed pulmonary infiltrations in the right lung field and severe eosinophilia. Because of suspected drug-induced PIE, TJ96 was stopped and 30 mg/day prednisolone was administered. Her symptoms and laboratory abnormalities subsequently resolved. To confirm the diagnosis of drug-induced PIE syndrome, drug-induced lymphocyte stimulation tests with TJ96 and other drugs were performed. TJ96 significantly induced lymphocyte blastogenesis with a stimulation index of 6.1. Moreover, the supernatant of the incubation mixture of TJ96 and peripheral lymphocytes from the patient showed marked eosinophil chemotactic activity. To our knowledge, there has been no previous report of PIE syndrome induced by TJ96. In addition, this is the first report of the detection of ECF activity in lymphocytes induced by an offending drug in vitro.

Asthma↗

[Studies of lymphocyte activation on late asthmatic response in adult asthma].

Late asthmatic response (LAR) as well as delayed asthmatic response (DeAR) is an important clinical characteristic in adult severe asthma. These responses might be based on cell to cell interaction following lymphocyte activation. Therefore, to clarify the pathogenesis of LAR, we studied the lymphocyte functions of adult asthmatics with LAR provoked by inhalation of house dust and Candida antigen. The results revealed that mite antigen-specific lymphocyte blastogenesis, IL-2 and ECF production were significantly higher in asthmatics with LAR provoked by house dust antigen than in normal subjects and asthmatics with IAR by house dust and LAR by Candida, though there was no significant difference in NCF. Candida antigen-specific lymphocyte blastogenesis, IL-2, ECF and NCF production were significantly higher in asthmatics with LAR provoked by Candida antigen than in normal subjects and asthmatics with IAR or LAR provoked by house dust. There was a positive correlation between Candida antigen-specific IL-2 and NCF production in asthmatics with LAR provoked by Candida antigen. These results suggest that antigen-specific lymphocyte activation may play an important role in the pathogenesis of LAR, especially in asthmatics with LAR provoked by Candida antigen, and that LAR and DeAR should be considered inclusively as cell-mediated allergy.

Adolescent↗

[Studies on the mechanism of late asthmatic response by Candida antigen inhalation using bronchoalveolar lavage].

To elucidate the mechanism of late asthmatic response (LAR), which is related to intractable asthma attack, the cellular and humoral components of LAR were examined in bronchoalveolar lavage fluid (BALF) obtained after bronchial inhalation tests with Candida allergen on Candida-sensitive asthma patients. BAL examination was carried out 2 hours after remission of LAR, and differential cell counts and measurements of leukotrienes (LTs) by high performance liquid chromatography were investigated in BALF and peripheral blood. The number of neutrophils and basophils in circulating blood showed a peak before LAR, and then decreased markedly at LAR. And an increase in the percentage of eosinophils (p less than 0.01) and neutrophils was evident in BALF after LAR compared with the level in the non-attack state. The percentage of basophil-mast cells, however, did not change in the same manner. The serum level of LTC4 increased significantly at LAR in comparison with its level in the phase before LAR. And the level of LTC4 was also significantly higher in BALF after LAR (p less than 0.01). However, LTD4 and LTB4 were at almost undetectable levels in BALF in the non-attack state and after LAR. The results indicate that neutrophils as well as eosinophils may accumulate and release several kinds of leukotrienes at local sites in late asthmatic response provoked by the inhalation of Candida antigen; this gives clues as to the mechanism of severe and intractable asthma attacks.

Adult↗

[Studies on IgG subclass antibodies in adult asthma. 2. Changes in serum antigen specific IgG subclass antibodies for aging and intractability in asthmatics].

To clarify the factors which induce intractable asthma, the level of serum IgG subclass antibodies to mite (Dermatophagoides farinae) and Candida antigens (Candida albicans) for aging and severity was investigated in 230 bronchial asthmatics (Male: 117, Female: 113) aged 6-81 years old (mean age = 40). Total IgE level and IgE antibodies to mite and Candida antigens were measured by radioimmunosorbent test (RIST) and radioallergosorbent test (RAST), respectively. The serum level of IgG and IgG1 antibodies to the antigens were measured by enzyme-linked immunosorbent assay (ELISA). The results were as follows: 1) The incidence of severe asthma in aged and late onset asthmatics, especially late onset intractable asthma (LOIA), was higher than that in young and early onset asthmatics. 2) The serum level of total IgE and IgE antibodies to mite in aged and late onset asthmatics was lower than that in young and early onset asthmatics. 3) The incidence of severe and intractable asthmatics in the group of low IgE levels (less than 300 IU/ml) was higher than that in the group of high IgE levels (over 500 IU/ml). The incidence of positive IgE (RAST) score to mite in severe and intractable asthmatics was lower than that in mild and moderate asthmatics. 4) Considering aging, the serum levels of IgG and IgG1 antibodies to mite and Candida in severe and intractable asthmatics was higher than those in mild asthmatics. These data indicate that the aged and late onset asthmatics may produce dominantly the IgG (IgG1) antibody to the antigens, and have severe asthma attacks caused by IgG (IgG1) rather than IgE antibody.

Adolescent↗

[Purification and reactivity of human lung mast cells].

To clarify the pathogenesis of allergic pulmonary diseases by analysis of the reactivity of human lung mast cells, we established a method of dispersion and purification of mast cells from human lung tissue. This method consisted of 4 steps; 1) mincing by scissors, 2) enzymatic treatment by a pronase-chymopapain and collagenase-elastase mixture, 3) percoll centrifugation and 4) exclusion of adherent cells. Using this method, dispersed human lung mast cells were obtained with 38.8% purity and more than 95% viability. These mast cells contained 4.1 pg of histamine per cell, which showed these cells had mild spontaneous histamine release after treatment. The mast cells released histamine in a dose-dependent manner after treatment with calcium ionophore A 23187 and anti-IgE, and these phenomena were dependent on extracellular calcium ions. However, the cells did not release histamine with less than 100 micrograms/ml of compound 48/80. These results indicate that the human lung mast cells obtained by this method are useful to make immunological and pharmacological analyses in allergic lung diseases.

Humans↗

[A case of occupational asthma caused by arrowhead scale in mandarin orange-worker].

A 50-year-old woman with occupational asthma, whose attacks were provoked by inhalation of Arrowhead scale (Unapsis Yanonensis Kuwana) attached to the leaves of mandarin oranges is reported. She experienced asthmatic attacks while picking leaves and harvesting mandarin oranges. Because Arrowhead scale-dust stuck to the leaves was suspected to be the allergen, tests of allergy were performed using an extract of the allergen prepared by Unger's method in our laboratory. Asthmatic attack was provoked 90 minutes after inhalation of the extract of cocoon. Histamine was not released, but leukotriene D4 production was induced by the addition of the extract to whole blood. Basophils were activated by addition of anti-IgG anti-sera as well as the extract. These data indicate that LT released from target cells in response to the worm elements, as well as histamine, is important as a chemical mediator.

Agricultural Workers' Diseases↗

[Studies on IgG subclass antibodies in adult asthma. 1. Serum antigen specific IgG subclass antibodies in asthmatics with late asthmatic response].

It is clear that immediate asthmatic response is mediated by IgE-dependent mechanisms. However, late asthmatic response is induced by inhalation of antigens without antigen specific IgE antibodies in some asthmatics, especially in intractable asthma induced by Candida antigen. To elucidate the relationship between those bronchial responses and antibodies, antigen specific IgG subclass antibodies in sera from asthmatics were measured and compared with IgE antibody. The results were as follows. 1. Avidin-biotin ELISA (enzyme-linked immunosorbent assay) method was established for the measurement of specific IgG and IgG subclass antibodies to mite or Candida antigen. 2. Serum levels of antigen specific IgG and IgG1 antibodies in asthmatics with LAR provoked by mite or Candida antigen were significantly higher than those in asthmatics without LAR (p less than 0.01). 3. Serum levels of specific IgE antibody to these antigens in asthmatics with LAR provoked by mite or Candida antigen were slightly lower than those in asthmatics without LAR, though the difference is not significant. These results suggest that high serum levels of specific IgG and IgG1 antibodies to these antigens play a role in inducing LAR in asthmatics with LAR.

Adolescent↗

Endothelial mediation is necessary for subsequent hepatocyte uptake of transferrin.

The authors previously have reported on the presence of transferrin (TF) receptors on liver endothelial cells and have shown that hepatic uptake of transferrin-iron (TF-Fe) complexes in the liver is mediated by the endothelium. We now provide evidence that this endothelial cell mediation may be necessary for hepatocyte uptake of TF-Fe complexes. Transport of TF-Fe from endothelial cell to hepatocyte was studied in mixed cell suspensions in which radiolabeled TF-Fe complexes were incubated at 37 degrees C with the two cell populations purified and then mixed in equal ratios. The mixtures were then refractionated at various times after incubation and cell-associated radioactivities measured. Radiolabeled TF was rapidly taken up by the endothelial cell fraction, but radioactivity began to decline in this fraction as it increased in the hepatocyte fraction. In double labeling experiments with 125I-TF-59Fe, both radiolabels moved across the endothelium in parallel fashion, indicating that Fe remains associated with TF during transcytosis. However, in hepatocytes the two radiolabels became dissociated, with Fe remaining cell-associated and TF being recycled. Hepatocyte uptake of processed TF was partially inhibitable by galactan and asialofetuin, indicating that hepatocyte uptake may occur via asialoglycoprotein receptors of hepatocyte.

Animals↗

[Clinical studies on steroid-dependent intractable asthma. Comparison between early and late onset of asthma].

The various components making for severe intractable asthma were clinically and allergo-immunologically studied in 90 patients with bronchial asthma, by comparison between early onset and late onset groups. 1. In the early onset asthma group, cases with low serum IgE levels showed a stronger tendency toward severe intractable asthma. 2. Late onset asthma cases with negative skin tests and negative specific IgE antibodies to house dust tended more often to be severe intractable cases. 3. There was no correlation between sensitization by specific antigens (house dust and Candida), especially Candida, and a tendency toward severe intractable asthma. 4. Severe intractable asthma might be caused by bronchospasm in cases under 30 years of age, by bronchospasm plus hypersecretion in cases between 31 and 40 years of age, and by bronchospasm plus bronchiolar obstruction in cases over 40 years of age.

Adolescent↗

[A case of bronchial asthma and PIE Syndrome induced by disodium cromoglycate].

A 54-year-old female with bronchial asthma and PIE syndrome induced by disodium cromoglycate (DSCG) was reported. She was referred to our hospital for further examination of the abnormal chest shadows and eosinophilia. She had been treated with DSCG, Cefaclor. Bromhexine and bronchodilator for bronchial asthma and bronchitis. Withdrawal of the drugs except for the bronchodilators alleviated her symptoms. Therefore, drug induced lymphocytes stimulation tests (DLST) were performed for those three drugs. Only DLST for DSCG showed a positive result. She had been asthmatic for ten years and treated by the drug for 18 months prior to admission. The skin test for the drug was negative and a precipitating antibody for the drug could not be found. To obtain a definite diagnosis, bronchial challenge by DSCG was performed, after her symptoms were under control. Severe asthmatic responses were provoked in 6 and 24 hours after the inhalation of DSCG. Bronchoalveolar lavage, performed 8 days after the provocation, revealed increased eosinophils and lymphocytes in BAL fluid. Although several cases of PIE syndrome induced by DSCG have been reported, this seems to be the first report of late and delayed type bronchial response and pulmonary infiltration with eosinophilia provoked by DSCG. The bronchial response to the drug was a late and delayed type reaction and sustained for a long period. This might indicate that PIE syndrome induced by the drug may be caused by a same mechanism as the provoked asthmatic response.

Asthma↗

[The clinical significance of Creola body in the sputum of asthmatic patients].

In order to clarify the relationship between agglomerated bronchial epithelial cells, i.e. Creola body (CrB), in the sputum and each pathogenetic factor of bronchial asthma, the incidence of CrB in sputum stained by Papanicolaou's method and observed under a light microscope was evaluated in 45 cases of bronchial asthma and 9 cases of obstructive pulmonary diseases. The following results were obtained: 1) CrB was observed specifically in the sputum of patients with bronchial asthma. In comparison with CrB-negative cases, CrB-positive cases had a greater number of days with attacks and a higher incidence of eosinophils in the sputum. 2) The presence of CrB in the sputum tended to be at a high rate in non-atopic cases with low serum IgE values, but had no obvious correlation with either the incidence of neutrophils in the sputum, the present age of the patient, the severity of the disease or bronchial hyperresponsiveness to methacholine. These results suggest that the involvement of histolesionable factors such as persistent bronchial contraction and release of major basic protein from eosinophils in the airway may lead to the formation of CrB.

Adult↗

The role of basophils and mast cells in cutaneous basophil hypersensitivity reaction.

Basophils are the main cell component in cutaneous basophil hypersensitivity (CBH) reactions, but the role of basophils and the factors which gather them into CBH reaction sites are unknown. To investigate these problems, we induced CBH reactions in guinea pigs and observed basophils and mast cells in the skin reaction sites using light and electron microscopy. Basophils infiltrated into CBH reaction site appeared at 5 h after the challenge with antigen, increased till 48 h and decreased thereafter. On the other hand, the number of mast cells and their granules decreased after the challenge with antigen and reached a minimum at 48 h, but recovered at 96 h. The changes in the number of basophils and mast cells were complementary. This result suggested that the granules of mast cells may have a factor to gather basophils into the CBH skin reaction site. Furthermore, basophils infiltrated in the CBH reaction site were degranulated by the rechallenge with antigen, which was considered to be by an anaphylactic reaction.

Animals↗

Liver endothelium mediates the uptake of iron-transferrin complex by hepatocytes.

We have previously shown that in the liver, transferrin (TF) receptors are limited to endothelial cells, and hepatocytes and Kupffer cells do not have TF receptors. To study the transport of iron into hepatocytes, we fractionated liver cell suspensions into endothelium and hepatocyte fractions. At 4 degrees C liver (but not umbilical cord) endothelium bound Fe-TF with a saturable kinetics. At 37 degrees C, the endothelial uptake was followed by its gradual release. Transendothelial transport of TF was visually demonstrated by perfusion of liver using colloidal gold-labeled TF. The released Fe-TF acquired the potential for binding to fresh target hepatocytes and binding was not inhibited by excess cold TF but was inhibitable by asialofetuin, suggesting galactosyl receptors and not TF receptors as a recognition mechanism. Isoelectrofocusing of the supernate after preincubation for 90 min at 37 degrees C with endothelial cells, demonstrated the presence of a newly generated band which co-migrated with asialotransferrin. We conclude that Fe-TF is initially removed by liver endothelium where it is modified probably by desialation to expose the galactosyl residues of the glycoproteins. The modified molecule is subsequently released and recognized by hepatocytes through a TF receptor-independent mechanism which may involve galactosyl receptors of hepatocytes. The findings indicate a key role for endothelium in the transport of Fe-TF into the liver and may suggest a physiological function for galactosyl receptors on hepatocyte surface.

Animals↗

Insulin uptake by rat liver endothelium studied in fractionated liver cell suspensions.

Cellular distribution of insulin receptors was studied in fractionated rat liver cell suspensions using 125I-insulin and a visual probe consisting of latex beads covalently linked to insulin (minibeads). Fractionation was done on metrizamide gradients which yielded two cellular fractions. The large cell fraction consisted mostly of hepatocytes and the small cell fraction consisted of 37% endothelial cells as well as Kupffer cells. The magnitude of insulin uptake by the endothelium-rich small cell fraction was at least double that of the uptake by the hepatocyte-rich fraction. The minibead technique demonstrated that in the small cell fraction only endothelial cells, and not Kupffer cells, were responsible for the insulin uptake. Our findings suggest that liver endothelium may be responsible for the uptake of circulating insulin and its transport to hepatocyte. This emphasizes the presence of a tissue-blood barrier in the liver.

Animals↗