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Biomedical subjects

R Soda

Publications and source records attributed to R Soda.

At least 37 records · Page 2Linked to original sources

[Successful treatment for advanced and refractory chronic lymphocytic leukemia with fludarabine phosphate].

53-year-old man with chronic lymphocytic leukemia resistant to alkylating agent containing regimens, was treated with fludarabine phosphate. Hematological data before the administration of fludarabine phosphate was as follows: RBC 216 x 10(4)/microliter, Hb 7.7 g/dl, WBC 69,400/microliter (lymphocyte 96%), PLT 0.2 x 10(4)/microliter. Bone marrow was fully occupied with lymphocytes. Red blood cells and platelets transfusions were frequently required. Fludarabine phosphate was administered at a dose of 40 mg (23 mg/m2) intravenously for 5 days every 4 weeks. After the start of the therapy, peripheral lymphocyte counts were markedly decreased and recovery of normal hematopoiesis was observed in bone marrow. Any transfusions were no longer necessary. Fludarabine phosphate may be active even for advanced, refractory and terminal stage chronic lymphocytic leukemia.

Antineoplastic Agents↗

Signal transduction by IgG receptors induces calcium mobilization, but not histamine release, in the human basophilic cell line KU812F.

Human blood basophils selectively express Fc gamma RII (CDw32) among IgG receptor subtypes, but its functional role in allergic reactions remains unknown. Using the human basophilic leukemia cell line KU812F as a model system, we investigated cellular signaling events mediated through IgG receptor stimulation. KU812F cells express Fc gamma RII on their surface. mRNAs for both Fc gamma RIIA and IIB subtypes were detected by reverse transcriptase-PCR analysis. In this cell line, Fc gamma RII stimulation induced mobilization of free intracellular calcium and actin polymerization. Yet, no significant histamine release was observed, nor did blood basophils stimulated by anti-Fc gamma RII monoclonal antibody IV.3 and by a secondary antibody release histamine. These data indicate that Fc gamma RII stimulation induces cellular signaling events such as calcium mobilization in human basophils. However, these events do not lead to histamine release.

Actins↗

[Interferon production in peripheral blood cells of patients with pulmonary mycobacterial disease].

Production of interferon (IFN)-alpha and IFN-gamma were examined in 31 patients with acute tuberculosis, 12 patients with atypical mycobacterial disease. IFN production was examined in cultures of unseparated fresh whole blood. Production of IFN-alpha was induced by hemagglutinating virus of Japan and production of IFN-gamma was induced by PHA. Patients with mycobacterial disease produced significantly less IFN-alpha than healthy subjects. In patients with acute tuberculosis, effective chemotherapy for 2 months restored IFN-alpha production. Patients produced less IFN-gamma than healthy subjects, but the difference was not significant. Patients with high serum CRP levels tended to produce little IFN-alpha. These results suggest that measurement of IFN production is useful for immunological evaluation of patients with mycobacterial disease.

Acute Disease↗

[Clinical study of bronchial asthma in adult, intractable asthmatics after introduction of guideline therapy].

Introduction of Guideline for asthma treatment proposed by the committee of Japanese allergology have a tremendous impact on patients with bronchial asthma. Intractable asthmatics who have had to take some oral steroid to overcome disease severity, may have also some merit by this treatment, so that some of them might be no longer considered as intractable asthmatics. To clarify this, multicenter study was conducted. In this study, a case who have had more than 5 mg of prednisolone and/or 800 mu g of beclomethasone dipropionate throughout the year, was diagnosed as intractable asthmatics. In 845 case, 14.7%, 123 cases were diagnosed as intractable. These cases were significantly to be non-atopic and adult onset. Also, they have a significant tendency to be deteriorated by infection and careless drug administrations. Using the multiquantification method to examine the most powerful factor on intractable asthmatics, type of asthmatics was the most important and the past history of severe attack was the second. When intractable asthmatics diagnosed mainly by their BDP usage (BDP-intractable) were compared with intractable diagnosed by oral PSL (PSL-intractables), BDP-intractables were significantly atopic compared to PSL-intractables.

Asthma↗

[Usefulness of inhaled steroids in steroid-dependent intractable asthma--equivalent dose of oral steroid to inhaled steroid].

Twenty-four steroid-dependent intractable asthmatics were treated with oral prednisolone (PSL) (basic dose) + additional PSL and oral PSL (basic dose) + inhaled beclomethasone (BDP) alternately, to assess the clinical symptoms in each administration period. Equivalent doses of PSL to BDP were calculated. 1. Peak expiratory flow rate (PEF) during additional administration of BDP was markedly higher both in the morning and at night compared with that during additional administration of BDP was markedly higher both in the morning and at night compared with that during additional administration of PSL (p < 0.01 and p < 0.05 respectively). 2. The relation between additional doses of either PSL or BDP and attack scores was analysed in regression to obtain a dose equivalence line. 3. BDP 400 micrograms was equivalent to PSL 7.04 mg on average. 4. The equivalent dose of PSL to BDP tended to be lower in cases where the period of dependency on oral steroids was longer, the basic dose was larger, or the asthma was more severe. These data indicate that the application of inhaled steroids may be useful in the therapeutic management of steroid-dependent intractable asthmatics.

Administration, Inhalation↗

[Therapeutic potential of sparfloxacin for preventing mycobacterial infections].

We studied the therapeutic potential of utilizing sparfloxacin (SPFX), a newly developed quinolone, to prevent various mycobacterial infections. The in vitro activity of SPFX as a preventive agent for various mycobacteria was determined using the actual count method on Ogawa egg medium. The minimal inhibitory concentrations (MICs) of SPFX were as follows: ofloxacin-sensitive M. tuberculosis, 0.16-0.32 microgram/ml; ofloxacin-resistant M. tuberculosis, 0.63-2.5 micrograms/ml; M. avium; 0.63-10 micrograms/ml (MICs were equal or less than 1.25 micrograms/ml in seven out of 11 strains); M. intracellulare, 2.5-10 micrograms/ml (MICs were equal or more than 10 micrograms/ml in 17 out of 23 strains); M. kansasii, < or = 0.08-0.16 microgram/ml; M. fortuitum, < or = 0.08 microgram/ml; M. chelonae subsp. abscessus, > 10 micrograms/ml; M. chelonae subsp. chelonae, 0.63 microgram/ml; M. scrofulaceum, < or = 0.08 microgram/ml; M. nonchromogenicum, 1.25 micrograms/ml; M. xenopi, < or = 0.08 microgram/ml; M. gordonae, < or = 0.08 microgram/ml. The average serum concentrations of SPFX during the period of multiple oral administration (200 mg once a day) were 0.35 +/- 0.16 microgram/ml before administration, 0.67 +/- 0.32 microgram/ml after one hour, 1.13 +/- 0.21 microgram/ml after two hours, 1.27 +/- 0.32 microgram/ml after four hours and 1.31 +/- 0.34 micrograms/ml after six hours. These results indicate that SPFX has a strong therapeutic potential to prevent infections due to M. tuberculosis, M. kansasii, M. fortuitum, M. chelonae subsp. chelonae, M. scrofulaceum, M. xenopi and M. gordonae. Moreover, it may be expected to be a promising agent against infections due to ofloxacin-resistant M. tuberculosis, M. avium and M. nonchromogenicum.

Anti-Infective Agents↗

[Henoch-Schönlein purpura associated with pulmonary tuberculosis].

A 34-year-old man was admitted to our hospital because of cough and fever. Chest radiograph showed multiple cavities mainly on the right lung. His sputum was positive for acid-fast bacilli on smear, and he was treated with daily isoniazide, rifampicin and streptomycin. Antituberculous treatment was successfully performed, so acid-fast bacilli of his sputa disappeared on smear and culture. Five months later, he developed a purpuric lesions over both legs accompanied by low grade fever and arthralgia, but proteinuria and abdominal pain could not be observed. Laboratory findings showed a normal platelet count and a normal bleeding time. High levels of serum IgG, IgA, C3 and C4 were evident. ASLO and ASK titer were elevated and they markedly increased within two weeks. A direct invasion of the vessel wall by tubercle bacilli is deniable because antituberculous treatment was successfully continued. Henoch-Schönlein purpura was diagnosed judging from these findings. High levels of ASLO and ASK suggest a preceding streptococcal infection for developing purpura but a possible infectious focus could not be identified. He was treated with 15 mg of prednisolone daily for two weeks and the lesion was subsided. The effect of prednisolone suggests that a subsequent antigen-antibody interaction caused by a streptococcal infection may participate in the formation of the purpura.

Adult↗

New flow cytometric method for surface phenotyping basophils from peripheral blood.

To clarify the role of basophils in the pathogenesis of allergic disease, we developed a new method for performing surface phenotyping of these cells in centrifugation-enriched mononuclear cell fraction. This method identified basophils on the basic of a negative reactivity with mixed FITC-conjugated monoclonal anti-bodies (mAbs) (anti-CD2, -CD14, -CD16, and -CD19) with analysis performed by flow cytometry. The validity of this approach was confirmed by sorting experiments. Various PE-conjugated mAbs were also used to examine binding to FITC-negative basophils. Basophils from asthmatic patients (n = 14) as well as from normal subjects (n = 6) were shown to express CDw32 (Fc gamma RII), CD25 (IL-2R), but not CD64 (Fc gamma RI). We also detected binding of IgG1 and IgG4 to basophils. This method of phenotyping was very rapid and simple. It thus appears to be useful in the study of allergic disease, as well as of the biology of the basophil.

Antibodies, Monoclonal↗

[Predicting the clinical efficacy of house dust mite immunotherapy in bronchial asthmatics by multiple quantification analysis type II].

To predict the clinical efficacy of house dust mite immunotherapy (IT) for bronchial asthma, clinical factors before IT were analyzed in relation to clinical efficacy. The factors analyzed were severity, skin test threshold, age at which IT was started, duration of asthma, onset of asthma, FEV1.0%, serum IgE levels before IT, the presence of allergens other than HD, family history of atopic disease, complications with other allergic diseases, sex, seasonality of attacks and the maintenance dose. The clinical efficacy ranging from good response to no benefit was well discriminated by this analysis. The rate of discrimination was about 90%, indicating clinical usefulness of the method. In this study, skin test threshold seemed to be the most important factor, followed by FEV1.0%. While severity and age have been reported to be important, those who show good FEV1.0% and low skin test threshold, regardless of their severity or age, may be good candidates for IT.

Adolescent↗

[A study to predict the clinical efficacy of house dust mite immunotherapy in bronchial asthmatics].

To predict the clinical efficacy of house dust mite immunotherapy (IT), clinical factors before IT were analyzed in relation to clinical efficacy in bronchial asthmatics treated by standard IT method. In 111 asthmatics treated by IT, 88 cases (80%) obtained favorable results over a one-year period, while only 39% of asthmatics without IT showed clinical improvement (p < 0.05, chi 2 test). Factors including severity, skin test threshold, age, age at which IT was started, duration of asthma, onset of asthma, FEV1.0% and serum IgE levels before IT were analyzed. Severity showed the most significant influence on clinical efficacy (r = 0.412, p < 0.01). A study to determine whether some specific criteria could be used to predict the clinical efficacy of IT was then carried out. Using multivariate analysis with the factors above mentioned, the clinical efficacy ranging from deteriorated to good response could be expressed as a formula with a multi-regression coefficient of 0.56, p < 0.05. Moreover, the application of linear discriminating analysis gave an 80% true positive discriminating rate in 75 asthmatics. In both methods, severity seemed to be the most important factor, skin test threshold next and FEV1.0% third. The other factors were not significant. Hopefully, the use of this formula in clinical practice will improve the efficacy of IT, thus providing further therapeutic benefits to bronchial asthmatics.

Adult↗

[Flow cytometry study on purification of human eosinophils and cell function].

The eosinophil is a well-known leukocyte acting as an effector cell in the allergic reaction mechanism. The application of appropriate materials has led to more exact results from allergic examinations. In an effort to further improve analysis, we established a novel purification method for eosinophils using the flow cytometry (PCM) of peripheral blood and bronchoalveolar lavage fluid (BALF) leucocytes from healthy and allergic subjects. We examined the function of these cells in chemotaxis by platelet activating factor (PAF) and recombinant human (rh) IL-5. We obtained following results. First, we were able to separate human eosinophils containing autofluorescence substance, which was detectable by FCM employing a 450 nm argon ion laser. Second, the purity and recovery rate of the eosinophils were 90.1 +/- 4.2% and 32.1 +/- 7.6% in the healthy subjects who had no peripheral eosinophilia (< 6%) and 93.7 +/- 4.4% and 37.2 +/- 7.5% in the allergic subjects who had eosinophila (> 6%). A relationship was readily apparent between the peripheral and purified eosinophil counts in the healthy subjects (r = 0.62). Autofluorescence of the eosinophil fraction on PCM was further found to be decreased in patients with marked eosinophilia because of an increase in hypodense eosinophils. Third, highly purified eosinophils (76%) were also obtained from the 6.5% eosinophils present in the bronchoalveolar lavage fluid of one bronchial asthma patient. Fourth, the maximal chemotaxis of these eosinophils was shown at 10(-6) M of platelet activating factor (PAF) and at 1 micrograms/ml of IL-5 in a dose-dependent manner. This activity in allergic patients was accelerated compared with that in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Clinical features of bronchial asthma with mucus hypersecretion].

Fifty patients with bronchial asthma were divided into four groups according to the amount of expectoration per day: 0-24, 25-49, 50-99 and 100+ ml/day. Clinical features of patients with mucus hypersecretion (more than 50 ml/day of expectoration) were evaluated by age, severity of disease, cellular composition of bronchoalveolar lavage (BAL) fluid, and ventilatory function. 1. The proportion of patients with steroid-dependent intractable asthma (SDIA) in each group increased with increase in mucus hypersecretion. 2. Many of the patients with mucus hypersecretion (more than 50 ml/day) were over the age of 40. 3. The proportion of BAL eosinophils was significantly higher in patients with hypersecretion (more than 50 ml/day) than in those with expectoration of less than 49 ml/day. There was a significant correlation between the proportion of BAL eosinophils and the amount of expectoration per day (r = 0.48, p < 0.05). Proportions of lymphocytes and neutrophils in the BAL fluid were not related to the amount of expectoration per day. 4. There was no significant correlation between the amount of expectoration per day and ventilatory function in patients with asthma in this study.

Adult↗

[Changes in bronchoalveolar cell profiles of asthma patients induced by long-term glucocorticoid therapy].

Effects of long-term glucocorticoid therapy on airway inflammatory cells were examined in 40 patients with bronchial asthma. 1. The dose of glucocorticoids required by asthmatic patients tended to increase and the level of serum cortisol tended to decrease with prolongation of the period of glucocorticoid therapy. 2. The proportion and number of lymphocytes in bronchoalveolar lavage (BAL) fluid decreased with prolongation of the period of glucocorticoid therapy. The proportion of BAL lymphocytes in asthmatic patients treated with glucocorticoids for more than 5 years was significantly lower than that in those treated for less than 4.9 years. 3. The proportion and number of BAL neutrophils increased with prolongation of the period of glucocorticoid therapy and the proportion of BAL neutrophils in patients treated with glucocorticoids for more than 10 years was significantly higher compared with those treated for less than 9.9 years. These findings indicate that long-term glucocorticoid therapy induces changes in airway inflammatory cell profiles, with a decrease in the number of lymphocytes and increase in the number of neutrophils.

Adult↗

[The measurement of superoxide generation and eosinophil peroxidase (EPO) from eosinophils].

Eosinophils play an important role in the field of allergy, and release several kinds of granule proteins, leukotrien and superoxide. The most popular method to measure superoxide is utilizing SOD-inhibitable reduction of ferricytochrome c. And recently, the microplate reader enables us to measure superoxide generation from eosinophils more easily using this method. To measure superoxide, we must pay attention to obtain a high purity of eosinophils and not to damage cells. It is also possible to measure eosinophil peroxidase (EPO) using the microplate reader. We are measuring EPO with colorimetric assay using OPD (o-phenylenediamine). OPD is specific to EPO and has no cross reaction to myeloperoxidase. We, now have numerous methods to evaluate eosinophil function, so a selection must be made to select the most correct method.

Cells, Cultured↗

[Correlation between proportion of BAL cells and ventilatory function in patients with asthma].

The correlation between proportions of cells in bronchoalveolar lavage (BAL) fluid and ventilatory function was examined in 52 patients with asthma. 1. There was no significant correlation between the proportion of BAL lymphocytes and ventilatory function. 2. The proportion of BAL eosinophils correlated to a certain extent with ventilatory function: the values of %MMF, %V50 and %V25 were lower in patients with BAL eosinophils of 10-19.9% than in those with BAL eosinophils below 4.9%, and %V25 value was significantly lower in patients with a high proportion of BAL eosinophils (10-19.9%) compared with those with a low proportion of BAL eosinophils (0-4.9%). However, ventilatory function was not decreased in patients with BAL eosinophils of more than 20%. 3. The values of ventilatory parameters showed a tendency to decrease with increase in BAL neutrophils. The values of all parameters of obstructive ventilatory dysfunction were significantly lower in patients with BAL neutrophils of > 10% than in those with BAL neutrophils < 4.9%. A significant difference between patients with BAL neutrophils > 10% and < 9.9% was found in values of %V50 and %V25, and the values of %V50 and %V25 were significantly lower in patients with a high proportion of BAL neutrophils (> 10%) than in those with BAL neutrophils < 9.9%. These results suggest that the proportion of BAL eosinophils is to a certain extent related to ventilatory function of asthma patients and that the increase in proportion of BAL neutrophils is closely related to a decrease in values of obstructive ventilatory parameters.

Adult↗

[The reactivity of dispersed human lung mast cells and peripheral blood basophils to acetylcholine].

To clarify the relation between human lung mast cells and parasympathetic nerve function as well as IgE mediated allergic reactions, highly purified dispersed human lung mast cells were obtained by using the techniques of scissors dispersion, enzymatic treatment, percoll centrifugation and exclusion of adherent cells. The reactivity to acetylcholine was examined by observing the histamine release of purified mast cells. Moreover, peripheral blood basophils, which have many functional similarities with mast cells, were also examined in the same manner. The following results were obtained; 1) Histamine was significantly released from dispersed human lung mast cells at a final concentration of 10(-5) M acetylcholine (p less than 0.05); the peak of histamine release was 10(-4) M of acetylcholine. Acetylcholine had the additional effect of releasing histamine in response to anti-IgE. Histamine release was partially inhibited by 10(-5) M atropine. 2) Basophils had no response to acetylcholine. These results suggest that human lung mast cells play an important role in the defensive mechanism as an effector cell of acetylcholine-mediated autonomic nerve system as well as IgE-mediated allergic reaction.

Acetylcholine↗