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Biomedical subjects

S Tomari

Publications and source records attributed to S Tomari.

At least 19 recordsLinked to original sources

Effects of primary and secondary low-grade respiratory syncytial virus infections in a murine model of asthma.

BACKGROUND: Respiratory syncytial virus (RSV) infection is known to develop and exacerbate asthma in young children. In adult, RSV causes recurrent but asymptomatic infections. However, the impact of asymptomatic RSV infection on adult asthma is yet to be determined. The present study is designed to determine the effects of primary and secondary low-grade RSV infections on allergic airway inflammation in a murine model of allergic asthma. METHODS: A low-grade RSV (2 x 10(3) plaque-forming units/mouse) was inoculated, and this caused neither pulmonary inflammation nor symptoms but induced significant IFN-gamma production in thoracic lymph nodes. To investigate interaction between low-grade virus and Dermatophagoides farinae (Df), airway hyper-responsiveness, lung inflammation and cytokine production from thoracic lymph nodes were compared after primary and secondary low-grade RSV infections in four groups of mice; control, Df allergen-sensitized, RSV-infected and Df-sensitized RSV-infected mice. A direct comparison between low- and high-grade RSV infections was also performed in primary infection. To investigate the role of IL-5 during secondary RSV infection, anti-IL-5 monoclonal antibody (anti-IL-5 mAb) was injected in mice and similar parameters were compared in four groups of mice. RESULTS: Primary high-grade RSV infection increased allergen-induced airway inflammation, while primary low-grade RSV infection attenuated allergen-induced airway inflammation concomitant with significant IFN-gamma production in lung-draining lymph nodes. In marked contrast, secondary low-grade RSV infection increased both IFN-gamma and IL-5 production, resulting in exacerbation of allergen-induced airway inflammation. Anti-IL-5 mAb treatment in secondary low-grade RSV infection and Df allergen-sensitized mice attenuated virus and allergen-induced airway inflammation. CONCLUSIONS: Low-grade RSV infection per se does not cause pulmonary inflammation, whereas it induces a significant immunological response in the allergen-sensitized host. These results indicate that subclinical and recurrent RSV infection may play an important role in exacerbation and maintenance of asthma in adults, wherein IL-5 is critically involved.

Animals↗

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma.

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.

Adolescent↗

Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen-specific tumour necrosis factor alpha production and nuclear factor kappa B nuclear translocation in peripheral blood monocytes from atopic asthmatics.

BACKGROUND: The cysteinyl leukotriene receptor 1 (cysLTR1) antagonists are useful for oral treatment of bronchial asthma. The underlying mechanism of cysLTR1 antagonists on inhibition of inflammatory cytokine production is yet to be determined. OBJECTIVE: The present study was designed to determine the effect of pranlukast, a cysLTR1 antagonist, on production of inflammatory cytokines by allergen-stimulated peripheral blood monocytes (PBM) from atopic asthmatics. METHODS: PBM were obtained from normal control (n = 10) and Dermatophagoides farinae (Der f) allergen-sensitized atopic asthmatics (n = 12), and were cultured in the presence of Der f allergen. The production of TNF-alpha and nuclear-translocation of nuclear factor kappa B (NF-kappa B) was determined. In atopic asthmatics, pranlukast, tacrolimus or dexamethasone was added before stimulation by Der f. The additive effect of pranlukast and dexamethasone was also determined. RESULTS: PBM from atopic asthmatics cultured with Der f exhibited a significant increase in TNF-alpha production and nuclear translocation of NF-kappa B compared with normal control (P < 0.01). Pranlukast, tacrolimus and dexamethasone significantly inhibited production of TNF-alpha and nuclear-translocation of NF-kappa B in PBM of atopic asthmatics (P < 0.01). An additive effect of pranlukast on low-dose dexamethasone was also demonstrated. However, LTD4 did not induce TNF-alpha production or NF-kappa B nuclear translocation. CONCLUSION: Our results suggest that pranlukast may inhibit TNF-alpha production via suppression of NF-kappa B activation through pathways distinct from cysLTR1 antagonism.

Adult↗

Glomerular crescents predominantly express cadherin-catenin complex in pauci-immune-type crescentic glomerulonephritis.

AIMS: To investigate the expression of the cadherin complex in human crescentic glomerulonephritis to elucidate the role of intercellular adherens junction molecules in crescent formation. METHODS AND RESULTS: Immunostaining revealed cadherin complexes localized in Bowman's epithelial cells, but not in podocytes, of normal human glomeruli. Eight adult cases with myeloperoxidase anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA)-related (pauci-immune type) crescentic glomerulonephritis were examined on immunofluorescence microscopy with anti-pan cadherin, p120 catenin, and beta-catenin antibodies. The specimens provided six cellular crescents, 12 fibrocellular crescents, and four fibrotic crescents. Immunofluorescence was semiquantitatively estimated by the rate of the field of localization within the whole area of the crescent, according to the four-grade system [(-) - (++)]. All the tested molecules consisting of the cadherin complex were abundantly observed in cytokeratin-positive epithelial components in crescents, each with an equivalent area of localization. The expression of the cadherin complex was closely associated with that of cytokeratin and both diminished as the crescents developed from cellular to fibrotic. CONCLUSIONS: The cadherin-catenin complex is a specific marker of Bowman's epithelial cells in human glomeruli. The cellular crescents in pauci-immune-type crescentic glomerulonephritis possess adherens junction molecules, indicating a principle parietal epithelial cell phenotype.

Adherens Junctions↗

Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma.

BACKGROUND: Although inhaled steroids are used as the first line of therapy in asthmatic patients, symptoms of asthma do not improve completely in some patients. OBJECTIVE: To investigate the effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when combined with beclomethasone dipropionate (BDP). METHODS: Protocol 1: After a 2-week observation period, 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day). The effect of treatment was evaluated by measuring AM peak expiratory flow rate, symptom score, frequency of beta2-agonists, and daily variability of peak expiratory flow rate. Protocol 2: 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP (group I), severe asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were additionally treated with pranlukast. RESULTS: Protocol 1: Both treatment regimens resulted in improvement in each clinical parameter. There were no significant differences in the effects of two treatment regimens. Protocol 2: Pranlukast was effective in group I and II, but not in group III. In groups I and II, pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma. CONCLUSIONS: Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids. Pranlukast is more effective in patients treated with BDP early after onset.

Administration, Inhalation↗

Efficacy and safety of long-term treatment of asthmatic patients with pranlukast, a cysteinyl-leukotriene-receptor antagonist: four-year followup study.

BACKGROUND: There are few studies that have examined the long-term efficacy and safety of pranlukast, a leukotriene receptor antagonist, in asthmatic patients. METHODS: Sixty-three asthmatic patients were entered in this 4-year study [group 1, mild or moderate (N = 22); group 2, severe without using oral prednisolone (N = 22); group 3, severe with using oral prednisolone (N = 19)]. Pranlukast was administered at 225 mg twice daily to 14 subjects in group 1 (group 1p), 14 in group 2 (group 2p), and 11 in group 3 (group 3p), chosen for pranlukast additional therapy at random. Another group of 24 asthmatic patients was assigned to conventional therapy group (groups 1c, 2c, and 3c). Efficacy was determined by improvement in symptom score, peak expiratory flow rate (PEFR) percentage predicted, reduced daily variability of PEFR (percentage), and reduced frequency of use of rescue beta2-agonist (times per week). RESULTS: In groups 1p and 2p, PEFR percentage predicted began to improve from 2 weeks after commencement of treatment. The symptom score, daily variability of PEFR, and use of rescue beta2-agonist diminished significantly. In group 3p, pranlukast was ineffective in improving PEFR percentage predicted. All but two patients continued to receive pranlukast and no adverse effects were noted, at least during the 16-week therapy. Further, 22 patients continued to receive pranlukast for 4 years, and none experienced any adverse effects. CONCLUSIONS: We showed in this study that long-term treatment with pranlukast is effective for asthmatic patients without any adverse effects.

Adult↗

Effects of pranlukast on aspirin-induced bronchoconstriction: differences in chemical mediators between aspirin-intolerant and tolerant asthmatic patients.

BACKGROUND: Aspirin inhibits cyclooxygenase activity and modifies production of the arachidonate cascade in aspirin-induced asthma. The aim of the present study was to examine the effects of leukotriene (LT) receptor antagonist on aspirin challenge on eosinophil activity and chemical mediators released into the airway of asthmatic patients. METHODS: Aspirin oral provocation test was performed in aspirin-intolerant asthmatic patients (AIA; N = 7) and aspirin-tolerant asthmatic patients (ATA; N = 7). In AIA, LT receptor antagonist (pranlukast) was administered orally 2 hours before the test, and its inhibitory effects on sputum LTC4+C4, eosinophil cationic protein (ECP), eosinophil count, urinary LTE4/creatinine (Cr), 11-dehydrothromboxane (11-dhTX) B2/Cr, serum LTC4+D4, ECP, and peripheral blood eosinophil count were compared with the findings in ATA subjects. RESULTS: In AIA, aspirin induced an immediate reaction associated with increased urinary LTE4/Cr and sputum ECP and a fall in urinary 11-dhTXB2/Cr. Pranlukast inhibited the bronchial reaction and an increase in sputum ECP after threshold dosed of ASA, but failed to change aspirin-induced LT production in sputum and urine. In ATA, aspirin challenge was only associated with a fall in urinary 11-dhTXB2. CONCLUSIONS: Our results indicated that aspirin-induced asthma is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade and that leukotriene receptor antagonist are useful for AIA through inhibition of production of LT and eosinophilic inflammation in the airway.

Adult↗

Screening for acetaldehyde dehydrogenase 2 genotype in alcohol-induced asthma by using the ethanol patch test.

BACKGROUND: We have previously reported that alcohol-induced asthma in Japanese patients is caused by increased blood acetaldehyde concentration resulting from abnormalities of acetaldehyde dehydrogenase 2 (ALDH2) enzyme activity on the basis of ALDH2 genotype differences. OBJECTIVES: The purpose of the present study was to determine whether the ethanol patch test could predict the ALDH2 genotype in Japanese asthmatic subjects. METHODS: An ethanol patch test on the upper arm and a questionnaire survey addressing the past history of alcohol-induced asthma were administered to 148 adult Japanese asthmatic subjects. The ALDH2 genotypes in these 148 subjects were also determined by means of PCR. RESULTS: The genotype distribution of ALDH2 determined by PCR in 68 subjects with positive ethanol patch test results was 4 (5.9%), 56 (82.4%), and 8 (11.8%) for genotypes NN (normal homozygote), NM (mutant heterozygote), and MM (mutant homozygote). The ALDH2 genotype in 80 subjects with a negative test result was only NN. The distribution of ALDH2 genotype in 78 (52.7%) subjects who had experienced alcohol-induced asthma symptoms on the basis of the questionnaire was 27 (34.6%), 44 (56.4%), and 7 (9.0%) for genotypes NN, NM, and MM, respectively. On the other hand, 70 subjects had never experienced alcohol-induced asthma symptoms. In these subjects the ALDH2 genotype was NN in 51 (72.9%), NM in 18 (25.7%), and MM in 1 (1.4%). CONCLUSIONS: Our results indicate that the results of ethanol patch testing correlate well with ALDH2 genotype, as determined by means of PCR, suggesting that the ethanol patch test is useful for the screening of alcohol-induced asthma.

Adult↗

Transplantation of the en bloc vascular system for coronary revascularization.

OBJECTIVES: Use of the free gastroepiploic artery graft for coronary revascularization has not been very popular because of its inclination toward vasospasm. We hypothesized that the cause of free gastroepiploic artery spasm was the graft damage caused by an interruption of venous drainage from the graft. To solve this problem, we developed a new method of free gastroepiploic artery grafting. METHODS: From January 1997 to October 1999, 33 patients underwent coronary artery bypass grafting with the free gastroepiploic artery according to our new method. The gastroepiploic artery graft was harvested en bloc with its satellite veins. The gastroepiploic vein was anastomosed to the right atrial appendage for venous drainage simultaneously with the gastroepiploic artery being grafted in the aortocoronary position. RESULTS: A total of 96 distal anastomoses were performed, including 33 free gastroepiploic artery grafts according to our method, 33 in situ left internal thoracic artery grafts, 26 saphenous vein grafts, and 4 radial artery grafts. Neither operative nor hospital death occurred. Early postoperative angiography revealed that all of the 33 free gastroepiploic artery grafts performed with our method were patent without spasm, and flow competition occurred only in 2 of those grafts. On late angiography, all 15 free gastroepiploic artery grafts were patent without spasm. CONCLUSIONS: The free gastroepiploic artery grafting with venous drainage technique we developed can prevent graft spasm, leading to improved patency rate.

Adult↗

Airway foreign body with clinical features mimicking bronchial asthma.

A 56-year-old Japanese male with persistent cough, stridor and diffuse wheezing for 6 months had obstructive pulmonary dysfunction and airway hyperresponsiveness (AHR) to inhaled methacholine. Because of a poor response to glucocorticoid therapy and neutrophilia in the peripheral blood and sputum, chest computed tomography was performed and a plate-like tumor in the truncus intermedius was identified. Fiberoptic bronchoscopy demonstrated a plate-like green-colored tumor firmly impacted into the truncus intermedius and diffuse inflammatory changes spreading to both main bronchi. A piece of 'kombu' (Japanese kelp) was successfully removed by fiberoptic bronchoscopy under general anesthesia. Pulmonary function and methacholine inhalation tests became normal after the removal of the foreign body. In this case, it is suggested that asthma-like symptoms were due to localized airflow limitation in the right bronchus as well as to AHR associated with diffuse airway neutrophilic inflammation.

Adrenal Cortex Hormones↗

Effects of amphotericin B gargles on oral colonization of Candida albicans in asthmatic patients on steroid inhalation therapy.

BACKGROUND: Early use of inhaled steroids is recommended for bronchial asthma. The side effects are rare, but oral discomfort and candidiasis are clinically important complications. Most previous studies reported that the use of spacer and water gargling was necessary to prevent oral complications. However, in some patients, this may fail to prevent such complications. OBJECTIVE: To compare the effects of water gargling with those of amphotericin B, in the prevention of oral complications in asthmatics using inhaled steroids. METHODS: Pharyngeal swab samples were obtained aseptically from the posterior pharyngeal wall of 128 asthmatics who have been using inhaled steroids (beclomethasone dipropionate) for more than 1 year. The amount of Candida albicans in cultured swabs was evaluated based on the following criteria: oral symptoms, method of gargling, dose of inhaled steroids, type of spacer and serum cortisol level. RESULTS: The number of isolated C. albicans was significantly higher in asthmatics with oral symptoms than in those free of symptoms. It was also significantly higher in patients who gargled with water or 1,000 times dilution than in those who gargled with 100 or 50 times dilutions of amphotericin B. Moreover, it was significantly higher in patients with low levels of serum cortisol than in those with normal serum cortisol. CONCLUSION: We demonstrated that at least in a subgroup of asthmatics using steroid inhalers, gargling with water or even weak concentrations of amphotericin B does not prevent colonization of the throat with C. albicans. This group at high risk of developing oral candidiasis should gargle with amphotericin B at concentrations higher than 100 times dilution that can prevent clinically detectable oral candidiasis.

Administration, Oral↗

Hexamethylene diisocyanate causes contraction of canine tracheal smooth muscles through activation of muscarinic receptors.

BACKGROUND: Asthma caused by occupational exposure to hexamethylene diisocyanate (HDI) is well known; however, the exact pathogenic mechanisms remain unclear. METHODS: Experiments were performed using a standard canine tracheal smooth muscle (CTSM) strip preparation in an isolated bath to determine the effect of HDI on tracheal smooth muscle contraction. HDI concentration-response curves were constructed and the effects of different receptor antagonists on HDI-induced smooth muscle contraction were determined. To determine whether HDI and acetylcholine (ACh) bind to a common muscarinic receptor, ACh concentration-response curves in the absence or presence of HDI and concentration-response curves for HDI and ACh in the presence or absence of atropine were plotted. RESULTS: HDI caused contraction of CTSM, with a threshold concentration of 10(-7) M. The EC(50) (HDI concentration that produced 50% of the maximal response) was 6.2+/-0.7 x10(-7) M and the maximal contractile response (174+/-55 g/g of tissue) occurred at a concentration of 5.0+/-0.8 x 10(-6) M. Atropine, a muscarinic blocker, significantly inhibited HDI-induced contractile responses. HDI shifted the ACh concentration-response curve to the right. The mean pA(2) for atropine against ACh (8.93+/-0.27) was not significantly different from that against HDI (8.03+/-0.12). CONCLUSIONS: Our results indicated that HDI causes contraction of CTSM through the activation of muscarinic receptors. Direct stimulation of muscarinic receptors by HDI may play an important role in HDI-induced asthma.

Acetylcholine↗

Coronary artery bypass grafting for spontaneous coronary artery dissection: a case report and a review of the literature.

A 37 year-old woman underwent coronary angiography because of chest pain at rest. Selective coronary angiography demonstrated dissection and stenosis with a filling delay from the left main trunk to the left anterior descending coronary artery. The patient was successfully managed with urgent coronary artery bypass grafting. Spontaneous coronary artery dissection is relatively rare and threatens both elderly and young patients with acute coronary disturbances. Patients can be divided etiologically into three groups. The first was comprised of those in the postpartum period. The second was those with atherosclerotic coronary artery disease, and the third was those associated with coronary vasospasm. Dissections are frequently fatal and most of the known cases have been diagnosed at autopsy. Only a few cases have been documented by coronary angiography, and operative cases of spontaneous coronary artery dissection have rarely been reported.

Adult↗

[Coronary artery bypass grafting by warm blood cardioplegia and normothermic cardiopulmonary bypass].

Warm blood cardioplegia and normothermic cardiopulmonary bypass (CPB) have been used in coronary artery bypass grafting (CABG). The method of myocardial protection was intermittent combined antegrade and retrograde warm blood cardioplegia with terminal warm blood cardioplegia. We performed elective CABG in 30 patients above the age of 70 years (elderly group). These patients were compared with 30 patients below 70 years who underwent elective CABG (young group). No significant differences were observed about the preoperative data between two groups. No significant differences were obtained in the postoperative cardiac function, cerebral or renal complication between two groups. Warm blood cardioplegia and normothermic CPB were not associated with adverse effects on postoperative recovery in elderly as well as young patients. We may conclude that warm blood cardioplegia with normothermic CPB is a safe procedure for CABG in elderly as well as young patients.

Aged↗

[Short-course chemotherapy of tuberculosis with pyrazinamide].

A 6-month regimen consisting of isoniazid (INH. 0.3-0.5 g).rifampicin (RFP. 0.3-0.45 g).pyrazinamide (PZA. 1.2-2.0 g) and streptomycin (SM. 0.75 g) or ethambutol (EB. 0.75-1.0 g) given for 2 month followed by isoniazid and rifampicin for 4 month is the preferred treatment for patients with fully susceptible organism, who adhere to treatment. Consideration should be given to treating all patients with directly observed treatment.

Antibiotics, Antitubercular↗

[Valve replacement concomitant with anulus reconstruction].

It is important that surgical treatment of infective endocarditis involves complete debridement of the affected tissue. In case of abscess formation in the mitral anulus and/or aortic root, disruption of the anulus occurs because of radical resection of the abscess. David et al. reported a new technique for mitral and aortic anulus reconstruction. The novel part of the technique was the endocardial repair, i.e., suturing of a pericardial patch to the endocardium of the left ventricle. We were surprised to learn that the left ventricular endocardium and muscle are capable of tolerating the stress induced by the prosthetic ring, especially in the mitral position. Since 1992, we treated eight cases of anulus disruption using this technique ; 5 cases involved the mitral anulus, 1 involved the aortic, and 2 involved both. We used a slightly different technique involving suturing of a patch not only to the left ventricular endocardium but also to left atrial wall for reinforcement. Two patients died in the perioperative period. One had a brain abscess ; the other had methicillin-resistant Staphylococcus aureus sepsis and mediastinitis. There was 1 late (sudden, unknown) death 3 years after the operation. No perivalvular leakage, dehiscence of the patch, hemolysis, prosthetic valve endocarditis, or thromboembolism have been observed in the other 5 patients.

Abscess↗

[Repair of mitral valve prolapse by resection and sliding plasty].

There have been many techniques applied to the repair of mitral valve prolapse, and the method used in a particular case is usually selected according to the position and extent of the lesion. To simplify and standardize the technique of mitral valve repair, we have adopted the resection, sliding plasty and ring annuloplasty methods since December 1992. Of 10 consecutive surgical cases, 2 involved prolapse of the anterior leaflet, 1 the posteromedial commissural, and 7 the posterior leaflet. One patient with posterior leaflet prolapse required valve replacement due to dehiscence of the plastied site on the 3rd postoperative day, and one died because of sepsis. However, the remaining patients were doing well without mitral regurgitation at a mean of 20 months (range: 8-32) after the operation. The advantages of these techniques include easy adjustment of the height of the leaflet and a good chance of long-term durability, since the affected lesion is resected.

Adult↗

[Surgical repair of post-infarction ventricular septal defects--reconstruction with pericardial patch].

Despite improvements in the pre- and postoperative management of patients with post-infarction ventricular septal defects, the results after surgery have been variable. This is in part due to advanced patient age, multi-vessel coronary disease. In addition, resection of the infarcted ventricular septum results in significant compromise in left ventricular function. Since January of 1993, we have used a new technique for the reconstruction of the left ventricle using a single pericardial patch. In this method, which was introduced by Komeda and David in 1990, a single patch is sutured to the interventricular septum and the lateral ventricular wall, excluding the infarcted muscle from the left ventricular cavity. This method was used in the treatment of four patients. There was no bleeding along the suture lines at operation, all of the patients survived. Postoperatively, all four were functional New York Heart Association Class 1. One patient underwent re-operation on the 12th day using the same technique because of a residual shunt. Another two patients had small residual shunts, which spontaneously resolved in 2 to 7 months. Left ventricular function evaluated 1 month after the operation utilizing cardiac catheterization revealed a mean stroke volume index of 40 (range: 32-45 ml/m2, and a mean left ventricular ejection fraction of 71 (range: 70-73%). An excellent functional outcome has thus been achieved with the reconstruction of post-infarction ventricular septal defects using a single pericardial patch.

Aged↗