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This paper deals with a development of a new rutting evaluation index based on the vehicle dynamics taking into account mt shape, the mtting/vehicle interaction, and driver sensitivity. The result of lane change at the proving ground shows that the mtting affects the vehicle rolling behavior consisted by the frequency band above 0.8Hz. The Half-Car model which is the conventional vehicle simulation model is effective to represent the roll response induced by the rutting. Then, we develop two indices which are accumulation value of roll angle/roll rate obtained from Half-Car simulation to evaluate the rutting. From result of the subjective assessment survey by a driving simulator, we conclude that the accumulation value of the roll rate as the index has the strong relationship with road usefs senses.

A 30-year-old woman with malnutrition due to alcoholism and eating disorders was found to have acute respiratory distress syndrome (ARDS) and sepsis due to severe Streptococcus pneumoniae pneumonia. S. pneumoniae was detected by an in vitro rapid immunochromatographic assay for S. pneumoniae antigen in urine on the day of admission and by blood culture 2 days after admission. Symptoms and laboratory findings improved after treatment with sivelestat sodium hydrate, antibiotics, and mechanical ventilation. Treatment with sivelestat sodium hydrate also decreased serum neutrophil elastase activity. This case demonstrates the usefulness of early treatment with sivelestat sodium hydrate in ARDS due to severe pneumonia.

Vehicle vibration is caused by road roughness. When wavelength and amplitude are at the same level and the road surface waveform is different, the vibration waveform can also be different. When vehicle–road interaction is strictly analyzed, it is necessary to divide the vehicle vibration data according to the type of road surface waveform. The lifting scheme theory, which is based on the wavelet transform, was used to consider the road surface waveform detection method, which is influenced by the unsprung mass vibration of a vehicle. The basis function used optimizes the shape corresponding to the analysis purpose, based on the spline function. This method can accurately monitor the unsprung mass vibration of a “convex” type waveform of high magnitude.

Correlation between the level of reactive oxygen species (ROS) generated by airway inflammatory cells and superoxide dismutase (SOD) activity of pulmonary tissue during an asthma attach was investigated in a guinea pig model of allergic asthma. In addition, the influence of SOD inhibition by diethyldithiocarbamate (DDC, Cu-chelating agent) on the airway was investigated in terms of pulmonary function during an asthma attach. Relative to controls, the capacity of bronchoalveolar lavage fluid (BAL) cells to release ROS was significantly increased in guinea pigs sensitized with ovalbumin (OA) as the antigen, and significantly increased in guinea pigs with an asthma attack provoked by the inhalation of OA. SOD activity was increased significantly in the antigen-sensitized group. The asthma provocation group showed a tendency for increase in total SOD activity, compared with the sensitization group, whose increase was dependent on the increase in copper, zinc-SOD (Cu, Zn-SOD) activity. Pretreatment with DDC increased the severity and duration of the asthma attack. These results were indicated that Cu, Zn-SOD was closely involved in the asthma process, particularly in the scavenging of oxygen radicals secreted from BAL cells.

Background: Airway hyperresponsiveness (AHR) is one of the characteristic features of human asthma. The presence of AHR and the precise mechanisms immediately after establishment of sensitization in guinea pigs are unclear, although there are many reports showing allergen exposure that causes an increase in bronchial responsiveness associated with eosinophil influx into the airway in sensitized guinea pigs. Objective: We investigated the inhibitory effects on AHR to histamine of ONO-1078, a leukotriene antagonist; indomethacin, a cyclooxygenase inhibitor; S-145, a thromboxane A2 (TXA2) antagonist, and Y-24180, a platelet-activating factor (PAF) antagonist, to assess the involvement of chemical mediators in AHR employing ovalbumin (OA) sensitized guinea pig models. Methods: Male Hartley guinea pigs were used. Each group comprised 4–7 animals. The animals were sensitized to OA, injecting intraperitoneally 30 mg of cyclophosphamide and 2,000 µg of OA together with 100 mg of aluminum hydroxide as the adjuvant. The guinea pigs were artificially ventilated via a cannula using a small-animal respirator after intraperitoneal anesthesia with pentobarbital sodium for tracheotomy. The pressure at the airway opening (PAO) was measured using a differential pressure transducer, and a differential pressure of peak PAO (peak ΔPAO) at inspiratory phase as an overall index of bronchial response to bronchoactive agents was used. While being artificially ventilated, the animals were exposed to physiological saline solution containing various concentrations of histamine (4.9, 9.8, 20, 39, 78, and 156 µg/ml) by inhalation for 30 s at 3-min intervals. Determinations were made at 1 min after each inhalation. The chemical mediators were each (30 mg/kg of ONO-1078, 3 mg/kg of S-1452, and 1 mg/kg of Y-24180) administered orally to sensitized guinea pigs, and the airway response to histamine was assessed. Each group comprised 4–7 animals. Results: The airway response to histamine was significantly greater in the sensitized group than in the nonsensitized group at histamine concentrations of 36 (p < 0.05), 78, and 156 mg/ml (p < 0.01). Leukotrienes C4 and D4: 30 mg/kg of ONO-178 did not show any inhibitory effect on airway response to inhaled histamine. Cyclooxygenase: 5 mg/kg of indomethacin did not show any inhibitory effect on the airway response to inhaled histamine. TXA2: the AHR to inhaled histamine at doses of 9.8, 39, 78, and 156 µg/ml was significantly inhibited by prior administration of 3 mg/kg of S-1452. PAF: the AHR to inhaled histamine at doses of 9.8, 39, and 78 µg/ml was significantly inhibited by prior administration of 1 mg/kg of Y-24180. Conclusions: S-1452 (3 mg/kg) and Y-24180 (1 mg/kg) significantly inhibited AHR to histamine, while ONO-108 (30 mg/kg) and indomethacin (5 mg/kg) did not. The results suggest that TXA2 and PAF are involved in AHR in OA-sensitized guinea pigs.

Objective: The aim of this study was to evaluate the oral steroid-sparing capacity of budesonide Turbuhaler®. Methodology: One hundred and thirteen oral steroid-dependent patients were treated for 6 months with placebo or budesonide 800 μg or 1600 μg daily. Every second week the oral steroid dose was reduced if asthma control permitted. Results: The reductions in oral steroid doses were 9, 35 and 60% in the placebo and budesonide 800 μg and 1600 μg groups, respectively. Oral steroid treatment could be discontinued in 4% (placebo), 15% (800 μg) and 23% (1600 μg). Mean peak expiratory flow values increased by 21 and 24 L/min in the budesonide groups but decreased by 6 L/min in the placebo group. Asthma attack, activity and sleep scores remained unchanged showing maintained efficacy. Plasma cortisol levels increased and an adrenocorticotropic hormone test showed improved adrenocortical response in both budesonide groups, indicating improved safety. Adverse drug reactions were infrequent and mild in all study groups. Conclusion: Budesonide Turbuhaler, 800 μg and 1600 μg daily, resulted in a significant reduction in oral steroid usage in steroid-dependent patients. The effect was achieved with maintained asthma control together with improvements in lung and adrenal functions.

Background: Adhesion molecules may play an important role in eosinophilic activation as well as adherence of extracellular matrix (ECM) including fibronectin (FN) in the inflamed focus. Tissue eosinophils expressed inter-cellular adhesion molecule-1 (ICAM-1, CD54), whereas peripheral blood eosinophils did not. The molecular mechanisms of ICAM-1 expression on eosinophils are not clear. We immunologically examined the effect of adherence to FN on the expression of adhesion molecules in an eosinophilic cell line (EoL-1). Methods: EoL-1 cells, suspended at a concentration of 2 × 106 cells/ml, were cultured at 37°C in BSA or FN-coated 24-well plates. After 4 h, the cells were removed by pipetting, and the expression of adhesion molecules was evaluated by immunofluorescence. Results: Adherence of EoL-1 to FN enhanced ICAM-1 (CD54) expression on EoL-1 (FN vs. BSA: 84.76 ± 17.90 vs. 43.73 ± 7.60, mean fluorescent intensity). Regarding other adhesion molecules on EoL-1 (CD11a, CD18, CD49d), the expression was not significantly augmented by adherence to FN. Conclusions: We concluded that the signal via adhesion of FN regulates the expression of ICAM-1 on eosinophilic cells. This study suggests that eosinophilic adhesion to ECM via adhesion molecules plays an important role in the pathogenesis of allergic inflammation through eosinophilic functional changes, including regulation of expressive adhesion molecules such as ICAM-1.

Objective: This study aimed to evaluate the efficacy of Saiboku-to, a Japanese traditional herbal medicine (Kampo), on the production of interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interferon-γ (IFN-γ) and interleukin-2 (IL-2) by peripheral blood mononuclear cells in bronchial asthma patients following antigenic stimulus by the house dust mite. Design: Twelve bronchial asthma patients with IgE RAST (radio-allergosorbent test) scores to mites of 3 and over were enrolled in the study. Separated mononuclear cells from the patients’ blood were suspended in a 24-hole plate with 10% fetal calf serum (FCS) and RPMI-1640 medium. Mite antigen was added to the above cell-suspension (final concentration 10 mg/ml) and cultured for 72 hours at 37°C in 5% CO2. Saiboku-to (TJ-96, Tsumura & Co.) was added to the above sample system at the same time as mite antigen and cultured for 72 hours under the same conditions. After 72 hours of incubation, the amount of various cytokines (IL-2, IL-3, IL-4, IL-5, INF-γ) was measured using enzyme-linked immunoabsorbent assay kits. Results: Saiboku-to 500 mg/L significantly inhibited the production of IL-3 and IL-4 from peripheral blood mononuclear cells. Moreover, it significantly increased the production of INF-γ from peripheral blood mononuclear cells. Conclusion: These preliminary findings suggest that Saiboku-to could be considered as one of a new class of anti-asthmatic drugs because of its influence on cytokine production.

1. To clarify part of the bronchodilating effects of theophylline, lymphocyte cyclic AMP (cAMP) and phosphodiesterase (PDE) activity in asthmatic patients and healthy adults were measured. 2. No clear differences in lymphocyte PDE activity were found regarding sexes, ages or the types of asthma. 3. Lymphocyte PDE activity in the asthma group was significantly higher than that in the control group. 4. Lymphocyte cAMP significantly increased at 30 and 60 min after intravenous injection of aminophylline in the asthma group. 5. Lymphocyte PDE activity significantly decreased 60 min after intravenous injection of aminophylline in the asthma group.

Inflammatory reactions in the airway in which various inflammatory cells are involved play an important role in the pathogenesis of bronchial asthma. In particular, the activation of T cells and the accompanying role of cytokines have attracted attention. We employed peripheral mononuclear blood cells and lymphocytes from mite-antigen positive patients with bronchial asthma to investigate the production of various cytokines following stimulation with mite-antigen and the relationship between IgE-the most important factor in the pathogenesis of bronchial asthma- and cytokines.The production of IL-1β, IL-2, sIL-2R, IL-3, IL-4, IL-5 and IL-6 from peripheral blood mononuclear cells (PBMC) following the addition of mite-antigen was determined by the sandwich ELISA method. The production of IL-1β, IL-2, sIL-2R, IL-3, IL-4, IL-5 and IL-6 in PBMCs was increased by stimulation with mite-antigen. When CD4+ and CD8+-enriched cell fractions were separated, the production of the cytokines IL-2, sIL-2R and IL-4 was elevated in the CD4+ T cells. IL-1β production from PBMCs increased in the presence of the CD4+-enriched cell fractions. Consequently, the effect of CD4+-enriched cell fractions in the production of IL-1β in mononuclear cells was considered.The results of a determination of IgE production from PBMCs, using a highly-sensitive method, showed that IgE production increased following the addition of IL-4 to a level similar to that induced by stimulation with mite-antigen. The addition of either IFN-γ or anti-IL-4 reduced the amount of IgE increased by the addition of IL-4 or stimulation with mite-antigen. The addition of IL-2 further increased the amount of IgE production, which had been increased by stimulation with mite-antigen or the addition of IL-4, suggesting the importance of IL-2 in IgE production in B cells.The results of our study indicate that mononuclear cells and lymphocytes, especially CD4+ T cells, are important for the onset of bronchial asthma as a Type I allergy.In patients with bronchial asthma, CD4-positive T-lymphocytes are activated, and various cytokines are produced, following stimulation of PBMC with specific antigens. It is suggested that IL-4 and IL-2, which promote the production of IgE-the most important factor in I-type allergic reactions, might produce serious allergic reactions.It is also concluded that the production of IL-3 and IL-5, which are considered to be cytokines activating eosinophils, is increased by stimulation with specific antigens which are potent inducers of further airway inflammation.The above results suggest that various cytokines play an important role in the pathogenesis of bronchial asthma in their interactions with each other.

γ-Aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the mammalian central nervous system and it is also found in peripheral tissues including the lung. Recent experiments have shown that GABA affects the contractile properties of airway smooth muscle. Therefore, to determine whether GABA affects the contractile properties of tracheal smooth muscle, we studied guinea pig trachea under isometric conditions in vitro in both normal and OA-sensitized guinea pigs. The following results were obtained.1) In normal guinea pig tracheal ring, GABA and its related substances, baclofen and muscimol, had no effect on the resting tension, but reversibly depressed contractions induced by electrical field stimulation (EFS) in a dose-dependent fashion.2) In OA-sensitized guinea pig tracheal ring, GABA and baclofen reversibly depressed the contractions induced by EFS, but to a lesser degree than in normal tracheal ring.3) In OA-sensitized guinea pig tracheal ring, muscimol reversibly depressed contractions induced by EFS as in the normal group.4) GABA inhibited tracheal contraction induced by EFS but had no effect on the contractile response to acetylcholine.In conclusion, our study suggests that prejunctional GABAB receptors attenuate neuronally induced cholinergic contraction of airway smooth muscle, and that there may be a dysfunction of these prejunctional receptors in asthmatic, OA-sensitized guinea pig.

The nature of bronchial asthma is an important question since it is the starting point in search for the pathogenetical and pathophysiological studies of asthma.I have investigated the pathophysiology of asthma, bronchial hypersensitivity, pulmonary function and pulmonary circulation. I have also studied pathogenesis, inhaled allergens, IgE antibody and allergic inflammations in patients with asthma and experimental animal models of asthma.The second main field of research in asthma is new perspectives in treatment. For example, the so-called anti-allergic drugs or inhaled corticosteroids are in common use.Asthmology has become a specialty but still needs the contribution of many scientists and specialists from other fields.

We evaluated eight cases of pulmonary mycosis in immuno compromised hosts. The underlying diseases were lung cancer with chemotherapy in one case, post bone marrow transplantation (post BMT) in two cases, acquired immunodeficiency syndrome (AIDS) in one case and bronchial asthma with massive steroid therapy in four cases. The causative fungi were Candida sp. in three cases, Aspergillus sp. in four cases, Tricosporon sp. in one case. Prognosis was guarded despite antifungal treatment. Five cases deteriorated and died of fungal infection. In five cases, who died of deterioration, 31.6 days was required from appearance of abnormal infiltration in the chest X-ray to determination of the causative fungi (including two cases who were diagnosed by autopsy) on the average. In three successfully treated cases, the average duration from the appearance of abnormal infiltration in the chest X-ray for the determination of the causative fungi was 8.3 days. On the contrary, the average duration between the appearance of abnormal infiltration in the chest X-ray and the initiation of antifungal treatment was 2.6 days who died of deterioration and 8.3 days who survived. We conclude that early identification of causative fungi and not quick institution of antifungal treatment was mandatory in the treatment of opportunistic fungal pneumonia.

We studied respiratory mucosa immune responses in bronchial asthma using guinea pigs and human respiratory epithelial cells. In asthma models (guinea pigs), CD4+ T cells enhanced LAR, and CD8+ T cells inhibited LAR after antigen inhalation. Regulatory effects of IL-5 and ICAM-1 on LAR were detected. PAF enhanced the adhesion of human respiratory epithelial cells and eosinophils. TNF-α stimulated the production of GM-CSF in human respiratory epithelial cells, while TGF-β1 depressed human eosinophil survival.

The effects of cytokines (interleukin-2, tumor necrosis factor-alpha and interferon-gamma) on the ability of peripheral blood monocytes and alveolar macrophages to produce oxygen radicals were examined by the chemiluminescence assay in patients with lung cancer. Oxygen radical production by peripheral blood monocytes before stimulation with cytokines was lower in the lung cancer group than in healthy controls, suggesting reduced immune function in lung cancer patients. However, the activity in the lung cancer group was elevated to the control level when the monocytes were stimulated by any of the three aforementioned cytokines. Oxygen radical production by alveolar macrophages did not differ significantly between nonstimulated monocytes from lung cancer patients and those from healthy controls. In the lung cancer group, stimulation of the macrophages with any of the three cytokines elevated their ability to produce oxygen radicals to the same extent as in the control group. The results suggest that stimulation of macrophages by interleukin-2, tumor necrosis factor-alpha or interferon-gamma can exert an antitumor action in patients with lung cancer.

To clarify the role of microvessels in the development of pulmonary hypertension of acute lung injury, we induced lung edema by oleic acid (OA) in ten artificially perfused cat lungs and measured microvascular pressure. Pulmonary artery pressure (Ppa) and pressure of 30-50 microns arteriole (Parteriole) increased from 19.2 +/- 1.4 and 15.7 +/- 1.0 cmH2O before to 30.5 +/- 5.0 cmH2O and 22.7 +/- 2.4 cmH2O after edema, respectively. Pressure of 30-50 microns venule (Pvenule) and venous occlusion pressure (Pvo) did not change significantly after edema. Double occlusion pressure (Pdo) which represents pulmonary microvascular pressure increased from 14.5 +/- 0.6 to 17.7 +/- 2.0 cmH2O. Pressure gradient in the artery, i.e., between Ppa and Parteriole and in the microvessels, i.e., between Parteriole and Pvenule increased when lung became edematous. Pressure gradient in vein, i.e., between Pvenule to left atrium was not affected by edema. Pdo was in the midst of Parteriole and Pvenule in both edematous and non-edematous lung. In acute lung injury, increase of microvascular resistance was followed by an increase of arterial resistance and caused pulmonary hypertension.

The relationship between human T-lymphotropic virus I (HTLV-I) infection and strongyloidiasis has recently become an important problem. This study compared the expression of CD23, CD32, Mac-1 and other adhesion molecules in eosinophils of patients with strongyloidiasis positive for anti-(HTLV-I) antibodies and in those negative for the antibodies. The expression of CD23, Mac-1 and intercellular adhesion molecule-1 (ICAM-1) on eosinophils of patients with strongyloidiasis was augmented in comparison with normal subjects and HTLV-I carriers. There were no significant differences, however, in the expression of CD23, CD32, Mac-1 and adhesion molecules (ICAM-1, leukocyte function-associated antigen-1 alpha (LFA-1 alpha), LFA-1 beta, very late antigen-4) on eosinophils of patients with strongyloidiasis positive for anti-HTLV-I antibodies in comparison with those negative for these antibodies.

Twenty-four previously treated patients with refractory or relapsed small cell lung cancer (SCLC) were entered into a prospective, multicenter phase II study. All 24 patients had been pretreated with some form of cisplatin-based chemotherapy. The median time of chemotherapy was 4.2 months (range 1.4-9.4 months). Patients were treated with a dose of 25 mg/m2 of vinorelbine weekly. Twenty-four patients were eligible for response and for toxicity. Partial response was observed in 3 out of 24 eligible patients (12.5%; 95% confidence interval, 2.7-32.4%). All 3 patients who responded had previous chemotherapy including vincristine. The most common toxicity was leukopenia (91.7%, 66.7% in WHO 3-4 grade) and anemia (70.8%, 20.8% in WHO 3 grade). Nonhematological toxicities were moderate and mild. These results support a two-state sequential study design of previously untreated patients for further phase II study in SCLC.

Fibronectin is an extracellular matrix (ECM) that binds to very late antigen-4 (a beta 1 integrin molecule) expressed by eosinophils. To investigate the effect of adherence to fibronectin on regulation of eosinophil cell death, survival of eosinophils was examined by trypan blue exclusion and Fas antigen expression on the cell surface using an eosinophilic cell line (EoL-1). Adhesion to fibronectin resulted in prolongation of eosinophil survival (fibronectin vs. bovine serum albumin (BSA), 62.9 +/- 5.10 vs. 53.9 +/- 4.30% viability at 72 h) and the decreasement of Fas antigen expression on EoL-1 (fibronectin vs. BSA, 24.3 +/- 2.15 vs. 74.5 +/- 8.25% positive). These findings suggest that eosinophil adhesion to ECM via adhesion molecules plays an important role in the pathogenesis of allergic inflammation, which involves eosinophil accumulation at the inflammatory site, through regulation of eosinophil cell death.

We examined the correlation between airway hyperreactivity and the density of muscarinic acetylcholine receptor (mACh-R), and reported that the density of mACh-R in OA-sensitized guinea pig was higher than that in a control group. We also examined the characteristics of the M1, M2 and M3 receptors in guinea pig pulmonary tissue, and the following results were obtained.1) For the M1 and M2 receptors, no difference was observed between the density and affinity of OA-sensitized lungs and those of the control lungs.2) The density of M3 receptors in the lung tissue of OA-sensitized guinea pigs washigher than that in the control group. No difference was observed between the affinity of M3 receptors in the OA-sensitized lungs and that in the control lungs.3) Pilocarpine, which is an M2 receptor agonist, increased the density of M3 receptors in the lung tissue of guinea pigs, and the rate of the increase in the density of M3 receptors in OA-sensitized guinea pigs was less than that in the control group. On the other hand, methoctramine, which is an M2 receptor antagonist, decreased the density of M3 receptors in the lung tissue of guinea pigs, and the rate of this decrease was as same as that in the control group.These results suggest that the increase in M3 receptors in the lung tissue of OA-sensitized guinea pigs is related to airway hyperreactivity and that there is a dysfunction of M2 receptors in OA-sensitized guinea pigs.

症例は73歳の男性. 前縦隔腫瘍の精査加療目的にて当院に入院. 患者は10年前に他院で縦隔腫瘍摘出術を受けており, 神経鞘腫と診断されている. 今回我々は経皮針生検を施行したが, 組織診断は得られなかった, 画像上前縦隔腫瘍と診断し, 腫瘍の摘出術を施行. 組織診断は悪性胸膜中皮腫であった. 前回の摘出標本の組織を検討したところ, 同じ組織構造であった. 悪性胸膜中皮腫の頻度は比較的少なく, 特に縦隔内発生の場合はまれであり, 本症例では縦隔腫瘍との鑑別が困難であった. また, 本症における10年以上の生存例もまれで, 本症例は本邦報告例として3例目となり, 興味ある症例であると思われた.

Phosphodiesterase is the only enzyme that catalyzes the hydrolysis of cyclic AMP to 5′AMP, and the relaxation of smooth muscle is the result of an intracellular increase in the level of cyclic AMP. It has been generally assumed that the bronchodilatory properties of theophylline in asthma therapy are due to its cyclic AMP-phosphodiesterase inhibitory capacity. In recent years, a number of studies on the action of theophylline have led to a general hypothesis which suggests that xanthine derivatives act as adenosine receptor antagonists. In the present study, we reported that the lymphocyte cyclic AMP level showed an obvious increase only in asthma patients after the administration of theophylline, while the level was the same in asthma patients and healthy adults before this administration.The difference in phosphodiesterase activity between patients and healthy adults in one of the causes of the difference in the lymphocyte cyclic AMP level.In this study, we examined lymphocyte phosphodiesterase activity and the following results were obtained.1) The lymphocyte phosphodiesterase activity was higher in patients with bronchial asthma than in healthy adults.2) The lymphocyte phosphodiesterase activity level showed an obvious decrease only in patients with asthma.These results suggest that phosphodiesterase activity is related to the mechanism of bronchial asthma, and the hypothesis that theophylline is an inhibitor of phosphodiesterase is confirmed.

A 61-year-old woman was admitted with a tumor-like lesion in the middle lobe of the right lung which showed substantial uptake on 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET). The chief complaint was dry cough. On the basis of these findings, lung cancer was first to be ruled out. However, subsequent examinations showed Aspergillus fumigatus in sputum and aspergillus-specific IgE and IgG antibodies in the serum. The tumor-like lesion gradually disappeared. Allergic bronchopulmonary aspergillosis without clinical symptom of bronchial asthma was diagnosed with Rosenberg's clinical criteria. The patient's condition stabilized after treatment with inhaled corticosteroid and oral itraconazole. To our knowledge, this is the second report of allergic bronchopulmonary aspergillosis with tumor-like lesions in the lung showing intense 18FDG-PET uptake.

We present a case of acute respiratory distress syndrome (ARDS) caused by allergic reactions to shiniseihaito. An 84-year-old woman showed acute interstitial pneumonia followed by ARDS after taking shiniseihaito for the treatment of rhinitis. The ARDS were markedly improved with corticosteroid therapy. This case was diagnosed as being induced by shiniseihaito because it was compatible with 4 of 5 of Camus's criteria. The stimulation index of the drug lymphocyte stimulation test with shiniseihaito increased after corticosteroid therapy had been tapered and suggested that the mechanism of acute interstitial pneumonia in this case was allergic reaction induced by shiniseihaito. This is the seventh reported case of drug induced lung injury by shiniseihaito. We recommend careful observation when this medicine is prescribed.

A 39-year-old woman, who had a history of recurrent oral and genital ulcerations and folliculitis and had had a low-grade fever since December 2003, consulted our hospital on February 5, 2004. Chest radiography and computed tomography (CT) showed multiple pulmonary abscess-like opacities. She was admitted to the Department of Respiratory Medicine and Allergology, Kinki University School of Medicine on February 19, 2004. A transbronchial lung biopsy showed nonspecific inflammation with lymphocytic infiltration. The patient was discharged after she showed improvement with antibiotic therapy. She was readmitted to our hospital on October 3, 2006, because of recurrence of pulmonary abscess-like opacities. Bronchoalveolar lavage showed lymphocytosis (53%) but yielded no significant bacteria on culture. Behçet's disease was diagnosed on the basis of the three major symptoms (recurrent oral and genital ulcerations and folliculitis). The frequent recurrence of pulmonary lesions was suspected to be due to immunological impairment associated with Behçet's disease, and the pulmonary lesions and inflammatory reaction tests showed improvement after colchicine was administered. The patient was discharged on October 28, 2006. To our knowledge this is the third reported case of frequently recurrent multiple pulmonary abscess-like opacities in Behçet's disease.

A 66-year-old man was admitted to our hospital with pyrexia up to 40 degrees C since one day after taking a public bath. Since multiple infiltrations on the lung were shown by chest radiography, severe pneumonia was diagnosed. Administration of antibiotics meropenem and erythromycin yielded no detected effect. Furthermore, rifampicin induced severe liver dysfunction. Improvement of clinical symptoms was seen after ciprofloxacine (CPFX) was given. Interstitial pneumonia, increases in KL-6 up to a level of 3545 U/ml and acute respiratory failure were improved by taking methylprednisolone. Since Legionella antigen was found in the urine, the use of CPFX was continued. Rhabdomyolysis and acute renal failure were successfully treated by transfusion, diuretic therapy, and glucocorticoid therapy. This was a very rare case of survival after Legionella pneumonia complicated with acute respiratory failure, acute renal failure, rhabdomyolysis, and interstitial pneumonia accompanied with a high KL-6 level, and successfully treated with steroids and CPFX.

A 73-year-old woman was followed up with high-resolution computed tomography (HRCT) from 2000 through 2002 because an area of ground-glass opacity in area S1 + 2 of the left upper lobe was found on HRCT in August 2000. The opacity was present on ordinary CT scans obtained in 1993, but had not been recognized. Thoracoscopic partial resection of the left lung was performed on October 8, 2002. Pathologic examination of the resected specimen showed localized bronchioloalveolar carcinoma (Noguchi's type B). Tumor doubling time was 1718 days from 1993 to August 2000 and 273 days from August 2000 through 2002. This case of adenocarcinoma with bronchioloalveolar growth was characterized by initial slow growth followed by accelerated growth, no mucin production, and a long interval from the detection of opacity to surgery.

The effect of platelet-activating factor (PAF) and platelet factor 4 (PF4) on the adhesion of isolated human eosinophils or eosinophilic cell lines (EoL-1, EoL-3) was examined. Both PAF and PF4 augmented eosinophil adhesion to plates coated with AB plasma or recombinant soluble intercellular adhesion molecule-1 (r-sICAM-1). These findings suggest that PAF and PF4 not only modulate chemotactic activity of eosinophils but also intensify the function of eosinophil adhesion. Since PAF and PF4 induce the expression of adhesion molecules (LFA-1 alpha, LFA-1 beta, CR3) on eosinophils, we could conclude that PAF or PF4 are closely related to eosinophil accumulation not only as chemotactic agents but also as augmentative agents for eosinophil adhesion through involvement in functional eosinophil adherence as well as surface expression of adhesion molecules on eosinophils.

We examined the density of muscarinic acetylcholine receptor (mACh-R) subtypes (M1R, M2R and M3R) in guinea pig lung. The density of M3R in the lung tissue of ovalbumin (OA)-sensitized guinea pigs was higher than that in the control group. However, no difference was observed in the affinity of M3R between the sensitized and the control lungs. No difference was observed in the density and affinity of M1R and M2R in sensitized and control lungs. Pilocarpine, which is an M2R stimulant, increased the density of M3R in the lung tissue and the rate of the increase in sensitized guinea pigs was less than that in the control group. In contrast, methoctranine, which is an M2R antagonist, decreased the density of M3R and the rate of this decrease was the same in the sensitized and control groups. These results suggest that, in OA-sensitized guinea pigs, a dysfunction of M2R leads to the abnormal density of M3R.

OBJECTIVE The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler with that of beclomethasone dipropionate (BDP) pMDI. METHODOLOGY Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (< 80% predicted normal)), taking BDP via pressurized metered-dose inhaler (pMDI), 400 microg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 microg or 400 microg twice daily via Turbuhaler or continued treatment with BDP, 100 microg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials. RESULTS At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 microg and 800 microg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 microg budesonide and 400 microg BDP treatment in the effect on PEF (P = 0.29), but 800 microg budesonide was significantly superior to BDP (P < 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P < 0.001). All treatments were well tolerated. CONCLUSION Budesonide Turbuhaler (200 microg) was as effective as 400 microg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 microg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose-response curve. Without that information, comparative studies are usually inconclusive.

The authors have successfully developed an animal model of dual-phase bronchial responses and very high IgG titer by sensitizing Hartley-strain male guinea pigs. Specific airway resistance, which was determined in a two-chamber body plethysmograph, was elevated to sevenfold during immediate response, followed by a late phase response with a smaller but marked elevation in resistance. Furthermore, hematological and histological examinations revealed that the total cell count increased in BAL obtained during both immediate and late bronchial responses as compared to pre-OVA challenges. A significant increase in BAL eosinophils was present only for the late bronchial samples, and this finding was supported by histological examination.

Background: In Japan in 1993, the Japanese Society of Allergology (JSA) developed guidelines for diagnosis and management of asthma (JGL), which were based on the concept that asthma is a chronic inflammatory disorder of the airway. Methods: This survey study was intended to investigate the recognition and utilization of JGL among physicians who had treated asthma. The survey comprised two methods: a quantitative mail survey and a qualitative door-to-door survey conducted by trained interviewers. Results: In the mail survey, a total of 1028 physicians responded; 552 members of the JSA and 476 nonmembers. Ninety-four percent of JSA members were aware of adult asthma management guidelines, while 53 nonmembers were aware of them. Although approximately half of the physicians, both member and nonmember, found differences between the asthma management policies in JGL and their previous policies, most of them utilized JGL, once they read it. In the qualitative door-to-door survey, 80–90% of physicians evaluated JGL as good after they read it. Conclusions: JGL was recognized and utilized by most JSA members, but only half of nonmember physicians were aware of JGL, although they utilized JGL after they read it. Further action to implement JGL among nonspecialist physicians is needed to improve management of asthma.

Histamine plays an important role in broncho constriction mediated by histamine receptors which provoke bronchial asthma attack. In this study, we measured H1 and H2 receptors in the guinea pig lung membrane fraction and obtained the following results. The maximum binding (Bmax) of H1 receptors in the guinea pig lung membrane fraction was significantly higher in the OA-sensitized group than that in the non-sensitized group, but affinity (Kd) did not differ between the groups. Otherwise, the maximum binding (Bmax) of H2 receptors in the guinea pig lung membrane fraction was significantly lower in the OA-sensitized group than that in the non-sensitized group. But affinity (Kd) did not differ between the groups. These findings suggest a close association of Histamine receptors both H1 and H2 in the pathology of asthma.

To elucidate the mechanism of the anti-inflammatory effect of theophylline, peripheral blood mononuclear cells (PBMCs) collected from patients with bronchial asthma who had a RAST score for Dermatophagoides farinae (Df) > = 3 were stimulated with Df antigen, and the interleukin-4 (IL-4) production by the stimulated PBMCs was determined in the presence and absence of theophylline. The stimulated IL-4 production in the PBMCs was significantly suppressed by simultaneous treatment with theophylline (8 μg/ml). Furthermore, the intracellular 3′,5′-adenosine monophosphate (cAMP) level following stimulation with Df was significantly higher in PBMCs simultaneously treated with theophylline (8 μg/ml) than in nontreated controls. These results suggest that theophylline suppresses the IL-4 production in inflammatory cells by increasing the intracellular cAMP level; this effect may thus provide an additional basis for the benefit of theophylline in antiasthmatic therapy.

Serum soluble ICAM-1 concentrations were measured in 10 patients with or without chronic graft-vs.-host disease (GVHD) after allogeneic bone marrow transplantation. The serum soluble ICAM-1 levels in the patients with chronic GVHD were significantly higher than that in the patients without chronic GVHD. The data indicated that serum soluble ICAM-1 is a useful parameter for predicting chronic GVHD.

BACKGROUND Cytokeratins are the intermediate filaments of the cytoskeletal protein located in normal epithelia, tumor, and cultured cells. Recently, a fragment of cytokeratin subunit 19, referred to as CYFRA 21-1, detected in the serum of patients with nonsmall cell lung cancer, has been reported as a new tumor marker. This article reports the results of a study of serum fragment CYFRA 21-1, measured by immunoradiometric assay, as a marker of lung cancer. METHODS One hundred fourteen patients with primary lung cancer, 6 patients with malignant solid tumor, 116 patients with a variety of benign diseases, and 29 normal individuals were entered into this study. Serum CYFRA 21-1 levels were obtained by means of immunoradiomentric assay using the CYFRA 21-1 EIA (enzyme immunoassay) kit. In addition, we studied other tumor markers, including carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and neuron specific enolase (NSE), as a means of lung cancer diagnosis. RESULTS The diagnostic acuracy and sensitivity of serum CYFRA 21-1 for the detection of lung cancer were highest among the four markers. The serum CYFRA 21-1 levels were most highly elevated in lung carcinoma patients (in particular UICC Stage IV patients) across different histologic types and attained 85.1% sensitivity when using a threshold of 3.5 ng/mL. The diagnostic sensitivity for detecting lung carcinoma was substantially enhanced by means of combined assays of CYFRA 21-1 with CEA overall for lung cancer, with SCC for squamous cell carcinoma, and with CEA for adenocarcinoma. CONCLUSIONS These findings suggest that serum assays of CYFRA 21-1 are clinically useful for the diagnosis of lung carcinoma. Cancer 1996;77:1274-7.

1. We measured the neopterin level in the supernatant of cultured alveolar macrophages from patients with interstitial lung diseases (ILD patients) as a marker for the activation of alveolar macrophage. 2. In ILD patients, the supernatant neopterin level (40.1 +/- 7.8 pmol/ml) was significantly higher (P0.01) than that in control subjects (10.0 +/- 1.6 pmol/ml). 3. We also found that macrophage-colony stimulating factor (M-CSF) and interleukin-2 (IL-2) augmented neopterin production from alveolar macrophage in both ILD patients (51.6 +/- 10.4 and 60.1 +/- 10.8 pmol/ml, respectively, P0.01) and control subjects (28.1 +/- 6.0 and 25.7 +/- 4.9 pmol/ml, respectively). 4. These findings suggest that alveolar macrophages produce neopterin by M-CSF or IL-2.