We tested the effects of four eosinophil granule cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), on guinea pig tracheal epithelium in vitro. Examination by inverted microscopy revealed that MBP, both the form stabilized by alkylation of sulfhydryl groups as well as the native form of the molecule, ECP, EPO by itself, as well as EPO + H2O2 + halide, but not EDN, cause dose-related damage to the tracheal epithelium. The lowest concentrations of MBP and ECP causing damage were 10 and 100 micrograms/ml, respectively. In contrast, EDN, although biochemically similar to ECP, did not damage the tracheal epithelium in concentrations of up to 200 micrograms/ml. MBP caused exfoliation, as well as bleb formation and ciliostasis. EPO in the presence of the H2O2-producing enzyme glucose oxidase (GO), Cl-, 0.11 M, and iodide caused ciliostasis, bleb formation, and exfoliation of epithelial cells at concentrations as low as 1 U/ml (3.9 micrograms/ml). EPO + GO in the presence of Cl-, 0.11 M, alone or with Cl- and l-, 10(-4) M, or Cl- and Br-, 5 x 10(-5) M, were all toxic to epithelium. Surprisingly, EPO by itself caused partial ciliostasis, bleb formation, and exfoliation of epithelial cells in a dose-related manner at concentrations as low as 10 to 30 U/ml (39 to 121 micrograms/ml). These results confirm prior observations showing the toxicity of MBP to tracheal epithelium and indicate that ECP and EPO alone, as well as EPO + GO + halide, cause damage. Thus, several eosinophil granule proteins are able to damage respiratory epithelium.

Inflammation of the airway wall and airway hyperresponsiveness are consistent features of chronic asthma. We investigated how damage of the bronchial epithelium is related to airway hyperresponsiveness and how bronchial infiltration of eosinophils and lymphocytes is related to bronchial epithelial damage. We examined the biopsy specimens of bronchial mucosa taken from 19 patients with chronic asthma by electron microscopy. We also measured the incidence of opening of epithelial tight junctions, the widening of intercellular spaces in the epithelium, and the density of infiltrated eosinophils and lymphocytes in bronchial mucosa. Airway responsiveness was accessed by measuring PC20-acetylcholine (PC20-ACh). The inflammatory cells in the airway mucosa were counted by electron microscopy. Lymphocytes were most abundant, being 54.5% of the cells counted; eosinophils were 22.1%, neutrophils were 4.9%, and mast cells were 4.6%. A significant correlation was noted between the density of eosinophils and that of lymphocytes infiltrated in the airway mucosa (r = 0.80, p less than 0.01), suggesting that T cells may potentiate eosinophil infiltration. With increased density of eosinophils infiltrated in bronchial mucosa, both the incidence of opening of tight junctions of epithelial ciliary cells and the degree of widening of intercellular spaces in epithelium increased significantly (r = 0.51, p less than 0.05; r = 0.52, p less than 0.05), suggesting that eosinophils are related to damage of the bronchial epithelium. No correlation was observed between the density of lymphocyte infiltration and the degree of epithelial damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Regularly coiled carbon filaments have been obtained by the catalytic pyrolysis of acetylene at 350–750 °C using Ni plate and powder as a catalyst. Morphology and extension characteristics of the obtained coiled filaments were examined in some detail. The regularly coiled filaments have generally a 0.1–0.3 μm thickness, a 2–8 μm coil diameter, and a 0.1–5 mm coil length. The coiled filaments were always formed by the entwistness of two pair coils which grew in the same direction simultaneously from a diamond-shaped Ni seed. We have found that the coiled filaments could be elastically extended up to about three times versus the original coil length.

Surfactant proteins (SP)-A and SP-D are collagen-like glycoproteins belonging to the "collectin" class of C-type lectins, which are primarily synthesized in type II cells. Recent studies reported the possibility of local production of SP-A and SP-D in the airways, but the amounts of surfactant proteins in patients with bronchial asthma have not been studied.The composition of surfactant proteins in mild, stable asthmatics in the first lavage as bronchial lavage (BL) and the second and third lavages consecutively as alveolar lavages (AL) were therefore, analysed separately. The co-relationships in the BL between the amounts of surfactant proteins and those of fucose, which is one of the markers of submucosal secretion were also analysed.Increased amounts of SP-A in BL and AL of in asthmatics were found as compared with those in controls. A high concentration of SP-D in the AL asthma patients was also found. The levels of SP-A correlated with those of fucose in patients with bronchial asthma (r=0.849, p<0.01).The observations in the present study suggested that surfactant protein A may be secreted from the airways with allergic inflammation in a different manner from the alveoli. The increased levels of surfactant proteins A and D may play a protective role in an allergic inflammation in the pathogenesis of bronchial asthma. Eur Respir J 2000; 16: 831±835.

A 75-year-old man with no significant past medical history presented with a 3-week period of fever, fatigue, and a 7-kg weight loss. Physical examination revealed a poor performance status (PS; Eastern Cooperative Oncology Group score 3), emaciation, and anemia of palpebral conjunctiva. Laboratory data included a WBC count of 15.7 K/L, moderate anemia (hemoglobin concentration of 7.2 g/dL), and a platelet count of 757 K/L. Serum chemistry showed total protein, albumin, and C-reactive protein (CRP) of 8.5 g/dL, 1.7 g/dL (␥globulin was 50% in the protein fraction), and 24.51 mg/dL, respectively. In addition, serum immunoglobulin G was increased (4.3 g/dL) as was interleukin-6 (IL-6; 172 pg/mL). A computed tomography (CT) scan of the thorax showed a 3-cm mass in the right hilum and swelling of mediastinal lymph nodes, although there was no evidence of metastasis in remote organs. Accordingly, we considered a differential diagnosis of lung cancer, Castleman's disease, or tuberculosis. Subsequent endobronchial ultrasound-guided transbronchial needle aspiration resulted in the detection of a large-cell carcinoma and a final diagnosis of primary lung cancer at clinical stage T2aN2M0 (stage IIIA) with cancer cachexia.Because it was difficult to start chemotherapy and radiotherapy as a result of the poor PS of the patient, we started prednisolone 0.5 mg/kg (a total of 30 mg) for cachexia. After 2 weeks, his symptoms and PS diminished slightly including a decrease of serum IL-6 level to 112 mg/mL. Consequently, we performed systemic chemotherapy (pemetrexed 500 mg/m 2 once every 3 weeks, two courses) and sequential radiotherapy. These treatments produced no adverse events and were completed. However, the PS of the patient deteriorated to an Eastern Cooperative Oncology Group score of 4, with a decrease in serum albumin to 0.8 g/dL as a result of the recurrence of cancer cachexia and an increase of the serum IL-6 level to 173 pg/mL. Accordingly, we diagnosed his condition as progressive cancer cachexia, which was resistant to treatment with prednisolone, and realized that supportive care is usually considered the best choice of treatment. However, on the basis of the clinical findings, we theorized that the cachexia might be controlled by inhibiting the IL-6 mediated inflammatory response with tocilizumab anti-IL-6 receptor antibody. After approval by the institutional review boards of our institution, agreement by the patient and his family, and receipt of a written informed consent, we began tocilizumab therapy for the patient at 8 mg/kg (a total of 400 mg) every 4 weeks.Soon after this treatment began, the symptoms of the patient rapidly lessened, his appetite improved, and his CRP levels normalized in 2 weeks (Table 1). His overall physical condition recovered enough so that he could walk short distances after 4 weeks; after 8 weeks, he was able to live at home without nursing support. The body weight and albumin level of the patient improved dramatically to 46 kg (from