Chronic airway inflammation, one of the pathophysiologic features of bronchial asthma, is suspected to be responsible for irreversible pathological changes of airways, called airway remodeling. To examine the mechanisms of airway remodeling in asthma, we investigated the expression of epidermal growth factor (EGF) and its receptor immunohistochemically in asthmatic human airways. Airway specimens from seven patients with asthma were obtained from autopsied and surgically resected lungs. Control specimens were obtained from lungs of eight subjects without asthma and other pulmonary complications at autopsy. We stained those specimens by the avidin-biotin-peroxidase complex (ABC) method with anti-human polyclonal EGF antibody and monoclonal EGF receptor antibodies. Three different portions of airways-large bronchi (about 1 cm in diameter), small bronchi (about 3 mm in diameter), and peripheral airways (less than 2 mm in diameter)-were examined. The thickness of the bronchial smooth muscle and basement membrane was significantly greater in the asthmatic airways than in controls. Clear immunoreactivities of EGF were widely observed on bronchial epithelium, glands, and smooth muscle in asthmatic airways. In the controls, the bronchial epithelium and the bronchial glands partially expressed faint EGF immunoreactivity. For the EGF receptor, clear immunoreactivities were also observed on bronchial epithelium, glands, smooth muscle, and basement membrane in asthmatic airways. In control airways, only part of the bronchial epithelium and smooth muscle weakly expressed EGF receptor immunoreactivity. These results suggest a possible contribution of EGF to the pathophysiology of bronchial asthma, including airway remodeling.

Soybean sudden-death syndrome has become a serious constraint to commercial production of this crop in North and South America during the past decade. To assess whether the primary etiological agent is panmictic in both hemispheres, morphological and molecular phylogenetic analyses were conducted on strains selected to represent the known pathogenic and genetic diversity of this pathogen. Maximum-parsimony analysis of DNA sequences from the nuclear ribosomal intergenic spacer region and the single copy nuclear gene translation elongation factor 1-␣, together with detailed morphological comparisons of conidial features, indicate that SDS of soybean in North and South America is caused by two phylogenetically and morphologically distinct species. Fusarium virguliforme sp. nov., formally known as F. solani f. sp. glycines, is described and illustrated for the SDS pathogen in North America, and F. tucumaniae sp. nov. is proposed for the South American pathogen. The molecular phylogenetic results challenge the forma specialis naming system because pathogenicity to soybean might have evolved convergently in F. tucumaniae and F. virguli

Three antifungal compounds, designated xanthobaccins A, B, and C, were isolated from the culture fluid of Stenotrophomonassp. strain SB-K88, a rhizobacterium of sugar beet that suppresses damping-off disease. Production of xanthobaccin A in culture media was compared with the disease suppression activities of strain SB-K88 and less suppressive strains that were obtained by subculturing. Strain SB-K88 was applied to sugar beet seeds, and production of xanthobaccin A in the rhizosphere of seedlings was confirmed by using a test tube culture system under hydroponic culture conditions; 3 μg of xanthobaccin A was detected in the rhizosphere on a per-plant basis. Direct application of purified xanthobaccin A to seeds suppressed damping-off disease in soil naturally infested by Pythiumspp. We suggest that xanthobaccin A produced by strain SB-K88 plays a key role in suppression of sugar beet damping-off disease.

Soybean sudden-death syndrome has become a serious constraint to commercial production of this crop in North and South America during the past decade. To assess whether the primary etiological agent is panmictic in both hemispheres, morphological and molecular phylogenetic analyses were conducted on strains selected to represent the known pathogenic and genetic diversity of this pathogen. Maximum-parsimony analysis of DNA sequences from the nuclear ribosomal intergenic spacer region and the single copy nuclear gene translation elongation factor 1-α, together with detailed morphological comparisons of conidial features, indicate that SDS of soybean in North and South America is caused by two phylogenetically and morphologically distinct species. Fusarium virguliforme sp. nov., formally known as F. solani f. sp. glycines, is described and illustrated for the SDS pathogen in North America, and F. tucumaniae sp. nov. is proposed for the South American pathogen. The molecular phylogenetic results challenge the forma specialis naming system because pathogenicity to soybean might have evolved convergently in F. tucumaniae and F. virguliforme. Phylogenetic evidence indicates the two SDS pathogens do not share a most recent common ancestor, since F. tucumaniae was resolved as a sister to a pathogen of Phaseolus vulgaris, F. phaseoli comb. nov. All three pathogens appear to have evolutionary origins in the southern hemisphere since they are deeply nested within a South American clade of the F. solani species complex.

Two acoustically different types of lung crackles, fine and coarse, occur in different pathophysiological conditions. To differentiate these crackles from objective characteristics of frequency information, crackles were recorded from 16 patients with pulmonary fibrosis judged clinically to have "fine" crackles and from 10 with chronic bronchitis who had mainly "coarse" crackles. Time expanded waveforms (1/4 cycle duration, initial deflection width, two cycle duration, and 9/4 cycle duration; duration of the first 1/4, 2/4, 8/4, and 9/4 cycles of crackle waveforms) were examined and fast Fourier transform analysis (peak and maximum frequencies) was performed. All waveform measurements for fine crackles were significantly smaller than those for coarse crackles. Peak and maximum frequencies for fine crackles were significantly higher than those for coarse crackles. Although there was some overlap in these values for individual crackles between the two groups when average values of these measurements were calculated for each patient, there was no overlap between fine and coarse crackles and the two groups could be clearly separated. Log peak frequency and log maximum frequency correlated better with 9/4 cycle duration (r = 085, 0 84) and two cycle duration (r = 0-87, 0 86) than with 1/4 cycle duration (r = 0-66, 0 77) or initial deflection width (r = 0-67, 0 79). Early and late segments of crackles have different characteristics, probably related to the origin of the sound and the resonance of the lung respectively. These results suggest that spectral and waveform characteristics may help to improve the accuracy of pulmonary auscultation and increase knowledge of how crackles are generated.

We prospectively followed 68 patients diagnosed as idiopathic interstitial pneumonia (IIP) over a period of 1-11 years. Thirteen patients (19%) subsequently developed systemic manifestations of collagen vascular diseases (CVD) and were diagnosed as having had interstitial pneumonia as the sole presentation of CVD (CVD-IP). Compared with the 55 IIP patients, the 13 CVD-IP patients were relatively younger, predominantly female, and had a lower incidence of dust inhalation in their history. They also had a higher erythrocyte sedimentation rate, higher incidence of the x-ray finding of discoid atelectasis in the lower lung fields, and a better prognosis than the IIP patients. However, these features did not clearly distinguish the two groups. We conclude that the patients clinically and/or histologically defined as suffering from IIP cannot be distinguished from CVD-IP patients before systemic signs of CVD appear in the latter group.

Toxic oxygen species and several proinflammatory cytokines are involved in the pathogenesis of silicosis. In order to understand whether factors that lead to susceptibility to ozone are also important in silicosis or not, we examined ozone-sensitive C57BL/6J mice and ozone-resistant C3H/HeJ mice as models of silicosis. We also analyzed the production of proinflammatory cytokines in both the acute and the chronic phases. On Day 2 after silica injection, the ozone-resistant C3H/HeJ mice showed significantly higher cellular responses as recognized by bronchoalveolar lavage (BAL) cell counts than did the C57BL/6J mice. In the chronic phase (Day 28 after silica injection), the ozone-sensitive C57BL/6J mice showed significantly greater responses to instilled silica judged by total protein and cell number in BAL fluid, hydroxyproline content, and histology than the ozone-resistant C3H/HeJ mice. TNF-alpha production by BAL cells after silica exposure was significantly higher in C57BL/6J mice than in C3H/HeJ mice in the chronic phase, whereas there was no significant difference in IL-1 alpha production between both strains of silica-injected mice. Also, the control C57BL/6J mice had significantly higher secretions of TNF-alpha than did the control C3H/HeJ mice in the acute phase. These results suggest that ozone-sensitive C57BL/6J mice are also more susceptible to silicosis than are ozone-resistant C3H/HeJ mice, and that the initial lower cellular responses and increase in TNF-alpha production may be related to the higher level of inflammatory and fibrotic response in the C57BL/6J mice.

Although the prevalence of serum precipitating antibodies for farmer's lung disease (FLD) is lower in smokers than in nonsmokersand FLDpredominates in nonsmokers, the affects of smoking on the clinical course of the disease is not known.Wecomparedthe clinical findings and the prognosis between 12 smokers (SM-FLD)and 31 non-smokers with FLD(NS-FLD). There was no difference in age, sex, working years on farm, clinical symptoms, laboratory findings, radiographic findings, between the two groups. However, for the type of onset on the first visit for FLD, "acute single episode" type was less common,and "recurrent" and "insidious onset" types were more common in SM-FLD than in NS-FLD (8.3 vs 58.1, 91.7 vs 41.9%, respectively, p<0.05). Although working status and mask wearing status were not significantly different between the two groups after the diagnosis of FLD, patients with symptoms and/or radiographic abnormalities of FLD of more than 6 months were found more frequently in SM-FLD than in NS-FLD (66.7 vs 19.4%, p<0.005). And also SM-FLDhad more recurrences of FLD than NS-FLD after the initial diagnosis ofFLD (1.58±1.56 vs 0.47±1.07, p<0.05). SM-FLDtended to have lower %VCthan NS-FLD (73.6±7.4 vs 88.5±3.9%, respectively, p=0.06). Regarding the prognosis, the 10-year survival rates were 70.7% in SM-FLD, and 91.5% in NS-FLD(p<0.05). These results suggest that smoking may make FLDinsidious and chronic, and deteriorates the clinical outcome. (Internal Medicine 34: 966-971, 1995)