Biomedical subjects
F Kuze
Publications and source records attributed to F Kuze.
[Primary ciliary dyskinesia].
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[A case of Mycobacterium avium complex pulmonary disease in the early phase].
A 51-year-old female was admitted to our hospital due to hemoptysis. Chest radiography revealed infiltrations in the middle lobe. Computed tomography (CT) of the thorax showed clusters of small nodules associated with a small cavity in the middle lobe, ligula and lower lobe of the right lung. Bronchiectasis was not detected. Transbronchial lung biopsy specimen (B4a) showed epithelioid cell granulomas with giant cells, and Mycobacterium avium was isolated in 4-week cultures of bronchial washings. This could be a case of early phase of pulmonary Mycobacterium avium complex infection in a patient without a so-called underlying condition. CT findings were characteristic and useful for the early diagnosis of MAC infection.
Lipopolysaccharide primes human alveolar macrophages for enhanced release of superoxide anion and leukotriene B4: self-limitations of the priming response with protein synthesis.
Human alveolar macrophages (AM) can produce potent reactive oxygen intermediates (ROI) and arachidonic acid metabolites (eicosanoids), which have important roles in host defense and the pathogenesis of some diseases of the lung. Bacterial lipopolysaccharide (LPS) is believed to cause profound lung injury and can prime mouse peritoneal macrophages for the enhanced secretion of ROI and eicosanoids. Therefore, we investigated the effect of LPS pretreatment on the ability of AM to release superoxide anions (O2-) and leukotriene B4 (LTB4). LPS can prime AM for the enhanced secretion of O2- and LTB4, regardless of whether they are derived from nonsmokers or smokers. Moreover, judging from the time-response characteristics, this priming for LTB4 release could be inhibited in the later stages of pretreatment, when the O2(-)-releasing capacity was enhanced. The priming inhibition was prevented, at least in part, by cycloheximide, but not by SOD and/or catalase. In addition, cycloheximide also inhibited the priming for O2- release. Hence, protein synthesis might be necessary for the priming for O2- release and for inhibiting the priming for LTB4 release. This phenomenon of self-limiting the priming response with LPS seems to be very important when we consider the high oxygen tension in the lungs and the many bacterial substances inspired into alveoli.
Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives.
As a part of our studies on the syntheses of benzoxazinorifamycin derivatives, 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives were synthesized, and tested for their antimicrobial activities. The antimicrobial activities of these compounds against gram-positive and gram-negative bacteria were almost identical to those of rifampicin (RFP) and rifabutain (RFB), however, antimicrobial activities against Mycobacterium tuberculosis were superior to RFP, while being similar to RFB. 3'-Hydroxy-5'-(4-alkyl-1-piperazinyl)benzoxazinorifamycin derivatives also had in vitro potent activities against Mycobacterium avium complex (MAC). Their minimal inhibitory concentration values against MAC were 2-256 times greater than RFP and RFB. Their in vivo efficacies against M. tuberculosis and MAC, after oral administration to mice, were superior to RFP and RFB, except for RFB against M. tuberculosis activity in vivo. Although they were absorbed from the gastrointestinal tract, their plasma levels were lower than that of RFP. Among these 5'-(4-alkyl-1-piperazinyl) derivatives, 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin, compound 19 (KRM-1648), was selected as the most promising and its preliminary pharmacokinetic characteristics in mice were investigated. Compound 19 was distributed much more in tissues, especially in spleen and lung, than in plasma and had a long elimination time from tissues.
[Clinical features of pulmonary Mycobacterium kansasii infection: comparison with M. tuberculosis and M. avium complex infection].
Six cases of pulmonary M. kansasii infection were studied. The ages of the patients ranged from 26 to 51, with a mean of 39.6 years. All the patients were male. None had any underlying systemic or lung diseases. On chest X-ray and CT scan, the majority of cases showed a solitary thin-walled cavitary lesion with little satellite or scattered lesions, which were predominantly located in S1 or S2. The strains of M. kansasii isolated from the 6 patients showed a certain pattern of antibiotic sensitivity being highly sensitive to TH, CS, EB and RFP. In 5 out of the 6 patients, chemotherapy with RFP combined with 2 or 3 other antituberculous drugs for 12 months was successful. In another patient, chemotherapy with RFP, EB and INH for 12 months was unsuccessful and surgical resection was required. Comparison of patients with M. kansasii (n = 6), M. tuberculosis (n = 112) and M. avium complex infection (n = 51) revealed that the former two had some common clinical features: predominance in males, younger age than the patients with M. avium complex infection, predominant involvement of S1, S2 and S6, and involving a single rather than multiple lung lobes. Even in cases clinically suspected of having M. tuberculosis infection, bacteriological examination should be carried out routinely to rule out M. kansasii infection.
[Airway inflammatory cell dynamics during late asthmatic reactions induced by toluene diisocyanate in guinea pigs. I. Bronchoalveolar lavage study].
We developed a guinea pig model of late asthmatic reactions (LAR) induced by toluene diisocyanate (TDI), and investigated airway inflammatory cell dynamics during LAR by bronchoalveolar lavage (BAL) in this model. The guinea pigs were sensitized by nasal application of 10% TDI solution once daily for 7 consecutive days. Thereafter, the animals were challenged with 5% TDI solution, in the same manner, on every 7th day for 4 to 11 times. Each guinea pig was pretreated with metyrapone before challenge. BAL was performed at each time point after the final challenge. The immediate asthmatic reaction and the LAR induced in the challenges were found to be 66% and 55%, respectively. A significant BAL fluid eosinophilia was observed in the guinea pigs during and after LAR (i.e., 3, 6, 24 and 168 hours after challenge), in comparison to the animals without LAR and to the control animals only exposed to ethyl acetate, a solvent for TDI. The number of eosinophils peaked at 6 hours after challenge. However, no significant changes were observed in the numbers of macrophages, lymphocytes or neutrophils in BAL fluid during LAR. We conclude that eosinophils play an important role in LAR in this model. This model seems to be useful in investigating the pathophysiology of TDI-induced asthma.
[A case of chronic aspiration pneumonia after total gastrectomy caused by gastroesophageal reflux revealed by a "modified-salivagram"].
A 76-year-old male patient suffered from recurrent bacterial pneumonia of the right upper lobe and both lower lobes since 2 years after total gastrectomy for gastric cancer. He was treated with antibiotics repeatedly without complete remission. Meanwhile, chronic cough, purulent sputum, and persistent bilateral pulmonary infiltration developed gradually. Upper digestive tract endoscopy showed moderate reflux esophagitis. For diagnosis, we performed upper digestive tract scintigraphy, a "modified-salivagram", to detect aspiration and GER. Although aspiration was not detected, GER reaching to the upper portion of the esophagus was observed 46 min after taking radio-labeled albumin, and chronic aspiration pneumonia with GER was thus diagnosed. Bed blocks and gragling with ponvidone-iodine after meals and before sleep greatly improved the symptoms of cough and sputum. The bilateral infiltrative shadows disappeared with resolution of symptoms. Chronic aspiration resulting from GER is an important cause of chronic airway infection. Even if a patient with reflux esophagitis is asymptomatic, chronic aspiration pneumonia should be suspected in cases of recurrent or persistent pneumonia in both lower lobes. The "modified-salivagram" is a sensitive test to detect aspiration and GER in hypoacidic states, such as in total gastrectomy and elderly patients.
[Airway inflammatory cell dynamics during late asthmatic reactions induced by toluene diisocyanate in guinea pigs. II. Histological study].
We investigated airway inflammatory cell dynamics during late asthmatic reactions (LAR) induced by toluene diisocyanate (TDI) in a guinea pig model developed by K. Tanaka et al. (Bull. Chest Dis. Res. Inst. Kyoto Univ. 1983: 16: 1-9). For sensitization, 10% TDI solution was applied once daily to the bilateral nasal mucosa of 41 guinea pigs for 7 consecutive days. One week after the sensitization, the animals were challenged with 5% TDI solution once a week. In addition, metyrapone (50 mg/kg) was injected intraperitoneally 24 h, and 30 min before the challenge, respectively. Airway tissue specimens (large bronchi and bronchioles) were obtained from the 41 guinea pigs at each time point (30 min, 3, 6, 24 and 168 h) after the challenge. Airway inflammatory cell dynamics were evaluated with regard to the onset and persistence of LAR. As a control, 7 guinea pigs were only exposed to ethyl acetate (a solvent for TDI) and sacrificed 6 h afterward. A histological examination of the airways revealed remarkable infiltration of eosinophils but failed to demonstrate infiltration of other inflammatory cells, including neutrophils, in the mucosal tissues of the bronchi and bronchioles during LAR at any time point (3, 6 and 24 h) after the challenge. Therefore, we conclude that eosinophils, but not neutrophils, play an important role in LAR in our model, a contrast to previous reports on human TDI-induced LAR in which neutrophils were also involved.
[DNA diagnostics of mycobacterial infection].
A diagnosis of mycobacterial infection may be suggested by a patient's symptoms, clinical or radiographic findings. However, the definite diagnoses of mycobacterial infections are dependent upon the isolation and identification of etiologic agents. Recently, nontuberculous mycobacteria are being increasingly recognized as the causes of lung diseases. Therefore, it is important to rapidly differentiate nontuberculous mycobacteria from Mycobacterium tuberculosis, since treatments, epidemiologic implications, and prognoses due to these various causative organisms may be considerably different. The isolation of mycobacteria from clinical samples takes several weeks for culture on presently available solid media, and biochemical identifications take additional several weeks after isolation of mycobacteria. Rapid, sensitive, and specific tests for detection of the organism as species in clinical specimens have been a long-standing goal. Recently, new diagnostic procedures based on molecular biology have been developed. The identifications of the species by DNA probes and PCR and a new test by means of luciferase reporter phages were discussed.
[Clinical features of the patients with "secondary infection" of Mycobacterium avium complex--Radiographic pattern of progressions in the patients with and without underlying pulmonary conditions].
We reviewed the radiographic features of 42 patients with Mycobacterium avium complex (MAC) infection. Six cases were definite "primary", 20 were "secondary", and 15 were indeterminate (probably "primary"). In the definite and probable "primary" cases, and some of the "secondary" cases, pulmonary lesions slowly progressed following a common and characteristic sequence from a cluster of small nodules or fibro-productive nodules to those with subpleural thickening, or with thickening of the draining bronchi, or with both subpleural and bronchial thickening, and to cystic bronchiectatic changes associated with collapse of the segment or the lobe, in the final stage. Cases of airspace pneumonia appeared rarely. In these cases, neither apical-subapical region prevalence, pleural effusion, nor mediastinal lymphadenopathy were found. On the contrary, in five cases of "secondary" infection, MAC lesions located at the same place with the predisposing lung disease and did not progress during more than five years of observation. In the progressive cases of "secondary" infection, however, the appearance of new lesions and the progressions thereafter showed the same pattern as in "primary" infection. These features would suggest that MAC infection would occur and progress slowly among patients who had unknown pathogenetical factor, whether they had underlying predisposing lung conditions or not.
Systemic hypersensitivity vasculitis associated with bronchiectasis.
Systemic hypersensitivity vasculitis developed in a 53-year-old man during acute exacerbation of bronchiectasis infected with Pseudomonas aeruginosa. High grade fever, mononeuropathy multiplex, cutaneous vasculitis, and biopsy specimen-proved mesangioproliferative glomerulonephritis with crescent formation and leukocytoclastic vasculitis associated with circulating immune complex occurred. Corticosteroid and cyclophosphamide therapy was effective for vasculitis and bronchiectasis.
Diagnosis and management of endobronchial tuberculosis.
We examined the records of sixty-one patients (17 males and 44 females) with endobronchial tuberculosis (EBTB). Smear tests of acid-fast bacilli were positive in 42 cases and cultures of tubercle bacilli (TB) were positive in 57. The main findings of chest roentgenogram on admission were as follows: no abnormal findings in 8, atelectasis in 30, infiltration in 25, and cavitary lesions in 6. The localization and cross-sectional extension of lesions confirmed bronchoscopically were as follows: trachea in 15, with 3 circular lesions (CLs). Right (R-) main bronchus in 19 with 11 CLs, left (L-) main bronchus in 18 with 11 of CLs, R-truncus intermedius in 14 with 6 of CLs, R-upper lobar bronchus (UB) in 17 with 12 CLs, R-middle lobar bronchus in 14 with 11 of CLs, R-lower lobar bronchus (LB) in 6 with 2 CLs, L-UB in 10 with 7 CLs and L-LB in 3 with 2 CLs. All cases were treated by combination chemotherapy with isoniazid, rifampicin, streptomycin and/or ethambutol and the rate of negative conversion of TB was good, but most of circular lesions resulted in severe bronchial stenosis or complete obstruction during and after chemotherapy, and no improvement was seen in any of the atelectasis cases at the cessation of chemotherapy. We discuss the points of early diagnosis and management of EBTB.
[A case of hypersensitivity pneumonitis presenting with copious sputum and marked obstructive impairment of lung function].
A 44-year-old male was hospitalized due to dyspnea and persistent cough with copious sputum (about 100 ml/day). Chest radiograph on admission showed hyperinflation and fine nodular shadows throughout both lungs, as well as a tram line appearance in the right lower lung field which suggested thickening of bronchial walls. Pulmonary function tests demonstrated moderate to severe reduction of %VC, FEV1.0 and PaO2. Fiberoptic bronchoscopy revealed inflammatory change in the walls of proximal bronchi. Although his dyspnea resolved rapidly, productive cough and impaired lung function were persistent and improved very slowly over the one-month-period following admission. After resolution, similar symptoms were provoked again 5 to 6 hours after returning to his home, suggesting the recurrence of hypersensitivity pneumonitis. Open lung biopsy was performed for the differential diagnosis of hypersensitivity, diffuse panbronchiolitis, and bronchial asthma, because neither transbronchial lung biopsy nor broncho-alveolar lavage was diagnostic. Histopathology of the open lung biopsy specimens revealed marked desquamation of bronchiolar epithelium in addition to bronchiolo-alveolitis with epithelial granulomas, consistent with hypersensitivity pneumonitis. Copious sputum is a very uncommon clinical feature in hypersensitivity pneumonitis. We consider that the large volume of airway fluid was caused by epithelial ulceration of bronchioles and catarrhal bronchitis associated with hypersensitivity pneumonitis.
[Two cases of idiopathic pulmonary hemosiderosis: analysis of chest CT findings].
Chest CT findings are reported in two cases of idiopathic pulmonary hemosiderosis. In both cases, CT was performed after remission of an acute exacerbation following corticosteroid therapy. Case 1 was a 17-year-old woman with Down's syndrome. Chest radiograph showed diffuse ground-glass like and reticulonodular shadows, which were predominant in the bilateral lower lung fields. Chest CT showed a diffuse increase of lung filed density, especially in the dorsal zone of both lower lobes. Open lung biopsy revealed hemorrhage and numerous hemosiderin-laden macrophages in the alveoli, and in addition, marked fibrous thickening of the alveolar septa. Case 2 was a 7-year-old girl. Chest radiograph showed diffuse micronodular shadows in both lungs. Chest CT showed diffuse poorly-circumscribed micronodular lesions with uniform distribution, and lung field density was normal except for the right upper lobe with patchy infiltrates. Although lung biopsy was not performed, fibrous thickening of the alveolar septa was presumed to be mild even if present, since pulmonary function and blood gas analysis were within normal limits. In these two cases, lung field density of CT seemed to reflect the degree of diffuse fibrous thickening of the alveolar septa, and it is suggested that CT is valuable in the evaluation of fibrous thickening of the alveolar septa secondary to recurrent pulmonary hemorrhages. Comprehensive review of CT findings of idiopathic pulmonary hemosiderosis was also performed.
[Two cases of pericardial diverticulum].
Two cases of resection of pericardial diverticulum are reported. The lesion was located in the right upper mediastinum in case 1 (66-year-old woman) and at the right anterior cardio-phrenic angle in case 2 (20-year-old woman). In case 1, the shape of the lesion varied on fluoroscopic observation when the position of the patient was changed, and in case 2, ICG instilled into the lesion operation diffused into the pericardial cavity. These procedures seemed to be useful in the diagnosis of pericardial diverticulum, differentiating it from pericardial cyst.
[The present status of nontuberculous (atypical) mycobacterial infections].
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[Clinical study on cough variant asthma].
Chronic cough may be the sole presenting manifestation of bronchial asthma (reference 3; Corrao et al, 1979), and "cough variant asthma (CVA)" has been used to categorize such patients. In order to clarify the clinical picture of CVA, we evaluated the clinical history, laboratory data, sputum cytology and pulmonary function in 14 subjects (5 males and 9 females, aged 14 to 65 years) compatible with the following diagnostic criteria: (1) chronic cough persistent for more than 8 weeks, (2) no wheeze nor dyspnea, (3) no rales, (4) no past history of asthma, (5) bronchial hyperreactivity to methacholine proven by Takishima's method (reference 13), (6) effectiveness of bronchodilators against cough, (7) normal chest X-ray film, (8) afebrile and negative CRP, (9) absence of sinusitis and postnasal drip, or if present, they are proved not to be responsible for the cough, and (10) no other causes of cough such as heart disease, prescription of ACE inhibitors, current smoking. The results were as follows. 1) Many of the subjects were atopic, with positive skin tests to one or more common allergens in 10 subjects, elevated serum IgE in 4 subjects, and past history and family history of atopy in 4 and 7 subjects, respectively. 2) Respiratory infection preceded the onset of CVA in 3 subjects. 3) Cough was generally nocturnal, but 2 subjects coughed only in the daytime. 4) FEV1.0% was decreased (less than 70%) in only 2 subjects, whereas V25 was decreased (less than 80% of predicted value) in 11 out of 12 evaluable subjects, which suggested peripheral airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)