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Biomedical subjects

R Amitani

Publications and source records attributed to R Amitani.

At least 37 records · Page 2Linked to original sources

Serum eosinophil cationic protein as a marker of eosinophilic inflammation in asthma.

BACKGROUND: The serum level of eosinophil cationic protein (ECP) has been used as a clinical marker in asthma, on the assumption that it reflects ongoing eosinophilic inflammation of the airways. However, only a few studies have investigated this issue, using bronchial secretions but not tissue specimens. OBJECTIVE: To evaluate cross-sectionally the correlation between serum ECP level or blood eosinophil count, and the degree of eosinophilia in bronchoalveolar lavage fluid (BALF) and bronchial biopsy tissue, and disease activity, in asthmatic patients. METHODS: Thirty-three adults with symptomatic asthma and six healthy controls were studied. The blood eosinophil count, ECP levels in serum and BALF, percentage of eosinophils in BALF, number of eosinophils in bronchial tissue, pulmonary function, and methacholine bronchial responsiveness of these subjects were clarified. An asthma severity score and inhaled beta2-agonist requirement (puffs/day) were also assessed for the asthmatic patients. RESULTS: The asthmatic patients, compared with the controls, had more obstructive (as tested by %FEV1, FEV1/FVC, and FEF25-75%) and more responsive airways, and showed a significant increase in the number of eosinophils in the blood, BALF, and tissue, and in the serum ECP levels. The ECP levels in BALF were below the detection limit for most of the subjects in both groups examined. In the asthmatic patients, serum ECP level demonstrated correlations with the number or percentage of eosinophils in BALF and tissue, whereas the blood eosinophil count correlated only with the percentage of eosinophils in BALF. Serum ECP level correlated with all indices of disease activity examined; %FEV1, FEV1/FVC, FEF25-75% bronchial responsiveness, severity score and beta2-agonist usage, whereas the blood eosinophil count correlated only with %FEV1 and bronchial responsiveness. CONCLUSION: The data suggest that serum ECP level reflects the intensity of eosinophilic airway inflammation, as well as the disease activity, and may be useful as an inflammatory marker in asthma.

Adult↗

[A clinical study of pulmonary cryptococcosis. The Study Group of Respiratory Mycosis in Kyoto].

During the 7 years from 1990, thirty-two patients (20 in male and 12 in female, mean age; 53 years old) were diagnosed as having pulmonary cryptococcosis. To clarify the essential points for early diagnosis of pulmonary cryptococcosis, we reviewed the clinical records and chest images. Three patients had a past history of pulmonary tuberculosis and eleven patients had underlying disorders such as malignancy, chronic pulmonary diseases and so on, but no HIV infection, which would affect this disease. Eighteen patients did not have any past history nor complications. The symptoms such as cough, sputum, chest pain and fever were generally of low-grade, 14 patients had no symptom at diagnosis. Except of some patients with severe infections and severe underlying disorders, laboratory findings such as inflamatory and nutritious markers were almost within near the normal range. On plain chest X-ray films the distribution of lesions was almost in proprtion to the volume of the lobes. The multifocal nudular and/or infitrative shadows wer observed in about 2/3 cases and single lesion in about 1/3. The width of lesions were minimal except of one case with interstitial pneumonia and two cases with multifocal segmental pneumonia. The cavity lesions were observed in 7 cases and hilar lymphadenopathy in 3 cases. On CT images, the lesions were almost located in the outer zone, the lesions which were adjacent to the pleura were observed in 15 cases. Cavitary lesions were almost smooth in edge and ubiquitous, the walls were also thick. The peripheral air-bronchogram in the nodular/infitrative shadows were observed in three cases. Pulmonary cryptococcosis is air-borne and almost a chronic infection except in AIDS patients, so careful planning for examination is essential with considerations of the characteristics of clinical and imaging features of this infection.

Adult↗

Modification of results of drug susceptibility tests by coexistence of Mycobacterium avium complex with Mycobacterium tuberculosis in a sputum sample: case report and experimental considerations.

We report on a patient whose sputum contained both Mycobacterium tuberculosis and Mycobacterium avium complex (MAC). The MAC failed to be detected by the PCR-based AMPLICOR test. The unrecognized coexistence of MAC in the sample modified the results of drug susceptibility tests. Experiments revealed that the presence of both M. tuberculosis and MAC was not detected by the AMPLICOR test under certain conditions.

Humans↗

Effects of Aspergillus fumigatus culture filtrate on antifungal activity of human phagocytes in vitro.

BACKGROUND: Aspergillus fumigatus can colonise the airways and the lungs with localised underlying conditions and occasionally invade the surrounding lung tissues even in subjects without systemic predisposing factors, presumably by escaping the local host defences. The aim of this study was to investigate the effects of A fumigatus culture filtrate (ACF) on the activities of human phagocytes--inhibition of germination of A fumigatus spores by alveolar macrophages (AMs) and hyphal damage by polymorphonuclear leucocytes (PMNs)--which are the critical host defences against A fumigatus. METHODS: Spores were incubated with AMs at a ratio of 1:1 in a medium containing different concentrations of ACF for 10 hours at 37 degrees C. Spore germination was visualised with light microscopy and the inhibition rate was calculated. The percentage of hyphal damage caused by PMNs pretreated with various concentrations of ACF was measured by a colorimetric tetrazolium metabolic assay. RESULTS: The inhibition rate of spore germination by AMs cultured with medium alone (control) was 90 (0.8)% whereas that by AMs cultured with the medium containing 10% ACF was significantly (p < 0.05) reduced to 41.7 (4.6)%. ACF suppressed the inhibition of spore germination in a dose dependent manner without altering the phagocytosing activity against the spores. The percentage of hyphal damage caused by PMNs pretreated with medium-199 (control) was 78.1 (2.3)% compared with 65.3 (2.8)% when PMNs were pretreated with 50% ACF (p < 0.05). CONCLUSIONS: A fumigatus releases biologically active substance(s) which suppress the inhibition of spore germination by AMs and also suppress PMN mediated hyphal damage, and thus may contribute to the pathogenicity of this fungus.

Adult↗

Clinical profiles of Chinese patients with diffuse panbronchiolitis.

BACKGROUND: Diffuse panbronchiolitis (DPB), characterised by progressive sinobronchial sepsis, is well characterised in Japanese subjects but not in other ethnic groups. The experience with DPB in seven Chinese patients is described and the clinical profiles compared with those of Japanese subjects. METHODS: Seven Chinese patients (three women; mean (SD) age 48(18.6) years, all never smokers) who attended a teaching hospital centre and fulfilled the diagnostic criteria for DPB were assessed prospectively for clinical, radiological, lung function, microbiological, and other "characteristic" laboratory parameters. RESULTS: Lung function assessment showed a typical obstructive pattern (n = 5) and air trapping (n = 7). Typical bronchiolar infiltration by lymphocytes and plasma cells and accumulation of foamy macrophages in the intraluminal tissue were detected in open lung biopsy specimens (n = 2). Chest radiographs and high resolution computed tomographic scans revealed hyperinflation, diffuse nodules, bronchial thickening and dilatation, peripheral hypoattenuation, and bronchiolectasis. Radiological improvement, manifest as a reduction in nodular density and bronchial thickening, and persistence of other abnormalities such as air trapping were not accurately depicted by the classical Nakata or Akira classifications. The other "characteristic" features such as HLA-B54, IgG subclass deficiency, raised CD4/CD8 T lymphocyte ratio, cold haemagglutinaemia, raised IgA, IgG, and rheumatoid factor were not present. Treatment with erythromycin led to excellent responses in symptoms, lung function indices, and the radiological picture. A review of the non-Japanese cases in the literature reveals that this absence of typical "additional features" in DPB might also be applicable to non-Japanese patients. CONCLUSIONS: We report the only series of non-Japanese Mongoloid patients with well characterised DPB who had uncharacteristic investigation profiles. This experience should help other clinicians in the investigation and management of DPB in non-Japanese patients.

Adult↗

Eosinophilic inflammation in cough variant asthma.

Eosinophils are considered to play a central pathogenetic role in asthma. We previously reported that sputum eosinophilia was observed in patients with cough variant asthma (CVA), as well as in "classic" asthma with wheezing. This study was undertaken to further investigate the involvement of eosinophils in CVA. The serum eosinophil cationic protein (ECP) level, the percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and the number of eosinophils in bronchial biopsy specimen were examined in 14 patients with CVA, 21 with classic asthma, and in seven healthy controls. For the two asthmatic groups, the clinical severity was classified with scores of 1-3. Pulmonary function and bronchial responsiveness were not significantly different between the patients with classic asthma and those with CVA. BAL, tissue eosinophil and serum ECP were all significantly increased in both classic asthma and CVA when compared with the controls but were not different between classic asthma and CVA. In both groups of asthmatics, the clinical severity significantly correlated with serum ECP and tissue eosinophils. In conclusion, eosinophilic inflammation is involved in cough variant asthma as well as in classic asthma. Anti-inflammatory treatment may be essential in patients with CVA, as in those with classic asthma.

Adult↗

Effects of alkaline protease or restrictocin deficient mutants of Aspergillus fumigatus on human polymorphonuclear leukocytes.

Several substances including proteases and restrictocin have been suggested as candidates for virulence determinants in invasive pulmonary aspergillosis. However, the roles of such substances are not well understood. This study compared the in vitro suppressive effects of Aspergillus fumigatus culture filtrates (ACFs), on the functions of human polymorphonuclear leukocytes (PMNLs), the principal cells in the host defence against aspergillus hyphae, from a clinically isolated wild-type and isogenic mutant strains which lack production of elastolytic alkaline protease (Alp) and/or restrictocin. ACFs were obtained by culturing conidia of each strain in Medium- 199 at 37 degrees C for 5 days. ACFs of the wild-type significantly (p<0.01) suppressed chemotaxis, superoxide anion (O2-) release and PMNL-mediated hyphal damage, compared with the control (Medium-199). ACFs of the mutant strains that lack Alp or restrictocin significantly (p<0.01) suppressed chemotaxis and O2(-)-release, but did not suppress hyphal damage, compared with the control. The wild-type significantly (p<0.01) suppressed chemotaxis of PMNLs compared with the mutant strains lacking Alp or restrictocin, whereas there were no significant differences in suppression of O2(-)-release and hyphal damage by PMNLs. ACF of a mutant strain that lacks both Alp and restrictocin had much less activity, but significantly (p<0.01) suppressed chemotaxis of PMNLs compared with the control. In conclusion, alkaline protease and restrictocin may play roles in the suppressive effect of Aspergillus fumigatus culture filtrates on the functions of human polymorphonuclear leukocytes. Other antiphagocytic substances produced by Aspergillus fumigatus remain to be identified.

Allergens↗

Polypoid bronchial lesions due to Scedosporium apiospermum in a patient with Mycobacterium avium complex pulmonary disease.

A 69 yr old female was hospitalized for further examination of abnormal shadows on chest radiographs. She had a history of tuberculous pleurisy, rheumatoid arthritis and gold-induced interstitial pneumonia. On admission she still suffered from rheumatoid arthritis. A chest computed tomography scan on admission showed clusters of small nodules in subpleural regions of both lungs combined with bronchiectasis. Mycobacterium avium complex was cultured repeatedly from the sputum. Bronchoscopic examination disclosed white-yellow polypoid lesions in the orifice of the left B4 bronchus. Cultures of the brushing specimen of the polypoid lesions and bronchial aspirates from the B4 bronchus yielded smoky-grey mycelial colonies that were later identified as Scedosporium apiospermum. It was concluded that the polypoid bronchial lesions due to Scedosporium apiospermum were formed in the preexisting dilated bronchus caused by Mycobacterium avium complex pulmonary disease.

Aged↗

A resected case of Mycobacterium szulgai pulmonary disease.

We present the first reported case of Mycobacterium szulgai pulmonary disease that needed surgical resection due to unsuccessful antimycobacterial chemotherapy. The patient was a non-immunocompromised 48-year-old male who presented with hemoptysis and whose sputum cultures repeatedly yielded M. szulgai. Antimycobacterial chemotherapy with isoniazid (INH) and rifampin (RMP)/ethambutol (EMB) for three years had been unsuccessful, and subsequent chemotherapy with RMP, EMB, ethionamide and kanamycin had to be discontinued due to liver dysfunction. Surgical resection was finally performed, and resulted in a favorable outcome. Although M. szulgai pulmonary disease is usually well controlled by antimycobacterial chemotherapy alone, surgical treatment may be necessary in some cases.

Antitubercular Agents↗

[A case of miliary tuberculosis with brain tuberculoma, following intraocular tuberculosis].

A 52-year-old woman with visual loss of her left eye consulted a ophthalmology clinic. She was conducted left vitrectomy and administered corticosteroid under the diagnosis of uveitis of unknown cause. But her visual acuity was not improved. Although re-surgery was planned, pus retention was found in her left eye. After her left eye was resected, fever and general malaise appeared suddenly. Her chest X-ray film revealed diffuse micronodular opacities. Acid-fast bacilli were detected from her sputum and identified to be Mycobacterium tuberculosis. She was diagnosed miliary tuberculosis, and then antituberculous chemotherapy consisting of 4 drugs was started. Granulomatous inflammation destructing retina and numerous acid-fact bacilli were found in histologic examination of the resected eye. This case was thought to be miliary tuberculosis disseminated from intraocular tuberculosis. After 2 months of therapy, neurologic symptoms which might be caused by brain tuberucloma appeared and deteriorated rapidly. But by adding corticosteroid to antituberculous therapy, symptoms were diminished gradually.

Anti-Inflammatory Agents↗

Evaluation of Roche Amplicor PCR assay for Mycobacterium avium complex in bronchial washing.

SETTING: A commercially available polymerase chain reaction (PCR) test (Roche AmplicorTM Mycobacterium avium and M. intracellulare assay-MAC-PCR) designed to detect M. avium complex (MAC) in bronchial washing was evaluated. DESIGN: A total of 141 specimens from 127 patients with various pulmonary conditions were examined. Results were compared with acid-fast smears, cultures with Ogawa egg medium, as is still commonly used in Japan, and final diagnoses. RESULTS AND CONCLUSIONS: A total of 14 bronchial washing specimens yielded MAC. Six smear- and culture-positive specimens were all MAC-PCR positive. In eight smear-negative and culture-positive specimens, six were MAC-PCR positive. The overall sensitivity versus culture was 85.7% (12/14). However, sensitivity might be over-estimated, as there is a lower recovery rate of MAC with egg-based medium compared with liquid media. In 127 patients, 15 were identified as having pulmonary MAC disease, of whom 13 had positive MAC-PCR in bronchial washing. In the remaining 112 patients, MAC-PCR was negative, which suggests that positive MAC-PCR was not a contaminated result. However, in terms of sensitivity and speed, we were unable to show any additional clinical benefit for using MAC-PCR as opposed to liquid media, in which MAC can frequently be detected in 7 to 14 days.

Adult↗

[Multidrug-resistant tuberculosis].

Multidrug-resistant tuberculosis (MDR-TB) is defined as one that is resistant to both isoniazid and rifampicin regardless of its resistance to any other antituberculosis drugs. According to "Study on the incidence of drug resistance for new admissions" reported by TB Sanatorium Council in 1992 in Japan, no increase of incidence was observed in either the first treatment or re-treatment as compared with former reports. However, U.S.A. study indicates a significant increase of MDR-TB, which is supposed to have been caused by a primary drug resistance prevailed in an infected area, or an acquired (secondary) drug resistance due to incomplete and/or faulty treatment for active TB. Many incidences were also reported for mass nosocomial infection of MDR-TB with HIV patients. In spite of these serious issues in U.S.A., MDR-TB has not yet been a major concern in Japan, while Japan should work out countermeasures in advance with careful observation of its tend. One of the causes of mass nosocomial infection of MDR-TB observed in U.S.A. is reported due to a delayed treatment after long procedures of TB identification and susceptibility tests followed specimen sampling. Rapid tests of identification and susceptibility for TB, MDR-TB in particular, are long expected. The introduction of recent molecular genetics technology will help to develop new rapid tests. While a relationship between drug resistance and TB gene is recently known to certain extent, total mechanism of TB resistance cannot be fully explained with only certain gene identified in the connection with drugs. Early treatment is critical for MDR-TB with HIV patient, as their prognosis is far worse than MDR-TB with non-HIV. Aside from HIV infection, very limited drugs are available for the treatment of MDR-TB. Drugs should be carefully selected based on the resistance patterns of each strain as well as its side effects anticipated.

Humans↗

Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase, in ciliary motility.

Macrophage-stimulating protein (MSP) is an 80-kD serum protein with homology to hepatocyte growth factor (HGF). Its receptor, RON tyrosine kinase, is a new member of the HGF receptor family. The MSP-RON signaling pathway has been implicated in the functional regulation of mononuclear phagocytes. However, the function of this pathway in other types of cells has not been elucidated. Here we show that in contrast to the HGF receptor, which was expressed at the basolateral surface, RON was localized at the apical surface of ciliated epithelia in the airways and oviduct. In addition, MSP was found in the bronchoalveolar space at biologically significant concentrations. MSP bound to RON on normal human bronchial epithelial cells with a high affinity (Kd = 0.5 nM) and induced autophosphorylation of RON. Activation of RON by MSP led to a significant increase in ciliary beat frequency of human nasal cilia. These findings indicate that the ciliated epithelium of the mucociliary transport apparatus is a novel target of MSP. Ciliary motility is critical for mucociliary transport. Our findings suggest that the MSP-RON signaling pathway is a novel regulatory system of mucociliary function and might be involved in the host defense and fertilization.

Animals↗

Interleukin-12 gene expression in human monocyte-derived macrophages stimulated with Mycobacterium bovis BCG: cytokine regulation and effect of NK cells.

Macrophage-derived interleukin-12 (IL-12) is essential for the activation of a protective immune response against intracellular pathogens. In this study, we examined the regulation of IL-12 mRNA expression by monocyte-derived macrophages (MDM) in response to Mycobacterium bovis BCG stimulation. A reverse transcription-PCR assay detected p40 mRNA of IL-12 at 3 h and showed a peak at 6 to 12 h with a subsequent decline. Semiquantitation of mRNA levels by competitive PCR revealed that pretreatment with gamma interferon (IFN-gamma) amplified the expression approximately 100-fold, while pretreatment with tumor necrosis factor alpha (TNF-alpha) or granulocyte-macrophage colony-stimulating factor augmented this expression about 10-fold. In contrast, pretreatment with IL-10 and IL-4 inhibited IL-12 mRNA expression. These results were further confirmed by measuring the p70 bioactive protein level in each conditioned medium by an enzyme-linked immunosorbent assay. Since IL-12 mRNA expression was weak without cytokine pretreatment and IFN-gamma strongly augmented production, we speculated that IFN-gamma might have a role in BCG stimulation of IL-12 mRNA expression. Unexpectedly, the addition of three different kinds of anti-IFN-gamma antibodies and anti-IFN-gamma receptor antibody and the coaddition of anti-TNF-alpha antibody with anti-IFN-gamma receptor antibody all failed to inhibit IL-12 mRNA expression. However, the MiniMACS method used to remove NK cells from a mononuclear cell suspension inhibited the expression of p40 mRNA but not the expression of mRNA of TNF-alpha or IL-1beta. We concluded that the coexistence of NK cells was essential for the induction of IL-12 in MDM stimulated with BCG rather than through the secretion of IFN-gamma.

Cytokines↗

Yield of computed tomography and bronchoscopy for the diagnosis of Mycobacterium avium complex pulmonary disease.

Mycobacterium avium complex (MAC) pulmonary disease with nodules and bronchiectasis is increasing. But the usefulness of computed tomography (CT) and bronchoscopy for diagnosis and the significance of MAC isolation from respiratory secretions are still unclear. For a 4-yr period, we prospectively examined the role of bronchoscopy with bronchial washing and transbronchial lung biopsy in 26 patients who had clusters of small nodules in the periphery of the lung associated with ectatic changes of the draining bronchi on the CT scan. None of them was infected with human immunodeficiency virus. Thirteen of the 26 patients (50%) had cultures positive for MAC, six in the sputum and 13 in the bronchial washing. Epithelioid granuloma was demonstrated in eight of 13 patients with culture-positive MAC and in two of 13 patients in whom MAC was culture-negative. Rapidly growing mycobacteria were cultured in the two patients. Seven of the eight biopsy-positive patients received treatment and responded by sputum conversion and/or radiographic improvement. We found that the CT finding was a useful clue to suspect MAC pulmonary disease and that the bronchial washing was more sensitive than the routine expectorated sputum for MAC isolation. Demonstration of granuloma in more than half of the MAC-positive patients would suggest that MAC may have invaded the lung tissue rather than colonized in the airways.

Adult↗

[2 cases of lung disease caused by Mycobacterium avium complex occurred in middle-aged women without underlying disorders, which we observed for more than 30 years].

We reported 2 cases of Mycobacterium avium complex lung disease occurred in middle-aged women without underlying disorders, which we could observe for more than 30 years. One case was a 42-year-old woman started with bloody sputum, and the other was a 43-year-old woman with cough and sputum. In both cases, chest X ray films were normal on their first visit. More than 15 years after their first visit, Mycobacterium avium complex was isolated from their sputum or bronchial washing. During the observation, a cluster of small nodules in the periphery of the lung and bronchiectasis appeared and deteriorated, and excretion of the bacilli increased gradually. Their past history and family history were normal. Since lung disease caused by Mycobacterium avium complex progresses very slowly, long-time observation would be necessary to consider its pathogenesis.

Adult↗

[Multiple extramedullary plasmacytomas from the whole respiratory system].

Extramedullary plasmacytoma occurs most commonly in the upper respiratory tract, but rarely develops in the lung. We have recently studied an unusual case of multiple extramedullary plasmacytomas, presumably preceding localized myelomatous bone lesions. This rather unique case is, to the best of our knowledge, the first documented report of widespread multiple extramedullary plasmacytomas confined to a single organ system. A 50-year-old man was hospitalized for assessment of bilateral hilar masses on a chest radiograph. An open lung biopsy specimen was obtained, revealing plasmacytoma of the lung. Biopsy specimens from the nasal fossa also demonstrated plasma cell tumor. Moreover, a bronchoscopy revealed that the both main-stem bronchi appeared to be involved by hemorrhagic tumorous lesions. However, a biopsy could not be done because of the high risk of bleeding. Electrophoresis revealed an IgA (kappa) type M-component (2.8 g/dl) in the serum and kappa type Bence Jones proteins (0.5 g/day) in the urine. The clinical course of the present case accurately corresponds to multiple extramedullary plasmacytomas with a localized bone involvement, but not to extensive extramedullary disease associated with aggressive multiple myeloma. The occurrence of multiple extramedullary plasmacytomas confined to the respiratory system may be due to an endobronchial metastatic process or to a multicentric autochthonous process.

Bence Jones Protein↗

[Evaluation of mycobacteria growth indicator tube (MGIT) for drug susceptibility testing of Mycobacterium tuberculosis isolates].

Fifty six clinical isolates of Mycobacterium tuberculosis were tested for drug susceptibility in Mycobacteria Growth Indicator Tube (MGIT) containing 0.1 microgram/ml of INH, 1.0 microgram/ml of RFP, 3.5 micrograms/ml of EB and 0.8 microgram/ml of SM. These results were compared with those obtained by testing the same M.tuberculosis isolates by the absolute concentration method using 1% Ogawa egg slant containing 0.1 microgram/ml of INH, 10 micrograms/ml of REP, 2.5 micrograms/ml of EB and 20 micrograms/ml of SM. Fifty six isolates consisted of 18 pansensitive strains, 27 multidrug resistant strains and 11 single drug resistant strains. The results of individual drugs showed excellent agreement between the MGIT and the Ogawa methods, and overall agreement rate of the two methods were 96.4%. The results were just the same for all drugs in 48 out of 56 strains studied. The drug resistance could be observed much earlier by the MGIT method (mean 5.9 days) than by the Ogawa method (more than 21 days). In conclusion, the MGIT system could be a promising new drug susceptibility test which might become available in Japan replacing the Ogawa method.

Antitubercular Agents↗