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Biomedical subjects

R Amitani

Publications and source records attributed to R Amitani.

At least 55 records · Page 3Linked to original sources
PubMed1997

Activity of KRM 1648 or rifabutin alone or in combination with clarithromycin against Mycobacterium avium complex in human alveolar macrophages.

SETTING: The activity of KRM 1648 (KRM), a new benzoxazinorifamycin, and rifabutin (RBT), alone or in combination with clarithromycin (CLA), was evaluated against Mycobacterium avium complex (MAC) that multiplied in human alveolar macrophages (AM). DESIGN: AM were recovered by bronchoalveolar lavage, incubated in RPMI 1640 medium with 10% human AB serum, infected with four strains of MAC (of non-acquired immune deficiency syndrome [AIDS] origin), and then treated with each drug alone or in combination. After incubation for 7 days, colony forming units in each well were counted on 7H10 agar. RESULTS: Although concentrations between 0.2 microgram/ml and 20 micrograms/ml of both rifamycins showed clear dose-dependent activities against all MAC strains tested, only 20 micrograms/ml of each drug had modest bactericidal effect. In combination with 2.0 micrograms/ml of CLA, however, 0.2 microgram/ml of both drugs caused a bactericidal response against two of the four MAC strains examined. CONCLUSION: According to this human alveolar macrophage model of MAC infection, KRM and RBT in combination with CLA was found to be a promising candidate against human pulmonary MAC infection, and deserves clinical evaluation.

Adult↗
PubMed1996

Late respiratory response and associated eosinophilic inflammation induced by repeated exposure to toluene diisocyanate in guinea pigs.

OBJECTIVE: The study was designed to establish an animal model of toluene diisocyanate (TDI)-induced late respiratory response and to investigate airway inflammatory cell dynamics in this model. METHODS: Guinea pigs were exposed to 2, 4-TDI dissolved in ethyl acetate by nasal application according to three schedules. Schedule 1 consisted of sensitization and multiple challenge (n = 58): 10% TDI was applied once daily for 7 days (sensitization) followed by challenges with 5% TDI once weekly for 4 weeks. Schedule 2 consisted of sensitization only (n = 5): 10% TDI was applied once daily for 7 days. Schedule 3 consisted of single challenge only (n = 12): 5% TDI was applied only once. As controls, ethyl acetate was applied according to the three schedules described above. Each animal was premedicated with metyrapone before each challenge. Bronchoalveolar lavage and histologic examination were performed at various times after the last challenge. RESULTS: Schedule 1 induced immediate and late respiratory responses at a prevalence of 63% and 56%, respectively. Schedules 2 and 3 induced an immediate response in some animals but no late response. Neither immediate nor late response was observed in control animals. All of the subgroups of schedule 1 that developed late responses (examined at 2, 3, 6, 24 and 168 hours) showed a significant increase of eosinophils in bronchoalveolar lavage fluid and tissue compared with the corresponding control of each (examined at the same time points). Two of the subgroups with late responses (examined at 3 and 6 hours) were compared with their corresponding subgroups, which were given the same treatment, failed to develop late response, and were examined at the same time points; they again proved to have a significant increase of eosinophils in both samples. Subgroups of schedule 1 without late response (30 minutes, 3 and 6 hours), schedule 2 (6 hours), or schedule 3 (2 and 6 hours) did not show significant changes in lavage or tissue cell composition, except for the schedule 1 subgroup examined at 6 hours, which showed a significant increase of eosinophils only in the tissue compared with its control. CONCLUSIONS: Sensitization and multiple challenge with TDI induced immediate and/or late respiratory responses at a high prevalence in guinea pigs. Eosinophilic but not neutrophilic inflammation was involved in the late response.

Animals↗
PubMed1996

Bronchial mucoid impaction due to the monokaryotic mycelium of Schizophyllum commune.

We report, to our knowledge, the first case of mucoid impaction of the bronchi due to a hypersensitivity reaction to the monokaryotic mycelium of Schizophyllum commune. The patient was hospitalized because of mild asthma attacks, persistent cough, peripheral eosinophilia, and "gloved finger" shadows on a chest roentgenogram. Bronchoscopic examination disclosed mucoid impactions that consisted of accumulations of eosinophils, Charcot-Leyden crystals, and nondichotomously branched hyphae in B3, B9, and B10 of the left lung. Cultures of the mucous plugs and sputum samples yielded white, felt-like mycelial colonies that were later identified as the monokaryotic mycelium of S. commune by use of mating tests with established monokaryotic and dikaryotic strains of S. commune. The results of tests for serum antibody to S. commune cytosol antigen were positive. Repeated bronchoscopies for performing bronchial toilet were effective in removing the mucous plugs and relieving the patient's symptoms. We suggest that the monokaryotic mycelium of S. commune should be considered as one of the fungi that can cause hypersensitivity-related lung diseases.

Aged↗
PubMed1996

In vitro bactericidal and in vivo therapeutic activities of a new rifamycin derivative, KRM-1648, against Mycobacterium tuberculosis.

The in vitro and in vivo activities of a new rifamycin derivative, KRM-1648, against Mycobacterium tuberculosis H37Rv were compared with those of rifampin. Bactericidal activity was evaluated by using a silicone-coated slide culture method. The MBC of KRM-1648 was 0.15 to 0.3 microgram/ml for 24 h of exposure, while that of rifampin was > 160 microgram/ml under the same conditions. Against experimental murine tuberculosis, KRM-1648 exhibited significant therapeutic effects, in terms of prolonged survival times for mice compared with those with rifampin treatment, even at lower doses, such as 1 and 3 mg/kg. At a dose of 3 mg/kg, KRM-1648 was at least as effective as rifampin at 10 mg/kg. The combination of KRM-1648 (3 mg/kg) plus isoniazid (3 mg/kg) plus ethambutol (10 mg/kg) exhibited much more activity than did rifampin (10 mg/kg) plus isoniazid (3 mg/kg) plus ethambutol (10 mg/kg). These findings suggest that KRM-1648 is a promising candidate for the treatment of tuberculosis.

Animals↗
PubMed1996

Activity of KRM-1648 alone or in combination with both ethambutol and kanamycin or clarithromycin against Mycobacterium intracellulare infections in beige mice.

The in vivo activities of KRM-1648 alone or in combination with both ethambutol (EB) and kanamycin (KM) or clarithromycin (CAM) were tested against Mycobacterium intracellulare infections in beige mice. KRM-1648 was more active than rifampin (RFP) when each drug was used alone, and the efficacy of KRM-1648 was similar to those of both kanamycin and clarithromycin. The combination KRM-1648-KM-EB was strongly active and rapidly reduced the numbers of bacilli both in lungs and in spleens compared with RFP-KM-EB. The combination KRM-1648-CAM had greater therapeutic effects than RFP-CAM; this difference in efficacy was more pronounced for lungs than for spleens. These findings suggest that KRM-1648 is a promising candidate for combination therapy with other potent antimycobacterial drugs.

Animals↗
PubMed1996

Murine model of invasive pulmonary aspergillosis following an earlier stage, noninvasive Aspergillus infection.

Aspergillus spp. occasionally cause invasive pulmonary aspergillosis following noninvasive infection in patients with underlying bronchopulmonary disorders regardless of their systemic immunological conditions. We developed a murine model of invasive pulmonary aspergillosis following an earlier stage, noninvasive Aspergillus infection. BALB/c mice were inoculated intratracheally with agarose beads containing Aspergillus fumigatus conidia. Two weeks after inoculation, half of the mice were immunosuppressed with cortisone acetate. During a 4-week observation period, the survival rate of infected immunosuppressed mice was significantly lower (P < 0.01) than that of infected nonimmunosuppressed mice. The number of CFU in the lungs gradually decreased in the nonimmunosuppressed mice, whereas a time-related significant increase (P < 0.05) of CFU was demonstrated in the immunosuppressed mice. In the lungs of the nonimmunosuppressed mice, there was marked accumulation of neutrophils, lymphocytes, and macrophages (in this order) around the agarose beads in the bronchi. Aspergillus hyphae were surrounded by the inflammatory cells and did not invade the lung parenchyma. In contrast, in the immunosuppressed mice, Aspergillus hyphae proliferated markedly and invaded the lung parenchyma after immunosuppression. In this model, the two-dimensional extents of the lesions were also evaluated with an image-processing system. Time-related increase of the area of peribronchial necrotic lesions was significant (P < 0.05) after immunosuppression. This model should therefore be useful for investigating the pathophysiology of noninvasive Aspergillus infection and invasive pulmonary aspergillosis and also for clarifying the mechanism of conversion to the invasive disease from the noninvasive stage.

Animals↗
PubMed1996

Suppressive effects of Aspergillus fumigatus culture filtrates on human alveolar macrophages and polymorphonuclear leucocytes.

Aspergillus spp., especially A. fumigatus (Af) can colonize the airways and the lungs with localized underlying conditions and further invade the surrounding lung tissues, even in subjects without systemic predisposing factors, presumably by escaping the local host defences. To clarify the mechanisms of colonization and invasion of Af, we investigated the in vitro effects of Af culture filtrates (ACFs) on the functions of human alveolar macrophages (AMs), and polymorphonuclear leucocytes (PMNs). ACFs were obtained by culturing clinically isolated Af in Medium-199 at 37 degrees C for 5 days. In the study of phagocytosis of Af conidia by human AMs, 52% of AMs ingested conidia during a 60 min incubation period in Medium-199. However, the percentage decreased to 24% when incubated with a final concentration of 30% ACF in Medium-199. With respect to the antichemotactic activity on human PMNs, 3% ACF was sufficient for significant suppression, and 30% ACF completely inhibited the migration of PMNs. In addition, phorbol myristate acetate (PMA)-induced O2- release from PMNs was significantly suppressed in Medium-199 which included 12.5% ACF or more. The antichemotactic activity of ACF was partially abolished by trypsin or chicken egg ovomacroglobulin. When ACF was separated into two fractions (molecular weight > 10 and < 10 kDa) by dialysis and centrifugation through CL-LGC filters, both fractions retained the antichemotactic activity. We conclude that Af produce several antiphagocytic factors, which can be responsible for the colonization of Af in the bronchopulmonary tissues and allow this species to invade surrounding lung tissues in pulmonary aspergillosis by suppressing local host defences.

Aspergillus fumigatus↗
PubMed1996

[A patient with myotonic dystrophy who presented with chest roentgenographic abnormalities and alveolar hypoventilation].

A 52-year-old man had been asymptomatic except for nasal speech since his third decade of life. A chest roentgenogram obtained during a health screening one year before admission revealed elevation of the right hemidiaphragm and infiltrates in the right lower lung field. Because the pulmonary shadows had gradually increased, he was admitted to the hospital, for further examination. Based on physiological findings and on the results of electromyography, myotonic dystrophy was diagnosed. The chest roentgenographic abnormalities were regarded as resulting from complications of this disease. Arterial blood gas analysis showed hypercapnic hypoxia and a spirogram showed that the vital capacity and maximum voluntary ventilation were about half of their respective predicted values. The hypercapnic ventilatory response was also abnormally low. An overnight study of oxygen saturation showed episodes of marked desaturation, and polysomnography revealed central sleep apnea. Inhalation of capsaicin showed an abnormally high cough threshold. Patients with undiagnosed myotonic dystrophy rarely present with chest roentgenographic abnormalities.

Electromyography↗
PubMed1995

Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium.

The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.

Aspergillus fumigatus↗
PubMed1995

Inflammatory bronchial polyps associated with asthma: resolution with inhaled corticosteroid.

In a 50 year old man who complained of cough and sputum, a small endobronchial tumour was found in the left main bronchus and was biopsied via bronchoscopy. The histological diagnosis was inflammatory polyp with marked infiltration of eosinophils. Six years later, the patient developed asthma. At the same time, another polyp was found in the posterior basal bronchus of the right lower lobe. The appearance of the first polyp was unchanged endoscopically and histologically. Inhalation of beclomethasone dipropionate, 200 micrograms b.i.d., was started and symptoms of asthma soon subsided. In addition, the two polyps regressed and eventually disappeared after one year of treatment. Inhaled corticosteroids, being noninvasive and relatively safe, appear to be a possible therapeutic option in inflammatory bronchial polyps, especially in cases where the patient has asthma as an underlying condition, or the polyps are small and their management is not urgent.

Administration, Inhalation↗
PubMed1995

Interstitial pneumonitis-like lesions in guinea-pigs following repeated exposure to toluene diisocyanate.

The inhalation of isocyanates, such as toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), and hexamethylene diisocyanate (HDI) can induce hypersensitivity pneumonitis (HP) as well as bronchial asthma in humans, but the precise pathological features and their pathogenetic mechanisms have not been elucidated. To provide insight into the pathological features of isocyanate-induced hypersensitivity pneumonitis in humans, we repeatedly exposed guinea-pigs to TDI following previous sensitization to TDI and examined the inflammatory response in the pulmonary lesions. Following sensitization with 10% TDI ethyl acetate solution for seven consecutive days, guinea-pigs were exposed to 5% TDI ethyl acetate solution once a week for 4 weeks. As a control, guinea-pigs were exposed to ethyl acetate alone in the same manner. Furthermore, other guinea-pigs received a single exposure to 5 or 20% TDI ethyl acetate solution. The TDI solutions or ethyl acetate were applied to the bilateral nasal mucosa of guinea-pigs for 30 s-day-1. Histological examination of lung specimens of guinea-pigs repeatedly exposed to TDI after previous sensitization by TDI inhalation revealed interstitial pneumonitis-like lesions in which mononuclear cells and eosinophils were mainly involved. Lungs of control and nonsensitized guinea-pigs showed insignificant histological changes. We demonstrated that interstitial pneumonitis-like lesions, indistinguishable from isocyanate-induced hypersensitivity pneumonitis in humans, can be caused by repeated but not single exposure to TDI in guinea-pigs.

Alveolitis, Extrinsic Allergic↗
PubMed1995

Aspergillus culture filtrates and sputum sols from patients with pulmonary aspergillosis cause damage to human respiratory ciliated epithelium in vitro.

Aspergillus species frequently colonize lower respiratory tracts and lungs with localized underlying conditions (healed tuberculous cavity, cystic fibrosis, bronchiectasis, etc.) even in subjects without systemic predisposing factors. We investigated the in vitro effects of culture filtrates of Aspergillus species and sputum sols from patients with pulmonary aspergillosis on ciliary beat frequency (CBF) and epithelial integrity of human respiratory ciliated epithelium. Culture filtrates of 25 clinically isolated fungi (16 Aspergillus fumigatus, three Aspergillus niger, one Aspergillus flavus, three Candida albicans, and two Cryptococcus neoformans) were obtained by culturing the fungi in Medium-199 at 37 degrees C for 7 days, and five sputum sols were obtained from patients with pulmonary aspergillosis infected by A. fumigatus. During 6 h experiments using a photometric technique, 14 out of 16 A. fumigatus culture filtrates caused progressive and significant reduction in CBF associated with marked epithelial disruption, whilst the culture filtrates of A. niger and A. flavus caused minor epithelial damage without slowing of CBF, and Medium-199 alone (Control) showed neither epithelial damage nor slowing of CBF. All of the sputum sols also caused significant slowing of CBF as well as epithelial disruption. Culture filtrates of C. albicans and Cr. neoformans had no effects on human respiratory epithelium. We conclude that Aspergillus species, especially A. fumigatus release a factor (or factors) which causes damage to respiratory epithelium and slows CBF, and that these factors may contribute to the colonization of the lower respiratory tracts by the Aspergillus species and may possibly contribute to the further proliferation and spread of the lesions in pulmonary aspergillosis.

Adult↗
PubMed1995

Rapid detection of Mycobacterium tuberculosis in sputa by the amplification of IS6110.

A polymerase chain reaction (PCR) assay for the rapid detection of Mycobacterium tuberculosis in sputum samples was studied. The target DNA was a 123-base pair (bp) fragment of IS6110, which was repeated in the M.tuberculosis genome and was specific for the M.tuberculosis complex. Glass beads (2mm diameter) and lysozyme were used to lyse the mycobacteria and DNA was extracted by the phenol-extraction method. The amplified PCR product was detected by examination of ethidium-bromide-stained agarose gel and by hybridization with an oligonucleotide alkali-phosphatase-labeled probe. A total of 70 samples were tested. PCR was positive in all 13 smear and culture-positive samples, in 5 of 8 smear-negative and culture-positive samples, and in 1 of 49 smear and culture negative samples. The overall sensitivity and specificity were 85.7% and 98%, respectively. Thus, IS6110 as a PCR target was found to be very useful for the rapid diagnosis of M.tuberculosis infection and start of anti-tuberculous chemotherapy.

Base Sequence↗
PubMed1995

[A case of Mycobacterium avium disease presenting as a solitary pulmonary nodule and resected under a suspicion of lung cancer].

A 43 year old female smoker was admitted to our hospital for evaluation of solitary pulmonary nodule (SPN). She had no symptoms, and no past history or family history that might suggest compromised defense against pulmonary infections. Physical examination and laboratory findings including humoral and cell-mediated immunity revealed no abnormality. The chest radiography taken 2 years ago looked normal, but those on admission showed SPN in a left lower field. Computed tomography (CT) revealed solitary elipsoid nodule in S5. Because two trials of transbronchial biopsy, brushing and washing could not give any diagnostic findings, thoracotomy was performed under tentative diagnosis of lung cancer. The lesion was located in the outer portion of S5 and was found to consist of 2 elastic hard nodule surrounded by a atelectasis with inflammation. The nodule had supprative substance with several acid fast bacilli, and its intraoperative pathology revealed epitheloid cell granulomas. The lesion was resected completely. In a mean while, seventy smooth colonies grew on an Ogawa egg medium, which was identified as M. avium by the probe analysis using SNAP TEST. The final diagnosis of pulmonary M. avium disease was made, and the patient was administered RFP, EB, OFLX, and CAM in a outpatient clinic. Some discussions were also made about CT findings of pulmonary M. avium complex disease developed in patients without any predisposing conditions.

Adult↗
PubMed1994

Nasal and paranasal sinus disease in patients with congenital velopharyngeal insufficiency.

OBJECTIVE: To investigate nasal and paranasal disease in patients with congenital velopharyngeal insufficiency (CVPI). DESIGN: Case series. SETTING: Patients with CVPI or cleft palate were investigated at Kyoto (Japan) University Hospital. PATIENTS AND OTHER PARTICIPANTS: Consecutive sample (60 patients with CVPI and 333 with cleft palate). No eligibility criteria or sociodemographic features. Random sample (normal subjects). MAIN OUTCOME MEASURES: The incidence of sinusitis and septal deviation, nasal airway resistance, nasal mucociliary function by saccharin test, and ciliary beating frequency were examined. These findings in patients with cleft palate and normal subjects were compared to clarify the features of nasal disease in CVPI. RESULTS: The incidence of sinusitis in CVPI was 46.7% and approximately equal to that in cleft palate (44.1%). The incidence of septal deviation in CVPI (26.7%) was low and nasal airway resistance was almost normal. In contrast, in patients with bilateral, unilateral, or incomplete cleft palate, the incidence of septal deviation was significantly more frequent (78.9%) than that in CVPI (P < 0.001), and nasal airway resistance was significantly higher than that in CVPI (P < .0001). In patients with submucosal cleft, septal deviation was found in 40.8% and nasal airway resistance was significantly higher than that in CVPI (P < .02). Although saccharin time was significantly prolonged (P < .001) and ciliary beating frequency was significantly lower (P < .005) in patients with cleft palate than in normal subjects, values for these tests in patients with CVPI were normal. CONCLUSIONS: The incidence of sinusitis was high in CVPI. However, the frequency of septal deviation and nasal airway resistance was almost normal. Nasal mucociliary function (saccharin time and ciliary beating frequency) was also normal.

Adolescent↗
PubMed1994

Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumour necrosis factor-alpha (TNF-alpha) activate human alveolar macrophages to inhibit growth of Mycobacterium avium complex.

We investigated the effects of certain macrophage-active cytokines on the phagocytosis and growth inhibition of Mycobacterium avium complex (MAC) by human alveolar macrophages (AM). We also evaluated the effects of pretreatment with each cytokine on the superoxide anion release (O2-) from AM. The cytokines that we used were recombinant GM-CSF, natural type TNF-alpha, recombinant interferon-gamma (IFN-gamma), and recombinant IL-2. We found that phagocytosis by the various cytokine-stimulated AM was similar to that of unstimulated AM. On the other hand, significant growth inhibition of MAC was observed in the macrophages treated with GM-CSF or TNF-alpha, while no growth inhibition of MAC was observed in the macrophages treated with IFN-gamma or IL-2. Pretreatment with all cytokines tested enhanced the O2- release from AM, but there was no correlation between the enhancement of O2- release and the growth inhibition of MAC. Thus, we concluded that GM-CSF or TNF-alpha could activate AM to inhibit growth of MAC, probably not through the enhanced production of reactive oxygen intermediates.

Adult↗
PubMed1994

[New drugs against tuberculosis and nontuberculous mycobacterial infections: a review].

The number of cases with tuberculosis is again increasing in many countries, and recently several nosocomial outbreaks of multidrug-resistant tuberculosis have occurred in the United States. The number of patients with disseminated Mycobacterium avium complex (MAC) infections in AIDS population, and patients with MAC pulmonary disease unassociated with HIV seem to be also increasing. It takes at least 6 to 9 months for an initial treatment of active tuberculosis due to drug-sensitive strains with the standard regimen which includes isoniazid (INH) and rifampicin (RFP). Treatment for the diseases caused by drug-resistant M. tuberculosis and MAC is much more time-consuming and more toxic than for the diseases caused by drug-sensitive strains, and often unsuccessful. For the reasons described above, the developments of new agents with potent antimycobacterial activities are highly desired. The new agents should also be useful for treating patients who have acquired resistance to many of the currently available drugs. In this review the new antimycobacterial drugs are summarized. Some of them have already been used clinically, but many are still in experimental evaluations. 1) Rifamycin derivatives: rifabutin (RBT), KRM-1648 (KRM), rifapentin (RPT), FCE-22250, FCE-22807, CGP-7040, SPA-S-565 and other rifamycin derivatives. New rifamycin derivatives including RBT, KRM have increased in vitro antimycobacterial activities. RBT and KRM are much more active in vitro and in vivo than RFP against both M. tuberculosis and MAC. KRM seems to be more potent than RBT against MAC in experimental studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗