Search PubMed⌕ Search

Biomedical subjects

S Maesaki

Publications and source records attributed to S Maesaki.

At least 55 records · Page 3Linked to original sources

Long-circulating immunoliposomal amphotericin B against invasive pulmonary aspergillosis in mice.

We investigated the efficacy of long-circulating immunoliposomal amphotericin B (AmB) against invasive pulmonary aspergillosis in mice using three types of liposomal AmB: conventional liposomal AmB (AmBisome), a long-circulating liposomal AmB and prepared by coating the liposome surface with polyethylene glycol (PEG; PEG-L-AmB), long-circulating immunoliposomal AmB (34A-PEG-L-AmB). The survival rates for mice with invasive pulmonary aspergillosis treated with an intravenous dose of 2 mg of AmBisome, PEG-L-AmB, or 34A-PEG-L-AmB per kg of body weight were 16.7, 83.3, and 100%, respectively. Treatment with 34A-PEG-L-AmB produced a marked reduction in the number of Aspergillus fumigatus organisms in the lungs. Pharmacokinetic studies showed the presence of high AmB concentrations in the plasma of mice treated with PEG-L-AmB (40.8 microg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 microg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.

Amphotericin B↗

In vitro activities of quinupristin-dalfopristin and the streptogramin RPR 106972 against Mycoplasma pneumoniae.

The in vitro activities of quinupristin-dalfopristin and streptogramin RPR 106972 were determined with 44 strains of Mycoplasma pneumoniae and compared to those of macrolides, minocycline, and quinolones. All isolates tested were highly susceptible to macrolides and to quinupristin-dalfopristin (MIC at which 90% of the isolates are inhibited [MIC90], 0.0625 microg/ml), followed by RPR 106972 (MIC90, 0.5 microg/ml), quinolones, and minocycline.

Anti-Bacterial Agents↗

Efficacy of NS-718, a novel lipid nanosphere-encapsulated amphotericin B, against Cryptococcus neoformans.

In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC for Cryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

Amphotericin B↗

Rapid detection and evaluation of clinical characteristics of emerging multiple-drug-resistant gram-negative rods carrying the metallo-beta-lactamase gene blaIMP.

Gram-negative rods (GNR) carrying the transferable carbapenem resistance gene blaIMP, including Pseudomonas aeruginosa and Serratia marcescens, have been isolated from more than 20 hospitals in Japan. Although the emergence of such multiple-drug-resistant bacteria is of utmost clinical concern, little information in regard to the distribution of blaIMP-positive GNR in hospitals and the clinical characteristics of infected patients is available. To address this, a system for the rapid detection of the blaIMP gene with a simple DNA preparation and by enzymatic detection of PCR products was developed. A total of 933 ceftazidime-resistant strains of GNR isolated between 1991 and 1996 at Nagasaki University Hospital, Nagasaki, Japan, were screened for the blaIMP gene; 80 isolates were positive, including 53 P. aeruginosa isolates, 13 other glucose-nonfermenting bacteria, 13 S. marcescens isolates, and 1 Citrobacter freundii isolate. Most of the patients from whom blaIMP-positive organisms were isolated had malignant diseases (53. 8%). The organisms caused urinary tract infections, pneumonia, or other infections in 46.3% of the patients, while they were just colonizing the other patients evaluated. It was possible that blaIMP-positive P. aeruginosa strains contributed to the death of four patients, while the other infections caused by GNR carrying blaIMP were not lethal. DNA fingerprinting analysis by pulsed-field gel electrophoresis suggested the cross transmission of strains within the hospital. The isolates were ceftazidime resistant and were frequently resistant to other antibiotics. Although no particular means of pathogenesis of blaIMP-positive GNR is evident at present, the rapid detection of such strains is necessary to help with infection control practices for the prevention of their dissemination and the transmission of the resistance gene to other pathogenic bacteria.

DNA Fingerprinting↗

Adherence to and penetration of human intestinal Caco-2 epithelial cell monolayers by Pseudomonas aeruginosa.

Clinical isolates of Pseudomonas aeruginosa from blood adhered to and penetrated intestinal Caco-2 cell monolayers to a greater degree than did isolates from sputum, with a concomitant drastic decrease in transepithelial electrical resistance. PAO-PR1, an avirulent exotoxin A mutant of PAO1, did not cause a decrease in the resistance. The Caco-2 monolayer system may be useful for the evaluation of certain P. aeruginosa virulence factor activities.

Bacterial Adhesion↗

Genetic relationship between blood and nonblood isolates from bacteremic patients determined by pulsed-field gel electrophoresis.

A total of 148 isolates from 55 bacteremic patients were examined by pulsed-field gel electrophoresis. Genetically different nonblood strains were isolated from 13.9% of patients with bacteremia caused by gram-positive cocci and 42.1% with Pseudomonas aeruginosa bacteremia, indicating that antibiograms of a single nonblood P. aeruginosa isolate are not always informative for treatment of bacteremia.

Bacteremia↗

Antimicrobial susceptibility testing of Bilophila wadsworthia isolates submitted for routine laboratory examination.

MICs of antibiotics against Bilophila wadsworthia isolates were measured by agar and broth microdilution with pyruvic acid and by Etest. The inoculum size influenced greatly agar dilution. Despite discrepancies in MICs depending on the measurement method used, clindamycin consistently showed potent activity. Broth microdilution and Etest appear to be candidates for laboratory susceptibility testing.

Aged↗

[Severe mycosis-factors with fungus and host].

The deep-seated mycosis occurred in immunocompromized patients. Normally, the deep-seated mycosis became sever infection because of the defects of host defense or the adverse effects of antifungal agents. The major factors of the reason on the severity of the deep-seated mycosis depends on the pathogenesity and the drug resistance for antifungal agents in infected fungi. The clinical factors related with hosts defenses are important to the other reason on the severity. We investigated that the multiple drug resistant (MDR) mechanism may be one of the major roles plays in the azole resistant Candida albicans strains isolated form the patients with oropharyngeal candidiasis infected HIV. We analyzed which clinical factors are related with the prognosis of the patients with pulmonary cryptococcosis and aspergilloma. The titer of cryptococcal capsular antigen was earlier improve in the patient without underline disease than in the patients with underline diseases diagnosed pulmonary cryptococcosis. CRP was higher in the death cases in the patients with pulmonary aspergilloma, compared with alive cases.

AIDS-Related Opportunistic Infections↗

[Drug delivery system for infectious diseases].

Various types of antimicrobial agents have been evolved to inhibit growth of or to kill different microorganisms. In recent years, encapsulation of antimicrobial agents in lipid formulations has been a popular practice in research work related to drug delivery system, although most of the studies are based primary on animal models. The recent developments of lipid formulations of anti-infectious drug (antibiotics, antifungals, and antiviral agents) with longer half-life opens new therapeutic avenues in treating infections. The passive targeting of liposomes to the sites of infection is of great value with respect to clinical application. Liposome entrapment can exchange their pharmacokinetics and, hence reduce their toxicity.

Anti-Bacterial Agents↗

[Cytokines produced by cells in bronchoalveolar lavage fluid from a patient with primary pulmonary cryptococcosis].

Cytokines in the culture supernatant of concanavalin A-stimulated macrophages/lymphocytes isolated from bronchoalveolar lavage (BAL) fluid in a 29-year-old patient with primary pulmonary cryptococcosis were evaluated to study the immune reaction against Cryptococcus neoformans in the lung. Before fungicidal therapy, levels of interferon-gamma and interleukin-10 were markedly elevated, and declined after therapy. There were no changes in interleukin-2 or interleukin-4 throughout the clinical course. This result suggests that IFN-gamma and IL-10 may be involved in the immune reaction against pulmonary cryptococcosis.

Adult↗

[Spontaneous resolution of pulmonary cryptococcosis--report of 2 cases].

We encountered two patients with pulmonary cryptococcosis that resolved spontaneously without antifungal treatment. A 59-year-old man (patient 1) and 37-year-old man (patient 2) were admitted to our hospital for the examination of abnormal shadows on their chest x-ray films. Transbronchial lung biopsies were performed, and cryptococci were detected in both patient's lung tissues. Latex aggultination tests for cryptococcal antigen were positive (1:16 and 1:4, respectively). The size of the shadows reduced spontaneously and the titers of the cryptococcal antigen in sera decreased within three months although no antifungal therapy was performed. Bronchoalveolar lavage fluid (BALF) was obtained from each patient and examined. In patient 1, the lymphocyte to CD 4/8 ratio was high in the BALF obtained on admission and the lymphocyte count was low; however, the CD 4/8 ratio was still high in a BALF sample obtained 3 months after discharge. In patient 2, the findings of the BALF analysis on admission were almost normal. The analysis of BALF may contribute to the immunological conditions to in the patients with pulmonary cryptococcosis.

Adult↗

[Genetic evaluation for rifampicin-susceptibility of Mycobacterium tuberculosis].

We evaluated the relationship between rifampicin (RFP)-susceptibility and genetic alterations in rpoB gene of clinically isolated Mycobacterium tuberculosis strains, collected from different geographic locations within Japan. Alterations in rpoB gene were detected by PCR-direct sequencing analysis, and the minimum inhibitory concentrations (MICs) of RFP were determined by broth microdilution method using Middlebrook 7H9 broth. One hundred and sixty six epidemiologically unrelated M. tuberculosis strains were examined. A total of 99 genetic alterations in the 69 bp core region of rpoB gene were detected in 95 out of 166 strains. Among them, 96 out of 166 strains showed RFP-resistant phenotypes with MICs > or = 2 micrograms/ml. Examination of the correlation between the MICs of RFP and amino acid substitutions in 69 bp core region of rpoB gene revealed that 58 out of 59 strains containing amino acid substitution in codon 531 showed highly RFP-resistant phenotypes with MICs > or = 64 micrograms/ml. In contrast, a variable level of RFP-susceptibility was observed among strains containing amino acid substitutions in either codon 516 or 526. On the other hand, the MICs of three strains with a point mutation in either codon 515 or 533 were all < or = 1 microgram/ml. Our results suggest that rpoB gene sequencing is useful for not only the detection of RFP-resistant M. tuberculosis strains, but also the prediction of RFP-susceptibility of the strains.

Antibiotics, Antitubercular↗

Detection of Cryptococcus neoformans gene in patients with pulmonary cryptococcosis.

Pulmonary cryptococcosis was diagnosed by nested PCR. Extraction of DNA was performed by mechanical destruction of the capsules of Cryptococcus neoformans by the glass bead technique. Nested PCR was positive for 4 of 5 culture-positive specimens but negative for 1 culture-positive specimen, 10 culture-negative specimens, and 1 specimen with undetermined culture results.

Base Sequence↗

(1-->3)-beta-D-glucan in culture fluid of fungi activates factor G, a limulus coagulation factor.

Two well-known polysaccharides, (1-->3)-beta-D-glucan and mannan, are major structural components of the fungus cell wall. The G test is a direct method to measure (1-->3)-beta-D-glucan using a (1-->3)-beta-D-glucan-sensitive component, factor G, fractionated from the limulus lysate. The concentration of (1-->3)-beta-D-glucan in culture supernatants of Candida albicans increased to 1,390.0 pg/ml at 24 hours. The concentration of mannan also increased parallel with fungal growth. However, after digestion of supernatants with endo-(1-->3)-beta-D-glucanase, the reactivity to factor G disappeared, although titers of antimannan monoclonal antibody-based latex agglutination were unchanged. Our study demonstrated that cell suspensions of both C. albicans and Cryptoccocus neoformans activated the limulus factor G, and that not only the conidia form but also the filamentous form of Aspergillus fumigatus reacted with factor G. Various Candida spp. (C. paraspilosis, C. glabrata, C. tropicalis, C. krusei), Saccharomyces cerevisiae, Rhodotorula rubra, Trichosporon beigelii, and A. fumigatus released soluble (1-->3)-beta-D-glucan into their culture supernatants, but C. neoformans and Cunninghamella bertholletiae showed only a small reaction to the G test during their culture. Our results indicate that the G test is a good method for serodiagnosis of deep mycosis and also as a screening tool for contamination of medical devices, drugs, and experimental materials with (1 --> 3)-beta-D-glucan.

Agglutination↗

Plasma (1-->3)-beta-D-glucan and fungal antigenemia in patients with candidemia, aspergillosis, and cryptococcosis.

(1-->3)-beta-D-Glucan is one of the major structural components of fungi, and it seems that it can be detected by the fractionated (1-->3)-beta-D-glucan-sensitive component from a Limulus lysate, factor G. We evaluated the concentration of (1-->3)-beta-D-glucan by using factor G and other fungal antigens in 24 patients with clinical evidence of mycosis and 36 healthy subjects. The mean concentration of (1-->3)-beta-D-glucan in the plasma of the healthy subjects was found to be 2.7 +/- 1.9 pg/ml (range, < 6.9 pg/ml), and it was found to be substantially higher in all 11 patients with candidemia (mean, 2,207.4 pg/ml; range, 325.4 to 8,449.0 pg/ml). Eight of those 11 patients with candidemia (73%) were positive for the Cand-Tec heat-labile candida antigen and only 3 patients (27%) were positive for mannan antigen. Three patients with invasive pulmonary aspergillosis were positive for galactomannan and had, in addition, high concentrations of (1-->3)-beta-D-glucan (mean, 323.3 pg/ml; range, 27.0 to 894.0 pg/ml). All 10 patients with cryptococcosis (including 2 patients with probable cryptococcosis) were positive for cryptococcal antigen by the Eiken latex test; however, (1-->3)-beta-D-glucan levels were not elevated in these patients (mean, 7.0 pg/ml; range, < 16.5 pg/ml). Our results indicated that (1-->3)-beta-D-glucan levels are elevated in patients with candidiasis and aspergillosis but not in those with cryptococcosis.

Adult↗

Detection of Cryptococcus neoformans in bronchial lavage cytology: report of four cases.

Four cases of pulmonary cryptococcosis were diagnosed by cytological detection of Cryptococcus neoformans in bronchial lavage. Three patients had underlying diseases, but not HIV infection. The chest X-rays showed 2 patients with nodular lesions and 2 with cavitary lesions. The cryptococcal antigen in the serum was positive in all four patients. In the cytology of bronchial lavage, Cryptococcus neoformans was detected after period-acid-Schiff (PAS) staining and was cultured in Sabouraud-dextrose agar. The cytology of bronchial lavage is useful for the rapid diagnosis of pulmonary cryptococcosis.

Adult↗

Detection of Candida enolase antibody in patients with candidiasis.

The serodiagnostic value of candida enolase antibody was evaluated in 27 patients with systemic candidiasis. The glycolytic enzyme enolase was prepared from Candida albicans IFM 40009 and used as the antigen for immunoblot assays. IgG class antibody was found in the sera of 17 of 27 patients (62.9%) obtained during the early course of the infection. Serial sampling of sera increased the number of patients with positive Candida enolase antibody, which was detected in 25 of 27 patients (92.5%). None of the patients with localized candidiasis showed a positive IgG titer more than 1:100. The specificity of Candida enolase IgG antibody was 95%. This antibody was observed in various candida species: Candida albicans (6/7, 85.7%); C. parapsilosis (7/9, 77.9%); C. tropicalis (5/5, 100%); C. guilliermondii (4/4, 100%); and C. glabrata (1/3, 33.3%).

Adult↗

The Eiken Latex test for detection of a cryptococcal antigen in cryptococcosis. Comparison with a monoclonal antibody-based latex agglutination test, Pastorex Cryptococcus.

A latex agglutination test for cryptococcal antigen, the Eiken Latex test (Eiken, Tokyo, Japan), was compared with a monoclonal antibody-based agglutination assay, Pastorex Cryptococcus (Diagnostics Pasteur, Marneur-la-Coquette, France). In a murine model of disseminated cryptococcosis, the kinetics of the antigen titers by the Eiken Latex were similar to those by the Pastorex Cryptococcus, but sensitivity was much higher. In HIV-negative patients with pulmonary cryptococcosis, a cryptococcal antigen was detected in 6 of 10 patients by the Eiken Latex test and in only 3 of those patients by the Pastorex Cryptococcus. The results indicate that the Eiken Latex is more sensitive for the detection of the cryptococcal antigen, even in non-disseminated cryptococcosis. The sensitivity and specificity of the Eiken Latex were examined using 195 sera from 25 patients with pulmonary cryptococcosis and 170 patients with non-cryptococcosis. The cutoff value of > or = 1:8 showed a sensitivity of 76% (19/25) and a specificity of 98.9% (168/170).

Agglutination Tests↗