Biomedical subjects

S Maesaki

Publications and source records attributed to S Maesaki.

At least 37 records · Page 2Linked to original sources

PubMed1999

Rhodamine 6G efflux for the detection of CDR1-overexpressing azole-resistant Candida albicans strains.

We investigated the drug efflux mechanism in azole-resistant strains of Candida albicans using rhodamine 6G (R6G). No significant differences in R6G uptake were observed between azole-sensitive B2630 (9.02 +/- 0.02 nmol/10(8) cells) and azole-resistant B67081 (8.86 +/- 0.03 nmol/10(8) cells) strains incubated in glucose-free phosphate buffered saline. A significantly higher R6G efflux (2.0 +/- 0.21 nmol/10(8) cells) was noted in the azole-resistant strain (B67081) when glucose was added, compared with that in the sensitive strain B2630 (0.23 < or = 0.14 nmol/10(8) cells). A fluconazole-resistant strain C40 that expressed the benomyl resistance gene (CaMDR) also showed a low R6G efflux (0.16 +/- 0.06 nmol/10(8) cells) as did the sensitive strains. Accumulation of R6G in growing C. albicans cells was inversely correlated with the level of CDR1 mRNA expression. Our data also suggest that measurement of intracellular accumulation of R6G is a useful method for identification of azole-resistant strains due to CDR1-expressed drug efflux pump.

Antifungal Agents↗

PubMed1999

In-vitro and in-vivo activities of SCH56592 against Cryptococcus neoformans.

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC(90)s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 +/- 0.21 log(10) cfu/g), as compared with fluconazole (7.77 +/- 0.07 log(10) cfu/g) and control (7.79 +/- 0.1 log(10) cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 +/- 0.62 ng/ml) than in plasma (2.16 +/- 0.86 ng/mL), and this was maintained for 12 h after administration.

Animals↗

PubMed1999

[A case of pulmonary cryptococcosis with lung cancer in a pulmonary lobe].

A 63-year old female was admitted because of an abnormal shadow on chest X-ray film. Chest CT showed a nodular shadow in the right S6 and a patchy shadow in the right S10. Right lower lobectomy was performed under a diagnosis of lung cancer made by TBLB in the right S6. Pathological examination of the resected lung revealed papillary adenocarcinoma in the right S6 and numerous cryptococci in the right S10. No cryptococcal infection was found in the resected lymph nodes.

Adenocarcinoma, Papillary↗

PubMed1999

In vitro and in vivo activities of NS-718, a new lipid nanosphere incorporating amphotericin B, against Aspergillus fumigatus.

We evaluated the in vitro and in vivo potencies of a new lipid nanosphere that incorporates amphotericin B (AmB), NS-718, against Aspergillus fumigatus. The in vitro activity of NS-718 (the MIC at which 90% of strains are inhibited [MIC90], 0.25 microgram/ml) against 18 isolates of A. fumigatus was similar to that of deoxycholate AmB (D-AmB; Fungizone; MIC90, 0.25 microgram/ml), but NS-718 was more potent than liposomal AmB (L-AmB; AmBi-some; MIC90, 1.0 microgram/ml). The in vivo efficacy of NS-718 in a rat model of invasive pulmonary aspergillosis was compared with those of D-AmB and L-AmB. A low dose (1 mg/kg of body weight) of L-AmB was ineffective (survival rate, 0%), although equivalent doses of D-AmB and NS-718 were more effective (survival rate, 17%). However, a higher dose of NS-718 (3 mg/kg) was more effective (survival rate, 100%) than equivalent doses of D-AmB and L-AmB (survival rate, 0%). To explain these differences, pharmacokinetic studies showed higher concentrations of AmB in the plasma of rats treated with NS-718 than in the plasma of those treated with D-AmB. Our results suggest that NS-718, a new preparation of AmB, is a promising antifungal agent with activity against pulmonary aspergillosis.

Amphotericin B↗

PubMed1999

Comparison between PCR and detection of antigen in sera for diagnosis of pulmonary aspergillosis.

We evaluated the usefulness of PCR and antigen detection for the diagnosis of pulmonary aspergillosis. Forty-four serum samples from patients with pulmonary aspergillosis (33 with pulmonary aspergilloma, 4 with allergic bronchopulmonary aspergillosis, 4 with invasive pulmonary aspergillosis, and 3 with aspergillus pyothorax) were used in this study. PCR detection of Aspergillus DNA in serum samples was successful in 39 patients. Galactomannan antigen was detected by sandwich enzyme-linked immunosorbent assay in 25 patients and by latex agglutination test in 13 patients. Detection of Aspergillus DNA in serum samples by nested PCR had the highest sensitivity of the three methods tested for the diagnosis of pulmonary aspergillosis.

Antigens, Fungal↗

PubMed1999

Invasive pulmonary aspergillosis diagnosed early by polymerase chain reaction assay.

We compared the usefulness of a polymerase chain reaction (PCR) assay for the early diagnosis of invasive pulmonary aspergillosis with the serodiagnosis of sufficient concentrations of galactomannan using the same serum samples. A patient was treated with prednisolone for the management of hepatitis. Computed tomography (CT) scan of the chest showed the nodular shadow with a cavity containing a clear fungus ball. DNA of Aspergillus spp. from a serum sample was detected and using the same serum sample, both latex agglutination and sandwich enzyme-linked immunosorbent assay (ELISA) of galactomannan were negative. PCR assay provides an early diagnosis of invasive pulmonary aspergillosis compared with ELISA of galactomannan.

Antibodies, Fungal↗

PubMed1999

Evaluation of sandwich ELISA galactomannan test in samples of positive LA test and positive aspergillus antibody.

OBJECTIVE: The detection of circulating Aspergillus galactomannan antigen is a useful tool for serodiagnosis of aspergillosis. However, the latex agglutination test for the detection of galactomannan is not completely reliable due to it's low sensitivity. The sandwich ELISA was developed to achieve high sensitivity. MATERIALS: The sandwich immunocapture ELISA was evaluated by testing 56 sero-positive and 56 sero-negative samples of circulating galactomannan detected by LA test retrospectively. RESULTS: Sixty of the samples were positive for galactomannan as measured by sandwich ELISA. Fifteen samples out of 56 samples negative by LA test were positive by ELISA and 4 samples out of 56 samples positive by LA test were negative by ELISA. Among 47 serum samples positive for anti-Aspergillus antibody, 14 samples were positive by ELISA. CONCLUSION: In conclusion, galactomannan may be detected in more samples of by the new sandwich ELISA than by LA test.

Antibodies, Fungal↗

PubMed1999

[The future of antifungal agents. Non azole antifungal agents].

We investigated the efficacy of non-azole antifungal agents. Long circulating immunoliposomal amphotericin B was potent in murine invasive pulmonary aspergillosis. The concentration of AMPH-B was still high in the lung after 6 hours of 34A-PEG-liposomal AMPH-B. Lipid nanosphere amphotericin B (NS-718) showed efficacy against pulmonary aspergillosis in rats and pulmonary cryptococcosis in mice. The renal toxicity of NS-718 was estimated to be lower than that of AMPH-B from the results of the toxicity study in the rat infusion model. FK 463, a novel (1,3)-beta-D-glucan synthase inhibitor, showed efficacy against azole-resistant Candida albicans in murine experimental disseminated candidiasis. FK463 could be a promising drug and the therapy of choice for azole resistant C. albicans infection.

Amphotericin B↗

PubMed1999

[A case of invasive aspergillosis in an amyloidosis patient].

A sixty-four-year-old male patient was admitted on 13 April 1995 with diagnosis of old pulmonary tuberculosis and pulmonary aspergilloma. He developed a tarry stool and frequent loose motion in early November 1995. Histopathological findings of endoscopic biopsy from the duodenum and colon were suggestive of secondary amyloidosis. In spite of antibiotic and steroid pulse, he developed shock, and massive infiltration shadow appeared in chest X-ray. The patient died on 29 December 1995. The postmortem examination in the specimens of the lung, heart, kidney, liver, and spleen revealed hyphae of Aspergillus sp. and in the specimens of the lung, kidney, spleen, esophagus, adrenal gland, and thyroid revealed amyloid. He was finally diagnosed as invasive aspergillosis with secondary amyloidosis.

Amyloidosis↗

PubMed1999

[Itraconazole-induced hypokalemia in a patient with pulmonary aspergilloma].

An 80-year-old man was admitted to the hospital with a diagnosis of pulmonary aspergilloma. A new azole antifungal agent, D 0870, was administered to the patient for 7 days orally, and itraconazole (400 mg/day) was started on March 5, 1997. After 1 month of chemotherapy, facial and pretibial edema were observed and the patient's serum potassium concentration decreased to 2.5 mEq/l. A chest radiograph disclosed cardiomegaly with cardiac effusion and right pleural effusion on admission. The serum potassium concentration rose after the cessation of itraconazole therapy. The serum ITCZ concentration remained high for 2 weeks after admission. Although reports of hypopotassemia induced by ITCZ are rare, we concluded that blood concentrations should be monitored more carefully when treating pulmonary aspergilloma patients with high-dose regimens of ITCZ.

Aged↗

PubMed1999

[The combination therapy of clarithromycin and sparfloxacin for pulmonary Mycobacterium gordonae infection].

Seventy years old woman had fever and hemosputum at May 1997. She was diagnosed as mycobacteriosis because of the positive acid fast bacilli smear from sputum. Mycobacterium gordonae was isolated from sputum, gastric juice, and bronchial aspirate. The combination therapy of isoniazid, rifampicin, ethambutol, and clarithromycin was administrated; however, M. gordonae was not eradicated from sputum. Sparfloxacin was administered instead of isoniazid based on the result of drug susceptibility test. The smear became negative and M. gordonae was eradicated from sputum one month after the initiation of treatment with the combination of clarithromycin and sparfloxacin.

Aged↗

PubMed1999

[A rare case of lung adenocarcinoma in cavity wall of pulmonary aspergilloma].

A 67-year-old man was admitted with the complaint of hemosputum. Chest X-ray films resulted in a diagnosis of pulmonary aspergilloma, and treatment with intravenous amphotericin B was initiated. However, therapy was discontinued due to renal insufficiency, an adverse effect of amphotericin B. The size of the fungus ball and cavity increased despite treatment with oral itraconazole (200 mg/day). Cavernostomy was performed and the fungus ball was removed from the upper lobe of the left lung. Computed tomographic scans disclosed thickening of the remaining wall of the cavity, with destruction of the ribs. The patient experienced worsening respiratory distress and died. Necropsy revealed adenocarcinoma of the left lung.

Adenocarcinoma↗

PubMed1998

Escherichia coli O157 interactions with human intestinal Caco-2 cells and the influence of fosfomycin.

It is not clear how Escherichia coli O157 invades human enteric epithelium and causes the haemolytic uraemic syndrome (HUS), and nor has the most appropriate treatment of E. coli O157 infection been established. Verotoxins, leucocytes and proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-8, are considered essential for the development of HUS. We used the Caco-2 cell monolayer system, well-known as an in-vitro model of human intestinal infection, to determine how E. coli O157 interacts with intestinal epithelial cells and also studied the influence of fosfomycin on the virulence of the bacteria. Results showed that the E. coli O157 used in this study did not penetrate the Caco-2 cell monolayer system, unlike Salmonella typhimurium SL1344, and verotoxin 1 (VT 1), but not VT 2, translocated across the system. In an in-vitro conventional assay, fosfomycin increased the amount of verotoxins but it did not influence penetration of bacteria and translocation of verotoxins in the Caco-2 cell monolayer system. The production of both IL-8 (a potent neutrophil activator) and TNF-alpha in the human monocytic THP-1 cell line was reduced by fosfomycin-treated basolateral medium in this system. These results indicate that fosfomycin may be a potent drug for preventing HUS caused by E. coli O157 infection.

Anti-Bacterial Agents↗

PubMed1998

Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis.

We compared the in-vitro antimycobacterial activities of rifabutin and KRM-1648, two rifamycin derivatives, with that of rifampicin against 163 strains of Mycobacterium tuberculosis. We also evaluated the correlation between the level of resistance to rifampicin, rifabutin and KRM-1648 and genetic alterations in the rpoB gene. All 82 strains susceptible to rifampicin or resistant to rifampicin with MICs < or = 16 mg/L were susceptible to rifabutin and KRM-1648 with MICs < or = 1 mg/L. Seventy-six of 81 strains resistant to rifampicin with MICs > or = 32 mg/L were resistant to both rifabutin and KRM-1648, but with lower MICs than those of rifampicin. KRM-1648 showed more potent antimycobacterial activity than rifabutin against organisms with low MICs (< or = 1 mg/L), while rifabutin was more active than KRM-1648 against organisms with high MICs (> or = 2 mg/L). A total of 96 genetic alterations around the 69 bp core region of the rpoB gene were detected in 92 strains. Alterations at codons 515, 521 and 533 in the rpoB gene did not influence the susceptibility to rifampicin, rifabutin and KRM-1648. Point mutations at codons 516 and 529, deletion at codon 518 and insertion at codon 514 influenced the susceptibility to rifampicin but not that to rifabutin or KRM-1648. With the exception of one strain, all alterations at codon 513 and 531 correlated with resistance to the three test drugs. The resistant phenotype of strains with an alteration at codon 526 depended on the type of amino acid substitution. Our results suggest that analysis of genetic alterations in the rpoB gene might be useful not only for predicting rifampicin susceptibility, but also for deciding when to use rifabutin for treating tuberculosis. Further studies may be required to determine the usefulness of KRM-1648.

Amino Acid Sequence↗

PubMed1998

Synergic effects of tactolimus and azole antifungal agents against azole-resistant Candida albican strains.

We investigated the effects of combining tacrolimus and azole antifungal agents in azole-resistant strains of Candida albicans by comparing the accumulation of [3H]itraconazole. The CDR1-expressing resistant strain C26 accumulated less itraconazole than the CaMDR-expressing resistant strain C40 or the azole-sensitive strain B2630. A CDR1-expressing Saccharomyces cerevisiae mutant, DSY415, showed a marked reduction in the accumulation of both fluconazole and itraconazole. A CaMDR-expressing S. cerevisiae mutant, DSY416, also showed lower accumulation of fluconazole, but not of itraconazole. The addition of sodium azide, an electron-transport chain inhibitor, increased the intracellular accumulation of itraconazole only in the C26 strain, and not in the C40 or B2630 strains. Addition of tacrolimus, an inhibitor of multidrug resistance proteins, resulted in the highest increase in itraconazole accumulation in the C26 strain. The combination of itraconazole and tacrolimus was synergic in azole-resistant C. albicans strains. In the C26 strain, the MIC of itraconazole decreased from >8 to 0.5 mg/L when combined with tacrolimus. Our results showed that two multidrug resistance phenotypes (encoded by the CDR1 and CaMDR genes) in C. albicans have different substrate specificity for azole antifungal agents and that a combination of tacrolimus and azole antifungal agents is effective against azole-resistant strains of C. albicans.

AIDS-Related Opportunistic Infections↗

PubMed1998

Analysis of genetic relationships and antimicrobial susceptibility of verotoxin-producing Escherichia coli strains isolated in Nagasaki Prefecture, Japan in 1996.

A total of 19 Escherichia coli O157 isolates were obtained in Nagasaki Prefecture, in the south-western part of Japan, between 1990 and 1996. Pulsed-field gel electrophoresis (PFGE) and computer-assisted analysis were applied to determine genetic relationships among these strains. Fragment patterns of the isolates in Nagasaki, as determined by PFGE, were compared with those of isolates in other areas where large outbreaks and sporadic cases of E. coli O157 infection occurred. Similarity values of all the strains isolated in Nagasaki Prefecture were over 0.65 except for E. coli O26. Some strains were identical to the strains isolated from the areas where large outbreaks occurred. All strains were susceptible to ampicillin, fosfomycin, minocycline, amikacin, ofloxacin and sulfamethoxazole-trimethoprim.

Anti-Bacterial Agents↗

PubMed1998

[Pulmonary infection in the emphysematous bulla due to Mycobacterium szulgai diagnosed by percutaneus needle aspiration].

A 73-year-old male was admitted to our hospital because of productive cough and infiltrate on the chest roentogenogram. The underlying diseases was found to be multiple myeloma. He received a physical examination in June, 1996. The chest X-ray and CT scan on admission showed an infiltrative shadow with multiple bulla in the left upper lung field. Internal use of antibiotics and drip infusion of IPM/CS were ineffective. The chest X-ray showed air-fluid level in left upper peripheral bullous lesion and a percutaneus needle aspiration of the lung was performed. The specimen was pus with blood and microscopical examination of smears revealed no acid-fast bacilli, but Mycobacterium szulgai was isolated and identified by DNA-DNA hybridization method. The patient was treated with isoniazid and rifampicin, and improved in a few months. There are a few case reports of pulmonary infection due to M. szulgai associated with emphysematous bulla of the lung in Japan. M. szulgai infection of the lung is similar to M. kansasii infection in respect to clinical features (improvement of chest abnormal shadow, efficacy of drug).

Aged↗

PubMed1998

[A study of virulence factors produced by MRSA strains isolated from blood samples].

Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are important virulence factors produced by Staphylococcus aureus. It is reported that these toxins are associated with septic shock and toxic shock syndrome. We investigated the toxin production and coagulase types of 701 MRSA strains isolated in Sasebo City General Hospital between 1994 and 1996 TSST-1 or/and enterotoxins were detected in 67% of all MRSA strains, and those were detected in 88% of MRSA strains isolated from blood samples. 45% of all MRSA strains produced both TSST-1 and enterotoxin C, and 70% of MRSA strains obtained from blood produced those toxins. Frequency of TSST-1 or/and enterotoxin production by MRSA strains isolated from blood samples was significantly higher than that by MRSA strains isolated from urine and pharynx (p < 0.05), and frequency of both TSST-1 and enterotoxin C production by MRSA isolates from blood was significantly higher than that by MRSA strains isolated from pharyngeal sample (p < 0.05). This study indicated that investigation of virulence factors produced by MRSA might give the useful information on prevention and treatment of MRSA infection.

Bacteremia↗