Biomedical subjects

K Tomono

Publications and source records attributed to K Tomono.

At least 37 records · Page 2Linked to original sources

PubMed2000

Determination of the stability constants in alkanol/alpha-cyclodextrin mixed system.

The simultaneous determination of the stability constants for inclusion of alkanols with alpha-cyclodextrin (alpha-CD) was investigated in a mixed alkanol system using static head-space gas chromatography (SHSGC). The 1:1 stability constants obtained were in fair agreement with those obtained previously using other methods. The time required for determination of the stability constant was markedly reduced using this simultaneous SHSGC method.

Chemical Phenomena↗

PubMed2000

Interaction of antimalarial agent artemisinin with cyclodextrins.

To obtain an effective solution of the poorly water soluble antimalarial agent artemisinin, the use of several kinds of cyclodextrins (CDs) as solubilizers was examined. The following CDs were used in this study: alpha-CD, beta-CD, gamma-CD as parent CDs, 2-hydroxypropyl-beta-CD (HP-beta-CD), sulfobutyl ether beta-CD (SBE7-beta-CD), heptakis (2,6-di-O-methyl)-beta-CD (DM-beta-CD), 2,3,6-partially methylated-beta-CD (PM-beta-CD) as modified CDs, and glucosyl-beta-CD (G1-beta-CD), and maltosyl-beta-CD (G2-beta-CD) as branched CDs. The solubility curves of artemisinin with CDs can all be classified as type AL. The apparent stability constants for artemisinin-parent CD complexes increased in the order of alpha- < gamma- < or = beta-CD. The constants for artemisinin-beta-CD derivative (and beta-CD) complexes increased in the order of G2-beta-CD approximately equal to G1-beta-CD approximately equal to PM-beta-CD approximately equal to beta-CD < HP-beta-CD < SBE7-beta-CD < DM-beta-CD. These results suggest that the addition of CDs enables the solubilization of artemisinin.

Antimalarials↗

PubMed2000

Combination therapy for chronic Pseudomonas aeruginosa respiratory infection associated with biofilm formation.

There had been no reports of investigations into biofilms in chronic respiratory infection in vivo. Recently, we established a new murine model of chronic respiratory infection with Pseudomonas aeruginosa. In the present study, we examined the bacteriological effect of combined clarithromycin and levofloxacin against chronic respiratory infection with P. aeruginosa. Scanning electron micrograph of the surface of the catheter intubated in mouse bronchus for 7 days demonstrated in vivo formation of a biofilm containing blood cells, complex fibrous structures and bacteria. Treatment with either clarithromycin alone or levofloxacin alone had no statistical effect on the number of viable bacteria in lung. The combined use of both drugs resulted in a significant decrease in the number of viable bacteria. The present experiment demonstrates that the newly established murine model was useful to investigate the treatment of biofilm-associated chronic respiratory infection with P. aeruginosa, and combination therapy with clarithromycin and levofloxacin was effective in biofilm-associated chronic respiratory infection.

Animals↗

PubMed2000

Attenuation of nephrotoxicity by a novel lipid nanosphere (NS-718) incorporating amphotericin B.

NS-718, a lipid nanosphere incorporating amphotericin B, is effective against pathogenic fungi and has low toxicity. We compared the toxicity of NS-718 with that of Fungizone (amphotericin B-sodium deoxycholate; D-AmB) in vitro using renal cell cultures and in vivo by biochemical analysis, histopathological study of the kidney and pharmacokinetic study of amphotericin B following intravenous infusion of the formulation in rats. Incubation with NS-718 resulted in significantly less damage of cultured human renal proximal tubular epithelial cells compared with D-AmB. Serum blood urea and creatinine concentrations increased significantly in rats given an iv infusion of D-AmB 3 mg/kg but not in those given the same dose of NS-718. Histopathological examination of the kidney showed tubular necrosis in D-AmB-treated rats but no change in NS-718-treated rats. Amphotericin B concentrations in the kidney in NS-718-treated rats were higher than those in D-AmB-treated rats. Our in vitro and in vivo results suggest that incorporation of amphotericin B into lipid nanospheres of NS-718 attenuates the nephrotoxicity of amphotericin B.

Alanine Transaminase↗

PubMed2000

Seroprevalence of antibodies to Chlamydia spp. in human immunodeficiency virus-infected subjects in Japan.

To evaluate the seropositivity of Chlamydia spp. in human immunodeficiency virus (HIV)-infected subjects in Japan, Chlamydia-specific antibodies in sera collected from 106 HIV-infected subjects were measured by the microimmunofluorescence test. The prevalence of C. pneumoniae-specific IgA, C. trachomatis-specific IgG and IgA and mean titers were significantly higher in the homosexual and heterosexual HIV-infected subjects than in the hemophilic patients and HIV-negative controls. These data indicate that the higher C. pneumoniae and C. trachomatis seroprevalence among HIV-infected subjects is probably due to an HIV risk factor, such as promiscuous sexual behavior, rather than to HIV infection itself.

Adolescent↗

PubMed2000

Th1-Th2 cytokine kinetics in the bronchoalveolar lavage fluid of mice infected with Cryptococcus neoformans of different virulences.

Th1 immune response plays an important role in protection against infection with Cryptococcus neoformans in mice. We investigated the effect of virulence of C. neoformans on cytokine production in the lung of a mouse model of pulmonary cryptococcosis. BALB/c mice were inoculated intratracheally with a high or low virulence strain of C. neoformans, followed by serial measurements of Th1 and Th2 cytokine concentrations in the bronchoalveolar lavage (BAL) fluid using appropriate enzyme-linked immunosorbent assay kits. The number of colony-forming units (CFU) increased with time, and all mice infected with the highly virulent strain were dead at 28 days after inoculation. In contrast, the number of microorganisms diminished with time in the mice infected with the low virulence strain during the 4-week study. The numbers of neutrophils and lymphocytes in the BAL fluid paralleled those of CFU. High neutrophil counts were observed in the BAL fluid of mice infected with the highly virulent strain, while lymphocyte counts were increased only in the later part of the study in mice infected with the high and low virulence strains. The concentrations of Th2 cytokine, interleukin (IL)-4 were significantly higher in mice infected with the highly virulent strain at days 14 and 21 of infection, whereas the level of Th1 cytokine, interferon-gamma, was significantly higher in the latter strain at days 7 and 14. Our results suggest that strain-specific difference in the organism's ability to induce (or evade) the host immune system contributes to the outcome of infection.

Animals↗

PubMed2000

In vitro activity of telithromycin (HMR3647), a new ketolide, against clinical isolates of Mycoplasma pneumoniae in Japan.

The in vitro activity of telithromycin (HMR3647), a new ketolide, against Mycoplasma pneumoniae was determined by the broth microdilution test using 41 clinical isolates obtained in Japan, as compared with those of five macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin), minocycline, and levofloxacin. Telithromycin was less potent than azithromycin, but it was more active than four other macrolides, minocycline, and levofloxacin; its MICs at which 50 and 90% of the isolates tested were inhibited were both 0.00097 microg/ml, justifying clinical studies to determine its efficacy for treatment of M. pneumoniae.

Anti-Bacterial Agents↗

PubMed2000

Efficacy of FK463, a (1,3)-beta-D-glucan synthase inhibitor, in disseminated azole-resistant candida albicans infection in mice.

The efficacy of FK463, a new (1,3)-beta-D-glucan synthase inhibitor, against azole-resistant Candida albicans strains has been studied. The MIC of FK463 was lower than those of azoles and amphotericin B against CDR1-expressing C26 and CaMDR-expressing C40 strains. All mice treated with FK463 (1 mg/kg) survived disseminated murine candidiasis. The fungal burden in the kidney after 6 days was markedly reduced after therapy with FK463 and amphotericin B sodium deoxycholate, and plasma (1,3)-beta-D-glucan concentration was found to be lower in FK463-treated mice. In our study, FK463 was found to be a potent antifungal agent against disseminated infection with azole-resistant C. albicans.

Animals↗

PubMed2000

Pharmacokinetic/pharmacodynamic relationship of eptazocine, a narcotic-antagonist analgesic, in rats.

The relationship between the pharmacokinetics and the pharmacodynamics of eptazocine, a narcotic-antagonist analgesic, was investigated in rats. The analgesic effect of eptazocine (2.5, 5 and 10 mg/kg) following intravenous (i.v) administration was evaluated by both the Randall-Selitto method and the D'Amour-Smith method. The analgesic effects were determined before and at designed intervals for a period of 120 min after eptazocine administration, and are expressed as area under the effect-time curve (AUC(E)). The plasma concentration of eptazocine was determined by fluorescence HPLC and was analyzed with a two compartment open model using the nonlinear least-squares method. Eptazocine produced a dose-dependent analgesic effect. It was demonstrated that eptazocine has a linear relationship between AUC(E) and the area under the plasma concentration-time curve (AUC) following i.v. administration for three different doses ranging from 2.5 to 10 mg/kg.

Analgesics↗

PubMed2000

Elevated levels of soluble adhesion molecules in sera and BAL fluid of individuals infected with human T-cell lymphotropic virus type 1.

STUDY OBJECTIVE: T-lymphocytic alveolitis and increased levels of interleukin-2 receptor-alpha (CD25)-bearing T cells in the BAL fluid (BALF) of human T-cell lymphotropic virus type 1 (HTLV-1) carriers have been reported. Several chemokines and adhesion molecules may contribute to the accumulation of T lymphocytes in the lungs of HTLV-1 carriers. To clarify the correlation between adhesion molecules and HTLV-1-associated pulmonary disorders, we compared the distribution of T-lymphocyte subsets and soluble adhesion molecules, including soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble L-selectin (sL-selectin), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin), in BALF and peripheral blood, between HTLV-1 carriers and noninfected healthy subjects. DESIGN: Flow cytometric analysis with monoclonal antibodies to cell-surface antigens was used to identify T-lymphocyte subsets in BALF samples from HTLV-1 carriers (n = 13) and noninfected healthy control subjects (n = 10). The levels of various soluble adhesion molecules in serum and in BALF were estimated by enzyme-linked immunosorbent assay. RESULTS: Higher percentages of CD3+ cells, CD3-expressing human leukocyte antigen-DR antigen, and CD3+CD25+ cells were detected in the BALF of HTLV-1 carriers than in that of noninfected control subjects. The concentrations of sICAM-1, sVCAM-1, sL-selectin, SE- selectin, and sP-selectin in the sera of patients were significantly higher than those in noninfected healthy control subjects. The concentration of sICAM-1 in the BALF of patients was significantly higher than that in noninfected healthy control subjects, and the concentration of sICAM-1 correlated well with the percentage of CD3+CD25+ cells. CONCLUSION: The concentrations of adhesion molecules in the sera of and sICAM-1 in the BALF of HTLV-1 carriers were significantly higher than those in noninfected individuals, and the concentration of sICAM-1 correlated well with the percentage of CD3+CD25+ cells in BALF. Our results suggest a possible interaction between activated T cells bearing CD25 and soluble adhesion molecules, especially sICAM-1, which may contribute to the pulmonary involvement in HTLV-1 carriers.

Adult↗

PubMed2000

Aspergillus fumigatus isolated from blood samples of a patient with pulmonary aspergilloma after embolization.

Aspergillus DNA was detected by PCR in the serum sample of a 78-year-old man and galactomannan antigen of Aspergillus by sandwich ELISA was found. However, the infiltrative hyphae were not detected by the histopathologic examination of the lung. He developed hemoptysis, which required embolization of bronchial arteries. Aspergillus fumigatus was isolated from blood samples after embolization by the lysis centrifugation method. To our knowledge, this is probably the first case in which Aspergillus spp. has been isolated from the systemic circulatory blood in a patient with pulmonary aspergilloma after embolization.

Aged↗

PubMed2000

Clinical evaluation of 61 patients with pulmonary aspergilloma.

OBJECTIVE AND METHODS: We retrospectively evaluated 61 cases with pulmonary aspergilloma representing patients admitted to Nagasaki University Hospital between January 1991 to June 1998. RESULTS: Fifty-two (85%) were males and 9 (15%) were females, aged between 14 to 80 years (average, 65 years). Forty-four (72%) patients had history of old pulmonary tuberculosis. Chest radiographs showed "fungus ball" in the cavities in 42 (67%) cases while 16 (26%) cases showed thickening of the cavity wall. Aspergillus fumigatus was isolated in 24 (39%) patients. Aspergillus antigen or antibody was positive in 8 (13%) and 43 (70%) patients, respectively. Oral itraconazole was used in 16 (26%) of patients, and surgical excision was performed in 15 (25%) patients. During hospitalization or after discharge, 19 (31 %) patients died. SUMMARY AND CONCLUSION: Pulmonary aspergilloma usually occurs in elderly patients with old tuberculosis and respiratory failure. Many cases did not respond to antifungal therapy with itraconazole or amphotericin B. Our analysis indicates that more effective and appropriate therapeutic regimens are needed for the treatment of patients with pulmonary aspergilloma.

Adolescent↗

PubMed2000

Pulmonary mycobacteriosis caused by rifampicin-resistant Mycobacterium szulgai.

We describe a rare case of pulmonary mycobacteriosis infected with rifampicin (RFP)-resistant Mycobacterium szulgai that was successfully eradicated with clarithromycin (CAM) treatment. An 80-year-old man was admitted to our hospital with a 4-week history of high fever, productive cough and malaise. Chest roentgenogram showed an infiltrative shadow in the left lower lung field. Isolated bacteria from sputum were acid-fast bacilli and identified as M. szulgai by the DNA-DNA hybridization method. Drug susceptibility tests showed resistance to RFP (MIC>100 microg/ml). Combined treatment with ethionamide, streptomycin and isoniazid based on the results of drug susceptibility tests resulted in clinical and radiologic improvement within two years. Additional treatment with CAM for another year resulted in complete eradication of the mycobacterium.

Aged↗

PubMed2000

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1998)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 18 institutions around the entire Japan, 532 strains of presumably etiological bacteria were isolated mainly from the sputa of 438 patients with lower respiratory tract infections during the period from October in 1998 to September in 1999. MICs of various antibacterial agents and antibiotics were determined against 85 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75 strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities of 517 strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%. Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml. The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's. Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below. Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good activities. The sensitive strains of them against ceftazidime (CAZ) decreased in 1997, but those have increased in 1998. Inversely, the susceptibility of them against cefotiam (CTM) had been higher in 1997, but those have been lower in 1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were active against K. pneumoniae. A quite few of K. pneumoniae showed low susceptibilities. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 48.6% of all the patients showing a slight increase in every year. About the proportion of diagnosed diseases as follows: Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has increased slightly, and the increased rate was 10% in patients with ages over 70 years compared with the results in 1997. Chronic bronchitis have decreased slightly with 27.6% in 1998. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these were almost same number in bacterial pneumonia. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus 13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa was 45.5% after administration over 15 days. The frequencies of S. pneumoniae decreased upon administration of antibiotics, these were only 4.5% over 15 days. The frequencies of H. (

Anti-Bacterial Agents↗

PubMed1999

Heat shock protein 70 (hsp70) as a major target of the antibody response in patients with pulmonary cryptococcosis.

Cryptococcus neoformans causes infection in individuals with defective T cell function, such as AIDS, as well as without underlying disease. It has been suggested that humoral as well as cellular immunity might play an important role in the immune response to C. neoformans infection. We have recently shown, using immunoblotting, that the 70-kD hsp family of C. neoformans was the major target molecule of the humoral response in murine pulmonary cryptococcosis. In this study we also used immunoblotting to define the antibody responses in the sera of 24 patients with pulmonary cryptococcosis: 21 proven and three suspected diagnoses. Anti-C. neoformans hsp70 antibody was detected in 16 of 24 (66.7%) patients with pulmonary cryptococcosis. Fourteen of 17 (82.3%) patients with high antigen titres (> or = 1:8) and two of seven (28.6%) patients with low titres (< or = 1:4) had detectable levels of anti-hsp70 antibody. Sera from patients positive for anti-hsp70 antibody showed high titres in the Eiken latex agglutination test for the detection of serum cryptococcal antigen. Our results indicate that the 70-kD hsp family from C. neoformans appears to be a major target molecule of the humoral response, not only in murine pulmonary cryptococcosis, but also in human patients with pulmonary cryptococcosis.

Adult↗

PubMed1999

Elevated levels of beta-chemokines in bronchoalveolar lavage fluid (BALF) of individuals infected with human T lymphotropic virus type-1 (HTLV-1).

Pulmonary complications are known to develop in HTLV-1 carriers, including T lymphocytic alveolitis, and increased IL-2 receptor alpha (CD25)-bearing T cells have been found in BALF. Several chemokines may contribute to accumulation of T lymphocytes in the lungs of HTLV-1 carriers. Here, we compared the distribution of T lymphocyte subsets and beta-chemokines, such as macrophage inflammatory peptide-1alpha (MIP-1alpha), regulated on activation normal T expressed and secreted (RANTES), and macrophage chemoattractant protein-1 (MCP-1), in BALF and peripheral blood between HTLV-1 carriers and non-infected healthy normal subjects. Flow cytometric analysis with MoAbs to cell surface antigens was used to identify T lymphocyte subsets in BALF samples from HTLV-1 carriers (n = 13) and non-infected healthy controls (n = 10). The levels of different beta-chemokines were estimated by ELISA. High percentages of CD3+ cells, CD3 expressing HLA-DR antigen and CD3+CD25+ cells were detected in BALF of HTLV-1 carriers compared with non-infected controls. The concentration of MIP-1alpha in BALF of patients was significantly higher than in non-infected healthy controls and correlated well with the percentage of CD3+CD25+ cells. The level of RANTES in BALF was also significantly high in HTLV-1 carriers, but did not correlate with the percentage of CD3+CD25+ cells. On the other hand, the level of MCP-1 in BALF of HTLV-1 carriers was not different from that of controls. Our results suggest a possible interaction between activated T cells bearing CD25 and beta-chemokines, especially MIP-1alpha, which may contribute to the pulmonary involvement in HTLV-1 carriers.

Adult↗

PubMed1999

Interaction of cyclomaltononaose (delta-CD) with several drugs.

The effects of delta-cyclodextrin (delta-CD; cyclomaltononaose) on solubility of 14 drugs that are slightly soluble or insoluble in water were studied and compared with those of conventional cyclodextrins (CDs) such as alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), and gamma-cyclodextrin (gamma-CD). In general, delta-CD had a weak complex-forming ability with the drugs examined in comparison with beta-CD and gamma-CD. However, in the case of digitoxin, delta-CD enhanced solubility of the guest molecules. To determine the mechanism of inclusion complex formation of delta-CD with digitoxin, the interaction of both drugs was investigated by the solubility method and spectroscopic methods such as ultraviolet (UV) and 1H-NMR (nuclear magnetic resonance). The changes in chemical shift (1H) and hypsochromic shift of UV suggested that digitoxin was partially included in the cavity of delta-CD.

Chemistry, Pharmaceutical↗

PubMed1999

Relationship between genetic alteration of the rpsL gene and streptomycin susceptibility of Mycobacterium tuberculosis in Japan.

We have investigated the effect of genetic alterations in the rpsL gene on the MICs of streptomycin for Mycobacterium tuberculosis strains. Direct DNA sequencing showed a point mutation in 23/121 strains; in 18 strains the mutation was associated with an amino acid change. The MICs of streptomycin in 22 out of 23 point-mutated strains were > or = 256 mg/L. Restriction fragment length polymorphism (RFLP) analysis showed mutations at codon 43 in all 18 strains with point mutations in the same codon. Our results suggest that both RFLP and base sequencing analysis of the rpsL gene are useful for the rapid prediction of highly streptomycin-resistant strains of M. tuberculosis.

Deoxyribonucleases, Type II Site-Specific↗