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Biomedical subjects

G Tanaka

Publications and source records attributed to G Tanaka.

At least 73 records · Page 4Linked to original sources

Influence of fucoidan on the intestinal absorption of iron, cobalt, manganese and zinc in rats.

Fucoidan was extracted from the seaweed Ascophyllum nodosum with boiling water and purified by repeated precipitation steps. Increasing doses of fucoidan (1.2--200 mg) were injected together with 360 nmol 59Fe-(FeCl3) or 60Co-(CoCl2) into tied-off jejunal segments of two groups of rats fed either a normal (160 mg Fe/kg) or a low iron diet (5 mg/kg). Fucoidan together with 360 nmol 54Mn-(MnCl2) or 65Zn-(ZnCl2) was administered in the same manner in rats fed a normal diet only. Fucoidan administered in doses above 30 mg decreased the absorption of iron, cobalt, manganese and zinc in normal rats, and the absorption of iron and cobalt in iron-deficient rats. This inhibitory effect of fucoidan on the absorption of heavy metals is apparently the consequence of the formation of metal complexes which are poorly absorbed from the intestinal lumen.

Animals↗

Effect of the growth rate of Pseudomonas aeruginosa biofilms on the susceptibility to antimicrobial agents: beta-lactams and fluoroquinolones.

The growth rate of biofilm bacteria of a leucine-requiring mutant Pseudomonas aeruginosa HU1 was regulated by the leucine concentration in a chemically-defined medium. The semiquantitative measurement of glycocalyx and scanning electron microscopy revealed that the kinetics of HU1-biofilm formation were dependent on the incubation time and the leucine concentration in the medium. The effect of the growth rate of biofilm cells on their susceptibility to antimicrobial agents, three beta-lactams and four fluoroquinolones, was evaluated. beta-Lactams showed weak bactericidal activity to biofilm cells; the activity was greater in younger biofilm cells growing in high concentrations of leucine. Fluoroquinolones revealed strong bactericidal activity to biofilm bacteria regardless of the growth rate. The following is suggested: the bactericidal action of beta-lactams against biofilm cells is affected by the cell growth rate, while that of fluoroquinolones is considerably greater and independent on the growth rate.

Anti-Bacterial Agents↗

Effect of clarithromycin on Pseudomonas aeruginosa biofilms.

Using an experimental in vitro culture system, we investigated the effect of clarithromycin on biofilm formation by a leucine-requiring Pseudomonas aeruginosa mutant strain (HU1). Biofilm formation on celldesks in a chemically defined medium was assessed by viable cell count as well as by measurement of glycocalyx production and scanning electron-microscopic observation. Cells proliferated exponentially until day 3 and remained stationary afterwards. The amount of glycocalyx, simultaneously semiquantified, showed a linear increase from day 1 to day 12. Scanning electron microscopy revealed firm biofilms on day 5. Three different concentrations of Clarithromycin (CAM) (minimum inhibitory concentration MIC 64 microg/ml) were added continuously at the early and late phases of biofilm formation, and the antibiofilm effect of CAM was evaluated by the changes in cell count and glycocalyx production. CAM was effective on biofilms at 100 microg/ml but neither at 1 nor at 10 microg/ml. It is suggested that glycocalyx production started following bacterial multiplication and continued even after the cells had entered the stationary phase to form mature biofilms. No antibiofilm effect of CAM was observed at sub-MIC.

Anti-Bacterial Agents↗

Permeation of antimicrobial agents through Pseudomonas aeruginosa biofilms: a simple method.

In this study, we evaluated the permeation of piperacillin (PIPC), imipenem (IPM), amikacin (AKM), gentamicin (GM), ofloxacin (OFLX), levofloxacin (LVFX), ciprofloxacin (CPFX) and sparfloxacin (SPFX) through Pseudomonas aeruginosa biofilm with a simple new method. Bacteria used were a leucine-requiring mucoid mutant. Bacteria were grown on the membrane of a cell culture insert in chemically defined medium and incubated at 37 degrees C for 5 days. At days 0, 1, 3 and 5, the penetration rates through the biofilms were measured. PIPC and IPM demonstrated relatively high permeation both with penetration rates at day 5 of 50%, whereas AMK and GM, which are aminoglycosides, showed low permeation both with penetration rates after day 1 of less than 25%. Among the 4 fluoroquinolones, LVFX and SPFX demonstrated excellent permeation with penetration rates that reached 100% from day 0 to 5, while OFLX and CPFX showed almost the same permeation as IPM. This method of measuring penetration rates of antimicrobial agents through biofilm is very simple and useful for the evaluation of antibiotics against biofilm-forming bacteria.

Anti-Bacterial Agents↗

Increased expression levels of cyclin-dependent kinase inhibitor p27 correlate with good responses to platinum-based chemotherapy in non-small cell lung cancer.

In order to determine whether expression of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer (NSCLC) correlates with chemotherapeutic response, resected tumors from 22 patients with recurrent lung cancer who had undergone complete resection and received chemotherapy after the initial tumor recurrence were subjected to p27 immunostaining. Histological examination of the resected tumors revealed 14 adenocarcinomas, 7 squamous cell carcinomas and one adenosquamous cell carcinoma. Fifty percent or less and over 50% of the cells in the resected tumors of 11 patients each (groups 1 and 2, respectively) were p27-immunopositive. All but one patient received platinum-based chemotherapy after recurrence. Only one in group 1 achieved a partial response (PR) in chemotherapy whereas 2 and 4 in group 2 achieved complete and PRs, respectively. The chemotherapy response rate of group 2 (54%) was significantly higher than that of group 1 (9%, p=0.022). The times to recurrence after tumor resection of the 2 groups did not differ significantly (log-rank p=0.23, Wilcoxon p=0. 32), but survival after chemotherapy of group 2 was significantly better than that of group 1 (log-rank p=0.045, Wilcoxon p=0.028). It is suggested that high p27 expression levels in tumors may predict the good responses to platinum-based chemotherapy for NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Increased expression levels of p53 correlate with good response to cisplatin-based chemotherapy in non-small cell lung cancer.

In order to determine whether expression of the tumor suppressor gene p53 in non-small cell lung cancer (NSCLC) correlates with chemotherapeutic response, resected tumors from 18 patients with recurrent lung cancer who had undergone complete resection and received chemotherapy after the initial tumor recurrence were subjected to p53 immunostaining. Histological examination of the resected tumors revealed 11 adenocarcinomas, 6 squamous cell carcinomas and one adenosquamous cell carcinoma. Group 1 was </=50% (n=9) and group 2 >50% (n=9) p53-immunopositive. All patients received cisplatin-based chemotherapy after recurrence. No patient in group 1 achieved response to chemotherapy whereas 2 and 3 in group 2 achieved complete and partial responses, respectively. The chemotherapy response rate of group 2 (56%) was significantly higher than that of group 1 (0%, p=0.009). The times to reoccurrence after tumor resection of group 2 was significantly better than that of group 1 (log-rank p=0.019, Wilcoxon p=0.042), and survival after chemotherapy of group 2 was also significantly better than that of group 1 (log-rank p=0.023, Wilcoxon p=0.034). It is suggested that high p53 expression levels in tumors correlate with both good response to cisplatin-based chemotherapy and good survival of patients with advanced NSCLC.

Aged↗

Randomized study of dose or schedule modification of granulocyte colony-stimulating factor in platinum-based chemotherapy for elderly patients with lung cancer.

It is generally believed that elderly patients are less able to tolerate aggressive cancer chemotherapy than their younger counterparts. Bone marrow cellularity diminishes with age and elderly patients may have decreased tolerance to myelosuppressive agents. Between November 1995 and October 1999, 68 chemotherapy-naive elderly (70 or more years old) patients with histologically or cytologically proven lung cancer who were to receive platinum-based chemotherapy were enrolled in this study. All patients had adequate cardiac, hematological, liver and renal function to receive chemotherapy. Patients were randomized into 3 groups. Patients in groups 1 and 2 received 2 microg/kg and 4 microg/kg granulocyte colony-stimulating factor (G-CSF, lenograstim), respectively, when grade 3 leukopenia (<2,000/microl) or neutropenia (<1,000/microl) appeared after chemotherapy. Patients in group 3 received 2 microg/kg G-CSF when grade 2 leukopenia (<3,000/microl) or neutropenia (<1,500/microl) appeared after chemotherapy. G-CSF was stopped in all groups when the leukocyte count increased to over 10,000/microl or the neutrophil count exceeded 5,000/microl. Full blood cell counts were examined 3 times a week after chemotherapy. All patients received platinum-based chemotherapy. Eighteen, 16 and 22 patients (78%, 73% and 96%) in groups 1, 2 and 3, respectively, received G-CSF when leukopenia or neutropenia appeared. The durations of G-CSF treatment required by groups 1 and 3 (5.7+/-3.6 and 6.6+/-3.2 days, respectively) did not differ significantly, but the duration of treatment required by group 2 (3.7+/-2.8 days) was significantly shorter than that of group 1 (p=0.048). The duration of grade 4 neutropenia in group 2 (0.7+/-1.1 days) was marginally shorter than that in group 1 (1.6+/-2.1 days, p=0.076). The neutrophil nadir of group 2 (949+/-757/microl) was marginally higher than that of group 1 (592+/-438/microl, p=0.058). No patients in group 2 experienced grade 4 neutropenia for 4 days or more or a neutrophil nadir less than 100/microl a significant difference from group 1, where 22% and 17% of patients experienced these events (p=0.02 and p=0.04, respectively). Similarly, no infections requiring antibiotics after chemotherapy occurred in patients in group 2, a significant difference from group 1 (26%, p=0.01). The rates of neutropenia and infection in groups 1 and 3 did not differ significantly. The peak plasma concentration of G-CSF in group 2 was significantly higher than in group 1 (p=0.0018), but did not differ significantly between groups 1 and 3. Doubling the dose of G-CSF could help to decrease neutropenia and prevent infection after chemotherapy in elderly patients with lung cancer.

Aged↗