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Biomedical subjects

Kazuo Hatano

Publications and source records attributed to Kazuo Hatano.

At least 19 recordsLinked to original sources
PubMed2006

In vitro and in vivo activities of a new cephalosporin, FR264205, against Pseudomonas aeruginosa.

FR264205 is a novel parenteral 3'-aminopyrazolium cephalosporin. This study evaluated the in vitro and in vivo activities of FR264205 against Pseudomonas aeruginosa. The MIC of FR264205 at which 90% of 193 clinical isolates of P. aeruginosa were inhibited was 1 microg/ml, 8- to 16-fold lower than those of ceftazidime (CAZ), imipenem (IPM), and ciprofloxacin (CIP). FR264205 also exhibited this level of activity against CAZ-, IPM-, and CIP-resistant P. aeruginosa. The reduction in the susceptibility of FR264205 by AmpC beta-lactamase was lower than that of CAZ, indicating a relatively high stability of FR264205 against AmpC beta-lactamase, the main resistance mechanism for cephalosporins. Neither expression of efflux pumps nor deficiency of OprD decreased the activity of FR264205. No spontaneous resistance mutants were selected in the presence of FR264205, and the reduction in susceptibility to FR264205 was lower than that to CAZ, IPM, and CIP after serial passage, suggesting that FR264205 has a low propensity for selecting resistance. In murine pulmonary, urinary tract, and burn wound models of infection caused by P. aeruginosa, the efficacy of FR264205 was superior or comparable to those of CAZ and IPM. These results indicate that FR264205 should have good potential as an antibacterial agent for P. aeruginosa.

Animals↗
PubMed2006

Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.

CONTEXT: In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. OBJECTIVE: To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. DESIGN, SETTING, AND PATIENTS: Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. INTERVENTIONS: Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients). MAIN OUTCOME MEASURES: The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. RESULTS: The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. CONCLUSIONS: Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: C000000412.

Adult↗
PubMed2006

Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT.

PURPOSE: We evaluated the clinical significance of hypofractionated high-dose irradiation using simultaneous integrated boost technique with intensity-modulated radiation therapy (IMRT) for the treatment of malignant astrocytomas (MAs). METHODS AND MATERIALS: Twenty-five patients with MAs were treated by IMRT. Three layered planning target volumes (PTVs) were contoured. PTV-1 was the area of enhanced lesion with 5-mm margin; PTV-2 was the area with 15-mm margin surrounding the PTV-1; PTV-3 was the area of perifocal edema. Irradiation was performed in 8 fractions, and only the dose for PTV-1 was escalated from 48 Gy to 68 Gy while maintaining the dose for PTV-2 (40 Gy) and PTV-3 (32 Gy). The clinical outcome of IMRT was compared with 60 MA patients treated by conventional external beam irradiation (EBI). RESULTS: The progression-free survival of patients in the IMRT group was significantly longer than that in the EBI group (p < 0.0001). No distant failure was observed in both groups. In the IMRT group, dissemination was the most frequent cause of death (70%). The overall survival of patients in the IMRT group was better than that in the EBI group (p = 0.043). CONCLUSIONS: Our regimen of IMRT contributed to the control of both the regional and infiltrating tumors, resulting in better survival of patients.

Adolescent↗
PubMed2006

[Combined effect of vancomycin or teicoplanin plus a beta-lactam antibiotic in mouse infection models caused by beta-lactam antibiotec-induced vancomycin resistant MRSA (BIVR)].

The concomitant use of low concentration beta-lactam antibiotics antagonizes the activity of vancomycin against some strains of MRSA. These strains, called beta-lactam antibiotic-induced vancomycin resistant MRSA (BIVR), have been increasing for a number of years. We previously reported that the combination of VCM and ceftizoxime displayed this antagonism not only in vitro, but also in vivo, in a systemic infection caused by BIVR in mice. In the present study, we validated the antagonism in combinations of VCM with other beta-lactams, i.e., flomoxef (FMOX), ampicillin (AMPC), azthreonam (AZT) and imipenem/cilastatin (IPM/CS), in systemic infections and pneumoniain in mice. The survival rate of the mice with systemic infections caused by BIVR treated with combinations of FMOX, AMPC, AZT, and IPM/CS with VCM were significantly lower than with VCM monotherapy, and the number of residual viable cells in the kidneys of mice treated with combinations of FMOX and IPM/CS with VCM were significantly higher than with VCM monotherapy The number of residual viable cells in the lungs of mice with pneumonia caused by BIVR treated with the combination of IPM/CS and VCM was significantly higher than with VCM monotherapy. On the other hand, the survival rate with combination therapy consistings IPM/CS plus teicoplanin (T EIC) was significantly higher, and the number of residual viable cells in the kidney was significantly lower, than with TEIC monotherapy alone. In the mice with pneumonia, the number of residual viable cells in the lung after combination therapy with IPM/CS and TEIC was significantly lower than with TEIC monotherapy. Combination therapy with beta-lactams plus VCM showed antagonistic in models of systemic infection and pulmonary infection caused by BIVR, whereas combination therapy consisting of a beta-lactam plus TEIC had a synergistic effect in the same models, even though VCM and TEIC are member of the same glycopeptide antibiotic class.

Animals↗
PubMed2005

Gender-based differences in bleomycin-induced pulmonary fibrosis.

The role of gender and sex hormones is unclear in host response to lung injury, inflammation, and fibrosis. To examine gender influence on pulmonary fibrosis, male and female rats were given endotracheal injections of either saline or bleomycin. Female rats showed higher mortality rates and more severe fibrosis than did male rats, as indicated by higher levels of lung collagen deposition and fibrogenic cytokine expression. To clarify the potential role of female sex hormones in lung fibrosis, female rats were ovariectomized and treated with either estradiol or vehicle plus endotracheal injections of either saline or bleomycin. The results showed diminished fibrosis in the ovariectomized, bleomycin-treated rats without hormone replacement. Estradiol replacement restored the fibrotic response to that of the intact female mice in terms of lung collagen deposition and cytokine expression, which was accompanied by higher plasma estradiol levels. Furthermore, fibroblasts from bleomycin-treated rats exhibited increased responsiveness to estradiol treatment, causing dose-dependent increases in procollagen 1 and transforming growth factor-beta1 mRNA expression relative to untreated controls. Taken together these findings suggest that female mice may have an exaggerated response to lung injury relative to male mice because of female sex hormones, which have direct fibrogenic activity on lung fibroblasts. This may provide a mechanism for a hormonally mediated intensification of pulmonary fibrosis.

Animals↗
PubMed2005

Electron microscopic findings for micafungin-treated experimental pulmonary aspergillosis in mice.

We performed a scanning and transmission electron microscopic study on the efficacy of micafungin (MCFG) to understand what kind of damage MCFG causes to Aspergillus and to confirm its previously reported in vitro killing activity against Aspergillus in a mouse model of pulmonary aspergillosis. Aspergillus hyphae in MCFG-treated mice displayed hyphal burst, evidenced as either flattened or atrophied appearance and leakage of cellular contents after collapse of the cell wall. Thus, MCFG can induce the destruction of Aspergillus hyphae at the focus of infection. The results of the present study indicate that MCFG improves pulmonary aspergillosis due to lethal damage to Aspergillus hyphae. This action can effectively reduce the invasive ability of Aspergillus even though MCFG does not sterilize the fungal burden.

Animals↗
PubMed2005

Characterization of a multigene-encoded sodium/hydrogen antiporter (sha) from Pseudomonas aeruginosa: its involvement in pathogenesis.

Sha (also known as Mrp/Mnh/Pha) is a Na+/H+ antiporter encoded by a cluster of six or seven genes that probably form a multisubunit transport complex. The Sha system is important for the homeostasis of H+, Na+, and other monovalent cations and plays a critical role in various functions, including alkaliphily, sporulation, and symbiosis. Here, we characterized the sha homologue genes from the opportunistic pathogen Pseudomonas aeruginosa, which exist as a cluster of six genes (PA1054 to PA1059). The gene cluster PA1054 to PA1059, but not the cluster with a deletion of PA1054, complemented a growth defect in the presence of 0.2 M NaCl and a defect in Na+/H+ antiport activity of the Escherichia coli TO114 mutant lacking the three major Na+/H+ antiporters, indicating that genes PA1054 to PA1059 are responsible for Na+/H+ antiport activity. We disrupted PA1054 (a shaA homologue gene) and determined its effect on Na+ tolerance during growth, Na+ efflux, and pathogenicity in mice. Disruption of PA1054 resulted in severe Na+ sensitivity during growth and decreased Na+ efflux activity. In mice, the deletion mutant of PA1054 also exhibited an attenuated virulence in systemic, pulmonary, and urinary tract infections and also a decrease in colonization of the infected organs. From these results, we conclude that the genes PA1054 to PA1059 encode a Na+/H+ antiporter that is largely responsible for Na+ extrusion in P. aeruginosa and has a role in the infection of the pathogen. We propose to designate PA1054 to PA1059 as the sha (sodium hydrogen antiporter) genes, shaABCDEFG.

Animals↗
PubMed2004

Semi-quantitative assessment of oral cavity squamous cell carcinoma using 201Tl SPECT for evaluating effectiveness of preoperative radiotherapy.

The aim of this study is to reveal the usefulness of semi-quantitative assessment using 201Tl chloride (Tl) single photon emission computed tomography (SPECT) (Tl SPECT) to evaluate the effectiveness of radiotherapy in 15 patients with oral cavity squamous cell carcinma (SCC). Fifteen patients were diagnosed with SCC by biopsy. All 15 patients enrolled in this study were planned to undergo preoperative radiotherapy with or without chemotherapy using carboplatin (CBDCA) and received reduction operation. Tl SPECTs were performed 15 minutes after intravenous administration of 111 MBq 201Tl chloride. Regions of Interest (ROI) were set up around tumor (T), and non-lesion (N) at the part of contralateral scalp at the height of the cerebellum. The ratios of mean counts in ROI of the tumor to those in non-lesion were measured as pre- and post-treatment T/N ratios (pre T/N, post T/N). Furthermore, reduction rate (RR) was obtained by calculating [(pre T/N - post T/N)/(pre T/ N)] x 100%. Each parameter (pre T/N, post T/N, and RR) was compared to histopathological grade of surgical specimen based on the Oboshi and Shimosato classification (grade I-IV). RR showed significantly higher values in grade III and IV than in grade I and II (p = 0.0008). In conclusion, semi-quantitative assessment using Tl SPECT, especially calculating RR, is useful to evaluate the effectiveness of preoperative radiotherapy.

Aged↗
PubMed2004

Correlation between angiogenesis and reduction ratio measured using 201Tl chloride single photon emission computed tomography in patients with oral cavity squamous cell carcinoma.

OBJECTIVE: The aim of this study is to examine the correlation between tumor angiogenesis and response to preoperative radiotherapy evaluated using 201Tl single photon emission computed tomography (Tl SPECT) in oral cavity squamous cell carcinoma (SCC). METHODS: Tl SPECTs before and after preoperative radiotherapy were obtained from 11 patients diagnosed with SCC in oral cavity. Regions of interest were set around the tumor and scalp respectively, and the ratio of mean counts in the tumor to those in the scalp was calculated (T/N). Immunohistochemical staining for investigating microvessel density of pre-treatment biopsy specimen was performed using CD31 monoclonal antibody. We compared microvessel density with semi-quantitative parameters obtained using Tl SPECT (T/N at pre- an post-treatment, reduction ratio) and prognosis. RESULTS: The subgroup with higher microvessel density showed a significantly higher reduction ratio than the one with lower microvessel density. Regarding prognosis, the subgroup with locoregional recurrent disease exhibited a significantly higher microvessel density than the one without recurrence. CONCLUSIONS: In SCC of the oral cavity, there was a significant correlation between microvessel density and response to preoperative radiotherapy. Namely, it was revealed that change of 201Tl uptake after preoperative radiotherapy correlated with tumor angiogenesis of oral cavity SCC.

Aged↗
PubMed2003

Comparison of barium swallow, CT and thallium-201 SPECT in evaluating responses of patients with esophageal squamous cell carcinoma to preoperative chemoradiotherapy.

The aims of this study were to compare the results of thallium-201 (Tl-201) SPECT, barium swallow and CT in the assessment of the effect of preoperative chemoradiotherapy. This study consisted of 28 patients with advanced esophageal squamous cell carcinoma (AESCC) who underwent the three imaging modalities before and after preoperative chemoradiotherapy. The results were quantified using the bidimensional method for barium swallow and contrast-enhanced CT and the tumor-to-lung ratio for SPECT. The percent decrease in these quantitative values after therapy was defined as %Dba, %Dct and %Dtl respectively. The histological effect of the chemoradiotherapy was determined from the resected surgical specimen of the esophagus: grade 0, 100% viable tumor cells; grade 1a, 99-67%; grade 1b, 66-34%; grade 2, 33-1%; grade 3, no viable cells. A statistically significant difference of %Dtl between the subgroups of each grade was evident (p = 0.0433), whereas no significant differences were evident for %Dba (p = 0.1778) or %Dct (p = 0.7377). However, the overlap of %Dtl between these groups was marked. Although thallium-201 SPECT cannot be used to evaluate the therapeutic effect with acceptable accuracy, SPECT may be of additional value to barium swallow and CT in assessing the response of AESCC to preoperative chemoradiotherapy.

Administration, Oral↗
PubMed2003

Evidence for the involvement of GABA(A) receptor blockade in convulsions induced by cephalosporins.

There is accumulating evidence that most beta-lactam antibiotics (i.e., cephalosporins and penicillins) have some degree of convulsive activity, both in laboratory animals as well as in clinical settings. The proposed mechanism is suppression of inhibitory postsynaptic responses, mainly mediated by gamma-amino butyric acid (GABA)(A)-receptors (GABA(A)-R). However, comprehensive studies on the convulsive activities of various beta-lactam antibiotics in vivo and in vitro have not been performed. We have therefore examined the convulsive activities of seven different cephalosporins using both in vivo and in vitro models: intracerebroventricular (ICV) administration in mouse; [(3)H]muscimol binding assay (BA) in mouse brain synaptosome; and inhibition of recombinant mouse alpha1beta2gamma2s GABA(A)-Rs in Xenopus oocyte (GR). The rank orders of convulsive activities in mouse (cefazolin>cefoselis>cefotiam>cefpirome>cefepime>ceftazidime>cefozopran) correlated with those of inhibitory potencies on [(3)H]muscimol binding and GABA-induced currents of GABA(A)-R in vitro, with correlation coefficients of ICV:GR, ICV:BA and BA:GR of 0.882, 0.821 and 0.832, respectively. In contrast, none of the antibiotics had affinities for N-methyl-D-aspartate (NMDA) receptors nor facilitatory actions on NMDA receptor-mediated current in oocytes. These results clearly demonstrate that the mechanism of cephalosporin-induced convulsions is mediated predominantly through the inhibition of GABA(A)-R function and not through NMDA receptor modulation.

Animals↗
PubMed2003

Killing activity of micafungin against Aspergillus fumigatus hyphae assessed by specific fluorescent staining for cell viability.

We studied the anti-Aspergillus activity of micafungin by using two fluorescent dyes to detect cell viability. Micafungin induced flattened hyphae, caused by the bursting of cells, which had lost their viability. Micafungin has killing activity against actively growing hyphae, even though it is not fungicidal against the whole burden of Aspergillus fumigatus.

Antifungal Agents↗
PubMed2003

Consolidation radiotherapy following brief chemotherapy for localized diffuse large B-cell lymphoma: a prospective study.

Many physicians administer involved field radiation therapy (RT) following brief chemotherapy for localized aggressive non-Hodgkin's lymphoma. Involved field irradiation usually implies treatment to the involved nodal regions with and without the contiguous lymphatic region, however, there is no agreements about its definition. Here we assess the appropriateness of RT irrespective of lymph node regions (localized field) following chemotherapy for patients with early stage diffuse large B-cell lymphoma. The localized field encompassed all original gross tumor volumes before chemotherapy with at least a 2- to 3-cm margin irrespective of lymphatic regions. We also evaluated the suitable radiation dose on the basis of response to chemotherapy. Twenty five eligible patients were treated with 3 cycles of chemotherapy (CHOP) followed by RT. All 25 patients had disease confined to Waldeyer's ring and/or cervical lymph nodes. Twenty two patients in complete response following chemotherapy received 30 Gy, and the remaining 3 in partial response received 40 Gy. With a median follow up of 42 months, both event free and overall survival rates at 2 years were 96.0%. There were no in-field recurrences, however, two patients experienced relapses. One developed central nervous system involvement and subsequently died of his disease. The other had mediastinal and submental lymph node relapse at 32 months, and is alive after salvage chemotherapy. Our study demonstrated that it should be possible to reduce treatment volume to less than the conventional involved field, and to limit the dose of RT in the range of 30-40 Gy.

Adult↗
PubMed2003

[3D-CRT and intensity modulated radiation therapy (IMRT)].

Three-dimensional conformal radiation therapy (3D-CRT) conforms a high dose region closer to the target volume than does 2D radiation therapy. IMRT is the advanced form of 3D-CRT. With IMRT technique, using multiple intensity modulated beams, one can deliver a high dose of radiation to the target and a low dose to the surrounding normal structures. IMRT planning provides improved tumor target coverage when compared to 3D-CRT treatment planning. There is significant sparing of critical structures and other normal tissues. IMRT also produces dose distributions capable of delivering different dose prescriptions to multiple targets, providing a new opportunity for differential dose painting to increase the dose selectively to specific image-defined regions. Preliminary findings indicate that IMRT is a new clinically feasible tool in radiation oncology. The initial results of clinical studies demonstrate reduced xerostomia in head and neck cancer and also effectively reduced acute and late occurring toxicities, improving the QOL of patients treated for prostate cancer. According to these studies, IMRT will allow dose escalation, leading to better tumor control without normal tissue damage. On the other hand, there are some problems for IMRT in Japan: There are few medical physicists, which results in radiation technologists playing most clinical technological roles, including some dosimetrical and physical activities. Social recognition and economical and legal support for medical physicists should be established in providing better patient care services.

Humans↗
PubMed2002

Detection and chemoradiotherapeutic evaluation of advanced esophageal squamous cell carcinoma using gallium-67 SPET: a preliminary study.

About 20 years ago, gallium-67 planar scintigraphy was introduced for the evaluation of advanced esophageal squamous cell carcinoma (AESCC). Although single-photon emission tomography (SPET) is now available in many institutions, there have been no reports regarding the evaluation of AESCC using (67)Ga SPET. The aims of this preliminary study were to assess the potential of (67)Ga SPET for the detection of AESCC and to further evaluate whether (67)Ga SPET can predict the effect of preoperative chemoradiotherapy on AESCC. Thirty-eight patients with histologically proven AESCC (35 men and 3 women, mean age 62+/-6.9 years) underwent (67)Ga SPET before and after preoperative chemoradiotherapy. The histological response to the chemoradiotherapy was determined from a surgical specimen of the esophagus: grade 0, 100% viable tumor cells; grade 1a, 99%-67%; grade 1b, 66%-34%; grade 2, 33%-1%; grade 3, no viable cells. Thirty-seven out of 38 AESCCs (97.4%) were detected on pre-chemoradiotherapy SPET. In these 37 cancers, the tumor-to-lung ratio (TLRpre) was 3.5+/-2 (range 1.5-9.6). Post-chemoradiotherapy SPET exhibited positive results in 22 cancers, with a TLRpost of 1.8+/-0.4 (range 1.1-2.6). No patient exhibiting a pathologically complete response had a positive post-chemoradiotherapy SPET result, whereas 80% of patients with negative post-chemoradiotherapy SPET (12/15) results had residual tumor. The percent reduction rate was defined as (TLRpre-TLRpost)/TLRpre x100 and did not correlate with histological response grade ( P=0.5169 for Kruskal-Wallis test). These results suggest that (67)Ga SPET is a powerful tool for the detection of AESCC. However, (67)Ga SPET seems to be of little use in predicting the effects of preoperative chemoradiotherapy on AESCC. Further studies are warranted in order to further clarify the clinical usefulness of (67)Ga SPET in patients with AESCC.

Aged↗
PubMed2002

[Dosimetric verification in intensity modulated radiation therapy].

As part of dosimetric verification for IMRT intensity modulated radiation therapy, we examined the selection of a dosimeter in accordance with the purpose of physical measurement and the process of data analysis. Because of the high dose conformation in the target volume and minimum dose in the organs at risk (OAR) in IMRT, dosimetric verification is essential. Because the performance of dosimetric verification in a patient is not allowed, a physical phantom and dosimeter must be used. Dose verification using a physical phantom, from which the beam data optimized for a patient slated for IMRT are transferred, may cause latent error as a result of change in the depth of each beam toward an isocenter. This effect may change the dose distribution and prescription dose. The basic methods of dosimetric verification with physical measurement are point dosimetry, when the reference dose is given at a point by planning software, and volumetric dosimetry, when planning software gives the dose as a volumetric configuration. While the most accurate dosimetry is done using a calibrated ionization chamber, IMRT requires volumetric dosimetry using some kind of portal film or a polymer gel dosimeter, because of the need for dosimetric verification for an irregular dose distribution in IMRT. The importance of indirect dosimetry using these methods is to provide calibration as a dosimeter, absolute dose, and preservation of calibration. In our study, the verification of dose distribution for IMRT using portal film and a RANDO phantom could be performed with an error of less than 2% in all cases. The measurement error for the central dose using a JARP-type ionization chamber and MixDP was less than 3% in all cases except for the case with the maximum error. At the moment, IMRT requires a great deal of effort in the processes of planning, dosimetric verification, and isocenter checking in every fraction to maintain high accuracy. Although the need for a large amount of effort in the service of maintaining accuracy may be reasonable, it could be enough to inhibit the spread of IMRT. It is hoped that an easy method of dosimetric verification that still maintains a high level of accuracy will develop as a result of this great effort.

Phantoms, Imaging↗