Biological properties of flutianil as a novel fungicide against powdery mildew.

Flutianil, chemically characterized as a cyano-methylene thiazolidine, showed antifungal activity against powdery mildew on various crops but not any other plant pathogens tested. Flutianil showed high residual and translaminar activities and rainfastness against Podosphaera xanthii. It also exhibited curative activity against P. xanthii on cucumber at an extremely low concentration of 10 mg/L. There was no cross-resistance between flutianil and other existing fungicides. Morphological studies revealed that flutianil did not inhibit the early infection behavior of Blumeria graminis f. sp. hordei i.e., conidium bursting, primary and appressorial germinations, appressorium development and hook formations, but it did inhibit haustorium formation and further fungal development. Nutrient absorption by haustoria and subsequent secondary hyphal elongation was inhibited by flutianil but not by the fungicide that showed a similar inhibitory pattern up to the haustorium formation stage of the infection process. These findings suggest that flutianil might have a novel mode of action.

Synthesis and biological activity of a novel fungicide, flutianil.

Flutianil was discovered as a novel fungicide chemically characterized as a cyano-methylene thiazolidine. This chemical showed particularly high fungicidal activities against powdery mildew on various crops. Optimization of the fungicidal performance of the series of synthesized chemicals finally led to the identification of flutianil, which could control powdery mildew diseases. In this report, details of the structure-activity relationships from the lead compound to flutianil are described.

Summary of Toxicity Studies with Flutianil.

We have evaluated the toxicity of flutianil, which was developed by OAT Agrio. Flutianil shows low toxicity, no carcinogenicity, no reproductive toxicity, and no genotoxicity. Based on these results, the ADI of flutianil has been set at 2.4 mg/kg bw/day with a safety factor of 100.

Optimization of transmission scan duration for 15O PET study with sequential dual tracer administration using N-index.

PURPOSE: Cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of O(2) (CMRO(2)) can be quantified by PET with the administration of H (2) (15) O and (15)O(2). Recently, a shortening in the duration of these measurements was achieved by the sequential administration of dual tracers of (15)O(2) and H (2) (15) O with PET acquisition and integration method (DARG method). A transmission scan is generally required for correcting photon attenuation in advance of PET scan. Although the DARG method can shorten the total study duration to around 30 min, the transmission scan duration has not been optimized and has possibility to shorten its duration. Our aim of this study was to determine the optimal duration for the transmission scan. We introduced 'N-index', which estimates the noise level on an image obtained by subtracting two statistically independent and physiologically equivalent images. The relationship between noise on functional images and duration of the transmission scan was investigated by N-index. METHODS: We performed phantom studies to test whether the N-index reflects the pixel noise in a PET image. We also estimated the noise level by the N-index on CBF, OEF and CMRO(2) images from DARG method in clinical patients, and investigated an optimal true count of the transmission scan. RESULTS: We found tight correlation between pixel noise and N-index in the phantom study. By investigating relationship between the transmission scan duration and N-index value for the functional images by DARG method, we revealed that the transmission data with true counts of more than 40 Mcounts results in CBF, OEF, and CMRO(2) images of reasonable quantitative accuracy and quality. CONCLUSION: The present study suggests that further shortening of DARG measurement is possible by abridging the transmission scan. The N-index could be used to determine the optimal measurement condition when examining the quality of image.

[Usefulness of attenuation correction with transmission source in myocardial SPECT].

Attenuation correction in SPECT has been used for uniformly absorptive objects like the head. On the other hand, it has seldom been applied to nonuniform absorptive objects like the heart and surrounding lungs because of the difficulty and inaccuracy of data processing. However, since attenuation correction using a transmission source recently became practical, we were able to apply this method to a nonuniform absorptive object. Therefore, we evaluated the usefulness of this attenuation correction system with a transmission source in myocardial SPECT. The dose linearity, defect/normal ratio using a myocardial phantom, and myocardial count distribution in clinical cases was examined with and without the attenuation correction system. We found that all data processed with attenuation correction were better than those without attenuation correction. For example, in myocardial count distribution, while there was a difference between men and women without attenuation correction, which was considered to be caused by differences in body shape, after processing with attenuation correction, myocardial count distribution was almost the same in all cases. In conclusion, these results suggested that attenuation correction with a transmission source was useful in myocardial SPECT.

[Multicenter comparative study of the recurrence-inhibitory effect of oral fluoropyrimidine drugs in patients with colorectal cancer following curative resection].

HCFU and UFT were reported effective in adjuvant chemotherapy for colorectal cancer. This investigation was planned as a randomized study to compare the usefulness of combination therapies with mitomycin C (MMC)+HCFU and MMC+UFT as postoperative adjuvant chemotherapy in patients with colorectal cancer following curative resection, in terms of survival rate, recurrence rate, and adverse drug reactions. A total of 501 patients consisting of 252 patients with stage III/IV colon cancer (Colorectal Cancer Handling Rules, 4th Ed.) for which macroscopic curative resection was possible and 249 patients with stage II/III/IV rectal cancer (ibid, 4th Ed.) were registered from 40 participating institutions. The patients were randomly allocated to two groups with colon cancer and rectal cancer employed as stratification factors. Beginning on Day 14 after surgery, HCFU at 300 mg/day was administered to one group and UFT at 300 mg/day or 400 mg/day to another group, both orally and daily for one year. MMC 6 mg/m2 was administered intravenously to both groups on the day of surgery and the day following. Among the 501 patients, 496 patients (99%) were eligible. The 5-year survival rates were 77.1% for the MMC+ HCFU group and 79.2% for the MMC+UFT group, with the 5-year recurrence-free survival rates were 76.1% and 72.9%, respectively, neither showing a significant difference between the groups. Adverse drug reactions appeared in 23% of patients in the MMC+HCFU group and in 19% in the MMC+UFT group, with no serious reactions. One year after surgery the administration completion rates were good, at 82% for the MMC+HCFU group and 83% for the MMC+UFT group. No clear difference in effectiveness was noted between MMC+HCFU therapy and MMC+UFT therapy as postoperative adjuvant chemotherapy for colorectal cancer. The administration completion rates were good, and no serious adverse drug reactions were observed for either therapy. It was thus considered that both therapies could be administered safely, and both were useful as postoperative adjuvant chemotherapies for colorectal cancer. It is considered necessary to compare them with standard therapies in Western countries in the future.

Superimposed display of coronary artery on gated myocardial perfusion scintigraphy.

UNLABELLED: Fusion of images of vascular anatomy and of myocardial perfusion images might be helpful for understanding the relationship between ischemia and the responsible vessels. The aim of this study was to develop a simple means of superimposing the images obtained from coronary angiography and gated myocardial perfusion SPECT. METHODS: Right and left oblique views from conventional coronary angiography and left ventriculography (LVG) were stored as 512 x 512 x 8-bit digital datasets and combined. We reconstructed images from routine gated myocardial perfusion imaging (MPI) by using (99m)Tc-tetrofosmin to match the oblique positions between the image from MPI and combined angiographic images. We then generated a 3-dimensional (3D) surface map by using the quantitative gated SPECT (QGS)/quantitative perfusion SPECT (QPS) program. Both the combined angiographic images and the 3D surface map were rescaled and unified by registering the internal landmarks between the 2 images. After subtraction of the LVG image, the coronary angiogram and the 3D surface map were fused into 1 image. All processes were performed with the QGS/QPS program and commercially available graphic software. We applied this method to datasets from a cardiac phantom and from several patients with coronary artery disease. RESULTS: In the phantom study, our technique could obtain a 3D surface map in which the oblique angle was identified as that of radiography and could realize image registration and superimposition of radiography on scintigraphy. The preliminary results from the patients indicated that the markedly stenotic vessels showed good coincidence with the regional myocardial perfusion abnormalities on the unified images. In addition, these images could show the relationship between the coronary artery and regional wall motion in the gated mode. CONCLUSION: We developed a simple method of superimposing the image of the coronary artery tree on images from gated MPI. The technique yielded useful information about myocardial perfusion and function as well as the supplying coronary artery.

[Final results of a randomized clinical trial of adjuvant intraportal chemotherapy for colorectal cancer: Intraportal Chemotherapy for Colorectal Cancer Group].

The purpose of the present multi-center collaborative study was to elucidate the efficacy of intraportal chemotherapy with the combination of 5-FU and MMC for the prevention of liver recurrence after resection for colorectal cancer. A total of 125 patients with Stage II, III, and IV colorectal cancer were enrolled in this study between June 1993 and December 1995. Of them, 45 patients were randomized to a portal group: 10 mg/body of mitomycin one shot portal infusion, before and after 500 mg/m2 of 5-FU per 24 h for 7 days portal infusion followed by administration of oral 5-FU. Fifty-three patients were randomized to a control group: oral administration of 5-FU. Twelve patients suffered from temporary mild liver damage. One patient (2%) in the portal group and 6 patients (11%) in the control group developed liver metastases; there was not a significant difference between these two groups regarding development of liver metastases. There was also no significant difference by tumor stage between the portal and control groups regarding development of liver metastases. The 5-year survival rate and 5-year disease-free survival were 84.3% and 81.9%, respectively, in the portal group, and 70.7% and 72.4%, respectively, in the control group; the difference was not significant. Although there was not a significant difference between the portal and control groups regarding the prognosis in stage II, there was a significant difference between the portal and control groups regarding the 5-year disease free survival in stage III (81.1% vs 54.2%). These results suggest that intraportal chemotherapy is effective for stage III colorectal cancer.

Evaluation of a commercial PET tomograph-based system for the quantitative assessment of rCBF, rOEF and rCMRO2 by using sequential administration of 15O-labeled compounds.

The purpose of this study was to develop a reliable and practical strategy that generates quantitative CBF and OEF maps accurately from PET data sets obtained with 15O-tracers. Sequential sinogram data sets were acquired after the administration of 15O-tracers, and combined single-frame images were obtained. The delay time between sampled input function and the brain was estimated from the H2(15)O study with the whole brain and the arterial time-activity curves (TACs). The whole-brain TACs were obtained from the reconstructed images (image-base method) and the sinogram data (sinogram-base method). Six methods were also evaluated for the dead-time and decay correction procedures in the process of generating a single-frame image from the dynamic sinogram. The estimated delay values were similar with both the sinogram-based and image-based methods. A lumped correction factor to a previously added single-frame sinogram caused an underestimation of CBF, OEF and CMRO2 by 16% at maximum, as compared with the correction procedure for a short sinogram. This suggested the need for a dynamic acquisition of a sinogram with a short interval. The proposed strategy provided an accurate quantification of CBF and OEF by PET with 15O-tracers.

[Measurement of left ventricular chamber and myocardial volume in hypertrophic cardiomyopathy patients by ECG-gated myocardial perfusion SPECT: application of a newly developed edge-detection algorithm].

Quantitative gated SPECT (QGS) software has been reported to demonstrate inaccurate edge detection in the left ventricular chamber in hypertrophic cardiomyopathy patients. In this study we developed a method to calculate left ventricular volume (LVV) and left myocardial volume (LMV) from gated SPECT data using a newly developed edge-detection algorithm, and we compared it with the QGS method of calculating LVV and LMV in a phantom study. Our method gave more accurate measurements LVV and LMV whereas the QGS method underestimated LMV. Compared with QGS LVV and LMV, our method yielded better results in the phantom study.