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Biomedical subjects

R Iwata

Publications and source records attributed to R Iwata.

At least 109 records · Page 6Linked to original sources

Lustromycin, a new antibiotic produced by Streptomyces sp.

A new antibiotic, lustromycin, was isolated from the cultured broth of Streptomyces sp. SK-1071. It exhibits selective antibacterial activity against anaerobic bacteria including Clostridium sp. The molecular formula C32H38O13 as determined by high resolution mass spectrometry, and elemental analysis and the NMR spectrum suggest structural resemblance of this antibiotic to luminamicin, an anti-anaerobic antibiotic reported previously.

Anti-Bacterial Agents↗

Clostomicins, new antibiotics produced by Micromonospora echinospora subsp. armeniaca subsp. nov. I. Production, isolation, and physico-chemical and biological properties.

A soil isolate named as Micromonospora echinospora subsp. armeniaca subsp. nov. KMR-593 was found to produce at least five related antibiotics, clostomicins, active against Gram-positive bacteria including anaerobes. From the physico-chemical properties, one of these components was identified with lipiarmycin and others were found to be new antibiotics. Each component includes two chlorine atoms and the molecular weights of A and B2, C, and D are 1,058, 1,042 and 1,056, respectively. The structural differences were characterized by NMR analyses.

Aminoglycosides↗

11C-labeling of indolealkylamine alkaloids and the comparative study of their tissue distributions.

Five indolealkylamines (N,N-dimethyltryptamine, N-methyltryptamine, bufotenine, O-methylbufotenine, N,N,N-trimethyltryptamine iodide) were labeled with 11C by use of 11CH3I. The labeled compounds were synthesized with a radiochemical yield of 2-50% (based on trapped 11CH3I) in 20-35 min with radiochemical purities of more than 92%. The tissue distributions of these labeled compounds were investigated in rats. In all cases, the accumulations in the liver, lung and small intestine were high. [11C]DMT and [11C]OMB also accumulated to a large extent in the brain, where their accumulation was retained. Brain uptake of three other radiopharmaceuticals was low. [11C]DMT is the radiopharmaceutical of choice for the study of the serotonin action mechanism in the brain, because it has the highest radiochemical yield and the highest brain uptake of these 11C-labeled compounds.

Animals↗

Placental transfer of positron-emitting radionuclides in metabolic substrates.

Experimental studies on the biodistribution and placental transfer of in vivo metabolic constituents in pregnant rats were investigated with positron-emitting compounds such as 18F-2-fluoro-2-deoxyglucose, a mixture of 11C-glucose and 11C-fructose, 11C-L-methionine, 11C-D,L-leucine, 11C-adenine, 18F-5-fluoro-2'-deoxyuridine, 11C-S-adenosyl-L-methionine and 11C-coenzyme Q10. Sugars and amino acids transferred easily through the placenta and distributed into the fetal tissues to a similar extent as into the maternal tissues. The fetus-to-placenta ratios for the amino acids were always over 1.0, which indicated active transport of the amino acids in the placenta. On the contrary, other compounds have some limitation to transfer through the placenta in comparison with the sugars and amino acids. The fetus-to-placenta ratios of 11C-adenine, 11C-S-adenosyl-L-methionine and 11C-coenzyme Q10 were much less than the placenta-to-blood ratios, which indicated the presence of a certain placental barrier against these compounds. 11C-S-adenosyl-L-methionine and 11C-coenzyme Q10 were incorporated more into the fetal brain than into the maternal brain which is probably due to the nutritional requirement of the fetal brain and/or an immature blood-brain barrier.

Adenine↗

Lung tumor imaging by positron emission tomography using C-11 L-methionine.

This paper described the first clinical study of lung tumor scanning by positron emission tomography (PET) using C-11-labeled L-methionine (11C-L-Met). Tumor images were clearly visualized by high contrast in eight lung cancer patients and also in a patient with a silicotic nodule. Quantitative evaluations of methionine uptake in tumor tissue and normal tissue by comparing differential uptake ratios suggested that the extent to which 11C-L-Met accumulates in a tumor is closely correlated to the tumor's viability such as benign or malignant, viable or necrotic. 11C-L-Met is considered to be an effective tumor marker for PET diagnosis which represents increased amino acid metabolism of tumors in the mediastinum and lung.

Carbon Radioisotopes↗

Biodistribution of a positron-emitting suicide inactivator of monoamine oxidase, carbon-11 pargyline, in mice and a rabbit.

Carbon-11 (11C) pargyline, which is a suicide inactivator of Type B monoamine oxidase (MAO), was synthesized by the reaction of N-demethylpargyline with 11CH3I. Biodistribution was investigated in mice, and positron tomographic images of the heart and lung in a rabbit were obtained. The distribution of 11C after administration of [11C]pargyline was measured in several organs and blood at various time intervals. After 30 min its concentrations in the organs were constant. Subcellular distribution studies in the brain, lung, liver, and kidney showed that 59-70% of the 11C became acid-insoluble and 9-33% was present in the crude mitochondrial fraction at 60 min after injection. However, a high loading dose influenced the subcellular distribution but had little effect on tissue distribution. The uptakes of the 11C in each organ except for the kidney and spleen seemed to correlate with the in vitro enzymatic activity of Type B MAO. At high loading dose a nonspecific uptake was observed.

Animals↗

Intestinal distribution, absorption and secretion of dimethylamine and its biliary and urinary excretion in rats.

In the gastro-intestinal tract of male Wistar rats fed a commercial diet containing 23.6 ppm dimethylamine (DMA), the concentration of DMA was highest (11.2 +/- 2.1 ppm) in the stomach and declined towards the lower regions. In contrast, the highest DMA concentration (6.6 +/- 2.5 ppm) was observed in the upper small intestine in rats fed a diet containing only 1.0 ppm DMA. DMA was absorbed in the intestines, and the disappearance curves were monoexponential. The t1/2 values for DMA in the ligated stomach, upper and lower small intestine, caecum and large intestine were 198, 8.3, 11.6, 31.5 and 11.0 min, respectively. The DMA concentration in the blood had increased to 3.0 +/- 1.0 ppm (from a pre-injection level of 0.28 +/- 0.06 ppm) 5 min after the injection of 250 micrograms DMA into the ligated upper small intestine. The disappearance curve for DMA in the blood was monoexponential and the t1/2 for the initial 15 min was 12.5 min when 250 micrograms DMA was injected into a femoral vein. The peak concentrations of DMA in the intestine and bile, respectively, were 15.6 +/- 12.6 ppm (at 15 min) and 3.7 +/- 1.9 ppm (at 30 min after the iv injection of DMA). In this 30-min period, urinary DMA increased from 17.3 +/- 9.4 to 139 +/- 23 ppm. These results show that, following ingestion, DMA is absorbed from the intestine into the blood, from which it disappears rapidly, the major part being excreted in the urine while a small proportion is excreted in the bile or secreted into the intestine, where it may be reabsorbed.

Animals↗

Syntheses of 18F-labeled pyrimidines and their usefulness for tumor imaging.

18F-Labeled 5-fluorouracil(FUra), 5-fluoro-2'-deoxyuridine(FdUrd) and 5-fluorouridine(FUrd) were synthesized with high radiochemical purities. Biodistribution of the 18F-pyrimidines in tumor-bearing rats, mice or a rabbit was examined. Blood clearance of the 18F-pyrimidines was very rapid. The kidney and liver showed the high uptake and rapid clearance which was due to the metabolism and excretion. The 18F-concentration in the tumor was due to the metabolism and excretion. The 18F-concentration in the tumor was also high and clearance was very slow compared with those in other organs. Tumor uptakes of 18F-FdUrd were also shown by positron emission tomography and autoradiography. Biodistributions of the 18F-FdUrd and radio-deoxythymidine(dThd) were different between several organs, but similar distribution patterns in the tumor were observed by autoradiography.

Animals↗

[Automated synthesis system for production of 11C-glucose].

A fully automated synthesis system of 11C-glucose by the photosynthesis method has been developed for clinical use. This system has been designed to be as convenient as possible for routine use, and the full automation of the whole procedure from the target gas recovery to collection of the final 11C-glucose/fructose mixture has been accomplished by microcomputer control. A mixture of 11C-glucose/fructose (1:1) was obtained with 20 approximately 35% of radiochemical yield within 60 min.

Carbon Dioxide↗

Absorption, secretion and excretion of dimethylamine in rats.

The dimethylamine (DMA) concentration in the gastrointestinal tract of Wistar male rats fed a commercial diet containing 23.6 mg/kg DMA was highest (11.2 +/- 2.1 mg/kg) in the stomach and decreased from the upper region to the lower region. In contrast, the highest DMA concentration (6.6 +/- 2.5 mg/kg) in the upper small intestine was observed in rats fed a low-DMA diet containing 1.0 mg/kg DMA. DMA absorption was observed in the intestines and the absorbtion curves were monoexponential. The biological half-lives (t1/2) of DMA in the ligated stomach, upper and lower small intestine, caecum and large intestine were 198, 8.3, 11.6, 31.5 and 11.0 min, respectively. The DMA concentration in blood increased from 0.3 +/- 0.1 mg/kg to 3.0 +/- 1.0 mg/kg 5 min after injection of 250 micrograms DMA into the ligated upper small intestine. The disappearance curve of DMA in blood was monoexponential and the half-life for the initial 15 min was 12.5 min when 250 micrograms DMA were injected through a femoral vein. Intestinal secretion of DMA (15.6 +/- 12.6 mg/kg) was observed 15 min after the injection. Urinary DMA increased from 17.3 +/- 9.4 to 139 +/- 23 mg/kg within 30 min of intravenous injection of DMA. These results show that the behaviour of DMA in rats is as follows: (Formula: see text)

Animals↗

Thiotetromycin, a new antibiotic. Taxonomy, production, isolation, and physicochemical and biological properties.

A new antibiotic, thiotetromycin, has been isolated from the culture filtrate of Streptomyces sp. OM-674 by solvent extraction and silica gel chromatography. The molecular formula of the antibiotic has been determined as C13H18O2S on the basis of elemental analysis and its high resolution mass spectrometry. The antibiotic contains a thiotetronic acid in the molecule and possesses a selective activity against Bacteroides fragilis.

Animals↗

Experimental study for cancer diagnosis with positron-labeled fluorinated glucose analogs: [18F]-2-fluoro-2-deoxy-D-mannose: a new tracer for cancer detection.

18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and 18F-2-fluoro-2-deoxy-D-mannose (18F-FDM) were tested as tumor diagnostic agents in a transplantable rat tumor and rabbit tumors. Tissue distribution studies in rats showed high tumor uptakes of both radiopharmaceuticals. The tumor uptake reached 2.65 +/- 0.61% dose 18 dose F-FDG/g and 2.65 +/- 0.81% dose 18F-FDM/g at 60 min and remained relatively constant until 120 min. Blood clearance both 18F-FDG and 18F-FDM was very rapid and tumor-to-blood ratios reached 22.1 and 29.4 at 60 min, respectively. Tumor-to-tissue ratios of both radiopharmaceuticals were very high in most organs, especially in the liver, kidney, and pancreas. Positron emission tomography (PET) of rabbit tumor with 18F-FDM clearly delineated the main tumor, central necrosis, and lymph node metastases. These data suggested that 18F-FDM, which is a by-product of 18F-FDG synthesis was also an excellent cancer diagnostic agent as well as 18F-FDG. This is not only a new feature of 18F-FDM, but also an economical improvement on cancer diagnosis by PET.

Animals↗

Aspects of the preparation of 18F-2-deoxy-2-fluoro-D-glucose (18FDG) for medical use.

Fluorine-18-2-deoxy-2-fluoro-D-glucose (18FDG) for medical use had been prepared with the attention regarding radiochemical yield and purity, specific activity and quality control. More than four 18F-by-products in 18F-adducts from the reaction of triacetyl glucal with 18F2 were detected by the autoradiography of thin layer plates in which two by-products could not be perfectly removed by a column chromatography, and selective collection of the eluate gave 18FDG with the purity of 96.7% as an average in 12 runs. At end of synthesis (EOS) 259-925 MB (7-25 mCi) of a sterilized, isotonic solution of 18FDG was obtained with the specific activity of 629-851 MBq (17-23 mCi)/mg at end of bombardment (EOB) after preparation time of 3-3.5 hr, in which bacteria and pyrogen were not detected.

Chromatography↗

Convenient 77Kr production method for medical use.

A convenient method of 77Kr production has been developed for its routine medical use in cerebral blood flow measurement. An aqueous solution of NaBr (40 wt%) was used as the target and 77Kr produced by the 79Br(p, 3n)77Kr reaction was rapidly recovered from the target under a He stream. The optimal target thickness was determined to be 5 approximately 6 mm by investigating radionuclidic purity and proton current effect on the yield. About 740 MBq (20 mCi) of 77Kr with a radionuclidic purity of 92% was obtained within 5 min after a 5 microA-20 min irradiation. The present method has been demonstrated to be suitable for routine 77Kr production.

Cerebrovascular Circulation↗