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Biomedical subjects

T Irie

Publications and source records attributed to T Irie.

At least 253 records · Page 14Linked to original sources

Synthesis of 18F-6-fluoropurine and 18F-6-fluoro-9-beta-d-ribofuranosylpurine.

Introduction of fluorine-18 into the 6-position of purines is described. 18F-6-fluoropurine and 18F-6-fluoro-9-beta-D-ribofuranosylpurine were prepared with high radiochemical yields by nucleophilic displacement of the trimethylammonio-group of purine with 18F-fluoride under mild conditions. 18F-labeling conditions such as reaction temperature and time, addition of crown ether and dose of a substrate have been studied. Under adequate conditions, yields of about 38% in the case of free base and about 63% in the case of ribofuranosyl derivative have been obtained. The latter compound has also been prepared in a non-carrier-added state. The stability of 18F-purines was examined in Tris buffer at 37 degrees.

Fluorouracil↗

Preparation of 18F-labeled 6- and 2-fluoro-9-benzylpurine as a potential brain-scanning agent.

The preparations of [18F]-6-fluoro-9-benzylpurine(I) and [18F]-2-fluoro-9-benzylpurine(II) are described. (I) was prepared by two methods: (i) halogen exchange of 6-chloro-9-benzylpurine with Ag 18F; and (ii) displacement of trimethylpurin-6-ylammonium chloride with K 18F, followed by 9N benzylation. The latter labeling method was far superior to the former, both in radiochemical yield and in specific activity. (I) was relatively stable in a Tris-HCl buffer (0.4 M, pH 7.6) at 37 degrees C, but was easily hydrolyzed in 1 N HCl. Biodistribution of (I) in mice demonstrated high uptake in the brain. (I) can be expected to be a potential brain-scanning radiopharmaceutical for positron computed tomography.

Animals↗

Stature, lung height, and spontaneous pneumothorax.

Relationship between stature and roentgenologically determined lung sizes were examined in 48 patients (mean age = 24.6 +/- 6.2 years) with spontaneous pneumothorax, 46 male patients (mean age = 24.6 +/- 3.8 years) with various diseases not related to the cardiopulmonary system, and 48 healthy male students (mean age = 24.3 +/- 2.2 years). Patients with spontaneous pneumothorax were slender compared to the control groups but the body height was not different. The patients had significantly longer lungs than the controls, although width and depth of the lungs were similar between the three groups. Mean differences for the lung height between patients and healthy students were so small (mean = 1.2-1.7 cm, which is equivalent to 0.3-0.7 cm H2O) that stress alone does not appear to be a major contributor to the pathogenesis of spontaneous pneumothorax.

Adult↗

Criteria for pulmonary and respiratory failure in COPD patients - a theoretical study based on clinical data.

In 58 patients with chronic obstructive pulmonary disease, pulmonary gas exchange efficiency was assessed by the ratio: arterial to mixed venous PO2 difference (efficient part) versus alveolar to mixed venous PO2 difference (driving pressure for O2 transport). Patients with PaO2 below 75 mm Hg had a ratio lower than 50%. Patients with PaO2 below 60 mm Hg had lower values for arterial to mixed venous O2 content difference and higher blood lactic acid concentration than patients with PaO2 over 60 mm Hg. Arterial to mixed venous PO2 difference decreased linearly against PaO2 till PaO2 reached 60 mm Hg from which the difference began to attenuate. These figures in PaO2 are in close agreement with the criteria for pulmonary failure presented by the Ciba guest symposium (PaO2 below 75 mm Hg) and for respiratory failure by the National Heart, Lung and Blood Institute (PaO2 below 60 mm Hg).

Humans↗

Familial factors affecting arterial blood gas values and respiratory chemosensitivity in chronic obstructive pulmonary disease.

Arterial blood gas determinations in patients with chronic obstructive pulmonary disease (COPD) and respiratory chemosensitivity, and arterial blood gas determinations in their sons were compared. Patients with silicosis (n=17) and their sons (n=22) served as control subjects. Arterial blood gases, pH, and HCO-3 concentration in 25 patients with COPD were averaged from at least 3 determinations (mean sample number, 10.1) to compare with the data on their sons (n-34; mean age, 33.9 yr). The Paco2 obtained during stable stages correlated positively between patients with COPD and their sons. The Pao2 of patients with COPD in stable stages correlated with the hypoxic ventilatory response of their sons. The Paco2 and Paco2 obtained during acute exacerbation of COPD correlated with the hypoxic ventilatory response of the sons. Deviations in FEV1 and V25 from predicted values correlated with deviations in Pao2 in the sons of the patients with COPD. In silicosis, significant relationships between patients and sons were not seen with respect to arterial blood gas determinations and ventilatory responses except for Paco2 of patients and hypercapnic ventilatory responses of sons. Smoking habits did not correlate between patients and sons both in COPD and in silicosis. However, the concordance ratio of smokers or nonsmokers between patients and sons was higher in COPD than in silicosis. These results indicate that familial factors are involved in determining the arterial blood gases and ventilatory response to hypoxia in COPD, and blunted chemosensitivity to hypoxia and incipient airway dysfunction antedate clinically manifest COPD.

Adult↗

Cyclodextrin-induced hemolysis and shape changes of human erythrocytes in vitro.

Cyclodextrins (CyDs) at higher concentrations were found to cause hemolysis of human erythrocytes in the order of beta- greater than alpha- greater than gamma-CyD in isotonic solution. Biphasic effects of CyDs were observed for the osmotic and heat-induced hemolysis; i.e. the protection at relatively low CyD concentrations and stimulation at higher CyD concentrations. From the scanning electron microscopic observations, CyDs induced shape changes of membrane internalization type on erythrocytes. CyDs caused the release of cholesterol from erythrocyte membrane in the order of beta- greater than gamma- greater than alpha-CyD. These results clearly indicate that CyD-induced hemolysis is probably a secondary event resulting from the membrane disruption which elicited the removal of membrane components from erythrocytes.

Cyclodextrins↗

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↗

Relationship of Mallory bodies to the cytoskeleton of hepatocytes in griseofulvin-treated mice.

The livers of control and griseofulvin-treated mice were perfused with a detergent solution to study the relationship of Mallory body formation to the hepatocyte microtubules and intermediate filaments using electron microscopy and morphometric analysis. Numerous microtubules and intermediate filaments were found throughout the cytoplasm of hepatocytes, especially around the nucleus and the cell border, in both the griseofulvin-treated mouse livers and controls. Intermediate filaments were numerous in the cytoplasm around Mallory bodies. Morphometric analysis revealed that griseofulvin feeding did not significantly alter the amount of microtubules and intermediate filaments in hepatocytes. There was no significant decrease in microtubules and intermediate filaments in Mallory body-containing hepatocytes. In griseofulvin-treated mice, typical Mallory bodies were observed as randomly oriented, relatively short, approximately 17-nm. thick filaments. After detergent extraction some Mallory bodies were observed to be composed of thinner (approximately 8.4 nm) filaments, which morphologically resembled intermediate filaments. Our results suggest that Mallory bodies are composed of intermediate filaments decorated with a nonfilamentous substance that can be extracted by the Triton X-100. The data do not support the theory that Mallory bodies form at the expense of intermediate filaments as has been suggested from immunofluorescence studies. Our results do not support the antimicrotubule hypothesis of Mallory body pathogenesis.

Animals↗

Effects of cyclodextrins on chlorpromazine-induced haemolysis and central nervous system responses.

Cyclodextrins (CyDs) protected the human erythrocytes from haemolysis induced with chlorpromazine (CPZ) in isotonic solution, depending upon the magnitude of the stability constant of CPZ-CyD complexes (beta-greater than-gamma-greater than alpha-CyD). From the observations of CPZ uptake into erythrocytes and changes in surface activity of CPZ, the protective effects of CyDs in vitro appeared to be due to the decrease in effective haemolytic concentration of CPZ through inclusion complex formation rather than the direct interaction of CyDs with the erythrocyte membrane. The effect of beta-CyD on some central nervous system (c.n.s.) actions of CPZ in rats was also investigated to see if there were any advantages in the use of beta-CyD complexes given by injection. The results suggest that beta-CyD does not after the time-course or magnitude of the effects of CPZ on the c.n.s.

Animals↗