Biomedical subjects

K Takemoto

Publications and source records attributed to K Takemoto.

At least 55 records · Page 3Linked to original sources

PubMed1993

Spontaneous and 2-nitropropane induced levels of 8-hydroxy-2'-deoxyguanosine in liver DNA of rats fed iron-deficient or manganese- and copper-deficient diets.

Rats (Wistar, female, 4 weeks old) were fed iron-deficient (Fe-; 2.2 micrograms Fe/g) or manganese- and copper-deficient (Mn.Cu-; 0.3 microgram Mn/g, 0.4 microgram Cu/g) diets for 8 weeks to determine the oxidative damage of DNA by element deficiency. After feeding of the diets, 2-nitropropane (2-NP, 80 mg/kg body weight) was administered i.p. as an inducer of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) to the element-deficient rats. The hemoglobin concentration of rats in the Fe- group showed an induction of severe anemia (8.4 g/100 ml whole blood). In the Mn.Cu- group, Mn-superoxide dismutase (SOD) activities of plasma and Cu.Zn-SOD activities were significantly lower than that of the normal diet group. However, total SOD activities of plasma were not depressed severely in contrast to that of the liver in the Mn.Cu- group. Background (spontaneous) levels of 8-OH-dG in normal diet group were 0.96 +/- 0.37/10(5) deoxyguanosine (dG), however, significantly higher levels were detected in the Fe- group (1.56 +/- 0.19, P < 0.01). Conversely, a lower (but not significant) level of 8-OH-dG than the normal diet group were detected in the Mn.Cu- group (0.78 +/- 0.08). Six hours after 2-NP treatment, 8-OH-dG levels in liver DNA were significantly induced to 1.44 +/- 0.24 in the normal diet fed group 1.89 +/- 0.22 in the Fe- and 1.08 +/- 0.12 in the Mn.Cu- groups. Compared to the normal diet group, these induced levels of 8-OH-dG in the Fe- group were significantly higher (P < 0.05), and that in Mn.Cu- group were significantly lower (P < 0.05). The high level of 8-OH-dG in severe iron deficiency might be the results of: (i) an increase of hydroxyl radical generation by accumulated copper in hepatocytes; or (ii), a depression of enzymatic activity for removing 8-hydroxy-2'-deoxyguanosine in DNA, which is dependent on divalent cations. On the other hand, the low level of 8-OH-dG in manganese and copper deficiency might be the result of a decrease of lipid peroxidation which has been suggested to be an intermediator from active oxygen species to hydroxyl radical.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1993

Carcinogenicity of benzotrichloride administered to mice by gastric intubation.

Epidemiological studies suggest that benzotrichloride (BTC) is a human carcinogen. In the present study, BTC was tested to evaluate its ability to induce lung tumors as a result of systemic exposure. Administration of BTC by gastric intubation, 2.0-0.0315 microliters/mouse (4 doses), twice a week for 25 weeks, in female ICR mice, produced forestomach tumors (squamous cell carcinoma and papilloma), lung tumors (adenocarcinoma and adenoma) and tumors of the hematopoietic system (thymic lymphosarcoma and lymphatic leukemia) with dose-related response by 18 months. The present and previous studies indicate that the target organs of BTC carcinogenesis in mice are the local tissue which is primarily exposed, and the lung and hematopoietic tissue when BTC is administered systematically.

Administration, Oral↗

PubMed1993

Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera.

Technetium-99m-teboroxime is characterized by a high extraction fraction over a wide range of blood flow rates, rapid myocardial clearance and avid hepatic uptake. This study determined the imaging parameters and examined the clinical efficacy of a rapid back to back adenosine stress/rest teboroxime myocardial perfusion SPECT protocol using a triple-detector camera. Acquisition parameters were determined using cardiac phantom studies which were then applied in SPECT studies of 51 catheterized patients (22 with prior myocardial infarction) and 20 patients with a "low" (7.9% +/- 4.3%) likelihood of coronary artery disease. Technetium-99m-teboroxime (20-25 mCi) was injected at the third minute of adenosine infusion. Teboroxime (20-25 mCi) was also injected at rest, 15 min later. Stress followed by rest SPECT were completed within 25 min using a triple-detector camera and sequential, 1-min continuous rotations in alternating directions. Summed raw data from the first to second (1-2 min), second to third (2-3 min) and second to fifth (2-5 min) minutes of imaging following stress teboroxime injection were reconstructed and compared for image quality, degree of liver interference, and accuracy for diagnostic efficacy. In a subgroup of 30 patients, 2-8-min summed images were also reconstructed to compare this more conventional imaging protocol with our rapid acquisition. Image quality was fair to good in 75% of the 1-2-min, 84% of the 2-3-min and 2-5-min studies and 53% of the 2-8-min scans. The frequency of severe liver interference appeared to increase with the duration of imaging time (1-2 min: 3%; 2-3 min: 7%; 2-5 min: 8%) and was greatest (30%, p = 0.08) with 2-8-min images. Three patients (4%) had uninterpretable studies due to intense hepatic uptake. Overall sensitivity (95%) and specificity (71%) were equal for the 2-3-min and 2-5-min stress images and appeared better than in the 1-2-min images (84% and 57%, respectively). For the 2-8-min scans, vessel sensitivity (69%) and specificity (63%) appeared poorer than with 2-3-min studies (83% and 81%, respectively). Normalcy rates were 89% for the 2-3-min and 2-5-min and 79% for 1-2-min images. The back to back adenosine stress/rest teboroxime SPECT can be performed in 30 min using a triple-detector camera. Although overall high sensitivity and normalcy rates were achieved, the protocol is technically demanding. Interference due to intense liver uptake remains problematic.

Adenosine↗

PubMed1992

Oxidative damage on DNA induced by asbestos and man-made fibers in vitro.

We compared the potential of asbestos and man-made fibers to attack DNA by the determination of the yield of 8-hydroxy-2'-deoxyguanosine (8-OH-dGuo) under several in vitro conditions. Asbestos induced 6.6-99.8 of 8-OH-dGuo per 10(5) dGuo in calf thymus DNA after 20 h of incubation, while the levels of 8-OH-dGuo in man-made fibers were low (3.6-9.4). The amounts of 8-OH-dGuo were strongly stimulated by the addition of H2O2 in asbestos, but not in man-made fibers. However, the yield of 8-OH-dGuo was induced more than that with asbestos by the further addition of FeSO4 in attapulgite, fiberglass, potassium titanate whisker, and metaphosphate polymer. The addition of ethylene diamine tetra-acetic acid (EDTA) promoted the induction of 8-OH-dGuo with asbestos and H2O2. The effects of mannitol (known as a hydroxy radical scavenger) were not dramatic on 8-OH-dGuo induction by all fibers except fiberglass and basic magnesium sulfate whisker, which induced higher amounts after mannitol addition than in these fibers and H2O2. Therefore, it was suggested that asbestos could damage DNA, resulting in 8-OH-dGuo as a cause of point mutation, and also several types of man-made fibers had similar effects to asbestos under certain conditions.

Animals↗

PubMed1992

Cardiovascular actions of OPC-18790: a novel positive inotropic agent with little chronotropic action.

OPC-18790 [(+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]- 2(1H)-quinolinone], a novel positive inotropic agent, was investigated in several in vitro and in vivo experiments to elucidate its cardiovascular effects and its mechanism of action. In isolated blood-perfused dog heart preparations, OPC-18790 increased contractile force at 10 to 1,000 nmol i.a.; increased coronary arterial blood flow at 30 to 1,000 nmol; and decreased sinus rate slightly at 1,000 nmol. Atrio-ventricular nodal conduction was slightly facilitated with OPC-18790 (10 to 1,000 nmol), whereas ventricular automaticity tended to decrease. OPC-18790 (10(-6) to 10(-4) M) increased contractile force in isolated ventricular muscles of dogs, cats, rabbits and guinea pigs but not rats. OPC-18790 increased left ventricular contractile force dose-dependently in anesthetized open-chest dogs and in conscious dogs with slight or no changes in heart rate and blood pressure. The positive inotropic effect of OPC-18790 was not affected by beta-blockade. OPC-18790 (10(-5) to 10(-4) M) prolonged the duration of action potential in guinea pig papillary muscles. Na+, K(+)-ATPase was not inhibited, but peak-III phosphodiesterase (low Km cyclic AMP specific fraction, inhibited by cyclic GMP) was inhibited by OPC-18790 (IC50 = 0.41 x 10(-6) M) in dog myocardium. However, such an inhibitory action of phosphodiesterase can hardly be reconciled with the lack of a positive chronotropic effect shown by OPC-18790. Thus, these results suggest that OPC-18790 may have an additional mechanism. The cardiovascular effects revealed by this study suggest that OPC-18790 may exert a beneficial effect in the treatment of congestive heart failure.

Animals↗

PubMed1992

Tumor incidence was not related to the thickness of visceral pleural in female Syrian hamsters intratracheally administered amphibole asbestos or manmade fibers.

Histological observations were performed on female Syrian hamsters 2 years after the intratracheal administration of amphibole asbestos, amosite, and crocidolite to evaluate the tumorigenicity of six types of fine manmade fibers (reported previously). A mesothelioma and a lung tumor were induced in 20 animals administered amosite, but no tumors were found in the crocidolite group. Because this incidence is not higher than that of manmade fibers, such as basic magnesium sulfate fiber [9 tumor-bearing hamsters in 20 hamsters (9/20)], metaphosphate fiber (5/20), calcium sulfate fiber (3/20), and fiberglass (2/20), it is suggested that some types of manmade fibers have a greater ability than asbestos to induce tumors. Moreover, as a specific observation in manmade fiber groups, tumors were induced at intracelial organs rather than at the pleural cavity. On the other hand, the average thickness of visceral pleura was higher in all asbestos and manmade fiber groups than in the control (2.9 microns), for instance, 36.95 microns in potassium titanate fiber group, 15.90 microns crocidolite group, 13.00 microns basic magnesium sulfate fiber group, and 10.45 microns in the rockwool group. Although both pleural thickening and mesothelioma are known as peculiar lesions in asbestos-exposed people, it might also be suggested that these lesions could be induced by different mechanisms from the result that there was no relation between the pleural thickening and mesothelioma incidence in hamsters.

Adenoma↗

PubMed1992

Modification of the clastogenic activity of X-ray and 6-mercaptopurine in mice by prefeeding with vitamins C and E.

The effect of a 30-d pretreatment with vitamin C (L-ascorbic acid) in the drinking water and vitamin E (all-rac-alpha-tocopherol) in the diet on the clastogenic activity induced by X-rays and 6-mercaptopurine was investigated in female ICR/Jcl mice by the bone-marrow micronucleus test. Prefeeding with vitamin E-deficient diets led to a significant decrease in serum vitamin E concentration and to an enhancement of micronucleus formation by X-rays in bone marrow cells. Although dietary supplementation with vitamin E significantly increased the vitamin E concentration in serum, it did not affect the frequency of X-ray-induced micronuclei. Treatment with a high level of vitamin C in drinking water was effective in protecting against micronucleus formation by X-rays. The increase in micronucleus frequency in the vitamin E-deficient mice compared with the mice fed vitamin E-normal diets was no longer observed when a high level of vitamin C in drinking water was given simultaneously. The most efficient protective action against X-rays was observed when vitamin E-supplemented diets and a high level of vitamin C in drinking water were used together as a pretreatment. Any combination of the vitamins did not affect the micronucleus induction by 6-mercaptopurine.

Animals↗

PubMed1992

Synthesis and interaction studies of watersoluble nucleic acid analogs containing serine as a spacer.

Watersoluble nucleic acid analogs containing L- or D-serine as a spacer were synthesized. Thymine was used as nucleic acid bases of these analogs. The base contents of these analogs were 93-94%. These analogs were found to form stable polymer complexes with Poly A or DNA by specific base-base interaction, which were observed from hypochromicity of UV spectra. In both cases, the maximum hypochromicity values of PEI-L-Ser-Thy were higher than that of PEI-D-Ser-Thy.

Circular Dichroism↗

PubMed1992

Immobilization of nucleoside on silica gel and specific separation of oligonucleotides.

Deoxyadenosine was immobilized on silica gel, in order to use as HPLC resins for selective separation of oligonucleotides. The longest retention time was observed for the complementary pd(T)4, and increased with decrease of temperature. This fact suggested that the main separation factor was the base pairing between complementary nucleic acid bases. These resins may be useful for separation of components of nucleic acids and polynucleotides as a specific separation system.

Chromatography, High Pressure Liquid↗

PubMed1991

Metal concentrations in human lung tissue, with special reference to age, sex, cause of death, emphysema and contamination of lung tissue.

Nine element concentrations in the lung tissues of 2,274 autopsies were determined in Japan by atomic absorption spectrometry. The metals determined were iron, calcium, magnesium, zinc, copper, cobalt, nickel, lead, and chromium. The range, mean, standard deviation, mode and median are described for each metal. Moreover, these data were analyzed statistically, based on their sex, age, degree of lung contamination (color and the amount of particle deposition), severity of pulmonary emphysema and cause of death. Iron, calcium, magnesium, zinc, copper and cobalt concentrations in the lung tissue seemed to be affected mostly by physiological variation and the levels in the blood. On the other hand, nickel, lead and chromium concentrations might reflect environmental exposure. Chromium concentration especially increased with age and showed a significantly positive correlation with the degree of contamination and severity of emphysema.

Age Factors↗

PubMed1991

Metal concentrations in lung tissue of subjects suffering from lung cancer.

Concentrations of nine metals (Fe, Ca, Mg, Zn, Cu, Co, Ni, Pb and Cr) concentrations in lung tissues from 224 lung cancer cases were compared with those in other cases to achieve an understanding of their contribution to the development of lung cancer and the varieties after the development of cancer. Comparisons of metal concentrations in each cell type of lung cancer were also performed. All cases were collected from routine autopsies in Tokyo and Saitama, Japan. The copper concentration in tissue from lung cancers was significantly higher than that in other specimens, although calcium, magnesium, zinc and cobalt concentrations in lung cancers were significantly lower than those in other cases. There were no significant differences in the 99% intervals (excluding extremely high values for occupationally exposed cases) for chromium, nickel and lead concentrations between lung cancers and other cases, although these values were lower in lung cancers. However, in comparisons of men only, the chromium concentration, the degree of lung contamination and the severity of pulmonary emphysema in lung cancer cases were significantly higher than those in other specimens. Moreover, percentages of lung cancer in men at each degree of contamination and each severity of emphysema increased with increasing grades. Thus, this finding could be evidence that the exposure to contaminants other than chromium and nickel in the air had affected the development of lung cancer, except for occupationally exposed individuals. Therefore, almost all chromium and nickel in lung tissue might not deposit in carcinogenic forms such as hexavalent chromium or nickel subsulfide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Frequency of late reversibility in stress-redistribution thallium-201 SPECT using an early reinjection protocol.

To assess the efficacy of an early thallium-201 reinjection protocol for reducing the need for late redistribution imaging, the frequency of thallium-201 late reversibility was prospectively assessed in 62 patients who had stress-redistribution thallium-201 studies by single-photon emission computerized tomography (SPECT), and who received 1 mCi of thallium-201 reinjection immediately following stress tomographic acquisition. These patients also demonstrated greater than or equal to 2 segments with nonreversible defects at 4-hour imaging and underwent late (18-to 72-hour) redistribution imaging. When the criterion of late reversibility was defined as greater than or equal to 1 segment with a 4-hour nonreversible defect demonstrating late reversibility, late reversibility was present in 36 (58%) of the 62 patients and in 88 (24%) of 368 SPECT segments. When the criterion of greater than or equal to 2 segments was used, late reversibility was found in 21 (34%) of the 62 patients and in 73 (20%) of the 368 segments. Of the 21 patients who had greater than or equal to 2 late reversible segments, 12 (57%) exhibited late reversibility in greater than or equal to 3 segments. The frequency of detected reversible defects increased from 32% by 4-hour imaging to 48% by combined 4-hour and late imaging (p less than 0.0001). The patients who demonstrated late reversibility could not be distinguished from those who had only late nonreversible defects by analysis of the clinical, exercise, and electrocardiographic (ECG) variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Tumorigenicity of fine man-made fibers after intratracheal administrations to hamsters.

Six types of man-made fibers were administered intratracheally (2.0 mg/animal each a week, for 5 weeks; total 10 mg/animal) to female Syrian hamsters that were observed histologically for 2 years after administration. The fibers were rock wool [average diameter (D) = 6.1 microns, average length (L) = 296 microns], fiberglass (D = 0.65 microns, L = 16.8 microns), potassium titanate fiber (D = 0.36 microns, L = 7.17 microns), calcium sulfate fiber (D = 1.0 microns, L = 17.8 microns), basic magnesium sulfate fiber (D = 0.45 microns, L = 22.4 microns), and metaphosphate fiber (D = 2.38 microns, L = 64.1 microns). Tumors were observed in hamsters that had received basic magnesium sulfate fiber (9/20), metaphosphate fiber (6/20), calcium sulfate fiber (3/20), and fiberglass (2/20) but not in the control, rock wool, or potassium titanate fiber groups. The primary sites of the tumors were not only in the pleural cavity but also in the intracelial organs, kidney, adrenal gland, bladder, and uterus. Only a few of the tumors were identified as mesotheliomas by histological examination. In addition to neoplastic lesions, fibrosis, pleural thickening, and chronic inflammatory changes in the lungs were observed in the hamsters, but these changes appeared too mild to foster a pneumoconiosis such as asbestosis.

Administration, Inhalation↗

PubMed1991

Promoting effect of sodium chloride solution mist on the induction of papillomas on Syrian hamster tracheal mucosa following administration of diethylnitrosamine.

The promoting effect of NaCl solution mist was studied in the induction of papillomas on Syrian hamster trachea following single subcutaneous injection of diethylnitrosamine (DEN). Sixty male hamsters were divided into three groups. Group A; Exposure to a 5% NaCl solution mist for 32 weeks following single subcutaneous injection of DEN at a dose of 3 mg/100 g body weight. Group B; Subcutaneous DEN injection alone. Group C; Exposure to the NaCl mist for 32 weeks alone. Total numbers of papillomas on the trachea in each group were 107 in group A, 64 in group B, and 0 in group C (P less than 0.05 between group A and B, P less than 0.01 between either groups A or B and C). Comparing the incidence of large papillomas with a diameter of more than 2 mm, that in group A hamsters was significantly greater than that of group B (22 large papillomas vs. 8 large papillomas, P less than 0.01). No difference in the effects on the epithelial cells of the nasal cavity, the bronchial or the alveolar cells in the lung was recognized between groups A and B. The hamsters in group C were not observed to have any changes in any of the respiratory organs. Inhalation of NaCl solution mist is considered to have a promoting effect on the induction of papillomas in the hamster trachea following DEN injection.

Adenocarcinoma↗

PubMed1991

[Cytogenetic analyses of diesel engine exhaust by sister chromatid exchange and micronucleus tests with mouse fetal liver cells].

The genotoxic effect of maternal exposure to diesel engine exhaust was studied by analyses of sister chromatid exchanges (SCEs) and formation of micronuclei with fetal liver cells. Fetal liver cells were obtained from pregnant ICR/JCl mice at the 16th day of gestation. Diesel engine exhaust was generated by running a small engine (YANMAR NSA-40CE, used as an electric generator, displacement: 269 cc). The concentrations of pollutants in the inhalation chamber were as follows; CO: 40-100 ppm, NO2: 2-4 ppm, and particulates: 2-4 mg/m3. Maternal mice were divided into three groups: the long-term exposure group, the short-term exposure group and the non-exposed control. Mice of the long-term group were exposed to the exhaust 4 hours daily from day 0 to the 16th day of gestation. Mice of the short-term group were similarly exposed but only on the 15th and 16th days of gestation. The number of SCEs of fetal liver cells was significantly increased in both the exposed groups. The long-term exposure group showed a significant increase in the number of SCEs in comparison with that of the short-term exposure group. In the micronucleus test with fetal liver cells, no significant change in the frequency of micronucleated cells was induced by exposure to diesel exhaust.

Animals↗

PubMed1991

[Effect of cigarette smoking and/or N-bis(2-hydroxypropyl)nitrosamine (DHPN) on the development of lung and pleural tumors in rats induced by administration of asbestos].

Occupationally induced lung cancer and mesothelioma have long been attributed to asbestos and moreover, several epidemiological studies have indicated a co-carcinogenic effect of cigarette smoking on the incidence of lung cancer in asbestos workers. The aim of the present study was to investigate the co-carcinogenic effects of asbestos and other carcinogens with emphasis placed on determining the effects of cigarette smoking on the incidence of asbestos induced carcinomas. Doses of 15 mg of chrysotile asbestos were administered intratracheally to Wistar rats alone and in conjunction with N-bis(hydroxypropyl)nitrosamine (DHPN) and/or cigarette smoking. DHPN at dose of 1 g/kg/B.W. was injected three times intraperitoneally, and the subject animals were exposed to smoke from 10 cigarettes per day, six days a week, for their entire life span. As a result, lung carcinomas were induced in one out of the 31 rats receiving only asbestos. Lung tumors were induced at a much higher incidence in the groups receiving DHPN alone and in conjunction with asbestos: of the 37 rats treated with DHPN alone 19 (51.4%) developed lung tumors, whereas those receiving asbestos as well showed an incidence of 68.4% (23/38) of carcinomas. The development of lung carcinomas (including adenocarcinomas, epidermoid carcinomas, anaplastic carcinomas, and combined carcinomas) was seen in 8 (21.6%) out of the 37 rats receiving DHPN alone and in 23 (60.5%) out of the 38 rats receiving asbestos as well. The incidence of lung carcinoma was significantly increased in combined treatment with asbestos than DHPN alone. In the group receiving asbestos in combination with cigarette smoke, 4 (13.8%) out of the 29 rats developed lung carcinomas, but these carcinomas were more common than in the group receiving only asbestos. Moreover, in the group administered asbestos, DHPN and smoking combined, lung tumors developed in 18 (62.1%) out of the 29, 15 (51.7%) of which proved to be malignant. Mesothelioma (pleura) was induced in three groups in the following combinations: DHPN plus asbestos, 8/38 (21.1%); smoking plus asbestos, 2/29 (6.9%); and smoking, DHPN and asbestos, 4/29 (13.8%). These tumors were extensively located, that is, on the parietal pleura, visceral pleura, epicardium and diaphragm surface. However, mesothelioma was not induced by asbestos alone nor by DHPN alone. Carcinogenicity of asbestos for pleural tumors was significantly promoted by combined treatment with DHPN to an extent greater than DHPN alone. It should be noted that asbestos plus smoking resulted in a higher incidence of mesothelioma than asbestos alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

PubMed1991

Synthesis and interaction studies of oligo and polyamino acids derivatives containing nucleosides.

Nucleic acid analogs of L-lysine derivatives containing uridine and/or adenosine were synthesized. As dimer models, Lys(Urd)-Lys(Urd) and Lys(Urd)-Lys(Ado) were prepared by activated ester method. These dimers were found to form complex with Poly A, which was observed from hypochromicity of UV spectra. Furthermore poly-L-lysine derivative containing uridine was also prepared. The maximum hypochromicity value of this polymer model with PolyA was higher than that of dimer models.

Adenosine↗

PubMed1990

cAMP regulation of the expression of prespore-specific genes, SP96 and Dp87, in disaggregated slug cells of Dictyostelium discoideum.

By Northern transfer and in vitro transcription assays, we examined how cAMP controlled the expression of prespore genes, Dp87 and SP96, in disaggregated slug cells of Dictyostelium discoideum. The transcription of these genes was halted soon after disaggregation and the remaining mRNAs were completely lost within 2 h. Addition of cAMP to cells which had lost the mRNAs induced the transcription of these genes, and the mRNAs were re-accumulated after a lag period of 30 min. The cAMP signal was transduced through the cell surface receptor. Protein synthesis was not needed for the induction of the transcription but was required for the accumulation of the mRNAs. We conclude that prespore gene expression is controlled by cAMP in two different ways: direct induction of transcription of the genes, and stabilization of the transcribed mRNAs by a protein(s) synthesized after addition of cAMP.

Blotting, Northern↗