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Biomedical subjects

J Takada

Publications and source records attributed to J Takada.

At least 55 records · Page 3Linked to original sources

Residual 60Co activity in steel samples exposed to the Hiroshima atomic-bomb neutrons.

Residual 60Co radioactivity produced by the neutrons from the Hiroshima atomic bomb has been measured by means of gamma-ray spectrometry for seven steel samples located up to 1,800 m slant range and one control sample obtained at 4.5 km from the hypocenter. After removing the main constituent of iron ions from the steel sample by the solvent extraction method, nickel and cobalt were chemically separated by the ion exchange process. Gamma-ray measurements were performed with a low background well-type germanium detector. Derived specific activities 60Co:Co were compared with previous measurements and with the calculation based on the neutron fluence of current dosimetry system DS86. It has been shown that a systematic discrepancy exists between the measured and calculated activity. The calculated-to-measured ratios for 60Co are consistent with those of 152Eu and 36Cl activity.

Chlorine↗

Case report: Insulin-like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia.

This case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin-like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour-associated IGF2.

Carcinoma, Hepatocellular↗

Estimation of dose absorbed fraction for 131I-beta rays in rat thyroid.

The dose absorbed fraction of rat thyroid by internal deposit of 131I has been calculated as a function of effective diameter of thyroid. The calculations were done using two types of Monte Carlo simulations: one was by a simple energy-loss calculation in spherical volume according to the electron stopping power, and another by a more realistic simulation using Monte Carlo N-Particle Transport code system Version 4A (MCNP). These two calculations were consistent with each other within a deviation of 5%. The absorbed fractions in spherical thyroid were drastically changed up to 5 mm diameter, and then almost all energy was deposited within 10 mm diameter. For the practical application to the animal experiment, the absorbed fractions of ellipsoid-shaped thyroids were also calculated for 1-, 4- and 9-week-old rats, where the fractions were estimated to be 0.61, 0.67 and 0.68, respectively. It was also found that the absorbed fraction of the ellipsoid with various dimensions can be simulated by a calculation for spherical volume with a comparable effective diameter.

Animals↗

The presence of a manganese-rich particle in lysosome of rat pancreas due to excess manganese treatment.

Manganese (Mn) accumulates at a higher level in the pancreas than in any other organs when excess Mn is administered to the rat. The present study is carried out to analyze the intracellular localization of Mn existed in the pancreatic cell of Mn-treated rats. Transmission electron microscope and X-ray micro-analysis connected with a rapid freezing fixation technique showed that a large amount of Mn was localized in lysosomal particles of the pancreatic cell of Mn-treated rats. The Mn-rich particles disappeared when the element-administration was discontinued, showing that the accumulation of Mn is reversible. To confirm that Mn is in the lysosomes, a centrifugal subcellular-fractionation and a neutron activation analysis were carried out. The result indicated that much Mn existed in the lysosomal fraction.

Animals↗

Long-term treatment of indomethacin reduces vertebral bone mass and strength in ovariectomized rats.

We investigated the effect of the long-term treatment of indomethacin, on lumbar spinal bone mineral density (LSBMD), cancellous bone mass, structure, and strength of vertebral body in old ovariectomized (OVX) rats. Ten-month-old female Wistar rats were divided into five groups: the sham operated + vehicle (sham + VEH) group, the OVX + vehicle (OVX + VEH) group, the OVX + indomethacin (IN) 1.5 mg/kg/week (OVX + IN1.5) group, the OVX + IN 6.0 mg/kg/week (OVX + IN6.0) group, and the OVX + IN 15.0 mg/kg/week (OVX + IN15.0) group. IN or vehicle were given by subcutaneous injection (s.c.) three times per week. The treatments were started at 1 week after operation and continued for 24 weeks. LSBMD (L2-L5) was measured at 0, 12, and 24 weeks after the beginning of treatment. At the end of the experimental period, the animals were sacrificed, and bone histomorphometrical and biomechanical analysis of lumbar vertebral body were done. LSBMD, trabecular bone volume (BV/TV), and trabecular thickness (Tb.Th) decreased significantly in a dose-related manner with IN. In the OVX + IN15.0 group, LSBMD decreased by 12.7%, BV/TV decreased by 65.5%, and Tb.Th decreased by 32.8%, compared with the OVX + VEH group. In addition, the maximum stress in a compressive mechanical test of L4 vertebral body in OVX groups was also decreased in a dose-related manner with IN, and this value in the OVX + IN15.0 group was 31.3% lower than in the OVX + VEH group. We conclude that long-term treatment with IN accentuated the OVX-related decrease in trabecular bone mass and the compressive strength of lumbar vertebrae.

Analysis of Variance↗

[Surgically treated unruptured sinus of Valsalva aneurysm: a case report].

A 73-year-old man was admitted because of progressive dyspnea. Echocardiography revealed a markedly dilated right sinus of Valsalva and severe aortic regurgitation. Coaptation loss of the aortic valve leaflets was thought to be the cause of regurgitation and congestive heart failure, a rare complication of the unruptured sinus of Valsalva aneurysm. Surgical treatment should be considered to prevent life-threatening heart failure and rupture of the aneurysm even in patients without overt heart failure.

Aged↗

Dexamethasone enhances the osteogenic effects of fluoride in human TE85 osteosarcoma cells in vitro.

The in vitro osteogenic effects of fluoride have not always been consistently observed in human bone cells. The present study sought to test if dexamethasone (Dex) could potentiate the action of fluoride to increase the detectability of the stimulatory effects of fluoride on [3H]thymidine incorporation, alkaline phosphatase (ALP) specific activity, collagen synthesis, and osteocalcin secretion in human TE85 osteosarcoma cells. Neither Dex at 10(-10)-10(-6) M or fluoride at a mitogenic dose (100 microM) had any consistent stimulatory effects on thymidine incorporation. When the cells were treated with both agents simultaneously, significant and highly reproducible stimulations were observed. The mitogenic effects of the two agents were confirmed with cell number counting. Analysis of variance (ANOVA) revealed a significant interaction (P < 0.001) between fluoride and Dex on cell proliferation. The enhancing effect of Dex on [3H]thymidine incorporation was not due to a shift of the optimal dose response of fluoride. Though fluoride alone or Dex alone also had no consistent effect on ALP specific activity, the co-treatment with fluoride and Dex for 24 hours produced significant (P < 0.001, ANOVA) stimulation in ALP specific activity. Fluoride alone had no consistent effect on collagen synthesis and on 1, 25(OH)2D3-dependent osteocalcin secretion, whereas Dex treatment consistently inhibited these two osteoblastic parameters in a dose-dependent manner. However, both the collagen synthesis and osteocalcin secretion rates were significantly higher (P < 0.001 ANOVA for each) when the cells were co-treated with Dex and fluoride (100 microM) than when they were treated with Dex alone. Thus, these data indicate that the response in collagen synthesis and osteocalcin secretion to fluoride stimulation was more readily observed in the presence of Dex than in its absence. ANOVA analysis revealed that the interaction between fluoride and Dex on collagen synthesis, but not the 1,25(OH)2D3-dependent osteocalcin secretion, was significant (P < 0.02). In summary, we have demonstrated for the first time that in TE85 cells (1) Dex potentiated the effects of fluoride on cell proliferation, ALP specific activity, and collagen synthesis; (2) while Dex at 10(-7)-10(-6) M alone inhibited the collagen synthesis and at 10(-9)-10(-6) M reduced osteocalcin secretion, Dex at 10(-8)-10(-6) M significantly stimulated the proliferation of TE85 cells; and (3) Dex interacted with fluoride to increase the percentage of experiments showing an osteogenic action of fluoride. In conclusion, the in vitro osteogenic actions of fluoride in human TE85 cells are more consistently observed in the presence than in the absence of Dex.

Alkaline Phosphatase↗

Determination of the relative neutron sensitivity of a C-CO2 ionization chamber.

The neutron sensitivity of a C-CO2 ionization chamber has been experimentally determined in the neutron energy range of 0.1-1.2 MeV. Eleven kU data were obtained which ranged from 0.04 to 0.1 as a function of neutron energy. There were two peaks in the spectrum of the kU factor, and their positions corresponded to the resonance energies of the kerma factors of carbon dioxide, of which the energies are about 0.4 and 1 MeV. The present data agree with the data obtained at the National Institute for Radiological Sciences in Chiba, Japan (NIRS). The energy dependences of the sensitivity were calculated by using the kerma and the W-value ratios of gas to soft tissue for comparison. The experimental data were reproduced well by the calculations.

Biophysical Phenomena↗

[Isolation and purification of pregnancy-associated plasma protein A].

We tried to purify pregnancy-associated plasma protein A (PAPP-A) from normal term maternal serum in this study by means of a three step chromatographic procedure. At first 30 ml of maternal serum samples were applied to a column for sieve chromatography and eluted according to molecular weight. PAPP-A was detected in the high molecular weight fraction area by radioimmunoassay for PAPP-A, and 91% of the total amount of PAPP-A in the maternal samples was recovered. Secondary PAPP-A containing fractions were applied to a Heparin-Sepharose column and eluted by a stepwise increase in NaCl 0.15, 0.30 and 0.60 M in 0.05 M Tris-HCl buffer, pH 7.8. Ninety-three percent of PAPP-A in applied samples was recovered under the 0.6 M NaCl condition. Thirdly the pooled fractions which contained PAPP-A after Heparin-Sepharose affinity chromatography were applied to DEAE-Sephacel Chromatography and eluted by a stepwise increase in NaCl 0.15, 0.30 and 0.45 M in 0.01 M acetate buffer, pH 5.5. Ninety-one percent of PAPP-A in applied samples was recovered under the 0.3 M NaCl condition. Finally PAPP-A containing fractions were concentrated 10 times and 3.8 IU (1.7 mg) of PAPP-A was isolated. The purification schedule removed approximately 99% of total protein in the maternal serum while 74% of PAPP-A was recovered. The purification factor (fold), which was calculated as the increase in specific activity (mIU:PAPP-A/mg:protein) in comparison with the starting value in the maternal serum, was 526. And the purity (mg:PAPP-A/mg:protein) of the final product was 68.4%. Analysis of the final purified material by SDS-PAGE showed a single band of 200kDa, and western blot analysis showed that the main purified protein was PAPP-A. The immunological identity of the PAPP-A purified in this study to the PAPP-A donated by Teisner et al., was recognized by crossed immunoelectrophoresis and tandem crossed immunoelectrophoresis. We hope that the new PAPP-A purified in this study can be utilized for the development of a sensitive and convenient assay for PAPP-A and its standard material, and also for basic study to clarify the biological function of PAPP-A in the human body.

Blotting, Western↗

Pretreatment with low doses of norethindrone potentiates the osteogenic effects of fluoride on human osteosarcoma cells.

We recently reported that picomolar doses of norethindrone (NET), a synthetic analog of 19-nortestosterone, significantly stimulated human TE85 osteosarcoma cell proliferation, differentiation, and activity in vitro. In the present study, we investigated the possibility that NET interacts with another osteogenic agent, i.e., fluoride, to stimulate human TE85 osteosarcoma cell proliferation, differentiation, and activities. Bone cell proliferation was measured by the stimulation in [3H]thymidine incorporation. Differentiation was monitored by the increase in alkaline phosphatase-specific activity. Osteoblastic activity was assessed by the stimulations in collagen synthesis and in osteocalcin secretion (in the presence of 1 nM 1,25-dihydroxyvitamin D3). When the human TE85 cells were incubated with mitogenic doses of NET and fluoride concurrently, the stimulatory effects of the two agents on these parameters exhibited no significant interaction. The enhancing effect of NET on the osteogenic effect of fluoride was not due to a shift of the fluoride dose response curve. Pretreatment with NET for 24 h followed by a treatment with a mitogenic dose (i.e., 100 microM) of fluoride for an additional 24 h significantly and synergistically potentiated the effects of fluoride on the [3H]thymidine incorporation, alkaline phosphatase-specific activity, collagen synthesis, and osteocalcin secretion, compared with those with the subsequent vehicle (0.05% ethanol) treatments. In contrast, pretreatment with fluoride for 24 h before the addition of NET for 24 h did not produce significant synergistic stimulations in the test parameters. Pretreatment of TE85 cells with the same doses of dihydrotestosterone or progesterone prior to treatment with fluoride under the same conditions did not induce synergistic potentiation of fluoride in [3H]thymidine incorporation, suggesting that the synergistic interaction with fluoride is probably not a common property of anabolic sex steroids. In summary, we found that: (1) the osteogenic effects of fluoride and NET were additive when cells were treated with both agents concurrently; (2) a 24-h pretreatment with picomolar doses of NET potentiated the osteogenic actions of fluoride in human TE85 osteosarcoma cells; and (3) pretreatment with NET produced a subsequent fluoride response that was synergistic. In conclusion, these findings led us to speculate that the osteogenic actions of NET and fluoride act through different mechanisms, and that NET at low doses has a permissive effect on the osteogenic effects of fluoride, and as such NET may be used in concert with fluoride to increase osteoblast proliferation, differentiation, and activity.

Alkaline Phosphatase↗

Mechanism on insulin-like action of vanadyl sulfate: studies on interaction between rat adipocytes and vanadium compounds.

When rats with streptozotocin (STZ)-induced diabetes were given a daily intraperitoneal (i.p.) injection of VOSO4 (+4 oxidation state of vanadium), their serum glucose dropped from hyperglycemic level to normal level within 2d and serum free fatty acid (FFA) level also dropped to normal level. Vanadium was incorporated in most organs as well as in the adipose tissues, as detected by neutron activation analysis (NAA). The mechanism for the insulin-like action vanadium in terms of FFA release from isolated rat adipocytes was investigated: (1) Vanadyl (IV) and vanadic (III) ions normalize the FFA release in the adipocytes treated with epinephrine; (2) vanadate (V) ion treated with ascorbic acid, cysteine or glucose is effective in normalizing the FFA release but vanadate ion alone has no effect on FFA release; (3) vanadyl ion is incorporated into the adipocytes, while vanadate ion is not, as indicated by ESR spectroscopy; and (4) vanadyl ion can act on the glucose transporter, as indicated by experiments using cytochalasin B which is an inhibitor of this transporter. From these results, the normalization of both serum glucose and FFA levels by vanadyl ion was concluded to be due to the incorporation of vanadyl ion into the adipocytes, in which the metal ion acts on the glucose transporter and induces both the promotion of glucose uptake and the decrease of FFA release form peripheral adipocytes. The vanadyl state was suggested to be a possible pharmacologically active form of vanadium allowing the insulin-like action.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗

[mRNA expression and protein localization of placental tissue protein 11, 12, 19 in gynecologic malignant tumors].

In recent years, the localization and function of placental tissue proteins (PPs), extracted by Bohn et al., have been extensively studied, the genetic code has been identified for each of the PPs. The present study was carried out to clarify the mRNA expression and protein localization of PP11, PP12, PP19 at the cell level and also to define PP19 the nature of which has remained obscure. PP19 was said to be placenta-derived S-100P. PP11 mRNA was not expressed in cytotrophoblast-derived normal placental tissue or endometrium-derived normal cells, but was expressed in syncytiotrophoblast-derived normal placental tissue, and in choriocarcinoma and endometrial adenocarcinoma, suggesting its involvement in carcinogenesis. PP12 mRNA was expressed in cytotrophoblast-derived normal placental tissue or endometrium-derived normal cells, but was not expressed in syncytiotrophoblast-derived normal placental tissue, choriocarcinoma or endometrial adenocarcinoma, suggesting that this protein serves in the function of normal cells. PP19 mRNA was expressed in the squamous epithelial cells of the uterine cervix and the villous cells, PP19 was localized in more differentiated regions, where cells tended toward keratinization, in both normal and dysplastic uterine cervices. In squamous cell carcinoma, PP19 was localized in more differentiated cells with a large cytoplasm. PP19 mRNA was not expressed in normal endometrial glands, but was detected in endometrial adenocarcinoma, suggesting its involvement in cell differentiation in cervical epitherial cells.

Base Sequence↗

The lipophilic weak base (Z)-5-methyl-2-[2-(1-naphthyl)ethenyl]-4-piperidinopyridine (AU-1421) is a potent protonophore type cationic uncoupler of oxidative phosphorylation in mitochondria.

The lipophilic weak base AU-1421 acts as a simple protonophoric uncoupler of oxidative phosphorylation in rat liver mitochondria judging from the following observations. In the absence of any carrier lipophilic anions or P(i), AU-1421 stimulated the rate of state 4 respiration maximally about 7-fold at a concentration of 30 nmol/mg mitochondrial protein. At the same maximum effective concentration, it also inhibited ATP synthesis, released oligomycin-inhibited state 3 respiration, dissipated the proton motive force in the energized state, and activated latent H(+)-ATPase. AU-1421 also allowed proton conduction in both mitochondrial membranes and liposomes. These actions of AU-1421 resemble those of the typical anionic uncoupler SF6847. A marked difference between the two was, however, that ATPase activation by AU-1421 was not suppressed at higher concentrations of AU-1421, whereas ATPase activated by SF6847 was suppressed on increase of the SF6847 concentration. The finding that this simple protonophoric cation acts as an uncoupler at a micromolar concentration is significant, because all true (i.e., protonophore type) uncouplers known so far are anionic not cationic. Thus, AU-1421 is a unique uncoupler of the protonophore type.

Adenosine Triphosphate↗

DNA cleavage by hydroxyl radicals generated in a vanadyl ion-hydrogen peroxide system.

Vanadyl ion (+4 oxidation state) has been shown to be an effective agent for chemoprotection of cancers in animals. For understanding the mechanism, distribution of vanadium was studied. More vanadium was found to accumulate in the nuclei of the liver of rats when it was given as vanadyl sulfate than when it was given as sodium vanadate (+5 oxidation state). The reactivity of vanadyl ion with DNA was investigated by the DNA cleavage technique and the reaction mechanism by ESR spectroscopy. Incubation of double-strand DNA with vanadyl ion and hydrogen peroxide resulted in marked concentration- and pH-dependent DNA cleavage. Studies by the ESR spin-trap method demonstrated that hydroxyl radicals are generated during the reactions of vanadyl ion with hydrogen peroxide. Thus the antineoplastic action of vanadyl ion is proposed to be due to DNA cleavage by hydroxyl radicals generated in the cells.

Animals↗