Biomedical subjects
Publications and source records attributed to M Onoda.
The liquid chromatography-mass spectrometry (LC-MS) following on from the two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) technique was applied for the analysis of proteins in a renal stone found in a hyperuricemic patient. This technique was sensitive enough to detect small quantities of proteins even in a renal stone.
As a source of hematopoietic stem cells for transplantation, the use of peripheral blood stem cells (PBSCs) has become routine and comparable to that of the use of bone marrow. Recently, elderly patients with hematological malignancies also have been allowed to receive minitransplantations with nonmyeloablative conditioning regimens under sufficient PBSC infusion. As a result of these minitransplantations, elderly donors have been chosen increasingly from the siblings of elderly patients. We analyzed factors influencing the condition of CD34+ cells in the first days of collection in 49 healthy donors from July 1995 to January 2001. The median dose of recombinant human granulocyte colony-stimulating factor was 8 microg/kg/day (range 8 - 10) over 3 days. The target number of CD34+ cells used in this study was > or = 3 x 10(6) cells/kg of recipient body weight. The median apheresis volume was 12 L. Except for one 60 year old man, we obtained an adequate number of stem cells. In the regression analysis, a negative correlation was seen between donor age and the number of CD34+ cells/kg of recipient body weight per 12 L volume (Y = aX + b; a = -0.07507; b = 6.629996; r = -0.50985; p = 0.000252). Significantly higher apheresis results were obtained in donors younger than 45 years compared with donors 45 years old and older (p < 0.0227). There were no correlations among the number of CD34+ cells, donor body weight, and the number of leukocytes in peripheral blood on the first day of apheresis.
Novel oligonucleotide analogues, containing a 3'-amino-2',4'-BNA unit, were successfully synthesized, and they showed superior duplex and triplex forming ability as well as BNA itself, along with remarkable enzymatic stability.
The structure of pseudohexagonal-type InFe(1--x--4 delta)Ti(x+3 delta)O(3+x/2) (x = 0.61, delta = 0.04), indium iron titanium oxide, was refined on the basis of a four-dimensional superspace group. The crystal has a compositely modulated structure consisting of two orthorhombic subsystems mutually incommensurate in b. The first subsystem InFe(1-x-4 delta)Ti(x+3 delta)O(2) has a delafossite structure with lattice parameters a = 5.835 (3), b(1) = 3.349 (1) and c = 12.082 (7) A. The second subsystem with b(2) = 2.568 (6) A consists of O atoms. The superspace group of the overall structure is Ccmm(1, 1.305, 0)s00, which can be converted to Amam(0, 0, 0.305)0s0 (No. 63.8). Refinement on 1105 unique reflections converged to R = 0.0303 and wR = 0.0325 with 63 structural parameters. The structure of the first subsystem is the alternate stacking of an edge-shared InO(6) octahedral layer and an Fe/Ti triangle-lattice plane along c. A sheet of O atoms in the second subsystem is also extending on the Fe/Ti plane, where displacive modulation of atoms is prominent.
The crystal structure of a layered compound Sc(2)B(1.1)C(3.2), scandium boride carbide (M(r) = 140.43), has been re-refined as a commensurate composite crystal using 1795 single-crystal X-ray diffraction intensities with I > 2 sigma(I) collected by Shi, Leithe-Jasper, Bourgeois, Bando & Tanaka [(1999), J. Solid State Chem. 148, 442--449]. The crystal is composed of two layered subsystem structures, i.e. Sc--C--Sc sandwiches and graphite-like layers of the composition B(1/3)C(2/3). The structure refinement was performed in a five-dimensional formalism based on the trigonal superspace group P3m1(p00)(0p0)0m0. The unit cell and other crystal data are a = b = 3.387 (1), c = 6.703 (2) A, V = 66.59 (1) A(3), sigma(1) = (9/7 0 0), sigma(2) = (0 9/7 0), Z = 1, D(x) = 3.501 Mg m(-3). Two different three-dimensional sections through the superspace were analyzed, corresponding to two different superstructure models, one with P3m1 and the other with P3m1. A random distribution of B and C was assumed in the graphite-like layer and 41 structural parameters were introduced. R(F)/wR(F) were 0.0533/0.0482 and 0.0524/0.0476, respectively, for the first and second models. Although the difference between these R(F) or wR(F) values was too fine to exclude one of the models definitely, the advantages of using a superspace group were obvious. It not only brought about better convergence of refinement cycles by virtue of fewer parameters, but also gave an insight into the problem of symmetry of the superstructure.
As an attempt to elucidate the factor(s) responsible for the poor performance of a copper(II)-phthalocyanine aminopropylsilica gels (CU-PCSD) column for HPLC, the silanol and/or amino groups remaining on Cu-PCSD were endcapped with trimethylchlorosilane (TMCS) or N-trimethylsilylimidazole (TMSI). The trimethylsilylated Cu-PCS(D)S (Cu-PCSD-TMCS and -TMSI) were investigated concerning their performance as an HPLC-stationary phase in the separation of pi-electron-rich polyaromatic hydrocarbons (PAHs), such as mutagenic anthracene and pyrene. As a result, trimethylsilylation with TMSI, which reacts only with silanol-groups, was not effective to improve the column efficiency. In contrast, trimethylsilylation by TMCS, which reacts with both the silanol- and amino-groups, improved the theoretical plate numbers (N) for PAHs separation with the Cu-PCS(D) column, indicating that the low N values on the Cu-PCSD column were caused by electrostatic interactions between PAHs and the remaining amino-groups on Cu-PCS(D). Furthermore, the retention data of mutagenic heterocyclic amines (HCAs) indicated that the remaining amino groups interact with the polar groups of HCAs.
To probe the nature of the even-fraction quantum Hall system, we have investigated the low-lying excitation spectrum by exact diagonalization for finite systems. We have found (i) a striking one-to-one correspondence (i.e., a shell structure) between the spectrum and those for free (composite) fermions, (ii) a surprisingly straight scaling plot for the excitation energy that gives a zero gap (metal) in the thermodynamic limit, (iii) the effective mass evaluated from the scaling becoming heavier for nu = 1/2,1/4,1/6, but (iv) some deviations from the single-mode or the Hartree-Fock composite fermion approximation.
We have hypothesized that one aspect of the antitumor activity of curcumin (diferuloylmethane) during the promotion stage of mammary gland tumorigenesis may be linked to reduction of free radicals (Inano et al., Carcinogenesis, 20: 1011-1018, 1999). Nitric oxide (NO) has been found to inflict damage on important biomolecules, and the overproduction of NO in diseases may be implicated in carcinogenesis and tumor progression. We have reported that the presence of three isoforms of nitric oxide synthases (NOS) and NO generation in the mammary gland correlate with the mammary gland development and mammary carcinogenesis. We, therefore, investigated the inhibitory activity of curcumin for the production of NO in rat mammary glands by using an organ culture system to validate the effectiveness and usefulness of curcumin in the pathophysiology of the mammary gland. A diced mammary gland (approximately 3 mm cubes) from the inguinal part of a female Wistar-MS rat treated with estradiol and progesterone was cultured with 2 ml of 5% FCS/DMEM in the presence or absence of LPS (0.5 microg/ml) for 2-3 days. Curcumin ( approximately 100 microM) was added at the same time to the LPS-treated cultures. In some experiments, curcumin was added to the culture after the LPS had been washed out. The NO production was significantly increased (by almost 20-fold compared to the control) by the addition of LPS to the culture system. This enhancement of NO production by LPS was reduced to 76 and to 56% by addition of 30 and 100 microM curcumin, respectively, to the culture. When LPS was eliminated from the culture after prestimulation for 1 day, the production of NO by the mammary gland dropped off, although some NO was still detectable. Curcumin did not further inhibit the production of NO by the prestimulated mammary gland after the elimination of LPS from the culture. The inducible nitric oxide synthase (iNOS, 122 kDa) and endothelial nitric oxide synthase (eNOS, 152 kDa) isoforms were detected in the mammary gland extracts at the end of the organ culture. The quantity of iNOS was apparently increased in the gland treated with LPS, while the eNOS expression was clearly diminished. Curcumin (100 microM) obviously suppressed the iNOS expression in the mammary glands cultured with LPS, and a recovery in the eNOS expression was observed. On the other hand, curcumin exhibited scavenging activity for the NO released from N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethanamine (NOC 12), a NO donor compound, in the coincubation mixture. These results indicate that curcumin has the ability to inhibit iNOS induction by LPS in the mammary gland and to scavenge NO radicals, which might explain, at least partly, its therapeutic properties in inflammation of the mammary gland.
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PURPOSE: This investigation evaluated the inhibitory effect of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721) against the initiation of mammary tumourigenesis by irradiation, and the antipromotion activity of tamoxifen in the development of radiation-initiated mammary tumours. MATERIALS AND METHODS: Lactating rats were injected with WR-2721 and then irradiated with gamma-rays (1.5 Gy) at day 21 of lactation. The rats were divided into three groups 1 month after irradiation and were implanted with a pellet either of cholesterol as an inert control, diethylstilbestrol (DES) as a tumour-promoting agent, or DES combined with tamoxifen. For the control experiments, non-irradiated and irradiated rats receiving saline instead of WR-2721 were treated with a pellet by the same procedures. RESULTS: The highest incidence (85%) for tumourigenesis of mammary glands was observed in the irradiated rats that had been previously injected with saline following treatment with DES Administration of WR-2721 prior to the irradiation significantly decreased the incidence of mammary tumours to 52.2%. The treatment with DES pellets combined with tamoxifen in the irradiated rats previously injected with saline also markedly suppressed the incidence of mammary tumours even further to 4.4%. Also, the development of mammary tumours was completely prevented in the rats treated with WR-2721 prior to irradiation and then implanted with DES pellets combined with tamoxifen. CONCLUSIONS: These results suggest that the administration of WR-2721 prior to irradiation has an inhibitory effect on the initiation phase, resulting in a partial reduction of mammary tumour development, and that the combination of WR-2721 at the initiation phase with tamoxifen at the promotion phase is quite effective in preventing mammary tumourigenesis induced by radiation.
This investigation evaluated the preventive effect of curcumin on radiation-induced tumor initiation in rat mammary glands. Fifty-four female rats were mated and then divided into two groups at day 11 of pregnancy. As the control group, 27 rats were fed a basal diet during the experimental period. As the experimental group, 27 rats were fed a diet containing 1% curcumin between day 11 of pregnancy and parturition (day 23 of pregnancy). All rats of both groups received whole body irradiation with 1.5 Gy gamma-rays from a (60)Co source at day 20 of pregnancy and were then implanted with a diethylstilbestrol pellet 1 month after weaning. A high incidence (70.3%) of mammary tumorigenesis was observed in the control group. The tumor incidence (18.5%) was significantly reduced in the rats fed curcumin during the initiation stage. The appearance of the first palpable tumor was delayed by 6 months in the curcumin-fed group and the average latent period until the appearance of mammary tumors was 2.5 months longer in the curcumin-fed group than in the control group. By histological examination, the proportion of adenocarcinoma (16.7%) in total tumors in the curcumin-fed rats was found to be decreased to half that (32.1%) in the control group. Compared with the control rats, the body weight of rats in the experimental group was decreased slightly by administration of the curcumin diet from day 11 of pregnancy, in spite of a similar intake of diet, but had recovered to the level of the control by the end of the experiment. At the time of irradiation, curcumin did not have any effect on organ weight or on the development and differentiation of mammary glands of pregnant rats. In addition, the serum concentrations of fatty acids, thiobarbituric acid-reactive substances and ovarian and pituitary hormones, except LH, remained at the control level. Also, no change in litter size and body weight of pups born from curcumin-fed rats indicated no toxicity of curcumin. These results suggest that curcumin does not have any side-effects and is an effective agent for chemoprevention acting at the radiation-induced initiation stage of mammary tumorigenesis.
Oral contraceptives are used among women worldwide, and radiation is being used increasingly for diagnosis or therapy. We have investigated the effects of contraceptive steroids on the risk of mammary tumors initiated by radiation. Virgin rats received whole-body irradiation with 2.6 Gy gamma-rays 1 month after the administration of low- or high-dose pellets of contraceptive steroids, such as 17alpha-ethinylestradiol (EE(2)) combined with 19-norethisterone (NET). The high-dose pellet was removed 1 month after irradiation, but administration of the low-dose pellet was continued for up to 1 year. The incidence (33.3%) of mammary tumors initiated with radiation was not modified by the long-term administration of the low-dose pellets. However, the incidence (58. 3%) was increased significantly by the irradiation during administration of the high-dose pellets, but no significant difference in the proportion of adenocarcinoma and fibroadenoma was observed. Meanwhile, parous rats were irradiated with 2.6 Gy gamma-rays at weaning, a period of greater susceptibility to radiation, and then were implanted with the low-dose pellets 1 month later. The highest incidence (90%) of mammary tumors was detected in the parous rats. The proportion of adenocarcinomas in the parous irradiated rats increased significantly on treatment with the low-dose pellets. The results suggest that administration of the high-dose pellets of EE(2)-NET, but not of the low-dose pellets, enhances susceptibility to the initiation by gamma-rays of mammary tumors in virgin rats, and that the low-dose pellets act as a tumor promoter in the mammary glands of parous rats irradiated at weaning.
We evaluated the effect of WR-2721 [S-2-(3-aminopropylamino)-ethylphosphorothioic acid] and cysteamine (2-mercaptoethylamine) on the development of radiation-induced mammary tumors in rats. Pregnant rats were treated with WR-2721 or cysteamine 30 min prior to whole-body irradiation with gamma rays from a (60)Co source at a dose of 1.5 or 2.6 Gy. Additional pregnant rats were given saline and then exposed to gamma rays at a dose of 0, 1.5 or 2.6 Gy as a control. All rats were implanted with pellets of diethylstilbestrol, a tumor promoter, 1 month after termination of nursing and were observed for 1 year to detect palpable mammary tumors. No mammary tumors developed in the saline-injected nonirradiated rats. However, when rats were irradiated with 1.5 or 2. 6 Gy after saline treatment, the incidence of mammary tumors was high (71.4 and 92.3%, respectively). Administration of WR-2721 or cysteamine prior to irradiation with 1.5 Gy significantly decreased the tumor incidence (23.8 and 20.8%, respectively). Tumor prevention by either agent was less effective at the higher dose. The appearance of the first mammary tumor occurred later in rats treated with WR-2721 or cysteamine than in the control rats. An increasing rate of adenocarcinoma in the control group was observed with increasing dose from 1.5 Gy up to 2.6 Gy. However, the development of adenocarcinoma did not increase after pretreatment with WR-2721 or cysteamine in rats irradiated with 2.6 Gy. Many of the mammary tumors that developed in the control rats were of the ER(+)PgR(+) type. Administration of WR-2721 produced no tumors of the ER(+)PgR(+) type. Cysteamine treatment increased the development of ER-negative tumors. The serum concentration of progesterone was significantly higher in rats treated with WR-2721 or cysteamine than in the control rats. On the other hand, the estradiol-17beta concentration was reduced by treatment with WR-2721, but not significantly compared to the control. WR-2721 and cysteamine had no effect on the prolactin concentration of the irradiated rats. The results suggest that administration of WR-2721 or cysteamine prior to the irradiation has a potent preventive effect on theinitiation phase during mammary tumorigenesis.
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An error in the figures is reported. In the paper by Onoda et al. [Acta Cryst. (1999), B55, 721-725] the figures are given in the wrong order. Fig. 1 on p. 723 should in fact be Fig. 2 on p. 724 and vice versa. The figure captions are given correctly.
The structure of the orthorhombic room-temperature phase of Cu(8)GeS(6) (copper germanium sulfide), M(r) = 773.27, has been refined on the basis of X-ray diffraction data from a 12-fold twinned crystal applying a six-dimensional twin refinement technique. For 1804 unique reflections measured using Mo Kalpha radiation, R(F) was 0.083 with 77 structure parameters and 12 scale factors. The symmetry operations, the unit cell and other crystal data are (0, 0, 0; (1/2), (1/2), 0) + x, y, z; y, x, z; (1/4) - x, (3/4) - y, (1/2) + z; (3/4) - y, (1/4) - x, (1/2) + z; a = b = 9.9073 (3) Å, c = 9.8703 (4) Å, alpha = beta = 90 degrees, gamma = 90.642 (4) degrees; V = 968.7 (1) Å(3), Z = 4, D(x) = 5.358 Mg m(-3), µ = 21.70 mm(-1). The standard setting of the space group and the reduced unit cell are Pmn2(1); a = 7.0445 (3), b = 6.9661 (3), c = 9.8699 (5) Å; Z = 2.
The role of prolactin in the initiation of mammary tumorigenesis by radiation was evaluated in ovarian hormone-free rats. Rats were bilaterally ovariectomized at 23 days of age, and then, at 2.5 months of age, two pituitaries obtained from mature rats of the same strain were transplanted underneath the kidney capsule as a means of increasing the serum prolactin level to provide stimulation of development of mammary glands. After 2 weeks, the ovariectomized rats with ectopic pituitary glands were exposed to whole body irradiation of 2.6 Gy of gamma-rays from a 60Co source and then treated with diethylstilbestrol as a tumor promoter. For the control, ovariectomized rats without ectopic pituitary glands were exposed and treated in the same way as the experimental group. A significant increase of serum prolactin level was observed at the time of irradiation by the pituitary transplanted rats, and intense immunohistochemical reaction with a specific anti-prolactin antiserum was detected in the ectopic pituitary glands. Also, mammary glands in the pituitary transplanted rats, ovariectomized before puberty, showed lactiferous ducts without alveolar buds at the time of tumor initiation. The pituitary transplanted rats showed a significantly increased incidence of adenocarcinoma and fibroadenoma compared with the control. Many of the mammary tumors induced in the pituitary transplanted rats given radiation were estrogen receptor (ER)(+) progesterone receptor (PgR)(+) and ER(+)PgR(-) tumors, whereas ER(-)PgR(-) tumors were mainly obtained in the control rats. In the experimental group, many of the fibroadenomas had low concentrations of ER and no PgR, while the adenocarcinomas had moderate concentrations of ER and high PgR. These results suggest that hypersecretion of prolactin from the pituitary transplants developed lactiferous ducts and accelerated the tumorigenesis of mammary glands initiated by radiation in the absence of synergism with ovarian hormones.
Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine (dG) to 8-hydroxydeoxyguanosine (8-OHdG) in DNA, which is linked to increased mitochondrial DNA (mtDNA) deletions. We investigated mtDNA deletions and 8-OHdG in the muscle DNA of non-insulin-dependent diabetes mellitus (NIDDM) patients. mtDNA deletion of 4977 bp (delta mtDNA4977) and the content of 8-OHdG in the muscle DNA of the NIDDM patients were much higher than those of the control subjects. There was a significant correlation between delta mtDNA4977 and the 8-OHdG content (P < 0.0001). Both delta mtDNA4977 and the 8-OHdG content were also correlated with the duration of diabetes. Delta mtDNA4977 and the 8-OHdG content in muscle DNA increased in proportion to the severity of diabetic nephropathy and retinopathy. This is the first report that an increase in delta mtDNA4977 and 8-OHdG is proportional to the severity of diabetic complications. Oxidative mtDNA damage is speculated to contribute to the pathogenesis of diabetic complications though a defect in mitochondrial oxidative phosphorylation or other mechanisms. 8-OHdG and delta mtDNA4977 are useful markers to evaluate oxidative mtDNA damage in the diabetic patients.