Interaction of hydrogen with TaC(111) and NbC(111) surfaces: Angle-resolved photoemission study.
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Biomedical subjects
Publications and source records attributed to S Otani.
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Impaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG-63 in a dose-dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3-induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose-dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3-induced increase in OC mRNA abundance in MG-63 cells, suggesting that the inhibition of the 1,25(OH)2D3-induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3 receptors in MG-63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3 by reducing 1,25(OH)2D3 receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diabetic osteopenia.
We investigated the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the expression of scavenger receptors in human monocytic cell line (THP-1 cells) treated for 24 h with 12-O-tetradecanoylphorbol-13-acetate (TPA) which induces their differentiation into macrophages. The capacity to degrade 125I-labeled acetyl low density lipoprotein (LDL) was developed in accordance with macrophage differentiation. The treatment with 10 nM 1,25(OH)2D3 for 72 h inhibited the degradation of acetyl LDL by THP-1 macrophages in a dose-dependent manner, suggesting that 1,25(OH)2D3 inhibits scavenging function in macrophages. In order to clarify the mechanism of its inhibitory effect on degradation of acetyl LDL, we performed the ligand binding assay using 125I-labeled acetyl LDL. Scatchard analysis revealed that 1,25(OH)2D3 decreased the number of scavenger receptors without changing the affinity for acetyl LDL. We next examined the effect of 1,25(OH)2D3 on the expression of scavenger receptor mRNA. The mRNA of type I scavenger receptor was first detected in THP-1 cells 4 days after the treatment with TPA, the mRNA level increased up to 6 days, and then decreased. The treatment with 1,25(OH)2D3 for 72 h dramatically decreased the mRNA levels after the acquisition of macrophage phenotypes as evidenced by nonspecific esterase staining. However, 1,25(OH)2D3 did not affect the activity of nonspecific esterase nor the induction of interleukin-1 beta mRNA by lipopolysaccharide in THP-1 macrophages. These findings suggest that 1,25(OH)2D3 exclusively decreases the expression of scavenger receptors in TPA-induced THP-1 macrophages without affecting the basic cellular functions as macrophages.
We examined the effect of inhibitors of tyrosine kinase and tyrosine phosphatase on DNA fragmentation, protein tyrosine phosphorylation, and polyamine metabolism in the murine T-cell line CTLL-2. When cells were exposed to herbimycin A, a specific inhibitor of tyrosine kinase (Uehara et al., 1989, Biochem. Biophys. Res. Commun., 163:803-809), in the presence of interleukin 2 (IL-2), DNA was degraded into oligonucleosomal fragments in a dose-dependent fashion. Genistein, another inhibitor of tyrosine kinase (Akiyama et al., 1987, J. Biol. Chem., 262:5592-5596), had similar effects. Exposure of CTLL-2 cells to vanadate, a tyrosine phosphatase inhibitor, blocked with the DNA fragmentation induced by herbimycin A. Tyrosine phosphorylation of 55 Kd protein was inhibited by herbimycin A, and the inhibition was reduced by vanadate. Ornithine decarboxylase (ODC) activity decreased rapidly after herbimycin A was added to CTLL-2 cell cultures, while vanadate increased ODC activity. The exogenous addition of putrescine or spermine, but not that of spermidine, attenuated herbimycin A-induced DNA fragmentation. These findings suggest that phosphorylation of tyrosine residues of 55 Kd protein prevents DNA fragmentation and that polyamines are involved in regulation of apoptosis.
We report herein the rare case of a patient who survived for 5 years and 10 months after commencing treatment for gastric cancer with simultaneous disseminated peritoneal metastasis. A 45-year-old man was diagnosed as having advanced gastric cancer following the discovery of numerous nodules in the peritoneal cavity at laparotomy. The patient was treated by palliative gastrectomy and continuous hyperthermic peritoneal perfusion (CHPP) immediately after surgery on November 11, 1987. Postoperatively, he underwent radiofrequency (RF) hyperthermia with intraperitoneal cisplatin a total of seven times. He continued on a combination of uracil and tegafur (UFT) administered orally with a protein-bound beta-D-glucan extracted from the mycelia of Cariolus versicolor (PSK). Long-term survival was achieved following the initial palliative gastrectomy despite simultaneous disseminated peritoneal metastasis.
We investigated the expression and changes in the intracellular localization of a 72-kDa heat shock protein (HSP72) in rat gastric pyloric and fundic mucosa before and after water-immersion stress. Severe mucosal damage was found in the fundic mucosal area of the stomach after this stress. However, no mucosal lesion developed in the pyloric mucosal area. HSP72 in both the soluble and insoluble fractions of the pyloric and the fundic mucosal areas was significantly increased after water-immersion stress, peaking 6h after the initiation of the stress. The increase in HSP72 was more significant in the pyloric mucosal area than in the fundic mucosal area under both normal and stress conditions. The increase of HSP72 in the pyloric mucosal cells occurred prior to the formation of the mucosal lesions, whereas the increase of HSP72 in the fundic mucosal cells was observed after ulcer formation. An immunohistochemical study showed that HSP72 was constitutively expressed in the cytoplasm of the gastric mucosal cells, and that the intranuclear induction of HSP72 was remarkably intense in the pyloric mucosal cells, especially in the proliferative zone, compared with the fundic mucosal cells. Our results may suggest that HSP72 has an important cytoprotective function in gastric mucosal cells and that there is a "biophysical" difference between pyloric and the fundic mucosal cells.
We investigated the relationship between dietary highly hydrogenated soybean oil (HSO) and cholesterol transport in rats. In the first study, to examine the effects on cholesterol transport of different concentrations of HSO in dietary oil, rats were given one of the three diets containing 0, 25, or 50% HSO in dietary oil with cholesterol (5 g/kg diet) or a diet without HSO and cholesterol for 22 d. Feeding the high concentration of HSO prevented the increase in plasma total cholesterol, hepatic total lipids, and cholesterol and the decrease in high-density lipoprotein-cholesterol, which were caused by dietary cholesterol. Moreover, HSO increased the fecal excretion, fecal lipids, and steroids in a dose-dependent manner. In the second study, to examine the effects on cholesterol transport of redistribution of steric acid in the triacylglycerol species contained in HSO, rats were given one of the six diets containing HSO (distearoylmonoacylglycerol and tristearoylglycerol)-rich, monostearoylglycerol-rich, or palmitic acid-rich oil with/without cholesterol (5 g/kg diet), for 30 d. Whereas the accumulation of cholesterol in the body was reduced, cholesterol excretion was enhanced effectively in rats given the HSO-rich diet compared with rats given the monostearoylglycerol-rich diet. These results suggested that not only the high concentration of stearic acid but also its uneven distribution in HSO-triacylglycerol contributed to the reduction in intestinal cholesterol absorption in rats.
The modifying effects of 22-oxa-calcitriol (OCT), a synthetic analog of 1 alpha,25-dihydroxyvitamin D3, were assessed in a multi-organ carcinogenesis model using male F344 rats initially treated with five kinds of carcinogens. In experiment 1 the rats were given OCT intraperitoneally at doses of 30 micrograms/kg (25 rats) or 3 micrograms/kg (25 rats), three times a week for 24 weeks after initial carcinogen exposure over 4 weeks and a 2 week non-treatment period. Twenty-two rats received the five carcinogens and were given the vehicle intraperitoneally as a control. A further group of 10 rats was given the 30 micrograms/kg dose of OCT without prior carcinogen application. At the end of the total observation period of 30 weeks the carcinoma incidence in the small intestine of rats given 30 micrograms/kg OCT after carcinogen treatment was 0%. This incidence was significantly smaller when compared with the control group. The incidence of large intestine carcinomas in the 30 micrograms/kg OCT group showed a tendency to decrease. The numbers of small and large intestinal carcinomas per rat were also significantly lower in the group given 30 micrograms/kg OCT than after 3 micrograms/kg OCT or carcinogens alone. Attention was, therefore, focused on colon carcinogenesis and in experiment 2 30 micrograms/kg OCT administered six times a week to rats for 8 weeks after the last injection of N,N'-dimethylhydrazine (DMH) exposure. OCT significantly reduced the formation of DMH-induced aberrant crypt foci, considered to be putative preneoplastic lesions. In experiment 3 30 micrograms/kg OCT was administered six times a week to rats for 4 weeks without prior carcinogen treatment. The proliferating cell nuclear antigen labeling index for the colonic epithelium of rats given 30 micrograms/kg OCT was decreased. Ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities in colonic epithelium, assayed as indicators of cell proliferation, were not significantly decreased as compared with control group values. Furthermore, vitamin D receptors in colonic epithelium were not significantly increased. Thus the present study indicates that OCT can exert inhibitory effects on tumor development in the small and large intestines, although the mechanism is unclear.
Expression of 40- and 47-kDa proteins recognized by anti-60-kDa heat shock protein antibody was investigated in colorectal adenocarcinoma tissue. In all cases of colorectal adenocarcinoma tissue (n = 9), 40- and 47-kDa proteins were detected by immunoblot analysis. However, expression of these two proteins was extremely low or was not expressed in control tissue. There was no correlation between the quantity of these two bands and histologic type or the location of the tumors. Our results first demonstrate the accumulation of structurally altered 60-kDa heat shock protein-associated antigens in carcinoma tissue and suggest that these two proteins could be a possible candidate for tumor-specific 60-kDa heat shock protein-related protein antigens.
Both cyclosporin (CyA) and ultraviolet radiation are effective in the treatment of psoriasis, but their precise mechanisms of action are uncertain. We investigated their effects on ornithine decarboxylase (ODC) activity, ODC gene expression, and cellular proliferation stimulated by epidermal growth factor (EGF), in cultured normal human epidermal keratinocytes. CyA (5 micrograms/ml) inhibited ODC activity, ODC mRNA level, and cell growth induced by 50 ng/ml EGF. Ultraviolet B (10 mJ/cm2) irradiation suppressed the induction of ODC, ODC mRNA, and cell proliferation stimulated by EGF, but ultraviolet A (0-15 J/cm2) irradiation inhibited neither EGF-stimulated ODC activity nor cell proliferation. These findings indicate that reduction of ODC activity in CyA- or ultraviolet B-treated human keratinocytes may contribute to the antiproliferative mechanism of these agents. These results also suggest that the regulation of ODC activity by ultraviolet B and A irradiation may be mediated by different signal transduction pathways.
The growth of bacteria is often enhanced by addition of carbon materials such as graphite or activated charcoal to the growth medium. In this work, bacterial strains that strictly require such carbon materials under the ordinarily lethal stress caused by high concentrations of salt were isolated. The organisms were gram-positive, spore-forming, sugar-nonfermenting aerobic bacilli and were provisionally designated "Bacillus carbophilus" Kasumi after examination of their phenotypic traits. The growth- and germination-promoting effects of graphite and activated charcoal were demonstrated either quantitatively on agar plates containing fine crystals of the carbon materials mixed with a nonpermissive growth medium or qualitatively on agar plates on nonpermissive growth media half-covered with fine carbon particles. Further experiments demonstrated a novel feature of the phenomenon; i.e., the ability to induce colony formation on the nonpermissive plate was transmissible through the air, as well as through plastic or glass barriers. The mechanism probably involves transmission of physical signals regulating cell growth.
1. Two independent Schaffer collateral pathways converging to the same pyramidal cell were alternately stimulated by 2-Hz trains (900 pulses) offset by a 150-ms interval in adult rat hippocampal slices. The second input underwent an immediate and persistent long-term depression (LTD). Depression in the first input was smaller than the second input. A narrower interpulse interval (20 ms) failed to induce LTD in either input. 2. Neither the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid nor the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxylphenyl-glycine blocked this associative LTD. However, coapplication of these two antagonists blocked LTD. 3. Associative LTD was blocked by prior injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid into the postsynaptic cell and by bath-applied L-NG-nitroarginine, a nitric oxide synthesis inhibitor. 4. We propose that temporally confined, asynchronous synaptic activity weakens the efficacy of naïve synapses in slices from the adult hippocampus.
An active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], is involved in the regulation of parathyroid cell proliferation as well as of parathyroid hormone synthesis. We examined the effects of 1,25-(OH)2D3 on the proliferation of parathyroid cells in relation to their effects on ornithine decarboxylase (ODC) activity. Exposure of bovine parathyroid cells to serum caused an elevation in [3H]thymidine incorporation, which was preceded by a rise in ODC activity. The biodegradative enzyme, spermidine/spermine N1-acetyltransferase (SAT) activity did not change by 12 h after serum exposure. Preincubation of the cells with 10(-8)M 1,25-(OH)2D3 for 48 h attenuated the serum-induced rise in ODC activity by 12 h. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, inhibited the serum-stimulated [3H]thymidine incorporation. Simultaneous addition of 25 microM putrescine reversed the inhibitory effect of DFMO. In summary, it was strongly suggested that polyamine is intimately involved in the proliferation of parathyroid cells and that 1,25-(OH)2D3 inhibited parathyroid cell growth through suppression of ODC activity.
It is known that osteopenia is frequently associated with diabetes mellitus. Although its mechanism is not well understood, impaired bone formation due to an osteoblast deficit seems to be a major factor as reflected by a fall in serum levels of osteocalcin and by the findings of low bone formation with bone histomorphometry. In the present study, we studied the effect of high glucose conditions on osteoblast by examining the responsiveness of human osteosarcoma (MG-63) cells to human parathyroid hormone 1-34 [hPTH-(1-34)]. MG-63 cells were cultured either with 5.5 mM glucose (normal glucose), 55.0 mM glucose (high glucose) or 5.5 mM glucose plus 49.5 mM mannitol (high mannitol) condition for 7 days. Both an increase in cAMP levels and an immediate increase in [Ca2+]i, induced by hPTH(1-34), were significantly lower in high glucose-treated cells than in those treated with normal glucose or high mannitol. Basal cAMP levels in the cells after a 7-day culture in high glucose conditions were significantly higher than in those in the other two groups. We concluded that high glucose specifically impaired the response to hPTH(1-34). This impairment seemed to arise from an increase in intracellular cAMP levels, which is reported to induce downregulation of PTH receptors.
This study was undertaken to estimate if dietary iron could stimulate factors which promote spontaneous lung tumorigenesis in A/J mice, by measuring biochemical parameters of oxidative stress on pulmonary nuclei, ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities as markers of tumor promotion. Feeding excessive iron (500%) to A/J mice for 28 weeks significantly elevated pulmonary DNA single strand break (DNA-SSB) as well as nuclear thiobarbituric acid reactive substances (TBARS) in connection with the increase of nuclear nonheme iron level. In contrast, nuclear alpha-tocopherol levels in the iron-loaded group significantly decreased as compared to that in the control group. Pulmonary ODC and SAT activities showed increasing tendency on feeding excess iron for 28 weeks. These results suggest that dietary iron stimulates spontaneous lung tumor promotion in A/J mice, partly due to the enhancement of oxidative damage to the pulmonary nuclei.
We report a rare complication of endocardial pacing electrode implantation. A 64-year-old man, who was implanted transvenous pacemaker system by the other hospital one month ago, visited our outpatient clinic with the complaint of diaphragmatic twitching. Left ventricular pacing was highly suspected because of right bandle branch block pattern by 12 leads ECG. Pericardial effusion was observed by echocardiography, and angiography revealed the pacing electrode coursing through the coronary sinus and perforated the cardiac vein towards the posterior wall of the left ventricle. A new generator and a pacing electrode were implanted on the other side. Pericardial drainage was not performed because hemodynamics was stable. The patient discharged hospital on 18th postoperative day without any complication.
The long-term results following intra or extracardiac implanted bioprosthetic valves were compared. Forty-one patients, whose average age at the operation was 43.3 +/- 10.7 (mean +/- SD) year-old, were implanted 33 Hancock and 11 Carpentier-Edwards porcine valves, 35 in mitral, 6 in aortic and 3 in tricuspid position. Twenty-five children, whose average age was 6.0 +/- 3.5 year-old (p < 0.01) at the operation, underwent right ventricular-pulmonary artery conduit repair with 16 Hancock, 7 Carpentier-Edwards porcine valves and 2 Ionescu-Shiley pericardial valves. There were only one late death and one operative death in the patients implanted intracardiac bioprosthetic valves. Seven intracardiac and 12 extracardiac implanted bioprosthetic valves were removed at the reoperation for prosthetic valve dysfunction. The probabilities free from reoperation after 7 and 9 years of follow-up was 91% and 82%, respectively, with intracardiac implanted valves, on the other hand 51% (p < 0.05) and 8.6% (p < 0.05), respectively, with extracardiac implanted valves. Valve dysfunction in extracardiac implantation was mainly related to the stenosis due to fusion of comissure and/or calcification. Regurgitation due to tear and/or perforation was mainly associated with intracardiac implanted bioprosthetic valves.
Effects of hyperthermia and cell densities on inhibitory activity of ascorbic acid on DNA synthesis in Ehrlich ascites tumor cells were studied. When cells at a low density of 5 x 10(3)/ml were treated with 75 microM ascorbic acid for 1 h, DNA synthesis was inhibited after treatment at 37 degrees C and the inhibition was significantly enhanced at 42 degrees C. At a cell density as high as 1 x 10(5)/ml, however, inhibition did not occur at 37 degrees C or 42 degrees C. In contrast, dehydroascorbic acid was inactive even at a low cell density under similar conditions. Inhibitory effects of ascorbic acid on DNA synthesis were also markedly enhanced by treatment at 40 degrees C. DNA synthesis was not inhibited in the absence of the drug. Furthermore, mice transplanted with cells treated with a combination of 75 microM ascorbic acid and hyperthermia at 42 degrees C, considerably prolonged their survival time in comparison with untreated cells. Addition of ascorbic acid to hyperthermia is suggested to be an advantageous treatment for cancer.