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H Sakurai

Publications and source records attributed to H Sakurai.

At least 325 records · Page 18Linked to original sources
PubMed1995

Detection of vanadyl-nitrogen interaction in organs of the vanadyl-treated rat: electron spin echo envelope modulation study.

ESEEM spectroscopy was applied for the first time to organs of an animal, viz. the kidney and liver of the rat treated with vanadyl sulfate. The aim of this study is to investigate the in vivo coordination structure of vanadyl ions administrated, and to gain information concerning the insulin-mimic activity of vanadium. ESEEM measurements for kidney and liver performed at 77 K have established nitrogen coordination to a certain percentage of vanadyl ion in the organs. The rotios of nitrogen-coordinating vanadyl ion were estimated as 70-80% in the liver, and 50-55% in the kidney. Isotropic portions of the 14N HFC were estimated as magnitude of Aiso approximately 5.0 MHz for liver, and approximately 5.2 MHz for kidney, indicating that the coordinating nitrogen is an amino nitrogen. Coordination of the Lys epsilon-amine or the N-terminal alpha-amine of a protein or (a peptide) to vanadyl ion in vivo is suggested.

Animals↗
PubMed1995

Detection of hydrogen peroxide and hydroxyl radicals in murine skin fibroblasts under UVB irradiation.

The purpose of this study was to identify the active oxygen species generated in murine skin fibroblasts under UVB irradiation. When fibroblasts were exposed to UV light (UVA + UVB), hydroxyl radicals were detectable by ESR-spin trapping using DMPO as a spin trapping agent. Cell damage induced by UVB irradiation was prevented by addition of DMSO, a typical hydroxyl radical scavenger. Fibroblasts treated with a catalase inhibitor 3-amino-1H-1,2,4-triazole were more sensitive to UVB irradiation than untreated-cells, but the sensitivity was improved by addition of DMSO. To find the origin of the hydroxyl radicals in fibroblasts during UVB irradiation, H2O2 was determined by dihydrorhodamine 123 and it was found that the formation of H2O2 increased under UVB irradiation. These results suggest that UVB-irradiated skin fibroblasts produce H2O2 and were followed by the formation of hydroxyl radicals, probably derived from the Fenton-like reaction (H2O2 + Fe2+ --> .OH + OH- + Fe3+), which in turn damages the cells.

Animals↗
PubMed1995

Mechanism for a new antitumor vanadium complex: hydroxyl radical-dependent DNA cleavage by 1,10-phenanthroline-vanadyl complex in the presence of hydrogen peroxide.

Among vanadium complexes which show inhibition of cell growth for human nasopharyngeal carcinoma KB cell, a newly synthesized 1:1 vanadyl-1,10-phenanthroline complex, VO(phen)2+, was found to cleave supercoiled plasmid Col E1 DNA effectively when hydrogen peroxide was added. But VO2+ ion was less effective. Lineweaver-Burk plots of the complex binding to calf thymus DNA indicated that VO(phen)2+ complex has a high affinity to DNA, as supported by CD spectral measurements. To examine the active species for DNA cleavage by the complex, ESR spin trapping was performed and was found that hydroxyl radicals are generated in a pH-dependent manner in the VO(phen)(2+)-H2O2 system, the optimal pH region being 8.5-9.5. In contrast, no optimum pH was observed in VO(2+)-H2O2 system. Thus, the VO(phen)2+ complex is proposed to bind DNA and cleave it when hydrogen peroxide is present.

Antineoplastic Agents↗
PubMed1995

Results of postoperative radiation therapy for patients with carcinoma of the uterine cervix: evaluation of intravaginal cone boost with an electron beam.

Retrospective analysis was carried out from the records of 108 patients with carcinoma of the uterine cervix treated with postoperative external whole pelvic irradiation (EWPI) followed by intravaginal cone boost with an electron beam to the vaginal cuff (IVCB) to evaluate the efficacy of this method. The 5-year cause-specific survival rates were 89% for 89 patients undergoing prophylactic radiation therapy and 56% for 19 patients undergoing salvage radiation therapy (P < 0.001). The 5-year survival rates were 62% for 11 patients with macroscopic residual tumors and 41% for 8 patients with microscopic residual tumors. Of the patients with pelvic lymph node (PLN) involvement, incidences of intrapelvic recurrence, extrapelvic recurrence, and distant metastases were 12, 9, and 3%, respectively. The prognosis for patients without PLN metastasis was significantly better than that for patients with PLN metastasis in the prophylactic radiation therapy group (P < 0.001). Recurrent tumors at the vaginal cuff were observed in only 2 patients in the prophylactic radiation therapy group. Vesicovaginal fistula was observed in 4 patients. Only 1 patient developed Grade 2 rectal complications. No other severe complications were observed. IVCB following EWPI is a safe and effective postoperative radiation therapy technique for patients with cervical cancer.

Adenocarcinoma↗
PubMed1995

Acetone excretion into urine of workers exposed to acetone in acetate fiber plants.

To develop a proper protocol for biological exposure monitoring of acetone, we evaluated whether exposure to acetone on the previous day affects the biological monitoring value at the end of a work day. One hundred and ten male workers exposed to acetone in three acetate fiber manufacturing plants were monitored using a liquid passive sampler on two consecutive working days after 2 days without exposure. Urine samples were collected at the start of the workshift and the end of the shift on both days for each subject. For ten exposed workers urine samples were collected approximately every 2 h during and after the first working day until the following morning. Acetone concentrations in urine (Cu) at the start of the first working day were 1.3 +/- 2.4 (range: ND-14.1) mg/l in nonexposed workers and 2.4 +/- 5.6 (range: ND-40.3) mg/l in exposed workers. The urinary acetone concentration at the beginning of the second working day indicated that urinary levels of acetone do not decline to background level by the following morning when exposure concentration exceeds 300 ppm. However, linear regression analysis demonstrated that the relationship between environmental exposure level and urine level was similar on the 1st day and the 2nd day. Thus, although urine acetone levels did not return completely to baseline after high exposures, under the present exposure levels the exposure on the previous day did not significantly affect urinary acetone at the end of the workshift of the next day.

Acetone↗
PubMed1995

Acute and subacute inhalation toxicity of diborane in male ICR mice.

To clarify the toxicity of diborane, we conducted acute (15 ppm for 1, 2, 4 or 8 h) and subacute (5 ppm for 2 or 4 weeks) inhalation studies on ICR mice. The concentration resulting in a 50% kill after 4 h exposure was 31.5 ppm. Body weight gain was suppressed and the lung weight was increased in diborane-exposed mice in both acute and subacute studies. In the acute study, diffuse pan bronchiolitis-like lesions developed in the lung in various degrees depending on exposure time, which can be pathologically characterized as infiltration of inflammatory cells into the terminal bronchioles and surrounding alveoli, pulmonary congestion and bleeding and/or edema. In the subacute study, we observed lymphoid hyperplasia in the perivascular and peribronchial areas, and infiltration of macrophage and plasma cells into the alveoli. In the mice exposed for 4 weeks, the lesions were more severe than in those exposed for 2 weeks, consisting of hyperplasia and desquamation of Clara cells. In the nasal cavity, we saw mucous exudate and inflammatory cells, suggesting irritation caused by diborane. The histopathological findings, except for the respiratory organs, did not reveal any exposure-related changes. No significant changes were seen in hematological and serum biochemical examinations either. In conclusion, the target organ of diborane inhalation is the respiratory organs, particularly the lung. Further inhalation experiments are essential to investigate the safety exposure levels of diborane.

Administration, Inhalation↗
PubMed1995

Rabbit anti-chromatin antibodies recognize similar epitopes on a histone H1 molecule as lupus autoantibodies.

Autoantibodies in systemic lupus erythematosus (SLE) are believed to be produced through an antigen-driven mechanism, i.e., autosensitization with autoantigens. If this is the case, it is conceivable that antigenic determinants reactive with SLE autoantibodies and induced antibodies raised by immunization are quite similar. To examine this issue, rabbits were immunized with purified histone H1 or chromatin. Although immunization with purified histone H1 did not produce detectable amounts of anti-histone H1 antibodies, immunization with chromatin mounted relatively good antibody responses against not only all histone subunits but also ssDNA. Epitopes on a histone H1 molecule reactive with SLE autoantibodies and rabbit antisera were determined using deletion mutants of a histone H1 molecule. At least two epitopes reactive with induced antibodies were found on a histone H1 and these were closely related to or the same as major autoepitopes in SLE. These data might indicate that B cells producing anti-histone H1 autoantibodies are quite similar to those induced by immunization and provide additional evidence that autosensitization with an autoantigen might be operative and a particulate antigen chromatin could be one of the immunogens for the production of anti-nuclear antibodies of various kinds in SLE.

Animals↗
PubMed1995

Establishment and characterization of a new human lung poorly differentiated adenocarcinoma cell line, GLL-1, producing carcinoembryonic antigen (CEA) and CA19-9.

A new human lung poorly differentiated adenocarcinoma cell line producing carcinoembryonic antigen (CEA) and CA19-9, designated GLL-1, was established from a serial xenograft established in our laboratory. In this paper, we investigated the characteristics of GLL-1 cells. The cell line grew in a monolayer and had a polygonal epithelioid appearance in phase-contrast microscopy. The doubling time of GLL-1 cells during exponential growth was approximately 28 h in RPMI-1640 with 10% fetal calf serum. Positive reactions for CEA and for CA19-9 were seen within the cytoplasm of GLL-1 cells by immunohistochemical staining. In log phase, the fractions for G0/G1, S and G2/M were 76.2%, 20.0% and 3.8%, respectively. Chromosome analysis revealed that GLL-1 cells contained the modal number of 72 chromosomes (range 66-97). GLL-1 cells exhibited numerous numerical and structural abnormalities. The Do value for radiation sensitivity, calculated by taking the reciprocals of the slope of the radiation dose response curve, was 109 cGy. The extrapolation number (n) for the radiation response curve was 1.57. Tumor take was observed in nude mice inoculated subcutaneously in the back with 2 x 10(6) GLL-1 cells. The histopathological features of the tumor induced by inoculation of GLL-1 cells were also the same as the original lung cancer.

Adenocarcinoma↗
PubMed1995

Clinical implication of symptoms in patients with non-small cell lung cancer treated with definitive radiation therapy.

To clarify clinical significance of symptoms presented at the beginning of treatment, we analyzed the symptoms in 240 patients with non-small cell lung cancer treated with definitive radiation therapy. Symptoms were classified into four groups: no symptom (Grade 0), cough, sputum/hemosputum and fever up (Grade 1), chest pain and breathlessness (Grade 2), appetite loss, body weight loss, SVC syndrome, hoarseness, and pain in the upper limb/shoulder (superior sulcus tumor) (Grade 3), and their therapeutic outcomes were examined. The 2- and 5-year overall actuarial survival rates for patients with squamous cell carcinoma were 38.5% and 15.4% for Grade 0, 40.5% and 20.1% for Grade 1, 17.9% and 2.6% for Grade 2, and 15.8% and 5.3% for Grade 3. A statistical difference was noted in survival between Grades 0-1 and Grades 2-3 (P < 0.01), but was not seen between Grades 0 and 1, or between Grades 2 and 3. As for patients with stage III disease alone, the difference in survival was still significant between Grades 0-1 and 2-3 (P < 0.05). In patients with adenocarcinoma/large cell carcinoma, however, no obvious relationship was found between symptoms and prognosis, except for body weight/appetite loss. In conclusion, though the symptoms closely related to clinical stage and performance status and not an independent prognostic factor, chest pain and breathlessness correlated with poor therapeutic outcome as well as body weight loss and T3-4 related symptoms, while cough, sputum (hemosputum), and fever were favorable symptoms in patients with squamous cell carcinoma who received definitive radiation therapy.

Actuarial Analysis↗
PubMed1995

Protective activity of hamamelitannin on cell damage of murine skin fibroblasts induced by UVB irradiation.

The protective activities of hamamelitannin (2',5-di-O-galloyl-hamamelose) in Hamamelis virginiana L. and its related compound, gallic acid, on damaged murine skin fibroblasts induced by UVB irradiation were investigated. In order to exclude the UV absorbing effect of the compounds, the protection study was performed such that the fibroblasts were pretreated with hamamelitannin or gallic acid for 24 h before UVB irradiation. At 200 microM concentration, hamamelitannin gave the higher survival of 72.6 +/- 0.4% in comparison with that of gallic acid (35.5 +/- 1.0%), while UVB absorbers such as 2-ethylhexyl p-methoxycinnamate and hexylbenzoate did not show such protection. The scavenging activities of hamamelitannin and gallic acid against active oxygens such as superoxide anion radicals, hydroxyl radicals and singlet oxygens were evaluated using electron spin resonance (ESR-spin trapping method). Hamamelitannin and gallic acid showed potent scavenging activities against all active oxygens tested. Furthermore, the association of hamamelitannin to fibroblasts was examined by comparing it with that of gallic acid, and the following results were obtained: (1) hamamelitannin reduces the reaction rate of liposome entrapped-nitroblue tetrazolium (NBT) with external superoxide anions, and (2) several glycosides associate with fibroblasts. From these results, it was concluded that hamamelitannin protects murine fibroblasts against external active oxygens by associating with the cell surface through its sugar moiety.

Animals↗
PubMed1995

Involvement of protein kinase C in Ca(2+)-signaling pathways to activation of AP-1 DNA-binding activity evoked via NMDA- and voltage-gated Ca2+ channels.

Stimulation of cultured cerebellar granule cells with N-methyl-D-aspartate (NMDA) or kainic acid (KA) leads to activation of activator protein-1 (AP-1) DNA-binding activity, which can be monitored by an increase in 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive element (TRE)-binding activity, in concert with c-fos induction. For this increase in TRE-binding activity, Ca2+ influx across the plasma membrane is essential. Treatment of cells with an intracellular Ca2+ chelator, BAPTA-AM, abolished this increase. Close correspondence between the dose-response curves of 45Ca2+ uptake and TRE-binding activity by NMDA or KA suggested that Ca2+ influx not only triggered sequential activation of Ca(2+)-signaling processes leading to the increase in TRE-binding activity, but also controlled its increased level. Stimulation of non-NMDA receptors by KA mainly caused Ca2+ influx through voltage-gated Ca2+ channels, whereas stimulation of NMDA receptors caused Ca2+ influx through NMDA-gated ion channels. The protein kinase C (PKC) inhibitors staurosporine and calphostin C inhibited the increase in TRE-binding activity caused by NMDA and KA at the same concentration at which they inhibited that caused by TPA. Furthermore, down-regulation of PKC inhibited the increase in TRE-binding activity by NMDA and KA. Thus, a common pathway that includes PKC could, at least in part, be involved in the Ca(2+)-signaling pathways for the increase in TRE-binding activity coupled with the activation of NMDA- and non-NMDA receptors.

Animals↗
PubMed1995

Gonadotroph responsiveness in orchidectomized sheep: IV. Effect of estradiol infusion during the breeding and anestrous seasons.

The interaction between estradiol (E2) and season on gonadotroph function was assessed in orchidectomized sheep (wethers). Wethers in the breeding (November) or anestrous (May) season received E2 (in 20% ethanol-saline [vehicle]) by continuous infusion at rates of 0.31, 1.25, 5, or 20 micrograms/h (n = 6 wethers/group). Controls received vehicle alone. Gonadotroph responsiveness (LH release induced by 500 ng GnRH, i.v.) was assessed at the end of the 48-h infusion period. Mean serum concentrations of E2 at the end of infusion were < 0.6 pg/ml in animals receiving vehicle, and 2.5 +/- 0.3, 10.7 +/- 0.4, 35.1 +/- 0.9, and 86.1 +/- 4.1 pg/ml in animals receiving 0.31, 1.25, 5, and 20 micrograms E2/h, respectively. Mean serum concentrations of LH and FSH, the amplitude and frequency of LH secretion, and gonadotroph responsiveness did not differ (p > 0.05) with season in controls. Infusion of E2 at 5 or 20 micrograms/h decreased (p < 0.05) serum concentrations of LH and FSH and eliminated episodic secretion of LH, regardless of season. Conversely, E2 infusion at 0.31 microgram/h resulted in significant suppression of gonadotropin secretion in May, but not November. Similarly, the reduction in serum concentrations of LH and FSH induced by E2 infusion at 1.25 micrograms/h was more pronounced (p < 0.05) in May than November. Compared to gonadotroph responsiveness in controls, responsiveness in the breeding, but not the anestrous, season increased (p < 0.05) after infusion of 0.31 microgram E2/h.(ABSTRACT TRUNCATED AT 250 WORDS)

Anestrus↗
PubMed1995

Squamous cell carcinoma of the uterine cervix: radiation therapy for patients aged 70 years and older.

PURPOSE: To evaluate the usefulness of radiation therapy for elderly patients with squamous cell carcinoma of the uterine cervix. MATERIALS AND METHODS: Two hundred ninety-three patients with squamous cell carcinoma of the uterine cervix underwent external pelvic irradiation and three sessions of low-dose-rate intracavitary irradiation. One hundred twenty-six patients were aged 70 years or older (elderly group), and 167 patients were aged 69 years or younger (younger group). Survival rates, pattern of failure, local control rates, and complications for the two groups were compared. RESULTS: The 5-year, cause-specific survival rates for the elderly group with stage I, II, III, or IV disease were 100%, 81%, 73%, and 54%, respectively. Corresponding rates for the younger group were 100%, 92%, 74%, and 32%. Differences in survival curves, patterns of failure, recurrence rates, and incidences of radiation complications for the two groups were not statistically significant. CONCLUSION: Age did not influence the effectiveness of radiation therapy for the elderly patients.

Adult↗
PubMed1995

Nitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritides.

In this study, we have identified the source of nitric oxide (NO) produced in the human inflammatory joints by analyzing expression of inducible NO synthase. In ex vivo organ cultures, both inflammatory synovium and cartilage from patients with rheumatoid arthritis produced NO. The NO production was suppressed by NG-monomethyl-L-arginine, an inhibitor of NO synthase. The amount of NO produced by the synovium correlated with the proportion of CD14+ cells in the corresponding tissue (r = 0.8, P < 0.05). Immunohistochemical analysis as well as in situ hybridization showed that inducible NO synthase was predominantly expressed in synovial lining cells, endothelial cells, chondrocytes, and to a lesser extent, in infiltrating mononuclear cells and synovial fibroblasts. The synovial lining cells and the infiltrating cells expressing inducible NO synthase were identified where CD14+ cells were located. Together with morphological features, this suggests that they are type A synoviocytes. NO production from freshly isolated synoviocytes and chondrocytes was up-regulated by in vitro stimulation with a combination of IL-TNF-beta, TNF-alpha, and LPS. In summary, the present results suggest that NO is produced primarily by CD14+ synoviocytes, chondrocytes, and endothelial cells in inflammatory joints of arthritides. NO production can be upregulated by cytokines present in inflamed joints. The increased NO production may thus contribute to the pathological features in inflammatory arthritides.

Arthritis, Rheumatoid↗
PubMed1995

Active-oxygen scavenging activity of plant extracts.

To find antioxidative compounds present in plants, 65 types of plant extract were tested using the neotetrazolium method for evidence of superoxide anion-scavenging effects and 7 plant extracts were selected for further investigation. The activity of active-oxygen scavengers such as superoxide anion radicals, hydroxyl radicals, singlet oxygens and lipid peroxides in the 7 plant extracts (Aeseclus hippocastanum L., Hamamelis virginiana L. Polygonum cuspidatum Sieb., Quercus robur L., Rosemarinous officinalis L., Salvia officinalis L. and Sanguisorba officinalis L.) was examined in detail by both ESR spin-trapping and malondialdehyde generation. Furthermore, the active-oxygen scavenging activity of these plant extracts was evaluated using a murine dermal fibroblast culture system. Both Aeseclus hippocastanum L. and Hamamelis virginia L. were found to have strong active-oxygen scavenging activity of and protective activity against cell damage induced by active oxygen. Both Aeseclus hippocastanum L. and Hamamelis virginiana L. are proposed as potent plant extracts with potential application as anti-aging or anti-wrinkle material for the skin.

Animals↗
PubMed1995

Protective activity of hamamelitannin on cell damage induced by superoxide anion radicals in murine dermal fibroblasts.

Previously we demonstrated that hamamelitannin (2',5-di-O-galloyl hamamelose) in Hamamelis virginiana L. exhibits potent superoxide-anion scavenging activity. We then examined the physiological and pharmacological activities of hamamelitannin as well as its functional homologues, gallic acid and syringic acid. The following results were obtained: (1) Hamamelitannin has a higher protective activity against cell damages induced by superoxide anions than gallic acid which is the functional moiety of hamamelitannin. The protective activity of hamamelitannin on murine fibroblast-damage induced by superoxide anions was found at a minimum concentration of 50 microM, while the corresponding figure for gallic acid was 100 microM. (2) Pre-treatment of fibroblasts with hamamelitannin enhances cell survival. (3) The superoxide-anion scavenging activity of the compound in terms of its IC50 value (50% inhibition concentration of superoxide anion radicals generated) was evaluated by ESR spin-trapping. Both hamamelitannin (IC50 = 1.31 +/- 0.06 microM) and gallic acid (IC50 = 1.01 +/- 0.03 microM) exhibited high superoxide-anion scavenging activity followed by syringic acid (IC50 = 13.90 +/- 2.38 microM). (4) When hamamelitannin was treated with superoxide anions generated by a KO2-crown ether system, HPLC analysis showed the disappearance of hamamelitannin and the concomitant formation of hamamelitannin-derived radicals (g = 2.005, delta H1 = 2.16 G, delta H2 = 4.69 G) was detected by ESR spectrometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

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↗