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Biomedical subjects

H Sakurai

Publications and source records attributed to H Sakurai.

At least 289 records · Page 16Linked to original sources
PubMed1996

Lack of increased coronary atherosclerotic risk due to elevated lipoprotein(a) in women > or = 55 years of age.

BACKGROUND: Numerous studies have indicated that there is an association between lipoprotein(a) [Lp(a)] and coronary artery disease (CAD) in middle-aged men; however, few studies have addressed this issue in women or the elderly. METHODS AND RESULTS: Serum Lp(a) concentrations were determined in 354 women and 706 men with or without angiographically defined CAD (one or more coronary arteries with narrowing of > or = 75%). The age-specific impact of elevated Lp(a) (> or = 30 mg/dL) on CAD was examined in each sex. In the younger age group (< 55 years old), elevated Lp(a) was independently associated with CAD in both sexes (adjusted odds ratio [OR]: women, 6.90, P < .01; men, 2.63, P < .05). The age-specific ORs declined with age, and elevated Lp(a) no longer conferred an increased CAD risk in either elderly men or women > or = 65 years old. In the age group of 55 to 64 years, elevated Lp(a) was positively associated with CAD for men (adjusted OR: 2.45, P < .05) but not for women (adjusted OR: 0.56, P = NS). CONCLUSIONS: For both sexes, elevated Lp(a) appears to be an independent risk factor for premature CAD and the importance of Lp(a) appears to decrease with age. However, for women, the risk estimate of Lp(a) began to decline at an age approximately 10 years younger than for men. These data suggest that not only age- but also sex-specific factors such as menstrual status may interact with the association between Lp(a) and CAD.

Aged↗
PubMed1996

Vanadyl ion suppresses nitric oxide production from peritoneal macrophages of streptozotocin-induced diabetic mice.

When vanadyl ion (vanadyl sulfate) was given intraperitoneally for 6 days to diabetic mice induced with low doses of streptozotocin (STZ), serum glucose levels were maintained in the normal range during vanadyl administration and serum insulin levels were partially improved. Since nitric oxide (NO) production from macrophages has been proposed to mediate the destruction of islet B-cells, we examined whether vanadyl ion contributes to the proposed mechanism and found that this metal ion suppresses No production from peritoneal macrophages of diabetic BALB/c mice induced with low doses of STZ. From these results, we propose a new mechanism for the vanadium-dependent inhibition of NO production from macrophages. Which in turn relates to the onset of diabetes.

Animals↗
PubMed1996

The yeast GAL11 protein binds to the transcription factor IIE through GAL11 regions essential for its in vivo function.

The GAL11 gene encodes an auxiliary transcription factor required for full expression of many genes in yeast. The GAL11-encoded protein (Gal11p) has recently been shown to copurify with the holoenzyme of RNA polymerase II. Here we report that Gal11p stimulates basal transcription in a reconstituted transcription system composed of recombinant or highly purified transcription factors, TFIIB, TFIIE, TFIIF, TFIIH, and TATA box-binding protein and core RNA polymerase II. We further demonstrate that each of the two domains of Gal11p essential for in vivo function respectively participates in the binding to the small and large subunits of TFIIE. The largest subunit of RNA polymerase II was coprecipitated by anti-hemagglutinin epitope antibody from crude extract of GAL11 wild type yeast expressing hemagglutinintagged small subunit of TFIIE. Such a coprecipitation of the RNA polymerase subunit was seen but in a greatly reduced amount, if extract was prepared from gal11 null yeast. In light of these findings, we suggest that Gal11p stimulates promoter activity by enhancing an association of TFIIE with the preinitiation complex in the cell.

Binding Sites↗
PubMed1996

Activation of transcription factor NF-kappa B in experimental glomerulonephritis in rats.

NF-kappa B plays a pivotal role in cells of the immune system as an inducible transcriptional activator. NF-kappa B regulates the transcription of many genes of pro-inflammatory cytokines and cell adhesion molecules, which could be involved in the pathogenesis of glomerulonephritis. Using a gel shift assay, we investigated NF-kappa B DNA-binding activity in glomeruli of WKY rats injected with nephrotoxic serum (NTS). Kinetic analysis indicated that the NF-kappa B DNA-binding activity in glomeruli, composed of p50 subunit determined by a supershift assay, increased on day 1 after NTS injection and the maximal activation was observed on day 3 to 5. NF-kappa B activation persisted at least until day 14. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappa B activation, inhibited the NTS-induced increase of glomerular NF-kappa B DNA-binding activity, followed by the inhibition of mRNA expression of IL-1 beta, MCP-1, ICAM-1 and iNOS, which are known to be regulated by NF-kappa B. PDTC also prevented urinary protein excretion which is a pathophysiological parameter for glomerulonephritis. These results suggest that NF-kappa B activation causes the induction of pro-inflammatory factors in nephritic glomeruli, which may play significant roles in the pathogenesis of glomerulonephritis.

Animals↗
PubMed1996

Alteration of c-fos gene methylation in human gliomas.

In an attempt to find a common DNA alteration occurring in human glioma, we examined DNA methylation in 34 gliomas of various pathological grades and compared them with those in normal cerebral subcortex DNA. The total methylated cytosine levels in the genome did not differ appreciably between the tumors and the normal tissues; however, the degree of DNA methylation in several proto-oncogenes and suppressor oncogenes showed some alterations. Among them, the c-fos gene demonstrated deviation from that of normal tissues in all cases examined, suggesting that the alteration of c-fos gene methylation plays a role in the early steps of human glioma development.

Adult↗
PubMed1996

The presence of costimulatory molecules CD86 and CD28 in rheumatoid arthritis synovium.

OBJECTIVE: To investigate the expressions of co-stimulatory molecules CD86 (B7-2, B70) and CD28 by cells obtained from the synovial tissues (ST) and synovial fluids (SF) of patients with rheumatoid arthritis (RA). METHODS: Monoclonal antibodies (MAb) against CD86 and CD28 were used for immunochemical study of synovia from 18 RA patients, 4 osteoarthritis (OA) patients, and 4 normal subjects. These MAb were also used for flow cytometry of isolated ST cells from 8 RA and 5 OA patients and of SF mononuclear cells from 5 RA and 5 OA patients. RESULTS: Immunohistochemical examination revealed that CD86+ cells occurred in 11 of the 18 RA synovia, but in none of the 4 OA or 4 normal synovia. Most of the positive cells had macrophage-like morphology, and surrounded lymphoid aggregates. Most cells within lymphoid aggregates were stained positively for CD28. Flow cytometry showed that CD86+ cells comprised 2.9-33.4% (average 14.3%) of the total ST cells and 2.1-14.9% (average 6.1%) of the total SF mononuclear cells from RA patients. Approximately 40% of the CD86+ cells expressed CD14. A majority (mean 72%, range 57-89%) of the T cells in ST and SF expressed CD28. RA synovia expressed more CD86 molecules than did OA synovia (mean frequency of positive cells 14.3% versus 2.8%; mean fluorescence intensity 104.6 versus 40.9).

Antigens, CD↗
PubMed1996

Prognostic significance of immunohistochemically detected p53 protein expression in stage IIIB squamous cell carcinoma of the uterine cervix treated with radiation therapy alone.

Immunohistochemical studies were performed to investigate the prognostic significance of p53 protein expression in 46 patients with stage IIIB squamous cell carcinoma of the uterine cervix who were treated with radiation therapy alone. Tumor cells showed p53 protein expression in 29 of 46 patients. The 5-year overall actuarial and cause-specific survival rates for the patients with p53-positive tumor were 52.9 and 70.4%, respectively. The corresponding rates for the patients with p53-negative tumor were 58.2 and 69.0%, respectively. There was no significant difference of local control rates and of distant metastases rates between the two groups. In conclusion, no relationship was observed between radiation treatment outcome and the immunohistochemically detected p53 protein expression in the patients with stage IIIB squamous cell carcinoma of the uterine cervix.

Adult↗
PubMed1996

Evaluation of the subacute pulmonary and testicular inhalation toxicity of diborane in rats.

This study aimed to clarify the subacute pulmonary and testicular inhalation toxicity of diborane (B2H6, CAS: 19287-45-7) in rats. Male Wistar rats were exposed for 8 weeks to 0.11 or 0.96 ppm of diborane for 6 hr/day, 5 days/week. The control group was exposed to filtered air. Bronchoalveolar lavage fluid (BALF), hematological, biochemical, and histopathological examinations were conducted. Sperm counts and spermatic morphological changes were examined in epididymides, and histopathological examination was carries out in testes. BALF examinations revealed that the percentage of neutrophils increased in a dose-dependent manner and that of macrophages decreased in rats exposed to 0.96 ppm. Quantities of total and individual phospholipids in BALF increased in rats exposed to 0.96 ppm. The proportion of phosphatidylglycerol plus sphingomyelin decreased, and phosphatidylethanolamine and phosphatidylinositol increased in rats exposed to 0.96 ppm. LDH increased in rats exposed to 0.96 ppm, and ALP showed a dose-dependent increase. In serum, alpha 1-antitrypsin and superoxide dismutase activities increased in rats exposed to 0.11 or 0.96 ppm. These changes showed dose-dependent effects on the lung in rats exposed to diborane, possibly indicating that the hyperenergia of type II cells with proliferation and/or hypertrophy without histopathological changes occurred even in rats exposed to 0.11 ppm. Testicular examinations revealed no particular findings. The TLV-TWA of diborane (0.1 ppm) seems to be high and possibly unsafe, considering that the no-observed-effect level over 8 weeks for rat lung was under 0.11 ppm.

Administration, Inhalation↗
PubMed1996

Relationship between acetone exposure concentration and health effects in acetate fiber plant workers.

In order to clarify the effects of acetone (AC) exposure on health, a cross-sectional study was carried out in 110 male AC-exposed and 67 male nonexposed shift workers. The AC workers ranged in age from 18.7 to 56.8 years (mean: 37.6 years) and in length of AC exposure from 0.5 to 34.3 years (mean: 14.9 years). The nonexposed workers ranged in age from 20.7 to 57.5 years (mean: 41.9 years). AC exposure levels assessed by personal passive monitors and biological monitoring indices measured at the end of the workshift were 19.6-1018 ppm in the breathing zone (AC-E, mean: 364 ppm), 2.5-422 ppm in alveolar air (AC-A, mean: 97.3 ppm) 4-220 mg/l in blood (AC-B, mean 66.0 ppm), and 0.75-170 mg/l in urine (AC-U, mean: 37.8 mg/l). Symptoms at the end of the workshift with good exposure-response relationships were eye irritation, tearing, and acetone odor, and symptoms within the previous 6 months with good exposure-response relationships were heavy, vague, or faint feeling in the head, nausea, loss of weight, and slow healing of an external wound. In the 30-44 year age range, simple reaction time and digit span scores in a short computerized neuro-behavioral test battery were significantly lower in AC workers, but exposure-response relationships were not clear. Manifest Anxiety Scale scores, Self-rating Depression Scale scores, R-R interval variation on the ECG, hematological examinations, serum biochemistry examinations for liver function, and phagocytic activity of peripheral neutrophils did not show any AC-related differences between the two groups. In view of the reported findings, the current occupational exposure limit of 750 ppm recommended by many governmental and academic associations seems to be too high to prevent the health effects of AC observed in this study.

Acetone↗
PubMed1996

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

Using male ICR mice, the LC50 and acute and subacute inhalation toxicity of dichlorosilane (SiH2Cl2, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron in diameter. The LC50 of DCS at 4-h exposure was 144 ppm (nominal concentration). In the acute inhalation study, ten mice in each group were exposed to 64 ppm (nominal concentration) DCS for 1, 2, 4 or 8 h. Body weight loss, wheezing and piloerection were observed in mice exposed for 2 h or more. Histopathologically, injury to the nasal mucosa and trachea were observed in all exposed mice. Mice exposed to 32 ppm (nominal concentration) DCS for 2 or 4 weeks also exhibited depression of body weight gain, wheezing and piloerection. Squamous metaplasia of the nasal mucosa and tracheal epithelium was observed in both 2- and 4-week exposure groups. Exposure to DCS was irritant or corrosive to the respiratory tract with both acute and subacute inhalation. Apart from silane (SiH4), toxic effects of DCS seem to be characterized by chloride compounds derived from DCS.

Administration, Inhalation↗
PubMed1996

Molecular assembly of RNA polymerase II from the fission yeast Schizosaccharomyces pombe: subunit-subunit contact network involving Rpb5.

BACKGROUND: Eukaryotic RNA polymerase II is composed of more than 10 polypeptide chains. The minimum and essential subunits for RNA synthesis have not yet been identified. Toward this ultimate goal, we analysed the topological arrangement of the putative subunits. Here we report a subunit-subunit contact network involving subunit 5 of the fission yeast Schizosaccharomyces pombe RNA polymerase II. RESULTS: The rpb5+ gene encoding subunit 5 of RNA polymerase II was cloned from the fission yeast Schizosaccharomyces pombe. The polypeptide predicted from DNA sequence of the rpb5+ gene consists of 210 amino acids with a calculated molecular weight of 23914. The homology of the amino acid sequence is 55% and 43% with Saccharomyces cerevisiae RPB5 and human hRPB25, respectively. Far-Western blot analysis of S. pombe RNA polymerase II using 32P-labelled recombinant Rpb5 fused to glutathione S-transferase (GST) as a probe, indicated that Rpb5 binds strongly to membrane-immobilized Rpb1, Rpb2 and Rpb3 and weakly to Rpb5 and a 15-kDa subunit (Rpb8 or Rpb11). In agreement with this result, the 32P-labelled Rpb3 probe showed a strong binding signal against Rpb5 in addition to Rpb1 and Rpb2. The existence of Rpb5-Rpb3 contact was supported by detection of complexes formed between these two proteins synthesized in vitro using protein-immobilized beads. CONCLUSION: Rpb3 and Rpb5, the putative subunits of RNA polymerase II, associate each other to form binary complexes. These two subunits also bind to the two large subunits, Rpb1 and Rpb2, independently.

Amino Acid Sequence↗
PubMed1996

An interaction of cisplatin and radiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro.

We investigated the interaction of cisplatin and radiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro. The effects were assessed by clonogenic assay. D0 for the radiosensitivity of the radioresistant variant cell line, NMT-1R was 139 cGy, which was 1.3 times larger than that for the parent radiosensitive cell line, NMT-1 (D0 = 107 cGy). The concentration of cisplatin required to reduce colony formation by 50% at 1 h treatment (ID50 of cisplatin) was 0.25 microgram/ml for NMT-1, whereas that for NMT-1R was 1.0 microgram/ml. Cisplatin potentiation of radiation sensitivity was manifested by the decrease in the slope of the radiation dose-response curve. D0's for NMT-1 and NMT-1R were 83 and 100 cGy in combined treatment with ID50 of cisplatin immediately before radiation. The enhancement ratios of cisplatin were therefore 1.30 for NMT-1 and 1.39 for NMT-1R respectively in D0. No different enhancement ratio for cisplatin was observed in the time course of combination treatment with cisplatin and radiation within the interval of 6 h. There was no clear change in cell cycle distribution within 6 h after treatment with ID50 of cisplatin for both cell lines. In conclusion, cisplatin had a synergistic effect on both cell lines which was independent of the time course and sequence in combination with radiation within 6 h.

Animals↗
PubMed1996

A radioresistant variant cell line, NMT-1R, isolated from a radiosensitive rat yolk sac tumour cell line, NMT-1: differences of early radiation-induced morphological changes, especially apoptosis.

A radioresistant variant cell line, NMT-1R, was isolated by repeated radiation exposure of a radiosensitive rat yolk sac tumour cell line, NMT-1, producing alpha-fetoprotein, with the potential for lymphatic metastasis in the inbred Wistar rat. Cultured NMT-1R cells showed more cobblestone-like appearances, although the morphological features were almost the same as radiosensitive NMT-1 cells reported previously. The doubling time of NMT-1R cells was 13.6 h, being shorter than that of NMT-1 cells (16.0 h). For NMT-1R cells, D0 for radiation sensitivity was 165 +/- 3 cGy, 1.7 times as large as for NMT-1 cells. The extrapolation number, n, was 1.48 +/- 0.17 for NMT-1R cells although that for NMT-1 cells was 1.08 +/- 0.15. The surviving fractions at 2 Gy (SF2) were 0.42 for NMT-1R cells and 0.28 for NMT-1 cells. The population of G2-M phase for NMT-1R cells was larger than for NMT-1 cells (32.5 versus 26.8%) in exponentially growing cells. Although a clear G2 delay was observed after irradiation with a dose of 182 cGy for both cell lines, NMT-1R cells had a shorter recovery time from G2 block than NMT-1 cells, G1 arrest was observed in NMT-1 cells. NMT-1 cells showed much higher incidence of early morphological changes, especially apoptosis, after irradiation with a dose > 500 cGy compared with NMT-1R cells.

Animals↗
PubMed1996

Results of radiation therapy for hypopharyngeal carcinoma: impact of accelerated hyperfractionation on prognosis.

We reviewed the results of treatment in 52 patients with hypopharyngeal carcinoma who underwent radical radiation therapy using a two-fractionation scheme--conventional fractionation (CF) and accelerated hyperfractionation (AHF)--in order to evaluate the impact of the fractionation scheme on prognosis. The 5-year survival rate for the 52 patients was 19.5%, and a significantly better rate was obtained with AHF (44.4%) than with CF (12.4%). Of 27 patients who showed a complete response (CR), a higher CR rate (61%) was achieved with AHF than with CF (47%). A similar trend was also observed for T3 and T4 tumors (55% with AHF vs. 36% with CF). Multivariate analysis demonstrated that neck node status was a significant factor related to local control, and that local response and the fractionation scheme employed were significant prognostic factors for survival. The recurrence rate and recurrence within the radiation field in the AHF group was lower than in the CF group (27% vs. 50%), although the time to recurrence in the two groups did not differ greatly. Voice preservation was achieved in 20% of the patients. Considering the better survival and local control rate compared with conventional fractionation, accelerated hyperfractionation seems a preferable treatment for hypopharyngeal carcinoma.

Adult↗
PubMed1996

Impact of tumor extent and location on treatment outcome in patients with stage III non-small cell lung cancer treated with radiation therapy.

The results of treatment of 141 patients with stage III non-small cell lung cancer (NSCLC) who received definitive radiation therapy at Gunma University Hospital between 1976 and 1989 were retrospectively analyzed. Radiation was given with standard fractionation for a planned prophylactic dose of 40 Gy over 4 weeks and a definitive dose of 60 Gy over 6 weeks or more. The two- and five-year survival rates were 27% and 12% for stage IIIA, and 18% and 8% for stage IIIB, respectively (P = 0.052). By univariate analysis, a primary tumor less than 5 cm in diameter was also an important predictor of survival (P = 0.008). As for tumor location, the patients with primary tumors in the upper lobes or the superior segment of the lower lobes of the lung lived longer than those with primary tumors at any other site (P = 0.032). Patients with epidermoid carcinoma had a higher survival rate at 5 years than those with other histologic types (14% vs 3%, P = 0.074). Multivariate analysis showed that among tumor characteristics, the site of the primary tumor, the pattern of tumor spread and N stage were significantly associated with overall survival. Among the patients with stage III NSCLC, those with stage IIIA epidermoid carcinoma in the upper lobe or the superior segment of the lower lobe of the lung were considered to be the most favorable candidates for definitive radiation therapy.

Aged↗
PubMed1996

Concentrations of gonadotropin-releasing hormone (GnRH) receptor messenger ribonucleic acid in pituitary tissue of orchidectomized sheep: effect of estradiol and GnRH.

The effects of estradiol (E2) and E2 withdrawal on tissue concentrations of GnRH receptor mRNA were assessed in orchidectomized sheep (wethers). Wethers received E2 (in 20% ethanol-saline [vehicle]) by continuous infusion at rates of 0.31, 1.25, 5, or 20 micrograms/h (n = 12 animals per group). Control animals received vehicle alone. Anterior pituitary tissue was collected at the end of the 48-h infusion period. Steady-state levels of GnRH receptor mRNA were quantified by solution hybridization. Tissue levels of mRNA were significantly increased above control levels (0.5 +/- 0.1 pg/microgram RNA) by E2 infusion at 1.25 micrograms/h (1.4 +/- 0.2 pg/microgram RNA). Maximal tissue concentrations of GnRH receptor mRNA were induced by E2 delivery at 5 micrograms/h (2.4 +/- 0.3 pg/micrograms RNA). In a second study, wethers (n = 6 animals per group) received 5 micrograms E2/h for 24 h. Pituitary tissue was collected at the end of the infusion period or at 12, 24, or 48 h after cessation of E2 delivery. Infusion of E2 induced a 6-fold increase in GnRH receptor mRNA (0.4 +/- 0.1 and 2.9 +/- 0.6 pg/micrograms RNA in control and E2-treated groups, respectively). Cessation of E2 delivery resulted in rapid reduction in steady-state levels of GnRH receptor mRNA. Tissue concentrations of receptor mRNA returned to pretreatment levels within 12 h of E2 withdrawal (0.6 +/- 0.1 pg/microgram RNA). In a third study, the concentration of GnRH receptor mRNA was determined in pituitary tissue collected during preovulatory surge-like secretion induced in E2-infused wethers by episodic delivery of high-amplitude GnRH (1600 ng GnRH per hourly pulse). Estradiol (5 micrograms/ml in 10% ethanol-saline) was delivered as a continuous infusion. Episodic delivery of GnRH was initiated 24 h after E2 infusion was begun, and concurrent administration of E2 and episodic GnRH was continued to slaughter. Anterior pituitary tissue was collected at 0, 3, 6, 12, or 24 h after beginning circhoral delivery of GnRH (n = 6 wethers per group). As noted above, continuous infusion of E2 for 24 h significantly increased tissue concentrations of GnRH receptor mRNA. However, steady-state levels of GnRH receptor mRNA were returned to pretreatment levels after 3 h of circhoral delivery of GnRH (0.4 +/- 0.1 pg/microgram RNA). Taken together, these data demonstrate that physiological concentrations of E2 increase steady-state levels of GnRH receptor mRNA in a dose-dependent manner. In addition, continued estrogenic support is required to maintain enhanced tissue concentrations of GnRH receptor mRNA. Finally, high-amplitude GnRH stimulation induces down-regulation of tissue levels of GnRH receptor mRNA. These data suggest that the dynamic changes in tissue concentrations of GnRH receptor mRNA during the periovulatory period may be due to the inductive effects of gonadal steroids from the developing follicle and to the combined suppressive effects of the increased GnRH stimulation and E2 withdrawal that are associated with the gonadotropin surge.

Animals↗