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Biomedical subjects

T Nagase

Publications and source records attributed to T Nagase.

At least 199 records · Page 11Linked to original sources
PubMed1991

Analyses of polypeptides in the liver of a novel mutant (LEC rats) to hereditary hepatitis and hepatoma by two-dimensional gel electrophoresis: identification of P29/6.8 as carbonic anhydrase III and triosephosphate isomerase.

1. Total cellular proteins from the livers of 4-, 16- and 52-week-old hepatitis- and hepatoma-predisposed Long-Evans Cinnamon (LEC) rats were compared to those from the livers of the corresponding control rats [Long-Evans Agouti (LEA) rats] by two-dimensional gel electrophoresis. 2. A polypeptide, p50/7.2 (molecular weight x 10(-3)/isoelectric point) was only found in the LEC rats, and the p43/6.4 component was greater and the p51/6.8 component was less in the LEC rats than in the LEA rats during aging. 3. A polypeptide, p29/6.8, was dramatically greater in 4-week-old LEC rats than in 4-week-old LEA rats. 4. By sequencing and Western blotting analysis, the marked differences in the level of the p29/6.8 component were found to be due to carbonic anhydrase III.

Aging↗
PubMed1991

Intravenous bolus of prednisolone decreases 15-hydroxyeicosatetraenoic acid formation in the rat model of acid aspiration.

BACKGROUND AND METHODS: To test the hypothesis that the effect of steroids on hydrochloric acid aspiration may be involved in the metabolism of eicosanoids, we investigated the effects of an iv bolus of prednisolone on the metabolism of 15-hydroxyeicosatetraenoic acid and 11-dehydrothromboxane B2 (11-dehydro-TxB2) in the rat model of acid aspiration. Wistar rats were randomly selected for three groups and treated with either a) an iv bolus of saline after intratracheal injection of saline (control group), b) an iv bolus of saline after intratracheal injection of acid (acid-saline group), or c) an iv bolus of prednisolone after intratracheal injection of acid (acid-prednisolone group). The concentrations of 15-hydroxyeicosatetraenoic acid and 11-dehydro-TxB2 in bronchoalveolar lavage fluid were measured by radioimmunoassay. RESULTS: The concentration of 15-hydroxyeicosatetraenoic acid in bronchoalveolar lavage fluid of either acid-saline group (804 +/- 129 pg/mL) or acid-prednisolone group (748 +/- 112 pg/mL) was significantly greater than that of the control group (143 +/- 27 pg/mL, p less than .01) 1 hr after the administration. The iv bolus of prednisolone caused a significant decrease in 15-hydroxyeicosatetraenoic acid (acid-saline group 1027 +/- 43 pg/mL; acid-prednisolone group 514 +/- 62 pg/mL; p less than .01) and cell counts of bronchoalveolar lavage fluid 48 hrs after intratracheal injection of acid, while there was no significant change in 11-dehydro-TxB2. CONCLUSION: These findings suggest that corticosteroid administration may contribute to the inhibition of the inflammatory process of lungs after acid aspiration by decreasing the release of 15-hydroxyeicosatetraenoic acid in the distal lung unit.

Animals↗
PubMed1991

Efficacy of oral administration of ofloxacin in lower respiratory tract infections in aged patients with chronic lung disease.

The efficacy of ofloxacin for the treatment of lower respiratory tract infection was evaluated in aged patients with chronic lung disease. Results are the following: improvement of leukocytosis and arterial oxygen tension was observed; peripheral blood cell analysis showed a decrease in natural killer cell counts and in helper/suppressor T cell ratio; superoxide production by peripheral blood white cells was decreased after treatment; interleukin-2 production was rather increased. We concluded that improvement in the immunological parameters indicated the efficacy of ofloxacin for lower respiratory tract infection in aged patients with chronic lung disease.

Administration, Oral↗
PubMed1991

[Pharmacological effects of the novel dopamine uptake inhibitor 1-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride (I-893) on the central nervous system].

The effects of 1-[2-[bis (4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl) piperazine dihydrochloride (I-893) on the central nervous system were behaviorally and electroencephalographically investigated. Intraperitoneally injected I-893 (5-10 mg/kg) dose-dependently increased spontaneous motor activity in mice, but repeated injections did not affect the increase in the locomotor activity. In reserpinized mice, spontaneous motor activity was not increased by oral I-893. In alpha-MPT-treated mice, the motor activity was lower than that in vehicle-treated animals with intermediate doses (10-40 mg/kg, p.o.) of I-893, but there was no difference between the two groups with high doses. In rats with unilaterally 6-OHDA-induced lesion of the nigrostriatal pathway, I-893 induced circling behavior toward the lesioned side. Haloperidol-induced catalepsy in rats was reduced by I-893. Tremorine-induced tremor in mice was inhibited by I-893. The effect was not altered in the mice treated with I-893 for 10 days. Oral I-893 induced stereotypy in rats, but it did not affect methamphetamine-induced stereotypy. Hypnosis induced by barbiturates was antagonized by I-893. In rats treated with I-893 for 6 days, pentobarbital-induced sleep was not different from that in vehicle-treated animals on the day after the final treatment. Intravenous I-893 altered EEGs in the cerebral cortex and amygdala nucleus to low voltage and fast waves and altered hippocampal EEG to theta waves in immobilized rabbits. These results suggest that I-893 inhibits re-uptake of dopamine released by exocytosis and indirectly has dopaminergic effects.

Animals↗
PubMed1990

Transcriptional control of the human Harvey ras proto-oncogene: role of multiple elements in the promoter region.

In the promoter region of the human c-Ha-ras1 gene, multiple elements for transcriptional control are dispersed. To examine the role of each element, we made a series of deletion mutants of this promoter region, including internal deletion mutants, and measured the promoter activities of these mutants. Any two of the four Sp1-binding sites upstream from the CCAAT-box element were sufficient for the maximal activity of the c-Ha-ras1 promoter. Either one of the two Sp1-binding sites downstream from the CACCC-box element was also necessary for the maximal promoter activity. Deletion of the CCAAT-box or CACCC-box elements reduced the level of transcription to 25% or 41% of that with the wild-type promoter. These results indicated that at least three Sp1-binding sites, and the CCAAT-box and CACCC-box elements contributed in concert to the activity of the human c-Ha-ras1 promoter.

CCAAT-Enhancer-Binding Proteins↗
PubMed1990

Promoter region of the human CRE-BP1 gene encoding the transcriptional regulator binding to the cyclic AMP response element.

Genomic clones containing the 5'-terminal portion of the human CRE-BP1 gene that encodes transcriptional regulator binding to the cyclic AMP response element (CRE) were isolated. Multiple transcriptional start sites in the promoter region were identified by nuclease S1 mapping and primer extension analysis. By DNase I footprinting with use of purified transcription factor Sp1 and nuclear extracts prepared from HeLa cells, 11 Sp1-binding sites, two CCAAT sequences, two CREs, and three unknown factor recognition elements were found. Transfection of chimeric chloramphenicol acetyltransferase plasmids containing various deletions of the promoter into CV-1 cells indicated that the region between nucleotides -50 and 90, which contained three Sp1-binding sites and one CRE, was sufficient for basal promoter activity. These results suggest that multiple sequence-specific DNA-binding proteins may control the expression of the CRE-BP1 gene, although Sp1 seems to be important for the basal promoter activity.

Base Sequence↗
PubMed1990

DNA binding activity and transcriptional activator function of the human B-myb protein compared with c-MYB.

Three members of the myb gene family have been identified in human cDNA libraries c-myb, A-myb, and B-myb. We compared the DNA binding properties of the B-myb and c-myb proteins (B-MYB and c-MYB) using bacterially synthesized B-MYB and c-MYB in DNase I footprinting. B-MYB bound to most of the c-MYB binding sites examined, including the c-MYB binding site, MBS-I, in the simian virus (SV) 40 enhancer, in which the most frequent sequence was CCTAACTG. The MBS-I site was an enhancer element dependent on B-MYB and c-MYB in a co-transfection assay that used the B-myb or c-myb expression plasmid. Some sites in the SV40 genome, including the MBS-BI site, had high affinity with B-MYB but little or no affinity with c-MYB, in which the most frequent sequence was AGAAANPyrG. The MBS-BI site was an enhancer element dependent on B-MYB and a very weakly dependent on c-MYB. Our results showed that B-MYB is a transcriptional activator, like c-MYB, and that although B-MYB and c-MYB have similar sequence specificity for DNA binding some sequences were recognized by B-MYB preferentially.

Base Sequence↗
PubMed1990

Increase in the active form of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human hepatocellular carcinoma: possible mechanism for alteration of cholesterol biosynthesis.

3-Hydroxy-3-methylglutaryl coenzyme A reductase activity and the rate of sterol biosynthesis are positively correlated with DNA synthesis and proliferation of mammalian cells. The total (active plus latent) activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and the activity of its active form in hepatocellular carcinoma (HCC) from seven patients were measured and compared with those in liver tissue from five control subjects. The activity of the active form in HCC was 61 +/- 21 (SD) pmol/min/mg microsomal protein, while it was only 17 +/- 9.8 pmol/min/mg protein in the liver tissue from the controls; the difference was significant (P less than 0.005). The total activity of the reductase was also higher in HCC although the difference was not significant. The microsomal contents of the enzyme protein also were not significantly different. The rate of cholesterol biosynthesis was 307 +/- 81 pmol/h/mg tissue in HCC and 79.6 +/- 52 in normal liver tissue, indicating a significant increase in the rate in HCC (P less than 0.001). Thus, enhanced synthesis of cholesterol in human HCC seems to result partly from an increase in the active form of the reductase.

Carcinoma, Hepatocellular↗
PubMed1990

Endothelin-1 stimulates arachidonate 15-lipoxygenase activity and oxygen radical formation in the rat distal lung.

We investigated the effects of intravenous bolus of endothelin-1 on the metabolism of eicosanoids and oxygen radicals in the distal lung unit of the rat. Intravenous bolus of endothelin-1 caused a significant increase in 15-hydroxyeicosatetraenoic acid of bronchoalveolar lavage fluid and oxygen radicals produced by the bronchoalveolar cells. Endothelin-1 exhibited a stimulatory effect on the 15-lipoxygenase activity in the lung homogenate. Thus, endothelin-1 may contribute to the inflammatory and hyperreactive process of lungs, by enhancing the release of 15-hydroxyeicosatetraenoic acid and oxygen radicals in the distal lung unit.

Animals↗
PubMed1990

Binding of the c-myb proto-oncogene product to the simian virus 40 enhancer stimulates transcription.

The proto-oncogene c-myb encodes a nuclear protein which binds to DNA. Here we find that bacterially synthesized c-myb protein binds to one site of the simian virus 40 enhancer. The c-myb protein purified from the human T-cell line, Molt4, was also shown to recognize the same sequence. In co-transfection experiments with a c-myb expression plasmid, tandem repeats of a c-myb-binding sequence were shown to function as a c-myb-dependent enhancer. These results indicate the c-myb protein is a simian virus 40 enhancer-binding protein that can positively regulate transcription.

Animals↗
PubMed1990

Requirement of protein co-factor for the DNA-binding function of the human ski proto-oncogene product.

We identified the human c-ski gene product (c-Ski) as a protein with the apparent molecular weight of 100,000, p100c-ski, by using a c-Ski-specific polyclonal antibody. p100c-ski was a nuclear protein and p100c-ski in nuclear extracts of Molt4 cells bound to calf thymus DNA cellulose, but the bacterially synthesized c-Ski did not, suggesting that Ski was associated with another protein(s) and that the Ski complex had DNA-binding activity. This hypothesis was supported by the finding that the bacterially synthesized Ski bounds to DNA cellulose after being mixed with a nuclear extract of Molt4 cells. By use of a series of deletion mutants of Ski synthesized in an in vitro translation system, two portions in Ski were found to be necessary for the DNA binding of the Ski complex: the N-proximal portion containing a cystein/histidine-rich domain and the C-terminal portion including a region rich in basic amino acids.

Chromosome Deletion↗
PubMed1990

Reduction of 15-hydroxyeicosatetraenoic acid (15-HETE) in tracheal fluid by high frequency oscillatory ventilation.

The effects of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) on tracheal secretion were compared in 6 anesthetized dogs. Using a double-balloon endotracheal catheter, 5 ml of saline was instilled into an isolated tracheal segment during HFOV and CMV for 10 min respectively. Two eicosanoids, 15-hydroxyeicosatetraenoic acid (15-HETE) and 11-dehydrothromboxane B2 (11-dehydro-TXB2) were measured by radioimmunoassay in each sample. HFOV (stroke volume: 6 ml/kg, f: 10 Hz, bias flow: 5 l/min) and CMV (stroke volume: 12 ml/kg, f: 15/min) were performed in random sequence and achieved comparable gas exchange. The concentration of 15-HETE in tracheal fluid during HFOV (87 +/- 67 pg/ml) was decreased to less than half of that during CMV (286 +/- 184 pg/ml, P less than 0.05), while there was no significant change of 11-dehydro-TXB2 either in tracheal fluid or in plasma. This reduction of 15-HETE was tended to be enhanced by vagotomy (HFOV: 42 +/- 14, CMV: 120 +/- 103 pg/ml) with the concentration ratio of CMV/HFOV remaining unchanged. HFOV may provide hitherto unrecognized advantage over CMV by reducing airway secretion of 15-HETE, a potent inflammatory mediator.

Animals↗
PubMed1990

Effect of endothelin-1 on pulmonary resistance in rats.

We examined the effect of endothelin-1 (ET-1), a novel 21-residue vasoconstrictor peptide, on pulmonary resistance (RL) in Wistar rats. The lung volume, tracheal flow, and transpulmonary pressure of tracheotomized and paralyzed rats were measured with a fluid-filled esophageal catheter and a pressure-sensitive body plethysmograph. RL was calculated by the method of von Neergaard. The femoral artery was cannulated to measure the mean arterial blood pressure. Intravenous bolus administration of synthetic ET-1 provoked a dose-dependent increase in RL in rats. The bronchoconstricting effect reached maximum at 500 pmol/kg. This bronchoconstriction was observed in less than 5 min, increased up to 15 min, and was sustained for 60 min. ET-1 increased the mean arterial blood pressure in a dose-dependent manner. We conclude that ET-1 is a hitherto unknown potent bronchoconstrictor that has a sustained effect in vivo. The potential physiological and pathophysiological role of this new peptide in the development of respiratory disease warrants further investigation.

Airway Resistance↗
PubMed1990

[An aged case of orthostatic hypotension possibly due to parasympathetic neurodysfunction].

94-year-old male patient, with orthostatic hypotension, possibly due to impairment of vasoconstriction and parasympathetic nervous system dysfunction was reported. This patient experienced faintness and lower muscle weakness on standing. The blood pressure was 180/90 mmHg in a supine position, while it significantly decreased to 100/58 mmHg in an upright position. There was no evidence indicating the presence of organic brain diseases, cardiovascular diseases, and endocrine diseases, plasma catecholamine, renin, aldosterone, and vasopressin levels at rest were within normal range. Thus, the cause of orthostatic hypotension of this patient was unknown. His systolic blood pressure decreased by 70 mmHg, and his diastolic blood pressure also decreased by 25 mmHg in response to a 70 degrees head-up tilting test (170/71-100/46 mmHg). Plasma vasopressin level significantly increased in response to this test (0.62-67.2 pg/ml). Plasma catecholamine levels also increased (Adr 0.01-0.10 ng/ml, Ndr 0.05-0.22 ng/ml). Other autonomic nervous system examinations revealed normal responses to mental arithmetic test, hyperventilation test, cold pressure test, and adrenalin test. However, the results of the carotid occlusion test, acetylcholine test, atropine test, phenylephrine test were considered to be abnormal. From these findings, we concluded that the functions of sympathetic nervous system were almost intact, while the parasympathetic functions were impared in this case. The orthostatic hypotension of the patient as effectively treated with fludrocortisone. This report suggests that impairment of vasoconstriction and parasympathetic neurodysfunction might be involved in the development of orthostatic hypotension in the elderly.

Acetylcholine↗
PubMed1990

[Cisplatin and vinca alkaloid combination chemotherapy of advanced non-small-cell lung cancer in the aged].

Fifteen patients aged over 65 years of age with advanced non-small-cl lung cancer (mean age = 70.7, stage IIIb: IV = 4:11) were treated with combination chemotherapy consisting of Cisplatin (50 or 80 mg/m2) and a vinca-alkaloid (Vindesine 3 mg/m2 or Etoposide 80 mg/m2). The effectiveness and side effects of this cisplatin therapy in different combinations of vinca-alkaloid regimens (Vindesine vs Etoposide) were examined. The mean dose of Cisplatin in the Etoposide combination group (75.2 mg/m2) was significantly higher than that in the Vindesine combination group (54.3 mg/m2) (p less than 0.01). A notable reduction the tumor size was observed in 25% of the Etoposide group, only. The 6-month survival rate and one-year survival rate were respectively 85.7%, 57.1% in the Vindesine + Cisplatin group, and 87.5%, 50% in the Etoposide + Cisplatin group. The common side effects were nausea, vomiting, anorexia, and alopecia. These symptoms were either alleviated by antiemetic drugs or followed by spontaneous recovery. Leucopenia, anemia and thrombocytopenia were found in both groups, and there was no difference in the time course of myelosuppression between the two groups. The extent of nephrotoxicity was assessed by creatinine clearance rate. Its decrease in the Vindesine group (60.1----38.9 ml/min) was higher than that in the Etoposide group (64.9----48.9 ml/min), while there was no significant change in BUN, serum creatinine and urine NAG between the two groups. There were no cases in which chemotherapy schedules had to be interrupted due to myelosuppression and nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[Analysis of ventilatory parameters of nocturnal disturbed breathing in the elderly].

To elucidate the effects of aging on ventilation in nocturnal disturbed breathing (NDB), we investigated 16 subjects aged 65 years or over with system developed by the authors using a respiratory inductive plethysmography connected to a personal computer. The subjects underwent 10 hours of continuous monitoring of lung volume and SaO2. Significant desaturation (SDS, greater than 4% drop in SaO2 from baseline value) and desaturation index [DI, sigma SDS(%) X duration (hr)] were calculated using the same program. The subjects with SDS below 50 were assigned to group A (n = 9, mean age = 79.7, male:female = 8:1) and the remaining subjects with SDS over 50 (n = 7, mean age = 74.7, male:female = 3:4) to group B. There was no significant difference in ventilatory parameters between group A and B. We then compared the male group (n = 11, mean age = 77.8) with the female group (n = 5, mean age = 76.8). The number of SDS in the female group (101.4 +/- 34.7) was significantly greater than that of the male group (33.4 +/- 8.3*, p less than 0.02), while minute ventilation of the female group (5.25 +/- 0.31 l/min) was significantly smaller than that of the male group (8.86 +/- 1.36* l/min, p less than 0.05). DI was found to significantly correlate with the SaO2 nadir and the number of apnea and SDS. There was no significant relationship between SDS and ventilatory parameters in this study. NDB among elderly female may be of more importance than has been reported.

Aged↗