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Biomedical subjects

T Nagase

Publications and source records attributed to T Nagase.

At least 217 records · Page 12Linked to original sources
PubMed1990

Influences of inhaled tobacco smoke on the senescence accelerated mouse (SAM).

We studied the influences of inhaled tobacco smoke on lung structure, biochemical changes in bronchoalveolar lavage (BAL) fluid, and glutathione (GSH) content of the lung in the senescence accelerated mouse (SAM), using 30 female SAM-P/8 as the "senescence-prone series", compared with SAM-R/1 as the "senescence-resistant series". At 18 wks of age, half of each series were housed in Hamburg II machines and exposed to an atmosphere of tobacco smoke for 5 wks, 10 min a day, 5 days a wk. At 24 wks of age, all of the animals were sacrificed. Blood, lung, liver, kidney and eyes were removed and the contents of GSH and thiol group (-SH) were measured (n = 5). We also performed BAL, to determine its total protein, albumin, and fibronectin contents, and elastase-like activity, elastase inhibitory capacity (EIC), and trypsin inhibitory capacity (TIC) (n = 5). Histological changes of the lungs from non-lavaged animals were also examined by light microscopy (n = 5). In SAM-P/8 not exposed to tobacco smoke, the mean linear intercept was longer than that in SAM-R/1. The exposure of SAM-P/8 to tobacco smoke caused increases in its lung weight and the ratio of albumin to total protein in BAL fluid, a decrease in the EIC/TIC ratio in BAL fluid, and a decrease in the GSH content and the GSH/-SH ratio of the lung, compared with those not exposed. We also observed focal infiltration of macrophages into alveoli with hyaline membrane and thickened alveolar wall in SAM-P/8 with tobacco exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

[Quantitative assessment of dyspnea by introducing new indices based on the Borg scale during exercise test and the correlation with parameters of pulmonary functions at rest].

Incremental exercise test with a bicycle ergometer was performed on thirty eight patients (11 patients with chronic obstructive pulmonary disease, 6 patients with interstitial lung disease, 21 patients with preoperative check up for respiratory disease). In 34 patients except four patients with interstitial lung disease, there was a close correlation between dyspnea expressed on the Borg scale (BS) and oxygen consumption (VO2) (r = 0.778-0.998). To evaluate dyspnea in more quantitative manner, we introduced three parameters by the BS-VO2 regression line. The Borg scale slope (BSS) represents the slope of the regression line, threshold load of dyspnea (TLD) represents the onset of dyspnea on the regression line, and the breakpoint load of dyspnea (BLD) represents the maximum oxygen consumption before the subject interrupted exercise. BSS had significant negative correlations with VC, %VC, FEV1.0, TLC, DLco, and %DLco. TLD and BLD had significant positive correlations with VC, FEV1.0, DLco, and %DLco. No correlation was found between dyspnea evaluated by the Hugh-Jones classification and the parameters of pulmonary functions (VC, FEV1.0, DLco) at rest. From these findings, we conclude that the degree of dyspnea sensation on exercise correlated with parameters of pulmonary function at rest, and that these newly introduced parameters using the Borg scale were useful for a quantitative assessment of dyspnea in health and disease.

Dyspnea↗
PubMed1989

Transcriptional trans-repression by the c-myb proto-oncogene product.

We report that the c-myb protein binds to another site, MBS-II, in the SV40 enhancer with low affinity. In co-transfection experiments with a c-myb expression plasmid, tandem repeats of the sequence containing the MBS-II site induced c-myb-dependent transcriptional repression. Results of mutational analyses of the sequence around the MBS-II site suggested that the c-myb protein represses transcription by competing with another trans-activator. These results indicate that c-myb protein can regulate transcription not only positively but also negatively.

Chromosome Mapping↗
PubMed1989

Delineation of three functional domains of the transcriptional activator encoded by the c-myb protooncogene.

The c-myb protooncogene encodes a sequence-specific DNA-binding protein (c-Myb) that induces transcriptional activation or repression. We have identified three functional domains of the mouse c-Myb protein that are responsible for DNA binding, transcriptional activation, and negative regulation, respectively. In addition to the DNA-binding domain, which is located near the N terminus, an adjacent region (the transcriptional activation domain) containing about 80 amino acids was found to be essential for transcriptional activation. Deletion of a region spanning about 175 amino acids of the C-proximal portion increased transcriptional activation markedly, revealing that this domain normally represses activation. Differences between the transcriptional activation and repression functions of c-Myb and v-Myb are discussed in the light of these functional domains. Our results suggest that transcriptional activation may be involved in transformation by myb gene products.

Actins↗
PubMed1989

[Cisplatin combination chemotherapy in advanced lung cancer in the aged].

Eleven aged patients over 65 years of age with advanced lung cancer (mean age = 70.8 +/- 1.4, non-small cell:small cell = 9:2, stage III:IV = 5:6) were treated with combination chemotherapy consisting of cisplatin (50 or 80 mg/m2) and vincaloids (vindesine 3 mg/m2 or etoposide 80 mg/m2). To evaluate this cisplatin combination therapy, the aged group was compared with a young group consisting of eleven patients (mean age = 53.3 +/- 1.7, non-small cell:small cell = 9:2, stage III:IV = 5:6) matched for cell type, stage and dose regimen. The mean dose of cisplatin was 58.2 mg/m2 in the aged and 63.6 mg/m2 in the younger group. A notable reduction in tumor size was observed in 9.1% of the aged and 27.3% of the young, while one-year survival rate was 63.6% in the aged and 72.7% in the young. The common side effects were nausea and vomiting, while diarrhea was seen in 18.2% of the aged. Neutropenia, anemia and thrombocytopenia were found in both groups and the time course of myelosuppression in the aged (18.2 +/- 0.8 days) was significantly shorter than that in the younger patients (22.0 +/- 1.4 days, p less than 0.05). With regard to nephrotoxicity, creatinine clearance rate in the aged decreased remarkably from 56.9 to 38.9 ml/min, while there was no significant change in BUN, serum creatinine and urine NAG between the aged and the young. Disorders of electrolytes such as hypokalemia and hyponatremia were seen in 45.5% of the aged. We conclude that advanced lung cancer in the aged was effectively treated with cisplatin combination therapy with tolerable nephrotoxicity and myelosuppression.

Aged↗
PubMed1989

[Immunologic evaluation in patients with lung cancer with special regard to peripheral blood natural killer cell activity and interleukin-2 productivity].

Thirteen patients with lung cancer and 62 age-matched control subjects were investigated in this study (68.5 +/- 2.7 y.o. and 70.5 +/- 1.1 y.o. respectively). The peripheral blood natural killer (NK) cell activity of patients with lung cancer and control subjects was 59.3 +/- 4.4% and 69.3 +/- 1.8%, respectively. The NK cell activity in these patients was significantly lower than the NK activity of control subjects (p less than 0.05). The Interleukin-2 (IL-2) productivity of stimulated peripheral lymphocytes from patients with lung cancer was 4.96 +/- 0.99 unit, and from control subjects was 12.31 +/- 1.51 unit. When compared with control subjects, the IL-2 productivity in the patients with lung cancer was significantly lower (p less than 0.05). There were no differences in values of OKT series or OKT4/OKT8 ratio between these patients and control subjects. Ten of the 13 patients received schizophyllan intramuscularly once a week (40 mg/week). The NK cell activity was significantly increased on the second day after the second injection of schizophyllan, but there was no change in IL-2 productivity. We conclude that the peripheral blood NK cell activity and IL-2 productivity of patients with lung cancer was decreased. The antitumor polysaccharide, schizophyllan, temporarily raised the NK cell activity of these patients.

Adenocarcinoma↗
PubMed1989

[The influence of cigarette smoke on metabolism of eicosanoids in rat lung in terms of variation of 15-hydroxyeicosatetraenoic acid and 11-dehydrothromboxane B2].

We investigated the effects of cigarette smoking on metabolism of two eicosanoids, 15-hydroxyeicosatetraenoic acid (15-HETE) and 11-dehydrothromboxane B2 (11-dehydro-TXB2) in the lung. Twelve female Wistar rats aged between 5 and 6 weeks were chosen and the smoking group (SG, n = 6) was compared to the control group (CG, n = 6). Cigarette smoke exposure was performed using a Hamburg-II inhalation apparatus and the dose was 10 cigarettes in 30 min. Bronchoalveolar lavage (BAL) was conducted 30 min after smoking exposure and the recovered BAL fluid was centrifuged at 3000 rpm for 10 min. The levels of 15-HETE and 11-dehydro-TXB2 of the supernatant were measured by radioimmunoassay in each sample. Recovered 15-HETE significantly increased in SG (SG: 490 +/- 109 pg, CG: 191 +/- 63 pg, p less than 0.05), while there was no significant difference in recovered protein (SG: 2.64 +/- 0.50 mg, CG: 2.23 +/- 0.10 mg), 11-dehydro-TXB2 (SG: 128 +/- 13 pg, CG: 156 +/- 7 pg). We conclude that acute cigarette smoke exposure increases recovered BAL fluid 15-HETE, a potent inflammatory mediator and that 15-HETE in BAL fluid may indicate lung injury induced by smoking.

Animals↗
PubMed1988

Differential transcriptional control of the two tRNA(fMet) genes of Escherichia coli K-12.

The metZ gene of Escherichia coli, which encodes the tRNA(f1Met), was cloned. Using the nucleotide sequence, in vitro transcription, and S1 nuclease mapping analyses, we identified the promoter region, transcriptional start point, the two tandem tRNA(f1Met) structural genes separated by an intergenic space of 33 bp, and the two Rho-independent transcriptional termination sites, in that order. We compared the promoter region of the metZ gene with that of the metY gene, which encodes the tRNA(f2Met) and is located in the promoter-proximal portion of the nusA operon. A G + C-rich sequence (5'-GCGCATCCAC-3'), similar to the corresponding sequence of the rrn promoters that are under stringent control, was found between the Pribnow box and the transcriptional start point of the metZ promoter, but not in the metY promoter region. We therefore examined the effect of guanosine 3'-diphosphate, 5'-diphosphate (ppGpp), the chemical mediator of stringent control, and found that ppGpp inhibited the transcription of the metZ gene, but not that of the metY gene. These data suggested that the promoters for metZ and metY have different physiological functions and are regulated by different mechanisms.

Base Sequence↗
PubMed1988

Production of leukotrienes from mouse peritoneal macrophages by treatment with a neutral subfraction of bakers' yeast mannan.

We concluded that a neutral subfraction of mannan from bakers' yeast (Saccharomyces cerevisiae wild type strain), abbreviated as WNM, was able to induce the release of leukotrienes from mouse peritoneal macrophages (M phi). The culture supernatant fluid of M phi from normal mice cultured with WNM caused a marked contraction of guinea pig ileum. This activity was inhibited by pretreatment of M phi with inhibitor of phospholipase A2 or lipoxygenase before M phi were treated with WNM, and by treatment of the incubation bath with a slow reacting substance antagonist, FPL55712. On the other hand, pretreatment of M phi with a cyclooxygenase inhibitor potentiated contractile response of ileum by culture supernatant fluid of M phi. A high performance liquid chromatographic analysis of a culture supernatant fluid of M phi treated with WNM demonstrated the presence of leukotrienes C4 and D4, and their related compounds.

Animals↗
PubMed1988

Veno-occlusive disease of the liver in a patient with allergic granulomatous angiitis.

A 45-yr-old woman, with asthma and skin erythema, was diagnosed as having allergic granulomatous angiitis. Leukocytosis accompanied by hypereosinophilia and characteristic histological findings of skin lesions also were present. Upon laparoscopy and liver biopsy, the liver showed a congestive appearance and, histologically, showed thickening of the central vein walls, as well as narrowing of the lumens with collagenous fibers, and pericentral hemorrhage with hepatocyte degeneration. A diagnosis of veno-occlusive disease of the liver was made. This is the first report on a case of veno-occlusive disease of the liver occurring in association with allergic granulomatous angiitis.

Female↗
PubMed1987

[Effects of 1-[2-[bis(fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride (I-893) on turnover of dopamine and norepinephrine in the brain].

Studies were performed to elucidate the effects of 1-[2-[bis (fluorophenyl) methoxy]ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride (I-893), a newly synthesized aryl-1,4-dialkyl-piperazine derivative, on turnover of dopamine and norepinephrine in the rat brain. The contents of both monoamines were not affected by I-893 at an oral dose of 10 mg/kg. The oral administration of 50-250 mg/kg produced a transient increase in dopamine content of the caudate nucleus and hypothalamus, and thereafter, the content dose-dependently decreased. Norepinephrine levels in the hypothalamus and frontal cortex were slightly decreased by I-893. I-893 potentiated the rate of alpha-methyl-p-tyrosine-induced depletion of dopamine and norepinephrine. The 3-methoxytyramine content in animals treated with pargyline was increased by I-893 in the caudate nucleus and olfactory tubercle. NSD-1015-induced accumulation of DOPA was suppressed by larger doses of I-893. Oral administration of I-893 (10-50 mg/kg/day) for 14 days slightly attenuated the inhibitory effects of the drug on the norepinephrine level, while it did not affect the inhibitory effect on the dopamine level. These results suggest that I-893 facilitates the release of dopamine and norepinephrine and/or inhibits the uptake of the monoamines in the presynaptic nerve terminals.

Animals↗