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T Nagase

Publications and source records attributed to T Nagase.

At least 181 records · Page 10Linked to original sources
PubMed1994

Airway and tissue responses during hyperpnea-induced constriction in guinea pigs.

It has been reported that hyperpnea-induced bronchoconstriction in guinea pigs is a potential model for exercise-induced asthma in humans. On the basis of recent studies that show increases in tissue resistance after allergen exposure in sensitized rats, we hypothesized that lung tissues might also be involved in the pathophysiology in this asthma model. We measured tracheal pressure (Ptr) and alveolar pressure (PA) using alveolar capsules in open-chested, mechanically ventilated (respiratory frequency [f] = 1 Hz, tidal volume [VT] = 9 ml/kg, positive end-expiratory pressure [PEEP] = 4 cm H2O) guinea pigs under control conditions (regular breathing of warm, humidified air) and after dry gas hyperpnea challenge (HC, mixture of 95% O2 and 5% CO2, 150 breaths/min, 7 min). We calculated lung elastance (EL) and resistance of lung (RL), tissue (Rti), and airway (Raw) by fitting the equation of motion to changes in Ptr and PA. To assess the effects of volume history, we applied a single deep inflation (three times VT) in five HC animals. We performed morphometric analysis in five control and five HC animals, freezing the lungs with liquid nitrogen and processing the tissues via freeze substitution. HC significantly increased RL, Rti, Raw, and EL (424 +/- 62, 771 +/- 230, 287 +/- 33, 259 +/- 31% baseline, respectively). A deep inflation reduced RL, Rti, Raw, and EL by 30 +/- 4, 31 +/- 4, 29 +/- 6, 23 +/- 5%, respectively. In HC animals, the degree of airway constriction was most prominent in the larger airways; extensive tissue distortion was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Airway and tissue responses to antigen challenge in sensitized brown Norway rats.

It has recently been shown in several species that lung tissue resistance increases after administration of exogenous bronchoconstrictors. This finding suggests the possibility that lung parenchymal tissues could be involved in the pathophysiology of pulmonary allergic responses. To test this hypothesis, we sensitized Brown Norway rats with ovalbumin (OA) and performed experiments in anesthetized, open-chested, mechanically ventilated (respiratory frequency [f] = 1 Hz, tidal volume [VT] = 9 ml/kg, positive end-expiratory pressure [PEEP] = 3 cm H2O) animals. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) under control conditions and after aerosol administration of saline (S) (n = 10) or OA (n = 14). To assess lung morphometry during the late response, the lungs of six S and six OA animals were frozen with liquid nitrogen (PEEP = 3 cm H2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed airway (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), an atelectasis index (ATI) derived by calculating the ratio of tissue/airspace, and the standard deviation (SD) of Lm and ATI. In the OA group, all animals demonstrated an early response (ER; RL, Rti, Raw = 183.5 +/- 7.7, 159.7 +/- 9.9, 232.5 +/- 17.2% baseline, respectively) and 11 animals showed a late response (LR; RL, Rti, Raw = 178.9 +/- 5.1, 191.3 +/- 11.5, 176.6 +/- 17.3% baseline, respectively). Neither ER nor LR were observed in the saline group.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1994

[Diffuse aspiration bronchiolitis (DAB) produced in animals by repeated HCl microaspiration].

We recently reported that diffuse aspiration bronchiolitis (DAB) was detected in 1% of autopsied lungs of aged cases of pneumonia. We hypothesized whether repeated HCl micro-aspiration (RHMA) is involved in DAB and established an animal model by administering HCl intratracheally to rats every two days for 2 weeks. Saline was given to control animals in the same fashion. Then, we performed bronchio-alveolar lavage (BAL) or excised lungs for histologic examination. There was no difference in BAL cell counts, TNF alpha-production, elastase-like activity or albumin levels between the HCl and control groups. Histologically, DAB-like findings were observed in the HCl-treated animals. These data suggest that RHMA might be involved in DAB, while neither TNF alpha-production nor elastase-like activity may play a significant role in inducing DAB.

Animals↗
PubMed1993

Complex formation between proteins encoded by the ski gene family.

The c-ski proto-oncogene product (c-Ski) is localized in the nuclei, but its function and biochemical properties are unclear. C-Ski can bind to DNA only in association with uncharacterized protein(s). A lambda gt11 cDNA library was screened with the biotinylated Ski to isolate genes encoding proteins capable of forming complexes with Ski. Two clones encoding Ski itself or the ski-related gene product SnoN were isolated in this manner, suggesting that Ski can form a complex with Ski itself or with SnoN. Trimerization of Ski with itself and SnoN was also confirmed by protein cross-linking and protein blot analysis. The carboxyl-terminal 1/5 regions of Ski and SnoN are required for complex formation. This region has a homology between two proteins and two putative leucine zipper-like structures, suggesting that these leucine zipper-like structures mediate trimerization by making side-to-side interactions between the conserved leucines. Thus, Ski and SnoN have the capacity to associate with other proteins, and a complex formation of c-Ski with itself, SnoN, and uncharacterized proteins might play a key role in the function of Ski.

Amino Acid Sequence↗
PubMed1993

Responsiveness of and interactions between airways and tissue in guinea pigs during induced constriction.

Mechanical interdependence between airways and tissues can modify the magnitude of induced bronchoconstriction. We questioned whether the guinea pig, an animal with abundant airway smooth muscle, would differ from other species in the relative responsiveness of and interactions between airways and tissues. Therefore we induced constriction with aerosolized methacholine (MCh) and partitioned responses into airway and tissue components. We measured tracheal and alveolar pressures using alveolar capsules in open-chest guinea pigs (n = 9) during mechanical ventilation [frequency = 1 Hz, tidal volume = 6 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) before and after administration of aerosols of MCh in progressively doubling concentrations (0.063-16 mg/ml). In separate animals (n = 10), measurements were made at 3-13 cmH2O PEEP. After aerosols of saline and MCh (0.125-32 mg/ml), measurements were repeated at 3, 7, and 11 cmH2O PEEP. At submaximal levels of constriction, the airways and lung tissues demonstrated similar responsiveness. Increasing PEEP increased RL and Rti and decreased Raw under baseline conditions. At low concentrations of MCh, increasing PEEP increased RL but decreased RL at the highest concentration. Increases in PEEP significantly increased Rti at all concentrations of MCh but decreased Raw only at 8 mg/ml of MCh. These observations demonstrate that, in guinea pigs, during submaximal constriction, airways and tissues behave similarly; moreover, airway-parenchymal interdependence is important in determining the level of bronchoconstriction.

Aerosols↗
PubMed1993

Comparative study of mechanical interdependence: effect of lung volume on Raw during induced constriction.

The mechanical load imposed by the parenchyma can decrease the magnitude of agonist-induced airway constriction. To examine whether variability in mechanical interdependence could account for differences in airway narrowing among different species, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine (MCh)-induced constriction in rats and guinea pigs. Direct measurements of Raw were made under baseline conditions at different levels of end-expiratory transpulmonary pressure (PL = 3-11 cmH2O). Then aerosolized MCh was delivered (128 mg/ml in rats, 8 mg/ml in guinea pigs), and measurements were obtained at different levels of PL (3-11 cmH2O). We measured tracheal flow and tracheal and alveolar pressure (using alveolar capsules) in open-chest animals during mechanical ventilation (tidal volume 6 ml/kg, frequency 1 Hz) and calculated Raw by subtracting tissue from total lung resistance. For interspecies comparisons, data were standardized using percent change in Raw (delta % Raw) at PL of 3 cmH2O during baseline and, after MCh, log-scaled delta % Raw at PL of 3 cmH2O. We found that increasing lung volume decreased Raw both at baseline and after MCh in both species. However, changes were far smaller in guinea pigs. During baseline, the slope of the delta % Raw/delta PL was -3.37 and -12.48 %/cmH2O for guinea pigs and rats, respectively (P < 0.001). After MCh, the slope of delta log %Raw/delta PL was -0.065 and -0.154 cmH2O-1 for guinea pigs and rats, respectively (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1993

[An aspiration pneumonia in acute airway damage model induced by HCl and/or LPS].

The purpose of this study is to evaluate chemical and pathological changes of the lung and to elucidate the role of TNF alpha and elastase in acute lung injury induced by HCl or lipopolysaccharide (LPS). Anesthetized rats were injected with pH 1.4 0.7 ml/kg body weight of HCl and 0.5 mg/kg body weight (BW) of LPS (E. coli) into the lung. Acute tracheal injury model (Mendelson Syndrome) were made. Control animals received only saline. Animals were sacrificed 1, 6, or 12 hours after the HCl or LPS or HCl and LPS injection, bronchoalveolar-lavage (BAL) was performed in the same way in control and experimental groups. The other animals which were treated as well were excised by histology. There was neither increase in TNF alpha-production nor increase in neutrophils resulting from HCl injection only. Elastase-like activity was not detected in animals treated only with HCl. However, 1 hour after LPS injection, the production of TNF alpha (37.0 +/- 8.0 Units/ml) was significantly greater than that of the control group (12.1 +/- 4.2 Units/ml) in BALF. Six hours after HCl and LPS injection, the concentration of elastase-like activity (0.023 +/- 0.002 nM) was significantly greater than that of the LPS group (0.011 +/- 0.001 nM). Only patches of intraalveolar hemorrhage and elevation of fibrin was observed in the HCl injected rats at 1 hour after injection. Six hours after LPS injection, the alveolar spaces were filled with large amounts of neutrophils. These findings suggest that TNF alpha and elastase play a significant role in HCl and LPS-induced acute lung injury.

Acute Disease↗
PubMed1993

[Successful weaning from mechanical ventilation in an aged subject with severe apneas due to brain damage].

A 73-year-old male was admitted to Tokyo University Hospital due to cardiac arrest secondary to ventricular arrhythmias. Although the patient survived after cardiopulmonary resuscitation, he needed mechanical ventilation. When we tried to wean the patient from mechanical ventilation, we found that he suffered from frequent sleep apneas of over 40 times/hour. To evaluate the severity and frequency of the apneas, we performed polysomnographic study on the patient under assist ventilation. The polysomnographic study revealed that frequency of apneas was very high but the magnitude of desaturation was not so severe during the night. Since we confirmed the lowest SaO2 in this patients was over 90% during day and night, we tried to wean from the patient from the ventilator again and succeeded. The clinical application and usefulness of nocturnal ventilatory monitoring for patients with mechanical ventilation was discussed.

Aged↗
PubMed1993

[Two elderly cases with acute exacerbation of interstitial pneumonia].

We studied two cases of the elderly with acute exacerbation of interstitial pneumonia to elucidate a prognostic role of super oxide generation in peripheral whole blood. The first case was a 70-year-old man, who presented with acute exacerbation of interstitial pneumonia and was hospitalized. Following steroid-pulse therapy, CRP, ESR, blood-gas and his physical condition improved, resulting in successful discharge. In this case, super oxide generation standardized by the number of neutrophils (K) decreased to less than 1.0 in association with the improvement of physical condition. The second case was a 92-year-old woman in whom acute exacerbation of interstitial pneumonia was diagnosed. While the pulse therapy, CRP, LDH and blood-gas temporarily improved, K was continuously greater than 1.0 and the physical condition worsened, resulting in her death. These cases suggest that the measurement of super oxide generation in peripheral whole blood may play a useful role in assessing the prognosis of the elderly with acute exacerbation of interstitial pneumonia.

Acute Disease↗
PubMed1992

Overlap of the p53-responsive element and cAMP-responsive element in the enhancer of human T-cell leukemia virus type I.

The wild-type p53 protein suppresses transformation, but certain missense mutants of p53 can transform cells. Although the wild-type p53 protein contains a transcriptional activation domain, no p53-responsive element has been identified. Here, we identified the p53-responsive element within the Tax-responsive element [21-base-pair (bp) enhancer] of human T-cell leukemia virus type I. Mutation analysis of the 21-bp enhancer indicated that the 16-bp sequence containing the cAMP-responsive element and its surrounding sequence was responsible for p53-induced transactivation. This 16-bp sequence was demonstrated to bind specifically to wild-type human p53 protein in vitro. Using a series of deletion mutants of p53, we showed that almost the entire region of p53 is needed for the transactivating capacity. Furthermore, the transforming mutants of p53 were unable to act as transcriptional activators. The p53-responsive element identified here should be useful to analyze the mechanism by which p53 regulates expression of a set of genes with a negative effect on cellular growth.

Animals↗
PubMed1992

Tissue viscance during induced constriction in rabbit lungs: morphological-physiological correlations.

Tissue viscance (Vti), the pressure drop across the lung tissues in phase with flow, increases after induced constriction. To gain information about the possible site of response, we induced increases in Vti with methacholine (MCh) and attempted to correlate these changes with alterations in lung morphology. We measured tracheal (Ptr) and alveolar pressure (PA) in open-chest rabbits during mechanical ventilation [frequency = 1 Hz, tidal volume = 5 ml/kg, positive end-expiratory pressure (PEEP) = 5 cmH2O] under control conditions and after administration of saline or MCh (32 or 128 mg/ml) aerosols. We calculated lung elastance (EL), lung resistance (RL), Vti, and airway resistance (Raw) by fitting the equation of motion to changes in Ptr and PA. The lungs were then frozen in situ with liquid nitrogen (PEEP = 5 cmH2O), excised, and processed using freeze substitution techniques. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed area (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), the standard deviation of Lm (SDLm), and an atelectasis index (ATI) derived by calculating the ratio of tissue to air space using computer image analysis. RL, Vti, and EL were significantly increased after MCh, and Raw was unchanged. A/Ar, Lm, SDLm, and ATI all changed significantly with MCh. Log-normalized change (% of baseline) in Vti significantly correlated with A/Ar (r = -0.693), Lm (r = 0.691), SDLm (r = 0.648), and ATI (r = 0.656). Hence, changes in lung tissue mechanics correlated with changes in morphometric indexes of parenchymal distortion and airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1992

Quantitative assessment of dyspnea during exercise before and after bullectomy for giant bulla.

Incremental exercise testing using a cycle ergometer was performed in eight patients with giant bulla before and after bullectomy to assess dyspnea. There was a significant positive linear relationship between dyspnea expressed in the Borg scale (BS) and oxygen consumption (VO2) during exercise in all subjects. From these correlations, we introduced the following three new parameters for quantitative assessment of dyspnea: the Borg scale slope (BSS); the threshold load of dyspnea (TLD); and the breakpoint load of dyspnea (BLD), representing the slope of the regression line, onset of dyspnea on the regression line, and the maximum oxygen consumption before the subjects interrupted exercise, respectively. After surgery, the BSS showed marked decrease, and the TLD and BLD showed significant increase. Therefore, the reduction in the dyspnea with peak exercise after surgery was thought to be, at least in part, based on the delay of dyspnea onset, the decrease in dyspnea sensitivity, and the improvement in exercise capacity. The improvement in dyspnea during exercise in patients with giant bulla after surgery was extensively evaluated by newly introduced parameters based on BS-VO2 regression line.

Blister↗
PubMed1992

A case of anorexia nervosa with acute renal failure induced by rhabdomyolysis; possible involvement of hypophosphatemia or phosphate depletion.

A 16-year-old girl with anorexia nervosa first presented with malnutrition, liver dysfunction, and rhabdomyolysis. Administration of fluid and nutrition saved her from the initial critical state, but acute renal failure followed. Laboratory examination revealed intrinsic renal failure induced by rhabdomyolysis. Latent phosphate depletion and refeeding-induced hypophosphatemia was implicated as the cause of rhabdomyolysis; however coexisting hypotension, dehydration, and liver dysfunction may have contributed to the renal failure. The patient recovered from azotemia by hemodialysis. This is the first reported case of anorexia nervosa with acute renal failure resulting from rhabdomyolysis induced by hypophosphatemia or phosphate depletion.

Acute Kidney Injury↗
PubMed1992

[Pharmacokinetics and clinical efficacy of ciprofloxacin in aged patients with chronic respiratory diseases].

Pharmacokinetics and clinical efficacy of ciprofloxacin (CPFX) were investigated in aged patients with chronic respiratory diseases. Serum and sputum concentrations of CPFX were determined upon oral administration of 200 mg CPFX in 6 aged patients with chronic respiratory diseases (mean age = 78.8 +/- 3.2 years, 2 cases diagnosed chronic obstructive pulmonary disease with pneumonia, 3 cases were diagnosed bronchiectasis with acute exacerbation, and 1 case diagnosed chronic lung abscess). Maximal serum concentrations in these patients were 0.88-1.29 micrograms/ml (mean = 1.08 micrograms/ml). Thus, maximal serum concentrations of CPFX after oral administration in these aged patients were slightly lower than those in young subjects. However, peak sputum levels of CPFX following oral administration of 200 mg CPFX ranged from 0.53 to 1.47 micrograms/ml at 1-4 hours. These sputum concentrations of the 6 patients were sufficiently high for the inhibition of most infecting organisms in vitro. Clinical responses to CPFX in these 6 patients were good in 5, fair in 1, with an efficacy rate of 100%. Upon administration of CPFX, these 6 patients did not show any adverse reactions. These results suggest that oral administration of CPFX may keep effective levels in serum and sputum over 3 hours in aged patients with chronic respiratory diseases, and good clinical responses should be obtained without side effects in such patients.

Aged↗
PubMed1991

A new murine model of aging lung: the senescence accelerated mouse (SAM)-P.

The senescence accelerated mouse (SAM) has recently been characterized as a unique model to investigate age-related disorders, including amyloidosis, cataract, osteoporosis and dementia. However, little is known as to the properties of the lung in these animals. Tobacco smoke is also associated with enhanced loss of elastic recoil and the development of emphysema. We have attempted to examine morphological as well as biochemical changes of the distal lung in SAM-P/2, as the senescence-prone series and SAM-R/1, as the senescence-resistant series. The animals were intermittently exposed to tobacco smoke or air by Hamburg II machines for 5 weeks. Then both groups of animals were killed for histologic and biochemical study. Compared with SAM-R/1, SAM-P/2, even with air exposure, showed a higher value of the mean linear intercept without alveolar wall destruction. It became even greater due to tobacco exposure with emphysematous change. Tobacco exposure accumulated inflammatory cells into alveoli in SAM-P/2, but not in SAM-R/1. Oxygen radical generation by those cells was also higher in SAM-P/2. Analysis of bronchoalveolar lavage fluid in SAM-P/2 after tobacco exposure disclosed increases in albumin content, total protein content and elastase-like activity. There were decreases in the ratio of elastase inhibitory capacity (EIC) to trypsin inhibitory capacity (TIC), contents of glutathione and total free thiol groups. Moreover, SAM-P/2 showed significantly lower EIC/TIC ratio in serum, even with air exposure, than that of SAM-R/1. These results indicate that SAM-P/2 can be a good model for the study of natural evolution of the aging lung as well as its susceptibility to tobacco smoke in the development of emphysema.

Aging↗
PubMed1991

HIV-EP2, a new member of the gene family encoding the human immunodeficiency virus type 1 enhancer-binding protein. Comparison with HIV-EP1/PRDII-BF1/MBP-1.

At least two different types of proteins, NF-kappa B/KBF1 and HIV-EP1/PRDII-BF1/MBP-1, which are members of a family of rel oncoproteins and metal-finger proteins, respectively, bind to the human immunodeficiency virus type (HIV-1) enhancer. As a new member of a HIV-EP1 family that is expressed at a high level in T cells, we have isolated cDNA clones of HIV-EP2 by cross-hybridization with HIV-EP1 cDNA. HIV-EP2 protein consists of 1,833 amino acids and has a molecular weight of 211,000. HIV-EP2 protein is highly homologous with HIV-EP1/PRDII-BF1/MBP-1 in three regions. These three regions contain the potential nuclear localization signal followed by a Ser/Thr-rich region, the DNA-binding domain consisting of a metal-finger structure, and a cluster of acidic amino acids. The DNA-binding property of HIV-EP2 was similar to that of HIV-EP1. Northern blot analysis of HIV-EP2 mRNA indicated relatively high expression in the T cell line Molt-4 and in some tumor cell lines. Furthermore, like HIV-EP1, expression of HIV-EP2 mRNA was greatly induced by mitogen and phorbol ester treatment of Jurkat T cells, suggesting that HIV-EP2 acts in HIV production from latently infected T cells.

Amino Acid Sequence↗