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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 343 records · Page 19Linked to original sources
PubMed1995

[Diagnosis of acute respiratory distress syndrome: analysis of bronchoalveolar lavage fluid].

To better understand the pathogenesis of acute respiratory distress syndrome (ARDS), we analyzed bronchoalveolar lavage fluid (BALF) from patients with ARDS (n = 89, survival rate = 56.2%), who were admitted to our intensive care units over the past 7 years. ARDS was diagnosed when the lung injury score proposed by Murray et al was greater than 2.5. The BALF had very high centrations of albumin, a marker of permeability edema, along with remarkably high neutrophil counts, percent neutrophils, neutrophil-elastase, and interleukin-8, markers of neutrophil-related lung injury. In addition, the level of IL-8 in BALF was higher in non-survivors than in survivors. Levels of thrombin-antithrombin complex fibrin degenerative product and soluble thrombomodulin (recently recognized as a natural anticoagulant combined with vascular endothelial cells) were very high in BALF from patients with ARDS. Moreover, the level of soluble thrombomodulin in BALF was higher in non-survivors than in survivors. There were significant relationships between these neutrophil-related markers and markers of abnormal coagulation. The results of the BALF analysis suggest that accumulation and activation of neutrophils can affect thrombomodulin on vascular endothelial cells, which can activate thrombin and cause the coagulopathy seen in ARDS.

Adult↗
PubMed1994

Angiotensin converting enzyme inhibitor but not calcium blocker down-regulates gene expression of vascular natriuretic peptide receptor in hypertensive rats.

We have recently found that vascular natriuretic peptide (NP)-A receptor mRNA is upregulated in genetically hypertensive (SHR-SP/Izm) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In the present study, we examined the effects of antihypertensive treatments on aortic NP-A receptor mRNA expression in these hypertensive rats using ribonuclease protection assay. Oral administration of an angiotensin converting enzyme inhibitor, derapril, but not a calcium channel blocker, manidipine, produced a significant decrease of the NP-A receptor mRNA level after 4 weeks, while both antihypertensive agents showed similar hypotensive effects. Plasma renin was high in SHR-SP/Izm and low in DOCA-salt rats. These results suggest that the vascular renin-angiotensin system rather than the blood pressure has an important role in the regulation of the vascular NP-A receptor.

Animals↗
PubMed1994

Proliferating cell nuclear antigen and Ki-67 in lung carcinoma. Correlation with DNA flow cytometric analysis.

BACKGROUND: To study the prognosis of patients with lung carcinomas, the efficacy of proliferating cell nuclear antigen (PCNA) in ensuring both the proliferative activity defined using Ki-67 labeling and the cell cycle data obtained using flow cytometry was determined. METHODS: The authors used immunostaining to study frozen and paraffin embedded sections of 165 surgically resected lung carcinomas [squamous cell carcinoma, n = 84; adenocarcinoma, n = 62; large cell carcinoma, n = 15; small cell carcinoma, n = 4] for the presence of PCNA and Ki-67 antibodies. Also studied were two parameter flow cytometric analysis of fluorescein isothiocyanate conjugated PCNA/propidium iodide for 165 fresh frozen tissues. Clinicopathologic data (sex, age, tumor stage, survival period, histologic type, degree of cell differentiation, and cellularity) were evaluated using the Statistical Analysis System. RESULTS: The percentages of PCNA positive cells per 1000 nuclei were 52% of squamous cell carcinoma; 49% in adenocarcinomas; 76% of large cell carcinoma; and 63% of small cell carcinoma. Positive PCNA staining was significantly correlated with stage, cellularity, and DNA index. Calculation of logistic regression coefficients indicated an association between overall survivals and tumor cellularity (P < 0.0003), percentage of cells stained with PCNA antibody (P < 0.02), DNA pattern (aneuploid versus diploid) (P < 0.009), DNA index (P < 0.009), and percentage of cells in S-phase (P < 0.04). Both cellularity (P = 0.03) and DNA (P = 0.08) retained its independent level of significance by multivariate analysis. CONCLUSIONS: In addition to clinical stage and histologic differentiation, both cellularity and DNA content may help predict the course of lung carcinomas.

Adenocarcinoma↗
PubMed1994

Cyclic nucleotide phosphodiesterase isoenzymes in guinea-pig tracheal muscle and bronchorelaxation by alkylxanthines.

In this study the phosphodiesterase (PDE) isoenzymes in guinea-pig trachealis smooth muscle were separated by DEAE-Sepharose anion exchange chromatography, identified, and characterized. Furthermore the effect of theophylline and 1-n-butyl-3-n-propylxanthine (BPX) on the isolated PDE isoenzymes and on their tracheal relaxant effect were investigated and compared with the nonxanthine PDE inhibitors amrinone and Ro 20-1724. We identified five distinct isoenzymes in guinea-pig tracheal muscle; calcium/calmodulin-stimulated cyclic AMP PDE (PDE I), cyclic GMP-stimulated cyclic AMP PDE (PDE II), cyclic GMP-inhibited and amrinone-sensitive cyclic AMP PDE (PDE III), cyclic AMP-specific and Ro 20-1724-sensitive PDE (PDE IV), and cyclic GMP-specific PDE (PDE V). BPX strongly inhibited the PDE IV isoenzyme with high selectivity, while the inhibitory effect of theophylline was weak. The PDE IV inhibitors BPX and Ro 20-1724 synergistically increased the relaxant effect of the beta 2-adrenoceptor agonist salbutamol in carbachol-contracted trachea much more strongly than theophylline. In contrast, amrinone, a PDE III inhibitor, hardly influenced the relaxant effect of salbutamol, suggesting that the PDE IV isoenzyme is functionally associated with beta 2-adrenoceptors in guinea-pig trachea and that inhibition of this enzyme potentiates the ability of salbutamol to increase the intracellular cyclic AMP content. These results indicate that the PDE IV isoenzyme plays a significant role in alkylxanthine-mediated relaxation of guinea-pig trachea.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Selective tracheal relaxation and phosphodiesterase-IV inhibition by xanthine derivatives.

The effects of substitutions in the xanthine nucleus on tracheal relaxant activity, atrium chronotropic activity, adenosine A1 affinity, and inhibitory activities on cyclic AMP-phosphodiesterase isoenzymes in guinea pigs were studied. Substitution with a long alkyl chain at the N1-position of xanthine nucleus increased the tracheal relaxant activity without leading to positive chronotropic action, and long alkyl chains at the N3-position increased both activities. N7-substitutions with n-propyl and 2'-oxopropyl groups, such as in denbufylline, increased bronchoselectivity. N7-substitution decreased the adenosine A1 affinity, but substitution at either the N1- or N3-position increased it. The bronchorelaxant activity of xanthine derivatives was closely correlated with their inhibition of phosphodiesterase-IV, but not with their adenosine A1 affinity; the positive chronotropic effects were related to their inhibition of phosphodiesterase-III. This study confirms that the bronchorelaxation of xanthine derivatives is mediated by inhibition of the isoenzyme phosphodiesterase-IV. The results of structure-activity analysis suggest that substitutions at the N1- and N7-positions should be tried in the development of xanthine derivatives that are selective bronchodilators and phosphodiesterase-IV inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Nitric oxide blocks the cell cycle of mouse macrophage-like cells in the early G2+M phase.

The effects of nitric oxide produced by macrophage-like cells (Mm1) on the cell cycle were investigated. Mm1 cells lost proliferative activity in the presence of interleukin-6 (IL-6) and a subpopulation accumulated in the G2+M phase. This level increased in proportion to the incubation time. The DNA content of the cells was slightly lower than that of Mm1 cells treated with vinblastine or demecolcine, drugs which block the cell cycle in the M phase. The peak of the early G2+M phase was reduced by treatment with NG-mono-methyl-L-arginine. However, after treatment with exogenous nitric oxide or sodium nitroprusside, the G0/G1 phase increased, but the early-G2+M and the S phase decreased. The flow cytometry pattern in IL-6-treated Mm1 was the same as that of cytochalasin B-treated Mm1. These data suggest that endogenous nitric oxide affects the microfilament system of IL-6-treated Mm1 cells and blocks the cell cycle in the early G2+M phase.

Animals↗
PubMed1994

Determination of tomatine in foods by liquid chromatography after derivatization.

A liquid chromatographic method for measuring tomatine levels in tomatoes and tomato products was developed. Tomatine was extracted with 1% acetic acid and purified on a C18 cartridge. Tomatine in the eluate was acetylated with acetic anhydride and isolated on a C18 cartridge. The solvent in the eluate was evaporated and the residue was dissolved in acetonitrile. An aliquot was injected into an Inertsil ODS-2 HPLC column and the acetylated tomatine was measured at 205 nm using a UV detector. The limit of determination was 1 microgram g-1. Tomatine was detected in the green portions of tomatoes and in tomato ketchups and juices at levels below 7 micrograms g-1.

Acetylation↗
PubMed1994

Role of sex steroids on the survival, neuritic outgrowth of neurons, and dopamine neurons in cultured preoptic area and hypothalamus.

Morphological sex differences in some discrete brain regions are thought to be developed by the influence of circulating androgen during the perinatal period. In order to know whether the effect of androgen is a direct one, cells derived from neonatal rat preoptic area (POA) and/or hypothalamus were cultured in a serum-free medium, and the effects on survival, process growth of neurons, and dopaminergic function were examined. When the POA cells were exposed to testosterone (T), neuronal survival was greater than the controls, and the frequency distribution of total process length and the number of process branchings were significantly deviated from the controls. Estradiol-17 beta (E2) and 5 alpha-dihydrotestosterone had less significant effects on these parameters than T. Moreover, the addition of T increased the dopamine (DA) contents of cells and medium DA in the hypothalamic culture. E2 also greatly increased DA content of the medium. These steroids failed to alter the DA levels in the POA cell cultures. These results generally conform to the notion of previous investigators that T has direct effects on the expansion of dendritic elements of the POA and the development of sex difference in the hypothalamic DA neurons, although the effect of T after conversion to E2 cannot be excluded.

Animals↗
PubMed1994

Kinetic interaction between theophylline and a newly developed anti-allergic drug, pemirolast potassium.

The effect of a newly developed anti-allergic drug, pemirolast potassium (TBX), on the pharmacokinetics and metabolism of theophylline was investigated under steady-state conditions in seven healthy male volunteers. A sustained-release theophylline formulation (100 mg twice daily at 12 h intervals) was given as monotherapy and coadministered with TBX (10 mg twice daily at 12 h). Plasma concentration-time curves and the urinary excretion of theophylline and its major metabolites after administration of theophylline alone and after coadministration with TBX were compared. No significant adverse effects from this study were observed. There were no significant differences in the total body clearance, renal clearance and maximum concentration of theophylline between the two treatments, although coadministration of TBX significantly delayed the time to reach maximum concentration of theophylline. In the case of urinary excretion, no significant changes in the fraction of urinary excretion of theophylline and its metabolites were observed. These results indicate that TBX has little or no effect on the pharmacokinetics and metabolism of theophylline and suggest that TBX is safe for asthma patients receiving theophylline therapy for treatment of chronic obstructive airway diseases.

Adult↗
PubMed1994

Sensitive colorimetric assay of serum diamine oxidase.

A simple and sensitive colorimetric assay for serum diamine oxidase (DAO) activity was based on a coupled reaction with peroxidase and a new chromogen, 10-(carboxymethyl-aminocarbonyl)-3,7-bis(dimethylamino) phenothiazine sodium salt (DA-67). In the presence of peroxidase and DA-67, peroxidase catalyzes the formation of methylene blue having an absorption maximum at 668 nm. The proposed method eliminates the interferences occurring in serum with use of ascorbate oxidase and stops the reaction with sodium diethyldithiocarbamate, leaving the methylene blue in the reaction mixture stable for about 2 h. Low normal basal values of serum DAO can be determined in the range 2.8-9.0 units/l. Since all reagents are commercially available the method is suitable for the clinical laboratory.

Adolescent↗
PubMed1994

Production of a group-specific antibody to 1 alpha,25-dihydroxyvitamin D and its derivatives having the 1 alpha,3 beta-dihydroxylated A-ring structure.

To obtain a group-specific antibody to 1 alpha,25-dihydroxyvitamin D and its derivatives having the 1 alpha,3 beta-dihydroxylated A-ring structure, 1 alpha-hydroxy-25,26,27-trinorvitamin D3-24-oic acid was synthesized as a haptenic derivative by a new convenient synthetic route. Three kinds of polyclonal antibodies were elicited in rabbits against the hapten conjugated with bovine serum albumin, and their specificity was examined by cross-reactivities in a radioimmunoassay procedure. One of the antibodies was found to show a suitable binding property by addition of a small amount of the plasma from vitamin D-deficient rats. Dose-response curves with measurable ranges applicable to biological specimens were obtained for 1 alpha,25-dihydroxyvitamin D3, 1 alpha,25-dihydroxyvitamin D2, (24R)-1 alpha,24,25-trihydroxyvitamin D3, (23S,25R)-1 alpha,25-dihydroxyvitamin D3 26,23-lactone, and 22-oxacalcitriol by the radioimmunoassay system using this improved antibody. The antibody will be widely useful for developing profile analyses of 1 alpha,25-dihydroxyvitamin D and its derivatives (metabolites or synthetic analogs) having the 1 alpha,3 beta-dihydroxylated A-ring, as well as immunoassays measuring each of these secosterols individually.

Animals↗
PubMed1994

Inhibitory mechanisms of antibody production by nitrogen oxides released from activated macrophages during the immune response: relationship to energy consumption.

We investigated the relationship between the sensitivity of mouse splenocytes in immune response to nitrogen oxides and energy consumption rate of the cells. Macrophage-like cells (Mm1) pretreated with IL-6 served as the source of the nitrogen oxides. The antibody production of both 2,4,6-trinitrophenyl-keyhole limpet haemocyanin-primed splenocytes and B cell hybridomas was markedly reduced; about 20-40% of splenocytes and B cell hybridomas were killed by co-culture with IL-6-treated Mm1. Cell viability and antibody production were completely restored by the addition of NG-monomethyl L-arginine to the culture medium. The cytotoxicity of the nitrogen oxides was correlated with the distance between effector and target cells. Under conditions of low cytotoxicity, antibody production by B cell hybridomas was suppressed by the nitrogen oxides, this suppression not being correlated with the reduction in cell growth. The sensitivity of the target cells differed in co-cultures of antigen-primed splenocytes and B cell hybridomas with IL-6-treated Mm1. The nitric oxide-sensitivity of the cells corresponded to their 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reducing activity and ATP consumption rate. These findings suggest that nitrogen oxides act as regulatory molecules in immune response in three ways: cytostasis, reduction of cell growth and suppression of antibody synthesis.

Animals↗
PubMed1994

Endoscopic resection of early gastric carcinoma: results of a retrospective analysis of 308 cases.

The purpose of this study was to define the indications and limitations of endoscopic resection (ER) of early gastric carcinoma (EGC). Over the 15 year period from 1978 to 1992, 308 early cancers were resected endoscopically either through a single operative intervention or in stages. Of 266 lesions resected in a single step, 222 (85%) entered remission. Forty-four cases had either residual or recurrent lesions. The size, histology and location affected the curability; 89% of Type IIa lesions less than 2 cm were resected curatively, while only 50% of those larger than 2 cm were resected completely. In Type IIc, 83% of lesions less than 1 cm and 57% of those greater than 1 cm were excised completely by ER. In Type IIc, curative ER was possible in 85% of differentiated carcinomas and 43% of undifferentiated carcinomas. The rate of incomplete resection was higher for lesions of the anterior or posterior wall, than for those of the lesser curvature. Semiserial sections of the resected specimens made at 2 mm intervals, indicated that, if the positive margin was confined to one section, cure may be possible by the burning effect. Follow-up showed that there was no single case undergoing endoscopic resection which subsequently died of gastric carcinoma. The lesions that are suitable for ER comprise Type IIa EGC of less than 2 cm in diameter, and Type IIc differentiated adenocarcinoma of less than 1 cm. Lesions in which the entire margin is difficult to observe by front-view endoscopy should be smaller than defined by the above criteria.

Adenocarcinoma↗
PubMed1994

Role of calcium-activated potassium channels in the relaxation of tracheal smooth muscles by forskolin.

1. The role of calcium-activated potassium (KCa) channels in bronchodilation produced by a direct adenylyl cyclase activator, forskolin, was investigated. The involvement of intracellular cyclic AMP (cAMP) in the process was also examined. 2. The isometric tension records from guinea-pig tracheal smooth muscles indicated that application of charybdotoxin (ChTX), a selective inhibitor of large conductance KCa channels, led to a suppression of the relaxant effect of forskolin in the precontracted tissue by carbachol (CCh). However, the inhibitory action by ChTX had a much greater effect on the relaxation caused by isoproterenol than by forskolin. 3. In contrast to the effect of ChTX, glybenclamide, a cromakalim-sensitive K+ channel inhibitor and apamin, a small conductance KCa channel blocker, had no effects on the bronchodilation produced by forskolin. 4. The effects of forskolin and nifedipine on tone produced by high K+ was compared. Concentration-inhibition curves in guinea-pig trachealis precontracted by 20 mmol/L K+ solution were similar for forskolin and nifedipine. Conversely, relaxation by forskolin was significantly diminished when tissues were contracted with 40 mmol/L K+ solution, whereas nifedipine relaxations were unaffected. 5. A single channel record from a cell-attached patch in a porcine tracheal myocyte demonstrated that forskolin stimulates reversibly KCa channels without affecting the unitary amplitude. 6. The results are consistent with forskolin-induced relaxation occurring at least in part through the opening of ChTX-sensitive KCa channels, by means of a cAMP-dependent channel modulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Empyema and mediastinitis complicating retropharyngeal abscess.

A 21 year old man with a retropharyngeal abscess complained of right sided chest pain, and chest radiography and thoracocentesis revealed an empyema. A computed tomographic scan of the chest showed a posterior mediastinal abscess communicating with the right pleural cavity. Emergency thoracotomy was performed and the mediastinal abscess and empyema were drained.

Acute Disease↗