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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 559 records · Page 31Linked to original sources
PubMed1990

Interaction between terbutaline and ethyl 2-(4'-carboxybenzamido)-4-propionamidobenzoate sodium salt in tracheal smooth muscle relaxation of guinea pig.

Ethyl 2-(4-carboxybenzamido)-4-propionamidobenzoate sodium salt (AM-682) is a new, orally active, antiallergic compound which has been reported to inhibit the release of histamine and leukotrienes from mast cells more than disodium cromoglycate (DSCG) or Tranilast. In the present study, the interaction between terbulatine, a beta 2-receptor agonist, and AM-682 or met-A, AM-682's main metabolite in humans, in guinea pig tracheal smooth muscle was investigated by measuring the isometric tension in vitro. Combinations of terbutaline and AM-682 or met-A produced more than additive relaxant effects. Comparing the combined effects with the calculated algebraic sums of single drug effects, the differences were statistically significant for terbutaline 10(-9) mol/l and AM-682 3 X 10(-6) mol/l, 10(-5) mol/l and 3 X 10(-5) mol/l (p less than 0.01) or met-A 3 X 10(-6) mol/l, 10(-5) mol/l (p less than 0.05) on the spontaneous tone of tracheal smooth muscle, and for terbutaline 10(-9) mol/l and AM-682 10(-5) mol/l (p less than 0.01), 3 X 10(-5) mol/l (p less than 0.05) on the tension of tracheal smooth muscle induced by 5.4 X 10(-7) mol/l carbachol. Thus the tracheal smooth muscle relaxant effects of AM-682 and the beta 2-receptor agonist terbutaline were synergistic. It is suggested that the combination of AM-682 and a beta 2-receptor agonist, rather than administration of each drug separately, may provide the therapeutic advantage in the treatment of bronchial asthma.

Aminobenzoates↗
PubMed1990

Three-dimensional ultrastructural distribution of cytoplasmic interdigitation between endothelium and pericyte of capillary in human granulation tissue by serial section reconstruction method.

Two- and three-dimensional electron microscopic observations in the capillaries with angiogenetic sprout of human granulation tissue revealed the cytoplasmic interdigitations (CID) between the endothelium and the pericyte, which were composed of unit of cytoplasmic projection and an indentation. Two types of interdigitation were observed: the interdigitation composed of cytoplasmic projection from the pericyte plugging into the endothelial indentation, CID(P-E); the interdigitation which had a reverse mode of composition of the cytoplasmic projection and indentation to the former one, CID(E-P). We investigated three-dimensional distribution of the two kinds of interdigitation in two cases of the capillaries with angiogenetic sprout. The two kinds of interdigitation exhibited a remarkable difference in the three-dimensional distribution. The CID(P-E) was rather uniformly distributed over the parent capillary endothelial area (6.4 per endothelium in average) and was not observed at all in the angiogenetic area; the other type of cytoplasmic interdigitation, CID(E-P), was located in only the angiogenetic sprouting endothelial area (3.5 per endothelium in average). The cytoplasmic interdigitation between the endothelium and the pericyte in vivo was the only site for cell contact and seemed to be involved in a conducting function which is biochemically proved to exist in vitro between the two cells.

Capillaries↗
PubMed1990

Effects of phospholipase A2 on numbers of histamine H1 receptors in guinea pig lungs.

Effects of phospholipase A2 on numbers of histamine H1 receptors and muscarinic acetylcholine receptors were estimated in guinea pig lungs. Histamine H1 and muscarinic acetylcholine receptors in lung membranes were studied by the direct binding technique using 3H-pyrilamine and 3H-quinuclidinyl benzilate, respectively. The control group had two orders (high-affinity and low-affinity) of binding sites of histamine H1 receptors. Pretreatment of lung membranes with phospholipase A2 destroyed high-affinity binding sites, and these sites could not be detected after treatment. Low-affinity sites were not affected by the treatment. In contrast, the numbers of muscarinic acetylcholine receptors did not change significantly in spite of the addition of phospholipase A2. These results indicate that resistance of receptors against phospholipase A2 treatment varies among receptors and even between the binding sites in the same receptor. These variations might modulate pathological conditions associated with inflammation in which phospholipase is activated. Easy establishment of histamine tachyphylaxis might be explained by this mechanism.

Animals↗
PubMed1989

Control of low density lipoprotein receptor gene promoter activity. Ketoconazole inhibits serum lipoprotein but not oxysterol suppression of gene transcription.

We have examined the effects of ketoconazole, a drug which inhibits enzymes involved in cholesterol biosynthesis and metabolism, on the suppressive effects of serum lipoproteins and 25-hydroxycholesterol on low density lipoprotein (LDL) receptor gene promoter activity. A LDL receptor promoter-chloramphenicol acetyltransferase (CAT) fusion gene construct (pLDLR-CAT 6500) was transfected into JEG-3 choriocarcinoma cells, and the transfected cells were cultured in the absence or presence of serum, LDL, or serum and 25-hydroxycholesterol. Serum, LDL, and serum + 25-hydroxycholesterol reduced chloramphenicol acetyltransferase activity in cells transfected with pLDLR-CAT 6500, whereas these treatments had no effect upon enzyme activity in cells transfected with a control construct (pSV2CAT). Ketoconazole (50 microM) overcame the effects of serum and LDL on suppression of pLDLR-CAT 6500 expression, but could not override the combination of serum + 25-hydroxycholesterol. Ketoconazole had no significant effect on expression of pSV2CAT. The drug inhibited cholesterol side chain cleavage enzyme in the cells, but appeared to have no impact on the ability of cells to take up LDL-carried lipids. Our observations are consistent with the idea that serum lipoprotein cholesterol is metabolized to an effector substance which acts to suppress LDL receptor gene transcription. The generation of this effector seems to be sensitive to ketoconazole.

Cell Line↗
PubMed1989

5-Hydroxytryptamine receptor subtypes participating in pulmonary edema in dogs.

The present study was undertaken to evaluate the effects of 5-hydroxytryptamine on pulmonary vascular resistances and vascular permeability with respect to the 5-hydroxytryptamine receptor subtypes. Left lower lobe of lungs isolated from the dog was perfused with constant heights of arterial and venous blood reservoirs and was maintained at zone III condition (pulmonary venous pressure greater than airway pressure). Drugs were administered into blood reservoir (1 l of total blood volume). Infusion of 5-hydroxytryptamine (100 micrograms/min) increased the pulmonary pre- and post-capillary resistances, but did not change the filtration coefficient. In the presence of ketanserin (10 mg), the infusion of 5-hydroxytryptamine caused an increase in filtration coefficient that was prevented by methysergide (30 mg). ICS 205-930 (10 mg) did not prevent such an increase in filtration coefficient. Infusion of 5-carboxamidotryptamine (100 micrograms/min) increased the filtration coefficient as well as both pre- and post-capillary resistances. These results suggested that the 5-HT1-like receptor mediates the increase in pulmonary vascular permeability.

Animals↗
PubMed1989

Sarcophytols A and B inhibit tumor promotion by teleocidin in two-stage carcinogenesis in mouse skin.

Sarcophytols A and B, isolated from a soft coral, Sarcophyton glaucum, are cembrane-type diterpenes with different numbers of hydroxyl groups. Sarcophytols A and B inhibited tumor promotion by teleocidin in two-stage carcinogenesis experiments on mouse skin. The inhibitory effect of sarcophytol A was demonstrated with two different initiating doses of 7,12-dimethylbenz[a]anthracene (DMBA): 50 micrograms (experiment 1) and 100 micrograms (experiment 2). In experiment 1, three groups of mice were treated with DMBA, and then twice a week with doses (1.6 micrograms, 16 micrograms, and 82 micrograms) of sarcophytol A followed by 2.5 micrograms teleocidin. In week 25, the incidences of tumors in these groups were only 7.1%, 20.0%, and 13.3%, respectively, whereas that in the control group treated with DMBA plus teleocidin was 53.3%. Moreover, at this time, the average numbers of tumors per mouse in these groups were 0.1, 0.3, and 0.3, respectively, while that in the control group was 2.1. In experiment 2 an amount of sarcophytol A (1.6 micrograms) or B (1.7 micrograms) equimolar to 2.5 micrograms teleocidin was applied twice a week, as in experiment 1, and results showed that sarcophytol B also inhibited tumor promotion by teleocidin. Both sarcophytols A and B caused delay in onset of tumor formation, and reduced the percentage of tumor-bearing mice and the average number of tumors per mouse. The effective concentrations of sarcophytols A and B were in the microgram range with an equimolar amount of teleocidin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Forskolin inhibits the Gs-stimulated adenylate cyclase in rat ascites hepatoma AH66F cells.

Forskolin increased intracellular cyclic AMP and augmented cyclic AMP formation by prostaglandin E1 (PGE1) in normal rat hepatocytes and ascites hepatoma AH66 cells. However, in AH66F cells which were derived from the AH66 cell line, the diterpene only slightly increased the cyclic AMP level, and dose-dependently inhibited the accumulation caused by PGE1. Forskolin dose-dependently activated adenylate cyclase in these membranes, and the magnitude of activation by forskolin was largest in the following order: hepatocytes, AH66 cells, and AH66F cells. This difference may be based on the number of forskolin-binding sites. The binding affinity of forskolin for each cell membrane was similar. The number and affinity of forskolin-binding sites in these cells were not influenced by 5'-guanylylimidodiphosphate [Gpp(NH)p]. In hepatocytes and AH66 cells, forskolin and other adenylate cyclase activators such as PGE1, GTP, Gpp(NH)p, F-, and Mn2+ synergistically increased the enzyme activity. In AH66F cells, the forskolin-stimulated activity was hardly influenced by the GTP analog, and forskolin diminished the activities induced by the GTP analog in a manner similar to that of diterpene alone. Forskolin (10 microM) also significantly inhibited the activities induced by PGE1, GTP, and F-. The effect of forskolin with Mn2+ was additive in AH66F cells. The data suggest that forskolin promotes the interaction between the stimulatory guanine nucleotide-binding protein and the catalytic unit in the membrane of normal hepatocytes and AH66 cells, but it interferes with the coupling in AH66F cells.

Adenylyl Cyclases↗
PubMed1989

Preoperative computed tomography staging of rectal carcinoma.

Pelvic computed tomography (CT) was analyzed in 48 patients with rectal carcinoma. Air was insufflated into the rectum before CT scanning. The areas of tumor (T) and rectosigmoid lumen (L) were determined for T/L ratio. Changes of the perirectal fatty tissues on CT were classified into five patterns: shaggy, granular, linear, clubbed, and wavy appearances. The T/L ratio and changes of the perirectal fatty tissue were correlated with transmural tumor extension. When the T/L ratio was above 1, tumors were frequently classified as Dukes' staging B and C, whereas a T/L ratio above 2 suggested Dukes' C classification. Clubbed or wavy appearance in the perirectal fatty tissues suggested that the tumor extended beyond the submucosa involving the muscularis propria. These findings were very useful for surgery.

Adipose Tissue↗
PubMed1989

Results of distal splenorenal shunt with versus without splenopancreatic disconnection.

From December 1973 to December 1987, we performed a distal splenorenal shunt (DSRS) in 112 cases of portal hypertension, including 107 with postnecrotic liver cirrhosis and 5 with idiopathic portal hypertension (IPH). They comprised about 50% of our surgical cases with esophageal varices. In 1981, we modified our operative procedure towards a more extended splenopancreatic disconnection (SPD) in order to prevent the "stealing" of the shunt through the pancreatic vein. In one group of 69 patients who underwent DSRS alone, the operative mortality was 2.9%; postoperative encephalopathy was seen in 17.4%, late hepatic failure in 40.6%, and recurrence of varices in 4.3%. In the other group, 43 patients who underwent DSRS with SPD, there were no operative deaths, no encephalopathy (better than DSRS alone at p less than 0.05), and late hepatic failure was seen in only 9.3% (better than DSRS alone at p less than 0.025), while the recurrence rate of 7% was the only statistical increase. These data show that DSRS + SPD can improve chances of survival.

Collateral Circulation↗
PubMed1989

Effect of colforsin on human neutrophil superoxide production and intracellular calcium mobilization.

1. The effects of dibutyryl cyclic AMP (cAMP), isoproterenol and colforsin (forskolin) were evaluated on respiratory burst in human polymorphonuclear neutrophils (PMN). 2. Dibutyryl cAMP showed a dose-dependent inhibition of n-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide production by human PMN. 3. Administration of isoproterenol induced a dose-dependent inhibition of FMLP-induced superoxide production by human PMN, and the inhibition was blocked by propranolol. 4. Administration of colforsin induced a dose-dependent inhibition of FMLP-induced superoxide production by human PMN, and the inhibition could not be blocked by propranolol. 5. Incubation with colforsin caused a significant increase in the cAMP level in human PMN. 6. Pretreatment with colforsin caused a dose-dependent inhibition in the elevation of intracellular free calcium (monitored by fura-2 fluorescence), which was observed in human PMN stimulated with FMLP. 7. These results suggest that cAMP is an inhibitory factor of superoxide production and intracellular calcium mobilization in human PMN stimulated with FMLP.

Adult↗
PubMed1989

Mechanism of xanthine-induced relaxation of guinea-pig isolated trachealis muscle.

1. Four 3-alkylxanthines (3-methylxanthine, 3-n-propylxanthine (enprofylline), 3-n-butylxanthine and 3-iso-butylxanthine) and four 1-methyl-3-alkylxanthines (1-methyl-3-methylxanthine (theophylline), 1-methyl-3-n-propylxanthine, 1-methyl-3-n-butylxanthine and 1-methyl-3-iso-butylxanthine (IBMX], were compared in terms of cyclic AMP phosphodiesterase (PDE) inhibition and trachealis muscle relaxation. The relationship between xanthine structure and cyclic AMP PDE inhibition was also studied. 2. Xanthine induced relaxation of guinea-pig isolated trachealis muscle was measured against spontaneous tone. 3. The four 1-methyl-3-alkylxanthines were each significantly more potent than the corresponding 3-alkylxanthines in relaxing the isolated trachealis muscle. The 1-methyl-3-alkylxanthines were similarly more potent than the corresponding 3-alkyl derivatives in inhibiting low Km cyclic AMP PDE. There was a strong positive correlation between low Km cyclic AMP PDE inhibition and the tracheal smooth muscle relaxation evoked by the xanthine derivatives. 4. Since methylation of the 1-position of each 3-alkylxanthine increased the potency of the derivative in inhibiting low Km cyclic AMP PDE and in relaxing trachealis muscle and since a strong positive correlation was observed between the relaxant EC50 and the Ki value of each xanthine derivative, it is suggested that low Km cyclic AMP PDE inhibition by xanthines plays an important role in their tracheal relaxant effect.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Correlation between hydrophobicity of N-alkylxanthine derivatives and their biological activities on guinea-pig isolated tracheal smooth muscle.

Cyclic (c) AMP phosphodiesterase (PDE) inhibitory activities of N-alkylxanthine derivatives (3-methyl-,3-ethyl-,3-propyl-,3-butyl-,1,3-dimethyl-,1-methyl-3-ethyl-,1-methyl - 3-propyl- and 1-methyl-3-butyl xanthines) and their relaxant effects on carbachol-induced contraction and on resting tone guinea-pig isolated tracheal smooth muscle have been investigated. The PDE inhibition constant (Ki) and the concentration producing 50% tracheal smooth muscle relaxation in-vitro (EC50) were determined. Significant correlations between the -log Ki values and the -log EC50 values on the carbachol-induced contraction or on the resting tone were found (r = 0.902 and 0.892). The apparent partition coefficient (P) between n-octanol and pH 7.4 phosphate-buffered saline (PBS) was measured as an index of hydrophobicity of the xanthine derivatives. There were significant correlations between log P and both -log EC50 values and between the log P and -log Ki values. These findings suggest that the cAMP PDE inhibitory activity of N-alkylxanthine derivatives contributes to the mechanism of bronchodilatory action, and that an increase in hydrophobicity of the xanthine molecule enhances the biological activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Control of low density lipoprotein receptor gene expression in steroidogenic cells.

Low density lipoprotein (LDL)-carried cholesterol is a primary substrate for steroid hormone synthesis by luteinized human granulosa cells. Chorionic gonadotropin and 8-bromo-cAMP both increase LDL receptor levels in granulosa cells by stimulating accumulation of the receptor mRNA. LDL and 25-hydroxycholesterol reduce LDL receptor expression, but this suppressive effect is partially overcome by 8-bromo-cAMP. Using fusion gene constructs containing the LDL receptor gene promoter transfected into JEG-3 cells, a cyclic AMP responsive enhancer could not be identified in the LDL receptor gene upstream promoter in transfection studies. We suggest that the LDL receptor gene in human steroidogenic cells is under negative control by a sterol effector, but that a cyclic AMP triggered process overcomes, to some extent, the sterol-mediated suppression. The detailed mechanisms by which sterol and cyclic AMP modulate LDL receptor gene expression remain to be elucidated.

Cholesterol, LDL↗
PubMed1989

Fetal blood values by percutaneous umbilical blood sampling.

Cordocentesis was performed, and fetal blood was sampled in 81 of 93 attempted procedures. In 45 fetuses, who proved to be normal later by normal pregnancy outcome, hematological analyses and blood chemistries were performed. The results showed an increase in total white blood cell count, red blood cell, hemoglobin, hematocrit and platelet count, while the mean corpuscular volume and mean corpuscular hemoglobin decreased during gestation. Total protein and albumin concentrations increased during pregnancy. These results provide information for the diagnosis of fetal hematological disorders, and assist in making decisions for possible fetal therapy in utero.

Female↗
PubMed1989

Capsaicin-sensitive nerves exert an inhibitory effect on the development of fibrin-induced pulmonary edema in rats.

This study was undertaken to evaluate the role of vagal nerves in the development of neurogenic pulmonary edema. We injected fibrinogen and thrombin into the cisterna magna of rats, a model of neurogenic pulmonary edema. When the vagal nerves were left intact, pulmonary edema occurred (fibrin-induced pulmonary edema) at a rate of 33%. Vagotomy at the midcervical portion increased the incidence of pulmonary edema to a rate of 100%, whereas pretreatment with atropine did not affect the incidence. These results suggested that vagal afferent nerves or nonadrenergic-noncholinergic efferent nerves played an important role in inhibiting the development of fibrin-induced pulmonary edema. Furthermore, in vagotomized and vagal nerve-intact rats pretreated with capsaicin, the incidence of pulmonary edema was 100%. Pretreatment with a substance P antagonist, [D-Pro2, D-Trp7,9]-SP, also increased the incidence to 100% in the vagal nerve-intact rats. On the other hand, intravenous administration of some neuropeptides that may be released from the capsaicin-sensitive nerves (e.g., substance P or calcitonin gene-related peptide) inhibited the development of pulmonary edema in vagotomized rats. We concluded that the vagal capsaicin-sensitive nerves exerted an inhibitory effect on the development of fibrin-induced pulmonary edema.

Animals↗
PubMed1989

Kinetic interaction between theophylline and a newly developed quinolone, NY-198.

The effect of a newly developed quinolone, NY-198, on the pharmacokinetics and metabolism of theophylline was investigated under steady-state conditions in six male healthy volunteers, in a crossover fashion. A sustained-release theophylline formulation (200 mg twice daily at 12 h intervals) was received as monotherapy or coadministration with NY-198 (200 mg twice daily at 12 h intervals). No significant change in the pharmacokinetic parameters of theophylline was observed during coadministration of NY-198. No significant change in urinary excretion of theophylline and its metabolites was also observed. These findings indicate that NY-198 does not influence the pharmacokinetics of theophylline and we can suggest that quinoline derivatives have less effect on theophylline disposition than 1,8-naphthyridine derivatives among quinolones.

4-Quinolones↗