Light beating spectroscopy of polarized and depolarized scattering in p-n-hexyl p'-cyanobiphenyl.
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Journal Article↗
Biomedical subjects
K Takagi
Publications and source records attributed to K Takagi.
Purification and molecular cloning of chymase from human tonsils.
A chymotrypsin-like protease was purified to homogeneity from human tonsils by a series of chromatographic procedures. The purified enzyme gave a single protein band with an apparent molecular mass of 30 kDa on SDS-PAGE. The sequence of the first 21 amino acids at the N-terminus of the enzyme was determined. A cDNA for the enzyme was cloned by PCR amplification from extracted tonsillar mRNA using a supposed N-terminal oligonucleotide primer and a conserved C-terminal primer of the chymase family. The deduced amino acid sequence of the isolated clone was identical to that of human chymase in connective tissue-type mast cells from heart except for a Ser instead of a Cys at the N-terminal 7th position.
Amino Acid Sequence↗
Bronchodilator activity of xanthine derivatives substituted with functional groups at the 1- or 7-position.
Xanthine derivatives with several functional groups at the 1- or 7-position were synthesized, and their pharmacological activities in guinea pigs were studied. In general, the in vitro tracheal relaxant action and positive chronotropic action of 3-propylxanthines were increased by substitutions with nonpolar functional groups at the 1-position, but decreased by any substitution at the 7-position. On the other hand, because positive chronotropic actions of substituents with allyl, aminoalkyl, alkoxyalkyl, and normal alkyl groups were much less than tracheal muscle became very high with substitutions of 3'-butenyl, (dimethylamino)ethyl, 2'-ethoxyethyl, 3'-methoxypropyl, and n-propyl groups at the 1-position and of 2'-ethoxyethyl, 2'-oxopropyl, and n-propyl groups at the 7-position, compared with theophylline and the corresponding unsubstituted xanthines, 3-propylxanthine and 1-methyl-3-propylxanthine. When compounds were intraduodenally administered to the guinea pig, 1-(2'-ethoxyethyl)-, 1-(3'-methoxypropyl)-, 1-(3'-butenyl)-, and 1-[(dimethylamino)-ethyl]-3-propylxanthines, 1-methyl-7-(2'-oxopropyl)-3-propylxanthine, and denbufylline (1,3-di-n-butyl-7-(2'-oxopropyl)xanthine) effectively inhibited the acetylcholine-induced bronchospasm without heart stimulation or central nervous system-stimulation at the effective dosage range. Particularly, the bronchodilatory effect of 1-(2'-ethoxyethyl)-3-propylxanthine was much stronger and more continuous than those of theophylline and pentoxifylline. On the other hand, there were certain relationships among the in vitro tracheal relaxant activities of these compounds, their affinities for adenosine (A1) receptors in the brain membrane, and their inhibition of cyclic AMP-phosphodiesterase (PDE) in the tracheal muscle. The affinity for A2 receptors of these compounds was very low or negligible. This suggests that both the action on A1 receptors or interaction with adenosine and the cyclic AMP-PDE inhibitory activity contribute to the bronchodilator action of 1- and 7-substituted xanthines. This study indicates that the substitutions with none or low polar functional groups at the 1-position could improve the selectivity and duration of the bronchodilator effects of xanthines.
Administration, Oral↗
Inhibition of multidrug resistance by a new staurosporine derivative, NA-382, in vitro and in vivo.
The effects of a newly synthesized compound, N-ethoxycarbonyl-7-oxo-staurosporine (NA-382), on multidrug resistance in tumor cells were investigated. Protein kinase-inhibitory activity of NA-382 was lower but more selective to Ca2+/phospholipid-dependent protein kinase than that of staurosporine. NA-382 at noncytotoxic concentrations effectively reversed in vitro multidrug resistance of Adriamycin-resistant P388 (P388/ADR) cells, without influencing the drug sensitivity of sensitive P388 cells. NA-382 inhibited extrusion of vinblastine (VBL) and increased intracellular accumulation of VBL, more in P388/ADR cells than in sensitive P388 cells, with higher potency than staurosporine. This compound also reduced VBL resistance of other multidrug-resistant cell lines, AH66 and K562/ADR, by inhibiting VBL efflux and promoting VBL accumulation. NA-382 also dose dependently potentiated the effects of VBL and Adriamycin in P388/ADR-bearing mice. The toxicity of staurosporine was too high to use the combination with VBL in vitro and in vivo. NA-382 accumulated VBL in P388/ADR cells even after desensitization of Ca2+/phospholipid-dependent protein kinase by treatment with 12-O-tetradecanoylphorbol-13-acetate and 18 h, while being suppressed by 12-O-tetradecanoylphorbol-13-acetate added simultaneously or shortly before NA-382. Both staurosporine and NA-382 inhibited the photolabeling of [3H]azidopine on M(r) 140,000 P-glycoprotein in the plasma membrane from P388/ADR cells. These results indicate that this new staurosporine analogue, NA-382, reverses multidrug resistance by directly inhibiting the drug binding to P-glycoprotein, but not by Ca2+/phospholipid-dependent protein kinase inhibitory action.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Size effect on variable-range-hopping transport in PrBa2Cu3O7-x.
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Journal Article↗
An unusual stress fracture of the lateral tibial plateau.
Stress fracture of the lateral tibial plateau is a rare occurrence. In this article we report a case of stress fracture of the lateral tibial plateau with a radiolucent fracture line in a 52-year-old man. To our knowledge, such a case has not yet been reported.
Fracture Fixation↗
Sigmoidoscopy and other tests for screening of colorectal cancer.
We have been carrying our mass detection for colorectal cancer with fecal occult blood test and sigmoidoscopy. The occult blood test is negative in 60% with colorectal cancer.
Adult↗
Micronucleus induction in mouse peripheral blood reticulocytes by 2,7-diaminophenazine and related compounds.
The peripheral blood micronucleus test using acridine orange (AO) supravital staining was performed with phenazine (Pz), 1-aminophenazine (1-APz), 2-aminophenazine (2-APz) and 2,7-diaminophenazine (2,7-DAPz). Male ICR mice and BDF1 mice were treated intraperitoneally once or twice 24 h apart with each chemical. Irrespective of the number of administrations, Pz and 1-APz were not clastogenic in either mouse strain. In the single treatment regime, 2-APz slightly increased micronucleated reticulocytes (MNRETs) 48 h after 200 mg/kg dosing in ICR mice and 72 h after 400 mg/kg dosing in BDF1 mice. The MNRET frequencies were not enhanced after double treatment in either mouse strain. The single treatment with 2,7-DAPz strongly and dose-dependently induced MNRETs in BDF1 mice, and the incidences of MNRETs, which peaked 48 or 72 h after treatment, were much higher than those in ICR mice. In both mouse strains, the frequencies of MNRETs observed after double treatment with 2,7-DAPz were higher than those after single treatment. The MNRET incidence induced 72 h after first 200 mg/kg dosing in BDF1 mice was 2.21%.
Animals↗
Poor correlation between functional results and radiographic findings in Colles' fracture.
We reviewed 83 consecutive patients with unilateral Colles' fracture in order to identify factors that predict poor functional outcome. All fractures were treated by closed reduction and cast immobilization, and followed-up for at least 2 years. Our results showed that only final dorsal angulation was correlated to loss of flexion. In contrast to other reports, we could not find any relationship between radial shortening and loss of grip strength or loss of range of motion. In addition, the severity of initial displacement, involvement of radio-carpal or distal radio-ulnar joints, and the presence of ulnar styloid fractures or their non-union did not affect the functional outcome.
Adolescent↗
Culture of rat brain preoptic area neurons: effects of sex steroids.
The aim of the present study was to investigate the direct effects of testosterone (T), estradiol-17 alpha (E2) and 5 alpha-dihydrotestosterone (5 alpha-DHT) on the survival of neurons and the morphology of neuronal processes (the total process length, the number of processes and the number of process branchings) of the cells derived from neonatal rat preoptic area (POA) to analyze the bases of morphological sexual dimorphism of the POA. The POA cells were exposed to sex steroids during 2-14 days of culture in serum-free medium. Neuronal survival was significantly greater in cultures treated with 1.0 nM T than controls. Although T at any concentration tested (0.1, 1.0 or 10.0 nM) failed to affect the mean value of the process length, a significant difference was observed in the frequency distribution of total process length between 1.0 nM T-treated cultures and control cultures. By 1.0 nM T, the number of process branchings was also significantly increased. In contrast, the number of neurons and the total process length of neurons were not affected by 5 alpha-DHT. However, the number of process branchings was significantly increased by 0.1 nM 5 alpha-DHT. E2 had no significant effect on any of these parameters. These results suggest that T directly enhances the survival of neurons and increases the dendritic and/or axonic field of the POA, which serves, at least partly, for the development of morphological sexual dimorphism in the rat.
Androgens↗
Steroid-related bilateral osteonecrosis of the patella.
We present a case of bilateral osteonecrosis of the patella in a patient during steroid therapy and demonstrate the radiological, arthroscopic, and histological features. Osteonecrosis of the patella should be considered as a possible cause of knee pain in patients receiving steroid therapy.
Arthroscopy↗
Changes in amino acid neurotransmitters and cerebral blood flow in the ischemic penumbral region following middle cerebral artery occlusion in the rat: correlation with histopathology.
We simultaneously measured neurotransmitter amino acids by the microdialysis technique and cortical CBF by laser-Doppler flowmetry in the ischemic penumbral cortex of rats subjected to 2-h normothermic (36.5-37.5 degrees C) transient middle cerebral artery (MCA) clip-occlusion. Brains were perfusion-fixed 3 days later and infarct volume measured. CBF (% of preischemic values) fell to 32 +/- 2% (mean +/- SD) during ischemia and rose to 157 +/- 68% during recirculation. Extracellular glutamate levels increased from a baseline value of 7 +/- 3 microM to a peak value of 180 +/- 247 microM 20-30 min following onset of ischemia but subsequently returned to near baseline levels after 70 min of ischemia despite ongoing MCA occlusion. The threshold CBF for moderate glutamate release was 48%. Massive glutamate release was seen during the first 60 min of MCA occlusion in the two animals showing the largest infarcts and occurred at CBF values < or = 20% of control levels. Mean CBF during ischemia exhibited an inverse relationship with infarct volume, and the magnitude of glutamate release during ischemia was positively correlated with infarct volume. Extracellular gamma-aminobutyrate and glycine changes were similar to those of glutamate but showed no significant correlation with infarct volume. These results suggest that (a) accumulation of extracellular glutamate is an important determinant of injury in the setting of reversible MCA occlusion and (b) reuptake systems for neurotransmitter amino acids may be functional in the penumbra during transient focal ischemia.
Amino Acids↗
Ductectatic-type mucinous cystadenoma and cystadenocarcinoma of the human pancreas: a novel clinicopathological entity.
A new type of mucinous cystic pancreatic neoplasm is described. The lesions, which have been recognized only recently with the progress of diagnostic techniques and have not previously been described in the literature, are characterized by multilocular cysts with papillary proliferation of the lining epithelium. They occur exclusively in the head and body, predominantly in males, and coexistence of well-differentiated adenocarcinoma as well as adenoma components is frequently encountered. These lesions are quite different from hitherto described mucinous cystic neoplasms of pancreas, not only in terms of gross features but also with regard to intrapancreatic location, and sex and age distributions. We propose to classify these lesions as a new pancreatic tumor entity: the ductectatic-type mucinous cystadenoma/cystadenocarcinoma.
Aged↗
Immunohistochemical analysis of cathepsin B expression in human lung adenocarcinoma: the role in cancer progression.
Production of cathepsin B by tumor cells has been linked to metastatic potential in several experimental models. Sections of 95 primary lung adenocarcinomas were examined for expression of cathepsin B using a standard avidin-biotin immunohistochemical technique. Staining for cathepsin B was observed in 22.1% of all cases and 28.0% of those of the Clara cell type. In Clara cell adenocarcinomas, cathepsin B expression correlated with positive lymph node status, presence of distant metastases, and poor prognosis (P < 0.05). However, no correlation with clinical outcome was observed in other cell types. Our data suggest that cathepsin B may be involved in invasion and metastasis in Clara cell lung adenocarcinoma.
Adenocarcinoma↗
Production of IL-1 and IL-1 receptor antagonist and the pathological significance in lipopolysaccharide-induced arthritis in rabbits.
Injection of lipopolysaccharide (LPS) into rabbit knee joints provoked leucocyte infiltration and loss of proteoglycan (PG) from the cartilage. We investigated the role of IL-1 and IL-1 receptor antagonist (IL-1Ra) and its significance in the pathogenesis of LPS-arthritis. Production of IL-1 beta peaked at 6 h (196.7 +/- 89.4 pg/joint) after injection of 10 ng of LPS, while IL-1Ra peaked at 9 h (34.5 +/- 13.4 ng/joint). The amount of IL-1Ra was 180-200-fold molar excess of IL-1, and a large amount of IL-1Ra was sustained for 1 week. Both IL-1 beta and IL-1Ra were mainly produced by synovial exudate cells. Arthritis was reproduced by rabbit IL-1 beta. LPS-induced leucocyte infiltration was inhibited 70-75% by rabbit IL-1Ra. Loss of PG in LPS-arthritis was prevented by IL-1Ra and also by neutrophil elastase inhibitor, and superoxide dismutase. In leucopenic rabbits, injection of LPS induced neither production of IL-1 beta nor loss of PG. Direct injection of inflammatory exudated cells in leucopenic rabbits reproduced loss of PG, and there was only a partial recovery by IL-1Ra. These results suggest that LPS-initiated IL-1 acts as a key mediator in LPS-arthritis and that endogenous IL-1Ra may suppress a part of IL-1 activity at the site, but its amount was too low for suppression of the produced IL-1. Loss of PG is a sequela of infiltrated leucocytes and leucocyte-derived elastase, and superoxide anion may play a pivotal role in the destruction of cartilage.
Animals↗
Relaxant effects of brain natriuretic peptide on guinea-pig tracheal smooth muscle.
1. The relaxant effects of brain natriuretic peptide (BNP) were investigated on guinea-pig tracheal smooth muscle. 2. Various amounts of BNP (10(-9)-10(-6) mol/L) showed concentration-dependent relaxant effects on resting tone, leukotriene D4 (LTD4; 10(-8) mol/L) and endothelin-1 (ET-1; 10(-8) mol/L) induced contraction of tracheal smooth muscle with EC50 values of 3.1 +/- 0.7 x 10(-8), 3.9 +/- 1.0 x 10(-8) and 3.5 +/- 1.0 x 10(-8) mol/L, respectively. 3. BNP increased tissue cyclic GMP levels in tracheal smooth muscle concentration dependently (187 +/- 26 fmol/mg protein in control, 334 +/- 77 fmol/mg protein at 10(-8) mol/L, 680 +/- 54 fmol/mg protein at 10(-7) mol/L, 2162 +/- 133 fmol/mg protein at 10(-6) mol/L). 4. With the addition of BNP, tissue cyclic GMP levels reached a maximum at 1-3 min. The relaxation of tracheal smooth muscle began at 1 min and reached a maximum level at 5 min after the superfusion of BNP (10(-6) mol/L). The elevation of cyclic GMP preceded the relaxation of tracheal smooth muscle. 5. These results suggest that BNP may have a potent relaxant effect on tracheal smooth muscle and this effect may be mediated by cyclic GMP level.
Animals↗
Effect of xanthine derivatives on chemotactic polypeptide-induced superoxide and enzyme release from human polymorphonuclear leucocytes.
1. We investigated the effects of new xanthine derivatives, 1-methyl-3-propyl xanthine (MPX) and 1,3-dipropyl xanthine (DPX), and several other xanthine derivatives on N-formyl-methionyl-leucyl-phenylalanine-induced superoxide and lysozyme release from human polymorphonuclear leucocytes (PMN). 2. MPX and DPX at low concentrations (10(-8) - 10(-9) mol/L) inhibited superoxide release from PMN by a maximum of 31.2 +/- 10.6% and 49.8 +/- 10.4% (mean +/- s.d.), respectively, and 10(-3) mol/L concentrations completely inhibited the release reactions (4.8 +/- 1.2 and 7.6 +/- 2.5% of control level). At 10(-5) mol/L, however, the inhibition did not occur (99.9 +/- 7.3 and 110.2 +/- 15.8% of control level). When PMN was pre-incubated with adenosine deaminase (ADA, 0.1 U/mL), superoxide release from PMN was inhibited in a dose-dependent manner by MPX and DPX and the interruption of the inhibition at 10(-5) mol/L was not observed. 3. Lysozyme release from PMN was inhibited by MPX at low concentrations (10(-7) - 10(-6) mol/L) and high concentrations (10(-3) mol/L). However 10(-4) mol/L of MPX facilitated the release (23.7 +/- 27.0%). When pretreated with ADA (0.1 U/mL), MPX suppressed lysozyme release in a dose-dependent manner and the facilitation of the release at 10(-4) mol/L was not observed. 4. When comparing effects of some other xanthine derivatives on superoxide release, the interruption of the inhibition of superoxide release at 10(-5) mol/L was commonly observed among xanthine derivatives with adenosine A2 antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)
3',5'-Cyclic-AMP Phosphodiesterases↗
Effect of staurosporine derivatives on protein kinase activity and vinblastine accumulation in mouse leukaemia P388/ADR cells.
Inhibition by staurosporine derivatives of cyclic AMP-dependent protein kinase (A-kinase) and protein kinase C (C-kinase), and drug resistance has been investigated. The substitution of an acetyl or an ethoxycarbonyl group for the amine N-ethoxycarbonyl-7-oxostaurosporine moiety on the tetrahydropyran ring of staurosporine decreased inhibition of both protein kinases, but increased selectivity for C-kinase by further modification of the lactam moiety to the imide (NA-382). The activities of SF-2370 on protein kinases were decreased by decarboxylation and hydroxyalkylation. These staurosporine derivatives enhanced accumulation of vinblastine in adriamycin-resistant P388 (P388/ADR) cells in a dose-dependent manner. The potency for the drug accumulation of these compounds was correlated with their inhibitory activity on the drug efflux, but was not correlated with their activity on protein kinases. Staurosporine and NA-382, with high potency for vinblastine accumulation, inhibited the photolabelling of [3H]azidopine on 140 kDa P-glycoprotein in the plasma membrane. The tetrahydrofuran compounds and NA-357, which had low potency for the drug accumulation, hardly interacted with azidopine on P-glycoprotein. Most of these compounds were highly cytotoxic by themselves, and only NA-382 was less cytotoxic among them and completely reversed the vinblastine-resistance of P388/ADR cells at a non-cytotoxic concentration. These results suggest that staurosporine derivatives can enhance drug accumulation and inhibit drug resistance through their direct action on the P-glycoprotein.
Affinity Labels↗