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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 595 records · Page 33Linked to original sources
PubMed1988

[Effects of prostaglandin F2 alpha on steroidogenesis of the PMSG-hCG primed rat ovary in luteolysis].

Activities of the steroidogenic enzymes involved in functional luteolysis and PGF2 alpha induced luteolysis were determined in PMSG-hCG primed immature rats to elucidate the luteolytic effects of PGF2 alpha. Plasma progesterone (P4), plasma 20 alpha dihydroprogesterone (20 alpha OHP4), in vitro production of pregnenolone (P5) from endogenous cholesterol in ovarian mitochondria (8,000 X g pellet; Mt), activities of 3 beta hydroxysteroid dehydrogenase (3 beta HSD) in ovarian microsome (105,000 X g pellet; Ms) and 20 alpha hydroxysteroid dehydrogenase (20 alpha HSD) in ovarian cytosol(105,000 X g supernatant; Sup) were determined. For the investigation of intramitochondrial transport of cholesterol, measurement of free cholesterol (FCh) of Mt and the Lineweaver-Burk plotting for cholesterol side-chain cleavage enzyme (CSCC), prepared by osmotic shock and sonication of Mt, were carried out. Functional life span of the rat corpus luteum was estimated as 12 days post hCG treatment from plasma P4. As plasma P4 decreased, concomitant increase in plasma 20 alpha OHP4 was observed. In vitro production of P5 in Mt correlated well with plasma P4 levels, indicating cholesterol side-chain cleavage reaction is the rate limiting step involved in ovarian steroidogenesis. In contrast, both values of Km and Vmax of CSCC did not change between day 7, on which the highest value of plasma P4 observed, and day 12, on which functional luteolysis was ascertained from plasma P4. Both FCh of Mt and the activity of 3 beta HSD in Ms remained unchanged during the functional life of the corpus luteum. The activity of 20 alpha HSD in Sup increased from day 10 post hCG treatment in accordance with plasma 20 alpha OHP4. These results indicate that 1) decrease in availability of FCh to CSCC within mitochondria and 2) increase in catabolism of P4 into inactive progestin, 20 alpha OHP4, may play key roles in the functional luteolysis. To compare the events observed in functional luteolysis with PGF2 alpha induced luteolysis, the animals were treated either with PGF2 alpha (1 mg/rat; s.c.), cycloheximide (5 mg/rat; i.p.; CX), or vehicle on day 7 post hCG treatment, and sacrificed 1 hour later for the analyses mentioned above. Both plasma P4 and in vitro production of P5 in Mt decreased significantly with PGF2 alpha or CX treatment, whereas the FCh of Mt and the activity of CSCC remained unchanged with PGF2 alpha treatment. Both plasma 20 alpha OHP4 and 20 alpha HSD in Sup increased with PGF2 alpha treatment. However, CX suppressed both of them.(ABSTRACT TRUNCATED AT 400 WORDS)

20-alpha-Dihydroprogesterone↗
PubMed1988

The upstream promoter of the human LDL receptor gene does not contain a cyclic AMP response element.

Fusion genes containing segments of the promoter region of the human LDL receptor gene and the coding sequence of the bacterial enzyme, chloramphenicol acetyltransferase (CAT), were introduced into JEG-3 human choriocarcinoma cells. Constructs containing 177 base pairs of 5'-flanking DNA (pLDLR-CAT 234) or 6500 base pairs (pLDLR-CAT 6500) promoted CAT activity in transient expression assays. Although both pLDLR-CAT 234 and pLDLR-CAT 6500 contain sequences related to the recently reported consensus sequence for cyclic AMP responsiveness, treatment of the transfected JEG-3 cells with 8-bromo-cAMP did not increase CAT activity. The cyclic AMP analog did, however, stimulate steroidogenesis and hCG secretion and increase CAT activity in cells transfected with p18X2SV1CAT, which contains two copies of an 18 base pair sequence corresponding to the cAMP-responsive element of the human alpha chorionic gonadotropin gene.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Inhibition of ornithine decarboxylase induction by retinobenzoic acids in relation to their binding affinities to cellular retinoid-binding proteins.

Retinobenzoic acids induce differentiation of human promyelocytic leukemia cells (HL-60). Like retinoic acid, 14 retinobenzoic acids inhibited the induction of ornithine decarboxylase (ODC) by teleocidin in mouse skin. The mechanism(s) of inhibition of ODC induction by 7 retinobenzoic acids, Am 80, Am 81, Am 580, Am 590, Am 68, Sa 80, and Ch 55 was compared with those by all-trans-retinoic acid and the arotinoid compound 19. Application of 114 nmol of Am 80, Am 81, Am 580, Am 590, Am 68, Sa 80, or Ch 55, 10 min before 11.4 nmol of teleocidin, resulted in 76.7%, 82.0%, 76.2%, 28.3%, 48.4%, 58.6%, and 85.1% inhibition of ODC induction, respectively. Since all-trans-retinoic acid and compound 19 were also inhibitory, we determined whether retinobenzoic acids bind to cellular retinoic acid-binding protein (CRABP) isolated from bovine adrenal glands. Am 80 and Am 580 inhibited the specific binding of 3H-retinoic acid to CRABP, but also showed less affinity than authentic unlabeled retinoic acid and compound 19. Am 81, Am 590, Am 68, Sa 80, and Ch 55 at up to 10 microM were not effective competitors of the binding of either 3H-retinoic acid or 3H-retinol. These results suggest that the inhibition of ODC induction can be mediated by pathways that do not involve CRABP or the cellular retinol-binding protein.

Animals↗
PubMed1988

Change in serum and biliary esterified bile acids in patients with extrahepatic cholestasis during percutaneous transhepatic cholangiodrainage.

Eighteen patients with total extrahepatic cholestasis undergoing PTCD were classified into three groups, depending on the bilirubin decrease rate at two weeks after PTCD. Serum and biliary esterified bile acids in each group were measured before PTCD and at 24 hours, 48 hours, 1 week, and 2 weeks after PTCD. Bile acids were measured by Okuyama's methods (HPLC), and esterified bile acids were calculated from the difference between samples treated with sulfatase or beta-glucuronidase for enzymatic hydrolysis and untreated samples measured at the same time. The following results were obtained. The percentages of biliary esterified bile acids in total bile acids were as follows: before PTCD, in the fair improvement group, sulfate (S) = 6.4 +/- 4.6% (mean +/- S.D.), glucuronide (G) = 11.7 +/- 9.0%; in the poor improvement group, S = 2.8 +/- 1.6%, G = 1.0 +/- 0.9% and at 24 hours after PTCD, in the fair group, S = 9.1 +/- 7.5%, G = 7.5 +/- 4.3%; in the poor group, S = 2.9 +/- 2.4%, G = 1.7 +/- 1.1%. The percentages of esterified bile acids in the fair group were higher than in the poor group, and significant differences were noted in G (p less than 0.05). Thus PTCD is expected to reduce jaundice in cases with high percentages of biliary esterified bile acids before and shortly after PTCD.

Adult↗
PubMed1988

The dissociation constant of verapamil estimated from its effect on Ca concentration-tension curves in guinea-pig tracheal muscle.

Concentration-tension curves for calcium ions (Ca2+) were studied in indomethacin-treated guinea-pig tracheal muscle in the presence of different concentrations of carbachol in media containing 5.9 mM K+ or 40 mM K+. The effect of verapamil was investigated taking into account the steepness (the Hill coefficient) of the Ca2+ curve. When carbachol (1 microM) was added to 40 mM K+ solution, the Ca2+ concentration to produce half maximum tension (EC50) was reduced from 0.2 mM to 0.08 mM and the Hill coefficient was increased from 1.4 to 2.0, respectively. In the presence of carbachol (1 microM), the Ca2+ concentration-tension curve was not much influenced by increasing the K+ concentration from 5.9 to 40 mM K+. Verapamil (0.5 microM) shifted the Ca2+ concentration-tension curve to the right in a parallel manner under all experimental conditions, the shift being greater with curves having a smaller Hill coefficient. The dissociation constant of verapamil was not altered by carbachol when estimated from the shift of the curve if the Hill coefficient is taken into consideration. It is concluded that the relatively low susceptibility of carbachol-induced contractions to verapamil in the presence of 40 mM K+, compared with these produced by K+ alone, is not due to a decreased verapamil affinity but to improved Ca(2+)-response coupling.

Animals↗
PubMed1988

Actinomycosis of urachal remnants.

We report a case of urachal actinomycosis. The patient presented with complaints of micturition pain and a lower abdominal mass. Computerized tomography and an echogram showed the mass extending from the dome of the bladder to just beneath the rectus muscle. Exploration revealed a hard mass in the urachal cord, which was near the dome of the bladder and extended to the umbilicus. The mass and urachal cord were resected, and histopathological examination revealed actinomycosis of the urachal remnants.

Actinomycosis↗
PubMed1988

Rearrangements of chromosome 3 in nonfamilial renal cell carcinomas from Japanese patients.

Cytogenetic studies were successfully carried out in 5 tumor tissues from Japanese patients with nonfamilial renal cell carcinoma, histologically diagnosed as clear cell subtype. Mitotic cells were obtained by a combined method of enzymatic disaggregation and short-term culture (6-12 days). The modal chromosome numbers were found to be diploid or near-diploid in all the cases examined. Every case showed characteristic structural and numerical abnormalities. Rearrangements in the short arm of chromosome 3 were observed as clonal abnormalities in all the cases, including a translocation t(3;6) resulting in a partial loss of 3p (3 cases), a terminal deletion of 3p (one case) and 2 different translocations involving 3p and 8p (one case). The other clonal abnormalities were a whole or partial trisomy of chromosome 7 and a loss of Y chromosome. The overall results in the present study were consistent with those of our previous data in American patients, and suggest that the rearrangements of chromosome 3 leading to a partial loss of its short arm may play primary and significant role(s) in the development of renal cell carcinoma.

Aged↗
PubMed1988

Diarrhetic shellfish toxin, dinophysistoxin-1, is a potent tumor promoter on mouse skin.

Dinophysistoxin-1, 35-methylokadaic acid, is a causative agent of diarrhetic shellfish poisoning. The biological activities and tumor-promoting activity of dinophysistoxin-1 were studied together with those of okadaic acid and 7-O-palmitoyl okadaic acid. Dinophysistoxin-1 is a skin irritant and induces ornithine decarboxylase in mouse skin with the same potency as okadaic acid. 7-O-Palmitoyl okadaic acid induced a lower activity than the other compounds. Dinophysistoxin-1 inhibited the specific [3H]okadaic acid binding to a particulate fraction of mouse epidermis. The binding affinities of dinophysistoxin-1 and okadaic acid to a particulate fraction were almost the same. Dinophysistoxin-1 showed a tumor-promoting activity as strong as that of okadaic acid in a two-stage carcinogenesis experiment on mouse skin. The percentages of tumor-bearing mice in the groups treated with 100 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) followed by 5 micrograms of dinophysistoxin-1, twice a week, and with DMBA followed by 5 micrograms of okadaic acid twice a week were 86.7% and 80.0% in week 30, respectively. The average number of tumors per mouse was 4.6 in the former group and 3.9 in the latter. Dinophysistoxin-1 and okadaic acid act on cells through different pathways from the 12-O-tetradecanoylphorbol-13-acetate-type tumor promoters.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Mechanism responsible for alterations in numbers of autonomic nerve receptors in experimental asthma.

This study was designed to elucidate the mechanism responsible for alterations in the numbers of autonomic nerve receptors in experimental asthma. In the in vivo experiment, guinea pigs sensitized by exposure to aerosol of 2% ovalbumin for 7-8 min for 10 successive days were used as the experimental asthma group. The control group was exposed to saline. Beta-, alpha-1-adrenergic and muscarinic acetylcholine receptors in lung membranes were studied by direct binding techniques using l-3H-dihydroalprenolol, 3H-bunazosin and l-3H-quinuclidinyl benzilate, respectively. The experimental asthma group showed a 33% decrease in the number of beta-adrenergic receptors, a 37% increase in the number of alpha-1-adrenergic receptors and no change in the number of muscarinic acetylcholine receptors compared with the control group. The endogenous phospholipase activity was determined by high-performance liquid chromatography using tridecanoyl phosphatidylcholine as a substrate. The phospholipase activity in lung membranes in the experimental asthma group was elevated by 50% compared with that in the control group. Lung membrane phospholipid composition was analyzed by thin-layer chromatography with a flame ionization detector. In the experimental asthma group, the amounts of phosphatidylcholine and phosphatidylethanolamine decreased significantly compared with those in the control group. In the in vitro experiment after pretreatment of lung membranes with phospholipase A2, a decreased number of beta-adrenergic receptors, an increased number of alpha-1-adrenergic receptors and no change in the number of muscarinic acetylcholine receptors were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Concerning the assays for autonomic nerve receptors. Effects of incubation temperature and time on alterations in the number of receptors.

Alterations in autonomic nerve receptors play an important role in various pathological conditions, including bronchial asthma. Nevertheless, receptor assay conditions such as incubation temperature and incubation time are not consistent among various investigators. This study was designed to clarify the effects of incubation temperature and time on alterations in the number of autonomic nerve receptors. Guinea pig lung membranes were divided into five groups which were incubated under different incubation temperatures and over different incubation times. After incubation, the following experiments were performed. Beta-, alpha-1-adrenergic, and muscarinic acetylcholine receptor assays were performed by direct binding technique using L-3H-dihydroalprenolol, 3H-bunazosin, and L-3H-quinuclidinyl benzilate, respectively. Elevation of incubation temperature and prolongation of incubation time caused a significant decrease in the number of beta-adrenergic receptors and an increase in the number of alpha-1-adrenergic receptors. The number of muscarinic acetylcholine receptors did not change significantly in spite of changes in incubation temperature and time. Adenylate cyclase activity was measured by following the synthesis of cyclic adenosine monophosphate from nonradioactive adenosine triphosphate. Isoproterenol-stimulated adenylate cyclase activity decreased significantly in correspondence with the elevation of incubation temperature and prolongation of the incubation time. Contents of free fatty acids in lung membranes were measured by high-performance liquid chromatography. Free fatty acid contents increased significantly in accordance with elevation of incubation temperature and prolongation of incubation time which reflected on the degradation of membrane phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1988

Increased immunoglobulin E Fc receptor bearing cells in germinal centers of hyperimmunoglobulinemia E patients.

Lymph nodes from 6 patients with hyperimmunoglobulinemia E (hyper-IgE; 4 with Kimura's disease, 1 with atopic dermatitis, and 1 with immunoblastic lymphadenopathy-like T cell lymphoma) and from 7 patients with normal IgE levels were studied to determine the localization of dendritic reticulum cells and of cells bearing Fc epsilon and C3d receptors and immunoglobulin E. The avidin-biotin-glucose oxidase method was used for unfixed biopsy specimens. To identify the above-mentioned cells, H107, a murine monoclonal antibody specific to the Fc epsilon receptor molecule, and corresponding antibodies specific to the other cell types were used. In 5 hyper-IgE patients (4 with Kimura's disease and 1 with atopic dermatitis) all germinal centers of the lymph nodes showed heavy reticular staining with H107, the dendritic reticulum cells being most intensely stained. In contrast, the germinal centers of the lymph nodes in the 7 patients with a normal IgE level only lightly or partially stained with H107. The staining pattern of anti-IgE was similar to that of H107 in the hyper-IgE cases. Likewise, C3d receptor and dendritic reticulum cell-related antigens were demonstrated very intensely in all germinal centers in lymph nodes of patients with hyper-IgE and normal IgE levels. These findings suggest that in a hyper-IgE state increased numbers of dendritic reticulum cells in a germinal center express the Fc epsilon receptor and that such cells may play a role in the differentiation of IgE-producing memory B cells.

Angiolymphoid Hyperplasia with Eosinophilia↗
PubMed1988

Structure-activity relationship in N3-alkyl-xanthine derivatives.

Structure-activity studies were carried out to compare the relaxant effects of various xanthine derivatives synthesized by substitution of the alkyl groups of the N3 position in the xanthine molecule. We evaluated the relaxant effects and the inhibitory activities on c-AMP phosphodiesterase (PDE) in tracheal smooth muscle isolated from guinea pigs. A comparative study on their pharmacokinetic characteristics was also carried out in rabbits. Dose-dependent relaxant effects were observed, and the relaxant effect of propylxanthine was nearly equal to the effects of butyl- and isobutylxanthines. Based on the estimation of the Ki values for PDE inhibition, it was found that butylxanthine is a potent inhibitor of PDE. There was good correlation between the alkyl chain length and the Ki value of these derivatives. The results showed that the alkyl chain length plays an important role in the inhibition of PDE. There were no significant differences in the volume of distribution, although the half-life showed significant differences. It is likely that the half-lives of these derivatives are affected by their chain lengths. The present study indicated that butylxanthine may be a new candidate as a bronchodilator. However, clinical studies have to be carried out to compare its efficacy and adverse effects with those of existing bronchodilators such as theophylline.

Animals↗
PubMed1988

Studies on alkyl-xanthine derivatives. II. Pharmacokinetic and pharmacodynamic studies of a new bronchodilator, 1-methyl-3-propylxanthine (MPX).

A new xanthine derivative bronchodilator, 1-methyl-3-propylxanthine (MPX), and 1-methyl-3-butylxanthine (MBX) were synthesized. We evaluated their relaxant effects on tracheal smooth muscle isolated from guinea pigs and pharmacokinetic characteristics in rats using 1,3-dimethylxanthine (theophylline, TPH) as the reference drug. Dose-dependent relaxant effects were observed in the concentration range of 1 x 10(-6) to 1 x 10(-4) M, and both MPX and MBX exert very much stronger relaxant effects than TPH with nearly equal potency. There were significant differences in the pharmacokinetic and physico-chemical properties among these drugs, both MPX and MBX having shorter half-lives, higher plasma protein binding in vivo and stronger hydrophobicity compared to TPH. The present study suggested that the N3-alkyl chain length is significant for increasing the relaxant effect and affecting the pharmacokinetic and physico-chemical properties of these drugs.

Animals↗
PubMed1988

Comparative studies on interaction between theophylline and quinolones.

A comparative study of the pharmacokinetic and metabolic interactions between theophylline and a newly developed quinolone, T-3262, was carried out under steady-state conditions in seven healthy male volunteers, using enoxacin as the reference drug. A sustained-release theophylline formulation (200 mg twice daily) was given as monotherapy and coadministered with T-3262 (150 mg three times a day) or enoxacin (200 mg three times a day). The total and free concentrations of theophylline in the plasma and the excreted concentration of theophylline and its metabolites in the urine were measured by a high-performance liquid chromatography method. The mean steady-state plasma theophylline concentration significantly increased by approximately 1.5-fold and threefold after coadministration of T-3262 and enoxacin, respectively. In both cases, a significant decrease in the total body clearance was found for T-3262 (34%) and enoxacin (63%), but the plasma protein binding of theophylline remained unchanged. There was a significant increase in urinary theophylline and a decrease in urinary 3-methylxanthine after coadministration of T-3262 or enoxacin. The degree of change in the steady-state plasma theophylline concentration as a result of coadministration of T-3262 was small compared to that of enoxacin. A decrease in the total body clearance in the case of coadministration of a quinolone probably resulted from inhibition of the 1-demethylation metabolic pathway.

Adult↗