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Biomedical subjects

H Takeda

Publications and source records attributed to H Takeda.

At least 361 records · Page 20Linked to original sources

[Study on azithromycin in treatment of diffuse panbronchiolitis].

In the treatment of diffuse panbronchiolitis, azithromycin (AZM), a new macrolide antibiotic with 15-membered lactone ring, was studied for its efficacy and safety. AZM, 250 mg, was intermittently administered to a total of 60 patients twice a weeks, for 3 months as a rule, and its efficacy was clinically evaluated in 52 patients and the safety in 55. The rate of efficacy was 84.6% (44/52). Clinical findings 12 weeks after the start of administration showed a decrease in sputum volume in 30 of 46 patients and amelioration of dyspnea on exertion in 23 of 46 patients, and no worsening of symptoms was observed in the patients. Vital capacity (4/22), FEV1.0 (6/21), cold agglutination reaction (22/28), and CRP (16/36) were also improved. The rate of eradication of organisms isolated from the sputum except for indigenous organisms was 39.5% (15/38); 4 of the 22 strains of Pseudomonas aeruginosa were eradicated. Adverse reactions were observed in 4 of the 55 patients (7.3%), 1 patient each with rash, itching, diarrhea, and a gastric symptom (heavy feeling in the stomach). 4 of the 54 patients (7.4%) exhibited abnormal changes in clinical laboratory test values values. These were an increase in eosinophil count in 2, elevation of GOT in 1, and elevation of Al-P in 1. These adverse reactions and abnormal changes in laboratory tests were mild or moderate. Therefore, long-term intermittent administration of AZM, twice a week, is expected to have the same effect in the treatment of diffuse panbronchiolitis as long-term small-dose administration of 14-membered macrolides such as erythromycin and clarithromycin, whose effects have already been established.

Adolescent↗

Activation of protein kinase C increases adenosine production in the hypoxic canine coronary artery through the extracellular pathway.

Both ischemia and hypoxia increase adenosine production in the heart. This study tested whether hypoxia increases adenosine production in the coronary artery via ecto-5'-nucleotidase and the role of protein kinase C in this condition. Canine left circumflex coronary artery was rapidly removed and incubated in 10 mL Krebs-Henseleit solution for 30 minutes. The Krebs-Henseleit solution contained 5'-iodotubercidin and 2'-deoxycoformycin, which inhibit adenosine kinase and adenosine deaminase, respectively. Adenosine production was measured in intact coronary arteries under normoxic conditions (16.2 +/- 1.2 pmol/mg protein). Adenosine production was reduced by 27% after removal of endothelium. Ecto-5'-nucleotidase activity of coronary arteries with and without endothelium was 51 +/- 6 and 41 +/- 4 nmol/mg protein per minute under normoxic conditions. Hypoxia increased adenosine production to 27.0 +/- 2.3 and 20.0 +/- 0.8 pmol/mg protein with and without endothelium. Hypoxia also increased ecto-5'-nucleotidase activity of coronary arteries with and without endothelium (74 +/- 8 and 53 +/- 5 nmol/mg protein per minute; P < .05). Increases in adenosine production under hypoxic conditions were blunted by both an inhibitor of ecto-5'-nucleotidase and inhibitors of protein kinase C. Activation of ecto-5'-nucleotidase was blunted by an inhibitor of protein kinase C. These results indicate that hypoxia increased extracellular adenosine production and activated ecto-5'-nucleotidase via activation of protein kinase C in coronary arterial smooth muscle and endothelial cells. Increased adenosine production in coronary arteries during hypoxia may contribute to coronary vasodilation and cardioprotection against ischemic injury.

5'-Nucleotidase↗

Effects of tyrosine phosphorylation on tight junctions in temperature-sensitive v-src-transfected MDCK cells.

We analyzed the direct effects of tyrosine phosphorylation on the structure and functions of tight junctions in temperature-sensitive v-src-transfected MDCK cells. When ts-v-src MDCK cells were plated at a low density at the nonpermissive temperature, they formed small, tight colonies with a typical epithelial appearance. When these colonies were cultured at the permissive temperature, cadherin-based cell adhesion was suppressed, so that individual cells scattered and assumed a fibroblastic appearance. This resulted in the destruction of tight junctions, making it difficult to analyze the direct effects of tyrosine phosphorylation on tight junctions. To suppress cell scattering, we cultured ts-v-src MDCK cells at confluence. Under these conditions, even at the permissive temperature, the cells assumed an epithelial appearance, and the structure of tight junctions were mostly maintained both at the immunofluorescence and electron microscopy levels. The transepithelial electrical resistance (TER) dropped to about 70% of the initial value after the temperature shift from the nonpermissive to the permissive. This temperature shift facilitated the tyrosine phosphorylation of the two tight junction proteins, ZO-1 and ZO-2. We concluded that the direct effects of tyrosine phosphorylation on tight junctions are not so remarkable as those on adherens junctions.

Animals↗

[Effect of fluvoxamine, a new antidepressant drug, on monoamine dynamics in the rat cerebral limbic system and its pharmacological characteristic].

The effect of fluvoxamine (FLU) on the amine dynamics in serotonergic, noradrenergic or dopaminergic nervous systems in the rat cerebral limbic system was investigated, with reference to the pharmacological characteristics of FLU. Following single oral administration of 30 and/or 60 mg/kg FLU, significant decreases in the 5-hydroxyindole-3-acetic acid (5-HIAA)/serotonin (5-HT) ratios in the amygdala and hippocampus and the 4-hydroxy-3-methoxyphenylglycol (MHPG)/norepinephrine (NE) ratio in the amygdala were produced. FLU at 15 mg/kg, p.o. also caused a significant increase in MHPG/NE ratio in the hippocampus. On the other hand, imipramine (IMI) at 30 mg/kg, p.o. induced significant decreases in 5-HIAA/5-HT ratio in the hippocampus, MHPG/NE ratios in the amygdala and hippocampus, and 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratios in the amygdala, hippocampus and septum. The 5-HIAA/5-HT ratios in the amygdala and hippocampus and the MHPG/NE ratio in the septum were significantly decreased after repeated oral administration of 30 mg/kg FLU twice daily for 14 days, but the MHPG/NE ratio in the amygdala was increased. In the septum, DOPAC/DA ratio was significantly decreased following repeated administration of IMI at 30 mg/kg, p.o. These findings suggest that FLU inhibits 5-HT turnover in the amygdala and hippocampus as a result of the interference with the neuronal re-uptake mechanism for 5-HT. Also, FLU has an effect on NE turnover in the cerebral limbic system, and the effect may appear in connection with a change in the interaction of nervous systems.

Administration, Oral↗

Studies on anti-allergic action of AH 21-132, a novel isozyme-selective phosphodiesterase inhibitor in airways.

The effects of AH 21-132, a type III and IV phosphodiesterase (PDE) inhibitor, on allergic reactions in the airway were studied by comparing them with the effects of rolipram, a type IV PDE inhibitor, and aminophylline, a non-selective PDE inhibitor. The following results were obtained: 1) AH 21-132, rolipram and aminophylline inhibited the antigen-induced contraction of isolated guinea pig tracheal muscle in vitro. 2) AH 21-132 and aminophylline inhibited antigen-induced histamine release from human lung tissue fragments. 3) Antigen-induced accumulation of inflammatory cells including eosinophils and macrophages in mice bronchoalveolar lavage fluid was clearly inhibited by AH 21-132 and rolipram, but not by aminophylline. 4) AH 21-132, rolipram and aminophylline inhibited immediate phase bronchocostriction induced by either an intravenous or an aerosol challenge of antigen in guinea pigs. 5) AH 21-132 and rolipram inhibited the aeroantigen challenge-induced late phase increase in the airway resistance in guinea pigs, but aminophylline did not. These results suggest that AH 21-132 has an anti-allergic effect in the airway and that these actions may be beneficial for the treatment of allergic bronchial asthma.

Aminophylline↗

Effects of NIP-502 on antigen-induced bronchial responses and allergic reactions in animal models.

We examined the effect of a newly synthesized pyridazinone derivative, NIP-502 [4-chloro-5-(3-ethoxy)-4-phenoxybenzamine)-3(2H)-pyridazinone], on antigen-induced bronchial responses and allergic reactions in several animal models. NIP-502 (10 mg/kg, p.o.) inhibited the antigen-induced immediate asthmatic response in passively sensitized guinea pigs. The inhibitory effect was also observed in metyrapone (an inhibitor of 11 beta-hydroxylase)-pretreated guinea pigs. NIP-502 improved ovalbumin (OA)-induced airway hyperresponsiveness to acetylcholine and inhibited the OA-induced increase in the number of inflammatory leukocytes in the bronchoalveolar lavage fluid. These inhibitory effects on OA-induced responses were similar to those of prednisolone. NIP-502 also showed an inhibitory effect on the passive cutaneous anaphylactic reaction in rats but did not inhibit the reversed cutaneous anaphylactic reaction, reversed Arthus reaction or delayed type hypersensitivity reaction. On the other hand, prednisolone showed broad inhibitory effects except for the reversed cutaneous anaphylactic reaction. In the in vitro study, NIP-502 (30 microM) significantly inhibited Formyl-Met-Leu-Phe-induced superoxide anion production by the guinea pig alveolar macrophages. These results indicate that the inhibitory effects of NIP-502 on bronchial responses are similar to those of prednisolone, but this compound seemed to act more selectively on the respiratory tract than prednisolone. Because of its effectiveness against a variety of bronchial responses, NIP-502 may be useful in the treatment of bronchial asthma.

Aminophylline↗

Cholecystokinin-A specific antagonism of KSG-504 to cholecystokinin receptor binding and pancreatic secretion in mammals.

The effects of KSG-504 ((S)-arginium (R)-4-[-N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2- naphthylsulfonyl) pentanoate monohydrate), a new cholecystokinin (CCK)-receptor antagonist, on 125I-CCK-8 binding to rat pancreatic, canine gallbladder and guinea pig cerebrocortical membranes and the pancreatic amylase release from isolated rat acini stimulated by several kinds of secretagogues, including CCK, were investigated. The 125I-CCK-8 saturation experiment showed that pancreatic, gallbladder and cerebrocortical CCK receptors had a single high affinity binding component with dissociation constants (Kd) of 0.18, 0.31 and 0.88 nM, respectively. The maximum numbers of specific binding sites (Bmax) in these membranes were 1012, 52 and 20 fmol/mg protein, respectively. KSG-504 and CCK-8 displaced specific 125I-CCK-8 binding to CCK receptors in all membrane preparations in a competitive manner. The affinity of KSG-504 for pancreatic (Ki = 173 nM) and gallbladder (Ki = 283 nM) CCK receptors were > 3 orders of magnitude higher than its affinity for cerebrocortical CCK receptors. KSG-504 also inhibited 125I-gastrin-I binding to guinea pig gastric glands, but the IC50 value (18.2 microM) was apparently much higher. CCK-8-stimulated amylase release from isolated pancreatic acini of rats was antagonized by KSG-504 in a concentration-dependent manner. KSG-504 did not affect amylase release stimulated by secretagogues such as gastrin-releasing peptide, carbachol, vasoactive intestinal peptide and A23187. These results indicate that KSG-504 acts as a CCK-A-receptor-specific antagonist in the pancreas and gallbladder.

Amylases↗

Oral low-dose etoposide therapy for refractory multiple myeloma with extramedullary involvement.

A 65-year-old man was hospitalized with IgG kappa-type multiple myeloma (MM) and enormous subcutaneous plasmacytomas. Two different combination chemotherapy regimens (MMCP and AVPP) and alpha-interferon therapy were ineffectual. Oral administration of etoposide at 50 mg/day was subsequently started, the tumors completely disappeared after 5 months. The blood level of monoclonal protein became undetectable after 8 months of continuous treatment. The side effect noted was loss of hair. The course in this patient suggests that long-term daily low-dose administration of etoposide should be attempted in patients with refractory MM and extramedullary plasmacytoma.

Administration, Oral↗

Hypocholesterolemic effect of dietary fiber: relation to intestinal fermentation and bile acid excretion.

Rat cecal contents were static-cultured with three kinds of dietary fibers and examined for the production of short-chain fatty acids after 24h of cultivation. The total amount and molar ratio of acetate, propionate and butyrate (n = 8) were 7.20 +/- 0.62 mM and 38:19:43 with indigestible dextrin (ID), a low-viscosity, water-soluble dietary fiber, 10.88 +/- 0.46 mM and 49:5:46 with pectin (PE), a high-viscosity, water-soluble dietary fiber, and 1.83 +/- 0.19 mM and 64:11:25 with corn fiber (CF), a water-insoluble dietary fiber, respectively (the corresponding values obtained with glucose were 10.59 +/- 0.37 mM and 15:27:58). Next, rats were kept on a cholesterol- and bile acid-free high-sucrose diet. At the completion of the 8-week feeding period, the serum total-cholesterol levels were significantly lower, at 57.6 +/- 3.8 (n = 8), 63.2 +/- 4.67 (n = 7), and 77.8 +/- 3.7 mg/dl (n = 9), in the ID-, PE-, and CF-supplemented diet groups, respectively, than in the control group given no dietary fiber (92.7 +/- 3.8 mg/dl, n = 7). The cecal propionate production was significantly increased in both the ID and PE groups, while the fecal excretion of bile acids was increased in all three fiber groups compared to the control group. In addition, there was a significantly negative correlation between the serum total-cholesterol level and cecal propionate production in the ID group, between the serum cholesterol level and bile acid excretion in the CF group, and between the serum cholesterol level and cecal propionate production or bile acid excretion in the PE group. These results suggest that the degree of intestinal fermentation and bile acid excretion, which are considered to be associated with the hypocholesterolemic action of dietary fiber, varies with each kind of dietary fiber.

Acetates↗

Effects of intravenous injection and intraperitoneal continual administration of sodium propionate on serum cholesterol levels in rats.

To examine the effects of sodium propionate on serum cholesterol levels, rats were given sodium propionate intravenously and intraperitonealy. Six-week-old male Sprague-Dawley rats were kept on a cholesterol-free semisynthetic diet for 2 weeks, fasted, and given 400 microliters of saline solution intravenously supplemented with 0.01-10 mg sodium propionate. Three hours after injection of 1 mg of sodium propionate, the serum total-cholesterol level was significantly reduced (85.4 +/- 4.0 mg/dl) compared with its starting level (102 +/- 3.4 mg/dl), with the reducing effect lasting for 24 h. The intensity of the reduction increased proportionately with increased sodium propionate concentrations from 0.01 to 1 mg. Next, to evaluate the influence of continual sodium propionate administration on serum cholesterol levels, 6-week-old male rats were implanted with an osmotic pump intraperitonealy (ALZET Model 2ML2, pumping rate: 5.0 microliter/h; duration: 14 days; reservoir volume: 2,000 microliters). At day 14, serum total-cholesterol levels were reduced by continual sodium propionate administration at both 0.12 and 1.2 mg/day. The maximum percentage change in the serum total-cholesterol level was 78.5 +/- 6.7% of its starting level (111 +/- 7.1 mg/dl), observed at 1.2 mg/day at day 7. These results indicate that sodium propionate can reduce serum total-cholesterol levels in vivo.

Animals↗

Evaluation of the sensitivity of an immunochemical fecal occult blood test for colorectal neoplasia.

OBJECTIVES: This study was designed to evaluate the sensitivity of OC-Hemodia, a immunochemical fecal occult blood test (IFOBT) based on the technique of latex agglutination for early stage colorectal cancer and clinically significant adenomas. METHODS: The study was conducted on 885 patients who underwent OC-Hemodia and a colonoscopy. RESULTS: Colorectal cancers were detected in 23 patients (10 Dukes' A, eight Dukes' B, and five Dukes' C or D). Adenomas were detected in 459 patients (16 villous adenomas 433 tubular adenomas with mild or moderate dysplasia, and 10 with severe dysplasia). The sensitivity of OC-Hemodia was 90% for those with Dukes' A colon cancer and 100% for those with Dukes' B, C, or D colon cancer. It was 18.8% for those with villous changes, and 40% for those with severe dysplasia. CONCLUSIONS: These results suggest that the IFOBT is not a reliable test for the screening of premalignant adenomas, although it is useful for detecting early stage colorectal cancers.

Adenoma↗

[Treatment with percutaneous transluminal balloon venoplasty for superior vena cava syndrome after permanent pacemaker implantation].

Superior vena cava (SVC) syndrome after transvenous implantation of a permanent pacemaker is relatively uncommon. We present a woman whose neck and face became swollen two years after implantation of a two-chamber pacemaker. Computed tomography and digital subtraction angiography revealed severe SVC stenosis. Percutaneous transluminal venoplasty (PTV) was performed to relieve the stenosis. PTV was effective to improve the swelling of her neck and face. PTV seems to be a good method to relieve SVC stenosis after implantation of a pacemaker.

Adult↗

[Post operative mediastinitis: the experience of two cases after graft replacement of the ascending aorta].

A mediastinitis after a graft replacement of the ascending aorta is serious complication and sometimes could be lethal. We have experienced two cases of such a condition, recently. In both cases, the debridement of the mediastinum and omental transposition were performed. Case 1 had a recurrent mediastinitis due to residual dead space infection, but was cured by a percutaneous drainage and a continuous irrigation. In case 2, the omentum was carefully positioned to occupy the dead space around the graft, because of the experience of the first case and gave a good result. We believe that omental transposition is an effective treatment for the postoperative mediastinitis.

Adult↗