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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 847 records · Page 47Linked to original sources
PubMed1990

[The inhibitory effects of glycyrrhizin and glycyrrhetinic acid on the metabolism of cortisol and prednisolone--in vivo and in vitro studies].

This experiment was carried out to investigate the inhibitory effects of glycyrrhizin and its aglycon, glycyrrhetinic acid, on the metabolism of cortisol and prednisolone in vivo and in vitro. The effects of glycyrrhetinic acid on the metabolism of cortisol were examined in vitro using rat and bovine liver homogenate. Glycyrrhetinic acid inhibits both hepatic delta 4-5-reductase and 11 beta-hydroxysteroid dehydrogenase in a dose-dependent manner, resulting in the decrease of conversion of cortisol to cortisone, dihydrocortisol and tetrahydrocortisol in rats. The concentrations of glycyrrhetinic acid inducing 50% inhibition of rat liver delta 4-5-reductase and 11 beta-hydroxysteroid dehydrogenase were 2.5 x 10(-6) M and 8.5 x 10(-6) M, respectively. Glycyrrhetinic acid also inhibits bovine liver 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase in a dose-dependent manner, resulting in the decrease of conversion of cortisol to dihydrocortisol and prednisolone to 20-dihydroprednisolone. The concentrations of this drug inducing 50% inhibition of 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase were 8.2 x 10(-6) M and 6.5 x 10(-6) M, respectively. This is the first report which demonstrates the marked inhibitory effects of glycyrrhetinic acid on 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase in vitro. The effects of glycyrrhizin on the rate of metabolism of cortisol as well as prednisolone were studied in 23 patients with or without adrenal insufficiency. Glycyrrhizin had no effect on diurnal rhythm of plasma cortisol in 7 control subjects with normal pituitary adrenal axis, whereas glycyrrhizin significantly increased the half-time (T 1/2) and area under the curve (AUC) for plasma cortisol in 4 patients with adrenocortical insufficiency taking oral cortisol. Glycyrrhizin also increased T 1/2 and AUC for plasma prednisolone in 12 patients taking an oral prednisolone for at least 3 months. These results indicate that the suppression of hepatic delta 4-5-reductase, 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase by glycyrrhizin and glycyrrhetinic acid may delay the clearance of cortisol and prednisolone and prolong the biological half-life of cortisol or prednisolone.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1990

[Adoptive immunotherapy against peritoneal metastases from stomach cancer--application of regional lymph node lymphocytes].

Twenty-four patients with advanced stomach cancer were treated with OK-432 combined adoptive immunotherapy [AIT] as prophylaxis or therapy against peritoneal metastases. Lymphocytes isolated mainly from regional lymph nodes were cultured for 9-13 days with T cell growth factor and sonicated tumor extract. OK-432 administration and cell transfer were performed via a catheter inserted into the abdominal cavity at surgery. The proliferation rate of regional lymph node lymphocytes was higher than that of peripheral blood lymphocytes (p less than 0.01). Cultured regional lymph node lymphocytes expressed CD25 and CD4+45R- more frequently than those of peripheral blood lymphocytes. On the other hand, cytotoxic activity of regional lymph node lymphocytes were slightly lower than that of peripheral blood lymphocytes. These results suggest that regional lymph node lymphocytes could be used in AIT because of their different function from that of peripheral blood lymphocytes. Survival of the patients with peritoneal metastasis at primary laparotomy was higher than that of the historical control group (4-9 months after surgery). These results show that OK-432 combined adoptive immunotherapy appears to be a new therapeutic approach to peritoneal metastases from stomach cancer.

Adult↗
PubMed1990

Specific inactivation of glutathione S-transferases in class Pi by SH-modifiers.

Treatment of Class Pi glutathione S-transferases (GST) such as rat GST P (7-7), human GST pi and mouse GST MII with 0.05-0.1 mM N-ethylmaleimide (NEM) in 0.1 M Tris-HCl (pH 7.8) resulted in almost complete inactivation of these forms, whereas no or less inactivation occurred for GSTs in Class Alpha and Mu under the same conditions. Inactivated GST P lost its S-hexyl-GSH-Sepharose column affinity. About 0.8 mol of [14C]NEM was found to be covalently bound to 1 mol of GST P subunit when 80% of the activity was lost. Similar treatment with N-dimethyl-amino-3,5-dinitrophenyl maleimide, a colored analogue of NEM, followed by trypsin digestion, HPLC and amino acid sequence analysis revealed that one cysteine residue at the 47th position from the N-terminal of the GST P subunit was preferentially modified. Subunits of GST P and GST pi are known to have 4 cysteine residues at the same corresponding positions. The present results suggest that the 47th cysteine residue may be located in the vicinity of the active site of Class Pi GSTs.

Animals↗
PubMed1990

The therapeutic effect of OK-432-combined adoptive immunotherapy against liver metastases from breast cancer.

We studied the therapeutic effect of OK-432 combined with adoptive immunotherapy in 19 cases of liver metastases from breast cancer. Of the 14 patients who received intraarterial OK-432 injection and transfer of cultured lymphocytes, 9 responded to this therapy, whereas no patients responded to intravenous administration. The minimum cell number for a therapeutic response was 8 x 10(8) cells. Metastatic lesions other than those in the liver regressed after therapy in 4 patients. The serum carcinoembryonic antigen level paralleled the therapeutic effect. There were no severe side-effects accompanying this therapy. These results indicate that intraarterial adoptive immunotherapy combined with OK-432 is effective as a new therapeutic approach against liver metastases from breast cancer.

Adult↗
PubMed1990

Nicorandil increases coronary blood flow predominantly by K-channel opening mechanism.

Nicorandil has a hybrid property between nitrates and potassium (K)-channel openers. In order to clarify which mechanism of action is responsible for its effect in increasing coronary blood flow, we investigated how this effect was antagonized by glibenclamide, which was recently found to behave as a pharmacologic antagonist of K-channel openers. Cromakalim, one of the most specific K-channel openers currently available, and nitroglycerin were used as reference drugs. In isolated, blood-perfused papillary muscle preparations of dogs, intraarterial injections of nicorandil and cromakalim increased (coronary) blood flow, and at high doses a negative inotropic effect and ventricular fibrillation occurred. Dose-response curves for the increase in coronary blood flow produced by nicorandil or cromakalim were shifted to the right in a parallel manner and to similar extents by glibenclamide given intravenously to support dogs. Schild analysis yielded pA2 values of 6.08 and 6.34 for glibenclamide versus nicorandil and cromakalim, respectively. Nitroglycerin injected intraarterially produced only an increase in coronary blood flow. This effect was not affected by glibenclamide. These results indicate that the effect of nicorandil in increasing coronary blood flow, like that of cromakalim, is predominantly due to its mechanism of action as a K-channel opener. The negative inotropy and ventricular fibrillation seen with high doses of nicroandil and cromakalim were also antagonized by glibenclamide, indicating that these effects are also due to K-channel opening.

Adenosine Triphosphate↗
PubMed1990

Cardiac versus coronary dilator effects of SD-3211, a new nondihydropyridine calcium antagonist, in isolated, blood-perfused dog hearts.

Coronary and cardiac effects of SD-3211 were compared in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. SD-3211 was administered intraarterially. In all preparations SD-3211 produced an increase in coronary blood flow. In SA node preparations, the drug produced a decrease in sinus rate, and in high doses atrial standstill occurred. The dose that produced a 15% decrease in sinus rate was about 5.6 times the dose that doubled coronary blood flow. In AV node preparations, when injected into the artery supplying the AV node, the drug produced an increase in AV conduction time, and in high doses second- or third-degree AV block occurred. The dose that produced a 15% increase in AV conduction time was about 1.6 times the dose that doubled coronary blood flow. In the same preparations the drug slightly increased AV conduction time only at high doses when injected into the artery supplying the His-Purkinje-ventricular system. In paced papillary muscle preparations, the drug produced a decrease in the force of contraction. The dose that produced a 50% decrease in the force of contraction of the paced papillary muscle was about 50 times the dose that doubled coronary blood flow. The drug was virtually ineffective on ventricular automaticity. In short, in doses that doubled coronary blood flow, SD-3211 depressed only AV nodal conduction. This cardiovascular profile differs from those of diltiazem and verapamil, which do not discriminate between coronary vasculature and the SA and the AV node.

Animals↗
PubMed1990

Activity of platelet-activating factor (PAF) acetylhydrolase in plasma from healthy habitual cigarette smokers.

The activity of platelet-activating factor acetylhydrolase, a specific metabolizing enzyme of platelet-activating factor (PAF), in plasma of 39 male subjects was determined radiochemically by the method of Stafforini et al., (1987) J Biol Chem 262: 4223-4230, to clarify to what extent PAF affects atherosclerotic disorders induced by habitual smoking. The subjects examined included 18 habitual smokers (mean age: 62 +/- 10.6 years) and 21 age-matched nonsmokers. Plasma PAF acetylhydrolase activity was higher in the smokers than in the nonsmokers. There was no difference between smokers and nonsmokers in platelet aggregability in response to PAF or ADP. A higher apoprotein B/apoprotein A-I ratio in smokers as compared to nonsmokers was the only manifestation of abnormal lipoprotein metabolism in the former group. In the smokers, plasma PAF acetylhydrolase activity was directly proportional to total cholesterol, LDL-cholesterol, triglyceride, apoprotein B, LDL-cholesterol/HDL-cholesterol or apoprotein B/apoprotein A-I, and inversely proportional to HDL-cholesterol or apoprotein A-I. The results obtained suggest that alterations in PAF acetylhydrolase levels result from a slightly abnormal lipoprotein metabolism. Determination of plasma PAF acetylhydrolase activity is useful to study the role of PAF in atherosclerotic changes induced by smoking.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1990

Comparison between crude interleukin-2 and recombinant interleukin-2 in maintaining killing activity of cultured lymphocytes.

Peripheral blood lymphocytes, regional lymph node lymphocytes or malignant effusion lymphocytes from cancer patients were incubated with crude IL-2 (cIL-2) for 13 days. These effectors, which frequently expressed IL-2 receptor (IL-2R), proliferated well and possessed augmented killing activity against fresh autologous tumor cells and K562. However, when recombinant IL-2 (rIL-2) was added for the last 4 days of culture instead of cIL-2, IL-2R expression and killing activity against fresh autologous tumor cells decreased significantly (P less than 0.05). Phenotypic analysis indicated that cIL-2 significantly promoted the expansion of the cytotoxic population (CD8+.11b-)(P less than 0.05). The decreases in killing activity and IL-2R expression were restored by 0.004% PHA plus rIL-2, but not in the presence of rIFN-gamma, rIL-1 alpha, rIL-1 beta, rIL-4 or rIL-6. PHA-free cIL-2 maintained killing activity, but not IL-2R expression. We conclude that some factors in cIL-2 and a low dose of PHA-P are necessary for the maintenance of killing activity and IL-2R expression of cultured lymphocytes in the late phase of culture.

Cell Division↗
PubMed1990

A case of rectal carcinoid with extensive sacral breakage.

A 48 year old woman with a massive retrorectal tumor extensively invading the sacrum is presented herein. A submucosal tumor, apparently of rectal origin, was found on the posterior rectal wall infiltrating posteriorly into the sacrum. Abdominosacral resection of the rectum with partial sacrectomy was thus performed and postoperative examination revealed the tumor to be carcinoid which has hitherto been associated with moderately benign behavior. Although remote metastasis was absent, extensive lymph node metastasis was observed, however, 2 years have passed since the operation without any evidence of recurrence.

Bone Neoplasms↗
PubMed1990

Studies of hexokinase activity in human and mouse oocyte.

Microdetermination methods were used to determine the activities of hexokinase in human and mouse oocytes, human spermatozoa, and other somatic cells. Human oocytes with intact germinal vesicle obtained from the growing follicle were freeze dried and weighed (mean +/- SD = 243 +/- 34 ng dry weight). Hexokinase activity in single oocytes was 17.9 +/- 3.6 pmol of reduced nicotinamide-adenine dinucleotide phosphate formed/oocyte/hr at 20 degrees C. Specific activity was estimated to be 104 +/- 30 nmol/mg protein/hr, which was remarkably lower than that in human spermatozoa (3570 +/- 550 nmol/mg protein/hr) and other somatic cells such as endometrium, brain, liver, and kidney. Mouse follicular oocytes and early embryos before the two-cell stage also had low hexokinase activities, but morulae and blastocysts had increasingly high activities; the former cannot use glucose as an energy source, whereas the latter can. These results suggest that human immature oocytes, as well as mouse oocytes, depend on pyruvate instead of glucose as a major energy source.

Adult↗
PubMed1990

DNA cleavage by phenylhydroquinone: the major metabolite of a fungicide o-phenylphenol.

The interaction of o-phenylphenol (OPP) and its metabolites with DNA was examined. As a model system, the reactivities of OPP and its metabolites with DNA were studied by using pUC18 DNA. The major metabolite formed in vitro from OPP by mixed function oxidase was phenylhydroquinone (PHQ). This result corresponds to the findings that PHQ in the form of glucuronide conjugate was the main product detected in bladder of OPP fed rats in vivo. When supercoiled pUC18 DNA (form I) was incubated with PHQ at concentrations from 1 X 10(-6) M to 2 X 10(-1) M, DNA strand scission by PHQ was observed at a concentration as low as 1 X 10(-5) M and the amount of linear form (form III) increased with increasing PHQ concentration. PHQ causes DNA strand scission. The DNA cleavage by OPP and phenyl-p-benzoquinone (PBQ) was barely detectable. The DNA cleavage by PHQ was inhibited by superoxide dismutase (SOD), catalase and several oxygen radical scavengers such as polyethylene glycol, tert-butanol, dimethyl sulfoxide, sodium azide, sodium benzoate, bovine serum albumin and methionine. The production of superoxide radical from PHQ was confirmed by cytochrome c reduction assay. These results indicate that the oxygen radicals such as superoxide, hydroxyl radicals and some others generated in the process of oxidation of PHQ in aqueous solution are responsible for the DNA cleavage. In order to identify the sites of cleavage of DNA by PHQ, a 5'-end 32P-labeled 206 base-pair EcoRI-BglI fragment of pUC18 DNA was incubated with PHQ. The DNA was then analyzed by sequencing gel electrophoresis followed by autoradiography. When the DNA was incubated with PHQ and further treated with piperidine, cleavage was detected relatively more frequently at guanine residues. The attack seemed to occur at guanine residues in general, but was not restricted to guanines with specific residues in the vicinity.

Animals↗
PubMed1990

Calcium-induced aggregation of the urea-deaggregated human lens insoluble protein.

Calcium-induced aggregation of the urea-deaggregated insoluble protein (US-fraction) derived from human lens was investigated by use of a simple light scattering method. The initial rate of aggregation was shown to increase with progress of senescence of the lens, and to be much higher in the nucleus as compared to the cortex. The aggregation was found to be more active in the US-fraction from cataractous lens than in that of normal lens at same age. A calcium sensitive polypeptide (CSP) was isolated from the US-fraction from cataractous human lenses by gel filtration followed by DEAE-cellulose column chromatography in the presence of 7 M urea. The molecular size of the CSP in the dissociated state was assessed to be 4.2 kDa by urea-SDS-PAGE, and the size in the associated state to be 450 kDa by thin layer gel filtration. With addition of calcium ion to the latter, it aggregates rapidly to form much larger aggregates and eventually precipitates out. The aggregation rate of the CSP is shown to increase exponentially with an increase in the concentration of both CSP and calcium ion, indicating the involvement of complicated mechanisms in the aggregation process. Effects of divalent ions other than calcium ion on the aggregation process were also examined. It is revealed that the effect of manganese ion is little less than that of calcium ion, whereas magnesium and strontium ions are much less effective as compared to the former two ions.

Calcium Chloride↗
PubMed1990

An inhibitor of prostaglandin biosynthesis from human decidua: partial purification and properties.

An inhibitor of prostaglandin synthetase which catalyzes the conversion of arachidonic acid into prostaglandin E2 was partially purified from the 105,000 x g supernatant fraction of the human decidual cell homogenate. By means of ammonium sulfate fractionation, Mono Q ion-exchange chromatography, and gel filtration chromatography, the inhibitor was purified about 15-fold, giving a preparation with a molecular weight of 55-60 KDa. The 50% inhibitory concentration of the purified substance was approximately 0.2 mg/ml. The inhibitor may play a role in suppression of prostaglandin production by decidua in early pregnancy.

Animals↗
PubMed1990

The role of the left ventricle in atrial natriuretic peptide secretion in acute mitral regurgitation.

To examine the role of the ventricle in ANP secretion, the atrial natriuretic peptide (ANP) concentration in the plasma, left atrial tissue and left ventricular tissue were observed in a canine during the course of experimental reversible mitral regurgitation (MR). For reversible MR, a basket catheter was inserted into the left atrium via the pulmonary vein and fixed at the mitral valve. The regurgitation arose when the tip basket wire was extended and disappeared immediately when it was closed. Left atrial pressure (LAP), right atrial pressure (RAP) and pulmonary artery pressure (PAP) increased significantly during MR, and decreased to the normal level after recovery from MR. Plasma ANP concentration showed a reversible change in correlation with LAP and RAP in each canine studied. The ANP level in the atrial and ventricular tissue decreased during MR, and the low levels were maintained after recovery from MR. Both the left arterial and left ventricular tissue ANP levels showed the same changes in acute MR. Therefore, it was suggested that normal ventricles might play a role in ANP secretion in acute MR.

Animals↗
PubMed1990

Heel and foot reconstruction using reverse-flow posterior tibial flap.

Island flaps supplied by the intermuscular cutaneous perforator (IMCP) from a deep vessel, such as the peroneal flap pedicled by IMCP from the peroneal vessel or the anterior tibial flap supplied by IMCP from the anterior tibial vessel, are reported to be useful in reconstructive procedures for soft-tissue defects of the lower leg. However, the posterior tibial flap, pedicled by IMCP from the posterior tibial vessel, has not yet been fully described. The posterior tibial flap can be used either as a normal-flow or as a reverse-flow flap. It is particularly versatile as a reverse-flow flap for reconstruction of soft-tissue defects of the heel and foot. Three reverse-flow posterior tibial flaps were clinically applied, without venous anastomosis, to reconstruct heel and foot defects, and all three survived completely. The operative procedure and its characteristics are described.

Aged↗
PubMed1990

Suprapopliteal flap.

To investigate the cutaneous artery in the popliteal region, cadaver dissections were performed on 16 lower limbs. Two types of the cutaneous vessel have been found. One is the direct cutaneous vessel from the popliteal vessels; the other is the cutaneous vessel branching from the muscular vessel to the semimembranous muscle from the popliteal vessels. In our cadaver dissections, the latter was found consistently in the 16 lower limbs. The location of the vascular pedicle is 12.5 to 24.0 cm from the tibial condyle. The newly developed suprapopliteal flap supplied by this vessel is described. We applied this flap in four clinical patients: in one as a free flap, in the others as an island flap. Three (one free, two pedicled) flaps survived completely. The upper part of a pedicled flap partially necrosed. The operative procedure and the characteristics of the suprapopliteal flap are discussed. This flap can be used as a free flap and is also a versatile way to reconstruct soft tissue defects around the knee joint.

Adult↗
PubMed1990

Effects of recombinant human erythropoietin on anaemic W/Wv and Sl/Sld mice.

The effects of recombinant human erythropoietin (rHuEPO) on anaemic W/Wv and Sl/Sld mice were investigated. rHuEPO was injected every day for a week in doses up to 86,000 iu/kg. Wv/+ and Sld+ mice, which have genetically a weak anaemia, received 17 or 86 iu/kg of rHuEPO and showed dose-dependent increases in haemoglobin, PCV, RBC and reticulocytes to the same extent as that in normal mice. W/Wv mice also showed increases in the haematological parameters in response to 8600 iu/kg of rHuEPO but the dose was much higher than that for normal mice. A reticulocyte increase in W/Wv mice appeared later than in normal mice and was not sustained for 2 weeks even though the rHuEPO treatment was continued. Sl/Sld mice, however, did not show any significant haematological effect from doses up to 86,000 iu/kg. In both W/Wv and Sl/Sld mice receiving 8600 and 86,000 iu/kg of rHuEPO, respectively, an increase in splenic or bone marrow CFU-E was observed regardless of the defect in their haemopoietic systems. The plasma erythropoietin (EPO) level in W/Wv and Sl/Sld mice was inversely correlated with the haemoglobin, indicating that EPO production was not influenced by the haemopoietic defect and was regulated by the hypoxic properties of the anaemia. These results indicate that a large dose of exogenous rHuEPO is effective for the anaemia in W/Wv mice caused by a stem cell defect but not for the anaemia in Sl/Sld mice caused by a defective microenvironment.

Anemia, Macrocytic↗