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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 1,063 records · Page 59Linked to original sources
PubMed1985

Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis.

A polypeptide of Mr 26,000 and pI 6.7 that was markedly increased in rat livers bearing hyperplastic nodules (HNs) induced by chemical carcinogens was identified immunochemically as the subunit of neutral glutathione (GSH) transferase (GSHTase; RX:glutathione R-transferase, EC 2.5.1.18; also called GSH S-transferase) purified from placenta (GSHTase-P) and was demonstrated immunohistochemically to be localized in preneoplastic foci and HNs. In the present study, GSHTase-P has been purified from the HN-bearing liver, and the distribution and inducibility have been examined quantitatively using anti-GSHTase-P antibody. Elevation of GSHTase-P in the HN-bearing livers was also confirmed by in vitro translation of mRNAs isolated from the HN-bearing livers. The purified GSHTase-P was homogeneous in size but had two charge isomers on two-dimensional gel electrophoresis. In normal tissues, including liver, placenta, and fetal liver, the protein content of GSHTase-P was generally low but was significantly high in kidney and pancreas. In contrast, the amount of GSHTase-P in HN-bearing livers (primary hepatomas) and transplantable Morris hepatoma 5123D were several 10-fold higher than that in normal liver but were undetectably low in transplantable Yoshida ascites hepatoma AH 130. Different from ordinary drug-metabolizing enzymes, GSHTase-P was uninducible by administration of drugs and carcinogens prior to appearance of the preneoplastic foci and HNs. In addition, species specificity of GSHTase-P was low as it was crossreactive among rat, hamster, and human.

Amino Acids↗
PubMed1985

Relative merits of immunohistochemical demonstrations of placental, A, B and C forms of glutathione S-transferase and histochemical demonstration of gamma-glutamyl transferase as markers of altered foci during liver carcinogenesis in rats.

The values of the immunohistochemical demonstrations of glutathione S-transferases (GSTs) A, B, C and P and histochemical demonstrations of gamma-glutamyl transpeptidase (gamma-GT) for detection of enzyme altered foci in F344 rat liver were compared. Rats were given a single i.p. injection of 200 mg/kg body weight of diethylnitrosamine (DENA), from 2 weeks later they were given 0.02% N-2-fluorenylacetamide (2-FAA), phenobarbital (PB), butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) in their diet for 6 weeks and then they were given basal diet and tap water for 4 weeks. They were subjected to partial hepatectomy at the end of week 3. Results showed that immunohistochemical demonstration of GSTs A, B and C for detection of foci were only effective when the administration of 2-FAA, PB, BHA or BHT in the diet was discontinued, because these GSTs were induced in surrounding hepatocytes by these compounds in the diet. gamma-GT was induced in periportal hepatocytes strongly by BHA and BHT and slightly by PB, and gamma-GT positive foci in periportal areas were not distinguishable from gamma-GT positive periportal hepatocytes. GST-P was also induced moderately by BHA and slightly by BHT in periportal hepatocytes, but all GST-P positive foci were clearly distinguishable. In addition, almost all gamma-GT positive foci gave a positive reaction for GST-P, but 5-10% of the GST-P positive foci were not gamma-GT positive.

Animals↗
PubMed1985

Bay K 8644, a dihydropyridine calcium agonist, augments vasoconstrictor responses to endogenous and exogenous noradrenaline in the peripheral vasculature of the dog.

The effect of Bay K 8644 (a substance known to increase calcium influx through the voltage-dependent calcium channel) on vasoconstrictor responses of resistance vessels to endogenous and exogenous noradrenaline (NA) was investigated in pentobarbitone-anaesthetized dogs which had also undergone spinal anaesthesia and bilateral vagotomy and received atropine. In these dogs the saphenous arterial bed was perfused at fixed flow rates with autologous blood to give perfusion pressure close to the systemic blood pressure. Electrical stimulation (3-30 Hz) of the saphenous nerve and single intra-arterial (i.a.) injections of noradrenaline (NA, 0.03-3 micrograms) produced an increase in perfusion pressure (vasoconstriction) in a frequency- and a dose-dependent manner, respectively. Intra-arterial infusions of Bay K 8644 (3 and 10 micrograms min-1) per se produced no significant change in perfusion pressure. However, these infusions augmented vasoconstrictor responses to both saphenous nerve stimulation (endogenous NA) and i.a. NA (exogenous NA). These results suggest that augmentation by Bay K 8644 of vasoconstrictor responses of resistance vessels to endogenous and exogenous NA is probably due to promotion of the calcium influx through calcium channels closely associated with alpha-adrenoceptors in smooth muscle cells there.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate.

Cultured human endothelial cells synthesize prostacyclin (PGI2), a potent inhibitor of platelet function, when stimulated with histamine, bradykinin, or ATP. Paradoxically, we report that these agonists also induced the rapid and sustained synthesis of platelet-activating factor (PAF) by endothelial cells. In fact, the synthesis of this potent activator of platelets and neutrophils was induced by stimulation of the same receptor subtype that induced PGI2 synthesis: stimulation of a histamine H1 or a bradykinin B2 receptor induced both PAF and PGI2 synthesis. However, two physiologically important differences exist between the production of PAF and PGI2 by endothelial cells. The synthesis of PGI2 proceeded for only 7.5 min before the abrupt termination of synthesis, whereas the synthesis of PAF was clearly detectable even 45 min after stimulation. Although maximal accumulation of PAF occurred after 10-15 min of stimulation, the prolonged synthesis resulted in the presence of PAF for up to 1 h after stimulation. Secondly, whereas PGI2 was released from the cell monolayer, PAF remained cell-associated without significant release to the external medium. Endothelial cell-generated PAF, therefore, does not function as a hormone. The prolonged association of this potent activator of platelets and neutrophils with endothelial cells may mediate some of the inflammatory properties of histamine and bradykinin. It may also be a factor in the formation of a thrombogenic vascular surface, an event suggested to play a primary role in the pathogenesis of thrombosis and atherosclerosis.

Adenosine Triphosphate↗
PubMed1985

Temporary increase in the circulating prolactin levels during and after consecutive administration of bromocriptine-mesilate (CB-154) in female mice.

Changes in circulating prolactin (Prl) levels during and after consecutive administration of bromocriptine-mesilate (CB-154; 0.2 mg/day), a potent suppressor of pituitary Prl secretion, were studied in virgin mice of SHN and BALB/c strains. Plasma Prl levels were lower in CB-154-treated SHN mice than in vehicle-treated controls until the first week of the daily treatment. However, the circulating Prl increased in the experimental mice and surpassed the control levels thereafter. The elevated levels of Prl were maintained throughout the treatment, then they decreased to control levels 1 month after the termination of the treatment. In BALB/c mice given CB-154, the pattern of changes of the circulating Prl levels was almost the same seen in SHN mice; a significant suppression of the Prl levels was observed on the 2nd day of the treatment and the levels increased and reached to the control levels thereafter. The results have demonstrated that in mice the inhibition of pituitary Prl secretion by CB-154 did not persist throughout the period of consecutive administration.

Adrenal Glands↗
PubMed1985

Amelioration of heart failure by MDL 17043 and MDL 19205, novel positive inotropic drugs, in dog heart-lung preparations.

The efficacies of MDL 17043 and MDL 19205 in ameliorating heart failure were assessed in dog heart-lung preparations in which cardiac function had been severely depressed by pentobarbital. Six preparations were used for each drug. Both drugs in doses of 1-30 mumol similarly improved cardiac function in a dose-dependent manner and at 30 mumol improved it beyond control values. AV conduction impaired by pentobarbital was restored by 30 mumol of the 2 drugs. In these doses, however, neither of the drugs produced a significant increase in heart rate or arrhythmias. These results indicate that the 2 drugs would be of use in the treatment of heart failure.

Animals↗
PubMed1985

Abolition of spontaneous rhythmic contractions of isolated monkey coronary arteries by diltiazem, nifedipine, verapamil and nicorandil but not by nitroglycerin.

Three of 12 coronary artery rings obtained from one of 9 rhesus monkeys (Macaca mulatta) (113 rings in all) and 4 of 12 coronary artery rings obtained from one of 2 patas monkeys (Erythrocebus patas patas) (28 rings in all) developed spontaneous rhythmic contractions. In 5 of these 7 coronary artery rings, rhythmic contractions occurred long enough to be subjected to examinations of drug effects. In these preparations the effects of the calcium entry blockers, diltiazem, nifedipine and verapamil, and nicorandil, a nitrate vasodilator thought to produce vasodilatation by an increase in membrane potassium permeability, and nitroglycerin were investigated on rhythmic contractions. Diltiazem (10(-7) and 10(-6) M), nifedipine (10(-8) and 10(-7) M), verapamil (10(-7) and 10(-6) M) and nicorandil (10(-5) and 10(-4) M) suppressed rhythmic contractions in a concentration-dependent manner, but nitroglycerin (10(-7)-10(-5) M) was entirely ineffective. The results were discussed in relation to the mechanisms underlying spontaneous rhythmic contractions of coronary arteries and their role in vasospastic angina pectoris.

Animals↗
PubMed1985

Is antagonism by Bay k 8644 of the negative dromotropic effect of nifedipine pharmacological?

The dromotropic effect of Bay k 8644 and its interaction with the negative dromotropic effects of nifedipine, verapamil, MnCl2 and tetrodotoxin were investigated by use of isolated, blood-perfused atrioventricular (AV) node preparations of dogs. These agents were injected into the AV node artery. Single injections of Bay k 8644 (0.1-10 micrograms) shortened AV conduction time, but the decrease remained only about 9 msec at 10 micrograms. This effect was not modified by nadolol. Dose-response curves for the negative dromotropic effect of nifedipine were shifted to the right by about 0.5 log units with infusions of Bay k 8644 into the AV node artery at rates of 3 and 10 micrograms/min. A similar shift of dose-response curves to verapamil occurred at 10 micrograms/min of Bay k 8644. However, Bay k 8644 (3 and 10 micrograms/min) failed to modify dose-response curves to MnCl2 and tetrodotoxin. Bay k 8644 (10 micrograms) produced a greater decrease in AV conduction time during the negative dromotropic effect of verapamil (10 or 30 micrograms) and a far greater decrease during the negative dromotropic effect of nifedipine (3 or 10 micrograms) than under control conditions. In contrast, Bay k 8644 (10 micrograms) produced a decrease in AV conduction time nearly to the same extent during the negative dromotropic effect of MnCl2 (10 or 30 mumol) or tetrodotoxin (10 or 30 micrograms) as under control conditions. From these results Bay k 8644 can be described as a rather specific pharmacological antagonist for dihydropyridine slow channel blockers.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Undifferentiated effects of calcium antagonists on pressor responses to selective alpha-1 and alpha-2 adrenoceptor agonists in anesthetized, spinal dogs.

Whether pressor responses mediated by alpha-2 adrenoceptors are more susceptible to calcium antagonists than those mediated by alpha-1 adrenoceptors was investigated in anesthetized, spinal dogs. All drugs were administered i.v. Methoxamine (3-100 mu/kg) or xylazine (3-300 micrograms/kg) produced a sustained increase in mean arterial pressure but almost no effect on heart rate. Both the initial and the sustained phase of the pressor response to methoxamine were selectively antagonized by prazosin, whereas those to xylazine were selectively antagonized by yohimbine. These results indicate that the peripheral arterial bed of the dog comprises alpha-1 and alpha-2 adrenoceptors and that both the initial and sustained phases of the pressor response to methoxamine are predominantly mediated by alpha-1 adrenoceptors, whereas those to xylazine are mediated by alpha-2 adrenoceptors. The calcium antagonists, i.e., nifedipine (0.3-3 micrograms/kg), diltiazem (10-100 micrograms/kg) and KB-944 (10-100 micrograms/kg), administered during the sustained phase of the pressor responses to equieffective doses of methoxamine (100 micrograms/kg) and xylazine (1000 micrograms/kg), lowered mean arterial pressure. The three calcium antagonists in these doses also lowered the baseline mean arterial pressure but to a lesser extent than the elevated one. These results altogether indicate that the calcium antagonists were more effective in lowering mean arterial pressure elevated by either an alpha-1 or alpha-2 adrenoceptor agonist than the base-line mean arterial pressure and that the sustained phase of the pressor response mediated by alpha-1 adrenoceptors would involve Ca++ influx as much as or more than those mediated by alpha-2 adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1985

Comparison of the various forms of glutathione S-transferase with glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase as markers of preneoplastic and neoplastic lesions in rat kidney induced by N-ethyl-N-hydroxyethylnitrosamine.

Alterations in gamma-glutamyl transpeptidase (gamma-GT) and alkaline phosphatase (ALP) activities and binding of specific antibodies to glucose-6-phosphate dehydrogenase (G6PDH), gamma-GT and the A, B, C, D, and P forms of glutathione S-transferase (GST-A, -B, -C, -D, and -P, respectively) in preneoplastic and neoplastic lesions induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the rat kidney were investigated. Morphologically the lesions were of basophilic type and were classified either as altered tubules or adenomas, the latter being further subdivided into microadenomas and adenomas depending on size and the presence of compression. The fact that all lesions demonstrated only weak (or negative) gamma-GT, ALP and GST-B stainings, all of which are normally evident in proximal tubules, and also the occasional finding of cells bearing a periodic acid-Schiff-positive apical brush border within altered tubules strongly positive for GST-A, indicated their histogenesis from the proximal segment of the nephron. Thus a directed shift to a phenotype opposite to that observed in the cells of origin was demonstrated. Comparison of phenotype within the range of EHEN-induced lesions strongly suggested putative preneoplastic character for the altered tubules. Transition to adenomas appeared to be correlated with progressive loss of GST-A and moderate to slight increase of G6PDH.

Adenoma↗
PubMed1985

[Flow cytometric study on the action of progestogen in patients with adenocarcinoma and precancerous lesions of the endometrium].

Synthetic progestogens have been used in 21 patients with endometrial adenocarcinoma and 6 patients with precancerous lesions. During a program of management with medroxyprogesterone acetate (MPA) in an attempt to identify the mechanism by which a remission rate in 30-40% occurred, adenocarcinoma cells were analysed. Histopathologic reactions of endometrial adenocarcinoma treated with MPA 400mg/day through 7 days have been found similar those of normal secretory endometrium such as subnuclear vacuolation, loss of mitotic figure, diminished nuclear size and stromal decidual reaction and regressive changes are highly dose dependent. In detailed analysis of the cell cycle, computerized flow cytometry was employed to quantitate total DNA content following propidium iodide fluorescent staining after RNase treatment. Possible modes of action of MPA on endometrial adenocarcinoma are an increase in the G0+1 fraction corresponding to ploidy reduction. Adenomatous hyperplastic lesions were able to be reversed completely in all patients compared with adenocarcinoma in sixty-six percent.

Adenocarcinoma↗
PubMed1985

[Study on the drug sensitivity of multiple drug-resistant Staphylococcus aureus].

Of clinically isolated Staphylococcus aureus showing resistance to multiple drugs among penicillins (PCs), cephem antibiotics (CEPs), aminoglycosides (AGs), minocycline (MINO) and fosfomycin (FOM), 64 strains were selected for the determination of MIC. Twenty-one drugs were used for the determination of MIC, with ampicillin (ABPC), cloxacillin (MCIPC), cephalothin (CET), cefazolin (CEZ), cefotiam (CTM), cefuroxime (CXM), cefamandole (CMD), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX), cefmetazole (CMZ), cefoxitin (CFX), latamoxef (LMOX), cefotetan (CTT), cefoperazone (CPZ), gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), MINO, and FOM. MIC80 of each drug at 10(6) CFU/ml were: ABPC, MCIPC, CEZ, CTM, CXM, CTX, CZX, CMX, CFX, LMOX, CTT, CPZ, GM, DKB and TOB greater than 100 micrograms/ml; CET 50 micrograms/ml; CMD and AMK 25 micrograms/ml; CMZ 12.5 micrograms/ml; FOM 6.25 micrograms/ml; and MINO 0.78 micrograms/ml. The ratio of highly resistant strains with MIC greater than 100 micrograms/ml at 10(6) CFU/ml varied according to drug, and a difference tended to be seen in the degree of influence by resistant factors reflected upon MIC, e.g. drugs for which a high resistance of more than 50% was confirmed were ABPC, CXM, CZX, LMOX and TOB, and 20 approximately 30% MCIPC, CTM, CTX, CMX and CFX. MIC on MCIPC which has a correlation of structural activity with methicillin correlated with cephems (CEPs) resistance to a high degree, but many of the so-called new CEPs showed resistance even to the strains with a low MIC on MCIPC. It was assumed that CEPs resistant strains have multiple drug resistant factors based on the fact that such strains showed multiple drug resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoglycosides↗