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Biomedical subjects

Y Fukushi

Publications and source records attributed to Y Fukushi.

At least 91 records · Page 5Linked to original sources
PubMed1986

Inhibitory effect of trimetazidine on utilization of myocardial glycogen during coronary ligation in dogs.

The left anterior descending coronary artery (LAD) of the dog was ligated completely for 1.5 min, and immediately after LAD ligation the heart was taken for determination of the glycogen phosphorylase and glycogen. Trimetazidine was injected intravenously 20 min before LAD ligation. LAD ligation increased the activity of glycogen phosphorylase and decreased the level of glycogen in both ischemic (LAD) and nonischemic (circumflex) areas. Trimetazidine at the dose of 0.3 or 1.0 mg/kg, being the dose that did not affect blood pressure and heart rate markedly, inhibited the ischemia-induced changes in glycogen phosphorylase and glycogen level. It is concluded that trimetazidine inhibits the ischemia-induced increase in the utilization of glycogen in the dog myocardium.

Animals↗
PubMed1986

Evidence for suppression of potassium conductance by noradrenaline in smooth muscle of guinea-pig vas deferens.

The ionic dependency was examined in the reversal potential of the NA-induced membrane depolarization of smooth muscle of the guinea-pig vas deferens, using the double sucrose-gap method. In the control (5.9 mM K) solution and solutions containing 20 and 60 mM K ions, replaced with equimolar amount of Na ions, the reversal potential was negative to the membrane potential at the steady state in each solution, by 19.5, 15.1 and 13.2 mV, respectively. Taking account that the higher external K concentration causes the larger membrane depolarization, these results indicate that the reversal potential shifted toward the positive direction as the external K concentration was increased. On the other hand, the calculated equilibrium potential of K ions in those solutions is -88, -52 and -24 mV, respectively. In those solutions, furthermore, the equilibrium potential of Na ions is 42, 38 and 29 mV, respectively. However, the equilibrium potentials of Ca and Cl ions should be unchanged. Therefore, it is suggested that the reversal potential of the NA-induced depolarization varied in the given different solutions compatibly only with the change in the K equilibrium potential. This provides evidence that in this tissue, NA induces a reduction in the K conductance of the cell membrane.

Animals↗
PubMed1986

Possible relationship between the release of calcium ions and inactivation of the potassium conductance induced by noradrenaline in smooth muscle of the guinea-pig vas deferens.

In order to examine whether any change in cytoplasmic Ca2+ concentration occurs during the noradrenaline (NA)-induced change in the membrane potential, the isometric tension of smooth muscle of the guinea-pig vas deferens was recorded together with membrane potentials using the sucrose-gap method. NA induced a depolarization and an increase in cytoplasmic Ca2+ comprising two (initial and second) phases. In time courses, the depolarization and the second phase of the increase in cytoplasmic Ca2+ were similar. Only at the phase around the onset of the depolarization, the membrane conductance was increased but then, it was decreased. Lowering the external Ca2+ concentration and application of D600 suppressed all of the NA-induced responses. In addition, D600 diminished the size of the NA-induced decrement in the membrane conductance. The present results suggest that the initial phase of the increase in the cytoplasmic Ca2+ is due to the influx of Ca2+ and the second phase, probably to the release of Ca2+ from some intracellular stores. It was discussed that the release of Ca2+ might occur at the internal surface of the membrane, and the membrane might be left less permeable to K+ as a result.

Animals↗
PubMed1986

Izupeptins A and B, new glycopeptide antibiotics produced by an actinomycete.

In the course of screening for new high molecular weight peptidoglycan synthesis inhibitors, izupeptins A and B, antibiotics active against Gram-positive bacteria including methicillin-resistant Staphylococci and Clostridium were discovered. The antibiotics were found to be new members of the glycopeptide antibiotic family, namely of the vancomycin type, based on chemical and spectroscopic data. The molecular weight of izupeptin A was determined to be 1,475 by SI (secondary ion)-MS (integer molecular weight, 1,473), and it contains two chlorine atoms.

Actinomycetales↗
PubMed1986

[Cancer-associated mucin detected by monoclonal anti-carbohydrate antibodies].

SSEA-1 antigen (stage-specific embryonic antigen-1) has been shown to be a series of carbohydrate antigens having type-2 chain and X-hapten structures. These carbohydrate antigens are remarkably accumulated in various human cancer tissues, and activity secreted into the blood stream. Frequently SSEA-1 antigens are further modified with fucoses or sialic acid in human cancer tissues, thus forming various subgroups of antigens such as fucosyl SSEA-1, sialyl SSEA-1 or polyfucosylated antigens. Many monoclonal antibodies are established which can discriminate each subgroup of antigens. Assay systems for these antigens in the sera of cancer patients have been developed using these monoclonal antibodies. Sialyl SSEA-1 is especially elevated in the sera of patients with adenocarcinoma of the lung. The antigens detected with these monoclonal antibodies are mucin-like glycoproteins(cancer-associated mucin, CAM). Various types of cancer-associated mucins can be characterized by respective monoclonal antibodies. It is therefore possible to classify cancer-associated mucins according to the structure of their carbohydrate side chains using these monoclonal antibodies.

Adenocarcinoma↗
PubMed1986

Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing fucosyl or sialyl-fucosyl type 2 chain polylactosamine.

The quantity of tumor-associated antigens carrying type 2 chain polylactosamines with four types of fucosyl determinants, LeX (X-hapten), poly-LeX, sialyl LeX, and LeY (Y-hapten), present in sera of patients with various malignant and non-malignant disorders, as well as the qualitative chemical properties of the carrier molecules in sera, have been investigated using four monoclonal antibodies, each of which defines one of these determinants. The following findings are of particular importance: the serum levels of LeX defined by antibody FH2 and poly-LeX defined by ACFH18 in patients with cancer were occasionally high (incidence about 10%); however, the majority of patients did not show elevated levels; the serum level of the antigen, defined by monoclonal antibody FH6 (termed sialyl LeX-i since this determinant is carried by i antigen), was significantly high in patients with cancers originating from organs from which adenocarcinomas often develop. For example, among various types of lung cancer, only adenocarcinoma but not squamous cell carcinoma, small cell carcinoma, or large cell carcinoma showed a high level of sialyl LeX-i antigen in sera. The incidence of high antigen levels in sera of patients with adenocarcinomas of lung was as high as 76% of the observed cases; the serum level of Ley (Y-hapten) was frequently high in patients with hepatoma (incidence, 34%); sialyl LeX-i antigen was separated on gel filtration as a glycoprotein with an average molecular weight greater than 10(6). It was characterized by its susceptibility to basehydrolysis, Pronase digestion, and sialidase and endo-beta-galactosidase treatment and is assumed to be a high molecular weight mucin-type glycoprotein; sialyl LeX-i antigen expressed in sera of patients with cancer was soluble in perchloric acid, while the same antigen in sera of patients with noncancerous diseases and normal subjects was mostly insoluble in perchloric acid. LeX, a poly-LeX, and essentially all LeY antigens in sera of patients with cancer were perchloric acid-insoluble.

Antibodies, Monoclonal↗
PubMed1986

Lewisx- and sialylated Lewisx-related antigen expression in human malignant and nonmalignant colonic tissues.

Biochemical studies have revealed that some normal cells express the LeX trisaccharide Gal beta 1----4(Fuc alpha 1----3)GlcNAc either on short-chain fucolipids or as a single immunodeterminant on glycolipid oligosaccharide side chains. Cancer cells, including those from colonic adenocarcinomas, express this antigen on longer type 2 blood group side chains as difucosylated or trifucosylated fucolipids. Moreover, sialylated forms of difucosylated LeX also accumulate in colon cancer but not in normal colonic mucosa. In the present study, six monoclonal antibodies which selectively recognize the various LeX-related antigens were used for immunohistochemical examination of these antigens in serial sections of human colonic tissue. All of these antigens were oncodevelopmental in human colon. Monoclonal antibodies anti-SSEA-1 and AH8-183, directed against short-chain, monofucosylated LeX, were unable to discriminate well between normal and malignant colonic tissue. However, the other four antibodies were much better at distinguishing cancer from normal tissue. FH6 was the most specific in that no normal tissues bound this antibody. However, FH6 failed to stain poorly differentiated cancers and some colloid-type carcinomas. FH4, which was also highly specific, stained almost all cancers, regardless of the degree of differentiation. FH4 primarily stained cancer cell cytoplasm, whereas the sialylated antigen defined by FH6 predominantly stained cell membranes. Differences were noted between the expression of LeX-related antigens in autopsied normal mucosa compared to mucosa of benign colonic diseases. Monoclonal antibodies recognizing long-chain polyfucosylated and sialylated LeX-related antigens appear to be useful tools for detection of colon cancer.

Antibodies, Monoclonal↗
PubMed1986

Effect of dilazep on decrease in myocardial pH during ischemia in dogs.

The present study was undertaken in order to examine whether dilazep (1,4-bis-[3-(3,4,5-trimethoxybenzoyloxy)propyl]perhydro-1, 4-diazepine dihydrochloride monohydrate) attenuates myocardial acidosis induced by coronary artery occlusion in dogs. In dogs with nonischemic normal heart, dilazep (300 or 500 micrograms/kg i.v.) increased blood flow in the left anterior descending coronary artery (LAD) with a decrease in heart rate and diastolic blood pressure. In other dogs, LAD flow was reduced by an occluder by 57 to 68% (partial occlusion) for 90 min. Partial occlusion for 30 min decreased myocardial pH by 0.67 to 0.87 pH units, increased ST segment of the surface electrocardiogram, and decreased regional myocardial contractile force. Dilazep was injected i.v. 30 min after partial occlusion. The decrease in myocardial pH induced by partial occlusion was attenuated by the injection of 300 micrograms/kg of dilazep insignificantly and by that of 500 micrograms/kg of dilazep significantly. Restoration of myocardial [H+] induced by dilazep was calculated from the myocardial pH data. Dilazep (500 micrograms/kg) restored myocardial [H+] induced by partial occlusion by 56.7%, and saline solution restored it by 27.4% 60 min after the drug injection, the actual restoration induced by dilazep being 29.3%. Dilazep, however, did not restore the ST segment elevation and contractile force decrease. It is concluded that dilazep attenuates myocardial acidosis during ischemia.

Animals↗
PubMed1985

Effects of methylmercuric chloride and bis (methylmercuric) selenide on responses of isolated intestinal smooth muscle of the guinea-pig.

The neurologically toxic substance, methylmercury, is detoxified by simultaneous application of selenite. In vivo formation of bis (methylmercuric) selenide has been suggested as the mechanism of detoxication by selenite. By using isolated guinea-pig taenia coli preparations, the effects of methylmercuric chloride and bis (methylmercuric) selenide on contractile responses to nerve and direct stimulation were investigated. Application of either drugs scarcely affected contractile responses to direct stimulation. However, contractile responses to nerve stimulation were severely reduced by methylmercuric chloride. The effect of bis (methylmercuric) selenide was considerably weaker than methylmercuric chloride. The site blocked by methylmercuric chloride and bis (methylmercuric) selenide in the taenia preparation was discussed.

Animals↗
PubMed1985

Inhibitory effect of methylmercuric chloride on the contraction mediated by muscarinic receptor of intestinal smooth muscle of the guinea-pig.

Effects of methylmercuric chloride (MMC) on the contractile responses to nerve and drug stimulation in the guinea-pig taenia coli were examined. MMC (25-50 microM) severely reduced both responses to electrical and pharmacological (nicotine) stimulation of cholinergic nerves without affecting the responses to direct stimulation of muscles. MMC also suppressed markedly the response to acetylcholine (ACh), but did not change the maximum response to ACh. Dose-inhibition curve for MMC on the response to nerve stimulation was quite similar to that on the response to externally applied ACh. MMC only at a high concentration slightly reduced the response to histamine. MMC depolarized the membrane of the smooth muscle by about 8 mV with the sucrose-gap method. However, conditioning depolarization of the muscle strip by a 25 mM-K solution did not suppress the response to ACh. It was suggested that MMC-induced inhibition of the responses of the guinea-pig taenia coli to cholinergic nerve stimulation resulted from the inactivation of the muscarinic receptor of the smooth muscle.

Acetylcholine↗
PubMed1985

Location and distribution of difucoganglioside (VI3NeuAcV3III3Fuc2nLc6) in normal and tumor tissues defined by its monoclonal antibody FH6.

The distribution of a novel difucoganglioside (6B ganglioside, NeuAc alpha 2----3Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----3Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----3Gal beta 1----4Glc beta 1----1Cer) in various normal adult and fetal tissues, as well as in cancer tissues, has been studied by immunoperoxidase staining with a specific monoclonal antibody, FH6, directed to this antigen. A large variety of embryonic and fetal tissues (stomach, colon, small intestine, pancreas, esophagus, lung, and heart) showed a diffuse, weakly positive staining, particularly in the epithelial layer, up to the 70th to 80th day of gestation. However, no staining was observed in various normal adult tissues, including gastrointestinal and glandular epithelial tissues which were stained positively by antibody N-19-9 (directed to sialyl-Lea) or CSLEXI (directed to sialyl-Lex). FH6-positive loci were limited to the proximal convoluted tubuli in kidney and granulocytes. In contrast, 44 of 76 cases of cancer tissue tested, including gastric, colonic, lung, breast, and renal cancers, showed clearly positive staining. The intensity of staining in gastric and colonic cancer tissues by FH6 antibody was weaker and less frequent, although the incidence of positive staining for lung (50%) and breast cancer (86%) was significantly higher than that of the antigen stained by monoclonal antibody FH4 (Y. Fukushi, S. Hakomori, and T. Shepard, J. Exp. Med., 159: 506-520, 1984), which is directed to the asialo core of the FH6 antigen. The antigen levels in the serum of patients with various cancers, inflammatory diseases, and normal subjects were determined by radioimmunoassay. The antigen level was found to be significantly higher in the serum of some patients with cancer, particularly lung, liver, and pancreatic cancers, as compared with the serum levels in other types of cancer, noncancerous diseases, and normal subjects.

Animals↗
PubMed1984

Novel fucolipids accumulating in human adenocarcinoma. III. A hybridoma antibody (FH6) defining a human cancer-associated difucoganglioside (VI3NeuAcV3III3Fuc2nLc6).

A new fucoganglioside, 6B, which accumulates in human colonic adenocarcinoma but is absent in normal colonic mucosa, was isolated from a monosialoganglioside fraction of colonic adenocarcinomas. The structure of this ganglioside was identified as shown below by methylation analysis, direct probe mass spectrometry, and enzymatic degradation followed by examination of the degradation products with specific monoclonal antibodies. (formula; see text) The hybridoma (FH6) secreting a monoclonal IgM antibody directed to this glycolipid was selected by reactivity of the antibody with this ganglioside and lack of reactivity with other glycolipids having a closely related structure, such as sialosyllactoneotetraosylceramide (IV3NeuAcnLc4), sialosyllactofucopentaosy(III)ceramide (IV3NeuAcIII3FucnLc4), sialosyllactofucopentaosy(II)ceramide (sialosyl-Lea glycolipid; IV3NeuAcIII4FucLc4), and 6C fucoganglioside (sialosyl 2 leads to 6 fucoganglioside; VI6NeuAcIII3FucnLc6). The antibody was highly reactive with a large variety of human cancer cells, but was less reactive or did not react with a variety of normal cells.

Adenocarcinoma↗
PubMed1984

Localization and alteration of mono-, di-, and trifucosyl alpha 1----3 type 2 chain structures during human embryogenesis and in human cancer.

Distribution patterns of specific fucose-containing antigens having X determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc) as well as the di- or trimeric X determinants (Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----3Gal beta 1----4[Fuc alpha 1----3]-GlcNAc) in the developing human embryo and fetus and in human cancer have been examined using immunohistological techniques. Tissue sections were stained with monoclonal antibody FH3, which defines X determinant, and with monoclonal antibody FH4, which defines di- or trimeric X determinant. The following general trends in the expression of the antigens defined by FH3 and FH4 have been observed: (a) A well-organized, orderly appearance and disappearance of the antigens was observed during the histogenesis of various epithelia of gastrointestinal and other organs. The developmental stage exhibiting the maximum antigen expression is different for each organ. (b) The X determinant defined by FH3 was expressed approximately 2 wk earlier than the di- or trimeric X determinant defined by FH4, and the antigen defined by FH4 regressed more rapidly and more completely than the X determinant defined by FH3 on further development of epithelial tissue. Thus, expression of the FH4 antigen is highly limited to specific types of cells in newborn and adult epithelial tissues. (c) The antigen defined by FH4 was strongly expressed in the majority of tubular and papillary adenocarcinoma of stomach, adenocarcinoma of colon, and infiltrating ductal carcinoma of breast and its metastatic lesions. No antigen was found in poorly differentiated stomach adenocarcinoma, squamous lung carcinoma, and many other types of tumors from ovary, testis, prostate, skin, and muscle. The presence of the antigen defined by FH4 is therefore limited to carcinoma of the stomach, colon, and breast and can be regarded as a retrograde expression of the antigen to a certain stage of fetal development in which expression of this antigen was maximal.

Adult↗
PubMed1984

Novel fucolipids accumulating in human adenocarcinoma. II. Selective isolation of hybridoma antibodies that differentially recognize mono-, di-, and trifucosylated type 2 chain.

A series of glycolipids having the X determinant (Gal beta 1----4 [Fuc alpha----3]GlcNAc) at the terminus and a fucosyl alpha 1----3 residue at the internal GlcNAc residue have been isolated and characterized from tumor tissues (Hakomori, S., Nudelman, E., Levery, S.B., and Kannagi, R. (1984) J. Biol. Chem. 259, 4672-4680. A series of monoclonal antibodies that differentially recognize glycolipids with mono-, di-, and trifucosylated type 2 chain have been isolated and characterized. The antibody FH4 shows a remarkable preferential reactivity towards di-/or trifucosylated type 2 chain, i.e. it does not react with monofucosylated structures, including lactofucopentaosyl (III) ceramide (III3FucnLc4), monofucosyl neolactonorhexaosylceramide (y2, V3FucnLc6), and monofucosyl neolactonoroctaosylceramide (Z1, VII3FucnLc8), but reacts well with di- and trifucosylated type 2 chain structures such as difucosyl neolactonorhexaosylceramide (III3V3Fuc2nLc6) and trifucosyl neolactonoroctaosylceramide (III3V3VII3Fuc3nLc8). Two other monoclonal antibodies, FH5 and ACFH18, preferentially react with trifucosylated type 2 chain structure (III3V3VII3Fuc3nLc8), although cross-reactivity with difucosylated type 2 chain (III3V3Fuc2nLc6) was observed. They showed a minimal cross-reaction with monofucosylated type 2 chain. In contrast, the antibody FH1 does not react with III3FucnLc4 but reacts with V3FucnLc6, III3V3Fuc2nLc6, and III3V3VII3Fuc3nLc8. Two monoclonal antibodies, FH2 and FH3, do not discriminate among various glycolipids having fucosylated type 2 chain, and their reactivities are essentially similar to previously established antibodies directed to the X determinant, such as anti-SSEA-1, WGHS 29, VEP8 and 9, My-1, etc. This series of antibodies will be useful to detect the specific type of glycolipid with fucosylated type 2 chain accumulating in human cancer and in undifferentiated cells.

Adenocarcinoma↗