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Biomedical subjects

Y Fukushi

Publications and source records attributed to Y Fukushi.

At least 73 records · Page 4Linked to original sources
PubMed1987

Involvement of cholinergic nerves in excitatory junction potentials through prejunctional nicotinic receptors in the guinea-pig vas deferens.

1. The effects of various drugs on excitatory junction potentials (EJPs) elicited by field stimulation of the longitudinal smooth muscle of the guinea-pig vas deferens were examined using the sucrose-gap method. 2. Field stimulation with a single pulse (1.0 ms, 20 Vcm-1) produced a depolarization of 3-7 mV. When a single pulse was repetitively applied, the depolarization showed summation, resulting in action potential firing. 3. Tetrodotoxin (1 microM) and guanethidine (1 microM) completely suppressed EJPs whilst propranolol (1 microM) or atropine (0.1 microM) did not affect them. Phentolamine (1 microM) slightly potentiated EJPs. 4. d-Tubocurarine (dTC) at lower concentrations (0.5-2 microM) suppressed EJPs, but at a higher concentration (20 microM) the drug little affected them. 5. Hexamethonium (C6) suppressed EJPs at low concentrations (0.5-5 microM), but potentiated them at a higher concentration (50 microM). 6. Either dTC or C6, each at a concentration of 0.5 microM, did not affect the depolarization induced by exogenously applied ATP or noradrenaline. 7. These results suggest that in this tissue cholinergic nerve activity can contribute to the magnitude of EJPs, and that this effect is mediated through nicotinic receptors.

Animals↗
PubMed1987

[Initial basic and clinical evaluation of a solid-phase immunoradiometric assay for sialyl SSEA-1 antigen: 1. Evaluation of assay conditions and normal values].

We describe a solid-phase immunoradiometric sandwich assay method for a new tumor marker, sialyl SSEA-1 (sialyl LeX-i), using RIA kits (prepared by Otsuka Assay Laboratories). The assay required only duplicate 20-microliter samples, and the concentration of sialyl SSEA-1 antigen in serum was determined with reference to a standard curve ranging from 0 to 224 arbitrary unit/ml. The intra- and inter-assay reproducibilities and analytical recovery of antigen were excellent. The cut-off value (38 unit/ml) was obtained as mean + 2SD, which was calculated from the antigen concentration in sera from 1,105 healthy individuals. Also described are the alterations of normal values by age, sex, and Lewis blood group status.

Antigens, Neoplasm↗
PubMed1987

[Initial basic and clinical evaluation of a solid-phase immunoradiometric assay for sialyl SSEA-1 antigen: 2. Evaluation of clinical significance].

The clinical significance of serum sialyl SSEA-1 antigen was evaluated using the sera of 1261 patients with malignant tumors and 717 patients with non-malignant diseases measured with Otsuka Assay Laboratories' RIA Kits. The results indicate that the antigen was frequently elevated in the sera from the patients with various adenocarcinomas, including lung (45%), pancreas (64%) and ovary (57%). The false positive incidence of antigens in the sera from the patients with non-malignant disorders was as low as 4.9%. No correlation was observed with other tumor markers examined in this study, and the diagnostic efficiency increased significantly by the combined determination of sialyl SSEA-1 antigen level with other markers. The serial determination of the serum sialyl SSEA-1 antigen level has a clinical utility also in monitoring the patients with adenocarcinoma receiving surgical operation and/or chemotherapy as indicated by the results of the longitudinal observation of the patients.

Adenocarcinoma↗
PubMed1987

Expression of LewisX and sialylated LewisX antigens in human colorectal polyps.

The LewisX (LeX) antigen [characterized by trisaccharide Gal beta 1----4 (Fuc alpha 1----3)N-acetylglucosamine] is an oncodevelopmental antigen in the human colon. Monoclonal antibodies (MoAbs), anti-SSEA-1 and AH8-183, which recognize LeX antigen either on short oligosaccharide side chains or as a terminal immunodeterminant on longer carbohydrate side chains of glycoconjugates, bind to most colon cancer tissues but also to some normal colon mucosae. However, the monoclonal antibodies FH1, FH4, FH6, and IB9, which recognize extended difucosylated and trifucosylated LeX structures or their sialylated derivatives, are more cancer-associated because they rarely bind to normal colon mucosa. In the present study, these MoAbs were used to compare the expression of various LeX-related antigens in premalignant (adenomatous) and nonpremalignant (hyperplastic) colorectal polyps. Antigen expression in polyps was also compared to antigen expressions of normal colon mucosa and colon cancer tissues. The four MoAbs recognizing extended LeX antigens bound to adenomatous polyps (APs) significantly more than to hyperplastic polyps (HPs). In contrast, anti-SSEA-1 and AH8-183 recognizing monofucosyl LeX were less able to distinguish between APs and HPs. In APs, staining with the four MoAbs recognizing extended LeX antigens correlated with the premalignant parameters of larger polyp size, more severe dysplasia, and increased villose component. However, staining with AH8-183 correlated only with polyp size, and anti-SSEA-1 correlated only with polyp size and degree of dysplasia. In general, the staining frequency of HPs was similar to that of normal colon mucosa, although FH6, which did not stain any specimens of normal mucosa, stained a few HPs. The staining frequency of APs was less than that of colon cancer tissues, but these differences were generally not statistically significant. In conclusion, extended LeX antigens and their sialylated derivatives are cancer-associated antigens that are expressed preferentially in premalignant colon polyps, that tend to correlate with malignant potential in these polyps, and that may eventually help to define mechanisms involved in the polyp-to-cancer sequence.

Antibodies, Monoclonal↗
PubMed1986

A novel disialoganglioside (IV3NeuAcIII6NeuAcLc4) of human adenocarcinoma and the monoclonal antibody (FH9) defining this disialosyl structure.

This ganglioside is highly immunogenic, and immunization of mice with this disialoganglioside fraction coated on Salmonella minnesota followed by fusion of immunized spleen cells with mouse myeloma and selection of the hybridoma by positive reactivity with the purified disialoganglioside resulted in the establishment of a hybridoma secreting immunoglobulin G2a antibody FH9 that reacts specifically with the ganglioside antigen above but not with monosialosyllactotetraosylceramide I (IV3NeuAcLc4), monosialosyllactotetraosylceramide II (III6NeuAcLc4), or any other gangliosides tested.

Adenocarcinoma↗
PubMed1986

Novel fucolipids of human adenocarcinoma: disialosyl Lea antigen (III4FucIII6NeuAcIV3NeuAcLc4) of human colonic adenocarcinoma and the monoclonal antibody (FH7) defining this structure.

A new fucoganglioside, disialosyl Lea, has been found in the disialoganglioside fraction of human colonic adenocarcinoma. The ganglioside has been isolated from four other disialogangliosides by high-performance liquid chromatography followed by preparative high-performance thin-layer chromatography. The structure of the antigen was characterized by its conversion to lactofucopentaosyl(II)ceramide (Lea-active ceramide pentasaccharide), methylation analysis, and high-mass range electron-impact as well as field-desorption mass spectrometry of the permethylated derivative, as shown below: (Formula; see text) Specific removal of alpha 2----3-linked sialosyl residue by influenza virus A2 sialidase, or preferential hydrolysis of the same residue by Clostridium perfringens sialidase in the absence of detergent, resulted in the formation of an intermediate product, monosialosyl LeaII (III4FucIII6NeuAcLc4), which reacted with anti-Lea antibody and with monoclonal antibody FH7 and may have a sialic acid linked at the 6 position of GlcNAc. The IgG3 monoclonal antibody FH7 was established, which reacts specifically with disialosyl Lea and monosialosyl LeaII as above, but does not react with disialosyllactotetraosylceramide (IV3NeuAcIII6Neu-AcLc4), monosialosyl LeaI (IV3NeuAcIII4FucLc4), and other mono- and disialogangliosides isolated from the same cancer tissue. The antibody FH7 may be useful in the detection of human cancer.

Adenocarcinoma↗
PubMed1986

Dual excitatory actions of acetylcholine at the neuromuscular junction in the guinea-pig vas deferens.

The action of acetylcholine (ACh) on the smooth muscle of guinea-pig vas deferens was studied using the sucrose-gap method. ACh, when applied at a concentration of 10(-6) M, evoked a depolarization of the smooth muscle membrane which was slow in time course (slow depolarization). When ACh was applied at higher concentrations, another depolarization which was fast in time course (fast depolarization) occurred, overlapping the early part of the slow depolarization. The magnitudes of both depolarizations were concentration-dependent on ACh. TTX and adrenergic receptor antagonists had little effect on either depolarizations, while guanethidine and nicotinic receptor antagonists mainly suppressed the fast depolarization. In contrast, atropine suppressed the slow depolarization. The membrane conductance observed by current application, was reduced during the slow depolarization, and the reversal potential of the depolarization was 18.3 mV negative to the resting membrane potential. Whereas, the reversal potential of the fast depolarization was 27.6 mV positive to the resting membrane potential. This reversal potential was quite similar to that of the adenosine triphosphate (ATP)-induced depolarization, previously observed in the same tissue. From these observations, it is suggested that in the guinea-pig vas deferens, ACh acts on nicotinic receptors at the sympathetic postganglionic nerve terminal, causing the release mostly of a non-adrenergic transmitter, probably ATP. In addition, ACh also acts on muscarinic receptors on the smooth muscle membrane, inducing membrane depolarization resulting from a reduction of the membrane conductance to potassium ions.

Acetylcholine↗
PubMed1986

Coordinate expression of X and Y haptens during murine embryogenesis.

The X hapten (Gal beta 1----4[Fuc alpha 1----3]GlcNAc) may play an important role in the adhesion of blastomeres during compaction. Therefore, we have investigated more thoroughly developmental changes in the fucosylation of lactoseries carbohydrate chains and the enzymatic basis of these fucosylation changes using well-characterized monoclonal antibodies. The Y hapten (Fuc alpha 1----2Gal beta 1----4[Fuc alpha 1----3]GlcNAc) and polymeric X haptens were detected by fluorescence-activated flow cytometry on murine embryonal carcinoma cells. In paraffin sections of postimplantation mouse embryos, the Y hapten was detected in the embryonic ectoderm and visceral endoderm on Days 5.5-7.5; this pattern of antigen expression is identical to that previously reported for the X hapten (SSEA-1). Thus, the Gal:alpha 1----2 (H) and GlcNAc:alpha 1----3 (X) fucosyltransferases appear to be co-regulated during embryogenesis. Reciprocal changes in X and Y hapten expression were observed, however, during preimplantation development. Unlike the X hapten, the Y hapten is expressed maximally on 16-cell morulae and 32- to 64-cell blastocysts. Eight-cell embryos cultured to the blastocyst stage in vitro did not acquire the Y hapten, however, suggesting a role for the uterine environment in carbohydrate antigen expression. Homogenates of F9 embryonal carcinoma cells were found to possess a potent GlcNAc:alpha 1----3 fucosyltransferase activity, as well as a weaker Gal:alpha 1----2 fucosyltransferase activity, using paragloboside as a substrate. The results suggest that embryonic cell surface carbohydrate phenotypes represent a balance in the competition between glycosyltransferases for available substrates. Rapid changes in carbohydrate expression during development may reflect intermediate states of cellular commitment and determination that are critical for lineage formation and morphogenesis.

Animals↗
PubMed1986

Changes of Lex and dimeric Lex haptens and their sialylated antigens during development of human kidney and kidney tumors.

The carbohydrate antigen termed Lex (Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----R), its di- or trimeric form, and their sialylated antigens have been characterized as developmentally regulated, tumor-associated antigens in human gastrointestinal epithelia. In this paper, remarkable changes of these antigens, defined by respective monoclonal antibodies FH3, FH4, and FH6, in fetal kidney (mesonephros and metanephros) and other urogenital organs, as well as in various types of kidney tumors, have been investigated. During the development of each organ and tissue, the antigens were found to be maximally expressed at a defined period of organogenesis, and a shifting of expression from one locus to another was observed. Each antigen showed a slightly but clearly different stage of maximum expression. The following changes in metanephros development are of particular interest. Expression of the antigen defined by FH3 followed by the antigen defined by FH4 appeared only after six weeks of gestation in the convoluted tubuli at the central region of metanephros, and propagated rapidly into those at the peripheral cortex region with a simultaneous regression at the central region. The regression of FH4 antigen was more rapid than that of FH3. All three antigens were expressed in the medullar thin tubuli, which develop into the thin-limb of Henle's loop, in which only the antigens defined by FH3 and FH4 persisted and FH6 antigen disappeared. Well-differentiated, but not undifferentiated, renal adenocarcinomas strongly expressed the antigens defined by FH4 and FH6, although the antigen defined by FH6 was expressed in more differentiated tumor cells than the antigen defined by FH4. Well-differentiated cells organized into tubular structures showed a strong expression of these differentiation antigens. However, some tumor cells that were organized into tubular structures, but were characterized by undifferentiated cytomorphology (larger nucleus and smaller volume of cytoplasm), did not express FH4 and FH6 antigens. Thus, cytodifferentiation and histotypic differentiation proceed independently within kidney tumors. The fucosylated type 2 chain structures defined by these three monoclonal antibodies are useful markers that indicate the degree of tumor differentiation.

Adenocarcinoma↗
PubMed1986

Human hepatocellular carcinoma-associated changes of glycosphingolipids detected by two monoclonal antibodies FH2 and IB9.

The changes of minor glycosphingolipids associated with human hepatocellular carcinomas were studied using monoclonal antibodies. Glycosphingolipids of twelve patients were isolated from the tumor tissues and their adjacent cirrhotic liver tissues. The immunoreactivities of glycosphingolipids with two monoclonal antibodies FH2 and IB9, that define x-structure (Gal beta 1-4[Fuc alpha 1-3]GlcNAc) and sialosyl alpha 2-6galactosyl residue, respectively, were studied by a solid phase enzyme-linked immunosorbent assay and a chromatogram immunobinding assay. X-structure was detected in the upper-phase neutral glycosphingolipids from both the cirrhotic liver tissues and the tumor tissues, but was generally expressed more strongly in the latter tissues. The thin-layer chromatography patterns of x-active glycosphingolipids were more complex in the tumor tissues. Sialosyl alpha 2-6galactosyl residue was detected in two ganglioside fractions. One ganglioside with faster migration on a thin-layer chromatogram was found in both the non-tumorous tissues and the tumor tissues. Another ganglioside with slower migration was more often detected in the tumor tissues. It was concluded that some of minor glycosphingolipids detected by monoclonal antibodies FH2 and IB9 could be the 'tumor-associated' antigens.

Antibodies, Monoclonal↗
PubMed1986

Possible interaction of cholinergic nerves with two different (pre and post) sites of the neuromuscular junction in guinea-pig vas deferens.

Effects of various drugs on the mechanical responses of the longitudinal smooth muscle of guinea-pig vas deferens evoked by ACh and field nerve stimulation were examined. ACh (28-280 microM) produced a contraction consisting of two phases. The first phase of the contraction was suppressed by guanethidine and by nicotinic antagonists. The second phase was suppressed only by atropine. Both phases were unaffected by TTX or prazosin. Field stimulation (0.1 msec, 40 Hz) evoked contractions which also consisted of two (early and late) phases. Guanethidine (0.1-1 microM) suppressed both phases whilst prazosin (1 microM) suppressed only the late phase. Atropine (0.1 microM) suppressed both phases whilst physostigmine (5 microM) potentiated both phases of field stimulation-evoked contractions. Pentolinium suppressed both phases of field stimulation-evoked contractions at low concentrations (2-10 microM), but potentiated them at a higher concentration (100 microM). dTC at a low concentration (0.5 microM) suppressed the early phase, but slightly enhanced the late phase of field stimulation responses. At a higher concentration (20 microM), dTC potentiated both phases of the response. Pentolinium and dTC did not affect the contractions induced by 90 mM-K ions, ATP or NA. These results suggest that cholinergic nerves possess an excitatory action not only directly at the smooth muscle but also at the noradrenergic nerve terminals. The role of each receptor is discussed further.

Adrenergic Fibers↗
PubMed1986

Pharmacological studies on the role of cholinergic nerves in the neuromuscular transmission in the circular smooth muscle of guinea-pig vas deferens.

Effects of various drugs were examined on the mechanical responses of the circular smooth muscle of guinea-pig vas deferens evoked by field stimulation and ACh. During field stimulation (0.1 msec, 3-80 Hz) a contraction consisting of two (initial and second) phases occurred. In addition, another contraction (after-response) occurred after the cessation of the stimulation particularly at higher frequencies (40-80 Hz). Guanethidine (2-20 microM) suppressed both the initial and second phases of the field stimulation-evoked responses. Prazosin (0.1-1 microM) suppressed the second phase but minimally affected the initial phase. Both phases were suppressed by atropine (0.1-1 microM) and potentiated by physostigmine (5 microM). dTC (0.5-20 microM) did not suppress either phase but potentiated the second phase. ACh (0.28-280 microM) produced a contraction, which was reduced by atropine but was little affected by either dTC or TTX. These results suggest that at the postsynaptic site of the neuromuscular junction in this tissue the sympathetic process activates the smooth muscle through two different types of receptor; one is non-noradrenergic and the other is an alpha-adrenoreceptor. In addition, a cholinergic process also activates the smooth muscle through muscarinic receptors.

Acetylcholine↗
PubMed1986

Attenuation by isosorbide dinitrate of coronary occlusion-induced acidosis in the dog myocardium.

In dogs anaesthetized with pentobarbitone, the thorax was opened and myocardial pH measured continuously by the use of a glass pH electrode inserted in the left ventricular wall. The left anterior descending coronary artery (LAD) was partially occluded so that the LAD flow could be reduced to a half or one-third of the original flow (partial occlusion). LAD partial occlusion was continued for 90 min, drug or saline being infused for the last 60 min of this period. LAD occlusion decreased myocardial pH significantly by 0.41 to 0.67 pH units, and increased ST segment of the surface electrocardiogram from 11.7 to 12.1 mV. In dogs with non-ischaemic normal hearts, isosorbide dinitrate (ISDN; 1 mg kg-1) did not change markedly either the LAD flow, myocardial pH or heart rate, whereas it decreased myocardial contractile force (determined by a strain gauge arch) slightly and both the systolic and diastolic blood pressure markedly. In dogs with partial LAD occlusion, ISDN (1 mg kg-1) increased myocardial pH significantly and decreased blood pressure, but did not change ST segment elevation in an epicardial lead. These results indicate that ISDN attenuates ischaemia-induced acidosis without attenuating ischaemia-induced ST elevation in the dog myocardium.

Acidosis↗