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Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 739 records · Page 41Linked to original sources
PubMed1993

Subtype selectivity of a novel endothelin antagonist, FR139317, for the two endothelin receptors in transfected Chinese hamster ovary cells.

We investigated the receptor-binding properties and the antagonist activities of FR139317, a novel endothelin (ET) antagonist, in transfected Chinese hamster ovary cells permanently expressing the two ET receptor subtypes (ETA and ETB). In displacement analysis using membrane preparations derived from the receptor-expressing cells, FR139317 showed a high affinity for ETA (Ki = 1 nM) and a lower affinity for ETB (Ki = 7.3 microM). FR139317 inhibited ETA-mediated phosphatidylinositol hydrolysis and arachidonic acid release and produced a parallel shift in the dose-response curve for ET-1, with respective pA2 values of 8.2 and 7.7. In contrast, FR139317 had no inhibitory effects on these ET-1-induced responses in ETB-expressing cells. FR139317 itself showed no stimulatory effects on phosphatidylinositol hydrolysis and arachidonic acid release in ETA- and ETB-expressing cells. Thus, FR139317 is a potent, competitive, and highly selective antagonist for ETA. This compound should be a powerful tool for investigation of the physiological properties of ETA and exploration of its role in diseases.

Animals↗
PubMed1993

Pharmacological profile of FR139317, a novel, potent endothelin ETA receptor antagonist.

The effects of FR139317 on the cardiovascular system were investigated in cultured cells, isolated organs and whole animals. FR139317 inhibited the specific binding of [125]endothelin(ET)-1 to porcine aortic microsomes in a concentration-dependent, monophasic fashion with an IC50 of 0.53 nM. In contrast, FR139317 showed low affinity for [125I]ET-1 specific binding sites in porcine kidney (IC50, 4.7 microM). In isolated rabbit aorta, FR139317 shifted the ET-1-induced concentration-contractile response curve to the right with a pA2 value of 7.2 and lacked agonist activity. A single (i.v.) bolus dose of FR139317 completely inhibited the pressor response to ET-1 in vivo, but had no effect on the initial depressor response in conscious normotensive rats. These data indicate that FR139317 is a potent, highly specific ETA receptor antagonist. In addition, FR139317 also inhibited ET-1 induced [3H]thymidine incorporation in cultured vascular smooth muscle cells from rat aorta (IC50, 4.1 nM), suggesting that ET-1-induced mitogenesis is mediated only by the ETA receptor. FR139317 could become a useful tool for investigating the physiological and pharmacological actions of ET.

Animals↗
PubMed1993

[Ogilvie's syndrome in pregnancy--a case report].

A 23-year-old female in the 28th week of pregnancy was admitted with an acute abdominal distension. The plain X-ray films showed a marked gaseous dilatation of the colon from the cecum to the splenic flexure. A tube colostomy was performed. Her postoperative course was uneventful and she improved progressively. Her pregnancy and delivery elapsed uneventfully there after. After the delivery she again complained of marked abdominal distension. The colonoscopic decompression in combination with the administration of Cisapride was successfully accomplished. Ogilvie's syndrome is characterized by an unobstructed colon which progresses to marked dilatation. When the colonic diameter becomes 12cm or more, surgical decompression should be recommended to avoid the hazard of spontaneous rupture. This is the first reported case of Ogilvie's syndrome in pregnancy in Japan.

Adult↗
PubMed1993

[Cyclosporine therapy of adult onset Still's disease with disseminated intravascular coagulation].

In April, 1991, a 61-year-old man was admitted to our hospital because of pancytopenia and disseminated intravascular coagulation (DIC). Five years prior to admission he had developed high fever, skin eruption and arthralgia which had been improved by antibiotics, but recurred. Steroid therapy was ineffective for pancytopenia and DIC. Laboratory findings were as follows: RBC count, 274 x 10(4)/microliters; WBC count, 470/microliters; Platelets, 6.4 x 10(4)/microliters; fibrinogen, 153mg/dl; FDP, 67.0 micrograms/ml; FDP-D.Dimer, 13040ng/ml; thrombin-antithrombin complex, > 60.0ng/ml; and plasmin alpha 2-plasmin inhibitor complex, 10.3 micrograms/ml. As we suspected adult onset Still's disease on the basis of clinical course, we treated him with methylprednisolone pulse therapy, which was, however, ineffective. leukocytopenia, thrombocytopenia and DIC improved after cyclosporine treatment. Since cyclosporine is known to be very effective to autoimmune diseases, we speculate that in this patient immunological mechanism may be involve in the pathogenesis of DIC.

Cyclosporine↗
PubMed1993

Reverse-phase high-performance liquid chromatographic assay of phospholipases: application of spectrophotometric detection to rat phospholipase A2 isozymes.

This paper appraises an HPLC method for assaying phospholipase A2 (PLA2). The procedure is based on heptane-isopropanol-H2SO4 extraction of fatty acids released by the enzyme in the presence of margaric acid as an internal standard, and precolumn derivatization with 9-anthryldiazomethane. The derivatives of naturally occurring long-chain fatty acids were accurately determined by reverse-phase HPLC with ultraviolet detection at 254 nm; the fatty acids were identical with margaric acid in terms of their extraction efficiency in the presence or absence of a bile salt, reactivity with the labeling reagent, and molar extinction coefficients of their derivatives. HPLC conditions were optimized so as to separate the derivatives of palmitic and oleic acids completely within 7 min. The use of the 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol/cholate system as substrate proved useful for the sensitive detection of PLA2 activities in rat tissue homogenates. Distribution of immunoreactive pancreatic and group II phospholipases A2 was estimated from the degree of inhibition of enzyme activities by specific antibodies raised against either forms of phospholipase A2 isozymes. The results were consistent with those of immunoblot analyses.

Animals↗
PubMed1993

Bending rigidity of composite resin coating clasps.

The purpose of this study is to examine the bending profiles of composite resin coating cast clasps. The cobalt-chromium alloy cast clasps were made using tapered wax pattern. Silane coupling method (Silicoater MD, Kulzer Co.) was used to attach composite resin to metal surface. The breakage and the bending rigidity of composite resin coating clasps were evaluated. Results were as follows: 1) After the repeated bending test to the tips of clasp arm at 10,000 times in 0.25 mm deflection, neither crack on composite resin surface nor separation at resin/metal interface was observed in any specimen. 2) There was no significant difference in the bending rigidity of clasp arms between before and after composite resin coating. From these results, it was demonstrated that the composite resin coating cast clasp was available in clinical cases and coating with composite resin had little influence on the bending rigidity of clasp arms. Therefore, it was suggested that our clasp designing and fabricating system to control the bending rigidity of clasp arms could be applied to composite resin coating clasps.

Chromium Alloys↗
PubMed1992

Changes of DNA methylation in protooncogenes in the process of radiation-induced transformation of mouse m5S/1M cells in vitro.

To assess the importance of changes in DNA methylation in an X-ray-induced cellular transformation process, methylation patterns of five nuclear protooncogenes in fifteen transformant clones were studied and compared to that of the parental non-transformed cell line m5S/1M. All transformants examined revealed an alteration in DNA methylation in some of the genes, although these changes were variable among them. A comparison of cellular characteristics with corresponding DNA methylation changes in different clones suggested that the loss of contact inhibition and the gain of anchorage independency were associated with increases of methylation in many genes, whereas the acquisition of tumorigenicity was often accompanied by a decrease of methylation in the N-myc and c-myc genes. Resultant data indicate that the alteration of DNA methylation is closely related to transformation process, yet how this involvement occurs is complex and remains unclear.

Animals↗
PubMed1992

Magnocellular neurosecretory neurons with ferritin-like immunoreactivity in the hypothalamic supraoptic and paraventricular nuclei of the rat.

Immunohistochemistry for rat liver ferritin (FRT) revealed an intensive labeling in some structures of the rat brain. In the supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei, almost all neurosecretory neurons with vasopressin (AVP)-like immunoreactivity were immunostained with FRT. After water deprivation, a marked enlargement of cell body and an immunoreactivity to transferrin receptors were found in AVP-, FRT- and double (AVP+FRT)-labeled neurons in the SON and PVN.

Animals↗
PubMed1992

Secretion of cell-adhesion-promoting factors, fibronectin, fibronectin fragments and a 53-kDa protein, by human rectal adenocarcinoma cells.

Production of cell-adhesion proteins was examined in 10 cell lines and 5 cultured human cancer cells at an early passage. Two-thirds of the tested cells produced and secreted into their culture medium variable amounts of material active in promoting cell attachment. One of the rectal carcinoma cell lines, CaR-I, grew well in serum-free medium and secreted a large amount of the active principle. The active principles produced by CaR-I cells were characterized after partial purification, and were found to be fibronectin and its fragments. The presence of fibronectin and its fragments was proved by the following facts: (1) reactivity to the monoclonal antibodies which recognize different epitopes of fibronectin, and (2) reactivity to RGD peptide which is the attachment sequence of fibronectin. In addition to fibronectin and its fragments, CaR-I cells were also shown to produce a 53-kDa attachment factor. Unexpectedly, the protein was proved to be most probably the p53 suppressor gene product.

Adenocarcinoma↗
PubMed1992

Structural and functional modulation of the manganese cluster in Ca(2+)-depleted photosystem II induced by binding of the 24-kilodalton extrinsic protein.

Depletion of functional Ca2+ from photosystem (PS) II membranes impairs O2 evolution. Redox properties of the Mn cluster as probed by thermoluminescence were modified differently in Ca(2+)-depleted PSII depending on the procedure for Ca2+ extraction. Ca2+ depletion by low-pH treatment gave rise to an abnormally modified S2 state exhibiting a thermoluminescence band with elevated peak temperature accompanied by a marked upshift in threshold temperature for its formation, whereas Ca2+ depletion by NaCl washing in the light followed by the addition of EDTA could generate a similarly modified S2 state only when the Ca(2+)-depleted PSII was reconstituted with the 24-kDa extrinsic proteins. These results indicated that manifestation of the abnormal properties of the Ca(2+)-depleted S2 state is significantly contributed by the association of the 24-kDa extrinsic protein to PSII. It was inferred that the 24-kDa extrinsic protein regulates the structure and function of the Mn cluster in the absence of functional Ca2+ through a conformational modulation of the intrinsic protein(s) that bind(s) both Mn and Ca. Features of the extrinsic protein-dependent modulation of the Mn cluster were discussed in relation to the function of Ca2+ in O2 evolution.

Calcium↗
PubMed1992

Detection of structural changes upon S1-to-S2 transition in the oxygen-evolving manganese cluster in photosystem II by light-induced Fourier transform infrared difference spectroscopy.

The light-induced Fourier transform infrared (FT-IR) difference spectrum between the S1 and S2 states of the O2-evolving photosystem II (PSII) was obtained for the first time. Detection of an S2/S1 difference spectrum virtually free from contributions by the acceptor-side signals was achieved by employing an exogenous electron acceptor, potassium ferricyanide, to trypsin-treated PSII membranes and using one-flash excitation at 250 K. A synthetic difference spectrum obtained by adding this S2/S1 spectrum to the QA-/QA spectrum measured with Mn-depleted PSII was almost identical with the difference spectrum of the S2QA-/S1QA charge separation measured with untreated PSII. This successful simulation verifies the correctness of the S2/S1 spectrum thus obtained. The observed S2/S1 spectrum reflects the structural changes within the water-oxidizing Mn cluster upon the S1-to-S2 transition, most probably changes in vibrational modes of ligands coordinating to the Mn ion(s) that is (are) oxidized upon the S2 formation and/or changes in protein conformation. The present results demonstrate that FT-IR difference spectroscopy is a promising method to investigate the structure of the intermediates of the Mn cluster involved in photosynthetic water oxidation.

Cell Membrane↗
PubMed1992

Ganglioside, adhesion molecule, and HLA antigen expression in basal cell carcinoma lesions.

The antigenic profile of basal cell carcinoma (BCC) cells was analyzed by immunoperoxidase staining of 27 surgically removed BCC lesions with antiganglioside, antiadhesion molecule, and antihistocompatibility locus antigen (HLA) monoclonal antibodies (MoAb). The large majority of BCC lesions were stained by antiganglioside MoAb; among the latter the anti-GD3 ganglioside MoAb R24 displayed the broadest reactivity. The GD3 ganglioside expression by BCC cells, which was corroborated by thin layer chromatography immunostaining with MoAb R24, appears to be a proliferation dependent phenomenon. Among the adhesion molecules tested vitronectin receptor and CDw44 were found in up to 70% of the lesions tested, while intercellular adhesion molecule 1 (ICAM-1) was detected in only a low percentage of BCC cells in one lesion. ICAM-1 was not induced on BCC cells in five and three lesions removed 24 and 48 h, respectively, following the intralesional injection of gamma-interferon. The latter enhanced HLA Class I antigen expression and induced ICAM-1 expression by the surrounding keratinocytes; furthermore gamma-interferon induced HLA Class II antigen expression by a small percentage of BCC cells in three lesions. These results suggest that malignant transformation of keratinocytes is associated with a selective loss of susceptibility to induction by cytokines of ICAM-1 expression. Besides confirming the low HLA Class I and Class II antigen expression by BCC cells, the present investigation has shown a differential expression of distinct monomorphic determinants of HLA Class I antigens and a lower expression of HLA-A antigens than of HLA-B antigens by BCC cells. Furthermore, the present study has shown that HLA Class II antigens can be induced on BCC cells by cytokines.

Aged↗
PubMed1992

Inhibition of DNA synthesis by TGF-beta 1 coincides with inhibition of phosphorylation and cytoplasmic translocation of p53 protein.

Immunostaining demonstrated that p53 protein was localized in the cytoplasm of growing MCF-7 cells and in the nuclei of cells that were growth arrested by serum starvation. Serum stimulation of the arrested cells induced marked increases in DNA synthesis and p53 phosphorylation, and translocation of the protein from the nucleus to the cytoplasm at 20 h after the stimulation. This increase in the DNA synthesis that was significantly inhibited by TGF-beta 1 was coincident with the inhibition of phosphorylation and cytoplasmic translocation of the p53 protein.

Breast Neoplasms↗
PubMed1992

Methylated cytosine level in human liver DNA does not decline in aging process.

In order to ascertain a generality of the age-dependent decrease in DNA methylation level among different mammalian species, methylated cytosine contents in human liver and spleen DNA at different ages have been determined using high performance liquid chromatography (HPLC). Unexpectedly, the liver DNA revealed no appreciable decline with age while the spleen DNA showed a slight reduction. It indicates that a decrease of methylation level in genomic DNA is not a common denominator of age-related changes in mammals.

Adolescent↗
PubMed1992

TFC-612, a prostaglandin E1 derivative, enhances fibrinolytic activity in rats.

TFC-612 inhibited thrombus formation on wire coils inserted into the lumen of the inferior vena cava of rats after 5 oral doses of 1.0 and 3.2 mg/kg and subcutaneous doses of 1.0 and 3.2 micrograms/rat/hr. This compound showed slight inhibition of platelet aggregation induced by collagen at 1.0 and 3.2 mg/kg (po) and significant inhibition at 10 mg/kg. TFC-612 had no effect on the plasma coagulation system at 3.2 mg/kg. Conversely, oral doses of 0.32-3.2 mg/kg dose- dependently enhanced fibrinolytic activity as measured by euglobulin clot lysis time and lysis area on fibrin plates by euglobulin fraction. TFC-612 did not enhance fibrinolytic activity in vitro. These results suggest that the enhancement of fibrinolytic activity by TFC-612, which may be due to an increase in tissue plasminogen activator release or reduction of plasminogen activator inhibitors release, contributes to its inhibition of thrombus formation.

Alprostadil↗
PubMed1992

Immunocytochemical localization of rat intestinal 15 kDa protein, a member of cytoplasmic fatty acid-binding proteins.

Rat intestinal 15 kDa protein (I-15P) is a member of the family of cytoplasmic fatty acid-binding proteins. Using a specific antiserum against I-15P, we studied the tissue distribution and subcellular localization of this protein in the entire rat body. By immunoblot analysis of cytosolic proteins, I-15P was detected not only in the distal portion of small intestine but also in the ovary and adrenal gland. Immunohistochemically, I-15P was localized to the absorptive epithelial cells as well as a subpopulation of enterochromaffin cells in the intestine, the lutein cells in the ovary, and subpopulations of cortical cells in the adrenal gland. Furthermore, I-15P-like immunoreactivity was also demonstrated in the surface mucous cells of stomach and the granular convoluted tubule cells of submandibular gland. Immuno-electron microscopy showed that the immunoreactivity was confined to the cytoplasmic matrix region, except in the enterochromaffin cells and granular convoluted tubule cells, where it was localized in the secretory granules. The present findings suggest that I-15P plays a role in the cellular metabolism of steroids.

Adrenal Glands↗
PubMed1992

Monkey hippocampal neuron responses to complex sensory stimulation during object discrimination.

The purpose of this study was to investigate, during the performance of an object discrimination task, responses of neurons in the monkey hippocampal formation to the sight of several objects that have biological meaning, and compare these responses with those of amygdalar neurons studied previously using the same task. Neuronal activity in the hippocampal formation of conscious monkeys was recorded during performance of a task that led to presentation of familiar rewarding, familiar aversive, or unfamiliar objects. Of 864 neurons recorded in the hippocampal formation and adjacent cortices, 160 (18.5%) responded to the sight of a certain object(s). Responses to the sight of different kinds of objects were analyzed in detail. Nondifferential neurons (n = 73) responded to different objects with no significant difference in response magnitudes, and differential neurons (n = 87) responded to different objects with different response magnitudes. Of the differential neurons, 23 responded more strongly to rewarding objects than to other objects (rewarding-object-dominant neurons), but the magnitude of responses to objects did not necessarily correlates with the order of preferences to the objects as determined from observation of animal behavior. Aversive-object-dominant neurons (n = 13) responded more to aversive objects than to other objects. Unfamiliar-object-dominant neurons (n = 7) responded more to unfamiliar objects than to familiar objects. Selective neurons (n = 10) responded selectively to only one object or one category of objects. Fourteen of the rewarding- or averse-object-dominant neurons were tested in extinction or reversal trials. In 12 of 14 neurons, responses to a rewarding or aversive object did not change, or slightly weakened, in extinction or reversal trials. The results suggest the following. (1) Responses of rewarding- or aversive-object-dominant neurons may be involved in object-reward or object-aversion association. However, responses of many of these neurons might reflect past inputs to reinforcement rather than extant emotional processing. (2) Responses of unfamiliar-object-dominant neurons may be involved in recognition of objects based on their familiar or unfamiliar aspects. These results are further discussed and compared with responsiveness of amygdalar neurons.

Acoustic Stimulation↗