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Biomedical subjects

Y Ishii

Publications and source records attributed to Y Ishii.

At least 19 recordsLinked to original sources
PubMed1992

Amitriptyline inhibits striatal efflux of neurotransmitters via blockade of voltage-dependent Na+ channels.

Amitriptyline, a tricyclic antidepressant, almost completely inhibited veratridine- or scorpion toxin-evoked efflux of endogenous dopamine (DA) and gamma-aminobutyric acid (GABA) from rat striatal slices without any effects of 30 mM K+ or 4-aminopyridine on basal and evoked efflux. The effects of amitriptyline on glutamate efflux were comparable to those on DA or GABA efflux. These effects of amitriptyline can be well explained by its blockade of voltage-dependent Na+ channels and may be independent of other activities of this drug such as re-uptake inhibition of monoamines and blockade of K+ channels.

Amitriptyline↗
PubMed1992

Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG.

In this paper, we demonstrate the synthesis of the complement component C2 and factors B and D by the human astroglioma cell line U105-MG. All three components were structurally and antigenically similar to their serum counterparts, as determined by biosynthetic labelling studies or Western blot analysis. Northern blot analysis demonstrated that the mRNAs of all three components had the same apparent sizes as the equivalent mRNAs from hepatocyte and monocyte cell lines. Interestingly, U105-MG cells produce two C2 transcripts with sizes of approximately 2.8 and 2.3 kb. Interferon-gamma (IFN-gamma) enhanced the expression of C2 and factor B mRNA and protein in a dose- and time-dependent fashion, while factor D expression was refractory to IFN-gamma. IFN-gamma appeared to predominantly enhance the expression of the large (2.8 kb) C2 transcript. Kinetic studies demonstrated peak C2 and factor B expression in 48 h in response to IFN-gamma, similar to the acute-phase response of factor B in serum. These data are the first to demonstrate the synthesis of C2 and factor D by astroglioma cells. Combined with previous reports documenting the synthesis of C3 by astrocytes, our data suggest that endogenous synthesis of complement proteins, and particularly of alternative pathway activation components (C3, factors B and D), may play an important role in host defence in the central nervous system.

Astrocytoma↗
PubMed1992

Neutrophil adhesion to TNF alpha-activated endothelial cells potentiates leukotriene B4 production.

Since adhesion of neutrophils (PMN) to endothelial cells may influence PMN activation responses, we examined whether adhesion of PMN to TNF alpha-activated human umbilical vein endothelial cells (HUVEC) stimulates leukotriene B4 (LTB4) production. Endothelial adhesivity towards PMN increased after HUVEC pretreatment with TNF alpha for 4 h. LTB4 production increased markedly in response to stimulation with arachidonic acid (20 microM) when PMN were added to the hyperadhesive HUVEC. In contrast, stimulation of PMN in suspension did not potentiate LTB4 production. LTB4 production persisted when PMN were applied to TNF alpha-pretreated HUVEC fixed with 1% paraformaldehyde excluding the possibility that metabolic activity of endothelium participates in this response. PMN adhesion to plastic and gelatin also enhanced LTB4 indicating that adhesion was a critical event in inducing LTB4 production. We used monoclonal antibodies (mAb) to adhesion molecules on endothelial cells (i.e., endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1)) or on PMN (CD18) to assess the role of PMN adhesion to the activated endothelium on LTB4 potentiation. Both anti-ELAM-1 mAb and anti-ICAM-1 mAb inhibited PMN adhesion (by 55 and 41%, respectively) as well as LTB4 production (by 65 and 50%, respectively). Anti-CD18 mAb also reduced the adhesion (65%) and the LTB4 production (66%). Furthermore, combination of anti-ELAM-1 mAb (H18/7) and anti-ICAM-1 mAb (RR1/1) or of anti-ELAM-1 mAb (H18/7) and anti-CD18 mAb (IB4) had an additive effect in inhibiting both PMN adhesion as well as LTB4 production. PMN adherence to immobilized recombinant soluble rELAM-1 or rICAM-1 also increased LTB4 production, which was prevented with relevant mAbs. However, neither rELAM-1 nor rICAM-1 stimulated LTB4 production of PMN in suspension. We conclude that PMN adhesion to TNF alpha-stimulated endothelial cells enhances LTB4 production by PMN, a response activated by binding of PMN to expressed endothelial cell surface adhesion molecules.

Antigens, CD↗
PubMed1992

Unfolding domains of recombinant fusion alpha alpha-tropomyosin.

The thermal unfolding of the coiled-coil alpha-helix of recombinant alpha alpha-tropomyosin from rat striated muscle containing an additional 80-residue peptide of influenza virus NS1 protein at the N-terminus (fusion-tropomyosin) was studied with circular dichroism and fluorescence techniques. Fusion-tropomyosin unfolded in four cooperative transitions: (1) a pretransition starting at 35 degrees C involving the middle of the molecule; (2) a major transition at 46 degrees C involving no more than 36% of the helix from the C-terminus; (3) a major transition at 56 degrees C involving about 46% of the helix from the N-terminus; and (4) a transition from the nonhelical fusion domain at about 70 degrees C. Rabbit skeletal muscle tropomyosin, which lacks the fusion peptide but has the same tropomyosin sequence, does not exhibit the 56 degrees C or 70 degrees C transition. The very stable fusion unfolding domain of fusion-tropomyosin, which appears in electron micrographs as a globular structural domain at one end of the tropomyosin rod, acts as a cross-link to stabilize the adjacent N-terminal domain. The least stable middle of the molecule, when unfolded, acts as a boundary to allow the independent unfolding of the C-terminal domain at 46 degrees C from the stabilized N-terminal unfolding domain at 56 degrees C. Thus, strong localized interchain interactions in coiled-coil molecules can increase the stability of neighboring domains.

Animals↗
PubMed1992

A comparative ultrastructural and histochemical study of the metacercarial cyst walls of four species of Paragonimus (Troglotrematidae: Trematoda).

The metacercarial cyst walls of Paragonimus westermani, P. miyazakii, P. ohirai, and P. iloktsuenensis were examined using ultrastructural and histochemical techniques. The cyst walls of P. westermani, P. miyazakii, and P. ohirai were found to have five distinct layers, whereas the wall of P. iloktsuenensis had only two. The so-called outer cyst wall recognized on light microscopy by Miyazaki (1961) was composed of layers I-III and the so-called inner cyst wall comprised layers IV and V. The outermost layer (I) consisted of collagen fibers and probably originated from the host. Layer III detached easily from layer IV on removal of the cysts from the host tissues. Layer IV was composed of proteoglycans, and layer V consisted of protein alone. A regular hexagonal pattern in layer V appeared to be characteristic of P. westermani. Although the basic morphological patterns observed in the layers constituting the cyst walls were similar in all species examined, the thickness of each layer was apparently different. This characteristic seems to be a suitable criterion for the identification of metacercarial cysts of Paragonimus species.

Animals↗
PubMed1992

Dual-energy X-ray absorptiometry in the lumbar spine, proximal femur and distal radius in children.

Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) in the lumbar spine, proximal femur and distal radius in 48 Japanese children aged 3-18 years. In the normal children (n = 32), BMD increased with age in all locations, with a nearly twofold increase from preschool age to adolescence. Most of the children with chronic diseases known to affect bone metabolism (e.g., steroid osteoporosis) (n = 16) had low BMD in every region, indicating that these disease states probably affect multiple sites of the skeleton in children.

Absorptiometry, Photon↗
PubMed1992

Evaluation of a cholinomimetic drug, 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta [b] quinoline (NIK-247), as an enhancer of endogenous efflux of acetylcholine from brain slices.

Basal and high K(+)-stimulated efflux of endogenous ACh from slices of brain was measured to evaluate the cholinomimetic effect of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b] quinoline monohydrate HCl (NIK-247) on the central nervous system. The drug NIK-247 dose-dependently accelerated the efflux of ACh from slices of striatum. The maximum increase produced by 1.0 x 10(-4) M of NIK-247 was 329% in basal and 1332% in 30 mM K(+)-stimulated efflux. This drug was nearly twice as potent as THA (9-amino-1,2,3,4-tetrahydroacridine HCl) but had the same potency as physostigmine, in enhancing basal efflux, although there was no significant difference between the efficacy of these drugs in enhancing the K(+)-stimulated efflux. Both basal and 50 mM K(+)-stimulated efflux of ACh were increased by NIK-247, not only from the striatum but also from slices of frontal cortex and hippocampus. The activity was more effective in the striatum than in other tissues, and more effective on K(+)-stimulated than on basal efflux, regardless of the region of the brain. These effects of NIK-247 may be a result mainly of its inhibition of cholinesterase and its other biological characteristics, such as K+ channel blockade, capable of modulating release of ACh, may not be of major importance.

Acetylcholine↗
PubMed1992

Role of adrenergic neuronal activity in the yawning induced by tacrine and NIK-247 in rats.

The present experiments were performed to investigate the potential role of central adrenergic neurons in regulating occurrence of yawning in rats. Intraperitoneal injection of tacrine (THA) or 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)-quinoline monohydrate HCl (NIK-247), cholinesterase inhibitors, induced yawning, which was markedly increased by pretreatment with the beta-adrenoceptor antagonist, pindolol. The yawning evoked by tacrine or NIK-247 given alone or in combination with pindolol was inhibited by pretreatment with scopolamine but not by mecamylamine or spiperone. Treatment with tacrine or NIK-247 increased acetylcholine content of the striatum, but this effect was not enhanced by pindolol, which per se did not affect basal acetylcholine content. Moreover, pretreatment with the central adrenaline synthesis inhibitors, (+-)-2,3-dichloro-alpha-methylbenzylamine HCl (LY-78335) and 2-cyclooctyl-2-hydroxyethylamine HCl (UK-1187A), increased tacrine-induced yawning. Subcutaneous injection of talipexole (B-HT 920), a dopamine D2 receptor agonist, evoked yawning, which was also increased by pindolol, LY-78335, and UK-1187A. These receptors antagonists and synthesis inhibitors per se did not cause yawning responses. The results suggest that the beta-adrenoceptor blockade and the inhibition of adrenaline synthesis facilitate the occurrence of yawning induced by cholinergic and dopaminergic agonists, and thus the central adrenergic neuronal systems may be implicated in the regulation of yawning responses.

Acetylcholine↗
PubMed1992

Tumor necrosis factor-alpha-mediated decrease in glutathione increases the sensitivity of pulmonary vascular endothelial cells to H2O2.

We examined the effects of tumor necrosis factor-alpha (TNF alpha) stimulation of endothelial cells on the increase in endothelial permeability induced by H2O2. Bovine pulmonary microvascular endothelial cells (BPMVEC) were grown to confluence on a microporous filter and the 125I-albumin clearance rate across the monolayer was determined. Pretreatment with TNF alpha (100 U/ml) for 6 h had no direct effect on transendothelial 125I-albumin permeability. However, TNF alpha pretreatment enhanced the susceptibility of BPMVEC to H2O2; that is, H2O2 (10 microM) alone had no direct effect, whereas H2O2 increased 125I-albumin permeability more than threefold when added to monolayers pretreated for 6 h with TNF alpha. Determination of lactate dehydrogenase release indicated that increased permeability was not due to cytolysis. We measured the intracellular contents of GSH and catalase to determine their possible role in mediating the increased susceptibility to H2O2. TNF alpha treatment (100 U/ml for 6 h) decreased total GSH content and concomitantly increased the oxidized GSH content, but did not alter the cellular catalase activity. The role of GSH was examined by pretreating endothelial cells with 2 mM GSH for 3 h, which produced an 80% increase in intracellular GSH content. GSH repletion inhibited the increased sensitivity of the TNF alpha-treated endothelial cells to H2O2. We tested the effects of xanthine oxidase (XO) inhibition since XO activation may be a source of oxidants responsible for the decrease in cellular GSH content. Pretreatment with 0.5 mM oxypurinol attenuated the synergistic effect of TNF alpha and H2O2 on endothelial permeability. The results indicate that decreased oxidant buffering capacity secondary to TNF alpha-induced reduction in intracellular GSH content mediates the increased susceptibility of endothelial cells to H2O2. This mechanism may contribute to oxidant-dependent vascular endothelial injury in septicemia associated with TNF alpha release.

Animals↗
PubMed1992

Concomitant increase in putrescine incorporation with transferrin uptake into rat reticulocytes.

Concomitant increase in putrescine incorporation with transferrin uptake into rat reticulocytes was found. [14C]Putrescine incorporation occurred in the presence of transferrin at 37 degrees C. The subcellular distribution of incorporated [14C]putrescine showed that the incorporation in the plasma membrane time dependently increased. Both 125I-labeled transferrin uptake and [14C]putrescine incorporation decreased when ethylene glycol bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid was added, while it increased with the addition of A23187.

Animals↗
PubMed1992

Inhibitory effects of cyclopiazonic acid on the spike after-hyperpolarization in rat sympathetic neurons.

Cyclopiazonic acid (CPA), a novel specific inhibitor of Ca(2+)-ATPase in muscle sarcoplasmic reticulum, shortened the Ca(2+)-dependent after-hyperpolarization (AHP) following a spike in the rat superior cervical ganglion. This inhibitory effect was reversible and dependent on concentrations between 1 and 5 microM. The AHP in the presence of 5 microM CPA was not depressed further by ryanodine, nor was it affected by repetitive stimulation. These results suggest that CPA inhibits the intracellular Ca2+ release, probably due to the depletion of Ca2+ stores induced by inhibition of the ATP-dependent Ca2+ pump.

Animals↗
PubMed1992

Thoracic extramedullary hematopoiesis associated with hereditary spherocytosis.

A 54-year-old man was diagnosed with hereditary spherocytosis. An X-ray of the chest disclosed bilateral round masses in the upper and lower posterior mediastinum. CT showed homogeneous round masses of soft tissue density in the posterior mediastinum. A needle biopsy of the mass showed hyperplastic erythroid bone marrow. Fatty metamorphosis of the masses was observed in CT 2 years after splenectomy but showed no change in size.

Hematopoiesis, Extramedullary↗
PubMed1992

Effects of 2-mercaptopropionylglycine on the development of X-ray-induced cataract in rats.

The effect of 2-mercaptopropionylglycine on the development of cataract induced by a single dose of X-ray (10 Gy) was investigated in rats. Intraperitoneal injection of 20 mg/kg, three times weekly starting 1 day after irradiation delayed the development of X-ray-induced cataracts significantly. The amounts of non-protein SH groups, malondialdehyde and the Na+/K+ ratio, in the lenses of rats post-treated with the drug were significantly maintained at normal levels even at 27 weeks after irradiation. On the other hand, a single administration of 250 mg/kg of the compound, 30 min prior to irradiation had no effect on cataract progression induced by X-ray.

Animals↗
PubMed1992

[Lipopolysaccharide binding protein enhances intratracheally administrated lipopolysaccharide-induced acute lung inflammation via a CD14 receptor].

We examined the role of lipopolysaccharide binding protein (LBP) in the airspace and the CD14 receptor on alveolar macrophages in TNF alpha production and neutrophil (PMN) sequestration in lungs induced by intratracheal injection of lipopolysaccharide (LPS). LPS alone (Salmonella minnesota wild-type; 20 ng) or LPS + LBP complex [LPS (20 ng) + rabbit LBP (500 ng); preincubated for 30 min at 37 degrees C] was injected intratracheally into isolated rabbit lungs perfused with lactate-Ringer-albumin solution. Human PMN (5 x 10(7)) were added to the perfusate after 2 hr perfusion. Samples of lung perfusate were collected every 30 min for 180 min, after which bronchoalveolar lavage (BAL) was also performed. TNF alpha concentration in the perfusate and BAL fluid were determined using a bioassay with L-929 fibroblasts. PMN accumulation in the lung was determined by myeloperoxidase assay of the lung homogenate. LPS alone did not significantly increase TNF alpha production or PMN accumulation in lungs, whereas LPS/LBP complex increased TNF alpha concentration in the perfusate and PMN accumulation. Intratracheal injection of anti-CD14 antibody (40 micrograms) with LPS/LBP complex prevented TNF alpha production and subsequent PMN sequestration. We conclude that LBP in the airspace enhances the effect of LPS on TNF alpha production via a CD14-dependent pathway, and this subsequently contributes to PMN sequestration in the lungs. Airspace accumulation of LBP secondary to increased vascular and epithelial permeability may play a critical role in the development of septic shock and lung injury by promoting TNF alpha production via a CD14-dependent mechanism.

Acute Disease↗
PubMed1992

Keratoepithelioplasty in rat: development of a model and histological study.

A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using this model. The entire corneal epithelium was removed mechanically and a 1.5-mm width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observations showed much less vascular invasion in the part of the cornea adjacent to the lenticule than in other parts of the cornea, and the cornea remained clear adjacent to the lenticule. Histologically, a few vessels were observed in the corneal stroma under the lenticule. Epithelial cells on the lenticule specimens showed histological characteristics of the corneal epithelium. These findings indicate that one of the functions of KEP is to block neovascularization in the newly developing corneal epithelium by transplanting the lenticule between the corneal epithelium and conjunctival vessels. The present study also confirmed that this model is useful in the research of the pathophysiological mechanism of KEP.

Animals↗
PubMed1992

The relationship of putrescine incorporation to transferrin uptake by reticulocytes.

We previously reported that putrescine incorporation occurred during transferrin uptake by rat reticulocytes (1). Both the putrescine incorporation and transferrin uptake were enhanced by the presence of Ca2+ and A23187. Furthermore, putrescine dose-dependently increased the transferrin uptake. Additionally, transglutaminase inhibitors partially blocked not only the putrescine incorporation but also the transferrin uptake.

Animals↗