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Biomedical subjects

F Ito

Publications and source records attributed to F Ito.

At least 181 records · Page 10Linked to original sources

Inhibitory effect of local anesthetics on Na+/H+ antiporter in brush border membrane-reconstituted vesicles.

The effects of three local anesthetics, lidocaine, dibucaine, and tetracaine, on Na+/H+ antiporter activity were examined in brush border membrane-reconstituted vesicles. Lidocaine at 10 microM inhibited H+ efflux in the presence of an inward Na+ gradient, suggesting that this anesthetic specifically inhibits the Na+/H+ antiporter. On the other hand, dibucaine and tetracaine decreased H+ efflux even in the absence of a Na+ gradient.

Anesthetics, Local↗

Glucuronate-modified liposomes with prolonged circulation time.

For the purpose of obtaining liposomes with long circulation time in blood, we synthesized 1-O-palmityl-D-glucuronic acid (PGlcUA) and incorporated it into the liposomal membranes. The clearance of the PGlcUA-liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol, and PGlcUA (40:40:20 as a molar ratio) from blood and their tissue distribution were compared with those of dipalmitoylphosphatidylglycerol (DPPG)-liposomes (DPPC/cholesterol/DPPG = 40:40:20). When [3H]inulin-loaded PGlcUA-liposomes and DPPG-liposomes were intravenously injected into rats, the half-life of the PGlcUA-liposomes in the blood appeared to be 1.7-fold longer than that of DPPG-liposomes. Radioactivities present in plasma and various tissues were measured 22 h after administration of these liposomes, and radioactivity remaining in the plasma was 2.5-fold greater when PGlcUA-liposomes were injected. The distribution pattern of [3H]inulin in PGlcUA-liposomes was similar to that in DPPG-liposomes. The radioactivity recovered in urine was 25% lower in rats treated with PGlcUA-liposomes than in those treated with DPPG-liposomes. Since both PGlcUA- and DPPG-liposomes exhibited similar size distribution and zeta-potential, glucuronic acid, rather than negative charge, on the liposomal surface appears to endow liposomes with a longer circulation time in the bloodstream.

Animals↗

Classification of the intrafusal muscle fibres in the frog muscle spindle: histochemical and immunofluorescent studies.

Intrafusal muscle fibres from bull-frog semitendinosus, iliofibularis and sartorius muscles were classified into three types using the histochemical, immunofluorescent and morphological characteristics, with reference to the extrafusal muscle fibres, which were classified into five types in accordance with Rowlerson & Spurway (1988). Immunofluorescent reactions with antibodies against slow or fast myosins obtained from anterior or posterior latissimus dorsi muscles (ALD or PLD), respectively, of chicken were used as the primary criterion. Histochemical profiles of muscle fibres were classified into nine types of myosin ATPase activity as the secondary criterion. Anti-PLD intrafusal fibres (polar zone) with ATPase profiles of moderate to high acid and alkaline stabilities correspond to large nuclear bag fibres in the classification of Diwan & Ito (1989), whereas anti-ALD fibres (polar zone) with alkaline-labile ATPase profiles correspond to medium nuclear bag fibres. On the basis of diameter, anti-PLD fibres (polar zone) with ATPase profiles of moderate to low acid stability and moderate to high alkaline stability seem to correspond to two types of small nuclear chain fibre. Variations between muscles, between intra- and extrafusal fibres and also between zones along intrafusal fibres are discussed.

Adenosine Triphosphatases↗

[Clinicopathological study of endometrial-type adenocarcinoma of uterus].

Seventy-one resected cases of endometrial-type adenocarcinoma of uterus were clinicopathologically investigated. As to the gross findings, the incidence of localized type and diffuse type was 47.9% and 52.1%, while that of extroversive type and introversive type was 59.1% and 40.9%, respectively. The incidence of the lesions less than 3 cm in diameter was 36.7% and that beyond 5 cm was 28.1%. The majority (88.7%) of the endometrial-type adenocarcinoma were histologically well-differentiated. Concerning depth of invasion, the incidence of the cases of intramucosal invasion, invasion within 1/3 of muscle layer, invasion between 1/3 and 2/3 of muscle layer, and invasion beyond 2/3 of muscle layer was 19.7%, 46.5%, 16.9%, and 16.9%, respectively. Lymphatic and venous invasion were more frequently found in diffuse, introversive, moderately-differentiated, and deep invasive types than the other types. Lymph nodal metastasis was found in 9.8% of all cases (16.2% in diffuse type, 20.8% in introversive type, 33.3% in moderately-differentiated type and 41.7% in the cases beyond 2/3 of muscle layer).

Adenocarcinoma↗

Possible role of prostaglandins as negative regulators in growth stimulation by tumor necrosis factor and epidermal growth factor in human fibroblasts.

Recombinant tumor necrosis factor (TNF), epidermal growth factor (EGF), and transforming growth factor beta (TGF-beta) stimulated growth of confluent human diploid fibroblasts (FS-4 cells) in the presence of fetal calf serum. TGF-beta synergistically enhanced both the TNF- and EGF-stimulated cell growth, whereas synergism between the mitogenic action of EGF and that of TNF was not observed. When indomethacin or acetylsalicylic acid, an inhibitor of prostaglandin production, was added to FS-4 cells, cell growth stimulated by EGF or TNF was increased, suggesting that prostaglandins induced by these mitogens antagonize their growth stimulatory actions. In contrast, neither indomethacin nor acetylsalicylic acid had a significant effect on the TGF-beta-induced growth of FS-4 cells. Mitogenic responses of indomethacin-treated cells to EGF, TNF, and TGF-beta were similarly suppressed by the addition of exogenous prostaglandin D2 (PGD2). Other prostaglandins such as PGE2 and PGF2 produced less inhibition of the cell growth.

Arachidonic Acids↗

Tumor necrosis factor is cytotoxic to human fibroblasts in the presence of exogenous arachidonic acid.

Recombinant human tumor necrosis factor (TNF) stimulated the growth of confluent human fibroblasts (FS-4) in serum-free culture medium. However, TNF had a cytotoxic effect upon the growth of FS-4 cells in combination with arachidonic acid. When arachidonic acid was added to culture medium in the absence of TNF, however, it had no effect on the cell growth. Arachidonic acid inhibited the TNF-induced cell growth in a dose-dependent manner: it reversed the TNF-stimulated growth to the control level at a concentration of 10 microM and was cytotoxic to TNF-treated FS-4 cells at higher concentrations. This cytotoxicity of TNF was not observed in FS-4 cells treated with palmitic acid. Indomethacin, a cyclooxygenase inhibitor, decreased the cytotoxic effect that TNF exerted in the presence of arachidonic acid. These results suggest that TNF becomes cytotoxic to FS-4 cells when arachidonic acid present in the culture medium is converted to prostaglandins.

Arachidonic Acids↗

Intrafusal muscle fibre types in frog spindles.

Muscle spindles from bullfrog semitendinosus, iliofibularis and sartorius muscles were examined with light and electron microscopy. Four types of intrafusal muscle fibre were identified according to their diameter, central nucleation and reticular zone arrangement: a large nuclear bag fibre, a medium nuclear bag fibre, and two types of small nuclear chain fibres with and without a reticular zone, respectively. It is suggested that they are comparable to the nuclear bag1, bag2 and chain fibres in mammalian muscle spindles.

Animals↗

[A clinical evaluation of the indications and utility of percutaneous gallbladder drainage].

Percutaneous gallbladder drainage (PGD) was performed in 78 patients with diseases of the bile duct system and pancreas, including 48 patients with acute cholecystitis. The procedure was utilized for the treatment of acute inflammation and obstructive jaundice, and this study was initiated to evaluate its utility and the potential indications. Following PGD, the inflammatory changes improved, and the clinical symptoms subsided, especially in cases of acute cholecystitis, in which it appears to have an excellent therapeutic value. Compared to cases of acute cholecystitis treated without PGD and used as controls, the clinical symptoms, laboratory findings and ultrasonographic findings were evaluated. Ultrasonographic findings, including signs of gallbladder swelling, thickening of the gallbladder wall, and as sonolucent layer in the wall were shown to be useful as positive indicators for the use of PGD. PGD also effective in cases of acute cholangitis, and cases of obstructive jaundice in which therapy was difficult using other bile drainage methods. PGD was also useful in establishing a visualization of the gallbladder and for cytological sampling of the bile in cases with negative cholecystography.

Acute Disease↗

Modification of sensory-terminal responses and membrane structure of frog muscle spindle by collagenase.

A preparation of decapsulated muscle spindles with intact sensory innervation has been developed to allow direct access to the sensory terminal for the application of drugs or to alter the extracellular ionic composition. Muscle spindles were isolated from semitendinosus muscles of the frog Rana catesbeiana, and were incubated in a calcium-free Ringer's solution containing 0.2% collagenase. Following optimal incubation at 34 degrees C for 30 min the response pattern of the spindles during stretch could not be distinguished from that of intact spindles, although the duration of individual afferent spikes was prolonged about 4 times normal. The spikes disappeared immediately after the Ringer's solution was replaced with an isotonic choline chloride solution, in contrast to those of intact spindles which remained for 30 min after the replacement. Electron microscopy showed that the outer and inner capsules were partially disrupted. No significant change was observed in the size or packing density of intramembrane particles in freeze-fracture replicas of spindles decapsulated under optimum conditions. More prolonged treatment with the enzyme resulted in abolition of the static component of the response during stretch, and also in an aggregation of the particles, whose size decreased and packing density increased.

Afferent Pathways↗

Effects of cyclic nucleotides and calcium on transduction and encoding processes in frog muscle spindle.

In decapsulated muscle spindles, application of dibutyryl cyclic AMP (d-cAMP, 0.1-10 mM) and forskolin (10-100 microM) increased the rate of spontaneous discharges and decreased the responsiveness to stretch. Addition of 2-5 mM CaCl2 or 0.5-2 mM BaCl2 to the above drugs prevented the deterioration of the responsiveness to stretch and the increase in the rate of spontaneous discharges. Similar changes in the afferent discharges were observed with application of isobutylmethyl-xanthine (IBMX, 0.5-2 mM) or carbonyl cyanide chlorophenylhydrazone (CCCP, 1-10 microM). Application of 0.1-1 mM quercetin resulted in a prolonged increase in the discharge rate, lasting 15-20 s after the release of stretch. These results suggest that cAMP is involved in the regulation of the sensory processes through a modification of intracellular calcium activity.

1-Methyl-3-isobutylxanthine↗

Pumiliotoxin alkaloids: relationship of cardiotonic activity to sodium channel activity and phosphatidylinositol turnover.

The cardiotonic activity of pumiliotoxin B (PTX-B, 6-(6',7'-dihydroxy-2',5'-dimethyl-(E)-4'-octenylidene)-8-hydroxy-8 -methyl-1- azabicyclo[4.3.0]nonane) as assessed in guinea pig atrial preparations is markedly dependent on the nature of the 6-alkylidene side chain. Pumiliotoxin A (PTX-A), which differs from PTX-B only in lacking the 7'-hydroxy moiety, is much less active than PTX-B. Alteration in the configuration of the 6'- and/or 7'-hydroxy side chain moieties in synthetic isomers of PTX-B reduces activity, while the lack of such moieties or replacement with methoxy or ketone moieties in PTX-B or PTX-A analogues yields cardiodepressant compounds. PTX-B markedly stimulates phosphoinositide turnover in atrial and brain preparations and sodium influx in brain preparations, while analogues that are cardiac depressant or have low cardiotonic activity have no or minimal effects on such parameters. It is suggested that activation of sodium channels and resultant stimulation of phosphoinositide breakdown play a role in the cardiotonic activity of pumiliotoxin alkaloids.

Alkaloids↗

Effects of tumor necrosis factor on cell growth and expression of transferrin receptors in human fibroblasts.

Human recombinant tumor necrosis factor (TNF) stimulated the growth of confluent human fibroblasts (FS-4) in the presence of fetal calf serum. Epidermal growth factor (EGF) similarly stimulated cellular growth; however other mitogenic factors such as insulin, fibroblast growth factor, 12-O-tetradecanoyl-phorbol-12-acetate and Ca2+ ionophore A23187 did not. The growth-stimulating action of TNF was not synergistic with the activity of EGF in the presence of serum. TNF induced a rapid increase in the binding of transferrin to the cell surface, followed by a return to the basal level within 5 min. A similar increase in transferrin binding was observed in FS-4 cells exposed to EGF. In contrast, insulin caused a prolonged stimulation of transferrin binding. These results suggest that TNF and EGF generate similar or identical intracellular signals for cellular growth and the regulation of transferrin receptor expression.

Cell Division↗

Reconstitution of the Na+/H+ antiporter: a new method for the determination of H+ efflux from Na+/H+ antiporter-reconstituted vesicles.

A Na+/H+ antiporter was solubilized with octyl-beta-D-glucopyranoside from rat renal brush border membrane and reconstituted in egg phosphatidylcholine liposomes. The activity of the antiporter was determined by a new method. Reconstitution was performed in a solution containing a pH-sensitive fluorescence dye, fluorescein isothiocyanate-dextran (FITC-dextran), at pH 5.5. The reconstituted vesicles, encapsulating FITC-dextran, were incubated at pH 8.0, and the intravesicular pH (pHi) was determined by monitoring fluorescence change of the dye. An increase in the fluorescence intensity which corresponded to an increase in pHi was observed. The rate of the increase was dependent on the concentration of the extravesicular Na+, and the efflux of H+ in the presence of 150 mM sodium gluconate was suppressed by the addition of amiloride. These results show that the Na+/H+ antiporter was functionally reconstituted and that its activity can be determined simply by the use of FITC-dextran.

Animals↗