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T Yajima

Publications and source records attributed to T Yajima.

At least 181 records · Page 10Linked to original sources

[Basic study on human interferon-beta: Part III. The mechanisms of its antitumor effect].

The mechanisms of the direct and indirect antitumor effects of human interferon-beta (IFN-beta, MR-21) were examined. IFN-beta suppressed DNA, RNA and protein synthesis in cells derived from human tumor. The expression of cellular oncogenes (c-Ha-ras and c-myc) in tumor-originated cells was also suppressed by IFN-beta. These results suggest that such suppression is one possible mechanism of the direct anticellular effect induced by IFN-beta. IFN-beta augmented NK cell activity and the ADCC activity of human peripheral blood lymphocytes. It is also suggested that these are two of the immune system-mediated mechanisms responsible for the indirect antitumor effect of IFN-beta in vivo.

Antibody-Dependent Cell Cytotoxicity↗

Contractile effect of short-chain fatty acids on the isolated colon of the rat.

The contractile effect of short-chain fatty acids on proximal, middle and distal segments of the rat colon was studied in vitro. A single contraction of the longitudinal muscle of the everted preparation of the middle and distal but not the proximal colon was induced by mucosal application of propionate, butyrate or valerate. Sigmoid dose-responses were observed between contraction and log dose of propionate, butyrate and valerate. The threshold concentration of short-chain fatty acids was between 0.02 and 0.04 mM. A maximal contraction was induced with 0.1 mM-propionate, butyrate and valerate. While acetate (up to 10 mM) and lactate (up to 30 mM) had no contractile effect at all. Serosal application of short-chain fatty acids was without effect, while the contractile response with up to 10 mM-propionate was abolished in both the middle and distal colon by scraping away the mucosa. Cumulative addition of short-chain fatty acids to the organ bath (without wash-out of the first dose) caused adaptation of the contractile response; thus, the effect of propionate (1 mM) was abolished by prior addition of acetate (10 mM) or lactate (30 mM) or propionate (1 mM) or butyrate (1 mM) or valerate (1 mM). The contractile effect of propionate was also inhibited by atropine (1 microM), procaine (0.4 mM) and tetrodotoxin (3 microM); was unaffected by hexamethonium (0.1 mM) and enhanced by eserine (10 nM). The results suggest that short-chain fatty acids, which are normal constituents of the colon, have the ability to stimulate colonic contractions, probably via an enteric reflex involving local sensory and cholinergic nerves.

Adaptation, Physiological↗

Separation of metallothionein into isoforms by column switching on gel permeation and ion-exchange columns with high-performance liquid chromatography-atomic-absorption spectrophotometry.

Metallothionein in tissue supernatant was separated into isoforms by on-line switching from gel filtration to ion-exchange columns and the metals bound to the isoproteins were directly determined by using a flame atomic-absorption spectrophotometer as a specific detector for metals. Conditions for elution of the gel filtration column were established and Tris-HCl buffer solutions in low concentration were shown to be applicable to the column-switching experiment. The effects of pH, buffer and salt concentrations on the elution of metallothionein are discussed.

Animals↗

Induction of rat hepatic and intestinal alkaline phosphatase activity produced by bile from bile duct-ligated animals.

Bile duct ligation caused a threefold elevation of not only hepatic but also intestinal alkaline phosphatase. The increase was transient in intestinal mucosa and peaked at 12 h. Hepatic phosphatase levels reached a plateau by 36 h. Intraperitoneal injection of bile from ligated animals into normal rats produced qualitatively similar results. Studies were performed to further characterize the induction of phosphatase activity in both tissues. The addition of bile from ligated animals to organ explants of liver and intestine produced a two- and threefold rise in activity, respectively. Therefore, neural and hormonal factors are not essential in producing this induction. The increased activity produced in vitro in both tissues was due to heat-stable and dialyzable factor(s) and was blocked by inhibitors of protein synthesis. In the intestine activity occurred over the entire brush border as demonstrated by electron microscopic histochemistry. In the liver, increased activity was noted over the entire plasma membrane and was not localized to the canalicular membrane. Tunicamycin treatment of liver and intestinal explants markedly suppressed the induced phosphatase activity. Simultaneous treatment with protease inhibitors restored some of the phosphatase activity. These findings suggest that glycosylation of the alkaline phosphatase might provide at least partial protection from proteolysis.

Alkaline Phosphatase↗

Interaction of prostaglandin E2 and bradykinin in the induction of afferent splanchnic nerve discharges in cats.

In anesthetized cats, the administration of either bradykinin (BK) (0.3-3 micrograms/kg) or prostaglandin E2 (PGE2) (1-30 micrograms/kg) into the cranial mesenteric artery dose-dependently evoked the firing discharge in the proximal end of the afferent greater splanchnic nerves with a latency of about 10 sec, the pronounced contraction of the longitudinal muscle of the jejunum, and changes in blood pressure. PGE2 at the doses of 1-10 micrograms-kg i.a. potentiated the BK (1 microgram/kg i.a.)-induced firing discharge of the afferent splanchnic nerves of which latency was also shortened, but did not alter the BK-induced jejunal contraction and blood pressure change. However, trimoprostil (30 micrograms/kg i.a.), a trimethyl PGE2 derivative, did not change all of these responses to BK. Aspirin at 50 mg/kg i.v. markedly prevented the BK-induced nerve discharges, but not the BK-induced jejunal contraction. These results taken together indicate that PGE2 may be involved in the facilitatory response of afferent splanchnic nerve discharges to BK, but not involved in the BK-induced jejunal contraction and blood pressure change. The findings on trimoprostil present the possibility that derivatization of PGE2 could modify its inherent ability to produce adverse side-effects.

Animals↗

Effect of sodium propionate on the contractile response of the rat ileum in situ.

Effects of short-chain fatty acids (SCFA) on the contractile response of rat ileum were studied in vivo. The contractile response was estimated by means of changes in the intraluminal pressure under the isometric condition. Intravenous administration of sodium salts of propionate, butyrate, valerate or caproate produced biphasic contractions: an initial phasic contraction and a subsequent tonic contraction. The effect of propionate was studied in detail. A sigmoid dose-response curve was obtained for the phasic contraction. Atropine, hexamethonium and tetrodotoxin inhibited the phasic contraction, while neostigmine vigorously enhanced it. On the other hand, the tonic contraction was not inhibited by atropine, hexamethonium or tetrodotoxin. Repeated administration of propionate at intervals of less than 3 min led to tachyphylaxis, and this tachyphylaxis disappeared by about 10 min. These results suggest that SCFA induced the biphasic contraction of the rat ileum, probably by neurogenic and myogenic mechanisms.

Animals↗

Ectopic mineralization in fibroblast cultures.

A human gingival fibroblast cell line was cultured in a DM-153 medium supplemented with 10% bovine serum. The cells in culture showed both intracellular and extracellular ectopic mineralization. Ultrastructurally, mineralization began within the round and irregularly shaped vesicles contained in large cytoplasmic vacuoles of fibroblasts. The first identifiable needle-shaped crystal was deposited on a point of the inner leaflet of the vesicle membrane. With the increase in size of the crystals, the membranous envelopes were gradually lost, and lattice planes (8.2 A) occurred within the crystal thickness. Crystals radiating from each mineralization center formed mineralized spherules in cytoplasmic vacuoles. The crystal clusters were extruded from the cells through membrane fusion or cellular degeneration in long-term cultures. These liberated clusters formed extracellular mineralizing matrices around the fibroblasts. In extracellular mineral deposition, the initial crystals arose within extracellular matrix vesicles, but were not associated with collagen, elastic fibers, and any other structures. These findings indicate that mineral accumulation and phase transformation of amorphous mineral to a crystalline form take place within the vesicular structures. This provides additional evidence for the view that the initiation of calcification and mineralization requires a microenvironment limited by a membranous (vesicular) structure derived from cells.

Adult↗

[Effects of bromazepam on responses of mucosal blood flow of the gastrointestinal tract and the gastric motility to stimulation of the amygdala and hypothalamus in conscious cats].

Electrical stimulation (ES) of the nucleus amygdaloideus centralis ( NAmC ) and basolateralis ( NAmBL ), like norepinephrine, decreased mucosal blood flow of the gastric antrum and duodenum and decreased antral motility amplitude in gallamine-immobilized cats. ES of the nucleus lateralis hypothalami (NHL) less extensively produced a similar action. The NAmC stimulation elevated BP and renal sympathetic discharges, whereas the NAmBL stimulation lowered BP. These findings indicate that the gastric and pressor responses to the NAmC stimulation may be attributed to an increase in cerebral sympathetic outflow. Bromazepam dose-dependently (0.1 approximately 1.0 mg/kg, i.v.) prevented these gastric, pressor and renal sympathetic responses to the NAmC stimulation, but it did not alter the depressor response to the NAmBL stimulation or the norepinephrine-induced reactions. Bromazepam less extensively attenuated the gastric and pressor responses to the NHL stimulation. Moreover, bromazepam inhibited stress-induced gastric ulcer formation in rats more markedly than cimetidine, sulpiride and metoclopramide. Bromazepam markedly decreased stress-induced selective increase in the glucose utilization rate in the NAmC among various amygdala nuclei. These results indicate that effects of bromazepam on the gastric and pressor responses to the NAmC stimulation may be due to the inhibition of central sympathetic outflow, and the NAmC are more sensitive to bromazepam than the NHL and other amygdala nuclei.

Amygdala↗

Alteration in sensitivity of transmural electrical response to propionate in rat colon after chronic luminal infusion of short-chain fatty acids.

The colon is always exposed to abundant short-chain fatty acids (SCFA) produced by gut fermentation. In order to know an effect of chronic load of SCFA on colonic functions, we studied that the acute and chronic effects of SCFA on transmural potential difference (p.d.) across the proximal colon of germ-free (GF), gnotobiotic (GB) and conventionalized (CV) rats in vivo. Intravenous administration of SCFA (acute effect), such as propionate, butyrate, valerate or caproate, caused a transient increase in the p.d. The acute effects of propionate were studied in detail. The dose-response curve of CV rats shifted markedly to the right compared to that of GF rats, suggesting that CV rats were less sensitive to the acute effects of propionate than GF rats. Decreased sensitivity also appeared in GB rats (monocontamination with Fusobacterium varium). By chronic luminal infusion of isotonic sodium propionate or butyrate (25.5 ml/day) into the proximal colon of GF rats for 7 days (chronic effect), the acute effects of propionate were reduced. Atropine reduced the p.d. increment produced by propionate and shifted the dose-response curve of propionate to the right. These results suggest that chronic luminal load of SCFA resulted in a type of chronic refractoriness.

Animals↗

Effects of epidermal growth factor on osteoblastic cells in vitro.

The effect of epidermal growth factor (EGF) on clone MC3T3-El cells that have osteoblastic activity was examined by phase-contrast microscopy and electron microscopy; hydroxyproline content, collagen synthesis, collagen pattern, and alkaline phosphatase (ALP) activity were also determined. We found that EGF (0.4 ng/ml) transformed the cells from their normal polygonal shape to a spindle-like morphology by 8 h. This hormone also caused dose-related suppression of hydroxyproline content and ALP activity which was detectable 2 days and 1 day, respectively, after EGF addition. Indomethacin did not affect hydroxyproline content and ALP activity, suggesting that the effect of EGF on the cells may not be mediated by prostaglandins. Epidermal growth factor at concentrations of 2 to 50 ng/ml significantly decreased collagen synthesis in the cells, whereas protein synthesis was stimulated. Electron microscopy demonstrated that collagen fiber formation was also reduced by EGF; an immature type of fibril was observed compared with the typical cross-striated one in the controls. Moreover, the hormone treatment also resulted in the appearance of type III collagen in addition to the type I already present in the cells. These suppressive effects of EGF on MC3T3-El cells in vitro suggest that this hormone may be involved in bone remodelling in vivo as well.

Alkaline Phosphatase↗

[Anti-ulcerogenic and cytoprotective effects of trimoprostil (Ro 21-6937), a trimethylprostaglandin E2 derivative].

Anti-ulcerogenic effects of trimoprostil, a prostaglandin E2 (PGE2) derivative, were studied in comparison with those of PGE2, cimetidine and sulpiride. Trimoprostil and PGE2 given p.o. prevented the formation of gastric lesions produced by absolute ethanol, 0.2N NaOH, 0.6N HCI and hypertonic NaCl solutions in rats and aspirin-induced fecal occult bleeding in dogs. Although both prostaglandins did not alter the gastric mucus content, they equivalently prevented the stress-induced decrease in the mucus content in rats. The duration of these effects of trimoprostil was longer than those of PGE2. Cimetidine and sulpiride did not exert such cytoprotective effects. Trimoprostil inhibited stress-induced gastric ulcer formation in rats more markedly than PGE2, cimetidine and sulpiride. Trimoprostil and PGE2 at the cytoprotective dose (30 micrograms/kg, p.o.) did not change the gastric blood flow in conscious rats. In Shay rats, trimoprostil at doses larger than the cytoprotective doses inhibited the gastric acid secretion when given p.o., but was not effective when given i.d. PGE2 exerted the similar action, but the potency was clearly weaker than that of trimoprostil. In Heidenhain-pouch dogs, trimoprostil also inhibited the gastric acid secretion stimulated by pentagastrin more markedly than did cimetidine. In conclusion, trimoprostil at doses smaller than the antisecretory doses exerted gastric cytoprotective action with a longer duration than that of PGE2, probably through the preservation of the mucus barrier. Such cytoprotection was not found with cimetidine and sulpiride.

Animals↗