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Biomedical subjects

H Nagaya

Publications and source records attributed to H Nagaya.

At least 37 records · Page 2Linked to original sources
PubMed1989

Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats.

The antisecretory and antiulcer activities of 2[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl] sulfinyl]-1H-benzimidazole (AG-1749) were investigated in dogs and rats. AG-1749 inhibited both the (H+ + K+)-adenosine triphosphatase activity in canine gastric microsomes and dibutyryl cyclic AMP-stimulated acid formation in isolated canine parietal cells and suppressed the acid secretion stimulated by histamine, pentagastrin, bethanechol or a peptone meal in Heidenhain pouch dogs; the ID50 values were between 0.2 and 0.7 mg/kg p.o. AG-1749 inhibited both the histamine-stimulated and the basal acid secretion in pylorusligated rats and prevented water immersion stress or aspirin-induced gastric lesions and mepirizole or cysteamine-induced duodenal ulcers in rats; the ID50 values were between 0.3 to 3.6 mg/kg p.o. or i.d. Furthermore, AG-1749 prevented gastric lesions induced by absolute ethanol or acidified aspirin, and accelerated the healing of acetic acid-induced gastric or duodenal ulcers in rats. The inhibitory potency of AG-1749 in dogs was much the same as that of omeprazole and about half that of ranitidine. However, it was about 2 to 10 times more potent than omeprazole and 4 to 34 times more potent than ranitidine in rats. These results suggest that AG-1749 exerts prominent antiulcer activities mainly by suppressing acid secretion via an inhibition of a proton pump in gastric parietal cells and partly by protecting the gastrointestinal mucosa against various ulcerative stimuli.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1987

Actions of antisecretory agents on proton transport in hog gastric microsomes.

The properties of K+-stimulated ATP hydrolysis (K+-ATPase) and vesicular accumulation of H+ (H+ accumulation) in hog gastric microsomes were investigated. The microsomes consisted of smooth surfaced vesicular particles, 70-300 nm in diameter. Both the activities of ATPase and the vesicular accumulation of H+ were stimulated by K+ in the presence of Mg2+, and enhanced by the K+-ionophore, valinomycin. However, there were differences in regulation of K+-ATPase and H+ accumulation by K+ ions, i.e. K+ at concentrations higher than 10 mM decreased K+-ATPase activity but further enhanced H+ transport. This observation suggests that the two reactions are partly independent. The H+ accumulation was inhibited by omeprazole, fenoctimine, spermine, and NaSCN, but not by cimetidine, prostaglandin E2, and atropine. The inhibitory effect of omeprazole on H+ accumulation paralleled the inhibition of K+-ATPase, while fenoctimine, spermine, and NaSCN suppressed H+ accumulation, without inhibiting K+-ATPase, under appropriate concentrations. In addition, the spontaneous diffusion of H+ across the microsomal membrane was markedly enhanced by fenoctimine, but not by the other agents used. These results indicate that omeprazole inhibits H+ accumulation by inhibiting K+-ATPase, fenoctimine suppresses H+ accumulation mainly by increasing the loss of accumulated H+ from the microsomal vesicles, spermine and NaSCN reduce H+ accumulation by inhibiting the transport of H+ into microsomal vesicles.

Adenosine Triphosphatases↗
PubMed1986

Spizofurone, a new anti-ulcer agent, increases alkaline secretion in isolated bullfrog duodenal mucosa.

The effect of spizofurone, a new anti-ulcer agent, on alkaline secretion was studied in an isolated sheet of bullfrog (10(-4)-10(-3) M) as well as prostaglandin E2 (PGE2, 10(-8)-10(-5) M) added to the nutrient solution increased alkaline secretion, transmucosal potential difference (PD) and short-circuit current (Isc), in a concentration-dependent manner. The maximum increases in alkaline secretion stimulated by spizofurone and PGE2 were much the same. Spizofurone also showed this effect when added to the secretory solution while PGE2 did not. Treatment with indomethacin partly but significantly inhibited the effect of spizofurone, but did not affect that of PGE2. These results indicate that the increase in alkaline secretion in bullfrog duodenal mucosa seen in the presence of spizofurone is mediated, at least in part, by stimulation of endogenous PGs synthesis.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Gastric mucosal protection by spizofurone.

The protective effect of spizofurone (AG-629) on the rat gastric mucosa was studied in the presence of various stimuli. Spizofurone given orally markedly inhibited gastric lesions induced by ethanol (ED50 = 6.5 mg/kg). Spizofurone inhibited ethanol-induced gastric lesions even when administered intraperitoneally (i.p.), but the onset of action after oral administration was shorter. Spizofurone given orally or i.p. in a dose range of 25-200 mg/kg inhibited indomethacin-induced gastric antral ulcers in re-fed rats. Furthermore, spizofurone potentiated the inhibitory effect of prostaglandin E2 on indomethacin-induced gastric antral ulcers. Spizofurone given i.p. prevented a decrease in potential difference and the formation of gastric lesions induced by intragastric instillation of 30 mM aspirin in 0.1 N HCl. Spizofurone given i.p. inhibited the increase in net fluxes of H+ and Na+ caused by intragastric instillation of 15% ethanol in 0.1 N HCl. These findings indicate that spizofurone, like prostaglandin E2, exerts gastric mucosal protection and even potentiates the anti-ulcer effect of prostaglandin E2. The gastric mucosal protection by spizofurone is ascribed in part to preservation of the mucosal barrier.

Animals↗
PubMed1985

Spizofurone (AG-629) increases gastric mucosal blood flow in dogs: a possible mechanism of its anti-ulcer effect.

The effect of spizofurone (AG-629), a new anti-ulcer agent, on gastric mucosal blood flow was investigated in anesthetized dogs and the effects were compared with those of prostaglandin E2. Intravenous administration of spizofurone in doses of 15 and 30 mg/kg caused a dose-related increase in gastric mucosal blood flow. Spizofurone (1-10 mg/ml) given intragastrically for 15 min produced a sustained increase in gastric mucosal blood flow in a concentration-dependent manner; with 3 mg/ml there was about a 50% increase in gastric mucosal blood flow at the peak and a 2 h duration of action. The mode of action of spizofurone was similar to that of prostaglandin E2. The reduction in the gastric mucosal blood flow as induced by indomethacin was markedly improved by spizofurone. The topical action of spizofurone was confirmed in an in situ experiment using a stomach flap fixed to a lucite chamber. These results indicate that spizofurone increases gastric mucosal blood flow after systemic and topical administration, and this increase in gastric mucosal blood flow would account for the anti-ulcer effects of this drug.

Aminopyrine↗
PubMed1985

Induction of antigen-specific suppressor cells in patients with hay fever receiving immunotherapy.

In order to evaluate the effect of immunotherapy on subpopulations of lymphocytes, peripheral blood mononuclear cells were fractionated into T and non-T cells by incubating in anti-immunoglobulin-coated plates. T cells were further fractionated into rye grass antigen-adherent and nonadherent fractions and human serum albumin (HSA)-adherent and nonadherent fractions by incubating in rye grass antigen-coated and HSA-coated plates, respectively. The mean rye antigen-stimulated proliferative response of rye antigen-adherent fraction was significantly lower than that of rye antigen-nonadherent fraction in patients with rye grass hay fever receiving immunotherapy. There was no difference in the rye antigen-stimulated proliferative response between the HSA-adherent and nonadherent fractions. Both the rye antigen-adherent and nonadherent fractions proliferated similarly when they were stimulated by an unrelated antigen, Candida albicans. The rye antigen-stimulated proliferative response of rye antigen-nonadherent cells could be suppressed by coculturing with rye antigen-adherent cells from patients receiving immunotherapy. Furthermore, the treatment of cocultures with monoclonal antibody against suppressor-cytotoxic T cell (OKT8) subpopulation and guinea pig serum complement reversed the suppression. In patients receiving no immunotherapy, there was no difference in the rye grass antigen-stimulated proliferative response between the rye antigen-adherent and nonadherent fractions. These results suggest that immunotherapy induces a subpopulation of T cells that are adherent to antigen-coated plates and are capable of suppressing T cell proliferation stimulated by the specific antigen.

Epitopes↗
PubMed1980

Long-term effects of conventional immunotherapy in southern California.

Long-term effects of conventional immunotherapy on a variety of immunological parameters were evaluated in 31 patients with grass hay fever who attended our allergy clinic for up to three years. The mean proliferative lymphocyte response decreased significantly after the first year and the mean antigen-specific Ig antibody level increased significantly after the second year. Neither the mean antigen-specific IgE nor the mean total serum IgE level changed significantly at any point in time during the three years of immunotherapy.

Antibodies↗
PubMed1979

Relationship between antigen-specific IgE antibody (RAST) and total serum IgE levels.

Although the total serum IgE level is generally higher in atopic than in non-atopic individuals, high total serum IgE levels and atopic diseases are not invariably associated. In 42 atopic patients with the total serum IgE levels less than 100 U/ml, 27% of RAST against 14 allergens were positive whereas in 45 atopic patients with the total serum IgE levels greater than 500 U/ml, 57% of RAST against 14 allergens were positive. The mean RAST values against four grass antigens expressed as a percentage of antigen-disc bound radioactivities were significantly lower in the group with the lower total serum IgE levels. Low or normal total serum IgE levels are likely to be found in atopic patients who are allergic to a relatively few grass antigens.

Antibody Specificity↗
PubMed1979

Reappraisal of prick test to tree and weed antigens.

Although 3+ or 4+ prick test reactions to olive tree or Russian thistle are valid, the RAST values to these antigens are significantly lower than those in patients with similar reactions to grass antigens, suggesting that nonimmunologic factors are partially responsible for the skin test reactions to the tree and weed antigens.

Antigens↗
PubMed1978

Reappraisal of intracutaneous tests in the diagnosis of reaginic allergy.

In an attempt to determine the clinical relevance of positive intracutaneous tests when epicutaneous tests are negative, 34 patients with symptoms of perennial rhinitis who had negative epicutaneous but positive intracutaneous tests were evaluated by radioallergosorbent (RAST) test, nasal provocation (NP) tests and leukocyte histamine release (LHR) assay. Nineteen patients with perennial rhinitis who had positive epicutaneous tests and 13 normal healthy volunteers were also studied as positive and negative controls, respectively. None of the 34 patients with negative epicutaneous but positive intracutaneous tests had positive RASTs or LHR assays, but 1 patient had a positive NP test. In contrast, of the 19 patients with positive epicutaneous tests, 12 patients had positive RASTs, 17 had positive LHR assays, and 17 had positive NP tests. In the negative control group of 13 subjects, none had positive RAST, LHR assays, or NP tests, although 3 subjects showed positive intracutaneous tests. These results indicate that when epicutaneous tests are negative in patients with perennial rhinitis, positive intracutaneous tests are not likely to indicate the presence of reaginic allergy.

Administration, Intranasal↗
PubMed1977

Lymphocyte response to grass pollen antigens: a correlation with radioallergosorbent test and effect of immunotherapy.

The deoxyribonucleic acid (DNA) synthetic response of cultured lymphocytes to grass pollen antigens was significantly higher in 66 untreated atopic patients than in 15 non-atopic subjects (p less than 0.05). There was no correlation between the DNA synthetic response and the specific IgE antibody level as measured by radioallergosorbent test in the 81 subjects (r= 0.13; p greater than 0.2). The effect of immunotherapy on proliferative lymphocyte response and specific IgE antibody response to grass pollen antigens was evaluated prospectively in 22 atopic patients. The DNA synthetic response to grass pollen antigens was significantly reduced after immunotherapy (p less than 0.01) but the specific IgE antibody level did not change significantly.

Antigens↗
PubMed1977

Agreement between radioallergosorbent test and skin test.

A total of 4,260 RAST results were compared with the same number of prick and intracutaneous skin test results. Intracutaneous test was done only when the prick test was negative. The mean agreement between positive RAST and positive prick test was 81.3% for five grasses, 45.1% for seven weeds, 42.2% for two trees, 42.6% for two molds, and 45.8% for two environmental antigens. The mean agreement between positive RAST and positive intracutaneous test ranged from 0 to 4.9% for the same antigens.

Adolescent↗