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Biomedical subjects

N Misaki

Publications and source records attributed to N Misaki.

28 records · Page 2Linked to original sources

Effects of phosphorylation of inhibitory GTP-binding protein by cyclic AMP-dependent protein kinase on its ADP-ribosylation by pertussis toxin, islet-activating protein.

Pretreatment of rat cardiac myocytes with the beta-adrenergic agonist, db-cAMP or forskolin decreased ADP-ribosylation of 40-41 kDa protein by islet-activating protein (IAP) in cell membranes. Addition of activated cyclic AMP-dependent protein kinase (protein kinase A) catalytic subunit and MgCl2 also decreased ADP-ribosylation of 40-41 kDa protein by IAP in cell membranes. The alpha- and beta-subunits of partially purified inhibitory GTP-binding protein (Gi) were both phosphorylated by protein kinase A. The amounts of phosphate incorporated into the subunits of Gi were 0.34 and 0.18 mol/mol protein. These show that phosphorylation of Gi by protein kinase A results in a decrease in its ADP-ribosylation by IAP.

Adenosine Diphosphate Ribose↗

[Experimental studies on gastric ulcer (6). Endoscopical evaluation of healing processes of acetic acid ulcer in rats (2): Healing, recurrence and relapse of ulcer].

The progress of acetic acid-induced gastric ulcers in rats were sequentially observed with an endoscope for 365 days, and the influences of the ulcer-induced site, age and sex on the healing, recurrence and relapse of these ulcers were investigated. Submucosal injections of 20% acetic acid at the region between the fundus and the pylorus on the anterior wall of the stomach (site A) in 7 weeks old male rats produced active round-shaped ulcers with blood coagulation and debris on the 3rd day after ulcer induction. The ulcers diminished in size with the progress of time (10--50 days), and 50% of the ulcerated rats healed with convergences of mucosal folds (35--154 days). On and after the 50th day, some diminished or healed ulcers showed signs of relapse (37% of used rats) or recurrence (40% of healed rats, 21% of used rats), with the cumulative relapse and recurrence percentage (CR%) reaching 59% on the 365th day. Ulcers in the glandular portion on the greater curvature (site B) healed significantly faster than those in site A. All of the ulcers in site B healed within 133 days and did not recur or relapse. The cumulative healing percentage (CH%) and the CR% of the ulcers in site A in 25 weeks old male rats were 33% and 67%, respectively, and those of the ulcers in site A in 7 weeks old female rats were 60% and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Experimental studies on gastric ulcer. (4). Sequential observation and evaluation of gastric ulcers by endoscope in the rat.

In the present study, a sequential observation of the gastric lesions or ulcers in rats weighing from 100 g was made with an endoscope. It was found that bleeding, edema, hyperemia, fur of ulcer and convergences of the mucosal folds in the stomach could be observed in rats with a SES-1717S (phi = 1.7 mm) or SES-2217S (phi = 2.2 mm) endoscope. Furthermore, we have devised a method which we named the "sohmen method" for measuring ulcer-sizes with an endoscope. The ulcer-size was compared with 5 mm lengths of sohmen (Japanease vermicelli) which were inserted through the sheath of the endoscope into the stomach. Therefore, the ulcer-size could be accurately measured by this method. By this observation method, it is possible to observe repeatedly over a long term the changes in gastric lesions or ulcers, to measure changes in ulcer-sizes and to evaluate the relapse or recurrence of ulcers in the same rats.

Acetates↗

[Experimental studies on gastric ulcer (5). Endoscopical evaluation of healing processes of acetic acid ulcer in rats (1). Ulcer reducing process].

The following results were obtained as the result of the sequential observations with an endoscope of the gastric ulcer produced by submucosal injection of acetic acid in rats. 1) The size of the ulcer produced by acetic acid injection observed on the 3rd day after ulcer induction depended on the concentration and volume of acetic acid. 2) The natural reducing rates of the size of ulcers in the region between the fundus and pylorus on the anterior wall (A) and in the glandular region on the greater curvature (B) were compared. The reducing rate of B ulcer was significantly faster than that of A ulcer. 3) No significant difference was observed in the reducing processes of untreated ulcers in 7 weeks old rats and 25 weeks old rats. 4) The ulcer reducing rate of female rats was found to be slightly faster than that of male rats. 5) The ulcer reducing rates of the aldioxa (ALD) and sucralfate (SUC) treated group were significantly faster than that of the control group. However, no difference in the ulcer reducing process between the cimetidine (CIM) treated group and the control group was observed. 6) The ulcer indices (UI) of both the combinations of ALD and SUC and of ALD and CIM were found to be significantly less than that of the control group on the 20th day. Treatment with drug combinations shortened the healing period of ulcers more than treatment with one drug alone. The percent healing by the combination of ALD and SUC was the highest among the groups treated. 7) An approximately linear relationship exists between the logarithm of the days after ulcer induction (x) and logarithm of UI (y), and the following equation was obtained: log y = a log x + b. Slope (a) indicates the ulcer reducing rate in evaluating the ulcer reducing process.

Acetates↗

Studies on an anti-inflammatory agent. III. Pharmacological investigations of a new non-steroidal anti-inflammatory agent: 2-oxo-3-[4-(1-oxo-2-isoindolinyl)-phenyl]-butanamide (GP 650).

The anti-inflammatory, analgesic, antipyretic and ulcerogenic activities and acute toxicity of 2-oxo-3-[4-(1-oxo-2-isoindolinyl)-phenyl]-butanamide (GP 650) were investigated in laboratory animals and compared with those of phenylbutazone, acetylsalicylic acid (ASA), ibuprofen, tiaramide-HCl and tinoridine-HCl. The anti-inflammatory and analgesic activities of GP 650 were found to be almost equivalent to those of phenylbutazone on the basis of various anti-inflammatory and analgesic tests while its antipyretic activity was less marked, and its ulcerogenic action and acute toxicity were much lower than those of the other agents. It is interesting to note that GP 650 possesses marked anti-inflammatory activity similar to acidic anti-inflammatory agents in chronic inflammatory models along with mild antipyretic and ulcerogenic activities found in basic anti-inflammatory agents. Therefore, GP 650 appears to be a promising anti-inflammatory and analgesic agent.

Analgesics↗

A method for evaluating analgesic agents in rats.

A method is described for evaluating antinociceptive activity in rats using writhing responses induced by 4% sodium chloride solution. Narcotic and nonnarcotic analgesics, narcotic antagonists except naloxone, and antipyretic and nonsteroidal antiinflammatory drugs were effectively evaluated at relatively low doses using this method. Parenteral ED50 values of these compounds ran parallel to their clinical doses. The method detected not only the analgesic action of the above drugs but also that of methamphetamine. In spite of its high sensitivity, the method was specific in the sense that CNS-depressant, muscle relaxant, anticholinergic, and antihistamine drugs and anesthetics were inactive even at toxic doses. On the other hand, the decrease in the analgesic activity of morphine upon chronic injection was also observed with this method. The writhing test with 4% sodium chloride in rats was concluded to be a sensitive and specific test for analgesic drugs and useful for examining changes in analgesic activity of drugs during chronic administration.

Acetates↗

Studies on combination dosing (III). Aspirin and ethenzamide.

In our studies with drug combinations, we search for mixtures which would enhance the effectiveness of the related active substances. Ethenzamide was found to possess a specific suppressive effect on the gastric damage induced by aspirin. Such effect could not be demonstrated in analgesic agents such as salicylamide, bucetin, acetaminophen and phenacetin. The combination of aspirin with ethenzamide had a potentiating effect on analgesic activity and reduced motor incoordination and loss of righting reflex. We calculated the safety margins of various ratios of combinations and concluded that the best was aspirin and ethenzamide at a ratio of 2:3.

Analgesics↗

[Thrombophlebitis following intravenous injection--an experimental study].

Thrombophlebitis similar to that which is frequently observed following i.v. injection of irritative drugs in clinical treatment has been successfully reproduced in experimental animals by utilizing a newly devised technique. Thrombophlebitis at a high rate resulted within a few days by allowing the sample to remain in the sealed section of the V. retroauricularis in rabbits for 3 min after injection. The effects of several drug preparations on the thrombus as well as on the inflammation formed by means of this technique were examined, and the results were in good parallel with clinical cases reported in medical literature. Histopathologically, it was observed that each thrombus was formed by the irritative effect of drugs on the portion on the veneous wall damaged when needles had been inserted.

Acetrizoic Acid↗