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Biomedical subjects

K Tabata

Publications and source records attributed to K Tabata.

At least 91 records · Page 5Linked to original sources
PubMed1989

Condensed thienopyrimidines. II. Synthesis and gastric antisecretory activity of thiazole and polymethylene condensed thienopyrimidine derivatives.

Thiazolo[3,2-a]thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (6, 11 and 16), and polymethylene condensed thieno[3,2-d]-, [3,4-d]- and [2,3-d]pyrimidin-5-one derivatives (19-21), in which the oxygen atom of the oxazolidine moiety in 3 was replaced by a sulfur atom or methylene groups, were synthesized and evaluated for gastric antisecretory activity in pylorus-ligated rats. The structure-activity relationships of these compounds are discussed.

Animals↗
PubMed1989

[Vascular responses in cerebrovascular "Moyamoya" disease--evaluated by positron emission tomography].

We investigated cerebral blood flow and metabolism, and cerebral vascular response in 9 patients with cerebrovascular Moyamoya disease or unilateral Moyamoya phenomenon using positron emission tomography (PET). The subjects consisted of 5 men and 4 women, and were from 9 to 60 years old. Five patients had bilateral occlusion in the carotid fork with Moyamoya vessels (fulfilled the criteria of cerebrovascular Moyamoya disease), and four patients had unilateral Moyamoya phenomenon. The PET scanner used was the HEADTOME III, of which spatial resolution in clinical use was 10 mm full width at half-maximum (FWHM) in the image plane. Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), cerebral oxygen extraction fraction (OEF), and cerebral blood volume (CBV) were measured in resting state by the 15O-labelled gases steady state method in every patient and 22 normal controls (17 men and 5 women, and from 26 to 64 years old). Consecutively cerebral vascular responses were measured by H215O autoradiographic method in resting state, hypercapnia, hypocapnia, and hypertension. Forced hypercapnia, hypocapnia, and hypertension were achieved by 7% CO2 inhalation, hyperventilation, and venous infusion of angiotensin II, respectively. CMRO2 of the whole brain was significantly lower in patients than in normal controls (p less than 0.05), and CBV of the lentiform nucleus significantly increased in patients (p less than 0.01). This reflected Moyamoya vessels in the basal ganglionic regions. In 3 of 5 patients with bilateral Moyamoya vessels, CBF and CMRO2 in the symptomatic cerebral hemisphere were lower than that in the nonsymptomatic hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Clinical application of dynamic CT].

10 patients with primary pulmonary cancer were performed using of dynamic CT scanning with dynamic curve and obtained radiograms were analyzed with computer. Blood is supplied usually via a bronchial artery to primary pulmonary cancer. But we could be analyzed four types on blood supplying to the primary pulmonary cancer which are via aorta, pulmonary artery, aorta and pulmonary artery and non classified type. This technique be able to suggest of effectiveness of radiotherapy with analyzing of exist of center necrosis of the tumor. Therefore we radiotherapist and radiation oncologist be able to avoid radiation-induced pulmonary pneumonia and pulmonary fibrosis especially high aged patients. We are recommended to take a this technique as preirradiative examination for patient with pulmonary cancer because of avoiding of no available radiotherapy.

Aged↗
PubMed1987

Prostaglandin deficiency by itself is not the cause of mepirizole-induced duodenal ulcers in rats.

The purpose of these studies was to determine the role played by endogenous prostaglandins in the development of gastric ulcers produced by indomethacin, and of duodenal ulcers produced by mepirizole in rats. Indomethacin (10 mg/kg subcutaneously) produced gastric ulcers, whereas mepirizole (100 mg/kg subcutaneously) produced exclusively duodenal ulcers. Both drugs, given at ulcerogenic doses, reduced the gastric and duodenal generation of PGE2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane B2. In this regard, the extent of reduction was more pronounced after indomethacin than after mepirizole. Despite this greater inhibition of prostaglandin synthesis by indomethacin, this drug did not produce duodenal ulcers, whereas mepirizole was duodenoulcerogenic. In addition, mepirizole increased gastric acid secretion by 74%, whereas indomethacin had no effect on acid secretion. Oral administration of 16,16-dimethyl PGE2, given at nonantisecretory doses (0.5-5 micrograms/kg), prevented formation of indomethacin-induced gastric ulcers, whereas antisecretory doses were required to prevent formation of mepirizole-induced duodenal ulcers. We conclude that a reduction of prostaglandin formation in the duodenal mucosa is not by itself sufficient to induce duodenal ulcers. We hypothesize that three changes, produced by mepirizole, must be present for duodenal ulcers to develop: increased gastric acid secretion, decreased duodenal bicarbonate secretion (as demonstrated earlier), and decreased duodenal content of prostaglandins. The decreased prostaglandin formation, although not causing duodenal ulcers, may lower the resistance of duodenal mucosa to the hyperacidity induced by mepirizole. On the other hand, in the case of gastric ulcers following administration of indomethacin, a decrease in gastric mucosal levels of prostaglandins may play a more important role than changes in gastric acidity.

16,16-Dimethylprostaglandin E2↗
PubMed1987

Relationship between ornithine decarboxylase activity and gastric damage.

Hypertonic NaCl increases the activity of gastric mucosal ornithine decarboxylase (ODC). Intragastric administration of concentrated NaCl solution also induces ulcers in the glandular gastric mucosa. The relationship between ODC activity and gastric mucosal damage and the significance of ODC increases in hypertonic NaCl-treated rats are unknown. Rats were fasted 24 h before being given 1.0 ml of 3.4 M NaCl, 120 mM aspirin in 100 mM HCl or 50% ethanol intragastrically. The oxyntic gland mucosa was removed and assayed for ODC and in some experiments DNA, RNA, and protein content. DNA, RNA, and protein content were decreased by 3.4 M NaCl, and these decreases were much greater if ODC was inhibited by pretreatment with alpha-difluoromethylornithine (DFMO). Both aspirin and 3.4 M NaCl induced ODC activity 6 h later. However, DFMO increased the lesion index only in NaCl-treated rats. Although ethanol produced damage, it had no effect on ODC levels, and DFMO did not alter the severity of ethanol lesions. When different concentrations (0.4, 0.8, 1.6, 2.5, and 3.4 M) of NaCl were administered, ODC activities were increased 6 h later in rats receiving 1.6, 2.5, and 3.4 M NaCl but not lower concentrations. Gross lesions appeared in response to the 2.5 M dose and increased with increasing NaCl concentration. However, microscopic damage of the gastric mucosa occurred at all the concentrations tested. These data show that 1) ODC activation is not necessarily produced by damage, 2) in the case of NaCl, increasing damage increases ODC, and 3) ODC appears to have a role in the prevention of a recovery to damage caused by NaCl.

Animals↗
PubMed1986

Ornithine decarboxylase and mucosal growth in response to feeding.

The purpose of this study was to examine the role of ornithine decarboxylase (ODC) in the stimulation of the growth of gastrointestinal mucosa following feeding. Rats were divided into five groups: 1) fasted for 2 days, 2) fasted for 2 days and refed for 2 days, 3) fasted for 2 days and refed with the addition of 5% difluoromethylornithine (DFMO) to the drinking water, 4) normally fed, and 5) normally fed plus 5% DFMO in the drinking water. In general the results show a significant dissociation between ODC activity and growth of gastrointestinal mucosa in response to feeding. In the gastric mucosa, growth was inhibited by fasting and DFMO and stimulated by feeding, but there were no significant changes in ODC activity in any of the five groups. In the ileum ODC activity increased dramatically in refed rats and was essentially eliminated in rats fed DFMO. DFMO, however, had no effect on mucosal growth in fed rats and only prevented part of the trophic response to refeeding. The results in the colon were much the same as in the ileum, except that DFMO prevented even less of the trophic response to refeeding, despite total inhibition of ODC. These data suggest that polyamines necessary for growth of gastrointestinal mucosa following feeding are not supplied by the rapid activation of mucosal ornithine decarboxylase.

Animals↗
PubMed1986

Mechanism of induction of mucosal ornithine decarboxylase by food.

Refeeding fasted rats dramatically increases ornithine decarboxylase (ODC) activity in the mucosa of the small intestine and colon. The agents responsible for that activation and pathways leading to activation, however, have not been identified. The current work examines whether stimulation of ODC activity is mediated humorally or directly and whether dietary amines might be in part responsible for activation. Male Sprague-Dawley rats were used 1 wk after they were surgically prepared with Thiry-Vella jejunal loops. Two hours after refeeding rats fasted for 48 h, ODC activity increased 40-fold in mucosa from the intact jejunum and 4-fold in the mucosa of the bypassed segments. The injection of intestinal contents (obtained from additional fed rats) into the bypassed loop caused a 10-fold increase in ODC activity in the loop measured 2 h later. Injection of gut contents, lyophilized to remove dietary amines, produced no change in enzyme activity. The addition of 400 mol dimethylamine to lyophilized gut contents restored enzyme activation to 80% of the previous level. These data allow the following conclusions: following a meal mucosal ODC is activated by both humoral and direct mechanisms, direct stimulation by dietary constituents appears to be the predominant mechanism involved, and dietary amines may be one of the agents involved in directly increasing enzyme activity.

Animals↗
PubMed1985

Release of secretin immunoreactivity from the ileum.

In the rat, about 80% of the intestinal content of secretin immunoreactivity is found distal to the duodenum with a peak in the ileum. This work therefore studied whether the secretin immunoreactivity in distal ileum could be released by substances normally found in the intestinal lumen. An isolated loop of ileum or duodenum was perfused with 100 mM HCl, 3 mM HCl, 50 mM taurocholate, 50 mM oleate, 308 mM glucose, 273 mM amino acids, or 308 mM NaCl in anesthetized rats. Release of secretin immunoreactivity was estimated by the integrated response above basal in portal blood. Substantial release of secretin immunoreactivity was seen after both ileal and duodenal perfusion with concentrated HCl and taurocholate, whereas perfusion with oleate was followed by a lesser response. The response to taurocholate was slower than that to HCl, but more likely represents a physiologic mechanism. The results show that the distal small intestine is capable of contributing to secretin immunoreactivity in the circulation and it is speculated that bile salts and secretin constitute parts of a negative feedback loop.

Animals↗
PubMed1985

Attenuation of trophic response to gastrin after inhibition of ornithine decarboxylase.

The mechanism by which the hormone gastrin induces growth of the gastrointestinal mucosa is unknown. Many hormones are inducers of ornithine decarboxylase (ODC), the rate-limiting enzyme in the synthesis of the polyamines putrescine, spermidine, and spermine. Although the exact biochemical function of the polyamines is not completely understood, they appear to be required for normal cell growth and differentiation. Rats were maintained on a liquid diet for 5 days and treated with difluoromethylornithine (DFMO, 200 mg/kg ip, 3 times/day), a selective, irreversible inhibitor of ODC, for 5 days. Half of these animals also received pentagastrin (250 mg/kg ip) during the final 3 days of the treatment schedule. DFMO alone had no effect on body weight or mucosal growth. Pentagastrin increased total RNA, DNA, and protein in the oxyntic gland and duodenal and colonic mucosa. Concurrent treatment with DFMO completely inhibited the trophic response to pentagastrin in the oxyntic gland area of the stomach and the duodenal mucosa. In contrast, DFMO was without effect on response of the colonic mucosa to pentagastrin. Pentagastrin treatment did not induce the mucosal ODC activity of the oxyntic gland area of the stomach, the duodenum, the ileum, or the proximal colon of either animals fasted for 48 h or animals maintained on a liquid diet. ODC activity was measured at 4, 8, 12, and 24 h after administration of hormone. These results suggest that, in at least the proximal bowel, the stimulation by gastrin of nucleic acid and protein synthesis requires intact polyamine synthesis but that gastrin itself does not induce ODC.

Adenosylmethionine Decarboxylase↗
PubMed1985

Effect of proglumide on rat pancreatic growth.

Proglumide, a glutaramic acid derivative, is a specific competitive inhibitor of gastrin and cholecystokinin (CCK) receptors. As such, it blocks gastrin-stimulated acid secretion, the trophic effect of gastrin, and CCK-stimulated smooth muscle contraction and acinar cell secretion. In the current study we have demonstrated that proglumide (100 mg/kg three times per day) blocks the trophic effect of a low dose of CCK octapeptide (300 ng/kg) given three times a day for 2 days. The same dose of proglumide when given alone for 6 days, however, resulted in a significant stimulation of pancreatic growth. Proglumide had no effect on the trophic response to a high dose of CCK-OP (5 micrograms/kg) administered for either 2 or 6 days. These results indicate that given over a period of several days proglumide behaves like a partial agonist of pancreatic growth.

Animals↗
PubMed1984

Gastric secretory conditions and plasma gastrin levels in rats after prolonged treatment with cimetidine.

Effects of 4 weeks of treatment with oral cimetidine, 100 mg/kg twice daily, on gastric secretion and plasma gastrin levels were studied in rats. Pylorus ligation-induced and pentagastrin-stimulated gastric secretions were little changed at days 1, 3, and 10 after cessation of cimetidine treatment as compared to the controls. Histamine-stimulated acid secretion was significantly higher in the cimetidine-treated group than in the controls at day 3 after cimetidine treatment but was unchanged at days 1 and 10. A single oral administration of cimetidine at 100 mg/kg significantly increased plasma gastrin levels 4 hr after the treatment in refed rats but not at 2 and 8 hr later. Plasma gastrin levels significantly decreased at days 3 and 10 after cessation of cimetidine treatment as compared to the controls. Thus, while prolonged treatment with cimetidine induces a transient increase in response of parietal cells to histamine and a reduction of food-stimulated gastrin release, it does not seem to induce other appreciable changes in gastric secretion.

Animals↗
PubMed1984

Role of lymphoid nodules in pathogenesis of indomethacin-induced gastric lesions in dogs.

Pathogenesis of indomethacin-induced gastric lesions in beagles was studied morphologically. While a single oral administration of indomethacin (20 mg/kg) did not induce visible lesions in the stomach of male beagles, repeated administration once daily for 5 or 10 days induced gastric erosions or ulcers, mainly in the antrum. When this compound was given once or repeatedly, histological examination showed that the total number of lymphoid nodules both in the fundus and antrum tended to increase or significantly increased. The number of large nodules (over 350 micron in diameter) was significantly increased, particularly in the antrum. Some of these enlarged nodules seen at the surface of the mucosa showed damage at the luminal area, and the lesions were microscopically visible. Indomethacin is known to disrupt the gastric mucosal barrier in dogs, leading to increased back-diffusion of acid. Our findings and those of others suggest that indomethacin may induce lesions in specific portions of the dog stomach, initiated by enlargement of lymphoid nodules followed by damage to some of these nodules, probably due to a corrosive effect of gastric juice through the disrupted mucosal barrier.

Administration, Oral↗