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Biomedical subjects

K Saigenji

Publications and source records attributed to K Saigenji.

At least 73 records · Page 4Linked to original sources

Efficacy of endoscopic variceal ligation for bleeding esophageal varices in patients with tumor thrombus of the portal vein trunk (Vp3) associated with hepatocellular carcinoma.

We studied the efficacy of endoscopic variceal ligation (EVL) in 16 patients with tumor thrombus of the portal vein trunk (Vp3) associated with hepatocellular carcinoma. The average (+/-SD) number of O rings used was 9.0 +/- 5.0 for the esophageal varices (n = 7) and 16.4 +/- 4.5 for the esophagogastric varices (n = 9). The variceal size was quickly reduced in 11 of the 13 cases whose therapeutic outcome was able to be assessed by endoscopy. The red color sign improved in 10 of the 13 cases, but the therapeutic end point (F0, RC-) was achieved in only two patients, who were also treated by endoscopic injection sclerotherapy. Emergency EVL achieved only short-term survival (17.14 +/- 6.64 days) and transient hemostasis. Elective EVL was associated with a survival duration of 90.0 +/- 64.25 days. The difference in the survival rate between emergency and elective cases was significant (P < .05). With regard to the timing of its application, EVL, being a less-invasive treatment, should be performed electively before variceal rebleeding for those patients with Vp3 hepatocellular carcinoma whose liver function is preserved.

Aged↗

Enhanced cellular proliferation and p53 accumulation in gastric mucosa chronically infected with Helicobacter pylori.

This study evaluated whether the increased risk of development of gastric carcinoma due to chronic Helicobacter pylori infection could be linked with elevated cell proliferative activity and expression of p53 and bcl-2. Forty-eight patients undergoing therapy for H pylori-positive gastroduodenal ulcers were separated into not eradicated (NE; n = 23) and eradicated (E; n = 25) groups 6 months after the treatment. Serum pepsinogen (PG) I:II ratios and histologic changes in the gastric corpus and the antrum, assessed according to the modified Sydney System, as well as epithelial cell proliferation (mitosis, Ki67, and proliferating cell nuclear antigen [PCNA]), and expression of oncoproteins (p53 and bcl-2) were examined before and at 3 months and 6 months after treatment for H pylori. Chronic persistent H pylori infection was associated with a low PG I:II ratio, increased inflammation and activity score, and elevated cell proliferation, as evidenced by the Ki67 and PCNA labeling indexes and the mitotic index in the NE group. Scattered accumulation of p53 protein continued to be observed in the NE group after treatment but was significantly decreased in the E group. We conclude that persistent H pylori infection causes gastritis, with epithelial degeneration and regeneration that result in accentuation of epithelial cell proliferation and accumulation of p53 protein, presumably heightening the genetic instability consistent with the development of carcinoma.

Adult↗

Stimulation of mucin biosynthesis in rat gastric mucosa by FRG-8813 and its structural analogs.

Certain chemical properties, which may determine the stimulatory actions of the new histamine H2 receptor antagonist, FRG-8813 (2-(furfurylsulfinyl)-N-(4-[4-(piperidinomethyl)-2-pyridyl]o xy-(Z)- 2-butenyl)acetamide), on mucin biosynthesis, were identified by considering the derivation of this drug using an organ culture system of the rat stomach. [3H]Glucosamine and [35S]sulfate incorporation was stimulated in the corpus region by FRG-8813 and its structural analog, compound A (N-[4-[[4- (piperidinylmethyl)pyridyl]-2-oxy]-(Z)-2-butenyl]phthalimide). The chronotropic response to histamine in the guinea pig right atria was suppressed by FRG-8813 in a concentration-dependent fashion. In contrast, compound A did not suppress the histamine-induced response. Ranitidine at 10(-4) M did not suppress the FRG-8813-induced increase in [3H]glucosamine incorporation into mucin. These results suggest that the pyridine derivative and amide structure are chemically important in FRG-8813 as a stimulant on mucus metabolism. Also, this effect is not directly due to histamine H2 receptor antagonism.

Acetamides↗

Mechanisms for cytoprotection by vitamin U from ethanol-induced gastric mucosal damage in rats.

A comparison was made of the effects of a nonsulfhydryl compound, vitamin U (methylmethioninesulfonium chloride, MMSC), and a sulfhydryl compound, cysteine (Cys), with regard to the inducement of acute gastric mucosal damage in the presence and absence of N-ethylmaleimide (NEM), a sulfhydryl-blocking reagent. The effects of MMSC, Cys, or NEM on gastric mucin content were examined using a newly developed biochemical method. MMSC and Cys inhibited mucosal damage due to 50% ethanol. The preinjection of NEM had no effect on cytoprotection of prostaglandins, but prevented the effects of Cys and MMSC. MMSC and Cys increased surface mucin content but lessened that of deep mucin. NEM decreased surface mucin and increased deep mucin. It thus follows that sulfhydryl compounds accelerate the secretion of deep mucin and accumulate surface mucin. The cytoprotective mechanism of MMSC may thus be mediated by sulfhydryl compounds, and the increase in surface mucosal mucin may possibly be related to cytoprotection.

Animals↗

Role of endogenous substance P in ethanol-induced mucosal damage in the rat stomach.

To determine the role of endogenous substance P in ethanol-induced mucosal damage, two experiments were performed. In the first experiment, the stomachs of anesthetized rats were doubly cannulated and gastric damage was induced with 5ml of 30% ethanol in the gastric lumen. The damage was ameliorated by pretreatment with capsaicin (0.16 and 1.6 mM) and spantide (100 mg/kg, i.v.). In the second experiment, the gastric mucosa of these rats was perfused with physiological saline containing pepstatin (10 microliters/ml). Endogenous substance P (SP) in the perfusate was measured by enzyme immunoassay (EIA). The peak SP levels were increased by capsaicin (0.16-1.6 mM) in a concentration-dependent manner. Perfusion with 50% ethanol for 5 min increased the SP levels approximately threefold. Perfusion with 1.6 mM capsaicin, followed by 50% ethanol, reduced the injured area to about one-quarter of the original injured area. The peak SP levels during perfusion with 50% ethanol after pretreatment with 1.6 mM capsaicin did not differ from those observed after vehicle pretreatment (control). The area under the curve for SP release during 50% ethanol perfusion after vehicle perfusion was not reduced by previous perfusion with 1.6 mM capsaicin followed by 50% ethanol, indicating that the prevention of ethanol-induced injury by capsaicin may be due to excess amounts of different neuropeptides released simultaneously.

Animals↗

[Recent advance of endoscopic ultrasonography for evaluating gastroenterologic early cancer].

Lutz et al. made the first report in which ultrasonographic probe could differentiate cystic tumor from solid one. After that, endoscopic ultrasonography (EUS) have advanced rapidly in engineering and clinical application. EUS is the most accurate diagnostic method presently available to determine the depth of gastrointestinal cancer invasion. We have proposed the pattern analysis for the differentiation between cancer invasion and ulcer fibrosis, because fibrosis and cancer invasion have of the same echo level. USP is more useful and easy than EUS in cases with small and flat lesion without ulcer, and EUS should perform in remaining lesions that look like early cancer with ulcer and advanced cancer. Clinically, it is believed that the invasion of early gallbladder cancer limited to the proper muscle, the early pancreas cancer is less than 1 cm. It is also practicable with EUS to detect the these cancer easily and diagnose the local stage of gall bladder and pancreas cancer. Now we are performing IDUS (ER-US, PT-US) and 3D-EUS, and believing that these technics will be used commonly in the near future.

Digestive System Neoplasms↗

Direct observation of microcirculation of the basal region of rat gastric mucosa.

We modified and improved techniques for the intravital microscopic observation of the rat gastric microcirculation. The stomach of anesthetized rats was cut along the greater curvature, and the posterior wall of the glandular stomach was fixed in a chamber with the serosal side up and perfused with warmed Tyrode's solution. A portion of the muscularis externa was resected with the serosa to make an observation window. Vascular casts were studied histologically after the injection of Monastral blue B gelatin solution. Vascular casts revealed that most of the microvasculature observed in the window was not located in the submucosa, but in the basal part of the mucosa. Microscopic observation showed that the basal mucosal arterioles branched to form the mucosal capillaries, and the collecting venules from the mucosal surface were seen in cross-sections to drain into the venules located in the basal mucosa, without penetrating the muscularis mucosae. Topical application of acetylcholine (0.03-10 microM) to the window dilated the arterioles, and topical application of epinephrine (0.03-3 microM) constricted them dose-dependently without affecting the collecting venules and the venules. This method made possible the direct observation of the microvasculature in the basal mucosa of the stomach, in which common microvessel characteristics were shown.

Acetylcholine↗

Effects of lansoprazole on gastric ulcer healing and mucin content.

The effect of lansoprazole, a new benzimidazole proton pump inhibitor, on the relationship between ulcer healing and changes in mucin content was studied in gastric ulcer patients. Twenty-one outpatients with active gastric ulcers received lansoprazole 30 mg once daily given in the morning for 8 weeks. The gastric mucin content was examined by HPLC analysis of hexosamines in gastric biopsy specimens obtained from the lesser curvature of the pylorus and the greater curvature of the upper body. The ulcer healing rate for lansoprazole was 85.7% at 8 weeks. The mucin content of both mucosal regions significantly decreased to approximately 70% (pylorus 70.9%; upper body 74.7%) of the value before drug treatment. The results of this study demonstrate that 30 mg lansoprazole once daily is remarkably effective in healing gastric ulcers because of its potent acid suppression. It appears that acid inhibition is the primary factor in initial treatment. However, maintaining an altered gastric mucosal defense mechanism may have implications for the long-term treatment of gastric ulcers.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Influence on glycemic control of improved diabetic gastroparesis by long-term cisapride therapy].

To investigate the effect on glycemic control of improving diabetic gastroparesis, we evaluated symptoms (scored), gastric motor functions (solid and liquid gastric emptying studies and electrogastrography), and glycemic control in 11 patients with diabetic gastroparesis (5 men, 6 women, 50.4 +/- 4.5 years old) before and after treatment with cisapride (15 mg/day p.o., 12 weeks). None of the patients had organic abnormalities on gastrointestinal endoscopy. The dysmotility symptom score (maximum: 18) on cisapride significantly improved from 13.1 to 4.0 (p < 0.01). Retention rates at 15 and 80 minutes after ingestion improved in a solid-food gastric emptying study using a test meal of instant noodles labeled with 37 MBq (1 mCi) technetium-99m (both p < 0.05). Liquid gastric emptying, evaluated using a sulfamethizole technique, also improved but not significantly. Electrogastrography revealed no significant changes after treatment, but the postprandial rate of normal frequency waves tended to increase. Glycemic control was assessed based on HbA1C, fructosamine and M value. There were no significant changes in glycemic control after treatment with cisapride. We conclude that long-term administration of cisapride reduced dysmotility symptoms and improved solid and liquid gastric emptying without adversely affecting glycemic control.

Adult↗

Different responses of arterioles and venules in rat gastric mucosal microcirculation to endothelin-1 and endothelin-3.

Responses of the microvessels in the basal part of the gastric mucosa of anesthetized rats to endothelin (ET)-1 and ET-3 were examined by intravital microscopy. The posterior wall of the stomach, which was incised along the greater curvature, was secured in an observation chamber and superfused with Tyrode's solution, and the microcirculation was observed through a window made by removing a limited area of smooth-muscle layers with the serosa and submucosal tissue. Topical application of the same ranges of ET-1 and ET-3 (0.1-10 microM, 20 microliters) to the window dose-dependently constricted collecting venules and venules downstream. The constriction was inhibited by BQ-123, an ETA receptor antagonist, but the equipotency of ET-1 and ET-3 did not support the presence of the ETA receptor (tentatively called ETR-m). Arterioles were constricted through ETR-m, particularly at higher doses (> 3 microM), but 1 microM ET-1 dilated the arterioles by generating prostaglandin through BQ-123-sensitive ET receptor (tentatively called ETR-e), as shown by the inhibition of dilatation by indomethacin. Furthermore, the dilatation component of the arteriolar smooth-muscle responses to ET-1 and ET-3 was elicited by BQ-123 and was inhibited by NG-monomethyl-L-arginine (L-NMMA), indicating the generation of nitric oxide. This dilating effect of the endothelins was mediated by the ETB receptor.

Animals↗

Effects of acid-inhibitory antiulcer drugs on mucin biosynthesis in the rat stomach.

The effects of the anti-acid secretory agents, cimetidine (N-cyano-N'-methyl-N"-(2-([(5-methyl-1H-imidazol-4-yl)methyl]thio)ethyl) guanidine), ranitidine (N-(2-(((-5-[(dimethylamino)methyl]-2-furanyl)methyl)thio)ethyl)-N'-meth yl- 2-nitro-1,1-ethene-diamine), roxatidine (2-acetoxy-N-(3-[m-(1-piperidinylmethyl)phenoxy]-propyl) acetamide hydrochloride), FRG-8813 (2-(furfurylsulfinyl)-N-(4-[4-(piperidinomethyl)-2-pyridyl]o xy-(z)-2- butenyl)acetamide), omeprazole (5-methoxy-2-([(4-methoxy-3,5-dimethylpyridinyl)methyl]sulfinyl)- 1H-benzimidazole), and NC-1300-O-3 (2-([2-(isobutylmethylamino)benzyl]sulfinyl)-1H- benzimidazole), on mucin biosynthesis were studied in rat gastric mucosa by using an organ culture technique. [3H]Glucosamine incorporation was stimulated in the corpus region by the histamine H2 receptor antagonists which have a six-membered aromatic ring, roxatidine and FRG-8813, and the new H+,K(+)-ATPase inhibitor, NC-1300-O-3. Thus, these drugs not only inhibit acid secretion but may also promote gastric mucosal protective actions. The present observations also demonstrate that the determination of mucin biosynthesis may be a useful tool for evaluation of mucosal protective activity.

Animals↗