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Biomedical subjects

K Saigenji

Publications and source records attributed to K Saigenji.

At least 37 records · Page 2Linked to original sources

Effects of rabbit gastrointestinal mucins and dextran on hydrochloride diffusion in vitro.

We compared a viscous fingering formation of hydrochloric acid (HCl) in rabbit corpus, antral and duodenal mucins and with dextran under neutral and acidic conditions with respect to relative viscosity, molecular mass, and carbohydrate composition. The effect of desialyzation of duodenal mucin on the viscous fingering formation of HCl was also examined. HCl (0.1 N) was injected into 1% solutions of mucins and dextran and a subsequent viscous fingering formation was assessed based on an influx volume rate of HCl. A low influx volume rate indicates a high ability of the solutions to produce viscous fingers. The influx volume rate of HCl was lowest in duodenal mucin followed bl corpus mucin, antral mucin, and dextran at pH 7. The influx volume rate of HCl was inversely correlated with the relative viscosity of the solution. Maximum molecular masses were large in the order of corpus, antral, and duodenal mucins, and they were larger than dextran T2000. Rabbit gastrointestinal mucins were very polydisperse system. Duodenal mucin contains more sialic acid than gastric mucins; the influx volume rate of HCl increased in desialylated duodenal mucin. It is suggested that the higher ability of gastric mucins to prevent HCl diffusion than dextran were due to the differences in the molecular mass. The ability of duodenal mucin to prevent HCl diffusion was probably attributed to its high sialic acid content, which may reflect a physiological role of duodenal mucin in the duodenum that has to deal with HCl influx from the stomach.

Animals↗

Effects of ecabet sodium, a novel gastroprotective agent, on mucin metabolism in rat gastric mucosa.

The effects of ecabet sodium (ecabet), 12-sulfodehydroabietic acid monosodium salt, on gastric mucin biosynthesis in rat antrum were compared with those in the corpus. Intragastric administration of ecabet significantly increased [3H]glucosamine incorporation into antral mucin as well as into corpus mucin during five successive hours of organ culture. In contrast, mucin biosynthesis in either antrum or corpus was not susceptible to the addition of ecabet to the culture medium. Ecabet-induced stimulation of prostaglandin E2 production in the antrum was essentially the same as that seen in the corpus. In antrum treated with 100 mg/kg ecabet, immunoreactivity with three distinct anti-mucin monoclonal antibodies was found not only in the specific mucus-producing cells, but also in the secreted mucus present at the surface gel layer. These results suggest that ecabet enhances the mucin metabolism, and this stimulation occurs in both the corpus and antrum, suggesting that ecabet might be a useful tool for the further clarification of the regulatory mechanism of antral mucin synthesis.

Abietanes↗

Mechanism of prevention by capsaicin of ethanol-induced gastric mucosal injury--a study in the rat using intravital microscopy.

BACKGROUND: Capsaicin acts specifically on primary afferent neurones to release neuropeptides, including calcitonin gene-related peptide (CGRP), and prevents ethanol-induced mucosal injury. AIM: To investigate the microvascular changes in the gastric mucosa in response to ethanol using intravital microscopy to elucidate the mechanism of capsaicin-induced gastroprotection. METHODS: The posterior gastric wall in the rat was secured in an observation chamber and perfused with Tyrode's solution. The microcirculation was observed through a window made by removing a limited area of smooth muscle. RESULTS: Ethanol (50%) applied to the mucosa constricted the collecting venules and venules but dilated arterioles. The constriction of the collecting venules resulted in mucosal congestion, which caused mucosal injury. Application of capsaicin to the mucosa dilated the arterioles but not the collecting venules or venules. Arteriolar dilation was inhibited by a CGRP antagonist, CGRP-(8-37). Prior application of capsaicin prevented ethanol-induced constriction of the collecting venules, and the action of capsaicin was inhibited by prior application of CGRP-(8-37). CONCLUSIONS: The results suggest that the inhibition of ethanol-induced gastric injury by capsaicin is attributable to the suppression of collecting venule constriction, via CGRP release.

Animals↗

Augmentative effects of L-cysteine and methylmethionine sulfonium chloride on mucin secretion in rabbit gastric mucous cells.

BACKGROUND: Our previous study showed that L-cysteine (Cys) and methylmethionine sulfonium chloride (MMSC) inhibited ethanol-induced gastric mucosal damage and increased the amount of surface mucin in rats. This study examined whether Cys and MMSC augmented mucin secretion and changed distribution of mucin vesicles ultrastructurally in mucous cells by using primary cultured mucous cells from rabbit glandular stomach. Changes in intracellular cyclic adenosine 3',5'-monophosphate (cAMP) and in levels of cytosolic free Ca2+ were investigated by treatment with Cys and MMSC. METHODS: Mucin content was measured by an enzyme-linked lectin assay. Transmission electron micrography was used to examine ultrastructural distribution of mucin granules. The amount of cAMP or levels of free Ca2+ were measured by enzyme immunoassay or by fura-2. 16,16-Dimethyl prostaglandin E2 (dmPGE2) or ATP was used as the positive control. RESULTS: L-Cysteine and MMSC increased mucin secretion and decreased cellular mucin content. The same was noted for dmPGE2. Accelerated mucin granule movements toward the plasma membrane were shown by these agents. Intracellular cAMP increased with exposure to dmPGE2 for 20 min, while neither Cys nor MMSC increased cAMP. No increase in cytosolic free Ca2+ levels occurred after treatment with Cys or MMSC, but an increase was induced 10 s after the addition of ATP. CONCLUSIONS: The present findings indicate that the increase in mucin secretion by Cys and MMSC was not mediated through the cAMP or Ca2+ signal transduction pathway, but might occur through non-receptor-mediated mechanisms.

Animals↗

Possible association of active gastritis, featuring accelerated cell turnover and p53 overexpression, with cancer development at anastomoses after gastrojejunostomy. Comparison with gastroduodenostomy.

To cast light on tumorigenesis in the remnant stomach after distal gastrectomy for peptic ulcer or gastric cancer, 45 cases in gastroduodenostomy (Billroth I, 17 cases) and gastrojejunostomy (Billroth II, 28 cases) groups were compared for a series of parameters. Cancers in Billroth II were significantly more predominant in the anastomosis area and more frequently associated with Epstein-Barr virus infection. Active gastritis, accelerated epithelial cell turnover (as assessed by measurements of apoptosis and cell proliferation), DNA damage, and foveolar cell hyperplasia were all greater in anastomotic areas after Billroth II than in proximal areas after Billroth II or either area after Billroth I. K-ras mutations were rare, but Epstein-Barr virus infection in cancers was seen frequently in anastomosis cases. In conclusion, active gastritis, possibly induced by enterogastric reflux, is linked to tumorigenesis in anastomosis sites in Billroth II cases.

Adult↗

A giant intramural gastric hematoma successfully treated by transcatheter arterial embolization.

We describe a case of intramural gastric hematoma with hemorrhagic shock caused by the formation of a large hematoma. Computed tomographic and angiographic examinations confirmed the presence of active bleeding into the hematoma. Transcatheter arterial embolization (TAE) was performed for hemostasis. To our knowledge, although 21 cases of intramural gastric hematoma have been reported in the literature, this is apparently the first case treated by TAE. We conclude that TAE is a safe and effective treatment option for intramural gastric hematoma confirmed to be associated with active bleeding into the hematoma.

Aged↗

Mixed carcinoid-adenocarcinoma of the liver.

A 61-year-old man with a mixed carcinoid-adenocarcinoma of the liver is described. Microscopic examination of the lesion showed a differentiated adenocarcinoma with distinct carcinoid components that stained positively for argyrophil. The tumor cells contained serotonin granules on immunohistochemical studies. Detailed examination disclosed no primary tumor in the gastrointestinal tract or in any other organ. Resection was considered impractical because there were multiple tumors. The patient received chemotherapy six times (cisplatin 60 mg/m2, epirubicin 40 mg/ m2 per month). The multiple tumors gradually shrank. At the time of this writing, the patient is still alive. To our knowledge, this is the first reported case of mixed carcinoid-adenocarcinoma of the liver.

Adenocarcinoma↗

[Antibacterial activity of 16 antibiotics against Helicobacter pylori].

The susceptibilities of 24 Helicobacter pylori isolates, which were originated from clinical materials, to 5 beta-lactam antibiotics [benzylpenicillin (PCG), ampicillin (ABPC), cephalothin (CET), ceftazidime (CAZ), cefotiam (CTM) and imipenem (IPM)], two macrolides [clarithromycin (CAM) and rokitamycin (RKM)], two aminoglycosides [amikacin (AMK) and gentamicin (GM)], two new quinolones [ciprofloxacin (CPFX) and levofloxacin (LVFX)], two tetracycline [tetracycline (TC) and minocycline (MINO)], rifampicin (RIF) and chloramphenicol (CP) were tested. All of the isolates showed similar susceptibilities against beta-lactam antibiotics. However, MICs of CTM and CAZ were two- to four-fold higher than those of PCG, ABPC, CET and IPM, MICs of rokitamycin for the tested strains were higher than those of clarithromycin. MICs of CPFX and LVFX showed two-modal distributions. The first peak of distributions was observed between 0.06 to 0.5 microgram/ml and second one was between 4 to 16 micrograms/ml. These distributions suggested that MIC values of 4 to 16 micrograms/ml could result from the expression of a resistance mechanism. In addition, some of H. pylori strains were observed drug resistances between CP and AMK, new quinolones and AMK respectively. From the molecular epidemiological study, cryptic plasmids were detected from the 3 isolates among 24 strains tested.

Aminoglycosides↗

Compensatory response of colon tissue to dextran sulfate sodium-induced colitis.

Depletion of goblet cells (the main mucin-producing cells in the colon) is one of the most reliable histological characteristics of ulcerative colitis, whereas a major symptom of this disease is bloody diarrhea containing a large amount of mucus. The discrepancy between these phenomena was investigated in a time-course study in rats with experimental colitis induced by treatment with oral dextran sulfate sodium (DSS) for 1, 3, or 5 days. Biochemical analysis showed a reduction in mucin content in the distal side of the colon that was proportional to the duration of DSS administration. In the proximal side of the colon, however, there was a significant increase in mucin content already on the first day of treatment with DSS. This increase in colonic mucin content continued for the 5 days of treatment. In the distal side, both sulfomucin and sialomucin decreased proportionally to the duration of DSS administration. In the proximal side, there was an increase in high iron diamine-Alcian blue-positive mucins, and confirming the proliferation of goblet cells. The proliferated glands were predominantly sialylated. Goblet cell depletion and an increase in mucin production occurred in different parts of the colon. This phenomenon may be a type of compensatory function of colon tissue in response to the localized decrease of mucin production in certain portions of the colon.

Animals↗

Usefulness of endoscopic aspiration mucosectomy as compared with strip biopsy for the treatment of gastric mucosal cancer.

BACKGROUND: Several techniques are available for the endoscopic treatment of gastric intramucosal cancers, but their advantages and disadvantages have not been adequately evaluated. We compared the therapeutic usefulness of endoscopic aspiration mucosectomy with that of strip biopsy. METHODS: Between May 1995 and May 1997, we performed strip biopsy (May 1995 through February 1996) or endoscopic aspiration mucosectomy (March 1996 through May 1997) in a consecutive series of patients with intestinal-type intramucosal cancer. Parameters of assessment included the following: size of removed specimens, en bloc resection rate, time required for resection, duration of hospitalization, and complications. RESULTS: Forty-nine patients with gastric intramucosal cancers underwent endoscopic aspiration mucosectomy and 44 underwent strip biopsy. The two groups were similar with respect to age, gender, and lesion macroscopic appearance, size, and site. The mean longest diameter of the resected specimens was significantly greater with endoscopic aspiration mucosectomy (20.3 +/- 3.4 mm) than with strip biopsy (15. 8 +/- 4.4 mm) (p < 0.001). The rate of en bloc resection (resection of an entire lesion in one procedure) was significantly higher with endoscopic aspiration mucosectomy (61.2%, 30 of 49) than with strip biopsy (36.4%, 16 of 44) (p < 0.05). The number of specimens obtained by piecemeal resection was slightly, but not significantly, higher with strip biopsy (2.4 +/- 1.7) than with endoscopic aspiration mucosectomy (2.0 +/- 1.7). The time required for treatment was similar for each procedure. The duration of hospitalization was significantly shorter with endoscopic aspiration mucosectomy (12.8 +/- 5.3 days) than with strip biopsy (15.9 +/- 74 days) (p < 0.05). As for complications, the rate of bleeding was 20. 5% (9 of 44) with strip biopsy and 10.2% (5 of 49) with endoscopic aspiration mucosectomy; bleeding was controlled in all cases by treatment with a heater probe. CONCLUSIONS: Endoscopic resection of large gastric intramucosal tumors is easier with endoscopic aspiration mucosectomy compared with strip biopsy. Endoscopic aspiration mucosectomy is a useful procedure for en bloc resection.

Adenocarcinoma↗

Dilatation and constriction of rat gastric mucosal microvessels through prostaglandin EP2 and EP3 receptors.

BACKGROUND: Prostaglandin (PG)E2 has both a vasodilating action and a protective function in the gastric mucosa. There are four subtypes of PGE2-sensitive, or EP, receptors. AIM: To identify the subtype of EP receptors in the microvessels of the rat gastric mucosa using EP2 and EP3 receptor agonists. METHODS: The posterior wall of the anaesthetized rat stomach was secured in a chamber and superfused with Tyrode's solution, and the gastric microcirculation of the mucosal base was observed through a window with transillumination. PGE2 and its derivatives (20 microL) were applied topically in the window. RESULTS: PGE2 (0.001-10 micromol/L), misoprostol (EP2/EP3 receptor agonist; 0.01-100 micromol/L) and butaprost (EP2 receptor agonist; 1-1000 micromol/L) dilated the arterioles dose-dependently, but M&B 28 767 (EP3 receptor agonist; 0.001-10 micromol/L) did not alter their diameters. M&B 28 767 constricted the venules and collecting venules dose-dependently whereas butaprost dilated them. PGE2 and misoprostol had bell-shaped dose-response curves: constriction by low doses of PGE2 and misoprostol (0.001-0.1 micromol/L and 0.01-1 micromol/L) and dilation by high doses of PGE2 and misoprostol (0.1-100 micromol/L and 1-100 micromol/L). CONCLUSIONS: These results suggest that PGE2 dilated both arterioles and venules in the rat gastric mucosa through the EP2 receptors and constricted the venules through the EP3 receptors.

Alprostadil↗

Cell kinetics, p53 and bcl-2 expression, and c-Ki-ras mutations in flat-elevated tubulovillous adenomas and adenocarcinomas of the colorectum: comparison with polypoid lesions.

BACKGROUND: Flat(-elevated) tubulovillous adenomas and adenocarcinomas of the colorectum constitute a specific type of neoplasm with superficial spreading growth. To establish their characteristics, a comparative investigation of a series of tumors was performed. METHODS: A total of 56 flat tubulovillous tumors (39 adenomas, 17 invasive carcinomas) and 154 polypoid tubular or villous tumors (77 adenomas, 77 invasive carcinomas) were comparatively assessed for cell kinetics and molecular alterations. RESULTS: Ki-67 labeling and p53 expression for both types of tumors increased along with degree of dysplasia or invasion, whereas bcl-2 expression showed an inverse decrease. However, apoptotic activity was invariably low in the flat tubulovillous tumors, as compared with the polypoid tumors, in which increase was apparent with tumor progression. The flat tubulovillous tumors also showed a higher frequency of c-Ki-ras mutations (92.9%) than the polypoid tubular tumors (40.0%). CONCLUSIONS: The flat tubulovillous tumor can be considered a distinct entity, with characteristics different from the polypoid counterpart.

Adenocarcinoma↗

Prediction of response to 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with inoperable advanced gastric cancer by immunostaining of thymidine phosphorylase/platelet-derived endothelial cell growth factor.

BACKGROUND: No reliable method is available for predicting the response to chemotherapy in patients with gastric cancer. The anticancer drug 5'-deoxy-5-fluorouridine (5'-DFUR) is converted into 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase). We studied the relation between the expression of dThdPase in tumor tissue and the response to treatment with 5'-DFUR to determine if this enzyme can be used to predict the response to chemotherapy. METHODS AND MATERIALS: We performed endoscopic biopsy and studied the expression of dThdPase by immunostaining with anti-dThdPase monoclonal antibody in 41 patients with inoperable advanced gastric carcinomas before they received multiple-drug chemotherapy, including 5'-DFUR. The relation between the expression of dThdPase and the response to chemotherapy was studied. We also studied the characteristics of positive cells against anti-dThdPase monoclonal antibody. RESULTS: The response rate among patients whose tumors were positive for dThdPase expression (56.8%, 21/37) was higher than that among patients whose tumors were negative for dThdPase expression (0%, 0/4; p = 0.048). Spindle-shaped cells darkly expressing dThdPase were sporadically seen surrounding cancer nests in some patients. Multiple-antibody immunostaining suggested that these spindle-shaped cells were perivascular mesenchymal cells. The response rate was 82.4% (14/17) among patients with spindle-shaped cells strongly positive for dThdPase, as compared with 29.2% (7/24) among those with spindle-shaped cells weakly positive or negative for dThdPase (p = 0.00131). The expression of spindle-shaped cells darkly stained with dThdPase was the factor most strongly related to the response to chemotherapy (odds ratio = 35.513, p = 0.0027). CONCLUSIONS: The expression of dThdPase in stromal spindle-shaped cells may be a useful index in predicting the response to 5'-DFUR in patients with gastric cancer.

Adult↗

Influence of L-365,260, a CCK-B/gastrin receptor antagonist, on tetragastrin-stimulated mucin metabolism in rat gastric mucosa.

The effect of L-365,260, a CCK-B/gastrin receptor antagonist, on gastric mucus metabolism induced by tetragastrin was investigated in rats. In vivo application of L-365,260 at a dose of 3 mg/kg p.o. significantly reduced the tetragastrin (12 microg/kg s.c. )-stimulated gastric acid secretion, but 0.3 mg/kg of L-365,260 did not affect the gastric acid secretion induced by the tetragastrin administration. A single administration of 12 microg/kg of tetragastrin caused an increase in gastric mucin content in the soluble mucus (175% of control), the mucus gel (155% of control) and the surface mucosa (125% of control). L-365,260 at the doses of 0.3 and 3 mg/kg considerably inhibited the tetragastrin-induced mucus secretion in the soluble mucus (70-80% of tetragastrin) and the mucus gel (45-70% of tetragastrin) and resumed the mucus accumulated in the surface mucosa to the control situation (80% of tetragastrin). In the in vitro incubation system of rat gastric mucosa, L-365,260 (0.1-10 micromol/l) caused no significant change in gastric mucin synthesis. An in vivo study also showed that the increase in total gastric mucin content and the distributional changes in mucin content induced by 12 microg/kg of tetragastrin reverted with 3 mg/kg of L-365,260 pretreatment to the control situation. It is evident from these results that the CCK-B/gastrin receptor is involved in the mechanism of the stimulation of mucus secretion and/or mucus accumulation in rat gastric mucosa and not directly concerned with the action of gastrin-induced gastric acid secretion.

Animals↗

[Effects of Helicobacter pylori eradication therapy on the healing process of peptic ulcers].

The advent of H2-receptor antagonists (H2RA) and proton pump inhibitors (PPI) has particularly revolutionized the treatment of peptic ulcer disease. Most cases can now be successfully controlled by medical treatment with H2RA and PPI, but a high rate of ulcer recurrence remains an important problem. The quality of ulcer healing (QOUH) has therefore received increasing attention, and various investigators have attempted to define the conditions required for nonrecurrence. Ulcer scars with a good QOUH are considered to have a very low risk of recurrence. Recent studies have confirmed that recurrence of peptic ulcer can be suppressed markedly by eradication of Helicobacter pylori (H. p). Moreover, various types of endoscopic examinations (conventional observation, dye-contrast endoscopy, magnifying endoscopy, endoscopic ultrasonography, pharmacoendoscopy) have confirmed that the QOUH after eradication of H. p is better than that after conventional anti-ulcer therapy. H. p eradication therapy may become treatment of first choice for peptic ulcers.

Anti-Bacterial Agents↗

[Two regimens of combined 5'-deoxy-5-fluorouridine and cisplatin showing different dose intensities--investigation based on relative performances].

Patients with inoperable gastric cancer were given either of two regimens of combined 5'-deoxy-5-fluorouridine and cisplatin with different dose intensities. The results were compared based on ratios of the actual and the scheduled total doses of the regimens [relative performance (RP)]. The overall response rates and survival curves between the regimens showed no differences, but the incidences of severe adverse drug reactions was higher with regimen A, which had a higher dose intensity. Furthermore, survivals with regimen A were no different between the responding and non-responding patients, whereas the survivals of responding patients under regimen B were significantly longer than those of non-responding patients. Average RP were 0.87 with regimen A and 0.93 with regimen B. The mean RP of responding and non-responding patients were 0.94 and 0.84, respectively, with regimen A, and 0.99 and 0.89 with regimen B. Regarding survivals in both the RP = 1.0 and the RP < 1.0 groups, no difference was observed with regimen A. However, with regimen B, the RP = 1.0 group exhibited significantly better survival curves. Furthermore, survivals of the RP = 1.0 group under regimen B were much more favorable than in the RP = 1.0 group under regimen A. The above findings show that a regimen with an appropriate dose intensity has a favorable survival effect on patients.

Antineoplastic Combined Chemotherapy Protocols↗

[Usefulness of endoscopic polypectomy in early colorectal cancer].

This study was carried out to clarify the usefulness of endoscopic polypectomy in early colorectal cancer. Six hundred and sixty-four patients with polypectomized early colorectal cancer were compared with 89 who underwent surgical resection. Among the polypectomized patients, 361 had pedunculated (Ip)-type, 255 semi-pedunculated (Isp)-type, and 48 sessile (Is)-type cancer. The early colorectal cancer was submucosal-invasive cancer (sm cancer) in 16.1% of Ip, 19.2% of I sp, and 22.9% of Is patients. Among the surgically resected patients, sm cancer was present in 41.2% of Ip. 62.1% of I sp. and 58.1% of Is patient in. The percentage of sm cancer and the tumor size surgically resected patients were greater than in polypectomized patients. Local recurrence and distant metastases were investigated after endoscopic polypectomy during follow-up. Two cases (0.4%) of local recurrence were detected after polypectomy among 555 patients with mucosal cancer. Twenty-three (19.8%) of 116 patients with sm cancer underwent surgical resection after polypectomy due to cancer invasion into the vessels and/or extension to the resected margin recognized in polypectomized specimens. Only one case (0.9%) of local recurrence and no distant metastases were detected after polypectomy in 116 patients with sm cancer. Endoscopic polypectomy is very useful as a minimally invasive surgical technique in the protruding type of early colorectal cancer.

Colonoscopy↗