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Biomedical subjects

M A Fujino

Publications and source records attributed to M A Fujino.

At least 19 recordsLinked to original sources

Quantification of sphingosine derivatives in human platelets: inducible formation of free sphingosine.

To elucidate the physiologic role of sphingolipid-derived products as signaling molecules, we analyzed the levels of endogenous sphingosine (Sph) derivatives in human platelets. When the platelets were stimulated with thrombin or 12-O-tetradecanoylphorbol 13-acetate, neither ceramide formation nor sphingomyelin hydrolysis was observed, which suggests that the sphingomyelin cycle may not be an essential part of the signaling pathway under these conditions. In contrast, Sph was found to increase in platelets upon stimulation. The level of Sph 1-phosphate, which is formed from Sph by the action of Sph kinase, was not affected under our conditions. Although it has been established that Sph inhibits protein kinase C, which regulates the functional responses of the platelets, Sph levels which exert an inhibitory effect on protein kinase C cannot be attained under physiological conditions (without exogenous Sph). Considering the stimulation of the synthesis of Sph by the physiological agonist thrombin, we speculate that Sph is a signaling molecule of physiological importance in platelets, but protein kinase C may not be its target.

Adult

Isolation, mapping and mutation analysis of a human cDNA homologous to the doc-1 gene of the Chinese hamster, a candidate tumor suppressor for oral cancer.

We have isolated a human cDNA encoding a 115-amino-acid polypeptide that revealed 97% identity to a candidate tumor suppressor gene for oral cancer in Mesocricetus auratus (deleted in oral cancer-1; doc-1). It also showed a high degree of homology to a gene induced by TNF-alpha in Mus musculus. To investigate its possible role in esophageal carcinogenesis, we examined genetic alterations and expression levels of the gene in 13 esophageal carcinoma cell lines and 10 primary esophageal carcinomas. No mutation nor reduction of expression was observed in any of the 23 cancer materials examined. These results imply that the human doc-1 homologue is unlikely to play a significant role in esophageal carcinogenesis, although its role in the TNF-alpha signaling pathway remains unclear. We mapped DOC1 to chromosome band 12q24.31 by fluorescence in situ hybridization.

Animals

Effect of peptide YY on gastric motor and secretory activity in vagally innervated and denervated corpus pouch dogs.

In this study, we examined the mechanism by which constant intravenous infusion of physiological doses of PYY affects gastric secretion and motility in the vagally innervated (Pavlov) and denervated (Heidenhain) corpus pouch. As a result, only in the Heidenhain pouch, PYY at a dose of 100 pmol/kg-h significantly inhibited gastric secretion in the interdigestive and postprandial states. A dose of 300 pmol/kg-h inhibited the gastric secretion in both types of pouch, but inhibition in the Pavlov pouch was less than in the Heidenhain pouch. The inhibitory effect of PYY on phase III contractile activity was dose-dependent and significant, except in the Heidenhain pouch, and no dose of PYY had any effect on postprandial gastric motility. After all, vagal denervation enhanced the inhibitory effect of PYY on gastric secretion, but abolished the inhibitory effect on phase III contractile activity. Our findings strongly suggest that the inhibitory effect of PYY on gastric secretion is in part mediated by a non-vagal pathway and the inhibitory effect of PYY on gastric motor activities is completely dependent on vagal innervation, but the vagus nerve acts as an inhibitory modulator of the inhibitory effect of PYY on gastric secretion.

Animals

Selective uptake of intraluminal dextran sulfate sodium and senna by macrophages in the cecal mucosa of the guinea pig.

The involvement of macrophages in the passage of intraluminal substances into the lamina propria was examined in the large intestine of the guinea pig. Dextran sulfate sodium (DSS) and senna, which, experimentally, induce ulcerative colitis and melanosis coli, respectively, were chosen for examination, since these substances are visible under the microscope without any special treatment. DSS (MW 50,000) and senna were orally administered to guinea pigs. In tissue sections of the intestine, the presence of DSS was demonstrated by toluidine blue staining, while senna was visible under the light microscope as brown pigment. In the large intestine of guinea pigs, macrophages were most numerous in the cecum, decreasing in number towards the rectum. Metachromatic reaction due to DSS was first recognized in the epithelium of the cecum, and was subsequently incorporated by macrophages. The presence of DSS, either in the epithelium or in macrophages, was not recognized in the small intestine or the distal colon. Senna pigmentation was also limited to the cecum and proximal colon, in which pigmented macrophages aggregated in the lamina propria. The two different substances administered orally were taken up in the cecum, and partly also in the proximal colon; the substances passed through the epithelium and were incorporated by macrophages. This finding suggests the existence of a weak point in the intestinal barrier in this particular portion of the intestine.

Animals

[An investigation of the factors influencing serum pepsinogen levels--sex, age, smoking, drinking].

BACKGROUND: Until now, the influence of sex, age, smoking, drinking on serum pepsinogen levels has been assessed by single regression analysis. However, the influence of those factors on pepsinogen levels should be assessed exactly by multiple regression analyses. SUBJECTS AND METHODS: 891 subjects were collected from by questionnaire and serum tests. Analyses were done with serum pepsinogen I (PG I), pepsinogen II (PG II) and pepsinogen I/II ratio (PG I/II) as a criterion variable and as categorized explanatory variables, sex, age, current or past smoking habit, and current drinking habit. And analyses are done by Mann-Whitney U test, correlation coefficient, single regression method, multiple regression method. RESULTS: PG I level is significantly higher in men than in women by Mann-Whitney U test. But the effect of sex factor is not remarkable by multiple regression analyses. PG II level increased and PG I/II level decreased with progression of age by all analyses methods. Current or past smoking elevates PG I level by Mann-Whitney U test, but current smoking dose and past smoking amount showed no dose-dependent associations with PG I level. Current drinking elevates PG I level by Mann-Whitney U test, but current drinking dose showed no dose-dependent associations with PG I. However, the effects of current smoking and current drinking to serum PG levels is not so large by multiple regression analyses. CONCLUSION: The effects of sex, current smoking and current drinking to serum PG levels are not remarkable by multiple regression analyses. Significantly, PG II level increased and PG I/II level decreased with progression of age. Therefore it may not be necessary to consider the effects of sex, smoking habit and drinking habit when serum pepsinogen levels are used as markers for gastric cancer.

Adult

Freeze-fracture immunocytochemistry for intracellular localization of serotonin in mast cells stimulated with compound 48/80.

Changes of intracellular localization of serotonin in rat mast cells were examined by freeze-fracture immunocytochemistry, to prevent the translocation of the serotonin antigen. Rat peritoneal cells including mast cells were stimulated in vitro with compound 48/80, at 17 degrees C for 0, 30 or 60 s for exocytosis to occur. The mast cells were fixed, quickly frozen and freeze-fractured to expose the antigen on the fractured surface. They were immunostained with serotonin antibody, and the immunoreactions on the fractured surface were examined on ultrathin sections by electron microscopy. Unstimulated mast cells exhibited serotonin localization mostly in each intragranular matrix. In contrast, mast cells stimulated for 30 s exhibited increased serotonin in their intergranular cytoplasm. Mast cells showed more distinct immunoreactions in the cytoplasm where degranulation would be promoted after 60 s. It is suggested that intracellular release of serotonin occurred in the stimulated mast cells.

Animals

Quality of peptic ulcer healing induced by lansoprazole and roxatidine.

This study reports preliminary results of a controlled, multicenter trial on the quality of ulcer healing induced by lansoprazole (LPZ) or roxatidine (R) in gastric ulcer (GU) or duodenal ulcer (DU) patients. Group A received LPZ 30 mg q.d. and group B received R 75 mg b.i.d. All drugs were given for 8 weeks in GU and for 6 weeks in DU. Endoscopy and gastric biopsy were performed to detect Helicobacter pylori before and on completion of treatment. The healing rates of groups A and B were 100 and 69.2%, respectively, in GU and 100 and 70.0%, respectively, in DU. This difference (p < 0.01) was significant between the two groups in GU. There was no significant difference between the two groups in the S2 stage shift rate in GU and DU. The H. pylori clearance rates of groups A and B were 33.3 and 20.0%, respectively, in GU and 62.5 and 33.3%, respectively, in DU. The differences in treatment response (healing rates and S2 shift rates) between the LPZ group and the R group may be related to the differences in suppression of acid secretion and in bactericidal effects on H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles

X-ray microanalysis of rat mast cells stimulated with compound 48/80 in combination with quick-freezing method.

X-ray microanalysis was performed on rat mast cells prepared by quick-freezing, cryosectioning and freeze-drying (QF-FD) method, or quick-freezing and freeze-substitution (QF-FS) method. Peritoneal cells including mast cells were stimulated with compound 48/80 for 0, 10 or 30 s at 17 degrees C, and the mast cells stimulated for 30 s started exocytosis. In X-ray spectra of the QF-FD specimen, mast cells stimulated for 10 s increased their levels of phosphorus, sodium and chlorine in the intergranular cytoplasm prior to exocytosis, and kept this increase until 30 s after stimulation. In the QF-FS specimen, where soluble elements were removed, peaks of phosphorus, sulphur and potassium could be detected as elements in X-ray spectra. Phosphorus increased and potassium decreased in intergranular cytoplasm of mast cells stimulated for 10 s, and these changes became more obvious after 30 s. However, supplemental increase of other cations such as sodium could not be detected in the QF-FS specimens.

Animals

Ultrastructural study of mast cells stimulated with compound 48/80 as revealed by quick-freezing method.

The ultrastructure of mast cells stimulated with compound 48/80 was examined by quick-freezing and deep-etching (QF-DE) or freeze-substitution (QF-FS) methods. Peritoneal cells including mast cells of adult male rats were stimulated in vitro with compound 48/80 at 17 degrees C for 0, 10, 30, 60 or 180 s. The QF-DE replicas revealed that the mast cells stimulated with compound 48/80 for 30 s decreased filamentous actin around secretory granules. In the QF-FS specimens, perigranular membranes in mast cells stimulated for 60 s formed pentalaminar structures between adjacent granules in their cytoplasm prior to degranulation. These findings suggest that preparatory states for degranulation occur in the whole cytoplasm of stimulated mast cells at early stages. Moreover, both QF-FS specimens and QF-DE replicas revealed a compact morphological appearance of discharged granules in the extracellular space, indicating the existence of considerable content within the granules. Skeletal structures in the granules were also demonstrated on QF-DE replicas prepared after extracting soluble elements from the cytoplasm. It is suggested that the granular contents associated with the skeletal structures are gradually detached from the discharged granules to ensure local concentration in the tissues.

Animals

Morphological study of rat mast cells stimulated with compound 48/80 at different temperatures.

Changes of mast cells stimulated with compound 48/80 were morphologically investigated at different temperatures. Peritoneal mast cells of male rats were stimulated in vitro at 4 or 17 degrees C. At 17 degrees C, mast cells stimulated for 10 s gave decreased fluorescent reactions for phalloidin. At 30 s stimulation, they showed typical exocytosis initiated by fusions of peripherally located secretory granules to the plasma membrane. In contrast, mast cells stimulated at 4 degrees C exhibited neither decrease of phalloidin reactions nor typical excytosis even after 30 s. It was inferred that the fusions were mediated by cytoplasmic elements, probably the actin filaments previously suggested to prevent release of secretory granules. Furthermore, the space between the perigranular membrane and granular contents was enlarged in some mast cells stimulated at 4 degrees C. The morphological changes suggested that equivocal events occurred also in the cytoplasm of these cells. The mast cells showed no typical exocytosis at 4 degrees C.

Animals

Morphologic changes in the pancreas detected by screening ultrasonography in a mass survey, with special reference to main duct dilatation, cyst formation, and calcification.

Subclinical morphologic changes in the pancreas detected by screening ultrasonography of 130,951 subjects were analyzed in relation to their incidence and background factors. Main pancreatic duct (MPD) dilatation, cystic lesion, and calcification were found in 644 (0.49%), 271 (0.21%) and 65 (0.05%) patients, respectively. The incidence of MPD dilatation and calcification was significantly higher in men (p < 0.0001), whereas cystic lesion was significantly more frequent in women (p < 0.01). Age-dependent increase in the incidence of MPD dilatation and cystic lesion was observed in both sexes whereas that of calcification was observed only in men. Further detailed examinations for 312 randomly selected patients with these findings revealed that 97% of MPD dilatation, 95% of cystic lesion, and 86% of calcification were correctly identified by ultrasonography. Finally, 18 (5.8%) patients with chronic pancreatitis, 16 (5.1%) with neoplastic cysts, 3 with mucin-producing tumors, and 3 with carcinomas (0.96%, respectively) were detected. On the other hand, in 84.0% of MPD dilatation, 87.4% of cystic lesion, and 50.0% of calcification, we could not attribute their etiology to any known pancreatic disease. It is indicated that aging and gender are major clinically related factors of these changes.

Adult

Gastric carcinoma, an endoscopically curable disease.

Following refinement of endoscopic diagnosis of gastric cancer, the concept of 'early gastric carcinoma' and its endoscopic features have become established. After the wide acceptance of the techniques of endoscopic mucosal resection (EMR), laser therapy and accurate endoscopic-endosonographic assessment of the depth of invasion, curative endoscopic treatment of intramucosal gastric carcinoma has become established. On the basis of the analysis of lymphatic metastasis, the indications for endoscopic treatment of gastric carcinoma have been defined as (1) well-differentiated, intramucosal adenocarcinoma of a superficial elevated lesion (diameter < 2 cm), and (2) well-differentiated, intramucosal adenocarcinoma of a superficial depressed lesion (diameter < 1 cm) having no ulcer or scar inside. The preferred procedure of endoscopic treatment is EMR with careful histological examination of the resected specimen. It is supplemented by repeat EMR, laser therapy, or surgical gastrectomy in case of incomplete resection. For detection of residual cancer and recurrence, periodic endoscopic follow-up is necessary. Early gastric carcinoma is endoscopically curable.

Adenocarcinoma

Electronic endoscopy in perspective.

Electronic endoscopy, developed in 1983, enables the endoscopic image to be transmitted through electric signals that can be easily processed by computer. An electronic endoscope is composed of three vital parts, i.e., a charge-coupled device (CCD) that converts the image to electric signals, a video processor that converts analog electric signals to the digital and processes them to become video signals, and a television monitor. The introduction of electronic endoscopy has enabled computer management of endoscopic images, on one hand, and provided an opportunity for image processing and analysis, on the other. A digital image management system will further develop into a database of endoscopic images. Combined with the technologies of remote control and remote sensing, the introduction of CCD to endoscopy has made it possible to transform the endoscope, so that it could become a capsule. Future advances in the research of image processing and analysis will lead to the development of a system of automated endoscopic diagnosis.

Electronics, Medical

Morphological changes of small pancreatic cysts in response to secretin stimulation. Observation by endoscopic ultrasonography.

It is difficult to discriminate clinically the etiology of small pancreatic cysts using conventional methods. Endoscopic ultrasonography can delineate small lesions. In order to help differentiate the etiology of cystic lesions of the pancreas by endoscopic ultrasonography, we investigated morphological changes following stimulation of the pancreatic secretion with secretin. After an intravenous injection of secretin (50 CU), the size, shape, and echogenicity of a cyst smaller than 2 cm were recorded for 15 min. Of 17 cases examined, 10 patients showed an alteration of these factors. These cases were thought to be nonneoplastic cysts, which included all six cases where communication to the main pancreatic duct was demonstrated by ERCP. Five cases of neoplastic cyst did not show the change in shape and size. These results indicate that secretin stimulation provides useful information in the diagnosis of the etiology of pancreatic cyst by endoscopic ultrasonography.

Aged