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Biomedical subjects

I Sasaki

Publications and source records attributed to I Sasaki.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lipopolysaccharide- and proinflammatory cytokine-induced energy production in intestinal and colonic epithelial cell lines.

BACKGROUND: Although epithelial cells in ulcerative colitis may be metabolically deficient, it remains unknown whether epithelial cells modulate energy metabolism in inflamed mucosa. The purpose of the present study is to investigate whether inflammatory mediators such as lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) alter energy metabolism in epithelial cells. METHODS: Adenosine 5'-triphosphate (ATP) levels in HT29 cells cultured with LPS, IL-1beta, IL-6, or TNF-alpha were measured with high-performance liquid chromatography, using a reversed-phase chromatography column. Cellular and mitochondrial (antimycin A-sensitive) respiration rates were determined polarographically, using a Clark-type oxygen electrode. RESULTS: When the cells were cultured with LPS, IL-6, and TNF-alpha but not IL-1beta, ATP levels increased significantly at 6 h, followed by a decrease at 24 h. Enhancement of oxygen consumption, which was completely blocked by antimycin A, was also shown at 3 h by the exposure to these substrates. CONCLUSION: LPS and proinflammatory cytokines induced cellular ATP generated by mitochondrial phosphorylation. An active energy production in epithelial cells on the exposure to inflammatory mediators may be critical for escape from chronic mucosal inflammation.

Adenosine Triphosphate↗
PubMed1999

Induction of epithelial Na+ channel in rat ileum after proctocolectomy.

In patients with colectomy, epithelial transport function in the remnant small intestine can be regulated in response to the increased fecal electrolyte and fluid loss. Using a rat colectomy model, we investigated the Na+ and K+ transport mechanisms underlying the intestinal response. Proctocolectomy with ileoanal anastomosis was performed on rats. The small intestinal mucosa was mounted in Ussing chambers; then short-circuit currents and 22Na+ fluxes were measured. mRNA expression of the epithelial Na+ channel (ENaC) was determined by Northern blotting. Amiloride-sensitive, electrogenic Na+ absorption appeared in the ileum after proctocolectomy. This functional change was accompanied by the chronological induction of mRNAs for alpha-, beta-, and gamma-subunits of the ENaC in the ileum. Tetraethylammonium-sensitive short-circuit current was also activated. We conclude that electrogenic Na+ absorption and probably K+ secretion are induced in the ileum after proctocolectomy. This induction of electrogenic Na+ absorption is probably mediated by the increase in the mRNA levels for all three types of subunits of the ENaC and may contribute to the recovery from the increased fecal Na+ loss.

Aldosterone↗
PubMed1999

Ultrastructural localization of S100A3, a cysteine-rich, calcium binding protein, in human scalp hair shafts revealed by rapid-freezing immunocytochemistry.

We have characterized the subcellular distribution of S100A3, a cysteine-rich calcium binding protein, in human scalp hair shaft. This was accomplished using rapid-freezing immunocytochemistry, a technique that combines rapid-freezing, freeze-substitution fixation without chemical fixatives, and subsequent electron microscopic detection of immunocytochemical labeling. This technique preserves both the antigenicity and the ultrastructural integrity of fully keratinized tissues, which are highly unmanageable when prepared for immunoelectron microscopy. In the hair shaft, S100A3 was primarily identified in the endocuticle and was also present in the intermacrofibrillar matrix surrounding macrofibril bundles of intermediate filament keratins in cortex cells. Double immunolabeling of S100A3 and hair keratins revealed the in situ spatial relationship between them. In the endocuticle, S100A3 was present on the inner portion of the endocuticle adjacent to the cell membrane complex, whereas hair keratins were present on the outer portion. These results provide the first ultrastructural evidence that an S100 protein is localized in specific subcompartments in human hair cells. (J Histochem Cytochem 47:525-532, 1999)

Adolescent↗
PubMed1999

Development of an oral formulation of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, using n-lauryl-beta-D-maltopyranoside as an absorption enhancer.

The effects of formulation factors on the enhancement of colonic absorption of azetirelin by n-lauryl-beta-maltopyranoside (LM) were studied in rats. Coadministration of LM with a small volume of azetirelin solution to the proximal colon increased the AUC of the drug by 8.7-fold. There were no significant differences in the LM-induced absorption profiles of azetirelin between unligated and ligated colon. The addition of a viscous polymer to the drug solution, which delayed the in vitro release of both azetirelin and LM, reduced the promoting effects of LM. These results suggest that the action of LM is not affected by sample spreading in the colonic lumen, whereas a rapid release of both azetirelin and LM from the formulation is necessary to maximize the efficacy of LM. Utilizing the balloon sonde method, the effects of LM were also confirmed in the colonic loop of dogs. Based on these results, an enteric capsule formulation of azetirelin containing LM and citric acid (CA), a potential inhibitor of the bacterial degradation of azetirelin in the distal intestine, was prepared and its performance was evaluated in fasted dogs. The bioavailability of azetirelin after the oral administration of this enteric capsule with LM and CA was 43.5% compared with a bioavailability of 14.9% in capsules without LM and CA. Therefore, the delivery of azetirelin and LM to the lower intestine, together with a rapid release of capsule contents, are feasible for the improved peroral bioavailability of azetirelin.

Administration, Oral↗
PubMed1999

Endotoxin contamination in isolation of lamina propria mononuclear cells.

Because the beginning of extraction of lamina propria mononuclear cells is to obtain mucosal tissues that are exposed to luminal bacteria, the contaminated endotoxin in this step and/or the enzymes for mucosal digestion may activate mucosal macrophages and other cells. To address this issue, endotoxin levels in isolation solutions were evaluated during the extraction of lamina propria mononuclear cells from 8 control, 7 Crohn's disease and 8 ulcerative colitis specimens. Endotoxin levels were measured using Toxicolor system based on the limulus tests. Endotoxin levels were consistently below 500 pg/ml, and more importantly, these in enzyme digestion solutions were comparable among control, Crohn's disease, and ulcerative colitis. Therefore, comparative experiments using lamina propria mononuclear cells from these mucosae can be appropriately carried out, at least as far as in a comparable amount of contaminated endotoxin. However, careful consideration is required for the comparative and functional study using peripheral blood and lamina propria mononuclear cells.

Aged↗
PubMed1999

Long term outcome of osteochondritis dissecans of the humeral capitellum.

Long term outcome of osteochondritis dissecans of the humeral capitellum was determined for 53 patients. The average age of the patients at the time of treatment was 16.6 years (range, 10-34 years). The average followup was 12.6 years (range, 3-25 years). Seven of 14 (50%) patients who were treated conservatively and 18 of 39 (46%) who were treated by surgical removal of the fragment were found to have residual elbow symptoms associated with daily living activities (poor outcome). The initial radiographs of the elbow were available for 45 patients; a poor outcome was seen in six of 19 (32%) early lesions and 13 of 26 (50%) advanced lesions. Fourteen elbows had evidence of osteoarthritis on the initial radiographs, and a poor outcome was seen for nine (64%) of these elbows. After removal or detachment of the fragment, seven osteochondral defects were assessed as large, and all seven had a poor outcome. These long term results suggest that the residual elbow symptoms associated with daily living activities in approximately 50% of patients may be associated with advanced lesions, osteoarthritis of the elbow, and a large osteochondral defect.

Activities of Daily Living↗
PubMed1999

[Vitamin B1 deficiency polyneuropathy presenting homolateral imitative synkinesia].

We report a 56-year-old woman with vitamin B1 polyneuropathy, showing bilateral homolateral imitative synkinesia. Needle electromyogram revealed neurogenic changes, and the amplitude of muscle action potential was low. Sural nerve biopsy showed a marked loss of myelinated fibers, and severe axonal degeneration was diagnosed. Spinal and brain MRI revealed no abnormalities. In the literature, these synkinesias were observed in patients with parietal, thalamic, and basal ganglia lesions and with chorea. We suggest that this synkinesia is the release phenomenon in the circuit of the motor programming system due to the disturbance of peripheral nerve or funiculus posterior.

Electromyography↗
PubMed1999

The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs.

BACKGROUND: The herbal medicine Dai-Kenchu-To, composed of zanthoxylum fruit, ginseng root, and dried ginger rhizome, is clinically effective for uncomplicated postoperative adhesive intestinal obstruction. We investigated the effect of Dai-Kenchu-To and each ingredient on upper gastrointestinal motility and its mechanism of action. METHODS: Five mongrel dogs were equipped with 4-strain gauge-force transducers on the gastric body, antrum, duodenum, and jejunum to measure contractile activity of the circular muscle. Dai-Kenchu-To (1.5 g) or the separate ingredients zanthoxylum fruit, ginseng root, or dried ginger rhizome (1.0 g each) were administered by bolus into the gastric lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intragastric Dai-Kenchu-To-induced contractions was studied. RESULTS: Intragastric Dai-Kenchu-To induced phasic contractions in the antrum, duodenum, and jejunum. Zanthoxylum fruit elicited phasic contractions mainly in the duodenum and jejunum, whereas dried ginger rhizome induced phasic contractions in the antrum. Ginseng root had no effect. Phasic contractions induced by intragastric Dai-Kenchu-To were inhibited by atropine and hexamethonium at all sites, although ondansetron inhibited these contractions in the antrum and duodenum. CONCLUSIONS: Intragastric Dai-Kenchu-To stimulates upper gastrointestinal motility through cholinergic and 5-hydroxytryptamine 3 receptors.

Animals↗
PubMed1998

Duodenal gastrinoma--clinical features and usefulness of selective arterial secretin injection test.

Duodenal gastrinoma is recognized as a relatively common cause of Zollinger-Ellison syndrome, but its clinical and biological features are not well known. Here we report a case of duodenal gastrinoma with lymph node metastasis which was confirmed by pathology examinations. Hypergastrinemia and gastric acid hypersecretion were documented, but the secretin test showed negative results. An enlarged peripancreatic lymph node lying close to the pancreas head was the only positive finding on preoperative imaging studies. The results of the selective arterial secretin injection (SASI) test suggested that the primary tumor was located in the gastrinoma triangle. Finally, surgical exploration was carried out and a submucosal tumor, approximately 15 mm in size, was detected by intraoperative palpation at the posterior wall of the proximal portion of the duodenum. Intraoperative pathology examination demonstrated metastases to regional lymph nodes. The present case calls attention to the unique features of duodenal gastrinomas, which differ from those of pancreatic origin: a highly malignant potential for its small size, and submucosal location in the proximal duodenum. The SASI test is recommended for assessing the location of a primary lesion if it cannot be identified by various conventional imaging studies.

Diagnosis, Differential↗
PubMed1998

Pretreatment staging of endoscopically early gastric cancer with a 15 MHz ultrasound catheter probe.

BACKGROUND: The usefulness of and problems associated with an ultrasound catheter probe in the pretreatment staging of endoscopically early gastric cancer remain unexplored. METHODS: Endoscopic ultrasonography using a 15 MHz catheter probe of 2.6 mm diameter was performed in a prospective study to determine the pretherapy staging of endoscopically early gastric cancer in 78 patients. The results of the ultrasound images were compared with the histologic findings of the specimens obtained by endoscopic mucosal resection or surgical resection. RESULTS: The accuracy of the catheter probe for depth of invasion of endoscopically early gastric cancers was 67% (52 of 78 patients). The accuracy in determining depth of invasion in relation to endoscopic type was significantly higher for the elevated type (91%) than for the depressed type of early cancer (56%) (p < 0.01). The staging accuracy classified by histologic type was significantly higher for differentiated (86%) than for undifferentiated (18%) cancer (p < 0.01). Staging accuracy decreased as tumor size increased. The accuracy, sensitivity, and specificity for nodal staging were 80%, 17%, and 90%, respectively. CONCLUSIONS: A 15 MHz ultrasound catheter probe is most useful for determining depth of invasion when the tumor is histologically differentiated and endoscopically of the small elevated type early gastric cancer, but it is unreliable in the diagnosis of metastatic lymph nodes.

Adenocarcinoma↗
PubMed1998

Sodium butyrate-induced liver-type alkaline phosphatase activity in a small intestinal epithelial cell line, IEC6.

Sodium butyrate is a well-recognized differentiating agent inducing alkaline phosphatase activity, one of the epithelial differentiation markers. When IEC6 cells, a nontransformed, small intestinal epithelial cell line, were cultured with butyrate, this substrate induced alkaline phosphate activity in a time- and dose-dependent fashion. However, the type of isoenzyme involved was a liver-type, not an intestinal-type. Electron microscopy revealed that the induced activity was strictly localized in the cytosol and not on the plasma membrane. However, disaccharidase activities, another kind of differentiation marker, were also enhanced by sodium butyrate. In addition, the positive cells demonstrating the presence of alkaline phosphatase activity were preferentially observed in tubular structures. These data show that butyrate-induced alkaline phosphatase activity is closely associated with differentiation-like phenomena in IEC6 cells, although the type of isoenzyme and cellular localization of the activity are different from those observed in mucosa.

Alkaline Phosphatase↗
PubMed1998

Surgical aspect of enteroinsular axis after gastrointestinal surgery with reference to incretin secretion.

An alteration of the enteroinsular axis (EIA) may be an important etiologic factor in postsurgical changes in gastrointestinal (GI) function. In this review, we present recent works, both from our laboratory and others, on how changes in the EIA function may be involved in postsurgical GI complications, especially late dumping syndrome (LDS). We found no or minimal direct role for vagal signals in the control of gastric inhibitory polypeptide (GIP) and enteroglucagon secretion, which regulate EIA function. In gastrectomized patients, it is suggested that the hypersecretion of glicentin and glucagon-like peptide-1 (GLP-1) induced by a rapid arrival of nutrients to the distal gut suppresses glucagon secretion and may be a cause of LDS. In patients who underwent proctocolectomy, we observed no significant postoperative changes in EIA function, although there are some conflicting reports. It seems unlikely that ordinary pancreaticobiliary diversion would cause a significant change in EIA function after an oral glucose load. Our experimental model of ileojejunal transposition produced marked hypersecretion of incretin secreted from the distal gut, which may alter EIA function. Further elucidation of the regulatory mechanism of EIA may provide a new strategy for the medical and surgical treatment of LDS.

Digestive System Surgical Procedures↗
PubMed1998

Second fracture of the distal humerus after varus malunion of a supracondylar fracture in children.

Nine children sustained a second fracture of the distal humerus after union of an ipsilateral supracondylar fracture which had healed with cubitus varus. There were eight boys and one girl with a mean age of five years (1 to 8) at the time of the second fracture which occurred at a mean of 1.5 years after the first. In all patients, the second fracture was an epiphyseal injury of the distal humerus, either associated with a fracture of the lateral metaphysis below the site of the previous supracondylar fracture, or a fracture-separation of the entire distal humeral epiphysis. This suggests that the physis and epiphysis tend to be more subject to injury than the metaphysis of the distal humerus in children who have had a previous supracondylar fracture with varus malunion.

Child↗
PubMed1998

Three-dimensional structure of mucosal and submucosal lymphatics in rat small intestine.

The organization of the lymphatic system in the rat ileum was investigated by the three-dimensional reconstruction using serial sections after dilatation of lymphatics. This method has an advantage to exclude possible artifacts in the conventional corrosion cast method. The villus possessed several lacteals and connected to each other by sinus. Two or three perpendicularly oriented lymphatics descended and led into the submucosal lymphatic network. In mucosa and submucosa, no valvular structure was detected. This study confirmed the voluminous lacteals and fine network structure of lymphatics in submucosa without valves, suggesting great potential to keep lymph and to drain soluble factors and cellular components.

Animals↗
PubMed1998

Preoperative staging of colorectal cancer by a 15 MHz ultrasound miniprobe.

BACKGROUND: Our objective was to examine the accuracy of a 15 MHz ultrasound miniprobe in the pre-operative staging of colorectal cancer by assessing the depth of tumor infiltration and involvement of pericolonic lymph nodes. METHODS: Thirty-three patients with colorectal cancer who underwent ultrasonography with a miniprobe were studied prospectively. The results of this imaging were compared with the histologic findings of the resected specimens. RESULTS: The accuracy of the miniprobe for depth of invasion (T category) was 82% (27 of 33) for all tumors, 76% (13 of 17) in pT1 cases, and 88% (14 of 16) in pT2 to pT4 cases. The accuracy of the miniprobe for nodal staging (N category) was 87% (26 of 30) overall. The sensitivity was 63% (5 of 8), the specificity was 95% (21 of 22), the positive predictive value was 83% (5 of 6), and the negative predictive value was 88% (21 of 24). CONCLUSIONS: The miniprobe is an accurate method for the preoperative TN staging of colorectal cancer. We recommend its preoperative use because the results may influence the surgical approach.

Aged↗