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S Matsuno

Publications and source records attributed to S Matsuno.

At least 127 records · Page 7Linked to original sources
PubMed1999

The degree of hepatic regeneration after partial hepatectomy in rats with peritonitis and the role of lipid peroxidation.

Bile accumulation in the peritoneal cavity after partial hepatectomy reduces hepatic regeneration. In 70% of hepatectomized rats with bile peritonitis, hepatic DNA synthesis showed a delayed initiation and diminished peak level. Because intraperitoneal bile significantly accelerated lipid peroxidation and decreased energy metabolism in the liver remnant, all hepatectomized rats with bile peritonitis died within 7 days. Subcutaneous administration of exogenous combined antioxidants SOD and catalase dramatically reduced lipid peroxidation and improved the survival rate. Although the slightly elevated serum endotoxin level in rats with peritonitis may play a role in the inhibition of hepatic regeneration, the result suggest that intraperitoneal accumulation of bile components may also directly accelerate lipid peroxidation in the liver remnant, inhibiting the hepatic regeneration.

Alanine Transaminase↗
PubMed1999

Induction of mineralocorticoid receptor by sodium butyrate in small intestinal (IEC6) and colonic (T84) epithelial cell lines.

Mineralocorticoid action is essential for colonic sodium and water absorption and is mediated via mineralocorticoid receptors in the upper half of colonic crypts. On the other hand, it has been established that sodium butyrate induces differentiation-like phenomenon in vitro. The aim of this study is to investigate whether this bacterial product participates in the regulation of gene and protein expression of mineralocorticoid receptor in vitro. IEC6 and T84 cells were stimulated by sodium butyrate and RNAs extracted. Gene expression of mineralocorticoid receptor was evaluated by northern blotting or semiquantitative RT-PCR. Protein expression was determined in T84 cells using immunohistochemistry. To investigate whether MR induction was associated with cellular differentiation, we also measured alkaline phosphatase in situ. The mineralocorticoid receptor gene was induced by sodium butyrate in both IEC6 and T84 cells. Immunoreactivity increased in butyrate-treated T84 cells, but receptor-containing cells were not uniformly distributed and often formed clusters. Induction of alkaline phosphate activity was also demonstrated in both IEC6 and T84 cells. Double staining by immunoreactivity and alkaline phosphatase activity clearly demonstrated the colocalization of both after butyrate treatment. In conclusion, sodium butyrate up-regulates gene and protein expression of the functionally important mineralocorticoid receptor in epithelial cells, after induction by differentiation-like condition in vitro.

Alkaline Phosphatase↗
PubMed1999

Intragastric capsaicin stimulates motility of upper gut and proximal colon via distinct pathways in conscious dogs.

The aim of the present study was to investigate the effect and mechanism of action of intragastric and intraduodenal capsaicin on gastrointestinal motility. Five mongrel dogs were equipped with eight strain gauge force transducers on the stomach, small intestine, and proximal colon. In the interdigestive state, capsaicin was administered into the gastric or duodenal lumen. The effects of atropine, hexamethonium, ondansetron, and FK888 on capsaicin-induced contractions were studied. Intragastric capsaicin induced contractions within 15 min in the gastric antrum, duodenum, proximal jejunum, and proximal colon. These stimulatory effects were inhibited by atropine at all sites; by hexamethonium in the small intestine and colon; by ondansetron in the antrum, duodenum, and colon; and by FK888 in the antrum and colon, respectively. Intraduodenal capsaicin had no effect on contractility. Stimulation of afferent fibers by capsaicin in the stomach but not in the duodenum augments contractile activity in local and distant regions of the gut via distinct pathways.

Animals↗
PubMed1999

Remodeling of vascular wall in Crohn's disease.

To clarify the changes in vascular resistance in Crohn's disease, we studied changes in the thickness of arterial media histometrically. The resected specimens of mesenterium and intestine from 18 patients with Crohn's disease were used. Each intestinal lesion was classified into three grades: no inflammation, exudative change, and fibrosing change. In the ileum, significant atrophy in the media of the submucosal peripheral arteries was noted during exudative and fibrosing changes, while in the submucosal larger vessels or in the mesenterium, the thickness of the arterial media did not change. In the colon, atrophy in the media of the submucosal arteries was noted in all stages except in the larger vessel during exudative change, while no significant changes were noted in the mesenterium. In conclusion, it is suggested that circulatory disturbance occurs even in the early stage in Crohn's disease, and there seems to be increased vascular resistance in the area between the deep submucosal and the distal mesenteric arteries.

Adult↗
PubMed1999

Type II 11beta-hydroxysteroid dehydrogenase expression in human colonic epithelial cells of inflammatory bowel disease.

Type IIbeta-hydroxysteroid dehydrogenase endows specificity on the mineralocorticoid receptor by metabolizing cortisol and regulates sodium absorption in renal and colonic epithelium. Altered expression of this enzyme may be associated with impaired sodium absorption often seen in colonic mucosa of inflammatory bowel disease. The aim of this study was to investigate possible abnormality of 11beta-hydroxysteroid dehydrogenase protein and mRNA expression in inflammatory bowel disease. In Crohn's disease, the colonic epithelium showed comparable levels of immunoreactivity and mRNA expression to those of control, except for the decreased immunoreactivity in severe inflamed lesions with deep ulcer. In contrary, a lack or decrease of immunoreactivity was relevant in ulcerative colitis regardless of the histological degree of inflammation. The mRNA expression was also significantly decreased in ulcerative colitis. This study demonstrates that abnormality of epithelial cells in ulcerative colitis includes the enzyme that regulates water and sodium absorption, which are physiologically essential.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed1999

Phase II study of docetaxel in patients with metastatic pancreatic cancer: a Japanese cooperative study. Cooperative Group of Docetaxel for Pancreatic Cancer in Japan.

Docetaxel has been reported to show promising anti-tumour activity in pancreatic ductal cancer (PC). This study was conducted to evaluate the activity and toxicity of moderate-dose (60 mg m(-2)) docetaxel in Japanese chemo-naive patients with measurable metastatic PC. The patients had a performance status of 0-2. They received docetaxel intravenously over a 1- to 2-h period without any premedication for hypersensitivity reactions. This treatment was repeated every 3-4 weeks with dose adjustments based on the toxic effects observed. Twenty-one patients were eligible and treated with docetaxel. The median number of courses was 2 (range, 1-4). None of the patients achieved an objective response; seven showed no change and 13 showed progressive disease. In one patient, the response was not assessable because of early death. The median survival time for all patients was 118 days. The main grade 3-4 toxicities by patient were leucocytopenia (67%) and neutropenia (86%). Other grade 3-4 toxicities included anaemia (10%), thrombocytopenia (5%), nausea/vomiting (29%), anorexia (29%), GOT/GPT increase (10%), alkaline phosphatase increase (14%), malaise/fatigue (33%) and alopecia (24%). In conclusion, docetaxel, administered on this schedule, did not show significant anti-tumour activity in patients with metastatic PC.

Adult↗
PubMed1999

Digest

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Infrequent somatic mutations of the p73 gene in various human cancers.

AIMS: It has already been reported that loss of heterozygosity (LOH) on chromosome 1p is frequent in a variety of human cancers. This finding implies the presence of some important tumour suppressor genes in this region. p73, a candidate tumour suppressor gene identified recently in chromosome band 1p36.33, encodes a protein highly homologous to p53. To investigate the role of the p73 gene in human carcinogenesis, we studied genetic alterations of this gene in various human cancers. METHODS: We analysed the entire coding exons as well as their surrounding exon-intron boundaries of the p73 gene in 185 cases of various types of tumours (47 breast cancers, 43 colorectal cancers, 31 gastric cancers, 23 neuroblastomas, 21 lung cancer cell lines, and 20 pancreatic cancer cell lines); they are known as a group of tumours with frequent LOHs in the 1p region. PCR-SSCP analysis was performed and tumours in which aberrant migrating sized bands were observed were subjected to direct sequencing analyses. RESULTS: Of the 185 cases, only one somatic mis-sense mutation of glutamine from arginine at codon 269 in exon 7 was found in one breast cancer. In addition, several polymorphisms were found at codons 137, 336, 349, and 610, as well as in introns 6, 8, and 9. Monoallelic expression was also observed in pancreatic cancer cell lines. CONCLUSIONS: Our results suggest that inactivation of the p73 gene does not play a major role in the tumour types analysed in the present study.

Alleles↗
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

Role of early continuous regional arterial infusion of protease inhibitor and antibiotic in nonsurgical treatment of acute necrotizing pancreatitis.

This paper reviewed our experience with the nonsurgical management of acute necrotizing pancreatitis (ANP) by continuous regional arterial infusion (CRAI) of protease inhibitor (nafamostat mesilate, 240 mg/day) and antibiotic (imipenem, 0.5 g every 12 h). 47 patients with ANP admitted within 7 days were treated with intensive care and CRAI for 5 days prospectively. 40 patients responded to CRAI therapy and the mortality rate in these patients was 2.5%. 7 patients (14. 9%) did not respond to CRAI. 5 of 7 nonresponders died of multiple organ failure although pancreatic necrosis was persistently sterile. The remaining 2 patients who underwent necrosectomy for infected pancreatic necrosis recovered after surgery. In 34 patients treated with CRAI in the early stage within 72 h after the onset, 31 (91.2%) responded. The mortality rate was 5.9% and the incidence of infected pancreatic necrosis was 2.9% in these 34 patients. These results demonstrated that most patients with ANP responded to conservative management combined with CRAI with nafamostat and imipenem when employed within 72 h after the onset. Early intervention of CRAI with protease inhibitor and antibiotic has a significant role in the nonsurgical management of ANP.

Adult↗
PubMed1999

A novel diamino-pyridine derivative prevents excessive leukocyte infiltration in aggravation of acute necrotizing pancreatitis.

Leukocyte infiltration in the pancreas is involved in the aggravation of acute pancreatitis from edematous phase into necrotic change, and mild disease into severe disease; however, the mechanism responsible for leukocyte accumulation is not fully understood. This study was designed to clarify the mechanism underlying leukocyte accumulation into the pancreas and to elucidate the therapeutic efficacy of a novel diamino-pyridine derivative, IS-741 on leukocyte-endothelial cell interaction using rat necrotizing pancreatitis model. The number of adherent leukocytes to pancreatic collecting venules assessed by in vivo fluorescence microscopy increased significantly in necrotizing pancreatitis animals in a time-dependent manner. The expression of CD11b on circulating neutrophils determined by flow cytometric analysis was enhanced to approximately 500% after 2 h. IS-741 attenuated the leukocyte adherence significantly, accompanied by a lower up-regulation of CD11b. These findings were further supported by the histological examination that the accumulation of leukocytes in the pancreas was remarkably inhibited by IS-741. These results suggest that the leukocyte accumulation in the early phase of acute necrotizing pancreatitis may be mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. IS-741 attenuated the leukocyte endothelial cell interaction as a consequence of its inhibitory effect on CD11b upregulation.

Animals↗
PubMed1999

Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma.

CONCLUSION: Abnormality of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 appears to play a limited role in pancreatic ductal carcinogenesis. BACKGROUND: Recently, a human G/T-specific TDG gene was identified. This protein acts in a system correcting G/T mispairs to G/C pairs. TDG was mapped to chromosome bands 12q22-q24.1, one of the regions frequently lost in pancreatic cancer. Therefore, there is the possibility that the TDG gene on 12q is one of the genes responsible for pancreatic ductal carcinogenesis. METHODS: Nucleotide sequences of the entire coding region of the TDG gene were analyzed in 21 human pancreatic cancer cell lines. mRNA expression of the TDG gene was also analyzed by Northern hybridization in several human tissues and 21 human pancreatic cancer cell lines. RESULTS: Decreased levels of mRNA expression were detected in the pancreatic cancer cell lines, but no somatic mutations were observed.

Adenocarcinoma↗
PubMed1999

Preventing effect of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies on murine islet allograft rejection.

Immunosuppressive potentials of the blockade of intercellular adhesion molecule-1 (ICAM)-1/leukocyte function-associated antigen 1 (LFA-1) were examined in a murine islet allotransplantation model by using blocking monoclonal antibodies (MAbs) against these molecules. Isolated islets from ICR mice were transplanted into the renal subcapsular space of streptozotocin-induced diabetic C57BL/6 mice. Antibodies were administered immediately after transplantation at a dose of 100 micrograms/mouse/d for 3 or 7 d. In non-treated mice, islet grafts were rejected within 16 d, but the treatment with an anti-ICAM-1 MAb (KAT-1) alone, with anti-LFA-1 MAb (KBA) alone, or with both MAbs significantly prolonged the graft survival. In particular, the combination of KAT-1 and KBA in a 7-d course produced a marked prolongation and induced indefinite graft survivals over 100 d in 88% of recipients. Expression of cytokine transcripts within the islet allografts was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR). In the mice treated with KAT-1 and KBA, the transcripts for Th1 cytokines (interleukin 2 [IL-2] and interferon gamma [IFN-gamma]) were not detected, but the expression of Th2 cytokines (IL-4 and IL-10) was enhanced and persisted over 140 d. In contrast, Th1 cytokines were dominantly expressed in the grafts from untreated mice. These results indicate that administration of anti-ICAM-1 and/or anti-LFA-1 MAbs prolongs murine islet allograft survival potentially by indicating a Th2 deviation.

Animals↗
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

Specific targeting immunotherapy of cancer with bispecific antibodies.

In order to enhance cell mediated cytotoxicity, bispecific antibodies (BsAbs), molecules combining two or more antibodies with different antigenic specificities, have been developed as new agents for immunotherapy. Our recent studies revealed that simultaneous administration of two kinds of BsAbs (anti-tumor x anti-CD3 plus anti-tumor x anti-CD28) together with lymphokine activated killer cells with a T cell phenotype (T-LAK cells) inhibited growth of human xenotransplanted tumors in severe combined immunodeficient (SCID) mice, while single BsAb was without effect. Three kinds of BsAbs (anti-tumor x anti-CD3, anti-tumor x anti-CD28, anti-tumor x anti-CD2) showed the highest cytotoxicity against tumor cells when given simultaneously with T-LAK cells or peripheral blood mononuclear cells in vitro and in vivo. BsAbs can be preserved for immediate application, while cytotoxic T lymphocytes (CTLs) must be made-to-order, and are time-consuming to prepare. Tumor associated antigens, such as MAGE antigens, SART antigens, MUC1 antigen, c-erbB 2 antigen or cancer/testis antigens can be served to target antigens for BsAb production. By conjugation with antibodies to effector cells (anti-CD3, anti-CD28, anti-CD16, anti-CD64, anti-CD89 or anti-CD2), many kinds of BsAbs can be produced to cover most types of cancers from different organs. Therefore this strategy might be ubiquitously applicable to most malignancies.

Animals↗
PubMed1999

Adjuvant immunotherapy using fibroblasts genetically engineered to secrete interleukin 12 prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model.

BACKGROUND: To explore effective therapeutic strategy against cancer of the gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin-12 (IL-12) was developed as an adjuvant therapy against murine tumor after surgical resection. METHODS: Initially, IL-12 was genetically engineered into fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro antitumor effects. In the vaccination model, irradiated C-26 tumor mass was reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to examine how much it suppresses tumor recurrence. RESULTS: IL-12/3T3 cells producing 7.2 ng/10(6) cells/24 h murine IL-12 in vitro exerted dose-dependent potent tumor suppression when coinoculated with C-26 cells in vivo. Specific immunity was also acquired in 63% of mice in vivo. In the vaccination model, protective immunity was developed in 70% of mice that were inoculated with irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not observed in vaccinated mice, although 44% of control mice had recurrence. CONCLUSIONS: Coinoculation of genetically engineered fibroblasts secreting IL-12 with irradiated tumor mass was proved to be an effective tumor vaccine. This system of vaccination is easily applicable to clinical situations, particularly to human gastrointestinal tract cancers.

Adenocarcinoma↗