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T Muto

Publications and source records attributed to T Muto.

At least 19 recordsLinked to original sources
PubMed1997

Differential effects of polyunsaturated fatty acids on chemosensitivity of NIH3T3 cells and its transformants.

Polyunsaturated fatty acids (PUFAs) have been suggested, on the basis of animal-model studies, to be related not only to cancer development but also to chemotherapeutic effects. Controversy persists, however, as to which types of PUFAs are beneficial in terms of chemosensitivity. In this study, we used the NIH3T3 cell line and its SIC(sigmoid colon cancer)-oncogene transformants to investigate the effects of PUFAs on the chemosensitivity of non-malignant and malignant cells in terms of cell proliferation. We also determined the fatty-acid composition of cells by high-performance liquid chromatography (HPLC). The results revealed that the sensitivity of SIC transformants to mitomycin C (MC) was lower than that of NIH3T3 cells cultured in 10% calf-serum DMEM without PUFA supplementation. When cells were cultured in DMEM supplemented with eicosapentaenoic acid (EPA) at a concentration (2 micrograms/ml) that does not influence cell proliferation, the sensitivity of SIC transformants to MC increased, whereas that of NIH3T3 cells decreased in comparison with the sensitivity of cells cultured without PUFA supplementation (p < 0.05). There was no difference between the 2 cell lines in the chemosensitivity of cells cultured in medium supplemented with arachidonic acid (ARA). The SIC transformants contained more stearic acid (C:18) and less lauric acid (C:12) than NIH3T3 cells cultured without PUFA. Culturing the cells in medium supplemented with EPA or ARA modified the cellular fatty-acid composition. EPA caused the relative combined percentage of lauric acid and myristic acid (C:14) in SIC transformants to decrease significantly, and the SIC transformants tended to accumulate additional EPA, in contrast to the NIH3T3 cells. We conclude that the alterations in fatty-acid composition in malignant transformants caused by exogenous EPA differ from those in non-malignant cells, and that these changes account for the increased chemosensitivity of malignant transformants. Although preliminary, these findings imply that EPA specifically enhances the chemosensitivity of malignant cells.

3T3 Cells↗
PubMed1997

Mutational analysis of the hMLH1 gene using an automated two-dimensional DNA typing system.

Searching for mutations in DNA mismatch repair genes is important not only for presymptomatic diagnosis, but also for documenting the spectrum of mutations among families carrying predispositions to hereditary nonpolyposis colorectal cancer (HNPCC). We utilized an automated two-dimensional DNA typing system for mutational analysis of the hMLH1 gene and established optimal conditions for application of the technique to analysis of hMLH1. This approach enabled us to visualize 21 spots covering all 19 coding exons on a single gel and to envisage whether and where any mutations existed. All mutations that we had detected previously by other means in a panel of HNPCC patients and in one patient with sporadic endometrial cancer were also detectable by this method. Furthermore, using the 2-D system, we screened the entire coding regions of the hMLH1 gene in DNAs isolated from affected individuals belonging to two large HNPCC kindreds and four HNPCC-like kindreds, and from four patients with multiple primary cancers as well as eight sporadic colorectal cancers with replication error (RER)-positive phenotypes. We detected novel germline mutations in one HNPCC proband and one sporadic colorectal cancer with the RER-positive phenotype and one polymorphism in two HNPCC-like kindreds. This new diagnostic method is applicable to mutational analysis of any disease-causing gene, and it offers a major improvement over current approaches.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Impact of lymph node metastasis on survival with early gastric cancer.

The impact of lymph node metastasis on the survival of early gastric cancer (EGC) cases remains controversial. A retrospective study of 621 patients with EGC undergoing gastrectomy with lymphadenectomy during the period 1966-1993 was performed to evaluate the influence of node involvement on long-term outcomes. Lymph node metastasis was observed in 63 cases (10.1%). Two groups, EGC with and without node involvement, were compared with respect to long-term results and various clinicopathologic factors. The median observation period was 123 months. EGC cases without metastatic nodes had significantly better outcomes than those with node involvement in terms of overall survival as well as survival excluding deaths due to diseases unrelated to the primary EGC. Survival rates for EGC patients with node involvement did not, however, differ significantly according to the number of metastatic nodes. Three factors-submucosal invasion, large tumor size, and recurrence-were significantly related to lymph node metastasis. Age, sex, family history of malignancy, histologic type, and multiple occurrence of gastric cancer were unrelated to the prevalence of node involvement. The frequency of recurrence in EGC cases without node involvement was low (1.8%, 10 of 558). Recurrence was not, however, exceptional in those with metastatic nodes (9.5%, 6 of 63). EGC patients with lymph node metastasis, even with only a single positive node, constitute a high risk group for EGC recurrence.

Aged↗
PubMed1997

Preoperative total parenteral nutrition influences postoperative systemic cytokine responses after colorectal surgery.

Previous human studies have investigated the influences of nutritional routes on the serum kinetics of cytokines following intravenous administration of lipopolysaccharide. However, it is unclear whether preoperative nutritional routes influence responses of systemic cytokines in patients after surgery. This study was designed to investigate whether preoperative total parental nutrition (TPN) influences systemic interleukin-6 (IL-6) and interleukin-8 (IL-8) responses in patients following surgery for colorectal cancer. Patients with colorectal cancer received TPN (TPN group, n = 6) or an oral diet (oral group n = 6) for more than 7 d before the operation. Patients in the TPN group received standard TPN. Patients in the oral group received an ordinary hospital diet. Blood samples were collected before the operation, on postoperative day 1 (POD1), POD3, and POD7. Levels of IL-6, IL-8, and C-reactive protein (CRP) in plasma were determined. The characteristics of patients in the TPN and oral groups were comparable. Mean carbohydrate intake was greater (28 versus 19 kCal/kg), and lipid intake was smaller (0 versus 7 kCal/kg) in the TPN group than in the oral group. Plasma CRP levels did not differ between the two groups. Plasma IL-6 and IL-8 levels were marginally higher before the operation and were significantly higher on POD1 in the TPN group than in the oral group. The IL-6 levels showed a positive regression relation with the amounts of blood loss only in the TPN group (P < 0.05, r = 0.881). The slope of the regression line was steeper in the TPN group than in the total enteral nutrition (TEN) group (P < 0.01). In conclusion, routes of nutritional supply have an impact on the production of systemic cytokines after insult. The postoperative systemic IL-6 and IL-8 responses in patients who received standard TPN preoperatively were greater than in patients who received an oral diet. Preoperative nutrition via the enteral route may provide better regulation of cytokine responses after surgery than parenteral nutrition.

Colorectal Neoplasms↗
PubMed1997

Renal cell carcinoma of the spindle cell type with metastasis to the pancreas: a case report.

We report a case of renal cell carcinoma in a 49-year-old man with multiple metastases, including some to the pancreas which were initially diagnosed as primary pancreatic carcinoma. The first clinical manifestation was jaundice caused by a large metastatic lymph node. Computed tomography showed tumors in the body and tall of the pancreas as well as in the left kidney. Angiography showed that all of the lesions were hypervascular. The patient was finally diagnosed as having renal cell carcinoma. Cholecystectomy and choledochojejunostomy were performed. Intraoperative biopsy of the lymph nodes along the common hepatic artery showed spindle cell carcinoma which was compatible with renal cell carcinoma. Since renal cell carcinoma with pancreatic metastasis is rare, special attention should be paid to its differentiation from primary pancreatic carcinoma in patients with tumors in both the pancreas and kidneys.

Adrenal Gland Neoplasms↗
PubMed1997

Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis.

Branched chain amino acids (BCAAs) and glutamine are both recommended in catabolic states. The object of this study was to compare the efficacies of alanylglutamine (Ala-Gln)-enriched and BCAA-enriched total parenteral nutrition (TPN) on the protein kinetics in peritonitis. Rats were divided into Ala-Gln and BCAA groups after intraperitoneal implantation of an osmotic pump, delivering a continuous infusion of Escherichia coli. Glutamine composed 30.0% (w/v) of the total amino acids in the Ala-Gln group, and BCAA composed 30.5% (w/v) of the total amino acids in the BCAA group. The two solutions were isocaloric and isonitrogenous. Whole body protein turnover and organ fractional protein synthetic rates (FSR) were measured on days 3 and 5. Serum amino acid levels and mucosal morphology were determined. Ala-Gln group had higher rates of whole body protein turnover, and hepatic FSR on both days. Serum glutamine levels correlated with hepatic and muscle FSR. Ala-Gln TPN group had greater mucosal thickness, numbers of mitoses per crypt, and FSR in distal intestine. Ala-Gln-enriched TPN may be a useful nutritional treatment modality in sepsis.

Amino Acids↗
PubMed1997

Distribution of a synthetic protease inhibitor in rat pancreatic acini after supramaximal secretagogue stimulation.

Protease inhibitors may have a beneficial effect in acute pancreatitis. The effects of E3123, a new low molecular weight protease inhibitor, on the ultrastructure of isolated pancreatic acini were examined using transmission electron microscopy. Acini supramaximally stimulated with cerulein (10(-8) M) formed large cytoplasmic vacuoles similar to those generated in the cerulein-induced in vivo model of pancreatitis. Pretreatment of isolated acini with E3123 significantly reduced the size and number of vacuoles associated with cerulein treatment. The distribution of 3H-E3123 in acinar cells was examined using a pulse-chase protocol and electron microscopic autoradiography. Cellular levels of 3H-E3123 increased about 30-fold in acinar cells treated with cerulein (10(-8) M) compared to unstimulated controls. In cerulein-treated acini examined after a 5-min chase, 47.4% of the autoradiographic grains were associated with the rough endoplasmic reticulum and 13.2% were associated with zymogen granules. After 30 min of incubation, the grains associated with the endoplasmic reticulum decreased to 18.5% but increased to 26.3% over zymogen granules. Thus, E3123 is taken up by the acinar cell and follows a cellular itinerary similar to that of newly synthesized secretory proteins. One potential conclusion from these studies is that the ability of E3123 to reduce the formation of vacuoles in supra-maximally stimulated acini may be due to its inhibition of proteases within the secretory pathway.

Amylases↗
PubMed1997

Interleukin-1 and tumor necrosis factor alter plasma concentration and interorgan fluxes of taurine in dogs.

We examined the effects of interleukin-1 beta (IL-1), tumor necrosis factor (TNF), and alanylglutamine (Ala-Gln) infusion on the plasma concentrations and interorgan fluxes of taurine and taurine precursors, including methionine and serine, using chronically catheterized awake dogs. In the first study, the dogs received 5 micrograms/kg/h of either human recombinant IL-1 or TNF intravenously for 2 h. Taurine fluxes in the liver and gut were calculated by blood flows and arteriovenous differences during infusion and for 2 h after discontinuation of the cytokine infusions. The 2 h continuous infusions of TNF and IL-1 resulted in 60 and 90% increases, respectively, in the arterial plasma taurine concentration. Hepatic taurine flux changed from uptake to release after 2 h of continuous IL-1 infusion. In the second study, we investigated whether Ala-Gln infusion affects taurine metabolism under normal and stress conditions. The dogs were given a constant 2 h intravenous infusion of IL-1 or saline. Ala-Gln (6 mumol/kg/min) was infused simultaneously during the second hour. Plasma concentrations and fluxes, across the liver, gut, and lung, of taurine and taurine precursors were studied. IL-1 administration increased the plasma concentration, hepatic release, and lung uptake of taurine. Ala-Gln infusion did not affect either plasma concentrations or organ fluxes of taurine. These data suggest that cytokines play a role in taurine metabolism under stress conditions.

Alanine↗
PubMed1997

Role of upper gastrointestinal surveillance in patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an inherited autosomal-dominant disease in which hundreds and thousands of adenomas with malignant potential are found throughout the colon and rectum. An increased risk for benign and malignant upper gastrointestinal neoplasia has long been recognized in patients with FAP. In this article, the authors report their findings from a study of 35 registered patients to assess the prevalence, anatomic distribution, depth of invasion, and natural history of upper gastrointestinal tumors in patients with FAP.

Adenoma↗
PubMed1996

Functional expression of CD11a on CD8+ cells is suppressed in regional lymph nodes with cancer involvement in patients with gastrointestinal carcinoma.

BACKGROUND: To evaluate the immunologic activity of regional lymph nodes, the phenotype of lymphocytes and the functional expression of cell adhesion molecules (CAMs) on lymph node lymphocytes (LNL-: uninvolved, LNL+: involved) were investigated in patients with gastrointestinal carcinoma. METHODS: The lymphocyte subpopulation and the expression of CD11a, CD44, and CD29 on CD4+ and CD8+ cells in peripheral blood lymphocytes (PBL), LNL- and LNL+ derived from 37 patients with gastrointestinal carcinoma were studied. In addition, the adherence of CD8+ cells to ICAM-1 which reflects the adhesive function of CD11a, was examined, and changes in this adherence were studied by experimental coculture with cancer cells (DLD-1). RESULTS: Although there were no differences in the overall proportion of T cells between the groups, CD8+ cells and CD16+ cells were considerably diminished in LNL+. The expression of CD11a and CD29 on CD4+ and CD8+ cells was significantly lower in LNL than in PBL, whereas the expression of CD44 showed no significant differences. The expression levels of these CAMs were almost the same in LNL- and LNL+. Only CD11a expression on CD8+ cells in LNL+ was significantly lower than that in LNL- (P < 0.005). The adherence of CD8+ cells in LNL+ to ICAM-1 was lower than that in PBL and LNL-, and was extremely enhanced by experimental coculture with cancer cells (DLD-1). CONCLUSIONS: These data indicate that the functional expression of CD11a (LFA-1) on CD8+ T cells is suppressed in cancer-involved regional lymph nodes in patients with gastrointestinal carcinoma.

Adenocarcinoma↗
PubMed1996

Cancer cell morphology at the invasive front and expression of cell adhesion-related carbohydrate in the primary lesion of patients with colorectal carcinoma with liver metastasis.

BACKGROUND: Liver metastasis from colorectal carcinoma is an important problem in surgical treatment and profoundly affects the prognosis of patients. If it were possible to identify characteristic features in the primary lesion strongly related to liver metastasis, these could be used as prognostic markers for liver metastasis. To search for such features, the primary lesions of patients with colorectal carcinoma with liver metastasis were investigated. METHODS: Three groups of colorectal carcinoma were examined: Group A with synchronous liver metastases; Group B with only lymph node metastases without recurrence for 5 years; and Group C with recurrence of liver metastases. Groups A and B included 24 cases and Group C, 20. We focused on cancer cell morphology at the invasive front and expression of sialyl Lewis X (sialyl Lex) in the primary cancer. RESULTS: At the invasive front in Group A it was frequently found that polygonal, not columnar, cancer cells with a single or solitary trabecular form with indistinct polarity, showed an infiltrative growth pattern. This type of morphology was termed "focal dedifferentiation" and graded four levels. Eleven of 24 cases (46%) had severe focal dedifferentiation in Group A, 1 of 24 (4%) in Group B, and 6 of 20 (30%) in Group C. Sialyl Lex staining was positive in 12 of 24 cases (50%) in Group A, in 3 of 24 cases (13%) in Group B, and in 7 of 20 cases (35%) in Group C in the primary carcinoma. In respect to the staining of (sialyl Lex) at focal dedifferentiation, it was positive in 17 of 24 cases (71%) in Group A, in 4 of 24 cases (17%) in Group B and in 11 of 20 cases (55%) in Group C. Focal dedifferentiation and sialyl Lex staining in the primary cancer showed a significant difference between Groups A and B. Sialyl Lex staining at focal dedifferentiation showed a significant difference between Groups A and B and Groups B and C. Other adhesion related molecules, sialyl LeA and CEA, showed no difference among Groups A, B, and C. CONCLUSIONS: Both focal dedifferentiation and expression of sialyl Lex antigen in the primary lesion are considered good markers for assessing the metastatic proclivity of colorectal cancer.

Adult↗
PubMed1996

HST-1/FGF-4 stimulates proliferation of megakaryocyte progenitors synergistically and promotes megakaryocyte maturation.

Megakaryocyte (MK) development is dependent on the complex interaction of MK progenitors, various cytokines and stromal elements. We previously reported that an injection of replication-deficient adenovirus containing HST-1/FGF-4 cDNA (Adex1HST-1) into mice caused a twofold increase in peripheral platelet count for 30 days without any other hematological or histological abnormality. In the present study using Adex1HST-1-infected human megakaryocytic Dami cells, we demonstrated for the first time that HST-1/FGF-4 promoted MK maturation, inducing increases in DNA ploidy, cytoplasmic and membrane maturation, and platelet-like particle release. Moreover, HST-1/FGF-4 acted on megakaryocytic cells to induce secretion of IL-6 and TNF-alpha, and increased adhesion of megakaryocytic cells to human endothelial cells primarily via VLA-4 and LFA-1 molecules; both mechanisms have been shown to lead to MK maturation. We also showed that HST-1/FGF-4 stimulates the proliferation of MK progenitors not alone but synergistically with IL-3 via IL-6 and with c-mpl ligand (thrombopoietin) not via IL-6. This result supports the hypothesis of the presence of two distinct populations of MK progenitors: IL-3-dependent and Tpo-dependent. All these results suggest that HST-1/FGF-4 can regulate MK development not only as an MK potentiating factor, but also as an inducer of cytokine secretion from MK, and as a modulator of adhesive interactions with endothelial cells.

Adenoviruses, Human↗
PubMed1996

The crystal structure of human glycosylation-inhibiting factor is a trimeric barrel with three 6-stranded beta-sheets.

Glycosylation-inhibiting factor (GIF) is a cytokine that is involved in the regulation of IgE synthesis. The crystal structure of recombinant human GIF was determined by the multiple isomorphous replacement method. The structure was refined to an R factor of 0.168 at 1.9 angstrom resolution. The overall structure is seen to consist of three interconnected subunits forming a barrel with three 6-stranded beta-sheets on the inside and six alpha-helices on the outside. There is a 5-angstrom-diameter "hole" through the middle of the barrel. The barrel structure of GIF in part resembles other "trefoil" cytokines such as interleukin 1 and fibroblast growth factor. Each subunit has a new class of alpha + beta sandwich structure consisting of two beta-alpha-beta motifs. These beta-alpha-beta motifs are related by a pseudo-twofold axis and resemble both interleukin 8 and the peptide binding domain of major histocompatibility complex protein, although the topology of the polypeptide chain is quite different.

Amino Acid Sequence↗
PubMed1996

Flat adenoma as a precursor of colorectal carcinoma in hereditary nonpolyposis colorectal carcinoma.

BACKGROUND: Because flat adenoma shows a higher malignancy rate compared with other types of polyps, it is considered to play an important role in the carcinogenesis of colorectal carcinoma. In the present study, we examined flat adenomas in hereditary nonpolyposis colorectal carcinoma (HNPCC) patients. METHODS: Nine HNPCC patients who presented with flat adenomas were examined. All patients underwent either surgery or endoscopic polypectomy for colorectal carcinoma and/or adenoma. In all patients, annual colonoscopy had been performed once a year throughout the follow-up period after the initial treatment. When colorectal polyps were detected during follow-up colonoscopy, all lesions were endoscopically excised. Clinicopathologic features and microsatellite instability of both malignant lesions and adenomas were examined. RESULTS: Thirteen malignant lesions were detected: seven advanced carcinomas and six early carcinomas. Among 4 early carcinomas with submucosal invasion, 3 lesions (75%) were categorized as superficial type, with a configuration similar to flat adenoma. The frequency of flat adenoma was strikingly high in HNPCC patients in the present study. Among 73 polyps detected, 37 (50.7%) were flat adenomas. Both malignant lesions and flat adenomas had proximal predominance, 61.5% and 59.5%, respectively. Eleven of 15 lesions (73.3%) showed replication error. CONCLUSIONS: These results suggest the importance of flat adenoma as a precursor of colorectal carcinoma in some groups of HNPCC patients. Further study is essential to elucidate the natural history of flat adenomas in HNPCC patients.

Adenoma↗
PubMed1996

Identification of genes differentially expressed in B16 murine melanoma sublines with different metastatic potentials.

B16-F10 and B16-BL6 are B16 mouse melanoma sublines that preferentially metastasize to the lung following i.v. and s.c. injections, respectively. To study molecular mechanisms underlying the different metastatic behaviors exhibited by the B16 melanoma sublines, we performed differential hybridization of the genes transcribed in these cells and compared their expression levels. We isolated four genes that were highly expressed in B16-F10 cells but not in B16-BL6 cells: TI-225 (polyubiquitin), TI-229 (pyruvate kinase), TI-241 (LRF-1 homologue), and TI-227 (novel gene). Triosephosphate isomerase, 10-formyltetrahydrofolate dehydrogenase, tyrosinase-related protein 2, cytochrome c oxidase, ATP synthetase alpha subunit, RNA helicase, and ribosomal protein (L37, J1, acidic phosphoprotein), however, showed higher expression in B16-BL6 cells than in B16-F10 cells. Among these clones, transfection of TI-241 into the low metastatic clone F1 converted the parental cells from low- into high-metastatic cells. TI-241 may regulate the expression of various genes as a transcription factor in the complex process of metastasis.

Amino Acid Sequence↗
PubMed1996

Exocrine function of caerulein-induced acute pancreatitis in anesthetized rats.

Exocrine function was studied in anesthetized rats that had received two specific doses of caerulein (maximal stimulation and supramaximal stimulation). Male Wistar rats (body weight, 200-250 g) were divided into three groups: the control group (4-h saline infusion), the maximal stimulation group (0.25 microgram/kg per h caerulein for 4 h), and the caerulein pancreatitis group (10 micrograms/kg per h for 4h). Histologically, interstitial edema and cytoplasmic vacuolization were observed only in the caerulein pancreatitis group, with no abnormal findings in the other groups. The volume of pancreatic juice was significantly increased in both the maximal stimulation group and the caerulein pancreatitis group. The protein output and the amylase output in the 1st h of caerulein infusion were also significantly increased, to 459% and 338% in the maximal stimulation group, and to 925% and 1430% respectively, in the caerulein pancreatitis compared to the baseline values. We also found that the pancreatic juice of the caerulein pancreatitis group contained precipitated protein, and high trypsin activity, and protein degradation was confirmed by electrophoresis. These findings were not observed in the other groups. These results strongly suggest that hypersecretion and the appearance of trypsin activity in pancreatic juice plays an important role in the induction of histological changes in this pancreatitis model in anesthetized rats.

Acute Disease↗