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T Muto

Publications and source records attributed to T Muto.

At least 253 records · Page 14Linked to original sources
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

Expressions of cell cycle regulators in human colorectal cancer cell lines.

To study the altered mechanisms of cell cycle regulation in colorectal cancer, the expressions of cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, p53 and retinoblastoma (Rb) protein were analyzed by western blotting in a series of human colorectal cancer cell lines. The colorectal cancer cell lines exhibited various expression patterns of cell cycle regulators, which may reflect differences in the biological characteristics of cancer cells and in the genetic backgrounds of carcinogenesis. A correlation was found between p53 gene alteration and p21 expression, suggesting that p53 gene mutation usually suppresses p21 expression, though p21 expression could be induced via both a p53-dependent and a p53-independent pathway in colorectal cancer. None of the cell lines studied expressed p16 protein, suggesting that inactivation of p16 may be a common alteration in colorectal cancer. Moreover, all the D-type cyclins, especially D2 and D3, were expressed at a high level in most of the cell lines. Loss of p16 expression and increased expression of D-type cyclins promote CDK-mediated Rb phosphorylation. All of the colorectal cancer cell lines studied herein expressed Rb protein, but the growth-suppressive properties of Rb may be inactivated by the loss of p16 expression and increased expressions of D-type cyclins. In view of the pivotal role of Rb in cell cycle regulation, loss of p16 expression and overexpression of D-type cyclins may be critical alterations in colorectal cancer.

Cell Cycle↗
PubMed1997

Heterogeneity of DNA ploidy pattern in carcinoma of the gallbladder: primary and metastatic sites.

There are few detailed reports on the heterogeneity of the nuclear DNA ploidy pattern in carcinoma of the gallbladder. We studied twelve autopsied cases who died of extended gallbladder carcinoma. Multiple samples were taken from the primary site (Pri), from direct invasion of the liver (Hinf), from hematogenous metastasis to the liver (H), from lymphatic metastasis (LN) and from peritoneal dissemination (P). The DNA ploidy pattern was investigated by image cytometry. Heterogeneity of the DNA ploidy pattern in Pri, Hinf, H, LN and P was found in 7/11, 2/10, 5/10, 2/6 and 3/6 cases, respectively. Aneuploidy was more frequently found in Hinf than at the Pri. The DNA index of Hinf was significantly higher than that of Pri. Several stemlines, with different quantities of DNA, were found in Pri. Most of these stemlines were also observed in other sites. These facts may suggest that polyclonal cancer cells rather than one cancer cell or monoclonal cancer cells of a Pri metastasize or infiltrate, and that various polyclonal cancer cells proliferate to different degrees under different circumstances.

Aged↗
PubMed1997

Molecular cloning of a novel gene similar to myeloid antigen CD33 and its specific expression in placenta.

We have isolated a novel gene that encodes a protein sharing significant similarity with myeloid antigen CD33. The complete cDNA contains an open reading frame of 1,326 nucleotides encoding 442 amino acids. The deduced amino acid sequence indicates that this molecule belongs to the immunoglobulin (Ig) superfamily and is likely to be a new member of the sialoadhesin sub-family. It is composed of three Ig-like domains; its high degree of similarity to CD33 (70% identity) in the first and second of these domains implies that the placenta-specific gene product is likely to be associated with cell-cell interaction. Northern-blot analysis revealed transcripts of four distinct sizes, 7.5 kb, 5.0 kb, 4.1 kb, and 2.0 kb, specifically in the placenta. Consequently, we termed this gene CD33L (CD33 antigen-like). An alternatively-spliced transcript encoding a 342-amino-acid peptide which lacked the transmembrane region and the cytoplasmic tail was also isolated. We mapped CD33L by fluorescence in situ hybridization (FISH) to human chromosome 19q13.3, where the CD33 gene is also located.

Alternative Splicing↗
PubMed1997

125I uptake competing with iodine absorption by the thyroid gland following povidone-iodine skin application.

Povidone-iodine solution is widely used to disinfect the skin surface or prevent suppuration during human and animal surgery. Using radioisotope 125I, we examined whether iodine may be absorbed and then concentrated in the thyroid gland when povidone-iodine solution is applied to the skin of rats or mice. The competition for 125I uptake was examined in mice and rats after the application of povidone iodine to the skin. We also traced the process of absorbed 125I in the thyroid glad during the fixation for tissue preparations. Povidone-iodine applied to the skin significantly reduced the uptake of 125I both in mice and rats. Significant flux of 125I from the thyroid gland in povidone-iodine treated animals was noted during the thyroid fixation of tissue preparations. From these results, povidone-iodine application to the skin instead of stable KI administration may be practical for preventing the uptake of 125I by the thyroid gland during 125I compound administration for medical therapy. In animal experiments concerning thyroid functions, careful attention must be paid when povidone-iodine is used for disinfection in animal surgery.

Administration, Cutaneous↗
PubMed1997

Relationship between weight change in young adulthood and the risk of NIDDM. The Sotetsu Study.

OBJECTIVE: To investigate the independent effect of weight change in young adulthood on the risk of prevalent NIDDM among middle-aged Japanese men. RESEARCH DESIGN AND METHODS: A case-control study was carried out in 895 male employees aged > or = 30 years of a railway company located in the vicinity of Tokyo. Adjusted odds ratios (ORs) were calculated for prevalent diabetes in each category of weight change (obtained from subjects' medical records) in young adulthood and adulthood. Adjustment for current age, initial BMI, and weight change in each age stratum was performed by the Mantel-Haenszel method or multiple logistic regression analysis. RESULTS: Weight change between 20 years of age and the age at maximum weight was not associated with the risk of NIDDM. Weight gain between 20 and 25 years of age was significantly and positively associated with the risk of NIDDM (OR 3.87 for gains > or = 10.0 kg, 2.53 for gains of 5.0-9.9%, and 3.73 for gains > or = 10.0%). On the other hand, moderate weight gain after 30 years of age was significantly inversely associated with NIDDM (OR 0.44 for gains of 5.0-9.9 kg, 0.15 for gains of 10.0-19.9%, and 0.38 for gains of 20.0-29.9%). CONCLUSIONS: Extreme weight gain between 20 and 25 years of age is a significant predictor of NIDDM, independent of current age, BMI at 20 years of age, and weight change within other age strata.

Adult↗
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↗
PubMed1997

Prognostic significance of non-gastric malignancy after treatment of early gastric cancer.

BACKGROUND: The recurrence rate of early gastric cancer is low and so second malignancies developing after treatment of this cancer have potential prognostic significance. METHODS: Some 633 patients with early gastric cancer were studied. The median observation time was 123 months. To examine the characteristics of patients with early gastric cancer and subsequent malignancy, two groups of patients, those with and those without non-gastric malignancy, were compared using univariate analysis with respect to various clinicopathological factors. To determine which parameters were independently significant, computer-based multivariate discriminant function analysis was applied. To estimate the prognostic significance of non-gastric malignancy, death rates from these diseases in patients treated for early gastric cancer were compared with the mortality rates attributable to the same diseases in the general population of Japan. RESULTS: The frequency of other malignancies, 9.6 per cent (61 of 633), was significantly higher than those gastric cancer recurrence rate of 2.4 per cent (15 of 633). After treatment for early gastric cancer patients with subsequent non-gastric malignancy had a significantly poorer outcome than those free from other cancers. Lung cancers were the major neoplasms occurring after the treatment of early gastric cancer. Univariate and multivariate analysis revealed male sex to be an independent risk factor for the subsequent development of non-gastric malignancy. Comparison of mortality rates revealed that men with early gastric cancer have a higher risk of death from non-gastric malignancy than the general male population. CONCLUSION: These results suggest that systemic surveillance is particularly important for male patients after the treatment of early gastric cancer.

Age Factors↗
PubMed1997

Effective prevention of thrombocytopenia using adenovirus-mediated transfer of HST-11FGF-4 gene: in vivo and in vitro studies.

A novel biological function of HST-1 protein (FGF-4) was investigated by constructing an adenovirus vector containing the HST-1 cDNA and applied for thrombocytopenia as a gene therapy. A single intraperitoneal injection of the replication-deficient adenovirus containing the HST-1 gene (Adex1HST-1) into mice caused a two-fold increase in peripheral platelet count for 30 days, and effectively prevented experimentally induced thrombocytopenia. Studies of Adex1HST-1-infected or HST-1 protein-treated megakaryocytic Dami cells suggested that HST-1 protein promotes megakaryocyte maturation, and increases cytokine secretion from megakaryocyte and adhesive interactions between megakaryocyte and endothelial cells. Colony assay revealed that HST-1 protein stimulated CFU-MK (colony-forming unit of megakaryocyte) not alone but synergistically with early-acting cytokines such as IL-3 or Tpo (c-mpl ligand) as a megakaryocyte potentiating factor. These results have important implications for clinical application of the Adex1HST-1 for thrombocytopenia.

Adenoviridae↗
PubMed1997

[Development of a bioartificial liver using porcine hepatocyte spheroids].

We have discussed hereby about the latest studies on bioartificial liver systems including those examined in human clinical trials. Based on the discussion and in order to meet the present requirement of clinical sides to the system, that is, maximal metabolic capacities up to 6 hours of plasma perfusion treatment, we have developed a new bioartificial liver based on high-cell density suspension perfusion culture of porcine hepatocyte spheroids, which have two or three times higher functional expressions that those of conventional cultures. The module developed can retain a large number of hepatocytes(4 x 10(9)) in 150 mL volume without any functional deterioration usually accompanied by high-cell density cultivation, even when compared with small-scale dish-level cultures.

Animals↗
PubMed1997

Grossly punched-out lesions in the aorto-iliac region can be histologically classified as false, pseudo-false, or disguised aneurysm.

Aneurysms are morphologically classified as true or false based on the nature of their walls. True aneurysms are composed of all or parts of layers of the vessel. False aneurysms are the result of rupture and their walls have only fibrous tissues. The orifice of false aneurysms is narrow relative to the aneurysmal diameter and thus they are grossly or angiographically referred to as punched-out lesions. Hence false aneurysms present with punched-out lesions, but in reverse, are all of punched-out lesions false aneurysms? We experienced some cases of punched-out lesions which histologically contained traces of elastin, and the purpose of this report was to histologically investigate grossly punched-out lesions. We examined 671 elderly autopsy cases, and a total of 21 grossly punched-out lesions in the aorto-iliac region were selected. They were histologically classified as false, "pseudo-false", or "disguised" aneurysm. False aneurysms were found in 3 patients (0.45%), and were histologically mycotic. A total of 5 "pseudo-false" aneurysms were found in 3 patients (0.45%). They histologically contained traces of elastin, and thus they were categorised in true aneurysms. A total of 13 "disguised" aneurysms were found in 6 patients (0.89%). They were true fusiform aneurysms with an eccentric thrombus, on which a fibrin-cap formed a narrow orifice. Partial sections are insufficient for diagnosis; cross-sections are necessary. To the best of our knowledge, there have been no reports of "pseudo-false" or "disguised" aneurysms in the aorto-iliac region.

Aged↗
PubMed1997

Anplag, a selective 5-HT2 receptor antagonist, reduces stenosis induced by balloon injury in the hypercholesterolaemic rabbit.

The purpose of this study was to examine the effect of anplag, a 5-HT2 receptor antagonist, on intimal hyperplasia (IH) after balloon injury. In 39 male New Zealand white rabbits, the left carotid artery was denuded of endothelium by an inflated balloon. The injury not only damaged the endothelium, but also caused damage to underlying smooth muscle cells. Twelve rabbits fed normal chow were divided into 2 groups: Group A; anplag was not administered, and Group B; anplag, 100 mg/kg, was given by gavage, including on the day of ballooning. The remaining 27 rabbits were fed chow containing 1% cholesterol and divided into 3 groups: Group C; anplag was not administered, Group D; anplag, 100 mg/kg, was given orally except on the day of ballooning, and Group E; anplag, 100 mg/kg, was given orally including on the day of ballooning. IH in Group B was 13.2% less than that in Group A and IH in Group D was 11.7% less than that in Group C. However, neither of these differences was significant. IH in Group E was significantly less (by 40.1%) than that in Group C. In conclusion, anplag significantly reduced IH after balloon injury in the hypercholesterolaemic rabbit by inhibiting proliferation of smooth muscle cells and cholesterol-uptake by macrophages when it was administered immediately before the procedure.

Administration, Oral↗
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↗