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T Muto

Publications and source records attributed to T Muto.

At least 91 records · Page 5Linked to original sources

Involvement of APC and K-ras mutation in non-polypoid colorectal tumorigenesis.

The aim of this study was to clarify the role of APC and K-ras mutations in non-polypoid colorectal tumorigenesis. DNA from 63 adenomas (31 polypoid, 17 superficial elevated, 15 superficial depressed), 66 submucosally invasive carcinomas (47 polypoid, 19 non-polypoid) and 34 advanced carcinomas were examined for K-ras codon 12 point mutations and APC mutations in the mutation cluster region. K-ras mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (0% vs 31%: P= 0.018). The frequency in non-polypoid carcinomas was lower than that in polypoid carcinomas (11% vs 56%: P = 0.0008), and was relatively low compared with that in polypoid adenomas (11% vs 31%). APC mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (7% vs 43%: P = 0.016), and that in polypoid carcinomas was similar to that in non-polypoid carcinomas. Polypoid adenomas, polypoid carcinomas and advanced carcinomas had almost the same frequency. There may be some pathway other than the conventional adenoma-carcinoma sequence in development of non-polypoid carcinomas. The precursors of most non-polypoid carcinomas are considered to be de novo or superficial depressed adenomas. In this non-polypoid pathway, APC mutation seems to be requisite but K-ras mutation not. It is possible that new APC mutations are acquired after the development of superficial depressed adenomas.

Adenoma↗

Effect of high ligation on the long-term result of patients with operable colon cancer, particularly those with limited nodal involvement.

OBJECTIVE: To find out what effect the extent of nodal dissection has on patients with operable colonic cancer. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. PATIENTS: 564 consecutive patients who had potentially curative operations for colon cancer. Patients treated by limited nodal dissection, in which only pericolonic nodes were dissected, were excluded. MAIN OUTCOME MEASURES: Disease free survival classified by extent of nodal dissection. RESULTS: High ligation gave no significant advantage when patients were subgrouped according to degree of nodal involvement. However, number of patients with aggressive involvement (including intermediate or central nodes) was small. 511 patients (91%) had limited nodal involvement (no nodal involvement or nodal involvement confined to pericolonic nodes). High ligation of the vessels gave no advantage even with meticulous subgrouping according to age, site, and depth of invasion. CONCLUSION: Most patients with colonic cancer had limited nodal involvement. High ligation did not affect the long term results in these patients, so, less invasive low ligation should be considered. A larger study will be necessary to clarify the indications for low and high ligation for patients with aggressive nodal involvement.

Aged↗

Clinical significance of MUC1 and MUC2 mucin and p53 protein expression in colorectal carcinoma.

BACKGROUND: Up-regulation of MUC1, down-regulation of MUC2 and p53 overexpression are seen in colorectal carcinomas. However, there have been few reports about the associations between MUC1, MUC2 and p53 expression and metastatic potential. The aim of this study was to investigate MUC1, MUC2 and p53 expression in colorectal carcinoma with special reference to regional and distant metastasis. METHODS: Eighty-six colorectal carcinomas were collected from patients undergoing tumor resection. Sections were used for MUC1, MUC2 and p53 immunostaining. Cancers were regarded as MUC1 or MUC2 positive when the positive cells were beyond 30% of cancer cells. Cancers with diffuse or nested patterns were regarded as having p53 overexpression. RESULTS: Of 86 cancers, 37 (43%) were MUC1 positive, 28 (33%) were MUC2 positive and 59 (69%) showed p53 overexpression. A difference was observed only in the frequency of MUC1 positivity with respect to depth of tumor invasion. Neither depth of tumor invasion nor histological differentiation had a positive correlation with MUC1, MUC2 and p53 overexpression. The frequency of MUC1 positive cells in Dukes' C and D tumors was significantly higher than that in Dukes' A and B tumors. The frequency of MUC1 positivity in tumors with hepatic involvement was significantly higher than that in tumors without hepatic involvement (100 vs 39%; p < 0.01). There was no difference in the frequency of MUC2 or p53 positivity in Dukes' stage or hepatic metastasis. MUC1 immunoreactivity of the surface was identical with that of the whole tumor in 81% (70/86) of carcinomas, MUC 2 in 87% and p53 in 100%. CONCLUSIONS: The results suggest that up-regulation of MUC1 is involved in the progression from the non-metastatic to the metastatic stage and that p53 abnormality is not directly involved in it. The data also imply that immunostaining of preoperative biopsy samples is useful for evaluating the immunoreactivity of the whole tumor.

Adult↗

Characterization of intracellular cytokine profile of CD4(+) T cells in peripheral blood and tumor-draining lymph nodes of patients with gastrointestinal cancer.

BACKGROUND: Analysis of serum cytokine levels has shown that cancer-bearing hosts have lower levels of IL-2 and IFN-gamma, suggesting that Th1-type immunity is impaired by cancer. However, the mechanisms of the Th1 dysfunction are not clearly understood. METHOD: The frequencies of Th1 cells in CD4(+) helper T cells were evaluated with an intracytoplasmic cytokine staining method in peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL) of patients with gastrointestinal cancer. RESULTS: Activation of lymphocytes with PMA + Ionomycin induced the expression of IL-2 and IFN-gamma in each lymphocyte population. Compared with PBL of non-malignant donors, PBL in cancer patients contained significantly lower frequencies of CD4(+) T cells that produced IL-2 and IFN-gamma. LNL in cancer patients also contained lower levels of IL-2- and IFN-gamma-producing CD4(+) T cells, although the percentages did not show significant differences from those of PBL in the same patients. CONCLUSION: Our data suggest that suppression of Th1 cytokine in cancer patients is, at least in part, due to the decreased frequency of Th1 cells with CD4(+) phenotype.

CD4-Positive T-Lymphocytes↗

Small advanced colorectal cancers: clinicopathological characteristics and pathogenetic origin.

BACKGROUND: Recently, increasing numbers of small but deeply invading colorectal cancers have been detected. We conducted the present study to examine the hypothesis that these small advanced cancers are more biologically malignant than larger cancers and to elucidate their pathogenetic origin. METHODS: We analyzed the clinicopathological characteristics of 23 advanced cancers not exceeding 2 cm in diameter (Small-Ca) in comparison with 1117 advanced cancers larger than 2 cm (Large-Ca). We compared the frequency of K-ras mutation and the growth pattern (polypoid growth, PG; non-polypoid growth, NPG) between Small-Ca and 60 submucosal cancers not exceeding 2 cm in diameter (Early-Ca). RESULTS: Generally, Small-Ca showed less malignant characteristics than Large-Ca. However, Small-Ca with NPG pattern invaded more deeply and metastasized more frequently than those with PG pattern. In Small-Ca, all ulcerated lesions showed NPG pattern, whereas only 14% of protruded lesions did. In Early-Ca, 90% of non-polypoid lesions showed NPG pattern, whereas only 16% of polypoid lesions did. K-ras mutation was less frequent in ulcerated Small-Ca than in polypoid cancers (33 vs 57%). In Early-Ca, non-polypoid cancers showed a lower frequency of K-ras mutation than polypoid cancers (9% vs 46%). CONCLUSIONS: Small-Ca, in general, were less malignant clinicopathologically than Large-Ca; however, Small-Ca with NPG pattern showed a tendency to be more aggressive than those with PG pattern. The similarity of the K-ras mutation rate and growth pattern of ulcerated Small-Ca and non-polypoid Early-Ca suggests that the majority of ulcerated Small-Ca may originate from non-polypoid Early-Ca.

Aged↗

Relative effects of glucose and glutamine on reactive oxygen intermediate production by neutrophils.

The energy source for neutrophils (PMNs) has long been believed to be glucose. However, it has been shown recently that PMNs use glutamine as well as glucose. Nevertheless, the comparative effects of glucose and glutamine on PMN function remain to be clarified. This study investigated the relative effects of glucose and glutamine on reactive oxygen intermediate (ROI) production by PMNs. In experiment 1, PMNs (1 x 10(6)/mL) isolated from healthy volunteers were incubated in RPMI 1640 medium containing neither glucose nor glutamine for 4, 12, 18, and 24 h at 37 degrees C. The medium was supplemented with 0 or 200 mg/dL (0 or 11 mM, respectively) glucose and glutamine (0, 0.5, 1, or 2 mM). PMN cell death was assessed on the basis of hypodiploid DNA by flow cytometry using propidium iodide DNA staining. ROI production by PMNs was determined by flow cytometry using dihydrorhodamine 123. In experiment 2, isolated PMNs were cultured in RPMI 1640 medium containing neither glucose nor glutamine. The medium was supplemented with glucose (0 or 11 mM) and a competitive inhibitor of glycolysis, 2-deoxy-D-glucose (2-DG; 0 or 20 mM). Each medium was supplemented with glutamine (0, 0.5, 1, or 2 mM) and incubated for 12 h at 37 degrees C. Then, ROI production by PMNs was measured. PMN cell death was not affected by glucose or glutamine in this experiment. In contrast, ROI production by PMNs was greater at 11 mM glucose than at 0 mM glucose at all incubation times studied. At 11 mM glucose, supplemental glutamine enhanced PMN ROI production after 18 and 24 h culture. In contrast, at 0 mM glucose, glutamine augmented ROI production by PMNs after 12 h as well as with 18 and 24 h incubations. PMN ROI production after 12 h culture was significantly greater at 11 mM glucose without 2-DG than at both 11 and 0 mM glucose with addition of 2-DG. In addition, supplemental glutamine enhanced ROI production by PMNs when 2-DG was added at 11 and 0 mM glucose. Glucose is essential for PMN ROI production. Under conditions of glucose depletion in vitro, glutamine is of importance in ROI production by PMNs, whereas the enhancing effect of glutamine on PMN ROI production is minor compared to that of glucose.

Cells, Cultured↗

Retrospective radiographic analysis of nonpedunculated colorectal carcinomas with special reference to tumor doubling time and morphological change.

OBJECTIVE: Our aim was to characterize the development of nonpedunculated colorectal carcinomas by retrospective radiographic analysis, with special reference to tumor doubling time and morphological change. METHODS: Eleven colorectal carcinomas, which were observed for >6 months by barium enema examinations, were collected and retrospectively reviewed. There were five early and six advanced carcinomas, including submucosally invasive, superficial depressed carcinomas. RESULTS: Mean diameter of lesions at initial barium enema examination was 13.5 mm (early, 10.4 mm; advanced, 16.0 mm) and that at final barium enema examination was 30.9 mm (early, 18.2 mm; advanced, 41.5 mm). Initial morphology of the lesions was superficial in three, sessile in seven, and semipedunculated in 1. There was no pedunculated lesion. Macroscopic morphology of the five early carcinomas was superficial depressed (IIc) in two cases, mostly depressed but partly elevated (IIc+IIa) in one case, and superficial elevated with a depressed component (IIa+IIc) in two cases; all of the advanced carcinomas were of the ulcerated type. Mean doubling time was 6.8 months (early, 9.4 months; advanced, 4.7 months). Early carcinomas had significantly longer doubling times than advanced carcinomas (p = 0.017, Wilcoxon's text). The lesions with the longest doubling times were superficial depressed lesions. CONCLUSIONS: Early carcinomas have longer doubling times than advanced carcinomas. Most nonpedunculated colorectal carcinomas grow without significant morphological changes. Superficial depressed type tumors grow slowly, maintaining their macroscopic morphology.

Adult↗

Fecal excretion of Salmonella enterica serovar typhimurium following a food-borne outbreak.

Fecal excretion of Salmonella enterica serovar Typhimurium organisms was observed in patients and in people not showing symptoms who were involved in an outbreak of food-borne infection with this organism. Excretion of organisms was prolonged in the patients who were given antimicrobial drugs compared with those who were not. The isolates were indistinguishable by their pulsed-field gel electrophoresis patterns and biotyping from the strain recovered from the roast pork that had been consumed by all of the people. This indicates that these isolates obtained from the infected people had originated in the contaminated pork.

Adolescent↗

Effects of a fermented milk drink containing Lactobacillus casei strain Shirota on the immune system in healthy human subjects.

Nine healthy volunteers drank fermented milk containing 4 x 10(10) live cells of Lactobacillus casei strain Shirota daily for 3 weeks, and their NK activity and other immunological functions were measured. NK activity significantly increased (p<0.01) 3 weeks after the start of intake and remained elevated for the next 3 weeks. The effect was particularly prominent in low-NK-individuals.

Adult↗

p53 gene mutations occurring in spontaneous benign and malignant mammary tumors of the dog.

Sixty-three cases of benign and malignant canine mammary tumors were analyzed to define the alteration of exons 5-8 for the p53 tumor suppressor gene using polymerase chain reaction direct sequence analysis with paraffin-embedded tissues. Four missense mutations were found in 38 benign mammary tumors (11%), and five missense (one tumor had two missense mutations) and one nonsense mutations were found in 25 mammary carcinomas (20%). These data suggest that the p53 gene alterations might be initiated at an early stage of canine mammary carcinogenesis and p53 mutations might be associated with malignancy. However, there was no evidence of any relationship between the p53 alterations and the histologic types of tumors or breeds of dogs.

Animals↗

Anthropometric obesity indices in relation to age and gender in Japanese adults.

The body mass index (BMI), waist circumference, waist to hip ratio, waist to height ratio and skinfolds (near-umbilical and iliac areas) in three age groups (35-44, 45-54 and 55-64 years) were compared in 3117 men and 997 women in Tokyo. In both genders, height was significantly shorter, while the waist to hip ratio and waist to height ratio were significantly higher, in the older groups. In the men, there were no significant differences in BMI and waist circumference among the three age groups, but the iliac skinfold was significantly thinner in each older group, and the paraumbilical skinfold was thinner in the group aged 55-64 years. In the women, the paraumbilical skinfold was significantly thicker in each older group, while waist circumference and the iliac skinfold were significantly larger or thicker in the group aged 55-64 years, and BMI was larger in the groups aged 45-54 and 55-64 years. There were age-related discrepancies between BMI and other obesity indices in the different genders, in that only the waist to height ratio and waist to hip ratio increased with age in both genders.

Adult↗

MMP-1 is a prognostic marker for hematogenous metastasis of colorectal cancer.

BACKGROUND: Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. MMP-1 is a member of collagenases, a family of MMPs that degrades collagens type I, II, and III, main components of the interstitial stroma. The purpose of this study was to investigate the expression of MMP-1 in colorectal cancer and its correlation with hematogenous metastasis. Patients and Methods. We examined 133 cases of colorectal cancer (Dukes A: 72; Dukes B: 26; Dukes C: 23; Dukes D: 12). Sections were cut from formalin-fixed, paraffin-embedded samples containing the deepest site of cancer invasion and stained immunohistochemically with a monoclonal antibody to MMP-1. According to the area of the tumor that was stained, patients were divided into high- and low-MMP-1 expression groups. RESULTS: MMP-1 expression was observed in the cytoplasm of cancer cells, some stromal cells, and a few normal epithelial cells of colonic mucosa. High MMP-1 expression was found in 47 (35.3%) cases and low in 86 (64.7%). Hematogenous metastasis was identified in 14 (29.8%) of high-MMP-1 groups and 12 (13.9%) of low-MMP-1 groups. MMP-1 expression significantly correlated with hematogenous metastasis of colorectal cancer, but no correlation was found between MMP-1 expression and the other clinicopathological features investigated. CONCLUSIONS: MMP-1 expression may be a novel marker for hematogenous metastasis of colorectal cancer, and its inhibition may be a strategy for prevention of metastasis.

Adult↗

Characteristics of coronary heart disease in Japanese taxi drivers as determined by coronary angiographic analyses.

Several epidemiological studies have shown that the prevalence of ischemic heart disease is higher in occupational drivers than in people with other occupations. Although occupation categories can be surrogate measures for coronary risk factors, the relationships between taxi driving and severity of coronary heart disease (CHD) has not been investigated. Even more important, the contribution of risk factors to the severity of CHD in taxi drivers remains unclear. Our study tested the hypothesis that taxi driving could be associated with the severity of CHD. We also examined the relation between this occupation and risk factors and social lifestyle. We analyzed the coronary angiograms of 57 consecutive male taxi driver patients and compared them with those of 215 age-adjusted male non-taxi-driver patients. The number of diseased vessels and risk factors were compared between two groups. The prevalence of myocardial infarction and multi-vessel disease was higher in the taxi-driver patients than in the non-taxi-driver patients. The taxi-driver patients had higher prevalence of body mass index (BMI), diabetes, and smoking, higher levels of low-density lipoprotein cholesterol (LDL-C), and lower levels of apolipoprotein AI (ApoAI). Multiple logistic regression analysis showed that multi-vessel disease was associated with BMI and diabetes mellitus in taxi-driver patients. The taxi-driver patients were characterized by more extensive coronary atherosclerosis associated with higher prevalence of diabetes mellitus and obesity. These characteristics may be explained by in part their working environment.

Automobile Driving↗

[Development of surgery in the 20th century].

The 100-year history of the Japan Surgical Society (JSS) spanned the 20th century. The first congress of the JSS was held in 1899 in Tokyo. In Japan, many specialist surgery societies and several closely related to surgery were established in the latter half of the 20th century although both the Japanese Association for Thoracic Surgery and the Japan Neurosurgical Society were founded before that in 1948. Significant advances in the field of surgery were witnessed in the second half of the 20th century in Japan as well as in other countries. The progress in biotechnology and medical engineering in the latter half of the 20th century and the beginning of the 21st will result in remarkable change in the field of surgery in the future. Significant changes in postgraduate and continuing education and training of surgeons will also be necessary to ensure that surgeons and surgical researchers adhere strictly to bioethical standards.

General Surgery↗

Direct and indirect effects of pulsatile shear stress on the smooth muscle cell.

BACKGROUND: Anastomotic intimal hyperplasia is still an unsolved problem after small caliber prosthetic bypass grafting. Oscillatory turbulent flow occurs at the end to side anastomosis, and produces various effects on smooth muscle cells (SMCs) and endothelial cells (ECs), which compose intimal hyperplasia. We examined the influences of pulsatile oscillating shear stress on smooth muscle cells mitogenic activity induced by sheared endothelial cells. METHODS: 1) Smooth muscle cells were cultured under three different pulsatile shear conditions (mean: 0, 6, and 60 dyne/cm2). 2) Endothelial cells were cultured under both static and sheared condition (mean: 60 dyne/cm2). Using the conditioned media from each well, SMCs were cultured under static and sheared conditions (60 dyne/cm2). Four groups of SMCs were devised by combining the two types of media and the two culture conditions. SMC colony spreading distances were measured as an index of combined migration and proliferation activity. An MTT assay and a cell counting assay were used to determine the proliferation activities of SMCs. RESULTS: 1) SMC spreading activity was suppressed by shear stress. SMC proliferative activity was stimulated by pulsatile turbulent shear stress. 2) SMC spreading activity was stimulated by mitogens derived from ECs under shear stress. However, this augmented SMC spreading activity was attenuated under sheared conditions. The mitogens derived from ECs under pulsatile shear stress had no effects on SMC proliferation activity. CONCLUSIONS: Pulsatile oscillating shear stress attenuates SMC migration activity induced by EC-denve mitogens and stimulates SMC proliferative activity.

Cell Division↗

Comparison between short-term food restriction and exercise on whole body glucose disposal in high-fat rats.

High-fat diets induce whole-body insulin resistance. The aim of this study was to compare effect of two interventions: 3-day food restriction (66% of ad libitum fed) and 3-day exercise training (voluntary running wheels), on decreased insulin-mediated whole body glucose uptake in high-fat fed rats (5 mo old) using the hyperinsulinemic euglycemic clamp procedure. The control group was maintained on rat chow alone. After high-fat feeding for 2 wk, insulin-stimulated whole body glucose utilization was significantly decreased by 26%. The exercise training was more effective than food restriction in lowering plasma concentrations of insulin and triacylglycerol and tissue concentrations of triacylglycerol in soleus muscles. Diminished whole-body glucose uptake resulting from high-fat feeding was reversed completely by exercise training, but only partially by food restriction. The time course of starvation on insulin-stimulated glucose uptake was also observed in high-fat fed rats. Although the extension of starvation time to 48 h resulted in decreased plasma glucose, insulin and triacylglycerol concentrations, whole body glucose uptake did not increase further. These findings suggest that short-term exercise has a higher restorative effect on insulin sensitivity in high-fat fed rats than food restriction, in spite of the same loss in body weight, presumably due in part to improved local lipid availability.

Animals↗

[Three cases of bilateral Acanthamoeba keratitis].

BACKGROUND: We encountered three cases of bilateral Acanthamoeba keratitis and reviewed six cases of bilateral Acanthamoeba keratitis including our three cases in Japan. CASES: 1. A 40-year-old woman had worn soft contact lenses (SCLs) and her visual prognosis was good because the lesion was at an initial stage in each eye. 2. A 35-year-old woman had worn hydrophobic SCLs, and needed bilateral superficial keratectomy, because the lesion was at a transient stage in each eye and her visual prognosis was poor. 3. A 37-year-old woman had worn hydrophobic SCLs and her visual prognosis was good because the lesion was at an initial stage in each eye. RESULT: The condition was observed only in SCL and hydrophobic SCL wearers. All SCL wearers were cured easily and their visual prognosis was good, but in hydrophobic SCL wearers, two cases out of three, visual prognosis was poor. CONCLUSION: Bilateral Acanthamoeba keratitis has been so far observed only in SCL or hydrophobic SCL wearers. Hydrophobic SCL wearers tend to have poor visual prognosis.

Acanthamoeba Keratitis↗