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Biomedical subjects

T Muto

Publications and source records attributed to T Muto.

At least 217 records · Page 12Linked to original sources

Isolation of a novel TP53 target gene from a colon cancer cell line carrying a highly regulated wild-type TP53 expression system.

We established a colon cancer cell line SW480-LOWTP53-1 carrying a wild-type TP53 transgene that is inducible under control of the lactose operon. Induction of this transgene by isopropyl-beta-D-thiogalactoside (IPTG) arrests growth of the transfected cells. To investigate cellular responses related to the TP53 signaling pathway to induce growth arrest, we applied a differential display method to screen mRNAs isolated from this cell line and looked for genes whose expression was activated or suppressed after induction of wild-type TP53. Subsequent Northern blot analysis confirmed that expression of one novel gene was regulated by wild-type TP53. The cDNA, termed TP53TG1 (TP53 target gene 1), contained an open reading frame of 270 nucleotides encoding 90 amino acids. Under conditions of cellular stress (ultraviolet irradiation or exposure to bleomycin or cisplatin), expression of TP53TG1 was induced in a wild-type TP53-dependent manner, indicating that this gene is likely to play an important role in the signaling pathway of TP53 and may function in response to cellular damage.

Amino Acid Sequence↗

[Carbohydrate chains and hematogenous metastasis: a review].

It is well known that the expression of carbohydrate chains on cell changes during the development and progression of carcinoma. Some carbohydrate chains have been used in clinical practice as tumor markers. Some, such as sialyl Lewis a (CA 19.9), sialyl Lewis X, and Tn, are known to function as adhesion molecules. However, their role in the development of hematogenous metastasis is still controversial. In this paper, many investigations concerning this issue are reviewed. Clinical trials for treatment of patients with advanced cancer using carbohydrate chains are also mentioned.

Animals↗

Relationship between disc displacement and morphologic features of skeletal Class III malocclusion.

The present study assessed the relationship between disc displacement and facial morphologic features in 48 patients with skeletal Class III malocclusion. Clinical examination, standardized lateral oblique temporomandibular joint radiographs, and cephalographs were used to investigate this relationship. Disc displacement was evaluated by the presence of joint sounds (clicking and crepitation) or restricted condylar translation at maximal mouth opening. Thirty-two patients with signs of disc displacement were compared with 16 patients without signs of disc displacement. Results showed that patients with signs of disc displacement had a significantly larger gonial angle and/or SN-MP of the mandible. Thus, morphologic features of patients with skeletal Class III malocclusion may represent a risk factor for the development of disc displacement.

Adult↗

Aneurysm induced by periarterial application of elastase heals spontaneously.

BACKGROUND: The pathogenesis of aortic aneurysms remains largely unknown, despite aneurysmal rupture being an increasingly common catastrophe. METHODS: This study was designed to elucidate the mechanism of arterial dilatation histologically and electron microscopically, utilising a new animal model. Elastase, 3.0 mg/ml, was applied to the abdominal aortae of 18 New Zealand white rabbits from the adventitia side for 3 hours. The rabbits were sacrificed at 0, 3, 14, 28, 42 and 90 days after the procedure (n=4, 3, 2, 2, 2, 3). RESULTS: Two rabbits were found to have developed aortic rupture. On day 0, elastase application induced fusiform aneurysms up to 1.62+/-0.14 times the pre-elastase application aortic diameter. Dilated walls revealed medial elastolysis, degeneration of smooth muscle cells (SMCs) and damaged endothelial cells. By day 3, the smooth muscle cells had changed to the synthetic type. Aneurysms did not progress, and after 42 days, showed gradual shrinkage. By day 90, aortic diameters had nearly normalised. CONCLUSIONS: Aortic walls also returned to the pre-elastase application thickness and some mature medial elastic lamellae showed regeneration. Medial smooth muscle cells reverted to the contractile type. Aortic dilatation induced by peri-aortic application of elastase heals spontaneously, accompanied by regeneration of smooth muscle cells. Irreversible degeneration of medial smooth muscle cells appears to be more critical to aneurysm formation than degeneration of elastic lamellae.

Animals↗

Advantages of straight graft for abdominal aortic aneurysm repair.

The advantages of aneurysm repair with straight tube graft were studied. Between January 1984 and March 1994, 277 patients with abdominal aortic aneurysm underwent operation using straight or bifurcated prosthetic grafts. Of those 277 patients, 37 patients (14%) received straight grafts and the remaining 240 patients received bifurcated ones. These two patient groups were compared in terms of influences of intraoperative aortic clamping, operative time, postoperative recovering condition, incidence of perioperative complications, and long-term results. Hemodynamic influences of aortic clamping were determined by the changes in systemic blood pressure. The duration of aortic clamping was significantly longer in the bifurcated graft group than in the straight graft group (p < 0.01). In addition, the elevation of blood pressure was significantly higher after aortic clamping in the bifurcated graft group than in the straight graft group (p < 0.05) although the blood pressure changes after release of the clamp did not differ significantly. The bifurcated grafts required significantly longer operating time than the straight grafts. There was a tendency for the patients of bifurcated grafts to suffer from complications associated with long duration of the laparotomy, such as pneumonia and bowel obstruction. During an average follow-up period of 5 years, only one patient had to undergo subsequent operation for an aneurysm of the remaining iliac artery. This patient had had a dilatation of the hypogastric artery 1.5 times as large as is normal in the first operation. The long-term results of the remaining 36 patients with straight graft was satisfactory and the remaining iliac arteries were found to be intact. It is concluded that the surgical repair with straight tube graft is a durable procedure for patients with abdominal aortic aneurysms as long as the dilatation of the iliac artery is limited to 1.5 times the normal dilatation.

Aged↗

[Ischemia/reperfusion injury and organ failure].

Reperfusion injury is recognized as a syndrome which impairs an ischemic organ as well as remote organs throughout the entire body. Previous research has revealed that the various inflammatory mediators, such as cytokines, platelet-activating factors, and free radicals, are involved and interact with each other in reperfusion injury. More recently, it has been demonstrated that neutrophils play an important role in the development of reperfusion injury. Thus the process of reperfusion injury is quite similar to that observed during the acute phase of inflammation. The same systemic reaction is also observed in multiple organ failure (MOF) or systemic inflammatory response syndrome (SIRS), where organ failure is a major determinant factor for the prognosis of patients. Regarding the treatment of organ failure due to reperfusion injury, several approaches using monoclonal antibody of adhesion molecules or receptor antagonist for cytokines have been introduced. Despite the current accumulation of knowledge, however, prevention is still the regimen for reperfusion injury and concomitant organ failure.

Humans↗

[Surgery in medical education. Division of surgical oncology].

Medical education is being required to make a big change over the last 10 years due to the rapidly expanding knowledge of medicine and socioeconomical demands from the public. The education system is now focusing on teaching medical students how to learn individual subjects by themselves leading to understand the concept of self learning and adult learning. It is also required for students and residents to improve clinical competence as early as possible. The purpose of this change in medical education is to produce better doctors for the future. In order to achieve our aim it is essential to have continuous education system during the pre and postgraduate periods and also to realize the importance of education. Standardized education program is also essential to be established. Evaluation system for teaching is needed to attract young doctors to teaching, otherwise enough staffs for education would not be obtained. Teaching experiences should be counted as a career pass at the time of promotion. For a surgeon clinical competence is most important task to achieve but experience of research is also important for young surgeons to become a research minded surgeon or academic surgeon who will make a breakthrough in the field of surgery in the future. It should be emphasized that dean and professors are most responsible in the development of medical education.

Education, Medical↗

Nitric oxide inhibition decreases neutrophil adhesion at the inflammatory site, while increasing adhesion in remote organs in peritonitis.

Nitric oxide (NO) is a regulator of leukocyte adhesion in the microcirculation. This study was designed to examine the effects of a NO synthase inhibitor on neutrophil adhesion in the peritoneum, lung, liver, and kidney in a rat peritonitis model using a fluorescence microscopic method. Sprague-Dawley rats were given normal saline (control) or N omega-nitro-L-arginine methyl ester (L-NAME) at dosages of 10 mg/kg (N10) or 100 mg/kg (N100) (n = 66) intraperitoneally. One hour after pretreatment fluorescein-labeled neutrophils were infused without bacterial challenge (0 hr). Other rats received an injection of 10(7) Escherichia coli into the peritoneal cavity 1 hr after pretreatment. Labeled neutrophils were infused 1 and 5 hr after bacterial challenge. Just 2 min after neutrophil injection, blood samples were obtained and the animals were killed. Five peritoneal samples (omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Combined plasma nitrite/nitrate levels were determined. In another set of rats (n = 36), an arterial catheter was inserted after L-NAME treatment and bacterial challenge. At 0, 1, 5, and 12 hr after challenge, blood pressure, heart rate, and arterial blood gas data were measured. One hour after E. coli challenge, the number of neutrophils in the peritoneum was significantly lower in both L-NAME-treated groups than in the control group. In contrast, the number of labeled neutrophils in the lungs was significantly higher in the N100 group than in the control group. Neutrophil accumulation in the lungs and peritoneum at 0 and 5 hr and in the liver and kidney at 0, 1, and 5 hr did not differ among groups, nor did combined plasma nitrite/nitrate levels. L-NAME treatment had no influence on either hemodynamic or blood gas data. In conclusion, administration of L-NAME increases neutrophil adhesion in the lung, while decreasing that in the peritoneum. NO plays an important role in neutrophil adhesion at the inflammatory site, as well as in remote organs, during peritonitis. NO inhibition may be detrimental, due to neutrophil sequestration, in this peritonitis model.

Animals↗

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↗

Influences of type and duration of antimicrobial prophylaxis on an outbreak of methicillin-resistant Staphylococcus aureus and on the incidence of wound infection.

OBJECTIVE: To clarify how antibiotic prophylaxis influenced an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) and postoperative infection. DESIGN: Retrospective review. SETTING: University-affiliated teaching hospital. PATIENTS: All patients (n=1824) undergoing subtotal esophagectomy, gastrectomy, or colorectal surgery during the period 1982 through 1995. MAIN OUTCOME MEASURES: Type, timing, and duration of prophylactic antibiotics. Postoperative infection by the Centers for Disease Control and Prevention definition and the organisms isolated. RESULTS: Third-generation cephalosporins were frequently administered for prophylaxis during the period 1982 through 1990. The rate of isolates of MRSA from the infected site increased, peaking in 1988 to 1990. Since 1991 to 1992, along with a marked decrease in third-generation cephalosporin use, the rates of MRSA isolated have declined dramatically. The timing of administration changed from postoperative to intraoperative. Although the duration was gradually decreased, coverage was still provided until about the fifth postoperative day, even during 1993 to 1995. Prolonged coverage did not reduce the rate of superficial incisional or organ/space surgical site infection or that of pneumonia. CONCLUSIONS: Overuse of third-generation cephalosporins for long periods caused an MRSA outbreak. Long-term prophylaxis did not lower infection rates. The briefest possible prophylaxis with first- or second-generation cephalosporins should be used in general surgery.

Antibiotic Prophylaxis↗

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↗

Cytomegalic colitis after total colectomy in ulcerative colitis: report of a case.

A 58-year-old man with ulcerative colitis underwent total colectomy and ileorectal anastomosis. Steroid suppositories were administered postoperatively, and he had had no exacerbation in the residual rectum for 12 years. He suddenly presented with frequent bloody stools and anal pain. An intensive intravenous regimen of prednisolone was ineffective. Cytomegalic inclusion bodies were identified in biopsy specimens. Administration of ganciclovir reduced the ulcers remarkably. The clinical course suggested that this deterioration was caused by cytomegalovirus infection from the beginning. Cytomegalovirus colitis should be recognized as an exacerbating factor, even in ulcerative colitis patients who have undergone surgery, especially when the residual bowel inflammation is resistant to steroid therapy.

Colitis↗

Excess glutamine exacerbates trinitrobenzenesulfonic acid-induced colitis in rats.

BACKGROUND: Although the pathogenesis of Crohn's disease remains unclear, an elemental diet has been shown to be clinically effective. Glutamine is an energy source for many cell types including colonocytes. PURPOSE: This study was designed to assess the potential clinical effects on colitis of changing the dietary quantity of glutamine. METHODS: Colitis was induced by intrarectal administration of 30 mg of trinitrobenzenesulfonic acid with 50 percent ethanol vehicle in Sprague-Dawley rats. Rats were randomly allocated into three dietary groups: Group 1, a commercial elemental diet-based diet without glutamine; Group 2, a commercial elemental diet (glutamine: 12 percent of amino acid content); Group 3, elemental diet with 24 percent glutamine. Diets were started one week before colitis induction and continued until sacrifice. Rats were killed at one, three, and five weeks after colitis induction, and colons were excised. Damage evaluation was based on the percentage of rats with ulcer, macroscopic damage score, average ulcer area, and microscopic damage score. RESULTS: Group 2 rats weighed more than Group 1 rats at three weeks because of their higher dietary intake. At one week after colitis induction, all groups had comparable damage. At three weeks, the macroscopic damage score was higher in Group 3 than in Groups 1 and 2. At five weeks, rats in Group 3 had significantly more severe damage than those in Groups 1 and 2 in terms of all four indexes. CONCLUSION: We conclude that excess glutamine has a deleterious effect on ulcers in trinitrobenzenesulfonic acid-induced colitis.

Animals↗

Colorectal carcinogenesis: historical review.

PURPOSE: In view of the changing concept of colorectal carcinogenesis during the last 20 years, a historical review of colorectal carcinogenesis is presented. METHODS: The changing concept of colorectal carcinogenesis was presented in four different periods: 1) carcinogenesis based on surgical materials; 2) carcinogenesis based on polypectomy materials; 3) carcinogenesis based on nonpolypoid neoplasms; 4) carcinogenesis based on molecular biology. RESULTS: In the first period, large adenomas were thought to play the most important role as precursors to colorectal carcinomas; however, in the second period, smaller and nonpedunculated adenomas were found to have a much higher malignancy potential than previously thought. The discovery of nonpolypoid neoplasms, including flat and depressed adenomas/carcinomas, shed light on the new precursor of colorectal carcinomas that were not recognized in the past. Molecular biology clarified a lack of K-ras mutation in nonpolypoid, particularly depressed, neoplasms, suggesting the presence of a novel pathway of colorectal carcinogenesis, different from that in polypoid neoplasms. CONCLUSIONS: The concept referred to as the "adenoma-carcinoma sequence" changed because colonoscopic polypectomy specimens were studied, and rather small, nonpedunculated adenomas were found to play an important role as precursors of colorectal carcinomas. The discovery of nonpolypoid neoplasms provides us with new precursors of colorectal carcinomas. The genetic alterations in nonpolypoid neoplasms seem to differ from those in polypoid neoplasms, and genetic alterations in so-called de novo carcinomas need to be clarified.

Adenomatous Polyps↗

Substance P containing nerve fibers in rectal mucosa of ulcerative colitis.

BACKGROUND AND PURPOSE: The intestine is rich in peptidergic innervation, which modulates mucosal immune responses. Among neuropeptides, substance P (SubP) has received considerable attention for stimulatory effects on various immunocytes in inflammatory diseases. In our prior study, we demonstrated increased innervation of SubP containing nerve fibers (SubP fibers) in ulcerative colitis (UC) surgically resected colonic specimens. In the present study, we examined the alterations of SubP fibers among various subgroups of UC, divided according to clinicopathologic features. METHODS: Distribution of SubP fibers were examined immunohistochemically in the rectal biopsy specimens of UC. The UC group was further divided into subgroups according to six clinicopathologic parameters. The linear density of SubP fibers was measured by digitalized morphometry for quantitative analysis. RESULTS: Multivariate analysis revealed significant correlations between linear density of SubP fibers vs. activity of diseases and total dose of prednisolone. Linear density was significantly increased in active cases of UC (active UC, 22.6 +/- 1.6 microm/1,000 microm2; vs. inactive UC, 12.2 +/- 0.8 microm/1,000 microm2; P < 0.01). Furthermore, the increase was pronounced in cases that showed persistent inflammation and, accordingly, needed a high dose or continuous administration of prednisolone. CONCLUSION: Alterations in SubP fibers appear to play an important role in the pathogenesis of UC.

Adolescent↗

Results of the double stapling procedure in colorectal surgery.

In this report we review our results with the double stapling technique (DST) in 162 patients with colorectal diseases in an attempt to identify some of the potential pitfalls of this new technique. Among these 162 patients, there were 125 patients with colorectal cancer, 25 with chronic ulcerative colitis (UC), 9 with familial adenomatous polyposis (FAP), 2 with adult Hirschsprung's disease, and 1 with sigmoid colon fistula. A total of 46 anastomoses (28 for rectal cancer, 13 for UC, 3 for FAP, and 2 for adult Hirschsprung's disease) were performed at or near the dentate line. Of these, 10 had protective diverting colostomy or ileostomy. The results showed that 6 patients with rectal cancer had anastomotic leakage (3.7%); however, 4 of the 6 patients had also received preoperative irradiation. All the leaks healed after the patients had undergone diverting colostomy, but 7 patients with rectal cancer suffered from neurogenic bladder postoperatively (4.3%). Wound infection occurred in 4 patients (2.5%), anastomotic bleeding in 3 (1.9%), and anal pain in 1 (0.6%), respectively. One patient with rectal cancer and multiple liver metastases died of disseminated intravascular coagulation (DIC). These results thus suggest that the double stapling technique provides a safe anastomosis at or near the dentate line not only for rectal cancer but also for UC, FAP, and adult Hirschsprung's disease.

Adenomatous Polyposis Coli↗

A small glucagonoma of the pancreas with evident ductular and tubular structures.

A 54-year-old woman was admitted to our department for assessment of a tumor of the pancreas found incidentally on abdominal ultrasonography. Examination revealed a hypovascular 1-cm sized tumor in the body of the pancreas. Surgical examination revealed that the tumor was solitary and located in the pancreas body, with no invasion to the adjacent organs iof lymph node involvement. Distal pancreatectomy, preserving the spleen, was performed. Histologically, the tumor was a glucagonoma with evident ductular and tubular structures, suggesting that its site of origin was ductal epithelia.

Female↗